JPH1059832A - Antibacterial agent for oral cavity and composition for oral cavity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antibacterial agent for oral cavity and composition formulates therewith, manifesting specifically an antibacterial activity to a causing bacterium for periodontosis by formulating a specific material obtained by a strain of the genus Arthrobacter with an antibacterial agent. SOLUTION: This antibacterial agent for oral cavity uses arthrobactin as an active ingredient. The arthrobactin is a material produced by a strain of the genus Arthrobacter sp. no.38 (fermentation research institute deposit no.13198) and is a material of formula I, especially formula II. The antibacterial agent for oral cavity using the arthrobactin as the active ingredient does not destroy a flora in the oral cavity even on administering in a large amount, but manifests specifically high antibacterial activity to Porphyromonas gingivalis. Also in the case of formulated the antibacterial agent to the composition for oral cavity, the formulation amount is approximately 0.0001-10wt.% based on the total amount of the composition for oral cavity. As the composition for oral cavity, a toothpaste, a liquid state dentifrice, a mouth washing agent, a gergling tablet, a paste for oral cavity, a troche, etc., are cited.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to Porphyromonas gingivalis, one of the periodontal disease-causing bacteria.
P. yomonas gingivalis;
Abbreviated. The present invention relates to an oral antibacterial agent which specifically exhibits antibacterial activity against) and an oral composition comprising the oral antibacterial agent, which is effective for the prevention and treatment of periodontal disease.

[0002]

BACKGROUND OF THE INVENTION Conventionally, Pg, Fusobacterium nucleatum (Fusobacteri) has been used as a cause of periodontal disease, bad breath and dental caries.
um nucleatum, Streptococcus mutans (Streptococcus mutans)
It is known that oral bacteria such as s) are involved.
For this reason, chlorhexidine, cetyl pyrimidinium chloride, etc. are blended as an antibacterial agent in the oral composition to remove the causative bacteria.

[0003] However, these antibacterial agents generally have a broad antibacterial spectrum and have a strong antibacterial activity. Therefore, when they are incorporated in a large amount into an oral composition, the bacterial flora in the oral cavity changes, and bacterial replacement occurs. Illness occurred and there was a problem in terms of safety.

That is, resident bacteria in the oral cavity have a function as a barrier to prevent harmful microorganisms from entering from outside the body. For this reason, the above-mentioned chlorhexidine, a broad antibacterial spectrum such as cetylpyrimidinium chloride, and using a large amount of a bactericide having a strong antibacterial activity,
The flora in the oral cavity changes, weakens the barrier function, and may cause infection by other harmful microorganisms.

Therefore, development of a highly safe oral antibacterial agent capable of specifically sterilizing only harmful bacteria without changing the bacterial flora in the oral cavity is desired.

[0006] The present invention has been made in view of the above circumstances, and specifically for Pg, which is one of the periodontal disease pathogens,
An oral antibacterial agent which exhibits strong antibacterial activity, does not change the bacterial flora in the oral cavity even when formulated in large amounts, and can effectively prevent and treat periodontal disease, and this oral antibacterial agent It is an object of the present invention to provide an oral composition comprising:

[0007]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result, have found that Arthrobacter
r) genus sp. No. 38 strains
No. 2) has an extremely strong antibacterial activity against Pg, which is one of the causative bacteria of periodontal disease. Fusobacterium nucleatum (Fusobacterium nuc)
leatum), Streptococcus mutans, Actinomyces viscousus (Actinomyces)
viscossus) and other bacteria resident in the oral cavity.

[0008] The oral composition containing the above-mentioned arthrofactin as an antibacterial agent does not change the bacterial flora in the oral cavity and maintains the barrier function in the oral cavity while maintaining the barrier function in the oral cavity. Pg only shows antibacterial activity specifically, is found to be extremely effective in preventing and treating periodontal disease,
The present invention has been completed.

[0009] Arthrofactin is disclosed in
Although it is known as a compound having surface activity as described in JP-A-184194, arthrofactin has a specific antibacterial activity against Pg as described above, has high safety, It is not known at all that it is suitable for the prevention and treatment of diseases, and this is a new finding of the present inventors.

[0010] Accordingly, the present invention provides an oral antibacterial agent containing arthrofactin as an active ingredient, and an oral composition containing the oral antibacterial agent.

Hereinafter, the present invention will be described in more detail. The oral antibacterial agent of the present invention contains arthrofactin as an active ingredient. Derivatives obtained by chemically modifying cutin are also included.

[0012] Here, Arthrofactin is, as described above, Arthrobacter sp. No. 38, which is a known substance disclosed in Japanese Patent Application Laid-Open No. 6-184194.
It is a compound represented by the following formula [I], particularly, formula [II].

[0013]

Embedded image

The oral antibacterial agent containing the above-mentioned arthrofactin as an active ingredient does not destroy the bacterial flora in the oral cavity even when administered in a large amount, and exhibits a specific high antibacterial activity only for Pg.
When this antibacterial agent is blended with the oral composition, the blending amount is 0.0001 to 10% of the whole oral composition.
(% By weight, hereinafter the same), preferably 0.001 to 5%. If the compounding amount of arthrofactin is less than 0.0001%, a satisfactory antibacterial effect may not be exhibited.
If it exceeds 0%, the stability of the composition may be impaired.

The oral composition of the present invention contains the above-mentioned arthrofactin as an antibacterial agent. The oral composition containing the oral antibacterial agent of the present invention includes toothpaste, liquid dentifrice, Examples include, but are not limited to, dentifrices such as lubricating toothpastes, mouthwashes, gargle tablets, oral pasta, troches, chewing gums, mouth fresheners, and the like.

The oral composition of the present invention may contain components commonly used in oral compositions according to the dosage form and the like.

For example, in the case of dentifrices, abrasives, binders, thickeners, surfactants, sweeteners, preservatives, coloring agents, various active ingredients, and the like can be blended. It can be manufactured by mixing.

Here, as the abrasive, precipitated silica,
Silica-based abrasives such as silica gel, aluminosilicate, zirconosilicate, dibasic calcium phosphate dihydrate and anhydrate, calcium pyrophosphate, calcium carbonate,
Aluminum hydroxide, alumina, magnesium carbonate, tertiary magnesium phosphate, zeolite, zirconium silicate, synthetic resin-based abrasives and the like are preferably used.

Examples of the thickener include glycerin, sorbitol, propylene glycol, polyethylene glycol,
Xylit, maltit, lactit and the like are preferred.

As the binder, sodium carboxymethylcellulose, hydroxyethylcellulose, carrageenan, sodium alginate, xanthan gum, carbopol, guar gum, montmorillonite, gelatin and the like are preferably used.

As the surfactant, an anionic surfactant, a cationic surfactant, a nonionic surfactant and the like can be blended. Specifically, sodium lauryl sulfate, α-
Sodium olefin sulfonate, N-acyl sarcosinate, N-acyl glutamate, 2-alkyl-N-
Carboxymethyl-N-hydroxyethyl imidazonium betaine, N-acyl taurate, sucrose fatty acid ester, alkylol amide, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, pluronic, polyoxyethylene sorbitan monostearate and the like are preferable. Used for

As sweeteners, sodium saccharin,
Stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perillartin and the like are preferred.

Examples of the preservative include paraoxybenzoate, sodium benzoate and the like.

Other various active ingredients include fluorine compounds such as sodium fluoride, potassium fluoride, ammonium fluoride, stannous fluoride, sodium monofluorophosphate, and potassium and sodium salts of orthophosphoric acid. Water-soluble phosphate compounds, allantochlorohydroxyaluminum, hinokitiol, ascorbic acid, lysozyme chloride, dextranase, mutanase, amylase, protease, glycyrrhizic acid and salts thereof, sodium chloride, tranexamic acid, epsilon aminocaproic acid, dl-tocopherol acetate, Azulene, glycyrrhetinic acid, sodium copper chlorophyllin, copper compounds such as copper gluconate, aluminum lactate, strontium chloride,
Potassium nitrate, berberine, hydroxamic acid and its derivatives, sodium tripolyphosphate, zeolite, methoxyethylene, maleic anhydride copolymer, polyvinylpyrrolidone, epidihydrocholesterine, dihydrocholesterol, zinc citrate, tomato soft extract, oak extract, butterfly, Extracts such as rosemary, ogre, safflower and the like are included.

Suitable fragrances include terpenes such as l-menthol, carvone, anethole, limonene and derivatives thereof and the like, and coloring agents such as Blue No. 1, Yellow No. 4, titanium dioxide, titanium oxide, alumina oxide And the like are preferred.

The amount of the above components can be a usual amount as long as the effects of the present invention are not impaired.

The oral composition of the present invention contains, in addition to the above-mentioned arthrofactin, other fungicides such as α-bisabolol, isopropylmethylphenol, chlorhexidine salts, chlorides, etc., as long as the effects of the present invention are not impaired. Cetylpyridinium, benzethonium chloride, trichlorocarbanilide and the like may be mixed.

[0028]

The oral antibacterial agent of the present invention shows a strong antibacterial activity specifically against Pg, which is one of the periodontal disease-causing bacteria. It can effectively prevent and treat periodontal disease without destroying it, and can be widely used for various compositions of oral compositions.

[0029]

EXAMPLES Hereinafter, the present invention will be described in detail with reference to Experimental Examples, Examples and Comparative Examples, but the present invention is not limited to the following Examples.

[Experimental Example] An antibacterial activity test (minimum inhibitory concentration, MIC) was carried out by the following method using the following strains and the liquid medium and the antibacterial components shown in Table 1.

A test tube (13 × 1) containing 4 ml of liquid medium
Test antimicrobial agent solution 0.0
Add 4 ml, mix, and pre-culture for 1 day.
4 ml was added and stirred. This was anaerobically cultured at 37 ° C. for 3 days, and the growth amount of the bacteria was measured by absorbance at 550 nm. An absorbance of less than 0.05 was regarded as effective, and a minimum growth inhibitory concentration (MIC) was determined. Table 1 shows the results. Bacterial strain used and composition of liquid medium Porphyromonas gingivalis 381 (Pg) Medium: Todd Hewitt broth (hereinafter abbreviated as THB) 3% hemin 3 ppm Menadione 0.5 ppm Fusobacterium nucleatum Usac b36 nucleatum 1436 (Fn)) Medium: THB 3% L-cysteine hydrochloride 0.05% Actinomyces viscousus T14V (Actinomyces viscosse T14V (Av)) Medium: THB 3% )) Medium: THB 3%

[0032]

[Table 1]

From the results in Table 1, arthrofactin was
It has strong antibacterial activity only against Pg and other Fn, A
It is confirmed that it does not have antibacterial properties against v and Sm.

Next, an embodiment will be described. [Example 1] Toothpaste Calcium carbonate 50.00% Glycerin 20.00 Carrageenan 0.50 Carboxymethylcellulose 1.00 Lauryl diethanolamide 1.00 Sucrose monolaurate 2.00 Fragrance 1.00 Saccharin sodium 0.10 Epsilon aminocapron Acid 0.20 Arthrofactin 0.50 Water Balance 100.00%

Example 2 Toothpaste Dibasic calcium phosphate dihydrate 50.00% Glycerin 20.00 Carboxymethylcellulose 2.00 Sodium lauryl sulfate 2.00 Fragrance 1.00 Saccharin sodium 0.10 Tocopherol acetate 0.10 Arthrofactin 0.20 water balance 100.00%

Example 3 Toothpaste Aluminum hydroxide 45.00% Gelling silica 2.00 Sorbit 25.00 Carboxymethylcellulose 1.00 Sodium lauryl sulfate 2.00 Fragrance 1.00 Saccharin sodium 0.10 α-Bisabolol 0.50 Tranexamic acid 0.05 Arthrofactin 0.10 Water 100.00%

Example 4 Toothpaste Precipitable silica 25.00% Glycerin 25.00 Sorbit 25.00 Lauroyl polyglycerin ester 1.00 Polyoxyethylene sorbitan monolaurate 2.00 Fragrance 1.00 Saccharin sodium 0.20 Dipotassium glycyrrhizinate 0.10 Arthrofactin 0.50 Water 100.00%

Example 5 Liquid Dentifrice Precipitable Silica 15.00% Xanthan Gum 0.20 Sodium Polyacrylate 0.20 Propylene Glycol 2.00 Sorbit 35.00 Glycerin 10.00 Fragrance 1.00 Saccharin Sodium 0.10 β -Glycyrrhetinic acid 0.02 Arthrofactin 0.10 Sodium lauryl sulfate 1.50 Butyl p-hydroxybenzoate 0.02 Purified water Balance 100.00%

Example 6 Oral Pasta Liquid Paraffin 15.00% Cetanol 10.00 Glycerin 20.00 Polyoxyethylene Sorbitan Fatty Acid Ester 5.00 Fragrance 0.50 Saccharin Sodium 0.10 Arthrofactin 0.50 Water Residue Total 100.00%

Example 7 Mouthwash Ethanol 20.00% Fragrance 1.00 Polyoxyethylene hydrogenated castor oil 2.00 Sodium monofluorophosphate 0.10 Sodium saccharin 0.05 Azulene 0.50 Arthrofactin 00 water balance 100.00%

Example 8 Gargle Tablets Sodium Bicarbonate 54.00% Citric Acid 17.00 Anhydrous Sodium Sulfate 12.80 Dibasic Sodium Phosphate 10.00 Polyethylene Glycol 3.00 Sodium Monofluorophosphate 0.10 Flavor 2.00 Oleic acid 0.10 Arthrofactin 1.00 Total 100.00%

Example 9 Lozenges Glucose 35.00% Palatinose 35.00 Gum Arabic 6.00 Fragrance 1.00 Arthrofactin 5.00 Water Balance 100.00%

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[Procedure amendment]

[Submission date] September 19, 1996

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0015

[Correction method] Change

[Correction contents]

The oral composition of the present invention contains the above-mentioned arthrofactin as an antibacterial agent. The oral composition containing the oral antibacterial agent of the present invention includes toothpaste, liquid dentifrice, Examples include, but are not limited to, dentifrices such as lubricating toothpastes, mouthwashes, gargle tablets, oral pasta, troches, mouth fresheners, and the like.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical display location C12R 1:06)

Claims (2)

[Claims] 1. An oral antibacterial agent comprising arthrofactin as an active ingredient. 2. An oral composition comprising the oral antibacterial agent according to claim 1.