JPH06287122A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for oral cavity effective for eliminating bacterial plaque and preventing periodontal disease, having excellent removing action on microorganisms. CONSTITUTION:A composition for oral cavity comprises a substance, composed of a compound having a purine skeleton or a pyrimidine skeleton bonded directly or through a spacer to a water-insoluble carrier, alone or in a combined state. Among the substances, preferably a composition for oral cavity is mixed with 0.01-10wt.% of a substance wherein the purine skeleton is adenine or guanine and the pyrimidine skeleton is uracil, cytosine or thymine.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an oral composition, and more particularly to an oral composition which exhibits an excellent plaque control effect by adsorbing and removing microorganisms in the oral cavity.

[0002]

2. Description of the Related Art It has been clarified that dental caries and periodontal disease are caused by plaque, and plaque is produced by specific bacteria such as Streptococcus mutans using sucrose as a substrate for glucosyltransferase. By its action, glucan, which is a water-insoluble polysaccharide, is produced, and other pathogenic bacteria (periodontal pathogenic bacteria) including Streptococcus mutans are involved in the formation of glucan. Also, Streptococcus mutans and the like produce acids from various sugars in dental plaque, which causes the tooth enamel surface to be decalcified. In addition, bacteria such as Porphyromonas gingivalis and Fusobacterium nucleatum produce enzymes that destroy periodontal tissues, and act as a cause of periodontal disease.

Therefore, suppressing and preventing the formation of dental plaque is effective in preventing dental caries and periodontal disease. Examples of means for suppressing plaque formation include a method of decomposing the formed glucan, a method of using an antibacterial agent, a method of using a bacterial adsorbent, and the like. As a method for degrading glucan, a method using dextranase is well known. Further, as a method of using an antibacterial agent, cetylpyridinium chloride, chlorhexidine and the like are known and their effectiveness has been recognized. However, at present, little research has been done on bacterial adsorbents.

[0004]

Means for Solving the Problems In view of such circumstances, the present inventors have earnestly studied, and as a result, surprisingly, an oral composition containing a water-insoluble compound having a purine skeleton or a pyrimidine skeleton has excellent teeth. The inventors have found that they have an effect of suppressing the formation of plaque, and have completed the present invention. That is, since the oral composition of the present invention adsorbs oral bacteria and surface layer constituents or their decomposition products, plaque formation can be effectively suppressed, and an excellent plaque control effect can be obtained.

The compound used as an active ingredient in the oral composition of the present invention is a compound having a purine skeleton or a pyrimidine skeleton bound to a water-insoluble carrier directly or via a spacer. As the spacer, a C1-C12 alkylene group or C1-C1
2 is an alkenylene group, each of which is bonded to a carboxyl group or an amino group of a water-insoluble carrier. The purine skeleton or pyrimidine skeleton and the spacer alkylene group may have a substituent such as a carboxyl group, an oxo group, an alkyl group, a hydroxyl group, an amino group or an acyl group.

The water-insoluble carrier used in the present application may be any one as long as it can be bonded to the compound having the purine skeleton or the pyrimidine skeleton directly or via a spacer. Examples of such a water-insoluble carrier include a water-insoluble carrier having a hydroxyl group, an amino group, a carboxyl group or a halogen group. Among these compounds, preferred purine skeletons or pyrimidine skeletons are adenine or guanine, uracil, cytosine, thymine, etc., and the carrier of the carrier is directly without a spacer or through an ethylene group or a carboxyl-substituted ethylene group. Examples include compounds bonded to a hydroxyl group, a carboxyl group, and an amino group. Examples of preferable carriers include polysaccharides such as cellulose, agarose and cross-linked dextrin, hydroxyalkylated polystyrene resins (for example, hydroxyalkylated styrene / divinylbenzene copolymer), polyvinyl alcohol and the like.

Preferred examples of the spacer used in the present invention include NH ₂ (CH ₂ ) nNH ₃ and HOOC (CH ₂ ).
nCOOH, NH ₂ (CH ₂ ) nCOOH, NH ₂ (C
H ₂₎ nOH (n is an integer of 1-12.) And the like. The compound used in the present invention can be synthesized by a known method and is disclosed, for example, in JP-A-57-183712.

The oral composition of the present invention contains the compound having a purine skeleton or pyrimidine skeleton thus obtained in an amount of about 0.01 to 50% by weight, preferably 0.1 to 10% by weight based on the total amount of the composition. It is prepared by blending in a weight percentage. If the blending amount is less than 0.01% by weight, the effect of adsorbing microorganisms is not sufficiently exhibited, while if it is more than 50% by weight, the properties of the composition become unstable.

The oral composition of the present invention is prepared by a conventional method such as toothpaste (eg toothpaste, powder toothpaste, water toothpaste etc.), mouthwash, irrigator liquid, paste composition (eg ointment, cream etc.). , Chewing gum and the like, and in addition to the above-mentioned components, the following components can be appropriately blended depending on the form of the composition.

For example, as the nonionic surfactant, a fatty acid ester of sugar or sugar alcohol, wherein the fatty acid residue has 12 to 18 carbon atoms and the average degree of esterification is 1.1 to 2.5, preferably The thing of 1.2-1.9 can be used. Examples of the fatty acid ester of sugar or sugar alcohol include sucrose fatty acid ester, maltose fatty acid ester, maltitol fatty acid ester, maltotriitol fatty acid ester, maltotetriitol fatty acid ester, maltopentitol fatty acid ester,
Examples thereof include maltohexaitol fatty acid ester, maltoheptitol fatty acid ester, sorbitan fatty acid ester, lactose fatty acid ester, and lactitol fatty acid ester. Further, as the nonionic surfactant, in addition to this, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate and other polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene fatty acid esters , Fatty acid monoglyceride, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene fatty acid ester and the like can also be used.

As the anionic surfactant, for example, a water-soluble salt of a higher alkyl sulfate ester having an alkyl group having 8 to 18 carbon atoms such as sodium lauryl sulfate and sodium myristyl sulfate, α-olefin sulfonate, and higher fatty acid salt. Sodium monoglyceride monosulfate, sodium-N-methyl-N-palmityl tauride, sodium-N-lauroyloo β-alanine, lauroyl sarcosinate, sodium-N-long-chain acyl basic amino acid and the like are used.

Further, as the amphoteric surfactant, for example, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, alkyldiaminoethylglycine hydrochloride, lauryldimethylaminoacetic acid betaine and the like are used.

These surfactants may be used alone or in combination of two or more. In addition, the content of the surfactant is usually 0.01 to 20% by weight, preferably 0.05 to 10% by weight, based on the entire composition.

The oral composition of the present invention further includes menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terbineol, methyl acetate, citronellyl acetate, methyl eugenol, Cineol, linalool, ethyl linalool, vanillin, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, diatom oil, perilla oil, winter green oil, clove oil, eucalyptus oil. Fragrances such as oils can be blended alone or in combination in an amount of 0.1 to 10% by weight, preferably 0.5 to 5% by weight, based on the entire composition. Further, 0.01 to 1% by weight, preferably 0.01 to 1% by weight, of a sweetener such as saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartine, thaumatin, asparatyl phenylalanine methyl ester, and p-methoxycinnamic aldehyde. Is from 0.05
0.5% by weight can be blended.

For example, in the case of a paste composition such as an ointment, an anionic cellulose derivative such as sodium carboxymethyl cellulose or sodium carboxymethyl hydroxylethyl cellulose is used as a binder.
Alkali metal alginates such as sodium alginate, propylene glycol alginate, xanthan gum, tragacanth gum, gums such as karaya gum, arabic gum, carrageenan, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, synthetic binders such as polyvinylpyrrolidone, silica gel, One or more kinds of inorganic binders such as aluminum silica gel, bee gum and laponite may be blended. The blending amount of these is usually 0.3 to 5% by weight.

Further, in the production of a paste-like or liquid oral composition, sorbit, glycerin,
One kind or two or more kinds of ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltite, lactit and the like may be blended. The blending amount of these is usually 10 to 70% by weight.

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, silica gel, One or more of aluminum silicate, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, polymethylmethacrylate, bentonite, zirconium silicate, synthetic resin and the like can be blended, and can be blended. The amount is usually 5.0
˜90 wt%, and in the case of toothpaste 5.0 to 60 wt%.

In the present invention, as the active ingredient, further, cetylpyridinium chloride, chlorhexidine salts, bactericides such as triclosan, dextranase,
Amylase, protease, mutanase, lysozyme,
Enzymes such as lytic enzymes (Litech Enzyme), alkali metal monofluorophosphates such as sodium monofluorophosphate, potassium monofluorophosphate, sodium fluoride, fluorides such as stannous fluoride, tranexamic acid, epsilon aminocaproic acid, aluminum Chlorhydroxylantalin, dihydrocholesterol, glycyrrhizin salts, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, caropeptide,
One type or two or more types of active ingredients such as a water-soluble inorganic phosphate compound may be blended.

Further, this component can be used alone or in combination, and can be used by kneading it into a filament such as a toothbrush, an interdental brush, a dental floss or a cloth, or by surface-coating it. Alternatively, it can be used by soaking it in a cotton swab or cotton.

[0020]

EXAMPLES Next, the present invention will be described more specifically by showing experimental examples and examples, but the present invention is not limited thereto. Experimental example 1. Bacterial fluid preparation method Staphylococcus aureus
occus aureus) ATCC 6538, Streptococcus mutans
us mutans) ATCC25175, Fusobacterium nucretum (Fusobacterium)
nucleatum) ATCC 25586, Porphyromonas
gingivalis) FDC381 as a test strain,
Each test bacterium was cultured in Brain Heart Infusion liquid medium at 37 ° C for 20 hours and then centrifuged (70
The cells were harvested by sterilizing physiological saline, and the bacterial concentration was about 10 ⁶ cells / ml (OD ₅₆₀ = 0. ₀₀₎ .
02) was suspended in sterile physiological saline to give a test bacterial solution. The three strains except Staphylococcus aureus were analyzed under anaerobic conditions (N ₂ : 85%, H ₂ :
10%, CO _2: was subjected to culturing at 5%).

2. Evaluation method of microbial removal ability The shake flask method was used to evaluate the microbial removal ability. 1
A predetermined amount of the sample was placed in a 00 ml Erlenmeyer flask, and 36 ml of sterilized water was added to disperse the sample sufficiently. The Erlenmeyer flask was placed in a constant temperature bath at 37 ° C., 4 ml of the test bacterial solution was added, and shaken at 120 strokes / minute for 3 minutes. After shaking, the Erlenmeyer flask was removed from the thermostat and allowed to stand for a while, then 1 ml of the supernatant was taken and diluted with sterile physiological saline, and 0.1 ml was smeared on a Brain Heart Infusion agar plate. After culturing at 48 ° C. for 48 hours, the number of formed colonies was counted. This makes it possible to calculate the viable cell count after contact with the sample for 3 minutes. Microbial removal rate (%) is calculated according to the following formula, 90%
The above was judged to have an excellent effect of removing microorganisms.

[0022]

[Equation 1] The results are shown in Table 1.

[0023]

[Table 1]

As is clear from the results shown in Table 1, Sample 1 in which purines such as adenine, cytosine, uracil, thymine and guanine, and pyrimidine compounds were bound to a water-insoluble carrier such as sepharose, agarose and crosslinked dextran.
5 show a clearly higher microbial removal rate as compared with Samples 6 to 8 containing only the carrier. In this experiment, Porphyromonas gingivalis was used as a test bacterium. Next, in order to investigate the effect of the compound of Sample 1 shown in Table 1 for removing microorganisms in more detail, the difference due to the difference in bacterial species was examined. The results are shown in Table 2. In addition, when spacers with various chain lengths were examined, the same effect as that without spacers was obtained.

[0025]

[Table 2]

As is clear from the results of Table 2, sample 1
The adenine-bound Sepharose of Staphylococcus
It adsorbs oral bacteria such as Streptococcus mutans ATCC25175, Fusobacterium nucleoteum ATCC25586, and Porphyromonas gingivalis FDC381 better than Aureus ATCC6538. In particular, Fusobacterium nucleatum A
TCC25586, Porphyromonas gingivalis 3
The adsorption removal rate of 81 was almost 100%, which seems to be effective for removal of periodontal pathogens.

Example 1 A toothpaste was produced according to a conventional method according to the following formulation. Ingredient name Blending amount (wt%) Dibasic calcium phosphate dihydrate 50.0 Glycerin 20.0 Sodium carboxymethyl cellulose 1.0 Perfume 1.0 Polyoxyethylene hydrogenated castor oil 1.0 Sample 1 (Table 1) 1. 0 Saccharin sodium 1.0 Sodium fluoride 1.0 Allantoin 1.0 Water balance The microbial removal effect of the obtained dentifrice was evaluated by the above method, and a good microbial removal effect and an excellent feeling of use were obtained.

Example 2 A toothpaste was produced according to the conventional method according to the following formulation. Ingredient name Blend amount (wt%) Xanthan gum 3.0 Glycerin 30.0 Saccharin sodium 0.1 Perfume 1.0 Chlorhexidine gluconate 0.01 Ethanol 3.0 Lauroyl sarcosinate 1.0 Sample 2 (Table 1) 0.5 Methyl paraoxybenzoate 0.06 Water balance The microbial removal effect of the resulting water toothpaste was evaluated by the above method. As a result, a good microbial removal effect and an excellent feeling of use were obtained.

Example 3 A gingival massage cream was produced according to the following formulation. Ingredient name Blending amount (wt%) White petrolatum 8.0 Propylene glycol 4.0 Dextranase 1.0 Stearyl alcohol 8.0 Polyethylene glycol 4,000 25.0 Polyethylene glycol 400 37.0 Sucrose stearate 0. 5 Sample 3 (Table 1) 2.0 Methyl paraoxybenzoate 0.1 Water balance The obtained gingival massage cream was evaluated for microbial removal effect by the above method, and a good microbial removal effect and excellent feeling of use were obtained. Was given.

Example 4 A mouthwash was produced according to a conventional method according to the following formulation. Ingredient name Blend amount (wt%) Ethanol 10.0 Saccharin sodium 0.05 Perfume 1.0 Sodium monofluorophosphate 0.1 Chlorhexidine hydrochloride 0.01 Sample 5 (Table 1) 0.5 Sucrose palmitate 0.5 Methyl paraoxybenzoate 0.06 Water balance When the mouthwash thus obtained was evaluated for the effect of removing microorganisms by the method described above, a good effect of removing microorganisms and an excellent feeling of use were obtained.

Example 5 A chewing gum was manufactured according to a conventional method according to the following formulation. Ingredient content (g) Natural chicle 20 g Vinyl acetate resin 30 g Ester gum 10 g Wax 15 g Emulsifier 5 g Sample 4 (Table 1) 20 g The chewing gum obtained was evaluated for microbial removal effect by the above method, and showed good microbial removal effect. And an excellent usability was obtained.

[0032]

EFFECTS OF THE INVENTION The oral composition of the present invention has an excellent effect of removing microorganisms and is effective in removing plaque in the oral cavity and preventing periodontal disease.

Claims (4)

[Claims] 1. A composition for oral cavity, which comprises a substance in which a compound having a purine skeleton or a pyrimidine skeleton is bound to a water-insoluble carrier either directly or through a spacer, alone or in combination. 2. The oral composition according to claim 1, wherein the purine skeleton is adenine or guanine. 3. The oral composition according to claim 1, wherein the pyrimidine skeleton is uracil, cytosine or thymine. 4. The oral composition according to claim 1, wherein the water-insoluble carrier is a polysaccharide.