JP2006151875A - Lipase inhibitor - Google Patents

Lipase inhibitor Download PDF

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JP2006151875A
JP2006151875A JP2004345099A JP2004345099A JP2006151875A JP 2006151875 A JP2006151875 A JP 2006151875A JP 2004345099 A JP2004345099 A JP 2004345099A JP 2004345099 A JP2004345099 A JP 2004345099A JP 2006151875 A JP2006151875 A JP 2006151875A
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oil
type
fat
lipase
uul
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Toshiharu Arishima
俊治 有島
Nobuhiko Tachibana
伸彦 橘
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Fuji Oil Co Ltd
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Fuji Oil Co Ltd
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Priority to JP2004345099A priority Critical patent/JP2006151875A/en
Priority to EP11000095A priority patent/EP2298293A1/en
Priority to KR1020067013989A priority patent/KR20060124679A/en
Priority to PCT/JP2004/019360 priority patent/WO2005067913A1/en
Priority to EP04807717A priority patent/EP1704861A4/en
Priority to CA2551119A priority patent/CA2551119C/en
Priority to US10/583,382 priority patent/US20070191495A1/en
Publication of JP2006151875A publication Critical patent/JP2006151875A/en
Priority to US12/662,405 priority patent/US20100210723A1/en
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Abstract

<P>PROBLEM TO BE SOLVED: To provide an oil-soluble lipase inhibitor contributing to prevent and treat obesity caused by excessive intake of fat and diseases caused by excessive ingestion of fat and able to be added to every fat and oil. <P>SOLUTION: The lipase inhibitor comprises LUU type and UUL type triacyl glycerols (wherein L expresses a 16-22C long chain saturated fatty acid; U expresses an asymmetrical triacyl glycerol constituted of a 16-22C long chain unsaturated fatty acid) as effective ingredients and is a lipid absorption inhibitor, an anti-obesity agent and a hyperlipidemia-improving agent. Foods and medicinal agent containing the same are claimed. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は、リパーゼ阻害剤及びそれを含有する食品に関する。さらに詳しくは、生体内での脂質の消化吸収をにない、肥満症、高脂血症の鍵となる膵臓リパーゼを有効に阻害してこれらの疾病の抑制や予防に寄与し得る安全性の高い油溶性のリパーゼ阻害剤に関する。   The present invention relates to a lipase inhibitor and a food containing the same. More specifically, it is highly safe to digest and absorb lipids in vivo and effectively inhibit pancreatic lipase, which is the key to obesity and hyperlipidemia, and contribute to the suppression and prevention of these diseases. The present invention relates to an oil-soluble lipase inhibitor.

近年、食事からの脂肪摂取の過剰による肥満と糖尿病・高脂血症・循環器疾患といった生活習慣病の関係が取り上げられ、問題とされている。これを改善する方法として、1.食品中の油脂含量の低下、2.油脂そのものの低カロリー化、3.油脂代替物での置換、4.代謝の促進、5.リパーゼ阻害剤などが提案されている。5.のリパーゼ阻害剤については、脂肪の膵臓リパーゼによる分解を阻害して肥満を抑制、予防する薬剤の開発が試みられている。
例えば、特許文献1では、紅景天、イワベンケイ、サボンソウ、ボルド、パスチャカ、トルメンチラ、エルカンプリ、ウコンイソマツ、チュチュウアシ、キャッツクロー、シナモン、山椒、センダングサ、ウコギ、ストロベリー、モージェ、バラ、柿、セイヨウオトギリソウ、杜仲及び白茶からなる植物の群より選ばれる少なくとも1種を含有するリパーゼ阻害剤が提案されている。
In recent years, the relationship between obesity due to excessive intake of fat from the diet and lifestyle-related diseases such as diabetes, hyperlipidemia, and cardiovascular disease has been taken up and has become a problem. As a method of improving this, 1. Reduction of fat content in foods 2. Reduce the calories of the oil itself; 3. Replacement with oil substitutes 4. Promotion of metabolism, Lipase inhibitors have been proposed. 5. As for lipase inhibitors, development of drugs that suppress and prevent obesity by inhibiting the degradation of fat by pancreatic lipase has been attempted.
For example, in Patent Document 1, Red Scenic Sky, Iwabenkei, Savonsou, Bold, Paschaca, Tormentilla, El Campuri, Turmeric islet, Chuchueashi, Cat's Claw, Cinnamon, Yam, Sendangsa, Ukogi, Strawberry, Mauger, Rose, Camellia, Hypericum perforatum, Lipase inhibitors containing at least one selected from the group of plants consisting of Tochu and white tea have been proposed.

また、特許文献2では、ユッカ、高麗人参、ジャスミン茶、山査子、黄杞茶、ルイボス茶、大豆胚芽、生姜、および杜仲茶よりなる群から選択される少なくとも1種以上の素材からの抽出エキスを有効成分とするリパーゼ阻害剤が提案されている。
しかしながら、抽出物が殆ど水溶性のものであり油脂に混ぜることが出来なかったり、喫食時に服用させるしか方法がなく煩雑であったり、また抽出物の効果が不充分であったりしてその殆どが市場に出ていない。
一方、油脂に溶解できる油溶性の物質としては、特許文献3において、テトラヒドロリプスタチンを胃腸リパーゼ阻害剤として使用することが提案されている。この阻害剤はリパーゼそのものと直接共有結合して失活させるといわれており、その効果はかなり強力で一部には下痢症状も観られ、食品としては安全性の面での懸念が残り、よりマイルドに効果を発揮するような油溶性のリパーゼ阻害剤が望まれている。
Further, in Patent Document 2, an active ingredient is an extract extracted from at least one material selected from the group consisting of yucca, ginseng, jasmine tea, yamazuko, yellow ginger tea, rooibos tea, soybean germ, ginger and tochu tea. A lipase inhibitor has been proposed.
However, the extract is almost water-soluble and cannot be mixed with fats and oils. Not on the market.
On the other hand, as an oil-soluble substance that can be dissolved in fats and oils, Patent Document 3 proposes the use of tetrahydrolipstatin as a gastrointestinal lipase inhibitor. This inhibitor is said to inactivate by covalent bonding directly with the lipase itself, its effect is quite strong, some diarrhea symptoms are also seen, food safety concerns remain, Oil-soluble lipase inhibitors that are mildly effective are desired.

特開2002−179586号公報JP 2002-179586 A 特開2002−275077号公報JP 2002-275077 A 米国特許第4598089号明細書US Pat. No. 4,598,089

本発明の目的は、脂肪の過剰摂取による肥満や肥満が原因で発生する疾病の予防や治療に寄与し得て、且つあらゆる油脂に添加し得る油溶性のリパーゼ阻害剤を提供することにある。   An object of the present invention is to provide an oil-soluble lipase inhibitor that can contribute to the prevention and treatment of obesity caused by excessive intake of fat and diseases caused by obesity, and that can be added to all fats and oils.

本発明者らは、上記の問題を解決するため鋭意研究をおこなった結果、グリセロールの1位が長鎖飽和脂肪酸、2位と3位が長鎖不飽和脂肪酸より構成される非対称型トリアシルグリセロール及びグリセロールの3位が長鎖飽和脂肪酸、1位と2位が長鎖不飽和脂肪酸より構成される非対称型トリアシルグリセロールが膵臓リパーゼの活性を阻害することを発見し、この非対称型トリアシルグリセロールをベース油脂中に少量含むことにより油脂全体の分解速度が緩和されることを見出したのである。
即ち本発明の第1は、LUU型及びUUL型トリアシルグリセロール(Lは炭素数18〜22の長鎖飽和脂肪酸、Uは炭素数16〜22の不飽和脂肪酸より構成される非対称型トリアシルグリセロール)を有効成分とするリパーゼ阻害剤である。第2は、第1記載の非対称型トリアシルグリセロールを有効成分とする脂質吸収阻害剤である。第3は、第1記載の非対称型トリアシルグリセロールを有効成分とする抗肥満剤である。第4は、第1記載の非対称型トリアシルグリセロールを有効成分とする高脂血症改善剤である。第5は、第1乃至第4何れか1に記載の剤を含有する食品である。第6は、第1乃至第4何れか1に記載の剤を含有する医薬である。
As a result of intensive studies to solve the above problems, the present inventors have found that an asymmetric triacylglycerol in which glycerol is composed of a long-chain saturated fatty acid at position 1 and long-chain unsaturated fatty acids at positions 2 and 3 It was discovered that asymmetric triacylglycerol composed of a long-chain saturated fatty acid at position 3 and a long-chain unsaturated fatty acid at positions 1 and 2 inhibits the activity of pancreatic lipase. It has been found that the degradation rate of the whole oil and fat is reduced by containing a small amount of in the base oil and fat.
That is, the first of the present invention is LUU type and UUL type triacylglycerol (L is a long-chain saturated fatty acid having 18 to 22 carbon atoms, U is an asymmetric type triacylglycerol composed of unsaturated fatty acid having 16 to 22 carbon atoms. ) As an active ingredient. The second is a lipid absorption inhibitor containing the asymmetric triacylglycerol described in the first as an active ingredient. The third is an anti-obesity agent containing the asymmetric triacylglycerol as described in the first item as an active ingredient. The fourth is a hyperlipidemia improving agent comprising the asymmetric triacylglycerol as described in the first item as an active ingredient. 5th is the foodstuff containing the agent in any one of 1st thru | or 4th. The sixth is a medicine containing the agent according to any one of the first to fourth.

本発明のLUU型及びUUL型トリアシルグリセロールはリパーゼ活性を強力に阻害し、かつ油溶性でありあらゆる油脂に添加でき、脂肪の過剰摂取による肥満や肥満が原因で発生する疾病の予防や治療に有効である。   The LUU type and UUL type triacylglycerol of the present invention strongly inhibits lipase activity and is oil-soluble and can be added to any fats and oils for the prevention and treatment of obesity caused by excessive intake of fats and diseases caused by obesity. It is valid.

本発明における、リパーゼによる加水分解を遅延させる油溶性物質LUU型及びUUL型トリアシルグリセロールは、そのグリセロールの1位、又は3位に結合する脂肪酸が飽和脂肪酸で炭素数16のパルミチン酸から炭素数22のベヘン酸までのものであってより長鎖脂肪酸が好ましく、2位と3位(LUU型の場合)又は1位と2位(UUL型の場合)に結合する脂肪酸が炭素数16のパルミトオレイン酸から炭素数22のエルシン酸までの脂肪酸で構成されるもので、長鎖不飽和脂肪酸はモノ不飽和脂肪酸からポリ不飽和脂肪酸までのいずれでも良いが、実際に使用する場合の酸化安定性の観点からはモノ不飽和が好ましい。このようなLUU型、又はUUL型トリアシルグリセロールの一部例をあげるとSOO(1位がステアリン酸、2,3位がオレイン酸)、OOS(3位がステアリン酸、1,2位がオレイン酸)、SLiLi(1位がステアリン酸、2,3位がリノール酸)、SLnLn(1位がステアリン酸、2,3位がリノレン酸)、BOO(1位がベヘン酸、2,3位がオレイン酸)、BLiO(1位がベヘン酸、2位がリノール酸、3位がオレイン酸)などが例示でき、これらの中ではBOO(1位がベヘン酸、2,3位がオレイン酸)、OOB(3位がベヘン酸、1,2位がオレイン酸)が好ましい。   In the present invention, the oil-soluble substance LUU type and UUL type triacylglycerol that delays hydrolysis by lipase is a saturated fatty acid whose fatty acid bonded to the 1st or 3rd position of the glycerol is a carbon number from palmitic acid having 16 carbon atoms. Long chain fatty acids are preferred, up to 22 behenic acids, and fatty acids that bind to the 2nd and 3rd positions (in the case of LUU type) or the 1st and 2nd positions (in the case of UUL type) have 16 carbon atoms. It is composed of fatty acids ranging from tooleic acid to erucic acid having 22 carbon atoms, and long-chain unsaturated fatty acids may be any of mono-unsaturated fatty acids to polyunsaturated fatty acids. From the viewpoint of safety, monounsaturation is preferable. Some examples of such LUU-type or UUL-type triacylglycerols are SOO (1st is stearic acid, 2nd and 3rd oleic acid), OOS (3rd is stearic acid, 1st and 2nd are olein) Acid), SLiLi (position 1 is stearic acid, positions 2 and 3 are linoleic acid), SLnLn (position 1 is stearic acid, positions 2 and 3 are linolenic acid), BOO (position 1 is behenic acid, positions 2 and 3 are Oleic acid), BLiO (behenic acid at the 1st position, linoleic acid at the 2nd position, oleic acid at the 3rd position), etc. Among these, BOO (behenic acid at the 1st position, oleic acid at the 2nd and 3rd positions), OOB (behenic acid at position 3 and oleic acid at positions 1 and 2) is preferred.

このLUU型及びUUL型トリアシルグリセロールの油脂は、そのグリセロールの1位、又は3位に結合する脂肪酸が長鎖飽和脂肪酸であるため、リパーゼによる加水分解を受け難い性質を有し、このLUU型及びUUL型トリアシルグリセロールをベース油脂中に0.5〜30重量%、好ましくは1〜15重量%、最も好ましくは1〜10重量%含むことで、リパーゼによる加水分解が緩和・遅延されるというものである。
油脂に対するリパーゼ阻害剤による加水分解の緩和・遅延程度としては、マイルドな阻害効果が好ましく、具体的には摂取油脂の1〜3割程度、好ましくは1〜2割程度が分解されにくい状態を理想とする。
また、LLU型やLUL型トリアシルグリセロールのように長鎖飽和脂肪酸が分子内に2本導入されたものでは融点が上昇し体温付近では結晶化してしまうため、生体内でリパーゼの基質として認識されにくくなり、阻害効果が期待できない。
The LUU type and UUL type triacylglycerol oils and fats have a property that they are not easily hydrolyzed by lipase because the fatty acid bonded to the 1- or 3-position of the glycerol is a long-chain saturated fatty acid. And containing UUL type triacylglycerol in the base fat and oil in an amount of 0.5 to 30% by weight, preferably 1 to 15% by weight, and most preferably 1 to 10% by weight, so that hydrolysis by lipase is alleviated / retarded. Is.
Mild inhibitory effect is preferable as the degree of hydrolysis and delay by lipase inhibitors for fats and oils. Specifically, about 10 to 30%, preferably 10 to 20% of ingested fats and oils are ideally resistant to degradation. And
In addition, when two long-chain saturated fatty acids are introduced into the molecule, such as LLU-type and LUL-type triacylglycerol, the melting point rises and crystallization occurs near the body temperature, so that it is recognized as a lipase substrate in vivo. It becomes difficult to expect an inhibitory effect.

このLUU型及びUUL型トリアシルグリセロールは一般的には動物・植物・魚由来の長鎖飽和脂肪酸を含む油脂あるいはそのエステル体と、長鎖不飽和脂肪酸を含む油脂とを任意の配合で混合した後、1,3位特異性のあるリパーゼを使用して公知の方法でエステル交換させることで得られる。植物油脂としては例えば、大豆油、菜種油、パーム油、綿実油、ヒマワリ油、コーン油、キャノーラ油などが挙げられ、動物油脂としては牛脂、豚脂、魚油などが挙げられる。また、非選択的エステル交換、例えばナトリウムメチラートなどのアルカリ系触媒を用いてつくることも可能ではあるが、位置異性体であるULU、UUU、LLU、LUL、LLLができるため、その後の濃縮操作が煩雑となり、あまり実用的ではない。かくして得られたLUU型及びUUL型油脂はその後、分別などの通常の加工処理を施して80%前後まで濃縮することが出来る。   This LUU-type and UUL-type triacylglycerol is generally a mixture of fats and oils containing long-chain saturated fatty acids derived from animals, plants and fish, or esters thereof, and fats and oils containing long-chain unsaturated fatty acids in any combination. Thereafter, it is obtained by transesterification by a known method using a lipase having 1,3-position specificity. Examples of vegetable oils include soybean oil, rapeseed oil, palm oil, cottonseed oil, sunflower oil, corn oil, canola oil, and animal oils include beef fat, pork fat, fish oil, and the like. Although it is possible to make non-selective transesterification, for example, using an alkaline catalyst such as sodium methylate, the regioisomers ULU, UUU, LLU, LUL, and LLL can be produced. Becomes cumbersome and not very practical. The LUU type and UUL type fats and oils thus obtained can then be concentrated to about 80% by subjecting them to ordinary processing such as fractionation.

本発明のLUU型及びUUL型トリアシルグリセロールはそのまま使用してもよいし、また任意に他のベース油脂にブレンドして使用してもよい。ブレンドされる比率は期待する効果や使用する系によって異なるが、ベース油脂は食用の動・植物油脂であればなんら制限はない。   The LUU type and UUL type triacylglycerols of the present invention may be used as they are, or optionally blended with other base oils and fats. The blend ratio varies depending on the expected effect and the system to be used, but the base fat is not limited as long as it is an edible animal / vegetable fat.

本発明のLUU型及びUUL型トリアシルグリセロールは、通常油脂を含有する食品に広く使用することができる。例えばクリーム・マーガリン・マヨネーズ・ドレッシング・乳製品といった乳化食品、チョコレートに代表される菓子類、パン類、ハム・ソーセージ等の食肉加工品、かまぼこ・ちくわ等の水産加工食品などに添加して風味・食感を損なうことなく使用できる。   The LUU type and UUL type triacylglycerols of the present invention can be widely used for foods usually containing fats and oils. For example, emulsified foods such as cream, margarine, mayonnaise, dressing, dairy products, confectionery represented by chocolate, processed meat products such as bread, ham and sausage, fishery processed foods such as kamaboko and chikuwa, etc. Can be used without impairing the texture.

本発明のリパーゼ阻害剤、脂質吸収阻害剤、抗肥満剤、高脂血症改善剤及びこれらを含有する医薬の投与方法は、経口投与または非経口投与のどちらでよい。投与に際しては、有効成分を経口投与、直腸内投与、注射などの投与方法に適した固体または液体の医薬用担体と混合して、製剤の形態で投与することができる。   The lipase inhibitor, lipid absorption inhibitor, anti-obesity agent, hyperlipidemia ameliorating agent of the present invention, and the method of administering a medicine containing these may be either oral or parenteral. In administration, the active ingredient can be mixed with a solid or liquid pharmaceutical carrier suitable for administration methods such as oral administration, rectal administration, and injection, and administered in the form of a preparation.

以下に本発明の実施例を示し本発明をより詳細に説明するが、本発明の精神は以下の実施例に限定されるものではない。なお、例中、%及び部は、いずれも重量基準を意味する。   EXAMPLES The present invention will be described in more detail with reference to the following examples, but the spirit of the present invention is not limited to the following examples. In the examples, “%” and “part” mean weight basis.

製造例1
沃素価84のハイオレイックヒマワリ油50部と純度95%のベヘン酸エチル50部を混合し、1,3位特異性のリパーゼ(Novozaymes, Lipozyme RM-IM)を用いてエステル交換を行うことにより反応油を得、蒸留によりエステル類を除去した後、さらにヘキサン100部を加え−5℃で晶析・分別を行うことにより純度70%のLUU/UUL画分20部、純度78%のLUL画分30部を得た。
Production Example 1
By mixing 50 parts of high oleic sunflower oil with an iodine value of 84 and 50 parts of ethyl behenate with a purity of 95%, transesterification using a 1,3-specific lipase (Novozaymes, Lipozyme RM-IM) After the reaction oil was obtained and the esters were removed by distillation, 100 parts of hexane was further added, and crystallization and fractionation were carried out at -5 ° C to obtain 20 parts of a 70% pure LUU / UUL fraction and a 78% pure LUL fraction. 30 parts per minute were obtained.

薬理試験1
この得られたLUU/UUL画分を大豆油中1部(LUU/UUL純度約0.7%),5部(LUU/UUL純度約3.5%),10部(LUU/UUL純度約7.0%)それぞれ置換した系やLUU/UUL画分そのもの(LUU/UUL純度70%)の系で、以下のリパーゼ活性測定を行った。各油脂80mgをサンプリングし、ホスファチジルコリン(Sigma社)80mg、タウロコール酸Na(和光純薬工業)5mg、0.1M NaClを含む0.1MTES緩衝液9ml(PH 7)を各加えた後、超音波発振子で1分間乳化したものを基質した。基質300μlを採取し、ブタ膵臓リパーゼ(Sigma社)を5μl(5U)加え、37℃で1時間反応後、3mlの抽出溶媒(クロロホルム/ヘプタン/メタノール=49部/49部/2部で混合したもの)を加え良く攪拌した後、2500rpmで5分間遠心分離を行い、上層を除去し、下層に銅試薬(トリエタノールアミン2.98g、硝酸銅2.42g、NaOH0.48gを水200mlに溶解し、さらにNaClを66g加えたもの)を1ml加え、10分間攪拌し、2500rpmで10分遠心分離し、上層1.5mlを採取し、発色試薬(バソクプロイン0.2g、ブチルヒドロキシアニソール0.1gをクロロホルム 200mlに溶解したもの)1.5mlを加えて遊離した脂肪酸をOD480 での吸光度にて定量した。表−1に大豆油そのものの系に対する相対活性を示した。表1に示されるようにLUU/UULで1部を置換した系で約15%、5部を置換した系で約25%活性が阻害されることが判明した。
Pharmacological test 1
The LUU / UUL fraction thus obtained was 1 part in soybean oil (LUU / UUL purity about 0.7%), 5 parts (LUU / UUL purity about 3.5%), 10 parts (LUU / UUL purity about 7%). 0.0%) The following lipase activity measurement was carried out in each of the substituted systems and the LUU / UUL fraction itself (LUU / UUL purity 70%). 80 mg of each fat and oil was sampled, phosphatidylcholine (Sigma) 80 mg, Taurocholate Na (Wako Pure Chemical Industries) 5 mg, 0.1 MTES buffer 9 ml (PH 7) containing 0.1 M NaCl were added and then ultrasonic oscillation The substrate emulsified for 1 minute was used as a substrate. 300 μl of the substrate was collected, 5 μl (5 U) of porcine pancreatic lipase (Sigma) was added, reacted at 37 ° C. for 1 hour, and then mixed with 3 ml of extraction solvent (chloroform / heptane / methanol = 49 parts / 49 parts / 2 parts). 1) and well stirred, centrifuged at 2500rpm for 5 minutes, the upper layer is removed, and copper reagent (2.98g triethanolamine, 2.42g copper nitrate, 0.48g NaOH) is dissolved in 200ml water in the lower layer. Add 1 ml of NaCl), stir for 10 minutes, centrifuge at 2500 rpm for 10 minutes, collect 1.5 ml of the upper layer, and add color reagent (0.2 g of bathocuproine, 0.1 g of butylhydroxyanisole to chloroform). The fatty acid liberated by adding 1.5 ml) was quantified by absorbance at OD480. Table 1 shows the relative activity of soybean oil itself to the system. As shown in Table 1, it was found that the activity was inhibited by about 15% in the system in which 1 part was replaced with LUU / UUL and about 25% in the system in which 5 parts were replaced.

比較薬理試験1
製造例1で得られたLUL画分を大豆油中1部(LUL純度約0.8%),5部(LUL純度約3.9%),10部(LUL純度約7.8%)それぞれ置換した系、及びLUL画分そのものの系(LUL純度78%)で先述の試験例と同様のリパーゼ活性測定を行った。表1に示されるようにLULの置換量が増加しても顕著な阻害効果は認められず、また結晶化による一部乳化破壊も確認され、リパーゼの加水分解抑制の効果は無いと判断された。
Comparative pharmacology test 1
The LUL fraction obtained in Production Example 1 was 1 part in soybean oil (LUL purity of about 0.8%), 5 parts (LUL purity of about 3.9%), and 10 parts (LUL purity of about 7.8%). The lipase activity was measured in the same manner as in the previous test example using the substituted system and the system of the LUL fraction itself (LUL purity 78%). As shown in Table 1, even when the substitution amount of LUL was increased, no significant inhibitory effect was observed, and partial emulsion breakage due to crystallization was confirmed, and it was judged that there was no effect of inhibiting lipase hydrolysis. .

比較製造例1
沃素価1のトリベヘン40部と純度98%のオレイン酸エチル60部、さらにヘキサン300部を混合して1,3位特異性のリパーゼ(Novozymes, Lipozyme RM-IM)を用いてエステル交換を行うことにより反応油を得、脱溶剤して蒸留によりエステル類を除去した後、さらにヘキサン100部を加え所定の温度で晶析・分別を行うことにより純度72%のLLU/ULL画分15部、純度70%のULU画分10部を得た。
Comparative production example 1
Mixing 40 parts of tribehen with an iodine value of 1, 60 parts of ethyl oleate with a purity of 98% and 300 parts of hexane, and transesterifying using 1,3-specific lipase (Novozymes, Lipozyme RM-IM) After removing the solvent by distillation and removing the esters by distillation, 100 parts of hexane was further added, and crystallization and fractionation were carried out at a predetermined temperature to obtain 15 parts of LLU / ULL fraction having a purity of 72%. 10 parts of the 70% ULU fraction were obtained.

比較薬理試験2
比較製造例1で得られたLLU/ULL画分を大豆油中1部(LLU/ULL純度約0.7%),5部(LLU/ULL純度約3.6%),10部(LLU/ULL純度約7.2%)それぞれ置換した系、及びLLU/ULL画分そのものの系(LLU/ULL純度72%)で先述の試験例と同様のリパーゼ活性測定を行った。表1に示されるように、LLU/ULLの置換量が増えるとややリパーゼの加水分解抑制効果は認められるが、LUU/UUL程の効果は認められなかった。
Comparative pharmacology test 2
The LLU / ULL fraction obtained in Comparative Production Example 1 is 1 part in soybean oil (LLU / ULL purity about 0.7%), 5 parts (LLU / ULL purity about 3.6%), 10 parts (LLU / The lipase activity was measured in the same manner as in the above-mentioned test examples in the substituted system and the LLU / ULL fraction itself (LLU / ULL purity 72%). As shown in Table 1, when the amount of substitution of LLU / ULL increased, the lipase hydrolysis inhibitory effect was somewhat recognized, but the effect as LUU / UUL was not observed.

比較薬理試験3
比較製造例1で得られたULU画分を大豆油中1部(ULU純度約0.7%),5部(ULU純度約3.5%),10部(ULU純度約7.0%)それぞれ置換した系、及びULU画分そのものの系(ULU純度70%)で先述の試験例と同様のリパーゼ活性測定を行った。表1に示されるように、ULUの置換量が増えても、顕著なリパーゼの加水分解抑制効果は認められなかった。
Comparative pharmacology study 3
The ULU fraction obtained in Comparative Production Example 1 was 1 part in soybean oil (ULU purity about 0.7%), 5 parts (ULU purity about 3.5%), 10 parts (ULU purity about 7.0%). The lipase activity was measured in the same manner as in the above-mentioned test example with the substituted system and the ULU fraction itself (ULU purity 70%). As shown in Table 1, no significant lipase hydrolysis inhibitory effect was observed even when the amount of ULU substitution increased.

Figure 2006151875
Figure 2006151875

マウスでの消化吸収試験
製造例1で得られたLUU/UUL画分を使用して約2ヶ月間のマウスでの消化吸収試験を行った。使用したマウスはC57BL/6Jで7週齢から1週間予備飼育後、食餌組成はAIN−93G組成を一部改良した表2の配合飼料にて大豆油群をコントロールにして各群6匹で約2ヶ月間飼育し、体重変化・飼料効率・体脂肪率の測定を行った。体脂肪率の測定は、実験マウス専用エックス線骨密度測定装置、PIXImus2(GE Medical Systems)を使用した。マウスでの56日間の消化吸収試験の結果、SUU/UUS画分を使用した群では体重で約9%、飼料効率で12%の低下が認められ、また体脂肪率では約13%の低下が観られ、脂肪の過剰摂取による肥満にのLUU/UUL微量添加が効果的であることが示唆された。これらの結果を表3に纏めた。
Digestion and absorption test in mice Using the LUU / UUL fraction obtained in Production Example 1, a digestion and absorption test in mice for about 2 months was performed. The mice used were C57BL / 6J pre-bred from 7 weeks of age for 1 week, and the diet composition was about 6 in each group with the soybean oil group as a control in the mixed feed of Table 2 with a partially improved AIN-93G composition. Breeding for 2 months, changes in body weight, feed efficiency, and body fat percentage were measured. The body fat percentage was measured using a PIXImus2 (GE Medical Systems), an X-ray bone density measuring device dedicated to experimental mice. As a result of the 56-day digestion and absorption test in mice, the group using the SUU / UUS fraction showed a decrease of about 9% in body weight and 12% in feed efficiency, and a decrease in body fat percentage of about 13%. It was observed that LUU / UUL micro-addition to obesity due to excessive intake of fat was suggested to be effective. These results are summarized in Table 3.

Figure 2006151875
Figure 2006151875

Figure 2006151875
Figure 2006151875

本発明により、リパーゼ活性を緩やかに阻害し、かつ油溶性であり、あらゆる食用油脂に添加でき、脂肪の過剰摂取による肥満や肥満が原因で発生する疾病の予防や治療に有効であるリパーゼ阻害剤、およびそれを含む油脂組成物を得ることが可能となったのである。   According to the present invention, a lipase inhibitor that gently inhibits lipase activity, is oil-soluble, can be added to any edible oil and fat, and is effective in the prevention and treatment of obesity caused by excessive intake of fat and obesity caused by obesity And an oil / fat composition containing the same can be obtained.

Claims (6)

LUU型及びUUL型トリアシルグリセロール(Lは炭素数16〜22の長鎖飽和脂肪酸、Uは炭素数16〜22の不飽和脂肪酸より構成される非対称型トリアシルグリセロール)を有効成分とするリパーゼ阻害剤。 Lipase inhibition containing LUU-type and UUL-type triacylglycerol (L is a long-chain saturated fatty acid having 16 to 22 carbon atoms, U is an asymmetric type triacylglycerol composed of unsaturated fatty acid having 16 to 22 carbon atoms) as an active ingredient Agent. 請求項1記載の非対称型トリアシルグリセロールを有効成分とする脂質吸収阻害剤。 A lipid absorption inhibitor comprising the asymmetric triacylglycerol according to claim 1 as an active ingredient. 請求項1記載の非対称型トリアシルグリセロールを有効成分とする抗肥満剤。 An anti-obesity agent comprising the asymmetric triacylglycerol according to claim 1 as an active ingredient. 請求項1記載の非対称型トリアシルグリセロールを有効成分とする高脂血症改善剤。 The hyperlipidemia improving agent which uses the asymmetric type | mold triacylglycerol of Claim 1 as an active ingredient. 請求項1乃至請求項4何れか1項記載の剤を含有する食品。 A food containing the agent according to any one of claims 1 to 4. 請求項1乃至請求項4何れか1項記載の剤を含有する医薬。 A medicament comprising the agent according to any one of claims 1 to 4.
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JP2008024647A (en) * 2006-07-21 2008-02-07 Fuji Oil Co Ltd Adiponectin secretion promoting agent
JP2008024648A (en) * 2006-07-21 2008-02-07 Fuji Oil Co Ltd Hepatic lipid reducing agent
JP2008247792A (en) * 2007-03-30 2008-10-16 Fuji Oil Co Ltd Bowel movement-improving agent
JP5625913B2 (en) * 2008-12-15 2014-11-19 不二製油株式会社 Additive oil and fat composition, chocolate using the same, and method for producing the same

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WO1994019953A1 (en) * 1993-03-04 1994-09-15 Loders Croklaan B.V. Bakery fats ans bakery doughs and batters containing them
WO1995007619A1 (en) * 1993-09-14 1995-03-23 Loders Croklaan B.V. Healthy spread fats
JPH10179027A (en) * 1996-12-26 1998-07-07 Fuji Oil Co Ltd Oily composition and frozen food
JP2001040387A (en) * 1999-07-30 2001-02-13 Showa Sangyo Co Ltd Low-calorie liquid oil and fat

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008024647A (en) * 2006-07-21 2008-02-07 Fuji Oil Co Ltd Adiponectin secretion promoting agent
JP2008024648A (en) * 2006-07-21 2008-02-07 Fuji Oil Co Ltd Hepatic lipid reducing agent
JP2008247792A (en) * 2007-03-30 2008-10-16 Fuji Oil Co Ltd Bowel movement-improving agent
JP5625913B2 (en) * 2008-12-15 2014-11-19 不二製油株式会社 Additive oil and fat composition, chocolate using the same, and method for producing the same

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