JPH0245412A - Mouth washing agent - Google Patents

Abstract

PURPOSE:To provide a mouth washing agent containing mutanase and a specific nonionic surfactant, having relatively good taste, low foamability and high stability and effective in preventing dental caries. CONSTITUTION:The objective agent is produced by compounding a mutanase- containing mouth wash agent with a surfactant selected from polyoxyethylene sorbitol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene phytosterol, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene beeswax derivative, polyoxyethylene polyoxypropylene block copolymer, polyoxyethylene sorbitan fatty acid ester and polyoxyethylene hardened castor oil or their combination. The objective agent is obtained by compounding 0.001-10wt.% of the mutanase and 0.01-5wt.% of the surfactant and preparing in the form of a drug by conventional method.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a mouthwash or other oral cleansing agent stably containing mutanase, which is a medicinal agent for caries prevention.

Conventional technologyThe mechanism of dental caries development has been known from the past! Streptococcus mutans, a caries-causing bacterium, produces a water-insoluble, sticky glucan (mutan) with α-1,3-glucoside bonds from sucrose, which firmly adheres to the tooth surface and absorbs lactic acid there. It is mentioned that it causes the production and demineralization of teeth (Clinical Science and Bacteria! Vol. 24, p. 974). Mutanase is an enzyme that decomposes the α-1,3-gelcondo bond of the glucan produced by Streptococcus mutans, and uses this action to decompose the glucan and prevent Streptococcus mutans from adhering to the tooth surface. Attempts have been made to prevent dental caries and thereby prevent dental caries (Journal of Dental Research, Vol. 51,
Supplement, p. 394, 1972). It has also been proposed that mutanase be added to toothpaste etc.
No. 5006), it has been recognized that mutanase is effective in preventing dental caries.

Problems to be Solved by the Invention However, in oral cleansers or oral compositions, generally,
Surface activity is used to solubilize fragrances, etc., but mutanase is extremely unstable to these surfactants and easily loses its enzymatic activity. Even if mutanase is incorporated, the enzyme activity will decrease and the caries prevention effect will be limited. However, it was difficult to put it into practical use.

Under these circumstances, in order to stably incorporate mutanase into oral compositions, N-acyl sarcosine salt (Japanese Patent Application Laid-Open No. 152314/1983), N-acyl sarcosine salt and sucrose have been used as surfactants. Fatty acid ester (JP-A-59-
152315). However, N-acylsarcosine salts are themselves relatively insufficiently stable for use as mouthwashes;
There were problems in that it tasted bad and foamed too much, making it difficult to clean.

Therefore, the present inventors conducted extensive research in order to obtain a mouthwash that stably contains mutanase, has a relatively good taste, and has low foaming properties. As a result, it was discovered that among nonionic activators that are generally said to have a relatively good taste, low foaming properties, and high stability, certain kinds of activators specifically stabilize mutanase, and the present invention was completed. I ended up doing it.

Means for Solving the Problems The present invention provides a mouthwash containing mutanase,
As a surfactant, polyoxyethylene sorbitol fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene phytosterol, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene beeswax derivative, polyoxyethylene poly The present invention provides a mouthwash characterized by containing one or a combination of oxypropylene block copolymers, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene hydrogenated castor oil. According to the present invention, the blended mutanase can maintain sufficient enzymatic activity for a long time and exhibit excellent dental caries prevention effects.

The polyoxyethylene sorbitol fatty acid ester to be used has an added mole number of ethylene oxide of 5 to 70. Fatty acids having 12 to 18 carbon atoms, such as commercially available Go-
460, GO-440, and GO-430 (Nikko Chemicals Co., Ltd.).

Examples of the polyoxyethylene glycerin fatty acid ester include those having an added mole number of ethylene oxide of 5 to 20 and a fatty acid having a carbon number of 8 to 18, such as commercially available TMGS-5,
TMGS-15 (Nikko Chemicals Co., Ltd.) is mentioned. Examples of polyoxyethylene alkyl ethers include commercially available BL-9BX, B
L21, BL-15TXSBS-20, BO-15TX
, BB-20 (Nikko Chemicals Co., Ltd.).

Examples of the polyoxyethylene phytosterol include those having an added mole of ethylene oxide of 5 to 30, such as commercially available BPS-10% BPS20 and BPS-30 (Nikko Chemicals Co., Ltd.). As polyoxyethylene polyoxypropylene alkyl ether, the number of added moles of ethylene oxide is 1 to 30, the number of added moles of propylene oxide is 2 to 1O, and the number of carbon atoms of alkyl is 12 to 2.
4, such as commercially available PBC-34, PEN463
0 (Nikko Chemicals Co., Ltd.).

Examples of polyoxyethylene beeswax derivatives include those containing 5 to 40 moles of ethylene oxide, such as commercially available GBW-125 and GBW-25 (Nikko Chemicals Co., Ltd.). As polyoxyethylene/polyoxypropylene block copolymers, for example, commercially available ethylene oxide polymerization degree 190-2601 propylene oxide polymerization degree 50-70 degrees Pluronic P10B, Pluronic F
127 (Asahi Denka Kogyo) is mentioned. As polyoxyethylene sorbitan fatty acid ester, the number of added moles of ethylene oxide is 5 to 20, and the number of carbon atoms of fatty acid is 12 to 18.
For example, commercially available TS-10, To-10M, T
o-30 (Nikko Chemicals Co., Ltd.). The polyoxyethylene hydrogenated castor oil has an added mole of ethylene oxide of 5 to 100, for example, commercially available H
Examples include CO-30, HCO-60, and HCO-30 (Nikko Chemicals Co., Ltd.). These nonionic activators may be used alone or in combination of two or more, and from the viewpoint of mutanase stabilizing effect, the amount of nonionic activators may be 0.01 to 5% based on the total amount of the oral cleansing agent.
It is blended in an amount of 0.1 to 2% by weight, preferably 0.1 to 2% by weight.

Mutanase can be used regardless of its origin as long as it has α-1,3-glucoside bond hydrolase activity, and examples of commonly available mutanase include Trichoderma harzianum OMZ779 and Cladosporium resinine. QM7998, Streptomyces veerensis, Aspergillus nidorans, Flavobacterium
Mutanase-producing bacteria such as Pseudomonas bii and Pseudomonas bii are cultured in a medium containing a normal nutrient source, or cultured in a medium to which α-1,3-glucan is added, or mutanase-producing bacteria are cultured with a gene. The supernatant of the mutanase-containing culture solution obtained by culturing the
Examples include those obtained by fractionation using salting-out methods, adsorption methods, solvent fractionation methods, and the like. In general, the properties of mutanase vary slightly depending on the type of producing bacteria, but the characteristics of mutanase are that the optimum pH is usually on the acidic side and that it has the ability to decompose mutan and liberate and solubilize reducing sugars. . In the present invention, usually 100% of the total mouthwash is used.
0 to 1 million units/g of mutanase from 0.001% to 1
By adding 0% by weight, the desired caries prevention effect can be obtained. Note that one unit of mutanase is defined as an enzyme bottle that decomposes mutan at 40° C. in a 0.1 M acetate buffer (pH 5, 7) and releases 1 μM of reducing sugar in terms of glucose per minute.

The oral cleansing agent of the present invention can be made into a net form such as a mouthwash by a conventional method, and other ingredients are not particularly limited, and as long as they do not impair the stability of mutanase.
Fragrances, solvents, preservatives, pH buffers, sweeteners, colorants, and other active ingredients typically used in this type of cleaning agent can be incorporated, and the mutanase-stabilizing effect of nonionic surfactants can then be enhanced. The results of the test are shown.

Test l Mutanase 17.0+9 (6500 units/g) 011
It was dissolved in 500-M acetate buffer (pH 5,7) to prepare an enzyme solution. This enzyme solution 10- was added with solutions of various surfactants shown in Table 1 prepared with acetic acid buffer (prepared so that the final active agent concentration was 0.5%) (however, for the control, acetic acid Buffer only) 10mf2 was added. Immediately after this addition, 0.1 mQ of the mixed solution was taken, 0.4 m (l) of 0.5% mutan suspension was added, and after reacting at 40°C for 10 minutes, free reducing sugars were quantified by the Somogyi-Nerlan method. As a control, a heat-inactivated enzyme solution was used.
Free reducing sugars were determined in the same manner. Next, the same quantitative operation was performed on a mixture of the enzyme solution and the surfactant solution that was left at 40° C. for 7 days after being mixed.

In this way, the mutanase activity of the control without surfactant immediately after addition in the surfactant addition reaction system is set as 100, and the relative mutanase activity in the control and various surfactant addition reaction systems after being left at 40°C for 7 days is calculated. The ratio was calculated. The results are shown in Table 1.

(40°C, 7 days) From the results in Table 1, among nonionic surfactants, polyoxyethylene sorbitol fatty acid ester,
Polyoquine ethylene glycerin fatty acid ester, polyoquine ethylene alkyl ether, polyoquine phytosterol, polyoxyethylene polyoquine propylene alkyl ether, polyoquine ethylene beeswax derivative, polyoxyethylene polyoxypropylene broth copolymer, polyoxyethylene sorbitan lucid It is observed that fatty acid esters and polyoxyethylene hydrogenated human oil specifically stabilize mutanase.

When 0.01% by weight or more of -chill is added, mutanase is more stabilized than the control, whereas in the case of sorbitan fatty acid ester, it tends to be inhibited as the amount increases.

Example Next, the present invention will be explained in more detail with reference to Examples.

Example 1 A mouthwash was manufactured according to a conventional method using the following formulation.

Ingredients Weight 1% Mutanase (10,000 units/g) 0.1 Citric acid 0.2 Polyoxyethylene hydrogenated Himashiura 1.0 (POE=60) Flavoring 0.3 Sorbiturate liquid 15.0 Saccharin sodium 0.03 Ethyl alcohol
2.0 water
Remaining Test 2 Next, based on the results in Table 1, studies were conducted in the same manner as in Table 1 by changing the blending amounts of polyoxyethylene alkyl ether, which had good stability, and sorbitan fatty acid ester, which had poor stability.

The results are shown in Table 2.

Table 2 (40°C 75% 7 days) From this result, polyoxyethylene alkyl
100.0% Example 2 A mouthwash was manufactured according to a conventional method using the following formulation.

Ingredients Weight% Mutanase (100,000 units/g) 0.1 Polyoxyethylene hydrogenated castor oil 5.0 (POE・50) Fragrance!・0 Glycerin liquid 40.0 Saccharin sodium 0.1 Ethyl alcohol
3.0 water
Remaining total: 100% This solution was diluted 10 times. Example 3 A mouthwash was manufactured according to a conventional method using the following formulation.

Ingredients Weight % Mutanase (10,000 units/g) 0.1 Polyoxene ethylene (POE = 196) Poly xO oxypropylene (POP = 67) block copolymer fragrance 0.5 Glycerin liquid 15.0 Satucarin sodium 0.02 Cetylpyridinium chloride 0. ol ethyl alcohol
! , 0 water Remaining total 100.0% Effects of the invention According to the present invention, by using a specific nonionic surfactant, an oral cleansing agent stably containing mutanase can be obtained, and exhibits an excellent caries prevention effect. can be done.

Claims (1)

[Claims] Mutanase, polyoxyethylene sorbitol fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene phytosterol, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene beeswax derivative, polyoxyethylene polyoxypropylene block 1. A mouthwash comprising a surfactant selected from a copolymer, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene hydrogenated castor oil, either alone or in combination.