JPH04279517A - Composition for application on oral cavity - Google Patents

Abstract

PURPOSE:To provide the title composition incorporated with at least one kind of extract from citrus seeds. CONSTITUTION:The objective composition incorporated with at least one kind of extract from citrus seeds. The present composition is capable of inhibiting Bacteroides gingivalis from adhering agglomeration onto Actinomyces viscosus leading to suppressing the colonization of Bacteroides gingivalis inside the oral cavity, thus being highly useful for the prevention or therapy of periodontosis.

Description

[Detailed description of the invention]

0001

[Industrial Application Field] The present invention provides an oral composition that can prevent or treat periodontal diseases by inhibiting the colonization of Bacteroides gingivalis, one of the causative bacteria of periodontal diseases, in the oral cavity. Regarding.

0002

[Background Art] Many people are affected by periodontal diseases such as alveolar leakage, and the incidence rate is particularly high among adults.In the future, as the population continues to age, prevention and treatment of periodontal diseases will continue. is an important issue. The main cause of periodontal disease is bacteria in plaque that accumulates in periodontal pockets.Most of the bacteria present in healthy gingival sulcus are usually Gram-positive bacteria, but as periodontal disease progresses, Gram-positive bacteria Negative bacteria, especially Bacteroides gingivalis, increase. Gram-negative bacteria are often detected in the lesions of patients with severe adult periodontitis, and Bacteroides gingivalis is particularly frequently isolated. Also,
It has been shown that periodontal disease can be induced by inoculating animals with Bacteroides gingivalis. These results indicate that Bacteroides gingivalis plays an important role in the establishment of periodontal disease.

[0003] Bacteroides gingivalis has adhesins such as cilia on the surface layer of its bacterial cells, and with these it attaches to the periodontal mucosa and dental plaque bacteria such as Actinomyces viscosus, multiplies, and spreads around the teeth. It is said to have a negative impact on the organization. Therefore, in order to prevent or treat periodontal diseases such as alveolar leakage, it is necessary to take measures such as preventing the adhesion and aggregation of Bacteroides gingivalis to Acnomyces viscosus to prevent the colonization or proliferation of Bacteroides gingivalis in the oral cavity. It is effective to suppress this.

[0004] Conventionally, methods for preventing or treating periodontal diseases include methods of sterilizing periodontal disease-causing bacteria with antibiotics, methods of eliminating periodontal disease-causing bacteria with peroxides such as hydrogen peroxide, Methods that utilize the antibacterial effect of antibacterial substances are being adopted.

[0005]

[Problems to be Solved by the Invention] However, methods using antibiotics have harmful effects due to changes in the oral and intestinal flora, and methods using peroxides have a negative effect on periodontal disease-causing bacteria, which are anaerobic. Since there are many bacteria, peroxide can kill the bacteria that cause periodontal diseases, but hydrogen peroxide has the problem of carcinogenicity, so it is not recommended to use it for the prevention of periodontal diseases from the viewpoint of safety. Furthermore, methods using antibacterial substances have problems such as the fact that there are few substances that are effective against Gram-negative bacteria, and that periodontal disease-causing bacteria cannot be effectively antibacterial.

[0006] The present invention was made in view of the above circumstances.
The object of the present invention is to provide an oral composition that exhibits preventive or therapeutic effects on periodontal diseases by inhibiting the colonization of Bacteroides gingivalis in the oral cavity.

[0007]

[Means and effects for solving the problem] The present inventors have
As a result of extensive research to achieve the above objectives, we found that citrus seed extract effectively suppresses the adhesion and aggregation of Bacteroides gingivalis to Actinomyces viscosus. The inventors have discovered that by using the composition, the colonization of Bacteroides gingivalis in the oral cavity can be suppressed and periodontal diseases can be effectively prevented or treated, leading to the present invention.

[0008] Conventionally, citrus leaf and peel extracts,
Various oral compositions containing citrus oils have been proposed (Japanese Patent Publications No. 47-16650, No. 54-44043, No. 5).
4-70443, 56-500448, 58-83
No. 611, No. 58-88308, No. 61-280258, etc.), it is an object of the present invention to incorporate citrus seed extract into an oral composition, thereby suppressing the colonization of Bacteroides gingivalis in the oral cavity. This was first proposed by the authors.

[0009] To explain the present invention in more detail below, the oral composition of the present invention contains one or more extracts extracted from citrus seeds as a component for preventing or treating periodontal disease. Things like toothpaste, Junsei toothpaste,
Liquid toothpastes and other toothpastes, mouthwashes, gargling tablets, gum massage creams, liquid or paste topical preparations, troches, chewing gum, etc. are available in paste, liquid, powder, granule, and solid forms for various purposes. It is prepared and used in dosage form.

[0010] Here, citrus refers to citrus (Rutaceae) (
It consists of the genera Citrus, Clymenia, Fortunella, and Poncirus, and includes Rutaceae plants such as grapefruit, Hassaku, summer mandarin, lemon, kabosu, Satsuma mandarin, orange, lime, and Bontang. It will be done. In the present invention, any of these citrus fruits can be used, but grapefruit, hassaku, summer mandarin orange, lemon, and kabosu are particularly 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. , petroleum ether and the like can be used, and mixed solvents such as aqueous ethanol and the like can also be used. The citrus seed extract used in the present invention is obtained by extracting the above-mentioned seeds with one or more of these solvents, removing the extraction residue, and distilling off the solvent from the extract as necessary. It can be manufactured by As an extraction method, a known method such as digesting the dry powder of the seeds in a solvent may be employed.

[0012] The amount of citrus seed extract blended is not particularly limited, but is usually 0.001 to 5% of the total oral composition.
(% by weight, the same applies hereinafter), 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 contain other appropriate components depending on the purpose, type of composition, etc.

For example, in the case of toothpaste, 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 more of aluminum, insoluble sodium metaphosphate, tertiary magnesium phosphate, magnesium carbonate, calcium sulfate, bentonite, zirconium silicate, polymethyl methacrylate, and other synthetic resins may be blended (the amount usually 20-90%, 20-60% for toothpaste).

In the case of paste compositions such as toothpastes, cellulose derivatives such as carrageenan, sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, sodium carboxymethylhydroxyethylcellulose, alginates, and propylene glycol alginate esters are used as binders. , gums such as xanthan gum, tragacanth gum, karaya gum, gum arabia, synthetic binders such as polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinylpyrrolidone, inorganic binders such as silica gel, aluminum silica gel, vegum, laponite, etc. One type or two or more types may be blended (the blending amount is usually 0.
3-5%).

Furthermore, in the production of pasty or liquid oral compositions such as dentifrices, sorbitol, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylitol, One or more types of maltitol, lactitol, etc. may be blended (compounding amount usually 10 to 70%).

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

Examples of anionic surfactants include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosinates such as sodium N-lauroyl sarcosinate and sodium N-myristoyl sarcosinate, and dodecylbenzene. Sodium sulfonate, sodium hydrogenated coconut fatty acid monoglyceride monosulfate, sodium lauryl sulfoacetate, sodium N-acylglutamate such as sodium N-palmitoylglutamate, sodium N-methyl-N-acyl taurate, sodium N-methyl-N-acylalanine , sodium α-olefin sulfonate, sodium dioctyl sulfosuccinate, etc. are used.

Examples of nonionic surfactants 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 monolayer. esters, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil, fatty acid diethanolamides such as lauric acid mono- or diethanolamide, myristic acid mono- or diethanolamide , sorbitan fatty acid ester, fatty acid monoglyceride, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene polyoxypropylene fatty acid ester, etc. are used.

Examples of the zwitterionic surfactant include N-alkyldiaminoethylglycine such as N-lauryldiaminoethylglycine and N-myristyldiaminoethylglycine, N-alkyl-N-carboxymethylammonium betaine, and 2-alkyl-1- Hydroxyethylimidazoline betaine sodium and the like are used.

The oral composition of the present invention further contains menthol, carvone, anethole, methyl salicylate, eugenol, isoeugenol, limonene, ocimene, n-
Decyl alcohol, citronellol, α-terpineol, methyl acetate, citronellyl acetate, cineole, linalool, ethyl linalool, vanillin, thymol, spearmint oil, peppermint oil, lemon oil,
Flavoring agents such as orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, cinnamon leaf oil, perilla oil, wintergreen oil, clove oil, and eucalyptus oil may be used alone or in combination to form 0 to 1% of the total composition.
In addition, saccharin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin,
Sweeteners such as thaumatin, asparatylphenylalanine methyl ester, p-methoxycinnamic aldehyde (compounding amount usually 0-1%, preferably 0.01-0.5%)
%) etc. may be blended.

[0022] In the present invention, in addition to citrus seed extract, chlorhexidine,
Cationic fungicides such as benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, dequalinium chloride, phenolic compounds such as triclosan, hinokitiol, biosol, dextranase, mutanase, lysozyme, amylase,
Enzymes such as protease, lytic enzyme, and superoxide dismutase, alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, and epsilon aminocaprone. Acid, aluminum chlorohydroxylalantoin, dihydrocholestanol, glycyrrhizic acids, glycyrrhetinic acid, bisabolol, glycerophosphate,
One or more active ingredients such as chlorophyll, sodium chloride, and water-soluble inorganic phosphoric acid compounds may be blended.

[0023]

[Example] First, the effects of the present invention will be specifically explained by showing experimental examples. [Experimental Example 1] Preparation of Citrus Seed Extract 100 ml of ethanol was added to 10 g of dried pieces of grapefruit seeds, and the mixture was refluxed for 1 hour using a cooling tube on a water bath at 60 to 70°C. Next, the ethanol fraction was filtered, 100 ml of fresh ethanol was added to the residue, and the same reflux was repeated to perform two extraction operations in total. The two ethanol extracts were combined and concentrated under reduced pressure to obtain 2.4 g of a pale brown paste. In addition, add 200% water to the ethanol extraction residue of the above seeds.
ml was added, 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 was added to the residue, and the same extraction and centrifugation operations were repeated to obtain a water-soluble fraction. The two aqueous extracts were combined and freeze-dried to obtain 1.1 g of a milky white powder.

[0024] Also, 100 ml of 50% glycerin was added to 10 g of dried pieces of grapefruit seeds, and 100 ml of 50% glycerin was added at room temperature.
Extraction was performed while stirring for a week, and 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] Experiment for inhibiting bacterial aggregation.
l buffer (50mM-KCl, 1mM-KH2PO4,
25 μl of citrus seed extract dissolved in 1 mM CaCl2, pH 6.0) was added, and 25 μl of a suspension of Actinomyces viscosus T14V (OD550 = 2.25) was added and stirred for 1 minute. A suspension of Bacteroides gingivalis 381 (OD550=1.
13) was added, and the mixture was further stirred for 5 minutes, and the bacterial agglutination was visually judged in 4 stages according to the criteria below. The results are also listed in Table 1. Judgment criteria for bacterial agglutination ++: Agglutination with large clumps +: Obvious aggregation ±: Slight aggregation observed -: No aggregation observed

[0027]

[Table 1]

[0028] From the results in Table 1, it can be seen that the extracts of seeds of grapefruit, Hasaku, summer tangerine, lemon, and kabosu strongly suppress the adhesion and aggregation of Bacteroides gingivalis to Actinomyces viscosus.

[0029] The 50% glycerin extract also showed the same effect as the ethanol extract and the water extract.

[0030] Hereinafter, the present invention will be specifically explained 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 sorbitol

25.0 Sodium carboxymethylcellulose 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 Flavor
1.0 water

Residue
total
100
．． 0%

[Example 2] Toothpaste precipitated silica
25.0% sorbitol
25.0 Glycerin

25.0 Polyvinylpyrrolidone

1.0 lauroyl polyglycerin ester
1.0 polyoxyethylene (60
mole) sorbitan monolaurate
0.5 Saccharin sodium
0.2 Ethyl paraoxybenzoate
0.1 Chlorhexidine hydrochloride
0.1 Grapefruit Seed Extract (
Ethanol extract) 0.1 Lemon seed extract (Ethanol extract) 0.1 Flavor

1.0 water

Residue
total
100.0
%

[Example 3] Toothpaste dicalcium phosphate dihydrate
20.0% dibasic calcium phosphate anhydrate 20.0 Gellable silica
2.0 sorbitol

20.0 Propylene glycol
2.
5 Carboxyl methylcellulose sodium
1.0 lauryl diethanolamide
1.0 Sodium lauryl sulfate
1.5 Sodium lauroyl sarcosine 0.3 Sodium saccharin
0.1 ethyl paraoxybenzoate
0.
1 Grapefruit seed extract (50% glycerin extract)
0.05 kabosu seed extract
(50% glycerin extract) 0.05 fragrance
0.8 water

Residue
total
100.
0%

[Example 4] Pastacetanol for oral cavity
5.0% squalane

20.0 precipitated silica

5.0 polyoxyethylene (40 moles) hydrogenated 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

Total remaining

100.0%

[0034]
[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

0.5benzethonium chloride
0.1 summer mandarin orange seed extract (ethanol extract)
0.1 fragrance
0
．． 5 water

Total remaining

100.0%

[Example 6] Mouthwash Sorvit
10.0% ethanol
5.0 Polyoxyethylene (60 moles) Hydrogenated castor oil
0.1 sucrose monopalmitate
0.2 Sodium lauryl sulfate
0.0
5 Saccharin Sodium
0.2 Benzethonium chloride
0.05 Grapefruit Seed Extract (50% Glycerin Extract)
0.02 fragrance

0.6 water

Total remaining

100.0%

[Example 7] Oral lozenge lactose

96.0% polyoxyethylene (60 mol) monostearate
0.2 Chlorhexidine gluconate
0.02 Stevia extract
0.2
Grapefruit seed extract (ethanol extract)
0.3 fragrance

0.02 hydroxyethyl cellulose
Total remaining

100.0%

[Example 8] Chewing gum gum base
20.0% sugar
15.0 isomaltose
20.0 Palatinose

20.0 corn syrup
12
．． 0 starch syrup
12.2
Grapefruit seed extract (water extract)
0.1 lemon seed extract (water extract)
0.1 fragrance

0.6 total
100.0%

003
8] [Example 9] Candy sugar
30.0% isomaltose
10.0 Palatinose

10.0 maltose

10.0 starch syrup

23.0 organic acid
2
．． 0 lemon seed extract (50% glycerin extract)
0.1 fragrance

0.5 water

Total remaining

100.0%

[0039]

Effects of the Invention The oral composition of the present invention contains one or more citrus seed extracts, thereby inhibiting the adhesion and aggregation of Bacteroides gingivalis to Actinomyces viscosus.・It suppresses colonization of C. gingivalis in the oral cavity and is very effective in preventing or treating periodontal diseases.

Claims (1)

[Claims] [Claim 1] An extract extracted from citrus seeds.
An oral composition comprising one species or two or more species.