JPH06287126A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for oral cavity exhibiting excellent controlling effect on plaque by removing microorganisms in the oral cavity by adsorption. CONSTITUTION:A composition for oral cavity is characterized by compounding a cationic amino acid or a cationic amino acid-containing peptide bonded directly or through a spacer to a water-insoluble carrier, alone or in a combined state.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates 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, which decalcify the tooth enamel surface. 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 glucan formed, 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 As a result of intensive studies made by the present inventors in view of such circumstances, surprisingly, a cationic amino acid or a peptide containing a cationic amino acid in the molecule was directly or spacer-attached to a water-insoluble carrier. Since the substance bound via the adsorbs to the oral bacteria and its surface layer constituents or their decomposition products, it was found that plaque formation can be effectively suppressed, and the present invention has been completed.

That is, the present invention is characterized in that a substance in which a cationic amino acid or a peptide containing a cationic amino acid in the molecule is bound to a water-insoluble carrier directly or via a spacer is added as an active ingredient. An oral composition is provided. The present invention will be specifically described below.

The oral composition of the present invention efficiently removes the microorganisms in the oral cavity and the surface layer constituents or their decomposition products, and prevents the accumulation and calcification of the products thereof, thereby providing an excellent plaque control effect. Indicates.

The compound used as an active ingredient in the present invention has the formula (1):

[Formula 1] (Wherein R represents an amino acid or a peptide, A represents a single bond, an alkylene group or an alkenylene group, and X represents A
Represents a hydrogen atom or a functional group when is a single bond, and represents a functional group when A is an alkylene group or an alkenylene group. It can be prepared by covalently bonding the amino acid compound represented by (4) and a water-insoluble carrier directly or via a spacer.

As an example of the amino acid compound according to the present invention, for example, R in the formula (1) is a cationic amino acid or a peptide containing a cationic amino acid in the molecule, and A
Is a single bond and X is a hydrogen atom, an amino group, a hydroxyl group or a carboxyl group, or A is a methylene group, an ethylene group, a propylene group, a butylene group, a hexylene group,
An alkylene group having 1 to 12 carbon atoms such as an octylene group, a decamethylene group, a dodecamethylene group or a vinylene group, a propenylene group, a butenylene group, a hexenylene group, an alkenylene group having a carbon number of 2 to 12 such as octynylene group, and X is an amino group And a compound having a hydroxyl group or a carboxyl group. The cationic modifying group represented by R and the alkylene group represented by A may have a substituent (for example, a carboxyl group, an oxo group, an alkyl group, a hydroxyl group, an amino group, an alkoxy group).

Among the above amino acid compounds, preferred examples are amino acids in which R is lysine or arginine in formula (1), more preferably histidine, or amino acids 3 having at least one of these amino acids.
A peptide of 0 or less, A is a single bond and X is a hydrogen atom, an amino group, a hydroxyl group or a carboxyl group,
Alternatively, a compound in which A is an ethylene group or a carboxyl-substituted ethylene group and X is an amino group, a carboxyl group or a hydroxyl group can be mentioned.

On the other hand, the water-insoluble carrier used in the present invention may be any as long as it can bind the amino acid compound represented by the formula (1) directly or via a spacer. Representative 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 atom.

Examples of these water-insoluble carriers include polysaccharides such as cellulose, agarose and cross-linked dextran, hydroxyalkylated polystyrene resins (for example, hydrosilylated styrene / divinylbenzene copolymer), polyvinyl alcohol and the like. Suitable examples include:

Prior to binding the water-insoluble carrier as described above and the compound represented by the formula (1), a spacer may be introduced into the carrier or the compound (1). As a typical example of the spacing element, Expression (2):

[Formula 2] And so on. A typical method for synthesizing a bacterial adsorbent used in the present invention is disclosed in JP-A-57-183712, and histidine-immobilized cellulose is commercially available from Daicel Chemical Industries, Ltd. under the trade name of PYROSEP. Has been done.

The oral composition of the present invention contains the cationic amino acid compound 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 can be prepared by a conventional method such as toothpaste (eg toothpaste, powder toothpaste, water toothpaste), mouthwash, irrigator liquid, paste composition (eg ointment, cream). It may be in the form of chewing gum or the like, and in addition to the above components, the following components may 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, an α-olefin sulfonate, and a 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. Also, 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, perillartin, 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 carboxymethylhydroxyl ethyl cellulose 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, synthetic binders such as polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, 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 acid 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 5-9
It is 0% by weight, and in the case of toothpaste, it is 5 to 60% by weight.

Further, in the present invention, as the active ingredient, 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 may be used alone or in combination, and may be kneaded or surface-coated into filaments such as toothbrush, interdental brush, dental floss, cloth and the like. Alternatively, it can be used by soaking it in a cotton swab or cotton.

[0025]

EXAMPLES Next, the present invention will be described more specifically by showing experimental examples and examples, but the present invention is not limited thereto. In addition, "%" is% by weight. Experimental example 1. Bacterial fluid preparation method Staphylococcus aureus
occus aureus) ATCC 6538, Streptococcus mutans
us mutans) ATCC 25175, Fusobacterium nucretum (Fusobacterium)
nucleatum) ATCC 25586, Porphyromonas
gingivalis) FDC381 is used as a test strain, each test strain is cultured in Brain Heart Infusion liquid medium at 37 ° C. for 20 hours, and then centrifuged (7,000 rpm, 10 minutes) to collect the cells, and then sterilized physiological saline. After washing with water, the bacterial concentration was about 10 ⁶ cells / ml (OD ₅₆₀ =
The test bacterial solution was suspended in sterilized physiological saline so as to obtain 0.02). The 3 strains except Staphylococcus aureus were cultured under anaerobic conditions (nitrogen 85%, hydrogen 10%, carbon dioxide 5%). 2. Evaluation method of microbial removal ability The shake flask method was used to evaluate the microbial removal ability. 1
Put a specified amount of sample in a 00 ml Erlenmeyer flask and use sterile water 3
6 ml was added and well dispersed. Replace the Erlenmeyer flask with 37
Place in a constant temperature bath at ℃, add 4 ml of the test bacterial solution,
Shake for 3 minutes at 0 strokes / minute. After shaking, remove the Erlenmeyer flask from the thermostat and let it stand for a while, then take 1 ml of the supernatant and dilute it with sterile physiological saline.
ml was smeared on a Brain Heart Infusion agar plate and incubated at 37 ° C. for 48 hours, and then 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. The microbial removal rate (%) was calculated according to the following formula, and 90% or more was determined to have an excellent microbial removal effect.

[Equation 1]

The adsorption effect was examined using Polyphilomonas gingivalis as a test bacterium. The results are shown in Table 1.

[Table 1] As is clear from the results of Table 1, samples 1 to 7 on which histidine, arginine, lysine, that is, cationic amino acids or peptides containing them are immobilized,
Compared with Samples 8 to 10 in which other amino acids or peptides containing only those amino acids and Samples 11 to 13 in which only amino acid-immobilized carriers were used, the effect of removing microorganisms was clearly higher. Regarding the spacer,
Examination using various alkylene groups (C1 to C12) and alkenylene groups (C2 to C12) having different chain lengths showed the same effect as the sample without a spacer.

Next, in order to examine the effect of the compound of Sample 1 shown in Table 1 on the removal of microorganisms in more detail, the difference due to the difference in bacterial species was examined. The results are shown in Table 2.

[Table 2] As is clear from the results in Table 2, the histidine-bonded sepharose of Sample 1 adsorbs oral bacteria such as Streptococcus mutans ATCC25175, Fusobacterium nucleoteum ATCC25586, and Porphyromonas gingivalis FDC381 better than Staphylococcus aureus ATCC6538. is doing. In particular, Fusobacterium nucleatum ATCC2
5586, Porphyromonas gingivalis FDC38
The adsorption removal rate of 1 was almost 100%, which seems to be effective for the removal of periodontal pathogens.

Example 1 A toothpaste was produced by the following method according to a conventional method. Ingredient name Blend amount (%) Dibasic calcium phosphate dihydrate 50 Glycerin 20 Sodium carboxymethyl cellulose 1.0 Fragrance 1.0 Lauroyl sarcosinate 1.0 Sample 1 (Table 1) 1.0 Sodium saccharin 1.0 Fluoride Sodium 1.0 Allantoin 1.0 Water balance When the dentifrice thus obtained was evaluated for the effect of removing microorganisms by the above method, a good effect of removing microorganisms 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 (%) Xanthan gum 3.0% Glycerin 30.0 Saccharin sodium 0.1 Perfume 1.0 Chlorhexidine gluconate 0.01 Ethanol 3.0 Polyoxyethylene hydrogenated castor oil 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 Blend amount (%) 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 ester 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 (%) Ethanol 10% Saccharin sodium 0.05 Perfume 1.0 Sodium monofluorophosphate 0.1 Chlorhexidine hydrochloride 0.01 Sample 4 (Table 1) 0.5 Sucrose palmitate 0.5 Paraoxybenzoic acid Methyl acid 0.06 water balance The microbial removal effect of the obtained mouthwash was evaluated by the above method. As a result, a good microbial removal effect and an excellent feeling of use were obtained.

Example 5 A chewing gum was produced according to a conventional method according to the following formulation. Gum Base (100 g) Natural Chickle 20 Vinyl Acetate Resin 30 Ester Gum 10 Wax 15 Emulsifier 5 Sample 5 (Table 1) 20 The resulting chewing gum was evaluated for microbial removal effect by the above-mentioned method and found to have excellent microbial removal effect A feeling of use was obtained.

[0033]

EFFECTS OF THE INVENTION According to the present invention, there is provided an oral composition having an excellent action of removing microorganisms, which contains a water-insoluble compound having a cationic modifying group.

Claims (4)

[Claims] 1. A composition for oral cavity comprising a substance in which a cationic amino acid or a peptide containing a cationic amino acid is bound to a water-insoluble carrier directly or via a spacer, alone or in combination. 2. The composition for oral cavity according to claim 1, wherein the cationic amino acid or the peptide containing the cationic amino acid has at least one of histidine, lysine and arginine. 3. The oral composition according to claim 1, wherein the cationic amino acid or the peptide containing the cationic amino acid is histidine. 4. The oral composition according to claim 1, wherein the water-soluble carrier is a polysaccharide.