WO2024057898A1 - Prophylactic or preventive agent, antibacterial agent, and oral composition - Google Patents
Prophylactic or preventive agent, antibacterial agent, and oral composition Download PDFInfo
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- WO2024057898A1 WO2024057898A1 PCT/JP2023/031000 JP2023031000W WO2024057898A1 WO 2024057898 A1 WO2024057898 A1 WO 2024057898A1 JP 2023031000 W JP2023031000 W JP 2023031000W WO 2024057898 A1 WO2024057898 A1 WO 2024057898A1
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- oral
- honey
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- bacteria
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- 239000003242 anti bacterial agent Substances 0.000 title claims abstract description 24
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Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/63—Arthropods
- A61K35/64—Insects, e.g. bees, wasps or fleas
- A61K35/644—Beeswax; Propolis; Royal jelly; Honey
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/13—Coniferophyta (gymnosperms)
- A61K36/15—Pinaceae (Pine family), e.g. pine or cedar
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9755—Gymnosperms [Coniferophyta]
- A61K8/9767—Pinaceae [Pine family], e.g. pine or cedar
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
- A61Q11/02—Preparations for deodorising, bleaching or disinfecting dentures
Definitions
- the present invention relates to a prophylactic or therapeutic agent for diseases caused by oral bacteria, an antibacterial agent, and an oral composition containing the prophylactic or therapeutic agent or the antibacterial agent.
- Periodontal disease is a disease accompanied by symptoms that cause inflammation in the periodontal tissue, such as gingivitis or alveolar pyorrhea.
- Oral bacteria that cause periodontal disease include Prevotella intermedia, Tannerella forsythensis, and Treponema denticola.
- the disease's red complex (the most important periodontal pathogen) is Prophyromonas gingivalis (hereinafter referred to as "gingivalis bacterium"). Plaque control is useful for preventing periodontal disease.
- Some periodontal diseases are not caused by plaque, and if the disease becomes severe, chemotherapy with antibiotics must be taken.
- Non-Patent Document 1 Bacillus subtilis
- Patent Document 1 discloses that an oral composition containing Streptococcus faecalis exhibits a selective effect on periodontal disease-related bacteria, Gingivalis, and inhibits oral flora. It is proposed to lead to a good environment.
- Patent Document 2 Yahashi honey and/or royal jelly exhibits a bactericidal effect on P. gingivalis and serves as an agent for preventing or improving periodontal disease. It has also been reported that Manuka honey has a higher antibacterial effect against Gingivalis bacteria than general flower honey (Non-Patent Document 5).
- Naoyuki Ishida et al. Periodontal disease worsens Alzheimer's disease, Journal of Periodontology 2018; 60: 147-152 Gaetti-Jardim, E. Jr, et al., Quantitative detection of periodontopathic bacteria in atherosclerotic plaques from coronary arteries., Journal of Medical Microbiology, 2009; 58: 1568-1575. Dorn, B. R., et al., Porphyromonas gingivalis Traffics toAutophagosomes in Human Coronary Artery Endothelial Cells., Infection and Immunity, 2001; 69: 5698-5708.
- the purpose of the present invention is to provide a new preventive or therapeutic agent for diseases caused by oral bacteria, and a new antibacterial agent for oral bacteria.
- the present invention uses honeydew honey as an active ingredient to suppress the growth of oral bacteria such as Gingivalis at a lower concentration than general flower honey. We have discovered that this can be done, and have completed the present invention.
- the present invention is a preventive or therapeutic agent for diseases caused by oral bacteria, wherein the disease is one or more selected from periodontal disease, tooth decay, bad breath, dementia, diabetes, and arteriosclerosis.
- This is a disease preventive or therapeutic agent containing honeydew honey as an active ingredient.
- Yet another invention is an antibacterial agent against oral bacteria that contains honeydew honey as an active ingredient.
- the oral bacterium can be Porphyromonas gingivalis.
- honeydew honey is a disease preventive or therapeutic agent and an antibacterial agent derived from pine trees, and toothpastes, mouth washes, liniments, mouth sprays, etc. containing the disease preventive or therapeutic agent and the antibacterial agent, Patch preparations, sheet preparations, oral sustained release preparations, chewing agents, oral dissolving agents, oral disintegrating agents, denture care agents, tongue care agents, mouth fresheners, troches, gargles, food compositions, supplements, and This is an oral composition selected from drinks.
- Honeydew honey is a natural substance that has already been consumed as a food all over the world, and has excellent antibacterial activity at low concentrations against oral bacteria such as Gingivalis bacteria. Therefore, when the present invention is used, the risk of emergence of resistant bacteria is low, and it is very useful for suppressing the growth of oral bacteria such as P. gingivalis and for preventing or treating diseases related to oral bacteria such as P. gingivalis. .
- the antibacterial agent refers to a composition that can inhibit the growth of oral bacteria such as Porphyromonas gingivalis, which is said to be the most important periodontal pathogen for periodontal disease.
- the antibacterial agent of the present invention can be used for the prevention or treatment of diseases associated with oral bacteria such as P. gingivalis.
- honeydew honey used as an active ingredient in the present invention is also called “honeydew honey” and “honeydew honey”, and is a tree-derived honey that is also called “forest honey” in Europe.
- Honeydew honey is made by bees collecting high-sugar honeydew secreted by aphids and scale insects that feed on tree sap.
- the main trees used are pine trees, oaks, linden trees, acacias, leatherwoods, horse chestnuts, oaks, firs, etc., and are mainly produced in Europe and parts of Asia. In Japan, much of the ⁇ island honey'' produced in the Ogasawara Islands is honeydew honey. It is generally known as a rare honey rich in minerals and polyphenols.
- honeydew honey as an active ingredient.
- honeydew honey is not particularly limited as long as it is honeydew honey, but pine honey derived from pine trees is preferred, and pine honey from Greece or Turkey is more preferred.
- the disease prevention or treatment agent and antibacterial agent of the present invention contain honey as an active ingredient, they can be generally used with any food material, such as milk, coffee, drinks such as tea and fruit juice, and milk such as yogurt. It can be added as a seasoning to products, foods such as bread and sandwiches, and various dishes such as curry.
- the preventive or therapeutic agent for diseases and the antibacterial agent of the present invention include toothpastes, mouth washes, liniments, mouth sprays, patches, sheets, oral sustained release agents, chewing agents, oral dissolving agents, oral It can be used as an oral composition selected from internally disintegrating agents, denture care agents, tongue care agents, mouth fresheners, troches, gargles, food compositions, supplements, and drinks.
- the disease preventive or therapeutic agent and antibacterial agent of the present invention may be in any form such as solid, liquid, or paste, and may be in the form of tablets, capsules, pills, powders, fine granules, granules, liquids, etc. It may be a form.
- These preparations contain pharmacologically or physiologically acceptable additives (e.g., excipients, lubricants, binders, disintegrants, stabilizers, suspending agents, emulsifiers, solubilizing agents, etc.). They can also be produced by mixing.
- the disease preventive or therapeutic agent and antibacterial agent of the present invention can be used as pharmaceuticals, quasi-drugs, cosmetics, foods, feeds, or components thereof.
- honeydew honey is preferably used in an amount of 0.01 to 100 g per day for an adult.
- honeydew honey is blended in an amount of 1 to 80% by weight based on the total mass. It is preferable that Further, in the case of a paste or a liquid, the concentration of honeydew honey is preferably blended in a range of 0.01 to 80% by weight based on the total weight.
- the disease preventive or therapeutic agent and antibacterial agent of the present invention may be blended so that honeydew honey is present in the saliva of a person or animal in a range of 2 to 100 mg/ml immediately after oral ingestion. preferable.
- the disease preventive or therapeutic agent and antibacterial agent of the present invention include various additives, for example, in the case of foods, various nutrients, various vitamins, minerals, flavonoids, polyphenols, amino acids, dietary fiber, polyunsaturated Stabilizers such as fatty acids, dispersants, and emulsifiers, colorants, fragrances, sweeteners, taste components, flavors, other honey components, royal jelly, propolis, and the like can be blended.
- various additives for example, in the case of foods, various nutrients, various vitamins, minerals, flavonoids, polyphenols, amino acids, dietary fiber, polyunsaturated Stabilizers such as fatty acids, dispersants, and emulsifiers, colorants, fragrances, sweeteners, taste components, flavors, other honey components, royal jelly, propolis, and the like can be blended.
- the disease preventive or therapeutic agent and antibacterial agent of the present invention are highly safe and can eliminate oral bacteria such as Gingivalis bacteria at low concentrations, so they are effective against various diseases caused by oral bacteria such as Gingivalis bacteria. It can be used for prevention or treatment.
- Diseases caused by oral bacteria such as C. gingivalis include periodontal disease, tooth decay, bad breath, dementia, diabetes, and arteriosclerosis. It also includes complications caused by these diseases.
- Porphyromonas gingivalis JCM 12257) and Porphyromonas gingivalis (ATCC 49417) were inoculated onto NV-added ABHK agar medium (manufactured by Nissui Pharmaceutical Co., Ltd.), and after culturing at 37°C under anaerobic conditions for 7 days, using physiological saline, The test bacteria solution was prepared so that the number of bacteria was 10 8 /mL. The test bacterial solution was inoculated into a modified GAM liquid medium (manufactured by Nissui Pharmaceutical Co., Ltd.) and cultured at 37°C under anaerobic conditions for 4 days. After culturing for 4 days, the presence or absence of bacterial growth was visually observed to determine the MIC (minimum inhibitory concentration).
- MIC minimum inhibitory concentration
- New Zealand Manuka Honey 573+/UMF16+ which is flower honey, was mixed into the liquid medium at a concentration of 20% by weight. Using this as a test sample, a total of 10 2-fold dilution series were prepared using a liquid medium. The results are shown in Table 1. The MIC for JCM 12257 was 2.5% by weight and the MIC for ATCC 49417 was 2.5% by weight.
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- Oral & Maxillofacial Surgery (AREA)
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Abstract
[Problem] To provide an antibacterial agent that is highly safe and inhibits, at a low concentration, the growth of oral bacteria such as Porphyromonas gingivalis causative of various diseases. [Solution] By using honeydew honey as an active ingredient, a composition, which efficiently inhibits the growth of oral bacteria such as Porphyromonas gingivalis and prevents or treats diseases caused by the oral bacteria such as periodontal disease, tooth decay, halitosis, dementia, diabetes and arteriosclerosis, has been found.
Description
本発明は、口腔細菌を原因とする疾患の予防又は治療剤、及び抗菌剤、並びに予防若しくは治療剤又は抗菌剤を含有する口腔用組成物に関する。
The present invention relates to a prophylactic or therapeutic agent for diseases caused by oral bacteria, an antibacterial agent, and an oral composition containing the prophylactic or therapeutic agent or the antibacterial agent.
歯周病は、歯肉炎又は歯槽膿漏等、歯周組織に炎症を引き起こす症状をともなう疾患である。歯周病の原因菌である口腔細菌としては、プレボテラ・インターメディア（Prevotella intermedia）、タンネレラ・フォーサイセンシス（Tannerella forsythensis）、トレポネマ・デンティコラ（Treponema denticola）等が知られているが、慢性歯周病のレッド・コンプレックス（最重要歯周病原細菌）はプロフィロモナス・ジンジバリス（Porphyromonas gingivalis. 以下、「ジンジバリス菌」と記す。）である。歯周病の予防にはプラークコントロールが有用である。歯周病の中には、プラークを原因としないものがあり、重症化した場合には、抗生物質による化学的療法等を受けなくてはならない。患者に投与される薬剤には、副作用として種々の消化器系疾患を誘発する懸念があり、安全な原因菌の除去剤が望まれていた。また、最近では、ジンジバリス菌は、歯周病以外の疾患との関連も多く報告されている。例えば、ジンジバリス菌成分が、アルツハイマー病患者の脳内で検出されたことから、アルツハイマー病を引き起こす一連の事象に関与している可能性が指摘されている（非特許文献１）。また、ジンジバリス菌等の歯周病原因菌が心血管疾患発症の要因である可能性があること（非特許文献２）、及び、ジンジバリス菌が脳梗塞や狭心症、心筋梗塞などを引き起こすアテローム性動脈硬化症という炎症反応を悪化させる可能性があること（非特許文献３）も指摘されている。さらには、歯周病菌の存在と糖尿病発症との強い相関があること（非特許文献４）も報告されている。
Periodontal disease is a disease accompanied by symptoms that cause inflammation in the periodontal tissue, such as gingivitis or alveolar pyorrhea. Oral bacteria that cause periodontal disease include Prevotella intermedia, Tannerella forsythensis, and Treponema denticola. The disease's red complex (the most important periodontal pathogen) is Prophyromonas gingivalis (hereinafter referred to as "gingivalis bacterium"). Plaque control is useful for preventing periodontal disease. Some periodontal diseases are not caused by plaque, and if the disease becomes severe, chemotherapy with antibiotics must be taken. There is a concern that drugs administered to patients may induce various gastrointestinal diseases as side effects, and a safe agent for removing causative bacteria has been desired. Furthermore, recently, there have been many reports that P. gingivalis is associated with diseases other than periodontal disease. For example, since B. gingivalis components have been detected in the brains of Alzheimer's disease patients, it has been pointed out that they may be involved in a series of events that cause Alzheimer's disease (Non-Patent Document 1). In addition, bacteria that cause periodontal disease, such as B. gingivalis, may be a factor in the development of cardiovascular diseases (Non-patent Document 2), and B. gingivalis causes atherogenesis, which causes cerebral infarction, angina pectoris, myocardial infarction, etc. It has also been pointed out that it may aggravate the inflammatory reaction called sexual arteriosclerosis (Non-Patent Document 3). Furthermore, it has been reported that there is a strong correlation between the presence of periodontal disease bacteria and the onset of diabetes (Non-Patent Document 4).
ジンジバリス菌と様々な疾患との関連が指摘される中で、ジンジバリス菌に作用して、上記のような疾患を予防又は治療することのできる予防又は治療剤への需要が高まっている。これに対し、例えば、特許文献１には、ストレプトコッカス・フェカリス（Streptococcus faecalis）菌を含有した口腔用組成物が歯周病関連細菌のジンジバリス菌類に対して選択的な作用を示し、口腔内フローラを良い環境に導くことが提示されている。
As the relationship between the P. gingivalis bacteria and various diseases has been pointed out, there is an increasing demand for preventive or therapeutic agents that can act on the P. gingivalis bacteria and prevent or treat the above-mentioned diseases. On the other hand, for example, Patent Document 1 discloses that an oral composition containing Streptococcus faecalis exhibits a selective effect on periodontal disease-related bacteria, Gingivalis, and inhibits oral flora. It is proposed to lead to a good environment.
ジンジバリス菌に作用して効果を発揮する成分をハチミツ類に限定すると、ヤハシハチミツ及び／又はローヤルゼリーがジンジバリス菌の除菌作用を示し、歯周疾患の予防又は改善剤となることが報告されている（特許文献２）。また、マヌカハニーはジンジバリス菌に対する抗菌作用が、一般的な花ハチミツよりも高いことも報告されている（非特許文献５）。
If we limit the ingredients that are effective against P. gingivalis to honey, it has been reported that Yahashi honey and/or royal jelly exhibits a bactericidal effect on P. gingivalis and serves as an agent for preventing or improving periodontal disease ( Patent Document 2). It has also been reported that Manuka honey has a higher antibacterial effect against Gingivalis bacteria than general flower honey (Non-Patent Document 5).
本発明は、口腔細菌を原因とする疾患に対する新規の予防又は治療剤、及び口腔細菌に対する新規の抗菌剤を提供することを目的とする。
The purpose of the present invention is to provide a new preventive or therapeutic agent for diseases caused by oral bacteria, and a new antibacterial agent for oral bacteria.
本発明は、上記課題を解決するために鋭意研究を重ねた結果、甘露ハチミツを有効成分として用いることで、一般的な花ハチミツよりもジンジバリス菌に代表される口腔細菌の増殖を低濃度で抑制できることを見出し、本発明を完成するに至った。
As a result of intensive research to solve the above problems, the present invention uses honeydew honey as an active ingredient to suppress the growth of oral bacteria such as Gingivalis at a lower concentration than general flower honey. We have discovered that this can be done, and have completed the present invention.
すなわち、本発明は、口腔細菌が原因で発症する疾病の予防又は治療剤であって、前記疾患が、歯周病、虫歯、口臭、認知症、糖尿病、動脈硬化症から選択される１種以上である、甘露ハチミツを有効成分とする疾病の予防又は治療剤である。さらに別の発明は、甘露ハチミツを有効成分とする、口腔細菌に対する抗菌剤である。口腔細菌は、ポルフィロモナス・ジンジバリスであり得る。
That is, the present invention is a preventive or therapeutic agent for diseases caused by oral bacteria, wherein the disease is one or more selected from periodontal disease, tooth decay, bad breath, dementia, diabetes, and arteriosclerosis. This is a disease preventive or therapeutic agent containing honeydew honey as an active ingredient. Yet another invention is an antibacterial agent against oral bacteria that contains honeydew honey as an active ingredient. The oral bacterium can be Porphyromonas gingivalis.
また、本発明は、甘露ハチミツが、松の木由来である疾病の予防又は治療剤及び抗菌剤であり、疾病の予防又は治療剤及び抗菌剤を含む歯磨き剤、洗口剤、塗布剤、マウススプレー、貼付剤、シート剤、口腔内徐放剤、咀嚼剤、口腔内溶解剤、口腔内崩壊剤、義歯ケア剤、舌ケア剤、口中清涼剤、トローチ剤、含嗽剤、食品組成物、サプリメント、及びドリンク剤から選ばれる口腔用組成物である。
In addition, the present invention provides that honeydew honey is a disease preventive or therapeutic agent and an antibacterial agent derived from pine trees, and toothpastes, mouth washes, liniments, mouth sprays, etc. containing the disease preventive or therapeutic agent and the antibacterial agent, Patch preparations, sheet preparations, oral sustained release preparations, chewing agents, oral dissolving agents, oral disintegrating agents, denture care agents, tongue care agents, mouth fresheners, troches, gargles, food compositions, supplements, and This is an oral composition selected from drinks.
甘露ハチミツは、すでに食品として全世界で食経験のある天然物質であり、ジンジバリス菌等の口腔細菌に対して低濃度で優れた抗菌作用を有している。したがって、本発明を用いた場合では、耐性菌出現のリスクが低く、ジンジバリス菌等の口腔細菌の増殖の抑制や、ジンジバリス菌等の口腔細菌に関連する疾患の予防または治療に非常に有用である。
Honeydew honey is a natural substance that has already been consumed as a food all over the world, and has excellent antibacterial activity at low concentrations against oral bacteria such as Gingivalis bacteria. Therefore, when the present invention is used, the risk of emergence of resistant bacteria is low, and it is very useful for suppressing the growth of oral bacteria such as P. gingivalis and for preventing or treating diseases related to oral bacteria such as P. gingivalis. .
以下、本発明の好適な実施形態について詳細に説明する。ただし、本発明は以下の実施形態に限定されるものではない。
Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.
本発明において、抗菌剤とは、歯周病の最重要歯周病原細菌であると言われているポルフィロモナス・ジンジバリス等の口腔細菌の増殖を抑制することができる組成物を意味する。本発明の抗菌剤は、ジンジバリス菌等の口腔細菌に関連する疾患の予防又は治療のために用いることができる。
In the present invention, the antibacterial agent refers to a composition that can inhibit the growth of oral bacteria such as Porphyromonas gingivalis, which is said to be the most important periodontal pathogen for periodontal disease. The antibacterial agent of the present invention can be used for the prevention or treatment of diseases associated with oral bacteria such as P. gingivalis.
本発明において有効成分として用いられる甘露ハチミツは、別名として「甘露蜜」、「ハニーデューハニー」と呼ばれ、ヨーロッパでは「森の蜜」とも呼ばれる樹木由来のハチミツである。甘露ハチミツは、樹液を食べるアブラムシやカイガラムシが分泌する糖分の高い甘露をミツバチが集めて作られたものである。利用される主な樹木は、松の木、オーク、菩提樹、アカシア、レザーウッド、トチ、樫の木、もみの木などであり、主にヨーロッパやアジアの一部で生産されている。国内では、小笠原諸島で生産されている「島ハチミツ」の多くが甘露ハチミツである。一般的には、ミネラルやポリフェノールが豊富な希少なハチミツとして知られている。
The honeydew honey used as an active ingredient in the present invention is also called "honeydew honey" and "honeydew honey", and is a tree-derived honey that is also called "forest honey" in Europe. Honeydew honey is made by bees collecting high-sugar honeydew secreted by aphids and scale insects that feed on tree sap. The main trees used are pine trees, oaks, linden trees, acacias, leatherwoods, horse chestnuts, oaks, firs, etc., and are mainly produced in Europe and parts of Asia. In Japan, much of the ``island honey'' produced in the Ogasawara Islands is honeydew honey. It is generally known as a rare honey rich in minerals and polyphenols.
本発明の疾患の予防又は治療剤及び抗菌剤は、甘露ハチミツを有効成分とする。ハチミツには、花の蜜をミツバチが集めて作る花ハチミツと、樹木由来の樹液を食べる昆虫が分泌する甘露をミツバチが集めて作る甘露ハチミツの、大きく分けて２種類が存在する。本発明では、甘露ハチミツであれば特に限定はされないが、松の木由来のパインハニーが好ましく、ギリシャ産もしくはトルコ産のパインハニーがさらに好ましい。
The disease preventive or therapeutic agent and antibacterial agent of the present invention contain honeydew honey as an active ingredient. There are two main types of honey: flower honey, which is made by bees collecting nectar from flowers, and honeydew honey, which is made by bees collecting honeydew secreted by insects that feed on tree sap. In the present invention, honeydew honey is not particularly limited as long as it is honeydew honey, but pine honey derived from pine trees is preferred, and pine honey from Greece or Turkey is more preferred.
本発明の疾患の予防又は治療剤及び抗菌剤は、ハチミツを有効成分としているため、一般的な使用方法として任意の食品素材、例えば、牛乳、コーヒー、紅茶や果汁等の飲料、ヨーグルト等の乳製品、パンやサンドウィッチ等の食品、カレーなど各種料理に調味料として添加して用いることができる。
Since the disease prevention or treatment agent and antibacterial agent of the present invention contain honey as an active ingredient, they can be generally used with any food material, such as milk, coffee, drinks such as tea and fruit juice, and milk such as yogurt. It can be added as a seasoning to products, foods such as bread and sandwiches, and various dishes such as curry.
また、本発明の疾患の予防又は治療剤及び抗菌剤は、歯磨き剤、洗口剤、塗布剤、マウススプレー、貼付剤、シート剤、口腔内徐放剤、咀嚼剤、口腔内溶解剤、口腔内崩壊剤、義歯ケア剤、舌ケア剤、口中清涼剤、トローチ剤、含嗽剤、食品組成物、サプリメント、及びドリンク剤から選ばれる口腔用組成物として用いることができる。
In addition, the preventive or therapeutic agent for diseases and the antibacterial agent of the present invention include toothpastes, mouth washes, liniments, mouth sprays, patches, sheets, oral sustained release agents, chewing agents, oral dissolving agents, oral It can be used as an oral composition selected from internally disintegrating agents, denture care agents, tongue care agents, mouth fresheners, troches, gargles, food compositions, supplements, and drinks.
本発明の疾病の予防又は治療剤及び抗菌剤は、固体、液体、ペースト等のいずれの形態であっても良く、タブレット、カプセル剤、丸剤、散剤、細粒剤、顆粒剤、液剤等の形態であっても良い。これらの製剤は、薬理学的又は生理学的に許容される添加物（例えば、賦形剤、滑沢剤、結合剤、崩壊剤、安定剤、懸濁化剤、乳化剤、溶解補助剤等）を混合して製造することもできる。
The disease preventive or therapeutic agent and antibacterial agent of the present invention may be in any form such as solid, liquid, or paste, and may be in the form of tablets, capsules, pills, powders, fine granules, granules, liquids, etc. It may be a form. These preparations contain pharmacologically or physiologically acceptable additives (e.g., excipients, lubricants, binders, disintegrants, stabilizers, suspending agents, emulsifiers, solubilizing agents, etc.). They can also be produced by mixing.
本発明の疾病の予防又は治療剤及び抗菌剤は、医薬品、医薬部外品、化粧品、食品、飼料又はそれらの成分などとして使用することができる。
The disease preventive or therapeutic agent and antibacterial agent of the present invention can be used as pharmaceuticals, quasi-drugs, cosmetics, foods, feeds, or components thereof.
さらに、本発明の疾患の予防又は治療剤及び抗菌剤においては、甘露ハチミツが、成人１日当たりの摂取量が０.０１～１００ｇとなるように用いられることが好ましい。疾患の予防剤又は治療剤及び抗菌剤が、錠剤、トローチ剤、顆粒、ガム、グミ等の固形の形態の場合は、甘露ハチミツが、総質量に対して１～８０重量％の範囲で配合されることが好ましい。また、ペースト、液状の場合に、甘露ハチミツの濃度が、総重量に対して０．０１～８０重量％の範囲で配合されることが好ましい。さらに、本発明の疾患の予防剤又は治療剤及び抗菌剤を経口摂取した直後の人又は動物の唾液中に、甘露ハチミツが２～１００ｍｇ/ｍｌの範囲で存在するように配合することが、さらに好ましい。
Furthermore, in the disease prevention or treatment agent and antibacterial agent of the present invention, honeydew honey is preferably used in an amount of 0.01 to 100 g per day for an adult. When the disease preventive or therapeutic agent and antibacterial agent are in solid form such as tablets, lozenges, granules, gums, gummies, etc., honeydew honey is blended in an amount of 1 to 80% by weight based on the total mass. It is preferable that Further, in the case of a paste or a liquid, the concentration of honeydew honey is preferably blended in a range of 0.01 to 80% by weight based on the total weight. Furthermore, the disease preventive or therapeutic agent and antibacterial agent of the present invention may be blended so that honeydew honey is present in the saliva of a person or animal in a range of 2 to 100 mg/ml immediately after oral ingestion. preferable.
本発明の疾患の予防又は治療剤及び抗菌剤には種々の添加物、例えば食品の場合には、各種栄養素、種々のビタミン、ミネラル、フラボノイド類、ポリフェノール類、アミノ酸、食物繊維、多価不飽和脂肪酸、分散剤、及び乳化剤等の安定剤、着色料、香料、甘味料、呈味成分、フレーバー、その他のハチミツ成分、ローヤルゼリー、プロポリス等を配合することができる。
The disease preventive or therapeutic agent and antibacterial agent of the present invention include various additives, for example, in the case of foods, various nutrients, various vitamins, minerals, flavonoids, polyphenols, amino acids, dietary fiber, polyunsaturated Stabilizers such as fatty acids, dispersants, and emulsifiers, colorants, fragrances, sweeteners, taste components, flavors, other honey components, royal jelly, propolis, and the like can be blended.
本発明の疾患の予防剤又は治療剤及び抗菌剤は、安全性が高く、低濃度でジンジバリス菌等の口腔細菌を除去することができることから、ジンジバリス菌等の口腔細菌を原因とする各種疾患を予防又は治療するために用いることができる。ジンジバリス菌等の口腔細菌を原因とする疾患としては、歯周病、虫歯、口臭、認知症、糖尿病、動脈硬化症などが挙げられる。また、これら疾患による合併症についても含まれる。
The disease preventive or therapeutic agent and antibacterial agent of the present invention are highly safe and can eliminate oral bacteria such as Gingivalis bacteria at low concentrations, so they are effective against various diseases caused by oral bacteria such as Gingivalis bacteria. It can be used for prevention or treatment. Diseases caused by oral bacteria such as C. gingivalis include periodontal disease, tooth decay, bad breath, dementia, diabetes, and arteriosclerosis. It also includes complications caused by these diseases.
以下、実施例を通じて本発明をさらに詳細に説明する。ただし、本発明の範囲がこれら実施例に限定されるものではない。
Hereinafter, the present invention will be explained in more detail through Examples. However, the scope of the present invention is not limited to these Examples.
Porphyromonas gingivalis (JCM 12257)、及び、Porphyromonas gingivalis (ATCC 49417)をNV加ABHK寒天培地（日水製薬製）に接種し、３７℃、嫌気条件下で７日間培養後、生理食塩水を用いて、菌数が108/mLになるように調製したものを試験菌液とした。変法GAM液体培地（日水製薬製）に試験菌液を接種し、３７℃、嫌気条件で４日間培養した。４日間の培養後、菌の発育有無を肉眼で観察して、ＭＩＣ（最少発育阻止濃度）を判定した。
Porphyromonas gingivalis (JCM 12257) and Porphyromonas gingivalis (ATCC 49417) were inoculated onto NV-added ABHK agar medium (manufactured by Nissui Pharmaceutical Co., Ltd.), and after culturing at 37°C under anaerobic conditions for 7 days, using physiological saline, The test bacteria solution was prepared so that the number of bacteria was 10 8 /mL. The test bacterial solution was inoculated into a modified GAM liquid medium (manufactured by Nissui Pharmaceutical Co., Ltd.) and cultured at 37°C under anaerobic conditions for 4 days. After culturing for 4 days, the presence or absence of bacterial growth was visually observed to determine the MIC (minimum inhibitory concentration).
甘露ハチミツであるトルコ産松の木由来パインハニーを２０重量％となるように液体培地に混合した。これを試験試料として、液体培地を用いて２倍希釈系列を合計１０段階調製した。その結果を表１、表２、表３に示す。JCM 12257に対するＭＩＣは、０．２６重量％であり、ATCC 49417に対するＭＩＣは０．３１重量％であった。
Pine honey derived from Turkish pine trees, which is honeydew honey, was mixed into the liquid medium at a concentration of 20% by weight. Using this as a test sample, a total of 10 2-fold dilution series were prepared using a liquid medium. The results are shown in Tables 1, 2, and 3. The MIC for JCM 12257 was 0.26% by weight and the MIC for ATCC 49417 was 0.31% by weight.
甘露ハチミツであるギリシャ産オーク由来オークハニーを２０重量％となるように液体培地に混合した。これを試験試料として、液体培地を用いて２倍希釈系列を合計１０段階調製した。その結果を表１に示す。JCM 12257に対するＭＩＣは、０．６２重量％であり、ATCC 49417に対するＭＩＣは０．６２重量％であった。
Oak honey derived from Greek oak, which is honeydew honey, was mixed into the liquid medium at a concentration of 20% by weight. Using this as a test sample, a total of 10 2-fold dilution series were prepared using a liquid medium. The results are shown in Table 1. The MIC for JCM 12257 was 0.62% by weight and the MIC for ATCC 49417 was 0.62% by weight.
オーストリア産もみの木由来の甘露ハチミツを２０重量％となるように液体培地に混合した。これを試験試料として、液体培地を用いて２倍希釈系列を合計１０段階調製した。その結果を表１に示す。JCM 12257に対するＭＩＣは、０．３１重量％であり、ATCC 49417に対するＭＩＣは０．６２重量％であった。
Honeydew honey derived from Austrian fir trees was mixed into the liquid medium at a concentration of 20% by weight. Using this as a test sample, a total of 10 2-fold dilution series were prepared using a liquid medium. The results are shown in Table 1. The MIC for JCM 12257 was 0.31% by weight and the MIC for ATCC 49417 was 0.62% by weight.
花ハチミツである国内産アカシアハチミツを２０重量％となるように液体培地に混合した。これを試験試料として、液体培地を用いて２倍希釈系列を合計１０段階調製した。その結果を表１に示す。JCM 12257に対するＭＩＣは、５重量％であり、ATCC 49417に対するＭＩＣは５重量％であった。
Domestic acacia honey, which is flower honey, was mixed into the liquid medium at a concentration of 20% by weight. Using this as a test sample, a total of 10 2-fold dilution series were prepared using a liquid medium. The results are shown in Table 1. The MIC for JCM 12257 was 5% by weight and the MIC for ATCC 49417 was 5% by weight.
花ハチミツであるニュージーランド産マヌカハニー５７３＋／ＵＭＦ１６＋を２０重量％となるように液体培地に混合した。これを試験試料として、液体培地を用いて２倍希釈系列を合計１０段階調製した。その結果を表１に示す。JCM 12257に対するＭＩＣは、２．５重量％であり、ATCC 49417に対するＭＩＣは２．５重量％であった。
New Zealand Manuka Honey 573+/UMF16+, which is flower honey, was mixed into the liquid medium at a concentration of 20% by weight. Using this as a test sample, a total of 10 2-fold dilution series were prepared using a liquid medium. The results are shown in Table 1. The MIC for JCM 12257 was 2.5% by weight and the MIC for ATCC 49417 was 2.5% by weight.
Claims (8)
- 口腔細菌が原因で発症する疾病の予防又は治療剤であって、前記疾患が、歯周病、虫歯、口臭、認知症、糖尿病、及び動脈硬化症から選択される１又は複数であり、甘露ハチミツを有効成分とする疾病の予防又は治療剤。 A preventive or therapeutic agent for diseases caused by oral bacteria, wherein the disease is one or more selected from periodontal disease, tooth decay, bad breath, dementia, diabetes, and arteriosclerosis, and honeydew honey A preventive or therapeutic agent for diseases containing as an active ingredient.
- 前記口腔細菌がポルフィロモナス・ジンジバリスである、請求項１に記載の予防又は治療剤。 The prophylactic or therapeutic agent according to claim 1, wherein the oral bacterium is Porphyromonas gingivalis.
- 前記甘露ハチミツが、松の木由来である請求項２に記載の予防又は治療剤。 The preventive or therapeutic agent according to claim 2, wherein the honeydew honey is derived from a pine tree.
- 甘露ハチミツを有効成分とする、口腔細菌に対する抗菌剤。 An antibacterial agent against oral bacteria that contains honeydew honey as an active ingredient.
- 前記口腔細菌がポルフィロモナス・ジンジバリスである請求項４に記載の抗菌剤。 The antibacterial agent according to claim 4, wherein the oral bacterium is Porphyromonas gingivalis.
- 前記甘露ハチミツが、松の木由来である請求項５に記載の抗菌剤。 The antibacterial agent according to claim 5, wherein the honeydew honey is derived from pine trees.
- 甘露ハチミツを有効成分として含み、口腔細菌の増殖を抑制するための口腔用組成物であり、前記口腔用組成物が、歯磨き剤、洗口剤、塗布剤、マウススプレー、貼付剤、シート剤、口腔内徐放剤、咀嚼剤、口腔内溶解剤、口腔内崩壊剤、義歯ケア剤、舌ケア剤、口中清涼剤、トローチ剤、含嗽剤、食品組成物、サプリメント、及びドリンク剤から選ばれる、口腔用組成物。 An oral composition containing honeydew honey as an active ingredient and for inhibiting the growth of oral bacteria, the oral composition comprising a toothpaste, a mouthwash, a liniment, a mouth spray, a patch, a sheet, selected from oral sustained release agents, chewing agents, oral dissolving agents, oral disintegrating agents, denture care agents, tongue care agents, mouth fresheners, troches, gargles, food compositions, supplements, and drink preparations, Oral composition.
- 前記口腔細菌がポルフィロモナス・ジンジバリスである、請求項７に記載の口腔用組成物。
The oral composition according to claim 7, wherein the oral bacterium is Porphyromonas gingivalis.
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Non-Patent Citations (4)
| Title |
|---|
| BOGDANOV S: "Nature and origin of the antibacterial substances in honey", LWT- FOOD SCIENCE AND TECHNOLOGY, ACADEMIC PRESS, UNITED KINGDOM, vol. 30, no. 7, 1 January 1997 (1997-01-01), United Kingdom , pages 748 - 753, XP003018432, ISSN: 0023-6438, DOI: 10.1006/fstl.1997.0259 * |
| BUCEKOVA MARCELA, BURIOVA MONIKA, PEKARIK LADISLAV, MAJTAN VIKTOR, MAJTAN JURAJ: "Phytochemicals-mediated production of hydrogen peroxide is crucial for high antibacterial activity of honeydew honey", SCIENTIFIC REPORTS, NATURE PUBLISHING GROUP, US, vol. 8, no. 1, 13 June 2018 (2018-06-13), US , pages 9061, XP093146280, ISSN: 2045-2322, DOI: 10.1038/s41598-018-27449-3 * |
| DINKOV DINKO: "The antibacterial activity of acacia, multifloral and oak honeydew honeys", INTERNATIONAL JOURNAL OF VETERINARY SCIENCES AND ANIMAL HUSBANDRY, vol. 1, no. 2, 1 January 2016 (2016-01-01), pages 7 - 10, XP093146287, ISSN: 2456-2912 * |
| NODA MITSUHIRO, MASATSUGU YAMAMURA, ICHIO TAKASE, SHOJIRO ASAI, TOSHIHIKO UMEMOTO, ISAMU NAMIKAWA: "Characteristics of Staphylococcus aureus isolated from the oral and nasal cavities of healthy young adults", JPN. J. ORAL BIOL, vol. 36, 1 January 1994 (1994-01-01), pages 263 - 273, XP093146289 * |
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