JP5710111B2 - ラクチトール、マルチトールからなる抗菌剤 - Google Patents
ラクチトール、マルチトールからなる抗菌剤 Download PDFInfo
- Publication number
- JP5710111B2 JP5710111B2 JP2009165554A JP2009165554A JP5710111B2 JP 5710111 B2 JP5710111 B2 JP 5710111B2 JP 2009165554 A JP2009165554 A JP 2009165554A JP 2009165554 A JP2009165554 A JP 2009165554A JP 5710111 B2 JP5710111 B2 JP 5710111B2
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- Prior art keywords
- maltitol
- growth
- lactitol
- sugar alcohol
- antibacterial
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- 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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- 235000010449 maltitol Nutrition 0.000 title claims description 27
- 229940035436 maltitol Drugs 0.000 title claims description 27
- 239000000832 lactitol Substances 0.000 title claims description 22
- 235000010448 lactitol Nutrition 0.000 title claims description 22
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 title claims description 22
- 229960003451 lactitol Drugs 0.000 title claims description 22
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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- 239000008101 lactose Substances 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
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- 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
- A61K8/60—Sugars; Derivatives thereof
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明では、特に歯周病の原因である歯周病原菌に関する新たな糖アルコールの有用性に注目し、糖アルコールの抗菌性及び歯周病原菌増殖抑制の評価を行った。
糖アルコールの抗菌性試験を以下のように行った。
1−1. 被験試料の調製方法
2%エタノールを用いて、キシリトール、エリスリトール、ラクチトール、マルチトールについては最終培地濃度が8%、チモールについては最終培地濃度が800ppm、塩化亜鉛については最終培地濃度が200ppmとなるようそれぞれ調製し、2%エタノールにより2倍希釈系列を作製した。
歯周病原菌としてPorphyromonas gingivalis ATCC33277株(以後P.gingivalisと略す)、Fusobacterium nucleatum ATCC25586株(以後F.nucleatumと略す)、Prevotella intermedia ATCC25611株(以後P.intermediaと略す)、Prevotella nigrescens JCM6322株(以後P.nigrescensと略す)、Treponema denticola ATCC35405株(以後T.denticolaと略す)、Tannerella forsythia JCM10827株(以後T.forsythiaと略す)を用いた。また、舌苔局在菌のなかで、舌苔における割合が高い口腔内細菌として、Prevotella melaninogenica JCM6325株(以後P.melaninogenicaと略す)、Veillonella parvula JCM12972株(以後V.parvulaと略す)、Veillonella dispar ATCC17748株(以後V.disparと略す)を用いた。
P.gingivalis、F.nucleatum、P.intermedia、P.nigrescens、P.melaninogenicaはYeast extract(3.0g/l)、Hemin (5.0mg/l)、Menadione(0.5mg/l)を添加したTripticase soy brothを用いて、37℃の嫌気条件下(10%CO2、10%H2、80%N2)で培養した。V.parvula、 V.disparはTrypticase(5.0g/l)、Yeast Extract(3.0g/l)、Sodium lactate(9.0g/l)、Sodium thioglycollate(0.75g/l)、Tween80(1.0g/l)、Glucose (1.0g/l)を加えた培地をK2CO2でpH7.5に調製し、同様の条件で培養した。T.forsythiaはYeast extract(5.0g/l)、Hemin(5.0mg/l)、Menadione(0.5mg/l)を添加したBrain heart infusion brothを120℃、15分滅菌処理した後、L-cysteine(1.0g/l)、N-acetylneuraminic acid(10.0mg/l)、Fetal Bovine Serum(50ml/l)を添加した培地を用いて同条件で培養した。T.denticolaはTYGVS培地を用いて同様の条件で培養した。
抗菌性試験は2倍希釈系列で希釈を行った液体希釈法を用いた。すなわち、2倍希釈系列を行った被験試料液を96穴プレートに加え (各穴の液量は100μl)、前記1−3の培地で培養した菌液を同一の培地に5%以下の濃度で希釈・混和し、これを96穴プレート上に100μl添加した。尚、菌液を含まない100μlの培地のみを添加したものをコントロールとし、24〜48時間の嫌気培養(10%CO2、10%H2、80%N2)を行い、分光光度計にてOD660値を測定した。コントロールと比較してOD660値が同程度のもの、かつ肉眼で菌の発育が認められない濃度を最小発育阻止濃度(以後MICと略す)とした。
各種糖アルコールの口臭原因菌に対する抗菌活性を確認する目的で抗菌試験を行った。各試験菌株のMICを表1に示す。全ての被験試料はP.nigrescens、P. melaninogenica、V.parvula、T.forsythiaに対し、8%以下(チモールは800ppm以下)の濃度で抗菌性を示さなかった。T.denticolaに対してはチモールで抗菌性が得られなかったものの、試験に用いた4種全ての糖アルコールで8%のMICが確認された。逆にV.disparに対してはチモールで400ppmのMICが示されたものの、糖アルコールに抗菌性は認められなかった。また、P.gingivalisに対しては塩化亜鉛の25ppm、チモールの200ppmと比較して活性は弱いものの、全ての糖アルコールで弱い抗菌性が確認された。弱い抗菌性とは完全に菌の増殖を抑制していないものの、他の濃度の半分程度のOD660値を示し、肉眼で菌の発育が若干認められる状態を指す。尚、塩化亜鉛はP.gingivalisに対してのみ抗菌試験を行った。F.nucleatumに対してはチモールの200ppmと比較して活性は弱いものの、キシリトール、エリスリトールが8%のMICを示した。P.intermediaに対してはチモールで抗菌性が確認されなかったものの、エリスリトールが8%のMICを示した。
糖アルコール濃度:0.0078%〜8%
チモール濃度:0.78ppm〜800ppm
塩化亜鉛濃度:0.195ppm〜200ppm
糖アルコールの増殖抑制試験を以下のように行った。
2−1. 被験試料の調製方法
キシリトール、エリスリトール、ラクチトール、マルチトールについて最終培地濃度が5%または10%となるよう調製した。
菌株としては、実施例1の供試菌株に記載のF.nucleatumとP.gingivalisを用いた。
P.gingivalis、F.nucleatum共にYeast extract(3.0g/l)、Hemin(5.0mg/l)、Menadione(0.5mg/l)を添加したTripticase soy brothを用いて、37℃の嫌気条件下(10%CO2、10%H2、80%N2)で培養した。増殖曲線測定時は上記培地に最終濃度5%または10%となるよう糖アルコールを添加、溶解後、120℃、15分滅菌処理したものを用いた。
前記2−3の培地で対数増殖期まで培養した菌液を、5%または10%の各糖アルコールを含む培地20mlに100μl添加した。尚、糖アルコールを含まない通常の培地20mlに菌液100μlを添加したものをコントロールとした。40〜47時間の嫌気培養(10%CO2、10%H2、80%N2)を行い、その間、分光光度計にてOD660値を適時測定した。
抗菌試験において、P.gingivalis、 F.nucleatum等4菌株に対して抗菌活性が認められたことから、糖アルコールがこれら菌株に対して増殖を抑制する可能性が示唆された。この可能性を確認する目的で、糖アルコールを含有した培地におけるP.gingivalis、 F.nucleatumの増殖曲線の測定を行った。F.nucleatumの増殖曲線を図1A、1B、1C及び1Dに、P.gingivalisの増殖曲線を図2A、2B、2C及び2Dに示す。なお、各糖アルコールについて、n=2(図中では1、2と表記)で試験を行い、コントロールは糖アルコール無添加培地を示す。
下記処方に従って含そう剤を製造した。
エタノール 2.0重量%
ラクチトール 10.0
香料 1.0
水 残
100.0
下記処方に従って練り歯磨きを製造した。
炭酸カルシウム 40.0重量%
グリセリン 10.0
マルチトール 20.0
カルボオキシメチルセルロース 2.0
ラルリル硫酸ナトリウム 2.0
香料 1.0
サッカリン 0.1
クロルヘキシジン 0.01
水 残
100.0
下記処方に従って口臭用スプレーを製造した。
エタノール 10.0重量%
グリセリン 5.0
ラクチトール 10.0
マルチトール 10.0
香料 0.05
着色料 0.001
水 残
100.0
下記処方に従ってトローチを製造した。
マルチトール 72.3重量%
キシリトール 20.0
アラビアガム 6.0
香料 1.0
モノフルオロリン酸ナトリウム 0.7
100.0
下記処方に従ってチューインガムを製造した。
ガムベース 20.0重量%
マルチトール 45.0
ラクチトール 33.0
香料 2.0
100.0
下記処方に従ってキャンディを製造した。
マルチトール 50.0重量%
還元水あめ 34.0
クエン酸 2.0
香料 0.2
水 残
100.0
下記処方に従って錠菓を製造した。
マルチトール 76.1重量%
ラクチトール 19.0
ショ糖脂肪酸エステル 0.2
香料 0.2
水 4.5
100.0
下記処方に従ってグミゼリーを製造した。
ゼラチン 60.0重量%
還元水あめ 21.40
マルチトール 11.5
植物油脂 4.5
リンゴ酸 2.0
香料 0.5
100.0
下記処方に従って飲料を製造した。
オレンジ果汁 30.0重量%
ラクチトール 15.0
クエン酸 0.1
ビタミンC 0.04
香料 0.1
水 残
100.0
Claims (1)
- 5%〜10%の濃度のラクチトールまたはマルチトールを有効成分とするPorphyromonas gingivalisの増殖抑制抗菌剤。
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PCT/JP2010/004530 WO2011007551A1 (ja) | 2009-07-14 | 2010-07-13 | 糖アルコールを含む歯周病原菌増殖抑制抗菌剤 |
CN2010800297408A CN102470113A (zh) | 2009-07-14 | 2010-07-13 | 包含糖醇的牙周病原菌增殖抑制抗菌剂 |
KR1020127003725A KR20120042968A (ko) | 2009-07-14 | 2010-07-13 | 당 알코올을 포함하는 치주병원균 증식 억제 항균제 |
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