JP3008525B2 - Oral composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an oral composition capable of inhibiting the establishment of Bacteroides gingivalis, one of the causative bacteria of periodontal disease, in the oral cavity and preventing or treating periodontal disease. About.

[0002]

2. Description of the Related Art Periodontal disease such as alveolar congestion affects a large number of people. Particularly, the incidence of adult disease is extremely high. In the future, as the population ages, the prevention and treatment of periodontal disease will occur. Is an important issue. The primary cause of periodontal disease is bacteria in the plaque that accumulate in the periodontal pockets, and the majority of bacteria in healthy gingival sulcus are usually gram-positive, but as periodontal disease progresses, gram Negative bacteria, especially Bacteroides gingivalis, increase. Gram-negative bacteria are frequently detected in the lesions of patients with severe adult periodontitis, and Bacteroides gingivalis is particularly frequently isolated. Also,
Inoculation of animals with Bacteroides gingivalis has been shown to induce periodontal disease. These results indicate that Bacteroides gingivalis plays an important role in establishing periodontal disease.

[0003] Bacteroides gingivalis has adhesion factors (adhesin) such as cilia on the surface of bacterial cells, and adheres to periodontal mucosa and plaque bacteria such as Actinomyces viscosus to proliferate and grow. It is said to have a negative effect on the organization. For this reason, in order to prevent or treat periodontal diseases such as alveolar thickening, Bacteroides gingivalis colonization or proliferation of Bacteroides gingivalis into the oral cavity by treatment such as preventing adhesion and aggregation of Bacteroides gingivalis to A. viscosus. Is effective.

Conventionally, methods for preventing or treating periodontal disease include a method of killing periodontal disease-causing bacteria with an antibiotic, a method of eliminating periodontal disease-causing bacteria with a peroxide such as hydrogen peroxide solution, A method utilizing the antibacterial action of an antibacterial substance is adopted.

[0005]

However, the method using an antibiotic has a harmful effect due to a change in the oral and intestinal flora, and the method using a peroxide has an anaerobic effect on periodontal disease-causing bacteria. Although periodontal disease-causing bacteria can be killed by peroxides due to the large number of bacteria, hydrogen peroxide has a carcinogenic problem and is not preferred for use in preventing periodontal disease in terms of safety. Furthermore, the method using an antibacterial substance has a problem that there are few substances effective against gram-negative bacteria, and thus it is not possible to effectively antibacterialize periodontal disease-causing bacteria.

The present invention has been made in view of the above circumstances,
An object of the present invention is to provide a composition for oral cavity that exerts a preventive or therapeutic effect on periodontal disease by suppressing the establishment of Bacteroides gingivalis in the oral cavity.

[0007]

Means and Action for Solving the Problems The present inventors have
As a result of intensive studies to achieve the above object, the extract of citrus seeds effectively suppresses the adhesion and aggregation of Bacteroides gingivalis to Actinomyces viscosus, and is therefore formulated for the oral cavity with the extract of citrus seeds. It has been found that the use of the composition suppresses the oral fixation of Bacteroides gingivalis in the oral cavity, and that periodontal disease can be effectively prevented or treated, and the present invention has been accomplished.

Conventionally, extracts of citrus leaves and pericarp,
Various oral compositions containing citrus oil have been proposed (JP-A-47-16650, JP-A-54-44043, and JP-A-5-44043).
4-70443, 56-500488, 58-83
611, 58-88308, 61-280258, etc.) that an extract of citrus seeds is incorporated into an oral composition, thereby suppressing the excellent oral fixation of Bacteroides gingivalis in the oral cavity. It was proposed for the first time by others.

Hereinafter, the present invention will be described in more detail. The oral composition of the present invention comprises one or more extracts extracted from citrus seeds as a component for preventing or treating periodontal disease. Depending on various uses, such as toothpaste, dentifrice such as toothpaste, liquid toothpaste, mouthwash, gargle tablets, gingival massage cream, liquid or pasty topical application, troche, chewing gum, etc. It is prepared and used in the form of a liquid, powder, granule, or solid.

[0010] Here, citrus is a citrus belonging to the genus Citrus and Crymenia.
The genus is composed of the genera, Fortunella, and Poncilus, and includes citrus plants such as grapefruit, hassaku, summer mandarin, lemon, kabos, unshu mandarin orange, lime, and bontan. In the present invention, any of these citrus fruits can be used, particularly grapefruit, hassaku,
Summer oranges, lemons and kabos are preferred.

Solvents used for extracting these citrus seeds include water, lower alcohols such as methanol and ethanol, polyhydric alcohols such as propylene glycol and glycerin, polar solvents such as acetone, ethyl ether and ethyl acetate, hexane and benzene. Non-polar solvents such as petroleum ether and petroleum ether can be used, and mixed solvents such as aqueous ethanol can also be used. The extract of citrus seeds used in the present invention is obtained by extracting the above-mentioned seeds with one or a mixture of two or more of these solvents, removing the extraction residue, and removing the solvent from the extract as necessary. Can be manufactured. In addition, as the extraction method, for example, a known method such as digestion of the dry powder of the seed in a solvent can be adopted.

The amount of the extract of citrus seeds is not particularly limited, but is usually 0.001 to 5% of the whole oral composition.
(% By weight, hereinafter the same), particularly preferably 0.02 to 2%. If the amount is less than 0.001%, the effect of inhibiting bacterial adhesion and aggregation may not be sufficiently exhibited, and if it is more than 5%, the flavor of the oral composition may be impaired.

[0013] In addition to the above-mentioned components, the oral composition of the present invention may further contain appropriate components according to the purpose, the type of the composition and the like.

For example, in the case of dentifrice, dibasic calcium phosphate dihydrate and anhydride, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, silicic anhydride, silicic acid One or two of aluminum, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, bentonite, zirconium silicate, polymethyl methacrylate, and other synthetic resins
More than one kind can be blended (the blending amount is usually 20 to 90%, and in the case of toothpaste, 20 to 60%).

In the case of a paste composition such as toothpaste, cellulose derivatives such as carrageenan, sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose and sodium carboxymethylhydroxyethylcellulose, alginates and propylene glycol alginate are used as binders. And gums such as xanthan gum, tragacanth gum, karaya gum, and arabic gum; synthetic binders such as polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, and polyvinylpyrrolidone; and inorganic binders such as silica gel, aluminum silica gel, veegum, and laponite. One or more kinds may be blended (the blending amount is usually 0.1%).
3-5%).

Further, in the production of paste or liquid oral compositions such as dentifrices, sorbitol, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylitol, as a thickener, One or more of maltitol, lactitol and the like may be blended (the blending amount is usually 10 to 70%).

As the surfactant, one or more of an anionic surfactant, a nonionic surfactant and an amphoteric surfactant can be blended (the blending amount is usually 0.1 to 5%,
Preferably 0.05-3%).

Examples of the anionic surfactant include sodium alkyl sulfate such as sodium lauryl sulfate and sodium myristyl sulfate; sodium N-acyl sarcosinate such as sodium N-lauroyl sarcosinate; sodium N-myristoyl sarcosinate; and dodecylbenzene. Sodium sulfonate, hydrogenated coconut fatty acid monoglyceride monosulfate, sodium lauryl sulfoacetate, N-acylglutamate such as sodium N-palmitoylglutamate, sodium N-methyl-N-acyltaurine, sodium N-methyl-N-acylalanine , Sodium α-olefin sulfonate, sodium dioctyl sulfosuccinate and the like.

Examples of the nonionic surfactant include sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester and lactose fatty acid ester, sugar alcohol fatty acid esters such as maltitol fatty acid ester and lactitol fatty acid ester, and polyoxyethylene sorbitan monolau. , Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil, lauric acid mono- or diethanolamide, fatty acid diethanolamide such as myristic acid mono- or diethanolamide , Sorbitan fatty acid ester, fatty acid monoglyceride, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropyl Emissions copolymer, polyoxyethylene polyoxypropylene fatty acid ester or the like is used.

Examples of the amphoteric surfactant include N-alkyldiaminoethylglycine such as N-lauryldiaminoethylglycine and N-myristyldiaminoethylglycine, N-alkyl-N-carboxymethylammonium betaine, and 2-alkyl-1-amine. Hydroxyethylimidazoline betaine sodium is used.

The oral composition of the present invention further comprises menthol, carvone, anethole, methyl salicylate, eugenol, isoeugenol, limonene, ocimene, n-
Decyl alcohol, citronellol, α-terpineol, methyl acetate, citronellyl acetate, cineole, linalool, ethyl linalool, crocodile, thymol, spearmint oil, peppermint oil, lemon oil,
Perfume such as orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, laurel oil, perilla oil, winter green oil, t-shaped oil, eucalyptus oil, etc., alone or in combination, from 0 to 1 of the total composition
0%, preferably about 0.5 to 5%, and saccharin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin,
Sweeteners such as thaumatin, asparatylphenylalanine methyl ester, and p-methoxycinnamic aldehyde (the amount is usually 0 to 1%, preferably 0.01 to 0.5%)
%) And the like.

In the present invention, as active ingredients, in addition to citrus seed extract, cationic bactericides such as chlorhexidine, benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride and decalinium chloride, and triclosan , Phenolic compounds such as hinokitiol and biosol,
Enzymes such as dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, superoxide dismutase, alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, sodium fluoride, stannous fluoride One active ingredient such as fluoride, tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholestanol, glycyrrhizic acids, glycyrrhetinic acid, bisabolol, glycerophosphate, chlorophyll, sodium chloride, water-soluble inorganic phosphate compound, etc. Alternatively, two or more kinds may be blended.

[0023]

First, the effects of the present invention will be specifically described with reference to experimental examples. Experimental Example 1 Preparation of Citrus Seed Extract 100 g of ethanol was added to 10 g of dried grapefruit seed fragments, and the mixture was refluxed for 1 hour on a 60-70 ° C. water bath using a cooling tube. Next, the ethanol fraction was filtered off, 100 ml of fresh ethanol was added to the residue, and the same reflux was repeated to perform a total of two extraction operations. The two ethanol extracts were combined and concentrated under reduced pressure to obtain 2.4 g of a pale brown paste. In addition, 200 ml of water was added to the ethanol extraction residue of the above seeds, extraction was performed at 50 to 60 ° C. for 1 hour, and a water-soluble fraction was obtained by centrifugation (3000 rpm, 10 minutes). 200 ml of fresh water is added to the residue,
The same extraction and centrifugation operations were repeated to obtain a water-soluble fraction, and the two aqueous extracts were collectively freeze-dried to obtain 1.1 g of a milky white powder.

Further, 100 ml of 50% glycerin was added to 10 g of dried grapefruit seeds, and
Extraction was performed with stirring for a week, and the mixture was filtered to obtain an extract.

The other plants shown in Table 1 were operated in the same manner as above to obtain extracts of each plant.

Experimental Example 2 Bacterial Agglutination Inhibition Experiment KCl buffer (50 mM-KCl, 1 mM-KH ₂ ) was added to each well of a 96-well plate V disco (manufactured by Sanko Junyaku).
25 μl of an extract of citrus seeds dissolved in PO ₄ , 1 mM CaCl ₂ , pH 6.0) was added thereto, and a suspension of Actinomyces viscosus T14V (OD ₅₅₀ = 2.2) was added.
25 μl of 5) was added and stirred for 1 minute. A suspension of Bacteroides gingivalis 381 (OD ₅₅₀ =
1.13) was added thereto, and the mixture was further stirred for 5 minutes, and the cohesion between bacteria was visually evaluated in four steps according to the following criteria. The results are also shown in Table 1. Criteria for judging agglutination between bacteria ++: agglutination with large lumps +: clear agglutination is observed ±: slight agglutination is observed-: no agglutination is observed

[0027]

[Table 1]

From the results shown in Table 1, it can be seen that the extract of grapefruit, hassaku, summer orange, lemon and kabosu seeds strongly inhibits the adhesion and aggregation of Bacteroides gingivalis to Actinomyces viscosus.

The 50% glycerin extract also showed the same effect as the ethanol extract and the water extract.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited to the following Examples. [Example 1] Toothpaste Aluminum hydroxide 45.0% Gelling silica 2.0 Sorbit 25.0 Sodium carboxymethyl cellulose 1.0 Sucrose monopalmitate 1.0 Sodium lauryl sulfate 1.5 Saccharin sodium 0.2 Ethanol 0.1 Sodium benzoate 0.1 Triclosan 0.1 Grapefruit seed extract (water extract) 0.1 Perfume 1.0 Water Balance 100.0%

Example 2 Toothpaste Precipitated silica 25.0% Sorvit 25.0 Glycerin 25.0 Polyvinylpyrrolidone 1.0 Lauroyl polyglycerin ester 1.0 Polyoxyethylene (60 mol) Sorbitan monolaurate 5 Sodium saccharin 0.2 Ethyl parahydroxybenzoate 0.1 Chlorhexidine hydrochloride 0.1 Grapefruit seed extract (ethanol extract) 0.1 Lemon seed extract (ethanol extract) 0.1 Perfume 1.0 Water Balance 100.0 %

[Example 3] Toothpaste dibasic calcium phosphate dihydrate 20.0% dibasic calcium phosphate anhydrous 20.0 gelling silica 2.0 sorbit 20.0 propylene glycol 2.5 carboxymethyl cellulose Sodium 1.0 Lauryl diethanol amide 1.0 Sodium lauryl sulfate 1.5 Sodium lauroyl sarcosine 0.3 Saccharin sodium 0.1 Ethyl parahydroxybenzoate 0.1 Grapefruit seed extract (50% glycerin extract) 0.05 Cabos seed extract (50% glycerin extract) 0.05 Perfume 0.8 Water Residual 100.0%

Example 4 Oral Pasta Cetanol 5.0% Squalane 20.0 Precipitated Silica 5.0 Polyoxyethylene (40 mol) Hardened Castor Oil 0.1 Sorbitan Monooleate 1.0 Sodium Lauryl Sulfate 0.2 Glycyrrhetinic acid 0.1 Saccharin sodium 0.6 Hassaku seed extract (water extract) 0.2 Fragrance 0.6 Water Balance 100.0%

Example 5 Oral Pasta Liquid Paraffin 15.0% Cetanol 7.0 Glycerin 20.0 Sorbitan Monopalmitate 0.6 Polyoxyethylene (40 mol) Sorbitan Monostearate 5.0 Saccharin Sodium 0.5 Benzethonium chloride 0.1 Summer orange seed extract (ethanol extract) 0.1 Perfume 0.5 Water Balance 100.0%

Example 6 Mouthwash Sorbit 10.0% Ethanol 5.0 Polyoxyethylene (60 mol) Hardened Castor Oil 0.1 Sucrose Monopalmitate 0.2 Sodium Lauryl Sulfate 0.05 Sodium Saccharin 0.2 Benzethonium chloride 0.05 Grapefruit seed extract (50% glycerin extract) 0.02 Fragrance 0.6 Water Balance 100.0%

Example 7 Oral Lozenges Lactose 96.0% Polyoxyethylene (60 mol) Monostearate 0.2 Chlorhexidine Gluconate 0.02 Stevia Extract 0.2 Grapefruit Seed Extract (Ethanol Extract) 0.3 Perfume 0.02 Hydroxyethylcellulose Balance 100.0%

Example 8 Chewing gum gum base 20.0% sugar 15.0 isomaltose 20.0 palatinose 20.0 corn syrup 12.0 syrup 12.2 grapefruit seed extract (water extract) 0.1 lemon seed extract (Water extract) 0.1 perfume 0.6 total 100.0%

Example 9 Candy Sugar 30.0% Isomaltose 10.0 Palatinose 10.0 Maltose 10.0 Syrup Cane 23.0 Organic Acid 2.0 Lemon Seed Extract (50% Glycerin Extract) 0.1 Flavor 0.5 water balance 100.0%

[0039]

EFFECTS OF THE INVENTION The oral composition of the present invention, which contains one or more citrus seed extracts, prevents Bacteroides gingivalis from adhering and coagulating to Actinomyces viscosus, thereby preventing Bacteroides. -Suppresses gingivalis in the oral cavity and is very effective in preventing or treating periodontal disease.

Claims (1)

(57) [Claims] An oral composition comprising one or more extracts extracted from citrus seeds.