JP5922863B2 - Motor function improver - Google Patents
Motor function improver Download PDFInfo
- Publication number
- JP5922863B2 JP5922863B2 JP2010022223A JP2010022223A JP5922863B2 JP 5922863 B2 JP5922863 B2 JP 5922863B2 JP 2010022223 A JP2010022223 A JP 2010022223A JP 2010022223 A JP2010022223 A JP 2010022223A JP 5922863 B2 JP5922863 B2 JP 5922863B2
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- Prior art keywords
- sphingomyelin
- motor function
- muscle
- group
- improving
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Images
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Description
本発明は、運動機能改善効果を発揮する運動機能改善剤に関する。 The present invention relates to a motor function improving agent that exhibits a motor function improving effect.
一般的に、持久力や筋力等の運動機能の向上には、運動トレーニングとバランスの良い栄養補給が重要と考えられている。最近では、運動愛好者やアスリートにおいて、より効率的に筋力向上を図るため、単にトレーニングを行うだけでなく、サプリメント等の栄養補給を併用する試みがなされている(特許文献1)。しかしながら、一部のタンパク質やアミノ酸を過剰摂取した状態でトレーニングを行うことは、腎機能等に悪影響を及ぼす原因になりうることが懸念されている(非特許文献1)。 In general, exercise training and balanced nutrition are considered important for improving motor functions such as endurance and muscle strength. In recent years, exercise enthusiasts and athletes have attempted to use nutrition supplements such as supplements in addition to training to improve muscle strength more efficiently (Patent Document 1). However, there is a concern that training with excessive intake of some proteins and amino acids may cause adverse effects on renal function and the like (Non-patent Document 1).
また、運動愛好者やアスリート以外においても、無理なダイエットよって栄養成分の体内補給が不足して骨格筋の減少や筋力低下を来たすことや、老化や筋肉不使用に伴う筋肉の減弱化によって筋力や持久力をはじめとする運動諸機能が衰退すること、更には、運動機能衰退に伴う疲労が問題視されている。 In addition to exercise enthusiasts and athletes, muscular strength and weakness due to dystrophy and muscle weakness due to aging and muscle non-use, due to insufficient dietary supplementation due to excessive dieting, It is regarded as a problem that various motor functions such as endurance decline, and further, fatigue due to the decline of motor function.
従って、パフォーマンス向上を目指す運動愛好者やアスリートだけでなく、広く一般人において、効率的な運動機能改善技術が望まれている。 Therefore, efficient motor function improvement technology is desired not only for exercise enthusiasts and athletes aiming at performance improvement but also for general people.
斯かる観点から、運動機能改善作用を有する成分の探索が行われ、例えば、茶カテキンによる持久力向上作用(特許文献2)、重合体果実ポリフェノール(特許文献3)やフィチン酸(特許文献4)による筋力向上作用等が報告されている。 From such a viewpoint, a component having a motor function improving action is searched, for example, endurance improving action by tea catechin (Patent Document 2), polymer fruit polyphenol (Patent Document 3) and phytic acid (Patent Document 4). It has been reported that muscle strength is improved.
更に、近年、リン脂質が運動機能に影響を及ぼす可能性が明らかにされつつあり、ホスファチジルコリンによる運動時の乳酸蓄積抑制作用(非特許文献2)や、ホスファチジルセリンによる持久力向上効果(非特許文献3)等が報告されている。 Furthermore, in recent years, it has been clarified that phospholipids may affect motor function. Inhibition of lactic acid accumulation during exercise by phosphatidylcholine (Non-patent Document 2) and endurance improvement effect by phosphatidylserine (Non-patent Document) 3) etc. have been reported.
一方、スフィンゴミエリンは、スフィンゴイド塩基と脂肪酸からなるセラミド骨格にホスホコリンが結合した構造を有する物質であり、体内では脳や神経組織に多く存在することが知られている。近年、その生理機能に関する研究が進められており、消化管の成熟や発達を促進する効果(特許文献5)や学習能向上効果(特許文献6)、シアロムチンの分泌促進効果(特許文献7)等の生理機能を有することが知られている。 On the other hand, sphingomyelin is a substance having a structure in which phosphocholine is bound to a ceramide skeleton composed of a sphingoid base and a fatty acid, and is known to exist in the brain and nerve tissues in the body. In recent years, research on the physiological function has been promoted, such as an effect of promoting the maturation and development of the digestive tract (Patent Document 5), an effect of improving learning ability (Patent Document 6), an effect of promoting the secretion of sialomucin (Patent Document 7) It is known to have the physiological function of
しかしながら、スフィンゴミエリンが、筋力や持久力等の運動機能に対して与える影響については、これまで全く知られていない。 However, the effects of sphingomyelin on motor functions such as muscular strength and endurance have not been known so far.
本発明は、食経験が豊富で安全性が高く、且つ、優れた運動機能改善効果を示す医薬品、医薬部外品、食品及び飼料に配合して用いる素材を提供することに関する。 The present invention relates to providing a material that is used in pharmaceuticals, quasi-drugs, foods, and feeds that have abundant dietary experience, are highly safe, and have excellent motor function improvement effects.
本発明者らは、運動機能改善において有効な成分の探索を行った結果、スフィンゴミエリンに持久力向上作用、筋力向上作用、又は筋力低下抑制作用の効果があり、これが当該作用効果を発揮し得る医薬品、医薬部外品、食品及び飼料の有効成分として有用であることを見出し、本発明を完成させた。 As a result of searching for an effective component in improving the motor function, the present inventors have an effect of improving endurance, improving muscular strength, or suppressing muscular strength in sphingomyelin, and this can exert the effect. The present invention was completed by finding it useful as an active ingredient of pharmaceuticals, quasi drugs, foods and feeds.
すなわち、本発明は、下記(1)〜(4)に係るものである。
(1)スフィンゴミエリンを有効成分とする持久力向上剤。
(2)スフィンゴミエリンを有効成分とする筋力向上剤。
(3)スフィンゴミエリンを有効成分とする筋力低下抑制剤。
(4)スフィンゴミエリンを有効成分とする抗疲労剤。
That is, the present invention relates to the following (1) to (4).
(1) An endurance improver comprising sphingomyelin as an active ingredient.
(2) A muscle strength improver comprising sphingomyelin as an active ingredient.
(3) A muscular strength reduction inhibitor comprising sphingomyelin as an active ingredient.
(4) An anti-fatigue agent containing sphingomyelin as an active ingredient.
本発明の持久力向上剤、抗疲労剤、筋力向上剤、及び筋力低下抑制剤は、高齢者を含む幅広い年齢層において、運動時、及び労働を含む日常の活動時における持久力向上、抗疲労、筋力向上、又は筋力低下抑制のための食品、医薬品、医薬部外品又は飼料に有効成分として配合するための素材として有用である。 The endurance improver, anti-fatigue agent, muscle strength improver, and muscle weakness inhibitor of the present invention are used in a wide range of ages including the elderly to improve endurance and anti-fatigue during daily activities including exercise and work. It is useful as a material for blending as an active ingredient in foods, pharmaceuticals, quasi drugs or feeds for improving muscle strength or suppressing muscle strength reduction.
本発明において用いることができるスフィンゴミエリンは、特に限定されず、化学的に合成されたものや、天然由来のものが挙げられる。
例えば、スフィンゴミエリンの化学的合成法として、1)ホスホロアミダイトを経由する方法(Weis、Chem Phys Lip、3、1999)、2)環状ホスフェートを経由する方法(Dong、Tetrahedron Lett、5291、1991)、あるいは3)環状ホスファイトを経由する方法(Byun、J Org Chem、6495、1994)により、セラミドの1位水酸基にホスホコリンを導入してスフィンゴミエリンに変換する方法が知られている。
また、牛乳から得られる乳脂肪球皮膜成分を、透析、硫安分画、ゲルろ過、等電点沈殿、イオン交換クロマトグラフィー、溶媒分画等の手法により精製(Sanchez−Juanes、Int Dairy J、273、2009)することで、高純度のスフィンゴミエリンを得ることができる。
さらに、スフィンゴミエリンとして市販品を用いることもできる。斯かる市販品としては、日油(株)「牛乳由来スフィンゴミエリン:NM-70」や「卵黄由来スフィンゴミエリン:NM-10」等が挙げられる。
The sphingomyelin that can be used in the present invention is not particularly limited, and examples thereof include chemically synthesized and naturally derived ones.
For example, as a chemical synthesis method of sphingomyelin, 1) a method via phosphoramidite (Weis, Chem Phys Lip, 3, 1999), 2) a method via cyclic phosphate (Dong, Tetrahedron Lett, 5291, 1991) Or 3) A method of converting to sphingomyelin by introducing phosphocholine into the 1-position hydroxyl group of ceramide by a method via a cyclic phosphite (Byun, J Org Chem, 6495, 1994) is known.
Furthermore, milk fat globule membrane components obtained from milk are purified by techniques such as dialysis, ammonium sulfate fractionation, gel filtration, isoelectric precipitation, ion exchange chromatography, solvent fractionation (Sanchez-Juanes, Int Dairy J, 273). , 2009), high-purity sphingomyelin can be obtained.
Furthermore, a commercial item can also be used as sphingomyelin. Examples of such commercially available products include NOF Corporation “milk-derived sphingomyelin: NM-70” and “egg yolk-derived sphingomyelin: NM-10”.
後記実施例に示すように、スフィンゴミエリンは、マウスにおいて、遊泳時間を有意に延長させ、ひらめ筋の筋力を有意に増大させたことから、持久力向上作用、筋力向上作用、及びこれら運動機能の向上に裏打ちされる抗疲労作用を有する。また、スフィンゴミエリンは、筋肉不使用(尾懸垂)処置により筋力が低下するマウスにおいて、筋力の低下を有意に抑制することから、筋力低下抑制作用を有する。
従って、スフィンゴミエリンは、持久力向上剤、筋力向上剤、抗疲労剤、筋力低下抑制剤(以下、「運動機能改善剤等」とする)として、使用することができ、さらにこれらの剤を製造するために使用することができる。このとき、当該運動機能改善剤等には、スフィンゴミエリンを単独で、又はこれ以外に、必要に応じて適宜選択した他のリン脂質、担体、安定化剤等の、配合すべき後述の対象物において許容されるものを使用してもよい。なお、当該製剤は配合すべき対象物に応じて常法により製造することができる。
As shown in the examples below, sphingomyelin significantly increased swimming time and significantly increased the strength of the soleus muscle in mice. Has anti-fatigue action that is backed by improvement. In addition, sphingomyelin significantly suppresses the decrease in muscle strength in a mouse whose muscle strength is reduced by non-muscle use (tail suspension) treatment, and thus has an effect of suppressing muscle strength reduction.
Therefore, sphingomyelin can be used as an endurance improver, muscle strength improver, anti-fatigue agent, muscle strength reduction inhibitor (hereinafter referred to as “motor function improver etc.”), and these agents are also produced. Can be used to At this time, in the motor function improving agent, etc., sphingomyelin alone or in addition to this, other phospholipids, carriers, stabilizers, etc., which are appropriately selected as necessary, should be added as described later. In this case, an acceptable material may be used. In addition, the said formulation can be manufactured by a conventional method according to the target object which should be mix | blended.
そして、本発明の運動機能改善剤等は、持久力向上、筋力向上、抗疲労、筋力低下抑制の各効果を発揮する、ヒト若しくは動物用の医薬品、医薬部外品、食品、又は飼料の有効成分として配合して使用可能である。また、本発明の運動機能改善剤等は、運動不足者や中高年者、ベッドレスト者、或いはアスリートや運動愛好者における持久力向上、筋力向上、抗疲労、筋力低下抑制をコンセプトとし、必要に応じてその旨を表示した食品、機能性食品、病者用食品、特定保健用食品に応用できる。 And the motor function improving agent of the present invention is effective for human or veterinary drugs, quasi-drugs, foods, or feeds that exert the effects of improving endurance, improving muscular strength, anti-fatigue, and suppressing muscular weakness. It can be used as a component. Further, the motor function improving agent of the present invention is based on the concept of improving endurance, improving muscle strength, anti-fatigue, and suppressing muscle weakness in those who are underexercise, middle-aged and elderly, bed rest persons, or athletes and exercise enthusiasts. It can be applied to foods, functional foods, foods for the sick, and foods for specified health use.
本発明の運動機能改善剤等を医薬品、医薬部外品の有効成分として用いた場合の投与形態としては、例えば錠剤、カプセル剤、顆粒剤、散剤、シロップ剤等による経口投与又は注射剤、坐剤、吸入薬、経皮吸収剤、外用剤等による非経口投与が挙げられる。また、このような種々の剤型の製剤を調製するには、本発明の運動機能改善剤等を単独で、又は他の薬学的に許容される賦形剤、結合剤、増量剤、崩壊剤、界面活性剤、滑沢剤、分散剤、緩衝剤、保存剤、嬌味剤、香料、被膜剤、担体、希釈剤、脂肪球皮膜成分以外の薬効成分等を適宜組み合わせて用いることができる。また、これらの投与形態のうち、好ましい形態は経口投与であり、経口用液体製剤を調製する場合は、嬌味剤、緩衝剤、安定化剤等を加えて常法により製造することができる。 Examples of the dosage form when the motor function improving agent of the present invention is used as an active ingredient of pharmaceuticals and quasi-drugs include oral administration or injections such as tablets, capsules, granules, powders, and syrups. Parenteral administration such as an agent, an inhalation agent, a transdermal absorption agent, and an external preparation. In addition, in order to prepare such various dosage forms, the motor function improving agent of the present invention alone or other pharmaceutically acceptable excipients, binders, extenders, disintegrants. , Surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents, medicinal components other than fat globule film components, and the like can be used in appropriate combinations. Of these dosage forms, the preferred form is oral administration, and when an oral liquid preparation is prepared, it can be produced by a conventional method by adding a flavoring agent, a buffering agent, a stabilizer and the like.
本発明の運動機能改善剤等を食品の有効成分として用いた場合の形態としては、牛乳、加工乳、乳飲料、ヨーグルト、清涼飲料水、茶系飲料、コーヒー飲料、果汁飲料、炭酸飲料、ジュース、ゼリー、ウエハース、ビスケット、パン、麺、ソーセージ等の飲食品や栄養食等の各種食品の他、さらには、上述した経口投与製剤と同様の形態(錠剤、カプセル剤、シロップ等)の栄養補給用組成物が挙げられる。
種々の形態の食品を調製するには、本発明の運動機能改善剤等を単独で、又は他の食品材料や、溶剤、軟化剤、油、乳化剤、防腐剤、香科、安定剤、着色剤、酸化防止剤、保湿剤、増粘剤、脂肪球皮膜成分以外の有効成分等を適宜組み合わせて運動機能改善用食品、持久力向上用食品、抗疲労用食品、筋力向上用食品、ペットフード等に配合することが可能である。
また、本発明の運動機能改善剤等は、適当量の栄養補給が困難な高齢者やベッドレスト状態の病者においては、経腸栄養剤等の栄養組成物の形態として配合することが可能である。
本発明の運動機能改善剤等を含む飲料、例えば乳飲料、清涼飲料水、茶系飲料等に対するスフィンゴミエリンの配合量(乾燥物換算)は、通常0.0001〜1.0質量%、さらに0.001〜0.5質量%、特に0.01〜0.2質量%とするのが好ましい。
Examples of the case where the motor function improving agent of the present invention is used as an active ingredient of food include milk, processed milk, milk beverage, yogurt, soft drink, tea-based beverage, coffee beverage, fruit juice beverage, carbonated beverage, juice In addition to foods and drinks such as jelly, wafers, biscuits, bread, noodles, sausages and various foods such as nutritional foods, nutritional supplements in the same form (tablets, capsules, syrups, etc.) as the above-mentioned oral preparations Composition for use.
To prepare various forms of food, the motor function improving agent of the present invention alone, or other food materials, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, colorants , Antioxidants, moisturizers, thickeners, active ingredients other than fat globule film components, etc., in combination as appropriate, food for improving motor function, food for improving endurance, food for anti-fatigue, food for improving muscle strength, pet food, etc. It is possible to blend in.
In addition, the motor function improving agent of the present invention can be blended in the form of a nutritional composition such as an enteral nutrient in elderly people who are difficult to supplement with an appropriate amount of nutrition or in bed rest. is there.
The amount of sphingomyelin in a beverage containing the motor function improving agent of the present invention, for example, a milk beverage, a soft drink, or a tea-based beverage (in terms of dry matter) is usually 0.0001 to 1.0% by mass, and further 0. 0.001 to 0.5% by mass, particularly 0.01 to 0.2% by mass is preferable.
本発明の運動機能改善剤等を含む飲料以外の食品や飼料、また医薬品、例えば錠剤、顆粒剤、カプセル剤等の経口用固形製剤、内服液剤、シロップ剤等の経口用液体製剤の場合には、スフィンゴミエリン(乾燥物換算)は、通常0.002〜50質量%、さらに0.02〜25質量%、特に0.2〜10質量%とするのが好ましい。尚、スフィンゴミエリンは、溶解状態であっても、分散状態であっても良く、その存在状態は問わない。 In the case of foods and feeds other than beverages containing the motor function improving agent of the present invention, and pharmaceuticals such as oral solid preparations such as tablets, granules and capsules, oral liquid preparations such as oral liquids and syrups The sphingomyelin (in terms of dry matter) is usually 0.002 to 50% by mass, more preferably 0.02 to 25% by mass, and particularly preferably 0.2 to 10% by mass. In addition, sphingomyelin may be in a dissolved state or in a dispersed state, and the presence state thereof does not matter.
本発明の運動機能改善剤等の摂取量は、剤形や用途によって異なるが、スフィンゴミエリンは、成人に対して1日あたり、0.1〜1000mg/60kg体重とするのが好ましく、特に1〜250mg/60kg体重、更に5〜100mg/60kg体重となるよう、医薬、飲食品や飼料への配合量等を調整すればよい。 The intake of the motor function improving agent and the like of the present invention varies depending on the dosage form and application, but sphingomyelin is preferably 0.1 to 1000 mg / 60 kg body weight per day for an adult, What is necessary is just to adjust the compounding quantity etc. to a medicine, food-drinks, and a feed so that it may become 250 mg / 60 kg body weight and also 5-100 mg / 60 kg body weight.
以下に本発明の代表的な実施例として、製造例、試験例、及び製剤例を示すが、本発明はこれに限定されるものではない。 As typical examples of the present invention, Production Examples, Test Examples, and Formulation Examples are shown below, but the present invention is not limited thereto.
製造例1: スフィンゴミエリンの調製
ミルクリン脂質PC−500(フォンテラジャパン社より入手、スフィンゴミエリン8.8%含有)201gをとり、アセトン4000mLを加え、氷冷下にホモミキサー(TKオートホモミキサー、特殊機化工業社製)にて分散した。その後、遠心分離により、アセトン可溶画分(中性脂質)を除去した。得られたアセトン不溶画分Aに、クロロホルム800mL、メタノール400mL、水300mLを加え、液々抽出し、クロロホルム層を採取した。クロロホルム層は減圧濃縮し、クロロホルム画分A 154gを得た。
得られたクロロホルム画分Aに、水酸化カリウム28.05gおよびメタノール1000mLを加え、窒素下、37℃で15時間攪拌し、加水分解を行なった。反応終了後、クロロホルム2000mL、水750mLを加え、液々分配し、クロロホルム層を採取した。クロロホルム層は、減圧濃縮した後、酢酸15mLで中和し、クロロホルム400mL、メタノール200mL、水150mLを加え、再度液々抽出を行なった。クロロホルム層を採取し、減圧濃縮し、クロロホルム画分B 90gを得た。
得られたクロロホルム画分Bに、アセトン1200mLを加え、氷冷下にホモミキサー(TKオートホモミキサー、特殊機化工業社製)にて分散した。その後、遠心分離により、アセトン可溶画分(遊離脂肪酸)を除去した。同様の操作をさらに2回繰り返し、アセトン不溶画分B 44gを得た。
得られたアセトン不溶画分Bに、ヘキサン400mL、メタノール400mL、水150mL、28%アンモニア水50mLを加え、液々抽出を行い、ヘキサン層を採取した。ヘキサン層には、さらにメタノール400mL、水150mL、28%アンモニア水50mLを加え、洗浄した。得られたヘキサン層は、減圧濃縮し、ヘキサン画分27gを得た。
得られたヘキサン画分のうち22gを用い、シリカゲルカラムクロマトグラフィーで精製を行った。すなわち、シリカゲル(シリカゲル60、Merck社製)1kgに、ヘキサン画分のクロロホルム溶液を吸着させた後、クロロホルム/メタノール混合溶媒で供雑物を溶出した後、メタノール21Lで溶出し、精製スフィンゴミエリン画分16g(収率:8%)を得た。
Production Example 1: Preparation of sphingomyelin Take 201 g of milk phospholipid PC-500 (obtained from Fontera Japan, containing 8.8% sphingomyelin), add 4000 mL of acetone, and add a homomixer (TK auto homomixer, special under ice cooling) Dispersed by Kika Kogyo Co., Ltd. Thereafter, the acetone-soluble fraction (neutral lipid) was removed by centrifugation. To the obtained acetone insoluble fraction A, chloroform (800 mL), methanol (400 mL), and water (300 mL) were added, followed by liquid-liquid extraction, and a chloroform layer was collected. The chloroform layer was concentrated under reduced pressure to obtain 154 g of a chloroform fraction A.
To the obtained chloroform fraction A, 28.05 g of potassium hydroxide and 1000 mL of methanol were added, and the mixture was stirred under nitrogen at 37 ° C. for 15 hours for hydrolysis. After completion of the reaction, 2000 mL of chloroform and 750 mL of water were added, and the liquid was partitioned, and the chloroform layer was collected. The chloroform layer was concentrated under reduced pressure and then neutralized with 15 mL of acetic acid, and 400 mL of chloroform, 200 mL of methanol, and 150 mL of water were added, and liquid-liquid extraction was performed again. The chloroform layer was collected and concentrated under reduced pressure to obtain 90 g of chloroform fraction B.
To the obtained chloroform fraction B, 1200 mL of acetone was added, and the mixture was dispersed with a homomixer (TK auto homomixer, manufactured by Tokushu Kika Kogyo Co., Ltd.) under ice cooling. Thereafter, the acetone-soluble fraction (free fatty acid) was removed by centrifugation. The same operation was further repeated twice to obtain 44 g of acetone insoluble fraction B.
To the obtained acetone insoluble fraction B, 400 mL of hexane, 400 mL of methanol, 150 mL of water, and 50 mL of 28% ammonia water were added, liquid-liquid extraction was performed, and a hexane layer was collected. The hexane layer was further washed with 400 mL of methanol, 150 mL of water, and 50 mL of 28% aqueous ammonia. The obtained hexane layer was concentrated under reduced pressure to obtain 27 g of a hexane fraction.
Purification was performed by silica gel column chromatography using 22 g of the obtained hexane fraction. That is, after adsorbing the chloroform solution of the hexane fraction to 1 kg of silica gel (
試験例1: スフィンゴミエリンの持久力向上、筋力向上効果
<方法> スフィンゴミエリンは、上記製造例1の方法に従い、ミルクリン脂質(PC−500、フォンテラジャパン)より抽出した。
1週間の予備飼育後、9週齢の雄性BALB/cマウス(日本チャールスリバー)を体重と遊泳持久力〔後記方法により、マウス用流水プール(京大松元式運動量測定流水槽:縦×横×深さ 90×45×45cm、水深38cm、水温34℃(Matsumoto、J Appl Physiol.81:1843−1849,1996))を用いて限界遊泳時間を測定〕が等しくなるように3群(Cont群、Ex群、SPM群)に分けた(各群8匹)。
群分け後、Cont群およびEx群のマウスにはコントロール食(10%脂質、20%カゼイン、55.5%ポテトスターチ、8.1%セルロース、0.2%メチオニン、2.2%ビタミン(商品名:ビタミン混合AIN−76、オリエンタルバイオサービス)、4%ミネラル(商品名:ミネラル混合AIN−76、オリエンタルバイオサービス)を、また、SPM群のマウスには、製造例1によるスフィンゴミエリンを含む試験食(10%脂質、20%カゼイン、55.25%ポテトスターチ、8.1%セルロース、0.2%メチオニン、2.2%ビタミン、4%ミネラル、0.25%スフィンゴミエリン)を、13週間給餌した。
給餌期間中、Ex群およびSPM群のマウスにおいては、マウス用流水プールを用いて限界遊泳時間を週に1度測定した。限界遊泳時間は、遊泳開始から、7L/minの流量でマウスが呼吸のために7秒間水面に浮上できなくなるまでの時間とした。尚、この間、マウスを運動に慣らすため、週2回の遊泳トレーニング(6L/min、30min)を施した。
13週間飼育後、解剖に供し、摘出ひらめ筋及び長指伸筋の筋力を測定した。摘出筋の筋力測定は、Cannonらの方法(Biomed Sci Instrum、2005)に準じて行った。すなわち、マウスよりひらめ筋及び長指伸筋を摘出、縫合糸(#5−0 silk)を用いてトランスデューサー(WPI、FORT100)に固定し、37℃のKrebs溶液中(95%−O2、5%−CO2通気)に浸漬した。2本のプラチナ電極より、40Hz、330ms、10Vの電気刺激を施し、トランスデューサーより得られるシグナルを筋力(g/mg muscle)として測定した。
Test Example 1: Endurance improvement and muscle strength improvement effect of sphingomyelin <Method> Sphingomyelin was extracted from milk phospholipid (PC-500, Fontera Japan) according to the method of Production Example 1 above.
After 1 week of pre-breeding, 9-week-old male BALB / c mice (Charles River Japan) were tested for body weight and swimming endurance. Depth: 90 × 45 × 45 cm, water depth: 38 cm, water temperature: 34 ° C. (Matsumoto, J Appl Physiol. 81: 1843-1849, 1996)). Ex group, SPM group) (8 animals in each group).
After grouping, the Cont and Ex mice had a control diet (10% lipid, 20% casein, 55.5% potato starch, 8.1% cellulose, 0.2% methionine, 2.2% vitamin (commodity Name: Vitamin-mixed AIN-76, Oriental Bioservice), 4% mineral (trade name: Mineral-mixed AIN-76, Oriental Bioservice), and mice in SPM group containing sphingomyelin according to Production Example 1 Diet (10% lipid, 20% casein, 55.25% potato starch, 8.1% cellulose, 0.2% methionine, 2.2% vitamin, 4% mineral, 0.25% sphingomyelin) for 13 weeks I was fed.
During the feeding period, in the Ex group and SPM group mice, the limit swimming time was measured once a week using a running water pool for mice. The limit swimming time was defined as the time from the start of swimming until the mouse was unable to rise to the surface for 7 seconds due to breathing at a flow rate of 7 L / min. During this time, swimming training (6 L / min, 30 min) was performed twice a week to acclimate the mouse to exercise.
After rearing for 13 weeks, it was subjected to dissection and the muscle strength of the extracted soleus and long extensor muscles was measured. The muscle strength of the isolated muscle was measured according to the method of Cannon et al. (Biomed Sci Instrument, 2005). Specifically, the soleus and long finger extensors were removed from the mouse, fixed to the transducer (WPI, FORT100) using a suture (# 5-0 silk), and in a Krebs solution at 37 ° C. (95% -O 2 , 5% -CO 2 aeration). Electrical stimulation of 40 Hz, 330 ms, and 10 V was applied from two platinum electrodes, and the signal obtained from the transducer was measured as muscle strength (g / mg muscle).
<結果> 図1に、スフィンゴミエリンが遊泳持久力に及ぼす影響を示す。スフィンゴミエリン投与マウスでは、投与開始後早期から持久力の向上が認められ、投与開始5週後以降は、Cont群に対して有意な持久力向上を認めた。また、図2に、スフィンゴミエリンが筋力向上に及ぼす影響について示す。スフィンゴミエリン投与マウスでは、ひらめ筋及び長指伸筋の筋力が有意な高値を示した。
持久力や筋力は身体を動かすための代表的な運動機能であり、また、運動機能が向上することにより、身体疲労に対する耐性が向上すると考えられる。したがって本試験において、スフィンゴミエリンは、運動持久力及び摘出筋の筋力を増加させたことから、持久力向上、筋力向上、および抗疲労に有効であることが明らかとなった。
<Results> FIG. 1 shows the effect of sphingomyelin on swimming endurance. In sphingomyelin-administered mice, an improvement in endurance was observed early after the start of administration, and after 5 weeks from the start of administration, a significant improvement in endurance was observed relative to the Cont group. FIG. 2 shows the effect of sphingomyelin on muscle strength improvement. In sphingomyelin-treated mice, the muscle strength of the soleus and long extensor muscles showed significantly high values.
Endurance and muscle strength are typical motor functions for moving the body, and it is considered that resistance to physical fatigue is improved by improving motor functions. Therefore, in this test, sphingomyelin increased the exercise endurance and the muscle strength of the extracted muscle, and it was revealed that sphingomyelin is effective in improving endurance, improving muscle strength, and anti-fatigue.
試験例2: スフィンゴミエリンの筋力低下抑制効果
<方法> 雄性BALB/cマウス(9週齢)を1週間予備飼育し、体重を基準に3群(Normal群、Cont群、SPM群)に群分けした(各群n=8)。
群分け後、Normal群およびCont群のマウスには、コントロール食(10%脂質、20%カゼイン、55.5%ポテトスターチ、8.1%セルロース、0.2%メチオニン、2.2%ビタミン、4%ミネラル)を、また、SPM群のマウスには、製造例1によるスフィンゴミエリンを含む試験食(10%脂質、20%カゼイン、55.25%ポテトスターチ、8.1%セルロース、0.2%メチオニン、2.2%ビタミン、4%ミネラル、0.25%スフィンゴミエリン)を、2週間給餌した。
試験飼料を2週間給餌した後、Cont群及びSPM群のマウスに尾懸垂処置を施し、後肢筋群(ひらめ筋等)への重力荷重を排した。荷重が減じた筋は廃用性筋萎縮を呈し、筋質量や筋力が低下する。Normal群のマウスには、尾懸垂処置を施さなかった。
尾懸垂処置7日後、マウスを解剖に供し、摘出ひらめ筋の筋力を測定した。摘出筋の筋力測定は、試験例1と同様の方法で行った。
Test Example 2: Sphingomyelin suppresses muscle weakness <Method> Male BALB / c mice (9 weeks old) are preliminarily raised for 1 week and divided into 3 groups (Normal group, Cont group, SPM group) based on body weight. (Each group n = 8).
After grouping, the Normal and Cont mice had a control diet (10% lipid, 20% casein, 55.5% potato starch, 8.1% cellulose, 0.2% methionine, 2.2% vitamins, 4% minerals), and mice in the SPM group also had a test meal (10% lipid, 20% casein, 55.25% potato starch, 8.1% cellulose, 0.2%) containing sphingomyelin according to Production Example 1. % Methionine, 2.2% vitamin, 4% mineral, 0.25% sphingomyelin) for 2 weeks.
After feeding the test diet for 2 weeks, the mice in the Cont group and the SPM group were subjected to tail suspension treatment, and the gravity load on the hindlimb muscle group (such as the soleus muscle) was eliminated. Muscles with reduced load exhibit disuse muscle atrophy and muscle mass and strength decrease. The normal group of mice received no tail suspension treatment.
Seven days after tail suspension treatment, the mice were subjected to dissection, and the muscle strength of the extracted soleus muscle was measured. The muscle strength of the extracted muscle was measured by the same method as in Test Example 1.
<結果> 図3に、摘出ひらめ筋の筋力を示す。尾懸垂処置に伴い、Cont群及びSPM群の筋力は、有意に低下した。一方、SPM群の筋力は、Cont群に対して有意な高値を示した。したがって本結果より、スフィンゴミエリンによる筋力低下抑制効果が明らかとなった。 <Results> FIG. 3 shows the strength of the extracted soleus muscle. With tail suspension treatment, the muscle strength of the Cont group and the SPM group significantly decreased. On the other hand, the muscular strength of the SPM group was significantly higher than that of the Cont group. Therefore, from these results, the effect of sphingomyelin in suppressing muscle weakness was clarified.
製剤例
処方例1 運動機能改善用ゼリー食品
カラギーナンとローカストビーンガムの混合ゲル化剤0.65%、グレープフルーツの50%の濃縮果汁5.0%、クエン酸0.05%、ビタミンC0.05%、およびスフィンゴミエリン(日油社製 NM-70)を0.1%混合し、これに水を加えて100%に調整し、65℃で溶解した。更に少量のグレープフルーツフレーバーを添加して85℃で5分間保持して殺菌処理後、100mLの容器に分注した。8時間静置して徐冷しながら5℃に冷却して、ゲル化させ、口に含んだ時に口溶け性が良好で、果実風味を有し食感良好なスフィンゴミエリンを含有するゼリー食品を得た。
処方例2 運動機能改善用錠剤
アスコルビン酸180mg、クエン酸50mg、アスパルテーム12mg、ステアリン酸マグネシウム24mg、結晶セルロース120mg、乳糖594mg、およびスフィンゴミエリン(日油社製 NM-10)120mgからなる処方(1日量2200mg)で、日本薬局方(製剤総則「錠剤」)に準じて錠剤を製造し、スフィンゴミエリンを含有する錠剤を得た。
Formulation Example 2 Tablet for improving motor function Formulation consisting of 180 mg of ascorbic acid, 50 mg of citric acid, 12 mg of aspartame, 24 mg of magnesium stearate, 120 mg of crystalline cellulose, 594 mg of lactose, and 120 mg of sphingomyelin (NM-10, manufactured by NOF Corporation) 2200 mg), a tablet was produced according to the Japanese Pharmacopoeia (general general rule “tablet”) to obtain a tablet containing sphingomyelin.
処方例3 運動機能改善用ビタミン内服液
タウリン800mg、ショ糖2000mg、カラメル50mg、安息香酸ナトリウム30mg、ビタミンB1硝酸塩5mg、ビタミンB2 20mg、ビタミンB6 20mg、ビタミンC 2000mg、ビタミンE 100mg、ビタミンD3 2000IU、ニコチン酸アミド20mg、精製スフィンゴミエリン(製造例1)50mg、ロイシン200mg、イソロイシン100mg、バリン100mgを適量の精製水に加えて溶解し、リン酸水溶液でpH3に調節した後、更に精製水を加えて全量を50mLとした。これを80℃で30分滅菌して、スフィンゴミエリン及びアミノ酸類を含有する運動機能改善用飲料を得た。
Formulation Example 3 Vitamin oral solution for improving motor function Taurine 800 mg, sucrose 2000 mg,
処方例4 運動機能改善用乳系飲料
乳カゼイン3.4g、分離大豆タンパク質1.67g、デキストリン14.86g、ショ糖1.3g、大豆油1.75g、シソ油0.18g、大豆リン脂質0.14g、グリセリン脂肪酸エステル0.07g、ミネラル類0.60g、ビタミン類0.06g、精製スフィンゴミエリン(製造例1)100mgに精製水を加え、常法に従い、レトルト殺菌し、スフィンゴミエリンを含有する運動機能改善用飲料(100mL)を得た。
Formulation Example 4 Milk Beverage for Improvement of Motor Function Milk Casein 3.4g, Isolated Soy Protein 1.67g, Dextrin 14.86g, Sucrose 1.3g, Soybean Oil 1.75g, Perilla Oil 0.18g,
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