JP2006232711A - Oil and fat having blood neutral fat-reducing activity, hepatic neutral fat synthesis-inhibiting activity and platelet aggregation-inhibiting activity - Google Patents

Oil and fat having blood neutral fat-reducing activity, hepatic neutral fat synthesis-inhibiting activity and platelet aggregation-inhibiting activity Download PDF

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JP2006232711A
JP2006232711A JP2005048265A JP2005048265A JP2006232711A JP 2006232711 A JP2006232711 A JP 2006232711A JP 2005048265 A JP2005048265 A JP 2005048265A JP 2005048265 A JP2005048265 A JP 2005048265A JP 2006232711 A JP2006232711 A JP 2006232711A
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neutral fat
activity
oil
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oils
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Yasushi Endo
泰志 遠藤
Yuko Osada
ゆう子 長田
Fumiko Kimura
ふみ子 木村
Kenshiro Fujimoto
健四郎 藤本
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Tohoku University NUC
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Abstract

<P>PROBLEM TO BE SOLVED: To provide oils and fats having an improving activity of serum lipid and/or a hepatic neutral fat-reducing activity and/or a platelet aggregation-inhibiting activity, obtained by utilizing general purpose oil seeds, having less adverse effects, simple and usable daily. <P>SOLUTION: The oils and fats having an extremely potent blood neutral fat-reducing activity and/or hepatic neutral fat synthesis-inhibiting activity and/or platelet aggregation-inhibiting activity are provided with that the ratio of 5,11,14-eicosatrienoic acid occupying the total fatty acids constituting triglycerides is 8-50 mass%. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は血中中性脂肪低下作用および/または肝臓中性脂肪合成抑制作用および/または血小板凝集抑制作用を有する油脂に関する。   The present invention relates to fats and oils having blood neutral fat lowering action and / or liver neutral fat synthesis inhibiting action and / or platelet aggregation inhibiting action.

血清中の脂質含量が増加した状態である高脂血症は、動脈硬化症を促進させ、冠動脈疾患や脳卒中等の要因とされている。特に中性脂肪の増加は、脂肪肝、膵炎の発症に結びつくほか、虚血性心疾患の危険因子とされている。とりわけ肝硬変や肝がんの原因となる脂肪肝は、アルコールの多飲や栄養過剰によっても引き起こされる。また、血小板凝集による血栓症も、虚血性心疾患や脳卒中を招くことが知られているが、これらは日常の食事に影響されることから、食習慣の改善が必要とされている。   Hyperlipidemia, which is a state in which the serum lipid content is increased, promotes arteriosclerosis and is considered to be a cause of coronary artery disease and stroke. In particular, an increase in neutral fat is associated with the onset of fatty liver and pancreatitis, and is considered a risk factor for ischemic heart disease. In particular, fatty liver, which causes cirrhosis and liver cancer, is also caused by excessive alcohol consumption and overnutrition. Thrombosis caused by platelet aggregation is also known to cause ischemic heart disease and stroke, but since these are affected by daily diet, improvement of eating habits is required.

これらの問題を解決する技術として、クロフィブラートやニコチン酸コレスチラミン等の抗高脂血症剤の投与があげられる。しかし、これらの薬剤は副作用として肝機能障害などの多くの副作用を発症させ、特に脂肪肝の治療に適していない。   As a technique for solving these problems, administration of antihyperlipidemic agents such as clofibrate and cholestyramine nicotinate can be mentioned. However, these drugs cause many side effects such as liver dysfunction as side effects, and are not particularly suitable for the treatment of fatty liver.

このような観点から、安価で日常的に用いることができ、かつ副作用もなく安全に高脂血症や脂肪肝、血栓症を予防、治療できるような方法が求められている。   From such a viewpoint, there is a need for a method that can be used inexpensively and routinely, and can safely prevent and treat hyperlipidemia, fatty liver, and thrombosis without side effects.

そこで、エイコサペンタエン酸(EPA)やドコサヘキサエン酸(DHA)等の高度不飽和脂肪酸が血清中性脂肪値やコレステロール値を低減させること、および血小板凝集を抑制することが明らかになったこと(非特許文献1)から、高脂血症や血栓症の予防と治療のために、このような脂肪酸を多く含む魚を意図的に摂取したり、魚油や魚油濃縮物を素材とする健康食品等が市販されるようになった。しかし、このような高度不飽和脂肪酸油脂は酸化されやすく、日常の調理に利用されるてんぷら油やサラダ油等の食用油脂として使用するには適さない。   Thus, it has been clarified that highly unsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce serum neutral fat level and cholesterol level and suppress platelet aggregation (non-patented). From literature 1), for the prevention and treatment of hyperlipidemia and thrombosis, intentionally ingesting fish containing a large amount of such fatty acids, and health foods made from fish oil or fish oil concentrate are commercially available. It came to be. However, such highly unsaturated fatty acid fats and oils are easily oxidized and are not suitable for use as edible fats and oils such as tempura oil and salad oil used for daily cooking.

一方、ナギ種子、ニオイヒバ種子、イチイ種子、コノテガシワ種子、チョウセンマツ種子、カイガンショウ種子などには、二重結合の配置が非メチレン介在型である高度不飽和脂肪酸の5,9,12−オクタデカトリエン酸(all cis −5,9,12−octadecatrienoic acid、ピノレン酸)および/または5,11,14−エイコサトリエン酸(all cis −5,11,14−eicosatrienoic acid、シアドン酸)および/または5,11,14,17−エイコサテトラエン酸(all cis −5,11,14、17−eicosatetraenoic acid酸、ジュニペロニック酸)が存在することが知られている。これらのうち、コノテガシワ、チョウセンマツ、カイガンショウの種子油に血清脂質の改善作用や肝臓中性脂肪の低下作用を有することが報告されている(非特許文献2〜7)。有効成分としては、非メチレン介在型高度不飽和脂肪酸が考えられているが、異なった構造の非メチレン介在型高度不飽和脂肪酸を複数含むことから、有効成分は特定されていない。   On the other hand, nagi seeds, scented hiyaba seeds, yew seeds, konotegasiwa seeds, Korean pine seeds, silkworm show seeds and the like are 5,9,12-octa of highly unsaturated fatty acids whose double bond arrangement is a non-methylene mediated type. Decatrienoic acid (all cis-5,9,12-octadecatrienoic acid, pinolenic acid) and / or 5,11,14-eicosatrienoic acid (all cis-5,11,14-eicosatrienoic acid, cyanidic acid) and / or Alternatively, it is known that 5,11,14,17-eicosatetraenoic acid (all cis-5,11,14,17-eicosatetraenoic acid acid, juniperonic acid) exists. Among these, it has been reported that seed oil of Konotegasiwa, Korean pine, and silkworm show has an action of improving serum lipids and an action of reducing liver neutral fat (Non-Patent Documents 2 to 7). As the active ingredient, non-methylene mediated highly unsaturated fatty acids are considered, but since an active ingredient contains a plurality of non-methylene mediated highly unsaturated fatty acids having different structures, no active ingredient is specified.

水産脂質−その特性と生理作用−、1993、恒星社厚生閣刊、pp.80−87Fishery lipids-Their properties and physiological effects-1993, published by Hoshiseisha Koseikaku, pp. 80-87 リピッズ(Lipids)、1992、Vol. 27、No. 7、pp.500−504Lipids, 1992, Vol. 27, No. 7, pp. 500-504 ブリティッシュ・ジャーナル・オブ・ニュートリッション(British Journal of Nutrition)、1994、Vol. 72、pp.775−783British Journal of Nutrition, 1994, Vol. 72, pp. 775-783 ジャーナル・オブ・ニュートリッション(Journal of Nutrition)、1999、Vol. 129、pp.1972−1978Journal of Nutrition, 1999, Vol. 129, pp. 1972-1978 リピッズ(Lipids)、1999、Vol. 34、No. 1、pp.39−44Lipids, 1999, Vol. 34, No. 1, pp. 39-44 ブリティッシュ・ジャーナル・オブ・ニュートリッション(British Journal of Nutrition)、2000、Vol. 84、pp.353−360British Journal of Nutrition, 2000, Vol. 84, pp.353-360 リピッズ(Lipids)、2001、Vol. 36、No. 6、pp.567−574Lipids, 2001, Vol. 36, No. 6, pp. 567-574

本発明の目的は、汎用的な油糧種子を利用した、副作用が少なく、簡便かつ日常的に使用可能な血清脂質の改善作用および/または肝臓中性脂肪低下作用および/または血小板凝集抑制作用を有する油脂を提供することにある。   An object of the present invention is to provide a serum lipid improving action and / or a liver triglyceride lowering action and / or a platelet aggregation inhibitory action using general-purpose oil seeds with few side effects and which can be used easily and daily. It is in providing the fats and oils to have.

上記目的に対し、本発明者らは種々の種子油と血清脂質及び肝臓脂質低下作用との相関を鋭意検討した結果、非メチレン介在型である高度不飽和脂肪酸のうち、5,11,14−エイコサトリエン酸のみを含むカヤ種子から抽出した油脂に、極めて強い血中中性脂肪低下作用および/または肝臓中性脂肪合成抑制作用および/または血小板凝集抑制作用があることを見出し、本発明を完成するに至った。   As a result of intensive studies on the correlation between various seed oils and serum lipid and liver lipid lowering effects, the present inventors have found that 5,11,14- The oil and fat extracted from kaya seeds containing only eicosatrienoic acid has been found to have an extremely strong blood neutral fat lowering action and / or liver neutral fat synthesis inhibiting action and / or platelet aggregation inhibiting action. It came to be completed.

本発明によれば、極めて強い血中中性脂肪低下作用および/または肝臓中性脂肪合成抑制作用および/または血小板凝集抑制作用のある、5,11,14−エイコサトリエン酸を含むカヤ種子などから抽出した油脂が提供される。この油脂は、単独で使用でき、あるいは公知の原材料に配合して飲食物、健康食品、動物用飼料もしくは医薬製剤となすことができ、副作用の懸念もなく、簡便に使用できる。   According to the present invention, kaya seeds containing 5,11,14-eicosatrienoic acid having a very strong blood neutral fat lowering action and / or liver neutral fat synthesis inhibiting action and / or platelet aggregation inhibiting action, etc. Oils and fats extracted from are provided. The fats and oils can be used alone, or can be blended with known raw materials to form foods, drinks, health foods, animal feeds or pharmaceutical preparations, and can be used simply without concern about side effects.

カヤ油もしくは、5,11,14−エイコサトリエン酸を含む他の油糧種子は、従来から食用油として幅広く用いられており、安全性については問題のないものである。また、本発明に係る油脂は一般に市販されている通常の食用油脂と同等あるいはそれ以上の風味を持ち、従来の食用油脂の代替品となりうる。通常の油脂と同様に、炒め物、揚げ物などのあらゆる調理に使用できるのはもちろんのこと油脂を含有する食品であるドレッシング、マヨネーズ、マーガリン、クリーム類、菓子類、パン、ケーキ、チョコレート、アイスクリームにも使用可能である。用途についても一般家庭用に止まることなく業務用、給食用、健康食品用、治療用及び病院給食用としても使用できる。つまり、本発明は、食用油脂としての日常摂取することで、血清中性脂肪および/または脂肪肝および/または血栓症の改善効果をえることができるものである。   Kaya oil or other oil seeds containing 5,11,14-eicosatrienoic acid have been widely used as edible oils, and have no safety problems. Moreover, the fats and oils which concern on this invention have the flavor equivalent to or more than the normal edible fats and oils generally marketed, and can replace the conventional edible fats and oils. Like normal oils and fats, it can be used for all kinds of cooking such as fried foods and fried foods, as well as dressings, mayonnaise, margarines, creams, confectionery, breads, cakes, chocolates, ice creams that contain oils and fats. Can also be used. It can also be used for business use, for lunch, for health food, for treatment, and for hospital use without stopping for general household use. That is, according to the present invention, an effect of improving serum neutral fat and / or fatty liver and / or thrombosis can be obtained by daily intake as an edible oil.

また、本発明に係る油脂は例えば他の食用動植物性油脂、ビタミンE、β−カロテン等とともにソフトカプセルやマイクロカプセル等のカプセル状にして摂取することもできる。このように本発明に係る油脂は高脂血症、脂肪肝、血栓症の予防および治療のために利用されることも期待できる。   The fats and oils according to the present invention can be ingested in the form of capsules such as soft capsules and microcapsules together with other edible animal and vegetable oils and fats, vitamin E, β-carotene and the like. Thus, the oil and fat according to the present invention can be expected to be used for the prevention and treatment of hyperlipidemia, fatty liver and thrombosis.

以下に本発明をより具体的に説明するために、試験例を示す。無論、本発明はそれらによって限定されるものではない。   In order to describe the present invention more specifically, test examples are shown below. Of course, the present invention is not limited thereto.

試験例について説明すると、4週齢のSD系雄性ラットに、カヤ油、大豆油、コーン油(各試験油の脂肪酸組成を表1に示す。)をそれぞれ10重量%配合した飼料(表2)を4週間自由摂取させた。4週間後に各試験群8匹ずつ解剖により採血し、血清脂質濃度を常法により測定した。また、各試験群のラットの肝臓組織の重量を測定すると共に、コレステロール、トリグリセリド、リン脂質量を測定した。また、血小板凝集の重要な因子である血中リン脂質の脂肪酸組成を分析した。大豆油添加群およびコーン油添加群を対照に統計処理を行い、危険率5%以下のものを有意な差とした。表3に血清脂質濃度を、表4に肝臓組織重量および肝臓脂質濃度を示す。各試験区とも飼料摂取量、体重増加量および肝臓重量に有意差は認められなかった。カヤ油を添加した試験群は、血清中性脂肪および肝臓中性脂肪濃度が、大豆油およびコーン油を添加した試験群よりも有意に低い値を示した。また、血中リン脂質の脂肪酸組成を分析した結果、表5に示すように、18:2と20:4の脂肪酸の割合が減少し、シアドン酸(20:3)が増加した。20:4および18:2は血小板凝集能の強いトロンボキサンA2の原料となるため、血中リン脂質中にこれら脂肪酸の濃度が高いと血小板凝集を起こしやすいことが知られている。また、シアドン酸は20:4と構造が似ているが、トロンボキサンA2の原料にはならないため、トロンボキサンA2の合成を拮抗的に抑制すると考えられる。従って、カヤ油の摂取によって血中リン脂質の脂肪酸組成が変化して、血小板凝集作用の強いトロンボキサンA2の産生が減少することから、カヤ油には血小板凝集抑制作用があるといえる。この実験結果から、本発明に係るトリグリセリド(カヤ油)はラットに対して副作用がなく、血清中性脂肪および肝臓中性脂肪値が顕著に低減すること、および血小板凝集抑制作用があることが明らかになった。   Explaining the test examples, feeds containing 10 wt% of kaya oil, soybean oil and corn oil (the fatty acid composition of each test oil is shown in Table 1) in 4 weeks old SD male rats (Table 2). For 4 weeks. Four weeks later, 8 animals were collected from each test group by dissection, and the serum lipid concentration was measured by a conventional method. Moreover, while measuring the weight of the liver tissue of the rat of each test group, the amount of cholesterol, triglyceride, and phospholipid was measured. In addition, the fatty acid composition of blood phospholipid, which is an important factor of platelet aggregation, was analyzed. Statistical processing was performed with the soybean oil added group and the corn oil added group as controls, and a risk rate of 5% or less was regarded as a significant difference. Table 3 shows serum lipid concentration, and Table 4 shows liver tissue weight and liver lipid concentration. There was no significant difference in feed intake, body weight gain, or liver weight in each test group. The test group to which kaya oil was added showed significantly lower serum neutral fat and liver neutral fat concentrations than the test group to which soybean oil and corn oil were added. Moreover, as a result of analyzing the fatty acid composition of blood phospholipid, as shown in Table 5, the ratio of 18: 2 and 20: 4 fatty acids decreased, and cyanidic acid (20: 3) increased. Since 20: 4 and 18: 2 are raw materials for thromboxane A2 having a strong platelet aggregation ability, it is known that platelet aggregation tends to occur when the concentration of these fatty acids in blood phospholipids is high. In addition, although the structure of siadonic acid is similar to that of 20: 4, it is not a raw material for thromboxane A2, and therefore, it is considered that the synthesis of thromboxane A2 is competitively suppressed. Therefore, the intake of kaya oil changes the fatty acid composition of blood phospholipids and decreases the production of thromboxane A2, which has a strong platelet aggregation action. Therefore, it can be said that kaya oil has a platelet aggregation inhibitory action. From these experimental results, it is clear that the triglyceride (kaya oil) according to the present invention has no side effects on rats, significantly reduces serum neutral fat and liver neutral fat levels, and has an effect of inhibiting platelet aggregation. Became.

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Claims (9)

5,11,14−エイコサトリエン酸を有効成分とすることを特徴とする血中中性脂肪低下剤。   A blood neutral fat lowering agent comprising 5,11,14-eicosatrienoic acid as an active ingredient. 5,11,14−エイコサトリエン酸を有効成分とすることを特徴とする肝臓中性脂肪合成抑制剤。   A liver neutral fat synthesis inhibitor comprising 5,11,14-eicosatrienoic acid as an active ingredient. 5,11,14−エイコサトリエン酸を有効成分とすることを特徴とする血小板凝集抑制剤。   A platelet aggregation inhibitor comprising 5,11,14-eicosatrienoic acid as an active ingredient. 5,11,14−エイコサトリエン酸グリセリドを有効量含んでなることを特徴とする血中中性脂肪低下作用を有する油脂。   An oil having a blood neutral fat lowering action, characterized by comprising an effective amount of 5,11,14-eicosatrienoic acid glyceride. 5,11,14−エイコサトリエン酸グリセリドを有効量含んでなることを特徴とする肝臓中性脂肪合成抑制作用を有する油脂。   An oil or fat having an action of inhibiting the synthesis of neutral fat in liver, comprising an effective amount of 5,11,14-eicosatrienoic acid glyceride. 5,11,14−エイコサトリエン酸グリセリドを有効量含んでなることを特徴とする血小板凝集抑制作用を有する油脂。   An oil having an action of inhibiting platelet aggregation, comprising an effective amount of 5,11,14-eicosatrienoic acid glyceride. 5,11,14−エイコサトリエン酸グリセリドがカヤ種子から得られるものまたはこれらを濃縮処理したものまたはこれらをエステル交換処理したものである請求項4〜6に記載の油脂。   The fats and oils according to claims 4 to 6, wherein 5,11,14-eicosatrienoic acid glyceride is obtained from kaya seeds, or is obtained by concentrating them or subjected to transesterification. 請求項4〜7いずれか1項に記載の油脂を含有する食用油脂。   Edible fats and oils containing the fats and oils of any one of Claims 4-7. 請求項4〜8いずれか1項に記載の油脂を含有する油脂加工品。   The fats and oils processed product containing the fats and oils of any one of Claims 4-8.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008126363A1 (en) * 2007-03-30 2008-10-23 Kowa Company, Ltd. Drug for preventing and/or treating fatty liver or nonalcoholic fatty liver disease

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008126363A1 (en) * 2007-03-30 2008-10-23 Kowa Company, Ltd. Drug for preventing and/or treating fatty liver or nonalcoholic fatty liver disease
JP5341749B2 (en) * 2007-03-30 2013-11-13 興和株式会社 Pharmaceuticals for the prevention and / or treatment of fatty liver or non-alcoholic steatohepatitis
US8673976B2 (en) 2007-03-30 2014-03-18 Kowa Company, Ltd. Medicament for prophylactic and/or therapeutic treatment of hepatic steatosis or non-alcoholic steatohepatitis
KR101461252B1 (en) 2007-03-30 2014-11-12 코와 가부시키가이샤 Drug for preventing and/or treating fatty liver or nonalcoholic fatty liver disease
CN101652134B (en) * 2007-03-30 2015-07-15 兴和株式会社 Drug for preventing and/or treating fatty liver or nonalcoholic fatty liver disease

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