JPS61151112A - Composition for suppressing formation of sordes on tooth - Google Patents

Abstract

PURPOSE:To provide a composition for suppressing the formation of sordes on tooth, having excellent caries-preventing effect and producible economically on an industrial scale, by using a specific amount of one or more components selected from water-soluble chitin and chitosan as active components. CONSTITUTION:The crust of e.g. crab, lobster, krill, etc. is crushed, treated with hydrochloric acid to remove calcium carbonate, treated with caustic soda to remove proteins and other impurities, washed with water, and dried to obtain chitin and chitosan (a deacetylated product of chitin) having white flaky form. The product is depolymerized by decomposition to obtain water-soluble chitin or chitosan. At least one kind of compound selected from the above compounds is added in an amount of 1ppm-10wt%, preferably 1ppm-0.5wt% to obtain the objective composition for suppressing the formation of sordes on tooth. EFFECT:The adsorption of Streptococcus mutans which is a kind of oral streptococci causing dental caries can be inhibited and the S. mutans adsorbed on the surface of the teeth is desorbed.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a dental plaque formation inhibitor composition used for the prevention or treatment of dental caries. It can take the form of dentifrices such as toothpaste, gingival preparations such as gingival ointments, mouthwashes, solid mouth fresheners, liquid mouth fresheners, and the like.

Conventional techniques are mainly associated with 5trep, a type of oral streptococcus.
It is a multifactorial disease caused by infection with Tococcus mutans in the presence of sucrose.

S, s+utans produces water-insoluble extracellular glucan by the action of glucodystransferase (GTF) using sucrose as a substrate, and firmly adheres to the tooth surface to form dental plaque. S. mutans decomposes the free fructose generated in the above process, monosaccharides produced from sucrose by the action of invertase, or various sugars in the diet to produce acids, and this acid damages tooth enamel. It is demineralized and becomes eroded. At this time, dental plaque locally retains the produced acid and promotes demineralization on the tooth surface.

Therefore, for the purpose of preventing dental caries, plaque has been removed with toothbrushes and toothpastes, and oral compositions such as dentifrices have been supplemented with antibacterial agents against S. mutans, such as chlorhexidine hydrochloride, chlorhexidine gluconate, and sarcosinate. A method of combining agents and degrading enzymes such as dextranase has been adopted. Although these products have shown a certain degree of caries prevention effect, further improvements are needed.

There was a demand for a more industrially advantageous material.

An object of the present invention is to provide a dental plaque formation inhibitor composition which has excellent caries preventive effects and is industrially advantageous to produce.

1. The dental plaque formation inhibitor composition of the present invention contains at least one compound selected from water-soluble chitin and chitosan.
It is characterized by containing ppm to 10% by weight.

The present invention will be explained in more detail below.

Chitin is a β-1 N-acetylated glucosamine represented by the general formula (I).
, 4, and chitin exists naturally as an organic skeletal material in arthropods and molluscs, and in plants, it is present in fungal hyphae and spores, and can be obtained from these. For example, when using the shells of crabs, shrimp, krill, etc. as raw materials, the shells are crushed, treated with hydrochloric acid to remove calcium carbonate, and then treated with caustic soda to remove proteins and other impurities, and then washed with water. By drying, chitin can be obtained as white flakes.

Xatosan is a deacetylated product of chitin.

For example, it can be obtained as white flakes by treatment with an alkali. Chitosan can be obtained, for example, from Kyowa Yushi Kogyo under the trade name "Fronac N".

Chitin and chitosan have chemical structures similar to cellulose, but their resistance to chemicals is much greater than that of cellulose, and they also have acetamide and amino groups in their molecules, so they have attracted much attention. It has certain characteristics. However, in practical use, chitin and chitosan have an extremely low degree of utilization compared to cellulose and other polysaccharides.

The present inventors focused on such chitin and chitosan,
By converting water-insoluble chitin and chitosan into water-soluble derivatives, the inventors discovered that the water-soluble chitin or chitosan is effective in preventing or treating dental caries, and based on this knowledge, the present invention was accomplished. .

Examples of water-soluble chitin or chitosan include the following.

(1) A water-soluble oligomer of chitin or chitosan obtained by decomposing chitin or chitosan into a low molecular weight product (provided that the degree of polymerization of glucosamine units is greater than 1).

Such oligomers can be obtained by ordinary molecular weight reduction methods, such as nitrite decomposition method, formic acid decomposition method, chlorine decomposition method (Japanese Patent Application No. 1982-432'82), enzyme or microbial decomposition method. It can be obtained by law etc.

(2) Aqueous chitosan with a degree of deacetylation of 40 to 60%.

For example, it can be obtained by controlling the degree of deacetylation by the method disclosed in JP-A-53-47479.

(3) A salt of an organic or inorganic acid of chitosan. Specific examples of the organic acid include acetic acid, malic acid, citric acid, ascorbic acid, etc.

Examples of inorganic acids include hydrochloric acid, sulfuric acid, and phosphoric acid.

(4) A derivative made water-soluble by introducing a hydrophilic group into chitin or chitosan. Specific examples of this include the following.

■ Polyoxyethylene/polyoxypropylene chitin or chitosan [in the formula, n:>1 R1: -H, -COCH, or 10 EO + reaction, 10 P
O-)-, 1H (However, IA, = Q ~ 5. Town = O ~
5. Q +m≠0)R, knee H or +EO+Q, 2
・+PO÷1I12H (However, Q, = O ~ 5.m, = 0
~5. Q2+m2≠0)R3: -H or 10EO+1
! 3・+po + mJ (However, sad, = 0~5.l1
13=0-5. 12. +i, ≠0). Here, EO represents an oxyethylene chain, PO represents an oxypropylene chain, and the order of bonding between EO and PO does not matter.
For example, first, PO may be added to the D-glucosamine skeleton, and then EO may be added, or EO and PO may be added at random. In addition, in each bonded D-glucosamine skeleton, R1, R2w R,, n
,, R2,n,.

Q, , Qs may be the same or different. ] ■ Carboxymethyl chitin or chitosan [wherein n:>I R4: -H or -COC)l.

R9: -I+, -CH,C0OH, -CH,COO
Na, -CH2COOK or -CH, GOONH4 R,: -H, -CH, COOH, -CI, COONa
, -CH, C00K or -CH2COONH4. However, R9 and R6 are never both -H. Furthermore, R, , R, , R, in each of the bonded D-glucosamine skeletons may be the same or different. ] ■ Ryu I oxidized chitin or chitosan [in the formula, n:〉1 0M1 0M.

is -H, Na, K or -NH,) ON.

R,: -H or -p = o (ua and M are -H, Na, 0M.

or -NH4) ON.

R,: -H or -p=oO+s and M6 is -H,
Na, 8G or -NH4), however, R and R9 cannot become -H at the same time.

0M.

represents -H, Na, K or Ikken 4), and each linked D-glucosamine skeleton is R7, R,, R,, R,. may be the same or different. ] ■ Sulfated chitin or chitosan [in the formula, n:>1 open.

R, ,: -H, -COCHa or -5=0 (M,
is -H, Na.

or -NH4) 0M111 R,: -〇 or -5=O(Ml, is -1(, Na
, K or -NH,) 0M11 R1,: -1 (or -5=O(M,, is -H, Na
, K or -NH,) 0M12 ■ R14: -H, -COCH, or -S=0(M, 2
is -H, Na.

K or -NH4). Moreover, R□□, R1□, R13, and R14 in each bonded D-glucosamine skeleton may be the same or different. ] [In the formula, n:>1 (X, is CQ or Br) (xi is CQ or Br) ■ Dihydropropyl chitin or chitosan [In the formula,
n:>I R1,: -H or -cOcH.

R1,: -H or one piece, -CH-CH,OHOH R1,: -H or -CI, -CH-CH,OHO
Represents H. However, R and R1 do not become -H at the same time. ] ■ N-2-hydroxypropylsulfonic acid chitosan [
In the formula, n:>1 (M13 is Na, K or -NH4) (M14 is Na, K or -NH4). However, R2° and R2□ do not become -H at the same time. ] The water-soluble chitin or chitosan of the present invention exhibits solubility in water with a pH of 7, and preferably has a solubility of 0 per 100 g of water.
．． It has a solubility of 1 g or more. Among the above-mentioned water-soluble chitins or chitosan, derivatives in which parent wood groups, particularly acid groups, are bonded to the D-glucosamine skeleton are preferred.

Next, a method for producing the above-mentioned water-soluble substituted chitin or chitosan will be described, but this is not limited to the method for producing chitin or chitosan used in the present invention.

Polyoxyethylene/polypropylene glycol chitin or chitosan is made by adding 1 to 5 kg/a+fG of chlorohydroxyethylene, chlorohydroxypropylene, ethylene oxide, or propylene oxide to alkali chitin or chitosan at room temperature and pressure or at 50 to 60°C.
It is obtained by reacting under the pressure of

Carboxymethyl chitin or chitosan can be obtained by reacting alkali chitin or chitosan with monochloroacetic acid at room temperature and pressure.

Phosphorylated chitin or chitosan is obtained by reacting chitin or chitosan dissolved or suspended in methanesulfonic acid with niline pentoxide under cooling. This method is described, for example, in Proceedings of the 48th Autumn Annual Meeting of the Chemical Society of Japan, page 570 (Norio Nishi et al.).

Sulfated chitin or chitosan can be obtained by reacting chitin or chitosan activated in pyridine with a 503-pyridine complex [Reference: M. Jolfr.
om et al,,The 5ulfona-tio
n of Chitosan, J., Am., Chem., S.
oc, 81.1764-1766 (1959)).

N-glycidyltrimethylammonium chitosan is obtained by adding glycidyltrimethylammonium chloride to chitosan under high temperature and high pressure under a highly concentrated alkali catalyst.

Dihydroxypropyl chitin or chitosan is obtained by ring-opening and adding epichlorohydrin to alkaline chitin or chitosan at high temperatures.

N-2-hydroxypropylsulfonic acid chitosan is obtained by adding glycidyl sulfonic acid to chitosan under an alkali catalyst at high temperature and pressure.

The water-soluble chitin or chitosan is blended in the plaque formation inhibitor composition in an amount of 1 ppm to 10% by weight, preferably 1 ppm.
m to 0.5% by weight. Water-soluble chitin or chitosan can effectively prevent S,mutans from adsorbing to tooth surface enamel (hydroxyapatite), and can also desorb S,i+utans from hydroxyapatite to which S,mutarts have been adsorbed. In this way, water-soluble chitin or chitosan inhibits the attachment of caries-causing bacteria to the tooth surface, suppresses the formation of dental plaque, and can effectively prevent caries. Furthermore, since dental plaque is a mass of bacteria, by inhibiting its formation, it is possible to prevent the production of mercaptan compounds generated by microbial metabolism, and also to prevent the occurrence of bad breath.

In addition to water-soluble chitin or chitosan, the dental plaque formation inhibitor composition of the present invention uses commonly contained components. These ingredients vary depending on the form of the anti-caries composition, but
For example, in toothpaste, glycerin, sorbitol,
Thickening agents such as propylene glycol, calcium diphosphate, calcium pyrophosphate, calcium carbonate, aluminum hydroxide, aqueous silica, and columnar silica.

Calcium sulfate, magnesium phosphate, calcium sulfite, zeolite, abrasives such as insoluble sodium metaphosphate, binders such as carboxymethylcellulose and carrageenan, sodium lauryl fernate, sodium α-olefin sulfonate, lauric acid monoglyceride sulfate, acyl tau anionic active agents such as ester, lauric acid monoglyceride sulfonate, lauryl sarcosinate, nonionic active agents such as sucrose ester, stearic acid monoglyceride, lauryl diethanolnamide, polyoxyethylene sorbitan monolaurate,
Amphoteric active agents, flavors such as menthol, anethole, sweeteners, chlorhexidine hydrochloride, chlorhexidine gluconate, epsilon-aminocaproic acid, dihydrocholestanol, tranexamic acid, allantoin, allantoin chlorhydroxyaluminum, sodium monofluorophosphate.

Medicinal ingredients such as dextranase, polyethylene glycol, and sodium chloride, preservatives, and water are used.

Similarly, various ingredients commonly used in mouth fresheners, mouth washes, etc. can be used. Since water-soluble chitin or chitosan has a caries-preventing effect, it goes without saying that part or all of the medicinal ingredients that have been formulated for this purpose can be replaced with water-soluble chitin or chitosan in the present invention.

According to the present invention, by incorporating water-soluble chitin or chitosan as an active ingredient in a dental plaque formation inhibitor composition,
It is possible to inhibit the adsorption of S and mutans to the tooth surface, and also to desorb the S and mutans adsorbed to the tooth surface.

Experimental Example 1 The ability of water-soluble chitin or chitosan to desorb S. mutans from teeth was evaluated.

S, + After culturing the wutans6715 strain, the bacterial cells were centrifugally washed with Tris-HCl buffer, 0D66゜nll+=2
Adjusted to.

20+og hydroxyapatite (manufactured by Bio-rad; trade name B) in a 9 mfl polycarbonate tube.
io-gel HTP + tooth surface substitute material, hereinafter HAp
) was weighed. To this, bacterial cells (S, +5utans
6715 strain culture) 2mff1 and 2mQ of Tris-HCl buffer were added, and the mixture was shaken for 30ml at 20°C. 3
After standing still for 0 minutes, discard the supernatant and add the first
0.25% of each water-soluble chitin or chitosan shown in the table
Tris-HCl buffer (pH 7,0) solution 411Q was added, and the mixture was shaken at 20°C for 30 minutes. After standing still for 30 minutes, the turbidity of the supernatant was measured using 66On11. As a control, the desorption rate of S and mutans adsorbed to HAP by water-soluble chitin or chitosan was quantified using Tris-HCl buffer. The results are shown in Table 1.

Note that the average molecular weight and degree of deacetylation in the table were measured as follows.

(1) Average molecular weight measurement method Shimadzu high performance liquid chromatograph LC-5A, RID-2
Measurement was performed by a GPC method using column Shim-pack 01 (B-805 for A) and dextran (Sigma) as a standard substance.

(2) Method for measuring the degree of deacetylation Using methylene blue as an indicator, the amount of nitrogen was determined by a colloidal titration method in which an aqueous solution of chitosan in acetic acid was titrated with an aqueous solution of potassium polyvinyl sulfate and was converted into a degree of deacetylation.

S adsorbed on HAP by water-soluble chitin or chitosan
, S. mutans adsorbed to HAp, which forms the enamel on the tooth surface.
mutans is 0. While stirring with IM's Tris-HCl solution does not cause desorption, adding only 0.25% of water-soluble chitin or chitosans causes approximately 2.
It was a surprising result that 0-80% of S,mutans was desorbed from the HAp surface.

These results indicate that by incorporating water-soluble chitin or chitosan into oral hygiene products such as toothpaste and mouthwash, S and mutans can be easily removed from the tooth surface and the oral cleaning effect can be improved. It can be seen that it prevents tooth decay and bad breath.

Example 2 The ability of water-soluble chitin or chitosan to prevent S. mutans from adsorbing to teeth was evaluated.

The water-soluble chitin or chitosan shown in Table 2 was mixed with 0.
The sample solution was adjusted to 0.5°, 0.05, and 0.005 wt% with 1M Tris-HCl buffer (pH 7.0). Separately, the bacterial cells after culturing S. mutans 6715 strain were centrifugally washed with Tris-HCl buffer, and then OD. . 6=2
Adjusted to. Weigh out 20 mg of HAP into a 9+F polycarbonate tube, and add 2 mQ of sample solution to this.
and 2 mQ of bacterial cells were added at the same time and shaken at 20°C for 30 minutes.

After that, the mixture was allowed to stand for 30 minutes, and the turbidity of the supernatant was measured at 660 nm. The same procedure was carried out in the case of only bacterial cells and in the case of only bacterial cells added to 1 (Ap), and the ability of water-soluble chitin or chitosans to inhibit the adsorption of S. mutans to HAp was quantified. It is shown in Table 2. The numerical values in Table 2 indicate the adsorption inhibition rate (unit: %).

(Margins below) Preventing dental caries pathogens S. utans from adsorbing to HAp on the tooth surface of the caries-affected area shows the prevention of dental caries, and further improves the oral and vaginal bacterial flora. This also prevents the formation of dental plaque, which leads to the formation of mercaptan compounds, which are microbial metabolites that cause bad breath, and also helps prevent bad breath. Furthermore, among the water-soluble chitins or chitosans used here, compounds into which acid groups have been introduced, such as carboxymethyl chitin Na salt, can 100% inhibit the adsorption of S and mutans even at an addition amount of only 25 ppm. This is a surprising effect and suggests efficacy at low concentrations. Even something like oligomer chitosan exhibits a higher inhibiting effect by increasing its blending amount.

Hereinafter, specific examples of the dental plaque formation inhibitor composition of the present invention will be shown.

Example 1 This example shows an example of the composition of a toothpaste. In the following tables, M indicates the average molecular weight and DS indicates the degree of substitution.

Degree of deacetylation: 40-60% For chitosan, the numerical value shown in parentheses indicates the degree of deacetylation. Further, the numerical values in the table indicate vt%.

(Margin below) Example 2 This example shows an example of the composition of a dentifrice.

*1) 1% of commercially available chitosan Fronac N was dissolved in a 1.4% malic acid aqueous solution and freeze-dried.

Example 3 This example shows an example of the composition of toothpaste *2) 1% of commercially available chitosan Fronac N was dissolved in a 1.2% aqueous citric acid solution and freeze-dried.

Example 4 In the present invention, an example of the composition of water toothpaste is shown.

Example 6 This example shows a solid mouth freshener composition. This solid mouth freshener is made by sufficiently pulverizing and mixing the solid raw materials in the ingredients shown below, adding the liquid raw materials to this, and mixing well.
This was adjusted by granulating it.

Peppermint oil 1% Lemon oil 0.2% Eugenol 0.1% Anethole 0.2% Carvone 0.3% Chitosan ascorbate Ill 10%
Licorice powder 40% Xylitol 7% Oris root powder 4% Cinnamon powder 3% Ginger powder 2% Kyoji powder
1% chitin 1lff
20% gum arabic solution Balance x 6) Chitosan (degree of deacetylation 77%) obtained from the shell of pine needle crab according to Hackman's method was dissolved at 1% in 2% ascorbic acid and freeze-dried.

*7) Chitin obtained from the shell of Matsuba crab according to Hackman's method.

Example 7 This example shows a composition example of a liquid mouth freshener.

Example 8 This example shows a composition example of a periodontal ointment. This ointment is
An aqueous phase containing water-soluble chitin or chitosan and an oil phase at 70%
Homogenized at ℃.

Claims (1)

[Claims] 1. A dental plaque formation inhibitor composition containing 1 ppm to 10% by weight of at least one compound selected from water-soluble chitin and chitosan.