WO2013035333A1 - 口腔用組成物 - Google Patents
口腔用組成物 Download PDFInfo
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- WO2013035333A1 WO2013035333A1 PCT/JP2012/005662 JP2012005662W WO2013035333A1 WO 2013035333 A1 WO2013035333 A1 WO 2013035333A1 JP 2012005662 W JP2012005662 W JP 2012005662W WO 2013035333 A1 WO2013035333 A1 WO 2013035333A1
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- extract
- plant
- biofilm formation
- biofilm
- acid
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
- A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
- A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
- A23G3/48—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing plants or parts thereof, e.g. fruits, seeds, extracts
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G4/00—Chewing gum
- A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
- A23G4/068—Chewing gum characterised by the composition containing organic or inorganic compounds containing plants or parts thereof, e.g. fruits, seeds, extracts
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
- A23L2/02—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof containing fruit or vegetable juices
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
- A23L2/52—Adding ingredients
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- 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
- A61K36/11—Pteridophyta or Filicophyta (ferns)
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- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
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- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0204—Specific forms not provided for by any of groups A61K8/0208 - A61K8/14
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0216—Solid or semisolid forms
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- 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
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
- A61K9/0058—Chewing gums
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/92—Oral administration
Definitions
- the present invention relates to an oral composition having an action of inhibiting the formation of Actinomyces naeslundii (hereinafter referred to as “A. naeslundii”) biofilm by a plant extract.
- A. naeslundii Actinomyces naeslundii
- microorganisms attached to the surface of the object do not exist alone, but form a biofilm with other microorganisms in a characteristic structure. If this biofilm is beneficial to humans as seen in the use of immobilized microorganisms, it has become clear that it causes caries and food contamination, and has been actively studied in recent years.
- the oral biofilm is composed of more than 700 kinds of bacteria, and 10 8 or more bacteria exist in 1 mg.
- A. naeslundii has recently attracted attention as a key microorganism in the transition from early plaques (caries plaques) to late plaques (periodontal disease plaques).
- Periodontal disease prevention In conventional periodontal disease prevention, the idea of killing periodontal pathogens such as Porphyromonas gingivalis (hereinafter referred to as “P. gingivalis”) and suppressing periodontal disease was the mainstream, but the actual periodontal lesions are Because it exists with the biofilm in the deep part of the periodontal pocket and prevents the penetration of antibacterial substances, it often fails to achieve the desired effect and is always next to the risk of the appearance of resistant bacteria. Therefore, a safer and more effective prevention method has been desired.
- P. gingivalis Porphyromonas gingivalis
- Short-chain fatty acids such as butyric acid are known to be present in high concentrations in periodontal pockets and dental plaques of patients with periodontal disease, and are involved in the development and progression of periodontal disease It is shown.
- acids such as SCFA produced by periodontal pathogens such as P. gingivalis have been confirmed to promote biofilm formation by A. naeslundii, and elucidation of the mechanism targeting this phenomenon and research on the control of pathogenic expression. (Nihon University School of Dentistry, National Institute of Infectious Diseases).
- Patent Document 1 is an example of a composition for oral cavity that exhibits antibacterial effects and gingivitis improving effects of oral biofilms.
- Patent Document 1 is characterized by containing (A) N-acyl sarcosine or a salt thereof and (B) benzylisothiocyanate, and having a mass ratio of (A) / (B) of 0.5 to 20. It is disclosed that the oral composition is excellent in the antibacterial effect and gingivitis improving effect of the oral biofilm which is the cause of oral diseases. However, no effect on periodontal disease is disclosed or suggested.
- A. naeslundii which is induced by acids, is extracted from extracts of cruciferous plants, mizuna, komatsuna, pungent radish, and pepper, as well as arachnid plants, arachnid, and vermicaceae. And the present invention was completed. Biofilm formation of A. naeslundii is increased by acid stimulation, but it was found that when 1000 ppm of the above plant was added to the culture system, biofilm formation was reduced to about 30%. At this time, since each plant extract did not affect the growth of A. naeslundii, this biofilm formation inhibitory effect is considered to be a mechanism different from the antibacterial action. A.
- naeslundii is a Gram-positive gonococci found in gingivitis and root caries sites and is said to be the causative bacterium of early periodontal disease. Because it co-aggregates with streptococci and periodontal pathogens, it is considered to be a key bacterium for the transition of flora to periodontal disease plaques, and controlling A. naeslundii will lead to effective periodontal disease prevention It is done. The present inventors have confirmed that biofilm formation is increased by the acid produced by oral bacteria.
- the present invention is a preventive agent for periodontal disease from a new point of view, and has advantages such as a low risk of appearance of resistant bacteria as compared with existing antibacterial agents.
- the present invention prevents periodontal disease by inhibiting the periodontal disease biofilm formed by A. naeslundii, an early periodontal pathogen, and the periodontal disease biofilm inhibitor is used as a mizuna, komatsuna, pungent radish, etc. It was found in a part of the cruciferous plant and an extract of the Taranoki ice plant.
- the present invention relates to an oral composition containing a plant extract, and the plant extract is a hot water extract of komatsuna, mizuna, fresh greens, pungent radish, cress, kogomi, taranoki, or ice plant.
- the present invention relates to an oral composition.
- the present invention relates to an acid-induced biofilm formation inhibitor containing a plant extract, wherein the plant extract is extracted with hot water from komatsuna, mizuna, fresh green vegetables, pungent radish, cress, kogomi, taranoki, or ice plant.
- the present invention relates to an acid-induced biofilm formation inhibitor.
- the present invention also includes a mouthwash comprising a composition of an oral cavity containing a plant extract that is a hot water extract of komatsuna, mizuna, green rape, pungent radish, cress, kogomi, taranoki, or an ice plant, and a toothpaste.
- a mouthwash comprising a composition of an oral cavity containing a plant extract that is a hot water extract of komatsuna, mizuna, green rape, pungent radish, cress, kogomi, taranoki, or an ice plant, and a toothpaste.
- the present invention relates to foods including agents, inhalants, lozenges, and chewing gum, candy, tablets and the like.
- Example 1 (Extract preparation) Each plant sample was purchased commercially and freeze-dried, and then 1 g was finely pulverized with a pulverizer and extracted with 50 ml of water at 70 ° C. for 2 hours. The obtained extract was centrifuged at 3000 rpm for 10 minutes, and the supernatant was filtered and lyophilized to be used as a test for each plant hot water extract.
- Example 2 Biofilm formation inhibitory activity evaluation.
- Biofilm formation was tested using 96-well microplates. To each well, add 60 ⁇ l of biofilm formation inhibition sample, 20 ⁇ l of butyric acid, 20 ⁇ l of A. naeslundii test bacteria suspension, 0.5% Sucrose added Toripticase soy broth 100 ⁇ l, and incubate at 37 ° C. under 5% CO 2 for 16 hours Went.
- Biofilm quantification The supernatant after the above culture was removed, and each well was washed twice with PBS. After washing, a 0.25% safranin solution was added to each well and allowed to stand for 15 minutes, after which the excess safranin solution was removed, and each well was washed twice with PBS. After washing, ethanol was added to each well, and the stained safranin was eluted by shaking for 30 minutes, and measured with an absorbance of 492 nm using a microplate reader to quantify the amount of biofilm formed. The amount of biofilm formed was expressed as a ratio when the amount formed when no sample was added was 100.
- Biofilm formation inhibitory effect of natural product extract We investigated whether biofilm formation inhibitory activity was observed in various natural product extracts in a butyric acid addition system. As a result of preparing hot water extracts from various plants and measuring their biofilm formation inhibitory activity, hot water extracts from komatsuna, mizuna, fresh green vegetables, pungent radish, cress, kogomi, taranoki, and ice plant were added to the test system. Then, no significant change was observed in the amount of biofilm formed in the system without addition of butyric acid, but it was confirmed that the amount of biofilm formation was reduced by 50 to 90% in the system to which butyric acid was added. This effect was particularly pronounced in the cruciferous plant hot water extract (Table 1).
- the ice plant (scientific name: Mesembryanthemum crystallinum) is one of the salt-tolerant halophytes native to Europe, West Asia, and Africa, and is a plant that can be hydroponically cultivated even in a sodium chloride solution similar to seawater. It is a plant that has been attracting attention in recent years at department stores and vegetable stores in supermarkets, but if it finds added value, such as a periodontal disease biofilm prevention effect, it will attract more attention in the future.
- a search for biofilm formation inhibitors of A. naeslundii induced by the addition of butyric acid revealed that it reduced the amount of biofilm by 50 to 90% in hot water extracts of five species of cruciferous plants such as komatsuna and mizuna and ice plant. was recognized.
- the active components of Brassicaceae plants may contain both water-soluble and fat-soluble substances.
- a mouthwash containing an acid-derived biofilm formation inhibitor containing the plant extract of the present invention toothpaste, spray for bad breath, troche, chewing gum, candy, tablet confectionery, gummy jelly, and beverage in a conventional manner Manufactured.
- Their formulations are shown below. Note that the scope of the present invention is not limited by these.
- Example 3 A mouthwash was prepared according to the following formulation. Ethanol 2.0% by weight Komatsuna extract 1.0 Fragrance 1.0 Water remaining 100.0
- Example 4 A toothpaste was produced according to the following formulation. Calcium carbonate 50.0% by weight Glycerin 19.0 Fresh green vegetable extract 1.0 Carboxymethylcellulose 2.0 Sodium ralyl sulfate 2.0 Fragrance 1.0 Saccharin 0.1 Chlorhexidine 0.01 Water remaining 100.0
- Example 5 A spray for halitosis was produced according to the following formulation. Ethanol 10.0% by weight Glycerin 5.0 Spicy radish extract 1.0 Fragrance 0.05 Coloring 0.001 Water remaining 100.0
- Example 6 A lozenge was produced according to the following formulation. Cress extract 92.3% by weight Gum arabic 6.0 Fragrance 1.0 Sodium monofluorophosphate 0.7 100.0
- Chewing gum was manufactured according to the following formulation. Gum base 20.0% by weight Xylitol 54.7 Maltose 15.0 Sorbitol 9.3 Fragrance 0.5 Mizuna extract 0.5 100.0
- Example 8 Candy was manufactured according to the following prescription. 50.0% by weight sugar Reduced water candy 33.0 Citric acid 1.0 Fragrance 0.2 L-Menthol 1.0 Mizuna extract 0.4 Water remaining 100.0
- Example 9 Tablet confectionery was produced according to the following prescription. 74.7% by weight sugar Lactose 18.9 Ice plant extract 2.0 Sucrose fatty acid ester 0.15 Water 4.25 100.0
- Example 10 Gummy jelly was manufactured according to the following prescription. Gelatin 60.0% by weight Reduced water candy 32.4 Taran extract 0.5 Vegetable oil 4.5 Malic acid 2.0 Fragrance 0.5 100.0
- Example 11 A beverage was produced according to the following formulation. Orange juice 30.0% by weight Kokomi extract 0.5 Citric acid 0.1 Vitamin C 0.04 Fragrance 0.1 Water remaining 100.0
- composition for oral cavity of the present invention is a new periodontal disease preventive agent that has an action different from that of conventional antibacterial agents for periodontal pathogens and exhibits an acid-induced periodontal disease biofilm formation inhibitory effect. Therefore, there are merits such that the risk of appearance of resistant bacteria is low compared to existing antibacterial agents and the like, and application to various products is possible.
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Abstract
Description
A. naeslundiiのバイオフィルム形成は酸刺激により増加するが、上記植物を培養系に1000ppm添加すると、バイオフィルム形成が約30%程度に低下することを発見した。このとき、各植物抽出物はA. naeslundiiの生育に影響を及ぼさなかったため、このバイオフィルム形成抑制効果は抗菌作用とは異なるメカニズムであると考えられる。
A. naeslundiiは、歯肉炎や根面う蝕部位から発見されるグラム陽性桿菌で、初期歯周病の原因細菌と言われている。連鎖球菌や歯周病原菌と共凝集するため、歯周病プラークへの菌叢遷移の鍵をにぎる細菌であると考え、A. naeslundiiをコントロールすることが効果的な歯周病予防に繋がると考えられる。
本発明者らは口腔細菌の産生する酸によりバイオフィルム形成が増加することを確認した。
すなわち、本発明は、植物抽出物を含有する口腔用組成物に関し、該植物抽出物が、小松菜、水菜、壬生菜、辛味大根、クレス、コゴミ、タラノキ、またはアイスプラントの熱水抽出物である口腔用組成物に関する。
(抽出物調製)
各植物サンプルは市販品を購入し凍結乾燥後、1gを粉砕機で細かく粉砕し、水50mlで70℃で2時間抽出した。得られた抽出液は、3000rpm・10分間遠心分離し、上清を濾過後、凍結乾燥したものを各植物熱水抽出物として試験に供した。
(バイオフィルム形成抑制活性評価)
1.バイオフィルム形成
A. naeslundii ATCC19039株を5mlのBrain Heart Infusion(BHI)液体培地にて37℃で10時間嫌気培養し、3000rpm・10分間遠心分離して集めた細菌を、PBSにてOD550nm=0.5に調製し、これを供試菌懸濁液とした。
バイオフィルム形成は、96穴マイクロプレートを用いて試験を行った。各ウェルに、バイオフィルム形成阻害サンプル60μl、酪酸20μl、A. naeslundii供試菌懸濁液20μl、0.5% Sucrose添加 Toripticase soy broth 100μlを添加し、37℃で5%CO2条件下で16時間培養を行った。
上記した培養後の上清を取り除き、PBSにて2回各ウェルの洗浄を行った。洗浄後、各ウェルに0.25%サフラニン溶液を添加し15分間静置後余剰サフラニン溶液を取り除き、PBSにて2回各ウェルの洗浄を行った。洗浄後各ウェルにエタノールを添加し、30分間振とうすることで染色させたサフラニンを溶出させ、マイクロプレートリーダーを用いて492nmの吸光度で測定し、バイオフィルム形成量を定量した。
バイオフィルム形成量は、サンプルを添加していないときの形成量を100としたときの割合で示した。
1. 天然物抽出物のバイオフィルム形成抑制効果
酪酸添加系において、さまざまな天然物の抽出物にバイオフィルム形成抑制活性が見られるかを検討した。さまざまな植物の熱水抽出物を調製し、バイオフィルム形成抑制活性を測定した結果、小松菜、水菜、壬生菜、辛味大根、クレス、コゴミ、タラノキ、アイスプラントの熱水抽出物を試験系に添加すると、酪酸を添加していない系ではバイオフィルム形成量に大きな変化は見られなかったが、酪酸を添加した系ではバイオフィルム形成量が50~90%低下することが確認された。この効果は、特にアブラナ科の植物熱水抽出物で顕著であった(表1)。
下記処方に従って含そう剤を製造した。
エタノール 2.0重量%
小松菜抽出物 1.0
香料 1.0
水 残
100.0
下記処方に従って練り歯磨きを製造した。
炭酸カルシウム 50.0重量%
グリセリン 19.0
壬生菜抽出物 1.0
カルボオキシメチルセルロース 2.0
ラルリル硫酸ナトリウム 2.0
香料 1.0
サッカリン 0.1
クロルヘキシジン 0.01
水 残
100.0
下記処方に従って口臭用スプレーを製造した。
エタノール 10.0重量%
グリセリン 5.0
辛味大根抽出物 1.0
香料 0.05
着色料 0.001
水 残
100.0
下記処方に従ってトローチを製造した。
クレス抽出物 92.3重量%
アラビアガム 6.0
香料 1.0
モノフルオロリン酸ナトリウム 0.7
100.0
下記処方に従ってチューインガムを製造した。
ガムベース 20.0重量%
キシリトール 54.7
マルトース 15.0
ソルビトール 9.3
香料 0.5
水菜抽出物 0.5
100.0
下記処方に従ってキャンディを製造した。
砂糖 50.0重量%
還元水あめ 33.0
クエン酸 1.0
香料 0.2
L-メントール 1.0
水菜抽出物 0.4
水 残
100.0
下記処方に従って錠菓を製造した。
砂糖 74.7重量%
乳糖 18.9
アイスプラント抽出物 2.0
ショ糖脂肪酸エステル 0.15
水 4.25
100.0
下記処方に従ってグミゼリーを製造した。
ゼラチン 60.0重量%
還元水あめ 32.4
タラノキ抽出物 0.5
植物油脂 4.5
リンゴ酸 2.0
香料 0.5
100.0
下記処方に従って飲料を製造した。
オレンジ果汁 30.0重量%
コゴミ抽出物 0.5
クエン酸 0.1
ビタミンC 0.04
香料 0.1
水 残
100.0
Claims (9)
- 植物抽出物を含有する口腔用組成物。
- 前記植物抽出物が、小松菜、水菜、壬生菜、辛味大根、クレス、コゴミ、タラノキ、またはアイスプラントの熱水抽出物である請求項1に記載の口腔用組成物。
- 植物抽出物を含有する酸誘導バイオフィルム形成抑制剤。
- 前記植物抽出物が、小松菜、水菜、壬生菜、辛味大根、クレス、コゴミ、タラノキ、またはアイスプラントの熱水抽出物である請求項3に記載の酸誘導バイオフィルム形成抑制剤。
- 請求項1または2に記載の口腔用組成物からなる含そう剤。
- 請求項1または2に記載の口腔用組成物からなる練り歯磨き剤。
- 請求項1または2に記載の口腔用組成物からなる吸入剤。
- 請求項1または2に記載の口腔用組成物からなるトローチ剤。
- 請求項1または2に記載の口腔用組成物を含有する食品。
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| KR1020147009143A KR102008035B1 (ko) | 2011-09-08 | 2012-09-06 | 구강용 조성물 |
| PH1/2014/500506A PH12014500506A1 (en) | 2011-09-08 | 2012-09-06 | Oral composition |
| CN201280043403.3A CN103781466A (zh) | 2011-09-08 | 2012-09-06 | 口腔用组合物 |
| US14/343,418 US20140227203A1 (en) | 2011-08-09 | 2012-09-06 | Oral composition |
| EP12830632.1A EP2754433A1 (en) | 2011-09-08 | 2012-09-06 | Oral composition |
| US15/453,355 US10201493B2 (en) | 2011-09-08 | 2017-03-08 | Method of reducing oral biofilm |
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| JP2011196315A JP6016343B2 (ja) | 2011-09-08 | 2011-09-08 | 口腔用組成物 |
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| US14/343,418 A-371-Of-International US20140227203A1 (en) | 2011-08-09 | 2012-09-06 | Oral composition |
| US15/453,355 Division US10201493B2 (en) | 2011-09-08 | 2017-03-08 | Method of reducing oral biofilm |
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| JP (1) | JP6016343B2 (ja) |
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| WO2014118829A1 (ja) * | 2013-02-01 | 2014-08-07 | 株式会社ロッテ | 口腔用組成物 |
| CN104000264B (zh) * | 2014-05-29 | 2015-05-20 | 陕西师范大学 | 一种荚果蕨饮料及其制备方法 |
| KR101561441B1 (ko) * | 2015-05-12 | 2015-10-20 | 대한민국(환경부 국립생물자원관장) | 도깨비가지 추출물을 유효성분으로 함유하는 치주질환 예방 또는 치료용 조성물 |
| EP3996658A1 (en) * | 2019-07-08 | 2022-05-18 | Basf Se | Oral care gummies |
Citations (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62265960A (ja) * | 1986-05-13 | 1987-11-18 | Akio Fujikawa | 吸収性に優れたCa食品 |
| JPH02207023A (ja) * | 1989-02-07 | 1990-08-16 | Moriyuki Hiramatsu | 生薬抽出物、その製造法および用途 |
| JPH0317010A (ja) * | 1989-06-13 | 1991-01-25 | Nippon Flour Mills Co Ltd | う蝕予防剤 |
| JPH06329544A (ja) * | 1993-05-24 | 1994-11-29 | Suntory Ltd | ヒアルロニダーゼ阻害剤 |
| JPH10259136A (ja) * | 1997-03-17 | 1998-09-29 | Taiyo Koryo Kk | ウイルス増殖抑制剤および該ウイルス増殖抑制剤を含有する薬学的組成物 |
| JPH11158011A (ja) * | 1997-11-27 | 1999-06-15 | Kagome Co Ltd | 植物の生長抑制剤 |
| JPH11158053A (ja) * | 1997-12-01 | 1999-06-15 | Nippon Shinyaku Co Ltd | 化粧料 |
| JP2000319120A (ja) * | 1999-05-10 | 2000-11-21 | Ichimaru Pharcos Co Ltd | 保湿性植物抽出物を含有する化粧料組成物 |
| JP2003113106A (ja) * | 2001-10-01 | 2003-04-18 | Pola Chem Ind Inc | 熱産生タンパク質発現促進剤及びそれを含有する組成物 |
| JP2003238987A (ja) * | 2001-12-27 | 2003-08-27 | Haarmann & Reimer Gmbh | 香味化合物としてのフェルラ酸アミドの使用 |
| JP2004115410A (ja) * | 2002-09-25 | 2004-04-15 | Ichimaru Pharcos Co Ltd | 起泡剤又は化粧料組成物 |
| JP2005281272A (ja) * | 2004-03-31 | 2005-10-13 | Suntory Ltd | 末梢血流改善剤 |
| WO2007037492A1 (ja) * | 2005-09-30 | 2007-04-05 | Kobayashi Pharmaceutical Co., Ltd. | ヤナギ科ヤナギ属植物の抽出成分を配合した歯周病用剤 |
| JP2007169246A (ja) * | 2005-12-26 | 2007-07-05 | Univ Kansai | 冬野菜スプラウトからの機能性抽出物の製造およびその用途 |
| WO2008060112A1 (en) * | 2006-11-15 | 2008-05-22 | Korea Research Institute Of Bioscience And Biotechnology | Composition comprising araliae cordatae radix extract or compounds isolated from the same for preventing or treating periodontitis |
| JP2008517052A (ja) * | 2004-10-19 | 2008-05-22 | メドビル カンパニー リミテッド | 花菅とたらの木の抽出物を含む組成物及びその用途 |
| JP2008174542A (ja) | 2006-12-18 | 2008-07-31 | Lion Corp | 口腔用組成物 |
| JP2011121919A (ja) * | 2009-12-14 | 2011-06-23 | Naraken Chusho Kigyo Sien Center | 脂質吸収抑制剤 |
| JP2011160798A (ja) * | 2010-01-15 | 2011-08-25 | Toyota Motor Corp | 変異体植物、その製造方法及び遺伝的組換え頻度を上昇させる方法 |
| WO2012096270A1 (ja) * | 2011-01-13 | 2012-07-19 | 株式会社カネカ | 生地物性改善剤及びそれを用いた食品用生地 |
| JP2012224568A (ja) * | 2011-04-18 | 2012-11-15 | Toyo Shinyaku Co Ltd | 保湿用組成物、それを含む皮膚外用剤および飲食品、およびその保湿用組成物の生産方法 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110189348A1 (en) * | 1998-10-28 | 2011-08-04 | San-Ei Gen F.F.I., Inc. | Compositions containing sucralose and application thereof |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| CN1552723A (zh) * | 2003-10-24 | 2004-12-08 | 吉林大学 | 辽东楤木叶总皂苷及其药物组合物 |
| CN1931212A (zh) * | 2005-09-16 | 2007-03-21 | 南京宇道科技开发有限公司 | 一种预防和治疗老年痴呆症的药物及其制剂和用途 |
| WO2007053945A1 (en) * | 2005-11-09 | 2007-05-18 | Kane Biotech Inc. | Oral anti-microbial composition comprising competence-stimulating peptide |
| US7879375B1 (en) * | 2006-06-23 | 2011-02-01 | Arizona Pharmaceuticals, LLC | Pharmaceutical composition |
| EP2094309A2 (en) * | 2006-11-17 | 2009-09-02 | Nya Hamlet Pharma AB | Alpha-lactalbumin composition |
| KR101517635B1 (ko) * | 2007-05-31 | 2015-05-04 | 큐피가부시키가이샤 | 파우치 패킹 액상 식품 |
| CN101244113A (zh) * | 2008-02-29 | 2008-08-20 | 周英 | 罗汉果抗微生物活性成分在防治口腔疾病中的应用方法 |
| CA2745376A1 (en) * | 2008-12-01 | 2010-06-10 | Lifespan Extension Llc | Methods and compositions for altering health, wellbeing, and lifespan |
| US20110278492A1 (en) * | 2009-02-13 | 2011-11-17 | Kaneka Corporation | Plant extract containing antifreeze substance and method for producing same |
| RU2526912C2 (ru) * | 2009-04-01 | 2014-08-27 | Колгейт-Палмолив Компани | Композиции карбонатных соединений, препятствующих образованию биопленки, для использования при уходе за полостью рта |
| JP2010285359A (ja) * | 2009-06-09 | 2010-12-24 | Kaneka Corp | 植物由来氷結晶化阻害剤 |
| US8865242B2 (en) * | 2010-03-31 | 2014-10-21 | Asahi Kasei Chemicals Corporation | Cellulose composite |
| MX2012013582A (es) * | 2010-06-24 | 2013-01-24 | Colgate Palmolive Co | Composiciones y metodos para el cuidado oral. |
| JP5906011B2 (ja) * | 2010-09-21 | 2016-04-20 | 株式会社ロッテ | 口腔用組成物 |
| CN103384526B (zh) * | 2011-01-24 | 2017-10-13 | 巴斯夫欧洲公司 | 改善口腔健康的组合物 |
-
2011
- 2011-09-08 JP JP2011196315A patent/JP6016343B2/ja active Active
-
2012
- 2012-09-06 CN CN201280043403.3A patent/CN103781466A/zh active Pending
- 2012-09-06 KR KR1020147009143A patent/KR102008035B1/ko active Active
- 2012-09-06 US US14/343,418 patent/US20140227203A1/en not_active Abandoned
- 2012-09-06 PH PH1/2014/500506A patent/PH12014500506A1/en unknown
- 2012-09-06 WO PCT/JP2012/005662 patent/WO2013035333A1/ja not_active Ceased
- 2012-09-06 EP EP12830632.1A patent/EP2754433A1/en not_active Withdrawn
-
2017
- 2017-03-08 US US15/453,355 patent/US10201493B2/en active Active
Patent Citations (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62265960A (ja) * | 1986-05-13 | 1987-11-18 | Akio Fujikawa | 吸収性に優れたCa食品 |
| JPH02207023A (ja) * | 1989-02-07 | 1990-08-16 | Moriyuki Hiramatsu | 生薬抽出物、その製造法および用途 |
| JPH0317010A (ja) * | 1989-06-13 | 1991-01-25 | Nippon Flour Mills Co Ltd | う蝕予防剤 |
| JPH06329544A (ja) * | 1993-05-24 | 1994-11-29 | Suntory Ltd | ヒアルロニダーゼ阻害剤 |
| JPH10259136A (ja) * | 1997-03-17 | 1998-09-29 | Taiyo Koryo Kk | ウイルス増殖抑制剤および該ウイルス増殖抑制剤を含有する薬学的組成物 |
| JPH11158011A (ja) * | 1997-11-27 | 1999-06-15 | Kagome Co Ltd | 植物の生長抑制剤 |
| JPH11158053A (ja) * | 1997-12-01 | 1999-06-15 | Nippon Shinyaku Co Ltd | 化粧料 |
| JP2000319120A (ja) * | 1999-05-10 | 2000-11-21 | Ichimaru Pharcos Co Ltd | 保湿性植物抽出物を含有する化粧料組成物 |
| JP2003113106A (ja) * | 2001-10-01 | 2003-04-18 | Pola Chem Ind Inc | 熱産生タンパク質発現促進剤及びそれを含有する組成物 |
| JP2003238987A (ja) * | 2001-12-27 | 2003-08-27 | Haarmann & Reimer Gmbh | 香味化合物としてのフェルラ酸アミドの使用 |
| JP2004115410A (ja) * | 2002-09-25 | 2004-04-15 | Ichimaru Pharcos Co Ltd | 起泡剤又は化粧料組成物 |
| JP2005281272A (ja) * | 2004-03-31 | 2005-10-13 | Suntory Ltd | 末梢血流改善剤 |
| JP2008517052A (ja) * | 2004-10-19 | 2008-05-22 | メドビル カンパニー リミテッド | 花菅とたらの木の抽出物を含む組成物及びその用途 |
| WO2007037492A1 (ja) * | 2005-09-30 | 2007-04-05 | Kobayashi Pharmaceutical Co., Ltd. | ヤナギ科ヤナギ属植物の抽出成分を配合した歯周病用剤 |
| JP2007169246A (ja) * | 2005-12-26 | 2007-07-05 | Univ Kansai | 冬野菜スプラウトからの機能性抽出物の製造およびその用途 |
| WO2008060112A1 (en) * | 2006-11-15 | 2008-05-22 | Korea Research Institute Of Bioscience And Biotechnology | Composition comprising araliae cordatae radix extract or compounds isolated from the same for preventing or treating periodontitis |
| JP2008174542A (ja) | 2006-12-18 | 2008-07-31 | Lion Corp | 口腔用組成物 |
| JP2011121919A (ja) * | 2009-12-14 | 2011-06-23 | Naraken Chusho Kigyo Sien Center | 脂質吸収抑制剤 |
| JP2011160798A (ja) * | 2010-01-15 | 2011-08-25 | Toyota Motor Corp | 変異体植物、その製造方法及び遺伝的組換え頻度を上昇させる方法 |
| WO2012096270A1 (ja) * | 2011-01-13 | 2012-07-19 | 株式会社カネカ | 生地物性改善剤及びそれを用いた食品用生地 |
| JP2012224568A (ja) * | 2011-04-18 | 2012-11-15 | Toyo Shinyaku Co Ltd | 保湿用組成物、それを含む皮膚外用剤および飲食品、およびその保湿用組成物の生産方法 |
Non-Patent Citations (2)
| Title |
|---|
| HIROSHI KIMURA: "Cervical Actinomycosis Due to Actinomyces Naeslundii", JOURNAL OF OTOLARYNGOLOGY OF JAPAN, vol. 114, no. 7, 20 July 2011 (2011-07-20), pages 620 - 623, XP055144139 * |
| SACHIKO MATSUBARA ET AL.: "Promoters of In Vitro Pollen Germination of Radish and Brassica campestris", JOURNAL OF THE JAPANESE SOCIETY FOR HORTICULTURAL SCIENCE, vol. 68, no. 2, 15 March 1999 (1999-03-15), pages 421 - 427, XP055144142 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6016343B2 (ja) | 2016-10-26 |
| PH12014500506A1 (en) | 2014-04-14 |
| US20170181962A1 (en) | 2017-06-29 |
| JP2013056855A (ja) | 2013-03-28 |
| US20140227203A1 (en) | 2014-08-14 |
| US10201493B2 (en) | 2019-02-12 |
| KR102008035B1 (ko) | 2019-08-06 |
| EP2754433A1 (en) | 2014-07-16 |
| CN103781466A (zh) | 2014-05-07 |
| KR20140062123A (ko) | 2014-05-22 |
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