JP5775657B2 - Anti-fatigue agent containing amino acid composition - Google Patents

Anti-fatigue agent containing amino acid composition Download PDF

Info

Publication number
JP5775657B2
JP5775657B2 JP2008521230A JP2008521230A JP5775657B2 JP 5775657 B2 JP5775657 B2 JP 5775657B2 JP 2008521230 A JP2008521230 A JP 2008521230A JP 2008521230 A JP2008521230 A JP 2008521230A JP 5775657 B2 JP5775657 B2 JP 5775657B2
Authority
JP
Japan
Prior art keywords
weight
parts
fatigue
amino acid
acid composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2008521230A
Other languages
Japanese (ja)
Other versions
JPWO2007145239A1 (en
Inventor
真人 斎藤
真人 斎藤
宏行 有田
宏行 有田
土田　博
博 土田
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Meiji Co Ltd
Original Assignee
Meiji Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Meiji Co Ltd filed Critical Meiji Co Ltd
Priority to JP2008521230A priority Critical patent/JP5775657B2/en
Publication of JPWO2007145239A1 publication Critical patent/JPWO2007145239A1/en
Application granted granted Critical
Publication of JP5775657B2 publication Critical patent/JP5775657B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic 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 or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, 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
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic 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
    • A61K31/401—Proline; Derivatives thereof, e.g. captopril
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic 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
    • A61K31/403—Heterocyclic 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
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Mycology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Food Science & Technology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Non-Alcoholic Beverages (AREA)

Description

本発明は特定種のアミノ酸からなるアミノ酸組成物を含有する疲労防止剤に関する。   The present invention relates to an anti-fatigue agent containing an amino acid composition comprising a specific type of amino acid.

現代社会に生きる人間にとって「疲労」という現象は、既に単純には無視できない状況となりつつある。近年の調査結果によると、全国民の６０％近くが疲労を感じており、そのうち４０％弱の人々が６ヶ月以上継続する疲労を感じていると回答している。これを就労人口に換算すると３０００万人近くの労働者が継続した疲労感を伴ったままで業務に従事していることになる。また、重篤な慢性疲労の場合には日常生活にも支障を来す場合もある。さらに、これらの疲労によって引き起こされる経済的損失は、回復措置に係る費用も含めると、数千億円から一兆円規模となると推測されている。   For people living in modern society, the phenomenon of “fatigue” is already becoming a situation that cannot be simply ignored. According to recent survey results, nearly 60% of all citizens feel fatigued, and nearly 40% of those responded that they feel tired for more than 6 months. When this is converted into the working population, nearly 30 million workers are engaged in work with continued fatigue. In the case of severe chronic fatigue, it may interfere with daily life. Furthermore, the economic loss caused by these fatigues is estimated to be in the range of several hundred billion yen to one trillion yen, including the cost of recovery measures.

疲労は、発現から分類した場合には急性疲労と慢性疲労とに大別され、前者は数分から数時間の単位で発生し、比較的短時間の休息で回復する場合が多い。後者は急性疲労が蓄積された場合に、回復せずに数日、長い場合には週間単位で回復するレベルのものであるが、上記のように長期に渡る場合には６ヶ月以上継続することもある。   Fatigue is broadly divided into acute fatigue and chronic fatigue when classified from the onset, and the former occurs in units of minutes to hours and often recovers after a relatively short rest. The latter is a level that recovers for several days without recovering when acute fatigue accumulates, and for weeks when it is long, but should continue for more than 6 months if it lasts for a long time as described above. There is also.

また、疲労が生じる部位から分類した場合には、肉体疲労と精神（神経）疲労とに大別される。但し、これらの疲労については筋肉疲労と神経疲労とで分類できるものではあるが、そのストレスから見た場合には、実際には常にお互いが複雑に関連して生じている。したがって、上記の単純な分類では対処方法は一義的には見いだせず、この点についての知見が得られれば、効果的な疲労回復措置を構築することにもつながる。   Moreover, when it classify | categorizes from the site | part which produces fatigue, it divides roughly into physical fatigue and mental (nerve) fatigue. However, these types of fatigue can be classified into muscle fatigue and nerve fatigue, but when viewed from the stress, they are always always associated with each other in a complicated manner. Therefore, in the above simple classification, a coping method cannot be found uniquely, and if knowledge about this point is obtained, it will lead to building an effective fatigue recovery measure.

疲労防止や回復の方法としては、入浴などの簡易的なストレス解消方法から、薬剤投与まで含めた治療方法が種々検討されている。これらの方法は、上記した筋肉疲労と神経疲労とのそれぞれの疲労を回復することを目的としているが、実際にはその双方を同時に満足するような方法は未だ得られていない。   As a method for preventing or recovering from fatigue, various treatment methods including simple stress relieving methods such as bathing and drug administration have been studied. These methods are aimed at recovering the above-mentioned fatigue of muscle fatigue and nerve fatigue, but in reality, no method that satisfies both of them at the same time has yet been obtained.

また、これらの方法においてはある種の薬剤又はサプリメントなどの投与を含んでいる場合がある。薬剤投与の場合には医者などによる診断や処方の対応が必要であることから煩雑である。一方、サプリメントとしての食餌による対応方法は、簡便であり日常生活に取り入れやすいこともあり、近年その研究開発・商品開発が進められており、サプリメント市場は拡大の一途をたどっている。例えば、クエン酸、ビタミン、コエンザイムＱ１０を初めとする疲労回復用サプリメントはコンビニエンスストア等でも市販されている。しかし、これらのサプリメントにおいても、上記した筋肉疲労と神経疲労とのそれぞれの疲労を回復する効果については明らかにされておらず、実際にはその双方を同時に満足するような明確な方法は未だ得られていない。   These methods may also include the administration of certain drugs or supplements. In the case of drug administration, it is complicated because diagnosis and prescribing by a doctor or the like is necessary. On the other hand, dietary supplements as supplements are simple and easy to incorporate into daily life. In recent years, research and development and product development have been promoted, and the supplement market is steadily expanding. For example, supplements for fatigue recovery such as citric acid, vitamins, and coenzyme Q10 are also commercially available at convenience stores and the like. However, in these supplements, the effects of recovering from the above-mentioned muscle fatigue and nerve fatigue have not been clarified. In fact, there is still no clear method for satisfying both of them. It is not done.

一方、主に運動能力向上の目的で注目を集め商品名「ＶＡＡＭ」（明治乳業株式会社製）として知られているスズメバチの幼虫が分泌するだ液中に含まれる複数のアミノ酸組成物については、疲労回復にも効果があるとされており（例えば特許文献１）、さらにこの技術から派生した種々のアミノ酸組成物についても開発が進められている。例えば特許文献２には、筋肉自体の疲労ならびにそれに伴う倦怠感などの精神的疲労を速やかに回復するアミノ酸組成物が開示されている。   On the other hand, for a plurality of amino acid compositions contained in the saliva secreted by wasp larvae, which is known mainly as a product name “VAAM” (manufactured by Meiji Dairies Co., Ltd.) It is said that it is effective for recovery from fatigue (for example, Patent Document 1), and various amino acid compositions derived from this technology are also being developed. For example, Patent Document 2 discloses an amino acid composition that quickly recovers fatigue of muscles themselves and mental fatigue such as fatigue associated therewith.

また、ＢＣＡＡとして知られているバリン、ロイシン、イソロイシンについては、これらにも運動能力向上としての用途以外に、中枢神経系の疲労（脳性疲労）予防若しくは脳疲労回復効果があるとして、これを用いた中枢神経系用疲労予防／回復剤が提供されている（特許文献３）。   In addition to valine, leucine, and isoleucine known as BCAA, these are used for preventing fatigue of the central nervous system (brain fatigue) or recovering from brain fatigue in addition to their use for improving exercise ability. An anti-fatigue / recovery agent for central nervous system has been provided (Patent Document 3).

一方、いくつかの疲労に関する研究の結果から、疲労に伴いある種のアミノ酸の血中濃度の低下や特定組織への取り込みが行われることが知られている。例えば、非特許文献１には自転車による長時間負荷を与えたヒトにおいて、プロリン、グリシン、アラニンなどのアミノ酸が有意に消費され低下することが開示されている。   On the other hand, it is known from the results of some studies on fatigue that blood concentrations of certain amino acids are lowered and taken into specific tissues with fatigue. For example, Non-Patent Document 1 discloses that amino acids such as proline, glycine, and alanine are significantly consumed and decreased in humans who have been subjected to a long-term bicycle load.

また非特許文献２には運動時における炭水化物の補給の有無条件での血漿中成分についての濃度変化について検討が行われている。この文献ではグリシン、アラニン、リジン、スレオニン、ヒスチジンの血漿中濃度低下がみられ、特にヒスチジンの低下率が大きいことが示されている。   Non-Patent Document 2 discusses changes in the concentration of plasma components under the condition of whether or not carbohydrate is replenished during exercise. This document shows that plasma concentrations of glycine, alanine, lysine, threonine, and histidine are decreased, and particularly, the rate of decrease of histidine is large.

非特許文献３にも運動時における給餌有無の系における各種血漿中成分の濃度変化についての研究結果が開示されている。ここでは特にトリプトファンの濃度低下率が大きいことが開示されている。   Non-Patent Document 3 also discloses the results of studies on changes in concentrations of various plasma components in a system with or without feeding during exercise. Here, it is disclosed that the concentration reduction rate of tryptophan is particularly large.

その量が低下したそれぞれのアミノ酸についての運動や疲労現象との因果関係は未だ明確にはされていないが、エネルギー代謝サイクルにおいてこれらのアミノ酸が何らかの関わりがあり消費されているものと推測される。したがって、これらの濃度低下が見られるアミノ酸を補充することで疲労回復することは容易に想像される。しかし、肉体疲労、精神疲労後にこれらを単純に補充することでも容易には疲労回復することは無く、またこれらを事前に投与したとしても、疲労回復効果が得られるという事実は未だ知られていない。   Although the causal relationship between exercise and fatigue for each amino acid whose amount has been reduced has not yet been clarified, it is presumed that these amino acids are consumed in some way in the energy metabolism cycle. Therefore, it is easily imagined that fatigue recovery can be achieved by supplementing these amino acids that show a decrease in concentration. However, simply replenishing them after physical fatigue or mental fatigue does not easily recover from fatigue, and the fact that they can be recovered even if administered in advance is not yet known. .

特許第２５１８６９２号公報Japanese Patent No. 2518692 特開平８−１９８７４８号公報JP-A-8-198748 再表２００２／０３４２５７号公報No. 2002/034257 Ｇ．アーボルグ等（G.Ahlborg et al），The Journal of Clinical Investigation,第53巻,1974年4月号,p.1080-1090G. A. Borg et al., The Journal of Clinical Investigation, Vol. 53, April 1974, p.1080-1090 Ｔ．Ｌ．バザーレ等（T.L.Bazzare et al），Journal of the American College of Nutrition,1992年,第11巻,第5号,p.501-511T. T. et al. L. T.L.Bazzare et al, Journal of the American College of Nutrition, 1992, 11th, 5th, p.501-511 Ａ．Ｈ．フォースランド等（A.H.Forslund et al），Am.J.Physiol Endocrinol Metab.,2000年,第278巻,p.857-867A. H. Forslund et al., Am. J. Physiol Endocrinol Metab., 2000, 278, p.857-867

上述のように、これら従来のアミノ酸組成物は、運動能力の向上が主たる目的であり、抗疲労効果、疲労防止という観点からの検討については未だ不十分であった。また、特に疲労回復や予防についての効果を謳う技術もあるが、いずれも筋肉疲労と神経疲労との防止効果についての検討は不十分なものであり、未だ解決されたとは言い難い。さらに、これら従来のアミノ酸組成物は多種かつ多量のアミノ酸を組成物として供給しなければならず、必然的に高コストなものとなってしまう問題点が潜在している。   As described above, these conventional amino acid compositions are mainly intended to improve athletic ability, and have not yet been sufficiently examined from the viewpoint of anti-fatigue effects and fatigue prevention. In addition, there is a technique that particularly has an effect on recovery from fatigue and prevention, but studies on the effects of preventing muscle fatigue and nerve fatigue are insufficient, and it is difficult to say that they have been solved yet. Further, these conventional amino acid compositions have to supply various and large amounts of amino acids as a composition, which inevitably has a problem of high cost.

本発明者等は、鋭意研究の結果、従来には無い組成と量比にてアミノ酸組成物を構成することで、従来不十分であった疲労防止効果を得ることを見出し、本発明を完成した。
従って、本発明の目的は、特定種類の特定量のアミノ酸からなるアミノ酸組成物を含有する疲労防止剤を提供することにある。As a result of intensive studies, the present inventors have found that an amino acid composition having an unprecedented composition and quantity ratio can provide a fatigue prevention effect that has been insufficient in the past, and completed the present invention. .
Accordingly, an object of the present invention is to provide an anti-fatigue agent containing an amino acid composition composed of a specific amount of a specific type of amino acid.

すなわち、本発明は以下のアミノ酸からなるアミノ酸組成物を含む疲労防止剤を提供する：
プロリン ３０〜２００重量部；
グリシン ６０〜１４０重量部；
アラニン ２５〜２６０重量部；
リジン ４０〜１３０重量部；
トリプトファン ２０〜７５重量部；
ヒスチジン １５〜４０重量部。That is, this invention provides the fatigue prevention agent containing the amino acid composition which consists of the following amino acids:
30-200 parts by weight of proline;
60-140 parts by weight of glycine;
25-260 parts by weight alanine;
40-130 parts by weight of lysine;
Tryptophan 20-75 parts by weight;
15-40 parts by weight of histidine.

また、上記構成のアミノ酸組成物にさらに、以下のアミノ酸を含有する疲労防止剤が好ましい：
スレオニン ３５〜６５重量部；
チロシン １５〜６５重量部；
アルギニン ２５〜４５重量部。Further, an anti-fatigue agent containing the following amino acids in addition to the amino acid composition having the above structure is preferable:
35-65 parts by weight of threonine;
Tyrosine 15-65 parts by weight;
Arginine 25-45 parts by weight.

また、上記構成のアミノ酸組成物にさらに、以下のアミノ酸を含有する疲労防止剤が好ましい：
バリン ３０〜５５重量部；
ロイシン ３５〜６０重量部；
イソロイシン ２５〜４５重量部。Further, an anti-fatigue agent containing the following amino acids in addition to the amino acid composition having the above structure is preferable:
30-55 parts by weight of valine;
35-60 parts by weight of leucine;
25 to 45 parts by weight of isoleucine.

さらに本発明は、筋肉疲労および神経疲労の双方を同時に防止する、前記の疲労防止剤に関する。
また本発明は、筋肉疲労が行動量測定によって評価されるものであり、神経疲労が血中バイオマーカー測定によって評価されるものである、前記の疲労防止剤に関する。
さらに本発明は、行動量測定による評価において、非投与群の行動量を１００とした場合に投与群の行動量（相対値）が１１０以上であり、かつ、血中バイオマーカー測定による評価において、非投与群の測定濃度を１００とした場合に投与群の測定濃度（相対値）が９６以下であり、筋肉疲労および神経疲労の防止効果を有すると評価される、前記の疲労防止剤に関する。Furthermore, the present invention relates to the anti-fatigue agent described above, which simultaneously prevents both muscle fatigue and nerve fatigue.
The present invention also relates to the anti-fatigue agent as described above, wherein muscle fatigue is evaluated by measuring the amount of behavior, and nerve fatigue is evaluated by measuring blood biomarkers.
Furthermore, in the evaluation by the behavior amount measurement, the present invention is that the behavior amount of the administration group (relative value) is 110 or more when the behavior amount of the non-administration group is 100, and in the evaluation by the blood biomarker measurement, When the measured concentration of the non-administered group is 100, the measured concentration (relative value) of the administered group is 96 or less, and the fatigue inhibitor is evaluated to have an effect of preventing muscle fatigue and nerve fatigue.

本発明の疲労防止剤に用いられる組成物は、従来には無い組成と量比によるアミノ酸組成物である。これにより、従来不十分であった疲労防止について高い効果を得ることが出来る。すなわち本発明により初めて、実際の筋肉疲労と神経疲労との双方を同時に防止することが出来る。   The composition used for the anti-fatigue agent of the present invention is an amino acid composition based on a composition and quantity ratio that have not existed before. Thereby, the high effect can be acquired about the fatigue prevention which was inadequate conventionally. That is, for the first time according to the present invention, both actual muscle fatigue and nerve fatigue can be prevented simultaneously.

本発明においては、その評価系として疲労時の行動量測定と疲労時の血中バイオマーカー測定との２種の評価系を特に用いて、それぞれを筋肉疲労と精神疲労の指標とした。その結果、本発明のアミノ酸組成物に関して特に両評価系における顕著な疲労防止効果を得ることが出来た。   In the present invention, two types of evaluation systems, namely, an action amount measurement during fatigue and a blood biomarker measurement during fatigue were used as the evaluation systems, and these were used as indicators of muscle fatigue and mental fatigue, respectively. As a result, the remarkable anti-fatigue effect in both evaluation systems could be obtained with the amino acid composition of the present invention.

また本発明によれば、従来のアミノ酸組成物よりも少ない種類のアミノ酸で高い疲労防止効果を得ることが出来るために、調製に必要な原材料種が減り、工業的にも経済的にも高い効果を奏する。   In addition, according to the present invention, since a high fatigue prevention effect can be obtained with fewer types of amino acids than conventional amino acid compositions, the number of raw material types required for preparation is reduced, and this is highly industrially and economically effective. Play.

さらに、従来のアミノ酸組成物よりも少ない量のアミノ酸により高い疲労防止効果が得られることからも、工業的にも経済的にも高い効果を奏する。また、従来同等の効果を得るように調製した場合には、それぞれのアミノ酸の使用量が少なく、これを飲料等に適するように調製した場合には飲料として低容量化を計ることができ、特にスポーツドリンクなど携帯用飲料として有効なものとなる。   Furthermore, since a high fatigue prevention effect can be obtained with a smaller amount of amino acid than the conventional amino acid composition, the effect is high both industrially and economically. In addition, when prepared so as to obtain the same effect as before, the amount of each amino acid used is small, and when it is prepared so as to be suitable for a beverage or the like, the volume can be reduced as a beverage. It becomes effective as portable drinks such as sports drinks.

以下、本発明を詳細に説明するが、本発明は以下に述べる個々の形態には限定されない。   Hereinafter, the present invention will be described in detail, but the present invention is not limited to the individual forms described below.

本発明の疲労防止剤に含まれるアミノ酸組成物としては、下記のアミノ酸を下記の量比で含むものが好ましい。
プロリン ３０〜２００重量部；
グリシン ６０〜１４０重量部；
アラニン ２５〜２６０重量部；
リジン ４０〜１３０重量部；
トリプトファン ２０〜７５重量部；
ヒスチジン １５〜４０重量部。As the amino acid composition contained in the fatigue inhibitor of the present invention, those containing the following amino acids in the following quantitative ratios are preferred.
30-200 parts by weight of proline;
60-140 parts by weight of glycine;
25-260 parts by weight alanine;
40-130 parts by weight of lysine;
Tryptophan 20-75 parts by weight;
15-40 parts by weight of histidine.

上記組成のアミノ酸組成物には、下記のアミノ酸をさらに含有することが好ましい。
スレオニン ３５〜６５重量部；
チロシン １５〜６５重量部；
アルギニン ２５〜４５重量部。The amino acid composition having the above composition preferably further contains the following amino acids.
35-65 parts by weight of threonine;
Tyrosine 15-65 parts by weight;
Arginine 25-45 parts by weight.

また、上記組成のアミノ酸組成物には、下記のアミノ酸をさらに含有することが好ましい。
バリン ３０〜５５重量部；
ロイシン ３５〜６０重量部；
イソロイシン ２５〜４５重量部。The amino acid composition having the above composition preferably further contains the following amino acids.
30-55 parts by weight of valine;
35-60 parts by weight of leucine;
25 to 45 parts by weight of isoleucine.

本発明の疲労防止剤に含まれるアミノ酸組成物としては、好ましくは下記のアミノ酸を下記の量比で含むものである。
プロリン ４０〜１５０重量部；
グリシン ７５〜１１０重量部；
アラニン ３０〜２２０重量部；
リジン ５５〜９５重量部；
トリプトファン ２５〜６５重量部；
ヒスチジン ２０〜３５重量部；
スレオニン ３５〜６５重量部；
チロシン １５〜６５重量部；
アルギニン ２５〜４５重量部。
また、この９種のみのアミノ酸からなるアミノ酸組成物を含む疲労防止剤が好ましい。The amino acid composition contained in the fatigue inhibitor of the present invention preferably contains the following amino acids in the following quantitative ratios.
40-150 parts by weight of proline;
75-110 parts by weight of glycine;
30-220 parts by weight of alanine;
Lysine 55-95 parts by weight;
Tryptophan 25-65 parts by weight;
20 to 35 parts by weight of histidine;
35-65 parts by weight of threonine;
Tyrosine 15-65 parts by weight;
Arginine 25-45 parts by weight.
Further, an anti-fatigue agent containing an amino acid composition consisting of only these nine amino acids is preferred.

さらに、本発明の疲労防止剤に含まれるアミノ酸組成物としては、好ましくは下記のアミノ酸を下記の量比で含むものである。
プロリン ４０〜１５０重量部；
グリシン ７５〜１１０重量部；
アラニン ３０〜２２０重量部；
リジン ５５〜９５重量部；
トリプトファン ２５〜６５重量部；
ヒスチジン ２０〜３５重量部；
バリン ３０〜５５重量部；
ロイシン ３５〜６０重量部；
イソロイシン ２５〜４５重量部。
また、この９種のみのアミノ酸からなるアミノ酸組成物を含む疲労防止剤が好ましい。Furthermore, the amino acid composition contained in the fatigue inhibitor of the present invention preferably contains the following amino acids in the following quantitative ratios.
40-150 parts by weight of proline;
75-110 parts by weight of glycine;
30-220 parts by weight of alanine;
Lysine 55-95 parts by weight;
Tryptophan 25-65 parts by weight;
20 to 35 parts by weight of histidine;
30-55 parts by weight of valine;
35-60 parts by weight of leucine;
25 to 45 parts by weight of isoleucine.
Further, an anti-fatigue agent containing an amino acid composition consisting of only these nine amino acids is preferred.

また、本発明の疲労防止剤に含まれるアミノ酸組成物としては、好ましくは下記のアミノ酸を下記の量比で含むものである。
プロリン ４０〜１２０重量部；
グリシン ６０〜８５重量部；
アラニン ２５〜１７０重量部；
リジン ４０〜７５重量部；
トリプトファン ２０〜５０重量部；
ヒスチジン ２０〜３０重量部；
スレオニン ３５〜５５重量部；
チロシン １５〜５５重量部；
アルギニン ２５〜４０重量部；
バリン ３０〜４０重量部；
ロイシン ３５〜５０重量部；
イソロイシン ２５〜４０重量部。
本発明においては、特に好ましくはこれら１２種のみのアミノ酸からなるアミノ酸組成物を含む疲労防止剤である。
なお、上記構成のアミノ酸組成物においては、チロシンはさらに好ましくは３５〜５５重量部である。The amino acid composition contained in the anti-fatigue agent of the present invention preferably contains the following amino acids in the following quantitative ratios.
40-120 parts by weight of proline;
60-85 parts by weight of glycine;
25-170 parts by weight alanine;
40-75 parts by weight of lysine;
Tryptophan 20-50 parts by weight;
20-30 parts by weight of histidine;
Threonine 35-55 parts by weight;
Tyrosine 15-55 parts by weight;
Arginine 25-40 parts by weight;
30-40 parts by weight of valine;
35-50 parts by weight of leucine;
25 to 40 parts by weight of isoleucine.
In the present invention, an anti-fatigue agent comprising an amino acid composition consisting of only these 12 amino acids is particularly preferred.
In the amino acid composition having the above structure, tyrosine is more preferably 35 to 55 parts by weight.

また本発明の疲労防止剤は、疲労時の行動量測定と疲労時の血中バイオマーカー測定との２種の評価系により、筋肉疲労および神経疲労の双方において疲労防止効果があると評価される。   Further, the anti-fatigue agent of the present invention is evaluated as having an anti-fatigue effect in both muscular fatigue and nerve fatigue by two types of evaluation systems, ie, an action amount measurement during fatigue and a blood biomarker measurement during fatigue. .

行動量測定による評価は、例えば、投与群（アミノ酸組成物を投与）と非投与群（コントロール群）との２つの群に対し、トレッドミルなどによって運動負荷を与え、２群の行動量をそれぞれ測定し、非投与群の行動量を１００とした場合の投与群の相対的な行動量を算出して行った。投与群の行動量（相対値）が、１００を越えた場合、好ましくは１１０以上、さらに好ましくは１２０以上、とくに好ましくは１９０以上の場合、投与したアミノ酸組成物は、筋肉疲労の防止効果を有すると評価できる。なお、投与群の行動量（相対値）は、数値が大きいほど筋肉疲労の防止効果が高いと評価できる。   Evaluation by the behavioral amount measurement is performed by, for example, applying exercise load by a treadmill or the like to the two groups of the administration group (administration of the amino acid composition) and the non-administration group (control group). The measurement was carried out by calculating the relative behavior amount of the administration group when the behavior amount of the non-administration group was 100. When the behavior amount (relative value) of the administration group exceeds 100, the administered amino acid composition has an effect of preventing muscle fatigue, preferably 110 or more, more preferably 120 or more, particularly preferably 190 or more. Then you can evaluate. In addition, it can be evaluated that the action amount (relative value) of the administration group has a higher effect of preventing muscle fatigue as the value increases.

血中バイオマーカー測定による評価は、例えば、投与群（アミノ酸組成物を投与）と非投与群（コントロール群）との２つの群に対し、トレッドミルなどによって運動負荷を与え、一定時間経過後に採血し、２群の血中バイオマーカーの濃度をそれぞれ測定し、非投与群の測定濃度を１００とした場合の投与群の相対的な測定濃度を算出して行った。任意の血中バイオマーカー（コルチゾール、インターフェロン−γ（ＩＦＮ−γ）、インターロイキン−１０（ＩＬ−１０）を含む）を指標とした場合、投与群の測定濃度（相対値）が１００未満の場合、好ましくは９６以下の場合、神経疲労の防止効果を有すると評価できる。   Evaluation by blood biomarker measurement is performed by, for example, applying exercise load by a treadmill or the like to two groups, an administration group (administration of amino acid composition) and a non-administration group (control group), and blood is collected after a lapse of a certain time. Then, the concentrations of the two groups of blood biomarkers were measured, and the relative measured concentration of the administration group was calculated when the measurement concentration of the non-administration group was 100. When any blood biomarker (including cortisol, interferon-γ (IFN-γ), interleukin-10 (IL-10)) is used as an index, and the measured concentration (relative value) of the administration group is less than 100 In the case of preferably 96 or less, it can be evaluated as having an effect of preventing nerve fatigue.

とくにコルチゾールを指標とした場合、投与群の測定濃度（相対値）が、好ましくは９５以下、さらに好ましくは８０以下の場合、神経疲労の防止効果を有すると評価できる。またＩＦＮ−γを指標とした場合、投与群の測定濃度（相対値）が、好ましくは６０以下、さらに好ましくは４５以下の場合、神経疲労の防止効果を有すると評価できる。さらにＩＬ−１０を指標とした場合、投与群の測定濃度（相対値）が、好ましくは７０以下、さらに好ましくは５０以下の場合、神経疲労の防止効果を有すると評価できる。
なお、投与群の測定濃度（相対値）は、数値が小さいほど神経疲労の防止効果が高いと評価できる。In particular, when cortisol is used as an index, when the measured concentration (relative value) of the administration group is preferably 95 or less, more preferably 80 or less, it can be evaluated as having an effect of preventing nerve fatigue. Further, when IFN-γ is used as an index, it can be evaluated that it has an effect of preventing nerve fatigue when the measured concentration (relative value) of the administration group is preferably 60 or less, more preferably 45 or less. Further, when IL-10 is used as an index, when the measured concentration (relative value) of the administration group is preferably 70 or less, more preferably 50 or less, it can be evaluated that it has an effect of preventing nerve fatigue.
In addition, it can be evaluated that the measured concentration (relative value) of the administration group has a higher effect of preventing nerve fatigue as the numerical value is smaller.

本発明の疲労防止剤には上記アミノ酸の他に、必要に応じて、メチオニン（好ましくは０．３〜０．７モル％、更に好ましくは０．４〜０．６モル％）、アスパラギン酸（好ましくは０．１〜０．３モル％）、タウリン（好ましくは３モル％以下）、リン酸エタノールアミン（好ましくは２モル％以下）、シスチン（好ましくは０．５モル％以下）、β−アラニン（好ましくは１モル％以下）、γ−アミノ酪酸（好ましくは０．５モル％以下）、オルニチン又はエタノールアミン（好ましくは３モル％以下）、アンモニア（好ましくは２モル％以下）、１−メチルヒスチジン（好ましくは３モル％以下）、３−メチルヒスチジン（好ましくは１モル％以下）を含んでいてもよい。本発明に使用するアミノ酸組成物中のアミノ酸は、特にＬ−アミノ酸であることが好ましい。   In addition to the above amino acids, the anti-fatigue agent of the present invention contains, as necessary, methionine (preferably 0.3 to 0.7 mol%, more preferably 0.4 to 0.6 mol%), aspartic acid ( Preferably 0.1 to 0.3 mol%), taurine (preferably 3 mol% or less), ethanolamine phosphate (preferably 2 mol% or less), cystine (preferably 0.5 mol% or less), β- Alanine (preferably 1 mol% or less), γ-aminobutyric acid (preferably 0.5 mol% or less), ornithine or ethanolamine (preferably 3 mol% or less), ammonia (preferably 2 mol% or less), 1- Methylhistidine (preferably 3 mol% or less) and 3-methylhistidine (preferably 1 mol% or less) may be contained. The amino acid in the amino acid composition used in the present invention is particularly preferably an L-amino acid.

本発明で使用する各アミノ酸は、各々、単品で高純度のものが好ましい。例えば、「食品添加物公定書」に規定する純度以上のアミノ酸を使用する。また、これらのアミノ酸としては、その生理学的に許容し得る塩の形態のものも使用可能である。   Each amino acid used in the present invention is preferably a single product and high purity. For example, an amino acid having a purity higher than that prescribed in the “Food Additives Official Document” is used. Further, as these amino acids, those in the form of physiologically acceptable salts thereof can also be used.

本発明のアミノ酸組成物を製造するにあたっては、市販の上記アミノ酸を上記の所定割合で混合すれば良い。また溶液として使用する場合にはこれを、蒸留水に溶解すれば良い。通常は粉末状で均一に混合して組成物としておき、使用時に蒸留水に溶解すれば良い。本発明の組成物を製造、保存する温度は特に限定されないが、室温以下で製造、保存することが好ましい。   In producing the amino acid composition of the present invention, the above-mentioned commercially available amino acids may be mixed in the above-mentioned predetermined ratio. Moreover, what is necessary is just to melt | dissolve this in distilled water when using it as a solution. Usually, it is powdered and mixed uniformly to obtain a composition, which may be dissolved in distilled water at the time of use. The temperature at which the composition of the present invention is produced and stored is not particularly limited, but it is preferably produced and stored at room temperature or lower.

本発明の疲労防止剤の投与形態としては、例えば錠剤、被覆錠剤、カプセル剤、顆粒剤、散剤、溶液、シロップ剤、乳液等による経口投与をあげることができる。これらの各種製剤は、常法に従って本発明によるアミノ酸組成物に賦形剤、結合剤、崩壊剤、滑沢剤、着色剤、矯味矯臭剤、溶解補助剤、懸濁剤、コーティング剤などの医薬の製剤技術分野において通常使用しうる既知の補助剤を用いて製剤化することができる。   Examples of the dosage form of the anti-fatigue agent of the present invention include oral administration using tablets, coated tablets, capsules, granules, powders, solutions, syrups, and emulsions. These various preparations are pharmaceuticals such as excipients, binders, disintegrants, lubricants, coloring agents, flavoring agents, solubilizing agents, suspending agents, coating agents, etc. in the amino acid composition according to the present invention in accordance with conventional methods. It can be formulated using known adjuvants that can be usually used in the field of pharmaceutical technology.

本発明の疲労防止剤の主成分であるアミノ酸組成物は極めて安全性が高く、投与量は広範に設定することができる。一般的には、投与経路、ヒトを含む投与対象動物の年齢、体重、症状など、種々の要因を考慮して、適宜設定することができる。本発明はこれに限定されないが、好ましくは、有効成分として１ｇ〜８ｇ／ｋｇ／ｄａｙが適当である。   The amino acid composition which is the main component of the anti-fatigue agent of the present invention is extremely safe, and the dose can be set widely. In general, it can be appropriately set in consideration of various factors such as the administration route, the age, weight, and symptoms of animals to be administered including humans. Although this invention is not limited to this, Preferably, 1g-8g / kg / day is suitable as an active ingredient.

本発明の組成物は、疲労を防止したい時に事前に投与し疲労防止剤として使用するばかりでなく、疲労を感じた時に事後的に投与して疲労回復剤としても使用でき、０．３〜６．０重量％溶液として、１日当たり１００〜５００ｍｌを１〜３回投与すればよい。注射剤としては０．３〜６．０重量％溶液として１回あたり１００〜４００ｍｌ、好ましくは１５０〜３００ｍｌを投与すればよい。
また本発明の疲労防止剤は、経口投与又は非経口投与（筋肉内、皮下、静脈内、坐薬、経皮等）のいずれでも投与できる。The composition of the present invention is not only administered in advance and used as an anti-fatigue agent when it is desired to prevent fatigue, but can also be used as an anti-fatigue agent after administration when fatigue is felt. As a 0 wt% solution, 100 to 500 ml per day may be administered 1 to 3 times. As an injection, it is sufficient to administer 100 to 400 ml, preferably 150 to 300 ml as a 0.3 to 6.0% by weight solution.
The anti-fatigue agent of the present invention can be administered either orally or parenterally (intramuscular, subcutaneous, intravenous, suppository, transdermal, etc.).

本発明の疲労防止剤をその組成で含有する特定保健用食品等の特別用途食品とすることも可能であり、また本発明の疲労防止剤は食品組成物に含ませ、栄養機能食品等の機能性食品として直接摂取することにより、疲労防止効果を簡便に得ることができる。   The anti-fatigue agent of the present invention can also be used as a special-purpose food such as a food for specified health use containing the composition, and the anti-fatigue agent of the present invention can be included in a food composition to function as a nutritionally functional food. By directly ingesting as a functional food, an effect of preventing fatigue can be easily obtained.

具体的には、食品組成物として使用する場合には、各種飲食品（牛乳、清涼飲料、発酵乳、ヨーグルト、チーズ、パン、ビスケット、クラッカー、ピッツァクラスト、調製粉乳、流動食、病者用食品、幼児用粉乳等食品、授乳婦用粉乳等食品、栄養食品等）に、本発明の疲労防止剤をその組成で添加し、これを摂取してもよい。さらに他の食品ないし食品成分と混合するなど、通常の食品組成物における常法にしたがって使用できる。また、その性状についても、通常用いられる飲食品の状態、例えば、固体状（粉末、顆粒状その他）、ペースト状、液状ないし懸濁状のいずれでもよい。   Specifically, when used as a food composition, various foods and drinks (milk, soft drinks, fermented milk, yogurt, cheese, bread, biscuits, crackers, pizza crusts, prepared milk powder, liquid foods, food for the sick The anti-fatigue agent of the present invention may be added to foods such as infant milk powder, foods such as milk powder for nursing women, and nutritional foods, and then ingested. Furthermore, it can be used according to a conventional method in a normal food composition such as mixing with other foods or food ingredients. Moreover, about the property, the state of the food / beverage products normally used, for example, any of solid (powder, granule, etc.), paste, liquid or suspension may be sufficient.

食品組成物として使用する場合に、その他の成分についても特に限定はないが、上記食品組成物に包含される、例えば飲食物には、水、タンパク質、糖質、脂質、ビタミン類、ミネラル類、有機酸、有機塩基、果汁、フレーバー類等を成分として使用することができる。タンパク質としては、例えば全脂粉乳、脱脂粉乳、部分脱脂粉乳、カゼイン、ホエイ粉、ホエイタンパク質、ホエイタンパク質濃縮物、ホエイタンパク質分離物、α―カゼイン、β―カゼイン、κ−カゼイン、β―ラクトグロブリン、α―ラクトアルブミン、ラクトフェリン、大豆タンパク質、鶏卵タンパク質、肉タンパク質等の動植物性タンパク質、これら加水分解物；バター、乳清ミネラル、クリーム、ホエイ、非タンパク態窒素、シアル酸、リン脂質、乳糖等の各種乳由来成分などが挙げられる。糖類、加工澱粉（デキストリンのほか、可溶性澱粉、ブリティッシュスターチ、酸化澱粉、澱粉エステル、澱粉エーテル等）、食物繊維などが挙げられる。脂質としては、例えば、ラード、魚油等、これらの分別油、水素添加油、エステル交換油等の動物性油脂；パーム油、サフラワー油、コーン油、ナタネ油、ヤシ油、これらの分別油、水素添加油、エステル交換油等の植物性油脂などが挙げられる。ビタミン類としては、例えば、ビタミンＡ、カロチン類、ビタミンＢ群、ビタミンＣ、ビタミンＤ群、ビタミンＥ、ビタミンＫ群、ビタミンＰ、ビタミンＱ、ナイアシン、ニコチン酸、パントテン酸、ビオチン、イノシトール、コリン、葉酸などが挙げられ、ミネラル類としては、例えば、カルシウム、カリウム、マグネシウム、ナトリウム、銅、鉄、マンガン、亜鉛、セレンなどが挙げられる。有機酸としては、例えば、リンゴ酸、クエン酸、乳酸、酒石酸などが挙げられる。これらの成分は、２種以上を組み合わせて使用することができ、合成品及び／又はこれらを多く含む食品を用いてもよい。   When used as a food composition, there are no particular limitations on other components, but included in the food composition, for example, food and drink include water, protein, carbohydrates, lipids, vitamins, minerals, Organic acids, organic bases, fruit juices, flavors and the like can be used as components. Examples of the protein include whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, α-casein, β-casein, κ-casein, β-lactoglobulin , Α-lactalbumin, lactoferrin, soy protein, chicken egg protein, meat protein and other animal and plant proteins, hydrolysates thereof; butter, whey minerals, cream, whey, non-protein nitrogen, sialic acid, phospholipid, lactose, etc. And various milk-derived components. Examples include sugars, modified starches (in addition to dextrin, soluble starches, British starches, oxidized starches, starch esters, starch ethers, etc.), dietary fibers, and the like. Examples of the lipid include animal oils such as lard, fish oil, etc., fractionated oils, hydrogenated oil, transesterified oil, etc .; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, Examples include vegetable oils such as hydrogenated oils and transesterified oils. Examples of vitamins include vitamin A, carotene, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline. Examples of minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, and selenium. Examples of the organic acid include malic acid, citric acid, lactic acid, and tartaric acid. These components can be used in combination of two or more, and synthetic products and / or foods containing a large amount thereof may be used.

以下、本発明の実施例を挙げて本発明についてさらに詳細に説明を行うが、本発明は、これらの具体的な実施例に限定されない。   EXAMPLES Hereinafter, although the Example of this invention is given and this invention is demonstrated further in detail, this invention is not limited to these specific Examples.

マウス（雄、８週齢、Ｃ５７ＢＬ／６Ｎ、飼育環境２３±３℃で明暗１２時間サイクル）を各群の体重が出来るだけ均一になるように割り付け、各群３〜４匹からなるサンプル群（実施例）とコントロール群（比較例）とに分けた。これらは絶食させずに、本発明の疲労防止剤又はコントロールとしての生理食塩水を強制経口投与した。投与後１時間後にトレッドミル試験（２５ｍ／ｍｉｎで６０分）による運動負荷を与えた。   Mice (male, 8 weeks old, C57BL / 6N, rearing environment 23 ± 3 ° C., 12 hours light / dark cycle) were allocated so that the weight of each group was as uniform as possible, and a sample group consisting of 3 to 4 animals in each group ( Example) and control group (comparative example). Without fasting, the anti-fatigue agent of the present invention or physiological saline as a control was orally administered by gavage. One hour after administration, exercise load was applied by a treadmill test (60 minutes at 25 m / min).

なお、投与量はアミノ酸換算で５００ｍｇ／ｋｇ体重（５％懸濁液を１０μＬ／ｇ体重にて投与）とした。ここで投与した本発明の疲労防止剤のアミノ酸組成を表１に示す（アミノ酸組成の数値は重量部にて示す）。   The dose was 500 mg / kg body weight in terms of amino acid (5% suspension was administered at 10 μL / g body weight). The amino acid composition of the anti-fatigue agent of the present invention administered here is shown in Table 1 (values of amino acid composition are shown in parts by weight).

［試験１］（疲労時の行動量測定）
トレッドミルによる運動負荷付与後に行動量測定を行った。なお行動量としては、赤色ランプ点灯下で３０分間に行動した道のりの合計を測定した。コントロール群（比較例１）を１００としたときのそれぞれの実施例における行動量を示した。すなわち、数値が大きいほど筋肉疲労が少ないものと考えられる。[Test 1] (Measurement of behavior during fatigue)
The amount of behavior was measured after the exercise load was applied by the treadmill. In addition, as the amount of action, the total of the distance which acted for 30 minutes under the red lamp lighting was measured. The amount of behavior in each example when the control group (Comparative Example 1) is 100 is shown. That is, the larger the value, the less muscle fatigue.

［試験２］（疲労時の血中バイオマーカー測定）
トレッドミル試験終了後一定時間経過後に採血し、血液中の免疫学的指標としてコルチゾール、インターフェロン−γ（ＩＦＮ−γ）、インターロイキン−１０（ＩＬ−１０）を測定した。コントロール群を１００としたときのそれぞれの実施例における濃度を示した。すなわち、数値が小さいほど疲労感が低く、精神的疲労が少ないものと考えられる。[Test 2] (Measurement of blood biomarkers during fatigue)
Blood was collected after a lapse of a certain time after completion of the treadmill test, and cortisol, interferon-γ (IFN-γ), and interleukin-10 (IL-10) were measured as immunological indicators in the blood. The concentration in each example when the control group was 100 was shown. That is, it is considered that the smaller the numerical value, the lower the feeling of fatigue and the less the mental fatigue.

なお、これらの評価方法は、大阪市立大学医学部生化学・分子病態学講座井上正康教授らが２００５年の日本生化学会で発表した方法（演題：運動疲労における免疫応答システムの性差解析、生化学、2005年、第77巻、p.1056）に基づいて行った。   In addition, these evaluation methods are the methods announced by Prof. Masayasu Inoue and others at Osaka City University School of Medicine, Biochemistry and Molecular Pathology (title: Gender difference analysis of immune response system in exercise fatigue, biochemistry, 2005, Vol. 77, p.1056).

Figure 0005775657
Figure 0005775657

本発明の実施例１〜６の疲労防止剤においては、比較例１と比べ、トレッドミルによる運動負荷を与えた後にもさらに行動することが出来るという筋肉疲労の防止効果が高いことが分かる。特に、実施例５及び６においては非常に高い運動後の行動量を示している。   In the anti-fatigue agents of Examples 1 to 6 of the present invention, it can be seen that, compared with Comparative Example 1, the effect of preventing muscular fatigue that can be further acted after applying an exercise load by a treadmill is high. In particular, Examples 5 and 6 show a very high amount of action after exercise.

また、血中バイオマーカー測定による結果では、本発明の実施例１〜６においては、コルチゾール、ＩＦＮ−γ、ＩＬ−１０の濃度上昇が著しく抑制されている。これら化合物は疲労感の上昇に比例して濃度が高くなるため、精神疲労の代替指標として評価することができる。即ち、本発明の実施例１〜６では精神疲労の防止効果においても高い効果を有することが分かる。さらに、この傾向は実施例５及び６においてより顕著に現れることが判る。   Moreover, according to the results of blood biomarker measurement, in Examples 1 to 6 of the present invention, increases in the concentrations of cortisol, IFN-γ, and IL-10 are remarkably suppressed. Since these compounds increase in concentration in proportion to the increase in fatigue, they can be evaluated as alternative indicators of mental fatigue. That is, it can be seen that Examples 1 to 6 of the present invention have a high effect in preventing mental fatigue. Further, it can be seen that this tendency appears more remarkably in Examples 5 and 6.

上記のように、本発明によるアミノ酸組成物を含んでなる疲労防止剤は、筋肉疲労と精神疲労との双方を同時に防止するという、高い疲労防止効果を提供することが出来る。また、従来のような運動能力などの向上を目的とするアミノ酸組成物と比較して、より少ない種類のアミノ酸種類からなる組成物であるため、調製に必要な原材料種が減り、工業的にも経済的にも優れた効果を奏する。したがって、産業上の利用価値は高いものである。   As described above, the anti-fatigue agent comprising the amino acid composition according to the present invention can provide a high anti-fatigue effect of simultaneously preventing both muscle fatigue and mental fatigue. In addition, since it is a composition consisting of fewer types of amino acids compared to conventional amino acid compositions aimed at improving athletic ability, the number of raw material species required for preparation is reduced, and industrially It has an excellent economic effect. Therefore, the industrial utility value is high.

Claims (10)

以下のアミノ酸からなる、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤用アミノ酸組成物。
プロリン ３０〜２００重量部；
グリシン ６０〜１４０重量部；
アラニン ２５〜２６０重量部；
リジン ４０〜１３０重量部；
トリプトファン ２０〜７５重量部；
ヒスチジン １５〜４０重量部。 An amino acid composition for anti-fatigue agents comprising the following amino acids, which simultaneously prevents both muscle fatigue and nerve fatigue .
Proline 30 to 200 parts by weight;
60-140 parts by weight of glycine;
25-260 parts by weight alanine;
40-130 parts by weight of lysine;
Tryptophan 20-75 parts by weight;
15-40 parts by weight of histidine. 以下のアミノ酸からなる、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤用アミノ酸組成物。
プロリン ３０〜２００重量部；
グリシン ６０〜１４０重量部；
アラニン ２５〜２６０重量部；
リジン ４０〜１３０重量部；
トリプトファン ２０〜７５重量部；
ヒスチジン １５〜４０重量部；
スレオニン ３５〜６５重量部；
チロシン １５〜６５重量部；
アルギニン ２５〜４５重量部。 An amino acid composition for anti-fatigue agents comprising the following amino acids, which simultaneously prevents both muscle fatigue and nerve fatigue .
Proline 30 to 200 parts by weight;
60-140 parts by weight of glycine;
25-260 parts by weight alanine;
40-130 parts by weight of lysine;
Tryptophan 20-75 parts by weight;
Histidine 15-40 parts by weight;
35-65 parts by weight of threonine;
Tyrosine 15-65 parts by weight;
Arginine 25-45 parts by weight. 以下のアミノ酸からなる、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤用アミノ酸組成物。
プロリン ３０〜２００重量部；
グリシン ６０〜１４０重量部；
アラニン ２５〜２６０重量部；
リジン ４０〜１３０重量部；
トリプトファン ２０〜７５重量部；
ヒスチジン １５〜４０重量部；
バリン ３０〜５５重量部；
ロイシン ３５〜６０重量部；
イソロイシン ２５〜４５重量部。 An amino acid composition for anti-fatigue agents comprising the following amino acids, which simultaneously prevents both muscle fatigue and nerve fatigue .
Proline 30 to 200 parts by weight;
60-140 parts by weight of glycine;
25-260 parts by weight alanine;
40-130 parts by weight of lysine;
Tryptophan 20-75 parts by weight;
Histidine 15-40 parts by weight;
30-55 parts by weight of valine;
35-60 parts by weight of leucine;
25 to 45 parts by weight of isoleucine. 以下のアミノ酸からなる、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤用アミノ酸組成物。
プロリン ３０〜２００重量部；
グリシン ６０〜１４０重量部；
アラニン ２５〜２６０重量部；
リジン ４０〜１３０重量部；
トリプトファン ２０〜７５重量部；
ヒスチジン １５〜４０重量部；
スレオニン ３５〜６５重量部；
チロシン １５〜６５重量部；
アルギニン ２５〜４５重量部；
バリン ３０〜５５重量部；
ロイシン ３５〜６０重量部；
イソロイシン ２５〜４５重量部。 An amino acid composition for anti-fatigue agents comprising the following amino acids, which simultaneously prevents both muscle fatigue and nerve fatigue .
Proline 30 to 200 parts by weight;
60-140 parts by weight of glycine;
25-260 parts by weight alanine;
40-130 parts by weight of lysine;
Tryptophan 20-75 parts by weight;
Histidine 15-40 parts by weight;
35-65 parts by weight of threonine;
Tyrosine 15-65 parts by weight;
Arginine 25-45 parts by weight;
30-55 parts by weight of valine;
35-60 parts by weight of leucine;
25 to 45 parts by weight of isoleucine. 請求項１〜４のいずれか一項に記載の疲労防止用アミノ酸組成物のみを有効成分として含む、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤。An anti-fatigue agent which simultaneously contains both muscle fatigue and nerve fatigue, comprising only the amino acid composition for fatigue prevention according to any one of claims 1 to 4 as an active ingredient. 以下のアミノ酸を混合する、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤用アミノ酸組成物の製造方法。The manufacturing method of the amino acid composition for anti-fatigue agents which mixes the following amino acids and prevents both muscle fatigue and nerve fatigue simultaneously.
プロリン ３０〜２００重量部；30-200 parts by weight of proline;
グリシン ６０〜１４０重量部；60-140 parts by weight of glycine;
アラニン ２５〜２６０重量部；25-260 parts by weight alanine;
リジン ４０〜１３０重量部；40-130 parts by weight of lysine;
トリプトファン ２０〜７５重量部；Tryptophan 20-75 parts by weight;
ヒスチジン １５〜４０重量部。15-40 parts by weight of histidine. 以下のアミノ酸を混合する、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤用アミノ酸組成物の製造方法。The manufacturing method of the amino acid composition for anti-fatigue agents which mixes the following amino acids and prevents both muscle fatigue and nerve fatigue simultaneously.
プロリン ３０〜２００重量部；30-200 parts by weight of proline;
グリシン ６０〜１４０重量部；60-140 parts by weight of glycine;
アラニン ２５〜２６０重量部；25-260 parts by weight alanine;
リジン ４０〜１３０重量部；40-130 parts by weight of lysine;
トリプトファン ２０〜７５重量部；Tryptophan 20-75 parts by weight;
ヒスチジン １５〜４０重量部；Histidine 15-40 parts by weight;
スレオニン ３５〜６５重量部；35-65 parts by weight of threonine;
チロシン １５〜６５重量部；Tyrosine 15-65 parts by weight;
アルギニン ２５〜４５重量部。Arginine 25-45 parts by weight. 以下のアミノ酸を混合する、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤用アミノ酸組成物の製造方法。The manufacturing method of the amino acid composition for anti-fatigue agents which mixes the following amino acids and prevents both muscle fatigue and nerve fatigue simultaneously.
プロリン ３０〜２００重量部；30-200 parts by weight of proline;
グリシン ６０〜１４０重量部；60-140 parts by weight of glycine;
アラニン ２５〜２６０重量部；25-260 parts by weight alanine;
リジン ４０〜１３０重量部；40-130 parts by weight of lysine;
トリプトファン ２０〜７５重量部；Tryptophan 20-75 parts by weight;
ヒスチジン １５〜４０重量部；Histidine 15-40 parts by weight;
バリン ３０〜５５重量部；30-55 parts by weight of valine;
ロイシン ３５〜６０重量部；35-60 parts by weight of leucine;
イソロイシン ２５〜４５重量部。25 to 45 parts by weight of isoleucine. 以下のアミノ酸を混合する、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤用アミノ酸組成物の製造方法。The manufacturing method of the amino acid composition for anti-fatigue agents which mixes the following amino acids and prevents both muscle fatigue and nerve fatigue simultaneously.
プロリン ３０〜２００重量部；30-200 parts by weight of proline;
グリシン ６０〜１４０重量部；60-140 parts by weight of glycine;
アラニン ２５〜２６０重量部；25-260 parts by weight alanine;
リジン ４０〜１３０重量部；40-130 parts by weight of lysine;
トリプトファン ２０〜７５重量部；Tryptophan 20-75 parts by weight;
ヒスチジン １５〜４０重量部；Histidine 15-40 parts by weight;
スレオニン ３５〜６５重量部；35-65 parts by weight of threonine;
チロシン １５〜６５重量部；Tyrosine 15-65 parts by weight;
アルギニン ２５〜４５重量部；Arginine 25-45 parts by weight;
バリン ３０〜５５重量部；30-55 parts by weight of valine;
ロイシン ３５〜６０重量部；35-60 parts by weight of leucine;
イソロイシン ２５〜４５重量部。25 to 45 parts by weight of isoleucine. 請求項１〜４のいずれか一項に記載の疲労防止用アミノ酸組成物のみを有効成分として混合する、筋肉疲労および神経疲労の双方を同時に防止する疲労防止剤の製造方法。The manufacturing method of the fatigue inhibitor which prevents both the muscle fatigue and nerve fatigue simultaneously which mixes only the amino acid composition for fatigue prevention as described in any one of Claims 1-4 as an active ingredient.
JP2008521230A 2006-06-13 2007-06-13 Anti-fatigue agent containing amino acid composition Active JP5775657B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2008521230A JP5775657B2 (en) 2006-06-13 2007-06-13 Anti-fatigue agent containing amino acid composition

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2006163683 2006-06-13
JP2006163683 2006-06-13
JP2008521230A JP5775657B2 (en) 2006-06-13 2007-06-13 Anti-fatigue agent containing amino acid composition
PCT/JP2007/061879 WO2007145239A1 (en) 2006-06-13 2007-06-13 Anti-fatigue agent containing amino acid composition

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2015008128A Division JP2015120715A (en) 2006-06-13 2015-01-19 Anti-fatigue agent containing amino acid composition

Publications (2)

Publication Number Publication Date
JPWO2007145239A1 JPWO2007145239A1 (en) 2009-11-05
JP5775657B2 true JP5775657B2 (en) 2015-09-09

Family

ID=38831753

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2008521230A Active JP5775657B2 (en) 2006-06-13 2007-06-13 Anti-fatigue agent containing amino acid composition
JP2015008128A Pending JP2015120715A (en) 2006-06-13 2015-01-19 Anti-fatigue agent containing amino acid composition

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2015008128A Pending JP2015120715A (en) 2006-06-13 2015-01-19 Anti-fatigue agent containing amino acid composition

Country Status (4)

Country Link
JP (2) JP5775657B2 (en)
KR (1) KR20090019813A (en)
CN (1) CN101454000A (en)
WO (1) WO2007145239A1 (en)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5775657B2 (en) * 2006-06-13 2015-09-09 株式会社明治 Anti-fatigue agent containing amino acid composition
CN101842094A (en) * 2007-10-31 2010-09-22 明治乳业株式会社 Anti-fatigue agent comprising amino acid composition
KR101325374B1 (en) 2008-02-19 2013-11-08 가부시키가이샤 오츠까 세이야꾸 고죠 Oral or enteral composition useful for recovery of physical functions
JPWO2010041647A1 (en) * 2008-10-06 2012-03-08 株式会社明治 Endurance improver, fatigue inhibitor, or fatigue recovery agent comprising an amino acid composition as an active ingredient
JP6154322B2 (en) * 2011-06-07 2017-06-28 味の素株式会社 Amino acid composition
JP2013060406A (en) * 2011-09-15 2013-04-04 Kyowa Hakko Bio Co Ltd Oral agent for brain fatigue improvement
CN104509919A (en) * 2013-09-30 2015-04-15 张自力 Functional nutrient beverage
JP6847578B2 (en) * 2013-10-09 2021-03-24 味の素株式会社 Foods containing histidine and their uses
JP6496599B2 (en) * 2014-06-13 2019-04-03 花王株式会社 Muscle protein synthesis signal activator
JP2016121194A (en) * 2016-04-05 2016-07-07 協和発酵バイオ株式会社 Oral agent for cerebral fatigue improvement
AU2016407955B2 (en) * 2016-05-26 2019-09-05 Profeat Biotechnology Co., Ltd. Method for reducing lactic acid
US10682325B2 (en) * 2017-08-14 2020-06-16 Axcella Health Inc. Compositions and methods for the treatment of liver diseases and disorders associated with one or both of hyperammonemia or muscle wasting
JP7275499B2 (en) 2018-08-27 2023-05-18 味の素株式会社 Composition for improving brain function
KR102235563B1 (en) 2020-08-26 2021-04-02 (주)이삼오구 Composition for fatigue recovery and sexual function improvement containing high content of arginine
JP7414676B2 (en) * 2020-09-14 2024-01-16 株式会社東芝 Load estimating device, method and program
JP7462127B1 (en) 2023-08-16 2024-04-05 株式会社Healthy Body Muscle Hypertrophy Composition

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5026721A (en) * 1989-06-05 1991-06-25 Dudrick Stanley J Amino acid nutritional supplement and regimen for enhancing physical performance through sound nutrition
JPH06336432A (en) * 1993-05-28 1994-12-06 Rikagaku Kenkyusho Adrenaline and noradrenaline secretion promoting composition
JP2518692B2 (en) * 1989-06-14 1996-07-24 理化学研究所 Muscle maintenance agent, nutrient tonic, infusion agent, nutritional supplement, fatigue recovery agent and lactic acid production regulator
JPH09249556A (en) * 1996-01-09 1997-09-22 Rikagaku Kenkyusho Amino acid composition
WO2004028528A1 (en) * 2002-09-30 2004-04-08 Riken Amino acid compositions for improving central functions
JP2004352696A (en) * 2003-05-30 2004-12-16 Institute Of Physical & Chemical Research Amino acids composition and fluid replacement

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0725838A (en) * 1993-05-13 1995-01-27 Yotsuba Yuka Kk Orally administering agent for preventing or recovering fatigue
JP3617102B2 (en) * 1995-01-27 2005-02-02 味の素株式会社 Amino acid nutritional composition with an early recovery effect on human muscle fatigue
JP4280310B2 (en) * 1995-08-10 2009-06-17 佐々木化学工業株式会社 Amino acid composition
JP2000009717A (en) * 1998-02-27 2000-01-14 Taisho Pharmaceut Co Ltd Evaluation method for nourishment and robustness effect
JP2001226272A (en) * 2000-02-18 2001-08-21 Zeria Pharmaceut Co Ltd Liquid medium for oral administration formulated with citric acid and royal jelly
JP3838038B2 (en) * 2001-02-05 2006-10-25 株式会社豊田中央研究所 Psychosomatic state evaluation method, evaluation method of sensibility quality of goods or environment, measurement kit for evaluation and quality display method of goods or environment
JP2003207495A (en) * 2002-01-10 2003-07-25 Toyota Central Res & Dev Lab Inc Device for judging psychological state
US20060093649A1 (en) * 2002-10-11 2006-05-04 Ajinomoto Co., Inc. Food composition for recovery from fatigue
GB0400031D0 (en) * 2004-01-03 2004-02-04 Univ Sheffield Depression treatment
US20070134156A1 (en) * 2004-02-17 2007-06-14 Soiken Inc. Fatigue evaluation apparatus, fatigue evaluation method, and application thereof
JP2005239579A (en) * 2004-02-24 2005-09-08 Ajinomoto Co Inc Fatigue-recovering agent and fatigue-recovering food
JP5775657B2 (en) * 2006-06-13 2015-09-09 株式会社明治 Anti-fatigue agent containing amino acid composition

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5026721A (en) * 1989-06-05 1991-06-25 Dudrick Stanley J Amino acid nutritional supplement and regimen for enhancing physical performance through sound nutrition
JP2518692B2 (en) * 1989-06-14 1996-07-24 理化学研究所 Muscle maintenance agent, nutrient tonic, infusion agent, nutritional supplement, fatigue recovery agent and lactic acid production regulator
JPH06336432A (en) * 1993-05-28 1994-12-06 Rikagaku Kenkyusho Adrenaline and noradrenaline secretion promoting composition
JPH09249556A (en) * 1996-01-09 1997-09-22 Rikagaku Kenkyusho Amino acid composition
WO2004028528A1 (en) * 2002-09-30 2004-04-08 Riken Amino acid compositions for improving central functions
JP2004352696A (en) * 2003-05-30 2004-12-16 Institute Of Physical & Chemical Research Amino acids composition and fluid replacement

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JPN7012003890; 小林寛道: 'スポーツとアミノ酸サプリメント' 食の科学 第２５５号, 1999, ｐ．９３-８８ *

Also Published As

Publication number Publication date
KR20090019813A (en) 2009-02-25
CN101454000A (en) 2009-06-10
JPWO2007145239A1 (en) 2009-11-05
JP2015120715A (en) 2015-07-02
WO2007145239A1 (en) 2007-12-21

Similar Documents

Publication Publication Date Title
JP5775657B2 (en) Anti-fatigue agent containing amino acid composition
JP5798648B2 (en) Anti-fatigue agent containing amino acid composition
JP5574561B2 (en) Total enteral nutrition composition
US20160058819A1 (en) Compositions of nutrition supplementation for nutritional deficiencies and method of use therefore
CA2914811C (en) Muscle preservation in overweight or obese adult during weight loss program
KR20180029963A (en) Amino acid supplement
JP5173230B2 (en) Amino acid composition and food and drink
JP2013100275A (en) Agent for increasing amount of muscle
JP6158565B2 (en) Muscle protein synthesis signal enhancer
JP2019099498A (en) Composition for promoting lipid metabolism
JP2016102064A (en) Lipid metabolism accelerating agent
JP2019099495A (en) Composition for promoting blood pressure fall
Komorowski et al. Inositol-Stabilized Arginine Silicate: A Novel Nitric Oxide-Boosting Ingredient for Sports Nutrition and Improved Cognition
JP2019099497A (en) Composition for improving liver function
CA3216989A1 (en) Nutritional compositions for preserving muscle mass
CN112135531A (en) Insulin control in overweight or obese adults during lifetime intervention
JP2019034894A (en) Composition for promoting lipid metabolism
JP2019030269A (en) Engineering method of protein composition with reduced protein metabolism requirement, and manufacturing method of protein-containing food and drink composition based on the engineering method
JP2001231496A (en) Nutritive composition

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20100531

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20121002

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20121130

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20130226

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20130527

A911 Transfer to examiner for re-examination before appeal (zenchi)

Free format text: JAPANESE INTERMEDIATE CODE: A911

Effective date: 20130717

A912 Re-examination (zenchi) completed and case transferred to appeal board

Free format text: JAPANESE INTERMEDIATE CODE: A912

Effective date: 20130809

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150119

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150518

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20150706

R150 Certificate of patent or registration of utility model

Ref document number: 5775657

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

S531 Written request for registration of change of domicile

Free format text: JAPANESE INTERMEDIATE CODE: R313531

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350