WO2021112217A1 - Composition for suppressing increase in amount of neutral fat in liver - Google Patents

Composition for suppressing increase in amount of neutral fat in liver Download PDF

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Publication number
WO2021112217A1
WO2021112217A1 PCT/JP2020/045224 JP2020045224W WO2021112217A1 WO 2021112217 A1 WO2021112217 A1 WO 2021112217A1 JP 2020045224 W JP2020045224 W JP 2020045224W WO 2021112217 A1 WO2021112217 A1 WO 2021112217A1
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weight
composition
parts
alanine
serine
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PCT/JP2020/045224
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French (fr)
Japanese (ja)
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しのぶ 秋好
遥 大橋
泰世 須賀
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味の素株式会社
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/175Amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics

Definitions

  • the present invention comprises a composition containing a specific amino acid for suppressing an increase in the amount of triglyceride in the liver (for example, a composition for suppressing fatty liver), a composition for improving insulin resistance, and visceral fat. It relates to a composition for suppressing an increase in the amount.
  • Non-Patent Document 1 the effects of leucine and valine on hepatic lipid accumulation in dietary obesity model mice are investigated.
  • Non-Patent Document 2 the effect of ketogenic essential amino acids on hepatic lipogenesis (DNL) is investigated.
  • DNL ketogenic essential amino acids on hepatic lipogenesis
  • composition (I) of the present invention was neutral in the liver. It has been found that the increase in triglyceride mass is suppressed, and a composition containing a specific amino acid described later (composition (II) of the present invention) suppresses the increase in triglyceride mass in the liver, insulin resistance. We have found that it improves sex and suppresses the increase in visceral fat mass, and further investigated it to complete the present invention.
  • the present invention provides the following.
  • [1] A composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients for suppressing an increase in the amount of triglyceride in the liver.
  • [2] The composition according to the above [1], which is used for suppressing fatty liver.
  • [3] When tyrosine is 1 part by weight, serine is 0.4 to 1.5 parts by weight, alanine is 0.4 to 1.5 parts by weight, and aspartic acid is 0.5 to 1.5 parts by weight.
  • [4] The composition according to any one of the above [1] to [3], which is a food product.
  • the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, and 0.5 to 1.5 parts by weight of aspartic acid.
  • the composition according to any one of the above [5] to [9] which is a food product.
  • a subject in need of suppressing an increase in triglyceride mass in the liver which comprises administering a composition containing an effective amount of tyrosine, serine, alanine, aspartic acid and glutamic acid.
  • a method of suppressing an increase in triglyceride mass [12] The method according to the above [11], wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  • tyrosine is 1 part by weight
  • serine is 0.4 to 1.5 parts by weight
  • alanine is 0.4 to 1.5 parts by weight
  • aspartic acid is 0.5 to 1.5 parts by weight.
  • a composition containing effective amounts of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine is administered to a subject who needs to suppress an increase in triglyceride mass in the liver.
  • the method according to the above [15], wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  • Insulin resistance in a subject in need of improved insulin resistance including administration of a composition containing an effective amount of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine. How to improve.
  • Viscera in a subject in need of suppression of an increase in visceral fat mass comprising administering to a subject a composition containing effective amounts of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine. A method of suppressing an increase in fat mass.
  • the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, and 0.5 to 1.5 parts by weight of aspartic acid.
  • a composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid for use in suppressing an increase in triglyceride mass in the liver [22] The composition according to the above [21], wherein the suppression of an increase in the amount of triglyceride in the liver is fatty liver suppression. [23] Assuming that tyrosine is 1 part by weight, serine is 0.4 to 1.5 parts by weight, alanine is 0.4 to 1.5 parts by weight, and aspartic acid is 0.5 to 1.5 parts by weight. The composition according to the above [21] or [22], which is 0.4 to 2.5 parts by weight of glutamic acid and glutamic acid.
  • the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, and 0.5 to 1.5 parts by weight of aspartic acid.
  • the composition according to any one of the above [25] to [29] which is a food product.
  • [31] Use of tyrosine, serine, alanine, aspartic acid and glutamic acid to produce compositions for suppressing the increase in triglyceride mass in the liver.
  • [32] The use according to the above [31], wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  • tyrosine is 1 part by weight
  • serine is 0.4 to 1.5 parts by weight
  • alanine is 0.4 to 1.5 parts by weight
  • aspartic acid is 0.5 to 1.5 parts by weight.
  • the use according to the above [31] or [32] which is 0.4 to 2.5 parts by weight of glutamic acid and glutamic acid.
  • compositions are a food product.
  • compositions for suppressing the increase in triglyceride mass in the liver.
  • suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  • Use of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine to produce compositions for improving insulin resistance.
  • tyrosine Use of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine to produce compositions for suppressing the increase in visceral fat mass.
  • the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, and 0.5 to 1.5 parts by weight of aspartic acid.
  • composition for suppressing an increase in the amount of triglyceride in the liver for example, a composition for suppressing fatty liver.
  • a composition for improving insulin resistance and a composition for suppressing an increase in visceral fat mass are possible.
  • FIG. 1 shows the results of Test Example 1.
  • FIG. 2 shows the results of Test Example 2.
  • FIG. 3 shows the results of Test Example 3.
  • FIG. 4 shows the results of Test Example 4.
  • the composition for suppressing an increase in the amount of neutral fat in the liver of the present invention is a composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients (in the present specification, tyrosine and serine). , Alanine, aspartic acid and glutamic acid may be referred to as the composition (I) of the present invention).
  • the composition (I) of the present invention is useful as a composition for suppressing fatty liver because it suppresses an increase in the amount of triglyceride in the liver.
  • the composition for suppressing an increase in the amount of neutral fat in the liver of the present invention contains tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients.
  • a composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine may be referred to as the composition (II) of the present invention.
  • the composition (II) of the present invention is useful as a composition for suppressing fatty liver because it suppresses an increase in the amount of triglyceride in the liver.
  • the composition (II) of the present invention is also useful as a composition for improving insulin resistance.
  • the composition (II) of the present invention is also useful as a composition for suppressing an increase in visceral fat mass.
  • “suppressing the increase in the amount of triglyceride in the liver” means that the amount of triglyceride in the liver (particularly, the amount of triglyceride) increases due to diet, aging, illness, obesity, constitution and the like. , Prevention, approaching or returning to normal, preventing exacerbations.
  • “fatty liver suppression” means preventing, bringing the fatty liver closer to normal, returning it to normal, or preventing exacerbation.
  • “improving insulin resistance” means preventing, bringing back or returning to normal insulin resistance, or preventing exacerbation due to diet, aging, illness, obesity, constitution, etc. To do.
  • insulin resistance refers to insulin because even if insulin is secreted from the pancreas into the blood, the response to insulin in the liver, skeletal muscle, and adipose tissue is slowed down (decreased sensitivity). It is a condition in which the function of lowering blood sugar is not fully exerted (insulin does not work well). Therefore, since insulin secretion is required more, the blood insulin concentration becomes high.
  • “suppressing the increase in visceral fat mass” means preventing, approaching, returning, or exacerbating the increase in visceral fat mass due to diet, aging, illness, obesity, constitution, etc. It means to prevent.
  • composition for suppressing increase in triglyceride mass of liver (for example, composition for suppressing fatty liver), “Composition for improving insulin resistance”, “Increase in visceral fat mass” of the present invention.
  • the use of the “composition for suppressing” may be therapeutic or non-therapeutic use for subjects such as humans.
  • non-therapeutic is a concept that does not include medical practice, that is, a concept that does not include a method of surgery, treatment, or diagnosis of a human being.
  • composition (I) of the present invention contains tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients.
  • the composition (II) of the present invention contains tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients.
  • the compositions (I) and (II) of the present invention are collectively referred to as the compositions of the present invention.
  • amino acids contained in the composition of the present invention are not limited as long as the effects of the present invention are not impaired, but L-form or DL-form is preferable, and L-form is more preferable.
  • the amino acid in the present invention may be produced by any production method such as a protein hydrolysis method, a chemical synthesis method, an enzyme method or a fermentation method, or a commercially available product may be used.
  • the amino acid in the present invention can also be obtained by enzymatically hydrolyzing a natural protein having the amino acid sequence.
  • the amino acid in the present invention can be used not only in the form of a free form but also in the form of a salt.
  • the terms tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine in the present specification are concepts that also include salts, respectively.
  • the form of the salt is not particularly limited as long as it is a salt that is acceptable as food or a salt that is pharmacologically acceptable, and examples thereof include acid addition salts and salts with bases. Specific examples thereof include inorganic bases, organic bases, inorganic acids, salts with organic acids, and salts with amino acids.
  • Examples of the salt with an inorganic base include salts with alkali metals such as lithium, sodium and potassium, salts with alkaline earth metals such as magnesium and calcium, and ammonium salts.
  • Examples of the salt with an organic base include salts with alkanolamines such as monoethanolamine, diethanolamine and triethanolamine, and salts with heterocyclic amines such as morpholine and piperidine.
  • Examples of the salt with the inorganic acid include salts with hydrochloric acid (hydrochloric acid, hydrobromic acid, hydroiodic acid, etc.), sulfuric acid, nitric acid, phosphoric acid, and the like.
  • salts with organic acids include salts with monocarboxylic acids such as formic acid, acetic acid and propanoic acid; salts with saturated dicarboxylic acids such as oxalic acid, malonic acid, malic acid and succinic acid; maleic acid and fumaric acid. Salts with unsaturated dicarboxylic acids such as; salts with tricarboxylic acids such as citric acid; salts with ketoic acids such as ⁇ -ketoglutaric acid and the like.
  • monocarboxylic acids such as formic acid, acetic acid and propanoic acid
  • salts with saturated dicarboxylic acids such as oxalic acid, malonic acid, malic acid and succinic acid
  • maleic acid and fumaric acid salts with unsaturated dicarboxylic acids
  • salts with tricarboxylic acids such as citric acid
  • salts with ketoic acids such as ⁇ -ketoglutaric acid and the like.
  • Salts with amino acids include salts with aliphatic amino acids such as glycine and alanine; salts with aromatic amino acids such as tyrosine; salts with basic amino acids such as arginine; salts with acidic amino acids such as aspartic acid and glutamic acid. Examples include salts with amino acids that form lactam, such as pyroglutamic acid.
  • the above-mentioned salts may be hydrates (hydrous salts), and examples of such hydrates include monohydrate to hexahydrate.
  • tyrosine is preferably a free form
  • serine is preferably a free form
  • alanine is preferably a free form
  • aspartic acid is preferably a free form and a sodium salt
  • glutamic acid is preferably a free form and a sodium salt.
  • isoleucine is preferably a free form
  • cystine is preferably a free form.
  • the blending ratio of tyrosine, serine, alanine, aspartic acid and glutamic acid is usually (2) in terms of L-form and free form, assuming that tyrosine is 1 part by weight. 0.4 to 1.5 parts by weight of serine, (3) 0.4 to 1.5 parts by weight of alanine, (4) 0.5 to 1.5 parts by weight of aspartic acid, (5) 0.4 to 2 parts by weight of glutamic acid. It is 5 parts by weight, preferably (2) 0.4 to 1.3 parts by weight, (3) 0.4 to 1.3 parts by weight, (4) 0.7 to 1.3 parts by weight, and (5). ) 0.4 to 2.1 parts by weight, more preferably (2) 0.4 to 1.1 parts by weight, (3) 0.4 to 1.1 parts by weight, (4) 0.9 to 0.9 parts. 1.1 parts by weight, (5) 0.4 to 2.1 parts by weight.
  • each amino acid in the composition (I) of the present invention is usually (1) tyrosine in terms of L-form and free form with respect to the total amount of tyrosine, serine, alanine, aspartic acid and glutamic acid. 12-40% by weight, (2) serine 12-28% by weight, (3) alanine 12-28% by weight, (4) aspartic acid 12-40% by weight and (5) glutamic acid 12-30% by weight, preferably.
  • the amino acids in the present invention mean free amino acids and do not include constituent amino acids in proteins and peptides.
  • the content and compounding ratio of each amino acid in the present invention are the content and compounding ratio of L-form amino acids, and when the amino acid is contained in the form of a salt, it is converted into a free form. It is expressed by the content of the product.
  • the dose (intake) of the composition (I) of the present invention may vary depending on age, sex, body weight, target disease, symptom, and dosage form, but is usually from 1 g per day for an adult (for example, body weight 60 kg). It is administered or ingested once or several times a day so as to be in the range of 30 g, preferably 2 g to 15 g, and more preferably 2 g to 12 g.
  • the dose (intake) of tyrosine is usually in the range of 0.28 g to 8.6 g per day for an adult, preferably in the range of 0.57 g to 4.3 g. , 0.57 g to 3.5 g is more preferable.
  • the dose (intake) of serin is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
  • the dose (intake) of alanine is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
  • the dose (intake) of aspartic acid is usually in the range of 0.28 g to 8.6 g, preferably in the range of 0.57 g to 4.3 g per day for adults. The range of 0.57 g to 3.5 g is more preferable.
  • the dose (intake) of glutamic acid is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0.
  • the range of .28 g to 1.8 g is more preferable.
  • the amount per adult can be appropriately changed in consideration of physical conditions such as gender, age, and disease.
  • the above-mentioned daily amount can be administered (ingested) at one time or in several divided doses.
  • the administration period is not particularly limited, and long-term administration (long-term ingestion) is possible because the active ingredient is an amino acid.
  • the ratio contained in the composition of amino acids other than tyrosine, serine, alanine, aspartic acid and glutamic acid in the present invention is converted into a free form with respect to the total weight of the composition. Therefore, it is 50% by weight or less, preferably 40% by weight or less, more preferably 30% by weight or less, further preferably not substantially contained, and particularly preferably not contained.
  • substantially free means 0.2% by weight or less, preferably 0.1% by weight or less, and more preferably 0.05% by weight or less.
  • composition (I) of the present invention can further contain other nutritional components such as sugars, lipids, proteins, vitamins and minerals in addition to the amino acids in the present invention.
  • composition (I) of the present invention is optionally other amino acids, other nutritional components, food-acceptable additives, and pharmaceutically acceptable.
  • Additives, etc. and use a formulation method well known in the field of formulation, for example, the method described in each article of the 17th Amendment of the Japanese Pharmacy Regulations [3] Formulation, to make solutions, suspensions, and emulsions. It can be in various forms such as liquid such as liquid; semi-solid such as gel and cream; and solid such as powder, granules, tablets and capsules.
  • the blending ratio of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine is (1) when tyrosine is 1 part by weight, it is converted into L form and free form.
  • tyrosine is 1 part by weight, it is converted into L form and free form.
  • serine is converted into L form and free form.
  • alanine is converted into L form and free form.
  • 0.5 to 1.5 parts by weight of aspartic acid (5) 0.
  • each amino acid in the composition (II) of the present invention is usually converted into L form and free form with respect to the total amount of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine.
  • Tyrosine 10 to 20% by weight (2) Serine 5 to 10% by weight, (3) Alanine 5 to 10% by weight, (4) Aspartic acid 10 to 20% by weight, (5) Glutamic acid 5 to 10% by weight , (6) 30-40% by weight of isoleucine, (7) 10-20% by weight of cystine, preferably (1) 12-18% by weight of tyrosine, (2) 5-10% by weight of serine, (3) 5 to 10% by weight of alanine.
  • 10% by weight, (4) aspartic acid 12-18% by weight (5) glutamic acid 5-10% by weight, (6) isoleucine 30-38% by weight and (7) cystine 12-18% by weight.
  • the dose (intake) of the composition (II) of the present invention may vary depending on age, sex, body weight, target disease, symptom, and dosage form, but is usually from 1 g per day for an adult (for example, body weight 60 kg). It is administered or ingested once or several times a day so as to be in the range of 30 g, preferably 2 g to 15 g, and more preferably 2 g to 12 g.
  • the dose (intake) of tyrosine is usually in the range of 0.28 g to 8.6 g per day for an adult, preferably in the range of 0.57 g to 4.3 g. , 0.57 g to 3.5 g is more preferable.
  • the dose (intake) of serin is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
  • the dose (intake) of alanine is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
  • the dose (intake) of aspartic acid is usually in the range of 0.28 g to 8.6 g, preferably in the range of 0.57 g to 4.3 g per day for adults. The range of 0.57 g to 3.5 g is more preferable.
  • the dose (intake) of glutamic acid is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
  • the dose (intake) of isoleucine is usually in the range of 0.7 g to 21 g, preferably in the range of 0.7 g to 10 g, and is preferably in the range of 0.7 g to 5 g per day for adults. The range of is more preferable.
  • the dose (intake) of cystine is usually in the range of 0.28 g to 2 g, preferably in the range of 0.28 g to 1.5 g, and 0.28 g per day for adults.
  • the range of ⁇ 1 g is more preferable.
  • the amount per adult can be appropriately changed in consideration of physical conditions such as gender, age, and disease.
  • the above-mentioned daily amount can be administered (ingested) at one time or in several divided doses.
  • the administration period is not particularly limited, and long-term administration (long-term ingestion) is possible because the active ingredient is an amino acid.
  • the proportion contained in the composition of amino acids other than tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine in the present invention is based on the total weight of the composition. In terms of free form, it is 50% by weight or less, preferably 40% by weight or less, more preferably 30% by weight or less, further preferably not substantially contained, and particularly preferably not contained.
  • substantially free means 0.2% by weight or less, preferably 0.1% by weight or less, and more preferably 0.05% by weight or less.
  • composition (II) of the present invention can further contain other nutritional components such as sugars, lipids, proteins, vitamins and minerals in addition to the amino acids in the present invention.
  • the composition (II) of the present invention contains, if necessary, other amino acids, other nutritional components, food-acceptable additives, and pharmaceuticals.
  • Add the additives, etc. which are permitted to be used, and use a formulation method well known in the field of formulation, for example, the method described in each article of the 17th revised Japanese Pharmacy Regulations [3] formulation, solution, suspension. It can be in various forms such as liquids such as liquids and emulsions; semi-solids such as gels and creams; solids such as powders, granules, tablets and capsules.
  • the above-mentioned food-acceptable additive or pharmaceutically acceptable additive can be appropriately selected depending on the form of the composition of the present invention, for example, excipients.
  • examples of the excipient include magnesium carbonate, sugars (glucose, lactose, cornstarch, etc.), sugar alcohols (sorbitol, mannitol, etc.) and the like.
  • examples of the binder include gelatin, pregelatinized starch, partially pregelatinized starch, cellulose and its derivatives (crystalline cellulose, hydroxypropyl cellulose, etc.) and the like.
  • examples of the disintegrant include crospovidone, povidone, crystalline cellulose and the like.
  • examples of the lubricant include talc, magnesium stearate and the like.
  • the coating agent examples include methacrylic acid / methyl methacrylate copolymer, methacrylic acid / ethyl acrylate copolymer, methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, ethyl acrylate / methacrylic acid.
  • examples thereof include a trimethylammonium ethyl methacrylate copolymer of methyl methacrylate.
  • Examples of the base include animal and vegetable fats and oils (olive oil, cacao butter, beef tallow, sesame oil, hydrogenated oil, castor oil, etc.), waxes (carnauba wax, beeswax, etc.), polyethylene glycol and the like.
  • Examples of the solvent include purified water, water for injection, monohydric alcohol (ethanol and the like), polyhydric alcohol (glycerin and the like) and the like.
  • Examples of the solubilizing agent include propylene glycol, medium-chain fatty acid triglyceride, and the like.
  • solubilizer, emulsifier, dispersant and suspending agent examples include sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester (polysorbate 20, polysorbate 80, etc.), polyoxyethylene hydrogenated castor oil, and sucrose.
  • surfactants such as fatty acid esters.
  • Examples of the stabilizer include adipic acid, ⁇ -cyclodextrin, ethylenediamine, sodium edetate and the like.
  • Examples of the thickener include water-soluble polymers (sodium polyacrylate, carboxyvinyl polymer, etc.), polysaccharides (sodium alginate, xanthan gum, tragant, etc.) and the like.
  • Examples of the soothing agent include ethyl aminobenzoate, chlorobutanol, propylene glycol, benzyl alcohol and the like.
  • Examples of the tonicity agent include potassium chloride, sodium chloride, sorbitol, physiological saline and the like.
  • Examples of the pH adjuster include hydrochloric acid, sulfuric acid, acetic acid, citric acid, lactic acid, sodium hydroxide, potassium hydroxide and the like.
  • antioxidants examples include dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), dl- ⁇ -tocopherol, erythorbic acid and the like.
  • preservatives and preservatives include parabens (methylparaben and the like), benzyl alcohol, sodium dehydroacetate, sorbic acid and the like.
  • Examples of the flavoring agent include ascorbic acid, erythritol, sodium L-glutamate and the like.
  • Examples of the sweetener include aspartame, licorice extract, saccharin and the like.
  • Examples of the fragrance include l-menthol, d-camphor, vanillin and the like.
  • Examples of colorants include tar pigments (edible red No. 2, edible blue No. 1, edible yellow No. 4, etc.), inorganic pigments (iron sesquioxide, iron yellow oxide, iron black oxide, etc.), and natural pigments (turmeric extract). , ⁇ -carotene, sodium copper chlorophyllin, etc.) and the like.
  • one kind or two or more kinds of the above additives can be used.
  • the total content of tyrosine, serine, alanine, aspartic acid and glutamic acid in the composition (I) of the present invention is usually 10% by weight to 100% by weight based on the total amount of the composition from the viewpoint of functionality. It is preferably 50% by weight to 100% by weight, more preferably 60% by weight to 100% by weight, further preferably 70% by weight to 100% by weight, and particularly preferably 80% by weight to 100% by weight. ..
  • the total content of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine in the composition (II) of the present invention is usually 10% by weight to 100% by weight based on the total amount of the composition from the viewpoint of functionality. It is% by weight, preferably 50% by weight to 100% by weight, more preferably 60% by weight to 100% by weight, further preferably 70% by weight to 100% by weight, and particularly preferably 80% by weight to 100% by weight. By weight%.
  • the composition of the present invention may be in a "unit packaging form" in which the composition is packaged in units of one-time or one-meal intake.
  • a form means a form in which the amount to be ingested per serving or one meal is predetermined and packaged.
  • the container or package used in the unit packaging form can be appropriately selected depending on the form of the composition of the present invention, but a paper container or bag, a plastic container or bag, a pouch, an aluminum can, etc. Examples include steel cans, bottles, PET bottles, and PTP (press through pack) packaging sheets.
  • the composition of the present invention is packaged in the form of one intake or one intake unit per meal.
  • a beverage or jelly in which the composition of the present invention is suspended or dissolved is filled in a pouch or the like in the form of a single drink or a complete meal.
  • a total of 0.5 g to 4 g, preferably 0.5 g to 2 g of tyrosine, serine, alanine, aspartic acid and glutamic acid can be contained in the one-time or one-meal intake.
  • a total of 0.5 g to 4 g, preferably 0.5 g to 2 g of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine may be contained in the one-time or one-meal intake. it can.
  • the required amount of the amino acid can be easily ingested by ingesting one or one meal intake unit.
  • a measuring container and a kit containing a composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients or a measuring container, and tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients.
  • the measuring container is not particularly limited as long as it is a container for measuring the single intake of the above amino acids, and examples thereof include a measuring cup and a measuring spoon.
  • the amount to be ingested at one time is the same as the amount described in the unit packaging form per meal.
  • the amount that can be measured with the measuring container can be determined according to the container, such as the amount of scraping or heaping. Further, the measuring container may have a scale on which the amount used at one time and the like are displayed.
  • the form of the composition of the present invention is liquid such as a beverage, jelly such as jelly, gel, jelly-like beverage, milky such as milk, milk beverage, yogurt, etc., gum-like, powdery, granular form. , Sheets, capsules, tablets, snack bars, solids such as cookies, etc.
  • Mammals eg, humans, monkeys, mice, rats, guinea pigs, hamsters, rabbits, cats, dogs, cows, horses, donkeys, pigs, sheep, etc.
  • birds eg, humans, monkeys, mice, rats, guinea pigs, horses, donkeys, pigs, sheep, etc.
  • Duck, chicken, goose, turkey, etc. the intake or dose of the composition of the present invention is the type, sex, body weight, etc. of the target animal. It may be set appropriately according to.
  • the composition of the present invention can be added to various foods and ingested.
  • the food to which the composition of the present invention is added is not particularly limited, and any food in a form generally used for meals or desserts may be used.
  • the composition of the present invention can be added to a beverage such as a soft drink and, if desired, an appropriate flavor can be added to obtain a drink.
  • the composition of the present invention may be added to, for example, soft drinks such as fruit juice drinks and sports drinks; dairy products such as milk and yogurt; confectionery such as jelly, chocolate, candy and biscuits. it can.
  • the total amount of amino acids (total amount converted into L-form and free form) in the present invention is the above-mentioned daily intake with respect to the above-mentioned various foods ingested per day. It is preferably added in an amount.
  • the composition of the present invention is a food product (hereinafter, also referred to as "food product of the present invention" in the present specification) by ordinary food manufacturing techniques, either as it is or by adding general food additives as needed.
  • the food product of the present invention can be in various forms such as liquid, suspension, milky, gel, cream, powder, granule, sheet, capsule, tablet and the like.
  • the food of the present invention is prepared by adding the composition of the present invention to various food raw materials, adding general food additives as necessary, and using a general food manufacturing technique to soften drinking water (fruit juice beverage).
  • Sports drinks, coffee drinks, tea drinks, etc. dairy products (lactic acid bacteria drinks, fermented milk, butter, cheese, yogurt, processed milk, defatted milk, etc.), livestock meat products (ham, sausage, hamburger, etc.), fish paste products (ham, sausage, hamburger, etc.) Gamo, bamboo ring, fried satsuma, etc.), egg products (dashi roll, egg tofu, etc.), confectionery (cookies, jelly, chewing gum, candy, snack confectionery, cold confectionery, etc.) , Foods of various forms, may be bottled foods, canned foods, retort pouch foods.
  • Examples of the above food additives include manufacturing agents (citric acid, binders, etc.), thickening stabilizers (xanthan gum, sodium carboxymethyl cellulose, etc.), gelling agents (gelatin, agar, carrageenan, etc.), gum bases (vinyl acetate resin, vinyl acetate, etc.).
  • emulsifiers glycolin fatty acid ester, sucrose fatty acid ester, saponin, lecithin, etc.
  • preservatives benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, ⁇ -polylysine, etc.
  • antioxidants ⁇ -polylysine, etc.
  • Ascorbic acid, erythorbic acid, catechin, etc. brighteners
  • fungicides thiaventazole, fludioxonyl, etc.
  • swelling agents sodium hydrogencarbonate, glucono ⁇ -lactone, myoban, etc.
  • Sweeteners aspartame, assesulfam potassium, kanzo extract, etc.
  • bitterness agents caffeine, narringine, nigayomogi extract, etc.
  • acidulants citric acid, tartaric acid, lactic acid,
  • the food of the present invention can be suitably ingested by a wide range of subjects for the purpose of suppressing an increase in the amount of triglyceride in the liver or suppressing fatty liver.
  • the food of the present invention is a food for specified health use, a food with a nutritional function, a food with a functional claim, or a sick person for suppressing an increase in the amount of neutral fat in the liver or for suppressing adipose liver. It can also be provided as food for special use such as food for the elderly, food for the elderly, health supplement, and the like.
  • the food of the present invention includes, for example, a medical food for obesity and the like.
  • the food product of the present invention is ingested by the above-mentioned application target so that the total amount of amino acids in the present invention (total amount converted into L-form and free form) in the above-mentioned daily intake is the above-mentioned daily intake. It is preferable to let it.
  • Example 1 Serine, aspartic acid, alanine, glutamic acid, and tyrosine were mixed in the weight ratios shown in Table 1 to prepare the amino acid composition of Example 1. For serine, aspartic acid, alanine, glutamic acid, and tyrosine, L-form and free form were used. Using BLACK6J male mice, obese mice were prepared from 6 weeks of age by loading with a high-fat, high-carbohydrate diet (Research Diet Co., Ltd. D12327).
  • the amino acid composition (1 g / kg body weight) and 0.5% methylcellulose solution (medium) of Example 1 were applied to the test group, and the 0.5% methylcellulose solution (medium) was applied to the control group in the morning and evening. Oral administration twice daily for 6 weeks. During this time, the diet used was a high-fat, high-carbohydrate diet. In the normal group, using BLACK6J male mice, 0.5% methylcellulose solution (medium) was orally administered twice a day in the morning and evening from 8 weeks of age for 6 weeks. During this time, a control diet was used as the bait.
  • the group composition is shown in Table 2.
  • triglyceride (TG) in the liver was extracted by a conventional method, and quantified using a kit (WAKO).
  • WAKO triglyceride
  • FIG. 1 In the control group, the amount of triglyceride (TG) was increased by the high-fat, high-carbohydrate diet as compared with the normal group, but in the test group to which the amino acid composition of Example 1 was administered, the amount of triglyceride (TG) was almost the same as that in the normal group. It was a quantity (Fig. 1). From this result, it was shown that the increase in triglyceride mass can be suppressed (returned to normal) by administration of the amino acid composition of Example 1.
  • KKAy male mice and BLACK6J male mice of the same age were bred from 6 weeks on a standard diet (Oriental Yeast Co., Ltd., AIN93G). From 11 weeks of age, the test group (KKAy mouse) was a standard diet (Oriental yeast, AIN93G) mixed with 2% (w / w) of the amino acid composition of Example 2, and the control group (KKAy mouse) was a standard diet (KKAy mouse). The oriental yeast, AIN93G) and normal group (BLACK6J mice) were fed a standard diet (oriental yeast, AIN93G) for 5 weeks. The group composition is shown in Table 4.
  • triglyceride (TG) in the liver was extracted by a conventional method, and quantified using a kit (WAKO).
  • WAKO triglyceride
  • FIG. 2 the amount of triglyceride (TG) was significantly increased as compared with the normal group, but in the test group to which the amino acid composition of Example 2 was administered, the amount of triglyceride (TG) was significantly decreased as compared with the control group. (Fig. 2). From this result, it was shown that the increase in triglyceride mass can be suppressed (approached to normal) by administration of the amino acid composition of Example 2.
  • obesity promotes fat accumulation in hepatocytes and exacerbates it by inflammation, the donation of the amino acid composition of Example 2 improved the increase in hepatic fat mass.
  • Test Example 3 The same amino acid composition of Example 2 used in Test Example 2 was used in Test Example 3. Using BLACK6J male mice, they were bred on a high-fat diet (Oriental yeast, HFD-60) for 4 weeks from 10 weeks of age to prepare a diet-induced obesity model (DIO model). From 14 weeks of age, the test group received a high-fat diet (HFD-60) mixed with 2% (w / w) of the amino acid composition of Example 2, and the control group received a high-fat diet (HFD-60). It was donated for 8 weeks. The normal group was bred from 10 weeks of age on a standard diet (Oriental Yeast Co., Ltd., AIN93G) for 12 weeks using BLACK6J male mice. The group composition is shown in Table 5.
  • the liver was sampled at autopsy, lipids in the liver were extracted by a routine method, and triglycerides and free fatty acids were quantified using a kit (WAKO).
  • WAKO epididymal fat, which is visceral fat, was collected and weighed.
  • FIG. Regarding the amount of triglyceride and free fatty acid in the liver, the amount of triglyceride and free fatty acid in the control group increased significantly as compared with the normal group, but in the test group to which the amino acid composition of Example 2 was administered, the amount was medium.
  • the amount of triglyceride and the amount of free fatty acid were significantly reduced as compared with the control group (left and middle figures in FIG. 3).
  • Test Example 4 The same amino acid composition of Example 2 used in Test Example 2 was used in Test Example 4. Using BLACK6J male mice, they were bred on a high-fat diet (Oriental yeast, HFD-60) for 4 weeks from 10 weeks of age to prepare a diet-induced obesity model (DIO model). From 14 weeks of age, the test group received a high-fat diet (HFD-60) mixed with 2% (w / w) of the amino acid composition of Example 2, and the control group received a high-fat diet (HFD-60). It was donated for 8 weeks. The normal group was bred from 10 weeks of age on a standard diet (Oriental Yeast Co., Ltd., AIN93G) for 12 weeks using BLACK6J male mice. The group composition is shown in Table 6.
  • tail vein blood sampling was performed at weeks 4, 6 and 8 of the high-fat diet (HFD-60) in which the amino acid composition of Example 2 was mixed at 2% (w / w), respectively, and fasting blood was collected.
  • the medium insulin level was measured with a kit (Morinaga Seigaku Kenkyusho).
  • the fasting blood insulin level was used as a kit (Morinaga Seigaku Kenkyusho).
  • FIG. In the control group, the fasting insulin level was significantly increased as compared with the normal group (left figure, middle figure, right figure in FIG.
  • the fasting insulin level was administered in the test group to which the amino acid composition of Example 2 was administered. However, it decreased significantly in the 4th and 6th weeks of the intervention compared to the control group (left figure and middle figure in FIG. 4), and decreased in the 8th week of the intervention as compared with the control group (right figure in FIG. 4). ).
  • An increase in fasting insulin levels suggests insulin resistance and decreased insulin sensitivity in organs. Insulin resistance promotes lipid accumulation in the liver. Diabetes induction is also inferred. From the results of FIG. 4, it was shown that insulin resistance promoted by obesity can be improved (approached to normal) by administration of the amino acid composition of Example 2. Obesity promotes insulin resistance, but donation of the amino acid composition of Example 2 improved insulin resistance.
  • composition for suppressing an increase in the amount of triglyceride in the liver for example, a composition for suppressing fatty liver.
  • a composition for improving insulin resistance and a composition for suppressing an increase in visceral fat mass are possible.

Abstract

The present invention addresses the problem of providing a composition (e.g., a fatty liver suppression composition) for suppressing increases in the amount of neutral fat in the liver, a composition for improving insulin resistance, and a composition for suppressing increases in amount of visceral fat. A composition (e.g., a fatty liver suppression composition) for suppressing increases in the amount of neutral fat in the liver, the composition containing, as active ingredients, tyrosine, serine, alanine, aspartic acid, and glutamic acid. A composition (e.g., a fatty liver suppression composition) for suppressing increases in the amount of neutral fat in the liver, a composition for improving insulin resistance, and a composition for suppressing increases in amount of visceral fat, the compositions containing, as active ingredients, tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine, and cystine.

Description

肝臓の中性脂肪量の増加抑制用組成物Composition for suppressing increase in triglyceride mass in liver
 本発明は、特定のアミノ酸を含有する、肝臓の中性脂肪量の増加を抑制するための組成物(例えば、脂肪肝抑制用組成物)、インスリン抵抗性を改善するための組成物、内臓脂肪量の増加を抑制するための組成物に関する。 The present invention comprises a composition containing a specific amino acid for suppressing an increase in the amount of triglyceride in the liver (for example, a composition for suppressing fatty liver), a composition for improving insulin resistance, and visceral fat. It relates to a composition for suppressing an increase in the amount.
 脂肪肝に対しては、直接的な効果のある医薬品やサプリメントがなく、運動療法、食事療法が推奨されているが、十分な効果は得られておらず、脂肪肝に対して直接的な効果のある医薬品やサプリメント等の開発が求められている。
 非特許文献1においては、食餌性肥満モデルマウスにおける肝臓脂質蓄積に及ぼすロイシンとバリンの効果について検討されている。非特許文献2においては、肝臓の脂質生成(de novo lipogenesis; DNL)に対するケト原性必須アミノ酸の効果について検討されている。
 しかし、後述する本発明の特定のアミノ酸組成物が、肝臓の中性脂肪量の増加を抑制すること、インスリン抵抗性を改善すること、内臓脂肪量の増加を抑制することは知られていない。
For fatty liver, there are no medicines or supplements that have a direct effect, and exercise therapy and diet therapy are recommended, but the effect is not sufficient and the effect is direct for fatty liver. There is a need to develop certain medicines and supplements.
In Non-Patent Document 1, the effects of leucine and valine on hepatic lipid accumulation in dietary obesity model mice are investigated. In Non-Patent Document 2, the effect of ketogenic essential amino acids on hepatic lipogenesis (DNL) is investigated.
However, it is not known that the specific amino acid composition of the present invention described later suppresses the increase in triglyceride mass in the liver, improves insulin resistance, and suppresses the increase in visceral fat mass.
 本発明は、肝臓の中性脂肪量の増加を抑制するための組成物(例えば、脂肪肝抑制用組成物)の提供を課題とする。
 また、本発明は、インスリン抵抗性を改善するための組成物、内臓脂肪量の増加を抑制するための組成物の提供を課題とする。
An object of the present invention is to provide a composition for suppressing an increase in the amount of triglyceride in the liver (for example, a composition for suppressing fatty liver).
Another object of the present invention is to provide a composition for improving insulin resistance and a composition for suppressing an increase in visceral fat mass.
 本発明者らは、上記課題を解決するために、鋭意検討を行ったところ、有効成分として後述する特定のアミノ酸を含有する組成物(本発明の組成物(I))が、肝臓の中性脂肪量の増加を抑制することを見出し、また、後述する特定のアミノ酸を含有する組成物(本発明の組成物(II))が、肝臓の中性脂肪量の増加を抑制すること、インスリン抵抗性を改善すること、及び内臓脂肪量の増加を抑制することを見出し、さらに検討して、本発明を完成させた。 The present inventors conducted diligent studies in order to solve the above-mentioned problems, and found that the composition containing a specific amino acid described later as an active ingredient (the composition (I) of the present invention) was neutral in the liver. It has been found that the increase in triglyceride mass is suppressed, and a composition containing a specific amino acid described later (composition (II) of the present invention) suppresses the increase in triglyceride mass in the liver, insulin resistance. We have found that it improves sex and suppresses the increase in visceral fat mass, and further investigated it to complete the present invention.
 すなわち、本発明は、下記を提供する。
[1]有効成分として、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含有する、肝臓の中性脂肪量の増加を抑制するための組成物。
[2]脂肪肝抑制用である、上記[1]記載の組成物。
[3]組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部及びグルタミン酸0.4~2.5重量部である、上記[1]又は[2]に記載の組成物。
[4]食品である、上記[1]~[3]のいずれかに記載の組成物。
[5]有効成分として、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する、肝臓の中性脂肪量の増加を抑制するための組成物。
[6]脂肪肝抑制用である、上記[5]記載の組成物。
[7]有効成分として、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する、インスリン抵抗性を改善するための組成物。
[8]有効成分として、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する、内臓脂肪量の増加を抑制するための組成物。
[9]組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部、グルタミン酸0.4~2.5重量部、イソロイシン1~4重量部及びシスチン0.1~2重量部である、上記[5]~[8]のいずれかに記載の組成物。
[10]食品である、上記[5]~[9]のいずれかに記載の組成物。
That is, the present invention provides the following.
[1] A composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients for suppressing an increase in the amount of triglyceride in the liver.
[2] The composition according to the above [1], which is used for suppressing fatty liver.
[3] When tyrosine is 1 part by weight, serine is 0.4 to 1.5 parts by weight, alanine is 0.4 to 1.5 parts by weight, and aspartic acid is 0.5 to 1.5 parts by weight. The composition according to the above [1] or [2], which is 0.4 to 2.5 parts by weight of glutamic acid.
[4] The composition according to any one of the above [1] to [3], which is a food product.
[5] A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients for suppressing an increase in the amount of triglyceride in the liver.
[6] The composition according to the above [5], which is used for suppressing fatty liver.
[7] A composition for improving insulin resistance, which contains tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients.
[8] A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients for suppressing an increase in visceral fat mass.
[9] When tyrosine is 1 part by weight, the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, and 0.5 to 1.5 parts by weight of aspartic acid. The composition according to any one of the above [5] to [8], which is 0.4 to 2.5 parts by weight of glutamic acid, 1 to 4 parts by weight of isoleucine, and 0.1 to 2 parts by weight of cystine.
[10] The composition according to any one of the above [5] to [9], which is a food product.
[11]肝臓の中性脂肪量の増加の抑制を必要とする対象に、有効量のチロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含有する組成物を投与することを含む、該対象における肝臓の中性脂肪量の増加を抑制する方法。
[12]肝臓の中性脂肪量の増加の抑制が、脂肪肝抑制である、上記[11]記載の方法。
[13]組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部及びグルタミン酸0.4~2.5重量部である、上記[11]又は[12]に記載の方法。
[14]組成物が対象に経口投与される、上記[11]~[13]のいずれかに記載の方法。
[15]肝臓の中性脂肪量の増加の抑制を必要とする対象に、有効量のチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物を投与することを含む、該対象における肝臓の中性脂肪量の増加を抑制する方法。
[16]肝臓の中性脂肪量の増加の抑制が、脂肪肝抑制である、上記[15]記載の方法。
[17]インスリン抵抗性の改善を必要とする対象に、有効量のチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物を投与することを含む、該対象におけるインスリン抵抗性を改善する方法。
[18]内臓脂肪量の増加の抑制を必要とする対象に、有効量のチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物を投与することを含む、該対象における内臓脂肪量の増加を抑制する方法。
[19]組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部、グルタミン酸0.4~2.5重量部、イソロイシン1~4重量部及びシスチン0.1~2重量部である、上記[15]~[18]のいずれかに記載の方法。
[20]組成物が対象に経口投与される、上記[15]~[19]のいずれかに記載の方法。
[11] A subject in need of suppressing an increase in triglyceride mass in the liver, which comprises administering a composition containing an effective amount of tyrosine, serine, alanine, aspartic acid and glutamic acid. A method of suppressing an increase in triglyceride mass.
[12] The method according to the above [11], wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
[13] When tyrosine is 1 part by weight, serine is 0.4 to 1.5 parts by weight, alanine is 0.4 to 1.5 parts by weight, and aspartic acid is 0.5 to 1.5 parts by weight. The method according to the above [11] or [12], which is 0.4 to 2.5 parts by weight of glutamic acid and glutamic acid.
[14] The method according to any one of [11] to [13] above, wherein the composition is orally administered to a subject.
[15] A composition containing effective amounts of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine is administered to a subject who needs to suppress an increase in triglyceride mass in the liver. A method of suppressing an increase in triglyceride mass in the liver in a subject.
[16] The method according to the above [15], wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
[17] Insulin resistance in a subject in need of improved insulin resistance, including administration of a composition containing an effective amount of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine. How to improve.
[18] Viscera in a subject in need of suppression of an increase in visceral fat mass, comprising administering to a subject a composition containing effective amounts of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine. A method of suppressing an increase in fat mass.
[19] When tyrosine is 1 part by weight, the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, and 0.5 to 1.5 parts by weight of aspartic acid. The method according to any one of [15] to [18] above, which comprises 0.4 to 2.5 parts by weight of glutamic acid, 1 to 4 parts by weight of isoleucine, and 0.1 to 2 parts by weight of cystine.
[20] The method according to any one of [15] to [19] above, wherein the composition is orally administered to a subject.
[21]肝臓の中性脂肪量の増加の抑制における使用のための、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含有する組成物。
[22]肝臓の中性脂肪量の増加の抑制が脂肪肝抑制である、上記[21]記載の組成物。
[23]組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部及びグルタミン酸0.4~2.5重量部である、上記[21]又は[22]に記載の組成物。
[24]食品である、上記[21]~[23]のいずれかに記載の組成物。
[25]肝臓の中性脂肪量の増加の抑制における使用のための、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物。
[26]肝臓の中性脂肪量の増加の抑制が脂肪肝抑制である、上記[25]記載の組成物。
[27]インスリン抵抗性の改善における使用のための、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物。
[28]内臓脂肪量の増加の抑制における使用のための、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物。
[29]組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部、グルタミン酸0.4~2.5重量部、イソロイシン1~4重量部及びシスチン0.1~2重量部である、上記[25]~[28]のいずれかに記載の組成物。
[30]食品である、上記[25]~[29]のいずれかに記載の組成物。
[21] A composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid for use in suppressing an increase in triglyceride mass in the liver.
[22] The composition according to the above [21], wherein the suppression of an increase in the amount of triglyceride in the liver is fatty liver suppression.
[23] Assuming that tyrosine is 1 part by weight, serine is 0.4 to 1.5 parts by weight, alanine is 0.4 to 1.5 parts by weight, and aspartic acid is 0.5 to 1.5 parts by weight. The composition according to the above [21] or [22], which is 0.4 to 2.5 parts by weight of glutamic acid and glutamic acid.
[24] The composition according to any one of the above [21] to [23], which is a food product.
[25] A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine for use in suppressing the increase in triglyceride mass in the liver.
[26] The composition according to the above [25], wherein the suppression of an increase in the amount of triglyceride in the liver is fatty liver suppression.
[27] A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine for use in improving insulin resistance.
[28] A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine for use in suppressing an increase in visceral fat mass.
[29] When tyrosine is 1 part by weight, the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, and 0.5 to 1.5 parts by weight of aspartic acid. The composition according to any one of the above [25] to [28], which is 0.4 to 2.5 parts by weight of glutamic acid, 1 to 4 parts by weight of isoleucine, and 0.1 to 2 parts by weight of cystine.
[30] The composition according to any one of the above [25] to [29], which is a food product.
[31]肝臓の中性脂肪量の増加を抑制するための組成物を製造するためのチロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸の使用。
[32]肝臓の中性脂肪量の増加の抑制が脂肪肝抑制である、上記[31]記載の使用。
[33]組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部及びグルタミン酸0.4~2.5重量部である、上記[31]又は[32]に記載の使用。
[34]組成物が食品である、上記[31]~[33]のいずれかに記載の使用。
[35]肝臓の中性脂肪量の増加を抑制するための組成物を製造するためのチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの使用。
[36]肝臓の中性脂肪量の増加の抑制が脂肪肝抑制である、上記[35]記載の使用。
[37]インスリン抵抗性を改善するための組成物を製造するためのチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの使用。
[38]内臓脂肪量の増加を抑制するための組成物を製造するためのチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの使用。
[39]組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部、グルタミン酸0.4~2.5重量部、イソロイシン1~4重量部及びシスチン0.1~2重量部である、上記[35]~[38]のいずれかに記載の使用。
[40]組成物が食品である、上記[35]~[39]のいずれかに記載の使用。
[31] Use of tyrosine, serine, alanine, aspartic acid and glutamic acid to produce compositions for suppressing the increase in triglyceride mass in the liver.
[32] The use according to the above [31], wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
[33] When tyrosine is 1 part by weight, serine is 0.4 to 1.5 parts by weight, alanine is 0.4 to 1.5 parts by weight, and aspartic acid is 0.5 to 1.5 parts by weight. The use according to the above [31] or [32], which is 0.4 to 2.5 parts by weight of glutamic acid and glutamic acid.
[34] The use according to any one of the above [31] to [33], wherein the composition is a food product.
[35] Use of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine to produce compositions for suppressing the increase in triglyceride mass in the liver.
[36] The use according to the above [35], wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
[37] Use of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine to produce compositions for improving insulin resistance.
[38] Use of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine to produce compositions for suppressing the increase in visceral fat mass.
[39] When tyrosine is 1 part by weight, the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, and 0.5 to 1.5 parts by weight of aspartic acid. The use according to any one of the above [35] to [38], which is 0.4 to 2.5 parts by weight of glutamic acid, 1 to 4 parts by weight of isoleucine and 0.1 to 2 parts by weight of cystine.
[40] The use according to any one of the above [35] to [39], wherein the composition is a food product.
 本発明により、肝臓の中性脂肪量の増加を抑制するための組成物(例えば、脂肪肝抑制用組成物)を提供することができる。
 また、本発明により、インスリン抵抗性を改善するための組成物、内臓脂肪量の増加を抑制するための組成物を提供することができる。
INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a composition for suppressing an increase in the amount of triglyceride in the liver (for example, a composition for suppressing fatty liver).
Further, according to the present invention, it is possible to provide a composition for improving insulin resistance and a composition for suppressing an increase in visceral fat mass.
図1は、試験例1の結果を示す。FIG. 1 shows the results of Test Example 1. 図2は、試験例2の結果を示す。FIG. 2 shows the results of Test Example 2. 図3は、試験例3の結果を示す。FIG. 3 shows the results of Test Example 3. 図4は、試験例4の結果を示す。FIG. 4 shows the results of Test Example 4.
 本発明の肝臓の中性脂肪量の増加を抑制するための組成物は、有効成分として、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含有する組成物である(本明細書において、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含有する組成物を、本発明の組成物(I)と記載することがある)。
 本発明の組成物(I)は、肝臓の中性脂肪量の増加を抑制することから、脂肪肝抑制用組成物として有用である。
The composition for suppressing an increase in the amount of neutral fat in the liver of the present invention is a composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients (in the present specification, tyrosine and serine). , Alanine, aspartic acid and glutamic acid may be referred to as the composition (I) of the present invention).
The composition (I) of the present invention is useful as a composition for suppressing fatty liver because it suppresses an increase in the amount of triglyceride in the liver.
 本発明の好ましい一態様として、本発明の肝臓の中性脂肪量の増加を抑制するための組成物は、有効成分として、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物である(本明細書において、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物を、本発明の組成物(II)と記載することがある)。
 本発明の組成物(II)は、肝臓の中性脂肪量の増加を抑制することから、脂肪肝抑制用組成物として有用である。
 また、本発明の組成物(II)は、インスリン抵抗性を改善するための組成物としても有用である。
 さらに、本発明の組成物(II)は、内臓脂肪量の増加を抑制するための組成物としても有用である。
As a preferred embodiment of the present invention, the composition for suppressing an increase in the amount of neutral fat in the liver of the present invention contains tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients. (In the present specification, a composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine may be referred to as the composition (II) of the present invention).
The composition (II) of the present invention is useful as a composition for suppressing fatty liver because it suppresses an increase in the amount of triglyceride in the liver.
The composition (II) of the present invention is also useful as a composition for improving insulin resistance.
Furthermore, the composition (II) of the present invention is also useful as a composition for suppressing an increase in visceral fat mass.
 本発明において、「肝臓の中性脂肪量の増加を抑制する」とは、食事、加齢、病気、肥満、体質などにより、肝臓の中性脂肪量(特に、トリグリセリド量)が増加することを、予防、正常に近づける、または戻す、増悪を阻止することをいう。
 本発明において、「脂肪肝抑制」とは、脂肪肝を、予防、正常に近づける、または戻す、増悪を阻止することをいう。
 本発明において、「インスリン抵抗性を改善する」とは、食事、加齢、病気、肥満、体質などにより、インスリン抵抗性の状態になることを、予防、正常に近づける、または戻す、増悪を阻止することをいう。
 本明細書において「インスリン抵抗性」とは、すい臓からインスリンが血液中に分泌されていても肝臓、骨格筋、脂肪組織でのインスリンに対する反応が鈍くなっている(感受性低下)ために、インスリンの血糖を下げる働きが十分に発揮されない(インスリンの効きが悪い)状態のことをいう。よって、インスリン分泌をより必要とするため、血中インスリン濃度が高値を示す状態となる。
 本発明において、「内臓脂肪量の増加を抑制する」とは、食事、加齢、病気、肥満、体質などにより、内臓脂肪量が増加することを、予防、正常に近づける、または戻す、増悪を阻止することをいう。
 本発明の「肝臓の中性脂肪量の増加を抑制するための組成物」(例えば、脂肪肝抑制用組成物)、「インスリン抵抗性を改善するための組成物」、「内臓脂肪量の増加を抑制するための組成物」は、ヒトなどの対象に対する使用は、治療的使用であっても非治療的使用であってもよい。ここで、「非治療的」とは、医療行為を含まない概念、すなわち人間を手術、治療又は診断する方法を含まない概念である。
In the present invention, "suppressing the increase in the amount of triglyceride in the liver" means that the amount of triglyceride in the liver (particularly, the amount of triglyceride) increases due to diet, aging, illness, obesity, constitution and the like. , Prevention, approaching or returning to normal, preventing exacerbations.
In the present invention, "fatty liver suppression" means preventing, bringing the fatty liver closer to normal, returning it to normal, or preventing exacerbation.
In the present invention, "improving insulin resistance" means preventing, bringing back or returning to normal insulin resistance, or preventing exacerbation due to diet, aging, illness, obesity, constitution, etc. To do.
As used herein, "insulin resistance" refers to insulin because even if insulin is secreted from the pancreas into the blood, the response to insulin in the liver, skeletal muscle, and adipose tissue is slowed down (decreased sensitivity). It is a condition in which the function of lowering blood sugar is not fully exerted (insulin does not work well). Therefore, since insulin secretion is required more, the blood insulin concentration becomes high.
In the present invention, "suppressing the increase in visceral fat mass" means preventing, approaching, returning, or exacerbating the increase in visceral fat mass due to diet, aging, illness, obesity, constitution, etc. It means to prevent.
"Composition for suppressing increase in triglyceride mass of liver" (for example, composition for suppressing fatty liver), "Composition for improving insulin resistance", "Increase in visceral fat mass" of the present invention. The use of the "composition for suppressing" may be therapeutic or non-therapeutic use for subjects such as humans. Here, "non-therapeutic" is a concept that does not include medical practice, that is, a concept that does not include a method of surgery, treatment, or diagnosis of a human being.
 本発明の組成物(I)は、有効成分として、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含む。
 本発明の組成物(II)は、有効成分として、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含む。
 以下、本発明の組成物(I)と(II)をまとめて、本発明の組成物と総称する。
The composition (I) of the present invention contains tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients.
The composition (II) of the present invention contains tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients.
Hereinafter, the compositions (I) and (II) of the present invention are collectively referred to as the compositions of the present invention.
 本発明の組成物に含まれるアミノ酸は、本発明の効果を損なわない限り限定されないが、L-体又はDL-体が好ましく、L-体がより好ましい。 The amino acids contained in the composition of the present invention are not limited as long as the effects of the present invention are not impaired, but L-form or DL-form is preferable, and L-form is more preferable.
 本発明におけるアミノ酸は、蛋白質加水分解法、化学合成法、酵素法又は発酵法など、いずれの製造方法で製造されたものでもよいし、市販品を用いることもできる。 The amino acid in the present invention may be produced by any production method such as a protein hydrolysis method, a chemical synthesis method, an enzyme method or a fermentation method, or a commercially available product may be used.
 また、本発明におけるアミノ酸は、当該アミノ酸配列を有する天然蛋白質を酵素的に加水分解することによっても得ることができる。 The amino acid in the present invention can also be obtained by enzymatically hydrolyzing a natural protein having the amino acid sequence.
 本発明におけるアミノ酸としては、遊離体のみならず、塩の形態でも用いることができる。本明細書におけるチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンという語は、それぞれ塩をも包含する概念である。塩の形態としては、食品として許容される塩又は薬理学上許容される塩であれば特に制限されず、酸付加塩や塩基との塩等を挙げることができる。
 具体的には、無機塩基、有機塩基、無機酸、有機酸との塩およびアミノ酸との塩等が挙げられる。
As the amino acid in the present invention, it can be used not only in the form of a free form but also in the form of a salt. The terms tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine in the present specification are concepts that also include salts, respectively. The form of the salt is not particularly limited as long as it is a salt that is acceptable as food or a salt that is pharmacologically acceptable, and examples thereof include acid addition salts and salts with bases.
Specific examples thereof include inorganic bases, organic bases, inorganic acids, salts with organic acids, and salts with amino acids.
 無機塩基との塩としては、たとえば、リチウム、ナトリウム、カリウム等のアルカリ金属との塩、マグネシウム、カルシウム等のアルカリ土類金属との塩、アンモニウム塩等が挙げられる。
 有機塩基との塩としては、たとえばモノエタノールアミン、ジエタノールアミン、トリエタノールアミン等のアルカノールアミンとの塩、モルホリン、ピペリジン等の複素環式アミンとの塩等が挙げられる。
 無機酸との塩としては、たとえば、ハロゲン化水素酸(塩酸、臭化水素酸、ヨウ化水素酸等)、硫酸、硝酸、リン酸等との塩等が挙げられる。
 有機酸との塩としては、たとえば、ギ酸、酢酸、プロパン酸等のモノカルボン酸との塩;シュウ酸、マロン酸、リンゴ酸、コハク酸等の飽和ジカルボン酸との塩;マレイン酸、フマル酸等の不飽和ジカルボン酸との塩;クエン酸等のトリカルボン酸との塩;α-ケトグルタル酸等のケト酸との塩等が挙げられる。
 アミノ酸との塩としては、グリシン、アラニン等の脂肪族アミノ酸との塩;チロシン等の芳香族アミノ酸との塩;アルギニン等の塩基性アミノ酸との塩;アスパラギン酸、グルタミン酸等の酸性アミノ酸との塩;ピログルタミン酸等のラクタムを形成したアミノ酸との塩等が挙げられる。
Examples of the salt with an inorganic base include salts with alkali metals such as lithium, sodium and potassium, salts with alkaline earth metals such as magnesium and calcium, and ammonium salts.
Examples of the salt with an organic base include salts with alkanolamines such as monoethanolamine, diethanolamine and triethanolamine, and salts with heterocyclic amines such as morpholine and piperidine.
Examples of the salt with the inorganic acid include salts with hydrochloric acid (hydrochloric acid, hydrobromic acid, hydroiodic acid, etc.), sulfuric acid, nitric acid, phosphoric acid, and the like.
Examples of salts with organic acids include salts with monocarboxylic acids such as formic acid, acetic acid and propanoic acid; salts with saturated dicarboxylic acids such as oxalic acid, malonic acid, malic acid and succinic acid; maleic acid and fumaric acid. Salts with unsaturated dicarboxylic acids such as; salts with tricarboxylic acids such as citric acid; salts with ketoic acids such as α-ketoglutaric acid and the like.
Salts with amino acids include salts with aliphatic amino acids such as glycine and alanine; salts with aromatic amino acids such as tyrosine; salts with basic amino acids such as arginine; salts with acidic amino acids such as aspartic acid and glutamic acid. Examples include salts with amino acids that form lactam, such as pyroglutamic acid.
 上記した塩は、それぞれ水和物(含水塩)であってもよく、かかる水和物としては、たとえば1水和物~6水和物等が挙げられる。 The above-mentioned salts may be hydrates (hydrous salts), and examples of such hydrates include monohydrate to hexahydrate.
 本発明におけるそれぞれのアミノ酸は、遊離体および上記塩の形態の1種を単独で用いてもよく、2種以上を組み合わせて用いてもよい。
 本発明においては、チロシンは、遊離体が好ましく、セリンは、遊離体が好ましく、アラニンは、遊離体が好ましく、アスパラギン酸は、遊離体およびナトリウム塩等が好ましく、グルタミン酸は、遊離体およびナトリウム塩等が好ましく、イソロイシンは、遊離体が好ましく、シスチンは、遊離体が好ましい。
As each amino acid in the present invention, one kind of free form and the above-mentioned salt form may be used alone, or two or more kinds may be used in combination.
In the present invention, tyrosine is preferably a free form, serine is preferably a free form, alanine is preferably a free form, aspartic acid is preferably a free form and a sodium salt, and glutamic acid is preferably a free form and a sodium salt. Etc., isoleucine is preferably a free form, and cystine is preferably a free form.
 本発明の組成物(I)において、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸の配合割合は、(1)チロシンを1重量部とすると、L体かつ遊離体に換算して、通常(2)セリン0.4~1.5重量部、(3)アラニン0.4~1.5重量部、(4)アスパラギン酸0.5~1.5重量部、(5)グルタミン酸0.4~2.5重量部であり、好ましくは、(2)0.4~1.3重量部、(3)0.4~1.3重量部、(4)0.7~1.3重量部、(5)0.4~2.1重量部であり、より好ましくは、(2)0.4~1.1重量部、(3)0.4~1.1重量部、(4)0.9~1.1重量部、(5)0.4~2.1重量部である。 In the composition (I) of the present invention, the blending ratio of tyrosine, serine, alanine, aspartic acid and glutamic acid is usually (2) in terms of L-form and free form, assuming that tyrosine is 1 part by weight. 0.4 to 1.5 parts by weight of serine, (3) 0.4 to 1.5 parts by weight of alanine, (4) 0.5 to 1.5 parts by weight of aspartic acid, (5) 0.4 to 2 parts by weight of glutamic acid. It is 5 parts by weight, preferably (2) 0.4 to 1.3 parts by weight, (3) 0.4 to 1.3 parts by weight, (4) 0.7 to 1.3 parts by weight, and (5). ) 0.4 to 2.1 parts by weight, more preferably (2) 0.4 to 1.1 parts by weight, (3) 0.4 to 1.1 parts by weight, (4) 0.9 to 0.9 parts. 1.1 parts by weight, (5) 0.4 to 2.1 parts by weight.
 本発明の組成物(I)中の各アミノ酸の重量(%)は、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸の合計量に対し、L体かつ遊離体に換算して、通常(1)チロシン12~40重量%、(2)セリン12~28重量%、(3)アラニン12~28重量%、(4)アスパラギン酸12~40重量%及び(5)グルタミン酸12~30重量%、好ましくは、(1)14~30重量%、(2)14~25重量%、(3)14~25重量%、(4)14~30重量%及び(5)12~30重量%、より好ましくは、(1)14~29重量%、(2)14~22重量%、(3)14~22重量%、(4)18~29重量%及び(5)13~30重量%である。 The weight (%) of each amino acid in the composition (I) of the present invention is usually (1) tyrosine in terms of L-form and free form with respect to the total amount of tyrosine, serine, alanine, aspartic acid and glutamic acid. 12-40% by weight, (2) serine 12-28% by weight, (3) alanine 12-28% by weight, (4) aspartic acid 12-40% by weight and (5) glutamic acid 12-30% by weight, preferably. (1) 14 to 30% by weight, (2) 14 to 25% by weight, (3) 14 to 25% by weight, (4) 14 to 30% by weight and (5) 12 to 30% by weight, more preferably ( 1) 14 to 29% by weight, (2) 14 to 22% by weight, (3) 14 to 22% by weight, (4) 18 to 29% by weight, and (5) 13 to 30% by weight.
 ここで本発明(本発明の組成物(I)及び(II))におけるアミノ酸とは、遊離アミノ酸を意味し、蛋白やペプチド中の構成アミノ酸は含まない。また、本明細書において、本発明における各アミノ酸の含有量、配合割合は、L体のアミノ酸の含有量、配合割合であって、当該アミノ酸が塩の形態で含有される場合、遊離体に換算した含有量で表す。なお本発明のアミノ酸組成物はD体のアミノ酸を含んでもよい。またDL体(L体:D体=1:1)のアミノ酸を含む場合にはL体のアミノ酸含有量、配合割合に基づいて換算することができる。例えば、DL-アラニンを28重量%含有する場合、L体換算値は、14重量%である。 Here, the amino acids in the present invention (compositions (I) and (II) of the present invention) mean free amino acids and do not include constituent amino acids in proteins and peptides. Further, in the present specification, the content and compounding ratio of each amino acid in the present invention are the content and compounding ratio of L-form amino acids, and when the amino acid is contained in the form of a salt, it is converted into a free form. It is expressed by the content of the product. The amino acid composition of the present invention may contain a D-form amino acid. When the DL-form (L-form: D-form = 1: 1) amino acid is contained, the conversion can be performed based on the amino acid content and blending ratio of the L-form. For example, when DL-alanine is contained in an amount of 28% by weight, the L-form conversion value is 14% by weight.
 本発明の組成物(I)の投与量(摂取量)は、年齢、性別、体重、対象疾患、症状、剤形によって変化しうるが、成人(例えば体重60kg)1日あたり、通常は1g~30gの範囲であり、好ましくは2g~15g、より好ましくは2g~12gとなるように、1日1回ないし数回投与又は摂取させる。 The dose (intake) of the composition (I) of the present invention may vary depending on age, sex, body weight, target disease, symptom, and dosage form, but is usually from 1 g per day for an adult (for example, body weight 60 kg). It is administered or ingested once or several times a day so as to be in the range of 30 g, preferably 2 g to 15 g, and more preferably 2 g to 12 g.
 また、本発明の組成物(I)において、チロシンの投与量(摂取量)は成人1日あたり、通常0.28g~8.6gの範囲であり、0.57g~4.3gの範囲が好ましく、0.57g~3.5gの範囲がより好ましい。
 本発明の組成物(I)において、セリンの投与量(摂取量)は成人1日あたり、通常0.14g~4.2gの範囲であり、0.28g~2.2gの範囲が好ましく、0.28g~1.8gの範囲がより好ましい。
 本発明の組成物(I)において、アラニンの投与量(摂取量)は成人1日あたり、通常0.14g~4.2gの範囲であり、0.28g~2.2gの範囲が好ましく、0.28g~1.8gの範囲がより好ましい。
 本発明の組成物(I)において、アスパラギン酸の投与量(摂取量)は成人1日あたり、通常0.28g~8.6gの範囲であり、0.57g~4.3gの範囲が好ましく、0.57g~3.5gの範囲がより好ましい。
 本発明の組成物(I)において、グルタミン酸の投与量(摂取量)は成人1日あたり、通常0.14g~4.2gの範囲であり、0.28g~2.2gの範囲が好ましく、0.28g~1.8gの範囲がより好ましい。
 上記成人1回あたりの量は、性別、年齢、疾患等の体の状態を加味して適宜変更しうる。
Further, in the composition (I) of the present invention, the dose (intake) of tyrosine is usually in the range of 0.28 g to 8.6 g per day for an adult, preferably in the range of 0.57 g to 4.3 g. , 0.57 g to 3.5 g is more preferable.
In the composition (I) of the present invention, the dose (intake) of serin is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
In the composition (I) of the present invention, the dose (intake) of alanine is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
In the composition (I) of the present invention, the dose (intake) of aspartic acid is usually in the range of 0.28 g to 8.6 g, preferably in the range of 0.57 g to 4.3 g per day for adults. The range of 0.57 g to 3.5 g is more preferable.
In the composition (I) of the present invention, the dose (intake) of glutamic acid is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
The amount per adult can be appropriately changed in consideration of physical conditions such as gender, age, and disease.
 本発明の組成物(I)において、上記1日あたりの量を一度にもしくは数回に分けて投与する(摂取する)ことができる。また投与期間(摂取期間)は特に限定されず、有効成分がアミノ酸であるため長期投与(長期摂取)が可能である。 In the composition (I) of the present invention, the above-mentioned daily amount can be administered (ingested) at one time or in several divided doses. The administration period (intake period) is not particularly limited, and long-term administration (long-term ingestion) is possible because the active ingredient is an amino acid.
 本発明の組成物(I)は、本発明におけるチロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸以外のアミノ酸の組成物中に含有される割合が、組成物の合計重量に対して、遊離体に換算して、50重量%以下であり、40重量%以下が好ましく、30重量%以下がより好ましく、実質的に含有しないのがさらに好ましく、含有しないことが特に好ましい。実質的に含有しないとは、0.2重量%以下、好ましくは0.1重量%以下、より好ましくは0.05重量%以下を意味する。 In the composition (I) of the present invention, the ratio contained in the composition of amino acids other than tyrosine, serine, alanine, aspartic acid and glutamic acid in the present invention is converted into a free form with respect to the total weight of the composition. Therefore, it is 50% by weight or less, preferably 40% by weight or less, more preferably 30% by weight or less, further preferably not substantially contained, and particularly preferably not contained. The term "substantially free" means 0.2% by weight or less, preferably 0.1% by weight or less, and more preferably 0.05% by weight or less.
 本発明の組成物(I)は、本発明におけるアミノ酸の他に、さらに糖質、脂質、タンパク質、ビタミン、ミネラル等の他の栄養成分を含有することができる。 The composition (I) of the present invention can further contain other nutritional components such as sugars, lipids, proteins, vitamins and minerals in addition to the amino acids in the present invention.
 本発明の組成物(I)は、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸以外に、必要に応じて、他のアミノ酸、他の栄養成分、食品として許容される添加剤、薬学的に許容される添加剤等を加えて、製剤の分野で周知の製剤化手段、たとえば第十七改正日本薬局方製剤総則[3]製剤各条に記載された方法等により、溶液、懸濁液、乳濁液等の液状;ゲル、クリーム等の半固形状;粉末、顆粒、錠剤、カプセル等の固形状等、種々の形態とすることができる。 In addition to tyrosine, serine, alanine, aspartic acid and glutamate, the composition (I) of the present invention is optionally other amino acids, other nutritional components, food-acceptable additives, and pharmaceutically acceptable. Additives, etc., and use a formulation method well known in the field of formulation, for example, the method described in each article of the 17th Amendment of the Japanese Pharmacy Regulations [3] Formulation, to make solutions, suspensions, and emulsions. It can be in various forms such as liquid such as liquid; semi-solid such as gel and cream; and solid such as powder, granules, tablets and capsules.
 本発明の組成物(II)において、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの配合割合は、(1)チロシンを1重量部とすると、L体かつ遊離体に換算して、通常(2)セリン0.4~1.5重量部、(3)アラニン0.4~1.5重量部、(4)アスパラギン酸0.5~1.5重量部、(5)グルタミン酸0.4~2.5重量部、(6)イソロイシン1~4重量部、(7)シスチン0.1~2重量部であり、好ましくは、(2)セリン0.4~1.3重量部、(3)アラニン0.4~1.3重量部、(4)アスパラギン酸0.7~1.3重量部、(5)グルタミン酸0.4~2.1重量部、(6)イソロイシン2~3重量部、(7)シスチン0.5~1.5重量部であり、より好ましくは、(2)セリン0.4~1.1重量部、(3)アラニン0.4~1.1重量部、(4)アスパラギン酸0.9~1.1重量部、(5)グルタミン酸0.4~2.1重量部、(6)イソロイシン2~3重量部、(7)シスチン0.5~1.5重量部である。 In the composition (II) of the present invention, the blending ratio of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine is (1) when tyrosine is 1 part by weight, it is converted into L form and free form. Usually (2) 0.4 to 1.5 parts by weight of serine, (3) 0.4 to 1.5 parts by weight of alanine, (4) 0.5 to 1.5 parts by weight of aspartic acid, (5) 0. 4 to 2.5 parts by weight, (6) 1 to 4 parts by weight of isoleucine, (7) 0.1 to 2 parts by weight of cystine, preferably (2) 0.4 to 1.3 parts by weight of serine, ( 3) 0.4 to 1.3 parts by weight of alanine, (4) 0.7 to 1.3 parts by weight of aspartic acid, (5) 0.4 to 2.1 parts by weight of glutamate, (6) 2 to 3 parts by weight of isoleucine Parts, (7) 0.5 to 1.5 parts by weight of cystine, more preferably 0.4 to 1.1 parts by weight of serine, (3) 0.4 to 1.1 parts by weight of alanine. (4) 0.9 to 1.1 parts by weight of aspartic acid, (5) 0.4 to 2.1 parts by weight of glutamate, (6) 2 to 3 parts by weight of isoleucine, (7) 0.5 to 1.5 parts of cystine It is a part by weight.
 本発明の組成物(II)中の各アミノ酸の重量(%)は、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの合計量に対し、L体かつ遊離体に換算して、通常(1)チロシン10~20重量%、(2)セリン5~10重量%、(3)アラニン5~10重量%、(4)アスパラギン酸10~20重量%、(5)グルタミン酸5~10重量%、(6)イソロイシン30~40重量%、(7)シスチン10~20重量%、好ましくは、(1)チロシン12~18重量%、(2)セリン5~10重量%、(3)アラニン5~10重量%、(4)アスパラギン酸12~18重量%、(5)グルタミン酸5~10重量%、(6)イソロイシン30~38重量%及び(7)シスチン12~18重量%である。 The weight (%) of each amino acid in the composition (II) of the present invention is usually converted into L form and free form with respect to the total amount of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine. (1) Tyrosine 10 to 20% by weight, (2) Serine 5 to 10% by weight, (3) Alanine 5 to 10% by weight, (4) Aspartic acid 10 to 20% by weight, (5) Glutamic acid 5 to 10% by weight , (6) 30-40% by weight of isoleucine, (7) 10-20% by weight of cystine, preferably (1) 12-18% by weight of tyrosine, (2) 5-10% by weight of serine, (3) 5 to 10% by weight of alanine. 10% by weight, (4) aspartic acid 12-18% by weight, (5) glutamic acid 5-10% by weight, (6) isoleucine 30-38% by weight and (7) cystine 12-18% by weight.
 本発明の組成物(II)の投与量(摂取量)は、年齢、性別、体重、対象疾患、症状、剤形によって変化しうるが、成人(例えば体重60kg)1日あたり、通常は1g~30gの範囲であり、好ましくは2g~15g、より好ましくは2g~12gとなるように、1日1回ないし数回投与又は摂取させる。 The dose (intake) of the composition (II) of the present invention may vary depending on age, sex, body weight, target disease, symptom, and dosage form, but is usually from 1 g per day for an adult (for example, body weight 60 kg). It is administered or ingested once or several times a day so as to be in the range of 30 g, preferably 2 g to 15 g, and more preferably 2 g to 12 g.
 また、本発明の組成物(II)において、チロシンの投与量(摂取量)は成人1日あたり、通常0.28g~8.6gの範囲であり、0.57g~4.3gの範囲が好ましく、0.57g~3.5gの範囲がより好ましい。
 本発明の組成物(II)において、セリンの投与量(摂取量)は成人1日あたり、通常0.14g~4.2gの範囲であり、0.28g~2.2gの範囲が好ましく、0.28g~1.8gの範囲がより好ましい。
 本発明の組成物(II)において、アラニンの投与量(摂取量)は成人1日あたり、通常0.14g~4.2gの範囲であり、0.28g~2.2gの範囲が好ましく、0.28g~1.8gの範囲がより好ましい。
 本発明の組成物(II)において、アスパラギン酸の投与量(摂取量)は成人1日あたり、通常0.28g~8.6gの範囲であり、0.57g~4.3gの範囲が好ましく、0.57g~3.5gの範囲がより好ましい。
 本発明の組成物(II)において、グルタミン酸の投与量(摂取量)は成人1日あたり、通常0.14g~4.2gの範囲であり、0.28g~2.2gの範囲が好ましく、0.28g~1.8gの範囲がより好ましい。
 本発明の組成物(II)において、イソロイシンの投与量(摂取量)は成人1日あたり、通常0.7g~21gの範囲であり、0.7g~10gの範囲が好ましく、0.7g~5gの範囲がより好ましい。
 本発明の組成物(II)において、シスチンの投与量(摂取量)は成人1日あたり、通常0.28g~2gの範囲であり、0.28g~1.5gの範囲が好ましく、0.28g~1gの範囲がより好ましい。
 上記成人1回あたりの量は、性別、年齢、疾患等の体の状態を加味して適宜変更しうる。
Further, in the composition (II) of the present invention, the dose (intake) of tyrosine is usually in the range of 0.28 g to 8.6 g per day for an adult, preferably in the range of 0.57 g to 4.3 g. , 0.57 g to 3.5 g is more preferable.
In the composition (II) of the present invention, the dose (intake) of serin is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
In the composition (II) of the present invention, the dose (intake) of alanine is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
In the composition (II) of the present invention, the dose (intake) of aspartic acid is usually in the range of 0.28 g to 8.6 g, preferably in the range of 0.57 g to 4.3 g per day for adults. The range of 0.57 g to 3.5 g is more preferable.
In the composition (II) of the present invention, the dose (intake) of glutamic acid is usually in the range of 0.14 g to 4.2 g, preferably in the range of 0.28 g to 2.2 g, and is 0. The range of .28 g to 1.8 g is more preferable.
In the composition (II) of the present invention, the dose (intake) of isoleucine is usually in the range of 0.7 g to 21 g, preferably in the range of 0.7 g to 10 g, and is preferably in the range of 0.7 g to 5 g per day for adults. The range of is more preferable.
In the composition (II) of the present invention, the dose (intake) of cystine is usually in the range of 0.28 g to 2 g, preferably in the range of 0.28 g to 1.5 g, and 0.28 g per day for adults. The range of ~ 1 g is more preferable.
The amount per adult can be appropriately changed in consideration of physical conditions such as gender, age, and disease.
 本発明の組成物(II)において、上記1日あたりの量を一度にもしくは数回に分けて投与する(摂取する)ことができる。また投与期間(摂取期間)は特に限定されず、有効成分がアミノ酸であるため長期投与(長期摂取)が可能である。 In the composition (II) of the present invention, the above-mentioned daily amount can be administered (ingested) at one time or in several divided doses. The administration period (intake period) is not particularly limited, and long-term administration (long-term ingestion) is possible because the active ingredient is an amino acid.
 本発明の組成物(II)は、本発明におけるチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチン以外のアミノ酸の組成物中に含有される割合が、組成物の合計重量に対して、遊離体に換算して、50重量%以下であり、40重量%以下が好ましく、30重量%以下がより好ましく、実質的に含有しないのがさらに好ましく、含有しないことが特に好ましい。実質的に含有しないとは、0.2重量%以下、好ましくは0.1重量%以下、より好ましくは0.05重量%以下を意味する。 In the composition (II) of the present invention, the proportion contained in the composition of amino acids other than tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine in the present invention is based on the total weight of the composition. In terms of free form, it is 50% by weight or less, preferably 40% by weight or less, more preferably 30% by weight or less, further preferably not substantially contained, and particularly preferably not contained. The term "substantially free" means 0.2% by weight or less, preferably 0.1% by weight or less, and more preferably 0.05% by weight or less.
 本発明の組成物(II)は、本発明におけるアミノ酸の他に、さらに糖質、脂質、タンパク質、ビタミン、ミネラル等の他の栄養成分を含有することができる。 The composition (II) of the present invention can further contain other nutritional components such as sugars, lipids, proteins, vitamins and minerals in addition to the amino acids in the present invention.
 本発明の組成物(II)は、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチン以外に、必要に応じて、他のアミノ酸、他の栄養成分、食品として許容される添加剤、薬学的に許容される添加剤等を加えて、製剤の分野で周知の製剤化手段、たとえば第十七改正日本薬局方製剤総則[3]製剤各条に記載された方法等により、溶液、懸濁液、乳濁液等の液状;ゲル、クリーム等の半固形状;粉末、顆粒、錠剤、カプセル等の固形状等、種々の形態とすることができる。 In addition to tyrosine, serine, alanine, aspartic acid, glutamate, isoleucine and cystine, the composition (II) of the present invention contains, if necessary, other amino acids, other nutritional components, food-acceptable additives, and pharmaceuticals. Add the additives, etc., which are permitted to be used, and use a formulation method well known in the field of formulation, for example, the method described in each article of the 17th revised Japanese Pharmacy Regulations [3] formulation, solution, suspension. It can be in various forms such as liquids such as liquids and emulsions; semi-solids such as gels and creams; solids such as powders, granules, tablets and capsules.
 本発明の組成物において、上記食品として許容される添加剤、又は薬学的に許容される添加剤は、本発明の組成物の形態に応じて適宜選択することができ、たとえば、賦形剤、結合剤、崩壊剤、滑沢剤、被覆剤、基剤、溶剤、溶解補助剤、可溶化剤、乳化剤、分散剤、懸濁化剤、安定化剤、粘稠剤、無痛化剤、等張化剤、pH調整剤、抗酸化剤、防腐剤、保存剤、矯味剤、甘味剤、香料、着色剤等が挙げられる。 In the composition of the present invention, the above-mentioned food-acceptable additive or pharmaceutically acceptable additive can be appropriately selected depending on the form of the composition of the present invention, for example, excipients. Binders, disintegrants, lubricants, coatings, bases, solvents, solubilizers, solubilizers, emulsifiers, dispersants, suspending agents, stabilizers, thickeners, soothing agents, isotonic Examples thereof include agents, pH adjusters, antioxidants, preservatives, preservatives, flavoring agents, sweeteners, fragrances, colorants and the like.
 具体的には、賦形剤としては、たとえば、炭酸マグネシウム、糖類(グルコース、ラクトース、コーンスターチ等)、糖アルコール(ソルビトール、マンニトール等)等が挙げられる。
 結合剤としては、たとえば、ゼラチン、アルファー化デンプン、部分アルファー化デンプン、セルロースおよびその誘導体(結晶セルロース、ヒドロキシプロピルセルロース等)等が挙げられる。
 崩壊剤としては、たとえば、クロスポビドン、ポビドン、結晶セルロース等が挙げられる。
 滑沢剤としては、たとえば、タルク、ステアリン酸マグネシウム等が挙げられる。
 被覆剤としては、たとえば、メタクリル酸・メタクリル酸メチル共重合体、メタクリル酸・アクリル酸エチル共重合体、メタクリル酸メチル・メタクリル酸ブチル・メタクリル酸ジメチルアミノエチル共重合体、アクリル酸エチル・メタクリル酸メチル・メタクリル酸塩化トリメチルアンモニウムエチル共重合体等が挙げられる。
Specifically, examples of the excipient include magnesium carbonate, sugars (glucose, lactose, cornstarch, etc.), sugar alcohols (sorbitol, mannitol, etc.) and the like.
Examples of the binder include gelatin, pregelatinized starch, partially pregelatinized starch, cellulose and its derivatives (crystalline cellulose, hydroxypropyl cellulose, etc.) and the like.
Examples of the disintegrant include crospovidone, povidone, crystalline cellulose and the like.
Examples of the lubricant include talc, magnesium stearate and the like.
Examples of the coating agent include methacrylic acid / methyl methacrylate copolymer, methacrylic acid / ethyl acrylate copolymer, methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, ethyl acrylate / methacrylic acid. Examples thereof include a trimethylammonium ethyl methacrylate copolymer of methyl methacrylate.
 基剤としては、たとえば、動植物性油脂(オリーブ油、カカオ脂、牛脂、ゴマ油、硬化油、ヒマシ油等)、ロウ(カルナウバロウ、ミツロウ等)、ポリエチレングリコール等が挙げられる。
 溶剤としては、たとえば、精製水、注射用水、一価アルコール(エタノール等)、多価アルコール(グリセリン等)等が挙げられる。
 溶解補助剤としては、たとえば、プロピレングリコール、中鎖脂肪酸トリグリセリド等が挙げられる。
Examples of the base include animal and vegetable fats and oils (olive oil, cacao butter, beef tallow, sesame oil, hydrogenated oil, castor oil, etc.), waxes (carnauba wax, beeswax, etc.), polyethylene glycol and the like.
Examples of the solvent include purified water, water for injection, monohydric alcohol (ethanol and the like), polyhydric alcohol (glycerin and the like) and the like.
Examples of the solubilizing agent include propylene glycol, medium-chain fatty acid triglyceride, and the like.
 可溶化剤、乳化剤、分散剤および懸濁化剤としては、たとえば、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル(ポリソルベート20、ポリソルベート80等)、ポリオキシエチレン硬化ヒマシ油、ショ糖脂肪酸エステル等の界面活性剤等が挙げられる。 Examples of the solubilizer, emulsifier, dispersant and suspending agent include sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester (polysorbate 20, polysorbate 80, etc.), polyoxyethylene hydrogenated castor oil, and sucrose. Examples thereof include surfactants such as fatty acid esters.
 安定化剤としては、たとえば、アジピン酸、β-シクロデキストリン、エチレンジアミン、エデト酸ナトリウム等が挙げられる。
 粘稠剤としては、たとえば、水溶性高分子(ポリアクリル酸ナトリウム、カルボキシビニルポリマー等)、多糖類(アルギン酸ナトリウム、キサンタンガム、トラガント等)等が挙げられる。
 無痛化剤としては、たとえば、アミノ安息香酸エチル、クロロブタノール、プロピレングリコール、ベンジルアルコール等が挙げられる。
 等張化剤としては、たとえば、塩化カリウム、塩化ナトリウム、ソルビトール、生理食塩水等が挙げられる。
 pH調整剤としては、たとえば、塩酸、硫酸、酢酸、クエン酸、乳酸、水酸化ナトリウム、水酸化カリウム等が挙げられる。
Examples of the stabilizer include adipic acid, β-cyclodextrin, ethylenediamine, sodium edetate and the like.
Examples of the thickener include water-soluble polymers (sodium polyacrylate, carboxyvinyl polymer, etc.), polysaccharides (sodium alginate, xanthan gum, tragant, etc.) and the like.
Examples of the soothing agent include ethyl aminobenzoate, chlorobutanol, propylene glycol, benzyl alcohol and the like.
Examples of the tonicity agent include potassium chloride, sodium chloride, sorbitol, physiological saline and the like.
Examples of the pH adjuster include hydrochloric acid, sulfuric acid, acetic acid, citric acid, lactic acid, sodium hydroxide, potassium hydroxide and the like.
 抗酸化剤としては、たとえば、ジブチルヒドロキシトルエン(BHT)、ブチルヒドロキシアニソール(BHA)、dl-α-トコフェロール、エリソルビン酸等が挙げられる。
 防腐剤および保存剤としては、たとえば、パラベン(メチルパラベン等)、ベンジルアルコール、デヒドロ酢酸ナトリウム、ソルビン酸等が挙げられる。
Examples of the antioxidant include dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), dl-α-tocopherol, erythorbic acid and the like.
Examples of preservatives and preservatives include parabens (methylparaben and the like), benzyl alcohol, sodium dehydroacetate, sorbic acid and the like.
 矯味剤としては、たとえば、アスコルビン酸、エリスリトール、L-グルタミン酸ナトリウム等が挙げられる。
 甘味剤としては、たとえば、アスパルテーム、カンゾウエキス、サッカリン等が挙げられる。
 香料としては、たとえば、l-メントール、d-カンフル、バニリン等が挙げられる。
 着色剤としては、たとえば、タール色素(食用赤色2号、食用青色1号、食用黄色4号等)、無機顔料(三二酸化鉄、黄酸化鉄、黒酸化鉄等)、天然色素(ウコン抽出液、β-カロテン、銅クロロフィリンナトリウム等)等が挙げられる。
Examples of the flavoring agent include ascorbic acid, erythritol, sodium L-glutamate and the like.
Examples of the sweetener include aspartame, licorice extract, saccharin and the like.
Examples of the fragrance include l-menthol, d-camphor, vanillin and the like.
Examples of colorants include tar pigments (edible red No. 2, edible blue No. 1, edible yellow No. 4, etc.), inorganic pigments (iron sesquioxide, iron yellow oxide, iron black oxide, etc.), and natural pigments (turmeric extract). , Β-carotene, sodium copper chlorophyllin, etc.) and the like.
 本発明においては、上記添加剤は、1種または2種以上を用いることができる。 In the present invention, one kind or two or more kinds of the above additives can be used.
 本発明の組成物(I)におけるチロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸の総含有量は、機能性の観点から、組成物の全量に対して、通常、10重量%~100重量%であり、好ましく50重量%~100重量%であり、より好ましくは60重量%~100重量%であり、さらに好ましくは70重量%~100重量%であり、特に好ましくは80重量%~100重量%である。 The total content of tyrosine, serine, alanine, aspartic acid and glutamic acid in the composition (I) of the present invention is usually 10% by weight to 100% by weight based on the total amount of the composition from the viewpoint of functionality. It is preferably 50% by weight to 100% by weight, more preferably 60% by weight to 100% by weight, further preferably 70% by weight to 100% by weight, and particularly preferably 80% by weight to 100% by weight. ..
 本発明の組成物(II)におけるチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの総含有量は、機能性の観点から、組成物の全量に対して、通常、10重量%~100重量%であり、好ましく50重量%~100重量%であり、より好ましくは60重量%~100重量%であり、さらに好ましくは70重量%~100重量%であり、特に好ましくは80重量%~100重量%である。 The total content of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine in the composition (II) of the present invention is usually 10% by weight to 100% by weight based on the total amount of the composition from the viewpoint of functionality. It is% by weight, preferably 50% by weight to 100% by weight, more preferably 60% by weight to 100% by weight, further preferably 70% by weight to 100% by weight, and particularly preferably 80% by weight to 100% by weight. By weight%.
 本発明の組成物は、1回ないしは1食摂取量単位で包装された形態「単位包装形態」であり得る。かかる形態とは、1回ないしは1食あたりに摂取する量が予め定められ、包装された形態をいう。単位包装形態に用いられる容器または包装体は、本発明の組成物の形態等に応じて適宜選択し得るが、紙製の容器または袋体、プラスチック製の容器または袋体、パウチ、アルミ缶、スチール缶、瓶、ペットボトル、PTP(press through pack)包装シート等が挙げられる。例えば、飲料、ゼリー、ヨーグルト、ガム、クッキー等の場合には、袋、パウチ、瓶、箱等の容器により1回の摂取量を包装した形態が挙げられ、顆粒、粉末、スラリー状等の場合には、パウチや袋等により1回の摂取量を個別包装する形態が挙げられる。特に、組成物が健康食品、機能性表示食品、栄養補助食品、特定保健用食品等である場合には、本発明の組成物が1回ないし1食あたりの摂取量単位の形態で包装された形態や、本発明の組成物が懸濁又は溶解された飲料又はゼリーが、1回あたりの飲み切り又は食べ切りの形態でパウチ等に充填された形態などが挙げられる。 The composition of the present invention may be in a "unit packaging form" in which the composition is packaged in units of one-time or one-meal intake. Such a form means a form in which the amount to be ingested per serving or one meal is predetermined and packaged. The container or package used in the unit packaging form can be appropriately selected depending on the form of the composition of the present invention, but a paper container or bag, a plastic container or bag, a pouch, an aluminum can, etc. Examples include steel cans, bottles, PET bottles, and PTP (press through pack) packaging sheets. For example, in the case of beverages, jelly, yogurt, gum, cookies, etc., there is a form in which one intake is packaged in a container such as a bag, pouch, bottle, box, etc., and in the case of granules, powder, slurry, etc. Examples include a form in which a single intake is individually wrapped in a pouch, a bag, or the like. In particular, when the composition is a health food, a food with a functional claim, a dietary supplement, a food for specified health use, etc., the composition of the present invention is packaged in the form of one intake or one intake unit per meal. Examples thereof include a form in which a beverage or jelly in which the composition of the present invention is suspended or dissolved is filled in a pouch or the like in the form of a single drink or a complete meal.
 上記1回ないしは1食摂取量中には、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を合計で0.5g~4g、好ましくは0.5g~2g含めることができる。別の態様として、上記1回ないしは1食摂取量中には、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを合計で0.5g~4g、好ましくは0.5g~2g含めることができる。
 これにより、1回ないしは1食摂取量単位を摂取することで、必要量の当該アミノ酸を簡便に摂取することができる。
A total of 0.5 g to 4 g, preferably 0.5 g to 2 g of tyrosine, serine, alanine, aspartic acid and glutamic acid can be contained in the one-time or one-meal intake. As another embodiment, a total of 0.5 g to 4 g, preferably 0.5 g to 2 g of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine may be contained in the one-time or one-meal intake. it can.
As a result, the required amount of the amino acid can be easily ingested by ingesting one or one meal intake unit.
 また別の態様として、計量容器、及び有効成分としてチロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含む組成物を含むキット、又は、計量容器、及び有効成分としてチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含む組成物を含むキットが挙げられる。
 計量容器は上記のアミノ酸の1回摂取量を計量するための容器であれば特に限定されないが、例えば計量カップ、計量スプーンなどが挙げられる。1回に摂取する量は、上記1食当たりの単位包装形態に記載の量と同様である。計量容器で計りうる量はすりきり又は山盛りの量など、容器に合わせて決めることができる。また計量容器には1回の使用量などが表示されている目盛を有してもよい。
In yet another embodiment, a measuring container and a kit containing a composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients, or a measuring container, and tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients. , Kits containing compositions containing isoleucine and cystine.
The measuring container is not particularly limited as long as it is a container for measuring the single intake of the above amino acids, and examples thereof include a measuring cup and a measuring spoon. The amount to be ingested at one time is the same as the amount described in the unit packaging form per meal. The amount that can be measured with the measuring container can be determined according to the container, such as the amount of scraping or heaping. Further, the measuring container may have a scale on which the amount used at one time and the like are displayed.
 本発明の組成物の形態は、飲料等のような液状、ゼリー、ジェル、ゼリー様飲料等のようなゼリー状、牛乳、乳飲料、ヨーグルト等のような乳状、ガム状、粉末状、顆粒状、シート状、カプセル状、タブレット状、スナックバー、クッキー等のような固形状などとすることができる。 The form of the composition of the present invention is liquid such as a beverage, jelly such as jelly, gel, jelly-like beverage, milky such as milk, milk beverage, yogurt, etc., gum-like, powdery, granular form. , Sheets, capsules, tablets, snack bars, solids such as cookies, etc.
 本発明の組成物の適用対象としては、哺乳動物(たとえば、ヒト、サル、マウス、ラット、モルモット、ハムスター、ウサギ、ネコ、イヌ、ウシ、ウマ、ロバ、ブタ、ヒツジ等)や、鳥類(たとえば、アヒル、ニワトリ、ガチョウ、七面鳥等)等が挙げられる。
 本発明の組成物をヒト以外の適用対象動物(以下、単に「対象動物」ともいう)に適用する場合、本発明の組成物の摂取量または投与量は、対象動物の種類、性別、体重等に応じて適宜設定すればよい。
Mammals (eg, humans, monkeys, mice, rats, guinea pigs, hamsters, rabbits, cats, dogs, cows, horses, donkeys, pigs, sheep, etc.) and birds (eg, humans, monkeys, mice, rats, guinea pigs, horses, donkeys, pigs, sheep, etc.) , Duck, chicken, goose, turkey, etc.).
When the composition of the present invention is applied to an application target animal other than humans (hereinafter, also simply referred to as "target animal"), the intake or dose of the composition of the present invention is the type, sex, body weight, etc. of the target animal. It may be set appropriately according to.
 本発明の組成物は、各種食品に添加して摂取させることができる。本発明の組成物が添加される食品は特に制限されず、一般的に食事やデザートに供される形態の食品であれば如何なるものでもよい。
 たとえば、本発明の組成物を清涼飲料水等の飲料に添加し、所望により適当な風味を加えて、ドリンク剤とすることができる。
 より具体的には、本発明の組成物は、たとえば、果汁飲料、スポーツ飲料等の清涼飲料水;牛乳、ヨーグルト等の乳製品;ゼリー、チョコレート、キャンディ、ビスケット等の菓子等に添加することができる。
The composition of the present invention can be added to various foods and ingested. The food to which the composition of the present invention is added is not particularly limited, and any food in a form generally used for meals or desserts may be used.
For example, the composition of the present invention can be added to a beverage such as a soft drink and, if desired, an appropriate flavor can be added to obtain a drink.
More specifically, the composition of the present invention may be added to, for example, soft drinks such as fruit juice drinks and sports drinks; dairy products such as milk and yogurt; confectionery such as jelly, chocolate, candy and biscuits. it can.
 本発明の組成物は、1日あたりに摂取される量の上記各種食品に対し、本発明におけるアミノ酸の総量(L体かつ遊離体に換算した量の総量)が、上記した1日あたりの摂取量となるように添加されることが好ましい。 In the composition of the present invention, the total amount of amino acids (total amount converted into L-form and free form) in the present invention is the above-mentioned daily intake with respect to the above-mentioned various foods ingested per day. It is preferably added in an amount.
 また、本発明の組成物は、そのまま、または必要に応じて一般的な食品添加物を加えて、通常の食品製造技術により、食品(以下、本明細書において「本発明の食品」とも称する)として提供することができる。
 本発明の食品は、液状、懸濁液状、乳状、ゲル状、クリーム状、粉末状、顆粒状、シート状、カプセル状、タブレット状等、種々の形態とすることができる。
 さらに、本発明の食品は、本発明の組成物を各種食品原材料に加え、必要に応じて一般的な食品添加物を加えて、一般的な食品等の製造技術により、清涼飲料水(果汁飲料、スポーツ飲料、コーヒー飲料、茶系飲料等)、乳製品(乳酸菌飲料、発酵乳、バター、チーズ、ヨーグルト、加工乳、脱脂乳等)、畜肉製品(ハム、ソーセージ、ハンバーグ等)、魚肉練り製品(蒲鉾、竹輪、さつま揚げ等)、卵製品(だし巻き、卵豆腐等)、菓子(クッキー、ゼリー、チューイングガム、キャンディ、スナック菓子、冷菓等)、パン、麺類、漬物、干物、佃煮、スープ、調味料等、種々の形態の食品とすることができ、瓶詰め食品、缶詰食品、レトルトパウチ食品であってもよい。
In addition, the composition of the present invention is a food product (hereinafter, also referred to as "food product of the present invention" in the present specification) by ordinary food manufacturing techniques, either as it is or by adding general food additives as needed. Can be provided as.
The food product of the present invention can be in various forms such as liquid, suspension, milky, gel, cream, powder, granule, sheet, capsule, tablet and the like.
Further, the food of the present invention is prepared by adding the composition of the present invention to various food raw materials, adding general food additives as necessary, and using a general food manufacturing technique to soften drinking water (fruit juice beverage). , Sports drinks, coffee drinks, tea drinks, etc.), dairy products (lactic acid bacteria drinks, fermented milk, butter, cheese, yogurt, processed milk, defatted milk, etc.), livestock meat products (ham, sausage, hamburger, etc.), fish paste products (ham, sausage, hamburger, etc.) Gamo, bamboo ring, fried satsuma, etc.), egg products (dashi roll, egg tofu, etc.), confectionery (cookies, jelly, chewing gum, candy, snack confectionery, cold confectionery, etc.) , Foods of various forms, may be bottled foods, canned foods, retort pouch foods.
 上記食品添加物としては、製造用剤(かんすい、結着剤等)、増粘安定剤(キサンタンガム、カルボキシメチルセルロースナトリウム等)、ゲル化剤(ゼラチン、寒天、カラギーナン等)、ガムベース(酢酸ビニル樹脂、ジェルトン、チクル等)、乳化剤(グリセリン脂肪酸エステル、ショ糖脂肪酸エステル、サポニン、レシチン等)、保存料(安息香酸、安息香酸ナトリウム、ソルビン酸、ソルビン酸カリウム、ε-ポリリシン等)、酸化防止剤(アスコルビン酸、エリソルビン酸、カテキン等)、光沢剤(セラック、パラフィンワックス、ミツロウ等)、防かび剤(チアベンタゾール、フルジオキソニル等)、膨張剤(炭酸水素ナトリウム、グルコノδ-ラクトン、ミョウバン等)、甘味料(アスパルテーム、アセスルファムカリウム、カンゾウ抽出物等)、苦味料(カフェイン、ナリンジン、ニガヨモギ抽出物等)、酸味料(クエン酸、酒石酸、乳酸等)、調味料(L-グルタミン酸ナトリウム、5’-イノシン酸二ナトリウム等)、着色料(アナトー色素、ウコン色素、クチナシ色素等)、香料(アセト酢酸エチル、アニスアルデヒド等の合成香料、オレンジ、ラベンダー等の天然香料)等が挙げられる。
 本発明において、上記食品添加物は、1種または2種以上を用いることができる。
Examples of the above food additives include manufacturing agents (citric acid, binders, etc.), thickening stabilizers (xanthan gum, sodium carboxymethyl cellulose, etc.), gelling agents (gelatin, agar, carrageenan, etc.), gum bases (vinyl acetate resin, vinyl acetate, etc.). Gelton, tickle, etc.), emulsifiers (glycerin fatty acid ester, sucrose fatty acid ester, saponin, lecithin, etc.), preservatives (benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, ε-polylysine, etc.), antioxidants (ε-polylysine, etc.) Ascorbic acid, erythorbic acid, catechin, etc.), brighteners (cellac, paraffin wax, beeswax, etc.), fungicides (thiaventazole, fludioxonyl, etc.), swelling agents (sodium hydrogencarbonate, gluconoδ-lactone, myoban, etc.), Sweeteners (aspartame, assesulfam potassium, kanzo extract, etc.), bitterness agents (caffeine, narringine, nigayomogi extract, etc.), acidulants (citric acid, tartaric acid, lactic acid, etc.), seasonings (sodium L-glutamate, 5' -Disodium inosinate, etc.), colorants (anato pigments, turmeric pigments, citrate pigments, etc.), fragrances (synthetic fragrances such as ethyl acetoacetate, anisaldehyde, natural fragrances such as orange and lavender) and the like.
In the present invention, one kind or two or more kinds of the above food additives can be used.
 本発明の食品は、肝臓の中性脂肪量の増加の抑制又は脂肪肝抑制を目的として、幅広い対象者に好適に摂取され得る。 The food of the present invention can be suitably ingested by a wide range of subjects for the purpose of suppressing an increase in the amount of triglyceride in the liver or suppressing fatty liver.
 従って、本発明の食品は、肝臓の中性脂肪量の増加を抑制するための、又は脂肪肝抑制用の、特定保健用食品、栄養機能食品、機能性表示食品等の保健機能食品、病者用食品、高齢者用食品等の特別用途食品、健康補助食品等としても提供され得る。本発明の食品には、例えば肥満症等に対する医療食が含まれる。 Therefore, the food of the present invention is a food for specified health use, a food with a nutritional function, a food with a functional claim, or a sick person for suppressing an increase in the amount of neutral fat in the liver or for suppressing adipose liver. It can also be provided as food for special use such as food for the elderly, food for the elderly, health supplement, and the like. The food of the present invention includes, for example, a medical food for obesity and the like.
 本発明の食品は、上記適用対象に、1日あたりに、本発明におけるアミノ酸の総量(L体かつ遊離体に換算した量の総量)が、上記した1日あたりの摂取量となるように摂取させることが好ましい。 The food product of the present invention is ingested by the above-mentioned application target so that the total amount of amino acids in the present invention (total amount converted into L-form and free form) in the above-mentioned daily intake is the above-mentioned daily intake. It is preferable to let it.
 以下の実施例において本発明をさらに具体的に説明するが、本発明はこれらの例によってなんら限定されるものではない。 The present invention will be described in more detail in the following examples, but the present invention is not limited to these examples.
[試験例1]
 セリン、アスパラギン酸、アラニン、グルタミン酸、チロシンを、表1に記載の重量比で混合し、実施例1のアミノ酸組成物を製造した。セリン、アスパラギン酸、アラニン、グルタミン酸、チロシンは、L体かつ遊離体を使用した。
 BLACK6J雄性マウスを用いて、6週齢から高脂肪高炭水化物食(リサーチダイエット社D12327)負荷によって肥満マウスを作製した。
 8週齢から、試験群には実施例1のアミノ酸組成物(1g/kg体重)及び0.5%メチルセルロース液(媒体)、コントロール群には0.5%メチルセルロース液(媒体)を朝・夕、2回/日経口投与を6週間実施した。この間、餌は高脂肪高炭水化物食を使用した。
 正常群は、BLACK6J雄性マウスを用いて、8週齢から、0.5%メチルセルロース液(媒体)を朝・夕、2回/日経口投与を6週間実施した。この間、餌はコントロール食を使用した。
 群構成を表2に示す。
 15週齢において麻酔下、肝臓を採材し、肝臓中の中性脂肪(TG;Triglyceride)を定法によって抽出し、キット(WAKO)を用いて定量した。結果を図1に示す。
 コントロール群では高脂肪高炭水化物食によりトリグリセリド(TG)量が正常群に比べて増加したが、実施例1のアミノ酸組成物を投与した試験群では、トリグリセリド(TG)量が、正常群とほぼ同じ量であった(図1)。この結果から、中性脂肪量の増加が、実施例1のアミノ酸組成物の投与により、抑制できる(正常に戻すことができる)ことが示された。
[Test Example 1]
Serine, aspartic acid, alanine, glutamic acid, and tyrosine were mixed in the weight ratios shown in Table 1 to prepare the amino acid composition of Example 1. For serine, aspartic acid, alanine, glutamic acid, and tyrosine, L-form and free form were used.
Using BLACK6J male mice, obese mice were prepared from 6 weeks of age by loading with a high-fat, high-carbohydrate diet (Research Diet Co., Ltd. D12327).
From 8 weeks of age, the amino acid composition (1 g / kg body weight) and 0.5% methylcellulose solution (medium) of Example 1 were applied to the test group, and the 0.5% methylcellulose solution (medium) was applied to the control group in the morning and evening. Oral administration twice daily for 6 weeks. During this time, the diet used was a high-fat, high-carbohydrate diet.
In the normal group, using BLACK6J male mice, 0.5% methylcellulose solution (medium) was orally administered twice a day in the morning and evening from 8 weeks of age for 6 weeks. During this time, a control diet was used as the bait.
The group composition is shown in Table 2.
At 15 weeks of age, the liver was sampled under anesthesia, triglyceride (TG) in the liver was extracted by a conventional method, and quantified using a kit (WAKO). The results are shown in FIG.
In the control group, the amount of triglyceride (TG) was increased by the high-fat, high-carbohydrate diet as compared with the normal group, but in the test group to which the amino acid composition of Example 1 was administered, the amount of triglyceride (TG) was almost the same as that in the normal group. It was a quantity (Fig. 1). From this result, it was shown that the increase in triglyceride mass can be suppressed (returned to normal) by administration of the amino acid composition of Example 1.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
[試験例2]
 セリン、アスパラギン酸、アラニン、グルタミン酸、チロシン、イソロイシン、シスチンを、表3に記載の重量比で混合し、実施例2のアミノ酸組成物を製造した。セリン、アスパラギン酸、アラニン、グルタミン酸、チロシン、イソロイシン、シスチンは、L体かつ遊離体を使用した。
 試験群及びコントロール群はKKAy雄性マウスを用い、正常群はBLACK6J雄性マウスを用いた。「KKAyマウス」は、KKマウスにA遺伝子を導入した合併モデルで、KKマウスより早期(7~8週齢)かつ重度な肥満・高血糖を発現するマウスである。
 KKAy雄性マウスおよび同週齢のBLACK6J雄性マウスを、6週齢から標準食(オリエンタル酵母工業、AIN93G)にて飼育した。
 11週齢から、試験群(KKAyマウス)は、実施例2のアミノ酸組成物を2%(w/w)混合した標準食(オリエンタル酵母、AIN93G)、コントロール群(KKAyマウス)は、標準食(オリエンタル酵母、AIN93G)、正常群(BLACK6Jマウス)は、標準食(オリエンタル酵母、AIN93G)を、5週間供与した。
 群構成を表4に示す。
 17週齢において麻酔下、肝臓を採材し、肝臓中の中性脂肪(TG)を定法によって抽出し、キット(WAKO)を用いて定量した。結果を図2に示す。
 コントロール群ではトリグリセリド(TG)量が正常群に比べて有意に増加したが、実施例2のアミノ酸組成物を投与した試験群では、トリグリセリド(TG)量が、コントロール群に比べて有意に減少した(図2)。この結果から、中性脂肪量の増加が、実施例2のアミノ酸組成物の投与により、抑制できる(正常に近づけることができる)ことが示された。
 肥満によって肝細胞内の脂肪蓄積が促進され、炎症によってさらに増悪するが、実施例2のアミノ酸組成物の供与によって肝臓脂肪量の増加が改善された。
[Test Example 2]
Serine, aspartic acid, alanine, glutamic acid, tyrosine, isoleucine, and cystine were mixed in the weight ratios shown in Table 3 to prepare the amino acid composition of Example 2. Serine, aspartic acid, alanine, glutamic acid, tyrosine, isoleucine, and cystine were L-form and free form.
KKAy male mice were used as the test group and the control group, and BLACK6J male mice were used as the normal group. The "KKAy mouse" is a combined model in which the Ay gene is introduced into the KK mouse, and is a mouse that expresses severe obesity and hyperglycemia earlier (7 to 8 weeks old) than the KK mouse.
KKAy male mice and BLACK6J male mice of the same age were bred from 6 weeks on a standard diet (Oriental Yeast Co., Ltd., AIN93G).
From 11 weeks of age, the test group (KKAy mouse) was a standard diet (Oriental yeast, AIN93G) mixed with 2% (w / w) of the amino acid composition of Example 2, and the control group (KKAy mouse) was a standard diet (KKAy mouse). The oriental yeast, AIN93G) and normal group (BLACK6J mice) were fed a standard diet (oriental yeast, AIN93G) for 5 weeks.
The group composition is shown in Table 4.
At 17 weeks of age, the liver was sampled under anesthesia, triglyceride (TG) in the liver was extracted by a conventional method, and quantified using a kit (WAKO). The results are shown in FIG.
In the control group, the amount of triglyceride (TG) was significantly increased as compared with the normal group, but in the test group to which the amino acid composition of Example 2 was administered, the amount of triglyceride (TG) was significantly decreased as compared with the control group. (Fig. 2). From this result, it was shown that the increase in triglyceride mass can be suppressed (approached to normal) by administration of the amino acid composition of Example 2.
Although obesity promotes fat accumulation in hepatocytes and exacerbates it by inflammation, the donation of the amino acid composition of Example 2 improved the increase in hepatic fat mass.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
[試験例3]
 試験例2で使用したものと同じ実施例2のアミノ酸組成物を、試験例3において用いた。
 BLACK6J雄性マウスを用いて、10週齢から高脂肪食(オリエンタル酵母、HFD-60)にて4週間飼育し、食事誘導性肥満モデル(DIOモデル)を作成した。
 14週齢から、試験群には、実施例2のアミノ酸組成物を2%(w/w)混合した高脂肪食(HFD-60)、コントロール群には高脂肪食(HFD-60)を、8週間供与した。
 正常群は、BLACK6J雄性マウスを用いて、10週齢から標準食(オリエンタル酵母工業、AIN93G)にて12週間飼育した。
 群構成を表5に示す。
 23週齢にて、剖検時に肝臓を採材し、肝臓中の脂質を定法によって抽出し、中性脂肪および遊離脂肪酸をキット(WAKO)を用いて定量した。また、剖検時に内臓脂肪である精巣上体脂肪を採材し、重量測定した。結果を図3に示す。
 肝臓中中性脂肪量及び遊離脂肪酸量について、コントロール群では中性脂肪量、遊離脂肪酸量が正常群に比べて有意に増加したが、実施例2のアミノ酸組成物を投与した試験群では、中性脂肪量、遊離脂肪酸量が、コントロール群に比べて有意に減少した(図3の左図及び中図)。この結果から、肝臓の脂肪量の増加が、実施例2のアミノ酸組成物の投与により、抑制できる(正常に近づけることができる)ことが示された。
 精巣上体脂肪重量について、コントロール群では精巣上体脂肪重量が正常群に比べて有意に増加したが、実施例2のアミノ酸組成物を投与した試験群では、精巣上体脂肪重量が、コントロール群に比べて有意に減少した(図3の右図)。この結果から、内臓脂肪量の増加が、実施例2のアミノ酸組成物の投与により、抑制できる(正常に近づけることができる)ことが示された。
 肥満によって肝細胞内の脂肪蓄積及び内臓脂肪蓄積が促進されるが、実施例2のアミノ酸組成物の供与によって肝臓脂肪量及び内臓脂肪量の増加が改善された。
[Test Example 3]
The same amino acid composition of Example 2 used in Test Example 2 was used in Test Example 3.
Using BLACK6J male mice, they were bred on a high-fat diet (Oriental yeast, HFD-60) for 4 weeks from 10 weeks of age to prepare a diet-induced obesity model (DIO model).
From 14 weeks of age, the test group received a high-fat diet (HFD-60) mixed with 2% (w / w) of the amino acid composition of Example 2, and the control group received a high-fat diet (HFD-60). It was donated for 8 weeks.
The normal group was bred from 10 weeks of age on a standard diet (Oriental Yeast Co., Ltd., AIN93G) for 12 weeks using BLACK6J male mice.
The group composition is shown in Table 5.
At 23 weeks of age, the liver was sampled at autopsy, lipids in the liver were extracted by a routine method, and triglycerides and free fatty acids were quantified using a kit (WAKO). At the time of autopsy, epididymal fat, which is visceral fat, was collected and weighed. The results are shown in FIG.
Regarding the amount of triglyceride and free fatty acid in the liver, the amount of triglyceride and free fatty acid in the control group increased significantly as compared with the normal group, but in the test group to which the amino acid composition of Example 2 was administered, the amount was medium. The amount of triglyceride and the amount of free fatty acid were significantly reduced as compared with the control group (left and middle figures in FIG. 3). From this result, it was shown that the increase in the amount of fat in the liver can be suppressed (approached to normal) by the administration of the amino acid composition of Example 2.
Regarding the epididymal fat weight, the epididymal fat weight was significantly increased in the control group as compared with the normal group, but in the test group to which the amino acid composition of Example 2 was administered, the epididymal fat weight was increased in the control group. It decreased significantly (right figure in FIG. 3). From this result, it was shown that the increase in visceral fat mass can be suppressed (approached to normal) by administration of the amino acid composition of Example 2.
Although obesity promotes fat accumulation and visceral fat accumulation in hepatocytes, the donation of the amino acid composition of Example 2 improved the increase in liver fat mass and visceral fat mass.
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
[試験例4]
 試験例2で使用したものと同じ実施例2のアミノ酸組成物を、試験例4において用いた。
 BLACK6J雄性マウスを用いて、10週齢から高脂肪食(オリエンタル酵母、HFD-60)にて4週間飼育し、食事誘導性肥満モデル(DIOモデル)を作成した。
 14週齢から、試験群には、実施例2のアミノ酸組成物を2%(w/w)混合した高脂肪食(HFD-60)、コントロール群には高脂肪食(HFD-60)を、8週間供与した。
 正常群は、BLACK6J雄性マウスを用いて、10週齢から標準食(オリエンタル酵母工業、AIN93G)にて12週間飼育した。
 群構成を表6に示す。
 試験群は、実施例2のアミノ酸組成物を2%(w/w)混合した高脂肪食(HFD-60)の介入4、6、8週目にそれぞれ尾静脈採血を実施し、空腹時血中インスリン値をキット(森永生科学研究所)にて測定した。正常群、コントロール群も、試験群と同じ時期(14週齢から4、6、8週目)にそれぞれ尾静脈採血を実施し、空腹時血中インスリン値をキット(森永生科学研究所)にて測定した。結果を図4に示す。
 コントロール群では空腹時インスリン値が正常群に比べて有意に増加したが(図4の左図、中図、右図)、実施例2のアミノ酸組成物を投与した試験群では、空腹時インスリン値が、介入4週目、介入6週目ではコントロール群に比べて有意に減少し(図4の左図、中図)、介入8週目でもコントロール群に比べて減少した(図4の右図)。
 空腹時インスリン値の増加はインスリン抵抗性、臓器のインスリン感受性の低下を示唆するものである。インスリン抵抗性によって、肝臓での脂質蓄積が助長される。糖尿病誘発も推察される。
 図4の結果から、肥満によって促進されるインスリン抵抗性が、実施例2のアミノ酸組成物の投与により、改善できる(正常に近づけることができる)ことが示された。
 肥満によってインスリン抵抗性が促進されるが、実施例2のアミノ酸組成物の供与によってインスリン抵抗性が改善された。
[Test Example 4]
The same amino acid composition of Example 2 used in Test Example 2 was used in Test Example 4.
Using BLACK6J male mice, they were bred on a high-fat diet (Oriental yeast, HFD-60) for 4 weeks from 10 weeks of age to prepare a diet-induced obesity model (DIO model).
From 14 weeks of age, the test group received a high-fat diet (HFD-60) mixed with 2% (w / w) of the amino acid composition of Example 2, and the control group received a high-fat diet (HFD-60). It was donated for 8 weeks.
The normal group was bred from 10 weeks of age on a standard diet (Oriental Yeast Co., Ltd., AIN93G) for 12 weeks using BLACK6J male mice.
The group composition is shown in Table 6.
In the test group, tail vein blood sampling was performed at weeks 4, 6 and 8 of the high-fat diet (HFD-60) in which the amino acid composition of Example 2 was mixed at 2% (w / w), respectively, and fasting blood was collected. The medium insulin level was measured with a kit (Morinaga Seigaku Kenkyusho). In the normal group and the control group, blood was collected from the tail vein at the same time as the test group (14 weeks to 4, 6 and 8 weeks), and the fasting blood insulin level was used as a kit (Morinaga Seigaku Kenkyusho). Was measured. The results are shown in FIG.
In the control group, the fasting insulin level was significantly increased as compared with the normal group (left figure, middle figure, right figure in FIG. 4), but in the test group to which the amino acid composition of Example 2 was administered, the fasting insulin level was administered. However, it decreased significantly in the 4th and 6th weeks of the intervention compared to the control group (left figure and middle figure in FIG. 4), and decreased in the 8th week of the intervention as compared with the control group (right figure in FIG. 4). ).
An increase in fasting insulin levels suggests insulin resistance and decreased insulin sensitivity in organs. Insulin resistance promotes lipid accumulation in the liver. Diabetes induction is also inferred.
From the results of FIG. 4, it was shown that insulin resistance promoted by obesity can be improved (approached to normal) by administration of the amino acid composition of Example 2.
Obesity promotes insulin resistance, but donation of the amino acid composition of Example 2 improved insulin resistance.
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
 本発明により、肝臓の中性脂肪量の増加を抑制するための組成物(例えば、脂肪肝抑制用組成物)を提供することができる。また、本発明により、インスリン抵抗性を改善するための組成物、及び内臓脂肪量の増加を抑制するための組成物を提供することができる。 INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a composition for suppressing an increase in the amount of triglyceride in the liver (for example, a composition for suppressing fatty liver). Further, according to the present invention, it is possible to provide a composition for improving insulin resistance and a composition for suppressing an increase in visceral fat mass.
 本出願は、日本で出願された特願2019-220717を基礎としており、その内容は本出願にすべて包含されるものである。 This application is based on Japanese Patent Application No. 2019-220717 filed in Japan, the contents of which are all included in this application.

Claims (40)

  1.  有効成分として、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含有する、肝臓の中性脂肪量の増加を抑制するための組成物。 A composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid as active ingredients to suppress an increase in the amount of triglyceride in the liver.
  2.  脂肪肝抑制用である、請求項1記載の組成物。 The composition according to claim 1, which is used for suppressing fatty liver.
  3.  組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部及びグルタミン酸0.4~2.5重量部である、請求項1又は2に記載の組成物。 Assuming that tyrosine is 1 part by weight, the compounding ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, 0.5 to 1.5 parts by weight of aspartic acid, and The composition according to claim 1 or 2, which is 0.4 to 2.5 parts by weight of glutamic acid.
  4.  食品である、請求項1~3のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 3, which is a food product.
  5.  有効成分として、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する、肝臓の中性脂肪量の増加を抑制するための組成物。 A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients to suppress an increase in the amount of triglyceride in the liver.
  6.  脂肪肝抑制用である、請求項5記載の組成物。 The composition according to claim 5, which is used for suppressing fatty liver.
  7.  有効成分として、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する、インスリン抵抗性を改善するための組成物。 A composition for improving insulin resistance, which contains tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients.
  8.  有効成分として、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する、内臓脂肪量の増加を抑制するための組成物。 A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine as active ingredients to suppress an increase in visceral fat mass.
  9.  組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部、グルタミン酸0.4~2.5重量部、イソロイシン1~4重量部及びシスチン0.1~2重量部である、請求項5~8のいずれか1項に記載の組成物。 Assuming that tyrosine is 1 part by weight, the compounding ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, 0.5 to 1.5 parts by weight of aspartic acid. The composition according to any one of claims 5 to 8, wherein the composition is 0.4 to 2.5 parts by weight of glutamic acid, 1 to 4 parts by weight of isoleucine, and 0.1 to 2 parts by weight of cystine.
  10.  食品である、請求項5~9のいずれか1項に記載の組成物。 The composition according to any one of claims 5 to 9, which is a food product.
  11.  肝臓の中性脂肪量の増加の抑制を必要とする対象に、有効量のチロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含有する組成物を投与することを含む、該対象における肝臓の中性脂肪量の増加を抑制する方法。 A subject in need of suppression of an increase in triglyceride mass in the liver comprises administering a composition containing effective amounts of tyrosine, serine, alanine, aspartic acid and glutamic acid to the triglyceride in the liver. A method of suppressing the increase in quantity.
  12.  肝臓の中性脂肪量の増加の抑制が、脂肪肝抑制である、請求項11記載の方法。 The method according to claim 11, wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  13.  組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部及びグルタミン酸0.4~2.5重量部である、請求項11又は12に記載の方法。 Assuming that tyrosine is 1 part by weight, the compounding ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, 0.5 to 1.5 parts by weight of aspartic acid, and The method according to claim 11 or 12, wherein the amount of glutamic acid is 0.4 to 2.5 parts by weight.
  14.  組成物が対象に経口投与される、請求項11~13のいずれか1項に記載の方法。 The method according to any one of claims 11 to 13, wherein the composition is orally administered to the subject.
  15.  肝臓の中性脂肪量の増加の抑制を必要とする対象に、有効量のチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物を投与することを含む、該対象における肝臓の中性脂肪量の増加を抑制する方法。 A subject in need of suppression of the increase in triglyceride mass in the liver, which comprises administering a composition containing effective amounts of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine. A method of suppressing an increase in triglyceride mass.
  16.  肝臓の中性脂肪量の増加の抑制が、脂肪肝抑制である、請求項15記載の方法。 The method according to claim 15, wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  17.  インスリン抵抗性の改善を必要とする対象に、有効量のチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物を投与することを含む、該対象におけるインスリン抵抗性を改善する方法。 Improving insulin resistance in a subject in need of improved insulin resistance, including administering to a subject a composition containing effective amounts of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine. Method.
  18.  内臓脂肪量の増加の抑制を必要とする対象に、有効量のチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物を投与することを含む、該対象における内臓脂肪量の増加を抑制する方法。 Of the visceral fat mass in a subject in need of suppression of the increase in visceral fat mass, including administration of a composition containing effective amounts of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine. How to control the increase.
  19.  組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部、グルタミン酸0.4~2.5重量部、イソロイシン1~4重量部及びシスチン0.1~2重量部である、請求項15~18のいずれか1項に記載の方法。 Assuming that tyrosine is 1 part by weight, the compounding ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, 0.5 to 1.5 parts by weight of aspartic acid. The method according to any one of claims 15 to 18, wherein the amount is 0.4 to 2.5 parts by weight of glutamic acid, 1 to 4 parts by weight of isoleucine, and 0.1 to 2 parts by weight of cystine.
  20.  組成物が対象に経口投与される、請求項15~19のいずれか1項に記載の方法。 The method according to any one of claims 15 to 19, wherein the composition is orally administered to a subject.
  21.  肝臓の中性脂肪量の増加の抑制における使用のための、チロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸を含有する組成物。 A composition containing tyrosine, serine, alanine, aspartic acid and glutamic acid for use in suppressing the increase in triglyceride mass in the liver.
  22.  肝臓の中性脂肪量の増加の抑制が脂肪肝抑制である、請求項21記載の組成物。 The composition according to claim 21, wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  23.  組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部及びグルタミン酸0.4~2.5重量部である、請求項21又は22に記載の組成物。 Assuming that tyrosine is 1 part by weight, the compounding ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, 0.5 to 1.5 parts by weight of aspartic acid, and so on. The composition according to claim 21 or 22, which is 0.4 to 2.5 parts by weight of glutamic acid.
  24.  食品である、請求項21~23のいずれか1項に記載の組成物。 The composition according to any one of claims 21 to 23, which is a food product.
  25.  肝臓の中性脂肪量の増加の抑制における使用のための、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物。 A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine for use in suppressing the increase in triglyceride mass in the liver.
  26.  肝臓の中性脂肪量の増加の抑制が脂肪肝抑制である、請求項25記載の組成物。 The composition according to claim 25, wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  27.  インスリン抵抗性の改善における使用のための、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物。 A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine for use in improving insulin resistance.
  28.  内臓脂肪量の増加の抑制における使用のための、チロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンを含有する組成物。 A composition containing tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine for use in suppressing an increase in visceral fat mass.
  29.  組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部、グルタミン酸0.4~2.5重量部、イソロイシン1~4重量部及びシスチン0.1~2重量部である、請求項25~28のいずれか1項に記載の組成物。 Assuming that tyrosine is 1 part by weight, the blending ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, 0.5 to 1.5 parts by weight of aspartic acid. The composition according to any one of claims 25 to 28, which comprises 0.4 to 2.5 parts by weight of glutamic acid, 1 to 4 parts by weight of isoleucine and 0.1 to 2 parts by weight of cystine.
  30.  食品である、請求項25~29のいずれか1項に記載の組成物。 The composition according to any one of claims 25 to 29, which is a food product.
  31.  肝臓の中性脂肪量の増加を抑制するための組成物を製造するためのチロシン、セリン、アラニン、アスパラギン酸及びグルタミン酸の使用。 Use of tyrosine, serine, alanine, aspartic acid and glutamic acid to produce compositions to suppress the increase in triglyceride mass in the liver.
  32.  肝臓の中性脂肪量の増加の抑制が脂肪肝抑制である、請求項31記載の使用。 The use according to claim 31, wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  33.  組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部及びグルタミン酸0.4~2.5重量部である、請求項31又は32に記載の使用。 Assuming that tyrosine is 1 part by weight, the compounding ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, 0.5 to 1.5 parts by weight of aspartic acid, and so on. The use according to claim 31 or 32, wherein the amount of glutamic acid is 0.4 to 2.5 parts by weight.
  34.  組成物が食品である、請求項31~33のいずれか1項に記載の使用。 The use according to any one of claims 31 to 33, wherein the composition is a food product.
  35.  肝臓の中性脂肪量の増加を抑制するための組成物を製造するためのチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの使用。 Use of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine to produce compositions for suppressing the increase in triglyceride mass in the liver.
  36.  肝臓の中性脂肪量の増加の抑制が脂肪肝抑制である、請求項35記載の使用。 The use according to claim 35, wherein the suppression of the increase in the amount of triglyceride in the liver is fatty liver suppression.
  37.  インスリン抵抗性を改善するための組成物を製造するためのチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの使用。 Use of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine to produce compositions to improve insulin resistance.
  38.  内臓脂肪量の増加を抑制するための組成物を製造するためのチロシン、セリン、アラニン、アスパラギン酸、グルタミン酸、イソロイシン及びシスチンの使用。 Use of tyrosine, serine, alanine, aspartic acid, glutamic acid, isoleucine and cystine to produce compositions to suppress the increase in visceral fat mass.
  39.  組成物中の配合割合が、チロシンを1重量部とすると、セリン0.4~1.5重量部、アラニン0.4~1.5重量部、アスパラギン酸0.5~1.5重量部、グルタミン酸0.4~2.5重量部、イソロイシン1~4重量部及びシスチン0.1~2重量部である、請求項35~38のいずれか1項に記載の使用。 Assuming that tyrosine is 1 part by weight, the compounding ratio in the composition is 0.4 to 1.5 parts by weight of serine, 0.4 to 1.5 parts by weight of alanine, 0.5 to 1.5 parts by weight of aspartic acid. The use according to any one of claims 35 to 38, which is 0.4 to 2.5 parts by weight of glutamic acid, 1 to 4 parts by weight of isoleucine and 0.1 to 2 parts by weight of cystine.
  40.  組成物が食品である、請求項35~39のいずれか1項に記載の使用。 The use according to any one of claims 35 to 39, wherein the composition is a food product.
PCT/JP2020/045224 2019-12-05 2020-12-04 Composition for suppressing increase in amount of neutral fat in liver WO2021112217A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04112825A (en) * 1990-09-03 1992-04-14 Rikagaku Kenkyusho Lipid metabolism regulation agent
WO2006061992A1 (en) * 2004-12-10 2006-06-15 Ajinomoto Co., Inc. Preventive/therapeutic composition for liver disease
WO2007049818A1 (en) * 2005-10-27 2007-05-03 Ajinomoto Co., Inc. Anti-fatty liver, anti-obesity or hypolipidemic composition
WO2019160103A1 (en) * 2018-02-15 2019-08-22 国立大学法人東北大学 Hepatic lipid-lowering agent

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04112825A (en) * 1990-09-03 1992-04-14 Rikagaku Kenkyusho Lipid metabolism regulation agent
WO2006061992A1 (en) * 2004-12-10 2006-06-15 Ajinomoto Co., Inc. Preventive/therapeutic composition for liver disease
WO2007049818A1 (en) * 2005-10-27 2007-05-03 Ajinomoto Co., Inc. Anti-fatty liver, anti-obesity or hypolipidemic composition
WO2019160103A1 (en) * 2018-02-15 2019-08-22 国立大学法人東北大学 Hepatic lipid-lowering agent

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