JPH0567608B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] This invention relates to an anti-caries agent, that is, an oral agent that prevents or inhibits the progression of caries. [Prior Art] In recent years, the prevalence of dental caries, or tooth decay, has increased significantly and has developed into a major social problem.
At the same time, research into the causes of caries is progressing, and the current theory is that the sucrose in food undergoes changes due to the action of caries-causing bacteria, producing insoluble and sticky glucans. It is said that Due to the glucan thus produced, caries-causing bacteria adhere to the tooth surface and multiply to form dental plaque. Using this plaque as a base, bacteria within it generate acid through sugar fermentation, and this acid causes dental caries to progress. To prevent dental caries, there are methods to increase the resistance of teeth, to eliminate sucrose or to use sweeteners instead of sucrose, to break down insoluble glucan produced from sucrose, or to inhibit the production of glucan, or to prevent caries. Possible methods include eradicating the causative bacteria. Each of the above methods has advantages and disadvantages, but since caries is essentially an infection caused by caries-causing bacteria, eradicating the caries-causing bacteria is considered to be the most effective way to prevent caries. . The above bacteria include Streptococcus mutans and Streptococcus sanguis.
Sanguis). Many attempts have been made to eliminate such caries-causing bacteria in order to prevent caries. For example, efforts are being made to use antibiotics such as penicillin and erythromycin, cell wall lytic enzymes that dissolve the cell walls of caries-causing bacteria, and bactericidal agents such as cyclohexidine.
However, these have the problem of disrupting the natural bacterial balance by disturbing the oral and intestinal flora, and causing side effects. Since the problem of such side effects has not been solved, it has not been widely used. [Problem to be solved by the invention] As described above, the reality is that there is no definitive method for preventing caries, and there is no prevention method that is better than the physical method of cleaning with a towel after eating. The current situation is that no law has been established. The present invention was made in view of the above circumstances, and an object of the present invention is to provide an anti-caries agent that does not cause side effects and can withstand long-term use. [Means to Solve the Problem] In order to achieve the above object, the anti-caries agent of the present invention contains at least component (A) as an active ingredient among the following components (A), (B), and (C). The structure is as follows. (A) cresyl acetate, methyleugenol,
At least one compound selected from the group consisting of heliotropin and ethyl salicylate. (B) Carboxylic acid (C) Lactone [Action] While conducting a series of studies aimed at preventing dental caries, the present inventors got a hint from the fact that certain fragrances have antibacterial effects, and developed a fragrance We have conducted a series of long-term studies on a huge number of fragrances to see if they could be used as anti-caries agents. As a result, it appears that excellent caries-causing bacteria sterilization effects can be obtained by using the fragrance component compounds that make up synthetic fragrances as they are, or by appropriately combining them with flavoring agents (food flavorings) such as carboxylic acids and lactones. This invention was achieved by discovering that As described above, the greatest feature of the anti-caries agent of the present invention is that it uses an extremely safe fragrance ingredient compound with no side effects as an essential component of the anti-caries agent. Next, this invention will be explained in detail. BACKGROUND ART There have been reports here and there that certain types of fragrance component compounds constituting fragrances have antibacterial effects. However, there are no reports regarding antibacterial activity against Myutans bacteria, which has the strongest cariogenic effect. Therefore, the present inventors first
The antibacterial activity against B. myutans was measured for synthetic fragrance compounds that have been reported to have some kind of antibacterial effect or are relatively widely used. The antibacterial activity was determined by making a 5% alcohol solution of each of the above synthetic fragrance ingredients (this is used as the test ingredient), and adding 1/100 to 1/1000 of this to a heart infusion medium containing 5% sucrose. Percentage (5
% alcohol solution ((test component)) concentration is 1/100~
After the medium had solidified, S. myutans (Streptococcus miutans RIMD3125001) was inoculated by puncture and incubated at 37℃ for 72 hours.
After culturing for more than an hour, the growth of the bacteria in the medium and on the surface of the medium was observed and measured. Those exhibiting antimyutans activity are shown in Table 1 below. Having anti-Myutans activity means that no growth of Myutans bacteria is observed when the test component is added at a ratio of 1/1000 and cultured at 37°C for 72 hours or more. Then, the concentration of the test component is gradually diluted, and the reciprocal of the minimum concentration (effective growth inhibitory concentration) at which anti-myutans activity is observed, for example, if the concentration of the test component is 1/1000, the reciprocal is 1000. It was shown as the antimyutans activity value. A similar experiment was conducted using Koboku extract, magnolol, which is an active ingredient of Koboku extract, and erythromycin, an antibiotic that has a bactericidal effect against P. myutans bacteria.
It is also shown in the table. The synthetic fragrance component compounds listed in Table 1 exhibit excellent antimyutans activity equivalent to that of Koboku extract (see JP-A-57-85319), which is known as an anti-caries agent. Since synthetic fragrance ingredients are extremely rich in anti-myutans activity, we expanded our search to the field of flavoring agents such as carboxylic acids and lactones to investigate substances with anti-myutans activity. The results are shown in Table 2 below. The carboxylic acids and lactones listed in Table 2 had extremely high antimyutans activity. Next, the fragrance ingredients shown in Tables 1 and 2 above were mixed and their antimyutans activity was examined. The results are shown in Table 3 below, and anti-myutans activity values higher than the arithmetic mean of the activity values of the anti-myutans bacteria of the fragrance ingredients in Tables 1 and 2 were obtained. This shows that a great synergistic effect can be obtained by mixing the fragrance ingredients shown in Tables 1 and 2. That is, in general, fragrance ingredients are rarely used alone, and various ingredients are mixed to create a mixed fragrance with a desired fragrance, which is then used. Therefore, it is extremely effective in practice that the large synergistic effects shown in Table 3 can be obtained by mixing and using the fragrance ingredients shown in Tables 1 and 2. As described above, the anti-caries agent of the present invention does not cause any side effects because it is composed of a highly safe flavor component compound that is widely and actually used in the food industry and the like. In other words, the anti-caries agent of this invention has a slightly lower anti-caries effect than the antibiotic erythromycin, but since the anti-caries agent of this invention is not an antibiotic, it does not cause side effects (in vivo microflora) that are seen with antibiotics. (disturbance of bacteria, emergence of resistant bacteria), and there is no problem at all even when used continuously for a long period of time. Moreover, since the anti-caries agent of the present invention is composed of a wide range of fragrance components such as synthetic fragrances, carboxylic acids, lactones, etc., suitable fragrance components can be combined with any desired desired product to which the anti-caries agent is added. It can add flavor. This effect is practical in clinical practice, considering that the administration of anti-caries agents lasts for a certain period of time, and that it is especially desirable to administer them to infants from around 1 year of age, when teeth begin to erupt, to prevent caries. , is extremely useful. Furthermore, since the anti-caries agent of the present invention can inhibit the growth of Myutans bacteria at extremely low concentrations, a large anti-caries effect can be obtained with a small amount of use. As described above, the anti-caries agent of the present invention is a fragrance ingredient compound and has an excellent anti-caries effect even when used in a small amount. It can also be effective. Moreover, its use does not cause any side effects unlike those of conventional antibiotics, and it is highly practical as it can withstand long-term continuous use. Moreover, the anti-caries agent of the present invention contains substances already known to have antibacterial effects, and they have antibacterial effects against pathogenic bacteria such as Escherichia coli and Shigella. However, there is nothing known about its antibacterial effect on special bacteria such as S. myutans (which does not belong to any of the streptococcal classifications), so it cannot be predicted based on what has been reported so far. It can be said that it can produce unprecedented effects. The anti-caries agent of the present invention is effective simply by adding a predetermined amount to the above-mentioned mouthwash, troche, toothpaste, etc. as it is. For example, in the case of mouthwash, the anti-caries agent is made into a 5% alcohol solution, and this is added to a 10% sucrose solution to give a concentration of 1/3000 to 1/5000 (as the concentration of the test ingredient, the same applies hereinafter). Just add it like this.

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[Table] Next, examples will be described. The following examples were carried out using the mixtures of Table 3, which give excellent synergistic effects upon mixing. Example 1 Targeting the No. 1 mixture listed in Table 3,
When the activity of B. myutans was determined, the effective growth-inhibiting concentration against B. myutans was 1/3000.
(Anti-myutans activity 3000). This No.
Even when a 5% alcohol solution of 1 mixture was added to a 10% sucrose solution to a concentration of 1/3000 and put into the mouth, no discomfort or irritation was felt at all. Example 2 The effective growth-inhibiting concentration against B. myutans was investigated using the mixture No. 2 in Table 3, and the effective growth-inhibiting concentration was found to be 1/4000 (anti-Myutans activity: 4000). Even when a 5% alcohol solution of this mixture was added to a 10% sucrose solution to a concentration of 1/4000 and placed in the mouth, no discomfort or irritation was felt at all. Example 3 Targeting the mixture No. 3 in Table 3, its effective growth-inhibiting concentration against P. myutans was determined. The effective growth-inhibiting concentration of this product was 1/4000 (anti-Myutans activity 4000). Even when a 5% alcohol solution of this mixture was added to a 10% sucrose solution to a concentration of 1/4000 and placed in the mouth, no discomfort or irritation was felt at all. Example 4 Targeting the mixture No. 4 in Table 3, the effective growth-inhibiting concentration of this mixture against B. mutans was determined. As a result, the effective growth-inhibiting concentration was 1/5000 (anti-Myutans activity 5000). Even when a 5% alcohol solution of this product was added to a 10% sucrose solution to a concentration of 1/5000 and placed in the mouth, no discomfort or irritation was felt at all.

Claims (1)

[Scope of Claims] 1. An anti-caries agent containing at least component (A) among the following components (A), (B), and (C) as an active ingredient. (A) cresyl acetate, methyleugenol,
At least one compound selected from the group consisting of heliotropin and ethyl salicylate. (B) Carboxylic acid (C) Lactone 2 Carboxylic acids are derived from capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, rosin acid, vanillic acid, undecanoic acid, undecylenic acid and enanthic acid. The anti-caries agent according to claim 1, which is at least one carboxylic acid selected from the group consisting of: 3. Claim 1, wherein the lactone is at least one lactone selected from the group consisting of d-decalactone, d-dodecalactone, d-undecalactone, d-tridecalactone, and d-tetradecalactone. Anti-caries agents as described.