JP3096052B2 - Lipid metabolism regulator - Google Patents

Lipid metabolism regulator

Info

Publication number
JP3096052B2
JP3096052B2 JP02240961A JP24096190A JP3096052B2 JP 3096052 B2 JP3096052 B2 JP 3096052B2 JP 02240961 A JP02240961 A JP 02240961A JP 24096190 A JP24096190 A JP 24096190A JP 3096052 B2 JP3096052 B2 JP 3096052B2
Authority
JP
Japan
Prior art keywords
proline
lipid metabolism
metabolism regulator
threonine
fatty acid
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.)
Expired - Fee Related
Application number
JP02240961A
Other languages
Japanese (ja)
Other versions
JPH04120020A (en
Inventor
岳 阿部
研一 山崎
好三 瀧口
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.)
Nippon Steel Corp
RIKEN Institute of Physical and Chemical Research
Original Assignee
Nippon Steel Corp
RIKEN Institute of Physical and Chemical Research
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 Nippon Steel Corp, RIKEN Institute of Physical and Chemical Research filed Critical Nippon Steel Corp
Priority to JP02240961A priority Critical patent/JP3096052B2/en
Publication of JPH04120020A publication Critical patent/JPH04120020A/en
Application granted granted Critical
Publication of JP3096052B2 publication Critical patent/JP3096052B2/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Description

【発明の詳細な説明】 (産業上の利用分野) この発明はプロリン及び/又はスレオニンを有効成分
とする脂質代謝調節剤に関する。
Description: TECHNICAL FIELD The present invention relates to a lipid metabolism regulator containing proline and / or threonine as an active ingredient.

(従来の技術及び発明の解決しようとする課題) 従来、スズメバチの幼虫に関する報告、特に幼虫が分
泌するだ液に関する報告はほとんどなく、その組成は全
く解明されていなかった。またスズメバチの驚異的な筋
持続力はどの様な栄養に由来するのかも全く不明であっ
た。
(Prior Art and Problems to be Solved by the Invention) Heretofore, there have been almost no reports on wasp larvae, particularly on saliva secreted by the larvae, and their composition has not been elucidated at all. It was also completely unclear what nutrition contributed to the muscular sustainability of the hornet.

本発明者らは、種々のスズメバチの幼虫が分泌するだ
液について研究し、その組成を明らかにするとともに、
その組成物が極めて有効な筋持続剤として作用すること
を見出し、その有効成分を解明して来た。そして、該組
成物が通常のタンパク質あるいはその水解物中に比較的
多量に含有されるアスパラギン酸やグルタミン酸をほと
んど含有せず、プロリンとグリシンを主成分とするアミ
ノ酸組成物であり、脂質代謝調節作用を有することを見
出した。
The present inventors studied the saliva secreted by various hornet larvae, clarified its composition,
They have found that the composition acts as a very effective muscle sustaining agent, and have elucidated the active ingredient. The composition is an amino acid composition containing almost no aspartic acid or glutamic acid contained in a relatively large amount in a normal protein or its hydrolyzate, and is mainly composed of proline and glycine, and has an effect of regulating lipid metabolism. Was found to have.

本発明者らは、上記のアミノ酸組成物の構成成分のう
ち、特にプロリンとスレオニンはメチオニンを含まなく
ても脂質代謝調節作用を有することを見出し、本発明を
完成したものである。
The present inventors have found that, among the components of the amino acid composition described above, proline and threonine in particular have a lipid metabolism regulating action even without containing methionine, and have completed the present invention.

(課題を解決するための手段) すなわち、本発明はプロリン及び/又はスレオニンを
有効成分として含み、メチオニンを含まないことを特徴
とする脂質代謝調節剤を提供することを目的とする。
(Means for Solving the Problems) That is, an object of the present invention is to provide a lipid metabolism regulator characterized by containing proline and / or threonine as an active ingredient and not containing methionine.

本発明の脂質代謝調節剤に含まれるプロリン、スレオ
ニンはそれぞれL−プロリン、L−スレオニンであるこ
とが好ましい。
The proline and threonine contained in the lipid metabolism regulator of the present invention are preferably L-proline and L-threonine, respectively.

本発明の脂質代謝調節剤を製造するにあたっては、市
販のプロリン、スレオニンを使用すればよく、両者を任
意の割合で混合して用いてもよい。通常は粉末状で製造
すればよいが、混合物とする場合には、両者を粉末状態
で混合するか、プロリン及びスレオニンを蒸留水に溶解
し、若しくは両者の溶液を混合した後に、水分を留去し
て製造しても良い。本発明の脂質代謝調節剤は室温以下
で製造することが好ましい。
In producing the lipid metabolism regulator of the present invention, commercially available proline and threonine may be used, and both may be used in a mixture at an arbitrary ratio. Usually, it may be manufactured in powder form, but when a mixture is used, both are mixed in a powder state, or proline and threonine are dissolved in distilled water, or after mixing both solutions, water is distilled off. It may be manufactured. The lipid metabolism regulator of the present invention is preferably produced at room temperature or lower.

本発明の脂質代謝調節剤はマウスに経口投与した場合
に20g/kgでも全く毒性を発現せず、LD50は20g/kgをはる
かに上まわる。
Lipid metabolism modulators of the present invention do not express no toxicity even 20 g / kg when orally administered to mice, LD 50 is around the top far the 20 g / kg.

本発明の脂質代謝調節剤は、血中遊離脂肪酸調節剤、
肝臓脂肪代謝調節剤、及び脂肪体脂肪代謝調節剤等の医
薬、及び飲料等の食品として有用である。医薬として用
いる場合の投与形態は特に限定されないが、経口投与、
直腸投与、注射、若しくは輸液による投与等の一般的投
与経路を経ることができる。経口投与の場合には、医薬
上許容される担体、賦形剤、希釈剤等とともに混合し、
散剤、顆粒剤、錠剤、カプセル剤、トローチ剤、シロッ
プ剤等として用いてもよい。固体散剤、錠剤では吸収に
時間がかかる場合もあるので、適当な添加剤、例えば塩
化ナトリウム等の塩類、pH調節剤、キレート剤等を添加
して水溶液として投与することが好ましい。本発明の脂
質代謝調節剤には他のアミノ酸、水溶性ビタミン類、ク
エン酸等の酸類を添加してもよく、また、適当な風味を
加えてドリンク剤、例えば清涼飲料、粉末飲料、滋養強
壮、栄養補給を目的とした医薬品としての飲料としても
よい。また、注射剤としては、適当な緩衝剤、等張剤等
を添加し、滅菌蒸留水に溶解したものを用いて、例えば
静脈内に点滴静注すればよい。
The lipid metabolism regulator of the present invention is a blood free fatty acid regulator,
It is useful as a medicine such as a liver fat metabolism regulator and a fat body fat metabolism regulator, and as a food such as a beverage. The dosage form when used as a medicament is not particularly limited, but oral administration,
It can be via a common route of administration, such as rectal administration, injection, or administration by infusion. For oral administration, mix with a pharmaceutically acceptable carrier, excipient, diluent, etc.
It may be used as powders, granules, tablets, capsules, troches, syrups and the like. Solid powders and tablets may take time to be absorbed, so that it is preferable to add appropriate additives such as salts such as sodium chloride, a pH adjuster, a chelating agent and the like, and administer the solution as an aqueous solution. Other amino acids, water-soluble vitamins, acids such as citric acid may be added to the lipid metabolism regulator of the present invention, and drinks such as soft drinks, powdered drinks, and tonics are added with an appropriate flavor. Alternatively, it may be a beverage as a pharmaceutical for nutritional supplementation. Injections may be prepared by adding an appropriate buffer, isotonic agent and the like and dissolving in sterile distilled water, for example, by intravenous drip infusion.

本発明の脂質代謝調節剤はきわめて低毒性であるので
その投与量は非常に広範に設定でき、さらに、投与方
法、使用目的により異なるが通常1回に0.5〜5g、好ま
しくは1回に1〜2g、1日投与量として1〜20g、好ま
しくは4〜10gとすることが好ましい。これらの溶液剤
とする場合には0.5〜10wt%溶液として10〜1000ml、好
ましくは1〜4wt%溶液として100〜400mlを1回投与量
とすればよい。注射剤としては0.5〜2wt%溶液として1
回あたり10〜500ml、好ましくは100〜300mlを投与すれ
ばよい。
Since the lipid metabolism regulator of the present invention has extremely low toxicity, its dosage can be set in a very wide range. Further, although it varies depending on the administration method and purpose of use, it is usually 0.5 to 5 g at a time, preferably 1 to 5 at a time. The daily dose is preferably 1 to 20 g, and more preferably 4 to 10 g. When these solutions are used, a single dose may be 10 to 1000 ml as a 0.5 to 10 wt% solution, preferably 100 to 400 ml as a 1 to 4 wt% solution. 0.5 to 2 wt% solution for injection
It is sufficient to administer 10 to 500 ml, preferably 100 to 300 ml per administration.

実施例 プロリン及びスレオニンについて、脂質代謝調節作用
を試験した。
Example Proline and threonine were tested for their lipid metabolism regulating action.

実験方法 (1)血中遊離脂肪酸の定量 検体としてそれぞれ2%のプロリン、グリシン、ス
レオニン、ロイシン、セリン、及び20%グルコースをg
体重当たり37.5μ投与したマウス(6週令)に、60分
間の強制負荷遊泳(0.3gの負荷)後、直ちにエーテルに
より麻酔を施し、開腹、腹部大静脈から採血を行った。
Experimental method (1) Quantification of blood free fatty acids 2% proline, glycine, threonine, leucine, serine, and 20% glucose were used as samples.
Mice (6 weeks old) administered 37.5 μm per body weight were immediately anesthetized with ether after 60 minutes of forced load swimming (0.3 g load), and laparotomy and blood collection from the abdominal vena cava were performed.

採血した血液は遠心分離を行い、血球成分を除い
た。
The collected blood was centrifuged to remove blood cell components.

遠心分離後の上清について脂肪酸定量を常法に基づ
き、和光純薬工業社製の臨床試薬にて行った。脂肪酸の
定量はアシル−CoA合成酵素とアシル−CoAオキシダーゼ
の作用により生じた過酸化水素を、ペルオキシダーゼと
反応させ、エチル−N−アニリンと4−アミノアンピリ
ンを呈色させたものを550nmで吸光度を測定した。
The supernatant after centrifugation was subjected to fatty acid determination using a clinical reagent manufactured by Wako Pure Chemical Industries, Ltd. based on a conventional method. Fatty acids were quantified by reacting hydrogen peroxide generated by the action of acyl-CoA synthase and acyl-CoA oxidase with peroxidase, and then coloring ethyl-N-aniline and 4-aminoampirin to absorb light at 550 nm. Was measured.

(2)脂肪体からの遊離脂肪酸の定量 ・ラットの脂肪体(Fat body) 200mg ・緩衝液(0.5M NaPB pH7.56:Ringer液=9:1)200μ ・アルブミン(BSA)溶液(100mg/ml) 200μ ・1mM CaCl2(最終濃度) 50μ これにプロリンとアドレナリンを加えて37℃で反応を
行い、15、30、60そして120分後の遊離脂肪酸を測定し
た。用いた脂肪体はウィスター系ラット(6週令)180
〜200gから摘出した。
(2) Determination of Free Fatty Acid from Fat Body ・ Fat body of rat 200mg ・ Buffer solution (0.5M NaPB pH7.56: Ringer solution = 9: 1) 200μ ・ Albumin (BSA) solution (100mg / ml) 200 μm 1 mM CaCl 2 (final concentration) 50 μl Proline and adrenaline were added thereto and reacted at 37 ° C., and the free fatty acids after 15, 30, 60 and 120 minutes were measured. The fat pad used was Wistar rat (6 weeks old) 180
Removed from ~ 200g.

(3)肝臓からの遊離脂肪酸の測定 十分に瀉血したラット肝臓(ウィスター系、180〜200
g)をスライスし、クレプスーリンガー液に40%ラット
血清あるいは40mg/mlのBSAを加え、これに2mg/mlになる
ようプロリンを加え、37℃で反応を行い経時的に変化す
る遊離脂肪酸の量を測定した。
(3) Measurement of Free Fatty Acid from Liver Fully phlebotomized rat liver (Wistar strain, 180-200
g), and add 40% rat serum or 40 mg / ml BSA to Kreps-Ringer solution, add proline to 2 mg / ml, react at 37 ° C, and change the free fatty acid The amount was measured.

結果 (1)血液中の脂肪酸値の変化 プロリン及びスレオニンが脂質代謝調節に及ぼす作用
を明らかにすべく、投与後静置、強制負荷遊泳後の脂肪
酸値を測定した。
Results (1) Changes in Blood Fatty Acid Level In order to clarify the effects of proline and threonine on the regulation of lipid metabolism, the fatty acid level was measured after standing and forced swimming after administration.

水投与群のコントロールは60分静置では0.87mEq/、
60分遊泳では1.55mEq/となった。プロリン投与群の脂
肪酸値は60分静置では0.87mEq/、60分遊泳では1.76mE
q/、グリシン投与群では60分静置で0.90mEq/、60分
遊泳では1.39mEq/、スレオニン投与群では60分静置で
0.72mEq/、60分遊泳では1.70mEq/、ロイシン投与群
では60分静置で0.84mEq/、60分遊泳では1.46mEq/、
セリン投与群では60分静置で0.83mEq/、60分遊泳では
1.43mEq/となった。20%グルコース投与群は60分静置
では0.64mEq/、60分遊泳では1.05mEq/となった。プ
ロリン及びスレオニン投与群において、コントロールよ
り優位に脂肪酸を遊離した(第1図)。
The control of the water administration group was 0.87 mEq /
It became 1.55mEq / after swimming for 60 minutes. Fatty acid value of the proline administration group was 0.87 mEq / for 60 minutes standing, and 1.76 mE for 60 minutes swimming
q /, in the glycine administration group, 0.90 mEq / in 60 minutes of standing, 1.39 mEq / in 60 minutes of swimming, and in 60 minutes of standing in the threonine administration group
0.72 mEq /, 1.70 mEq / for 60 min swimming, 0.84 mEq / for 60 min standing in leucine administration group, 1.46 mEq / for 60 min swimming,
0.83 mEq / for 60 minutes standing in the serine administration group, 60 minutes swimming
It was 1.43 mEq /. In the 20% glucose-administered group, the concentration was 0.64 mEq / for 60 minutes of standing and 1.05 mEq / for 60 minutes of swimming. In the proline and threonine administration groups, fatty acids were released more significantly than the control (FIG. 1).

(2)脂肪体からの脂肪酸の遊離 従来、アドレナリンは脂肪体中のアドレナリン感受性
リパーゼを活性化し脂肪を分解し、脂肪酸を遊離するこ
とが知られているが本実験においても同様の結果が得ら
れた(第2図)。同じ条件下でアドレナリンの代わりに
プロリンを反応させたところ、コントロールよりも高
い、しかしアドレナリンよりも低い脂肪酸の遊離がみら
れた(第2図)。これらの結果はプロリンが脂肪体から
脂肪酸を遊離させる作用を有することを示している。
(2) Release of Fatty Acid from Fat Body Conventionally, it is known that adrenaline activates adrenaline-sensitive lipase in fat body to decompose fat and release fatty acid, but similar results are obtained in this experiment. (FIG. 2). When proline was reacted in place of adrenaline under the same conditions, release of fatty acids higher than that of the control but lower than that of adrenaline was observed (FIG. 2). These results indicate that proline has the effect of releasing fatty acids from fat bodies.

(3)肝臓から脂肪酸の遊離 プロリンが血中の遊離脂肪酸値を高める作用を示した
ので、肝臓についても脂肪酸の遊離を測定した。肝臓の
スライスをBSAを主成分とするメディウムでプロリン添
加による脂肪酸の遊離をみたところ、経時変化に伴いコ
ントロールに比べて僅かに高い値を示した(第3図)。
メディウムの主成分をBSAからラット血清に変えたとこ
ろ、プロリンの作用は大幅に増加し、顕著な脂肪酸の遊
離が検出された。これは肝組織が血清に対して安定した
活性を保つことと、血清中にプロリンによる脂肪酸の遊
離を促進する効果があることを示唆している。以上の結
果は、プロリンが肝組織から脂肪酸を遊離させることを
示している。そして、プロリンによって増加する血中の
遊離脂肪酸が脂肪体と肝臓から動員されることが明らか
である。
(3) Release of Fatty Acid from Liver Since proline showed an action of increasing the free fatty acid level in blood, the release of fatty acid was also measured for the liver. When the liver slices were examined for the release of fatty acids by the addition of proline with a medium containing BSA as a main component, the values were slightly higher than those of the control with the lapse of time (FIG. 3).
When the main component of the medium was changed from BSA to rat serum, the action of proline was greatly increased, and significant release of fatty acids was detected. This suggests that liver tissue maintains a stable activity with respect to serum and that serum has an effect of promoting fatty acid release by proline. The above results indicate that proline releases fatty acids from liver tissue. And it is clear that blood free fatty acids, which are increased by proline, are mobilized from the fat body and liver.

【図面の簡単な説明】[Brief description of the drawings]

第1図はプロリン及びスレオニンの遊泳時の血中遊離脂
肪酸値への影響を示す。第2図はプロリンが脂肪体から
脂肪酸の遊離に及ぼす影響を示す。第3図は肝臓から脂
肪酸の遊離に及ぼす影響を示す。
FIG. 1 shows the effects of proline and threonine on blood free fatty acid levels during swimming. FIG. 2 shows the effect of proline on the release of fatty acids from fat bodies. FIG. 3 shows the effect on the release of fatty acids from the liver.

───────────────────────────────────────────────────── フロントページの続き (72)発明者 瀧口 好三 東京都千代田区大手町2丁目6番3号 新日本製鐵株式會社内 (56)参考文献 特開 平4−112825(JP,A) (58)調査した分野(Int.Cl.7,DB名) A61K 31/198,31/401 A23L 1/305 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Yoshizo Takiguchi 2-6-3 Otemachi, Chiyoda-ku, Tokyo Nippon Steel Corporation (56) References JP-A-4-112825 (JP, A) (58) Field surveyed (Int. Cl. 7 , DB name) A61K 31/198, 31/401 A23L 1/305

Claims (5)

(57)【特許請求の範囲】(57) [Claims] 【請求項1】プロリン及び/又はスレオニンを含み、メ
チオニンを含まないことを特徴とする脂質代謝調節剤。
1. A lipid metabolism regulator comprising proline and / or threonine but not methionine.
【請求項2】請求項1に記載の脂質代謝調節剤を有効成
分とする血中遊離脂肪酸調節剤。
2. A blood free fatty acid regulator comprising the lipid metabolism regulator according to claim 1 as an active ingredient.
【請求項3】請求項1に記載の脂質代謝調節剤を有効成
分とする脂肪体脂肪代謝調節剤。
3. A fat body fat metabolism regulator comprising the lipid metabolism regulator according to claim 1 as an active ingredient.
【請求項4】請求項1に記載の脂質代謝調節剤を有効成
分とする肝臓脂肪代謝調節剤。
4. A hepatic fat metabolism regulator comprising the lipid metabolism regulator according to claim 1 as an active ingredient.
【請求項5】請求項1に記載の脂質代謝調節剤を有効成
分とする食品。
5. A food comprising the lipid metabolism regulator according to claim 1 as an active ingredient.
JP02240961A 1990-09-11 1990-09-11 Lipid metabolism regulator Expired - Fee Related JP3096052B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP02240961A JP3096052B2 (en) 1990-09-11 1990-09-11 Lipid metabolism regulator

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP02240961A JP3096052B2 (en) 1990-09-11 1990-09-11 Lipid metabolism regulator

Publications (2)

Publication Number Publication Date
JPH04120020A JPH04120020A (en) 1992-04-21
JP3096052B2 true JP3096052B2 (en) 2000-10-10

Family

ID=17067232

Family Applications (1)

Application Number Title Priority Date Filing Date
JP02240961A Expired - Fee Related JP3096052B2 (en) 1990-09-11 1990-09-11 Lipid metabolism regulator

Country Status (1)

Country Link
JP (1) JP3096052B2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3312944B2 (en) * 1993-03-24 2002-08-12 伊藤ハム株式会社 Adipocyte differentiation inhibitory peptide and adipocyte differentiation inhibitor comprising the peptide as active ingredient
KR19990077107A (en) 1996-01-09 1999-10-25 코바야시 순이치 Amino acid composition
JP4742489B2 (en) * 2002-07-08 2011-08-10 大正製薬株式会社 Composition for preventing or improving hypertriglyceridemia
WO2007049818A1 (en) * 2005-10-27 2007-05-03 Ajinomoto Co., Inc. Anti-fatty liver, anti-obesity or hypolipidemic composition

Also Published As

Publication number Publication date
JPH04120020A (en) 1992-04-21

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