JP2014140373A - Method for adding active oxygen-induced disorder inhibiting function to food and drink, and method of producing food and drink having active oxygen-induced disorder inhibiting function added thereto - Google Patents

Method for adding active oxygen-induced disorder inhibiting function to food and drink, and method of producing food and drink having active oxygen-induced disorder inhibiting function added thereto Download PDF

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JP2014140373A
JP2014140373A JP2014058248A JP2014058248A JP2014140373A JP 2014140373 A JP2014140373 A JP 2014140373A JP 2014058248 A JP2014058248 A JP 2014058248A JP 2014058248 A JP2014058248 A JP 2014058248A JP 2014140373 A JP2014140373 A JP 2014140373A
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active oxygen
olide
carbon atoms
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Kojiro Morimitsu
康次郎 森光
Kikue Kubota
紀久枝 久保田
Mihoko Hiruma
美穂子 比留間
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Soda Aromatic Co Ltd
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Abstract

PROBLEM TO BE SOLVED: To provide an active oxygen-induced disorder inhibiting agent, and a method for adding an active oxygen-induced disorder inhibiting function to food and drink.SOLUTION: This invention relates to a method for adding at least one selected from cyclic carbonyl compounds represented by the formulae 1, 2 and 3 to food and drink.

Description

本発明は、活性酸素起因障害抑制剤に関する。さらには、活性酸素に起因して発生又は進行する老化、生活習慣病などの改善に関する。   The present invention relates to an active oxygen-induced disorder inhibitor. Furthermore, the present invention relates to improvement of aging, lifestyle-related diseases and the like that occur or progress due to active oxygen.

活性酸素は殺菌作用による生体防御の役割を持っている。しかし過剰な生成や、あってはならない場所での生成は生体膜を構成するリン脂質やDNA、組織を構成する生体内分子を攻撃して、各種疾患を誘発する。例えばパーキンソン病やアルツハイマー病などは、ミトコンドリアの酸化的損傷を伴っているといわれている。また活性酸素に起因する酸化的損傷が老化現象に関与していると考えられている。このように活性酸素はあまりにも高い反応性のために、様々な生体分子に対して酸化的傷害を与えることが知られている。この活性酸素による酸化を防ぐ、あるいは抑制する抗酸化物質として、生体内酵素としてスーパーオキシドジスムターゼ（SOD）、カタラーゼ、グルタチオンペルオキシターゼが、食品成分としてβ−カロチン、リコピン、アスタキサンチンなどのカロチノイド類やビタミンＣ、ビタミンE、フェノール化合物類が知られている。   Reactive oxygen has a role of biological defense by bactericidal action. However, excessive production or production at a place where it should not attack attacks phospholipids and DNA that constitute biological membranes, and biological molecules that constitute tissues, thereby inducing various diseases. For example, Parkinson's disease and Alzheimer's disease are said to be accompanied by mitochondrial oxidative damage. It is thought that oxidative damage caused by active oxygen is involved in the aging phenomenon. Thus, active oxygen is known to cause oxidative damage to various biomolecules because of its too high reactivity. Antioxidants that prevent or suppress oxidation by active oxygen include superoxide dismutase (SOD), catalase, and glutathione peroxidase as in vivo enzymes, and carotenoids such as β-carotene, lycopene, astaxanthin, and vitamin C as food ingredients. Vitamin E and phenolic compounds are known.

近年では高齢化社会において容貌及び体力の衰えを遅らせ、できる限り質のよい生活を長く維持することへの関心が高まっている。中でも特に抗老化に対する関心が高まってきており、前記の老化の一因子である酸化を防ぐ方法が注目されている。例えばアブラナ科植物中のω−メチルスルフィニルアルキルイソチオシアネートによる皮膚老化防止剤および化粧品（特許文献１参照）、抗酸化活性を有する本ワサビ由来の化合物（特許文献２参照）、香辛料抽出物による活性酸素抑制剤（特許文献３参照）、羽毛処理物による活性酸素生成抑制物質およびそれを含む機能性食品素材（特許文献４参照）が知られている。これらの有効成分は天然物の抽出物、あるいは抽出物の化学的処理物であり、一般に品質の安定性や安定供給の面で不安があった。   In recent years, there has been a growing interest in aging societies to slow down the decline in appearance and physical strength and to maintain a quality life as long as possible. In particular, interest in anti-aging has been increasing, and a method for preventing oxidation, which is a factor of the aging, has attracted attention. For example, skin aging inhibitors and cosmetics (see Patent Document 1) by ω-methylsulfinylalkylisothiocyanate in Brassicaceae plants, compounds derived from this horseradish having antioxidant activity (see Patent Document 2), active oxygen by spice extract Inhibitors (see Patent Document 3), active oxygen production-inhibiting substances using processed feathers, and functional food materials containing the same are known (see Patent Document 4). These active ingredients are natural product extracts or chemically processed products of extracts, and generally have anxiety in terms of quality stability and stable supply.

特開２００６−２４１００５公報JP 2006-241005 A 特開２００６−６９９８２公報JP 2006-69982 A 特開平０８−１１９８６９公報Japanese Patent Laid-Open No. 08-111986 特開２００７−１０６６９５公報JP 2007-106695 A

本発明は、生体内活性酸素が原因で引き起こされる様々な生体への悪影響の症状を軽減し、もしくは予防することができる新規な活性酸素に起因する障害を抑制する手段を提供すること、さらには、より簡便に入手できるとともに、大量生産が容易に実現可能な活性酸素起因障害抑制剤を提供することを目的とする。   The present invention provides a novel means for suppressing a disorder caused by active oxygen, which can reduce or prevent various adverse symptoms caused by active oxygen in the living body. It is an object of the present invention to provide an active oxygen-induced disorder inhibitor that can be obtained more easily and can be easily mass-produced.

本発明は、生体内において活性酸素が原因で引き起こされる様々な生体への悪影響の症状を軽減すること、もしくは予防することを目的として用いられるものであって、下記式１   The present invention is used for the purpose of reducing or preventing various symptoms of adverse effects on living bodies caused by active oxygen in a living body.

Figure 2014140373
（式中、Ｘは炭素数１〜２、又は炭素数１０〜１４の環構成炭素鎖を表す。但し、Ｘの炭素数が１０〜１４のときはＸで表される炭素鎖に二重結合もしくは酸素原子を１個含んでもよい。Ｒ１はＸが炭素数１〜２の場合は炭素数６〜１３のアルキル基を表し、Ｘが炭素数１０〜１４の場合は水素原子であることを表す。破線部はＸが炭素数１〜２の場合に当該箇所の炭素間結合が単結合又は二重結合のいずれでもよいことを表す。）で示される化合物群、及び下記式２
Figure 2014140373
 (In the formula, X represents a C1-C2 or C10-C14 ring-constituting carbon chain. However, when X has 10 to 14 carbon atoms, a double bond is formed on the carbon chain represented by X. Alternatively, it may contain one oxygen atom, R1 represents an alkyl group having 6 to 13 carbon atoms when X is 1 to 2 carbon atoms, and represents a hydrogen atom when X is 10 to 14 carbon atoms. The broken line part indicates that when X is 1 to 2 carbon atoms, the carbon-carbon bond at the position may be either a single bond or a double bond.), And the following formula 2

Figure 2014140373
（式中、ｎは１０〜１２の整数を表す。）で示される化合物群、及び下記式３
Figure 2014140373
 (Wherein n represents an integer of 10 to 12) and the following formula 3

Figure 2014140373
（式中、Ｙは炭素数１０〜１４の環構成炭素鎖を表し、炭素鎖Ｙは１箇所の二重結合を含んでもよく、１箇所の水素原子がメチル基で置換されていてもよい。）で示される化合物群からなる環状カルボニル化合物から選ばれる１種以上を有効成分として含有する活性酸素起因障害抑制剤である。
Figure 2014140373
 (In the formula, Y represents a ring-constituting carbon chain having 10 to 14 carbon atoms, and the carbon chain Y may include one double bond, and one hydrogen atom may be substituted with a methyl group. The active oxygen-induced disorder inhibitor containing as an active ingredient at least one selected from cyclic carbonyl compounds consisting of the compound group represented by

さらに本発明は、ドデカン−４−オリド、ペンタデカン−４−オリド、３−テトラデセン−４−オリド、トリデカン−５−オリド、テトラデカン−５−オリド、ペンタデカン−５−オリド、ヘキサデカン−５−オリド、ペンタデカン−１５−オリド、１１−ペンタデセン−１５−オリド、１２−ペンタデセン−１５−オリド、ヘキサデカン−１６−オリド、６−ヘキサデセン−１６−オリド、１０−オキサ−ヘキサデカン−１６−オリド、１１−オキサ−ヘキサデカン−１６−オリド、１２−オキサ−ヘキサデカン−１６−オリド、１，４−ジオキサシクロヘプタデカン−５，１７−ジオン、５−シクロヘキサデセン−１−オン、３−メチル−シクロペンタデカン−１−オン、３−メチル−４−シクロペンタデセン−１−オン、３−メチル−５−シクロペンタデセン−１−オンから選ばれる少なくとも１種を有効成分として含有する活性酸素起因障害抑制剤である。   Further, the present invention relates to dodecane-4-orido, pentadecane-4-orido, 3-tetradecen-4-orido, tridecane-5-olide, tetradecane-5-olide, pentadecane-5-olide, hexadecane-5-olide, pentadecane. -15-Olide, 11-Pentadecene-15-Olide, 12-Pentadecene-15-Olide, Hexadecan-16-Olide, 6-Hexadecene-16-Olide, 10-Oxahexadecan-16-Olide, 11-Oxahexadecane -16-Olide, 12-Oxa-hexadecane-16-Olide, 1,4-Dioxacycloheptadecane-5,17-dione, 5-Cyclohexadecene-1-one, 3-Methyl-cyclopentadecan-1-one 3-methyl-4-cyclopentadecene-1-one, 3-methyl- - is the active oxygen caused disorder inhibitor comprising at least one as an active component selected from cyclopentadienyl decene-1-one.

本発明の活性酸素起因障害抑制剤によれば活性酸素が関与する細胞や組織の障害を抑制し、例えば体内及び体表面の老化、生活習慣病などの発症予防あるいは緩和効果を得ることができる。   According to the active oxygen-induced disorder inhibitor of the present invention, it is possible to suppress damage to cells and tissues in which active oxygen is involved, and to obtain, for example, the onset prevention or alleviation effects of aging of body and body surface, lifestyle-related diseases and the like.

本発明の活性酸素起因障害抑制剤は、その多くが香料として使用実績のある化合物であり、飲食品、化粧品類、医薬部外品、たばこ用添加物及び日用雑貨等に使用することができる。また本発明の化合物群は、製法が確立され容易に合成ができるため、大量生産が可能である。   Most of the active oxygen-induced disorder inhibitors of the present invention are compounds that have been used as a fragrance, and can be used in foods and drinks, cosmetics, quasi drugs, tobacco additives, daily goods, and the like. . The compound group of the present invention can be mass-produced because its production method is established and can be easily synthesized.

本発明の下記式１   The following formula 1 of the present invention

Figure 2014140373
（式中、Ｘは炭素数１〜２、又は炭素数１０〜１４の環構成炭素鎖を表す。但し、Ｘの炭素数が１０〜１４のときはＸで表される炭素鎖に二重結合もしくは酸素原子を１個含んでもよい。Ｒ１はＸが炭素数１〜２の場合は炭素数６〜１３のアルキル基を表し、Ｘが炭素数１０〜１４の場合は水素原子であることを表す。破線部はＸが炭素数１〜２の場合に当該箇所の炭素間結合が単結合又は二重結合のいずれでもよいことを表す。）で示される化合物は、環内に１又は２個の酸素原子を有する環状カルボニル化合物である。具体的には、Ｘが炭素数１である一般にγ−ラクトン類とよばれる化合物群と、Ｘが炭素数２である一般にδ−ラクトン類とよばれる化合物群、及びＸが炭素数１０〜１４である一般に大環状ラクトン類とよばれる化合物群からなる一連の環状カルボニル化合物である。これらの環状カルボニル化合物はその多くが香料として使用されており、製法も確立されているため公知の方法で製造することができる。これら化合物群においては、Ｘが炭素数１又は２である場合はＲ１の炭素数が大きい方が活性が高いためより好ましく、Ｘが炭素数１０〜１４の場合はＸが飽和で酸素を含まない方がより活性が高いため好ましい。より具体的には、３−テトラデセン−４−オリド、ペンタデカン−４−オリド、ペンタデカン−５−オリド、ヘキサデカン−５−オリド、ペンタデカン−１５−オリド、１１−ペンタデセン−１５−オリド、１２−ペンタデセン−１５−オリド、ヘキサデカン−１６−オリド及び６−ヘキサデセン−１６−オリドが活性が高く、且つ製法が確立されおり容易に入手可能であるため特に好ましい。
Figure 2014140373
 (In the formula, X represents a C1-C2 or C10-C14 ring-constituting carbon chain. However, when X has 10 to 14 carbon atoms, a double bond is formed on the carbon chain represented by X. Alternatively, it may contain one oxygen atom, R1 represents an alkyl group having 6 to 13 carbon atoms when X is 1 to 2 carbon atoms, and represents a hydrogen atom when X is 10 to 14 carbon atoms. The broken line part indicates that when X is 1 to 2 carbon atoms, the carbon-carbon bond at that position may be either a single bond or a double bond.) The compound represented by 1 or 2 in the ring It is a cyclic carbonyl compound having an oxygen atom. Specifically, a group of compounds generally called γ-lactones where X is 1 carbon atoms, a group of compounds generally called δ-lactones where X is 2 carbon atoms, and X is 10 to 14 carbon atoms. Is a series of cyclic carbonyl compounds consisting of a group of compounds generally called macrocyclic lactones. Many of these cyclic carbonyl compounds are used as perfumes, and their production methods have been established, so that they can be produced by known methods. In these compound groups, when X is 1 or 2 carbon atoms, a larger carbon number of R1 is more preferable because of higher activity, and when X is 10 to 14 carbon atoms, X is saturated and does not contain oxygen. Is more preferable because of its higher activity. More specifically, 3-tetradecene-4-olide, pentadecane-4-olide, pentadecane-5-olide, hexadecane-5-olide, pentadecane-15-orido, 11-pentadecene-15-orido, 12-pentadecene- 15-Olide, hexadecane-16-orido, and 6-hexadecene-16-orido are particularly preferable because they have high activity and are easily available because their production methods are established.

また、下記式２   In addition, the following formula 2

Figure 2014140373
（式中、ｎは１０〜１２の整数を表す）で示される化合物は、環内に２個の酸素原子を含む環状カルボニル化合物である。これらの化合物では、１，４−ジオキサシクロヘプタデカン−５，１７−ジオンが活性が高く、製法が確立され市販もされており入手が容易であるため特に好ましい。
Figure 2014140373
 A compound represented by the formula (wherein n represents an integer of 10 to 12) is a cyclic carbonyl compound containing two oxygen atoms in the ring. Among these compounds, 1,4-dioxacycloheptadecane-5,17-dione is particularly preferable because of its high activity, production process established and commercially available, and easy availability.

また、下記式３   In addition, the following formula 3

Figure 2014140373
（式中、Ｙは炭素数１０〜１４の環構成炭素鎖を表し、炭素鎖Ｙは１箇所の二重結合を含んでもよく、１箇所の水素原子がメチル基で置換されていてもよい。）で示される化合物は、環内に酸素原子を含まない環状カルボニル化合物である。これらの化合物では、５−シクロヘキサデセン−１−オン、３−メチル−４−シクロペンタデセン−１−オン及び３−メチル−５−シクロペンタデセン−１−オンが活性が高く、製法が確立され市販もされており入手が容易であるため特に好ましい。
Figure 2014140373
 (In the formula, Y represents a ring-constituting carbon chain having 10 to 14 carbon atoms, and the carbon chain Y may include one double bond, and one hydrogen atom may be substituted with a methyl group. ) Is a cyclic carbonyl compound containing no oxygen atom in the ring. Among these compounds, 5-cyclohexadecene-1-one, 3-methyl-4-cyclopentadecene-1-one and 3-methyl-5-cyclopentadecene-1-one are highly active, and the production method has been established. It is particularly preferable because it is commercially available and is easily available.

本発明の活性酸素起因障害抑制剤で使用される前記有効成分は、常温で固体のものも含まれるが、これらは操作性の面から溶剤に溶解せしめて液状にしてから製剤化することが好ましい。   The active ingredients used in the active oxygen-induced disorder inhibitor of the present invention include those that are solid at room temperature, but from the viewpoint of operability, these active ingredients are preferably dissolved in a solvent and then formulated into a liquid form. .

本発明の活性酸素起因障害抑制剤は、用途に応じてエタノール、水、プロピレングリコール、グリセリン、食用油脂又はそれらの混合溶液などの溶剤、医薬や食品に適用可能な塩類、糖、糖アルコール、賦形剤、可溶化剤、乳化剤、分散剤、安定化剤、抗酸化剤、色素、香料などを適宜配合することができる。   The active oxygen-induced disorder inhibitor of the present invention is a solvent such as ethanol, water, propylene glycol, glycerin, edible oil or fat, or a mixed solution thereof, salts applicable to pharmaceuticals and foods, sugars, sugar alcohols, additives depending on the use. Shapes, solubilizers, emulsifiers, dispersants, stabilizers, antioxidants, pigments, fragrances and the like can be appropriately blended.

本発明の活性酸素起因障害抑制剤において、前記の化合物群の含有量は特に限定されないが、単独の化合物もしくは複数化合物を組み合わせた組成物で、０．０００１〜１００質量％であることが好ましい。   In the active oxygen-induced failure inhibitor of the present invention, the content of the compound group is not particularly limited, but it is preferably 0.0001 to 100% by mass with a single compound or a combination of multiple compounds.

本発明の活性酸素起因障害抑制剤の形態は、特に限定されない。例えば、液状でもよく、公知の方法によって乳化、分散、粉末化するなど、用途に応じて適宜選択することができる。   The form of the active oxygen-induced disorder inhibitor of the present invention is not particularly limited. For example, it may be liquid and can be appropriately selected depending on the application, such as emulsification, dispersion, and powdering by a known method.

本発明の活性酸素起因障害抑制剤は、ビタミン、ミネラル、アミノ酸、などの栄養強化剤、抗酸化剤、抗菌剤、その他の薬剤などと配合して使用することができる。また、本発明の活性酸素起因障害抑制剤は他の活性酸素生成阻害剤や活性酸素捕捉剤、活性酸素消去剤と併用してもよい。   The active oxygen-induced disorder inhibitor of the present invention can be used in combination with nutrition enhancing agents such as vitamins, minerals and amino acids, antioxidants, antibacterial agents and other agents. The active oxygen-induced failure inhibitor of the present invention may be used in combination with other active oxygen production inhibitors, active oxygen scavengers, and active oxygen scavengers.

本発明の活性酸素起因障害抑制剤を、医薬品もしくは医薬部外品として製剤化する場合は、必要に応じて安定化剤、着色剤、嬌味剤、香料、賦形剤、溶剤、界面活性剤、乳化剤、保存剤、溶解補助剤、等張化剤、緩衝剤、保湿剤、結合剤、被覆剤、潤沢剤、崩壊剤、経皮吸収剤などを加え、液剤、粉剤、散剤、顆粒剤、錠剤、糖衣剤、カプセル剤、懸濁剤、座剤、浴剤、軟膏、クリーム、ゲル、貼付剤、注射剤、点眼剤など任意の剤形を選択することができる。   When formulating the active oxygen-induced disorder inhibitor of the present invention as a pharmaceutical product or quasi-drug, a stabilizer, a coloring agent, a flavoring agent, a fragrance, an excipient, a solvent, and a surfactant as necessary. , Emulsifiers, preservatives, solubilizers, isotonic agents, buffers, humectants, binders, coatings, lubricants, disintegrants, transdermal absorbents, etc., liquids, powders, powders, granules, Arbitrary dosage forms such as tablets, dragees, capsules, suspensions, suppositories, bath preparations, ointments, creams, gels, patches, injections, eye drops and the like can be selected.

本発明の活性酸素起因障害抑制剤に用いる有効成分は、その多くが従来から主に香料として使用されている化合物であるため、飲食品に添加することもできる。例えば、乳飲料、清涼飲料、嗜好飲料、アルコール飲料などの飲料、チョコレート、キャンディ、錠菓、ガム、スナック菓子、クッキー、ケーキ、その他焼き菓子などの菓子類、氷菓、アイスクリームなどの冷菓類、即席麺類、レトルト食品、冷凍食品などの調理食品、調味料、栄養補助食品などの食品類に添加することで、活性酸素が関与する体内及び体表面の老化、生活習慣病、白内障などの発症予防あるいは緩和効果を得ることができる。   Since many of the active ingredients used in the active oxygen-induced disorder inhibitor of the present invention are compounds that have been used mainly as fragrances, they can be added to food and drink. For example, beverages such as milk drinks, soft drinks, taste drinks, alcoholic drinks, chocolate, candy, tablet confectionery, gum, snack confectionery, cookies, cakes, other baked confectionery, frozen confectionery such as ice confectionery, ice cream, and instant By adding to cooked foods such as noodles, retort foods, frozen foods, seasonings, nutritional supplements, etc., it is possible to prevent the onset of internal and body aging, lifestyle-related diseases, cataracts, etc. involving active oxygen or A relaxation effect can be obtained.

本発明の活性酸素起因障害抑制剤を飲食品に添加する場合、特に添加量の制限はないが、０．００１〜５質量％であることが好ましい。   When the active oxygen-induced failure inhibitor of the present invention is added to a food or drink, the amount of addition is not particularly limited, but is preferably 0.001 to 5% by mass.

本発明の活性酸素起因障害抑制剤を飲食品に添加する方法は、特に制限はないが必要に応じて、乳化剤、分散剤、安定化剤などを加えることもできる。   The method for adding the active oxygen-induced disorder inhibitor of the present invention to a food or drink is not particularly limited, but an emulsifier, a dispersant, a stabilizer and the like can be added as necessary.

本発明の活性酸素起因障害抑制剤を飲食品に添加する場合は、ビタミン、ミネラル、アミノ酸などの栄養強化剤、抗酸化剤、抗菌剤、食物繊維、血流促進剤、抗血栓剤など他の機能性成分を本発明の活性酸素起因障害抑制剤の機能を阻害しない範囲で併用することもできる。   When the active oxygen-induced disorder inhibitor of the present invention is added to foods and drinks, other nutrient enhancers such as vitamins, minerals, amino acids, antioxidants, antibacterial agents, dietary fiber, blood flow promoters, antithrombotic agents, etc. The functional component may be used in combination as long as the function of the active oxygen-induced disorder inhibitor of the present invention is not inhibited.

（試験方法）
活性酸素生成はＨＬ−６０細胞（ヒト急性前骨髄球性白血病細胞）にジメチルスルホキシドを加えて好中性顆粒球に分化誘導させた後、ＴＰＡ（フォルボール １２−ミリステート １３−アセテート）を加えることでＯ２ −を産生させる系を用いた。またこのＨＬ−６０細胞を用いた活性酸素生成を阻害する作用の測定試験としては、スーパーオキシドラジカルＯ２ −生成量をシトクロムＣを用いて測定するシトクロムＣ還元法を用いた。生体内で生じる活性酸素の内、スーパーオキシドラジカルＯ２ −は短寿命である。そこでより長寿命で検出しやすい化学種に変換することでＯ２ −生成量を測定する間接法が用いられる。シトクロムＣ還元法はこのＯ２ −に着目した検出方法のひとつで、発色プローブとしてシトクロムＣを用いている。酸化型シトクロムＣがＯ２ −から電子を１個受け取って還元されると、吸光度５５０ｎｍ（緑色）に強い吸収を持つ還元型シトクロムＣに変わることを利用した方法である。この還元型シトクロムＣの生成量を、５５０ｎｍの吸光度測定をすることでＯ２ −生成量を算出することができる。 (Test method)
For reactive oxygen generation, dimethyl sulfoxide is added to HL-60 cells (human acute promyelocytic leukemia cells) to induce differentiation into neutrophilic granulocytes, and then TPA (phorbol 12-myristate 13-acetate) is added. Thus, a system for producing O 2 − was used. Further, as a test for measuring the action of inhibiting the production of active oxygen using the HL-60 cells, a cytochrome C reduction method in which the amount of superoxide radical O 2 − produced was measured using cytochrome C was used. Of the active oxygen generated in the living body, the superoxide radical O 2 − has a short life. Therefore, an indirect method is used in which the amount of O 2 − produced is measured by converting the chemical species to a longer life and easy to detect. The cytochrome C reduction method is one of the detection methods focusing on this O 2 − and uses cytochrome C as a coloring probe. This method utilizes the fact that when oxidized cytochrome C receives one electron from O 2 − and is reduced, it changes to reduced cytochrome C having a strong absorption at an absorbance of 550 nm (green). The production amount of the reducing cytochrome C, and by the measurement of absorbance 550 nm O 2 - can be calculated production amount.

被検物質にジメチルスルホキシド（ＤＭＳＯ）を加え最終濃度が２５μｌ／ｍｌになるように濃度を調整した。ＴＰＡ溶液は最終濃度２μＭになるように調整した。シトクロムＣ溶液はシトクロムＣ（牛心臓由来：Ｓｉｇｍａ社製）１００ｍｇをＨＢＳＳ（Ｃａ２＋、Ｍｇ２＋含有、フェノールレッド不含：ハンクスのバランス塩溶液Ｇｉｂｃｏ社製）５ｍｌに溶解し、使用時は最終濃度７６μＭで用いた。 Dimethyl sulfoxide (DMSO) was added to the test substance, and the concentration was adjusted so that the final concentration was 25 μl / ml. The TPA solution was adjusted to a final concentration of 2 μM. As for the cytochrome C solution, 100 mg of cytochrome C (derived from bovine heart: manufactured by Sigma) is dissolved in 5 ml of HBSS (containing Ca 2+ , Mg 2+ , phenol red free: Hanks balanced salt solution manufactured by Gibco), and the final concentration is used. Used at 76 μM.

測定前にＨＬ−６０細胞をインキュベーターにて４日間培養し、好中性顆粒球に分化誘導させる。分化誘導した細胞を遠心分離し培養液を除く、さらに細胞液の濃度を１×１０６セル／ｍｌの濃度になるようにＨＢＳＳで調整、細胞懸濁液１ｍｌを、あらかじめコントロール（ＤＭＳＯ）又は被検物質５μｌを３７℃で１５分間温浴する。次に６６００ｒｐｍで５分間遠心分離し、上澄みを除く。さらにＨＢＳＳを加え同様な操作を繰り返す。新たにＨＢＳＳ１ｍｌを加え、３７℃で５分間温浴する。ＴＰＡ溶液５μｌを加え活性酸素を生成させる。９０秒後シトクロムＣ溶液５０μｌを加える。これを３７℃で１５分間温浴し、十分反応させる。氷中に５分静置して反応を止めた後、６６００ｒｐｍで５分間遠心分離をする。得られた上澄み２００μｌを９６穴プレート（ＮＵＣＫ社製）に加え、マイクロプレートリーダー（Ｍｏｌｅｃｕｌａｒ Ｄｅｖｉｃｅｓ 社）５５０ｎｍで吸光度を測定する。 Prior to measurement, HL-60 cells are cultured in an incubator for 4 days to induce differentiation into neutrophilic granulocytes. The differentiation-induced cells are centrifuged to remove the culture solution, and the concentration of the cell solution is adjusted with HBSS to a concentration of 1 × 10 6 cells / ml. 5. Bath 5 μl of test material at 37 ° C. for 15 minutes. Next, centrifuge at 6600 rpm for 5 minutes and remove the supernatant. Add HBSS and repeat the same operation. Add 1 ml of HBSS freshly and bath at 37 ° C. for 5 minutes. Add 5 μl of TPA solution to generate active oxygen. After 90 seconds, 50 μl of cytochrome C solution is added. This is warmed for 15 minutes at 37 ° C. and allowed to react sufficiently. After leaving the reaction in ice for 5 minutes to stop the reaction, centrifuge at 6600 rpm for 5 minutes. 200 μl of the obtained supernatant is added to a 96-well plate (manufactured by NUCK), and the absorbance is measured with a microplate reader (Molecular Devices) at 550 nm.

スーパーオキシドラジカルＯ２ −の生成抑制効果の算出はコントロールの活性酸素生成量を１００％として被検物質添加時の活性酸素生成量との差を次の計算で求めた。
活性酸素Ｏ２ −量（ｎｍｏｌ／ｍｌ）＝４７．７×Ａ５５０ｎｍ Superoxide radical O 2 - calculation of the formation inhibitory effect of was calculated the difference between the active oxygen generation amount when added test substance active oxygen production of the control as 100% by the following calculation.
Active oxygen O 2 - amount (nmol / ml) = 47.7 × A 550nm

（試験結果）
前記試験方法において、被験物質の濃度が２５μｇ／ｍｌあるいは２．５μｇ／ｍｌの活性酸素生成阻害率（％）を表１に示す。 (Test results)
In the test method, the active oxygen production inhibition rate (%) at a test substance concentration of 25 μg / ml or 2.5 μg / ml is shown in Table 1.

Figure 2014140373
Figure 2014140373

表１に示すように本発明の化合物には、２５μｇ／ｍｌ以下の濃度においても強い阻害活性が確認された。またその１／１０の低濃度でもその活性が維持されるものも確認された。   As shown in Table 1, the compound of the present invention was confirmed to have a strong inhibitory activity even at a concentration of 25 μg / ml or less. It was also confirmed that the activity was maintained even at a low concentration of 1/10.

以下に本発明の活性酸素起因障害抑制剤の食品への配合例について一例を示す。   An example of a formulation example of the active oxygen-induced disorder inhibitor of the present invention in a food is shown below.


アイスクリーム配合例（質量比）
────────────────────────
全脂練乳 １０．０
生クリーム ９．４
無塩バター ２．０
脱脂粉乳 ３．４
砂糖 １２．０
安定剤 ０．３
乳化剤 ０．２
ｐＨ調整剤 ０．１
カラメル色素 ０．１
本発明の活性酸素起因障害抑制剤 ０．０１
香料 ０．０１
水 ４９．０
────────────────────────
Ice cream formulation example (mass ratio)
────────────────────────
Whole fat condensed milk 10.0
Fresh cream 9.4
Unsalted butter 2.0
Nonfat dry milk 3.4
Sugar 12.0
Stabilizer 0.3
Emulsifier 0.2
pH adjuster 0.1
Caramel pigment 0.1
Active oxygen-induced disorder inhibitor of the present invention 0.01
Fragrance 0.01
Water 49.0
────────────────────────


クッキー生地配合例（質量比）
────────────────────────
薄力粉 ６２．５
全粒粉 ３７．５
ショートニング ３０．０
全卵 ３０．０
砂糖 ２０．０
水飴 １．０
脱脂粉乳 ５．０
食塩 １．２
食用油脂 ３０．０
重炭酸ソーダ １．０
重炭酸アンモニウム １．０
本発明の活性酸素起因障害抑制剤 ０．１
香料 ０．３
水 １１．０
────────────────────────
Cookie dough formulation example (mass ratio)
────────────────────────
Soft flour 62.5
Whole grain 37.5
Shortening 30.0
Whole egg 30.0
Sugar 20.0
Minamata 1.0
Nonfat dry milk 5.0
Salt 1.2
Edible oils and fats 30.0
Sodium bicarbonate 1.0
Ammonium bicarbonate 1.0
Active oxygen-induced disorder inhibitor of the present invention 0.1
Fragrance 0.3
Water 11.0
────────────────────────


チョコレート配合例（質量比）
─────────────────────────
カカオ液 １２．０
カカオバター ２４．０
ショ糖 ３３．０
フルクリームミルクパウダー １９．０
スキムミルクパウダー １１．４
レシチン ０．５
本発明の活性酸素起因障害抑制剤 ０．０１
香料 ０．１
─────────────────────────
Chocolate formulation example (mass ratio)
─────────────────────────
Cocoa liquor 12.0
Cocoa butter 24.0
Sucrose 33.0
Full cream milk powder 19.0
Skim milk powder 11.4
Lecithin 0.5
Active oxygen-induced disorder inhibitor of the present invention 0.01
Fragrance 0.1
─────────────────────────


ノンオイルドレッシング配合例（質量比）
─────────────────────────
濃口醤油 １０．０
醸造酢 ６．０
リンゴ酢 ５．０
レモン果汁 ４．０
液糖 ７．０
食塩 ２．０
調味料 ７．０
香料 ０．２
本発明の活性酸素起因障害抑制剤 ０．０１
水 ５０．０
─────────────────────────
Non-oil dressing formulation example (mass ratio)
─────────────────────────
Dark soy sauce 10.0
Brewing vinegar 6.0
Apple cider vinegar 5.0
Lemon juice 4.0
Liquid sugar 7.0
Salt 2.0
Seasoning 7.0
Fragrance 0.2
Active oxygen-induced disorder inhibitor of the present invention 0.01
Water 50.0
─────────────────────────


飲料配合例（質量比）
――――――――――――――――――――――───
果糖ぶどう糖液糖 ６０．０
アップル透明果汁 ４．３
クエン酸 ２．３
クエン酸三ナトリウム ０．８
アスコルビン酸 ０．２
スクラロース ０．０３
アセスルファムカリウム ０．０２
香料 ０．９９
本発明の活性酸素起因障害抑制剤 ０．１
水 ３１．０
――――――――――――――――――――――───
Beverage formulation example (mass ratio)
―――――――――――――――――――――――― ──
Fructose glucose liquid sugar 60.0
Apple transparent fruit juice 4.3
Citric acid 2.3
Trisodium citrate 0.8
Ascorbic acid 0.2
Sucralose 0.03
Acesulfame potassium 0.02
Perfume 0.99
Active oxygen-induced disorder inhibitor of the present invention 0.1
Water 31.0
―――――――――――――――――――――――― ──


チューインガム配合例（質量比）
――――――――――――――――――――――─
ガムベース ２０．０
砂糖 ６０．０
ブドウ糖 １０．０
水飴 ８．０
グリセリン ５．０
香料 ０．９
本発明の活性酸素起因障害抑制剤 ０．１
───────────────────────
Chewing gum formulation example (mass ratio)
――――――――――――――――――――――――
Gum base 20.0
Sugar 60.0
Glucose 10.0
Minamata 8.0
Glycerin 5.0
Fragrance 0.9
Active oxygen-induced disorder inhibitor of the present invention 0.1
───────────────────────

本発明の活性酸素起因障害抑制剤は、その多くが香料として使用実績がある化合物であり、刺激性などは極めて小さく、飲食品添加に添加することできる。また、本発明の化合物群は容易に合成ができるため、大量生産が可能である。   Most of the active oxygen-induced disorder inhibitors of the present invention are compounds that have been used as a fragrance, have extremely low irritation and the like, and can be added to food and drink additions. In addition, since the compound group of the present invention can be easily synthesized, mass production is possible.

Claims (3)

下記式１
Figure 2014140373
 （式中、Ｘは炭素数１〜２、又は炭素数１０〜１４の環構成炭素鎖を表す。但し、Ｘの炭素数が１０〜１４のときはＸで表される炭素鎖に二重結合もしくは酸素原子を１個含んでもよい。Ｒ１はＸが炭素数１〜２の場合は炭素数６〜１３のアルキル基を表し、Ｘが炭素数１０〜１４の場合は水素原子であることを表す。破線部はＸが炭素数１〜２の場合に当該箇所の炭素間結合が単結合又は二重結合のいずれでもよいことを表す。）で示される化合物群、及び下記式２
Figure 2014140373
 （式中、ｎは１０〜１２の整数を表す。）で示される化合物群、及び下記式３
Figure 2014140373
 （式中、Ｙは炭素数１０〜１４の環構成炭素鎖を表し、炭素鎖Ｙは１箇所の二重結合を含んでもよく、１箇所の水素原子がメチル基で置換されていてもよい。）で示される化合物群からなる環状カルボニル化合物から選ばれる１種以上を有効成分として含有する活性酸素起因障害抑制剤を添加する、飲食品への活性酸素起因抑制機能を付加する方法。 Formula 1 below
Figure 2014140373
 (In the formula, X represents a C1-C2 or C10-C14 ring-constituting carbon chain. However, when X has 10 to 14 carbon atoms, a double bond is formed on the carbon chain represented by X. Alternatively, it may contain one oxygen atom, R1 represents an alkyl group having 6 to 13 carbon atoms when X is 1 to 2 carbon atoms, and represents a hydrogen atom when X is 10 to 14 carbon atoms. The broken line part indicates that when X is 1 to 2 carbon atoms, the carbon-carbon bond at the position may be either a single bond or a double bond.), And the following formula 2
Figure 2014140373
 (Wherein n represents an integer of 10 to 12) and the following formula 3
Figure 2014140373
 (In the formula, Y represents a ring-constituting carbon chain having 10 to 14 carbon atoms, and the carbon chain Y may include one double bond, and one hydrogen atom may be substituted with a methyl group. A method for adding an active oxygen-induced inhibition function to foods and drinks, which comprises adding an active oxygen-induced disorder inhibitor containing as an active ingredient at least one selected from cyclic carbonyl compounds consisting of a compound group represented by the formula: ドデカン−４−オリド、ペンタデカン−４−オリド、３−テトラデセン−４−オリド、トリデカン−５−オリド、テトラデカン−５−オリド、ペンタデカン−５−オリド、ヘキサデカン−５−オリド、ペンタデカン−１５−オリド、１１−ペンタデセン−１５−オリド、１２−ペンタデセン−１５−オリド、ヘキサデカン−１６−オリド、６−ヘキサデセン−１６−オリド、１０−オキサ−ヘキサデカン−１６−オリド、１１−オキサ−ヘキサデカン−１６−オリド、１２−オキサ−ヘキサデカン−１６−オリド、１，４−ジオキサシクロヘプタデカン−５，１７−ジオン、５−シクロヘキサデセン−１−オン、３−メチル−シクロペンタデカン−１−オン、３−メチル−４−シクロペンタデセン−１−オン、３−メチル−５−シクロペンタデセン−１−オンからなる化合物群から選ばれる少なくとも１種を有効成分として含有する活性酸素起因障害抑制剤、飲食品への活性酸素起因抑制機能を付加する方法。 Dodecane-4-olide, pentadecane-4-olide, 3-tetradecen-4-olide, tridecane-5-olide, tetradecane-5-olide, pentadecane-5-olide, hexadecane-5-olide, pentadecane-15-olide, 11-pentadecene-15-oride, 12-pentadecene-15-oride, hexadecan-16-orido, 6-hexadecene-16-oride, 10-oxa-hexadecan-16-orido, 11-oxa-hexadecane-16-oride, 12-oxa-hexadecane-16-olide, 1,4-dioxacycloheptadecane-5,17-dione, 5-cyclohexadecen-1-one, 3-methyl-cyclopentadecan-1-one, 3-methyl- 4-cyclopentadecene-1-one, 3-methyl-5-cyclopenta At least one active oxygen caused disorder inhibitor comprising as an active ingredient, a method of adding the active oxygen caused suppression function to food or drink selected from the compound group consisting of-1-one. 請求項１又は請求項２に記載の方法によって、活性酸素起因障害抑制効果を付加する工程を有する活性酸素起因障害抑制機能を付加した飲食品の製造方法。 The manufacturing method of the food-drinks which added the active-oxygen cause disorder suppression function which has the process of adding the active-oxygen cause disorder suppression effect by the method of Claim 1 or Claim 2.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002038148A1 (en) * 2000-11-08 2002-05-16 Soda Aromatic Co.,Ltd ANTICANCER AGENTS, PERFUMES OR FOODS AND DRINKS CONTAINING φ-HYDROXYFATTY ACIDS
WO2008068683A1 (en) * 2006-12-01 2008-06-12 Firmenich Sa Antimicrobial flavouring composition

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002038148A1 (en) * 2000-11-08 2002-05-16 Soda Aromatic Co.,Ltd ANTICANCER AGENTS, PERFUMES OR FOODS AND DRINKS CONTAINING φ-HYDROXYFATTY ACIDS
WO2008068683A1 (en) * 2006-12-01 2008-06-12 Firmenich Sa Antimicrobial flavouring composition

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