JP6824506B2 - Lipid composition - Google Patents
Lipid composition Download PDFInfo
- Publication number
- JP6824506B2 JP6824506B2 JP2016042660A JP2016042660A JP6824506B2 JP 6824506 B2 JP6824506 B2 JP 6824506B2 JP 2016042660 A JP2016042660 A JP 2016042660A JP 2016042660 A JP2016042660 A JP 2016042660A JP 6824506 B2 JP6824506 B2 JP 6824506B2
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- JP
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- Prior art keywords
- residues
- phospholipids
- epa
- dha
- phospholipid
- Prior art date
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- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims description 75
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Description
本発明は、脂質組成物に関する。本発明の脂質組成物によれば、生体内のプラスマローゲンを顕著に増加させることができる。 The present invention relates to lipid compositions. According to the lipid composition of the present invention, plasmalogen in vivo can be significantly increased.
プラスマローゲンとはｓｎ−１位にビニルエーテル結合による炭化水素鎖を持ち、ｓｎ−２位には脂肪酸が結合しているグリセロリン脂質のサブクラスであり、アルケニルアシル型リン脂質ともいう。動物では脳、心臓、脾臓などに比較的多く含まれる。極性基はエタノールアミンとコリンがほとんどで、ｓｎ−２位にはヒトの場合、アラキドン酸やドコサヘキサエン酸等の多価不飽和脂肪酸に富むこと等が知られている。
プラスマローゲンの機能は未だ不明な点が多いが、プラスマローゲン合成部位であるペルオキシソームに障害を持つペルオキシソーム病では、精神遅滞を初めとする種々の重篤な症状を呈することから、プラスマローゲンが正常な細胞や生体の機能維持に重要な役割を果たしていることが推測される。
また、このような先天的な異常がなくても、血液又はリンパ液中のプラスマローゲンが加齢と共に減少すること、アルツハイマー病患者では脳のプラスマローゲンが減少していること、プラスマローゲンがＬＤＬコレステロールの酸化を抑制すること等、プラスマローゲンが加齢や酸化ストレスが関与する疾病と関係していることが明らかになりつつある（非特許文献１及び非特許文献２）。
Plasmalogen is a subclass of glycerophospholipids having a hydrocarbon chain formed by a vinyl ether bond at the sn-1 position and a fatty acid bonded at the sn-2 position, and is also called an alkenylacyl phospholipid. In animals, it is relatively abundant in the brain, heart, spleen, etc. Most of the polar groups are ethanolamine and choline, and it is known that humans are rich in polyunsaturated fatty acids such as arachidonic acid and docosahexaenoic acid at the sn-2 position.
The function of plasmalogen is still unclear, but plasmalogen is normal because peroxisome disease, which is a disorder of peroxisome, which is a site for plasmalogen synthesis, presents with various serious symptoms including mental retardation. It is presumed that it plays an important role in maintaining the functions of cells and living organisms.
In addition, even in the absence of such congenital abnormalities, plasmalogen in blood or lymph decreases with age, plasmalogen in the brain decreases in patients with Alzheimer's disease, and plasmalogen is LDL cholesterol. It is becoming clear that plasmalogen is associated with diseases associated with aging and oxidative stress, such as suppressing oxidation (Non-Patent Document 1 and Non-Patent Document 2).
つまり、生体内のプラスマローゲンが減少することがさまざまな疾患の原因となっていると考えられている。従って、生体内のプラスマローゲン量を増加させることは種々の疾病の改善、予防に有効と思われることから、血液又はリンパ液中のプラスマローゲンを増加させる方法が求められている。
特に飲食品や経口医薬品は、継続的に且つ簡易に摂取可能なことから、経口摂取により血液又はリンパ液中のプラスマローゲン含量を増加させることができるプラスマローゲン増加剤が提案されている。
In other words, it is thought that the decrease in plasmalogen in the living body is the cause of various diseases. Therefore, since increasing the amount of plasmalogen in the living body seems to be effective for improving and preventing various diseases, a method for increasing the amount of plasmalogen in blood or lymph is required.
In particular, since foods and drinks and oral drugs can be continuously and easily ingested, a plasmalogen increasing agent capable of increasing the plasmalogen content in blood or lymph by oral ingestion has been proposed.
現在までに報告されている生体内でプラスマローゲンを増加させる効果のあるものとして、例えば、アルキルグリセロール（非特許文献３及び特許文献１）、プラスマローゲンに富む牛脳リン脂質（非特許文献４）、イノシトール（特許文献２）、コリン型プラスマローゲン（特許文献３）、炭素数１６以上の直鎖モノ不飽和脂肪酸化合物（特許文献４）等が開示されている。
しかし、アルキルグリセロール、イノシトール、炭素数１６以上の直鎖モノ不飽和脂肪酸化合物摂取によるプラスマローゲン増加は１．５倍程度と弱かった。また、牛脳リン脂質摂取ではプラスマローゲンやコリン型プラスマローゲンの摂取では数倍に増加するが、これらは風味が悪く飲食品に対し多量に添加することが困難であることに加え、酸化安定性が低いため長期保存の飲食品、特に常温保管の飲食品における保存性の低さが問題であった。
Examples of substances having an effect of increasing plasmalogen in vivo reported to date include alkyl glycerol (Non-Patent Document 3 and Patent Document 1) and plasmalogen-rich bovine brain phospholipid (Non-Patent Document 4). , Inositol (Patent Document 2), choline-type plasmalogen (Patent Document 3), linear monounsaturated fatty acid compounds having 16 or more carbon atoms (Patent Document 4), and the like are disclosed.
However, the increase in plasmalogen due to the intake of alkylglycerol, inositol, and a linear monounsaturated fatty acid compound having 16 or more carbon atoms was as weak as about 1.5 times. Ingestion of bovine cerebral phospholipids increases plasmalogen and choline-type plasmalogen several times, but these have a bad flavor and are difficult to add to foods and drinks in large amounts, and are oxidatively stable. Therefore, there was a problem of low storage stability in foods and drinks stored for a long period of time, especially foods and drinks stored at room temperature.
本発明者らは、１−アルキルエーテル型リン脂質を投与することによって、生体内のプラスマローゲンが増加することを開示している（特許文献５，６）。しかし、１−アルキルエーテル型リン脂質は腸管吸収率が低く、生体内のプラスマローゲンを増加させる効果に改善の余地があった。
従って、本発明の目的は、保存性が良好であり、体内のプラスマローゲン量を効率的に増加させる脂質組成物を提供することにある。
The present inventors have disclosed that administration of 1-alkyl ether type phospholipids increases plasmalogen in vivo (Patent Documents 5 and 6). However, the 1-alkyl ether type phospholipid has a low intestinal absorption rate, and there is room for improvement in the effect of increasing plasmalogen in the living body.
Therefore, an object of the present invention is to provide a lipid composition having good storage stability and efficiently increasing the amount of plasmalogen in the body.
本発明者は、体内のプラスマローゲンを効率的に増加させることについて、鋭意研究した結果、驚くべきことに、脂質を構成する脂肪酸残基のうち、リン脂質由来のエイコサペンタエン酸（以下、ＥＰＡということもある）残基とドコサヘキサエン酸（以下、ＤＨＡということもある）残基の合計と、リン脂質以外に由来するＥＰＡ残基とＤＨＡ残基の合計が特定の条件を満たす脂質組成物を摂取することにより、体内のプラスマローゲンが効率的に増加することを見出した。
本発明は、こうした知見に基づくものである。
従って、本発明は、
［１］１−アルキルエーテル型リン脂質を含有し、そして（ａ）脂質を構成する脂肪酸残基のうち、リン脂質由来のエイコサペンタエン酸（ＥＰＡ）残基及びドコサヘキサエン酸（ＤＨＡ）残基の合計量１質量部に対して、リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１．８質量部以下であることを特徴とする脂質組成物、
［２］（ｂ）脂質を構成する脂肪酸残基のうち、リン脂質以外に由来するＤＨＡ残基及びＥＰＡ残基の合計量と、リン脂質以外に由来するω６脂肪酸残基の量との比率（［ＤＨＡ＋ＥＰＡ］／ω６）が０．１４０以下である、［１］に記載の脂質組成物、
［３］（ｃ）リン脂質を構成する脂肪酸残基のうち、１−アルキルエーテル型リン脂質由来のＥＰＡ残基及びＤＨＡ残基の合計量１質量部に対して、１−アルキルエーテル型リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１０．０質量部以下である、［１］又は［２］に記載の脂質組成物、
［４］［１］〜［３］のいずれかに記載の脂質組成物を含有するプラスマローゲン増加用飲食品、
［５］カプセル剤である［４］に記載の飲食品、
［６］［１］〜［３］のいずれかに記載の脂質組成物を含有するプラスマローゲン増加用医薬組成物、
［７］カプセル剤である［６］に記載の医薬組成物、及び
［８］カプセル剤で投与される、［６］又は［７］に記載の医薬組成物、
に関する。
As a result of diligent research on the efficient increase of plasmalogen in the body, the present inventor surprisingly found that among the fatty acid residues constituting lipids, phospholipid-derived eicosapentaenoic acid (hereinafter referred to as EPA). Ingest a lipid composition in which the sum of (sometimes) residues and docosahexaenoic acid (hereinafter sometimes referred to as DHA) residues and the total of EPA residues and DHA residues derived from other than phospholipids satisfy specific conditions. It was found that by doing so, plasmalogen in the body is efficiently increased.
The present invention is based on these findings.
Therefore, the present invention
[1] The total of eicosapentaenoic acid (EPA) residues and docosahexaenoic acid (DHA) residues derived from phospholipids among the fatty acid residues containing 1-alkyl ether type phospholipids and (a) constituting the lipids. A lipid composition characterized in that the total amount of EPA residues and DHA residues derived from other than phospholipids is 1.8 parts by mass or less with respect to 1 part by mass of the amount.
[2] (b) Ratio of the total amount of DHA residues and EPA residues derived from other than phospholipids to the amount of ω6 fatty acid residues derived from other than phospholipids among the fatty acid residues constituting the lipid ( The lipid composition according to [1], wherein [DHA + EPA] / ω6) is 0.140 or less.
[3] (c) Of the fatty acid residues constituting the phospholipid, the 1-alkyl ether type phospholipid is based on 1 part by mass of the total amount of the EPA residue and the DHA residue derived from the 1-alkyl ether type phospholipid. The lipid composition according to [1] or [2], wherein the total amount of EPA residues and DHA residues derived from the above is 10.0 parts by mass or less.
[4] A food or drink for increasing plasmalogen containing the lipid composition according to any one of [1] to [3].
[5] The food or drink according to [4], which is a capsule.
[6] A pharmaceutical composition for increasing plasmalogen containing the lipid composition according to any one of [1] to [3].
[7] The pharmaceutical composition according to [6], which is a capsule, and the pharmaceutical composition according to [6] or [7], which is administered as a capsule.
Regarding.
本発明の脂質組成物によれば、体内のプラスマローゲン量を効率的に増加させることができる。更に、本発明による組成物は保存安定性に優れており、容易に飲食品に混合できる。 According to the lipid composition of the present invention, the amount of plasmalogen in the body can be efficiently increased. Further, the composition according to the present invention has excellent storage stability and can be easily mixed with foods and drinks.
〔１〕脂質組成物
本発明の脂質組成物は、１−アルキルエーテル型リン脂質を含有し、そして（ａ）脂質を構成する脂肪酸残基のうち、リン脂質由来のエイコサペンタエン酸（ＥＰＡ）残基及びドコサヘキサエン酸（ＤＨＡ）残基の合計量１質量部に対して、リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１．８質量部以下である。本発明の脂質組成物は、好ましくは（ｂ）脂質を構成する脂肪酸残基のうち、リン脂質以外に由来するＤＨＡ残基及びＥＰＡ残基の合計量と、リン脂質以外に由来するω６脂肪酸残基の量との比率（［ＤＨＡ＋ＥＰＡ］／ω６）が０．１４０以下である。本発明の脂質組成物は、より好ましくは、（ｃ）リン脂質を構成する脂肪酸残基のうち、１−アルキルエーテル型リン脂質由来のＥＰＡ残基及びＤＨＡ残基の合計量１質量部に対して、１−アルキルエーテル型リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１０．０質量部以下である。
[1] Lipid composition The lipid composition of the present invention contains 1-alkyl ether type phospholipid, and (a) phospholipid-derived eicosapentaenoic acid (EPA) residue among the fatty acid residues constituting the lipid. The total amount of EPA residues and DHA residues derived from other than phospholipids is 1.8 parts by mass or less with respect to 1 part by mass of the total amount of groups and docosahexaenoic acid (DHA) residues. The lipid composition of the present invention preferably comprises (b) the total amount of DHA residues and EPA residues derived from other than phospholipids among the fatty acid residues constituting the lipid, and the ω6 fatty acid residue derived from other than phospholipids. The ratio to the amount of groups ([DHA + EPA] / ω6) is 0.140 or less. The lipid composition of the present invention is more preferably (c) based on 1 part by mass of the total amount of EPA residues and DHA residues derived from 1-alkyl ether type phospholipid among the fatty acid residues constituting the phospholipid. The total amount of EPA residues and DHA residues derived from other than 1-alkyl ether type phospholipids is 10.0 parts by mass or less.
（ａ）エイコサペンタエン酸（ＥＰＡ）残基及びドコサヘキサエン酸（ＤＨＡ）残基の比率
本発明の脂質組成物においては、（ａ）脂質を構成する脂肪酸残基のうち、リン脂質由来のエイコサペンタエン酸（以下、ＥＰＡと称することがある）残基及びドコサヘキサエン酸（以下、ＤＨＡと称することがある）残基の合計量１質量部に対して、リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１．８質量部以下である。
本発明において、エイコサペンタエン酸（ＥＰＡ）残基及びドコサヘキサエン酸（ＤＨＡ）残基等の脂肪酸残基は、リン脂質の場合、ｓｎ−１位又はｓｎ−２位に隣接した酸素に結合している基を表し、リン脂質以外の場合、例えば中性脂質では、ｓｎ−１位、ｓｎ−２位又はｓｎ−３位に隣接した酸素に結合している基を表している。中性脂質には、グリセリンに１つの脂肪酸が結合したモノグリセリド、グリセリンに２つの脂肪酸が結合したジグリセリド、及びグリセリンに３つの脂肪酸が結合したトリグリセリドが含まれるが、動物ではトリグリセリドが多い。なお、本明細書においては特に記載のない場合は、上記脂肪酸残基は脂肪酸から−ＯＨを除いた基を意味するものとする。
本発明の脂質組成物においては、リン脂質由来のＥＰＡ残基及びＤＨＡ残基の合計量１質量部に対して、リン脂質以外に由来するＥＰＡ残基とＤＨＡ残基の合計が１．８質量部以下であり、好ましくは１．５質量部以下であり、より好ましくは１．２質量部以下であり、最も好ましくは１．０質量部以下である。リン脂質由来のＥＰＡ残基とＤＨＡ残基の合計１質量部に対して、リン脂質以外に由来するＥＰＡ残基とＤＨＡ残基の合計が１．８質量部よりも多いと１−アルキルエーテル型リン脂質の吸収が抑制され、本発明の効果が得られない。リン脂質由来のＥＰＡ残基とＤＨＡ残基の合計１質量部に対してリン脂質以外に由来するＥＰＡ残基とＤＨＡ残基の合計が１．８質量部以下であることによって、プラスマローゲンが増加する機構は明確ではないが、脂質を構成する脂肪酸残基としてＥＰＡとＤＨＡが吸収される際にリン脂質由来のＥＰＡ及びＤＨＡと、非リン脂質由来のＥＰＡ及びＤＨＡとが競合するが、前記条件を満たすことで、リン脂質由来のＥＰＡ残基とＤＨＡ残基が優勢となると推定される。しかしながら、この推定により、本願発明が限定されるものではない。
(A) Ratio of eicosapentaenoic acid (EPA) residue and docosahexaenoic acid (DHA) residue In the lipid composition of the present invention, (a) of the fatty acid residues constituting the lipid, eicosapentaenoic acid derived from phospholipaenoic acid. EPA residues and DHA residues derived from other than phospholipids with respect to 1 part by mass of the total amount of residues (hereinafter sometimes referred to as EPA) and docosahexaenoic acid (hereinafter sometimes referred to as DHA) residues. The total amount of is 1.8 parts by mass or less.
In the present invention, fatty acid residues such as eicosapentaenoic acid (EPA) residue and docosahexaenoic acid (DHA) residue are bound to oxygen adjacent to sn-1 position or sn-2 position in the case of phospholipids. It represents a group, and in cases other than phospholipids, for example, in neutral lipids, it represents a group bound to oxygen adjacent to the sn-1, sn-2, or sn-3 position. Neutral lipids include monoglyceride in which one fatty acid is bound to glycerin, diglyceride in which two fatty acids are bound to glycerin, and triglyceride in which three fatty acids are bound to glycerin, but triglyceride is abundant in animals. Unless otherwise specified in the present specification, the fatty acid residue means a group obtained by removing -OH from a fatty acid.
In the lipid composition of the present invention, the total amount of EPA residues and DHA residues derived from other than phospholipids is 1.8 mass by mass with respect to 1 part by mass of the total amount of EPA residues and DHA residues derived from phospholipids. It is 5 parts or less, preferably 1.5 parts by mass or less, more preferably 1.2 parts by mass or less, and most preferably 1.0 part by mass or less. 1-alkyl ether type when the total of EPA residues and DHA residues derived from other than phospholipids is more than 1.8 parts by mass with respect to the total of 1 part by mass of EPA residues and DHA residues derived from phospholipids. The absorption of phospholipids is suppressed, and the effects of the present invention cannot be obtained. Plasmalogen increases when the total of EPA residues and DHA residues derived from other than phospholipids is 1.8 parts by mass or less with respect to the total of 1 part by mass of EPA residues and DHA residues derived from phospholipids. Although the mechanism of this is not clear, EPA and DHA derived from phospholipids and EPA and DHA derived from non-phospholipids compete with each other when EPA and DHA are absorbed as fatty acid residues constituting the lipid. It is presumed that phospholipid-derived EPA residues and DHA residues become predominant when the condition is satisfied. However, this estimation does not limit the invention of the present application.
（ｂ）リン脂質以外に由来するＤＨＡ残基及びＥＰＡ残基とω６脂肪酸残基との比率
本発明の脂質組成物においては、限定されるものではないが、好ましくは（ｂ）脂質を構成する脂肪酸残基のうち、リン脂質以外に由来するＤＨＡ残基及びＥＰＡ残基の合計量と、リン脂質以外に由来するω６脂肪酸残基の量との比率（［ＤＨＡ＋ＥＰＡ］／ω６）が０．１４０以下である。
ω６脂肪酸は、炭素と炭素の二重結合がω−6位（脂肪酸のメチル末端から6番目の結合）に存在する不飽和脂肪酸である。具体的には、リノール酸、γ−リノレン酸、及びアラキドン酸等を挙げることでき、ベニバナ油、グレープシードオイル、ヒマワリ油、コーン油、大豆油、又はゴマ油などに多く含まれている。
リン脂質以外のＤＨＡ残基及びＥＰＡ残基とω６脂肪酸残基との比率は、０．１４０以下であり、好ましくは０．１２０以下であり、より好ましいは０．１００以下であり、更に好ましくは０．８０以下であり、最も好ましくは０．０６０以下である。リン脂質以外に由来するＤＨＡ残基及びＥＰＡ残基が含まれていても、リン脂質以外に由来するω６脂肪酸残基が一定量以上含まれると、１−アルキルエーテル型リン脂質の吸収阻害が抑制される傾向がみられる。
(B) Ratio of DHA residue and EPA residue derived from other than phospholipid and ω6 fatty acid residue The lipid composition of the present invention preferably constitutes (b) lipid, although it is not limited. Of the fatty acid residues, the ratio of the total amount of DHA residues and EPA residues derived from other than phospholipids to the amount of ω6 fatty acid residues derived from other than phospholipids ([DHA + EPA] / ω6) is 0.140. It is as follows.
The ω6 fatty acid is an unsaturated fatty acid in which a carbon-carbon double bond exists at the ω-6 position (the sixth bond from the methyl end of the fatty acid). Specific examples thereof include linoleic acid, γ-linolenic acid, and arachidonic acid, which are abundant in safflower oil, grape seed oil, sunflower oil, corn oil, soybean oil, sesame oil, and the like.
The ratio of DHA residues other than phospholipids and EPA residues to ω6 fatty acid residues is 0.140 or less, preferably 0.120 or less, more preferably 0.100 or less, still more preferably. It is 0.80 or less, most preferably 0.060 or less. Even if DHA residues and EPA residues derived from other than phospholipids are contained, if a certain amount or more of ω6 fatty acid residues derived from other than phospholipids are contained, inhibition of absorption of 1-alkyl ether type phospholipids is suppressed. There is a tendency to be done.
（ｃ）１−アルキルエーテル型リン脂質由来のＥＰＡ残基及びＤＨＡ残基と１−アルキルエーテル型リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基との比
本発明の脂質組成物においては、限定されるものではないが、好ましくは（ｃ）リン脂質を構成する脂肪酸残基のうち、１−アルキルエーテル型リン脂質由来のＥＰＡ残基及びＤＨＡ残基の合計量１質量部に対して、１−アルキルエーテル型リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１０．０質量部以下である。
１−アルキルエーテル型リン脂質由来のＥＰＡ残基及びＤＨＡ残基は、１−アルキルエーテル型リン脂質のｓｎ−１位及びｓｎ−２位に存在する脂肪酸残基である。１−アルキルエーテル型リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基としては、限定されるものではないが、ジアシル型リン脂質及びリゾリン脂質由来のＥＰＡ残基及びＤＨＡ残基、並びに中性脂質由来のＥＰＡ残基及びＤＨＡ残基などを挙げることができる。
本発明の脂質組成物においては、１−アルキルエーテル型リン脂質由来のＥＰＡ残基及びＤＨＡ残基の合計量１質量部に対して、１−アルキルエーテル型リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１０．０質量部以下であり、好ましくは９．０質量部以下であり、より好ましくは８．０質量部以下であり、更に好ましくは７．０質量部以下であり、最も好ましくは６．０質量部以下である。１−アルキルエーテル型リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１０．０質量部以下であることにより、更に効率的に生体内のプラスマローゲンを増加させることができる。
(C) Ratio of EPA and DHA residues derived from 1-alkyl ether phospholipids to EPA residues and DHA residues derived from other than 1-alkyl ether phospholipids In the lipid composition of the present invention, Although not limited, preferably (c) among the fatty acid residues constituting the phospholipid, with respect to 1 part by mass of the total amount of the EPA residue and the DHA residue derived from the 1-alkyl ether type phospholipid. The total amount of EPA residues and DHA residues derived from other than 1-alkyl ether type phospholipids is 10.0 parts by mass or less.
The EPA and DHA residues derived from 1-alkyl ether phospholipids are fatty acid residues present at sn-1 and sn-2 positions of 1-alkyl ether phospholipids. The EPA residue and DHA residue derived from other than 1-alkyl ether type phospholipid are not limited, but are not limited, and EPA residue and DHA residue derived from diacyl type phospholipid and lysophospholipid, and neutral lipid. Derived EPA residues, DHA residues and the like can be mentioned.
In the lipid composition of the present invention, with respect to 1 part by mass of the total amount of EPA residues and DHA residues derived from 1-alkyl ether type phospholipids, EPA residues derived from other than 1-alkyl ether type phospholipids and EPA residues and The total amount of DHA residues is 10.0 parts by mass or less, preferably 9.0 parts by mass or less, more preferably 8.0 parts by mass or less, and further preferably 7.0 parts by mass or less. Most preferably, it is 6.0 parts by mass or less. When the total amount of EPA residue and DHA residue derived from other than 1-alkyl ether type phospholipid is 10.0 parts by mass or less, plasmalogen in the living body can be increased more efficiently.
《リン脂質》
本発明の脂質組成物には、リン脂質として１−アルキルエーテル型リン脂質が含まれる。１−アルキルエーテル型リン脂質以外のリン脂質として、ジアシル型リン脂質、アルケニルアシル型リン脂質（プラスマローゲン）、スフィンゴリン脂質、及びリゾリン脂質を含んでもよい。
ジアシル型リン脂質は、ｓｎ−１位及びｓｎ−２位にエステル結合を有するリン脂質であり、ｓｎ−３位の塩基により、コリン型、エタノールアミン型、又はホスファチジン酸型に分類することができる。プラスマローゲンは、ｓｎ−１位に、ビニルエーテル結合を有し、ｓｎ−２位にはアシル結合を有する脂肪酸残基を有するリン脂質であり、極性基として、エタノールアミン、コリン、又はホスファチジン酸を有している。１−アルキルエーテル型リン脂質及びプラスマローゲンを、まとめてエーテル型リン脂質と称することがある。スフィンゴリン脂質は、スフィンゴシンと脂肪酸が結合したセラミドに塩基やリン酸基が結合したものであり、スフィンゴミエリン等が挙げられる。リゾリン脂質は、リン脂質が有する２本の脂肪酸残基のうち１本を失ったものである．
従って、これらのジアシル型リン脂質、プラスマローゲン、スフィンゴリン脂質、リゾリン脂質、及び１−アルキルエーテル型リン脂質は基本骨格が異なっているが、ＥＰＡ残基及びＤＨＡ残基は、これらのリン脂質に、脂肪酸残基として存在することができる。
《Phospholipids》
The lipid composition of the present invention contains 1-alkyl ether type phospholipids as phospholipids. As the phospholipid other than the 1-alkyl ether type phospholipid, a diacyl type phospholipid, an alkenylacyl type phospholipid (plasmalogen), a spingophospholipid, and a lysophospholipid may be included.
The diacyl type phospholipid is a phospholipid having an ester bond at the sn-1 position and the sn-2 position, and can be classified into a choline type, an ethanolamine type, or a phosphatidic acid type according to the base at the sn-3 position. .. Plasmalogen is a phospholipid having a vinyl ether bond at the sn-1 position and a fatty acid residue having an acyl bond at the sn-2 position, and has ethanolamine, choline, or phosphatidic acid as a polar group. doing. 1-alkyl ether type phospholipids and plasmalogens may be collectively referred to as ether type phospholipids. The sphingolipid is a ceramide in which sphingosine and a fatty acid are bound, and a base or a phosphate group is bound, and examples thereof include sphingomyelin. Risophospholipids are those that have lost one of the two fatty acid residues of phospholipids.
Therefore, these diacyl-type phospholipids, plasmalogens, sphingolin lipids, lysophospholipids, and 1-alkyl ether-type phospholipids have different basic skeletons, but EPA residues and DHA residues are added to these phospholipids. , Can be present as fatty acid residues.
（１−アルキルエーテル型リン脂質）
本発明の脂質組成物に含まれる１−アルキルエーテル型リン脂質は、下記一般式（Ｉ）で表されるリン脂質である。
前記Ｒ１の炭化水素基はアルキル基、又はアルケニル基でもよく、具体的には、ペンタデシル基、ヘプタデシル基、又はヘプタデセル鎖基を挙げることができる。なお、本明細書において、１−アルキルエーテル型リン脂質の「ｓｎ−１位の脂肪酸残基」については、脂肪酸からカルボキシル基（−ＣＯＯＨ）を除いたものを意味し、具体的には一般式（１）のＲ１とエーテル基の炭素を含む「−ＣＨ２−Ｒ１」を意味し、１６：０、１８：０、又は１８：１（炭素数：不飽和結合数）などと表記する。
また、前記Ｒ２の脂肪酸残基としては、具体的には、パルミトイル基、オレイル基、アラキドイル基、エイコサペンタエノイル基、又はドコサヘキサエノイル基等を挙げることができる。エイコサペンタエン酸（ＥＰＡ）残基及びドコサヘキサエン酸（ＤＨＡ）残基の量は、前記（ａ）及び（ｃ）の条件を満たすことが好ましい。
(1-alkyl ether type phospholipid)
The 1-alkyl ether type phospholipid contained in the lipid composition of the present invention is a phospholipid represented by the following general formula (I).
The hydrocarbon group of R 1 may be an alkyl group or an alkenyl group, and specific examples thereof include a pentadecyl group, a heptadecyl group, and a heptadecel chain group. In the present specification, the "fatty acid residue at the sn-1 position" of the 1-alkyl ether type phospholipid means a fatty acid obtained by removing a carboxyl group (-COOH), and specifically, a general formula. It means "-CH 2- R 1 " containing R 1 of (1) and the carbon of the ether group, and is expressed as 16: 0, 18: 0, or 18: 1 (number of carbon atoms: number of unsaturated bonds). ..
Specific examples of the fatty acid residue of R 2 include a palmitoyl group, an oleyl group, an arachidoyl group, an eikosapentaenoyl group, and a docosahexaenoyl group. The amounts of eicosapentaenoic acid (EPA) residue and docosahexaenoic acid (DHA) residue preferably satisfy the conditions of (a) and (c) above.
なお、本明細書において、１−アルキルエーテル型リン脂質のｓｎ−２位の脂肪酸残基とは、脂肪酸から−ＯＨを除いたものを意味し、１６：０、１８：１、２０：４、又は２２：６（炭素数：不飽和結合数）などと表記する。
本発明の脂質組成物においては、１−アルキルエーテル型リン脂質の脂肪酸残基の由来となる脂肪酸が、どの脂肪酸であっても本発明の効果を有するが、好ましくはｓｎ−２位の脂肪酸残基の由来となる脂肪酸のうち１０％以上がＤＨＡ又ＥＰＡであることが好ましく、２０％以上がＤＨＡ又はＥＰＡであることがより好ましい。
In the present specification, the fatty acid residue at the sn-2 position of the 1-alkyl ether type phospholipid means a fatty acid obtained by removing −OH from the fatty acid, and 16: 0, 18: 1, 20: 4, Alternatively, it is expressed as 22: 6 (carbon number: unsaturated bond number) or the like.
In the lipid composition of the present invention, the fatty acid from which the fatty acid residue of the 1-alkyl ether type phospholipid is derived has the effect of the present invention regardless of the fatty acid, but the fatty acid residue at the sn-2 position is preferable. Of the fatty acids from which the groups are derived, 10% or more is preferably DHA or EPA, and more preferably 20% or more is DHA or EPA.
本発明に含まれる１−アルキルエーテル型リン脂質は、グリセリンを１−アルキルエーテルグリセロールに変換し、エステル化やリン酸化を行うことにより、化学合成することも可能であるが、入手の容易性や生産性から、天然物から抽出及び分離したものが好ましい。１−アルキルエーテル型リン脂質を抽出、分離する天然物としては、一般的に１−アルキルエーテル型リン脂質含量が高いことが知られている各種の動物、植物、微生物、例えば、マグロ、イワシなどの魚類、ホタテ、カキ、ムール貝などの貝類、タコ、イカなどの頭足類、エビ、フジツボ、オキアミ、カラヌスなどの甲殻類、ウシ、ブタ、ニワトリなどの家禽動物などの、その個体そのもの、その筋肉組織や、脂肪組織、あるいは脳などの神経組織、腸などの内臓組織、更にはその卵などを使用することができる。エーテル型リン脂質中の１−アルキルエーテル型リン脂質含量比が高い天然物であり、組織を分離することなく生体そのものを直接抽出源とすることができ、資源量が豊富であり、入手が容易であることに加え、更にはアスタキサンチンを含有することから保存安定性が良好である脂質組成物を得ることが可能であることから、オキアミを用いることが特に好ましい。 The 1-alkyl ether type phospholipid contained in the present invention can be chemically synthesized by converting glycerin into 1-alkyl ether glycerol and performing esterification or phosphorylation, but it is easy to obtain. From the viewpoint of productivity, those extracted and separated from natural products are preferable. As natural products for extracting and separating 1-alkyl ether type phospholipids, various animals, plants and microorganisms known to have a high content of 1-alkyl ether type phospholipids, such as tuna and barnacle, etc. Fish, shellfish such as scallops, oysters and mussels, cephalopods such as octopus and squid, crustaceans such as shrimp, barnacles, oysters and caranus, and poultry animals such as cows, pigs and chickens. Muscle tissue, adipose tissue, nerve tissue such as brain, visceral tissue such as intestine, and its egg can be used. It is a natural product with a high 1-alkyl ether-type phospholipid content ratio in ether-type phospholipids, and the living body itself can be directly used as an extraction source without separating tissues, and the amount of resources is abundant and easily available. In addition to the above, it is particularly preferable to use krill because it is possible to obtain a lipid composition having good storage stability because it contains astaxanthin.
本発明の脂質組成物では、これら各種動物、植物、微生物から、溶剤抽出などによって抽出された、エーテル型リン脂質含有脂質、更には、必要に応じて、前記脂質から液液抽出やカラムクロマトグラフィー、酵素処理などでリン脂質を分離した、リン脂質画分や、更にエーテル型リン脂質を濃縮した濃縮物、また、更に精製した、精製エーテル型リン脂質を使用することができる。例えば、前記各種動物、植物、微生物等の組織からの抽出方法としては、Ｆｏｌｃｈ法（Ｆｏｌｃｈ ｅｔ ａｌ．：Ｊ．Ｂｉｏｌ．Ｃｈｅｍ．，２２６，４９７−５０５，１９５７）、Ｂｌｉｇｈ＆Ｄｙｅｒ法（Ｂｌｉｇｈ ｅｔ ａｌ．：Ｃａｎ．Ｊ．Ｂｉｏｃｈｅｍ．Ｐｈｙｓｉｏｌ．，３７，９１１−９１７，１９５９）、あるいは安全性の高い有機溶媒であるヘキサンや低級アルコールを用いた混合溶媒を用いる方法（Ｈａｒａ ｅｔ ａｌ．：Ａｎａｌ．Ｂｉｏｃｈｅｍ．，９０（１）：４２０−６，１９７８、特開２００５−１７９３４０）、また、安全性が高く、かつ液液抽出の界面分離性が優れるヘキサンとエタノールの混合溶媒を用いる方法（特開２００９−２２７７６５）などがある。また、抽出効率を高めるために、前記動物組織を脱水処理したものを用いてもよい。 In the lipid composition of the present invention, ether-type phospholipid-containing lipids extracted from these various animals, plants, and microorganisms by solvent extraction or the like, and if necessary, liquid- liquid extraction or column chromatography from the lipids. , A phospholipid fraction obtained by separating phospholipids by enzyme treatment or the like, a concentrate obtained by further concentrating ether-type phospholipids, or a further purified purified ether-type phospholipid can be used. For example, as a method for extracting from tissues of various animals, plants, microorganisms and the like, a solvent method (Folch et al .: J. Biol. Chem., 226, 497-505, 1957), a Blig & Dyer method (Bligh et al.). : Can. J. Biochem. Physiol., 37, 911-917, 1959), or a method using a mixed solvent using hexane or a lower alcohol, which is a highly safe organic solvent (Hara et al .: Anal. Biochem. , 90 (1): 420-6, 1978, JP-A-2005-179340), and a method using a mixed solvent of hexane and ethanol, which is highly safe and has excellent interfacial separability for liquid-liquid extraction (Japanese Patent Laid-Open No. 2009-). 227765) and the like. Further, in order to increase the extraction efficiency, the animal tissue dehydrated may be used.
また、前記分離方法としては、アセトン沈殿法（山川民夫監修：生化学実験講座３，脂質の化学（日本生化学会編），ｐ．１９−２０，１９６３，東京化学同人）、カラムクロマトグラフィー法（Ｊａｍｅｓ ｅｔ ａｌ．：Ｌｉｐｉｄｓ，２３，１１４６−１１４９，１９８８）等によるトリグリセリドや部分グリセリドを除去し、エーテル型リン脂質を含むリン脂質画分のみを分離精製することができる。 The separation methods include acetone precipitation method (supervised by Tamio Yamakawa: Biochemistry Experiment Course 3, Lipid Chemistry (edited by Japan Society for Biochemistry), p.19-20, 1963, Tokyo Chemistry Dojin), column chromatography method ( Triglycerides and partial glycerides by James et al .: Lipids, 23,1146-1149, 1988) can be removed, and only the phospholipid fraction containing ether-type phospholipids can be separated and purified.
更に、前記濃縮方法としては、弱アルカリ処理（Ｈａｎａｈａｎ ｅｔ ａｌ．：Ｊ．Ｂｉｏｌ．Ｃｈｅｍ．２３６，５９−６０，１９６１）、あるいは哺乳動物膵臓由来リパーゼ又は微生物由来のホスホリパーゼＡ１処理によるジアシル型リン脂質の分解（Ｗｏｅｌｋ ｅｔ ａｌ．：Ｚ Ｐｈｙｓｉｏｌ．Ｃｈｅｍ．３５４，１２６５−７０，１９７３）の方法を用いて、エーテル型リン脂質以外のリン脂質を除去することでエーテル型リン脂質を濃縮することができる。 Further, as the concentration method, a diacyl-type phospholipid by weak alkaline treatment (Hanahan et al .: J. Biol. Chem. 236, 59-60, 1961), or treatment with mammalian pancreatic lipase or phospholipase A1 derived from microorganisms. (Woelk et al .: Z Phospholip. Chem. 354, 1265-70, 1973) can be used to concentrate phospholipids other than ether-type phospholipids. ..
ホスホリパーゼＡ１を用いて濃縮する場合、具体的には、エーテル型リン脂質含有脂質に対し、ホスホリパーゼＡ１、好ましくはＡｃｔｉｎｏｍａｄｕｒａ ｓｐ．由来のホスホリパーゼＡ１を添加し、好ましくは少量のジエチルエーテルと弱酸性緩衝液下で、分解反応させ、分解生成物を親水性溶媒と疎水性溶媒の混合溶媒、例えば、ヘキサン／エタノール混合溶媒により再抽出することで得ることができる。
更に詳しく述べると、エーテル型リン脂質含有脂質１ｇにホスホリパーゼＡ１を０．１〜２．０Ｕ、酢酸緩衝液ｐＨ５．０〜６．０を２〜２０％、好ましくは５〜１０％添加し、３０〜６０℃で、２〜１００時間、攪拌しながら分解反応させる。反応溶液にヘキサン／エタノール／水の混合溶媒、例えばヘキサン６５〜９０に対し、エタノール５〜２０、水４〜１０、好ましくはヘキサン７５〜８５、エタノール１０〜１８、水５〜８の比の混合溶媒を加えて再抽出することで、ホスホリパーゼＡ１反応で生じた１−リゾリン脂質は下層の水層に、エーテル型リン脂質は上層のヘキサン層に分離することができる。ここで、上層のヘキサン層を分取し、定法によりヘキサンを除去することで、エーテル型リン脂質以外のリン脂質を除去し、エーテル型リン脂質のみを濃縮することができる。
When concentrated with phospholipase A1, specifically, with respect to ether-type phospholipid-containing lipids, phospholipase A1, preferably Actinomadura sp. The derived phosphorlipase A1 is added, preferably subjected to a decomposition reaction with a small amount of diethyl ether under a weakly acidic buffer, and the decomposition product is reconstituted with a mixed solvent of a hydrophilic solvent and a hydrophobic solvent, for example, a mixed solvent of hexane / ethanol. It can be obtained by extracting.
More specifically, to 1 g of ether-type phospholipid-containing lipid, 0.1 to 2.0 U of phospholipase A1 and 2 to 20%, preferably 5 to 10% of acetate buffer pH 5.0 to 6.0 were added to 30 The decomposition reaction is carried out at ~ 60 ° C. for 2 to 100 hours with stirring. The reaction solution is mixed with a mixed solvent of hexane / ethanol / water, for example, hexane 65 to 90 in a ratio of ethanol 5 to 20, water 4 to 10, preferably hexane 75 to 85, ethanol 10 to 18, and water 5 to 8. By adding a solvent and re-extracting, the 1-lysophospholipid produced by the phosphorlipase A1 reaction can be separated into the lower aqueous layer, and the ether-type phospholipid can be separated into the upper hexane layer. Here, by separating the upper hexane layer and removing hexane by a conventional method, phospholipids other than ether-type phospholipids can be removed, and only ether-type phospholipids can be concentrated.
なお、前記エーテル型リン脂質の濃縮の前又は後、好ましくは後に、トリグリセリドに代表される中性脂質を分画除去し、エーテル型リン脂質含有リン脂質とすることが好ましい。この中性脂質の除去方法としては、アセトン沈殿法やカラムクロマトグラフィーなどの公知の方法を採ることができる。そして、除去した中性脂質を前記（ａ）、（ｂ）、及び／又は（ｃ）の条件となるように、エーテル型リン脂質含有リン脂質画分に添加することができる。 Before or after the concentration of the ether-type phospholipid, preferably after, the neutral lipid typified by triglyceride is fractionally removed to obtain an ether-type phospholipid-containing phospholipid. As a method for removing the neutral lipid, a known method such as an acetone precipitation method or column chromatography can be adopted. Then, the removed neutral lipid can be added to the ether-type phospholipid-containing phospholipid fraction so as to meet the conditions of (a), (b), and / or (c).
更には、シリカゲルクロマトグラフィーによってｓｎ−３位の塩基の種類別に濃縮することも可能である。例えば、シリカゲルをヘキサン／エタノール混合溶媒、好ましくは９５：５〜６０：４０の混合溶媒で充填したカラムに、エーテル型リン脂質含有脂質やエーテル型リン脂質含有リン脂質を充填し、同溶媒をカラム体積の２〜８倍量通液させて中性脂質を溶出させた後、ヘキサン／エタノール混合溶媒、好ましくは５：９５〜０：１００、あるいはエタノール／水の混合溶媒、好ましくは１００：０〜９５：５をカラム体積の６〜１５倍量通液させることにより、エタノールアミン型やホスファチジン酸型を分画することができ、続いてエタノール／水の混合溶媒、好ましくは９０：１０〜７０：３０をカラム体積の８〜２０倍量通液させることにより、コリン型を分画することができる。
これらの画分に、前記のように中性脂質を前記（ａ）、（ｂ）、及び／又は（ｃ）の条件となるように、エーテル型リン脂質含有リン脂質画分に添加することができる。
本発明の脂質組成物における１−アルキルエーテル型リン脂質含有量は、好ましくは０．２質量％以上、より好ましくは１．０質量％以上、更に好ましくは２．０質量％以上である。
Furthermore, it is also possible to concentrate by type of the base at the sn-3 position by silica gel chromatography. For example, a column filled with silica gel in a mixed solvent of hexane / ethanol, preferably a mixed solvent of 95: 5 to 60:40 is filled with an ether-type phospholipid-containing lipid or an ether-type phospholipid-containing phospholipid, and the same solvent is used in the column. After passing 2 to 8 times the volume of the solution to elute the neutral lipid, a hexane / ethanol mixed solvent, preferably 5:95 to 0:100, or an ethanol / water mixed solvent, preferably 100: 0 to 0 The ethanolamine type and phosphatidic acid type can be fractionated by passing 95: 5 in an amount of 6 to 15 times the column volume, followed by a mixed solvent of ethanol / water, preferably 90: 10 to 70 :. The choline type can be fractionated by passing 30 in an amount of 8 to 20 times the column volume.
To these fractions, the neutral lipid may be added to the ether-type phospholipid-containing phospholipid fraction so as to meet the conditions of (a), (b), and / or (c) as described above. it can.
The 1-alkyl ether type phospholipid content in the lipid composition of the present invention is preferably 0.2% by mass or more, more preferably 1.0% by mass or more, still more preferably 2.0% by mass or more.
《中性脂質》
リン脂質以外のＥＰＡ残基及びＤＨＡ残基としては、中性脂質、又は食用油脂部分グリセリドのＥＰＡ残基及びＤＨＡ残基を挙げることできる。これらのＥＰＡ残基及びＤＨＡ残基を含む脂質のうち、中性脂質はグリセリン脂肪酸エステルであり、グリセリンに１つの脂肪酸が結合したモノグリセリド、グリセリンに２つの脂肪酸が結合したジグリセリド、及びグリセリンに３つの脂肪酸が結合したトリグリセリドがある。
中性脂質に含まれるＥＰＡ残基及びＤＨＡ残基は、前記グリセリンに結合したエイコサペンタエン酸及びドコサヘキサエン酸由来の脂肪酸残基である。
《Neutral fat》
Examples of EPA residues and DHA residues other than phospholipids include EPA residues and DHA residues of neutral lipids or partial glycerides of edible fats and oils. Among the lipids containing these EPA residues and DHA residues, the neutral lipid is a glycerin fatty acid ester, which is a monoglyceride in which one fatty acid is bound to glycerin, a diglyceride in which two fatty acids are bound to glycerin, and three to glycerin. There are triglycerides to which fatty acids are bound.
The EPA residue and DHA residue contained in the neutral lipid are fatty acid residues derived from eicosapentaenoic acid and docosahexaenoic acid bound to the glycerin.
〔２〕飲食品
本発明の飲食品は、前記脂質組成物を含有する。本発明の１−アルキルエーテル型リン脂質を含む脂質組成物を含有する飲食品は、前記の（ａ）、（ｂ）、及び／又は（ｃ）の条件を満たす脂質組成物を含むこと以外は、公知の飲食品の製造方法を用いて製造することができる。本発明の飲食品は、前記脂質組成物を含有することにより、生体内においてプラスマローゲン含量を増加させることが可能であり、機能性食品又は健康食品（飲料も含む）として用いることができる。また動物には、飼料として与えることができる。本発明の飲食品は、例えば、動物、植物、微生物から、好ましくはオキアミから分離した前記脂質組成物を含むことが好ましい。
[2] Food and drink The food and drink of the present invention contains the lipid composition. The food or drink containing the lipid composition containing the 1-alkyl ether type phospholipid of the present invention except that it contains the lipid composition satisfying the above conditions (a), (b), and / or (c). , It can be produced by using a known method for producing food and drink. The food or drink of the present invention can increase the plasmalogen content in vivo by containing the lipid composition, and can be used as a functional food or a health food (including a beverage). It can also be fed to animals. The food or drink of the present invention preferably contains, for example, the lipid composition separated from animals, plants and microorganisms, preferably krill.
本発明の飲食品における前記脂質組成物の含有量は、使用する飲食品により異なるが、成人の場合、脂質組成物として１日当たり１０ｍｇ〜４ｇ、より好ましくは１００ｍｇ〜２ｇを摂取できる量の組成物を飲食物中に含有できれば良い。具体的には、飲食品中０．１〜１００質量％であることが好ましい。
なお、本発明における飲食品としては、特に限定されるものではなく、例えば味噌、醤油、めんつゆ、たれ、だし、パスタソース、ドレッシング、マヨネーズ、トマトケチャップ、ウスターソース、とんかつソース、又はふりかけ等の調味料、お吸い物の素、カレールウ、ホワイトソース、お茶漬けの素、又はスープの素等の即席調理食品、味噌汁、お吸い物、コンソメスープ、又はポタージュスープ等のスープ類、焼肉、ハム、又はソーセージ等の畜産加工品、かまぼこ、干物、塩辛、佃煮、又は珍味等の水産加工品、漬物等の野菜加工品、ポテトチップス、又は煎餅等のスナック類、食パン、菓子パン、又はクッキー等のベーカリー食品類、煮物、揚げ物、焼き物、カレー、シチュー、グラタン、ごはん、おかゆ、又はおにぎり等の調理食品、パスタ、うどん、又はラーメン等の麺類食品、マーガリン、ショートニング、ファットスプレッド、又は風味ファットスプレッド等の油脂加工食品、フラワーペースト、餡等の製菓製パン用素材、パン用ミックス粉、ケーキ用ミックス粉、又はフライ食品用ミックス粉等のミックス粉、チョコレート、キャンディ、ゼリー、アイスクリーム、又はガム等の菓子類、饅頭、又はカステラ等の和菓子類、コーヒー、コーヒー牛乳、紅茶、ミルクティー、豆乳、栄養ドリンク、野菜飲料、食酢飲料、ジュース、コーラ、ミネラルウォーター、又はスポーツドリンク等の飲料、ビール、ワイン、カクテル、又はサワー等のアルコール飲料類、牛乳、ヨーグルト、又はチーズ等の乳や乳製品等が挙げることができる。
The content of the lipid composition in the food and drink of the present invention varies depending on the food and drink used, but in the case of an adult, the composition in an amount capable of ingesting 10 mg to 4 g, more preferably 100 mg to 2 g per day as the lipid composition. Should be contained in food and drink. Specifically, it is preferably 0.1 to 100% by mass in foods and drinks.
The food or drink in the present invention is not particularly limited, and is, for example, a seasoning such as miso, soup, mentsuyu, sauce, dashi, pasta sauce, dressing, mayonnaise, tomato ketchup, Uster sauce, tonkatsu sauce, or sprinkle. , Soup stock, curry roux, white sauce, Ochazuke base, or soup stock, etc., instant cooked foods, miso soup, soup, consomme soup, or potage soup, and other soups, roasted meat, ham, or sausage. Processed products, kamaboko, dried foods, salted foods, boiled fish, processed vegetables such as pickles, snacks such as potato chips or roasted rice cakes, bakery foods such as bread, sweet bread, or cookies, boiled foods, Cooked foods such as fried foods, grilled foods, curry, stew, gratin, rice, porridge, or rice balls, noodle foods such as pasta, udon, or ramen, oil-processed foods such as margarine, shortening, fat spread, or flavored fat spread, flowers Confectionery bread ingredients such as paste and soup, mixed powder for bread, mixed powder for cake, mixed powder such as mixed powder for fried foods, confectionery such as chocolate, candy, jelly, ice cream, or gum, bun, Or Japanese sweets such as castella, coffee, coffee milk, tea, milk tea, soy milk, nutritional drinks, vegetable drinks, vinegar drinks, juices, colas, mineral water, sports drinks and other beverages, beer, wine, cocktails, or sour Alcoholic beverages such as, milk, yogurt, milk such as cheese, dairy products and the like can be mentioned.
〔３〕医薬組成物
本発明の医薬組成物は、本発明の脂質組成物を含有する。本発明の医薬組成物は、前記脂質組成物を含有するため、効率的に血液又はリンパ液中のプラスマローゲンを増加させることが可能である。本発明の脂質組成物を含有する医薬組成物は、前記の（ａ）、（ｂ）、及び／又は（ｃ）の条件を満たす脂質組成物を含むこと以外は、公知の飲医薬組成物の製造方法を用いて製造することができる。
医薬組成物における、脂質組成物の含有量は、使用する医薬組成物により異なるが、成人の場合、脂質組成物として１日当たり１０ｍｇ〜４ｇ、より好ましくは１００ｍｇ〜２ｇを摂取できる量の組成物を医薬組成物中に含有できれば良い。具体的には、１−アルキルエーテル型リン脂質量は医薬組成物中、０．１〜１００質量％であることが好ましく、０．５〜９９質量％であることが好ましく、１〜８０質量％であることが最も好ましい。
[3] Pharmaceutical Composition The pharmaceutical composition of the present invention contains the lipid composition of the present invention. Since the pharmaceutical composition of the present invention contains the lipid composition, it is possible to efficiently increase plasmalogen in blood or lymph. The pharmaceutical composition containing the lipid composition of the present invention is a known drinking pharmaceutical composition except that it contains a lipid composition satisfying the above conditions (a), (b), and / or (c). It can be manufactured using a manufacturing method.
The content of the lipid composition in the pharmaceutical composition varies depending on the pharmaceutical composition used, but in the case of an adult, a composition in an amount capable of ingesting 10 mg to 4 g, more preferably 100 mg to 2 g per day as the lipid composition. It suffices if it can be contained in a pharmaceutical composition. Specifically, the amount of 1-alkyl ether type phospholipid is preferably 0.1 to 100% by mass, preferably 0.5 to 99% by mass, and 1 to 80% by mass in the pharmaceutical composition. Is most preferable.
医薬組成物は、１−アルキルエーテル型リン脂質を含む脂質組成物を単独で、あるいは、好ましくは薬剤学的又は獣医学的に許容することができる通常の担体又は希釈剤とともに、プラスマローゲンの低下又は消失に起因する疾患の治療及び／又は予防が必要な対象［例えば、動物、好ましくは哺乳動物（特にヒト）］に有効量で投与することができる。
医薬組成物は、プラスマローゲンの濃度を上昇させることのできる物質を含むこともできる。このような物質としては、例えばアルキルグリセロール、イノシトールを挙げることができる。
医薬組成物の投与剤型としては、特に限定がないが、例えば、散剤、細粒剤、顆粒剤、錠剤、カプセル剤、懸濁剤、エマルジョン剤、シロップ剤、エキス剤、若しくは丸剤等の経口剤が好ましく、特にカプセル剤（ハードカプセル、ソフトカプセル、マイクロカプセル等）の形状が好ましい。
経口剤は、例えば、ゼラチン、アルギン酸ナトリウム、澱粉、コーンスターチ、白糖、乳糖、ブドウ糖、マンニット、カルボキシメチルセルロース、デキストリン、ポリビニルピロリデン、結晶セルロース、大豆レシチン、ショ糖、脂肪酸エステル、タルク、ステアリン酸マグネシウム、ポリエチレングリコール、ケイ酸マグネシウム、無水ケイ酸、又は合成ケイ酸アルミニウムなどの賦形剤、結合剤、崩壊剤、界面活性剤、滑沢剤、流動性促進剤、希釈剤、保存剤、着色剤、香料、矯味剤、安定化剤、保湿剤、防腐剤、又は酸化防止剤等を用いて、常法に従って製造することができる。
本発明の医薬組成物を用いる場合の投与量は、例えば、使用する有効成分の種類、病気の種類、患者の年齢、性別、体重、生上の程度、又は投与方法に応じて適宜決定することができ、経口的に又はカテーテルなどを用いて直接消化管に投与することが可能である。
The pharmaceutical composition is a reduction in plasmalogen of the lipid composition containing the 1-alkyl ether phospholipid alone, or preferably with a conventional carrier or diluent which is pharmaceutical or veterinarily acceptable. Alternatively, it can be administered in an effective amount to a subject [eg, an animal, preferably a mammal (particularly a human)] who needs treatment and / or prevention of a disease caused by disappearance.
The pharmaceutical composition can also include substances capable of increasing the concentration of plasmalogen. Examples of such a substance include alkyl glycerol and inositol.
The dosage form of the pharmaceutical composition is not particularly limited, and for example, powders, fine granules, granules, tablets, capsules, suspensions, emulsions, syrups, extracts, pills, etc. Oral preparations are preferable, and the shape of capsules (hard capsules, soft capsules, microcapsules, etc.) is particularly preferable.
Oral preparations include, for example, gelatin, sodium alginate, starch, corn starch, sucrose, lactose, glucose, mannit, carboxymethyl cellulose, dextrin, polyvinylpyrrolidene, crystalline cellulose, soy lecithin, sucrose, fatty acid ester, talc, magnesium stearate. , Polyethylene glycol, magnesium silicate, dextrinic acid, or synthetic aluminum silicate and other excipients, binders, disintegrants, surfactants, lubricants, fluidity enhancers, diluents, preservatives, colorants , Fragrance, flavoring agent, stabilizer, moisturizing agent, preservative, antioxidant, etc., can be produced according to a conventional method.
When the pharmaceutical composition of the present invention is used, the dose should be appropriately determined according to, for example, the type of active ingredient used, the type of disease, the age, sex, body weight, degree of life, or administration method of the patient. It can be administered orally or directly to the gastrointestinal tract using a catheter or the like.
《カプセル剤》
本発明の脂質組成物、飲食品、及び医薬組成物は、同時に摂取する食品に由来する脂質成分によって吸収に影響を受けることから、脂質組成物のみを摂取することのできる経口剤、中でもカプセル剤は、特に好ましい形態である。
更に、投与形態も医薬品に限定されるものではなく、種々の形態、例えば、機能性食品や健康食品（飲料も含む）、又は飼料として飲食物の形態で与えることも可能である。
《Capsule》
Since the lipid composition, food and drink, and pharmaceutical composition of the present invention are affected by absorption by lipid components derived from foods to be ingested at the same time, oral preparations, especially capsules, which can ingest only the lipid composition. Is a particularly preferred form.
Further, the administration form is not limited to pharmaceutical products, and various forms such as functional foods, health foods (including beverages), or foods and drinks as feed can be given.
（プラスマローゲン）
プラスマローゲンは、ＬＤＬコレステロールの酸化を抑制する。ＬＤＬコレステロールの酸化は、動脈硬化症を誘導するため、プラスマローゲンを増加させることによって、動脈硬化症を予防又は治療することが可能である。更に、動脈硬化を基礎疾患とする、心筋梗塞及び脳梗塞を予防又は治療することが可能である。更に、加齢及び酸化ストレスがプラスマローゲンにより、抑制されると考えられている。加齢及び酸化ストレスが関与する疾患として癌、動脈硬化症、糖尿病、及びアルツハイマー病があり、プラスマローゲンを増加させることにより、癌、動脈硬化症、糖尿病、及びアルツハイマー病を予防又は治療することが可能である。従って本発明による経口投与剤、飲食品、又は医薬組成物が、予防又は治療することのできるプラスマローゲンの低下又は消失に起因する疾患としては、癌、動脈硬化症、糖尿病、及びアルツハイマー病を挙げることができる。更に加齢を抑制することも可能である。
(Plasmalogen)
Plasmalogen suppresses the oxidation of LDL cholesterol. Oxidation of LDL cholesterol induces arteriosclerosis, so it is possible to prevent or treat arteriosclerosis by increasing plasmalogen. Furthermore, it is possible to prevent or treat myocardial infarction and cerebral infarction, which have arteriosclerosis as an underlying disease. Furthermore, it is believed that aging and oxidative stress are suppressed by plasmalogens. Diseases associated with aging and oxidative stress include cancer, arteriosclerosis, diabetes, and Alzheimer's disease, and increasing plasmalogen can prevent or treat cancer, arteriosclerosis, diabetes, and Alzheimer's disease. It is possible. Therefore, diseases caused by a decrease or disappearance of plasmalogen that can be prevented or treated by the orally administered agent, food or drink, or pharmaceutical composition according to the present invention include cancer, arteriosclerosis, diabetes, and Alzheimer's disease. be able to. It is also possible to suppress aging.
本発明の脂質組成物、飲食品、又は医薬組成物を生体内に投与、特には経口投与することにより、生体内特にリンパ液や血液中のプラスマローゲンを増加させることが可能である。すなわち、１−アルキルエーテル型リン脂質を含有する本発明の組成物、飲食品、又は医薬組成物を生体内に投与、特には経口投与することにより、生体内においてプラスマローゲンを増加させる方法を提供することが可能である。
本発明の飲食品や医薬組成物を経口摂取する場合の摂取量は、前記のとおり、例えば成人の場合、１−アルキルエーテル型リン脂質として１日当たり１０ｍｇ〜４ｇ、より好ましくは１００ｍｇ〜２ｇを摂取できる量の脂質組成物を医薬組成物中に含有できる量である。
By administering the lipid composition, food or drink, or pharmaceutical composition of the present invention in vivo, particularly orally, it is possible to increase plasmalogen in vivo, especially in lymph and blood. That is, a method for increasing plasmalogen in vivo by administering the composition, food or drink, or pharmaceutical composition of the present invention containing a 1-alkyl ether type phospholipid in vivo, particularly orally, is provided. It is possible to do.
As described above, for example, in the case of an adult, the intake amount of the food or drink or the pharmaceutical composition of the present invention is 10 mg to 4 g, more preferably 100 mg to 2 g per day as a 1-alkyl ether type phospholipid. The amount of the lipid composition that can be contained in the pharmaceutical composition.
以下、実施例によって本発明を具体的に説明するが、これらは本発明の範囲を限定するものではない。 Hereinafter, the present invention will be specifically described with reference to Examples, but these do not limit the scope of the present invention.
《製造例１：中性脂質画分の製造》
ヘキサン：エタノール（６０：４０）の混合溶媒１０８Ｌに、冷凍ボイルオキアミの捏練品（オキアミＣＰＭ−ＭＤ、ＡＤＥＫＡファインフーズ）３０ｋｇを加えた。１０分間攪拌後に、脂質を含むろ液の上層（ヘキサン層）を抽出液として回収した。ヘキサン６５Ｌに、ろ液下層及びろ過残渣を加えた。１０分間攪拌後に、同様に脂質画分を含む抽出液を回収した。更に、同じ操作を繰り返して、抽出液を回収した。得られた抽出液を混合し、エバポレーターを使用して溶媒を除去した。１−アルキルエーテル型リン脂質含有脂質として、１．１ｋｇのオキアミ油を得た。
<< Production Example 1: Production of triglyceride fraction >>
To 108 L of a mixed solvent of hexane: ethanol (60:40), 30 kg of a krill krill (krill CPM-MD, ADEKA Fine Foods) was added. After stirring for 10 minutes, the upper layer (hexane layer) of the filtrate containing lipid was recovered as an extract. The lower layer of the filtrate and the filtration residue were added to 65 L of hexane. After stirring for 10 minutes, the extract containing the lipid fraction was similarly recovered. Further, the same operation was repeated to collect the extract. The resulting extracts were mixed and the solvent was removed using an evaporator. 1.1 kg of krill oil was obtained as a 1-alkyl ether type phospholipid-containing lipid.
オキアミ油２００ｇにアセトン２．５Ｌを添加し、４℃で１時間静置した。吸引ろ過により沈殿物をろ過した上清を回収した。上清のアセトンをエバポレーターにて除去し、残渣として得られた１１３ｇをオキアミ中性脂質画分とした。
得られたオキアミ油及び中性脂質画分の中性脂質、遊離脂肪酸、ジアシル型リン脂質、１−アルキルエーテル型リン脂質、及びリゾリン脂質の含量を表１に示す。
2.5 L of acetone was added to 200 g of krill oil, and the mixture was allowed to stand at 4 ° C. for 1 hour. The supernatant obtained by filtering the precipitate by suction filtration was collected. Acetone in the supernatant was removed by an evaporator, and 113 g obtained as a residue was used as a krill triglyceride fraction.
Table 1 shows the contents of the obtained triglyceride oil and triglyceride fraction, neutral lipid, free fatty acid, diacyl phospholipid, 1-alkyl ether type phospholipid, and lysophospholipid.
《製造例２：１−アルキルエーテル型リン脂質画分の製造》
ＬｅｃｉｔａｓｅＵｌｔｒａ（Ｎｏｖｏｚｙｍｅｓ）５０ｋＵを、４８ｍＬのジエチルエーテル及び１０２．５ｍＬの０．２Ｍ酢酸緩衝液（ｐＨ５．０）の混合液に混濁した。製造例１で得られたオキアミ油１ｋｇに、前記混合液に混濁したＬｅｃｉｔａｓｅＵｌｔｒａを加え、４０℃で７０時間攪拌することにより反応させた。これに９Ｌのヘキサン、エタノール、及び水の混合液（８０：１４：６）を添加した。混合液を１０分間攪拌し、上層を回収した。残った下層に、ヘキサン７Ｌを加え、１０分間攪拌して、上層を回収した。更に、同様の操作を繰り返し、上層を回収した。得られた抽出液を合わせて、混合溶媒をエバポレーターによって除去した。９７５ｇの残渣が得られた。
３００ｍＬのヘキサン／エタノール（８０：２０）の混合液に、得られた残渣分２００ｇを溶解した。ヘキサン／エタノール（８０：２０）の混合溶媒でけん濁したシリカゲル（Ｗａｋｏｓｉｌ２００）４００ｇを充填したガラスカラム（１００ｃｍ×３ｃｍ）に、前記溶解液を添加した。ヘキサン／エタノール（８０：２０）の混合溶媒を４Ｌ通液させて中性脂質を溶出した。その後、エタノール８Ｌを通液させてエタノールアミンリン脂質を溶出させた。次にエタノール／水（８０：２０）の混合溶媒１１Ｌを通液させてコリンリン脂質を溶出させた。溶出液をエバポレーターで濃縮し、７．２ｇの１−アルキルエーテル型リン脂質画分を得た。
１−アルキルエーテル型リン脂質画分の中性脂質、遊離脂肪酸、ジアシル型リン脂質、１−アルキルエーテル型リン脂質、及びリゾリン脂質の含量を表１に示す。
<< Production Example 2: Production of 1-alkyl Ether Type Phospholipid Fraction >>
Recitalse Ultra (Novozymes) 50 kU was turbid with a mixture of 48 mL diethyl ether and 102.5 mL 0.2 M acetate buffer (pH 5.0). To 1 kg of krill oil obtained in Production Example 1, a turbid Recitase Ultra was added to the mixture, and the mixture was reacted by stirring at 40 ° C. for 70 hours. To this was added a mixture of 9 L of hexane, ethanol and water (80: 14: 6). The mixture was stirred for 10 minutes and the upper layer was recovered. 7 L of hexane was added to the remaining lower layer, and the mixture was stirred for 10 minutes to recover the upper layer. Further, the same operation was repeated to recover the upper layer. The resulting extracts were combined and the mixed solvent was removed by an evaporator. A residue of 975 g was obtained.
200 g of the obtained residue was dissolved in a 300 mL mixture of hexane / ethanol (80:20). The solution was added to a glass column (100 cm × 3 cm) packed with 400 g of silica gel (Wakosil 200) turbid with a mixed solvent of hexane / ethanol (80:20). A mixed solvent of hexane / ethanol (80:20) was passed through 4 L to elute the neutral lipid. Then, 8 L of ethanol was passed through the solution to elute ethanolamine phospholipids. Next, 11 L of a mixed solvent of ethanol / water (80:20) was passed through the mixture to elute the choline phospholipid. The eluate was concentrated on an evaporator to give 7.2 g of a 1-alkyl ether phospholipid fraction.
Table 1 shows the contents of the neutral lipid, free fatty acid, diacyl phospholipid, 1-alkyl ether phospholipid, and lysophospholipid of the 1-alkyl ether type phospholipid fraction.
《比較例１》
製造例２で得られた１−アルキルエーテル型リン脂質２．８ｇに大豆油３４．２ｇと造例１で得られたオキアミ中性油脂画分１１．５ｇを添加し、１００ｈＰａ減圧、６０℃下でローテーターにより混合して溶解させ、１−アルキルエーテル型リン脂質の大豆油およびオキアミ中性油脂画分の溶解物を得た。
<< Comparative Example 1 >>
To 2.8 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 34.2 g of soybean oil and 11.5 g of the krill neutral oil / fat fraction obtained in Production Example 1 were added, and the pressure was reduced by 100 hPa at 60 ° C. The mixture was mixed and dissolved by a rotator to obtain a lysate of 1-alkyl ether type phospholipid soybean oil and a krill neutral fat fraction.
《実施例１》
製造例２で得られた１−アルキルエーテル型リン脂質４．０ｇに大豆油３７．６ｇと製造例１で得られたオキアミ中性油脂画分６．９ｇを添加し、１００ｈＰａ減圧、６０℃下でローテーターにより混合して溶解させ、１−アルキルエーテル型リン脂質の大豆油および製オキアミ中性油脂画分の溶解物を得た。
<< Example 1 >>
To 4.0 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 37.6 g of soybean oil and 6.9 g of the krill neutral oil / fat fraction obtained in Production Example 1 were added, and the pressure was reduced to 100 hPa at 60 ° C. The mixture was mixed and dissolved by a rotator to obtain a solution of 1-alkyl ether type phospholipid soybean oil and a krill neutral fat fraction.
《比較例２》
製造例２で得られた１−アルキルエーテル型リン脂質４．０ｇに大豆油２４．２ｇと造例１で得られたオキアミ中性油脂画分２０．３ｇを添加し、１００ｈＰａ減圧、６０℃下でローテーターにより混合して溶解させ、１−アルキルエーテル型リン脂質の大豆油およびオキアミ中性油脂画分の溶解物を得た。
<< Comparative Example 2 >>
To 4.0 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 24.2 g of soybean oil and 20.3 g of the krill neutral oil / fat fraction obtained in Production Example 1 were added, and the pressure was reduced by 100 hPa at 60 ° C. The mixture was mixed and dissolved by a rotator to obtain a lysate of 1-alkyl ether type phospholipid soybean oil and a krill neutral fat fraction.
《比較例３》
製造例２で得られた１−アルキルエーテル型リン脂質４．０ｇに大豆油３７．３ｇと魚油７．２ｇを添加し、１００ｈＰａ減圧、６０℃下でローテーターにより混合して溶解させ、１−アルキルエーテル型リン脂質の大豆油および魚油の溶解物を得た。
<< Comparative Example 3 >>
To 4.0 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 37.3 g of soybean oil and 7.2 g of fish oil were added, mixed and dissolved by a rotator at 100 hPa reduced pressure and 60 ° C. to dissolve 1-alkyl. Soybean oil and fish oil lysates of ether-type phospholipids were obtained.
《比較例４》
製造例２で得られた１−アルキルエーテル型リン脂質４．０ｇに大豆油３０．１ｇと魚油１４．４ｇを添加し、１００ｈＰａ減圧、６０℃下でローテーターにより混合して溶解させ、１−アルキルエーテル型リン脂質の大豆油および魚油の溶解物を得た。
<< Comparative Example 4 >>
To 4.0 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 30.1 g of soybean oil and 14.4 g of fish oil were added, mixed and dissolved by a rotator at 100 hPa reduced pressure and 60 ° C. to dissolve 1-alkyl. Soybean oil and fish oil lysates of ether-type phospholipids were obtained.
《実施例２》
製造例２で得られた１−アルキルエーテル型リン脂質２５．８７ｇに製造例１で得られたオキアミ中性油脂画分２２．６３ｇを添加し、１００ｈＰａ減圧、６０℃下でローテーターにより混合して溶解させ、１−アルキルエーテル型リン脂質と中性脂質の混合物を得た。
（［リン脂質以外に由来するＥＰＡ+ＤＨＡ］／［リン脂質由来のＥＰＡ+ＤＨＡ］＝０．３２、［リン脂質以外に由来するＤＨＡ+ＥＰＡ］／［リン脂質以外に由来するω６］＝０．０２３、［１−アルキルエーテル型リン脂質以外に由来するＤＨＡ+ＥＰＡ］／［１−アルキルエーテル型リン脂質由来のＤＨＡ+ＥＰＡ］＝４．３０）
<< Example 2 >>
To 25.87 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 22.63 g of the krill triglyceride fraction obtained in Production Example 1 was added, and the mixture was mixed with a rotator at 100 hPa reduced pressure and 60 ° C. It was dissolved to obtain a mixture of 1-alkyl ether type phospholipid and neutral lipid.
([EPA + DHA derived from other than phospholipids] / [EPA + DHA derived from phospholipids] = 0.32, [DHA + EPA derived from other than phospholipids] / [ω6 derived from other than phospholipids] = 0 .023, [DHA + EPA derived from other than 1-alkyl ether type phospholipid] / [DHA + EPA derived from 1-alkyl ether type phospholipid] = 4.30)
《比較例５》
大豆油を比較例５とした。
<< Comparative Example 5 >>
Soybean oil was designated as Comparative Example 5.
《動物試験（摂食試験）》
５週齢の雄Wistar-ST系ラットを、７群（１群６匹）に分け、飼料及び水を自由に摂取させた。飼料はＡＩＮ９３Ｇに準じた精製飼料（基本飼料：大豆油７％を含む）を用いた（表３）。なお、基本飼料は毎日交換し、飲水の水道水は３日毎に交換した。前記条件で７日間飼育した後、基本飼料の大豆油７％の代わりに１−アルキルエーテル型リン脂質の大豆油およびオキアミ中性油脂画分の溶解物を使用した飼料（実施例１、比較例１、２）、１−アルキルエーテル型リン脂質の大豆油および魚油の溶解物を使用した飼料（比較例３、４）、１−アルキルエーテル型リン脂質含量を調製した大豆油溶解物を使用した飼料（実施例２）のいずれかを与え、７日間飼育した。また、そのまま基本飼料を継続して与えた群を（比較例５）とし、血清中のプラスマローゲン量の比較対象とした。
なお、試験期間中、各群のラットの体重増加量及び餌の摂取量への影響は認められなかった。
《Animal test (feeding test)》
Five-week-old male Wistar-ST rats were divided into 7 groups (6 rats per group) and fed freely with feed and water. As the feed, a refined feed conforming to AIN93G (basic feed: containing 7% soybean oil) was used (Table 3). The basic feed was changed every day, and the tap water for drinking was changed every three days. After breeding under the above conditions for 7 days, a feed using 1-alkyl ether type phospholipid soybean oil and a solution of the neutral fat fraction of okiami instead of 7% of soybean oil as the basic feed (Example 1, Comparative Example). 1, 2), feed using a solution of 1-alkyl ether type phospholipid soybean oil and fish oil (Comparative Examples 3 and 4), and a soybean oil solution having a 1-alkyl ether type phospholipid content prepared were used. One of the feeds (Example 2) was given and the animals were bred for 7 days. In addition, the group in which the basic diet was continuously fed as it was (Comparative Example 5) was used as a comparison target for the amount of plasmalogen in serum.
During the test period, no effect on the weight gain and food intake of the rats in each group was observed.
７日間の給餌後、採血し、その血清画分の脂質を抽出し、血清中のプラスマローゲン含量をＬＣ−ＭＳ／ＭＳにより測定し、その結果を表４に記載した。また、比較例５（大豆油のみ）を１とした場合の増加率も示した。 After feeding for 7 days, blood was collected, the lipid of the serum fraction was extracted, the plasmalogen content in the serum was measured by LC-MS / MS, and the results are shown in Table 4. The rate of increase when Comparative Example 5 (soybean oil only) was set to 1 was also shown.
表４からわかるように、基本飼料（比較例５）に対し、１−アルキルエーテル型リン脂質中のＤＨＡおよびＥＰＡ量に対してその他の混合脂質中のＤＨＡおよびＥＰＡ量が１．８以下に調製した組成物を使用した飼料では（実施例１、２）、血清中のプラスマローゲン量が２倍以上に増加するのに対し、１．８以上の組成物を使用した飼料では（比較例１〜４）、血清中のプラスマローゲン量の増加が小さいことがわかる。 As can be seen from Table 4, the amount of DHA and EPA in the other mixed lipids was adjusted to 1.8 or less with respect to the amount of DHA and EPA in the 1-alkyl ether type phospholipid with respect to the basic feed (Comparative Example 5). In the feed using the above composition (Examples 1 and 2), the amount of plasmalogen in serum increased more than twice, whereas in the feed using the composition of 1.8 or more (Comparative Examples 1 to 1). 4) It can be seen that the increase in the amount of plasmalogen in serum is small.
《実施例３》
製造例２で得られた１−アルキルエーテル型リン脂質０．８ｇに、大豆油３．２ｇ、タウロコール酸０．２ｇおよびリン酸緩衝生理食塩水（ＰＢＳ）１５．８ｍＬを添加し、超音波発生装置（ＴＯＭＹ、ＵＤ−２０１）を用いて２分間処理し、１−アルキルエーテル型リン脂質と大豆油混合物のエマルジョンを得た。
<< Example 3 >>
To 0.8 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 3.2 g of soybean oil, 0.2 g of taurocholic acid and 15.8 mL of phosphate buffered saline (PBS) were added to generate ultrasonic waves. Treatment was carried out for 2 minutes using an apparatus (TOMY, UD-201) to obtain an emulsion of a 1-alkyl ether type phospholipid and a soybean oil mixture.
《比較例６》
製造例２で得られた１−アルキルエーテル型リン脂質０．８ｇに、製造例１で得られたオキアミ中性脂質画分３．２ｇ、タウロコール酸０．２ｇおよびリン酸緩衝生理食塩水（ＰＢＳ）１５．８ｍＬを添加し、超音波発生装置（ＴＯＭＹ、ＵＤ−２０１）を用いて２分間処理し、１−アルキルエーテル型リン脂質とオキアミ中性脂質画分混合物のエマルジョンを得た。
<< Comparative Example 6 >>
To 0.8 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 3.2 g of the triglyceride fraction of okiami obtained in Production Example 1, 0.2 g of taurocholic acid and phosphate buffered saline (PBS). ) 15.8 mL was added and treated with an ultrasonic generator (TOMY, UD-201) for 2 minutes to obtain an emulsion of a 1-alkyl ether type phospholipid and an okiami neutral lipid fraction mixture.
《比較例７》
製造例２で得られた１−アルキルエーテル型リン脂質０．８ｇに、魚油３．２ｇ、タウロコール酸０．２ｇおよびリン酸緩衝生理食塩水（ＰＢＳ）１５．８ｍＬを添加し、超音波発生装置（ＴＯＭＹ、ＵＤ−２０１）を用いて２分間処理し、１−アルキルエーテル型リン脂質と魚油混合物のエマルジョンを得た。
<< Comparative Example 7 >>
To 0.8 g of the 1-alkyl ether type phospholipid obtained in Production Example 2, 3.2 g of fish oil, 0.2 g of taurocholic acid and 15.8 mL of phosphate buffered saline (PBS) were added, and an ultrasonic generator was added. Treatment with (TOMY, UD-201) for 2 minutes gave an emulsion of 1-alkyl ether type phospholipid and fish oil mixture.
《リンパ液中のプラスマローゲン増加試験》
１０週齢の雄Wistar-ST系ラット（各実施あたり７匹）の十二指腸および胸管にカテーテルを挿入し、実施例３、比較例６、比較例７のいずれかで得られた１−アルキルエーテル型リン脂質含有エマルジョンを投与させた。
３０分ごとに回収したリンパ液について、脂質を抽出し、吸収された１−アルキルエーテル型リン脂質量をＬＣ−ＭＳ／ＭＳにより測定し、その結果を図１に記載した。
本発明の脂質組成物により、リンパ液中のプラスマローゲンが顕著に増加した。
<< Plasmalogen increase test in lymph >>
Catheter was inserted into the duodenum and thoracic duct of 10-week-old male Wistar-ST rats (7 in each practice), and the 1-alkyl ether obtained in any of Example 3, Comparative Example 6, and Comparative Example 7 was obtained. A type phospholipid-containing emulsion was administered.
Lipids were extracted from the lymph fluid collected every 30 minutes, and the amount of absorbed 1-alkyl ether type phospholipids was measured by LC-MS / MS, and the results are shown in FIG.
The lipid composition of the present invention markedly increased plasmalogen in lymph.
本発明の脂質組成物は、生体内のプラスマローゲンを増加させることができる。従って、プラスマローゲンが低下することによって起きる疾患に有効である。 The lipid composition of the present invention can increase plasmalogen in vivo. Therefore, it is effective for diseases caused by a decrease in plasmalogen.
Claims (6)
（ａ）脂質を構成する脂肪酸残基のうち、リン脂質由来のエイコサペンタエン酸（ＥＰＡ）残基及びドコサヘキサエン酸（ＤＨＡ）残基の合計量１質量部に対して、リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が１．０質量部以下であり、
（ｂ）脂質を構成する脂肪酸残基のうち、リン脂質以外に由来するＤＨＡ残基及びＥＰＡ残基の合計量と、リン脂質以外に由来するω６脂肪酸残基の量との比率（［ＤＨＡ＋ＥＰＡ］／ω６）が０．０６０以下であり、そして
（ｃ）リン脂質を構成する脂肪酸残基のうち、１−アルキルエーテル型リン脂質由来のＥＰＡ残基及びＤＨＡ残基の合計量１質量部に対して、１−アルキルエーテル型リン脂質以外に由来するＥＰＡ残基及びＤＨＡ残基の合計量が６．０質量部以下であることを特徴とするプラスマローゲン増加用脂質組成物。 Contains 1-alkyl ether type phospholipids derived from fish or shellfish, and (a) phospholipid-derived eicosapentaenoic acid (EPA) residues and docosahexaenoic acid (DHA) residues among the fatty acid residues constituting the lipids. The total amount of EPA residues and DHA residues derived from other than phospholipids is 1.0 part by mass or less with respect to 1 part by mass of the total amount of groups.
(B) Ratio of the total amount of DHA residues and EPA residues derived from other than phospholipids to the amount of ω6 fatty acid residues derived from other than phospholipids among the fatty acid residues constituting the lipid ([DHA + EPA]] / Ω6) is 0.060 or less, and (c) of the fatty acid residues constituting the phospholipid, with respect to 1 part by mass of the total amount of EPA residues and DHA residues derived from 1-alkyl ether type phospholipids. A lipid composition for increasing plasmalogen, wherein the total amount of EPA residues and DHA residues derived from other than 1-alkyl ether type phospholipid is 6.0 parts by mass or less.
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