JP2005298357A - Composition for oral cavity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a composition for the oral cavity, prepared by mixing a biosurfactant produced by a microorganism thereinto, capable of inhibiting the formation of pathogenic bacterial plaques, by conducting disinfection and bacteriostasis of pathogenic bacteria in the plaque adhered to the inside of the oral cavity, without producing an influence on oral cavity indigenous bacterial flora, and capable of effectively preventing or treating oral diseases. <P>SOLUTION: This composition for the oral cavity contains the biosurfactant selected from a glycolipid produced by the microorganism, a polypeptide produced thereby, and a derivative thereof, and further contains one, two, or more kinds of essential oil components selected from a thymol, anethole, eugenol, bisabolol, farnesol, and nerolidol. The composition for the oral cavity is prepared by mixing the specified essential oil components into the biosurfactant or the derivative thereof and further mixing a specified dicarboxylic acid salt thereinto by combining therewith, so that the composition inhibits the formation of the pathogenic bacterial plaque, by conducting the disinfection and the bacteriostasis of the pathogenic bacteria in the plaque, without inhibiting growth of an Sg bacterium, an An bacterium, or the like, which are oral cavity indigenous bacteria. Therefore, the composition is effective for preventing or treating the oral diseases. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a composition for oral cavity containing a biosurfactant produced by microorganisms, and more specifically, pathogenic plaque is formed by sterilizing and bacteriostatic pathogenic bacteria in plaque adhering to the oral cavity. It is related with the composition for oral cavity which can suppress an oral disease and can prevent or treat an oral disease.

  More than 300 types of bacteria live in the oral cavity, and they are intertwined in a complex manner to form plaque. Plaque is a cause of oral diseases such as caries, periodontal disease, and bad breath, and it has been effective to prevent plaque bacteria with bactericides such as cetylpyridinium chloride and triclosan. It is known.

  However, it has been confirmed that these bactericides have a weak penetrating ability to plaque and do not have a sufficient effect on pathogenic bacteria existing in the plaque. Moreover, the plaque suppression method by these disinfectants may have a problem of disinfecting bacteria having almost no pathogenicity and destroying oral bacterial flora. Therefore, a technique capable of penetrating into dental plaque and suppressing only pathogenic bacteria inside is desired.

  The applicant of the present invention has selective antibacterial activity against Porphyromonas gingivalis (hereinafter abbreviated as Pg fungus), which is a biosurfactant produced by microorganisms, which is one of the causative agents of periodontal disease. Furthermore, it has already been proposed that the effect is improved by using these biosurfactants in combination with a certain disinfectant (see Patent Document 1).

  However, it is possible to maximize the advantage that these biosurfactants do not affect the resident bacterial flora, that is, to improve the effects of these biosurfactants without using a bactericidal agent. On the other hand, development of technology having selective antibacterial activity is desired.

JP 2003-246717 A

  The present invention has been made in view of the above circumstances, and is an oral composition containing a biosurfactant produced by a microorganism, and without affecting the normal oral bacterial flora, the dental plaque adhered to the oral cavity. It is an object of the present invention to provide a composition for oral cavity that can effectively prevent or treat oral diseases by suppressing pathogenic plaque formation by sterilizing and bacteriostatic pathogenic bacteria.

  In order to achieve the above object, the present inventor is represented by, for example, Streptococcus gordonii (hereinafter abbreviated as Sg), Actinomyces naeslundii (hereinafter abbreviated as An), and the like. As a result of various studies using oral microbes that constitute the normal bacterial flora and periodontopathic bacteria Pg bacteria, the combination of biosurfactants produced by microorganisms and specific essential oil components Furthermore, by adding a specific dicarboxylate, the effect of selectively suppressing only pathogenic bacteria such as Pg bacteria is enhanced without inhibiting the growth of oral resident bacteria such as Sg bacteria and An bacteria. Even without the addition of bactericides, the effect of biosurfactant is synergistically improved Found that selective antimicrobial activity against bacteria is exhibited, the present invention has been accomplished.

Therefore, the present invention
(I) Contains a biosurfactant selected from glycolipids, lipopeptides and derivatives thereof produced by microorganisms, and one or more essential oil components selected from thymol, anethole, eugenol, bisabolol, farnesol, and nerolidol Oral composition (ii) characterized in that it is further selected from tartrate, succinate, malonate, malate, fumarate, adipate, pimelate, sebacate Provided is the above oral composition containing one or more dicarboxylates.

  The composition for oral cavity of the present invention contains a specific combination of a specific essential oil component and a specific dicarboxylate in a biosurfactant, thereby suppressing the growth of oral resident bacteria such as Sg bacteria and An bacteria. It is possible to suppress the formation of pathogenic plaque by sterilizing and bacteriostatic pathogenic bacteria in the plaque, and is effective in preventing or treating oral diseases.

Hereinafter, the present invention will be described in more detail.
As the biosurfactant that can be used in the present invention, those having relatively low molecular weight can be preferably used. In addition, lipopeptides such as lichenisin, and derivatives of these alkali metal salts and the like can be preferably used. These lipopeptide-type compounds can be used regardless of whether they are cyclic or linear. Among these, from the viewpoint of bactericidal power against pathogenic bacteria, viscosin, surfactin, and derivatives thereof can be preferably used.

  In the present invention, one of these biosurfactants can be blended singly or in combination of two or more. However, the blending amount is 0% of the total composition in terms of exerting bactericidal power against pathogenic bacteria. 0.0001 to 5% (mass%, the same applies hereinafter), particularly 0.001 to 2% is preferable. If the blending amount is less than 0.0001%, a satisfactory plaque formation inhibiting effect may not be obtained, and if it exceeds 5%, the taste of the composition may be affected.

  In the present invention, specific essential oil components are blended for the purpose of synergistically enhancing the effects of these biosurfactants. As the essential oil component to be used in combination, for example, one or more selected from thymol, anethole, eugenol, bisabolol, farnesol, nerolidol and the like can be suitably used. Among these, thymol, anethole, and eugenol can be preferably used in that the effect of biosurfactant can be effectively enhanced.

  The blending amount of the essential oil component is preferably 0.005 to 5%, particularly preferably 0.01 to 0.5% of the whole composition, and if it is less than 0.005%, a satisfactory blending effect may not be obtained. If it exceeds 50%, the taste of the composition may be affected.

  Furthermore, it is preferable to mix | blend dicarboxylate with this invention composition in order to improve the above-mentioned effect. Examples of the dicarboxylate include tartrate, succinate, malonate, malate, fumarate, adipate, pimelate, sebacate, etc., and the salts include alkali metal salts, In particular, sodium salts and potassium salts can be preferably used. Among them, sodium tartrate, sodium malate, and sodium sebacate can be suitably used in terms of enhancing the above-described effects.

  These dicarboxylates can be used singly or in combination of two or more, and the blending amount is preferably 0.01 to 10%, particularly 0.1 to 3% of the entire composition. If the blending amount is less than 0.01%, a satisfactory blending effect may not be obtained, and if it exceeds 10%, the feeling of use may be impaired.

  These biosurfactants, specific essential oil components, and specific dicarboxylates are capable of recognizing a bactericidal effect against pathogenic bacteria in a concentration-dependent manner within the range of the above-mentioned blending amounts, exceeding the above-mentioned blending concentration range. When it mix | blends, the usability | use_condition of a composition may be impaired remarkably.

  The composition for oral cavity of the present invention can be made into various dosage forms such as a dentifrice such as toothpaste, a mouthwash, a gingival massage cream, a topical application agent, a troche, a chewing gum and the like. In this case, the oral composition of the present invention can be prepared according to a conventional method by blending various base components used in a normal oral composition as optional components in addition to the components described above.

  In this case, for example, in a toothpaste composition, a polishing agent, a binder, a thickener, a surfactant, a fragrance, a sweetener, various active ingredients, and the like as components other than the above components do not hinder the effects of the present invention. Can be blended.

  Specific abrasives include calcium hydrogen phosphate / anhydrous, calcium hydrogen phosphate dihydrate, tertiary calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, anhydrous silicic acid, aluminum silicate, insoluble One or more of sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, bentonite, zirconium silicate, polymethyl methacrylate, and other synthetic resins can be blended.

  In addition, as a binder, cellulose derivatives such as carrageenan, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, alginic acid derivatives such as sodium alginate, propylene glycol alginate, gums such as gellan gum, tragacanth gum, karaya gum, synthesis of polyvinyl alcohol, etc. One type or two or more types of inorganic binders such as a binder, silica gel, bee gum, and laponite can be blended.

  As the thickener, one or more of polyethylene glycol, sorbit, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol and the like can be blended.

  As the surfactant, an anionic surfactant, a nonionic surfactant, an amphoteric surfactant and the like can be blended. Examples of anionic surfactants include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosinate such as sodium N-lauroyl sarcosinate, sodium N-myristoyl sarcosinate, sodium dodecylbenzenesulfonate, hydrogen Added coconut fatty acid monoglyceride sodium monosulfate, sodium lauryl sulfoacetate, N-acyl glutamate such as sodium N-palmitoyl glutamate, N-methyl-N-acyl taurine sodium, N-methyl-N-acylalanine sodium, α-olefin sulfone Sodium acid or the like is used.

  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, polyoxyethylene sorbitan monolaurate, poly Polyoxyethylene sorbitan fatty acid esters such as oxyethylene sorbitan monostearate, polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil, lauric acid mono or diethanolamide, fatty acid mono or diethanolamide such as myristic acid mono or diethanolamide, Sorbitan fatty acid ester, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene poly Carboxy propylene fatty acid ester or the like is used.

  Examples of the fragrance component include menthol, carvone, limonene, n-decyl alcohol, citronellol, α-terpineol, cineol, linalool, ethyl linalool, vanillin, thymol, peppermint oil, spearmint oil, winter green oil, clove oil, eucalyptus oil, etc. A fragrance | flavor may be mix | blended individually or in combination.

  As the sweetener, sweeteners such as sodium saccharin, stevioside, dipotassium glycyrrhizinate, perilartin, thaumatin and the like can be blended.

  In addition, the oral composition of the present invention includes dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, superoxide dimutase (SOD) and other enzymes, sodium monofluorophosphate, potassium monofluorophosphate, etc. Alkali metal monofluorophosphate, fluoride such as sodium fluoride, stannous fluoride, tranexamic acid, epsilon aminocaproic acid, allantoin, dihydrocholestanol, glycyrrhizic acid, glycerophosphate, chlorophyll, sodium chloride, xylitol, chloride One or more known active ingredients such as zinc, water-soluble inorganic phosphate compounds, vitamins A, vitamin B group, vitamins such as vitamin C and vitamin E, and derivatives thereof can be blended. In addition, it is more preferable that the composition for oral cavity of this invention does not contain germicides, such as a nonionic germicide and a cationic germicide, so that growth of an oral resident bacteria may not be suppressed.

The composition for oral cavity of the present invention is preferably adjusted and maintained at pH 5-9 using a pH adjuster, and more preferably 6-8.
Examples of pH adjusters include inorganic acids such as hydrochloric acid, phosphoric acid and boric acid, organic acids such as lactic acid and citric acid, sodium hydroxide, potassium hydroxide, alkylamines such as triethylamine, tripropylamine, and trilaurylamine, Monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, tripropanolamine, triisopropanololamine, ethyldiethanolamine, alkanolamines such as trometamol, various amines such as N-methylpiperidine, potassium hydrogenphosphate, hydrogenphosphate Examples thereof include phosphates such as sodium, and organic salts such as sodium citrate and sodium lactate. The amount of the pH adjusting agent can be appropriately selected depending on the set pH.

EXAMPLES Hereinafter, although an experiment example and an Example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, the blending amount is mass%.
[Experimental Example 1]

(1) Model plaque preparation method A 20-mm diameter hydroxyapatite (HA) plate (manufactured by Pentax) treated with human unstimulated saliva filtered through a 0.45 μm filter as a carrier for model plaque preparation The culture medium used was a solution obtained by adding hemin (manufactured by Sigma) and menadione (manufactured by Sigma) to trypticase soy broth (manufactured by Difco) so as to be 5 mg / L and 0.5 mg / L, respectively. It was.
In order to produce model plaques, Streptococcus gordonii ATCC 51656 strain (Sg) and Actinomyces naesrandi ATCC 51655 strain (An) were used as oral resident bacteria, and Porphyromonas gingivalis ATCC 33277 strain (Pg) was used as a pathogenic bacterium. These three bacterial species were inoculated into the above-mentioned culture solution so as to be 2 × 10 ⁷ cfu / mL (cfu: colony forming units), respectively, at 37 ° C. under anaerobic conditions (5% carbon dioxide gas, 95% nitrogen) was continuously cultured for 2 weeks (the replacement rate of the culture solution was set to 10 Vol%), and model plaque mixed with 3 bacterial species was formed on the HA surface.

(2) Bactericidal effect on model plaque The biosurfactant, essential oil component and dicarboxylate shown in Table 1 were combined to prepare a chemical solution having the following composition, and the bactericidal effect on model plaque was tested by the following method. The results are shown in Table 1.

Chemical composition;
Biosurfactant Amount of essential oil component shown in Table 1 (manufactured by Sigma) Amount of dicarboxylate salt shown in Table 1 (manufactured by Wako Pure Chemical Industries) Amount of ethanol shown in Table 1 5%
pH adjuster (hydrochloric acid or sodium hydroxide)
Purified water balance
Total 100%
(PH = 7.0)

Evaluation method of bactericidal effect;
The formed model plaque was immersed in the above chemical solution for 3 minutes and washed 6 times with sterile physiological saline. Thereafter, the model plaque is dispersed by ultrasonication (200 μA, 10 seconds), and contains 10% cotton defibrinated blood-containing trypticase soy agar plate (Difco) and kanamycin sulfate (200 mg / L: manufactured by Sigma) It was cultured on trypticase soy blood agar plate under smear, aerobic and anaerobic conditions. The grown colonies were counted, and the number of remaining Sg bacteria, An bacteria, and Pg bacteria (cfu) was determined. In addition, the viscosin, serawetin, and likenaisin used were roughly purified based on the following References 1 to 3, and Trehalolipid and Surfactin were commercially available products (manufactured by Sigma).

Reference 1: Appl. microbiol. Biotechnol. 32: 521-525 (1990).
Reference 2: Appl. Environ. Microbiol. 53: 1186-11
88 (1991).
Reference 3: Appl. Environ. Microbiol. 61: 1706-17 13 (1995).

  As is apparent from Table 1, by using a biosurfactant in combination with a specific essential oil component, and also using a dicarboxylate, the selective bactericidal effect of the biosurfactant against pathogenic bacteria (Pg fungus) It was observed that the resident bacteria group (Sg fungus and An fungus) in the plaque increased dramatically with little effect.

  Examples are shown below. In addition, the biosurfactant and the specific fragrance | flavor component used for the Example used the thing made from Sigma, and the dicarboxylate used the thing made from Wako Pure Chemical Industries. In the following components, thymol, anethole, eugenol, bisabolol, farnesol, and nerolidol are not blended in the “fragrance”.

[Example 1] Dentifrice aluminum hydroxide 45.0%
Gelling silica 2.0
Sorbit (70% aqueous solution) 25.0
Sodium carboxymethylcellulose 1.0
Sucrose monopalmitate 1.0
Sodium lauryl sulfate 1.0
Saccharin sodium 0.2
Ethanol 0.1
Sodium benzoate 0.1
Timor 0.05
Surfactin 0.5
Sodium malate 1.0
Fragrance 1.0
Hydrochloric acid or sodium hydroxide
Water remaining
Total 100.0%
(PH = 7.4)

[Example 2] Mouthwash ethanol 18.0%
Polyoxyethylene (60) hydrogenated castor oil 2.0
Glycerin 10.0
Palmitoyl sarcosine sodium 0.1
Citric acid 0.01
Trisodium citrate 0.3
Cetylpyridinium chloride 0.05
Linear Surfactin Sodium 0.3
Farnesol 0.05
Sodium tartrate 1.0
Fragrance 0.5
0.1% green 201 No.0.8
Hydrochloric acid or sodium hydroxide
Water remaining
Total 100.0%
(PH = 6.8)

[Example 3] Oral pasta hydroxyethyl cellulose 3.0%
Carrageenan 1.0
Sorbit (70% aqueous solution) 40.0
Sucrose palmitic acid monoester 2.0
Lauroyl sarcosine sodium 0.3
Aluminum lactate 0.8
Saccharin sodium 0.1
Trehalo lipid 0.02
Sodium tartrate 1.0
α-bisabolol 0.02
Fragrance 1.0
Hydrochloric acid or sodium hydroxide
Water remaining
Total 100.0%
(PH = 7.6)

[Example 4] Chewing gum gum base 20.0%
Sugar 15.0
Isomaltose 20.0
Palatinose 10.0
Xylitol 10.0
Corn syrup 12.0
Minamata 11.15
Trehalo lipid 0.1
Surfactin 0.05
Sodium malate 1.0
Timor 0.05
Biosol 0.05
Fragrance 0.6
Total 100.0%

Claims (4)

  A biosurfactant selected from glycolipids produced by microorganisms, lipopeptides and derivatives thereof, and one or more essential oil components selected from thymol, anethole, eugenol, bisabolol, farnesol and nerolidol The composition for oral cavity characterized by the above-mentioned.   The composition for oral cavity according to claim 1, wherein the biosurfactant is selected from viscosin, surfactin and derivatives thereof.   Furthermore, it contains one or more dicarboxylates selected from tartrate, succinate, malonate, malate, fumarate, adipate, pimelate and sebacate. The composition for oral cavity according to 1 or 2. The composition for oral cavity of Claim 1 which does not contain a nonionic germicide and a cationic germicide.