JPH0419205B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula () (However, n = 0 to 5) By blending the carboxyalkyl phenyl ester of tranexamic acid or its salt, the formation of plaque by periodontitis-causing bacteria is suppressed, and the teeth are prevented from developing marginal caries and The present invention relates to an oral composition that can effectively suppress periodontitis. BACKGROUND ART Various oral compositions for the purpose of preventing dental caries and periodontitis have been proposed and are actually commercially available. For example, a method of incorporating fluorine compounds such as sodium monofluorophosphate into oral compositions has been adopted, and this is a method to prevent caries by improving the acid resistance of teeth with fluorine compounds. However, it has almost no effect on dental plaque. In addition, a method has been proposed for sterilizing fungi in the oral cavity by adding chlorhexidine to oral compositions, but this method has doubts about the stability of chlorhexidine in oral compositions, and it does not last long. There were also problems with storage. Furthermore, there is a method of inhibiting the adhesion of dental plaque by adding dextranase to the oral composition. Although it was highly effective in inhibiting dental plaque caused by bacteria, it was weakly effective in inhibiting marginal plaque caused by periodontitis-causing bacteria, such as Actinomyces viscosus bacteria. For this reason, it has conventionally been required to suppress the formation of marginal dental plaque. The present inventors aim to effectively prevent marginal caries and periodontitis by suppressing plaque formation on teeth, particularly by suppressing plaque formation on tooth margins caused by periodontitis-causing bacteria. As a result of intensive research into oral compositions that can be used, the general formula () (However, n = 0 to 5) By incorporating the carboxyalkyl phenyl ester of tranexamic acid or its salt into an oral composition, Actinomyces viscosus, a type of periodontitis-causing bacteria, can be used. We have discovered that the above objects can be achieved by strongly suppressing bacterial plaque formation and effectively suppressing marginal dental caries and periodontitis, leading to the present invention. It is. The present invention will be explained in more detail below. The oral composition according to the present invention contains a carboxyalkyl phenyl ester of tranexamic acid represented by the above general formula (), and this carboxyalkyl phenyl ester of tranexamic acid is disclosed in JP-A-48-78143. It can be produced by the method described in et al., and in the general formula (), n = 2. The compound has the generic name cetraxate. Here, the hydrochloride of cetraxate has the effect of improving gastric mucosal microcirculation, suppressing the activation of intramucosal pepsinogen, suppressing gastric juice secretion due to anti-kallikrein effect, and ulcer healing effect. It is a new finding of the present inventors that the formation of marginal dental plaque by periodontitis-causing bacteria can be inhibited by incorporating it into a composition. The acute toxicity (LD ₅₀ ) of this compound is over 8000 mg/Kg in mice and over 8000 mg/Kg in rats.
5000 mg/Kg or more, and no abnormality was observed in chronic toxicity even after continuous oral administration of 600 mg/Kg for 6 months using rats. As mentioned above, the oral composition of the present invention contains a compound of the general formula () and/or a salt thereof, and among the compounds of the general formula (), carboxyethyl phenyl ester with n=2 is preferred. Furthermore, examples of the salt of the compound of general formula () include inorganic acid salts such as hydrochloride, sulfate, and phosphate, and organic acid salts such as oxalic acid, acetic acid, and gluconic acid. Hydrochloride, acetate and gluconic acid are preferably used. In addition, the compound of general formula () and its salt may be used alone or in combination of two or more. The compounding amount of the compound of the general formula () or its salt is preferably 0.001 to 1% (weight%, same hereinafter) of the entire oral composition, particularly 0.02 to 0.1%, and the compounding amount is 0.001% of the total. If it is below, the effect may not be fully exhibited. The oral composition according to the present invention is used as a toothpaste, a toothpaste, a liquid toothpaste, a mouthwash, a troche, a chewing gum, a topical application, etc. As the components, appropriate commonly used components may be blended depending on the type, purpose of use, etc. For example, in the case of toothpaste, dibasic calcium phosphate,
Calcium carbonate, calcium pyrophosphate, insoluble sodium metaphosphate, amorphous silica, crystalline silica, aluminosilicate, aluminum oxide,
Abrasives such as aluminum hydroxide and resin, binders such as carboxymethyl cellulose, hydroxyethyl cellulose, alginate, carrageenan, gum arabic, and polyvinyl alcohol, thickening agents such as polyethylene glycol, sorbitol, glycerin, and propylene glycol, and sodium lauryl sulfate. , Sodium Dodecylbenzenesulfonate, Hydrogenated Coconut Fatty Acid Monoglyceride Sodium Monosulfate, Sodium Lauryl Sulfoacetate, Sodium N-Lauroyl Sarcosinate, N
- Foaming agents such as acyl glutamates and sucrose fatty acid esters, essential oils such as peppermint and spearmint, fragrance materials such as l-menthol, carvone, eugenol, and anethole, saccharin sodium, stevioside, neohesperidyl dihydrochalcone , sweeteners such as glycyrrhizin, perillartin, p-methoxycinnamic aldehyde, and preservatives are mixed with water,
Manufactured according to conventional methods. Furthermore, in mouthwashes and other mouthwashes, ingredients are appropriately blended depending on the properties of the product. In addition, in the present invention, dextranase,
Mutanase, sorbic acid, alexidine, β-glycyrrhetinic acid, hinokitiol, chlorhexidic acid, alkylglycine, alkyldiaminoethylglycine salt, allantoin, ε-aminocaproic acid, tranexamic acid, azulene, vitamin E, water-soluble primary or secondary phosphate Active ingredients such as salts, quaternary ammonium compounds such as cetylpyridinium chloride, sodium chloride, and crude drug extracts can also be blended. Examples are shown below to specifically demonstrate the effects of the present invention. Experimental example 1 Test method for dental plaque inhibition effect Actinomyces viscosus was precultured in THB medium containing 2% sucrose and supplemented with a predetermined amount of cetraxate hydrochloride or tranexamic acid.
Ny1 was inoculated and cultured at 37° C. for 16 hours in an Anaeroboccus gas exchanged with N ₂ :CO ₂ :H ₂ =80:10:10. After culturing, add 0.01M phosphate buffer (PH=7.2)
Wash gently twice with Absorbance (turbidity) at wavelength 550nm
was measured to determine the amount of attached plaque. The results are shown in Table 1. Experimental result

[Table] From the results in Table 1, it is found that cetraxate hydrochloride significantly inhibits plaque formation. Experimental Example 2 Experimental Method for Improving Gingivitis in Rats ODU rats (7 weeks old) were used as animals and fed powdered feed for 2 months to accumulate dental plaque on the lower anterior teeth to induce experimental periodontitis. . From this point (day 0), the drug was administered twice a day, with 5 animals per group.
It was rubbed with a spatula on two places on the left and right side of the gingiva of the anterior teeth of the mandible for 20 days, and the area of gingival inflammation was measured under a stereomicroscope on day 0 and day 20 to determine the degree of improvement in inflammation. The drug is cetraxate hydrochloride or tranexamic acid at 0.5
A gel with the following formulation containing % by weight was used, and a gel containing no drug was used as a control. Ethanol 28% Polyethylene glycol 54.5 Carbopol 1.5 Drug 0.5 Water Balance 100.0% Experimental results

[Table] From the results in Table 2, it is found that cetraxate hydrochloride effectively suppresses gingivitis. Examples are shown below. Examples Example 1 Aluminum hydroxide 45.0% Gellable silica 2.0 Sorbit 25.0 Sodium carboxymethylcellulose 1.0 Sucrose monolaurate 1.0 Sucrose monopalmitate 1.5 Saccharin sodium 0.2 Ethanol 0.1 Sodium benzoate 0.1 Cetraxate hydrochloride 0.5 Flavor 1.0 Water Total remaining 100.0% Example 2 Toothpaste precipitated silica 25% Sorbit 25 Glycerin 25 Polyvinylpyrrolidone 1.0 Lauroyl polyglycerin ester 1.0 Polyoxyethylene (60 mol) Sorbitan laurate 0. 5 Satucalin sodium 0.2 Ethyl paraoxybenzoate 0.1 Chlorhexidine hydrochloride 0.1 Cetraxate hydrochloride 0.05 Fragrance 1.0 Water Remaining 100.0% Example 3 Toothpaste dibasic calcium phosphate dihydrate 20.0% dibasic calcium phosphate anhydrate 20.0 Gelling silica 2.0 Sorbit 20.0 Sodium carboxymethylcellulose 1.0 Lauryl diethanolamide 1.0 Sucrose monolaurate 1.5 Satucalin sodium 0.1 Ethyl paraoxybenzoate 0.1 Cetraxate hydrochloride 0.1 Magnesium phosphate 1.0 Sodium monofluorophosphate 0.76〃 Incense Material 0.8〃Water Residual total 100.0% Example 4 Pastacetanol for oral use 10.0% Scrawane 20.0〃 Precipitated silica (abrasive) 5.0〃 Polyoxyethylene (40) Hydrogenated castor oil 0.1〃 Sorbitan monooleate ester 1.0〃 Glycyrrhetinic acid 0.1〃 Satucalin sodium 0.6〃 Flavor 0.6〃 Cetraxate hydrochloride 0.5〃 Water Remaining total 100.0% Example 5 Mouthwash sorbit 10.0% Ethanol 5.0〃 Polyoxyethylene (60) Hydrogenated castor oil 0.1〃 Sucrose monopalmitate 0.2〃 Satucalin sodium 0.2〃 Flavoring 0.6〃 Cetraxate hydrochloride 0.2 Water Remaining total 100.0%

Claims (1)

[Claims] 1 General formula () (However, n=0 to 5) An oral composition characterized by containing a carboxyalkyl phenyl ester of tranexamic acid or a salt thereof. 2. The oral composition according to claim 1, wherein the compound of general formula () is cetraxate or a salt thereof, where n=2 in general formula (). 3. The oral composition according to claim 1 or 2, wherein the salt of the compound of general formula () is a hydrochloride, an acetate, or a gluconate.