JP2006096745A - Health function-improving agent - Google Patents

Health function-improving agent Download PDF

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JP2006096745A
JP2006096745A JP2005218435A JP2005218435A JP2006096745A JP 2006096745 A JP2006096745 A JP 2006096745A JP 2005218435 A JP2005218435 A JP 2005218435A JP 2005218435 A JP2005218435 A JP 2005218435A JP 2006096745 A JP2006096745 A JP 2006096745A
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health function
improving agent
health
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JP4814567B2 (en
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Masao Kondo
雅雄 近藤
Naomi Aeba
直美 饗場
Setsuko Miyanari
節子 宮成
Toru Tanaka
徹 田中
Masahiro Ishizuka
昌宏 石塚
Takaya Suzuki
貴也 鈴木
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Cosmo Oil Co Ltd
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Cosmo Oil Co Ltd
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Priority to EP14153023.8A priority patent/EP2727589B1/en
Priority to CN2005800295100A priority patent/CN101010076B/en
Priority to US11/661,688 priority patent/US8790712B2/en
Priority to KR1020077007605A priority patent/KR100966318B1/en
Priority to CA2752569A priority patent/CA2752569C/en
Priority to PCT/JP2005/015560 priority patent/WO2006025286A1/en
Priority to CA2579032A priority patent/CA2579032C/en
Priority to ES05774552.3T priority patent/ES2459366T3/en
Priority to CN201010150020A priority patent/CN101822661A/en
Priority to EP05774552.3A priority patent/EP1785132B1/en
Priority to AU2005278649A priority patent/AU2005278649B8/en
Priority to KR1020097023324A priority patent/KR20100016341A/en
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a health function-improving agent which can be taken for long periods. <P>SOLUTION: This health function-improving agent contains a δ-amino acid, its derivative or its salt as an active ingredient. Preferably, the health function-improving agent is characterized by improving motor functions to improve the health functions. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は、健康機能向上剤に関する。   The present invention relates to a health function improving agent.

人や動物の健康機能は、疲労、病気、妊娠、加齢、栄養障害、栄養欠乏により低下する。この疲労には肉体疲労と精神疲労があり、現代人の疲労は肉体疲労だけでなく精神疲労が大きく関与している。   Human and animal health functions are reduced by fatigue, illness, pregnancy, aging, malnutrition, and nutritional deficiencies. This fatigue includes physical fatigue and mental fatigue, and not only physical fatigue but also mental fatigue is greatly involved in modern human fatigue.

このうち、肉体疲労に有効な栄養としては、糖分、でんぷんからなる複合炭水化物等が用いられている。また薬物としては、ビタミンB1、ビタミンB2、ニコチン酸等のビタミンB群、メラトニン、ビタミンC、ビタミンE、マグネシウムなどが用いられている。 Among these, as a nutrient effective for physical fatigue, complex carbohydrates such as sugar and starch are used. Further, vitamin B 1 , vitamin B 2 , vitamin B group such as nicotinic acid, melatonin, vitamin C, vitamin E, magnesium and the like are used as drugs.

また、最近、必須アミノ酸や非必須アミノ酸を含む特定の組成のアミノ酸類に疲労時の運動機能を向上させる効果があることが報告されている(特許文献1)。必須アミノ酸は、バリン、ロイシン、イソロイシン、リジン、スレオニン、メチオニンなど、また非必須アミノ酸としては、アルギニン、グルタミン、プロリンなどがある。
特開平9−249556号公報
Recently, it has been reported that amino acids having a specific composition including essential amino acids and non-essential amino acids have an effect of improving motor function during fatigue (Patent Document 1). Essential amino acids include valine, leucine, isoleucine, lysine, threonine, and methionine. Non-essential amino acids include arginine, glutamine, and proline.
Japanese Patent Laid-Open No. 9-249556

しかしながら、アミノ酸のうち、グルタミンは溶解度が低く不安定で、体内でグルタミン酸とアンモニアに分解するという問題があり、またアルギニンは、肌荒れ、皮膚が厚くなる、関節の肥大、骨の奇形という副作用があることが知られており、その摂取については大変な注意が必要である。
従って、本発明の目的は、長期間摂取できる健康機能向上剤を提供することにある。
However, among the amino acids, glutamine has low solubility and is unstable and has the problem of breaking down into glutamate and ammonia in the body, and arginine has side effects such as rough skin, thick skin, joint enlargement, and bone malformation. It is known that there is a great deal of caution regarding its consumption.
Accordingly, an object of the present invention is to provide a health function improving agent that can be taken for a long time.

そこで本発明者は、種々のアミノ酸の薬理作用を検討してきたところ、5−アミノレブリン酸に代表されるδ−アミノ酸類が、特に老齢化した動物の健康機能を有意に増加させる作用を有することを見出し、本発明を完成するに至った。
すなわち、本発明は、δ−アミノ酸、その誘導体又はその塩を有効成分とする健康機能向上剤を提供するものである。
Therefore, the present inventor has examined the pharmacological action of various amino acids, and found that δ-amino acids represented by 5-aminolevulinic acid have an action of significantly increasing the health function of an aged animal in particular. The headline and the present invention were completed.
That is, this invention provides the health function improving agent which uses (delta) -amino acid, its derivative (s), or its salt as an active ingredient.

本発明によれば、健康機能が低下した動物、例えば高齢化に伴ない、健康機能が低下した人を含む動物の健康機能を向上させることができる。   ADVANTAGE OF THE INVENTION According to this invention, the health function of the animal which the health function fell, for example, the animal containing the person whose health function fell with aging can be improved.

本発明の健康機能向上剤の有効成分は、δ−アミノ酸、その誘導体又はその塩である。当該δ−アミノ酸類としては、次式(1)   The active ingredient of the health function improving agent of the present invention is a δ-amino acid, a derivative thereof or a salt thereof. The δ-amino acids include the following formula (1)

Figure 2006096745
Figure 2006096745

(式中、R1は水素原子又はアシル基を示し、R2は水素原子又は置換基を有していてもよい炭化水素基を示す)
で表される5−アミノレブリン酸、その誘導体類又はその塩(以下、「5−アミノレブリン酸類」と称する)が挙げられる。
(Wherein R 1 represents a hydrogen atom or an acyl group, and R 2 represents a hydrogen atom or a hydrocarbon group which may have a substituent)
And a derivative thereof or a salt thereof (hereinafter referred to as “5-aminolevulinic acid”).

当該5−アミノレブリン酸類は、光動力学的治療における光増感剤(特表2004−505105号)、植物成長調節剤(特開平07−53487号)、除草剤(特開平05−117110号)、魚類病原性微生物、寄生虫の感染治療(特開2001−316255号)、豚成育促進剤(特開2003−40770号)等として有用であることは知られている。   The 5-aminolevulinic acids are photosensitizers in photodynamic therapy (Japanese Patent Publication No. 2004-505105), plant growth regulators (JP 07-53487 A), herbicides (JP 05-117110 A), It is known to be useful as fish pathogenic microorganisms, parasitic infection treatment (Japanese Patent Laid-Open No. 2001-316255), pig growth promoter (Japanese Patent Laid-Open No. 2003-40770) and the like.

式(1)中、R1で示されるアシル基としては、例えば炭素数1〜24のアルカノイル基、芳香族アシル基、ベンジルオキシカルボニル基等が挙げられる。好ましいアシル基の具体例としては、例えばアセチル基、n−プロパノイル基、n−ブタノイル基、n−ペンタノイル基、n−ヘキサノイル基、n−ノナノイル基、ベンジルオキシカルボニル基等が挙げられる。このうち、炭素数1〜6のアルカノイル基がより好ましい。 In formula (1), examples of the acyl group represented by R 1 include an alkanoyl group having 1 to 24 carbon atoms, an aromatic acyl group, and a benzyloxycarbonyl group. Specific examples of preferable acyl groups include acetyl group, n-propanoyl group, n-butanoyl group, n-pentanoyl group, n-hexanoyl group, n-nonanoyl group, benzyloxycarbonyl group and the like. Among these, a C1-C6 alkanoyl group is more preferable.

また、R2で示される置換基を有していてもよい炭化水素基としては、例えば、ヒドロキシ、アルコキシ、アシルオキシ、アルコキシカルボニルオキシ、アミノ、アリール、オキソ、フロロ、クロロ及びニトロから選ばれる基が置換していてもよい炭化水素基を示す。ここで、炭化水素基としては、アルキル基、アルケニル基、アラルキル基又はアリール基が好ましい。ここで、アルキル基としては、直鎖、分岐鎖又は環状のアルキル基が挙げられ、炭素数1〜40、更に1〜18、特に1〜7のアルキル基が好ましい。アルケニル基としては、直鎖、分岐鎖又は環状のアルケニル基が挙げられ、炭素数2〜40、更に2〜18のアルケニル基が好ましい。アラルキル基としては炭素数6〜20のアリール基と炭素数1〜6のアルキル基から構成されるものが挙げられる。また、アリール基としては炭素数6〜20のアリール基が挙げられる。
アルコキシ基としては炭素数1〜18のアルコキシ基、特に炭素数1〜7のアルコキシ基が好ましい。アシルオキシ基としては、炭素数1〜18のアルカノイルオキシ基、特に炭素数2〜8のアルカノイルオキシ基が好ましい。アルコキシカルボニルオキシ基としては、C1-18アルコキシ−カルボニルオキシ基、特にC1-7アルコキシ−カルボニルオキシ基が好ましい。
炭素数1〜18の好ましいアルキル基としては例えば、メチル基、エチル基、n−プロピル基、イソプロピル基、n−ブチル基、イソブチル基、tert−ブチル基、n−ペンチル基、イソペンチル基、ネオペンチル基、tert−ペンチル基、2−メチルブチル基、n−ヘキシル基、イソヘキシル基、3−メチルペンチル基、エチルブチル基、n−ヘプチル基、2−メチルヘキシル基、n−オクチル基、イソオクチル基、tert−オクチル基、2−エチルヘキシル基、3−メチルヘプチル基、n−ノニル基、イソノニル基、1−メチルオクチル基、エチルヘプチル基、n−デシル基、1−メチルノニル基、n−ウンデシル基、1,1−ジメチルノニル基、n−ドデシル基、n−トリデシル基、n−テトラデシル基、n−ペンタデシル基、n−ヘキサデシル基、n−ヘプタデシル基、n−オクタデシル基等が挙げられる。
炭素数1〜7のより好ましいアルキル基としては例えば、メチル基、エチル基、n−プロピル基、イソプロピル基、n−ブチル基、イソブチル基、tert−ブチル基、n−ペンチル基、イソペンチル基、ネオペンチル基、tert−ペンチル基、2−メチルブチル基、n−ヘキシル基、イソヘキシル基、3−メチルペンチル基、エチルブチル基、n−ヘプチル基、2−メチルヘキシル基が挙げられる。
ヒドロキシが置換した炭素数1〜18のアルキル基としては、2−ヒドロキシエチル、3−ヒドロキシプロピル、4−ヒドロキシブチル、5−ヒドロキシペンチル、6−ヒドロキシヘキシル等が挙げられる。
アルコキシが置換した炭素数1〜18のアルキル基としては、C1-7アルコキシ−C1-18アルキル基、例えば2−メトキシエチル、2−エトキシエチル、3−メトキシプロピル、3−エトキシプロピル、4−メトキシブチル、4−エトキシブチル、2−(2−メトキシエチル)エチル等が挙げられる。
アシルオキシ基が置換したアルキル基としては、C2-7アルカノイルオキシ−C1-18アルキル基が挙げられる。アルコキシカルボニルオキシ基が置換したアルキル基としては、C1-18アルコキシ−カルボニルオキシ−C1-18アルキル基が挙げられる。アミノ基が置換したアルキル基としては、アミノ−C1-18アルキル基が挙げられる。
炭素数2〜18のアルケニル基としては、ビニル基、アリル基、イソプロペニル基、2−ブテニル基、2−メチルアリル基、1,1−ジメチルアリル基、3−メチル−2−ブテニル基、3−メチル−3−ブテニル基、4−ペンテニル基、ヘキセニル基、オクテニル基、ノネニル基、デセニル基、シクロプロペニル基、シクロブテニル基、シクロペンテニル基、シクロヘキセニル基、シクロヘプテニル基、シクロオクテニル基、4−メチルシクロヘキセニル基、4−エチルシクロヘキセニル基、2−シクロペンテニルエチル基、シクロヘキセニルメチル基、シクロヘプテニルメチル基、2−シクロブテニルエチル基、2−シクロオクテニルエチル基、3−(4−メチルシクロヘキセニル)プロピル基、4−シクロプロペニルブチル基、5−(4−エチルシクロヘキセニル)ペンチル基、オレイル基、バクセニル基、リノレイル基、リノレニル基、trans−9−オクタデセニル基、9E,12E−オクタデカジエニル基、9E,12E,15E−オクタデカトリエニル基等が挙げられる。
炭素数7〜26のアラルキル基としては、炭素数1〜6のアルキル基と炭素数6〜20のアリール基とから構成されるものが好ましい。炭素数1〜6のアルキル基としては、例えば、メチル基、エチル基、n−プロピル基、イソプロピル基、n−ブチル基、イソブチル基、tert−ブチル基、n−ペンチル基、n−ヘキシル基、シクロプロピル基、シクロブチル基、シクロヘキシル基等が挙げられ、炭素数6〜20のアリール基としては、フェニル基、ナフチル基等が挙げられる。炭素数7〜26のアラルキル基のうち、ベンジル基、フェネチル基、9−フルオレニルメチル基が好ましく、ベンジル基、フルオレニルメチル基が特に好ましい。当該アラルキル基のアリール基は、上記記載の炭素数1〜6のアルキル基、メトキシ基、エトキシ基、n−プロポキシ基、n−ブトキシ基、イソブトキシ基、tert−ブトキシ基等の炭素数1〜6のアルコキシ基、水酸基、アミノ基、ニトロ基、シアノ基、フッ素、塩素、臭素、ヨウ素等のハロゲン原子、カルボキシ基等の置換基1〜3個によって置換されていてもよい。
炭素数6〜20のアリール基としては、フェニル基、ナフチル基等が挙げられ、例えば、メチル基、エチル基、n−プロピル基、イソプロピル基、n−ブチル基、イソブチル基、tert−ブチル基、n−ペンチル基、n−ヘキシル基、シクロプロピル基、シクロブチル基、シクロヘキシル基等の炭素数1〜6のアルキル基、メトキシ基、エトキシ基、n−プロポキシ基、n−ブトキシ基、イソブトキシ基、tert−ブトキシ基等の炭素数1〜6のアルコキシ基、水酸基、アミノ基、ニトロ基、シアノ基、フッ素、塩素、臭素、ヨウ素等のハロゲン原子、カルボキシ基等の置換基1〜3個によって置換されていてもよい。尚、上記R1は、アミノ基の置換基、R2はカルボン酸基の置換基を示しているが、例示したこれらの置換基は5−アミノレブリン酸類のみならず、δ−アミノ酸類の置換基でもある。
Examples of the hydrocarbon group optionally having a substituent represented by R 2 include a group selected from hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, amino, aryl, oxo, fluoro, chloro and nitro. The hydrocarbon group which may be substituted is shown. Here, the hydrocarbon group is preferably an alkyl group, an alkenyl group, an aralkyl group or an aryl group. Here, as an alkyl group, a linear, branched or cyclic alkyl group is mentioned, A C1-C40, Furthermore, a 1-18, especially 1-7 alkyl group is preferable. Examples of the alkenyl group include linear, branched or cyclic alkenyl groups, and alkenyl groups having 2 to 40 carbon atoms and more preferably 2 to 18 carbon atoms are preferable. Examples of the aralkyl group include those composed of an aryl group having 6 to 20 carbon atoms and an alkyl group having 1 to 6 carbon atoms. Moreover, as an aryl group, a C6-C20 aryl group is mentioned.
As an alkoxy group, a C1-C18 alkoxy group, especially a C1-C7 alkoxy group are preferable. The acyloxy group is preferably an alkanoyloxy group having 1 to 18 carbon atoms, particularly an alkanoyloxy group having 2 to 8 carbon atoms. As the alkoxycarbonyloxy group, a C 1-18 alkoxy-carbonyloxy group, particularly a C 1-7 alkoxy-carbonyloxy group is preferable.
Preferred examples of the alkyl group having 1 to 18 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, and neopentyl group. Tert-pentyl group, 2-methylbutyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, ethylbutyl group, n-heptyl group, 2-methylhexyl group, n-octyl group, isooctyl group, tert-octyl group Group, 2-ethylhexyl group, 3-methylheptyl group, n-nonyl group, isononyl group, 1-methyloctyl group, ethylheptyl group, n-decyl group, 1-methylnonyl group, n-undecyl group, 1,1- Dimethylnonyl group, n-dodecyl group, n-tridecyl group, n-tetradecyl group, n-pentadecyl group, - hexadecyl group, n- heptadecyl group, n- octadecyl group.
More preferable examples of the alkyl group having 1 to 7 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, and neopentyl. Group, tert-pentyl group, 2-methylbutyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, ethylbutyl group, n-heptyl group and 2-methylhexyl group.
Examples of the alkyl group having 1 to 18 carbon atoms substituted by hydroxy include 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 5-hydroxypentyl, 6-hydroxyhexyl and the like.
Examples of the C1- C18 alkyl group substituted by alkoxy include C 1-7 alkoxy-C 1-18 alkyl groups such as 2-methoxyethyl, 2-ethoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 4 -Methoxybutyl, 4-ethoxybutyl, 2- (2-methoxyethyl) ethyl and the like.
Examples of the alkyl group substituted with an acyloxy group include a C 2-7 alkanoyloxy-C 1-18 alkyl group. Examples of the alkyl group substituted by an alkoxycarbonyloxy group include a C 1-18 alkoxy-carbonyloxy-C 1-18 alkyl group. Examples of the alkyl group substituted with an amino group include an amino-C 1-18 alkyl group.
Examples of the alkenyl group having 2 to 18 carbon atoms include vinyl group, allyl group, isopropenyl group, 2-butenyl group, 2-methylallyl group, 1,1-dimethylallyl group, 3-methyl-2-butenyl group, 3- Methyl-3-butenyl group, 4-pentenyl group, hexenyl group, octenyl group, nonenyl group, decenyl group, cyclopropenyl group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group, cyclooctenyl group, 4-methylcyclohexenyl Group, 4-ethylcyclohexenyl group, 2-cyclopentenylethyl group, cyclohexenylmethyl group, cycloheptenylmethyl group, 2-cyclobutenylethyl group, 2-cyclooctenylethyl group, 3- (4-methylcyclo Hexenyl) propyl group, 4-cyclopropenylbutyl group, 5- (4 Ethylcyclohexenyl) pentyl group, oleyl group, bacenyl group, linoleyl group, linolenyl group, trans-9-octadecenyl group, 9E, 12E-octadecadienyl group, 9E, 12E, 15E-octadecatrienyl group, etc. It is done.
The aralkyl group having 7 to 26 carbon atoms is preferably one composed of an alkyl group having 1 to 6 carbon atoms and an aryl group having 6 to 20 carbon atoms. Examples of the alkyl group having 1 to 6 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group, n-hexyl group, A cyclopropyl group, a cyclobutyl group, a cyclohexyl group, etc. are mentioned, As a C6-C20 aryl group, a phenyl group, a naphthyl group, etc. are mentioned. Of the aralkyl groups having 7 to 26 carbon atoms, a benzyl group, a phenethyl group, and a 9-fluorenylmethyl group are preferable, and a benzyl group and a fluorenylmethyl group are particularly preferable. The aryl group of the aralkyl group has 1 to 6 carbon atoms such as the above-described alkyl group having 1 to 6 carbon atoms, methoxy group, ethoxy group, n-propoxy group, n-butoxy group, isobutoxy group, tert-butoxy group and the like. May be substituted by 1 to 3 substituents such as a carboxy group or a halogen atom such as an alkoxy group, a hydroxyl group, an amino group, a nitro group, a cyano group, fluorine, chlorine, bromine or iodine.
Examples of the aryl group having 6 to 20 carbon atoms include a phenyl group and a naphthyl group. For example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, C1-C6 alkyl group such as n-pentyl group, n-hexyl group, cyclopropyl group, cyclobutyl group, cyclohexyl group, methoxy group, ethoxy group, n-propoxy group, n-butoxy group, isobutoxy group, tert -Substituted by 1 to 3 substituents such as a C1-C6 alkoxy group such as a butoxy group, a hydroxyl group, an amino group, a nitro group, a cyano group, a halogen atom such as fluorine, chlorine, bromine or iodine, or a carboxy group It may be. R 1 represents an amino group substituent, and R 2 represents a carboxylic acid group substituent. These exemplified substituents are not only 5-aminolevulinic acids but also δ-amino acid substituents. But there is.

δ−アミノ酸又はその誘導体の塩としては、例えば塩酸塩、臭化水素酸塩、ヨウ化水素酸塩、リン酸塩、メチルリン酸塩、エチルリン酸塩、亜リン酸塩、次亜リン酸塩、硝酸塩、硫酸塩、酢酸塩、プロピオン酸塩、トルエンスルホン酸塩、コハク酸塩、シュウ酸塩、乳酸塩、酒石酸塩、グリコール酸塩、メタンスルホン酸塩、酪酸塩、吉草酸塩、クエン酸塩、フマル酸塩、マレイン酸塩、リンゴ酸塩等の酸付加塩、及びナトリウム塩、カリウム塩、カルシウム塩等の金属塩、アンモニウム塩、アルキルアンモニウム塩等が挙げられる。なお、これらの塩は使用時において水溶液又は粉体として用いられる。   Examples of the salt of δ-amino acid or a derivative thereof include hydrochloride, hydrobromide, hydroiodide, phosphate, methyl phosphate, ethyl phosphate, phosphite, hypophosphite, Nitrate, sulfate, acetate, propionate, toluenesulfonate, succinate, oxalate, lactate, tartrate, glycolate, methanesulfonate, butyrate, valerate, citrate And acid addition salts such as fumarate, maleate and malate, and metal salts such as sodium salt, potassium salt and calcium salt, ammonium salt and alkylammonium salt. These salts are used as an aqueous solution or powder at the time of use.

以上のδ−アミノ酸、その誘導体又はそれらの塩は、水和物又は溶媒和物を形成していてもよく、またいずれかを単独で又は2種以上を適宜組み合わせて用いることができる。   The above δ-amino acids, derivatives thereof or salts thereof may form hydrates or solvates, and any of them may be used alone or in combination of two or more.

δ−アミノ酸、その誘導体又はそれらの塩(以下、「δ−アミノ酸類」と称する。)は、化学合成、微生物による生産、酵素による生産のいずれの方法によっても製造することができる。また前記δ−アミノ酸類のうち、5−アミノレブリン酸類は、特開昭48−92328号公報、特開昭62−111954号公報、特開平2−76841号公報、特開平6−172281号公報、特開平7−188133号公報、特開平11−42083号公報等に記載の方法に準じて製造することができる。上記のようにして製造されたδ−アミノ酸類、それらの精製前の化学反応溶液や発酵液は、有害な物質を含まない限り、分離精製することなくそのまま用いることができる。
また市販品なども使用することができる。
δ-amino acids, derivatives thereof or salts thereof (hereinafter referred to as “δ-amino acids”) can be produced by any method of chemical synthesis, production by microorganisms, and production by enzymes. Among the δ-amino acids, 5-aminolevulinic acids are disclosed in JP-A-48-92328, JP-A-62-11954, JP-A-2-76841, JP-A-6-172281, It can be produced according to the methods described in Kaihei 7-188133, JP-A-11-42083, and the like. The δ-amino acids produced as described above, the chemical reaction solution and the fermentation solution before purification thereof can be used as they are without separation and purification as long as they do not contain harmful substances.
Moreover, a commercial item etc. can also be used.

上記δ−アミノ酸類は、後記実施例に示すように、特に老齢化して健康機能が低下したマウスの自然運動量を増加させ、又体重増加を促進させ、低下した健康機能、狭義には、運動機能を向上させる作用をする。又、δ−アミノ酸類は、肝機能向上剤であり、後記実施例で示すように、マウスに経口投与することで、マウスのγ−GTP値を減少させる作用をする。従って、上記δ−アミノ酸類は人を含む動物の健康機能向上剤として有用であり、特に加齢により健康機能が低下した人を含む動物の健康機能向上剤として有用である。   The δ-amino acids, as shown in the examples below, increase the amount of natural exercise in mice that have deteriorated in health function due to aging, and promote weight gain. It works to improve. In addition, δ-amino acids are liver function improvers and, as shown in Examples below, are administered orally to mice and act to reduce the γ-GTP value of mice. Therefore, the above-mentioned δ-amino acids are useful as an agent for improving the health function of animals including humans, and are particularly useful as an agent for improving the health function of animals including humans whose health functions have deteriorated due to aging.

また、本発明の健康機能向上剤は、ミネラルを含有させるか、同時に摂取することにより、さらにその効果を向上させることができる。ミネラルとしては、鉄、亜鉛、銅、リン、カルシウム、マグネシウム、カリウム、セレン、クロム、マンガン、ヨウ素、ホウ素、ケイ素、バナジウム、モリブデン、コバルトなどが挙げられるが、特に好ましくは鉄、マグネシウム、マンガンである。これらのミネラル分は単独で、又は二種以上を組み合わせて用いることができる。ミネラルの化学的性状としては生物に害を与えるものでなければどんなものを用いてもよい。   Moreover, the health-function improving agent of this invention can improve the effect further by containing a mineral or ingesting simultaneously. Examples of minerals include iron, zinc, copper, phosphorus, calcium, magnesium, potassium, selenium, chromium, manganese, iodine, boron, silicon, vanadium, molybdenum, cobalt, etc., particularly preferably iron, magnesium, manganese. is there. These mineral components can be used alone or in combination of two or more. Any chemical properties of minerals may be used as long as they do not harm the organism.

本発明の健康機能向上剤には、必要に応じて栄養剤等を加えることができる。栄養剤としては、例えば、必須アミノ酸類、非必須アミノ酸類、ビタミン類、タウリン、コエンザイムQ10、αリポ酸などの体内因子、ハーブ類、プロテイン、種々の酵素、ポリフェノール類などの抗酸化剤などが挙げられる。   A nutritional agent etc. can be added to the health function improving agent of this invention as needed. Examples of nutrients include essential amino acids, non-essential amino acids, vitamins, taurine, coenzyme Q10, alpha lipoic acid and other body factors, herbs, proteins, various enzymes, antioxidants such as polyphenols, and the like. Can be mentioned.

本発明の健康機能向上剤は、δ−アミノ酸類の粉末、δ−アミノ酸類を水に溶かした水溶液、上記方法で製造したδ−アミノ酸類を含む発酵液を、賦形剤等の担体に吸着させて使用することもできる。担体の種類としては、一般的なものでよく、結晶性セルロース、ゼラチン、でんぷん、デキストリン、油かす、パン酵母、ビール酵母、酒酵母、ワイン酵母、脱脂粉乳、乳糖、動物性及び植物性油脂、無水リン酸カルシウム、炭酸カルシウム、ステアリン酸マグネシウム、ケイ酸アルミン酸マグネシウム、メタケイ酸アルミン酸マグネシウムなどが挙げられる。   The health function improver of the present invention adsorbs a powder of δ-amino acids, an aqueous solution in which δ-amino acids are dissolved in water, and a fermentation broth containing δ-amino acids produced by the above method to a carrier such as an excipient. It can also be used. As a kind of carrier, it may be a general one, crystalline cellulose, gelatin, starch, dextrin, oil cake, baker's yeast, brewer's yeast, liquor yeast, wine yeast, skim milk powder, lactose, animal and vegetable oils and fats, Anhydrous calcium phosphate, calcium carbonate, magnesium stearate, magnesium aluminate silicate, magnesium metasilicate aluminate and the like can be mentioned.

本発明の健康機能向上剤の剤型としては、注射剤、錠剤、カプセル剤、細粒剤、シロップ剤、坐薬等が挙げられる。これらは溶剤、分散媒、増量剤、賦形剤等を適宜用い、常法に従って製造することができる。また、食品の形態として摂取してもよい。   Examples of the dosage form of the health function improving agent of the present invention include injections, tablets, capsules, fine granules, syrups, suppositories and the like. These can be produced according to a conventional method using a solvent, a dispersion medium, an extender, an excipient and the like as appropriate. Moreover, you may ingest as a form of food.

本発明の健康機能向上剤を水溶液として調製する場合には、δ−アミノ酸類が5−アミノレブリン酸類の場合、有効成分である5−アミノレブリン酸類の分解を防ぐため、水溶液がアルカリ性とならないように留意する必要がある。アルカリ性となってしまう場合は、酸素を除去することによって有効成分の分解を防ぐことができる。   When the health function improving agent of the present invention is prepared as an aqueous solution, when the δ-amino acids are 5-aminolevulinic acids, care should be taken so that the aqueous solution does not become alkaline in order to prevent decomposition of the active ingredient 5-aminolevulinic acids. There is a need to. When it becomes alkaline, decomposition of the active ingredient can be prevented by removing oxygen.

本発明の健康機能向上剤は、本剤を摂取してその健康機能を向上させることができればよく、本剤の使用方法に制限はないが、好ましい態様について以下に示す。   The health function improving agent of the present invention is not limited as long as the health function can be improved by ingesting the agent, and the method of using the agent is not limited, but preferred embodiments are shown below.

本剤を用いた健康機能向上剤の対象となる動物は特に限定されないが、哺乳類、爬虫類、鳥類、両生類、魚類などの脊椎動物が好ましい。これらの例としては、人、牛、豚、羊、やぎ、マウス、ラット、ウサギ、犬、猫、鶏、鶉、ニジマス、コイ、ウナギ、イワナなどの淡水魚、ギンザケ、ブリ、マダイ、サバ、マグロなどの海水魚、及び熱帯魚や爬虫類などの観賞生物などが挙げられる。   There are no particular limitations on the animal that is the target of the health function improver using this agent, but vertebrates such as mammals, reptiles, birds, amphibians, and fish are preferred. Examples of these include freshwater fish such as humans, cows, pigs, sheep, goats, mice, rats, rabbits, dogs, cats, chickens, salmon, rainbow trout, carp, eel, char, coho salmon, yellowtail, red sea bream, mackerel, tuna And marine ornamental fish such as tropical fish and reptiles.

本剤の健康機能向上剤の使用は動物の成育のどの時点でも可能であるが、人であれば15歳以降が好ましく、35歳以降が特に好ましい。   Although the use of this agent for improving the health function is possible at any time during the growth of the animal, humans are preferably 15 years old or later, and particularly preferably 35 years old or later.

本発明の健康機能向上剤の摂取方法としては特に限定されないが、経口摂取、注射による摂取、経管による摂取又は経腸による摂取が挙げられ、なかでも経口摂取が好ましい。   The method for ingesting the health function improving agent of the present invention is not particularly limited, and examples include oral ingestion, ingestion by ingestion, ingestion by tube, and ingestion by intestine, and oral ingestion is particularly preferable.

本剤は、1度の摂取でも十分な効果を示すが、さらに効果を強めるために複数回摂取することもできる。摂取する剤あたりの効果は複数回摂取の方が効果的であり、毎日少量ずつ摂取するのが効率的な使用方法である。   This drug shows a sufficient effect even if it is taken once, but it can be taken multiple times to further enhance the effect. The effect per ingested agent is more effective when taken multiple times, and it is an efficient usage method to take a small amount every day.

本剤の対象動物1kgあたり1回の摂取量は、δ−アミノ酸類として0.001mg〜1000mgが好ましく、さらには0.001mg〜100mg、特に0.001mg〜50mgが好ましい。本剤の摂取量は、成育が旺盛な時期ほど、また摂取回数の少ないほど多くの量が必要である。適切な範囲を超えた摂取は不経済であるばかりか日光傷害を起こす可能性があるため望ましくない。   The amount of intake of this drug per 1 kg of the target animal is preferably 0.001 mg to 1000 mg, more preferably 0.001 mg to 100 mg, particularly preferably 0.001 mg to 50 mg as δ-amino acids. The intake of this drug should be increased as the period of growth increases and as the number of intakes decreases. Ingestion beyond the appropriate range is not desirable because it is not economical and can cause sun injury.

またミネラル類を併用する場合は同時に使用してもよいし別々に使用してもよい。使用するミネラルの種類、その使用方法及びその使用量は通常市販されているミネラル類と同じで差し支えない。その使用量は、例えば鉄の場合には成人男性で1日あたり1〜45mgであればよく、5〜20mgが好ましい。マグネシウムの場合には50mg〜700mgであればよく、100〜500mgが好ましい。マンガンの場合には0.1〜11mgであればよく、2〜8mgが好ましい。   Moreover, when using together minerals, you may use simultaneously and may use separately. The kind of mineral to be used, the method of using the same, and the amount of the mineral used may be the same as those of commercially available minerals. For example, in the case of iron, the amount of use may be 1 to 45 mg per day for an adult male, and 5 to 20 mg is preferable. In the case of magnesium, it may be 50 mg to 700 mg, preferably 100 to 500 mg. In the case of manganese, it may be 0.1 to 11 mg, preferably 2 to 8 mg.

次に実施例を挙げて本発明をさらに詳細に説明するが、本発明はこれに何ら限定されない。   EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, this invention is not limited to this at all.

実施例1
一週間予備飼育したマウス(35〜45週齢、BALB/cAJcl)にマウス体重1kgあたり5−アミノレブリン酸(以下、ALAと称す)塩酸塩10mgを一日一回、7日間連続して摂取させた。ALA塩酸塩は蒸留水で0.5g/mLの濃度に調整し、マウスに経口投与した。試験後、床面積が20cm×20cmのゲージに入れ、5分間の移動距離を計測した。試験は1区あたり雄と雌のマウス各5匹、計10匹で実施、値は平均値を示した。ALAを処理した区においては、雄、雌いずれの場合も移動距離が多く、運動能力が向上していることを確認した。また試験中、ALA処理したマウスには肉眼的に異常な興奮・行動などの症状は観察されなかった。
Example 1
Mice preliminarily raised for one week (35 to 45 weeks of age, BALB / cAJcl) were given 10 mg of 5-aminolevulinic acid (hereinafter referred to as ALA) hydrochloride per kg of mouse body weight once a day for 7 consecutive days. . ALA hydrochloride was adjusted to a concentration of 0.5 g / mL with distilled water and orally administered to mice. After the test, it was placed in a gauge having a floor area of 20 cm × 20 cm, and the moving distance for 5 minutes was measured. The test was carried out with 5 male mice and 5 female mice per group, for a total of 10 mice, and the values showed average values. In the section where ALA was treated, it was confirmed that the movement distance was large in both males and females and the exercise ability was improved. During the test, no abnormal symptoms such as abnormal excitement / behavior were observed in the mice treated with ALA.

Figure 2006096745
Figure 2006096745

実施例2
一週間予備飼育した老齢のリタイアマウス(35〜45週齢、BALB/cAJcl)にマウス体重1kgあたりALA塩酸塩10mgを一日一回、7日間連続して摂取させた。ALA塩酸塩は蒸留水で0.5g/mLの濃度に調整し、マウスに経口投与した。試験後、マウスを解剖しマウスの血液を採取し血液1mLあたりのALA酸脱水酵素(ALAD)活性(5−アミノレブリン酸が二量化し、1分子のピロール物質であるポルホビリノーゲン(以下、PBGと称す)を形成する活性)及びポルホビリノーゲンデアミナーゼ(PBGD)活性(PBGからヒドロキシメチルビランに変換する活性)を測定した。ALAがPBGを形成するパス及びPBGからヒドロキシメチルビランに変換するパスは、ヘム合成の重要なパスの一部である。ヘパリン処理したマウスの全血0.02mLに蒸留水を0.33mL加えた後、0.5M Na−phosphate buffer pH6.4、0.05mL、0.1M DTT(1mM ZnSO4を含む)を0.05mL、50mM ALA塩酸塩を0.05mL加え、総量0.5mLとし、これを37℃、30分間保持した後、1M トリクロロ酢酸を0.5mL加え、反応を停止した後3000rpmの上清にエールリッヒ試薬を等量加え、正確に10分後、分光光度計を用いて、エールリッヒ試薬とPBGが反応して生成する化合物の特性吸収である553nmの吸光度を測定した(OD)。
Example 2
Aged retired mice (35-45 weeks old, BALB / cAJcl) preliminarily kept for 1 week were ingested 10 mg of ALA hydrochloride per kg of mouse body weight once a day for 7 consecutive days. ALA hydrochloride was adjusted to a concentration of 0.5 g / mL with distilled water and orally administered to mice. After the test, the mouse was dissected, the blood of the mouse was collected, ALA acid dehydrase (ALAD) activity per mL of blood (5-aminolevulinic acid was dimerized, and porphobilinogen, which is one molecule of pyrrole substance (hereinafter referred to as PBG). Activity) and porphobilinogen deaminase (PBGD) activity (activity for converting PBG to hydroxymethylbilane). The path where ALA forms PBG and the path from PBG to hydroxymethylbilane are some of the important paths for heme synthesis. After adding 0.33 mL of distilled water to 0.02 mL of heparinized mouse whole blood, 0.5 M Na-phosphate buffer pH 6.4, 0.05 mL, 0.1 M DTT (containing 1 mM ZnSO 4 ) 05 mL, 0.05 mL of 50 mM ALA hydrochloride was added to make a total volume of 0.5 mL, this was maintained at 37 ° C. for 30 minutes, 0.5 mL of 1M trichloroacetic acid was added, the reaction was stopped, and the Ehrlich reagent was added to the 3000 rpm supernatant. After exactly 10 minutes, the absorbance at 553 nm, which is the characteristic absorption of the compound produced by the reaction of the Ehrlich reagent and PBG, was measured using a spectrophotometer (OD).

計算はALAD活性によって得られる反応産物PBGの分子吸光係数61000を用いて以下のごとく行った。空試料は反応時間0分を用いた(OD0)。 The calculation was performed as follows using the molecular extinction coefficient 61000 of the reaction product PBG obtained by the ALAD activity. An empty sample was used with a reaction time of 0 minutes (OD 0 ).

ALAD活性=1M×(OD-OD0)/61000×2/1000×1/反応試料量mL×1
=32.8×(OD-OD0)/反応試料量(mL)nmolPBG/mL/h
ALAD activity = 1M x (OD-OD 0 ) / 61000 x 2/1000 x 1 / mL of reaction sample x 1
= 32.8 × (OD-OD 0 ) / reaction sample volume (mL) nmolPBG / mL / h

またPBGD活性は以下の通り測定した。ヘパリン処理したマウスの全血0.02mLに蒸留水を0.38mL加えた後、0.6mM PBG(0.38M Na−phosphate buffer pH7.8を含む)を0.05mL加えた後、37℃、30分間保持した。5M トリクロロ酢酸(0.8%ヨウ素を含む)を0.05mL加え、反応を停止した後、3000rpm5分間の遠心上清をそのまま蛍光分光光度計にて励起波長405nm、蛍光波長597nmの蛍光強度を測定した。   The PBGD activity was measured as follows. After adding 0.38 mL of distilled water to 0.02 mL of whole blood of mice treated with heparin, 0.05 mL of 0.6 mM PBG (including 0.38 M Na-phosphate buffer pH 7.8) was added, Hold for 30 minutes. After stopping the reaction by adding 0.05 mL of 5M trichloroacetic acid (containing 0.8% iodine), the fluorescence intensity at an excitation wavelength of 405 nm and a fluorescence wavelength of 597 nm was measured with a centrifugal supernatant at 3000 rpm for 5 minutes. did.

計算はPBGD活性によって得られるウロポルフィリノーゲン1型異性体の標準物質を用いて比例計算した。   The calculation was carried out in proportion using a standard substance of uroporphyrinogen type 1 isomer obtained by PBGD activity.

すなわち、標準物質0.536nmol URO/mLのときにFU(Em=597nmの蛍光強度)=139
したがって、PBGD活性=0.536/139×0.5/0.01×2×FU/Ht
That is, FU (Em = 597 nm fluorescence intensity) = 139 when the standard substance is 0.536 nmol URO / mL
Therefore, PBGD activity = 0.536 / 139 × 0.5 / 0.01 × 2 × FU / Ht

試験は1区あたり雄のマウス5匹で実施、値は平均値を示した。ALAを処理した区においては、ALAD活性及びPBGD活性が向上していることを確認した。   The test was carried out with 5 male mice per section, and the values showed average values. In the section treated with ALA, it was confirmed that ALAD activity and PBGD activity were improved.

Figure 2006096745
Figure 2006096745

上記のように、ALAを摂取することにより、呼吸電子伝達系の重要な因子であるヘムタンパク質を構成するヘム合成経路の活性(ALAD活性、PBGD活性)を向上させることを見出した。よって、本経路が活性化することにより、動物体内でエネルギー代謝を行うクエン酸回路(TCAサイクル)が活性化され、運動機能が向上したと考えられる。   As described above, it has been found that by ingesting ALA, the activity (ALAD activity, PBGD activity) of the heme synthesis pathway constituting the heme protein, which is an important factor of the respiratory electron transport system, is improved. Therefore, when this pathway is activated, it is considered that the citric acid circuit (TCA cycle) that performs energy metabolism in the animal body is activated and the motor function is improved.

実施例3
一週間予備飼育したマウス(35〜45週齢、BALB/cAJc1)にマウス体重1kgあたりALA塩酸塩10mgを一日一回、7日間連続して摂取させた。ALA塩酸塩は蒸留水で0.5g/mLの濃度に調整し、マウスに経口投与した。試験前後で、回転式運動量測定器(回転篭:直径200mm×巾50mm、飼育篭:W90mm×D220mm×H90mm、(株)シナノ製作所社製)に入れ、16時間の回転数を計測した。試験は回転式運動量1個にマウス1匹で実施し、無処理5匹、ALA処理5匹を1区として雌のマウスに対し実施し、値は平均値を示した。ALAを処理した区においては、回転量が多く、運動能力が向上していることを確認した。
Example 3
Mice preliminarily raised for one week (35 to 45 weeks old, BALB / cAJc1) were ingested with 10 mg of ALA hydrochloride per kg of mouse body weight once a day for 7 consecutive days. ALA hydrochloride was adjusted to a concentration of 0.5 g / mL with distilled water and orally administered to mice. Before and after the test, it was put in a rotary momentum measuring device (rotary rod: diameter 200 mm × width 50 mm, breeding rod: W90 mm × D220 mm × H90 mm, manufactured by Shinano Manufacturing Co., Ltd.), and the number of rotations for 16 hours was measured. The test was carried out with one mouse per rotational momentum, and was carried out on female mice with 5 untreated animals and 5 ALA-treated animals as one group, and the values showed average values. In the section where ALA was treated, it was confirmed that the amount of rotation was large and the exercise ability was improved.

Figure 2006096745
Figure 2006096745

実施例4
日本医科学動物資材研究所(株)生産のddY−N系マウスを120頭(雄、雌各60頭)を約4週齢で導入し、1週間の検疫を行って健康状態に異常ないこと確認し試験に用いた。試験区は、注射用水を供試マウスの体重1kgあたり10mLの割合で28日間連続して胃ゾンデを用いて強制経口投与する対照区、ALA酸塩酸塩を供試マウスの体重1kgあたり5mg、10mg及び25mgの割合で同様に投与する3試験区の計4区を設定した。供試マウスを各群の平均体重がほぼ均等となるように、雄、雌毎に1群を5匹とした12群に区分し、各区に雄、雌各3群ずつを割付けて、28日間飼育した。供試マウスは、室温23.0±2.0℃、照射時間12時間/日に設定した飼育室に設置したステンレス製5連ケージを用いて群毎に飼育した。試験開始時より1週間間隔で固体別体重を測定して増体量を算出した。
Example 4
Introduce 120 ddY-N mice (60 males and 60 females) produced by Nippon Medical Science Animal Materials Co., Ltd. at about 4 weeks of age, and conduct a one-week quarantine to ensure no abnormal health It confirmed and used for the test. The test group is a control group in which water for injection is administered by oral gavage using a gastric sonde at a rate of 10 mL per kg body weight of the test mice for 28 days, and ALA hydrochloride is 5 mg per kg body weight of the test mice, 10 mg. And a total of 4 groups of 3 test groups administered similarly in the ratio of 25 mg were set. The test mice were divided into 12 groups with 5 groups of 1 group for each male and female so that the average body weight of each group was almost equal, and 3 groups of male and female were assigned to each group for 28 days. Raised. The test mice were reared for each group using a stainless steel five-unit cage installed in a rearing room set at a room temperature of 23.0 ± 2.0 ° C. and an irradiation time of 12 hours / day. The weight gain was calculated by measuring the body weight of each solid at weekly intervals from the start of the test.

その結果、試験期間中の発育曲線(雄、雌の平均、図1)で示すように、10mg/kg投与区が他の3区より優れる発育を示し、実施例3の結果と併せると、運動機能が向上し、体重増加効果も認められることから、健康機能向上剤として有用であることがわかった。
なお、ALA添加群においても、健康状態に異常は認められなかった。
As a result, as shown in the growth curve during the test period (average of males and females, FIG. 1), the 10 mg / kg administration group showed growth superior to the other 3 groups. Since the function was improved and the effect of weight gain was also observed, it was found that it was useful as a health function improver.
In the ALA addition group, no abnormality was observed in the health condition.

実施例5
養豚場で同日に生産されたLW・D種子豚を14頭(去勢、雌各7頭)ずつ3回に分けて導入し、9〜12日間の予備飼育を行って健康状態に異常ないこと確認したのち、各回とも、12頭(去勢、雌各6頭)ずつを選抜して試験に用いた。試験区は、ALA塩酸塩無添加の対照飼料(表4)を供給する対照区と、ALA塩酸塩を10ppm及び50ppm添加した飼料を供給する試験区2区の計3区を設定した。供試豚を、体重の分布がほぼ均等となるように4頭(去勢、雌各2頭)ずつ3群に区分し、各区に1群ずつを割付けて6週間飼育した。供試豚舎は1.8×2.7mのコンクリート床豚房が14房ずつ並列した開放型豚舎でブロック毎に隣接した3豚房を用いて群飼した。敷科は稲ワラを用いた。各豚房内には試験開始後3週まで保温箱を設置した。飼料及び飲水は不断供与した。試験開始時より1週間間隔で固体別体重を測定して増体量を算出した。
その結果、試験期間中の発育曲線(去勢、雌の平均、図2)で示すように、10ppm、50ppm添加区で対照区より優れる発育を示し、実施例3の結果と併せると、運動機能が向上し、体重増加効果も認められることから、健康機能向上剤として有用であることがわかった。
なお、ALA添加群においても、健康状態に異常は認められなかった。
Example 5
14 LW / D seed pigs produced on the same day at the pig farm (7 castrates, 7 females each) were introduced in 3 portions and pre-raised for 9-12 days to confirm that there was no abnormal health After that, each time, 12 animals (castrated, 6 females each) were selected and used for the test. The test plots were set for a total of three plots: a control plot for supplying a control feed (Table 4) without addition of ALA hydrochloride, and a test plot for feeding a feed supplemented with 10 ppm and 50 ppm of ALA hydrochloride. The test pigs were divided into 3 groups of 4 (castrated, 2 females each) so that the weight distribution was almost uniform, and 1 group was assigned to each group and raised for 6 weeks. The test pig house was an open-type pig house in which 14 x 1.8-2.7m concrete floor pig bunches were juxtaposed, and grouped using 3 pig bunches adjacent to each block. The floor was made from rice straw. A heat insulation box was installed in each pig chamber until 3 weeks after the start of the test. Feed and drinking water were provided constantly. The weight gain was calculated by measuring the body weight of each solid at weekly intervals from the start of the test.
As a result, as shown by the growth curve during the test period (castration, female average, FIG. 2), 10 ppm and 50 ppm added group showed growth superior to the control group. Since it improved and the weight gain effect was also recognized, it turned out that it is useful as a health function improvement agent.
In the ALA addition group, no abnormality was observed in the health condition.

Figure 2006096745
Figure 2006096745

実施例6
ブロイラー初生ヒナ(チャンキー)雌雄各150羽、合計300羽を導入した。導入後異常の認められるヒナ(衰弱や矮小)を除外し、個体識別のため翼帯を装着して、個体別に体重を測定した。雌雄別に、体重により3グループ(1グループ当たり45羽以上)に分け、各グループ内で無作為に15羽ずつ3群に割り付けた。閉鎖型畜舎内に設置したチックガードに、雌雄各15羽(計30羽)を1群として収容し、動物用赤外線ランプを設置して保温した。チックガードは、ヒナの発育に伴なって拡大した。飼料及び飲水は、不断給与した。試験群は、ALA塩酸塩無添加の対照飼料(初生から3週齢までは試験用標準飼料SDB No.1、3週齢から7週齢までは試験用標準飼料SDB No.2(いずれも日本配合飼料(株)製、表5)を用いた)を供給する対照群とALA塩酸塩を10ppm及び50ppm添加した飼料を供給するALA−10ppm添加群とALA−50ppm添加群2群の計3群を設定し、各群3反復区を配した。各試験群の供試羽数は表6のとおりとした。試験期間は初生(添加飼料給与開始)から7週間(7週齢)とし、初生時及びそれ以降1週ごとに、反復区ごとに雌雄別総体重を測定した。また、3週齢及び7週齢に各群18羽(雌雄各3羽/反復)の上腕静脈(尺側皮静脈)から約2mLの血液を採取し、そのうち約1.5mLを、ヘパリン−リチウム塩を用いて凝固防止処理した後、血漿を分離し、LDH、GOT(AST)、γ-GTP、ALP、総タンパク、アルブミン、グロブリン、総コレステロール、中性脂肪、血糖、尿酸、総ビリルビン、尿酸、クレアチニン、カルシウム、無機リンの項目を検査した。その結果、試験期間中の体重(雌雄の平均)は、表7に示すように、初生から3週齢までの体重に、試験群間で差はみられなかったが、3週齢以降の体重は、ALA−10ppm添加群とALA−50ppm添加群2群で対照群より大きくなった。また、血液検査の結果では、表8に示すようにγ−GTP(ガンマグルタミルトランスペプチダーゼ)がALA−10ppm添加群とALA−50ppm添加群2群で対照群より減少していることが認められ、ALAが肝機能向上効果を有し、健康機能向上剤として有用であることがわかった。
なお、ALA添加群においても、試験期間中の一般状態に異常は認められず、育成率及び剖検所見にも添加によると考えられる異常は認められなかった。
Example 6
A total of 300 broilers, 150 chicks (chunky) each, were introduced. We removed chicks (weakness and dwarf) in which abnormalities were observed after the introduction, wore wings for individual identification, and weighed each individual. Each male and female was divided into 3 groups (more than 45 birds per group) according to body weight, and 15 birds were randomly assigned to each group within each group. A tick guard installed in a closed barn housed 15 males and 15 females (30 in total) as a group, and an infrared ray lamp for animals was installed and kept warm. Chick guard expanded with the development of chicks. Feed and drinking water were constantly fed. The test group consisted of a control feed without ALA hydrochloride (standard feed for test SDB No. 1 from the beginning to 3 weeks of age, standard feed for test SDB No. 2 from 3 weeks to 7 weeks of age (all in Japan) A total of 3 groups: a control group that supplies a feed containing 10 ppm and 50 ppm of ALA hydrochloride, and an ALA-10 ppm addition group and an ALA-50 ppm addition group that supply a feed containing 10 ppm and 50 ppm. Was set, and each group had 3 repeat sections. Table 6 shows the number of test feathers in each test group. The test period was 7 weeks (7 weeks of age) from the beginning (start of feeding the supplemented feed), and the total body weight by sex was measured for each repeated section at the time of initial birth and every week thereafter. In addition, about 2 mL of blood was collected from the brachial vein (ulcer lateral vein) of 18 birds (3 males and 3 females / repeated) at 3 weeks and 7 weeks of age, about 1.5 mL of which was collected from heparin-lithium. After anticoagulation treatment with salt, plasma is separated, LDH, GOT (AST), γ-GTP, ALP, total protein, albumin, globulin, total cholesterol, neutral fat, blood sugar, uric acid, total bilirubin, uric acid The items of creatinine, calcium and inorganic phosphorus were examined. As a result, as shown in Table 7, the body weight during the test period (average of males and females) was not different among the test groups in the body weight from the beginning to 3 weeks of age, but the body weight after 3 weeks of age. Became larger than the control group in the ALA-10 ppm added group and the ALA-50 ppm added group. Moreover, in the results of the blood test, as shown in Table 8, γ-GTP (gamma glutamyl transpeptidase) was found to be decreased from the control group in the ALA-10 ppm added group and the ALA-50 ppm added group, It was found that ALA has a liver function improving effect and is useful as a health function improving agent.
In addition, in the ALA addition group, no abnormality was observed in the general state during the test period, and no abnormality considered to be due to the addition was also observed in the growth rate and autopsy findings.

Figure 2006096745
Figure 2006096745

Figure 2006096745
Figure 2006096745

Figure 2006096745
Figure 2006096745

Figure 2006096745
Figure 2006096745

マウスの発育曲線を示す図である。It is a figure which shows the growth curve of a mouse | mouth. 養豚の発育曲線を示す図である。It is a figure which shows the growth curve of a pig farm.

Claims (8)

δ−アミノ酸、その誘導体又はその塩を有効成分とする健康機能向上剤。   A health function improving agent comprising δ-amino acid, a derivative thereof or a salt thereof as an active ingredient. 運動機能が向上することにより、健康機能が向上することを特徴とする、請求項1記載の健康機能向上剤。   The health function improving agent according to claim 1, wherein the health function is improved by improving the motor function. 肝機能が向上することにより、健康機能が向上することを特徴とする、請求項1記載の健康機能向上剤。   The health function improving agent according to claim 1, wherein the health function is improved by improving the liver function. δ−アミノ酸、その誘導体又はその塩が、次式(1)
Figure 2006096745
(式中、R1は水素原子又はアシル基を示し、R2は水素原子又は置換基を有していてもよい炭化水素基を示す)
で表される化合物又はその塩である請求項1〜3のいずれか1項記載の健康機能向上剤。
The δ-amino acid, its derivative or its salt is represented by the following formula (1)
Figure 2006096745
(Wherein R 1 represents a hydrogen atom or an acyl group, and R 2 represents a hydrogen atom or a hydrocarbon group which may have a substituent)
The health function improving agent according to any one of claims 1 to 3, which is a compound represented by the formula:
さらにミネラルを含むものである請求項1〜4のいずれか1項記載の健康機能向上剤。   Furthermore, the health function improving agent of any one of Claims 1-4 which contains a mineral. ミネラルが、鉄又は銅である請求項5記載の健康機能向上剤。   The health function improving agent according to claim 5, wherein the mineral is iron or copper. 経口、注射、経管又は経腸摂取用剤である請求項1〜6のいずれか1項記載の健康機能向上剤。   The health function improving agent according to any one of claims 1 to 6, which is an agent for oral, injection, tube, or enteral ingestion. δ−アミノ酸、その誘導体又はその塩を、1日に体重1kgあたり0.001〜1000mg摂取するためのものである請求項1〜7のいずれか1項記載の健康機能向上剤。   The health function improving agent according to any one of claims 1 to 7, which is for ingesting 0.001 to 1000 mg of δ-amino acid, a derivative thereof or a salt thereof per kg of body weight per day.
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