JPS6258324B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an oral composition containing 2-hydroxy-6-alkylbenzoic acid to inhibit dental plaque formation and acid production to prevent dental caries and periodontal disease. Dental plaque that adheres to the tooth surface is made up of about 70% bacteria, about 20% polysaccharide formed by bacteria, and about 10% food residue, and is firmly stuck to the tooth surface. The acid stored inside demineralizes the enamel, and the bacteria and toxins produced are said to cause gingivitis, periodontitis, and even pyorrhea, two major oral diseases. It is attracting attention as a cause of caries and alveolar pyorrhea. This dental plaque is formed by oral bacteria, mainly Streptococcus miutans, using sucrose present in the oral cavity. That is, Streptococcus miutans produces GTF (glucosyltransferase, dextran synthase), which synthesizes sticky polysaccharides such as dextran and mutan from sucrose. This synthesized polysaccharide then attracts Streptococcus miutans and other bacteria (pathogens), forming dental plaque with a certain bacterial flora. Furthermore, bacteria such as Streptococcus miutans produce acids using various sugars, and this acid demineralizes the enamel surface by staying in the walls of polysaccharides and bacteria. Furthermore, dead bacteria and various substances produced,
Toxins have a negative effect on the gums and act as a cause of pyorrhea. Therefore, suppressing or inhibiting the formation of dental plaque and inhibiting acid production are very effective in preventing dental caries and periodontal diseases. Taking these points into consideration, the present inventors have investigated caries, caries,
As a result of intensive research into oral compositions suitable for the prevention of periodontal diseases, it was discovered that the above objectives could be achieved by incorporating 2-hydroxy-6-alkylbenzoitic acid as an active ingredient. . That is, 2-hydroxy-6-alkylbenzoic acid (anacardic acid) has been known to have anthelmintic, enzyme-inhibiting, antitoxin, antipyretic, and bactericidal effects; As a result of investigation, 2-hydroxy-6
- Even at relatively low concentrations, alkyl benzoitukacids inhibit plaque formation by Streptococcus miutans and, as a result, acid production; We discovered that it is effective in preventing caries and periodontal disease as an active ingredient in products.
This has led to the present invention. The present invention will be explained in detail below. The oral composition according to the present invention can be used as dentifrices such as toothpaste, powdered toothpaste, water toothpaste, mouthwash, troche, pasta, liniment, gargling tablet, gingival massage cream, chewing gum, etc. , 2-hydroxy- as an active ingredient
It contains 6-alkylbenzoic acid. In this case, as the 2-hydroxy-6-alkylbenzoic acid, the number of carbon atoms in the alkyl group is
13 to 17 in which 0 to 3 double bonds are present in the alkyl group can be suitably used, and these 2-hydroxy-6-alkyl benzoitic acids can be used singly. They may also be blended as a mixture of two or more. Note that the alkyl group may be a straight chain or a branched chain. 2-hydroxy-6-
Alkylbenzoitukacid is a mixture of alkyl groups with 13 to 17 carbon atoms and alkyl groups with 0 to 3 double bonds, such as Ginkgo biloba L.
) fruits and leaves of Anacardium
occidentale L.), seeds of Oriental oak (Semicarpus anacardium L.), etc., and therefore, 2-hydroxy-6-alkylbenzoitic acid can be obtained by extracting from these plants. A mixture of these can be blended. The amount of 2-hydroxy-6-alkylbenzoitic acid added to the oral composition is
0.0001~1% (weight%, same below), especially 0.001~
It is preferably 0.1%. As other components of the present invention, appropriate components are used depending on the type of oral composition. For example, in the case of toothpaste, dibasic calcium phosphate, calcium carbonate, insoluble sodium metaphosphate, amorphous silica, crystalline silica, abrasives such as aluminum oxide, carboxymethyl cellulose, hydroxyethyl cellulose, alginate, carrageenan, gum arabic, etc. , binders such as polyvinyl alcohol, polyethylene glycol, sorbitol,
Thickening agents such as glycerin and propylene glycol,
Foaming agents such as sodium lauric sulfate, sodium dodecylbenzenesulfonate, sodium hydrogenated coconut fatty acid monoglyceride monosulfate, sodium lauryl sulfoacetate, sodium N-lauroylsarcosinate, N-acylglutamate, sucrose fatty acid ester, and sweeteners. , fragrance, preservatives and other ingredients are mixed with water and manufactured according to conventional methods. Also, in mouthwashes and other mouthwashes, ingredients are appropriately blended depending on the properties of the product. In addition, in the present invention, 2-hydroxy-6
-In addition to alkylbenzoitic acid, lysozyme chloride, dextranase, lytic enzyme, mutanase, chlorhexidine, sorbic acid, alexidine, hinokitiol, cetylpyridinium, alkylglycine, alkyldiaminoethylglycine salt, tranexamic acid, ε-aminocaproic acid, allantoin , azulene, vitamin E, sodium monofluorophosphate, sodium fluoride, stannous fluoride, water-soluble primary or secondary phosphates, quaternary ammonium compounds, sodium chloride, and other active ingredients may also be included. can. The oral composition according to the present invention contains 2-hydroxy-6-alkylbenzoic acid, thereby effectively suppressing the formation of dental plaque caused by Streptococcus miutans, and suppressing acid production. Therefore, the occurrence of dental caries and periodontal disease can be effectively prevented. In addition, when the oral composition of the present invention contains 2-hydroxy-6-alkylbenzoitic acid as an active ingredient, it has a high plaque formation inhibiting effect and acid production inhibiting effect even at a relatively low concentration. Since the amount to be blended can be reduced, the safety in use is also high. Next, experimental examples will be shown to specifically explain the effects of the present invention. [Experimental example] 100 g of dry powder of curvaceous leaves was extracted three times with petroleum ether at room temperature, the extract was concentrated, and the fractions were dissolved in ethyl ether. Add 1% sodium carbonate solution to this and shake thoroughly three times, add 1N hydrochloric acid solution to the acidic substance that will transfer to 1% sodium carbonate solution to lower the pH (to PH2), and dissolve in ethyl ether again. and concentrated to give 2.1 g of brown paste. This was further dissolved in 50 ml of a mixture of petroleum ether and acetic acid = 100:1 (volume ratio), and silica gel (Wako Gel C-
200) and eluted with the same mixture as above to obtain 1.7 g of 2-hydroxy-6-alkylbenzoic acid as a pale yellow oil. In addition, 100 g of roasted oak seed husk powder was treated in the same manner as above to obtain 5.0 g of 2-hydroxy-6-alkylbenzoic acid. In addition, 2-hydroxy-6-
The number of carbon atoms, number and position of double bonds in the alkyl group of the alkyl benzoitic acid, 2-hydroxy-6-alkyl benzoitic acid from oak seed husk are as shown in Table 1.

[Table]
Next, the above-mentioned 2-hydroxy-6-alkyl benzoitic acid derived from the Gulbus leaves and Oak seed husks were used as test samples, and their effectiveness in inhibiting dental plaque formation was evaluated by the following culture attachment method and reaction attachment method. Culture adhesion method A predetermined amount of the above test sample (amount shown in Table 2) was added to BHI medium containing 1% sucrose, and Streptococcus miutans was precultured therein.
The 6715 strain was inoculated and cultured at 37°C for 16 hours in an Anaerobox gas exchanged with N ₂ :CO ₂ :H ₂ =80:10:10. After culturing, add 0.01M phosphate buffer (PH
7.0), then added the same amount of the same buffer as the culture solution, stirred vigorously, and measured the absorbance (turbidity) at 550 nm using a photometer to determine the amount of attached plaque. . Reactive deposition method 1% sucrose, 0.01% fungicide (NaN ₃ ) and heat sterilized Streptococcus miutans 6715
A predetermined amount (amount shown in Table 2) of the above test sample was added to a 0.05M phosphate buffer solution (PH7.0) containing the bacterial cells of the strain, and Streptococcus miutans 6715 strain prepared in advance was added thereto. Extracellular enzyme was added and the mixture was reacted at 37°C for 16 hours. After the reaction, wash twice with water, then add the same amount of water as the reaction system, perform ultrasonic treatment for about 20 seconds to uniformly suspend the plaque, and then use a photometer to disperse the plaque at 550 nm. The absorbance (turbidity) was measured to determine the amount of attached plaque. The results are shown in Table 2. The results are expressed as a percentage, with the amount of plaque attached to the control to which no test sample was added as 100%.

[Table] From the results in Table 2, it is found that 2-hydroxy-6-alkylbenzoic acid has the effect of inhibiting plaque formation. In addition, 2-hydroxy-6- derived from Gypsophila leaf
The results of examining the acute toxicity of alkyl benzoitic acid were LD ₅₀ >1 g/Kg mouse (oral administration). Examples are shown below. In addition, all percentages are weight percent, and 2-hydroxy-6-alkylbenzoic acid (Japanese currant) and 2-hydroxy-6-alkylbenzoic acid (Japanese sardine) were obtained using the same method as in the experimental example. 2-Hydroxy-6-alkylbenzoic acid derived from leaves and 2-hydroxy-6-alkyl benzoic acid derived from oak seed husk are shown. [Example 1] Toothpaste dicalcium phosphate dihydrate 50.0% Glycerin 20.0 Carboxymethyl cellulose 1.0 Sodium lauryl sulfate 1.0 Fragrance 1.0 2-Hydroxy-6-alkylbenzo 0.1 Itsuquaside (Sweetroot) Satucalin 0.1 Sodium fluoride 0.1 Water remaining 100.0% [Example 2] Toothpaste dicalcium phosphate x dihydrate 50.0% Sorbit 10.0 Glycerin 10.0 Carboxymethylcellulose 1.0 Sodium lauryl sulfate 2.0 Fragrance 1.0 2-Hydroxy-6-alkylbenzoic 0.1 Acid ) Sodium monofluorophosphate 0.3 Ethanol 2.0 Saccharin 0.1 Mutanase 0.1 Water Remaining 100.0% [Example 3] Toothpaste calcium carbonate 50.0% Glycerin 20.0 Carrageenan 0.5 Carboxymethyl cellulose 1.0 Lauryl diethanolamide 1.0% Sucrose monolaurate 2.0 2-Hydroxy- 6-Alkylbenzoic acid 0.1 Acid Flavoring 1.0 Saccharin 0.1 Chlorhexidine 0.005 Dextranase 0.01 Water Remaining 100.0% [Example 4] Toothpaste dicalcium phosphate dihydrate 50.0% Glycerin 20.0 Carboxymethyl cellulose 2.0 Sodium lauryl Sulfate 2.0 Flavor 1.0 2-Hydroxy-6-alkylbenzoic acid 0.05 Acid Chlorhexidine 0.01 Satucalin 0.1 Water Remaining 100.0% [Example 5] Toothpaste Silicic anhydride 30.0% Glycerin 30.0 Sorbit 20.0 Carboxymethyl cellulose 1.0 sodium lauryl Sulfate 2.0 Flavor 1.0 Saccharin 0.1 2-Hydroxy-6-alkylbenzoic acid 0.1 Acid Ethanol 2.0 Water Remaining 100.0% [Example 6] Toothpaste dicalcium phosphate dihydrate 50.0% Calcium carbonate 30.0 Glycerin 10.0 α-Olefin sulfonate 1.0 Flavor 1.0% Saccharin 0.1 2-Hydroxy-6-alkylbenzoic acid 0.05 Acid 2-hydroxy-6-alkyl benzoic acid 0.05 Acid Sodium monofluorophosphate 0.1 Dextran 0.5 Water Remaining 100.0% [Example 7] Liquid toothpaste Sodium polyacrylate 50.0% Glycerin 30.0 Saccharin 0.1 Fragrance 0.9 Chlorhexidine 0.01 2-Hydroxy-6-alkylbenzoic acid 0.1 Acid Ethanol 3.0 Linoleic acid 0.05 Water Remaining % 100.0% [ Example 8] Mouthwash ethanol 20.0% Saccharin 0.05 Fragrance 1.0 Sodium monofluorophosphate 0.1 Chlorhexidine 0.01 Lauryl diethanolamide 0.3 2-Hydroxy-6-alkylbenzoic acid 0.1 Acid water Remaining 100.0% [Example 9] Chewing gum gum base 44.0% Calcium carbonate 2.0 Starch syrup 15.0 Powdered sugar 30.0 Cane sugar palmitate 1.0 Fucultose 4.0 Maltose 3.0% 2-Hydroxy-6-alkylbenzoic acid 0.1 Acid flavoring 0.9 100.0% [Example 10] For gargling Tablet Sodium bicarbonate 54.0% Sodium diphosphate 10.0 Polyethylene glycol 3.0 Flavor 2.0 Oleic acid 0.1 Sodium monofluorophosphate 0.1 Chlorhexidine 0.1 2-Hydroxy-6-alkyl benzoic acid 0.1 Acid (Galcanthus) Citric acid 17 Sodium sulfate (anhydrous ) ) 13.6 100.0% [Example 11] Gingival pine surge cream white petrolatum 8.0% Propylene glycol 4.0% Dextranase 1.0 Stearyl alcohol 8.0 Polyethylene glycol 4000 25.0 〃 400 37.0 Sucrose stearate 0.5 2-hydroxy-6-alkylbenzoic acid 0.1 Acid water remaining 100.0%

Claims (1)

[Scope of Claims] 1. An oral composition characterized by containing 2-hydroxy-6-alkylbenzoic acid. 2. The oral composition according to claim 1, wherein the 2-hydroxy-6-alkylbenzoic acid has an alkyl group having 13 to 17 carbon atoms and an alkyl group having 0 to 3 double bonds. . 3. The oral composition according to claim 1 or 2, wherein the content of 2-hydroxy-6-alkylbenzoitic acid is 0.0001 to 1% by weight of the total amount.