JP2021080200A - Composition for improving allergic rhinitis and/or sinusitis symptoms - Google Patents
Composition for improving allergic rhinitis and/or sinusitis symptoms Download PDFInfo
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- JP2021080200A JP2021080200A JP2019208246A JP2019208246A JP2021080200A JP 2021080200 A JP2021080200 A JP 2021080200A JP 2019208246 A JP2019208246 A JP 2019208246A JP 2019208246 A JP2019208246 A JP 2019208246A JP 2021080200 A JP2021080200 A JP 2021080200A
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- allergic rhinitis
- sinusitis
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Images
Abstract
Description
本発明はアレルギー性鼻炎及び／又は副鼻腔炎症状改善用組成物に関する。より詳細には、大気汚染物質によるアレルギー性鼻炎及び／又は副鼻腔炎症状改善用組成物に関する。 The present invention relates to a composition for improving allergic rhinitis and / or sinus inflammation. More specifically, it relates to a composition for improving allergic rhinitis and / or sinus inflammation caused by air pollutants.
産業の発展や人口の増加に伴い、世界中で大気汚染が深刻な問題となっている。ＰＭ２．５や排気ガス、黄砂など様々な大気汚染物質が存在する中で、これまでに喘息や気管支炎といった呼吸器疾患や心臓病などの循環器疾患を引き起こすことが報告されてきた。 With industrial development and population growth, air pollution has become a serious problem all over the world. In the presence of various air pollutants such as PM2.5, exhaust gas, and yellow sand, it has been reported to cause respiratory diseases such as asthma and bronchitis and cardiovascular diseases such as heart disease.
アレルギー性鼻炎や副鼻腔炎への大気汚染物質の関与については長年注目されてきた。非特許文献１では、非大気汚染区域に比べて大気汚染区域では、アレルギー性鼻炎や副鼻腔炎の罹患率が高いことが疫学調査にて明らかになっている。非特許文献２では、都市大気粉塵を吸入した男女の鼻分泌液中にて、炎症性サイトカインであるＩＬ−１βが７２．３％、ＩＬ−６は４２．２％、ＩＬ−８は１９．７％と有意に増加しており、これらのサイトカインが、鼻の炎症と密接に関連していることが伺える。また、非特許文献３では、副鼻腔炎患者の鼻分泌液中にてＩＬ−１βが有意に増加しており、副鼻腔炎の原因となっていることが示されている。また、非特許文献４では、ＰＭ２．５中のマスト細胞株の水溶性成分が脱顆粒を引き起こすことや、ディーゼル排気微粒子等がアレルギー性鼻炎の抗原抗体反応のアジュバントとなっていることが示されている（非特許文献５）。
The involvement of air pollutants in allergic rhinitis and sinusitis has been the focus of attention for many years. In
しかしながら、大気汚染物質によるアレルギー性鼻炎や副鼻腔炎に奏功する物質についてはほとんど報告がなく、分子メカニズムから対応策を提案していくことが必要とされている。 However, there are few reports on substances that are effective against allergic rhinitis and sinusitis caused by air pollutants, and it is necessary to propose countermeasures from the molecular mechanism.
そこで、本発明は、大気汚染物質によるアレルギー性鼻炎や副鼻腔炎を効果的に改善する組成物を提供することを目的とする。 Therefore, an object of the present invention is to provide a composition that effectively improves allergic rhinitis and sinusitis caused by air pollutants.
上記課題を解決するために、本発明者等が鋭意検討した結果、生薬の一種であるシンイ（辛夷）及びその抽出物が、炎症性のサイトカインであるＩＬ−１βの発現を抑制すること、βヘキソサミニダーゼの遊離を抑制することを見出し、本発明を完成するに至った。 As a result of diligent studies by the present inventors in order to solve the above problems, Shini (spicy), which is a kind of crude drug, and its extract suppress the expression of IL-1β, which is an inflammatory cytokine, β. We have found that it suppresses the release of hexosaminidase, and have completed the present invention.
すなわち、本発明は、下記に掲げる組成物を提供する。
［１］シンイ又はその抽出物を有効成分として含有する、大気汚染物質によるアレルギー性鼻炎及び／又は副鼻腔炎並びにそれらの症状の改善用組成物。
［２］前記症状が、くしゃみ、鼻みず、鼻づまり、なみだ目、のどの痛み及び頭重からなる群より選ばれる１種又は２種以上である、［１］に記載の組成物。
［３］シンイ又はその抽出物を有効成分として含有する、βヘキソサミニダーゼ遊離抑制用、又は、ＩＬ−１β発現抑制用組成物。
［４］大気汚染物質によるアレルギー性鼻炎、副鼻腔炎、及び、それらの症状を改善する、［３］に記載の組成物。
［５］大気汚染物質が、都市大気粉塵及び／又はディーゼル排気微粒子である、［４］に記載の組成物。
［６］シンイ又はその抽出物を有効成分として含有する、粘膜上皮細胞の繊毛機能改善用組成物。
［７］鼻づまりによる咳（或いは、咳を伴う鼻づまり）、鼻みずの流れやすさ、又は、痰の詰まりを改善する、［６］に記載の組成物。
That is, the present invention provides the compositions listed below.
[1] A composition for improving allergic rhinitis and / or sinusitis caused by air pollutants and their symptoms, which contains Shini or an extract thereof as an active ingredient.
[2] The composition according to [1], wherein the symptom is one or more selected from the group consisting of sneezing, nasal congestion, stuffy nose, sore throat, sore throat and heavy head.
[3] A composition for suppressing the release of β-hexosaminidase or for suppressing the expression of IL-1β, which contains Shini or an extract thereof as an active ingredient.
[4] The composition according to [3], which improves allergic rhinitis due to air pollutants, sinusitis, and their symptoms.
[5] The composition according to [4], wherein the air pollutant is urban air dust and / or diesel exhaust particles.
[6] A composition for improving ciliary function of mucosal epithelial cells, which contains Shini or an extract thereof as an active ingredient.
[7] The composition according to [6], which improves coughing due to stuffy nose (or stuffy nose accompanied by coughing), ease of flow of nasal fluid, or clogging of sputum.
本発明によれば、大気汚染物質によるアレルギー性鼻炎及び／又は副鼻腔炎が生じている場合に効果的にそれらの症状を改善することが可能となる。 According to the present invention, it is possible to effectively improve allergic rhinitis and / or sinusitis caused by air pollutants.
［大気汚染物質によるアレルギー性鼻炎及び／又は副鼻腔炎並びにそれらの症状の改善用組成物］
一つの実施形態において、本発明の組成物は、生薬のシンイ又はその抽出物を含有する。また、本発明は、特に大気汚染物質によるアレルギー性鼻炎及び／又は副鼻腔炎並びにそれらの症状の改善に適している。また、本発明は、限定はされないが、日常のアンチポリューション対策としても適用可能である。
[Composition for improving allergic rhinitis and / or sinusitis caused by air pollutants and their symptoms]
In one embodiment, the composition of the present invention contains the crude drug Faith or an extract thereof. The present invention is particularly suitable for improving allergic rhinitis and / or sinusitis caused by air pollutants and their symptoms. Further, the present invention is not limited, but can be applied as a daily anti-pollution measure.
また、本発明は、都会の空気（大気）が気になる方、自動車の排気ガスが気になる方、ＰＭ１０やＰＭ２．５が気になる方、黄砂が気になる方、アンチポリューションの対策を行いたい方、タバコの煙が気になる方等に好適に用いられる。 Further, the present invention relates to those who are concerned about urban air (atmosphere), those who are concerned about automobile exhaust gas, those who are concerned about PM10 and PM2.5, those who are concerned about yellow sand, and anti-pollution measures. It is suitable for those who want to do this, those who are concerned about cigarette smoke, etc.
本明細書において、シンイは、限定はされないが、モクレン、ハモクレン、シモクレン、コブシ、タムシバ等のモクレン科植物、又はその他近縁植物の花蕾を乾燥したものから得られ、マグノフロリン等が含まれている。 In the present specification, Shini is obtained from, but is not limited to, dried flower buds of magnolias, magnolias, magnolias, magnolia kobus, anise magnolia, and other related plants, and includes magnoflorin and the like. There is.
シンイを抽出物（エキス）として用いる場合、抽出溶媒としては、水（熱水を含む）、メタノール、エタノール、イソプロパノール、エチレングリコール、グリセリン等のアルコール類、酢酸エチル等のエステル類、アセトンやメチルエチルケトン等のケトン類、アセトニトリルなどのニトリル類、ジエチルエーテル、テトラヒドロフラン等のエーテル類、ペンタン、ヘキサン、シクロペンタン、シクロヘキサンなどの飽和炭化水素類、トルエンなどの芳香族炭化水素類、ジクロロメタン、クロロホルムなどのハロゲン化炭化水素類、その他ジメチルホルムアミド、ジメチルスルホキシドなどの有機溶媒（すべて含水であってもよい）などを適宜用いることができ、１種または２種の任意の混合液であってもよい。これらの溶媒のうち、水、エタノール、またはこれらの混合溶液が、安全性の観点から好ましい。 When Shini is used as an extract, the extraction solvent includes water (including hot water), methanol, ethanol, isopropanol, ethylene glycol, alcohols such as glycerin, esters such as ethyl acetate, acetone, methyl ethyl ketone and the like. Ketones, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, saturated hydrocarbons such as pentane, hexane, cyclopentane and cyclohexane, aromatic hydrocarbons such as toluene, halogenation of dichloromethane and chloroform. Hydrocarbons, other organic solvents such as dimethylformamide and dimethylsulfoxide (all may be water-containing) and the like can be appropriately used, and one or two arbitrary mixed solutions may be used. Of these solvents, water, ethanol, or a mixed solution thereof is preferable from the viewpoint of safety.
また、シンイを抽出物（エキス）として用いる場合、第十七改正日本薬局方の製剤総則に記載の、生薬関連製剤「エキス剤」を製する方法に準じて製造されたものを用いることもできる。上記方法としては、例えば、適切な大きさとした生薬に適切な抽出剤を加えて、一定時間冷浸、温浸して抽出液を得る方法や、適切な大きさとした生薬を処方に従って一定量ずつ量り、その全量に約１０〜２０倍量の水を加えて一定時間加熱して抽出液を得る方法があげられる。なお、得られた抽出液は、通常、遠心分離、ろ過等の固液分離に供され、固形分が除去されて用いられる。 In addition, when Shini is used as an extract, it can also be manufactured according to the method for producing a crude drug-related preparation "extract" described in the 17th revised Japanese Pharmacopoeia's general preparation rules. .. As the above method, for example, a method of adding an appropriate extractant to an appropriately sized crude drug and cold-immersing and warm-immersing it for a certain period of time to obtain an extract, or a method of measuring an appropriately sized crude drug in a fixed amount according to a prescription , A method of adding about 10 to 20 times the amount of water to the total amount and heating for a certain period of time to obtain an extract can be mentioned. The obtained extract is usually subjected to solid-liquid separation such as centrifugation and filtration, and the solid content is removed before use.
熱水による抽出法としては、例えば、シンイをそのまま、又は、破砕して熱水に浸漬する方法が挙げられ、熱水による抽出温度は、４０〜１００℃が好ましく、７０〜１００℃がより好ましい。熱水による抽出時間は、１０〜１２０分が好ましく、６０〜１００分がより好ましい。アルコール類による抽出法としては、エタノールを用いることが好ましく、抽出温度は、２０〜５０℃が好ましく、抽出時間は、１０〜１２０分が好ましく、６０〜１００分がより好ましい。 Examples of the extraction method using hot water include a method in which the faith is directly or crushed and immersed in hot water. The extraction temperature with hot water is preferably 40 to 100 ° C, more preferably 70 to 100 ° C. .. The extraction time with hot water is preferably 10 to 120 minutes, more preferably 60 to 100 minutes. As the extraction method using alcohols, ethanol is preferably used, the extraction temperature is preferably 20 to 50 ° C., and the extraction time is preferably 10 to 120 minutes, more preferably 60 to 100 minutes.
シンイの抽出物は、液状のものを使用してもよいが、必要に応じて、減圧乾燥、凍結乾燥、噴霧乾燥等の乾燥処理を行って液体分を低減又は除去することにより、濃縮液状、半固形状、固形状、又は粉末状にしたものを使用してもよい。 A liquid extract may be used, but if necessary, a concentrated liquid can be obtained by performing drying treatments such as vacuum drying, freeze drying, and spray drying to reduce or remove the liquid content. Semi-solid, solid, or powdered ones may be used.
シンイの抽出物は、市販品を用いることも可能であり、例えば、デルタインターナショナル株式会社、松浦薬業株式会社等のシンイエキスを用いることが可能である。 As the extract of Shini, a commercially available product can be used, and for example, Shini extract of Delta International Co., Ltd., Matsuura Pharmaceutical Co., Ltd., etc. can be used.
本発明におけるシンイ又はその抽出物は、漢方処方の構成生薬となっているものも含まれる。シンイを構成生薬に含む漢方処方としては、具体的には、柴葛湯加川▲弓▼辛夷、辛夷清肺湯、麗沢通気湯加辛夷などがあるが、これに限定されない。 The Shini or its extract in the present invention also includes those which are constituent crude drugs of Chinese medicine prescription. Specific examples of Chinese herbal prescriptions containing Shini in herbal medicines include, but are not limited to, Shibakatsuyu Kagawa ▲ bow ▼ Shin'iseihai, Shin'iseihaito, and Reisawa aerated hot water.
本発明の組成物における１日あたりのシンイの用量（投与量）は、他の成分の種類や量、服用者の状態（体重、年齢、性別、症状、体調等）、及び剤形等に応じて適宜設定でき、限定はされないが、本発明の効果をより顕著に発揮させる観点から、原生薬換算量で表すと、例えば、約１〜約５０００ｍｇとすることができ、より好ましくは、約５０〜約４０００ｍｇ、さらに好ましくは、約１００〜約３５００ｍｇ、特に好ましくは、約１５０〜約３５００ｍｇ、最も好ましくは、約２００〜約３０００ｍｇとすることができる。また、別の実施態様において、本発明の組成物における１日あたりのシンイの用量（投与量）は、原生薬換算量で表すと、例えば、約２００〜約２５００ｍｇ、約２００〜約２２００ｍｇ、約２００〜約１８００ｍｇ、約２００〜約１５００ｍｇとすることもできる。 The daily dose (dose) of Shini in the composition of the present invention depends on the type and amount of other ingredients, the condition of the user (body weight, age, gender, symptoms, physical condition, etc.), dosage form, etc. However, from the viewpoint of exerting the effect of the present invention more remarkably, the amount in terms of crude drug can be, for example, about 1 to about 5000 mg, more preferably about 50. It can be from about 4000 mg, more preferably from about 100 to about 3500 mg, particularly preferably from about 150 to about 3500 mg, and most preferably from about 200 to about 3000 mg. In another embodiment, the daily dose (dose) of Faith in the composition of the present invention is expressed in terms of crude drug equivalent, for example, about 200 to about 2500 mg, about 200 to about 2200 mg, and about. It can also be 200 to about 1800 mg and about 200 to about 1500 mg.
また、シンイ抽出物の１日あたりの経口投与量は、エキスの乾燥固形分換算で表すと、例えば、約０．０１〜約２７００ｍｇとすることができ、より好ましくは、約０．１〜約１８００ｍｇ、さらに好ましくは、約０．５〜約１５００ｍｇ、特に好ましくは、約１〜約１２００ｍｇ、最も好ましくは、約３〜約９００ｍｇとすることができる。また、別の実施態様において、シンイ抽出物の１日あたりの経口投与量は、エキスの乾燥固形分換算で表すと、例えば、約３〜約９００ｍｇ、約３〜約８００ｍｇ、約３〜約７００ｍｇ、約３〜約６００ｍｇ、約３〜約５００ｍｇ、約３〜約４００ｍｇ、約３〜約３００ｍｇ、約３〜約２５０ｍｇとすることもできる。 The daily oral dose of the Faith extract can be, for example, about 0.01 to about 2700 mg in terms of the dry solid content of the extract, and more preferably about 0.1 to about 0.1 to about 2. It can be 1800 mg, more preferably about 0.5 to about 1500 mg, particularly preferably about 1 to about 1200 mg, and most preferably about 3 to about 900 mg. In another embodiment, the daily oral dose of the Shini extract is, for example, about 3 to about 900 mg, about 3 to about 800 mg, and about 3 to about 700 mg in terms of dry solid content of the extract. , About 3 to about 600 mg, about 3 to about 500 mg, about 3 to about 400 mg, about 3 to about 300 mg, and about 3 to about 250 mg.
本明細書において「原生薬換算」とは、その成分量を得るために必要な原生薬（生薬混合物）の重量（乾燥重量）として表したものを意味する。生薬として抽出物を用いる場合には、その抽出物の量を得るために必要な原生薬の乾燥重量が原生薬換算量となる。１日あたりの服用量は、１〜６回、好ましくは１〜３回に分けて服用してもよい。 As used herein, the term "herbal medicine equivalent" means the weight (dry weight) of the crude drug (herbal medicine mixture) required to obtain the amount of the component thereof. When an extract is used as a crude drug, the dry weight of the crude drug required to obtain the amount of the extract is the amount converted to the crude drug. The daily dose may be divided into 1 to 6 times, preferably 1 to 3 times.
シンイの含有量は、他の成分の種類や量、服用者の状態（体重、年齢、症状、体調等）、および剤形等によって異なり得るが、組成物が固形製剤である場合、組成物の総量を基準として、通常０．０１〜９９重量％、好ましくは０．０５〜９５重量％、さらに好ましくは０．１〜９０重量％、特に好ましくは１〜８５重量％である。また、鼻炎系生薬の総含有量は、組成物が液状製剤である場合、組成物全量に対して、通常０．０１〜８０重量％、好ましくは０．０５〜７０重量％、さらに好ましくは０．１〜６０重量％、特に好ましくは１〜５５重量％である。なお、固形製剤が液状調製物を包含する場合、液状調製物全量に対して、通常０．０１〜７０重量％、好ましくは０．０５〜６０重量％、さらに好ましくは０．１〜５０重量％、特に好ましくは１〜５０重量％である。 The content of Shini may vary depending on the type and amount of other ingredients, the condition of the user (weight, age, symptoms, physical condition, etc.), dosage form, etc., but if the composition is a solid preparation, the composition Based on the total amount, it is usually 0.01 to 99% by weight, preferably 0.05 to 95% by weight, more preferably 0.1 to 90% by weight, and particularly preferably 1 to 85% by weight. When the composition is a liquid preparation, the total content of the rhinitis crude drug is usually 0.01 to 80% by weight, preferably 0.05 to 70% by weight, more preferably 0, based on the total amount of the composition. .1 to 60% by weight, particularly preferably 1 to 55% by weight. When the solid preparation includes the liquid preparation, it is usually 0.01 to 70% by weight, preferably 0.05 to 60% by weight, more preferably 0.1 to 50% by weight, based on the total amount of the liquid preparation. , Particularly preferably 1 to 50% by weight.
本発明の組成物は、所望により、シンイに加えて、その他の生理活性成分を含有してもよい。 If desired, the composition of the present invention may contain other physiologically active ingredients in addition to Faith.
このような生理活性成分としては、例えば
（１）抗ヒスタミン成分（例えば、メキタジン、ロラタジン、ケトチフェンフマル酸塩、セチリジン塩酸塩、エピナスチン塩酸塩、フェキソフェナジン塩酸塩、オロパタジン塩酸塩、イソチペンジル塩酸塩、イプロヘプチン塩酸塩、ジフェテロール塩酸塩、ジフェニルピラリン塩酸塩、ジフェンヒドラミン塩酸塩、トリプロリジン塩酸塩水和物、トリペレナミン塩酸塩、トンジルアミン塩酸塩、プロメタジン塩酸塩、メトジラジン塩酸塩、ジフェンヒドラミンサリチル酸塩、ジフェニルジスルホン酸カルビノキサミン、アリメマジン酒石酸塩、ジフェンヒドラミンタンニン酸塩、ジフェニルピラリンテオクル酸塩、カルビノキサミンマレイン酸塩、クロルフェニラミンマレイン酸塩、プロメタジンメチレンジサリチル酸塩）、
（２）副交感神経遮断成分（例えば、ベラドンナ総アルカロイド、ヨウ化イソプロパミド、ダツラエキス、ロートエキスなど）、
（３）交感神経興奮成分（例えばメチルエフェドリン、プソイドエフェドリン、フェニレフリン、メトキシフェナミン又はそれらの塩など）、
（４）消炎酵素類（例えば、リゾチーム、ブロメラインなど）、
（５）グリチルリチン酸類（例えば、グリチルリチン酸又はその塩など）、
（６）キサンチン誘導体（例えば、安息香酸ナトリウムカフェイン、カフェイン水和物、無水カフェイン等のカフェインなど）、
などが挙げられる。
Examples of such physiologically active components include (1) antihistamine components (for example, mequitazine, loratazine, ketotiphenfumarate, cetilidine hydrochloride, epinastine hydrochloride, hexofenazine hydrochloride, olopatadine hydrochloride, isotipendyl hydrochloride, etc. Iproheptin Hydrochloride, Dipheterol Hydrochloride, Diphenylpyraline Hydrochloride, Diphenhydramine Hydrochloride, Triprolysine Hydrochloride Hydrate, Tryperenamine Hydrochloride, Tondylamine Hydrochloride, Promethazine Hydrochloride, Metodylazine Hydrochloride, Diphenhydramine Salicylate, Diphenyldisulfonate Carbinoxamine, Alimemazine Tartrate, diphenhydramine tannate, diphenylpyraline theocrate, carbinoxamine maleate, chlorphenylamine maleate, promethazine methylene disalicylate),
(2) Parasympathetic nerve blocking components (for example, belladonna total alkaloid, isopropamide iodide, dicula extract, scopolia extract, etc.)
(3) Sympathetic nerve excitatory components (eg, methylephedrine, pseudoephedrine, phenylephrine, methoxyphenamine or salts thereof, etc.),
(4) Anti-inflammatory enzymes (for example, lysozyme, bromelain, etc.),
(5) Glycyrrhizic acid (for example, glycyrrhizic acid or a salt thereof),
(6) Xanthine derivatives (for example, caffeine such as sodium benzoate caffeine, caffeine hydrate, anhydrous caffeine, etc.),
And so on.
これらの生理活性成分は、フリー体であっても、塩であってもよい。 These physiologically active ingredients may be free or salts.
本発明の効果を安定的に発揮する観点から、これらの生理活性成分としては、メキタジン、メチルエフェドリン及びその塩（メチルエフェドリン塩酸塩など）、プソイドエフェドリン及びその塩（プソイドエフェドリン塩酸塩など）、ベラドンナ総アルカロイド、グリチルリチン酸又はその塩（グリチルリチン酸二カリウムなど）、及び無水カフェインからなる群より選択される少なくとも１種が好ましい。 From the viewpoint of stably exerting the effects of the present invention, these physiologically active ingredients include mequitadine, methylephedrine and its salts (methylephedrine hydrochloride, etc.), pseudoephedrine and its salts (psoidephedrine hydrochloride, etc.), and veradonna total alkaloids. , Glycyrrhizic acid or a salt thereof (such as dipotassium glycyrrhizinate), and at least one selected from the group consisting of anhydrous caffeine is preferable.
本発明の組成物は、例えば、医薬品、医薬部外品、又はこれらの原料であることができる。 The composition of the present invention can be, for example, a pharmaceutical product, a quasi drug, or a raw material thereof.
本発明の組成物は、当業者に公知の方法に従って、固形製剤として種々の剤形に調製することができる。固形製剤の形状や大きさには特に限定はなく、例えば内服剤としては、錠剤［口腔内崩壊錠、チュアブル錠（咀嚼可能錠）、発泡錠、分散錠、溶解錠、フィルムコーティング錠、素錠及び糖衣錠等を含む］、カプセル剤［硬カプセル剤及び軟カプセル剤等を含む］、顆粒剤［発泡顆粒剤を含む］、散剤、粉末剤、細粒剤、丸剤、口腔用錠剤［トローチ剤、舌下錠、バッカル錠、付着錠及びガム剤等を含む］、フィルム剤、ドライシロップ剤、ゼリー剤、口腔用半固形剤、製菓剤［キャンディー（飴）、グミ剤及びヌガー剤等を含む］などの固形製剤が挙げられる。また、本発明の組成物は、液状製剤として種々の剤形に調製することができ、例えば内服剤としては、シロップ剤、液剤、懸濁剤などの液状製剤が挙げられる。これらのなかでも、本発明の効果をより顕著に発揮させる観点から、本発明の組成物は、固形製剤に用いることが好ましく、錠剤、カプセル剤、顆粒剤、散剤、フィルム剤に用いることがより好ましく、錠剤、カプセル剤に用いることがさらに好ましい。 The composition of the present invention can be prepared in various dosage forms as a solid preparation according to a method known to those skilled in the art. The shape and size of the solid preparation are not particularly limited. For example, as an internal preparation, tablets [orally disintegrating tablets, chewable tablets (chewable tablets), effervescent tablets, dispersion tablets, dissolving tablets, film-coated tablets, uncoated tablets And sugar-coated tablets], capsules [including hard capsules and soft capsules], granules [including effervescent granules], powders, powders, fine granules, pills, oral tablets [troches] , Sublingual tablets, buccal tablets, adhesive tablets, gum agents, etc.], film agents, dry syrup agents, jelly agents, oral semi-solid agents, confectionery agents [including candy (candy), gummy agents, granule agents, etc.] Examples include solid preparations such as. In addition, the composition of the present invention can be prepared in various dosage forms as a liquid preparation, and examples of the oral preparation include liquid preparations such as syrups, liquids and suspensions. Among these, from the viewpoint of exerting the effect of the present invention more remarkably, the composition of the present invention is preferably used for a solid preparation, and more preferably used for tablets, capsules, granules, powders and films. It is preferable, and it is more preferable to use it for tablets and capsules.
［用途］
本発明を用いることにより、炎症性のサイトカインであるＩＬ−１βの発現の抑制、及び、βヘキソサミニダーゼの遊離抑制を効果的にもたらすことが可能となる。これにより、ＩＬ−１βの発現やβヘキソサミニダーゼの遊離が関与する症状や状態の予防・治療・改善等に有効である。
[Use]
By using the present invention, it is possible to effectively suppress the expression of IL-1β, which is an inflammatory cytokine, and the release of β-hexosaminidase. This is effective for the prevention / treatment / improvement of symptoms and conditions associated with the expression of IL-1β and the release of β-hexosaminidase.
本発明の組成物は、症状として鼻炎を伴う病態や鼻炎の関連症状（鼻汁（鼻漏、鼻水、鼻汁過多）、鼻閉（鼻づまり）、くしゃみ、なみだ目、そう痒、のどの痛み、頭重（頭が重い）、鼻粘膜の腫れ、鼻腔のうっ血、鼻出血、および鼻粘膜の萎縮または硬化等）の全てに適応が可能と考えられ、急性鼻炎や副鼻腔炎、アレルギー性鼻炎に効果が高い。特に、本発明の組成物は、鼻汁、鼻閉、若しくはくしゃみ、又は、アレルゲンによる急性鼻炎、副鼻腔炎、若しくはアレルギー性鼻炎に好適に用いられ得る。限定はされないが、本発明の組成物は、ネバネバした鼻汁、喉に落ちる鼻汁、外鼻孔から出る鼻汁、息苦しさ、頭がぼーっとする症状に対しても好適に用いられ得る。本発明の組成物は、例えば、内服用（経口投与用）に用いることができる。 The composition of the present invention includes pathological conditions accompanied by rhinitis and related symptoms of rhinitis (nasal discharge (rhinorrhea, runny nose, excessive nasal discharge), nasal congestion (stuffy nose), squeezing, swelling eyes, itching, sore throat, It is considered to be applicable to all of head weight (heavy head), nasal mucus swelling, nasal congestion, nasal bleeding, and nasal mucus atrophy or hardening), and is effective for acute rhinitis, sinusitis, and allergic rhinitis. Is high. In particular, the compositions of the present invention can be suitably used for nasal discharge, nasal congestion, or sneezing, or allergen-induced acute rhinitis, sinusitis, or allergic rhinitis. The compositions of the present invention may also be suitably used for sticky nasal discharge, nasal discharge that falls in the throat, nasal discharge from the nostrils, suffocation, and dull head symptoms. The composition of the present invention can be used, for example, for oral administration (oral administration).
特に、炎症を抑制することで、鼻粘膜の繊毛運動を活発にし、鼻づまりによる咳（或いは、咳を伴う鼻づまり）、鼻みずの流れやすさ、又は、痰の詰まりを改善できることが推測される（非特許文献６、７）。 In particular, it is speculated that by suppressing inflammation, the ciliary movement of the nasal mucosa can be activated, and cough due to nasal congestion (or nasal congestion accompanied by cough), nasal congestion, or sputum congestion can be improved. (Non-Patent Documents 6 and 7).
上記アレルゲンが、大気汚染物質の場合、本発明の組成物は、アンチポリューション対策としても有用である。身体のアンチポリューション対策が近年重要視されてきているが、多くの製品は、皮膚外用剤である。本発明の組成物では、限定はされないが、例えば、内服用（経口投与用）に用いることにより、体内からアンチポリューション対策ができることができ有用である。非特許文献７に記載されているように、アンチポリューション対策のため、粘液分泌や粘液繊毛運動などの生体防御機構が発達しているが、粘膜上皮細胞等に炎症が生じるとこれらの生体防御機構が破綻してしまい、大気汚染物質を適切に排出することが困難となる。本発明の組成物を用いることにより、粘膜上皮細胞等に炎症を抑制することで、鼻粘膜の繊毛運動を活発にし、大気汚染物質に対する生体防御機構の改善、増進を行うことが可能となる。 When the allergen is an air pollutant, the composition of the present invention is also useful as an anti-pollution measure. Although anti-pollution measures for the body have been emphasized in recent years, many products are topical skin preparations. The composition of the present invention is not limited, but is useful because it can be used for oral administration (oral administration), for example, to prevent anti-pollution from the body. As described in Non-Patent Document 7, biological defense mechanisms such as mucus secretion and mucous ciliary movement have been developed for anti-pollution measures, but when inflammation occurs in mucosal epithelial cells, these biological defense mechanisms Will collapse, making it difficult to properly discharge air pollutants. By using the composition of the present invention, it is possible to activate the ciliary movement of the nasal mucosa by suppressing inflammation in mucosal epithelial cells and the like, and to improve and enhance the biological defense mechanism against air pollutants.
本発明の組成物の投与量は、その形態、投与方法、投与目的及び当該組成物の投与対象者の年齢、体重、症状、体調によって適宜設定され、一定ではない。また、本発明の組成物の投与は、所望の投与量範囲内において、１日あたり単回で、又は数回に分けて行ってもよく、食前、食間、食後、又は食事と同時に投与されてもよい。なお、本明細書中の用語「投与」は、「服用」を包含することを意図して用いられる。 The dose of the composition of the present invention is appropriately set according to the form, administration method, purpose of administration, age, weight, symptomatology, and physical condition of the subject to be administered the composition, and is not constant. In addition, the composition of the present invention may be administered once per day or in several divided doses within a desired dose range, and may be administered before, between meals, after meals, or at the same time as meals. May be good. The term "administration" in the present specification is used with the intention of including "dosing".
本発明の組成物は、通常、１日１〜６回、好ましくは１日１〜３回投与することができる。したがって、１回の投与のための本発明の組成物は、前記の１日あたりの投与量を１日の投与回数で割った量を、含有することが好ましい。なお、本発明の組成物は、水に対する溶解性が向上し、薬物の速溶解性及び／又は速放出性に優れるため、１日１〜３回の投与が好ましく、１日１回、１日２回、又は１日３回の投与で用いることが可能である。 The composition of the present invention can usually be administered 1 to 6 times a day, preferably 1 to 3 times a day. Therefore, the composition of the present invention for a single dose preferably contains the above-mentioned daily dose divided by the number of daily doses. Since the composition of the present invention has improved solubility in water and is excellent in rapid solubility and / or rapid release of the drug, it is preferably administered 1 to 3 times a day, once a day, a day. It can be used twice or three times a day.
次に、実施例により本発明を具体的に説明するが、本発明は以下の実施例に限定されるものではない。なお、使用した試薬で特段記載がない場合は、和光純薬の特級試薬を用いた。 Next, the present invention will be specifically described with reference to Examples, but the present invention is not limited to the following Examples. Unless otherwise specified, Wako Pure Chemical's special grade reagent was used.
［試験例１：ヒト鼻中隔扁平上皮由来細胞におけるシンイのＩＬ−１β抑制試験］
（１−１）培養条件
ヒト鼻中隔扁平上皮由来細胞（ＲＰＭＩ２６５０細胞）は、ＥＭＥＭ（ＡＴＣＣ）に、血清としてＦｅｔａｌ ｂｏｖｉｎｅ ｓｅｒｕｍ（ＦＢＳ）、抗生物質としてＡｎｔｉｂｉｏｔｉｃ−Ａｎｔｉｍｙｃｏｔｉｃ（以下、Ａ．Ａとも記載する）（ｇｉｂｃｏ）、Ｌ−Ｇｌｕｔａｍｉｎｅ（ｇｉｂｃｏ）を加えた、ＥＭＥＭ（１０％ ＦＢＳ，＋Ａ．Ａ）を用いた。培養はｔｉｓｓｕ Ｃｕｌｔｕｒｅ Ｄｉｓｈ ６０ｍｍ、１００ｍｍを用いた。培地交換は３日毎に行った。本試験では、１２ ｗｅｌｌ ｐｌａｔｅに１．０ｘ１０６ｃｅｌｌｓ／ｍｌで用意した細胞懸濁液を１ｍｌずつ播種し、１ｗｅｌｌ当たり１．０ｘ１０６ｃｅｌｌｓの細胞数で行った。
[Test Example 1: IL-1β suppression test of Shini in cells derived from human nasal septal squamous epithelium]
(1-1) Culture conditions Human nasal septal squamous epithelial-derived cells (RPMI2650 cells) are added to EMEM (ATCC) as serum, fetal bovine serum (FBS), and as an antibiotic, Antibiotic-Antimycotic (hereinafter, also referred to as AA). (Gibco) and L-Glutamine (gibco) were added, and EMEM (10% FBS, + A.A.) was used. For culturing, dish Culture Dish 60 mm and 100 mm were used. Medium exchange was performed every 3 days. In this test, 12 well plate cell suspension prepared in 1.0x10 6 cells / ml in a seeded by 1 ml, were carried out at 1.0x10 6 cells number of cells per one well.
（１−２）添加試料の調整方法
シンイエキス（第十七改正日本薬局方に収載されるシンイの項目を満たすもの、以下同じ）は、ＥＭＥＭ（１０％ ＦＢＳ，＋Ａ．Ａ）で１０、５０ｍｇ／ｍｌ（原生薬換算量で、それぞれ、１２５ｍｇ／ｍｌ、６２５ｍｇ／ｍｌ）になるように調整し、１２，０００ｒｐｍ、２ｍｉｎで遠心後、その上清をシンイエキス添加溶液とした。
(1-2) Preparation method of added sample Shini extract (satisfying the items of Shini listed in the 17th revision of the Japanese Pharmacopoeia, the same shall apply hereinafter) is 10, 50 mg / 50 mg / EMEM (10% FBS, + AA) The mixture was adjusted to ml (125 mg / ml and 625 mg / ml, respectively, in terms of crude drug equivalent), centrifuged at 12,000 rpm for 2 min, and the supernatant was used as a solution containing Shini extract.
ＴＮＦα（Ｒｅｃｏｍｂｉｎａｎｔ Ｈｕｍａｎ ＴＮＦα Ｒ＆Ｄ ｓｙｓｔｅｍｓ）は１００μｇ／ｍｌ ｓｔｏｃｋをＥＭＥＭ（１０％ ＦＢＳ，＋Ａ．Ａ）で１００倍希釈したものをＴＮＦα添加溶液とした。 TNFα (Recombinant Human TNFα R & D systems) was prepared by diluting 100 μg / ml stock 100-fold with EMEM (10% FBS, + A.A.) as a TNFα-added solution.
（１−３）試験条件
１２ ｗｅｌｌ ｐｌａｔｅで４８時間培養したＲＰＭＩ２６５０細胞にシンイエキス添加溶液（１０、５０ ｍｇ／ｍｌ）を１０μｌ／ｗｅｌｌで添加し、３７℃、５％ＣＯ２下で１時間インキュベートした。その後、ＴＮＦα添加溶液（１ μｇ／ｍｌ）を１０ μｌ／ｗｅｌｌで添加し、３７℃、５％ＣＯ２下で６時間インキュベートした。Ｖｅｈｉｃｌｅ（（−））には、各サンプル添加時に同量のＥＭＥＭ （１０％ ＦＢＳ，＋Ａ．Ａ）を添加した。
(1-3) Test conditions To RPMI2650 cells cultured on a 12-well plate for 48 hours, a solution containing Shini extract (10, 50 mg / ml) was added at 10 μl / well and incubated at 37 ° C. for 1 hour under 5% CO 2. .. Then, a TNFα-added solution (1 μg / ml) was added at 10 μl / well and incubated at 37 ° C. under 5% CO 2 for 6 hours. To Vehicle ((−)), the same amount of EMEM (10% FBS, + A.A.) was added at the time of adding each sample.
（１−４）遺伝子解析方法
ＲＮＡの抽出はＲＮｅａｓｙ（登録商標）Ｍｉｎｉ ｋｉｔ（ＱＩＡＧＥＮ）を用いて推奨プロトコールに従って行った。ＲＮＡ ｓａｍｐｌｅは、ＲＮＡ濃度をＮａｎｏＤｒｏｐ ＮＤ−１０００（Ｔｈｅｒｍｏ Ｆｉｓｈｅｒ Ｓｃｉｅｎｔｉｆｉｃ）で測定後、ＤＮａｓｅ処理を行い、逆転写反応によりｃＤＮＡ化させた。
逆転写終了後のｃＤＮＡサンプルは、ＲＮａｓｅ ｆｒｅｅ ｗａｔｅｒで５倍希釈し、−３０℃で保管した。
(1-4) Gene analysis method RNA was extracted using RNeasy (registered trademark) Mini kit (QIAGEN) according to the recommended protocol. The RNA sample was converted into cDNA by DNase treatment after measuring the RNA concentration with NanoDrop ND-1000 (Thermo Fisher Scientific).
After completion of reverse transcription, the cDNA sample was diluted 5-fold with RNase free water and stored at −30 ° C.
遺伝子発現解析は、ＱｕａｎｔＳｔｕｄｉｏ（登録商標） ３リアルタイムＰＣＲシステム（Ｔｈｅｒｍｏ Ｆｉｓｈｅｒ Ｓｃｉｅｎｔｉｆｉｃ）による、ＴａｑＭａｎ ｐｒｏｂｅを用いたＲｅａｌ−Ｔｉｍｅ ＰＣＲ法により行った。内部標準はＡＣＴＢとし、データ解析は、ΔΔＣＴ法を用いることで行った。
Gene expression analysis was performed by the Real-Time PCR method using TaqMan probe using the
（１−５）結果
シンイエキスの抗炎症作用について検証した結果を図１に示す。シンイエキスは、ＴＮＦαによって上昇するＩＬ−１βのｍＲＮＡ発現レベルを、濃度依存的に、有意に減少させた。（＊ｐ ＜ ０．０５、＊＊＊ｐ ＜ ０．０００５）
(1-5) Results The results of verifying the anti-inflammatory effect of Shini extract are shown in FIG. Shini extract significantly reduced the mRNA expression level of IL-1β increased by TNFα in a concentration-dependent manner. (* P <0.05, *** p <0.0005)
［試験例２：ラット好塩基球性白血病細胞におけるシンイのβヘキソサミニダーゼ遊離抑制試験］
シンイエキスが脱顆粒に及ぼす作用を検証するため、Ｆｃ Ｒ１−ＩｇＥ−抗原架橋により誘導されるβ−ヘキソサミニダーゼの遊離抑制活性を評価した。
[Test Example 2: Faith β-hexosaminidase release inhibition test in rat basophilic leukemia cells]
In order to verify the effect of Shini extract on degranulation, the release inhibitory activity of β-hexosaminidase induced by Fc R1-IgE-antigen cross-linking was evaluated.
（２−１）培養条件
ラット好塩基球性白血病細胞（ＲＢＬ−２Ｈ３細胞）は、ＤＭＥＭに、血清としてＦｅｔａｌ ｂｏｖｉｎｅ ｓｅｒｕｍ（ＦＢＳ）、抗生物質としてＡｎｔｉｂｉｏｔｉｃ−Ａｎｔｉｍｙｃｏｔｉｃ （Ａ．Ａ）（ｇｉｂｃｏ）、Ｌ−Ｇｌｕｔａｍｉｎｅ（ｇｉｂｃｏ）を加えたＤＭＥＭ（１０％ ＦＢＳ，＋Ａ．Ａ）を用いた。培養はＣｅｌｌ Ｃｕｌｔｕｒｅ Ｆｌａｓｋｓ ７０ｍｌ（Ｆａｌｃｏｎ）を用いた。培地交換は３日毎に行った。本試験では、２４ｗｅｌｌ ｐｌａｔｅに５．０ｘ１０５ｃｅｌｌｓ／ｍｌで用意した細胞懸濁液を０．５ｍｌずつ、１ｗｅｌｌ当たり２．５ｘ１０５ｃｅｌｌｓの細胞を播種した。そして、３７℃、５％ＣＯ２下でｏｖｅｒ ｎｉｇｈｔで培養したＲＢＬ−２Ｈ３細胞をＡｓｓａｙに用いた。
(2-1) Culture conditions Rat basophil leukemia cells (RBL-2H3 cells) were added to DMEM with Fetal bovine serum (FBS) as serum, Antibiotic-Antimicotic (AA) (gibco) as antibiotics, and L. DMEM (10% FBS, + A.A.) supplemented with −Glutamine (gibco) was used. For culturing, 70 ml (Falcon) of Cell Culture Flashs was used. Medium exchange was performed every 3 days. In this test, 0.5 ml of a cell suspension prepared at 5.0 x 10 5 cells / ml was seeded on a 24-well plate at 2.5 x 10 5 cells per well. Then, RBL-2H3 cells cultured in over night at 37 ° C. and 5% CO 2 were used for Assay.
（２−２）添加試料の調整方法
シンイエキスは、ＰＩＰＥＳ ｂｕｆｆｅｒで０．１、１、１０ｍｇ／ｍｌ（原生薬換算量で、それぞれ１．２５ｍｇ／ｍｌ、１２．５ｍｇ／ｍｌ、１２５ｍｇ／ｍｌ）になるように調整し、１２，０００ｒｐｍ、２ｍｉｎで遠心後、その上清をシンイエキス添加溶液とした。
(2-2) Preparation method of added sample Shini extract is 0.1, 1 and 10 mg / ml (1.25 mg / ml, 12.5 mg / ml and 125 mg / ml, respectively, in terms of crude drug equivalent) with PIPES buffer. After centrifuging at 12,000 rpm and 2 min, the supernatant was used as a Shini extract-added solution.
（２−３）試験条件
ＲＢＬ−２Ｈ３細胞の培地を除去し、ＰＢＳで２回洗浄した。ＤＭＥＭ（１０％ ＦＢＳ，＋Ａ．Ａ）で１００ｎｇ／ｍｌに調整した抗ＤＮＰ−ＩｇＥ抗体混合培地を加え、３７℃、５％ＣＯ２下で２時間培養した。
(2-3) Test conditions The medium of RBL-2H3 cells was removed, and the cells were washed twice with PBS. Anti-DNP-IgE antibody mixed medium adjusted to 100 ng / ml with DMEM (10% FBS, + A.A.) was added, and the cells were cultured at 37 ° C. under 5% CO 2 for 2 hours.
混合培地を除去し、ＰＩＰＥ ｂｕｆｆｅｒで２回洗浄した。ＰＩＰＥＳ ｂｕｆｆｅｒで溶解した４９０μｌのシンイエキス、トラニラストまたはＰＩＰＥＳ ｂｕｆｆｅｒのみを加え、３７℃、５％ＣＯ２下で１０分間反応させた。ＰＩＰＥＳ ｂｕｆｆｅｒで溶解した１５０ｎｇ／ｍｌのＤＮＰ−ＢＳＡを１０μｌ加え、３７℃、５％ＣＯ２下で３０分間培養した。培養上清回収後、０．１％ Ｔｒｉｔｏｎ Ｘ−１００／ＰＩＰＥＳ ｂｕｆｆｅｒで細胞を溶解し、細胞溶解液を回収した。９６ｗｅｌｌ ｐｌａｔｅに上清、溶解液を５０μｌずつ加え、３７℃で５分間加温した。５０μｌのＳｕｂｓｔｒａｔｅ Ｂｕｆｆｅｒ（下記表１及び２に記載の処方により調製）を加え、３７℃で２５分間反応させた。反応液に１００μｌのＳｔｏｐ Ｂｕｆｆｅｒ（下記表３に記載の処方により調製）を加えて反応停止後、４０５ｎｍの吸光度を測定した。β−ヘキソサミニダーゼの放出率を次の式１により求めた。
The mixed medium was removed and washed twice with PIPE buffer. Only 490 μl of Shini extract, tranilast or PIPES buffer dissolved in PIPES buffer was added and reacted at 37 ° C. under 5% CO 2 for 10 minutes. 10 μl of 150 ng / ml DNP-BSA dissolved in PIPES buffer was added, and the cells were cultured at 37 ° C. under 5% CO 2 for 30 minutes. After collecting the culture supernatant, the cells were lysed with 0.1% Triton X-100 / PIPES buffer, and the cytolytic solution was collected. 50 μl of the supernatant and 50 μl of the solution were added to the 96-well plate, and the mixture was heated at 37 ° C. for 5 minutes. 50 μl of Substrate Buffer (prepared according to the formulation shown in Tables 1 and 2 below) was added and reacted at 37 ° C. for 25 minutes. After stopping the reaction by adding 100 μl of Stop Buffer (prepared according to the formulation shown in Table 3 below) to the reaction solution, the absorbance at 405 nm was measured. The release rate of β-hexosaminidase was determined by the following
［式１］
β−ヘキソサミニダーゼ放出率＝
（培養上清の吸光度／培養上清の吸光度＋細胞溶解液の吸光度）×１００
[Equation 1]
β-hexosaminidase release rate =
(Absorbance of culture supernatant / Absorbance of culture supernatant + Absorbance of cytolytic solution) × 100
（２−４）結果
シンイエキスのβヘキソサミニダーゼの遊離に対する作用を検証した結果を図２に示す。シンイエキスの前処理により、濃度依存的に、有意にβ‐ヘキソサミニダーゼの遊離を抑制した。（＊ｐ ＜ ０．００００１、＊＊ｐ ＜ ０．０００５(ｖｓ.ｃｏｎｔｒｏｌ)）
(2-4) Results Figure 2 shows the results of verifying the effect of Shini extract on the release of β-hexosaminidase. Pretreatment with Shini extract significantly suppressed the release of β-hexosaminidase in a concentration-dependent manner. (* P <0.00001, ** p <0.0005 (vs.control))
［試験例３：ヒト血管内皮細胞におけるシンイエキスの接着因子ＶＣＡＭ−１発現抑制試験］
（３−１）培養条件
ヒト臍帯静脈内皮細胞（ＨＵＶＥＣ）は、ＨｕＭｅｄｉａ ＥＧ２（クラボウ）を用いた。培養はＣｏｒｎｉｎｇ（登録商標） ＣｅｌｌＢＩＮＤ（登録商標） Ｓｕｒｆａｃｅ ｃｅｌｌ ｃｕｌｔｕｒｅ ｆｌａｓｋｓ ＣｅｌｌＢＩＮＤ ７５ｃｍ２（Ｃｏｒｎｉｎｇ）を用いた。培地交換は３日毎に行った。本試験では、２４ ｗｅｌｌ ｐｌａｔｅに２．０ｘ１０５ ｃｅｌｌｓ／ｍｌで用意した細胞懸濁液を０．５ｍｌずつ播種し、１ｗｅｌｌ当たり１．０ｘ１０5 ｃｅｌｌｓの細胞数で行った。
[Test Example 3: Suppression test of adhesion factor VCAM-1 expression of Shini extract in human vascular endothelial cells]
(3-1) Culture conditions As human umbilical vein endothelial cells (HUVEC), HuMedia EG2 (Kurabo Industries) was used. For culturing, Corning (registered trademark) CellBIND (registered trademark) Surface cell culture flashes CellBIND 75 cm 2 (Corning) was used. Medium exchange was performed every 3 days. In this test, 0.5 ml of a cell suspension prepared at 2.0 x 10 5 cells / ml was seeded on a 24-well plate, and the number of cells was 1.0 x 10 5 cells per well.
（３−２）添加試料の調整方法
シンイエキスは、ＨｕＭｅｄｉａ ＥＧ２で１ ｍｇ／ｍｌ（原生薬換算量で、１２．５ｍｇ／ｍｌ）になるように調整し、１２，０００ｒｐｍ、２ｍｉｎで遠心後、その上清をシンイエキス添加培地とした。
(3-2) Preparation method of added sample Shini extract is adjusted to 1 mg / ml (12.5 mg / ml in terms of crude drug equivalent) with HuMedia EG2, centrifuged at 12,000 rpm, and then centrifuged. The supernatant was used as a medium containing Shini extract.
ＴＮＦα（Ｒｅｃｏｍｂｉｎａｎｔ Ｈｕｍａｎ ＴＮＦα Ｒ＆Ｄ ｓｙｓｔｅｍｓ）は１００μｇ／ｍｌをＨｕＭｅｄｉａ ＥＧ２で１００倍希釈した１μｇ／ｍｌをＴＮＦα添加溶液とした。 For TNFα (Recombinant Human TNFα R & D systems), 100 μg / ml was diluted 100-fold with HuMedia EG2, and 1 μg / ml was used as a TNFα-added solution.
（３−３）試験条件
２４ ｗｅｌｌ ｐｌａｔｅで２４時間培養したＨＵＶＥＣは０．５ｍｌのシンイエキス添加培地（１ｍｇ／ｍｌ）に培地交換し、３７℃、５％ＣＯ２下で１時間インキュベートした。その後、ＴＮＦα添加溶液（１μｇ／ｍｌ）を５μｌ／ｗｅｌｌで添加し、３７℃、５％ＣＯ２下で４時間インキュベートした。Ｖｅｈｉｃｌｅ（（−））には、各サンプル添加時に同量のＨｕＭｅｄｉａ ＥＧ２を添加した。
(3-3) Test Conditions HUVEC cultured on a 24-well plate for 24 hours was exchanged with 0.5 ml of Shini extract-added medium (1 mg / ml) and incubated at 37 ° C. under 5% CO 2 for 1 hour. Then, a TNFα-added solution (1 μg / ml) was added at 5 μl / well and incubated at 37 ° C. under 5% CO 2 for 4 hours. To Vehicle ((−)), the same amount of HuMedia EG2 was added at the time of adding each sample.
（３−４）遺伝子解析方法
遺伝子解析は１−４の方法と同様に行った。尚、内部標準はＧＡＰＤＨで行った。
(3-4) Gene analysis method The gene analysis was performed in the same manner as in the method 1-4. The internal standard was GAPDH.
（３−５）結果
シンイエキスの接着因子ＶＣＡＭ−１に与える影響を検証した結果を図３に示す。シンイエキスは、ＴＮＦαによって上昇するＶＣＡＭ−１のｍＲＮＡ発現レベルを有意に減少させた。
（＊ｐ ＜ ０．００１、＊＊ｐ ＜ ０．０１）
(3-5) Results The results of verifying the effect of Shini extract on the adhesion factor VCAM-1 are shown in FIG. Shini extract significantly reduced the mRNA expression level of VCAM-1 increased by TNFα.
(* P <0.001, ** p <0.01)
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| JP2017048186A (en) * | 2015-09-04 | 2017-03-09 | ロート製薬株式会社 | Pharmaceutical composition |
| JP2018188377A (en) * | 2017-04-28 | 2018-11-29 | ロート製薬株式会社 | Pharmaceutical composition |
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| CN101313938A (en) * | 2008-07-11 | 2008-12-03 | 吉林省辉南天泰药业股份有限公司 | Magnolia flower volatile oil spray for nose |
| JP2017048186A (en) * | 2015-09-04 | 2017-03-09 | ロート製薬株式会社 | Pharmaceutical composition |
| JP2018188377A (en) * | 2017-04-28 | 2018-11-29 | ロート製薬株式会社 | Pharmaceutical composition |
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