JP2848679B2 - Oral composition - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to an oral composition, more specifically, a toothpaste, a lubricating dentifrice, and a liquid dentifrice stably blended with mutanase, which is a medicinal agent for preventing dental caries. Oral compositions such as mouthwashes, pastas, and denture cleansers.

2. Description of the Related Art Conventionally, as one of the mechanisms of tooth caries, Streptococcus mutans, which is a cariogenic bacterium, is composed of water-insoluble, sticky glucan having α-1,3-glucoside bond from sucrose ( Mutan) and firmly adhere to the tooth surface, where lactic acid is produced to demineralize the teeth (Clinical and Bacteria, Vol. 1, p. 24, 1974). Mutanase is an enzyme that decomposes the α-1,3-glucoside bond of glucan produced by Streptococcus mutans, and utilizes its action to decompose the glucan to prevent adhesion of Streptococcus mutans to the tooth surface. Attempts to prevent and thereby prevent dental caries (Journal of Dental Research, Volume 51,
Addendum, p. 394, 1972). The mutanase used for this is derived from Trichoderma harzianum, but also those derived from the genus Flavobacterium (Japanese Patent Publication No. 52-38113) and the genus Pseudomonas (Japanese Patent Publication No. 56-1070) have been reported. . It has also been proposed to mix mutanase in toothpastes and the like (JP-B-55-50006, JP-B-57-368).
No. 90), mutanase has been recognized to be effective in preventing dental caries.

Problems to be Solved by the Invention However, mutanase is unstable in the presence of water, a surfactant, or a change in pH, and easily loses its enzyme activity, while, for example, surfactants are generally solubilized. Since it is an essential component in the oral composition as an agent, a foaming agent, a dispersant, and / or a cleansing agent, it has been quite difficult to stably mix mutanase in the oral composition. Under these circumstances, JP-A-2-45415 discloses that
It has been proposed to stably mix mutanase by using a polyoxyethylene alkyl ether phosphate as a surfactant. From the viewpoint of effervescence, an alkyl phosphate to which ethylene oxide has not been added is more preferable, but if ethylene oxide is not added, mutanase cannot be stabilized.

In view of such circumstances, the present inventors have intensively studied to stably mix mutanase and obtain an oral composition having excellent foamability and stability. As a result, they have found that the stabilization of mutanase can be achieved by using a combination of an alkyl phosphate and a specific nonionic surfactant as surfactants, and completed the present invention.

Means for Solving the Problems The present invention provides an oral composition comprising a mutanase, wherein an alkyl phosphate and a nonionic active agent are blended as surfactants. It is. ADVANTAGE OF THE INVENTION According to this invention, the mutanase mix | blended with the composition for oral cavity can maintain sufficient enzyme activity for a long period of time, and can exhibit the excellent tooth caries prevention effect.

The alkyl phosphate used is represented by the formula: R—O—PO ₃ M ₂ [wherein, R represents an alkyl group and M represents a cation forming a salt]. Those having 12 to 18 carbon atoms are preferred from the viewpoint of the properties and dispersibility of other components. As the cation represented by M, sodium and triethanolamine are preferable from the viewpoint of availability. Representative examples of such alkyl phosphates include sodium lauryl phosphate, triethanolamine lauryl phosphate, and the like. Usually, the alkyl phosphate is preferably blended in an amount less than 15 times the amount of the mutanase, and for the total amount of the composition, in consideration of system stability and the like,
It is preferable to mix at a ratio of 0.005 to 2.5% by weight.

Examples of the nonionic activator used include polyoxyethylene sorbitan fatty acid esters having 5 to 30 moles of ethylene oxide and 12 to 18 carbon atoms of fatty acid, and 6 to 60 moles of ethylene oxide and 12 to 18 carbon atoms of fatty acid. Ethylene sorbite fatty acid ester, ethylene oxide added mole number 5-20, polyoxyethylene glycerin fatty acid ester having 8-18 carbon atoms, polyethylene glycol molecular weight 40-2800, polyethylene glycol fatty acid ester having 12-18 carbon atoms, ethylene oxide Number of moles of addition 2 to 50, polyoxyethylene alkyl ether having 12 to 22 carbon atoms of alkyl, number of moles of addition of ethylene oxide 3
Polyoxyethylene castor oil having a molecular weight of 1 to 100, a polyoxyethylene lanolin derivative having an addition mole number of 1 to 100 of ethylene oxide, a polyoxyethylene nonylphenyl formaldehyde condensate having an addition mole number of 1 to 50 of ethylene oxide, and having 10 to 18 carbon atoms Sucrose fatty acid ester, ethylene oxide average polymerization degree 190-260, propylene oxide average polymerization degree 50-
70 polyoxyethylene polyoxypropylene block copolymers, and C8-18 fatty acid alkylolamides. Usually, these nonionic activators are preferably mixed in a range of 0.2 to 1000 times with respect to the mutanase, and with respect to the total amount of the composition, considering the stability of the system,
It is blended at a rate of 0.01 to 5% by weight. The total amount of the anionic and nonionic activators is desirably 5% by weight or less based on the total amount of the composition.

Mutanase can be used irrespective of microbial origin as long as it has α-1,3-glucoside bond hydrolyzing activity, and usually available ones include, for example, Trichoderma harzianum OMZ779, Cladosporium. A medium containing normal nutrients such as Regine QM7998, Streptomyces verensis, Aspergillus nidulans, Flavobacterium sp.Pseudomonas sp.
A culture obtained by culturing in a medium supplemented with 1,3-glucan or a mutanase-producing bacterium is genetically manipulated, and a supernatant of a mutanase-containing culture solution obtained by culturing the resultant is subjected to salting-out, adsorption, and solvent fractionation. And those obtained by separation by a method. In general, the properties of mutanase vary slightly depending on the type of producing bacteria, but usually the optimal pH is on the acidic side,
It is characterized as having a function of decomposing mutans to release and solubilize reducing sugars.

In the present invention, usually, 1000 to the total composition.
By mixing 0.001 to 10% by weight of 1,000,000 units / g of mutanase, a desired caries preventive effect can be obtained. One unit of mutanase is obtained by decomposing mutan at 40 ° C. in a 0.1 M acetate buffer (pH 5.7) to obtain 1 μm of glucose per minute.
It is defined as the amount of enzyme that releases M reducing sugars.

The oral composition of the present invention can be made into a usual dosage form such as toothpaste, lubricating dentifrice, liquid dentifrice, mouthwash, pasta, denture cleaning agent, etc. according to a conventional method, and other components are particularly limited. Not as long as it does not impair the stability of the mutanase
Generally, any of those used in this type of composition can be used. For example, in the case of toothpaste, an abrasive, a binder, a humectant, a sweetener, a flavor, a preservative, and other medicinal agents are appropriately compounded.

Next, the results of examining the mutanase stabilizing effect when the alkyl phosphate and the nonionic activator are used in combination are shown.

Test 1 Pseudomonas sp. (Microtechnical Laboratory No. 4273)
17 mg (6500 units / g) of the derived mutanase was dissolved in 500 ml of 0.1 M acetate buffer (pH 5.7) to obtain an enzyme solution. This enzyme solution 10
To each ml, 10 ml of a solution of various surfactants shown in Table 1 was added and mixed. After leaving this mixture in a water bath at 25 ° C. for 3 hours, the enzyme activity in the mixture was measured. The enzyme activity was measured by quantifying the reducing sugar released by the enzyme by the Somogyi-Nelson method. Table 1 shows the relative ratio of the mutanase activity in the reaction system in which the surfactant was added, where the initial mutanase activity in the reaction system in which no surfactant was added was 100%.

As shown in Table 1, the ratio of mutanase to sodium lauryl phosphate was 1 / 7.5, the ratio of mutanase to various nonionic activators was 1 / 22.5, that is, the ratio of sodium lauryl phosphate to nonionic activator was 1: 3. , And left with mutanase, the stability of mutanase, among nonionic activators, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene Ethylene alkyl ether, polyoxyethylene castor oil, polyoxyethylene lanolin, polyoxyethylene alkylphenyl formaldehyde condensate, sucrose fatty acid ester, polyoxyethylene polyoxypropylene block copolymer, fat It was found that specifically improved when using acid alkylolamides.

Test 2 Among nonionic activators, using polyoxyethylene sorbitan fatty acid ester and polyoxyethylene alkyl ether, which had good stability, the ratio of anionic activator to nonionic activator, and enzyme to anionic activator, nonionic activator The test similar to the test 1 was performed by changing the ratio of. The results are shown in Table 2.

From the results shown in Table 2, the ratio of the alkyl phosphate to the nonionic activator was examined when the ratio of the alkyl phosphate to the nonionic activator was changed. Is 3: 1 or less (in the direction of decreasing alkyl phosphate)
In this case, it was confirmed that mutanase was stabilized.

Examples Next, the present invention will be described in more detail with reference to examples.

Example 1 Toothpaste was manufactured according to a conventional method according to the following formulation.

 Ingredient Weight% Dibasic calcium phosphate 45.0 Sorbitol 25.0 Sodium carboxymethylcellulose 1.0 Sodium lauryl phosphate 0.5 Polyoxyethylene (20 mol) 1.5 Sorbitan monooleate Saccharin sodium 0.2 Fragrance 1.0 Mutanase (10,000 units / g) 0.1 Purified water Remaining Example 2 According to the following formulation, toothpaste was manufactured according to a conventional method.

 Ingredient Weight% Dibasic calcium phosphate 40.0 Glycerin 20.0 Sodium carboxymethylcellulose 1.0 Sodium lauryl phosphate 0.8 Polyoxyethylene (60 mol) 2.4 Sorbitol tetraoleate Saccharin sodium 0.2 Mutanase (10,000 units / g) 0.1 Perfume 1.0 Purified water Remaining Example 3 Water dentifrices were manufactured according to the following formulation according to a conventional method.

 Ingredient Weight% Glycerin 10.0 Sodium saccharin 0.1 Sodium lauryl phosphate 0.3 Polyoxyethylene (15 mol) 1.0 Glycerin monostearate mutanase (100,000 units / g) 0.01 Ethanol 5.0 Perfume 0.2 Purified water Remainder Example 4 Water toothpaste was manufactured according to the method.

 Ingredients Weight% Sorbit 10.0 Stevia extract 0.1 Sodium lauryl phosphate 0.2 Polyethylene glycol (45 mol) 1.0 Monostearate mutanase (100,000 units / g) 0.01 Ethanol 5.0 Fragrance 0.3 Purified water Remainder Example 5 A toothpaste was manufactured in accordance with the following.

 Ingredient Weight% Aluminum hydroxide 45.0 Sorbit 15.0 Sodium lauryl phosphate 1.0 Polyoxyethylene (9 mol) 3.0 Lauryl ether Carrageenan 0.8 Saccharin sodium 0.2 Mutanase (5000 units / g) 0.2 Perfume 1.0 Purified water Remainder Example 6 Toothpaste was manufactured according to a conventional method.

Ingredients Weight% Silicic anhydride 15.0 Sorbit 60.0 Xanthan gum 0.7 Sodium lauryl phosphate 1.2 Polyoxyethylene (60) 1.5 Castor oil Sodium saccharin 0.2 Mutanase (10,000 units / g) 0.1 Perfume 1.0 Purified water Remainder Example 7 A mouthwash was manufactured according to a conventional method.

Ingredients Weight% Glycerin 15.0 Saccharin sodium 0.05 Ethanol 3.0 Fragrance 0.2 Triethanolamine lauryl phosphate 0.2 Polyoxyethylene lanolin 1.0 Mutanase (5000 units / g) 0.1 Purified water Remaining Example 8 Manufactured.

 Ingredient Weight% Sodium percarbonate 30.0 Tartaric acid 30.0 Sodium tripolyphosphate 4.0 Lactose 34.8 Sodium lauryl phosphate 0.5 Polyoxyethylene (1 mol) nonyl 0.5 Phenylformaldehyde condensate Mutanase (1000 units / g) 0.2 Example 9 According to the following formulation: Toothpaste was manufactured according to a conventional method.

Ingredient Weight% Dibasic calcium phosphate 35.0 Sorbit 45.0 Carrageenan 1.0 Sodium lauryl phosphate 0.5 Sucrose laurate ester 1.5 Saccharin sodium 0.2 Mutanase (10,000 units / g) 0.05 Fragrance 0.8 Purified water Remainder Example 10 A mouthwash was manufactured.

Component Weight% Glycerin 15.0 Saccharin sodium 0.05 Ethanol 5.0 Flavor 0.3 Sodium lauryl phosphate 0.2 Polyoxyethylene (196 mol) 0.8 Polyoxypropylene (67) Block copolymer Mutanase (1000 units / g) 1.0 Purified water Balance ADVANTAGE OF THE INVENTION According to this invention, the composition for oral cavity which stably mix | blend mutanase and which has favorable foamability is obtained.

Claims (2)

(57) [Claims] The present invention relates to an oral composition containing mutanase, wherein a surfactant is used in an amount of 15
An oral composition comprising less than twice the amount of an alkyl phosphate and a nonionic surfactant. 2. The oral composition according to claim 1, wherein the content of the alkyl phosphate is less than 3 times the amount of the nonionic surfactant.