JP2021031406A - 歯肉組織破壊抑制剤 - Google Patents
歯肉組織破壊抑制剤 Download PDFInfo
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- JP2021031406A JP2021031406A JP2019149853A JP2019149853A JP2021031406A JP 2021031406 A JP2021031406 A JP 2021031406A JP 2019149853 A JP2019149853 A JP 2019149853A JP 2019149853 A JP2019149853 A JP 2019149853A JP 2021031406 A JP2021031406 A JP 2021031406A
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- gingival
- mmp
- suppressing
- tissue
- hinokitiol
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- YUOWTJMRMWQJDA-UHFFFAOYSA-J tin(iv) fluoride Chemical compound [F-].[F-].[F-].[F-].[Sn+4] YUOWTJMRMWQJDA-UHFFFAOYSA-J 0.000 description 1
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- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- YSJNWPJHMDWGAA-UHFFFAOYSA-H tricalcium;[oxido-[oxido(phosphonatooxy)phosphoryl]oxyphosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O YSJNWPJHMDWGAA-UHFFFAOYSA-H 0.000 description 1
- ICUTUKXCWQYESQ-UHFFFAOYSA-N triclocarban Chemical compound C1=CC(Cl)=CC=C1NC(=O)NC1=CC=C(Cl)C(Cl)=C1 ICUTUKXCWQYESQ-UHFFFAOYSA-N 0.000 description 1
- 229960001325 triclocarban Drugs 0.000 description 1
- VXYADVIJALMOEQ-UHFFFAOYSA-K tris(lactato)aluminium Chemical compound CC(O)C(=O)O[Al](OC(=O)C(C)O)OC(=O)C(C)O VXYADVIJALMOEQ-UHFFFAOYSA-K 0.000 description 1
- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
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- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- GFQYVLUOOAAOGM-UHFFFAOYSA-N zirconium(iv) silicate Chemical compound [Zr+4].[O-][Si]([O-])([O-])[O-] GFQYVLUOOAAOGM-UHFFFAOYSA-N 0.000 description 1
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Birds (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
項2.ヒノキチオールを有効成分として含有することを特徴とする、歯肉退縮抑制または改善剤。
項3.ヒノキチオールを有効成分として含有することを特徴とする、歯周組織におけるコラーゲン分解酵素MMP−1の産生抑制剤。
項4.ヒノキチオールを口腔組成物に配合することにより、当該口腔組成物に対して、歯肉組織破壊抑制作用、歯肉退縮抑制または改善作用、及び歯周組織におけるコラゲナーゼ分解酵素MMP−1の産生抑制作用よりなる群から選択される少なくとも1つの作用を付与することを特徴とする、ヒノキチオールの使用方法。なお、当該使用方法は、歯肉組織破壊抑制剤、歯肉退縮抑制または改善剤、及び歯周組織におけるMMP−1の産生抑制剤よりなる群から選択される少なくとも1つの口腔組成物を製造するための、ヒノキチオールの使用と言い換えることもできる。
グネシウム、第三リン酸マグネシウム、ゼオライト、ケイ酸ジルコニウム、ハイドロキシアパタイト、フルオロアパタイト、カルシウム欠損アパタイト、第三リン酸カルシウム、第四リン酸カルシウム、第八リン酸カルシウム、合成樹脂系研磨剤。
油、ローレル油、カモミル油、キャラウェイ油、マジョラム油、ベイ油、レモングラス油、オリガナム油、パインニードル油、ネロリ油、ローズ油、ジャスミン油、イリスコンクリート、アブソリュートペパーミント、アブソリュートローズ、オレンジフラワー等の天然香料、及び、これら天然香料の加工処理(前溜部カット、後溜部カット、分留、液液抽出、エッセンス化、粉末香料化等)した香料や、メントール、カルボン、アネトール、シネオール、サリチル酸メチル、シンナミックアルデヒド、オイゲノール、3−l−メントキシプロパン−1,2−ジオール、チモール、リナロール、リナリールアセテート、リモネン、メントン、メンチルアセテート、N−置換−パラメンタン−3−カルボキサミド、ピネン、オクチルアルデヒド、シトラール、プレゴン、カルビールアセテート、アニスアルデヒド、エチルアセテート、エチルブチレート、アリルシクロヘキサンプロピオネート、メチルアンスラニレート、エチルメチルフェニルグリシデート、バニリン、ウンデカラクトン、ヘキサナール、プロピルアルコール、ブタノール、イソアミルアルコール、ヘキセノール、ジメチルサルファイド、シクロテン、フルフラール、トリメチルピラジン、エチルラクテート、メチルラクテート、エチルチオアセテート等の単品香料、更に、ストロベリーフレーバー、アップルフレーバー、バナナフレーバー、パイナップルフレーバー、グレープフレーバー、マンゴーフレーバー、バターフレーバー、ミルクフレーバー、フルーツミックスフレーバー、トロピカルフルーツフレーバー等の調合香料等。
ヒト歯肉線維芽細胞(HGF−1)を、ポルフィロモナス・ジンジバリス由来のリポポリサッカライド(LPS−PG)の存在下、ヒノキチオールの存在または非存在の条件で培養して、経時的に1型ヒト線維芽細胞コラゲナーゼ(MMP−1)の産生量を測定し、歯肉細胞におけるコラーゲン分解酵素の発現及び産生に対するヒノキチオールの作用を評価した。
細胞:正常ヒト歯肉線維芽細胞(HGF−1細胞)(ATCC CRL−2014)
培地:D−MEM High Glucose(富士フイルム和光純薬株式会社製)
生細胞測定用試薬:
(1)MMP−1 ELISAキット(Human Total MMP−1 DuoSet ELISA、R&Dシステムズ社製)
(2)Cel Counting Kit−8Cel(株式会社同仁化学研究所製)
LPS−PG:ポルフィロモナス・ジンジバリス[Pg]由来のリポポリサッカライド(ナカライテスク株式会社製)
ヒノキチオール:東京化成工業株式会社
ヒノキチオール用溶媒:ジメチルスルホキシド50ppm、POE硬化ヒマシ油50ppm
(1)MMP−1量の測定
正常ヒト歯肉線維芽細胞(HGF−1細胞)を、培地を入れた96ウェルプレートに、1×104個/ウェルの割合で播種し、インキュベーター(37℃、5% CO2)内で、24時間培養(初期培養)した。初期培養(24時間)後に、培地を除去し、表1に記載する被験試料液(比較例、実施例1及び2)、及びLPS−PG(終濃度10μg/mL)を添加して、さらにインキュベーター(37℃、5% CO2)で24時間、または48時間培養した(曝露培養)。培養から24時間及び48時間後に、それぞれ検体液(培養液)を回収して、MMP−1 ELISAキットのマニュアルに従って、ELISA法により培養液中のMMP−1量(pg/mL)を測定した。
前記培養24時間及び48時間後に回収した検体液(培養液)中の生細胞数は、前記CCKキットを用いて測定した。具体的には、まず前記初期培養により得られたサンプル(初期サンプル)について、ウェルから培地を除去し、歯肉線維芽細胞をPBSで洗浄し、CCKキット付属のCCK希釈溶液(CCK溶液:培地=1:10)を100μL添加して、インキュベーター(37℃、5% CO2)内にて1時間静置した後、波長450nm及び650nmにおける吸光度を測定した。また、前記曝露培養により得られたサンプル(曝露サンプル)については、ウェルから回収した検体液から培地と被験試料液を除去して、歯肉線維芽細胞をPBSで洗浄し、CCK希釈溶液(同上)を100μL添加して、インキュベーター(37℃、5% CO2)内にて1時間静置した後、波長450nm及び650nmにおける吸光度を測定した。曝露サンプル(検体液)中の生細胞数は、測定した波長450nmの吸光度と650nmの吸光度の差(吸光度450nm−吸光度650nm)を、初期サンプルについて測定した当該差(吸光度450nm−吸光度650nm)と比較して、算出した。
比較例、並びに実施例1及び2について、検体液(培養液)中のMMP−1量(pg/mL)を表2及び図1に示す。なお、表2及び図1に示す値は、いずれも比較例のサンプルを24時間または48時間培養した後のサンプルに含まれる生細胞数を1として、生細胞数(相対値)あたりのMMP−1量(pg/mL)に換算したものである。また、結果は試験数(n=6)の平均値である。
下記の処方に従って、歯磨剤(表3)、洗口液(表4)、及びゲル剤(表5)の形態を有する本発明の製剤を調製することができる。
Claims (4)
- ヒノキチオールを有効成分として含有することを特徴とする、歯肉組織破壊抑制剤。
- ヒノキチオールを有効成分として含有することを特徴とする、歯肉退縮抑制または改善剤。
- ヒノキチオールを有効成分として含有することを特徴とする、歯周組織におけるコラーゲン分解酵素MMP−1の産生抑制剤。
- ヒノキチオールを口腔組成物に配合することにより、当該口腔組成物に対して、歯肉組織破壊抑制作用、歯肉退縮抑制または改善作用、及びコラーゲン分解酵素MMP−1の発現または産生抑制作用よりなる群から選択される少なくとも1つの作用を付与することを特徴とする、ヒノキチオールの使用方法。
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JPS63188619A (ja) * | 1987-01-29 | 1988-08-04 | Shiseido Co Ltd | 口腔用組成物 |
JP2002047162A (ja) * | 2000-08-01 | 2002-02-12 | Asahi Kasei Corp | 口腔用組成物 |
JP2009298724A (ja) * | 2008-06-12 | 2009-12-24 | Hinoki Shinyaku Kk | コラーゲン産生促進剤及び皮膚外用剤 |
JP2013121954A (ja) * | 2011-11-08 | 2013-06-20 | Earth Chemical Co Ltd | 歯肉のコラーゲン密度増強剤、歯肉のコラーゲン密度増強組成物および歯肉のコラーゲン密度の増強方法 |
WO2018066341A1 (ja) * | 2016-10-06 | 2018-04-12 | ライオン株式会社 | 口腔用組成物、及びその製剤変色及び液分離の抑制方法 |
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JPS63188619A (ja) * | 1987-01-29 | 1988-08-04 | Shiseido Co Ltd | 口腔用組成物 |
JP2002047162A (ja) * | 2000-08-01 | 2002-02-12 | Asahi Kasei Corp | 口腔用組成物 |
JP2009298724A (ja) * | 2008-06-12 | 2009-12-24 | Hinoki Shinyaku Kk | コラーゲン産生促進剤及び皮膚外用剤 |
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