WO2013118759A1 - Bactericide - Google Patents

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Publication number
WO2013118759A1
WO2013118759A1 PCT/JP2013/052701 JP2013052701W WO2013118759A1 WO 2013118759 A1 WO2013118759 A1 WO 2013118759A1 JP 2013052701 W JP2013052701 W JP 2013052701W WO 2013118759 A1 WO2013118759 A1 WO 2013118759A1
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Prior art keywords
honey
porphyromonas gingivalis
royal jelly
disinfectant
present
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PCT/JP2013/052701
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French (fr)
Japanese (ja)
Inventor
藤井 彰
功治 平尾
山口 喜久二
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ジャパンローヤルゼリー株式会社
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Priority to JP2013557541A priority Critical patent/JP6047105B2/en
Publication of WO2013118759A1 publication Critical patent/WO2013118759A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56Materials from animals other than mammals
    • A61K35/63Arthropods
    • A61K35/64Insects, e.g. bees, wasps or fleas
    • A61K35/644Beeswax; Propolis; Royal jelly; Honey
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/987Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of species other than mammals or birds
    • A61K8/988Honey; Royal jelly, Propolis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier 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
    • A61Q17/005Antimicrobial preparations

Definitions

  • the present invention relates to a disinfectant for periodontal disease-causing bacteria and a preventive or ameliorating agent for periodontal disease.
  • the main causative bacterium of periodontal disease is Porphyromonas gingivalis, and it is considered that the progression of periodontal disease can be suppressed by suppressing this bacterium.
  • the present invention provides a disinfectant for periodontal disease-causing bacteria and a preventive or ameliorating agent for periodontal disease.
  • the present inventors examined anti-porphyromonas gingivalis activity using yah honey and / or royal jelly.
  • the present invention provides the following: 1. Porphyromonas gingivalis disinfectant containing Yahashi honey and / or royal jelly, 2. A preventive or ameliorating agent for periodontal disease, including yah honey and / or royal jelly, About.
  • the Porphyromonas gingivalis disinfectant of the present invention has an excellent disinfecting action against Porphyromonas gingivalis and is a natural substance, so it is highly safe and has problems such as the appearance of resistant bacteria. At the same time, it can be applied without the help of a dentist. Therefore, it is very useful for eradication of Porphyromonas gingivalis and prevention or improvement of diseases related to Porphyromonas gingivalis.
  • FIG. 1 shows the antibacterial effect of honey on Porphyromonas gingivalis.
  • the Porphyromonas gingivalis disinfectant means a composition capable of suppressing the growth of Porphyromonas gingivalis.
  • the disinfectant of the present invention can be used for prevention or amelioration of diseases associated with Porphyromonas gingivalis.
  • Yahashi honey is a unique honey that is harvested from Elsholtzia rugulosa flowers that grow naturally in the relatively high grounds of Yunnan, China. It is also sold in Japan (Japan Royal Jelly Co., Ltd., Honey (registered trademark)).
  • Royal jelly is a secreted product produced by the reaction of different components secreted from the pharyngeal glands of the upper and lower jaws of a young worker bee, and a health food made from it.
  • the disinfectant of the present invention can be added to any food material, for example, milk, fruit juices such as orange and lemon, dairy products such as yogurt, bread, and other foods.
  • the daily intake amount of yah honey per adult is usually 0.01 to 10.0 g.
  • concentration of honey honey in the disinfectant varies depending on the form, but in the case of solid forms such as tablets (tablets), troches, granules, and gums, it is in the range of 10 to 100% by weight based on the total mass. It is. In the case of a paste or liquid, it is in the range of 10 to 80% by weight with respect to the total weight.
  • the final concentration in saliva is 5 to 10 mg / ml.
  • Examples of the disinfectant of the present invention include dentifrices, oral ointments, mouth washes, gargles, troches, tablets (tablets and mouth tablets), and granules.
  • the disinfectant of the present invention includes various additives such as various nutrients, various vitamins, minerals, dietary fiber, polyunsaturated fatty acids, stabilizers such as dispersants and emulsifiers, sweeteners, taste ingredients, flavors. Etc. can be blended.
  • a liquid it may be prepared from the beginning as a liquid, but it can be prepared in a powder or paste form and dissolved in a predetermined amount of an aqueous liquid.
  • the disinfectant of the present invention can remove Porphyromonas gingivalis in the oral cavity, it can be used to prevent or ameliorate diseases related to Porphyromonas gingivalis.
  • diseases related to Porphyromonas gingivalis there is periodontal disease (alveolar pyorrhea) as a typical one in the oral cavity.
  • periodontal disease alveolar pyorrhea
  • diabetes, cardiovascular disease and the like which are considered to be strongly associated with periodontal disease.
  • Method 1 Preparation of honey and royal jelly solution
  • the honey solution is 20% w / v (200 mg / ml) in phosphate buffered saline (PBS) or Brain Heart Infusion for Porphyromonas gingivalis ( (BHI)
  • PBS phosphate buffered saline
  • BHI Brain Heart Infusion for Porphyromonas gingivalis

Abstract

The invention relates to a Porphyromonas gingivalis bactericide and an agent for preventing or improving periodontal disease which comprise Yahashi honey and/or royal jelly.

Description

除菌剤Disinfectant
 本発明は、歯周疾患の原因菌の除菌剤及び歯周疾患の予防又は改善剤に関する。 The present invention relates to a disinfectant for periodontal disease-causing bacteria and a preventive or ameliorating agent for periodontal disease.
 歯槽膿漏などの歯周疾患に罹患した歯の一般的な治療は、歯周外科、歯周組織再生療法、歯石除去及び歯肉マッサージ等であり、失われた機能を回復することはほぼ不可能であることから、疾患の進行を止めることに主眼が置かれている。 Common treatments for teeth suffering from periodontal diseases such as alveolar pyorrhea are periodontal surgery, periodontal tissue regeneration therapy, calculus removal and gingival massage, and it is almost impossible to restore lost function Therefore, the main focus is on stopping the progression of the disease.
 歯周疾患の主な原因菌は、ポルフィロモナス・ジンジバリス(Porphyromonas gingivalis)であり、この菌を抑制することによって歯周疾患の進行を抑制することができると考えられている。 The main causative bacterium of periodontal disease is Porphyromonas gingivalis, and it is considered that the progression of periodontal disease can be suppressed by suppressing this bacterium.
 従来行われている方法には、抗菌薬のミノサイクリンの軟膏を盲嚢内に貼付する方法、消毒薬を含有する洗口剤による洗口等があるが、ミノサイクリンの盲嚢内適用は歯科医師が行わなければならないという制約があり、週に一回歯科医院に通院しなければならないという問題があった。また、消毒剤によるものには、決定的な効果が見られにくいという欠点があった。 Conventional methods include the application of an antibacterial minocycline ointment in the cecum and the mouthwash with a disinfectant-containing mouthwash, but dentist must apply minocycline in the sac. There was a problem of having to go to the dental clinic once a week. Moreover, the thing by a disinfectant had the fault that a decisive effect was hard to be seen.
 歯科疾患実態調査によると、日本においては歯周疾患の目安となる歯周ポケットが4mm以上存在している割合が、50代の人で約半数に達しており、また、高齢者の歯周疾患患者が増加していることが示されている。 According to a survey on the actual conditions of dental diseases, the proportion of periodontal pockets of 4 mm or more, which is a standard for periodontal diseases, in Japan is about half of those in their 50s. It has been shown that patients are increasing.
 したがって、このような欠点を有さないポルフィロモナス・ジンジバリスの除菌剤の開発が待たれていた。 Therefore, development of a disinfectant of Porphyromonas gingivalis that does not have such drawbacks has been awaited.
 本発明は、歯周疾患の原因菌の除菌剤及び歯周疾患の予防又は改善剤を提供する。 The present invention provides a disinfectant for periodontal disease-causing bacteria and a preventive or ameliorating agent for periodontal disease.
 上記課題を解決するために、本発明者らは、ヤハシハチミツ及び/又はローヤルゼリーを用いた抗ポルフィロモナス・ジンジバリス活性の検討を行った。 In order to solve the above-mentioned problems, the present inventors examined anti-porphyromonas gingivalis activity using yah honey and / or royal jelly.
 そして、驚くべきことに、ヤハシハチミツ及び/又はローヤルゼリーがポルフィロモナス・ジンジバリスを効果的に除菌することができることを見出し、本発明を完成させた。 Surprisingly, the inventors have found that Yasushi honey and / or royal jelly can effectively sterilize Porphyromonas gingivalis, and completed the present invention.
 すなわち、本発明は、下記:
 1.ヤハシハチミツ及び/又はローヤルゼリーを含む、ポルフィロモナス・ジンジバリス除菌剤、
 2.ヤハシハチミツ及び/又はローヤルゼリーを含む、歯周疾患の予防又は改善剤、
に関する。
That is, the present invention provides the following:
1. Porphyromonas gingivalis disinfectant containing Yahashi honey and / or royal jelly,
2. A preventive or ameliorating agent for periodontal disease, including yah honey and / or royal jelly,
About.
 本発明のポルフィロモナス・ジンジバリス除菌剤は、ポルフィロモナス・ジンジバリスに対して優れた除菌作用を有し、かつ天然物質であることから安全性が高く、耐性菌の出現等の問題がなくなると同時に、歯科医の手を借りずに適用することができる。したがって、ポルフィロモナス・ジンジバリスの除菌、ポルフィロモナス・ジンジバリスに関連する疾患の予防または改善に非常に有用である。 The Porphyromonas gingivalis disinfectant of the present invention has an excellent disinfecting action against Porphyromonas gingivalis and is a natural substance, so it is highly safe and has problems such as the appearance of resistant bacteria. At the same time, it can be applied without the help of a dentist. Therefore, it is very useful for eradication of Porphyromonas gingivalis and prevention or improvement of diseases related to Porphyromonas gingivalis.
図1は、皇蜜のポルフィロモナス・ジンジバリスに対する抗菌作用を示す。FIG. 1 shows the antibacterial effect of honey on Porphyromonas gingivalis.
 本発明において、ポルフィロモナス・ジンジバリス除菌剤とは、ポルフィロモナス・ジンジバリスの増殖を抑制することができる組成物を意味する。本発明の除菌剤は、ポルフィロモナス・ジンジバリスに関連する疾患の予防または改善のために用いることができる。 In the present invention, the Porphyromonas gingivalis disinfectant means a composition capable of suppressing the growth of Porphyromonas gingivalis. The disinfectant of the present invention can be used for prevention or amelioration of diseases associated with Porphyromonas gingivalis.
 ヤハシハチミツは、中国雲南省の比較的高地に自生するヤハシ(Elsholtzia rugulosa)の花から採蜜される独特のハチミツであり、バターのように硬化することから硬蜜とも言われる,ヤハシハチミツは、最近、わが国でも販売されている(ジャパンローヤルゼリー社、皇蜜(登録商標))。 Yahashi honey is a unique honey that is harvested from Elsholtzia rugulosa flowers that grow naturally in the relatively high grounds of Yunnan, China. It is also sold in Japan (Japan Royal Jelly Co., Ltd., Honey (registered trademark)).
 ローヤルゼリーとは、若い働き蜂であるミツバチの、上顎と下顎の咽頭腺から分泌されるそれぞれ異なった成分が反応する事により生成される分泌物及びそれを原料とする健康食品である。 Royal jelly is a secreted product produced by the reaction of different components secreted from the pharyngeal glands of the upper and lower jaws of a young worker bee, and a health food made from it.
 本発明の除菌剤は、任意の食品素材、例えば、牛乳、オレンジやレモン等の果汁、ヨーグルト等の乳製品、パン、その他の食品に添加して用いることもできる。 The disinfectant of the present invention can be added to any food material, for example, milk, fruit juices such as orange and lemon, dairy products such as yogurt, bread, and other foods.
 また、本発明の除菌剤においては、ヤハシハチミツの成人1日当たりの摂取量は、通常0.01~10.0gである。通常、除菌剤中のヤハシハチミツの濃度は、その形態により異なるが、錠剤(タブレット)、トローチ剤、顆粒、ガム等の固形の形態の場合は、総質量に対して10~100重量%の範囲である。また、ペースト、液状の場合には総重量に対して10~80重量%の範囲である。好ましくは、唾液中の最終濃度が5~10mg/mlになるように調製する。 In addition, in the disinfectant of the present invention, the daily intake amount of yah honey per adult is usually 0.01 to 10.0 g. Usually, the concentration of honey honey in the disinfectant varies depending on the form, but in the case of solid forms such as tablets (tablets), troches, granules, and gums, it is in the range of 10 to 100% by weight based on the total mass. It is. In the case of a paste or liquid, it is in the range of 10 to 80% by weight with respect to the total weight. Preferably, the final concentration in saliva is 5 to 10 mg / ml.
 本発明の除菌剤の形態としては、歯磨剤、口腔軟膏剤、洗口剤、含嗽剤、トローチ剤、錠剤(タブレット・口中錠)、顆粒を挙げることができる。 Examples of the disinfectant of the present invention include dentifrices, oral ointments, mouth washes, gargles, troches, tablets (tablets and mouth tablets), and granules.
 さらに本発明の除菌剤には種々の添加物、例えば各種栄養素、種々のビタミン、ミネラル、食物繊維、多価不飽和脂肪酸、分散剤および乳化剤等の安定剤、甘味料、呈味成分、フレーバー等を配合することができる。また、液状の場合には、最初から液状として調製してもよいが、粉末またはペースト状で調製し、所定量の水性液体に溶解することができる。 Further, the disinfectant of the present invention includes various additives such as various nutrients, various vitamins, minerals, dietary fiber, polyunsaturated fatty acids, stabilizers such as dispersants and emulsifiers, sweeteners, taste ingredients, flavors. Etc. can be blended. In the case of a liquid, it may be prepared from the beginning as a liquid, but it can be prepared in a powder or paste form and dissolved in a predetermined amount of an aqueous liquid.
 本発明の除菌剤は、口腔内のポルフィロモナス・ジンジバリスを除去することができることから、ポルフィロモナス・ジンジバリスに関連する疾患を予防または改善するために用いることができる。ポルフィロモナス・ジンジバリスに関連する疾患としては、口腔内の代表的なものとして歯周病(歯槽膿漏)がある。また、歯周病と強く関連すると考えられている糖尿病、循環器疾患等がある。 Since the disinfectant of the present invention can remove Porphyromonas gingivalis in the oral cavity, it can be used to prevent or ameliorate diseases related to Porphyromonas gingivalis. As a disease related to Porphyromonas gingivalis, there is periodontal disease (alveolar pyorrhea) as a typical one in the oral cavity. In addition, there are diabetes, cardiovascular disease and the like which are considered to be strongly associated with periodontal disease.
本発明を下記の実施例により詳細に説明するが、本発明はこれに限定されるわけではない。 The present invention will be described in detail by the following examples, but the present invention is not limited thereto.
 使用薬物
1)ローヤルゼリー
 RJ原乳20050407はジャパンローヤルゼリー株式会社(東京)から供与された。
2)皇蜜
 ヤハシ純粋蜂蜜(4 582260 890998)はジャパンローヤルゼリー株式会社(東京)から供与された。
Drugs Used 1) Royal Jelly RJ raw milk 20050407 was provided by Japan Royal Jelly Co., Ltd. (Tokyo).
2) Imperial honey Yahashi pure honey (4 582260 890998) was provided by Japan Royal Jelly Co., Ltd. (Tokyo).
方法
1) 皇蜜およびローヤルゼリー溶液の調整
 皇蜜溶液は20%w/v(200mg/ml)となるようにリン酸緩衝生理食塩液(PBS)、またはポルフィロモナス・ジンジバリス用ブレインハートインフージョン(BHI)培地に溶解した後、0.22μmフィルターにて濾過滅菌し調製した。ローヤルゼリー溶液は50%w/vになるようにPBS中に懸濁し、4℃、12,000rpmで10分間遠心分離し、上清を0.22μmフィルターにて濾過滅菌し調製した。
2) ポルフィロモナス・ジンジバリスに対する皇蜜およびローヤルゼリーの最少発育阻止濃度(minimum inhibitory concentration;MIC)測定
 ポルフィロモナス・ジンジバリスに対する皇蜜およびローヤルゼリーのMICを96ウェルマイクロプレートを用い、連続希釈法により測定した。
3)、皇蜜とローヤルゼリー(RJ)の協力作用
 ローヤルゼリ(RJ)0、1、2、3、および5%と皇蜜0、2.5、5、10、20%を含有するポルフィロモナス・ジンジバリス用ブレインハートインフージョンを作成し、96ウェルマイクロプレートを用い測定した。
Method 1) Preparation of honey and royal jelly solution The honey solution is 20% w / v (200 mg / ml) in phosphate buffered saline (PBS) or Brain Heart Infusion for Porphyromonas gingivalis ( (BHI) After being dissolved in a medium, the solution was sterilized by filtration through a 0.22 μm filter. The royal jelly solution was suspended in PBS to 50% w / v, centrifuged at 12,000 rpm at 4 ° C. for 10 minutes, and the supernatant was sterilized by filtration through a 0.22 μm filter.
2) Minimum inhibitory concentration (MIC) measurement of honey and royal jelly against Porphyromonas gingivalis MIC of honey and royal jelly against Porphyromonas gingivalis was measured by serial dilution method using 96-well microplate. did.
3) Co-operation of honey and royal jelly (RJ) Porphyromonas containing 0, 1, 2, 3, and 5% royal jelly (RJ) and 0, 2.5, 5, 10, 20% honey A brain heart infusion for Gingivalis was prepared and measured using a 96-well microplate.
結果
 連続希釈法にてポルフィロモナス・ジンジバリスに対するMICを測定した。その結果陽性対照のABPCのMICは0.25μg/ml、皇蜜のMICは50mg/mlであった(図1)。 なお、この皇蜜溶液のpHは6.74であった。
 次に、皇蜜とローヤルゼリー(RJ)の協力作用を検討した。その結果ローヤルゼリーが1%以上存在することにより皇蜜5%で完全にポルフィロモナス・ジンジバリスを死滅させることができた。ローヤルゼリーが5%存在する場合には、皇蜜2.5%で完全にポルフィロモナス・ジンジバリスを死滅させることができた。なお、ローヤルゼリーが存在しない場合には、皇蜜10%で完全にポルフィロモナス・ジンジバリスを死滅させることができた。
Results MIC against Porphyromonas gingivalis was measured by a serial dilution method. As a result, the MIC of ABPC as a positive control was 0.25 μg / ml, and the MIC of honey was 50 mg / ml (FIG. 1). The pH of this honey solution was 6.74.
Next, we examined the cooperation between honey and royal jelly (RJ). As a result, it was possible to completely kill Porphyromonas gingivalis with 5% of honey by the presence of 1% or more of royal jelly. When 5% of royal jelly was present, Porphyromonas gingivalis could be completely killed with 2.5% of honey. In the absence of royal jelly, Porphyromonas gingivalis could be completely killed with 10% of honey.

Claims (2)

  1.  ヤハシハチミツ及び/又はローヤルゼリーを含む、ポルフィロモナス・ジンジバリス除菌剤。 Porphyromonas gingivalis disinfectant containing yahashi honey and / or royal jelly.
  2.  ヤハシハチミツ及び/又はローヤルゼリーを含む、歯周疾患の予防又は改善剤。 ¡A preventive or ameliorating agent for periodontal disease, including honey honey and / or royal jelly.
PCT/JP2013/052701 2012-02-10 2013-02-06 Bactericide WO2013118759A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005314266A (en) * 2004-04-28 2005-11-10 Sangi Co Ltd Oral composition
JP2007277210A (en) * 2006-04-04 2007-10-25 Masami Kanda Periodontitis curative agent with manuka honey as main ingredient and supplement
WO2008133098A1 (en) * 2007-04-16 2008-11-06 Kikuji Yamaguchi Eradicating agent for helicobacter pylori

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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