JP2022162035A - Composition for preventing or treating oral disease - Google Patents
Composition for preventing or treating oral disease Download PDFInfo
- Publication number
- JP2022162035A JP2022162035A JP2022132596A JP2022132596A JP2022162035A JP 2022162035 A JP2022162035 A JP 2022162035A JP 2022132596 A JP2022132596 A JP 2022132596A JP 2022132596 A JP2022132596 A JP 2022132596A JP 2022162035 A JP2022162035 A JP 2022162035A
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- oral
- quasi
- present
- composition
- preventing
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Links
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Abstract
Description
本発明は、天然化合物を有効成分として含む、口腔疾患の予防又は治療用組成物に関し、より詳細には、う蝕、歯周疾患、歯痛、知覚過敏、口臭を予防又は改善する効果を有する医薬部外品組成物に関する。また、本発明は、天然化合物を有効成分として含む薬学的組成物、食品組成物及び口腔用組成物に関する。 TECHNICAL FIELD The present invention relates to a composition for preventing or treating oral diseases, which contains a natural compound as an active ingredient, and more particularly, a medicament having an effect of preventing or improving dental caries, periodontal disease, toothache, hypersensitivity, and halitosis. It relates to quasi-product compositions. The present invention also relates to pharmaceutical compositions, food compositions and oral compositions containing natural compounds as active ingredients.
健康な歯は五福の一つと言われるほどに生活の質を決定する重要な要素である。口腔疾患のうちう蝕(dental cavities, 虫歯)と歯周疾患(periodontal disease, 歯周病)は、世界的に発症率の高い疾患であり、痛み、咀嚼機能障害、歯周組織の破壊、口臭、知覚過敏などの様々な臨床症状を誘発し、歯牙喪失を招く主な要因として知られており、食生活の変化により口腔疾患の原因要素がさらに増加している現状である。 Healthy teeth are said to be one of the five good fortunes, and are an important factor that determines the quality of life. Among oral diseases, dental cavities (cavities) and periodontal disease (periodontal disease) are diseases with a high incidence rate worldwide, and cause pain, masticatory dysfunction, destruction of periodontal tissue, and bad breath. It is known to induce various clinical symptoms such as hyperesthesia, hyperesthesia, etc., and to be a major factor leading to tooth loss.
ヒトの口腔には約600~800種以上の微生物が存在することが知られており、これらの微生物は唾液に含まれるリゾチーム(lysozyme)などの酵素により制御されている。しかし、栄養分と水分が豊富な口腔環境は微生物が成長しやすい条件を有し、舌や歯垢(dental plaque)は微生物の好適な生息場所となる。このような微生物の一部は日和見病原菌であり、う蝕、歯周疾患、知覚過敏(象牙質知覚過敏症)などの疾患及び口臭の原因となる。 About 600 to 800 or more kinds of microorganisms are known to exist in the human oral cavity, and these microorganisms are controlled by enzymes such as lysozyme contained in saliva. However, an oral environment rich in nutrients and moisture provides favorable conditions for the growth of microorganisms, and the tongue and dental plaque are suitable habitats for microorganisms. Some of these microorganisms are opportunistic pathogens and cause diseases such as dental caries, periodontal disease, hypersensitivity (dentin hypersensitivity), and halitosis.
歯垢内に生息してう蝕、歯周疾患、口臭及び知覚過敏を誘発する口腔病原菌の増殖を抑制する方法として抗菌剤の使用があり、口腔病原菌に対する殺菌及び静菌作用を有する抗生剤を含む各種抗菌製剤が虫歯、歯周疾患、歯髄及び歯根端感染の抑制及び治療剤として開発されている。 Antibacterial agents are used as a method of suppressing the growth of oral pathogens that live in dental plaque and cause caries, periodontal disease, bad breath, and hypersensitivity. Various antibacterial preparations, including antibacterial preparations, have been developed as inhibitors and therapeutic agents for dental caries, periodontal disease, pulpal and root-tip infections.
しかし、抗生剤は、人体における全身的な副作用と共に口腔内の耐性菌の出現及び菌交代症(superinfection)を誘発するので、長期的な使用が困難であり、単に治療剤としてのみ用いられるという欠点がある。また、口腔洗浄に用いられる抗菌製剤としては、サンギナリン(Sanguinarine)、リステリン(Listerine)、ペルオキシド(Peroxide)、クロルヘキシジン(Chlorhexidine)などが挙げられるが、サンギナリンは、口腔内での細菌に対する効果が不明であり、歯周疾患に対する治療効果も不明であるだけでなく、価格も高いという欠点があり、リステリンは、アルコールが主成分であるので僅かな静菌作用があるが、実際の口腔内では一時的な効果を発揮するだけで、長期間使用すると組織に危害を及ぼすという欠点がある。さらに、近年、美白効果のために添加されているペルオキシドは、細菌に対する毒性があるが、それと同時に人体の組織にも毒性を示すので、安全性に問題があるだけでなく、時には細菌においてペルオキシドに対する耐性菌が出現することもある。さらに、クロルヘキシジンは、歯垢形成の抑制と共に歯周疾患の予防及び治療剤として従来の製剤のうち最も優れていることが知られているが、組織に対する刺激、組織の着色及び変性を誘発し、特に刺激的な味や匂いが強いという問題があるだけでなく、菌交代症を誘発することがあり、発癌性があるので、妊娠婦においては使用が制限されるなど、治療や予防の目的で長期間用いることができないという欠点がある。 However, antibiotics cause systemic side effects in the human body, as well as the emergence of resistant bacteria and superinfection in the oral cavity, so they are difficult to use for a long time and are used only as therapeutic agents. There is Sanguinarine, Listerine, Peroxide, and Chlorhexidine are examples of antibacterial preparations used for mouthwash, but the effect of Sanguinarine on bacteria in the oral cavity is unknown. However, its therapeutic effect on periodontal disease is not only unknown, but it is also expensive. However, it has the drawback of causing tissue harm if used for a long period of time. Furthermore, in recent years, peroxides that have been added for whitening effect are toxic to bacteria, but at the same time they are toxic to human tissues, so not only are there safety problems, Some resistant strains may emerge. Furthermore, chlorhexidine is known to be the most excellent agent among conventional preparations as a preventive and therapeutic agent for periodontal disease as well as for suppressing plaque formation, but it induces tissue irritation, tissue discoloration and degeneration, Not only does it have the problem of having a particularly pungent taste and strong odor, but it can also induce bacterial superstition and is carcinogenic, so its use is restricted to pregnant women. It has the disadvantage that it cannot be used for a long period of time.
さらに、化学反応により人為的に合成された化合物は、細胞毒性を示したり、人体に蓄積されるなどの副作用が発生することがあるので、安全性の面から、副作用が発生する可能性の低い天然化合物の薬理活性についての研究が求められている。 Furthermore, compounds artificially synthesized through chemical reactions may show cytotoxicity or cause side effects such as accumulation in the human body. There is a need for research into the pharmacological activity of natural compounds.
本発明者らは、このような副作用に対する恐れがなく、う蝕、歯周疾患、歯痛、知覚過敏、口臭などの口腔疾患の予防及び改善効果に優れる天然素材を見出すために研究を重ねてきた。その結果、人体に安全で安心して用いることのできる天然化合物がう蝕及び歯周疾患誘発細菌に対する抗菌効果、PGE2抑制効果による歯痛緩和効果、歯肉炎発症抑制効果、知覚過敏抑制効果及び口臭除去効果を発揮することを解明し、それを活用した医薬部外品組成物、薬学的組成物、食品組成物及び口腔用組成物を完成するに至った。 The present inventors have conducted extensive research to find natural materials that are free from such side effects and have excellent preventive and ameliorative effects on oral diseases such as dental caries, periodontal disease, toothache, hyperesthesia, and bad breath. . As a result, natural compounds that can be used safely and securely in the human body have an antibacterial effect against caries and periodontal disease-causing bacteria, an effect of alleviating toothache by suppressing PGE2, an effect of suppressing the onset of gingivitis, an effect of suppressing hypersensitivity, and an effect of removing halitosis. and completed quasi-drug compositions, pharmaceutical compositions, food compositions and oral compositions utilizing it.
本発明は、天然化合物又はその薬学的に許容される塩を有効成分として含む、口腔疾患の予防又は改善用医薬部外品組成物を提供することを目的とする。 An object of the present invention is to provide a quasi-drug composition for preventing or improving oral diseases, containing a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
また、本発明は、天然化合物又はその薬学的に許容される塩を有効成分として含む、口腔疾患の予防又は治療用薬学的組成物を提供することを目的とする。 Another object of the present invention is to provide a pharmaceutical composition for preventing or treating oral diseases, which contains a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
さらに、本発明は、天然化合物又はその食品学的に許容される塩を有効成分として含む、口腔疾患の予防又は改善用食品組成物を提供することを目的とする。 A further object of the present invention is to provide a food composition for preventing or improving oral diseases, containing a natural compound or a food-acceptable salt thereof as an active ingredient.
さらに、本発明は、天然化合物又はその許容される塩を有効成分として含む、口腔用組成物を提供することを目的とする。 A further object of the present invention is to provide an oral composition containing a natural compound or an acceptable salt thereof as an active ingredient.
本発明の天然化合物又はその薬学的に許容される塩を有効成分として含む医薬部外品組成物は、口腔疾患の予防又は改善効果に優れる。具体的には、本発明の組成物は、う蝕及び歯周疾患誘発細菌に対する抗菌活性に優れ、痛み及び炎症マーカーであるPGE2を濃度依存的に抑制し、歯肉炎発症抑制効果、知覚過敏症状抑制効果及び口臭除去効果に優れ、う蝕、歯周疾患、知覚過敏及び口臭からなる群から選択される少なくとも1つの口腔疾患の予防又は改善用医薬部外品組成物としての活用度が高い。また、本発明の天然化合物を含む組成物は、薬学的組成物及び食品組成物として有用である。 A quasi-drug composition containing the natural compound of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient is excellent in preventing or improving oral disease. Specifically, the composition of the present invention has excellent antibacterial activity against caries- and periodontal-disease-inducing bacteria, inhibits pain and inflammation marker PGE2 in a concentration-dependent manner, inhibits the onset of gingivitis, and hyperesthesia symptoms. It has excellent inhibitory effect and bad breath removing effect, and is highly utilized as a quasi-drug composition for preventing or improving at least one oral disease selected from the group consisting of dental caries, periodontal disease, hypersensitivity and bad breath. Compositions containing the natural compounds of the present invention are also useful as pharmaceutical and food compositions.
本発明の一態様は、前記課題を解決し、前記目的を達成するために、天然化合物又はその薬学的に許容される塩を有効成分として含む、口腔疾患の予防又は改善用医薬部外品組成物を提供する。 In order to solve the above problems and achieve the above objects, one aspect of the present invention provides a quasi-drug composition for preventing or improving oral diseases, comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. offer things.
本発明の他の態様は、天然化合物又はその薬学的に許容される塩を有効成分として含む、口腔疾患の予防又は治療用薬学的組成物を提供する。 Another aspect of the present invention provides a pharmaceutical composition for preventing or treating oral diseases, comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
本発明のさらに他の態様は、天然化合物又はその食品学的に許容される塩を有効成分として含む、口腔疾患の予防又は改善用食品組成物を提供する。 Yet another aspect of the present invention provides a food composition for preventing or improving oral diseases, containing a natural compound or a food-acceptable salt thereof as an active ingredient.
本発明のさらに他の態様は、天然化合物又はその許容される塩を有効成分として含む、口腔用組成物を提供する。 Yet another aspect of the present invention provides an oral composition comprising a natural compound or an acceptable salt thereof as an active ingredient.
本発明においては、天然化合物又はその薬学的に許容される塩を有効成分として含む医薬部外品組成物を提供する。 The present invention provides a quasi-drug composition containing a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
前記「天然化合物」とは、微生物、植物、動物などの生物から直接作製され、それから抽出、分離又は精製できる物質を意味し、前記天然化合物の具体例として、アルビフロリン(Albiflorin)、アストラガロシドI(Astragaloside I)、ブラシノリド(Brassinolide)、エレウテロシドE(Eleutheroside E)、ゲンチオピクリン(Gentiopicrin)、グラミン(Gramine)、リエンシニン(Liensinine)、マクラントイジンB(Macranthoidin B)、ネオヘスペリジンジヒドロカルコン(Neohesperidin dihydrochalcone)、オバクノン(Obacunone)、オキシソホカルピン(Oxysophocarpine)、スクラレオリド(Sclareolide)、ソホリコシド(Sophoricoside)、スウェロシド(Sweroside)、シネフリン(Synephrine)などが挙げられるが、これらに限定されるものではない。 The "natural compound" means a substance that is directly produced from living organisms such as microorganisms, plants, and animals and can be extracted, separated, or purified therefrom. Specific examples of the natural compound include albiflorin and astragaloside. Astragaloside I, Brassinolide, Eleutheroside E, Gentiopicrin, Gramine, Liensinine, Macranthoidin B, Neohesperidin Dihydrochalcone dihydrochalcone, Obacunone, Oxysophocarpine, Sclareolide, Sophoricoside, Sweroside, Synephrine, etc., but not limited thereto.
本発明における前記アルビフロリン(Albiflorin)は、化学式1で表され、分子式C23H28O11、分子量408.4を有する有機化合物である。 Albiflorin in the present invention is an organic compound represented by Chemical Formula 1 , having a molecular formula of C23H28O11 and a molecular weight of 408.4 .
本発明における前記アストラガロシドI(Astragaloside I)は、化学式2で表され、分子式C45H72O16、分子量869.0を有する有機化合物である。 The Astragaloside I in the present invention is an organic compound represented by Chemical Formula 2 and having a molecular formula of C 45 H 72 O 16 and a molecular weight of 869.0.
本発明における前記ブラシノリド(Brassinolide)は、化学式3で表され、分子式C28H48O6、分子量480.6を有する有機化合物である。 The brassinolide in the present invention is an organic compound represented by Chemical Formula 3 and having a molecular formula of C 28 H 48 O 6 and a molecular weight of 480.6.
本発明における前記エレウテロシドE(Eleutheroside E)は、化学式4で表され、分子式C34H46O18、分子量742.7を有する有機化合物である。 The eleutheroside E in the present invention is an organic compound represented by Chemical Formula 4 and having a molecular formula of C 34 H 46 O 18 and a molecular weight of 742.7.
本発明における前記ゲンチオピクリン(Gentiopicrin)は、化学式5で表され、分子式C16H20O9、分子量356.3を有する有機化合物である。 The gentiopicrin in the present invention is an organic compound represented by Chemical Formula 5 and having a molecular formula of C 16 H 20 O 9 and a molecular weight of 356.3.
本発明における前記グラミン(Gramine)は、化学式6で表され、分子式C11H14N2、分子量174を有する有機化合物である。 The gramine in the present invention is an organic compound represented by Chemical Formula 6 and having a molecular formula of C 11 H 14 N 2 and a molecular weight of 174.
本発明における前記リエンシニン(Liensinine)は、化学式7で表され、分子式C37H42N2O6、分子量610.7を有する有機化合物である。 Liensinine in the present invention is an organic compound represented by Chemical Formula 7 and having a molecular formula of C37H42N2O6 and a molecular weight of 610.7 .
本発明における前記マクラントイジンB(Macranthoidin B)は、化学式8で表され、分子式C65H106O32、分子量1399.5を有する有機化合物である。 The Macranthoidin B in the present invention is an organic compound represented by Chemical Formula 8 and having a molecular formula of C 65 H 106 O 32 and a molecular weight of 1399.5.
本発明における前記ネオヘスペリジンジヒドロカルコン(Neohesperidin dihydrochalcone)は、化学式9で表され、分子式C28H36O15、分子量612.5を有する有機化合物である。 The neohesperidin dihydrochalcone in the present invention is an organic compound represented by Chemical Formula 9 and having a molecular formula of C28H36O15 and a molecular weight of 612.5 .
本発明における前記オバクノン(Obacunone)は、化学式10で表され、分子式C25H30O7、分子量455を有する有機化合物である。 Obacunone in the present invention is an organic compound represented by Chemical Formula 10 and having a molecular formula of C 25 H 30 O 7 and a molecular weight of 455.
本発明における前記オキシソホカルピン(Oxysophocarpine)は、化学式11で表され、分子式C15H22N2O2、分子量262.4を有する有機化合物である。 The Oxysophocarpine in the present invention is an organic compound represented by Chemical Formula 11 , having a molecular formula of C15H22N2O2 and a molecular weight of 262.4 .
本発明における前記スクラレオリド(Sclareolide)は、化学式12で表され、分子式C16H26O2、分子量250.3を有する有機化合物である。 The sclareolide in the present invention is an organic compound represented by Chemical Formula 12, having a molecular formula of C 16 H 26 O 2 and a molecular weight of 250.3.
本発明における前記ソホリコシド(Sophoricoside)は、化学式13で表され、分子式C21H20O10、分子量432を有する有機化合物である。 The sophoricoside in the present invention is an organic compound represented by Chemical Formula 13, having a molecular formula of C 21 H 20 O 10 and a molecular weight of 432.
本発明における前記スウェロシド(Sweroside)は、化学式14で表され、分子式C16H22O9、分子量358.3を有する有機化合物である。 The sweroside in the present invention is an organic compound represented by Chemical Formula 14 and having a molecular formula of C16H22O9 and a molecular weight of 358.3 .
本発明における前記シネフリン(Synephrine)は、化学式15で表され、分子式C9H13NO2、分子量167.2を有する有機化合物である。 The synephrine in the present invention is an organic compound represented by Chemical Formula 15, having a molecular formula of C 9 H 13 NO 2 and a molecular weight of 167.2.
本発明における前記化合物の取得方法は、特に限定されるものではなく、当該技術分野で公知の方法で化学的に合成してもよく、市販の物質を用いてもよい。 The method for obtaining the compound in the present invention is not particularly limited, and it may be chemically synthesized by a method known in the art, or a commercially available substance may be used.
本発明の前記化合物は、溶媒和の形態だけでなく、非溶媒和(unsolvated)の形態で存在してもよい。本発明の前記化合物は、結晶又は無定形の形態で存在してもよく、これら全ての物理的形態が本発明に含まれる。 The compounds of the invention may exist in unsolvated as well as solvated forms. The compounds of the invention may exist in crystalline or amorphous forms, and all these physical forms are included in the invention.
本発明の一態様は、前記天然化合物又はその薬学的に許容される塩を有効成分として含む、口腔疾患の予防又は改善用医薬部外品組成物を提供する。 One aspect of the present invention provides a quasi-drug composition for preventing or improving oral diseases, comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
また、具体的には、本発明は、前記天然化合物又はその薬学的に許容される塩を有効成分として含む、う蝕、歯周疾患(歯周炎又は歯肉炎)、歯痛、知覚過敏及び口臭からなる群から選択される少なくとも1つの口腔疾患の予防又は改善用医薬部外品組成物を提供する。 More specifically, the present invention provides dental caries, periodontal disease (periodontitis or gingivitis), toothache, hyperesthesia and halitosis, which contain the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. Provided is at least one quasi-drug composition for preventing or improving oral diseases selected from the group consisting of:
前記「天然化合物」については前述した通りである。 The "natural compound" is as described above.
本発明における「口腔疾患」とは、口腔領域において発生する様々な疾患を意味し、前記口腔領域とは、前方の唇から後方の口峡において咽頭に連結される口の中の空間を意味する。本発明における前記口腔疾患は、口腔に発生する疾患であればその病症に関係なく全て含まれる概念であり、前記口腔疾患としては、例えばう蝕、歯周疾患(歯周炎又は歯肉炎)、歯痛、知覚過敏、口臭などが挙げられるが、これらに限定されるものではない。 The term "oral disease" in the present invention refers to various diseases that occur in the oral cavity, and the oral cavity refers to the space in the mouth that is connected to the pharynx from the anterior lip to the posterior isthmus. . The oral disease in the present invention is a concept that includes all diseases occurring in the oral cavity regardless of the disease, and examples of the oral disease include caries, periodontal disease (periodontitis or gingivitis), Examples include, but are not limited to, toothache, hypersensitivity, bad breath, and the like.
本発明における「う蝕(dental cavities)」とは、歯面に生息する細菌による感染性疾患であり、虫歯ともいい、歯の硬組織が侵食されて欠損する症状を示す。具体的には、歯の上部表面を覆い、象牙質を保護する乳白色の半透明で硬い物質を琺瑯質又はエナメル質というが、口の中に生息する口腔病原菌により砂糖、デンプンなどが分解されて酸が生成され、それにより歯の琺瑯質が損傷して虫歯が生じることを意味する。う蝕が生じる主な原因としては、歯の表面に生成された細菌膜である歯垢(dental plaque, プラーク)が挙げられるが、唾液が歯に粘りのある薄膜を形成し、その上に連鎖状球菌の一種であるストレプトコッカス・ソブリヌス(Streptococcus sobrinus)菌、ストレプトコッカス・ミュータンス(Streptococcus mutans)などの口腔微生物が付着してバイオフィルム(biofilm)を形成することにより歯垢(dental plaque, プラーク)が生成され、フソバクテリウム(Fusobacterium)によりさらに厚くなる。本発明におけるう蝕の原因菌は、う蝕を引き起こす原因菌であればその種類に関係なく全て含まれ、具体的にはストレプトコッカス・ミュータンス(Streptococcus mutans)、ストレプトコッカス・サングイニス(Streptococcus sanguinis)、ストレプトコッカス・ソブリヌス(Streptococcus sobrinus)、ストレプトコッカス・ラッティ(Streptococcus ratti)、ストレプトコッカス・クリセティ(Streptococcus criceti)、ストレプトコッカス・アンギノサス(Streptococcus anginosus)及び乳酸菌からなる群から選択される少なくとも1種の菌であり、より具体的にはストレプトコッカス・ミュータンスである。 The term "dental cavities" as used in the present invention is an infectious disease caused by bacteria living on tooth surfaces, and is also called tooth decay. Specifically, enamel or enamel is a translucent milky-white hard substance that covers the upper surface of teeth and protects dentin. is produced, which damages the enamel of the tooth and causes caries. The main cause of dental caries is dental plaque, which is a film of bacteria formed on the surface of teeth. Oral microorganisms such as Streptococcus sobrinus and Streptococcus mutans, which are types of Morphoidococcus, adhere to form a biofilm, resulting in dental plaque. Produced and further thickened by Fusobacterium. The caries-causing bacteria in the present invention include all caries-causing bacteria regardless of their types, specifically Streptococcus mutans, Streptococcus sanguinis, and Streptococcus. - At least one bacterium selected from the group consisting of Streptococcus sobrinus, Streptococcus ratti, Streptococcus criceti, Streptococcus anginosus and lactic acid bacteria, more specifically is Streptococcus mutans.
前記ストレプトコッカス・ミュータンスは、連鎖状球菌の一種でグラム陽性菌であり、虫歯菌とも呼ばれる。前記ストレプトコッカス・ミュータンスは、歯の表面でのみ増殖するが、生後30カ月前後までは乳歯が完成していない。よって、この時期までは、幼児期以降のようなミュータンス菌の増殖は困難である。幼児期に大人の口からミュータンス菌が感染することなく、口の中に他の口腔細菌が定着すると、既にバランスが取れている口腔内の生態系にミュータンス菌が新たに侵入することは困難であり、幼児期以降、一生を通じて虫歯にかかる確率が大幅に低くなる。既に大人の口から原因菌に感染した場合は、歯磨きを頻繁に行い、口の中を清潔に維持することが虫歯の予防に役立つ。しかし、一度ミュータンス菌が口腔内に定着すると、ミュータンス菌の撲滅は不可能である。 The Streptococcus mutans is a type of streptococcus and is a gram-positive bacterium, and is also called a cariogenic bacterium. The Streptococcus mutans proliferates only on the surface of teeth, but milk teeth are not completed until around 30 months after birth. Therefore, until this stage, it is difficult to propagate Streptococcus mutans, as it was after infancy. If Streptococcus mutans does not infect the adult's mouth during childhood and other oral bacteria colonize the mouth, it is unlikely that Streptococcus mutans will newly invade the already balanced oral ecosystem. It is difficult, and after infancy, the probability of developing tooth decay is greatly reduced for the rest of one's life. If you have already been infected with the causative bacteria from the mouth of an adult, frequent tooth brushing and keeping your mouth clean can help prevent tooth decay. However, once Streptococcus mutans colonizes the oral cavity, eradication of Streptococcus mutans is impossible.
本発明の一実施例において、ストレプトコッカス・ミュータンスを塗抹した培地に本発明の前記天然化合物を含むディスクを接種し、その後生育阻止円の大きさを測定した結果、前記化合物を含む実験群の生育阻止円の直径が10.0mm以上であり、ストレプトコッカス・ミュータンスに対して非常に優れた抗菌活性を示したので、前記天然化合物を含む組成物はう蝕の予防又は改善用途に有用であることが確認された(表2)。 In one embodiment of the present invention, a medium smeared with Streptococcus mutans was inoculated with a disc containing the natural compound of the present invention, and then the size of the growth inhibition circle was measured. The diameter of the circle of inhibition is 10.0 mm or more, and the composition containing the natural compound is useful for caries prevention or amelioration because it exhibits excellent antibacterial activity against Streptococcus mutans. was confirmed (Table 2).
本発明における「歯周疾患(periodontal disease)」とは、歯を支えている歯肉、歯周靱帯及び骨組織に炎症が生じる疾患であり、一般に歯周病ともいい、疾患の程度によって歯肉炎(gingivitis)と歯周炎(periodontitis)に分けられる。比較的軽く、回復が速い状態の歯周疾患であって、歯茎、すなわち軟組織に限定される状態を歯肉炎といい、その炎症が歯茎と歯槽骨の周辺まで進んだものを歯周炎という。歯肉(歯茎)と歯の間にはV字状の間隙があるが、その溝(sulcus)の歯茎線の下側を口腔病原菌が攻撃すると、炎症刺激源であるリポ多糖(Lipopolysaccharide, LPS)が放出されることにより、歯茎が腫れて出血する炎症が形成され、歯周靱帯と隣接組織が損傷する。歯周炎が進むと、歯周靱帯や歯槽骨にまで損傷を与え、最終的には歯を喪失する。タンパク質、ビタミンなどの栄養不足、妊娠や糖尿病などによるホルモン障害、喫煙、後天性免疫不全症候群(AIDS)などが疾患を悪化させることがある。また、歯周疾患の他の原因として、歯垢及び歯石が挙げられる。本発明における歯周疾患の原因菌には、歯周疾患を引き起こす原因菌であればその種類に関係なく全て含まれ、具体的にはアクチノバチルス・アクチノミセテムコミタンス(Actinobacillus actinomycetemcomitans)、ポルフィロモナス・ジンジバリス(Porphyromonas gingivalis)、タンネレラ・フォーサイシア(Tannerella forsythia)、トレポネーマ・デンティコラ(Treponema denticola)及びフソバクテリウム・ヌクレアタム(Fusobacterium nucleatum)からなる群から選択される少なくとも1種の菌であり、より具体的にはポルフィロモナス・ジンジバリスである。 The term "periodontal disease" as used in the present invention refers to a disease in which inflammation occurs in the gingiva, periodontal ligament and bone tissue that support the teeth, and is generally referred to as periodontal disease. gingivitis) and periodontitis. Gingivitis is a periodontal disease that is relatively mild and recovers quickly and is confined to the gums, that is, soft tissues. Periodontitis is when the inflammation progresses to the gums and around the alveolar bone. There is a V-shaped gap between the gingiva (gums) and the teeth, and when oral pathogens attack the lower side of the gum line in the sulcus, lipopolysaccharide (LPS), which is an inflammatory stimulus, is released. The release creates an inflammation that causes the gums to swell and bleed, and damages the periodontal ligaments and adjacent tissues. As periodontitis progresses, it damages the periodontal ligament and alveolar bone, eventually leading to tooth loss. Nutrient deficiencies such as protein and vitamins, hormonal disorders due to pregnancy and diabetes, smoking, acquired immunodeficiency syndrome (AIDS), etc. may exacerbate the disease. Other causes of periodontal disease include dental plaque and tartar. The causative bacteria for periodontal disease in the present invention include all causative bacteria that cause periodontal disease regardless of their types, specifically Actinobacillus actinomycetemcomitans, Porphyro At least one fungus selected from the group consisting of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Fusobacterium nucleatum, more specifically is Porphyromonas gingivalis.
前記ポルフィロモナス・ジンジバリスは、バクテロイデス(Bacteroide)の類縁菌の一種でグラム陰性菌であり、嫌気性菌である。前記ポルフィロモナス・ジンジバリスは、歯周疾患が発生した口腔内に見られ、その他胃腸の上部、呼吸器及び結腸にも見られる。慢性歯周疾患の患者においては、前記菌のコラゲナーゼ酵素によりコラーゲンが分解される。前記菌は、歯肉線維芽細胞に侵入し、高濃度の抗生剤下でも生存することができる。また、前記菌は、歯肉上皮細胞に侵入して長時間生存することができる。 The Porphyromonas gingivalis is a gram-negative, anaerobic bacterium that is a kind of bacteria related to Bacteroides. Said Porphyromonas gingivalis is found in the oral cavity where periodontal disease occurs, as well as in the upper gastrointestinal tract, respiratory tract and colon. In patients with chronic periodontal disease, collagen is degraded by the bacterial collagenase enzyme. The bacteria can invade gingival fibroblasts and survive even under high concentrations of antibiotics. In addition, the bacteria can invade gingival epithelial cells and survive for a long period of time.
本発明の一実施例において、ポルフィロモナス・ジンジバリスを塗抹した培地に本発明の前記天然化合物を含むディスクを接種し、その後生育阻止円の大きさを測定した結果、前記化合物を含む実験群の生育阻止円の直径が10.0mm以上であり、ポルフィロモナス・ジンジバリスに対して非常に優れた抗菌活性を示したので、前記化合物を含む組成物は歯周疾患の予防又は改善用途に有用であることが確認された(表2)。 In one embodiment of the present invention, a medium smeared with Porphyromonas gingivalis was inoculated with a disk containing the natural compound of the present invention, and then the size of the growth inhibition circle was measured. The diameter of the growth-inhibitory circle was 10.0 mm or more, and the composition showed excellent antibacterial activity against Porphyromonas gingivalis. Therefore, the composition containing the compound is useful for preventing or improving periodontal disease. It was confirmed that there is (Table 2).
また、本発明の一実施例において、歯肉炎症を有する実験対象者を選択して臨床実験を行った結果、前記化合物を含む実験群歯磨き粉を用いた実験群の歯肉炎症抑制効果が優れ、6カ月経過しても正常出血状態を維持し、歯肉炎症抑制効果を持続したので、前記天然化合物を含む組成物は歯肉炎を含む歯周疾患の予防又は改善用途に有用であることが確認された(表4)。 In addition, in one example of the present invention, as a result of conducting a clinical experiment by selecting experimental subjects with gingival inflammation, the experimental group using the experimental group toothpaste containing the above compound had an excellent effect of suppressing gingival inflammation, and the effect of suppressing gingival inflammation was excellent for 6 months. It was confirmed that the composition containing the natural compound is useful for the prevention or improvement of periodontal diseases including gingivitis ( Table 4).
本発明における「歯痛」とは、甘い食べ物、非常に冷たい食べ物、非常に熱い食べ物などを食べたときに歯に痛みを感じることを意味するが、一般には、歯自体の痛みだけでなく、歯を顎の骨に固定している歯周組織の痛みも含まれる。通常は、噛むときに痛みが生じ、歯茎が腫れて不快な匂いのする分泌物が出る。歯痛は、原因疾患によって多少異なる痛みが見られる。具体的には、う蝕の場合は、初期には痛みがないが、次第に進行して歯の中の神経まで達すると痛みが現れ、埋伏歯がある場合は、歯の周辺組織の炎症により痛みが誘発され、歯が潰れたり、ひびが入った場合は、冷たい食べ物に触れたり、強く噛んだときに歯が広がって神経に刺激を与えて痛みが生じる。歯髄炎の場合は、初期には冷たい食べ物が触れたときに痛みを感じ、進行すると熱い食べ物に触れたときに痛みを感じ、さらに炎症が進行して歯髄組織が壊死すると冷たい食べ物や熱い食べ物に対する反応がなくなり、歯根端(歯の根の先)の炎症による痛みが生じる。 The term "toothache" as used in the present invention means pain in the tooth when eating sweet food, very cold food, very hot food, etc. In general, not only pain in the tooth itself but also pain in the tooth It also includes pain in the periodontal tissue that holds the tooth to the jawbone. It usually causes pain when chewing, swollen gums, and foul-smelling discharge. Toothache presents somewhat different pain depending on the causative disease. Specifically, in the case of dental caries, there is no pain in the early stages, but as it progresses and reaches the nerve inside the tooth, pain appears. is induced and the tooth is crushed or cracked, when touching cold food or chewing hard, the tooth spreads and stimulates the nerve, causing pain. In the case of pulpitis, pain is felt when cold food is touched in the early stages, and when it progresses, pain is felt when hot food is touched. Loss of response and pain due to inflammation of the root apex (tip of the root) of the tooth.
本発明の一実施例において、痛み及び炎症マーカーとして知られるPGE2の抑制効果を確認した結果、本発明の前記天然化合物を含む実験群で濃度依存的にPGE2を抑制する効果を発揮することが確認された(表5)。 In one example of the present invention, as a result of confirming the inhibitory effect of PGE2, which is known as a marker of pain and inflammation, it was confirmed that the experimental group containing the natural compound of the present invention exhibits the effect of inhibiting PGE2 in a concentration-dependent manner. (Table 5).
本発明における「知覚過敏」とは、知覚過敏象牙質(hypersensitive dentine)を意味し、知覚過敏症状とは、象牙質知覚過敏症(dentine hyperesthesia)を意味する。知覚過敏症状は、露出した歯の象牙質部分が冷たい空気や刺激的な食べ物などに触れたときに敏感に感じられる歯のしみであり、歯周疾患を有する成人の60~98%に症状が現れる。知覚過敏症状は、誤った歯磨き習慣、過度な咬合力、酸の溶解による歯茎への歯の食い込み、口腔衛生状態の不良、歯周治療、修復治療、酸性化による歯の溶解により現れる。知覚過敏症状の根本的な原因として、歯の象牙質に存在する多くの細管が外部に露出することが挙げられ、露出により全ての刺激をそのまま歯髄内の神経に伝達するので、同じ刺激に対しても普段より敏感に反応して痛みが誘発される。知覚過敏症状は、軽い症状から激しく持続的な痛みまで様々であるが、歯の特性上、再生されないので、鎮痛剤や消炎剤などの服用は歯のしみの根本的な解決策にはならない。知覚過敏症状は、歯全体に全般的に現れることもあり、上顎や下顎、右側や左側など、特定部位に限定されて現れることもある。多く発症する部位は、原因によって異なるが、主に犬歯、小臼歯であり、最もひどく痛みが現れる部位は、90%以上が歯茎と歯の境界部分である歯頚部である。 "Hypersensitivity" in the present invention means hypersensitive dentine, and hypersensitivity symptom means dentine hyperesthesia. Hypersensitivity symptoms are tooth stains that are felt sensitively when the exposed dentin part of the teeth comes into contact with cold air or irritating food, and 60 to 98% of adults with periodontal disease have symptoms. appear. Hypersensitivity symptoms appear due to incorrect tooth brushing habits, excessive bite force, teeth digging into the gums due to acid dissolution, poor oral hygiene, periodontal treatment, restorative treatment, and tooth dissolution due to acidification. The underlying cause of hyperesthesia symptoms is that many tubules in the dentin of the tooth are exposed to the outside. However, it reacts more sensitively than usual and causes pain. Symptoms of hypersensitivity range from mild symptoms to severe and persistent pain, but because teeth do not regenerate, taking pain relievers and anti-inflammatory agents is not a fundamental solution to tooth stains. Hypersensitivity symptoms may appear in general over the entire tooth, or they may appear in specific sites such as the upper jaw, lower jaw, right side, or left side. Although the most frequently affected sites differ depending on the cause, they are mainly canines and premolars, and the most painful site is the cervical region, which is the interface between gums and teeth in 90% or more.
本発明の一実施例において、知覚過敏象牙質を有する実験対象者を選択して臨床実験を行った結果、本発明の前記化合物を含む実験群歯磨き粉を用いた実験群の知覚過敏症状抑制効果が優れ、前記天然化合物を含む組成物は知覚過敏の予防又は改善用途に有用であることが確認された(表7)。 In one example of the present invention, as a result of conducting a clinical experiment by selecting an experimental subject with hypersensitive dentin, the experimental group using the experimental group toothpaste containing the compound of the present invention showed an inhibitory effect on hypersensitivity symptoms. It was confirmed that the composition containing the natural compound is excellent and useful for preventing or improving hypersensitivity (Table 7).
本発明における「口臭」とは、口腔及び隣接器官に由来する匂いを意味し、口臭の85~90%が口腔に由来し、特に舌の後側に由来する。口臭の主な成分は揮発性硫黄化合物であるが、揮発性硫黄化合物の総量の90%がシステインから生成される硫化水素(hydrogen sulfide)と、メチオニンから生成されるメチルメルカプタン(methyl mercaptan)及びジメチルスルフィド(dimethyl sulfide)である。これらの成分は、主に嫌気性細菌が分泌するタンパク質酵素により生成され、舌の後側が最も重要な生息地となる。この部位は、唾液による洗浄作用が行われにくく、多くの小さな陥没があるので、細菌が生息し続ける場所となる。嫌気性細菌による揮発性硫黄化合物の生成が口臭の原因として最も重要であるが、その他、う蝕、歯周炎、口腔乾燥症などの口腔疾患によっても発生する。口臭の発生には各種嫌気性細菌が関与しており、口臭発生の原因菌としては、例えば様々な種類の多量の酵素を分泌するポルフィロモナス・ジンジバリス(Porphyromonas gingivalis)が挙げられるが、これに限定されるものではない。 The term "halitosis" as used in the present invention means an odor originating from the oral cavity and adjacent organs, and 85-90% of halitosis originates from the oral cavity, particularly from the back of the tongue. The main components of bad breath are volatile sulfur compounds, and 90% of the total amount of volatile sulfur compounds is hydrogen sulfide produced from cysteine, methyl mercaptan produced from methionine and dimethyl sulfide. It is a sulfide (dimethyl sulfide). These components are mainly produced by protein enzymes secreted by anaerobic bacteria, and their most important habitat is the back of the tongue. This area is poorly cleaned by saliva and has many small depressions, making it a habitat for bacteria. The most important cause of halitosis is the production of volatile sulfur compounds by anaerobic bacteria, but oral diseases such as dental caries, periodontitis, and xerostomia also cause halitosis. Various anaerobic bacteria are involved in the generation of halitosis, and the causative bacteria of halitosis include, for example, Porphyromonas gingivalis, which secretes a large amount of various kinds of enzymes. It is not limited.
本発明の一実施例において、う蝕のない実験対象者を対象に臨床実験を行った結果、本発明の前記天然化合物を含む実験群歯磨き粉を用いた実験群の口臭除去効果が優れ、前記化合物を含む組成物は口臭の予防又は改善用途に有用であることが確認された(表8)。 In one example of the present invention, as a result of conducting a clinical trial on experimental subjects without dental caries, the experimental group using the experimental group toothpaste containing the natural compound of the present invention showed excellent bad breath removal effect, and the compound It was confirmed that the composition containing is useful for preventing or improving halitosis (Table 8).
本発明の医薬部外品組成物は、口腔用医薬部外品を含んでもよい。本発明の医薬部外品組成物に含まれる成分は、前記有効成分以外に、口腔用医薬部外品組成物に通常用いられる成分を有効成分として含んでもよく、例えば研磨剤、湿潤剤、結合剤、起泡剤、甘味剤、防腐剤、薬効成分、香味剤、色素、溶剤、増白剤、可溶化剤又はpH調整剤を含んでもよい。 The quasi-drug composition of the present invention may contain an oral quasi-drug. Ingredients contained in the quasi-drug composition of the present invention may include, in addition to the active ingredients described above, ingredients commonly used in oral quasi-drug compositions, such as abrasives, wetting agents, and binding agents. agents, foaming agents, sweeteners, preservatives, active ingredients, flavoring agents, dyes, solvents, brighteners, solubilizers or pH adjusters.
本発明の口腔用医薬部外品組成物は、当該技術分野で通常製造されるいかなる剤形に製造してもよく、例えば歯磨き粉、口腔洗浄剤、口腔清浄剤、ガム、キャンディー類、口腔スプレー、口腔用軟膏剤、口腔用ワニス、マウスウォッシュ、歯茎マッサージクリームなどの剤形を有してもよいが、これらに限定されるものではない。 The oral quasi-drug composition of the present invention may be produced in any dosage form commonly produced in the art, such as toothpaste, mouthwash, mouthwash, gum, candies, oral spray, It may have dosage forms such as, but not limited to, oral ointments, oral varnishes, mouthwashes, gum massage creams, and the like.
一例として、本発明の口腔用医薬部外品組成物が歯磨き粉の剤形である場合、湿潤剤、研磨剤、結合剤、起泡剤、香味剤、甘味剤、着色剤、保存剤、薬効成分、溶剤、pH調整剤などを含んでもよい。 As an example, when the oral quasi-drug composition of the present invention is in the form of toothpaste, wetting agents, abrasives, binders, foaming agents, flavoring agents, sweetening agents, coloring agents, preservatives, and medicinal ingredients are used. , solvents, pH adjusters, and the like.
前記湿潤剤は、歯磨剤の成分中の粉末がペースト状になるようにし、歯磨剤が空気中で固まることを防止するためのものであり、グリセリン、ソルビット液、プロピレングリコール、ポリエチレングリコールなどを単独で又は2種以上を混合して組成物の総重量の1~60重量%、具体的には10~50重量%になるように用いる。 The humectant is used to make the powder in the dentifrice into a paste and to prevent the dentifrice from solidifying in the air. It is used alone or in combination of two or more in an amount of 1 to 60% by weight, specifically 10 to 50% by weight, of the total weight of the composition.
前記起泡剤は、歯磨剤を口腔内に拡散させて清掃効果を向上させ、界面活性剤として作用して口腔汚染を洗浄するものであり、ラウリル硫酸ナトリウム、ラウリルサルコシン酸ナトリウム、アルキルスルホコハク酸ナトリウム、ショ糖脂肪酸エステルなどの界面活性剤を単独で又は2種以上を混合して組成物の総重量の0.5~10重量%、具体的には0.5~5重量%になるように用いる。 The foaming agent diffuses the dentifrice into the oral cavity to improve the cleaning effect, and acts as a surfactant to cleanse the oral cavity, and includes sodium lauryl sulfate, sodium lauryl sarcosinate, and sodium alkyl sulfosuccinate. , Surfactants such as sucrose fatty acid esters alone or in combination of two or more so that the total weight of the composition is 0.5 to 10% by weight, specifically 0.5 to 5% by weight. use.
前記結合剤は、歯磨剤中の粉末と液体成分間の分離を防止するものであり、カルボキシメチルセルロースナトリウム、メチルセルロース、ヒドロキシプロピルセルロースなどのセルロース誘導体、アルギン酸ナトリウム、カラギーナン、キサンタンガムなどを単独で又は2種以上を混合して組成物の総重量の0.1~5重量%、具体的には0.3~2重量%になるように用いる。 The binder prevents separation between the powder and the liquid component in the dentifrice, and is composed of cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylcellulose, sodium alginate, carrageenan, xanthan gum, etc. alone or in combination. The above are mixed and used in an amount of 0.1 to 5% by weight, specifically 0.3 to 2% by weight, of the total weight of the composition.
前記研磨剤は、歯の表面を傷つけることなく歯の表面の付着物を除去し、歯本来の光沢が出るようにするものであり、炭酸カルシウム(CaCO3)、第二リン酸カルシウム(CaHPO4,CaHPO4・2H2O)、無水ケイ酸(SiO2・2H2O)、水酸化アルミニウム(Al(OH)3)、ピロリン酸カリウム、炭酸マグネシウムなどを単独で又は2種以上を混合して組成物の総重量の1~60重量%、具体的には10~50重量%になるように用いる。 The abrasive removes deposits on the surface of the teeth without damaging the surface of the teeth and allows the original luster of the teeth to appear. 4.2H.sub.2O ), silicic anhydride ( SiO.sub.2.2H.sub.2O ), aluminum hydroxide (Al(OH) .sub.3 ), potassium pyrophosphate, magnesium carbonate, etc., either alone or in combination of two or more to form a composition 1 to 60% by weight, specifically 10 to 50% by weight of the total weight.
前記香味剤は、歯磨き粉に爽快感と香りを加え、使用感を向上させるためのものであり、ペパーミントオイル、スペアミントオイル、メントールなどを単独で又は2種以上を混合して組成物の総重量の1~60重量%、具体的には0.01~5重量%になるように用いる。 The flavoring agent is for adding a refreshing feeling and fragrance to the toothpaste and improving the feeling of use. It is used in an amount of 1 to 60% by weight, specifically 0.01 to 5% by weight.
前記甘味剤は、歯磨剤の原料による不快な味を除去し、清涼感をよくするためのものであり、サッカリン酸、アスパルテーム、キシリトール、グリチルリチン酸などを単独で又は2種以上を混合して組成物の総重量の1~60重量%、具体的には0.01~5重量%になるように用いる。 The sweetening agent removes the unpleasant taste of the raw material of the dentifrice and improves the cooling sensation, and is composed of saccharic acid, aspartame, xylitol, glycyrrhizic acid, etc. alone or in combination of two or more. It is used in an amount of 1 to 60% by weight, specifically 0.01 to 5% by weight, of the total weight of the product.
薬効成分は、う蝕予防、歯周疾患予防、歯痛予防、知覚過敏予防、口臭除去などの効果のためのものであり、フッ化物、塩化亜鉛、クロルヘキシジン、アミノカプロン酸、トラネキサム酸、塩化セチルピリジニウム、塩化ピリドキシン、トリクロサン、酢酸トコフェロール、モノフルオロリン酸ナトリウムなどを単独で又は2種以上を混合して用いる。本発明においては、前記化合物を追加の薬効成分として用いる。 The medicinal ingredients are for caries prevention, periodontal disease prevention, toothache prevention, hypersensitivity prevention, bad breath elimination, etc., and include fluoride, zinc chloride, chlorhexidine, aminocaproic acid, tranexamic acid, cetylpyridinium chloride, Pyridoxine chloride, triclosan, tocopherol acetate, sodium monofluorophosphate and the like are used alone or in combination of two or more. In the present invention, said compound is used as an additional medicinal ingredient.
本発明の口腔用医薬部外品組成物は、単独で又は組み合わせて用いることもでき、本発明以外の他の口腔用医薬部外品組成物と組み合わせて用いることもできる。 The oral quasi-drug composition of the present invention can be used alone or in combination, and can also be used in combination with other oral quasi-drug compositions other than the present invention.
本発明の他の態様は、前記天然化合物又はその薬学的に許容される塩を有効成分として含む薬学的組成物を提供する。また、具体的には、本発明は、前記天然化合物を有効成分として含む、う蝕、歯周疾患(歯周炎又は歯肉炎)、歯痛、知覚過敏及び口臭からなる群から選択される少なくとも1つの口腔疾患の予防又は治療用薬学的組成物を提供する。前記天然化合物、口腔疾患、う蝕、歯周疾患、歯痛、知覚過敏及び口臭については前述した通りである。 Another aspect of the present invention provides a pharmaceutical composition comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. More specifically, the present invention provides at least one toothpaste selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, hypersensitivity and halitosis, which contains the natural compound as an active ingredient. Provided are pharmaceutical compositions for the prevention or treatment of two oral diseases. The natural compounds, oral diseases, dental caries, periodontal diseases, toothache, hypersensitivity and halitosis are as described above.
本発明の薬学的組成物は、口腔疾患を予防、治療するための通常の方法により、錠剤、丸剤、散剤、顆粒剤、カプセル剤、懸濁剤、内用液剤、乳剤、シロップ剤、エアゾール剤、滅菌注射溶液などの形態に剤形化することができる。 The pharmaceutical composition of the present invention can be prepared as tablets, pills, powders, granules, capsules, suspensions, liquids for internal use, emulsions, syrups and aerosols by conventional methods for preventing and treating oral diseases. It can be formulated in the form of pharmaceutical agents, sterile injectable solutions, and the like.
経口用固形製剤には、錠剤、丸剤、散剤、顆粒剤、カプセル剤などが含まれ、これらの固形製剤は、少なくとも1つの賦形剤、例えばデンプン、炭酸カルシウム、スクロース、ラクトース、ゼラチンなどを混合して調製されてもよい。また、通常の賦形剤以外に、ステアリン酸マグネシウム、タルクなどの滑沢剤も用いられる。経口用液体製剤には、懸濁剤、内用液剤、乳剤、シロップ剤などが含まれ、通常用いられる通常の希釈剤である水、流動パラフィン以外にも種々の賦形剤、例えば湿潤剤、甘味剤、芳香剤、保存剤などが用いられる。 Oral solid dosage forms include tablets, pills, powders, granules, capsules, etc., and these solid dosage forms contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, and the like. It may be prepared by mixing. Besides ordinary excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used diluents, various excipients such as wetting agents, Sweeteners, flavoring agents, preservatives and the like may be used.
非経口用製剤には、滅菌水溶液、非水性溶剤、懸濁剤、乳剤、凍結乾燥製剤、坐剤などが含まれる。非水性溶剤、懸濁剤としては、プロピレングリコール、ポリエチレングリコール、オリーブ油などの植物性油、オレイン酸エチルなどの注射可能なエステルなどが用いられる。 Parenteral formulations include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories and the like. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
また、本発明の薬学的組成物は、担体、賦形剤又は希釈剤をさらに含んでもよい。担体、賦形剤又は希釈剤としては、ラクトース、グルコース、スクロース、ソルビトール、マンニトール、キシリトール、エリトリトール、マルチトール、デンプン、アカシアゴム、アルギン酸塩、ゼラチン、リン酸カルシウム、ケイ酸カルシウム、セルロース、メチルセルロース、ヒドロキシプロピルメチルセルロース、微晶質セルロース、ポリビニルピロリドン、水、ヒドロキシ安息香酸メチル、ヒドロキシ安息香酸プロピル、タルク、ステアリン酸マグネシウム、二酸化ケイ素などの鉱油などが用いられる。 Additionally, the pharmaceutical composition of the present invention may further comprise a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, hydroxypropyl. Mineral oils such as methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and silicon dioxide are used.
本発明による薬学的組成物の具体的な投与量は、製剤化方法、患者の状態、体重、性別、年齢、疾患の程度、薬物の形態、投与経路及び期間、排泄速度、反応感度などの要因に応じて当業者であれば様々に選択することができ、投与量及び回数は、いかなる面においても本発明を限定するものではない。 The specific dosage of the pharmaceutical composition according to the present invention depends on factors such as formulation method, patient condition, body weight, sex, age, degree of disease, form of drug, administration route and period, excretion rate, reaction sensitivity, etc. A person skilled in the art can make various selections depending on the situation, and the dosage and frequency are not intended to limit the present invention in any aspect.
本発明の薬学的組成物は、ラット、マウス、家畜、ヒトなどの哺乳動物に様々な経路で投与することができる。投与におけるあらゆる方法が可能であるが、例えば経口、静脈、筋肉又は皮下注射により投与することができる。 The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, domestic animals and humans by various routes. Although any method of administration is possible, it can be administered, for example, by oral, intravenous, intramuscular or subcutaneous injection.
本発明のさらに他の態様は、前記天然化合物又はその食品学的に許容される塩を有効成分として含む食品組成物を提供する。また、具体的には、本発明は、前記化合物を有効成分として含む、う蝕、歯周疾患(歯周炎又は歯肉炎)、歯痛、知覚過敏及び口臭からなる群から選択される少なくとも1つの口腔疾患の予防又は改善用食品組成物を提供する。前記天然化合物、口腔疾患、う蝕、歯周疾患、歯痛、知覚過敏及び口臭については前述した通りである。前記食品組成物は、機能性食品の形態で用いられてもよいが、これに限定されるものではない。 Yet another aspect of the present invention provides a food composition comprising the natural compound or its food-acceptable salt as an active ingredient. Further, specifically, the present invention provides at least one selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, hypersensitivity and halitosis, which contains the compound as an active ingredient. Provided is a food composition for preventing or improving oral diseases. The natural compounds, oral diseases, dental caries, periodontal diseases, toothache, hypersensitivity and halitosis are as described above. The food composition may be used in the form of a functional food, but is not limited thereto.
本発明の食品組成物に含まれる前記天然化合物又はその食品学的に許容される塩は、前記化合物を含む動植物、その抽出物、その分画物又はその加工物の形態で含まれてもよい。また、前記組成物は、有効成分以外に、食品学的に許容される食品補助添加剤を含んでもよい。 The natural compound or food-acceptable salt thereof contained in the food composition of the present invention may be contained in the form of an animal or plant containing the compound, an extract thereof, a fraction thereof, or a processed product thereof. . In addition, the composition may contain a food supplementary food additive in addition to the active ingredient.
本発明における「食品補助添加剤」とは、食品に補助的に添加する構成要素を意味し、各剤形の機能性食品を製造する際に添加されるものであり、当業者が適宜選択して用いることができる。食品補助添加剤の例としては、様々な栄養剤、ビタミン、ミネラル(電解質)、合成風味剤や天然風味剤などの風味剤、着色剤及び充填剤、ペクチン酸及びその塩、アルギン酸及びその塩、有機酸、保護コロイド、増粘剤、pH調整剤、安定化剤、防腐剤、グリセリン、アルコール、炭酸飲料に用いられる炭酸化剤などが挙げられるが、前記例に本発明の食品補助添加剤の種類が限定されるものではない。 "Food supplementary additive" in the present invention means a component that is supplementarily added to food, is added when producing functional foods of each dosage form, and can be appropriately selected by those skilled in the art. can be used Examples of food supplement additives include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, coloring agents and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloids, thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages, etc.; The type is not limited.
本発明の食品組成物には機能性食品が含まれてもよい。本発明における「機能性食品」とは、人体に有用な機能性を有する原料や成分を用いて、錠剤、カプセル剤、粉末剤、顆粒剤、液剤、丸剤などの形態に製造及び加工した食品を意味する。ここで、「機能性」とは、人体の構造及び機能に対して栄養素を調節するか、生理学的作用などの保健用途に有用な効果を与えることを意味する。本発明の機能性食品は、当該技術分野で通常用いられる方法により製造することができ、その製造時には当該技術分野で通常添加する原料及び成分を添加して製造することができる。また、前記機能性食品の剤形も、機能性食品として認められる剤形であれば限定されるものではない。本発明の食品組成物は、様々な形態の剤形に製造することができ、一般薬品とは異なり、食品を原料とするので、薬品の長期服用時に発生し得る副作用などがないという利点があり、携帯性に優れるので、本発明の機能性食品は、口腔疾患を予防又は改善する補助剤として摂取することができる。 The food composition of the present invention may contain functional foods. "Functional food" in the present invention means food manufactured and processed into forms such as tablets, capsules, powders, granules, liquids, and pills using raw materials and ingredients that have functionality useful for the human body. means Here, "functionality" means regulating nutrients on the structure and function of the human body or providing beneficial effects for health applications, such as physiological effects. The functional food of the present invention can be produced by a method commonly used in the technical field, and can be produced by adding raw materials and components that are commonly added in the technical field. Also, the dosage form of the functional food is not limited as long as it is a dosage form recognized as a functional food. The food composition of the present invention can be prepared in various dosage forms, and unlike general drugs, it has the advantage that it does not have side effects that may occur during long-term administration of drugs because it is made from food. Because of its excellent portability, the functional food of the present invention can be ingested as an adjuvant for preventing or improving oral diseases.
本発明の機能性食品が用いられる形態には制限がなく、通常の意味の食品が全て含まれ、健康機能食品などの当該技術分野で公知の用語と混用されてもよい。また、本発明の機能性食品は、当業者の選択により食品に含まれ得る好適な他の補助成分や公知の添加剤を混合して製造することができる。添加できる食品の例としては、肉類、ソーセージ、パン、チョコレート、キャンディー類、スナック類、菓子類、ピザ、ラーメン、その他の麺類、ガム類、アイスクリーム類をはじめとする乳製品、各種スープ、清涼飲料水、茶、ドリンク剤、アルコール飲料、ビタミン複合剤などが挙げられ、本発明による前記化合物を主成分として作製した汁、茶、ゼリー、ジュースなどに添加することにより製造することができる。また、動物用の飼料として用いられる食品も含まれる。 The form in which the functional food of the present invention is used is not limited, and includes all foods in the usual sense, and may be mixed with terms known in the art such as health functional food. In addition, the functional food of the present invention can be produced by mixing other suitable supplementary ingredients and known additives that can be contained in the food according to the selection of those skilled in the art. Examples of foods that can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products such as ice cream, various soups, and refreshing beverages. Drinking water, tea, drinks, alcoholic beverages, vitamin complexes, etc., can be mentioned, and can be produced by adding the compounds of the present invention to juices, teas, jellies, juices, etc. prepared as main ingredients. Also included are foods used as animal feed.
以下、実施例及び実験例を挙げて本発明の構成及び効果をより詳細に説明する。これらの実施例及び実験例はあくまで本発明を例示するものにすぎず、本発明がこれらの実施例及び実験例に限定されるものではない。 Hereinafter, the configuration and effects of the present invention will be described in more detail with reference to Examples and Experimental Examples. These Examples and Experimental Examples are merely to illustrate the present invention, and the present invention is not limited to these Examples and Experimental Examples.
実験例1:う蝕及び歯周炎の原因菌に対する抗菌効果
化学式1~15の化合物のう蝕及び歯周炎に対する予防又は治療効果を確認するために、抗菌活性実験を行った。口腔病原菌生育抑制効果を確認するために、う蝕の代表的な誘発細菌であるストレプトコッカス・ミュータンス(Streptococcus mutans)と、歯周疾患の代表的な誘発細菌であるポルフィロモナス・ジンジバリス(Porphyromonas gingivalis)を用いて、ペーパーディスク検査法により抗菌力テストを行った。
Experimental Example 1 Antibacterial Effect on Causative Bacteria of Caries and Periodontitis An antibacterial activity experiment was conducted to confirm the preventive or therapeutic effect of the compounds of formulas 1 to 15 on caries and periodontitis. In order to confirm the effect of suppressing the growth of oral pathogens, Streptococcus mutans, a representative bacterium that induces dental caries, and Porphyromonas gingivalis, a representative bacterium that induces periodontal disease, were tested. ) was used to perform an antibacterial activity test by the paper disc test method.
前記各口腔病原菌の活性を表1の最適培養条件で増加させ、その後各菌の最適培地で約4~6時間培養して培養液の濁度がMacfarland turbidity No.0.5(1.5×108)になるようにし、前記各口腔病原菌0.1mlを平板培地に均等に塗抹した。その後、滅菌したペーパーディスク(Whatman no.5 paper, 8mm diameter)に化学式1~15の化合物をそれぞれ10mg/discの濃度で接種し、1時間吸収乾燥させた。次に、前記各口腔病原菌の最適温度で24~48時間培養し、その後生育阻止円の大きさ(直径mm)を測定した。その結果を表2に示す。 The activity of each of the oral pathogens was increased under the optimum culture conditions shown in Table 1, and then cultured in the optimum medium for each bacterium for about 4 to 6 hours. 0.5 (1.5×10 8 ), and 0.1 ml of each oral pathogen was evenly smeared on the plate medium. Then, each of the compounds of Formulas 1 to 15 was inoculated on a sterilized paper disc (Whatman no.5 paper, 8 mm diameter) at a concentration of 10 mg/disc, and dried for 1 hour. Next, each oral pathogen was cultured at the optimum temperature for 24 to 48 hours, and then the size (diameter mm) of the growth inhibition circle was measured. Table 2 shows the results.
表2から分かるように、無処理群と比較すると、化学式1~15の化合物で処理した群は、前記2種の口腔病原菌に対する生育阻止円の直径が9.5mm以上であり、ストレプトコッカス・ミュータンス及びポルフィロモナス・ジンジバリスに対する非常に優れた抗菌活性を示した。よって、化学式1~15の化合物はう蝕又は歯周疾患の予防又は治療用途に有用であることが分かった。 As can be seen from Table 2, compared with the untreated group, the group treated with the compounds of formulas 1 to 15 had a growth inhibition circle diameter of 9.5 mm or more against the two oral pathogens, and Streptococcus mutans and showed excellent antibacterial activity against Porphyromonas gingivalis. Therefore, it was found that the compounds of formulas 1 to 15 are useful for preventing or treating dental caries or periodontal disease.
実験例2:歯肉炎発症抑制効果
化学式1~15の化合物の歯肉炎に対する予防又は治療効果を確認するために、実験対象群を選択して臨床実験を行った。
Experimental Example 2: Effect of Inhibiting the Development of Gingivitis In order to confirm the preventive or therapeutic effect of the compounds of formulas 1 to 15 on gingivitis, a group of experimental subjects was selected and a clinical experiment was conducted.
まず、歯磨き粉を製造する際に一般に用いられるカルボキシメチルセルロースナトリウム、ラウリル硫酸ナトリウム、グリセリン、コロイド状二酸化ケイ素、シリカ類、ココイルイセチオン酸ナトリウム、ドジシン、甘味剤、芳香剤、着色剤などを用いて対照群歯磨き粉を作製し、前記対照群歯磨き粉に化学式1~15の化合物のいずれかの化合物を0.01重量%含有させて実験群歯磨き粉を作製した。 First, a control was performed using sodium carboxymethylcellulose, sodium lauryl sulfate, glycerin, colloidal silicon dioxide, silicas, sodium cocoyl isethionate, dodicin, sweeteners, flavoring agents, coloring agents, etc., which are commonly used in the manufacture of toothpaste. A group toothpaste was prepared, and an experimental group toothpaste was prepared by adding 0.01% by weight of any compound of formulas 1 to 15 to the control group toothpaste.
実験対象者を選択するために、歯並びが良く、欠損歯のない歯肉炎症患者を対象に、年令別に30才から50才まで10才毎に男女各30人に精密な口腔検診を行い、次いで120人の実験対象群を選択してそれを60人ずつに分け、歯肉炎症治療効果に対する臨床実験を次のように行った。 In order to select subjects for the experiment, 30 males and 30 males and 30 females were selected every 10 years from 30 years old to 50 years old. A group of 120 experimental subjects was selected and divided into 60 subjects each, and a clinical experiment on the therapeutic effect of gingival inflammation was conducted as follows.
具体的には、実験対象群を対照群と実験群に分け、対照群には前記対照群歯磨き粉を食後2時間経過した時点に1日3回用いるように教育し、実験群には前記実験群歯磨き粉を前記対照群と同一時間に1日3回用いるように教育した。その後、歯口清掃を行って初期歯肉炎指数を点数化し、対照群には前記対照群歯磨き粉を、実験群には前記実験群歯磨き粉を使用させ、1週間、1カ月、3カ月及び6カ月経過後に口腔検診を行って歯肉炎指数を検査した。歯肉炎指数の測定方法は、歯周プローブ(periodontal probe)を歯肉溝内に挿入して力を加えない状態で各歯の周囲に沿って探針し、30秒経過後に出血した状態を測定し、表3に示す基準で点数化した。その結果を表4に示す。 Specifically, the experimental subject group was divided into a control group and an experimental group, the control group was educated to use the control group toothpaste 3 times a day 2 hours after eating, and the experimental group was educated to use the experimental group. They were educated to use toothpaste three times a day at the same time as the control group. After that, the mouth was cleaned and the initial gingivitis index was scored, and the control group used the control group toothpaste, and the experimental group used the experimental group toothpaste, after 1 week, 1 month, 3 months and 6 months. A post-oral examination was performed to examine the gingivitis index. The method of measuring the gingivitis index is to insert a periodontal probe into the gingival sulcus and probe along the periphery of each tooth without applying force, and measure the state of bleeding after 30 seconds. , were scored according to the criteria shown in Table 3. Table 4 shows the results.
表4から分かるように、対照群と比較すると、化学式1~15の化合物のいずれかの化合物を含む歯磨き粉を用いた実験群は、6カ月経過後も正常出血状態を維持しており、歯肉炎症抑制効果が持続していた。よって、化学式1~15の化合物は歯肉炎の予防又は治療用途に有用であることが分かった。 As can be seen from Table 4, compared with the control group, the experimental group using toothpaste containing any of the compounds of formulas 1 to 15 maintained a normal bleeding state even after 6 months, and gingival inflammation The inhibitory effect persisted. Therefore, it was found that the compounds of formulas 1 to 15 are useful for preventing or treating gingivitis.
実験例3:痛み及び炎症マーカーであるPGE2の抑制効果
化学式1~15の化合物の歯痛に対する予防又は治療効果を確認するために、痛み及び炎症マーカーとして知られるPGE2の抑制効果を確認した。
Experimental Example 3: Inhibitory Effect of PGE2, a Marker of Pain and Inflammation In order to confirm the preventive or therapeutic effect of the compounds of Formulas 1 to 15 on toothache, the inhibitory effect of PGE2, a marker of pain and inflammation, was confirmed.
まず、10%FBSを含むDMEM培地にマクロファージを1.5×105cells/mlの濃度で接種し、37℃、5%CO2の条件にて、24 well plateで24時間培養した。次に、炎症誘導刺激源であるLPS 1μg/mlと各濃度の化学式1~15の化合物で処理して24時間追加培養し、その後PGE2 ELISA assay kit(Thermo SCIENTIFIC)により、上清を用いて化学式1~15の化合物の各濃度におけるPGE2抑制能を分析した(表5)。 First, macrophages were inoculated in a DMEM medium containing 10% FBS at a concentration of 1.5×10 5 cells/ml and cultured in a 24 well plate at 37° C. and 5% CO 2 for 24 hours. Next, it is treated with 1 μg/ml of LPS, which is an inflammation-inducing stimulus, and compounds of chemical formulas 1 to 15 at various concentrations, and cultured for 24 hours. Compounds 1-15 were analyzed for their ability to inhibit PGE2 at each concentration (Table 5).
表5から分かるように、LPSのみで処理した群と比較すると、化学式1~15の化合物は、全て濃度依存的にPGE2抑制効果を発揮することが確認され、歯痛の予防及び治療効果に優れることが確認された。 As can be seen from Table 5, when compared with the group treated with LPS alone, all compounds of formulas 1 to 15 were confirmed to exert a PGE2 inhibitory effect in a concentration-dependent manner, exhibiting excellent prophylactic and therapeutic effects on toothache. was confirmed.
実験例4:知覚過敏抑制効果
化学式1~15の化合物の知覚過敏に対する予防又は治療効果を確認するために、実験対象者を選択して臨床実験を行った。臨床実験において用いた対照群歯磨き粉及び実験群歯磨き粉は、実験例2の歯磨き粉と同様にそれぞれ作製した。
Experimental Example 4 Inhibitory Effect of Hypersensitivity In order to confirm the preventive or therapeutic effect of the compounds of formulas 1 to 15 on hypersensitivity, a clinical experiment was conducted by selecting experimental subjects. The control group toothpaste and experimental group toothpaste used in the clinical experiment were prepared in the same manner as the toothpaste of Experimental Example 2, respectively.
実験対象者は、知覚過敏象牙質を有する人であって、この実験への参加に同意した志願者40人であった。全実験対象歯は80本であった。また、実験対象者のうち男性は20人、女性は20人であり、年齢は20才から50才であった。実験対象者に歯磨き粉の内容物が分からないようにし、全実験期間は2週間とした。 The experimental subjects were 40 volunteers with hypersensitive dentine who consented to participate in the experiment. There were 80 teeth in total for the experiment. In addition, 20 males and 20 females were among the test subjects, and their ages ranged from 20 to 50 years old. The experimental subjects were blinded to the contents of the toothpaste and the total experimental period was 2 weeks.
実験は、温度刺激を加えて実験対象者の反応を測定する方法で行った。実験を行う前に、予め各実験対象者の知覚過敏象牙質の過敏部位をチェックし、歯がしみる部位に約5℃の冷水をスポイトで滴下して表6に示す基準で評点しておき、その後対照群には前記対照群歯磨き粉を、実験群には前記実験群歯磨き粉を2週間にわたって1日3回使用させ、2週間経過後に再び約5℃の冷水をスポイトで滴下して評点した。統計処理は、実験前と2週間後の刺激点数を対応標本T検定(paired Student-t test)で検定した。温度刺激に対する2週間後の反応点数を表7に示す。 The experiment was conducted by adding a temperature stimulus and measuring the reaction of the experiment subject. Prior to conducting the experiment, the sensitive site of the hypersensitive dentin of each test subject was checked in advance, and cold water of about 5°C was dripped on the site where the teeth were stinging with a dropper, and the score was scored according to the criteria shown in Table 6. After that, the control group used the control group toothpaste, and the experimental group used the experimental group toothpaste 3 times a day for 2 weeks. For statistical processing, the stimulation scores before and two weeks after the experiment were tested by a paired student-t test. Table 7 shows the reaction scores after 2 weeks to the temperature stimulation.
表7から分かるように、対照群と比較すると、化学式1~15の各化合物を含む歯磨き粉を用いた実験群は、2週間経過後に知覚過敏現象が抑制された。よって、化学式1~15の化合物は知覚過敏の予防又は治療用途に有用であることが分かった。 As can be seen from Table 7, the hypersensitivity phenomenon was suppressed after 2 weeks in the experimental group using the toothpaste containing each compound of formulas 1 to 15, compared with the control group. Therefore, it was found that the compounds of formulas 1 to 15 are useful for preventing or treating hypersensitivity.
実験例5:口臭除去効果
化学式1~15の化合物の口臭に対する予防又は治療効果を確認するために、実験対象者を選択して臨床実験を行った。臨床実験において用いた対照群歯磨き粉及び実験群歯磨き粉は、実験例2の歯磨き粉と同様にそれぞれ作製した。
Experimental Example 5: Effect of Eliminating Halitosis In order to confirm the preventive or therapeutic effect of the compounds of Formulas 1 to 15 on halitosis, a clinical experiment was conducted by selecting experimental subjects. The control group toothpaste and experimental group toothpaste used in the clinical experiment were prepared in the same manner as the toothpaste of Experimental Example 2, respectively.
実験対象者としてう蝕のない男女50人を選定し、前記対照群歯磨き粉及び実験群歯磨き粉を用いて交差試験(Cross-over test)を行った。市販のニンニク粉を水に分散させて24時間放置し、その後希釈してハリメーター(Halimeter)での測定値が700ppb以上になるようにし、その希釈液を口臭誘発源として用いた。実験対象者にニンニク粉希釈液15mlで30秒間うがいをさせ、1分後にハリメーターで口臭の程度を測定し、その後対照群には前記対照群歯磨き粉を、実験群には前記実験群歯磨き粉をそれぞれ使用させて30秒~1分間歯磨きをさせた。歯磨き後1分、5分、30分経過時にハリメーターで口臭の程度を測定し、口臭抑制が持続されるかを測定した。その結果を表8に示す。 50 males and females without dental caries were selected as experimental subjects, and a cross-over test was conducted using the control group toothpaste and the experimental group toothpaste. Commercially available garlic powder was dispersed in water and allowed to stand for 24 hours, then diluted to a Halimeter reading of 700 ppb or more, and the diluted solution was used as a halitosis inducer. The test subjects were asked to gargle with 15 ml of diluted garlic powder for 30 seconds, and after 1 minute, the degree of bad breath was measured with a halimator. They were allowed to use it to brush their teeth for 30 seconds to 1 minute. Halitometer was used to measure the degree of bad breath after 1 minute, 5 minutes, and 30 minutes after brushing the teeth, and it was determined whether the suppression of bad breath was maintained. Table 8 shows the results.
表8から分かるように、対照群と比較すると、化学式1~15の各化合物を含む歯磨き粉を用いた実験群は、歯磨き後1分経過時に約95%以上口臭が除去され、歯磨き後30分経過時にも口臭除去率が80%以上であり、はるかに優れた口臭除去効果を示した。よって、化学式1~15の化合物は口臭予防又は治療用途に有用であることが分かった。 As can be seen from Table 8, compared with the control group, the experimental group using the toothpaste containing each compound of formulas 1 to 15 removed about 95% of bad breath 1 minute after brushing, and 30 minutes after brushing. In some cases, the bad breath removal rate was 80% or more, showing a far superior breath removal effect. Therefore, it was found that the compounds of formulas 1 to 15 are useful for preventing or treating halitosis.
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