JP2011236169A - Inhibitor for potential-dependent cation channel - Google Patents

Inhibitor for potential-dependent cation channel Download PDF

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JP2011236169A
JP2011236169A JP2010110193A JP2010110193A JP2011236169A JP 2011236169 A JP2011236169 A JP 2011236169A JP 2010110193 A JP2010110193 A JP 2010110193A JP 2010110193 A JP2010110193 A JP 2010110193A JP 2011236169 A JP2011236169 A JP 2011236169A
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JP5733909B2 (en
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Hiroko Takatoku
博子 高徳
Mitsuyoshi Sakasai
充好 逆井
Hiroshi Kusuoku
比呂志 楠奥
Kentaro Kumihashi
堅太郎 組橋
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Kao Corp
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Abstract

PROBLEM TO BE SOLVED: To provide an excellent inhibitor for a potential-dependent cation channel.SOLUTION: The inhibitor for a potential-dependent channel uses a plant selected from celery and basil or an extract thereof as an active ingredient.

Description

本発明は、電位依存性カチオンチャネル抑制剤に関する。   The present invention relates to a voltage-gated cation channel inhibitor.

近年、生活環境の変化に起因する化学物質やハウスダスト等の外来刺激物質の増加によるアレルギー等の過敏症の増加や、自己の体臭や家庭における種々の生活臭を初めとする生活環境の臭気を嫌悪する傾向の高まり等、過敏な感覚に起因する日常の不快感が問題となっている。
感覚は、皮膚感覚や深部感覚等の体性感覚、内臓痛等の内臓感覚、視覚、聴覚、味覚、嗅覚等の特殊感覚に分類することができる。感覚の情報は、例えば、皮膚の各種受容器、筋紡錘、網膜、嗅粘膜、味蕾、蝸牛の有毛細胞等の末梢の感覚受容器等によって受容され、知覚感覚において神経インパルスに変換された後、電気信号として中枢まで伝達される。
In recent years, there has been an increase in hypersensitivity such as allergies due to an increase in external stimulating substances such as chemical substances and house dust caused by changes in the living environment, as well as the odors of the living environment, including the body odor and various living odors at home. Daily discomfort resulting from irritability, such as an increased tendency to dislike, is a problem.
Sensations can be classified into somatic sensations such as skin sensations and deep sensations, visceral sensations such as visceral pain, and special sensations such as vision, hearing, taste, and smell. Sensory information is received by peripheral sensory receptors such as various receptors on the skin, muscle spindle, retina, olfactory mucosa, taste buds, cochlear hair cells, etc., and after being converted into nerve impulses in sensory sensation It is transmitted to the center as an electrical signal.

例えば、痛覚は、皮膚の自由神経終末で受容される侵害刺激(温度刺激、化学刺激、機械刺激)によって惹起される。自由神経終末には、各々の刺激に感受性のイオンチャネルが存在しており、刺激を受けた場合、これらのイオンチャネルが開口することでカチオンが細胞内に流入し、結果として電位依存性カチオンチャネルが活性化されて、神経の活動電位(インパルス)が発生する(非特許文献1)。また、かゆみを起こす刺激としては、機械刺激、熱刺激、電気刺激等の物理的刺激と、起痒物質等の化学的刺激とが知られている。これらの刺激は、主として真皮内のマスト細胞からヒスタミンを放出させ、放出されたヒスタミンは自由神経終末上の受容体と結合してカルシウムイオンの流入を引き起こし、最終的に神経の活動電位を発生させると考えられている(非特許文献2)。   For example, pain sensations are triggered by nociceptive stimuli (temperature stimuli, chemical stimuli, mechanical stimuli) received at the free nerve endings of the skin. At the free nerve ending, there are ion channels that are sensitive to each stimulus, and when these stimuli are received, the cations flow into the cell by opening these ion channels, resulting in voltage-gated cation channels. Is activated and a nerve action potential (impulse) is generated (Non-patent Document 1). As stimuli that cause itching, physical stimuli such as mechanical stimuli, thermal stimuli, and electrical stimuli, and chemical stimuli such as pollutants are known. These stimuli release histamine mainly from mast cells in the dermis, and the released histamine binds to a receptor on the free nerve endings, causing calcium ion influx and ultimately generating a neural action potential. (Non-patent document 2).

同様に、他の何れの感覚の発生にも、情報は、最終的には、神経細胞の電位依存性カチオンチャネルの活性化によって発生する活動電位の形態で中枢に伝達される。電位依存性カチオンチャネルは更に、こうした活動電位の発生や伝導だけでなく、シナプス間隙や神経筋終末への神経伝達物質の放出にも関与している。
従って、電位依存性カチオンチャネルの活性化を阻害すれば、感覚を変化させることが可能である。実際、電位依存性カチオンチャネル阻害剤を利用して感覚を抑制させる方法は、従来から医療現場等で使用されている。例えば、局所麻酔剤や抗不整脈薬として使用されるリドカイン(例えばキロシカイン(登録商標))は、電位依存性ナトリウムチャネル阻害剤である。電位依存性カルシウムチャネル阻害剤であるガバペンチン(例えば、ガバペン(登録商標)、ニューロンチン(登録商標))、は抗痙攣剤或いは鎮痛補助薬として使用されている。また、電位依存性カルシウムチャネル又はナトリウムチャネルのインヒビター(例えば、バラパミル)が、外的攻撃に対する皮膚の耐性閾値を増加させ、皮膚の過敏症に適用できることが報告されている(特許文献1)。
Similarly, in any other sensory development, information is ultimately transmitted to the center in the form of action potentials generated by activation of nerve cell voltage-gated cation channels. Voltage-gated cation channels are not only involved in the generation and conduction of these action potentials, but also in the release of neurotransmitters into synaptic clefts and neuromuscular terminals.
Therefore, if the activation of the voltage-gated cation channel is inhibited, the sense can be changed. Actually, methods for suppressing sensation using a voltage-gated cation channel inhibitor have been used in the medical field. For example, lidocaine (eg, kilosicaine®) used as a local anesthetic and antiarrhythmic agent is a voltage-gated sodium channel inhibitor. A voltage-dependent calcium channel inhibitor gabapentin (for example, gabapen (registered trademark), neurontin (registered trademark)) is used as an anticonvulsant or analgesic. In addition, it has been reported that inhibitors of voltage-gated calcium channels or sodium channels (for example, valapamil) increase the skin resistance threshold against external attack and can be applied to skin hypersensitivity (Patent Document 1).

知覚神経の電位依存性カチオンチャネルを阻害することによって、医療目的での感覚抑制効果が得られるだけでなく、日常感じる過敏な感覚又は不快な感覚を抑制又は調整することにより、生活の質を改善することができる可能性がある。   Inhibiting the sensory nerve's voltage-gated cation channel not only provides a sensory suppression effect for medical purposes, but also improves quality of life by suppressing or adjusting the sensitive or unpleasant sensations that are felt daily There is a possibility that you can.

ところで、セロリにはビフィズス菌増殖促進作用(特許文献2)、セロリの葉・茎の50%エタノール水溶液抽出物には皮膚保湿効果及び肌荒れ改善効果(特許文献3)、セロリ種子のヘキサン抽出物にはプロテアーゼ阻害作用(特許文献4)があることが知られている。
また、バジルの葉のエタノール又は50%エタノール水溶液抽出物にはチロシナーゼ活性阻害作用(特許文献5)、バジルの葉のエタノール抽出物には活性酸素抑制作用(特許文献6)があるものの、一方でバジルの葉の50%エタノール水溶液抽出物にはかゆみ防止効果がほとんどなく、バジルの種子の50%エタノール水溶液抽出物にかゆみ防止効果及びアトピー性皮膚炎の治療効果(特許文献7)があることが知られている。
しかしながら、セロリ、バジルに電位依存性チャネル阻害作用があることは知られていない。
By the way, bifidobacteria growth promoting action on celery (Patent Document 2), 50% ethanol aqueous extract of celery leaves and stems on skin moisturizing effect and skin roughening effect (Patent Document 3), hexane extract of celery seeds Is known to have a protease inhibitory action (Patent Document 4).
In addition, basil leaf ethanol or 50% aqueous ethanol extract has tyrosinase activity inhibitory action (Patent Document 5), while basil leaf ethanol extract has active oxygen inhibitory action (Patent Document 6). The 50% ethanol aqueous extract of basil leaves has almost no itching prevention effect, and the 50% ethanol aqueous extract of basil seeds has an itching prevention effect and a therapeutic effect on atopic dermatitis (Patent Document 7). Are known.
However, celery and basil are not known to have a voltage-dependent channel inhibitory action.

特表2002−505268号公報JP-T-2002-505268 特開平11−266860号公報JP-A-11-266860 特開2005−12014号公報JP 2005-122014 A 特開2005−2008号公報Japanese Patent Laid-Open No. 2005-2008 特開平9−77636号公報JP-A-9-77636 特開平8−119869号公報Japanese Patent Laid-Open No. 8-119869 特開平9−118628号公報JP-A-9-118628

富永真琴,実験医学, vol.24, No.15: 54-59 (2006)Makoto Tominaga, Experimental Medicine, vol.24, No.15: 54-59 (2006) 豊田雅彦,綜合臨床、Vo.53, No.5: 1629-1636 (2004)Masahiko Toyoda, Sogo Clinic, Vo.53, No.5: 1629-1636 (2004) ZHOU Pら, Phytochemistry、Vo.53, No.6: 689-697 (2000)ZHOU P et al., Phytochemistry, Vo.53, No.6: 689-697 (2000)

本発明は、感覚の抑制又は調整、或いは日常感じる過敏な感覚又は不快な感覚の低減に利用することができる電位依存性カチオンチャネル阻害剤に関する。   The present invention relates to a voltage-gated cation channel inhibitor that can be used for suppression or adjustment of sensation, or reduction of daily sensitive sensation or unpleasant sensation.

本発明者らは、電位依存性チャネルを効果的に阻害し、感覚の抑制又は調整に利用し得る物質を探索した結果、セロリ、バジルこれらの各抽出物に、有効な電位依存性チャネル阻害効果が認められることを見出した。   As a result of searching for substances that can effectively inhibit voltage-gated channels and can be used for suppression or adjustment of sensation, the present inventors have found that celery and basil are effective in inhibiting voltage-gated channels. Was found to be accepted.

すなわち、本発明は以下の1)〜3)に係るものである。
1)セロリ及びバジルから選ばれる植物又はその抽出物を有効成分とする電位依存性チャネル阻害剤、マスキング剤又は知覚過敏抑制剤。
2)セロリ種子抽出物及び/又はバジル葉抽出物である上記1)記載の電位依存性チャネル阻害剤、マスキング剤又は知覚過敏抑制剤。
3)抽出物が、水及び/又はアルコールの抽出物である上記1)又は2)記載の電位依存性チャネル阻害剤、マスキング剤又は知覚過敏抑制剤。
That is, the present invention relates to the following 1) to 3).
1) A voltage-dependent channel inhibitor, masking agent, or hypersensitivity inhibitor comprising a plant selected from celery and basil or an extract thereof as an active ingredient.
2) The voltage-dependent channel inhibitor, masking agent or hypersensitivity inhibitor according to 1) above, which is a celery seed extract and / or a basil leaf extract.
3) The voltage-dependent channel inhibitor, masking agent or hypersensitivity inhibitor according to 1) or 2) above, wherein the extract is an extract of water and / or alcohol.

本発明の電位依存性カチオンチャネル阻害剤は、種々の感覚を効果的に抑制又は調整することで、医薬品の分野のみならず食品、化粧品、家庭用品等の分野においても有用であり、日常感じる過敏な感覚又は不快な感覚を低減することができる。   The voltage-gated cation channel inhibitor of the present invention is useful not only in the field of pharmaceuticals but also in the field of foods, cosmetics, household products, etc. by effectively suppressing or adjusting various sensations. Sensations or unpleasant sensations can be reduced.

試験物質による電位依存性カチオンチャネル活性抑制能の測定実験データを示す。The measurement experimental data of the voltage-dependent cation channel activity suppression ability by a test substance are shown. 電位依存性カチオンチャネル阻害活性率とマスキングスコアとの相関関係を示す。The correlation of a voltage-dependent cation channel inhibitory activity rate and a masking score is shown.

本発明におけるセロリとは、セリ科オランダミツバ属セロリ(Apium graveolens)を意味し、このうち、Apium graveolens var. dulceが好ましい。 In the present invention, celery means Apium graveolens , which is a genus of the celery family, among which Apium graveolens var. Dulce is preferable.

本発明におけるバジルとは、シソ科メボウキ属バジル(Ocimum basilicum)を意味する。 Basil in the present invention means Labiatae Basilcum ( Ocimum basilicum ).

本発明における植物としては、その植物の全草、葉(葉身、葉柄等)、樹皮、木質部、枝、果実(成熟、未熟等)、種子、花(花弁、子房等)、根、塊根、根茎等を、そのまま、破砕、粉砕、搾取して用いるか、又はこれら処理されたものを乾燥若しくは粉末化して用いることができる。
用いる部位としては、セロリについては種子を;バジルについては葉を使用するのが好ましい。
尚、本発明に用いる上記植物を単独で、又は上記植物から選ばれる2種以上のものを混合して用いてもよい。
Examples of plants in the present invention include whole plants, leaves (leaf blades, petiole, etc.), bark, woody parts, branches, fruits (mature, immature, etc.), seeds, flowers (petals, ovary, etc.), roots, tuberous roots. The rhizome and the like can be used by crushing, crushing, and squeezing them as they are, or those treated can be dried or powdered.
It is preferable to use seeds for celery and leaves for basil.
In addition, you may use the said plant used for this invention individually or in mixture of 2 or more types chosen from the said plant.

本発明における抽出物とは、本発明に用いる植物を一定温度(低温、常温又は加温)下にて抽出すること;又はソックスレー抽出器等の抽出器具を用いて抽出すること等の抽出手段により得られる各種溶剤抽出液、その希釈液、その濃縮液又はその粉末を意味するものである。   The extract in the present invention refers to extraction means such as extraction of the plant used in the present invention at a constant temperature (low temperature, normal temperature or warming); or extraction using an extractor such as a Soxhlet extractor. It means various obtained solvent extracts, diluted solutions thereof, concentrated solutions or powders thereof.

本発明の植物の抽出物を得るために用いられる抽出溶剤としては、極性溶剤、非極性溶剤の何れをも使用することができる。当該抽出溶剤としては、例えば、水;メタノール、エタノール、プロパノール、ブタノール等のアルコール類;プロピレングリコール、ブチレングリコール等の多価アルコール類;アセトン、メチルエチルケトン等のケトン類;酢酸メチル、酢酸エチル等のエステル類;テトラヒドロフラン、ジエチルエーテル等の鎖状又は環状のエーテル類;ポリエチレングリコール等のポリエーテル類;スクワレン、ヘキサン、シクロヘキサン、石油エーテル等の炭化水素類;ベンゼン、トルエン等の芳香族炭化水素類;ジクロロメタン、クロロホルム、ジクロロエタン、四塩化炭素等のハロゲン化炭化水素類;ピリジン類;二酸化炭素、超臨界二酸化炭素;油脂、ワックス、その他のオイル等が挙げられる。これら溶剤は、単独で又は2種以上混合して混合液として使用することができる。
この溶剤のうち、水、アルコール(好ましくは炭素数1〜5)、水−アルコール混合液が好ましい。このうち、水、エタノール、水−エタノール混合液が好ましい。
水−エタノール混合液を用いる場合、当該混合液中のエタノール濃度(V/V)は、0.01〜100容量%であるのが好ましく、20〜80容量%であるのがより好ましく、40〜60容量%であるのが更に好ましい。
As the extraction solvent used for obtaining the plant extract of the present invention, either a polar solvent or a nonpolar solvent can be used. Examples of the extraction solvent include water; alcohols such as methanol, ethanol, propanol and butanol; polyhydric alcohols such as propylene glycol and butylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate. Linear or cyclic ethers such as tetrahydrofuran and diethyl ether; polyethers such as polyethylene glycol; hydrocarbons such as squalene, hexane, cyclohexane and petroleum ether; aromatic hydrocarbons such as benzene and toluene; dichloromethane Halogenated hydrocarbons such as chloroform, dichloroethane and carbon tetrachloride; pyridines; carbon dioxide, supercritical carbon dioxide; fats and oils, waxes, and other oils. These solvents can be used alone or in admixture of two or more.
Among these solvents, water, alcohol (preferably having 1 to 5 carbon atoms), and a water-alcohol mixed solution are preferable. Among these, water, ethanol, and a water-ethanol mixed liquid are preferable.
When using a water-ethanol mixed solution, the ethanol concentration (V / V) in the mixed solution is preferably 0.01 to 100% by volume, more preferably 20 to 80% by volume, and 40 to 40%. More preferably, it is 60% by volume.

溶剤の使用量は、植物1質量部(乾燥物換算)に対して、1〜50質量部であるのが好ましく、5〜40質量部であるのが好ましい。抽出温度は、0〜100℃であるのが好ましく、より4〜50℃、更に10〜40℃であるのが好ましい。抽出時間は、1分〜150日間であるのが好ましく、より30分〜50日間、更に1時間〜15日間であるのが好ましい。
一例として、抽出物を得る際、植物1質量部(乾燥物換算)に対して、40〜60容量%エタノール−水混液、エタノール又は水の1〜50質量部の溶剤を用い、4〜40℃の温度(好ましくは、20〜30℃)で、1〜30日間(好ましくは10〜20日間)抽出するのが好ましい。
また、抽出の際、煮沸脱気や窒素ガス等の不活性ガスを通気して溶存酸素を除去しつつ、非酸化的雰囲気下で行なってもよい。
It is preferable that the usage-amount of a solvent is 1-50 mass parts with respect to 1 mass part (dry matter conversion) of a plant, and it is preferable that it is 5-40 mass parts. The extraction temperature is preferably 0 to 100 ° C, more preferably 4 to 50 ° C, and further preferably 10 to 40 ° C. The extraction time is preferably 1 minute to 150 days, more preferably 30 minutes to 50 days, and further preferably 1 hour to 15 days.
As an example, when obtaining an extract, 40 to 60 volume% ethanol-water mixed solution, 1 to 50 parts by mass of ethanol or water is used with respect to 1 part by mass of the plant (in terms of dry matter), and 4 to 40 ° C. It is preferable to extract for 1 to 30 days (preferably 10 to 20 days) at a temperature of (preferably 20 to 30 ° C.).
In addition, the extraction may be carried out in a non-oxidizing atmosphere while removing dissolved oxygen by bubbling degassing or inert gas such as nitrogen gas.

上記にて得られた植物抽出物は、単独で又は混合して、そのまま用いることもできるが、当該抽出物を希釈、濃縮又は凍結乾燥して、液状、粉末状又はペースト状に調製して用いることもできる。
また、得られた植物抽出物は、クロマトグラフィー、液々分配、濾過分離、活性炭処理等の公知の分離技術により、当該抽出物から不活性な夾雑物を除去して用いることができる。
The plant extract obtained above can be used alone or mixed and used as it is, but the extract is diluted, concentrated or freeze-dried to prepare a liquid, powder or paste. You can also.
In addition, the obtained plant extract can be used after removing inactive impurities from the extract by known separation techniques such as chromatography, liquid-liquid distribution, filtration separation, activated carbon treatment and the like.

後記実施例に示すように、本発明の植物又はその抽出物は、生体由来受容器細胞の電位依存性カチオンチャネルにより生じる電気的活動を抑制すること、言い換えれば、神経の活動電位の発生や伝達を抑制できること、すなわち電位依存性カチオンチャネル阻害作用を有することから、生物の種々の感覚を抑制又は調整するために用いることができる。例えば、皮膚末梢神経系のナトリウム又はカルシウムチャネル阻害は皮膚耐性閾値を増加させることができる(特許文献1)。また、後記参考例に示すように、電位依存性カチオンチャネル抑制率とマスキングスコア(不快臭)とに相関関係が認められることから、本発明の植物又はその抽出物は、不快臭のマスキングのために用いることもできる。   As shown in the examples described later, the plant of the present invention or an extract thereof suppresses the electrical activity generated by the voltage-gated cation channel of living body-derived receptor cells, in other words, generation and transmission of nerve action potentials. Can be used, in order to suppress or regulate various sensations of an organism. For example, inhibition of sodium or calcium channels in the skin peripheral nervous system can increase the skin tolerance threshold (Patent Document 1). In addition, as shown in the reference examples described later, since there is a correlation between the voltage-dependent cation channel inhibition rate and the masking score (unpleasant odor), the plant of the present invention or its extract is used for masking unpleasant odor. It can also be used.

ここに、「皮膚耐性閾値」とは、この値を超えると皮膚は外部刺激に対し、知覚不全の兆候、すなわち皮膚領域における多かれ少なかれ痛みのある感覚、例えば刺痛、チクチクする痛み、痒み又は掻痒、火傷感、暖温感、不快感、激痛および/又は赤み又は紅斑等を伴った反応を起こすようになる皮膚の興奮性閾値を意味するものである。
また、「外部刺激」とは、例えば界面活性剤や防腐剤、又は香料など刺激性を有する化合物、及び環境、食物、風、摩擦、シェービング、石鹸、カルシウム濃度の高い硬水、温度変化、毛糸などを意味するものである。
Here, the “skin tolerance threshold” means that the skin is in response to external stimuli a sign of sensory failure, ie a more or less painful sensation in the skin area, eg stinging, tingling pain, itching or pruritus It means a skin excitability threshold that causes a reaction with burns, warmth, discomfort, severe pain and / or redness or erythema.
In addition, “external stimuli” include, for example, compounds having stimulating properties such as surfactants, preservatives, and fragrances, and the environment, food, wind, friction, shaving, soap, hard water with high calcium concentration, temperature change, yarn, etc. Means.

ここで、本発明における電位依存性カチオンチャネル阻害とは、電位依存性カチオンチャネルからの細胞内へのイオンの流入を阻害することを云う。本発明において阻害される電位依存性カチオンチャネルとしては、電位依存性Na+チャネル、電位依存性K+チャネル、電位依存性Ca2+チャネルが挙げられる。このうち、電位依存性Ca2+チャネルは、更に、電気生理学的、薬理学的性質から、L−,N,P−,Q−,R−,及びT−typeに分類することができ、これらは何れも本発明の化合物の標的である。
また、上記抑制又は調整される種々の感覚としては、皮膚や粘膜で受容される触覚、圧覚、温覚、冷覚、痛覚、及び筋、腱や関節からの感覚を含む、体性感覚;臓器感覚及び内臓痛を含む内臓感覚;視覚、聴覚、味覚、嗅覚及び平衡感覚を含む特殊感覚;ならびに、その他の感覚(例えば、掻痒感、しびれ、神経痛、疼痛、その他不快感等)が挙げられる。これらのあらゆる感覚は、電位依存性カチオン阻害物質により抑制、軽減又は改善され得る。又、これらの種々の感覚は、しばしば刺激への感受性が亢進し、嗅覚過敏、又は痛覚過敏(hyperalgesia)、異痛症(alodynia)、痒み過敏などの皮膚知覚過敏といった不快な症状を呈するが、電位依存性カチオンチャネルを阻害すれば、これらの症状のうち末梢知覚神経活動の亢進に起因する症状の予防、改善又は治療に利用できる。なお、皮膚痛覚過敏とは、痛みの感覚が亢進し、痛みとなる刺激をより強く感じる感覚異常のことを、異痛症とは通常では疼痛をもたらさない刺激でも全て疼痛として認識される感覚異常のことを、痒み過敏とは普段であれば痒みを感じない刺激に対しても痒みを感じる感覚異常のことをいう。
Here, the inhibition of the voltage-dependent cation channel in the present invention refers to inhibiting the inflow of ions from the voltage-dependent cation channel into the cell. Examples of the voltage-gated cation channel inhibited in the present invention include voltage-gated Na + channel, voltage-gated K + channel, and voltage-gated Ca 2+ channel. Among these, voltage-gated Ca 2+ channels can be further classified into L-, N, P-, Q-, R-, and T-type based on electrophysiological and pharmacological properties. Are both targets of the compounds of the present invention.
In addition, the various sensations that are suppressed or adjusted include somatic sensations including tactile sensation, pressure sensation, warm sensation, cold sensation, pain sensation, and sensations from muscles, tendons, and joints; Visceral sensations including sensations and visceral pain; special sensations including vision, hearing, taste, olfaction and balance sensation; and other sensations (eg, pruritus, numbness, neuralgia, pain, other discomfort, etc.). Any of these sensations can be suppressed, reduced or improved by voltage-dependent cation inhibitors. These various sensations are often more sensitive to stimuli and exhibit unpleasant symptoms such as hypersensitivity, or hyperalgesia, allodynia, and hypersensitivity to the skin such as itching. If the voltage-gated cation channel is inhibited, it can be used for the prevention, amelioration, or treatment of symptoms caused by increased peripheral sensory nerve activity among these symptoms. Cutaneous hyperalgesia is a sensory abnormality in which the sensation of pain is enhanced and the stimulus that causes pain becomes stronger. Allodynia is a sensory abnormality that is recognized as pain even if the stimulus does not normally cause pain. That is, itching sensitivity is a sensory abnormality that feels itching even for stimuli that do not usually feel itching.

よって、本発明の植物又はその抽出物は、ヒトを含む動物に摂取又は投与して、又は不快臭低減を望む対象物に混合、噴霧若しくは塗布等して、電位依存性カチオンチャネル阻害、皮膚知覚過敏改善及び嗅覚マスキングを図るために使用することができる。また、本願発明の植物又はその抽出物は、電位依存性カチオンチャネル阻害剤、皮膚知覚過敏改善剤及び嗅覚マスキング剤(以下、「電位依存性カチオンチャネル阻害剤等」とも云う)となり得、また当該電位依存性カチオンチャネル阻害剤等を製造するために使用することができる。
従って、本発明の電位依存性カチオンチャネル阻害剤等は、電位依存性カチオンチャネル阻害、知覚過敏改善又はマスキングのための医薬品、医薬部外品、化粧品、ハウスケア製品、食品、機能性食品若しくは飼料等として、又はこれら医薬品等に配合するための素材又は製剤として有用である。
Therefore, the plant of the present invention or the extract thereof is ingested or administered to animals including humans, or mixed, sprayed, or applied to an object that desires reduction of unpleasant odor, thereby inhibiting voltage-dependent cation channel inhibition, skin perception. It can be used to improve hypersensitivity and olfactory masking. Further, the plant of the present invention or an extract thereof can be a voltage-dependent cation channel inhibitor, a skin hypersensitivity improving agent, and an olfactory masking agent (hereinafter also referred to as “voltage-dependent cation channel inhibitor etc.”). It can be used to produce voltage-gated cation channel inhibitors and the like.
Therefore, the voltage-gated cation channel inhibitor of the present invention is a drug, quasi-drug, cosmetic, house care product, food, functional food or feed for voltage-gated cation channel inhibition, hypersensitivity improvement or masking. It is useful as a raw material or a preparation for blending with these medicines and the like.

本発明の植物又はその抽出物を含む医薬品、医薬部外品又はその他の組成物等としては、医学または獣医学分野で使用される麻酔剤、鎮静剤、鎮痛剤、鎮咳剤、抗炎症剤、過敏症やアレルギー反応などの過剰な感覚の抑制剤、痒み止め、ペインクリニック用医薬や介護や旅行で使用される吸引・点鼻による嗅覚抑制剤等の医薬品及び医薬部外品;抗カビ剤、液体タイプの衣料用抗菌仕上げ剤、衣料用洗剤、衣料用柔軟剤、衣料用漂白剤、住居用洗剤、排水口用洗剤、浴室用洗剤、トイレ用洗剤、トイレ用芳香防臭洗浄剤、洗濯機用洗剤、台所用洗浄剤、食器用洗浄剤、消臭剤等のハウスケア製品;皮膚過敏症抑制作用を有する入浴剤や化粧料、知覚過敏抑制作用を有する歯磨き粉やマウスウォッシュ等やウエットティッシュ、制汗剤、ふき取りシート等のボディケア製品等が挙げられる。   Examples of the pharmaceutical, quasi-drug or other composition containing the plant of the present invention or an extract thereof include anesthetics, sedatives, analgesics, antitussives, anti-inflammatory agents, hypersensitivity used in the medical or veterinary field. Drugs and quasi-drugs such as inhibitors of excessive sensation such as symptom and allergic reaction, anti-itching, pain clinic medicine, aspiration and nasal olfactory inhibitor used in nursing care and travel; antifungal agent, liquid Antibacterial finishing agents for clothing, clothing detergents, clothing softeners, clothing bleaches, residential cleaners, drain cleaners, bathroom cleaners, toilet cleaners, toilet deodorant cleaners, washing machine cleaners , Kitchen cleaners, dish cleaners, deodorants, and other house care products; bathing agents and cosmetics that suppress skin hypersensitivity, toothpastes and mouthwashes that suppress hypersensitivity, wet tissues, and antiperspirants Wiping agent Body care products such as sheet, and the like.

本発明の植物又はその抽出物を含む医薬品、医薬部外品は、標的とする感覚、又は標的とする対象や身体部位等に応じて、任意の投与形態で投与することができる。標的とする感覚としては上述のとおりであり、標的とする対象や身体部位としては、例えば、生体、ならびに生体由来の組織、器官及び細胞が挙げられる。
投与形態としては、経口投与及び非経口投与が挙げられる。経口投与のための剤型としては、錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤のような固形投薬形態、あるいはエリキシル、シロップおよび懸濁液のような液体投薬形態が挙げられる。非経口投与のための経路としては、注射、輸液、経皮、経粘膜、経鼻、経腸、吸入、坐剤、ボーラス等が挙げられ、剤型としては、錠剤、カプセル、液体、粉末、顆粒、軟膏、スプレー、ミスト、クリーム、乳液、ジェル、ペースト、ローション、パップ、プラスター、スティック、シート等が挙げられる。
The pharmaceutical or quasi-drug containing the plant of the present invention or an extract thereof can be administered in any dosage form depending on the target sensation, target target, body part or the like. The target sensation is as described above, and examples of the target and body part to be targeted include living bodies and tissues, organs and cells derived from living bodies.
Examples of the dosage form include oral administration and parenteral administration. Dosage forms for oral administration include solid dosage forms such as tablets, coated tablets, granules, powders, capsules, or liquid dosage forms such as elixirs, syrups and suspensions. Routes for parenteral administration include injection, infusion, transdermal, transmucosal, nasal, enteral, inhalation, suppository, bolus, etc., and dosage forms include tablets, capsules, liquids, powders, Granules, ointments, sprays, mists, creams, emulsions, gels, pastes, lotions, pops, plasters, sticks, sheets and the like.

上記製剤には、本発明の植物又はその抽出物に、必要に応じて、任意の他の成分と組み合わせて使用されてもよい。好ましい他の成分としては、薬学的に許容される担体が挙げられる。薬学的に許容される担体の具体的な例としては、賦形剤、結合剤、崩壊剤、滑沢剤、希釈剤、浸透圧調整剤、pH調整剤、乳化剤、防腐剤、安定剤、酸化防止剤、着色剤、紫外線吸収剤、保湿剤、増粘剤、光沢剤、活性増強剤、矯味剤、矯臭剤等が挙げられる。本発明の電位依存性カチオンチャネル阻害剤は、さらに、公知の他の薬効成分(例えば、他のイオンチャネル阻害剤、感覚抑制若しくは調整剤、抗炎症剤、殺菌剤等)と組み合わせて使用してもよい。   In the said formulation, you may use it in combination with arbitrary other components for the plant of this invention or its extract as needed. Preferred other ingredients include pharmaceutically acceptable carriers. Specific examples of pharmaceutically acceptable carriers include excipients, binders, disintegrants, lubricants, diluents, osmotic pressure adjusting agents, pH adjusting agents, emulsifiers, preservatives, stabilizers, oxidation Inhibitors, colorants, ultraviolet absorbers, humectants, thickeners, brighteners, activity enhancers, flavoring agents, flavoring agents and the like can be mentioned. The voltage-gated cation channel inhibitor of the present invention is further used in combination with other known medicinal ingredients (for example, other ion channel inhibitors, sensory suppression or regulators, anti-inflammatory agents, fungicides, etc.). Also good.

医薬品、医薬部外品、その他の組成物等における本発明の植物又はその抽出物の配合量は、その使用形態や目的により異なるが、例えば感覚抑制に使用する場合、通常、乾燥物換算で、0.01〜50質量%、好ましくは0.1〜10質量%、より好ましくは0.1〜5質量%である。   The amount of the plant of the present invention or its extract in pharmaceuticals, quasi-drugs, other compositions, etc. varies depending on the use form and purpose, but for example, when used for sensory suppression, usually in terms of dry matter, It is 0.01-50 mass%, Preferably it is 0.1-10 mass%, More preferably, it is 0.1-5 mass%.

また、本願発明を含む食品及び飼料等には、例えば、パン類、麺類、菓子類、ゼリー類、乳製品、冷凍食品、インスタント食品、澱粉加工製品、加工肉製品、その他加工食品、飲料、スープ類、調味料及び栄養補助食品等の食品;牛、豚、鶏、羊、馬等に用いる家畜用飼料、ウサギ、ラット、マウス等に用いる小動物用飼料、マグロ、ウナギ、タイ、ハマチ、エビ等に用いる魚介類用飼料、犬、猫、小鳥、リス等に用いるペットフード等の飼料等が挙げられる。   The food and feed containing the present invention include, for example, breads, noodles, confectionery, jelly, dairy products, frozen foods, instant foods, processed starch products, processed meat products, other processed foods, beverages and soups. Foods such as seafood, seasonings and dietary supplements; livestock feed for cattle, pigs, chickens, sheep, horses, etc., feed for small animals for rabbits, rats, mice, etc., tuna, eel, Thailand, hamachi, shrimp, etc. And feed for fish and shellfish used for food, and feed for pet food used for dogs, cats, small birds, squirrels and the like.

上記食品や飼料には、本発明の植物又はその抽出物に、必要に応じて、任意の他の成分と組み合わせて使用されてもよい。好ましい他の成分としては、食品や飼料分野で許容される担体が挙げられる。当該許容される担体の具体的な例としては、溶剤、軟化剤、油脂、乳化剤、防腐剤、香料、安定剤、着色剤、紫外線吸収剤、酸化防止剤、保湿剤、増粘剤、ゲル化剤、保型剤、pH調整剤、調味料、防腐剤、栄養補強剤等が挙げられる。
食品や飼料の形態としては、特に限定されないが、液状、半固体状、固体状の他、上記の経口投与製剤と同様の、錠剤、丸剤、カプセル剤、液剤、シロップ剤、粉末剤、顆粒剤等の形態であってもよい。
In the said foodstuff and feed, you may use it in combination with arbitrary other components for the plant of this invention, or its extract as needed. Preferred other components include carriers that are acceptable in the food and feed fields. Specific examples of such acceptable carriers include solvents, softeners, fats and oils, emulsifiers, preservatives, fragrances, stabilizers, colorants, UV absorbers, antioxidants, humectants, thickeners, gelling. Agents, shape-preserving agents, pH adjusters, seasonings, preservatives, nutritional supplements and the like.
The form of food and feed is not particularly limited, but in addition to liquid, semi-solid and solid forms, tablets, pills, capsules, liquids, syrups, powders and granules similar to those for oral administration It may be in the form of an agent or the like.

また、食品又は飼料中の、本発明の植物又はその抽出物の含有量は、その使用形態により異なるが、乾燥物換算で、通常0.001〜50質量%であり、0.01〜10質量%が好ましく、0.1〜5質量%がより好ましい。   Moreover, although content of the plant of this invention in the foodstuff or feed or its extract changes with the usage forms, it is 0.001-50 mass% normally in dry matter conversion, and 0.01-10 mass % Is preferable, and 0.1 to 5% by mass is more preferable.

本発明の植物又はその抽出物を医薬品や機能性食品として或いはこれらに配合して使用する場合の投与・摂取量は、効果が得られる量であれば特に限定されない。またその投与・摂取量は、対象者の状態、体重、性別、年齢又はその他の要因に従って変動し得るが、経口投与・摂取の場合の成人1人当たりの1日の投与・摂取量は、通常、本発明の植物又はその抽出物として、乾燥物換算で、0.001〜100gが好ましい。また、上記製剤は、任意の投与・摂取計画に従って投与・摂取され得るが、1日1回〜数回に分け、数週間〜数カ月間継続して投与・摂取するのが好ましい。   When the plant of the present invention or the extract thereof is used as a pharmaceutical or functional food or used in combination with these, the administration / intake amount is not particularly limited as long as the effect is obtained. The dose / intake may vary according to the subject's condition, weight, gender, age or other factors, but the daily dose / intake per adult for oral administration / intake is usually As a plant of this invention or its extract, 0.001-100g is preferable in conversion of a dry matter. Moreover, although the said formulation can be administered and ingested according to arbitrary administration and ingestion plans, it is preferable to divide once to several times a day, and to administer and ingest continuously for several weeks to several months.

本発明の電位依存性カチオンチャネル阻害剤等の投与又は摂取対象者としては、それを必要としていれば特に限定されないが、上述の種々の感覚を抑制又は調整すること、例えば皮膚知覚過敏改善や嗅覚マスキングを目的とするヒトやヒト以外の哺乳動物が好ましい。   The subject of administration or ingestion of the voltage-dependent cation channel inhibitor or the like of the present invention is not particularly limited as long as it is necessary, but it can suppress or adjust the above various sensations, for example, improvement of skin hypersensitivity or olfaction Humans and non-human mammals intended for masking are preferred.

以下、本発明を具体的に説明するために実施例及び試験例を挙げるが本発明はこれらの実施例に限定されるものではない。   Hereinafter, examples and test examples will be given to specifically describe the present invention, but the present invention is not limited to these examples.

エキス調製例1:セロリ
セリ科セロリ(Apium graveolens var. dulce)の種子(アメリカ産、サカタのタネより入手)1gに、50vol%エタノール水10mLを加え、室温(20〜30℃)下、7日間浸漬抽出した。不溶物をろ別した後、減圧濃縮および凍結乾燥し抽出物を得た(0.11g)。これを、再度50vol%エタノール水に濃度1w/v%となるように溶解し、試験サンプルとした。
Extract preparation example 1: Celery 10 ml of 50 vol% ethanol water is added to 1 g of seeds (obtained from Sakata Seed, USA) and seeds of Celium family Celery ( Apium graveolens var. Dulce ) for 7 days at room temperature (20-30 ° C.). Immersion extracted. The insoluble material was filtered off, concentrated under reduced pressure, and lyophilized to obtain an extract (0.11 g). This was again dissolved in 50 vol% ethanol water so as to have a concentration of 1 w / v% to obtain a test sample.

エキス調製例2:バジル
シソ科バジル(Ocimum basilicum)の葉(アメリカ産、エスビー食品(株)より入手)4gに、50vol%エタノール水40mLを加え、室温(20〜30℃)下、7日間浸漬抽出した。不溶物をろ別した後、減圧濃縮および凍結乾燥し抽出物を得た(0.76g)。これを、再度50vol%エタノール水に濃度1w/v%となるように溶解し、試験サンプルとした。
Extract Preparation Example 2: Basil Lactobacillus basil ( Ocimum basilicum ) leaves (obtained from USA, SB Foods Co., Ltd.) 4g, 50vol% ethanol water 40mL was added and immersed for 7 days at room temperature (20-30 ° C) Extracted. The insoluble material was filtered off, concentrated under reduced pressure, and lyophilized to obtain an extract (0.76 g). This was again dissolved in 50 vol% ethanol water so as to have a concentration of 1 w / v% to obtain a test sample.

試験例1
1.嗅細胞の単離
アカハライモリより公知の方法(Kurahashiら, J. Physiol. (1989), 419: 177-192)に従って嗅細胞を単離し、正常リンガー液に浸した。単離方法を簡単に示すと、氷水中で冬眠状態にしたイモリにダブルピスを施し、頭蓋を切開し嗅粘膜を取り出す。取り出した嗅粘膜を0.1%コラゲナーゼ溶液中で37℃にて5分間インキュベートし、コラゲナーゼを洗い流したあと、ガラスピペットにて組織を粉砕し細胞を単離した。正常リンガー液としては、NaCl 110mM、KCl 3.7 mM、CaCl2 3 mM、MgCl2 1 mM、グルコース 15 mM、ピルビン酸ナトリウム 1 mM、HEPES 10 mM、フェノールレッド 0.001%(w/v)、pH 7.4(NaOHで調整)を用いた。
Test example 1
1. Isolation of olfactory cells Olfactory cells were isolated according to a method known from Kakarai Mori (Kurahashi et al., J. Physiol. (1989), 419: 177-192) and immersed in normal Ringer's solution. To briefly show the isolation method, a double piss is applied to a newt hibernated in ice water, the skull is cut open, and the olfactory mucosa is removed. The removed olfactory mucosa was incubated in a 0.1% collagenase solution at 37 ° C. for 5 minutes to wash away the collagenase, and the tissue was crushed with a glass pipette to isolate cells. As normal Ringer's solution, NaCl 110 mM, KCl 3.7 mM, CaCl 2 3 mM, MgCl 2 1 mM, glucose 15 mM, sodium pyruvate 1 mM, HEPES 10 mM, phenol red 0.001% (w / v), pH 7.4 ( Adjusted with NaOH).

2.電気的活動の測定
〔A.設定〕 単離した嗅細胞を全細胞記録法により膜電位を固定し、膜電流の計測を行った(Kawaiら, J. Gen. Physiol. (1997), vol.109: 265-272)。電極は、ホウケイ酸ガラスキャピラリー(直径1.2mm)を用い、電極作成用プラー(P-97, SUTTER INSTRUMENT CO.)にて作製した(電極抵抗6.0MΩ前後)。電極内には、電極内溶液と銀塩化銀線を挿入し、銀塩化銀線はパッチクランプアンプ(EPC10, HEKA Elektronik)と接続し、膜電位の固定、脱分極刺激を行った。電極内溶液としては、CsCl 119 mM、HEPES 10 mM、CaCl2 1mM、EGTA 5mM、フェノールレッド 0.001%(w/v)、pH7.4(CsOHで調整)を用いた。膜電流の記録は、パッチクランプアンプに接続したコンピュータ(IBM互換機)にて行い(Sampling frequency, 1kHz)、測定、解析にはPatch Masterソフトウェア(HEKA Elektronik)を用いた。セロリ、バジル、各エキスの添加(吹きかけ)には、圧力制御装置を用いた。圧力制御装置とは、エアーコンプレッサーより送り込まれた圧縮空気を、コンピューター制御にて任意の圧力まで減圧し、設定した時間、その圧縮空気を試験物質を充填したガラスピペット尾部へ送り込む装置である(Itoら、日本生理学雑誌, 1995,vol.57,127-133)。
2. Measurement of electrical activity [A. Setting] Membrane currents were measured after the isolated olfactory cells were fixed by whole cell recording (Kawai et al., J. Gen. Physiol. (1997), vol. 109: 265-272). The electrode was prepared using a borosilicate glass capillary (diameter 1.2 mm) with an electrode creation puller (P-97, SUTTER INSTRUMENT CO.) (Electrode resistance around 6.0 MΩ). The electrode solution and silver-silver chloride wire were inserted into the electrode, and the silver-silver chloride wire was connected to a patch clamp amplifier (EPC10, HEKA Elektronik) to fix the membrane potential and stimulate depolarization. As the solution in the electrode, CsCl 119 mM, HEPES 10 mM, CaCl 2 1 mM, EGTA 5 mM, phenol red 0.001% (w / v), pH 7.4 (adjusted with CsOH) were used. The membrane current was recorded by a computer (IBM compatible machine) connected to a patch clamp amplifier (Sampling frequency, 1 kHz), and Patch Master software (HEKA Elektronik) was used for measurement and analysis. A pressure controller was used to add (spray) celery, basil, and each extract. A pressure control device is a device that reduces the compressed air sent from an air compressor to an arbitrary pressure by computer control, and sends the compressed air to a glass pipette tail filled with a test substance for a set time (Ito Et al., Physiological Journal of Japan, 1995, vol.57, 127-133).

〔B.手順〕 試験物質(セロリエキス)による電位依存性カチオンチャネル活性への影響を調べるため、単離した嗅細胞の膜電位を-90 mVに固定し、200ミリ秒間隔で20ミリ秒間、膜電位を-20 mVへ脱分極させ、脱分極直後に生じる内向き電流のピーク強度(図1、|a|=〔脱分極直後に生じる内向き電流値〕−〔ベースライン値〕)を測定した。脱分極刺激を繰り返し続けながら、エキス(2%溶液/溶媒:エタノール)を、正常リンガー液1 mLあたり20μLの量で混合し、嗅細胞近傍(10 μm)に先端が来るようにセットしたガラスピペット(先端口径 1 μm)を通じて吹きかけることにより(650ミリ秒間、圧力100kPa)嗅細胞に添加し、それに伴う内向き電流の変化(図1、|b|=〔ピーク強度が最も抑制されたときの内向き電流値〕−〔ベースライン値〕)を調べた。この吹きかけは5回連続して行った。さらに、エキス添加直前の脱分極によって生じた内向き電流のピーク強度(a)の平均値Aを、エキス添加直後の脱分極によって生じた内向き電流のピーク強度(b)の平均値Bを算出した。
尚、試験中、稀に試験物質添加に伴い、嗅覚受容体が応答し、CNGチャネルに由来する内向き電流が観察される場合が起きるが、このようなケースは除外した。このケースは、試験物質が試験に用いた嗅細胞上の嗅覚受容体のアゴニストとして作用することにより生じたと考えられる。CNGチャネル電流は、その強度、ピーク形状、持続時間などから電位依存性チャネル電流と容易に区別することができる。
セロリエキスをバジルエキスに代え、新たな嗅細胞を用いて、この測定を同様にして行った。
[B. Procedure] To investigate the effect of the test substance (celery extract) on the voltage-gated cation channel activity, the membrane potential of the isolated olfactory cells was fixed at -90 mV, and the membrane potential was adjusted at 200 ms intervals for 20 ms. It was depolarized to −20 mV, and the peak intensity of the inward current generated immediately after depolarization (FIG. 1, | a | = [inward current value generated immediately after depolarization] − [baseline value]) was measured. A glass pipette in which extract (2% solution / solvent: ethanol) is mixed in an amount of 20 μL per 1 mL of normal Ringer solution and the tip is placed near the olfactory cells (10 μm) while continuing depolarization stimulation repeatedly. It is added to the olfactory cells by spraying through (tip diameter 1 μm) (650 milliseconds, pressure 100 kPa), and the inward current change (FIG. 1, | b | = [inner peak intensity is most suppressed) Direction current value]-[baseline value]). This spraying was performed five times in succession. Further, the average value A of the inward current peak intensity (a) generated by depolarization immediately before the addition of the extract is calculated, and the average value B of the inward current peak intensity (b) generated by depolarization immediately after the addition of the extract is calculated. did.
During the test, the olfactory receptor responds rarely with the addition of the test substance, and an inward current derived from the CNG channel is observed, but this case was excluded. This case is thought to be caused by the test substance acting as an agonist of the olfactory receptor on the olfactory cells used in the test. The CNG channel current can be easily distinguished from the voltage-dependent channel current due to its strength, peak shape, duration, and the like.
This measurement was carried out in the same manner using a new olfactory cell instead of the celery extract.

〔C.結果〕
以下の式で、「B:ピーク強度が最も抑制されたときの内向き電流値(b)の平均値」及び「A:エキス添加直前の脱分極直後に生じる内向き電流値(a)の平均値」から「内向き電流抑制率(%)」を算出し、この結果をもとに、各エキス添加による電位依存性カチオンチャネルの電気的活動に対する抑制能を評価し、各エキスの内向き電流抑制率を表1に示した。なお、内向き電流抑制率が高い成分ほど、電位依存性カチオンチャネル阻害効果が高いものとなる。
[C. result〕
In the following formula, “B: average value of inward current value (b) when peak intensity is most suppressed” and “A: average of inward current value (a) generated immediately after depolarization immediately before addition of extract” "Inward current inhibition rate (%)" was calculated from the "value", and based on this result, the ability to inhibit the electrical activity of the voltage-dependent cation channel by adding each extract was evaluated. The inhibition rate is shown in Table 1. In addition, a component with a higher inward current suppression rate has a higher potential-dependent cation channel inhibitory effect.

内向き電流抑制率(%)=〔1−(A/B)〕×100   Inward current suppression rate (%) = [1- (A / B)] × 100

Figure 2011236169
Figure 2011236169

参考例:電位依存性チャネル阻害作用とマスキング効果との相関関係
図2及び表2に示すように、内向き電流抑制率(%)とマスキングスコアとに相関関係が認められたので、電位依存性カチオンチャネル阻害作用のある成分は不快臭のマスキング素材として有用である。
〔官能評価試験〕
官能評価の嗅覚マスキング試験をパネラー20名に対して実施した。悪臭物質として1%イソ吉草酸を、対照として悪臭に対する嗅覚感度低下効果が知られている1,8−シネオールを用いた。
悪臭 2μLと、表2に示す 0.1%濃度の評価化合物の試験溶液 4μLを別々の綿球(直径 1cm)にしみこませ、別々の 50mL注射筒内で12時間、室温で揮発させた。注射筒内で気化したイソ吉草酸と評価化合物をフタ付きのPP容器(容積 500mL)内へ注入し、混和させた。
評価は、パネラー自身がPP容器のフタをわずかに開け、容器内の匂いを嗅ぎ、イソ吉草酸の匂いに対するマスキング強度を判定した。
マスキング強度の評価は、気化したイソ吉草酸のみを注入したPP容器内の臭気強度と比較し、以下の6段階のマスキングスコアにより行った。この結果を表2に示した。
0:マスキングされていない
1:マスキング効果がごくわずかに認められる
2:マスキング効果がやや認められる
3:マスキング効果が十分認められる
4:ほとんどマスキングされている
5:完全にマスキングされている
Reference example: Correlation between voltage-dependent channel inhibitory action and masking effect As shown in Fig. 2 and Table 2, there was a correlation between the inward current suppression rate (%) and the masking score. A component having a cation channel inhibitory action is useful as a masking material for unpleasant odors.
[Sensory evaluation test]
An olfactory masking test for sensory evaluation was performed on 20 panelists. As a malodorous substance, 1% isovaleric acid was used, and as a control, 1,8-cineole, which is known to have an effect of reducing olfactory sensitivity to malodor, was used.
2 μL of malodor and 4 μL of the test solution of 0.1% concentration test compound shown in Table 2 were soaked in separate cotton balls (1 cm in diameter) and volatilized at room temperature for 12 hours in separate 50 mL syringes. The isovaleric acid vaporized in the syringe and the evaluation compound were poured into a PP container (capacity 500 mL) with a lid and mixed.
In the evaluation, the paneler himself opened the lid of the PP container slightly, sniffed the smell in the container, and judged the masking strength against the smell of isovaleric acid.
The masking strength was evaluated by comparing the odor strength in the PP container into which only vaporized isovaleric acid was injected, and the following six levels of masking score. The results are shown in Table 2.
0: Not masked 1: Slight masking effect 2: Slight masking effect 3: Sufficient masking effect 4: Almost masked 5: Completely masked

Figure 2011236169
Figure 2011236169

Claims (6)

セロリ及びバジルから選ばれる植物又はその抽出物を有効成分とする電位依存性チャネル阻害剤。   A voltage-dependent channel inhibitor comprising a plant selected from celery and basil or an extract thereof as an active ingredient. セロリ種子抽出物及び/又はバジル葉抽出物である請求項1記載の電位依存性チャネル阻害剤。   The voltage-dependent channel inhibitor according to claim 1, which is a celery seed extract and / or a basil leaf extract. 抽出物が、水及び/又はアルコールの抽出物である請求項1又は2記載の電位依存性チャネル阻害剤。   The voltage-dependent channel inhibitor according to claim 1 or 2, wherein the extract is an extract of water and / or alcohol. セロリ及びバジルから選ばれる植物又はその抽出物を有効成分とする知覚過敏抑制剤。   A hypersensitivity inhibitor comprising as an active ingredient a plant selected from celery and basil or an extract thereof. セロリ種子抽出物及び/又はバジル葉抽出物である請求項4記載の知覚過敏抑制剤。   The hypersensitivity inhibitor according to claim 4, which is a celery seed extract and / or a basil leaf extract. 抽出物が、水及び/又はアルコールの抽出物である請求項4又は5記載の知覚過敏抑制剤。   The hypersensitivity inhibitor according to claim 4 or 5, wherein the extract is an extract of water and / or alcohol.
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