JPH0273007A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for the oral cavity useful as a toothpaste, wet dentrifice, liquid dentrifice, mouthwash, pasta, etc., by using an N- acylsarcosine salt with a specific nonionic surfactant as a surfactant in combination and stably blending mutanase (a drug for preventing dental caries) therewith. CONSTITUTION:A composition for the oral cavity, obtained by blending a composition containing mutanase with (A) an N-acylsarcosine salt and (B) POE (polyoxyethylene) sorbitol esterof a fatty acid, POE glycerol ester of a fatty acid, POE alkyl ether, POE lanolin derivative, POE nonyl phenyl formaldehyde condensate, POE.polyoxypropylene block copolymer, POE sorbitan ester of a fatty acid, POE hardened castor oil, POE castor oil and/or polyethylene glycol ester of a fatty acid as a surfactant and capable of exhibiting excellent preventive effects on dental caries with the mutanase sustaining sufficient enzymic activity for a long period.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides an oral composition, more specifically, a toothpaste stably containing mutanase, which is a medicinal agent for preventing dental caries.
The present invention relates to oral compositions such as moist toothpaste, liquid toothpaste, mouthwash, pasta, and denture cleaner.

Conventional techniques and problems It has been known that one of the mechanisms of dental caries development is that Streptococcus mutans, a caries-causing bacterium, converts sucrose into a water-insoluble, sticky substance containing α-1,3-glucoside bonds. It is said that it produces glucan (mutan) and firmly adheres to the tooth surface, where it produces lactic acid and demineralizes the tooth (Clinic and Bacteria, vol. 1, p. 24, 1974).
. Mutanase is an enzyme that decomposes the α-1,3-glucoside bond of the glucan produced by Streptococcus mutans, and uses this action to decompose the glucan and prevent the adhesion of Streptococcus mutans to the tooth surface. Attempts have been made to prevent caries by preventing caries (Journal of Dental Research, Vol. 51, Supplement, p. 394, 1972). The mutanase used for this purpose may be derived from Trichoderma harzianum, or may also be derived from Flavobacterium (Special Publication No. 51).
-38113), Pyodomonas (Special Publication No. 56107)
No. 0) origin, etc. have been reported.

It has also been proposed to incorporate mutanase into toothpaste, etc.
890), it has been recognized that mutanase is effective in preventing dental caries. However, mutanase is extremely unstable in the presence of moisture and surfactants and to changes in p)I and is prone to lose its enzymatic activity; for example, surfactants are generally used as blowing agents, dispersants and/or Also, since mutanase is an essential component in oral compositions as a cleaning agent, it has been difficult to stably incorporate mutanase into oral compositions. Under these circumstances, JP-A-59-
No. 152314 and JP-A-59-152315 propose that mutanase be stably incorporated into oral compositions by using N-acyl sarcosine salt or a combination of N-acyl sarcosine salt and Nyotang fatty acid ester. ing.

The present inventors further sought to improve the stability of mutanase blended into oral compositions by adding N-acylsarcosine salts as foaming aids, which have a nocotic effect and are pleasant to use.
By adding a nonionic active agent, we conducted repeated decolorization research to obtain an oral composition with excellent feel, foaming properties, and stability. As a result, by using certain nonionic activators,
The present inventors have discovered that mutanase can be stabilized to an extent equivalent to or better than the combined use of N-acylsarcosine salt and saccharide fatty acid ester, and have completed the present invention.

Means for Solving the Problems The present invention provides an oral composition containing mutanase, which contains N-acylsarcosine salt, polyoxyethylene sorbitol fatty acid ester, polyoquinoethylene glycerin fatty acid ester, polyoxyethylene as a surfactant. Alkyl ethers, polyoxyethylene lanolin derivatives, polyoxyethylene nonylphenyl formaldehyde condensates, polyoxyethylene/polyoquinopropylene blocks (polymer, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fecalized hemanpo, polyoxyethylene 1 or 2 selected from the group consisting of Himanike and polyethylene glycol fatty acid ester.
It is characterized by containing more than one type of nonionic activator. According to the present invention, mutanase blended into an oral composition can maintain sufficient enzymatic activity for a long period of time, and exhibit excellent dental caries preventive effects.

The N-acyl sarcosine salt used is represented by the formula % (in the formula, R is an alkyl group and M is an alkali metal or ammonium), and the alkyl group R has a carbon number of I+ from the viewpoint of solubility and dispersibility of other components. -17 ra is preferred. Moreover, as the group M that forms a salt, sodium, potassium, and ammonium are preferable from the viewpoint of easy availability.

Representative examples of such N-acylsarcosine salts include N-lauroylsarcosine salt, N-myristoylsarcosine salt, N-balmitoylsarcosine salt, and N-stearoylsarcosine salt. Usually, the N-acylsarcosine salt is less than 3000 times the amount of mutanase mixed.
It is blended in a proportion of 0.01% to 3% by weight based on the total amount of the composition.

The polyoxyethylene sorbitol fatty acid ester to be used is typically POE(
Examples include 60) sorbitol tetraoleate, POE(60) sorbitol tetrastearate, and POE(6) sorbitol monolaurate. Examples of the polyoxyethylene glycerin fatty acid ester include those with an added mole number of ethylene ogizide of 5 to 20 and a fatty acid having a carbon number of 8 to I8;
Representative examples include POE(15) glyceryl monooleate and POE(15) glyceryl monostearate. As polyoxyethylene alkyl ether,
Addition molar loss of ethylene oxite is 2 to 50, alkyl carbon number is 12 to 22, typically POE(9) lauryl ether, POE(15) cetyl ether, POE(l
O) Oleylethyl is mentioned. Examples of polyoxyethylene lanolin derivatives include those with an added mole number of ethylene oxide of 1 to 100, typically POE (30
) lanolin, POE (40) lanolin alcohol. Examples of the polyoxyethylene nonylphenyl formaldehyde condensate include those having an added mole of ethylene oxide of ~50, typically a POE(20) nonylphenyl formaldehyde condensate. As the polyoxyethylene polyoxine propylene block copolymer, the average degree of polymerization of ethylene oxide is 190 to 260,
Examples of propylene oxide having an average degree of polymerization of 50 to 70 include POE (196) POP (67) block copolymer. As polyquinoethylene sorbitan fatty acid ester, addition mole of ethylene oxide ¥1
．． 5 to 30, fatty acid carbon number 12 to 18, typically POE (20) sorbitan monostearate, P
OE(20) sorbitan monooleate is mentioned.

As polyoxyethylene hydrogenated manganese oil, the number of added moles of ethylene oxide is 5 to +00, and typically,
Examples include POE (50) hardened castor AL, POE (60) hardened castor oil, and POE (80) hardened castor oil. Polyethylene ethylene Himasoura is typically POE (polyethylene oxide) having an added mole number of 3 to 70 ethylene oxide.
60) Castor M1], POE (50) Castor oil. Examples of polyethylene glycol fatty acid esters include polyethylene glycol with a molecular weight of 40 to 2,800, fatty acids with a carbon number of 12 to 18, and typically POE (
40) monostearate and POE (45) monostearate. These nonionic surfactants may be used alone or in combination of two or more.

Usually, these nonionic activators have a weight ratio of N-acylsarcosine salt to nonionic activator of 51 or less (in the direction of decreasing N-acylsarcosine salt) from the viewpoint of stabilizing mutanase.
It is desirable that the amount of the nonionic activator is 3% by weight or less per 1 roll weight of the composition.

Further, the total amount of the N-acylsarcosine salt and the nonionic activator is preferably 4% by weight or less, considering the stability of the composition system.

Mutanase can be used regardless of its microbial origin as long as it has α-1,3-glucosidase activity, but commonly available ones include, for example, Trichoderma harzianum OMZ779 and Talatosborium reginae QM7998. , Streptomyces veerens, Aspergillus nidorans, Flavobacterium
Mutanase-producing bacteria, such as Nis. bi and N. nis p., are cultured in a medium containing a normal nutrient source or a medium to which α-1,3-glucan is added, or mutanase-producing bacteria are cultured in Examples include those obtained by fractionating the supernatant of a mutanase-containing culture solution obtained as a result of genetic manipulation using a salting-out method, an adsorption method, a solvent fractionation method, or 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 mutano and release and solubilize reducing sugars. Can be mentioned.

In the present invention, usually 1000
By incorporating 0.001 to 10% by weight of mutanase at ~1 million units/g, the desired caries prevention effect can be obtained.

Note that 1 unit of mutanase is 0.1M acetate buffer (p!
(5, 7), it is defined as the amount of enzyme that decomposes mutan at 40°C and releases 1 μM of reducing sugar in terms of glucose per minute.

The oral composition of the present invention can be made into conventional dosage forms such as toothpaste, moisturized toothpaste, liquid toothpaste, mouthwash, pasta, and denture cleaner according to conventional methods, and other ingredients are particularly limited. It is not limited to the above, but any one commonly used in this type of composition may be used. For example, in the case of toothpaste, abrasives, binders, wetting agents, sweeteners, fragrances, preservatives, and other medicinal agents are appropriately added.

Effects of the Invention Next, the results of testing the stabilizing effect of mutanase when an N-acyl sarcosine salt and a nonionic activator are used together are shown.

Test-1 Mutanase I 7H (6500 units/9) derived from P. varnish Bii flavor, Microtechnical Research Institute No. 4273 was added to 0.
The enzyme solution was dissolved in 500 mQ of 1M acetate buffer (pH 5,7). 10×C of solutions of various surfactants shown in Table 1 were added to 10×C of this enzyme solution and mixed. After this mixture was left in a water bath at 25°C for 13 hours, the enzyme activity in the mixture was measured. Table 1 shows the relative ratio of mutanase activity in the reaction system with addition of surfactant, when the initial mutanase activity in the reaction system without addition of surfactant is taken as 100%.

As shown in Table 1, the ratio of mutanase to N-anolsarconone salt is 1300, and the ratio of mutanase to various nonionic activators is 1.300, that is, the ratio of N-acylsarconone salt to nonionic activator is 1:1. The stability of mutanase is significantly increased when mixed with mutanase at a ratio of Polmaldehyde condensate, polyoxoethylene brobylene brosok (polymer, polyoxyethylene solpitan fatty acid ester, polyoxyethylene hydrogenated Himasoura, polyoxoethylene human oil, polyethylene glycol fatty acid ester, polyoxy When ethylene alkyl ether was used, it was found that stability equal to or higher than that of a combined system of N-anorsulfcon salt and noyosaccharide fatty acid ester was observed.

Test-2 Next, we used N-anolzarcone salt with a reduced alkyl chain length and polyoxyethylene alkyl ether, which had particularly good stability among nonionic activators, to determine the ratio of anionic activator to nonionic activator. The same study as in Table 1 was conducted by changing the ratio of enzyme, anionic activator, and nonionic activator. The results are shown in Table 2.

From the results in Table 2, the alkyl of N-anlusarkonone salt! Even if the length or the salt content was changed, the stabilizing effect of mutanase did not change.

As a result of similar studies with different ratios of N-anolsarconone salt and nonionic activator, it was found that if the ratio of N-acylsarconone salt to nonionic activator was less than 5-1 (in the direction of decreasing N-anolsarconone salt), mutanase was stabilized. was observed, and further increase of N-azolsarcone salt would inhibit mutanase activity.

Test ~ 3 Next, the ratio of the combination system of N-anlesarcone salt and polyoquinoethylene lauryl ether with high stability, 4
- That is, the same study was conducted by changing the ratio of anionic activator to nonionic activator to enzyme at a ratio of 5:1.

As a result, as shown in Table 3, the ratio of anionic activator to nonionic activator was 5:l, and the enzyme and anionic activator were 1:1.
+3000 and the anionic activator was 3% by weight or less based on the weight of the composition, it was found that mutanase was stabilized.

EXAMPLES Next, the present invention will be explained in more detail with reference to examples.

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

Ingredients Weight (%) Dibasic phosphate 45.0 Sorbitol
25.0 carboxymethyl cellulose)
・Rium 1, O N-Lauroyrusarcon sodium O Polyoxyethylene (60 mol) hardened Himasoura O Saccharin sodium 0.2 Drink
10 casein
0°5 mutanase (10,000 ri/9)
O, l purified water
Remaining Example 2 A toothpaste was manufactured according to a conventional method using the following formulation.

Ingredients Weight (%) Carnoum diphosphate 40.0 Glycerin
200 carrageenan
1ON-Lauroyrus Sarconone Sodium 1.5 Polyoxyethylene (9 mol) Lauryl Ether Saccharin Sodium 02 Mutanase (10
00,000'l'jiff-/9) O, OOl Purified water Remainder Example 3 Mouthwater was produced according to a conventional method using the following recipe.

Ingredients Weight @ (%) Glycerin
15,0 Saccharin Sodium
0.03 ethanol
3.0 fragrance
03 Zein hydrolyzate 05 N-myristoylsarconate sodium 0.2 Polyoxyethylene (196 mol) Polypropylene (6
7 mol) block copolymer 08 Mutanase (1000 units/9) 1.0 Purified water
Remainder X Application A denture cleaning agent was manufactured according to the conventional method using the following formulation.

Ingredients Weight (%) Sodium percarbonate 30.0 Tartaric acid
300 Sodium Tripolyphosphate
4.0 Lactose 34
．． 78N-palmitoylsarconate sodium 0.5 Magnenium stearate mutanase (100,000 units/9)

Claims (1)

[Claims] (1) In the oral composition containing mutanase, as a surfactant, N-acylsarcosine salt, polyoxyethylene sorbitol fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene lanolin derivative ,
Selected from the group consisting of polyoxyethylene nonylphenyl formaldehyde condensate, polyoxyethylene/polyoxypropylene block copolymer, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, and polyethylene glycol fatty acid ester An oral composition comprising one or more surfactants.