JP2000256155A - Oral composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an oral composition capable of totally controlling harmful bacteria in the oral cavity to contribute the health of the whole body, and useful for a toothpaste, a liquid dentifrice or the like by including an effective amount of a bactericide manifesting bacteriocidal activities against oral bacteria of a caustic bacteria of the disease of the whole body. SOLUTION: This oral composition contains an effective amount of a bactericide (preferably a cationic surfactant such as laurylpyridinium chloride) manifesting bacteriocidal activities against bacteria in the oral cavity (preferably, Streptococcus pneumoniae or the like) which are caustic bacteria of the disease of the whole body. An effective amount of the bactericide (preferably, a cationic bactericide such as cetylpylidinium chloride) manifesting bacteriocidal activities against the caustic bacteria of a disease in the oral cavity (preferably, periodontal disease) is preferably included therein. The cationic surfactant is preferably formulated in the proportion of 0.01-0.1 wt.% based on the whole composition. The composition is useful for a mouth wash, a rinse, a dentifrice or the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an oral composition that can control oral bacteria that are causative bacteria of systemic diseases and contribute to systemic health.

[0002]

2. Description of the Related Art It is important for oral hygiene to remove plaque (plaque) and prevent plaque (plaque control) which cause dental caries and periodontitis. For plaque bacteria,
Conventionally, oral compositions containing a cationic antibacterial agent for the purpose of sterilizing the same have been proposed. On the other hand, 3
It is said that more than 00 kinds of bacteria inhabit, and dozens of kinds of bacteria involved in caries, periodontitis, or other infectious diseases alone, and bacteria and bacterial properties related to senile pneumonia Bacteria related to endocarditis are one example. Conventionally, considerable consideration has been given to the causative bacteria of oral diseases, but also to the bacteria involved in systemic diseases living in the oral cavity, and to the harmful oral bacteria. There was no idea to provide oral preparations that contribute not only to the oral cavity but also to general health by taking comprehensive measures. That is, conventionally, only the response to the causative bacteria of the oral disease has been made.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide an oral composition which can comprehensively control harmful oral bacteria and contribute to systemic health.

[0004]

Means for Solving the Problems In view of such circumstances, the present inventors have made intensive studies on oral compositions having an effect on the causative bacteria of systemic diseases living in the oral cavity.
The present invention has been completed. That is, the present invention provides an oral composition containing an effective amount of a bactericide that exhibits bactericidal efficacy against oral bacteria that are the causative bacteria of systemic diseases.

[0005] The oral composition of the present invention may further contain a bactericidal agent having a bactericidal effect against bacteria causing oral diseases, typically, bacteria causing caries and / or periodontal disease. .

[0006] In the present specification, a causative bacterium of a systemic disease refers to a bacterium causing a disease in a site different from the oral cavity and living in the oral cavity. For example, Streptococcus pneumoniae, Klebsiell
a pneumoniae), Staphylococcus aureu
s), Pseudomonas aeruginosa, and Streptoc
occus sanguis. Examples of the causative bacteria of the target caries in the present invention include Streptococcusmut
ans, Streptococcus sobrinus and lactobacilli. Examples of the causative bacteria of periodontal disease targeted in the present invention include Porphyromonas gingivalis, Prevotella inte
rmedia, Treponema denticola, Actinobacillus acti
nomycetemcomitans, Eikenella corrodens, Campyrob
acter rectus, Bacteroides forsythus, Fusobacteri
um nucleatum, and Capnocytophaga.

[0007] Examples of fungicides which are effective against oral bacteria which are the causative bacteria of systemic diseases include cationic surfactants, such as laurylpyridinium chloride, stearyldimethylbenzylammonium chloride, distearyldimethylammonium chloride. , Cetyltrimethylammonium saccharin, stearyltrimethylammonium chloride, cetyltrimethylammonium chloride, lauryltrimethylammonium chloride, lauroylcholaminoformylmethylpyridinium chloride, cetyltrimethylammonium bromide alone or in combination of two or more, especially laurylpyridinium chloride and chloride Stearyl dimethyl benzyl ammonium is preferred. Such a cationic surfactant is incorporated at a ratio of about 0.01 to 1% by weight, preferably 0.01 to 0.1% by weight, based on the total amount of the composition.

[0008] Examples of fungicides effective against the causative bacteria of oral diseases include cationic fungicides, such as cetylpyridinium chloride, benzalkonium chloride, and the like.
Benzethonium chloride, domiphen bromide, chlorhexidine hydrochloride, and chlorhexidine gluconate can be used alone or in combination of two or more. Particularly preferred are cetylpyridinium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate. Such a cationic fungicide is used in an amount of about 0.001 to 10% by weight, preferably 0.1% by weight, based on the total amount of the composition.
It is blended at a ratio of 01 to 1% by weight. 0.001% by weight
If the amount is less than this, a sufficient bactericidal effect is not exhibited, and if it is more than 10% by weight, a problem of tooth coloring may occur.

In the oral composition of the present invention, preferably,
For the purpose of solubilizing the oil-soluble component, a nonionic surfactant can be blended. Examples of the nonionic surfactant include a polyoxyethylene polyoxypropylene block copolymer type nonionic surfactant, and polyoxyethylene hydrogenated castor oil. , Polyoxyethylene fatty acid ester such as polyoxyethylene sorbitan fatty acid ester, sucrose fatty acid ester, maltose fatty acid ester, lactose fatty acid ester, fatty acid alkanolamide, sorbitan fatty acid ester, fatty acid monoglyceride, polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl Ether and the like. These nonionic surfactants may be used alone or in combination of two or more, and the compounding amount is 0.01 to 50% by weight based on the total amount of the composition. In particular, polyoxyethylene polyoxypropylene block copolymer type nonionic surfactants or polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil and polyoxyethylene sorbitan fatty acid ester are preferable. In the case of the polyoxyethylene polyoxypropylene block copolymer type nonionic surfactant, it is blended in an amount of about 0.1 to 50% by weight, preferably 1 to 40% by weight based on the total amount of the composition. In the case of polyoxyethylene hydrogenated castor oil or polyoxyethylene sorbitan fatty acid ester, the amount is about 0.5% based on the total amount of the composition.
It is blended in an amount of from 0.01 to 5% by weight, preferably from 0.1 to 1% by weight. When the content is less than 0.01% by weight, the polyoxyethylene polyoxypropylene block copolymer type nonionic surfactant does not have sufficient solubilizing power,
If it is more than 50% by weight or if it is more than 5% by weight in a polyoxyethylene fatty acid ester such as polyoxyethylene hydrogenated castor oil, a decrease in bactericidal activity due to incorporation of a bactericide into micelles is a practical problem. .

[0010] The oral composition of the present invention preferably comprises
For the purpose of improving the effect of cationic fungicides,
An N-long-chain acyl basic amino acid lower alkyl ester or a salt thereof is blended. These basic amino acid moieties are particularly preferably ornithine, lysine and arginine, which may be either optically active or racemic. The acyl group is a saturated or unsaturated natural or synthetic fatty acid base having 8 to 22 carbon atoms, for example, a single fatty acid residue such as a lauroyl group, a myristyl group, a palmitoyl group, a stearoyl group, and a coconut oil. Natural mixed fatty acid residues such as fatty acid residues and beef oil fatty acid residues may be used. Lower alkyl esters may be used, and methyl esters, ethyl esters, and propyl esters are suitable. Salts of these lower alkyl esters of N-long-chain acyl basic amino acids include inorganic acid salts such as hydrochloride, sulfate or organic acid salts such as acetate, tartrate, citrate, p-toluene sulfone Acid salts, fatty acid salts, acidic amino acid salts and the like are included, and glutamate, pyroglutamate, acetate and citrate are particularly preferred. Specifically, N-cocoyl-L-arginine ethyl ester / pyrrolidone carboxylate (CAE)
-Lauryl-L-arginine ethyl ester / pyrrolidone carboxylate; The above amount is at least 1/5, usually 1/5, of the weight of the cationic fungicide.
It is preferably from 10 to 10 times, and more preferably 0.005 to 5% by weight, particularly 0.01 to 1% by weight, based on the whole liquid preparation for oral cavity.

The oral composition of the present invention can be in the form of toothpaste, liquid toothpaste, mouthwash, rinse, toothpaste, gel, gingival massage cream, chewing gum, confectionary tablet, and other oral means. .

The oral composition of the present invention may further contain, in addition to the above-mentioned components, the following suitable components according to the form of the composition, as long as the effects of the present invention are not impaired.

For example, surfactants selected from amphoteric surfactants can be blended. For example, N-alkyldiaminoethylglycine such as N-lauryldiaminoethylglycine and N-myristyldiethylglycine;
-Alkyl-N-carboxymethylammonium betaine and sodium 2-alkyl-1-hydroxyethylimidazoline betaine. These surfactants may be used alone or in combination of two or more. The compounding amount is usually 0.1% based on the total amount of the composition.
It is from 0.01 to 5% by weight, preferably from 0.01 to 0.2% by weight.

In the oral composition of the present invention, menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronell, α-terbineol, methyl acetate, citronenyl acetate, Methyl eugenol,
Cineol, linalool, ethyl linalool, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, perilla oil,
Perfume such as winter green oil, clove oil, eucalyptus oil, and Pimento oil, alone or in combination of two or more, is used in an amount of about 0.1 to about 5% by weight, preferably about 0.5 to about 5% by weight, based on the total amount of the composition. Can be blended.

A sweetener such as saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin, thaumatin, asparatyl phenylalanyl methyl ester, p-methoxynamic aldehyde, etc., is added to the total amount of the composition. It can be added at a ratio of 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight.

Also, gums such as cationized hydroxyethylcellulose, propylene glycol alginate, xanthan gum, tragacanth gum, karaya gum, arabia gum, carrageenan, synthetic binders such as polyvinyl alcohol and polyvinyl pyrrolidone, silica gel, aluminum silica gel, aluminum magnesium silicate And one or more inorganic binders such as synthetic sodium magnesium silicate. These blending amounts are usually from 0.3 to 5 with respect to the total amount of the composition.
% By weight.

Further, as humectants, sorbitol, glycerin, ethylene glycol, propylene glycol,
1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltitol, lactit and the like can be used alone or in combination of two or more. The compounding amount is usually 5 to 70% by weight based on the total amount of the composition.

In the case of dentifrices, abrasives include dibasic calcium phosphate dihydrate and anhydride, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide,
Alumina, silicic anhydride, silica glue, aluminum silicate, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl bentonite methacrylate, zirconium silicate and synthetic resin They can be combined and combined. The compounding amount is usually 5 to 70% by weight, preferably 10 to 50% by weight, based on the total amount of the composition.

The oral composition of the present invention contains vitamin E such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate as an active ingredient other than cetylpyridinium chloride and chlorhexidine hydrochloride, and dodecyldiamino acid. Amphoteric fungicides such as ethylglycine, nonionic fungicides such as triclosan and isopropylmethylphenol, dextranase,
Amylase, protease, mutanase, lysozyme,
Enzymes such as lytic enzymes (Litec enzyme), alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid and epsilon aminocaproic acid , Aluminum chlorohydroxyl allantoin, dihydrocholesterol,
Glycyrrhizin salts, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, caropeptide, water-soluble inorganic phosphoric acid compound alone or 2
A combination of more than one species can also be blended.

[0020]

The present invention will be described in more detail with reference to the following experimental examples and examples, but the present invention is not limited to these examples. In Examples,% represents% by weight unless otherwise specified. Experimental example Bactericidal activity test In a 10 ml Brain Heart Infection (BHI) liquid medium containing vitamin K ₃ and hemin at 37 ° C. under 85% N ₂ , 10% H ₂ , 5% CO ₂ anaerobic conditions.
About 10 ⁴ cfu of various oral bacteria cultured for ⁴ to 72 hours
/ Ml, add 100 μl to 900 μl of test solution, and contact for 30 seconds. This mixed test solution is
Serially dilute 0-fold, and 100 μl of each dilution was smeared on a triptycase soy agar (TSA) medium containing 10% equine deciliated blood and vitamin K ₃ and hemin.
After culturing at 7 ° C for 48 to 72 hours, the number of colonies was counted, and the bactericidal effect was evaluated according to the following evaluation criteria.
In addition, 12 types of test solutions were prepared (Experimental Examples 1 to 6 and Comparative Examples 1 to 6), and the components contained in each test solution are shown in Table 1 below. 2. Test bacteria: Streptococcus mutans as cariogenic bacteria
Porphyromonas gingivalis as the causative agent of periodontal disease, Streptococcus pneumoniae as the causative agent of senile pneumonia and
Staphylococcus aureus was used. 3. Evaluation criteria: The number of surviving bacteria is expressed as follows as compared to the negative control (PBS aqueous solution). 1/10 0 1/10 1/10 ² +1 1/10 ² 1/10 ³ +2 1/10 ³ 1/10 ⁴ +3 1/10 ⁴ ＋ +4 The larger the value of the evaluation standard, the more effective the sterilization effect. It was high and +3 or more was considered effective.

The results are shown in Table 1.

[Table 1] According to the results in Table 1, laurylpyridinium chloride or
The test liquids of Examples 1 and 2 containing stearyl dimethylbenzylammonium chloride had a much higher bactericidal effect against the causative bacteria of oral diseases and the causative bacteria of systemic diseases than the test solutions of Comparative Examples 1 and 2 containing no stearyl dimethylbenzyl ammonium chloride. It is clear that it is excellent. Further, when the amount of the nonionic surfactant exceeds 50% by weight as in the test liquids of Comparative Examples 3 and 6, the bactericidal effect as in the test liquids of Examples 3 and 6 was not observed, and instead, the bacteric acid was sterilized. It was found that the bactericidal effect of the agent was reduced.

Example 7 A toothpaste was produced according to the following formulation according to a conventional method. Component name Amount (%) Dibasic calcium phosphate 30 Glycerin 20 Carrageenan 1.0 Fragrance 1.0 Saccharin sodium 0.1 Chlorhexidine hydrochloride 0.1 Sodium monofluorophosphate 0.1 N-lauryl-L-arginine ethyl ester / pyrrolidone carboxylic acid Acid salt 0.5 Stearyl dimethylbenzylammonium chloride 0.1 Purified water Residue The obtained dentifrice was evaluated by the bactericidal test described above, and was superior to bacteria causing oral diseases and bacteria causing systemic diseases. Showed a bactericidal effect.

Example 8 Toothpaste was manufactured according to the following formulation according to a conventional method. Component name Amount (%) Dibasic calcium phosphate 20 Glycerin 20 Cetylpyridinium chloride 0.1 Polyoxyethylene polyoxypropylene block copolymer 40 N-cocoyl-L-arginine ethyl ester / pyrrolidone carboxylate 0.1 Fragrance 1.0 Saccharin sodium 0.1 Sodium monofluorophosphate 4.0 Laurylpyridinium chloride 1.0 Tocopherol acetate 0.1 Purified water Residue The obtained dentifrice was evaluated by the bactericidal test method described above. Excellent bactericidal effect against causative bacteria of systemic disease.

Example 9 A mouthwash was produced according to the following formulation according to a conventional method. Component name Amount (%) Ethanol 20 Glycerin 10 Polyoxyethylene hydrogenated castor oil 1.5 N-cocoyl-L-arginine ethyl ester / pyrrolidone carboxylate 0.1 Fragrance 0.1 Saccharin sodium 0.1 Cetylpyridinium chloride 0. 02 Sodium citrate 0.05 Tocopherol acetate 0.02 Stearyl dimethylbenzylammonium chloride 0.02 Purified water Residue The obtained dentifrice was evaluated by the bactericidal test described above. Showed an excellent bactericidal effect on the causative bacteria of the rice.

[0025]

According to the present invention, not only oral diseases, but also
The present invention provides an oral composition having a bactericidal effect on oral bacteria that cause pathogenesis in a site other than the oral cavity, and enables comprehensive control of harmful oral bacteria. This can provide a composition for the oral cavity that contributes to general health as well as the oral cavity.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) A61K 31/4425 A61K 31/44 608 31/55 31/55 31/765 31/765 45/00 45/00 F-term (Reference) 4C083 AB292 AB472 AC102 AC122 AC302 AC401 AC432 AC612 AC661 AC662 AC691 AC692 AC741 AC742 AC851 AC852 AC861 AC862 AD051 AD052 AD352 AD662 BB04 BB06 BB48 CC41 DD22 DD23 DD27 EE36 4C084 AA17 MA17 MA28A81 BC FA02 MA03 MA05 MA10 MA17 MA28 MA57 NA14 ZA67 ZB35 4C206 AA01 AA02 FA41 HA32 MA03 MA05 MA37 MA48 MA77 NA14 ZA67 ZB35

Claims (9)

[Claims] Claims: 1. An oral composition comprising an effective amount of a bactericide having a bactericidal effect on oral bacteria that are the causative bacteria of systemic diseases. 2. The oral composition according to claim 1, further comprising an effective amount of a bactericide having a bactericidal effect against bacteria causing oral diseases. 3. The germ of the systemic disease is Staphylococcus aureus,
2. Pseudomonas aeruginosa, Streptococcus pneumoniae or Klebsiella pneumoniae.
Or the oral composition according to 2 above. 4. The composition for oral cavity according to claim 1, wherein the oral disease is dental caries and / or periodontal disease. 5. The bactericidal agent having a bactericidal effect on oral bacteria which is a causative bacterium of a systemic disease is a cationic surfactant, and said bactericidal agent having a bactericidal effect on a causative bacterium of an oral disease. The oral composition according to any one of claims 1 to 4, wherein the agent is a cationic fungicide. 6. The composition according to claim 1, further comprising a lower alkyl ester of an N-long-chain acyl basic amino acid or a salt thereof, and 0.01% to 50% by weight of a nonionic surfactant relative to the total amount of the composition. The oral composition according to any one of the above. 7. The method according to claim 7, wherein the cationic fungicide is cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride,
The oral composition according to any one of claims 1 to 6, wherein the composition is at least one selected from the group consisting of domiphen bromide, chlorhexidine hydrochloride, and chlorhexidine gluconate. 8. The nonionic surfactant is at least one selected from the group consisting of a polyoxyethylene polyoxypropylene block copolymer type nonionic surfactant and a polyoxyethylene fatty acid ester.
An oral composition according to any one of claims 1 to 7. 9. The cationic surfactant is laurylpyridinium chloride, stearyldimethylbenzylammonium chloride, distearyldimethylammonium chloride, cetyltrimethylammonium saccharin, stearyltrimethylammonium chloride, cetyltrimethylammonium chloride, lauryltrimethylammonium chloride, lauroyl chloride. The oral composition according to any one of claims 1 to 8, which is at least one selected from the group consisting of colaminoformylmethylpyridinium and cetyltrimethylammonium bromide.