JP4203120B2 - 口腔内用殺菌剤、及び該殺菌剤を含有する食品添加剤 - Google Patents
口腔内用殺菌剤、及び該殺菌剤を含有する食品添加剤 Download PDFInfo
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- JP4203120B2 JP4203120B2 JP2008517664A JP2008517664A JP4203120B2 JP 4203120 B2 JP4203120 B2 JP 4203120B2 JP 2008517664 A JP2008517664 A JP 2008517664A JP 2008517664 A JP2008517664 A JP 2008517664A JP 4203120 B2 JP4203120 B2 JP 4203120B2
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Description
(1) 有効成分としてラクトパーオキシダーゼ、グルコースオキシダーゼ、グルコース、及びpH調節成分を含有する、口腔内細菌の殺菌のための口腔内用殺菌剤。
(2) pH調節成分が、有機酸及び/又は有機酸の塩類である、請求項1に記載の口腔内用殺菌剤。
(3) 有機酸が、クエン酸、乳酸、リンゴ酸、コハク酸、酒石酸、及びグルタミン酸からなる群から選択された少なくとも1種以上の酸である、(2)に記載の口腔内用殺菌剤。
(4) pH調節成分によって、pH5.9〜pH4.4の範囲のpH条件に調節される、(1)〜(3)の何れかに記載の口腔内用殺菌剤。
(5) 口腔内細菌が、アクチノバチルス・アクチノミセテムコミタンス(Actinobacillus actinomycetemcomitans)である、(1)〜(4)の何れかに記載の口腔内用殺菌剤。
(6) (1)〜(5)の何れかの口腔内用殺菌剤を含有する、食品添加剤。
(7) (1)〜(5)の何れかの口腔内用殺菌剤を含有する、歯周病、口臭症、又は誤嚥性肺炎の予防及び/又は治療用の食品添加剤。
(8) (1)〜(5)の何れかの口腔内用殺菌剤を含有する、歯周病、口臭症、又は誤嚥性肺炎の予防及び/又は治療用の医薬組成物。
(9) (1)〜(5)の何れかの口腔内用殺菌剤、又は(6)〜(7)の何れかの食品添加剤を含有する、飲食品。
(10) (1)〜(5)の何れかの口腔内用殺菌剤、又は(6)〜(7)の何れかの食品添加剤を含有する、歯周病、口臭症、又は誤嚥性肺炎の予防及び/又は治療用の飲食品。
(11) 口腔内細菌の殺菌のための口腔内用殺菌剤を製造するための、ラクトパーオキシダーゼ、グルコースオキシダーゼ、グルコース、及びpH調節成分の使用(use)。
(12) 食品添加剤を製造するための、ラクトパーオキシダーゼ、グルコースオキシダーゼ、グルコース、及びpH調節成分の使用(use)。
(13) 飲食品を製造するための、ラクトパーオキシダーゼ、グルコースオキシダーゼ、グルコース、及びpH調節成分の使用(use)。
(14) (1)〜(5)の何れかの口腔内用殺菌剤、(6)〜(7)の何れかの食品添加剤、(8)の医薬組成物、又は(9)〜(10)の飲食品の有効量を口腔内に投与することによって、歯周病、口臭症、又は誤嚥性肺炎の予防及び/又は治療をする方法(method)。
(1)口腔内細菌を効果的に殺菌することが可能である。
(2)口腔内細菌に起因する疾患の予防及び/又は治療に効果を有する。
(3)ヒトに対する安全性が高く、日常的に摂取することが可能である。
(4)飲食品に添加することによって、歯周病予防等に効果を有する飲食品を提供することができる。
以下に実施例を挙げて本発明を詳細に説明する。本発明は以下の実施例に限定されるものではない。
次に試験例を示して本発明の口腔内用殺菌剤の作用を詳細に説明する。
本試験は、口腔内細菌に対する口腔内用殺菌剤による効果を調べるために行った。
(1)試料の調製
エリスリトール(日研化学社製)15g、還元麦芽糖水飴(東和化成社製)52.5g、ソルビトール(東和化成社製)30g、コーンスターチ(王子コーンスターチ)15g、アセロラ香料(高砂香料工業社製)0.75g、ショ糖脂肪酸エステル(三菱化学フーズ社製)6g、クエン酸・一水和物(国産化学社製)2.58g、クエン酸三ナトリウム・二水和物(国産化学社製)5.21g、キシリトール(和光純薬社製)18g、グルコース(和光純薬社製)4.5g、ラクトパーオキシダーゼ(バイオポール社製)0.05g、グルコースオキシダーゼ(新日本化学工業社製)0.4g各粉末を添加して乳鉢で均一に混合した混合物を作成し、試験試料とした。また、対照試料としてラクトパーオキシダーゼのみを添加しない混合物を作成した。
アクチノバチルス・アクチノミセテムコミタンスJCM8578(理化学研究所より分譲)をブレイン・ハート・インフュージョン液体培地(BD社製)で一晩培養し、菌液を調製した。
容量50mlの滅菌ディスポーザブルチューブに試験試料又は対照試料0.5gを添加した。次に、ヒトの唾液と同じレベルの0.5mMチオシアン酸ナトリウムを含むリン酸緩衝生理食塩水3.3mlを添加して懸濁した後、33.3μlの上記菌液を添加、攪拌して15分間、37℃、10%炭酸ガスを充填したインキュベーター中で保持した。この混合液をリン酸緩衝生理食塩水で10倍ずつ段階希釈し、10%ウマ血清、0.1%酵母エキス、75μg/mlバシトラシン、5μg/mlバンコマイシンの添加によりアクチノバチルス・アクチノミセテムコミタンスを選択的に生育させるトリプチケースソイ寒天培地(ジャーナル・オブ・クリニカル・マイクロバイオロジー(Journal of Clinical Microbiology)、アメリカ、第15巻、1982年、p.606〜609)に塗布して3日間、37℃、10%炭酸ガスを充填したインキュベーター中で培養した後、寒天培地上に形成されたコロニーの数を測定した。検出されたアクチノバチルス・アクチノミセテムコミタンスのコロニー数から、上記懸濁液1ml当りの生菌数の対数値(log10 cfu/ml)を求めた。
本試験の結果を表1に示す。
本試験は、口腔内細菌に対する口腔内用殺菌剤の効果におけるpH調整剤及びグルコースの影響を調べるために行った。
(1)試料の調製
エリスリトール(日研化学社製)15g、還元麦芽糖水飴(東和化成社製)52.5g、ソルビトール(東和化成社製)30g、コーンスターチ(王子コーンスターチ)15g、アセロラ香料(高砂香料工業社製)0.75g、ショ糖脂肪酸エステル(三菱化学フーズ社製)6g、キシリトール(和光純薬社製)18g、ラクトパーオキシダーゼ(バイオポール社製)0.05g、グルコースオキシダーゼ(新日本化学工業社製)0.4g各粉末を添加して乳鉢で均一に混合し、グルコース、酸、及び塩類を含有しない混合物を作成した。
試験例1と同様の方法でアクチノバチルス・アクチノミセテムコミタンスの菌液を調製した。
容量50mlの滅菌ディスポーザブルチューブに上記のpH調整剤とグルコースを含有しない混合物0.459gを添加した。次に、3倍濃度のリン酸緩衝水溶液1.11ml、100mMクエン酸緩衝液(pH4.6、5.0、5.4、5.8、又は6.2)又は100mMリン酸緩衝液(pH6.6、7.0、又は7.4)1.0ml、50mMチオシアン酸ナトリウム33.3μlを添加し、さらに15mg/mlグルコース水溶液と精製水をグルコース終濃度0、0.045、0.15、0.45、1.5又は4.5mg/ml、合計添加液量3.3mlとなるように添加して懸濁した後、33.3μlの上記菌液を添加、攪拌して15分間、37℃、10%炭酸ガスを充填したインキュベーター中で保持した。この混合液中のアクチノバチルス・アクチノミセテムコミタンスの生菌数を試験例1と同様の方法で測定した。本試験の殺菌活性の評価基準として、生菌数が接種菌数の10分の1以下に低下した場合、有効と判定した。
本試験の結果を表2に示す。
本試験は、ヒトの口臭に対する本発明の口腔内用殺菌剤による効果を調べるために行った。
(試験試料)
実施例1の方法において、錠剤1錠当り質量を0.6gとして打錠したこと以外は、実施例1と同様の方法にて製造したタブレット(本発明の口腔内用殺菌剤)を試験試料とした。
また、前記試験試料において、ラクトパーオキシダーゼとグルコースオキシダーゼの代わりに、これらを還元麦芽糖水飴に置換したこと以外は、その他の成分については同様の組成で、実施例1と同様の方法で製造したタブレットを対照試料とした。
(試験群)
試験日の起床後、歯磨き・うがい等の歯の清掃、飲水、および飲食を禁止した健常人3名の被験者に対して、試験日の午前中に試験試料(タブレット)を1錠ずつ口腔内で溶かし、連続的に3錠服用させた(試験群)。タブレット摂取前、並びに、摂取1時間後、及び2時間後の各時点において口腔内の呼気を採取し、口臭原因物質として知られている硫化水素の変化量、および揮発性硫黄化合物の変化量(硫化水素、メチルメルカプタン、ジメチルサルファイドの総変化量)を口臭測定器(アビリット社製、オーラル・クロマ)によって測定し、被験者3名の平均値を呼気10ml当たりのng数で表示した。
また、対照試験として、前記試験日程とは別に、試験日の起床後、歯磨き・うがい等の歯の清掃、飲水、および飲食を禁止した健常人3名の被験者に対して、対照試料(タブレット:ラクトパーオキシダーゼ、グルコースオキシダーゼ不含)を前記試験群と同様の方法で3錠服用させ、口腔内の呼気を口臭測定器により測定した(対照群)。
さらに、試験群、対照群とは別の試験日程で、試験群及び対照群と同様に、試験日の起床後、歯磨き・うがい等の歯の清掃、飲水、および飲食を禁止した健常人3名の被験者に対して、タブレットを一切摂取させることなく、口腔内の呼気における硫化水素の変化量、および揮発性硫黄化合物の変化量を口臭測定器により測定した(無摂取群)。
本試験の結果を表3及び表4に示す。表3は、各群における呼気中の硫化水素の変化量を示す。また、表4は、各群における呼気中の揮発性硫黄化合物の変化量を示す。さらに、図1および図2は、表3および表4をグラフ化したものである。
表3および図1から明らかなとおり、被験者が何も摂取しない状態(無摂取群:図1の□で示す)では、1時間後に呼気中の硫化水素量は0.50ng/10mlと僅かに上昇し、さらに、2時間後には呼気中の硫化水素の変化量は3.14ng/10mlにまで達したが、本発明のタブレットを摂取(試験群:図1の●で示す)することによって、1時間後には摂取前に比べ2.54ng/10ml減少し、2時間後であっても、1時間後に比べ0.17ng/10ml増加するものの、依然として摂取前に比べ2.37ng/10mlだけ低い状態を維持していることが判明した。なお、ラクトパーオキシダーゼ、グルコースオキシダーゼ不含のタブレットを摂取した群(対照群:図1の▲で示す)において、摂取から1時間後は摂取前に比べ、一旦1.02ng/10mlだけ減少するものの、2時間後には、呼気中の硫化水素量は摂取前の状態にまで戻ってしまい、呼気中の硫化水素量を低い状態で保持する効果は確認されなかった。すなわち、試験群は、摂取1時間後において対照群と比較して約2.5倍の硫化水素の減少量を示した。さらに対照群で硫化水素の変化が増大に転じた2時間後においても、試験群ではその硫化水素の減少状態が摂取1時間後と同程度に維持されていることがわかった。
表4および図2から明らかなように、被験者が何も摂取しない状態(無摂取群:図2の□で示す)では、1時間後に呼気中の揮発性硫黄化合物の変化量は0.37ng/10mlと僅かに上昇し、さらに、2時間後には呼気中の揮発性硫黄化合物の変化量は5.30ng/10mlにまで達したが、本発明のタブレットを摂取(試験群:図2の●で示す)することによって、1時間後には摂取前に比べ3.93ng/10ml減少し、2時間後であっても、1時間後に比べ1.99ng/10ml増加するものの、依然として摂取前に比べ1.94ng/10mlだけ低い状態を維持していることが判明した。なお、ラクトパーオキシダーゼ、グルコースオキシダーゼ不含のタブレットを摂取した群(対照群:図2の▲で示す)において、摂取から1時間後は摂取前に比べ、一旦1.48ng/10mlだけ減少するものの、2時間後には、呼気中の揮発性硫黄化合物の総量は摂取前の状態にまで戻ってしまい、呼気中の揮発性硫黄化合物の総量を低い状態で保持する効果は確認されなかった。すなわち、試験群は、摂取1時間後において対照群と比較して約2.6倍の揮発性硫黄化合物の減少量を示した。さらに対照群で揮発性硫黄化合物の変化が増大に転じた2時間後においても、試験群ではその揮発性硫黄化合物の減少状態が摂取1時間後の約半分程度に維持されていることがわかった。
Claims (4)
- 有効成分としてラクトパーオキシダーゼ、グルコースオキシダーゼ、グルコース、及びpH調節成分を含有する(ただし、チオシアン酸及びその塩を添加されて含有しない)、アクチノバチルス・アクチノミセテムコミタンス(Actinobacillus actinomycetemcomitans)の殺菌のための口腔内用殺菌剤であって、
pH調節成分によって、pH5.4〜pH4.4の範囲に調節される、口腔内用殺菌剤。 - pH調節成分が、有機酸及び/又は有機酸の塩類である、請求項1に記載の口腔内用殺菌剤。
- 有機酸が、クエン酸、乳酸、リンゴ酸、コハク酸、酒石酸、及びグルタミン酸からなる群から選択された少なくとも1種以上の酸である、請求項2に記載の口腔内用殺菌剤。
- 請求項1〜3の何れかの口腔内用殺菌剤を含有する、歯周病、口臭症、又は誤嚥性肺炎の予防及び/又は治療用の医薬組成物。
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JP6165077B2 (ja) * | 2014-02-10 | 2017-07-19 | 森永乳業株式会社 | 含硫アミノ酸リアーゼ阻害剤 |
GB201417386D0 (en) | 2014-10-01 | 2014-11-12 | Nofima As | Sugar-depleted fruit or vegetable juice product, method of producing the same and use thereof to maintain health and treat and to prevent medical ailments |
WO2017033616A1 (ja) * | 2015-08-21 | 2017-03-02 | 森永乳業株式会社 | 上気道保護剤及び上気道保護用飲食品組成物 |
JP6811541B2 (ja) * | 2016-03-24 | 2021-01-13 | 株式会社明治 | 口臭抑制用組成物 |
EP3445387A4 (en) * | 2016-04-21 | 2019-12-11 | Quantec Limited | COMBINATION, THERAPEUTIC USES AND PROPHYLACTIC USES |
US20210128439A1 (en) * | 2017-08-03 | 2021-05-06 | Morinaga Milk Industry Co., Ltd. | Edible Film |
WO2019136168A1 (en) * | 2018-01-03 | 2019-07-11 | Penn State Research Foundation | Glucose oxidase compositions as a neonate anticonvulsant |
CN111885996A (zh) * | 2018-03-23 | 2020-11-03 | 森永乳业株式会社 | 臭味成分失活用组合物 |
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US5176899A (en) * | 1991-11-25 | 1993-01-05 | Montgomery Robert E | Antimicrobial dentifrice |
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US20120177624A1 (en) | 2012-07-12 |
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