JPH0717839A - Composition for oral cavity application - Google Patents

Abstract

PURPOSE:To obtain an oral cavity composition having remarkable suppressing effect on the formation of bacterial plaque and excellent caries preventive effect. CONSTITUTION:This composition for oral cavity application contains 1ppm to 20wt.% (especially 1ppm to 3wt.%) of a galactomannan derivative having introduced anionic group, e.g. a phosphorylated galactomannan obtained by reacting galactomannan with an alkali metal phosphate or a sulfated galactomannan obtained by reacting galactomannan with SO3-pyridine complex. A galactomannan derivative having introduced anionic group has high affinity with the enamel on the tooth surface to inhibit the adhesion of pathogenic bacteria deeply participating in the formation of bacterial plaque, suppress the formation of plaque and effectively prevent the dental caries. Since the composition can suppress the formation of bacterial plaque which is an agglomerate of sundry bacteria, it is also effective for preventing foul breath by suppressing the formation of mercaptan compounds produced by microbial metabolism.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for oral cavity which has a high effect of suppressing plaque formation and an excellent effect of preventing caries.

[0002]

2. Description of the Related Art Dental caries is mutans, which is one of oral streptococci.
In addition to infection with streptococci, it is a multifactorial disease caused in the presence of sucrose. In this case Mut
An streptococci specifically adsorbs on the tooth surface, and glucosyltransferase acts as a substrate to produce water-insoluble glucan outside the cells, which firmly adheres to the tooth surface to form plaque.
Furthermore, Mutans streptococci decomposes fermentable sugars such as sucrose, glucose, and fructose to produce acids such as lactic acid, and this acid decalcifies tooth enamel to cause caries. At this time, dental plaque locally retains the produced acid and promotes decalcification on the tooth surface.

Therefore, conventionally, for the purpose of preventing dental caries, toothpaste,
M for oral compositions such as mouth rinses such as chlorhexidine hydrochloride, chlorhexidine gluconate, and acyl sarcosinate
A method of inhibiting plaque formation by incorporating an antibacterial agent against utans streptococci and a degrading enzyme such as dextranase is used. However, although these may have a corresponding preventive effect, oral compositions are usually exhaled after use,
Especially for toothpaste, it is customary to rinse with water after use.
Therefore, in the composition for the oral cavity, in order to expect the desired effect of the medicinal component, the amount of the compound must be considerably increased, while conversely considering the safety to the human body. There is no choice but to limit the blending amount, therefore
There was a disadvantage that the effect was not fully expressed.

On the other hand, galactomannan, which is a polysaccharide composed of galactose and mannose and is mainly contained in the endosperm part of the seeds of legumes, utilizes its high viscosity to make textiles, papers, foods, cosmetics, etc. Widely used in. Industrially, guar with high galactomannan content
Guar gum made from seeds of Cyamopsis tetragonolobus is known.

This galactomannan (or guar gum) is generally used as a binder for toothpaste for oral compositions (JP-A 61-103817 and JP-A 62-126117). In addition, JP-A-53-34934 proposes that guar gum serves as a compounding stabilizer of a medicinal component.

Further, as a means for effectively utilizing galactomannan (or guar gum) or a derivative thereof as a medicinal component of an oral composition, JP-A-54-157842 proposes an anticaries preparation containing a cationized guar gum. ing. Further, Japanese Patent Application Laid-Open No. 1-213222 proposes a plaque inhibitor containing a polysaccharide containing guar gum as an active ingredient, and is disclosed in US Pat.
Japanese Patent No. 053638 proposes an anticaries preparation containing an aldehyde compound containing dialdehyde galactomannan.

However, the above-mentioned cationized guar gum has a drawback that it has a poor effect of suppressing plaque formation and cannot coexist with an anionic compound which is usually an dentifrice activator, and the guar gum described in JP-A No. 1-213222. Polysaccharides containing saccharin are not sufficiently expressed unless their aggregation-suppressing action is higher than a high concentration, and their effects are hardly expected from a clinical viewpoint. Furthermore, dialdehyde galactomannan has a serious problem in practical use in terms of safety to the human body.

[0008]

Means and Actions for Solving the Problems In view of the above circumstances, the present inventor has conducted a thorough study on a substance having a high plaque formation suppressing effect, a caries preventing effect, and a high safety, Unexpectedly, the galactomannan derivative introduced with an anionic group has the extremely high effect described above, and by blending this as an active ingredient, it is excellent in the effect of suppressing plaque formation and has no safety problem. It has been found that it is possible to obtain an oral composition capable of effectively exerting its effect even if the mouth is rinsed with water.

That is, the anionic galactomannan derivative has an excellent affinity for tooth surface enamel (saliva-treated hydroxyapatite), as will be seen from the experimental examples described later, and saliva-treated hydroxy even with a relatively small amount used. Mutans streptoco on apatite
In addition to being able to effectively inhibit the adsorption of cci,
Mutan adsorbed on saliva-treated hydroxyapatite
The s streptococci can also be detached. In this way, the anionic galactomannan can inhibit the formation of plaque by inhibiting the adhesion of the pathogenic bacterium closely related to plaque formation to the tooth surface, and thus can effectively prevent dental caries, and further Since it is possible to suppress the formation of plaque, which is a mass of various bacteria, it is possible to suppress the production of mercaptan compounds generated by microbial metabolism to prevent bad breath, and the present invention has been completed.

Accordingly, the present invention provides an oral composition characterized by containing a galactomannan derivative having an anionic group introduced therein.

The present invention will be described in more detail below. The composition for oral cavity of the present invention contains anionic galactomannan as an active ingredient, and contains toothpaste, powdered toothpaste, liquid toothpaste, mouthwash, It is prepared and used as a mouth-freshening agent, gingival massage cream, liquid or paste topical application agent, troche, chewing gum and the like.

Here, examples of the anionic galactomannan include phosphorylated galactomannan and sulfated galactomannan, and phosphorylated galactomannan is particularly preferably used. The phosphorylated galactomannan can be obtained by reacting galactomannan with an alkali metal phosphate as described in US Pat. No. 4,320,226, and the sulfated galactomannan can be obtained by reacting galactomannan with, for example, galactomannan. SO ₃ −
Obtained by reacting with a pyridine complex (reference J. Hoffman, et al . : Studies) .
on the bloudanticoagulant
activity of sulphated po
lysaccharides with differ
enturonic acid content, Ca
rbohydrate Polymer, 2: 115-
121, 1982. ).

The amount of the anionic galactomannan compounded is not particularly limited, but it is usually 1 ppm to the total amount of the oral composition.
20% by weight, especially 1 ppm to 3% by weight is preferred. If the blending amount is less than 1 ppm, the effect of preventing plaque formation and caries may not be obtained, and if it exceeds 20% by weight, the composition may not be blended in the composition due to an excessive increase in viscosity. There are cases.

In the oral composition of the present invention, in addition to the above-mentioned anionic galactomannan, appropriate components can be added depending on the purpose, type of composition and the like.

For example, in toothpaste, as a polishing agent, dibasic calcium phosphate dihydrate and anhydrous, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate,
Calcium pyrophosphate, aluminum hydroxide, alumina, silicic acid anhydride, aluminum silicate, insoluble sodium metaphosphate, magnesium triphosphate, magnesium carbonate, calcium sulfate, bentonite, zirconium silicate, polymethylmethacrylate, other synthetic resins, etc. Abrasives, carrageenan, sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, cellulose derivatives such as sodium carboxymethylhydroxyethylcellulose, gums such as xanthan gum, tragacanth, karaya gum, arabic gum, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinyl Binders such as pyrrolidone, glycerin, sorbit, ethylene glycol, propylene glycol , Thickeners such as 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, sodium lauryl sulfate, sodium alkylsulfates such as sodium myristyl sulfate, sodium N-lauroyl sarcosinate, N- N-acylglutamates such as sodium myristoyl sarcosinate and the like, sodium dodecylbenzene sulfonate, hydrogenated coconut fatty acid monoglyceride sodium monosulfate, sodium lauryl sulfoacetate, sodium N-palmitoyl glutamate, N- and the like.
Methyl-N-acyl taurine sodium, N-methyl-
Anionic surfactants such as sodium N-acylalanine, sodium α-olefinsulfonate, sodium dioctylsulfosuccinate, sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester, lactose fatty acid ester, maltose fatty acid ester, lactose fatty acid ester Sugar alcohol fatty acid ester such as, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate and other polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil and other polyoxyethylene fatty acid ester, lauric acid mono or diethanolami , Fatty acid mono- or diethanolamide such as myristic acid mono- or diethanolamide, sorbitan fatty acid ester, fatty acid model Glycerides, polyoxyethylene polyoxypropylene copolymer, nonionic surfactants such as polyoxyethylene polyoxypropylene fatty acid ester, N- lauryl-di-aminoethyl glycine, N-
Amphoteric surfactants such as N-alkyldiaminoethylglycine such as myristyldiaminoethylglycine, N-alkyl-N-carboxymethylammonium betaine, sodium 2-alkyl-1-hydroxyethylimidazoline betaine, and further menthol, carvone, anethole, eugenol , Limonene, Methyl salicylate, Spearmint oil, Peppermint oil, Lemon oil, Orange oil, Sage oil, Rosemary oil, Pillar oil, Pimento oil,
Perilla oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, and other fragrances, as well as saccharin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin, p-methoxycinnamic aldehyde, and other sweeteners, gelatin, peptone, Arginine hydrochloride, albumin, casein, titanium dioxide, pigments, preservatives, water and the like are used. In addition, other medicinal ingredients chlorhexidine hydrochloride, chlorhexidine gluconate, isocipron-aminocaproic acid, dihydrocholestanol,
Tranexamic acid, allantoin, allantoin chlorohydroxyammonium, sodium fluoride, sodium monofluorophosphate, dextranase, triclosan, sodium chloride and the like may be used in combination. Similarly, various components commonly used in mouthwashes, mouthwashes, etc. can be used.

[0016]

The composition for oral cavity of the present invention contains an anionic galactomannan as an active ingredient,
Mutans streptococci on the tooth surface
Mutant that can inhibit the adsorption of teeth and is adsorbed on the tooth surface
It is possible to desorb an streptococci, therefore, it has a high plaque formation inhibitory effect and an excellent caries prevention effect, and further, it can suppress the formation of plaque, which is a mass of various bacteria, by microbial metabolism. Generation of the generated mercaptan compound can be suppressed, bad breath can be prevented, and safety is also good.

[0017]

EXAMPLES The present invention will be specifically described below by showing experimental examples and examples, but the present invention is not limited to the following examples. In the following examples,% means% by weight.

[Experimental Example 1] Mutans strep of phosphorylated galactomannan
Evaluation of Tococci Adsorption Inhibitory Ability on Tooth Surface (1) Preparation of Bacterial Suspension Streptococcus mutans NCTC
After culturing the strain 10449 (serotype c) aerobically in a brain heart infusion liquid medium at 37 ° C. for 18 hours,
The cells were collected by centrifugation. The cells were treated with KCl buffer (0.005M KCl, 1 mM PO ₄ , 1 mM C
aCl ₂ , 0.1 mM MgCl ₂ , pH 6.0), washed twice by centrifugation, and then turbidity 1.4 with the same buffer.
The suspension was prepared so as to be (660 mn).

(2) Preparation of saliva-treated hydroxyapatite (substance of tooth surface substitute) Human whole saliva was sampled under ice cooling by paraffin stimulation, and 60
After heat treatment at 30 ° C. for 30 minutes, a saliva supernatant was obtained by centrifugation. Next, 20 mg of hydroxyapatite (manufactured by Central Glass Co., Ltd.) was precisely weighed in a test tube made of polycarbonate, 2 ml of distilled water was added, and washing was performed to remove fine particles.
1 ml of the above saliva supernatant was added and mixed. After leaving it at 4 ° C. for 18 hours, it was washed twice with 1 ml of KCl buffer (pH 6.0) and subjected to the following experiment.

(3) Adsorption Experiment 1 ml of the above-mentioned bacterial suspension and 1 ml of a KCl buffer solution in which a required amount of the test sample shown in Table 1 was dissolved were added to the saliva-treated hydroxyapatite and shaken at 20 ° C. for 20 minutes. Then, the mixture was allowed to stand for 20 minutes to remove the suspension of bacterial cells not adsorbed on the saliva-treated hydroxyapatite. Further, 2 ml of 0.5 N HCl was added and mixed to dissolve hydroxyapatite, and then the amount of adsorbed cells was measured by turbidity (660 nm). As a control, a KCl buffer solution containing no test sample was also subjected to the same operation, and the adsorption inhibition rate of the test sample was quantified. The results are shown in Table 1. The numerical values in the table indicate the adsorption inhibition rate (%).

[0021]

[Table 1]

From the results shown in Table 1, unmodified galactomannan has a low ability to inhibit the adsorption of Mutans streptococci on saliva-treated hydroxyapatite, and there was almost no effect at 10 ppm, whereas phosphorylated galactomannan at 10 ppm had no effect. About 75%, 1p
It was found that a remarkable effect of exhibiting an effect is exhibited even at a very low concentration of about 50% in pm.

Experimental Example 2 Mutans strept of galactomannan phosphate
Evaluation of the Desorption Ability from the Tooth Surface for Ococci Similar to Experimental Example 1, a saliva-treated hydroxyapatite contained in a polycarbonate test tube was used to suspend a bacterial suspension (OD ₆₆₀ =
0.70) was added and shaken at 20 ° C. for 20 minutes. Then, the mixture was allowed to stand for 20 minutes to remove the suspension of the cells not adsorbed on the saliva-treated hydroxyapatite, and then 2 ml of KCl buffer solution in which the required amount of the test sample shown in Table 2 was dissolved was added, and the mixture was added again at 20 ° C. for 20 minutes. Shake for minutes. Then, after leaving still for 20 minutes to remove the suspended liquid of the desorbed cells from the saliva-treated hydroxyapatite, 0.5N HCl was added to 2
ml was added and mixed to dissolve the hydroxyapatite. The amount of residual adsorbed cells was measured by turbidity (660 nm), and a KCl buffer solution containing no test sample was also subjected to the same operation as a control to quantify the adsorption inhibition rate of the test sample. The results are shown in Table 2. The numerical values in the table indicate the adsorption inhibition rate (%).

[0024]

[Table 2]

From the results shown in Table 2, Mutan adsorbed on hydroxyapatite which is an enamel component on the tooth surface.
s streptococci, phosphorylated galactomannan was about 50% even at a low concentration of 10 ppm or less.
Had a surprising effect of desorbing Mutans streptococci. Unmodified galactomannan was clearly inferior to that, which confirmed that it had an action on an anionic substituent called a phosphorylation group.

[Example 1] Toothpaste Aluminum hydroxide 45.0% Gelling silica 1.5 Sorbitt 25.0 Sodium carboxymethyl cellulose 1.5 Sodium lauryl sulfate 1.5 Sucrose monopalmitate 0.8 Saccharin 0 .2 Sodium benzoate 0.02 Phosphorylated galactomannan 0.1 Perfume 1.0 Water Balance meter 100%

Example 2 Powdered dentifrice Light calcium carbonate 50.0% Aluminum hydroxide 20.0 Dibasic calcium phosphate 20.0 Sodium lauryl sulfate 1.6 Saccharin 0.2 Phosphorylated galactomannan 1.0 Perfume 1.0 Water balance meter 100%

[Example 3] Liquid toothpaste Glycerin 30.0% Sodium polyacrylate 1.5 Paraffin sulfonate 1.5 Saccharin 0.1 Sodium monofluorophosphate 0.8 Dipotassium phosphate 0.1 Sodium phosphate 1 0.2 Phosphorylated galactomannan 0.05 Perfume 1.0 Water Balance 100%

[Example 4] Mouthwash Ethyl alcohol 15.0% Glycerin 10.0 Polyoxyethylene (60 mol) hydrogenated castor oil 1.0 Saccharin 0.04 Chlorhexidine gluconate 0.001 Phosphorylated galactomannan 03 Perfume 1.0 Water 100% balance

Example 5 Oral Pasta Cetanol 12.0% Liquid Paraffin 15.0 Glycerin 20.0 Sorbitan Monopalmitate 0.5 Polyoxyethylene (40 mol) Hydrogenated Castor Oil 0.1 Sodium Lauryl Sulfate 0. 15 Saccharin 0.5 Phosphorylated galactomannan 0.01 Perfume 0.5 Water Balance 100%

[Example 6] Lozenges for oral cavity Lactose 95.0% Polyoxyethylene (60 mol) monostearate 0.5 Sodium lauryl sulfate 0.05 Stevia extract 0.2 Phosphorylated galactomannan 0.2 Perfume 0 .05 Hydroxyethyl cellulose balance meter 100%

Example 7 Chewing gum Vinyl acetate gum base 33.3% Maltitol 53.1 Lactulose 5.5 Sorbitol liquid 5.0 Phosphorylated galactomannan 0.1 Perfume 3.0 Total 100%

Claims (2)

[Claims] 1. An oral composition comprising a galactomannan derivative having an anionic group introduced therein. 2. The anionic group is a phosphate group.
The oral composition described.