JPWO2010041647A1 - Endurance improver, fatigue inhibitor, or fatigue recovery agent comprising an amino acid composition as an active ingredient - Google Patents

Endurance improver, fatigue inhibitor, or fatigue recovery agent comprising an amino acid composition as an active ingredient Download PDF

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JPWO2010041647A1
JPWO2010041647A1 JP2010532916A JP2010532916A JPWO2010041647A1 JP WO2010041647 A1 JPWO2010041647 A1 JP WO2010041647A1 JP 2010532916 A JP2010532916 A JP 2010532916A JP 2010532916 A JP2010532916 A JP 2010532916A JP WO2010041647 A1 JPWO2010041647 A1 JP WO2010041647A1
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fatigue
amino acid
tyrosine
endurance
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宏行 有田
宏行 有田
雅子 常松
雅子 常松
浩 越膳
浩 越膳
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Meiji Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/4172Imidazole-alkanecarboxylic acids, e.g. histidine
    • 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
    • A23L2/00Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52Adding ingredients
    • 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
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/401Proline; Derivatives thereof, e.g. captopril
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • A61K31/405Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/02Nutrients, e.g. vitamins, minerals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

本願発明は、アミノ酸組成物から、持久力向上、疲労防止、又は疲労回復に有効なアミノ酸の成分や濃度の特定を図ると共に、溶解度の低いアミノ酸の成分の低減を図ることを課題とする。本願発明者らは、持久力向上に寄与するアミノ酸がチロシンであることを初めて同定し、さらに、水への溶解度が低いチロシンについて持久力向上などに必要な濃度を検討した後に、溶解度が高く、持久力向上などに優れたアミノ酸組成物を見出した。This invention makes it a subject to aim at reduction of the component of an amino acid with low solubility while trying to specify the component and density | concentration of an amino acid effective in endurance improvement, fatigue prevention, or fatigue recovery from an amino acid composition. The present inventors identified for the first time that the amino acid that contributes to improving endurance is tyrosine, and after examining the concentration necessary for improving endurance for tyrosine with low solubility in water, the solubility is high, The present inventors have found an amino acid composition excellent in improving endurance.

Description

本願発明は、持久力向上、疲労防止、又は疲労回復のための組成物の技術分野に属する。より具体的には、持久力を向上させる、疲労を防止する、又は疲労を回復させる、アミノ酸組成物に関する。   The present invention belongs to the technical field of compositions for improving endurance, preventing fatigue, or recovering from fatigue. More specifically, the present invention relates to an amino acid composition that improves endurance, prevents fatigue, or recovers fatigue.

糖尿病などの生活習慣病は動脈硬化などを引き起し、人口の高齢化に伴い、生活習慣病の予防の克服は重大な課題となっている。例えば、これら生活習慣病の予備軍は我が国だけでも2000万人とも言われている。そこで、生活習慣病の対策として、メタボリックシンドロームの概念を応用した健診・保健指導が行われるようになっている。そして、このメタボリックシンドロームの予防には運動が有効であり、持久力の向上が大きなポイントとなっている。   Lifestyle-related diseases such as diabetes cause arteriosclerosis, etc. With the aging of the population, overcoming prevention of lifestyle-related diseases has become an important issue. For example, it is said that the reserve army for these lifestyle-related diseases is 20 million in Japan alone. Therefore, as a countermeasure for lifestyle-related diseases, medical examinations and health guidance using the concept of metabolic syndrome have been performed. And exercise is effective in preventing this metabolic syndrome, and improvement in endurance is a major point.

また、持久力向上では、運動トレーニングのみならず、食品やサプルメント、あるいはその他の有効成分を含む医薬などの摂取により試みられている。例えば、リンゴ酸やクエン酸には、持久力増強効果があると言われている(非特許文献1)。さらに、ロイヤルゼリーより分離された特定の分子量(57KDa)のタンパク質には、心肺機能向上や持久力向上に有効な有酸素運動の促進成分があると報告されている(特許文献1)。   In addition, in order to improve endurance, attempts have been made not only by exercise training but also by ingestion of foods, supplements, and medicines containing other active ingredients. For example, malic acid and citric acid are said to have an endurance enhancing effect (Non-patent Document 1). Furthermore, it is reported that a protein having a specific molecular weight (57 KDa) isolated from royal jelly has an aerobic exercise promoting component effective for improving cardiopulmonary function and endurance (Patent Document 1).

また、カカオニブ及び/又はその加工物(特許文献2)、コエンザイムQ10及び(-)-ヒドロキシクエン酸を含む食品組成物(特許文献3)、チオクト酸又はチオクト酸及びクレアチンを含む組成物(特許文献4)などが持久力向上の有効成分として知られている。そして、パンテチン類及び分岐アミノ酸を含む組成物には持久力低下の防止作用があるとされている(特許文献5)。   Further, cacao nibs and / or processed products thereof (Patent Document 2), food compositions containing Coenzyme Q10 and (-)-hydroxycitric acid (Patent Document 3), compositions containing thioctic acid or thioctic acid and creatine (Patent Documents) 4) is known as an active ingredient for improving endurance. And it is supposed that the composition containing panthetins and branched amino acids has an effect of preventing endurance reduction (Patent Document 5).

他方、アミノ酸組成物には以前から様々な作用が知られている。スズメバチ由来のアミノ酸組成物は筋力持続剤、滋養強壮剤、輸液用剤、栄養補給剤、疲労回復剤、又は乳酸生成調節剤として用いられている(特許文献6)。さらに、WO2003-011056号(特許文献7)には、アスパラギン酸を有効成分とする疲労回復用の組成物が記載されている。また、特開2008-105954(特許文献8)には、アラニン、セリン、グルタミン、チロシン、アスパラギンのうちの少なくとも1種を有効成分とする骨髄赤血球の前駆細胞の分化促進剤や貧血治療剤が記載されている。そして、特開2008-081498(特許文献9)には、スレオニンやロイシンを有効成分とする脂肪蓄積の抑制用の組成物が記載されている。
特開2001-172195号 特開2006-282576号 特開2004-81010号 特開2007-131609号 特開2006-16358号 特許第2518692号 WO2003-011056号 特開2008-105954号 特開2008-081498号 日本ヘモレオロジー学会誌、第6巻、第2号(2003年)83−88頁
On the other hand, various actions have been known for amino acid compositions. A wasp-derived amino acid composition is used as a muscle strength-retaining agent, a nutritional tonic, an infusion solution, a nutritional supplement, a fatigue recovery agent, or a lactic acid production regulator (Patent Document 6). Furthermore, WO2003-011056 (Patent Document 7) describes a composition for recovering fatigue comprising aspartic acid as an active ingredient. JP 2008-105954 (Patent Document 8) describes an agent for promoting differentiation of bone marrow erythrocyte progenitor cells and an anemia treatment agent containing at least one of alanine, serine, glutamine, tyrosine and asparagine as an active ingredient. Has been. Japanese Patent Application Laid-Open No. 2008-081498 (Patent Document 9) describes a composition for suppressing fat accumulation containing threonine or leucine as an active ingredient.
JP 2001-172195 A JP 2006-282576 A JP 2004-81010 A JP 2007-131609 JP 2006-16358 Patent No.2518692 WO2003-011056 JP2008-105954 JP2008-081498 Journal of the Japan Society of Hemorheology, Vol. 6, No. 2 (2003) 83-88

アミノ酸組成物には以前から種々の活性が知られていたが、持久力向上や疲労防止あるいは疲労回復に最適な組成は未だに知られておらず、さらに、例えば、スズメバチ由来のアミノ酸組成物についても、アミノ酸組成物(混合物)中の何れのアミノ酸が特別に持久力向上などに有効であり、どの程度のアミノ酸の濃度が持久力向上などに有効であるかが特定されていなかった。   Various activities have been known in the past for amino acid compositions, but the optimal composition for improving endurance, preventing fatigue or recovering from fatigue has not been known yet, and for example, amino acid compositions derived from wasps It has not been specified which amino acid in the amino acid composition (mixture) is particularly effective for improving endurance and what concentration of amino acid is effective for improving endurance.

また、アミノ酸組成物は例えば、液体飲料又は液剤として用いられることが多いが、アミノ酸毎の溶解度の違いから、アミノ酸組成物中には溶解させることが問題となる成分もある。例えば、チロシンでは水への溶解度が低いために、可能な限り、その使用量の低下が望まれている。   In addition, amino acid compositions are often used, for example, as liquid beverages or liquids, but there are also components that can be dissolved in amino acid compositions due to differences in solubility for each amino acid. For example, since tyrosine has low solubility in water, it is desired to reduce its use amount as much as possible.

そこで、本願発明は、アミノ酸組成物中から持久力向上、疲労防止、又は疲労回復に有効なアミノ酸の成分や濃度の特定を図ると共に、溶解度の低いアミノ酸の成分の低減を図るものである。   Therefore, the present invention aims to identify amino acid components and concentrations effective for improving endurance, preventing fatigue, or recovering from fatigue in an amino acid composition, and reducing amino acid components with low solubility.

本願発明者等は以前から、スズメバチ由来のアミノ酸組成物の各種の作用を研究してきた。アミノ酸組成物中の組成を鋭意研究することにより、持久力向上に寄与するアミノ酸がチロシンであることを初めて同定し、さらに、水への溶解度が低いチロシンについて持久力向上に必要な濃度を検討した後に、溶解度が高く持久力向上に優れたアミノ酸組成物を見出した。   The inventors of the present application have been studying various effects of amino acid compositions derived from wasps. By intensive research on the composition of amino acid composition, we first identified tyrosine as an amino acid that contributes to improving endurance, and further examined the concentration required for improving endurance for tyrosine with low water solubility. Later, an amino acid composition having high solubility and excellent endurance was found.

本明細書は本願の優先権の基礎である日本国特許出願2008-259678号の明細書および/または図面に記載される内容を包含する。   This specification includes the contents described in the specification and / or drawings of Japanese Patent Application No. 2008-259678, which is the basis for the priority of the present application.

本願発明では初めて、持久力を向上させる、疲労を防止する、又は疲労を回復させる、アミノ酸の成分を提供することとなる。   For the first time, the present invention provides an amino acid component that improves endurance, prevents fatigue, or restores fatigue.

実験期間中の体重の変化(Value are mean ± SE)を示す。各群の体重に有意差は認められなかった。The change in body weight (Value are mean ± SE) during the experimental period is shown. There was no significant difference in the weight of each group. 単回投与による遊泳時間への影響(Value are mean ± SE)を示す。The effect on swimming time by single administration (Value are mean ± SE) is shown. 反復投与による遊泳時間への影響(Value are mean ± SE)を示す。* : p < 0.05、** : p < 0.01 vs. control。The effect on swimming time by repeated administration (Value are mean ± SE) is shown. *: p <0.05, **: p <0.01 vs. control. 血液中のグルコース(Value are mean ± SE)の測定値を示す。The measured value of glucose in blood (Value are mean ± SE) is shown. 血液中の乳酸(Value are mean ± SE)の測定値を示す。* : p < 0.05 vs. control。The measured value of lactic acid (Value are mean ± SE) in blood is shown. *: p <0.05 vs. control. 血液中の遊離脂肪酸(Value are mean ± SE)の測定値を示す。*** : p < 0.005 vs. control。The measured value of free fatty acid (Value are mean ± SE) in blood is shown. ***: p <0.005 vs. control. ヒドロキシル酪酸(Value are mean ± SE)の測定値を示す。* : p < 0.05 vs. control。The measured value of hydroxyl butyric acid (Value are mean ± SE) is shown. *: p <0.05 vs. control. クレアチンキナーゼ(Value are mean ± SE)の測定値を示す。The measured value of creatine kinase (Value are mean ± SE) is shown. 肝臓と筋肉(ヒフク筋)のグリコーゲン(Value are mean ± SE)の測定値を示す。* : p < 0.05 vs. control。The measured value of glycogen (Value are mean ± SE) of liver and muscle (hyfuku muscle) is shown. *: p <0.05 vs. control. 精巣周囲の脂肪組織重量(Value are mean ± SE)の測定値を示す。** : p < 0.01 vs. control。The measured value of the fat tissue weight (Value are mean ± SE) around the testis is shown. **: p <0.01 vs. control. 腓腹筋・大腿四頭筋の筋肉重量(Value are mean ± SE)の測定値を示す。* : p < 0.05 vs. control。The measured values of gastrocnemius and quadriceps muscle weight (Value are mean ± SE) are shown. *: p <0.05 vs. control.

本明細書で引用した全ての刊行物、特許および特許出願をそのまま参考として本明細書にとり入れるものとする。   All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety.

1.持久力向上・疲労防止・疲労回復
本願発明は、持久力向上のためのアミノ酸組成物、及び前記アミノ酸組成物を有効成分とする持久力向上剤を包含する。本願発明の持久力向上のためのアミノ酸組成物は、食用あるいは医療用若しくは健康食品用のアミノ酸組成物とすることもできる。本願発明の持久力向上剤は、局所持久力及び全身持久力の何れの向上にも有効である。
1. Endurance improvement / fatigue prevention / fatigue recovery The present invention includes an amino acid composition for improving endurance and an endurance improver comprising the amino acid composition as an active ingredient. The amino acid composition for improving endurance of the present invention may be an edible, medical or health food amino acid composition. The endurance improver of the present invention is effective for improving both local endurance and systemic endurance.

持久力の測定では、例えば、以下の実施例に示される方法を用いて、動物実験により計測することもできるが、例えば、全身持久力の測定では、最大酸素摂取量(VO2max)の呼気ガス分析により計測することもできる。これは、運動する被験者より、ガス・マスク経由で直接に採気して計測することができる。In the measurement of endurance, for example, it can be measured by animal experiments using the method shown in the following examples. For example, in the measurement of whole body endurance, the expiration of the maximum oxygen uptake (VO 2 max) It can also be measured by gas analysis. This can be measured by sampling directly from a moving subject via a gas mask.

さらに、本願発明は、疲労を防止したい時に、事前に摂取(投与)することにより、疲労防止剤としても用いることができるアミノ酸組成物、及び疲労を感じた時に事後に摂取(投与)することにより、疲労回復剤としても用いることができるアミノ酸組成物をも包含する。   Furthermore, the present invention provides an amino acid composition that can be used as an anti-fatigue agent by taking (administering) in advance when it is desired to prevent fatigue, and by taking (administering) after the fact when fatigue is felt. Also included are amino acid compositions that can be used as fatigue recovery agents.

2.持久力向上剤、及び持久力向上作用を有するアミノ酸組成物
本願発明は、少なくともチロシンを有効成分として含有することを特徴とする、持久力向上剤、疲労防止剤、及び疲労回復剤を包含する。より具体的には、本願発明は、チロシンのみからなる持久力向上剤、疲労防止剤、及び疲労回復剤、並びにチロシン以外のアミノ酸を含有する持久力向上剤、疲労防止剤、及び疲労回復剤を包含する。チロシン以外のアミノ酸として、例えば、分岐鎖アミノ酸(BCAA)などとすることができ、具体的には、バリン、ロイシン、イソロイシン、アルギニン、グルタミン酸、アスパラギン酸、アラニン、プロリン、リジン、及びフェニルアラニンからなる群から選択される、任意の1種以上のアミノ酸とすることができる。
2. Endurance improving agent and amino acid composition having endurance improving action The present invention includes an endurance improving agent, an anti-fatigue agent, and a fatigue recovery agent characterized by containing at least tyrosine as an active ingredient. More specifically, the present invention relates to an endurance improver comprising only tyrosine, an anti-fatigue agent, and a fatigue recovery agent, and an endurance improvement agent containing an amino acid other than tyrosine, an anti-fatigue agent, and a fatigue recovery agent. Include. Examples of amino acids other than tyrosine include branched chain amino acids (BCAA), and specifically include the group consisting of valine, leucine, isoleucine, arginine, glutamic acid, aspartic acid, alanine, proline, lysine, and phenylalanine. Any one or more amino acids selected from

より具体的には、(1)アミノ酸組成物として、チロシン、バリン、ロイシン、イソロイシン、アルギニン、グルタミン酸、アスパラギン酸、アラニン、プロリン、リジン、及びフェニルアラニンのみからなるアミノ酸組成物を有効成分とする、持久力向上剤、疲労防止剤、及び/又は疲労回復剤、さらに、(2)チロシン、バリン、ロイシン、イソロイシン、アルギニン、グルタミン酸、アスパラギン酸、アラニン、プロリン、リジン、フェニルアラニン、スレオニン、グリシン、セリン、メチオニン、ヒスチジン、及びトリプトファンのみからなるアミノ酸組成物を有効成分とする、持久力向上剤、疲労防止剤、及び/又は疲労回復剤が挙げられる。   More specifically, (1) as an amino acid composition, an amino acid composition comprising only tyrosine, valine, leucine, isoleucine, arginine, glutamic acid, aspartic acid, alanine, proline, lysine, and phenylalanine as an active ingredient, Strength improver, fatigue inhibitor, and / or fatigue recovery agent, and (2) tyrosine, valine, leucine, isoleucine, arginine, glutamic acid, aspartic acid, alanine, proline, lysine, phenylalanine, threonine, glycine, serine, methionine , Endurance improver, anti-fatigue agent, and / or fatigue recovery agent comprising an amino acid composition consisting of only histidine and tryptophan as an active ingredient.

また、本願発明には、(3)チロシン3〜5モル、バリン4〜8モル、ロイシン2〜12モル、イソロイシン3〜9モル、アルギニン0.1〜5モル、グルタミン酸0.1〜4モル、アスパラギン酸0.1〜5モル、アラニン0.1〜12モル、プロリン4〜30モル、リジン5〜11モル、及びフェニルアラニン0.5〜5モルの割合からなるアミノ酸組成物を有効成分とする、持久力向上剤、疲労防止剤、及び/又は疲労回復剤、さらに、(4)チロシン3〜4モル、バリン4〜8モル、ロイシン2〜12モル、イソロイシン3〜9モル、アルギニン0.1〜5モル、グルタミン酸0.1〜4モル、アスパラギン酸0.1〜5モル、アラニン0.1〜12モル、プロリン4〜30モル、リジン5〜11モル、フェニルアラニン0.5〜5モル、スレオニン2〜15モル、グリシン15〜25モル(あるいは20.5〜25モル)、セリン0.1〜5モル、メチオニン0.1〜5モル、ヒスチジン0.1〜5モル、及びトリプトファン0.1〜5モルの割合からなるアミノ酸組成物を有効成分とする、持久力向上剤、疲労防止剤、及び/又は疲労回復剤を包含する。   In the present invention, (3) 3-5 mol tyrosine, 4-8 mol valine, 2-12 mol leucine, 3-9 mol isoleucine, 0.1-5 mol arginine, 0.1-4 mol glutamic acid, As an active ingredient, an amino acid composition comprising aspartic acid 0.1 to 5 mol, alanine 0.1 to 12 mol, proline 4 to 30 mol, lysine 5 to 11 mol, and phenylalanine 0.5 to 5 mol, Endurance improver, fatigue inhibitor, and / or fatigue recovery agent, (4) 3-4 mol tyrosine, 4-8 mol valine, 2-12 mol leucine, 3-9 mol isoleucine, 0.1 0.1 arginine 5 mol, glutamic acid 0.1-4 mol, aspartic acid 0.1-5 mol, alanine 0.1-12 mol, proline 4-30 mol, lysine 5-11 mol, phenylalanine 0.5-5 , Threonine 2-15 mol, glycine 15-25 mol (or 20.5-25 mol), serine 0.1-5 mol, methionine 0.1-5 mol, histidine 0.1-5 mol, and tryptophan 0 It includes an endurance improver, an anti-fatigue agent, and / or a fatigue recovery agent containing an amino acid composition having a ratio of 1 to 5 mol as an active ingredient.

そして、本願発明には、(5)チロシン3.5〜4モル、バリン5〜7モル、ロイシン6〜8モル、イソロイシン4〜6モル、アルギニン3〜5モル、グルタミン酸3〜5モル、アスパラギン酸0.1〜1モル、アラニン6〜8モル、プロリン15〜20モル、リジン8〜10モル、及びフェニルアラニン3〜5モルの割合からなるアミノ酸組成物を有効成分とする、持久力向上剤、疲労防止剤、及び/又は疲労回復剤、さらに、(6)チロシン3.8〜4モル、バリン5.8〜6モル、ロイシン6.2〜6.4モル、イソロイシン4.5〜4.7モル、アルギニン3.5〜3.7モル、グルタミン酸3.2〜3.4モル、アスパラギン酸0.15〜0.17モル、アラニン6.1〜6.3モル、プロリン18〜19モル、リジン8.7〜8.9モル、フェニルアラニン3.8〜4モル、スレオニン7.2〜7.4モル、グリシン19〜21モル(あるいは20.5〜21モル)、セリン2.5〜2.7モル、メチオニン0.53〜0.55モル、ヒスチジン2.6〜2.8モル、及びトリプトファン2.2〜2.4モルの割合からなるアミノ酸組成物を有効成分とする、持久力向上剤、疲労防止剤、及び/又は疲労回復剤をも包含する。   And this invention includes (5) tyrosine 3.5-4 mol, valine 5-7 mol, leucine 6-8 mol, isoleucine 4-6 mol, arginine 3-5 mol, glutamic acid 3-5 mol, aspartic acid Endurance improver, fatigue comprising as an active ingredient an amino acid composition comprising 0.1 to 1 mol, alanine 6 to 8 mol, proline 15 to 20 mol, lysine 8 to 10 mol, and phenylalanine 3 to 5 mol Inhibitor and / or fatigue recovery agent, (6) tyrosine 3.8-4 mol, valine 5.8-6 mol, leucine 6.2-6.4 mol, isoleucine 4.5-4.7 mol , Arginine 3.5 to 3.7 mol, glutamic acid 3.2 to 3.4 mol, aspartic acid 0.15 to 0.17 mol, alanine 6.1 to 6.3 mol, proline 18 to 19 mol, lysine 8 .7-8 9 mol, phenylalanine 3.8-4 mol, threonine 7.2-7.4 mol, glycine 19-21 mol (or 20.5-21 mol), serine 2.5-2.7 mol, methionine 0.53 An endurance improver, an anti-fatigue agent, and / or an active ingredient comprising an amino acid composition comprising ˜0.55 mol, histidine 2.6 to 2.8 mol, and tryptophan 2.2 to 2.4 mol Or a fatigue recovery agent is also included.

このとき、より具体的には、チロシンの濃度が従来のスズメバチ由来のアミノ酸組成物(V.A.A.M.)に比べて好ましくは50〜90%、より好ましくは70〜90%、さらに好ましくは75〜85%、特に好ましくは約80%であり、チロシンの濃度を好ましくは2.4〜4.3モル%(3.5〜6.3重量%)、より好ましくは3.3〜4.3モル%(4.8〜6.3重量%)、さらに好ましくは3.6〜4.1モル%(5.2〜5.9重量%)に設定した上で、チロシンが、0.05〜0.065モル%で水溶液中に含有される水溶液が挙げられる。   In this case, more specifically, the concentration of tyrosine is preferably 50 to 90%, more preferably 70 to 90%, still more preferably 75 to 85%, compared to the conventional amino acid composition (VAAM) derived from wasps. Particularly preferred is about 80%, and the tyrosine concentration is preferably 2.4 to 4.3 mol% (3.5 to 6.3 wt%), more preferably 3.3 to 4.3 mol% (4 .8 to 6.3 wt%), more preferably 3.6 to 4.1 mol% (5.2 to 5.9 wt%), and tyrosine is 0.05 to 0.065 mol. An aqueous solution contained in the aqueous solution in%.

さらに好適なアミノ酸組成物として、チロシンを約3.9モル(約5.5重量部)、バリンを約6.0モル(約5.6重量部)、ロイシンを約6.3モル(約6.5重量部)、イソロイシンを約4.6モル(約4.8重量部)、アルギニンを約3.6モル(約5.0重量部)、グルタミン酸を約3.3モル(約3.8重量部)、アスパラギン酸を約0.16モル(約0.22重量部)、アラニンを約6.3モル(約4.4重量部)、プロリンを約18.4モル(約16.8重量部)、リジンを約8.8モル(約12.8重量部)、フェニルアラニンを約3.9モル(約5.1重量部)、スレオニンを約7.3モル(約6.9重量部)、グリシンを約19.5モル(約11.6重量部)、セリンを約2.5モル(約2.1重量部)、メチオニンを約0.54モル(約0.64重量部)、ヒスチジンを約2.6モル(約3.2重量部)、及びトリプトファンを約2.2モル(約3.6重量部)からなるアミノ酸組成物が挙げられる。   As a more preferred amino acid composition, tyrosine is about 3.9 mol (about 5.5 parts by weight), valine is about 6.0 mol (about 5.6 parts by weight), and leucine is about 6.3 mol (about 6 parts by weight). 0.5 parts by weight), about 4.6 moles (about 4.8 parts by weight) of isoleucine, about 3.6 moles (about 5.0 parts by weight) of arginine, and about 3.3 moles (about 3.8 parts) of glutamic acid. Parts by weight), about 0.16 moles (about 0.22 parts by weight) of aspartic acid, about 6.3 moles (about 4.4 parts by weight) of alanine, and about 18.4 moles (about 16.8 parts by weight) of proline. Part), about 8.8 moles (about 12.8 parts by weight) of lysine, about 3.9 moles (about 5.1 parts by weight) of phenylalanine, and about 7.3 moles (about 6.9 parts by weight) of threonine. Glycine about 19.5 mol (about 11.6 parts by weight), serine about 2.5 mol (about 2.1 parts by weight), methionine Amino acid composition comprising about 0.54 mole (about 0.64 parts by weight), histidine about 2.6 moles (about 3.2 parts by weight), and tryptophan about 2.2 moles (about 3.6 parts by weight) Things.

3.本願発明の持久力向上剤、疲労防止剤、及び/又は疲労回復剤の使用の形態
本願発明の持久力向上剤、疲労防止剤、又は疲労回復剤の使用形態は特に限定されないが、医療用としても、飲食用、栄養補助飲食用としても用いることができる。
3. Form of use of endurance improver, fatigue inhibitor, and / or fatigue recovery agent of the present invention The use form of the endurance improver, fatigue inhibitor, or fatigue recovery agent of the present invention is not particularly limited, but for medical use Can also be used for food and drink and for nutritional supplements.

医療用とする場合には、経口投与、直腸投与、注射や輸液による投与などの一般的な投与経路により用いることができる。経口投与の場合には、上記の組成物自体あるいは薬学上許容される担体、賦形剤、希釈剤などと共に混合し、散剤、顆粒剤、錠剤、カプセル剤、トローチ剤、シロップ剤などとすることもできる。また、注射剤として例えば、適当な緩衝剤、等張剤などを添加し、滅菌蒸留水に溶解したものを用いればよい。   In the case of medical use, it can be used by general administration routes such as oral administration, rectal administration, administration by injection or infusion. For oral administration, mix with the above composition itself or a pharmaceutically acceptable carrier, excipient, diluent, etc. to form powders, granules, tablets, capsules, troches, syrups, etc. You can also. In addition, for example, a suitable buffer, isotonic agent, etc. may be added as an injection and dissolved in sterilized distilled water.

本願発明の持久力向上剤、疲労防止剤、又は疲労回復剤は、散剤、顆粒剤、錠剤、カプセル剤、液剤などの適宜の剤形とすることがでる。製剤化には賦形剤、結合剤、崩壊剤、滑沢剤などの製剤化で常用される補助剤を添加することができる。賦形剤として、デンプン、乳糖、白糖、メチルセルロース、カルボキシメチルセルロース、アルギン酸ナトリウム、リン酸水素カルシウム、合成ケイ酸アルミニウム、微結晶セルロース、ポリビニルピロリドン(PVP)、ハイドロキシプロピルスターチ(HPS)などがある。 また、結合剤として、デンプン、微結晶セルロース、カルボキシメチルセルロースナトリウム、ポリビニルピロリドン(PVP)、アラビアゴム末、ゼラチン、ブドウ糖、白糖などの水溶液、又はそれらの水・エタノール溶液などがある。崩壊剤として、デンプン、カルボキシルメチルセルロース、カルボキシルメチルセルロースカルシウム、微結晶セルロース、ハイドロキシプロピルスターチ、リン酸カルシウムなどがある。滑沢剤として、カルナバロウ、軽質無水ケイ酸、合成ケイ酸アルミニウム、天然ケイ酸アルミニウム、合成ケイ酸マグネシウム、硬化油、硬化植物油誘導体(ステロテックスHM)、ゴマ油、サラシミツロウ、酸化チタン、乾燥水酸化アルミニウム・ゲルステアリン酸、ステアリン酸カルシウム、ステアリン酸マグネシウム、タルク、リン酸水素カルシウム、ラウリル硫酸ナトリウムなどがある。   The endurance improver, fatigue inhibitor, or fatigue recovery agent of the present invention can be made into an appropriate dosage form such as a powder, granule, tablet, capsule, and liquid. For formulation, adjuvants commonly used in formulation, such as excipients, binders, disintegrants, and lubricants, can be added. Examples of excipients include starch, lactose, sucrose, methyl cellulose, carboxymethyl cellulose, sodium alginate, calcium hydrogen phosphate, synthetic aluminum silicate, microcrystalline cellulose, polyvinyl pyrrolidone (PVP), and hydroxypropyl starch (HPS). Examples of the binder include starch, microcrystalline cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), gum arabic powder, gelatin, glucose, sucrose, and aqueous / ethanol solutions thereof. Examples of disintegrants include starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, microcrystalline cellulose, hydroxypropyl starch, and calcium phosphate. As lubricants, carnauba wax, light anhydrous silicic acid, synthetic aluminum silicate, natural aluminum silicate, synthetic magnesium silicate, hardened oil, hardened vegetable oil derivative (Sterotex HM), sesame oil, white beeswax, titanium oxide, dry hydroxide There are aluminum gel stearic acid, calcium stearate, magnesium stearate, talc, calcium hydrogen phosphate, sodium lauryl sulfate and the like.

本願発明のアミノ酸組成物を含む持久力向上剤、疲労防止剤、又は疲労回復剤は、極めて安全であるので、その投与量は非常に広範に設定できる。一般的には投与経路や、ヒトを含む投与対象動物の年齢、体重、症状などの種々の要因を考慮しながら、適宜設定することができる。本願発明は、これに限定されないが、適当な有効成分として好ましくは0.3g〜8g/kg/day、より好ましくは0.4g〜5g/kg/day、さらに好ましくは0.5g〜3g/kg/dayである。   Since the endurance improver, fatigue inhibitor, or fatigue recovery agent containing the amino acid composition of the present invention is extremely safe, its dosage can be set very broadly. In general, it can be appropriately set in consideration of various factors such as the administration route and the age, weight, and symptoms of animals to be administered including humans. Although this invention is not limited to this, As an appropriate active ingredient, Preferably it is 0.3g-8g / kg / day, More preferably, it is 0.4g-5g / kg / day, More preferably, it is 0.5g-3g / kg / Day.

本願発明の持久力向上剤、疲労防止剤、又は疲労回復剤では、0.3〜6.0重量%溶液、好ましくは1.0〜2.0重量%溶液として、1日当たりに100〜500mlを1〜3回で投与することができる。注射剤では0.3〜6.0重量%溶液として、1回当たりに100〜400ml、好ましくは150〜300mlを投与することができる。また、本願発明の持久力向上剤、疲労防止剤、又は疲労回復剤では、経口投与又は非経口投与(筋肉内、皮下、静脈内、坐薬、経皮など)の何れでも投与できる。   In the endurance improver, anti-fatigue agent, or fatigue recovery agent of the present invention, a 0.3-6.0 wt% solution, preferably a 1.0-2.0 wt% solution, is added at 100-500 ml per day. It can be administered 1 to 3 times. In the case of injection, a solution of 0.3 to 6.0% by weight can be administered in an amount of 100 to 400 ml, preferably 150 to 300 ml per time. The endurance improver, fatigue inhibitor, or fatigue recovery agent of the present invention can be administered either orally or parenterally (intramuscular, subcutaneous, intravenous, suppository, transdermal, etc.).

食用とする場合には、本願発明の持久力向上剤、疲労防止剤、又は疲労回復剤を、そのまま食用できるが、各種の食品への添加物とすることもできる。また、本願発明のアミノ酸組成物を、水に溶解して飲料とすることもでき、その場合には、他の栄養成分、例えば、水溶性のビタミン類、タウリンなどをさらに添加することもできる。そして、嗜好性の改善のために、塩化ナトリウムなどの塩類、クエン酸などの酸類(酸味料)及び/又は他の適当な風味を加えて飲料とすることもできる。このとき、安定性を向上させるために、pH調整剤、キレート剤をさらに添加することもできる。   In the case of edible use, the endurance improver, fatigue inhibitor, or fatigue recovery agent of the present invention can be edible as it is, but can also be used as an additive to various foods. In addition, the amino acid composition of the present invention can be dissolved in water to make a beverage. In that case, other nutritional components such as water-soluble vitamins and taurine can be further added. And in order to improve palatability, it can also be set as a drink by adding salts, such as sodium chloride, acids (acidulant), such as a citric acid, and / or other suitable flavors. At this time, in order to improve stability, a pH adjuster and a chelating agent can be further added.

本願発明の持久力向上剤、疲労防止剤、又は疲労回復剤は、継続投与することが望ましく、好適には1週間以上で投与することが望ましい。   The endurance improver, anti-fatigue agent, or fatigue recovery agent of the present invention is desirably administered continuously, and preferably administered for one week or longer.

以下の実施例では、次の実験試料を用いた。   In the following examples, the following experimental samples were used.

(A)実験試料: 蒸留水に懸濁させて、次のように調製した。 (A) Experimental sample: The sample was suspended in distilled water and prepared as follows.

(1)DW(蒸留水)= 対照(コントロール)
(2)スズメバチ由来のアミノ酸組成物の水溶液(V.A.A.M.の水溶液):500mg/kg。なお、その組成は次のとおりである。
(1) DW (distilled water) = control
(2) Aqueous solution of amino acid composition derived from wasp (VAAM aqueous solution): 500 mg / kg. The composition is as follows.

チロシンを約4.8モル(約6.9重量部)、バリンを約6.0モル(約5.6重量部)、ロイシンを約6.3モル(約6.5重量部)、イソロイシンを約4.6モル(約4.8重量部)、アルギニンを約3.6モル(約5.0重量部)、グルタミン酸を約3.3モル(約3.8重量部)、アスパラギン酸を約0.16モル(約0.22重量部)、アラニンを約6.3モル(約4.4重量部)、プロリンを約18.4モル(約16.8重量部)、リジンを約8.8モル(約12.8重量部)、フェニルアラニンを約3.9モル(約5.1重量部)、スレオニンを約7.3モル(約6.9重量部)、グリシンを約19.5モル(約11.6重量部)、セリンを約2.5モル(約2.1重量部)、メチオニンを約0.54モル(約0.64重量部)、ヒスチジンを約2.6モル(約3.2重量部)、及びトリプトファンを約2.2モル(約3.6重量部)。   About 4.8 mol (about 6.9 parts by weight) of tyrosine, about 6.0 mol (about 5.6 parts by weight) of valine, about 6.3 mol (about 6.5 parts by weight) of leucine, and isoleucine About 4.6 mol (about 4.8 parts by weight), Arginine about 3.6 mol (about 5.0 parts by weight), Glutamic acid about 3.3 mol (about 3.8 parts by weight), Aspartic acid about 0.16 mol (about 0.22 parts by weight), alanine about 6.3 mol (about 4.4 parts by weight), proline about 18.4 mol (about 16.8 parts by weight), and lysine about 8. 8 moles (about 12.8 parts by weight), phenylalanine about 3.9 moles (about 5.1 parts by weight), threonine about 7.3 moles (about 6.9 parts by weight), and glycine about 19.5 moles (About 11.6 parts by weight), serine about 2.5 moles (about 2.1 parts by weight), methionine about 0.54 moles (about 0.64 parts by weight) , Histidine about 2.6 moles (about 3.2 parts by weight), and about 2.2 moles of tryptophan (about 3.6 parts by weight).

(3)チロシンのみを80%に減じたスズメバチ由来のアミノ酸組成物の水溶液:500mg/kg。なお、以下及び図面中では、Tyr 80%と標記することがある。 (3) An aqueous solution of an amino acid composition derived from a wasp with only tyrosine reduced to 80%: 500 mg / kg. In the following and the drawings, it may be marked as Tyr 80%.

(4)チロシンのみを20%に減じたスズメバチ由来のアミノ酸組成物の水溶液:500mg/kg。なお、以下及び図面中では、Tyr 20%と標記することがある。 (4) Aqueous solution of wasp-derived amino acid composition in which only tyrosine is reduced to 20%: 500 mg / kg. In the following and the drawings, it may be indicated as Tyr 20%.

(B)持久力の試験は、Jpn. J. Phys. Fitness Sports Med. 1995, 44:225-238に記載の方法により行った。要約すると、マウス(各群10匹)を室温、16時間で絶食させた後に、アミノ酸の組成物を、1.8重量%の水溶液として、37.5μl/g体重 で経口投与し、次いで、室温に30分間で休ませた。これを流水プール(直径32cm、深さ30cmの円筒型の水槽に水を入れて35℃に保持し、循環装置で8m/分の速度の水流を作ったもの)で、以下の所定の錘(おもり)を、マウスの尻尾に取り付けて遊泳させ、限界遊泳時間を計測した。  (B) The endurance test was performed by the method described in Jpn. J. Phys. Fitness Sports Med. 1995, 44: 225-238. In summary, after mice (10 per group) were fasted at room temperature for 16 hours, the amino acid composition was orally administered as a 1.8 wt% aqueous solution at 37.5 μl / g body weight and then at room temperature. I took a rest in 30 minutes. This is a flowing water pool (water is placed in a cylindrical water tank of 32 cm in diameter and 30 cm in depth and kept at 35 ° C., and a water flow at a speed of 8 m / min is created by a circulation device). A weight was attached to the tail of the mouse and allowed to swim, and the limit swimming time was measured.

(C)実験方法: 次の手順で実施した。 (C) Experimental method: The following procedure was carried out.

(1)4週齢のddY雄マウスを12日間の馴化後に持久力の評価を指標にして、4群に分けた(群分け、1群:n = 10)。なお、この時点を-1 week(−1週)とする。全実験期間中の体重変化を図1に示す。各群の体重に有意差は認められなかった。 (1) Four-week-old ddY male mice were divided into 4 groups after acclimation for 12 days using endurance evaluation as an index (grouping, 1 group: n = 10). In addition, this time is set to -1 week (-1 week). The change in body weight during the whole experiment is shown in FIG. There was no significant difference in the weight of each group.

以下の(2)〜(4)の持久力の評価では、体重の5%相当の錘を、マウスの尻尾に取り付けて、限界遊泳時間を計測した。   In the following endurance evaluations (2) to (4), a weight equivalent to 5% of the body weight was attached to the tail of the mouse, and the limit swimming time was measured.

(2)遊泳の群分けから1週間後に、上記実験試料の経口投与を開始し、その投与の開始から1日目に遊泳時間を測定した(単回投与試験)。なお、この時点を0 week(0週 = 0日)とする。このとき、各群には上記の実験試料で対照、スズメバチ由来のアミノ酸組成物の水溶液(V.A.A.M.水溶液)、チロシンのみを80%に減じたスズメバチ由来のアミノ酸組成物の水溶液(Tyr 80%)、又はチロシンのみを20%に減じたスズメバチ由来のアミノ酸組成物の水溶液(Tyr20%)を経口投与した。 (2) One week after swimming grouping, oral administration of the experimental sample was started, and swimming time was measured on the first day from the start of the administration (single administration test). This time is 0 week (0 week = 0 day). At this time, each group includes a control, an aqueous solution of an amino acid composition derived from a wasp (VAAM aqueous solution), an aqueous solution of an amino acid composition derived from an wasp obtained by reducing only tyrosine to 80% (Tyr 80%), or An aqueous solution (Tyr20%) of a wasp-derived amino acid composition in which only tyrosine was reduced to 20% was orally administered.

その結果を図2に示す。図2に示されるように、単回投与では、遊泳時間の延長は認められなかった。   The result is shown in FIG. As shown in FIG. 2, the swimming time was not prolonged by single administration.

(3)その後には、実験試料の経口投与を毎日1回、7週間に亘り継続した。この期間で基本的には、通常固形食(ラボMRストック:日本農産工業)を自由摂取とした。ただし、遊泳時間の測定、採血、解剖では、前夜(22時)から絶食させた。 (3) Thereafter, oral administration of the experimental sample was continued once a day for 7 weeks. Basically, during this period, a normal solid food (Lab MR Stock: Nippon Agricultural Industry) was freely ingested. However, in the swimming time measurement, blood collection, and dissection, the fasting was performed from the previous night (22:00).

(4)遊泳時間の測定では、1週間毎に、5 week(5週目)まで実施した。遊泳時間の測定日には、遊泳の開始の30分前に、実験試料を経口投与した。 (4) Measurement of swimming time was carried out every week up to 5 weeks (5th week). On the day of measurement of the swimming time, the experimental sample was orally administered 30 minutes before the start of swimming.

その結果を図3に示す。チロシン(Tyr)100%群と80%群では対照群と比較し、投与開始の1週目より、有意に遊泳時間の延長が認められた。Tyr100%群と80%群の間に差異は認められなかった。Tyr20%群では対照群と比較し、投与開始の5週目でも、遊泳時間の延長は認められなかった。   The result is shown in FIG. In the tyrosine (Tyr) 100% group and the 80% group, the swimming time was significantly prolonged from the first week of administration compared to the control group. There was no difference between Tyr 100% group and 80% group. In the Tyr20% group, as compared with the control group, no increase in swimming time was observed even at the fifth week after the start of administration.

(5)実験試料の経口投与から6 week(6週目)に、体重の5%相当の錘を、マウスの尻尾に取り付け、15分間で遊泳させてから採血し、血糖値、血中の乳酸値、血中の遊離脂肪酸(NEFA、Non-esterifiedfatty acid)値を測定した。なお、投与前、投与30分後(運動直前)にも採血し、前記と同様に測定した。血糖値の測定には、グルコースCII-テストワコー(和光純薬社製)、乳酸値の測定には、デタミナーLA(協和メデックス社製)、遊離脂肪酸値の測定には、NEFA C-テストワコー(和光純薬社製)を使用した。 (5) At 6 weeks after the oral administration of the experimental sample, a weight equivalent to 5% of the body weight was attached to the tail of the mouse, allowed to swim for 15 minutes, blood was collected, blood sugar level, lactic acid in blood Value, blood free fatty acid (NEFA, Non-esterified fatty acid) value. Blood was also collected before administration and 30 minutes after administration (immediately before exercise) and measured in the same manner as described above. Glucose CII-Test Wako (manufactured by Wako Pure Chemical Industries) is used to measure blood glucose levels, Determiner LA (manufactured by Kyowa Medex) is used to measure lactic acid levels, and NEFA C-Test Wako (manufactured by Kyowa Medex Co., Ltd.). Wako Pure Chemical Industries, Ltd.) was used.

血糖値の測定結果を図4に示す。各群の血中のグルコース値に有意差は認められなかった。   The measurement result of the blood glucose level is shown in FIG. There was no significant difference in the blood glucose level of each group.

血中の乳酸値の測定結果を図5に示す。投与前、投与30分後(運動直前)には、各群の血中の乳酸値に有意差は認められなかった。Tyr100%群とTyr 80%群では対照群と比較し、運動直後には、有意に乳酸値の低下が認められ、運動に伴う乳酸の上昇を抑制した。   The measurement result of the lactic acid level in blood is shown in FIG. Before administration and 30 minutes after administration (immediately before exercise), there was no significant difference in the lactic acid level in the blood of each group. Compared with the control group, the Tyr100% group and the Tyr80% group showed a significant decrease in lactic acid level immediately after exercise, and suppressed the increase in lactic acid associated with exercise.

血中の遊離脂肪酸(NEFA)値の測定結果を図6に示す。Tyr100%群、Tyr 80%群、Tyr 20%群の何れでも対照群と比較し、運動直後には、有意に遊離脂肪酸(NEFA)値の上昇が認められた。   The measurement result of the free fatty acid (NEFA) value in blood is shown in FIG. In any of the Tyr 100% group, the Tyr 80% group, and the Tyr 20% group, a significant increase in free fatty acid (NEFA) value was observed immediately after exercise compared to the control group.

(6)同じく7 week(7週目)に、同様に採血して、ケトン(3-ヒドロキシ酪酸、3-Hydroxybutylic acid)値、クレアチンキナーゼ(CK、Creatine kinase)値を測定した。ケトンの測定には、ケトレックス「三和」(三和化学社製)、クレアチンキナーゼの測定には、CPKII-テストワコー(和光純薬社製)を使用した。 (6) Similarly, at 7 week (seventh week), blood was collected in the same manner, and a ketone (3-hydroxybutyric acid) value and a creatine kinase (CK) value were measured. Ketorex “Sanwa” (manufactured by Sanwa Chemical Co., Ltd.) was used for the measurement of ketone, and CPKII-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) was used for the measurement of creatine kinase.

ケトンの測定結果を図7に示す。運動に伴い、ヒドロキシル酪酸(ケトン)値は全体的に上昇し、Tyr100%群とTyr 80%群では対照群と比較し、運動直後には、有意にケトンの上昇が認められた。   The measurement result of ketone is shown in FIG. With exercise, hydroxylbutyric acid (ketone) levels generally increased, and in the Tyr 100% group and Tyr 80% group, a significant increase in ketone was observed immediately after exercise, compared with the control group.

クレアチンキナーゼの測定結果を図8に示す。運動に伴い、クレアチンキナーゼ(CK)値は全体的に上昇したが、各群のクレアチンキナーゼ値に有意差は認められなかった。   The measurement result of creatine kinase is shown in FIG. With exercise, creatine kinase (CK) levels generally increased, but there was no significant difference in the creatine kinase levels of each group.

(7)投与開始の8week(8週目)に、各群を非運動群と運動群(遊泳)に分けた。  (7) Each group was divided into a non-exercise group and an exercise group (swimming) at 8 weeks (8th week) after the start of administration.

同じく8週目に、マウスを解剖して、臓器重量(肝臓・腎臓・脾臓・副精巣周囲脂肪・腓腹筋・大腿四頭筋)を測定した。肝臓と腓腹筋では、グリコーゲン量も測定した。グリコーゲンの測定には、グルコースCII-テストワコー(和光純薬社製)を使用した。   Similarly, at 8 weeks, the mice were dissected and the organ weights (liver, kidney, spleen, peri-testicular fat, gastrocnemius, quadriceps) were measured. Glycogen levels were also measured in the liver and gastrocnemius muscle. Glucose CII-Test Wako (Wako Pure Chemical Industries, Ltd.) was used for glycogen measurement.

半数のマウスでは、体重の5%相当の錘を、尻尾に取り付け、15分間で遊泳させた直後に解剖した(運動群 = 運動あり)。残りの半数のマウスでは、遊泳させずに解剖した(非運動群 = 運動なし)。   In half of the mice, a weight equivalent to 5% of the body weight was attached to the tail and dissected immediately after swimming for 15 minutes (exercise group = with exercise). The other half of the mice were dissected without swimming (non-motor group = no exercise).

グリコーゲン量の測定結果を図9に示す。非運動群(運動なし)において、各群では肝臓と筋肉のグリコーゲン量に差異は認められなかった。他方、運動群(運動あり)において、Tyr100%群と80%群では対照群と比較し、有意に肝臓と筋肉のグリコーゲン量の上昇が認められた。   The measurement result of the amount of glycogen is shown in FIG. In the non-exercise group (no exercise), there was no difference in liver and muscle glycogen levels in each group. On the other hand, in the exercise group (with exercise), the Tyr100% group and the 80% group showed significantly increased liver and muscle glycogen levels compared to the control group.

また、臓器重量の測定結果を図10及び11に示す。精巣周囲において、Tyr100%群では対照群と比較し、有意に脂肪組織重量の低下が認められた。また、Tyr100%群では対照群と比較し、有意にヒフク筋重量と大腿四頭筋重量の増加が認められた。その他の諸臓器(肝臓・腎臓・脾臓)の差異は認められなかった。   Moreover, the measurement result of organ weight is shown to FIG. Around the testis, the Tyr 100% group showed a significant decrease in adipose tissue weight compared to the control group. In addition, the Tyr100% group significantly increased the weight of the typhoid muscle and quadriceps muscle compared with the control group. There were no differences in other organs (liver, kidney, spleen).

本願発明は、スポーツ競技者や肉体労働者、家畜など、持久力向上、疲労回復、疲労防止などに役立つ、医薬、保健健康食品、飲料、又は飼料として利用することができる。   INDUSTRIAL APPLICABILITY The present invention can be used as medicines, health and health foods, beverages, or feeds that are useful for improving endurance, recovering from fatigue, preventing fatigue, and the like for sports athletes, manual workers, livestock, and the like.

Claims (10)

チロシンを有効成分とする持久力向上剤、疲労防止剤、又は疲労回復剤。   Endurance improver, fatigue inhibitor, or fatigue recovery agent containing tyrosine as an active ingredient. チロシンを含むアミノ酸組成物を有効成分とする持久力向上剤、疲労防止剤、又は疲労回復剤。   Endurance improver, fatigue inhibitor, or fatigue recovery agent comprising an amino acid composition containing tyrosine as an active ingredient. チロシンを含むアミノ酸組成物が、チロシン、バリン、ロイシン、イソロイシン、アルギニン、グルタミン酸、アスパラギン酸、アラニン、プロリン、リジン、及びフェニルアラニンのみからなる請求項2記載の持久力向上剤、疲労防止剤、又は疲労回復剤。   The endurance improver, fatigue inhibitor, or fatigue according to claim 2, wherein the amino acid composition containing tyrosine comprises only tyrosine, valine, leucine, isoleucine, arginine, glutamic acid, aspartic acid, alanine, proline, lysine, and phenylalanine. Recovery agent. チロシンを含むアミノ酸組成物が、チロシン、バリン、ロイシン、イソロイシン、アルギニン、グルタミン酸、アスパラギン酸、アラニン、プロリン、リジン、フェニルアラニン、スレオニン、グリシン、セリン、メチオニン、ヒスチジン、及びトリプトファンのみからなる請求項2記載の持久力向上剤、疲労防止剤、又は疲労回復剤。   The amino acid composition containing tyrosine consists of only tyrosine, valine, leucine, isoleucine, arginine, glutamic acid, aspartic acid, alanine, proline, lysine, phenylalanine, threonine, glycine, serine, methionine, histidine, and tryptophan. Endurance improver, fatigue inhibitor, or fatigue recovery agent. チロシンを含むアミノ酸組成物が、チロシン3〜5モル、バリン4〜8モル、ロイシン2〜12モル、イソロイシン3〜9モル、アルギニン0.1〜5モル、グルタミン酸0.1〜4モル、アスパラギン酸0.1〜5モル、アラニン0.1〜12モル、プロリン4〜30モル、リジン5〜11モル、及びフェニルアラニン0.5〜5モルの割合からなる請求項3記載の持久力向上剤、疲労防止剤、又は疲労回復剤。   An amino acid composition containing tyrosine is 3-5 mol tyrosine, 4-8 mol valine, 2-12 mol leucine, 3-9 mol isoleucine, 0.1-5 mol arginine, 0.1-4 mol glutamic acid, aspartic acid The endurance improver and fatigue according to claim 3, comprising 0.1 to 5 mol, alanine 0.1 to 12 mol, proline 4 to 30 mol, lysine 5 to 11 mol, and phenylalanine 0.5 to 5 mol. An inhibitor or a fatigue recovery agent. チロシンを含むアミノ酸組成物が、チロシン3〜4モル、バリン4〜8モル、ロイシン2〜12モル、イソロイシン3〜9モル、アルギニン0.1〜5モル、グルタミン酸0.1〜4モル、アスパラギン酸0.1〜5モル、アラニン0.1〜12モル、プロリン4〜30モル、リジン5〜11モル、フェニルアラニン0.5〜5モル、スレオニン2〜15モル、グリシン15〜25モル、セリン0.1〜5モル、メチオニン0.1〜5モル、ヒスチジン0.1〜5モル、及びトリプトファン0.1〜5モルの割合からなる請求項4記載の持久力向上剤、疲労防止剤、又は疲労回復剤。   An amino acid composition containing tyrosine is 3-4 mol tyrosine, 4-8 mol valine, 2-12 mol leucine, 3-9 mol isoleucine, 0.1-5 mol arginine, 0.1-4 mol glutamic acid, aspartic acid 0.1-5 mol, alanine 0.1-12 mol, proline 4-30 mol, lysine 5-11 mol, phenylalanine 0.5-5 mol, threonine 2-15 mol, glycine 15-25 mol, serine 0. The endurance improver, anti-fatigue agent, or fatigue recovery according to claim 4, comprising 1 to 5 mol, methionine 0.1 to 5 mol, histidine 0.1 to 5 mol, and tryptophan 0.1 to 5 mol. Agent. チロシンを含むアミノ酸組成物が、チロシン3.5〜4モル、バリン5〜7モル、ロイシン6〜8モル、イソロイシン4〜6モル、アルギニン3〜5モル、グルタミン酸3〜5モル、アスパラギン酸0.1〜1モル、アラニン6〜8モル、プロリン15〜20モル、リジン8〜10モル、フェニルアラニン3〜5モル、スレオニン7〜9モル、グリシン15〜25モル、セリン2〜4モル、メチオニン0.5〜1.5モル、ヒスチジン2〜4モル、及びトリプトファン2〜4モルの割合からなる請求項4記載の持久力向上剤、疲労防止剤、又は疲労回復剤。   A tyrosine-containing amino acid composition comprises tyrosine 3.5 to 4 mol, valine 5 to 7 mol, leucine 6 to 8 mol, isoleucine 4 to 6 mol, arginine 3 to 5 mol, glutamic acid 3 to 5 mol, aspartic acid 0. 1-1 mol, alanine 6-8 mol, proline 15-20 mol, lysine 8-10 mol, phenylalanine 3-5 mol, threonine 7-9 mol, glycine 15-25 mol, serine 2-4 mol, methionine 0. The endurance improver, fatigue inhibitor, or fatigue recovery agent according to claim 4, comprising 5 to 1.5 mol, histidine 2 to 4 mol, and tryptophan 2 to 4 mol. チロシンを含むアミノ酸組成物が、チロシン3.8〜4モル、バリン5.8〜6モル、ロイシン6.2〜6.4モル、イソロイシン4.5〜4.7モル、アルギニン3.5〜3.7モル、グルタミン酸3.2〜3.4モル、アスパラギン酸0.15〜0.17モル、アラニン6.1〜6.3モル、プロリン18〜19モル、リジン8.7〜8.9モル、フェニルアラニン3.8〜4モル、スレオニン7.2〜7.4モル、グリシン19〜21モル、セリン2.5〜2.7モル、メチオニン0.53〜0.55モル、ヒスチジン2.6〜2.8モル、及びトリプトファン2.2〜2.4モルの割合からなる請求項4記載の持久力向上剤、疲労防止剤、又は疲労回復剤。   The amino acid composition containing tyrosine is 3.8-4 mol tyrosine, 5.8-6 mol valine, 6.2-6.4 mol leucine, 4.5-4.7 mol isoleucine, 3.5-3 arginine. 0.7 mol, glutamic acid 3.2-3.4 mol, aspartic acid 0.15-0.17 mol, alanine 6.1-6.3 mol, proline 18-19 mol, lysine 8.7-8.9 mol , Phenylalanine 3.8-4 mol, threonine 7.2-7.4 mol, glycine 19-21 mol, serine 2.5-2.7 mol, methionine 0.53-0.55 mol, histidine 2.6- The endurance improver, fatigue inhibitor, or fatigue recovery agent according to claim 4, comprising 2.8 moles and tryptophan 2.2 to 2.4 moles. チロシンが、0.05〜0.065モル%で水溶液中に含有されることを特徴とする請求項1〜8のいずれか1項記載の持久力向上剤、疲労防止剤、又は疲労回復剤。   The endurance improver, fatigue inhibitor, or fatigue recovery agent according to any one of claims 1 to 8, wherein tyrosine is contained in the aqueous solution at 0.05 to 0.065 mol%. 前記請求項1〜9のいずれか1項記載の持久力向上剤、疲労防止剤、又は疲労回復剤を含有する飲食品又は栄養補助用飲食品。   The food / beverage products or food / beverage products for nutrition assistance containing the endurance improver, fatigue inhibitor, or fatigue recovery agent of any one of Claims 1-9.
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