JP2021097622A - ヒト抗菌ペプチド産生促進剤 - Google Patents
ヒト抗菌ペプチド産生促進剤 Download PDFInfo
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- JP2021097622A JP2021097622A JP2019230852A JP2019230852A JP2021097622A JP 2021097622 A JP2021097622 A JP 2021097622A JP 2019230852 A JP2019230852 A JP 2019230852A JP 2019230852 A JP2019230852 A JP 2019230852A JP 2021097622 A JP2021097622 A JP 2021097622A
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- Prior art keywords
- human
- antibacterial peptide
- lipoic acid
- acid
- oil
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 102000044503 Antimicrobial Peptides Human genes 0.000 title claims abstract description 8
- 108700042778 Antimicrobial Peptides Proteins 0.000 title claims abstract description 8
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- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims abstract description 46
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims abstract description 45
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Abstract
Description
〔1〕α−リポ酸又はその誘導体を含有する、ヒト抗菌ペプチド産生促進剤。
〔2〕ヒト抗菌ペプチドが、歯周病原因菌、口臭原因菌、う蝕原因菌及びカンジダ菌からなる群より選ばれる1以上の菌に対し抗菌活性を有するペプチドである〔1〕記載のヒト抗菌ペプチド産生促進剤。
〔3〕ヒト抗菌ペプチドが、カテリシジン、ヒトβディフェンシン2、ヒトβディフェンシン3、及びカルプロテクチンからなる群より選ばれる少なくとも1つである、〔1〕又は〔2〕に記載のヒト抗菌ペプチド産生促進剤。
〔4〕粘膜、口腔粘膜及び歯肉からなる群より選ばれる少なくとも1つの部位におけるヒト抗菌ペプチドの産生を促進する、〔1〕〜〔3〕のいずれか1項に記載のヒト抗菌ペプチド産生促進剤。
〔5〕α−リポ酸又はその誘導体を有効成分として含有する、ヒト抗菌ペプチド産生促進用口腔用組成物。
〔6〕α−リポ酸又はその誘導体を機能成分として含有する、ヒト抗菌ペプチド産生促進用飲食品組成物。
〔7〕α−リポ酸又はその誘導体を有効成分として含有する、ヒト抗菌ペプチド産生促進用医薬品又は医薬部外品組成物。
〔8〕α−リポ酸又はその誘導体を含有する、歯周病、口臭、う蝕及びカンジダ菌感染症から選ばれる少なくとも1つの症状のヒト抗菌ペプチド産生促進による予防又は緩和剤。
本発明の剤は、α−リポ酸及又はその誘導体を含有する。これにより、ヒト抗菌ペプチドの産生促進作用を発揮できる。本発明の剤は、α−リポ酸及びその誘導体からなる群より選ばれる少なくとも1つを含有すればよく、2種以上を含有してもよい。
本発明の剤のα−リポ酸及びその誘導体の含有量(α−リポ酸及びその誘導体から選ばれる2種以上を含む場合、それらの総含有量)は、特に限定されないが、α−リポ酸の量として0.00001質量%以上が好ましく、0.0001質量%以上がより好ましい。これにより良好な抗菌ペプチド産生促進効果を得ることができる。上限は特に限定されないが、1質量%以下が好ましく、0.1質量%以下がより好ましい。これにより、細胞障害による産生促進作用の低下を抑制できる。従って通常は0.00001〜1質量%、好ましくは0.0001〜0.1質量%である。
本発明の剤は、溶解補助剤を更に含んでいてもよい。これにより各種用途においてα−リポ酸及びその誘導体の溶解性を高めることができる。溶解補助剤としては、例えば、エタノール、シクロデキストリンが挙げられる。溶解補助剤が含まれる場合、α−リポ酸及びその誘導体の含有量は、α−リポ酸及びその誘導体と溶解補助剤の合計量に対し好ましくは0.0001質量%以上、より好ましくは0.001質量%以上である。上限は特に制限されないが、好ましくは15質量%以下、より好ましくは1.5質量%以下である。
本発明の剤は、ヒト抗菌ペプチド産生促進作用を有する。本明細書において、ヒト抗菌ペプチドとは、ヒトの体内で産生される抗菌ペプチドであり、具体的には例えば、ヒトの粘膜、好ましくはヒトの口腔組織由来の抗菌ペプチドである。本発明の剤は、口腔疾患の原因菌、例えば、歯周病原因菌(例えば、ポルフィロモナス属菌(ポルフィロモナス・ジンジバリス等)、アグリゲイティバクター属菌(アグリゲイティバクター・アクチノミセテムコミタンス等))、口臭原因菌(例えば、フゾバウテリウム属菌(フゾバウテリウム・ヌクレアタム等))、う蝕原因菌(例えば、ストレプトコッカス属菌(ストレプトコッカス・ミュータンス等))及びカンジダ菌に対して抗菌作用を有するヒト抗菌ペプチドの産生促進作用を有する。そのため、本発明によれば、ヒト抗菌ペプチドの増加による歯周病、口臭、う蝕、カンジダ菌感染症等口腔疾患の予防又は改善を意図した口腔用組成物、飲食品、医薬品、医薬部外品への応用が期待できる。
本発明の剤の形状は特に限定されないが、粘膜(好ましくは口腔粘膜)、歯肉への適用が容易な形状が好ましく、例えば、液体系(液剤、ペースト、ジェル等)、固体系(粒剤、錠剤、固形剤等)が挙げられる。
飲食品としては、例えば、飲料(例、清涼飲料、炭酸飲料、栄養飲料、粉末飲料、果実飲料、乳飲料、ゼリー飲料)、食品類(例、ガム、キャンディー、タブレット、グミ、フィルム、トローチ、クッキー、ゼリー)が挙げられる。機能性食品(健康食品)としては、例えば、ヒト抗菌ペプチド産生促進用食品、歯周病予防又は改善用食品、口臭予防又は改善用食品、う蝕予防又は改善用食品、カンジダ由来疾患予防又は改善用食品挙げられる。本発明の剤を飲食品(好ましくは機能性食品)として利用する場合、必要に応じて補助的原料又は添加物を配合し得る。
口腔用組成物としては、例えば、歯磨剤、洗口剤、口腔用パスタ、マウススプレー、塗布剤、シート剤等が挙げられる。本発明の剤を口腔用組成物として利用する場合、必要に応じて任意成分を配合し得る。任意成分としては、研磨剤、界面活性剤、粘結剤、湿潤剤、甘味料、防腐剤、香料、着色剤、pH調整剤、溶剤、溶媒、賦形剤、各種薬効成分、及びこれらから選ばれる2以上の組み合わせが挙げられる。
なお、研磨剤は、1種単独で又は2種以上を組み合わせて使用し得る。
医薬品としては、例えば、口腔内崩壊錠、口腔内溶解錠、トローチ、うがい薬、軟膏等が挙げられ、外用剤が好ましい。本発明の剤を医薬品として利用する場合、必要に応じて任意成分を配合し得る。任意成分としては、口腔用組成物の任意成分として例示したものの中から日本薬局方等医薬品規格に適合したものを適宜選択して用いればよい。
ヒト歯肉上皮細胞を0.5×105cells/ウェルで48ウェルプレートに播種し、基本培地Humedia−KG2(クラボウ株式会社製)でコンフルエントまで培養した。その後、表1〜2に示す量(培地中濃度、質量%)の各評価物質を添加した培地で2日間培養した。添加2日後、培養上清を回収しELISAキットを用いて上清中のカテリシジン(実施例1〜6)、ディフェンシン2(実施例7)、ディフェンシン3(実施例8)、カルプロテクチン(実施例9)濃度を測定した。評価物質無添加の基本培地単独(コントロール)で培養した際の上清中のカテリシジン、ヒトβディフェンシン2、ヒトβディフェンシン3、及びカルプロテクチン濃度を100%としたときの培養後の濃度%を各抗菌ペプチドの産生促進率として算出し、以下の評点にて評価した。
+++:抗菌ペプチド産生促進率130%以上
++:抗菌ペプチド産生促進率110%以上130%未満
+:抗菌ペプチド産生促進率105%以上110%未満
−:抗菌ペプチド産生促進率105%未満
α−リポ酸:α−リポ酸−WSP7(オリザ油化株式会社製)
α−リポ酸アミド:5−(1,2−dithiolan−3−yl)pentanamide(Sigma−Aldrich製)
処方例1:チューインガム
砂糖 50.0%
ガムベース 20.0%
水飴 15.0%
グルコース 14.0%
α−リポ酸 0.5%
香料 0.5%
計 100.0%
還元水飴 40.0%
グラニュー糖 20.0%
ブドウ糖 20.0%
ゼラチン 5.0%
香料 0.5%
α−リポ酸 0.1%
色素 0.02%
水 バランス
計 100.0%
砂糖 50.0%
水飴 33.0%
有機酸 2.0%
α−リポ酸 1.0%
香料 0.5%
水 バランス
計 100.0%
砂糖 76.0%
グルコース 20.0%
ショ糖脂肪酸エステル 0.2%
α−リポ酸 0.001%
水 バランス
計 100.0%
乳糖 55.0%
結晶セルロース 25.0%
澱粉分解物 10.0%
グリセリン脂肪酸エステル 5.0%
α−リポ酸 0.002%
水 バランス
計 100.0%
ソルビット(AI=100) 30.0%
無水ケイ酸 20.0%
プロピレングリコール 3.0%
ラウリル硫酸Na 1.0%
キサンタンガム 1.0%
香料 1.0%
サッカリンNa 0.1%
α−リポ酸 0.005%
水 バランス
計 100.0%
エタノール 8.0%
グリセリン(AI=100) 5.0%
キシリトール 3.0%
プロピレングリコール 3.0%
POE(60)硬化ヒマシ油 0.5%
クエン酸Na 0.3%
香料 0.2%
クエン酸 0.1%
α−リポ酸 0.0001%
水 バランス
計 100.0%
ソルビット(70%水溶液) 40.0%
ヒドロキシエチルセルロース 3.0%
ショ糖パルミチン酸モノエステル 2.0%
カラギーナン 1.0%
酒石酸ナトリウム 1.0%
α−リポ酸 1.0%
香料 1.0%
乳酸アルミニウム 0.8%
ラウロイルサルコシンナトリウム 0.3%
サッカリンナトリウム 0.1%
塩酸又は水酸化ナトリウム 適量
水 バランス
計 100.0%
Claims (8)
- α−リポ酸又はその誘導体を含有する、ヒト抗菌ペプチド産生促進剤。
- ヒト抗菌ペプチドが、歯周病原因菌、口臭原因菌、う蝕原因菌及びカンジダ菌からなる群より選ばれる1以上の菌に対し抗菌活性を有するペプチドである請求項1記載のヒト抗菌ペプチド産生促進剤。
- ヒト抗菌ペプチドが、カテリシジン、ヒトβディフェンシン2、ヒトβディフェンシン3、及びカルプロテクチンからなる群より選ばれる少なくとも1つである、請求項1又は2に記載のヒト抗菌ペプチド産生促進剤。
- 粘膜、口腔粘膜及び歯肉からなる群より選ばれる少なくとも1つの部位におけるヒト抗菌ペプチドの産生を促進する、請求項1〜3のいずれか1項に記載のヒト抗菌ペプチド産生促進剤。
- α−リポ酸又はその誘導体を有効成分として含有する、ヒト抗菌ペプチド産生促進用口腔用組成物。
- α−リポ酸又はその誘導体を機能成分として含有する、ヒト抗菌ペプチド産生促進用飲食品組成物。
- α−リポ酸又はその誘導体を有効成分として含有するヒト抗菌ペプチド産生促進用医薬品又は医薬部外品組成物。
- α−リポ酸又はその誘導体を含有する、歯周病、口臭、う蝕及びカンジダ菌感染症から選ばれる少なくとも1つの症状のヒト抗菌ペプチド産生促進による予防又は緩和剤。
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JP2011063606A (ja) * | 2007-12-14 | 2011-03-31 | Ezaki Glico Co Ltd | α−リポ酸ナノ粒子およびその調製方法 |
JP2009242309A (ja) * | 2008-03-31 | 2009-10-22 | Ezaki Glico Co Ltd | 皮膚外用剤、口腔用組成物および飲食品 |
JP2013216604A (ja) * | 2012-04-06 | 2013-10-24 | Yokohama Yushi Kogyo Kk | α−リポ酸含有組成物 |
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CN115814106B (zh) * | 2022-12-09 | 2024-03-22 | 东南大学 | 一种高亲和性包合肽制剂及其制备方法 |
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