JPH0140005B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to an anti-caries composition, that is, a composition used to prevent caries or inhibit its progression. [Prior Art] In recent years, the incidence of caries, that is, dental caries, 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 glucan. 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, attempts have been 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. [Problems to be Solved by the Invention] However, these methods 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. In addition, attempts have been made to kill the caries-causing bacteria using hinokitiol, a component of the natural essential oil cypress oil, but the anti-caries properties of hinokitiol are also limited, and when used alone, loses its anti-caries properties relatively quickly. Therefore, even if it is added to something that is chewed for a relatively long time, such as chewing gum, a sufficient caries prevention effect cannot be expected. Therefore, the reality is that there is currently no definitive method for preventing caries, and no preventive method has been established that is superior to the physical method of cleaning with a toothbrush after meals. . The present invention was made in view of the above circumstances, and an object of the present invention is to provide an anti-caries composition that has no side effects, is highly safe, can be used repeatedly, and has an excellent caries preventive effect. [Means for Solving the Problems] In order to achieve the above object, the anti-caries composition of the present invention contains the following components (A), (B) and (C) as active ingredients. Contains at least one of the components, and the content of component (A) above is
The composition is set to 0.01% by weight or more. (A) Hinokitiol. (B) _C3 - _C18 carboxylic acid. (C) _C9 - _C14 lactone. [Effect] Specifically, the present inventors focused on the excellent anti-caries properties of hinokitiol itself, and conducted a series of studies focusing on improving its caries-preventing effect. As a result, it was found that when hinokitiol is not used alone but in combination with various other compounds, the caries prevention effect increases depending on the combination of compounds. As a result of further research, it was discovered that carboxylic acids and lactones were the most effective among the various compounds mentioned above in terms of effectiveness, and the present invention was achieved. As described above, the greatest feature of the present invention is that hinokitiol, which has no side effects and is extremely safe, carboxylic acid, and lactone are used as the active ingredients of the anti-caries composition. Next, this invention will be explained in detail. There are reports that natural essential oils, natural substances, fragrance compounds, or certain of their active ingredients have antibacterial effects. However, there are no reports regarding antibacterial activity against Myutans bacteria, which has the strongest cariogenic effect. Therefore, prior to confirming the antibacterial effect of hinokitiol, the present inventors first measured the antibacterial activity against B. mutans using natural essential oils that have been reported to have some antibacterial effect or are relatively widely used. The antibacterial activity was determined by making a 5% alcohol solution of each of the above natural essential oils (this was used as the test component), and adding this to a heart infusion medium containing 5% sucrose, with a proportion of the natural essential oil to the entire medium. 1/100 to 1/1000 (natural essential oil concentration in 5% alcohol solution is 1/100 to 1/1000), and after the medium has solidified, Streptococcus miutans
RIMD3125001) was inoculated by puncture and cultured at 37°C for over 72 hours, and 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. Anti-myutans activity means that natural essential oil is added to the culture medium at a ratio of 1/1000 and incubated at 37°C.
This means that no growth of M. myutans was observed when cultured for 72 hours or more. Then, the concentration of natural essential oil in the test component is gradually diluted, and the reciprocal of the minimum concentration (effective growth inhibitory concentration) at which antimyutans activity is observed, for example, when the concentration of natural essential oil is 1/1000, reciprocal
1000 was shown as the antimyutans activity value. Similar experiments were carried out using Koboku extract, magnolol, which is an active ingredient of Koboku extract, and erythromycin, an antibiotic that has a bactericidal effect on B. myutans, and are shown in Table 1.
The natural essential oils listed in Table 1 are Koboku extract (see Japanese Patent Application Laid-Open No. 57-85319), which is known as an anti-caries agent.
It shows an excellent antimyutans activity that is equal to or better than that of . Next, the active ingredients of each of the natural essential oils shown in Table 1 were investigated, and from among the active ingredients, ingredients that were recognized to have antibacterial properties were extracted and a similar test was conducted. The results were as shown in Table 2 below. As is clear from Table 2, the anti-myutans activity value of hinokitiol, the active ingredient of hiba oil, is 10,000, while that of hiba oil is 2,000, indicating that it has extremely high anti-myutans activity. It could be confirmed. This invention uses hinokitiol, which has such surprisingly high antimyutans activity, as an active ingredient of an anti-caries composition. Next, in order to identify compounds that, when combined with the above-mentioned hinokitiol, would improve their caries-preventing effect, we expanded our scope to include natural essential oils, synthetic fragrances, carboxylic acids, and lactones, and investigated their antimyutans activity. The results are shown in Table 3 below. The synthetic fragrances, carboxylic acids and lactones listed in Table 3 have high antimyutans activity. However, they are all significantly lower than that of hinokitiol when used alone.

【table】

【table】

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【table】

[Table] Next, hinokitiol was used as an essential component, and the components shown in Tables 1, 2, and 3 above were mixed with it to examine its antimyutans activity and glucan formation rate. However, the above glucan formation rate is
It was measured as follows. <Glucan formation rate measurement method> 200 ml of the mixture with the compositions No. 1 to No. 5 in Table 4
Weigh 1 ml of each into test tubes, add 100 ml of pure water, and stir. Weigh 1 ml of each of the solutions thus obtained into separate test tubes, and add 2 ml of pure water to each. Add 0.2M sodium phosphate buffer (PH6.0) containing 5% sucrose and _0.1NaN3 to each test tube.
Add 1.5ml and inoculate with Streptococcus miutans (Streptococcus RIMD3125001).
Incubate at 37°C for 18 hours. The glucan produced after culturing is dispersed using ultrasound,
Measure turbidity at absorbance 550 nm. A system in which no anti-caries composition was added was used as a blank, and the glucan formation rate was determined using the following formula. Formation rate (%)=measured value/blank×100 The results are shown in Table 4 below.

【table】

〔Effect of the invention〕

As described above, the anti-caries composition of the present invention contains hinokitiol and one or both of carboxylic acid and lactone as active ingredients, and the amount of hinokitiol is set at 0.01% by weight or more based on the total amount. Because of its excellent anti-caries effect, it is used in mouthwashes, troches, toothpaste,
Ideal for chewing gum, etc. 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 use. Next, the present invention will be explained based on examples. However, in the following examples, mixtures shown in Table 4 were used, in which excellent synergistic effects can be obtained by mixing hinokitiol with other ingredients. [Example 1] The mixture No. 1 in Table 4 was investigated for its effective growth inhibitory concentration against Myutans bacteria, and the effective growth inhibitory concentration was 1/4000 (anti-Myutans activity value 4000). Ta. This mixture has a herbal lemon flavor, and it can be added to a 10% sucrose solution with a 5% alcohol solution at a ratio of 1/4000 and taken in the mouth. I felt no discomfort or irritation at all. [Example 2] Targeting the mixture No. 2 in Table 4, the effective growth-inhibiting concentration of this mixture against P. mutans was determined. As a result, the effective growth inhibitory concentration was 1/8000
(Antimyutans activity value 8000). Even when a 5% alcohol solution of this product was added to a 10% sucrose solution at a ratio of 1/8000 of the above-mentioned mixture and put into the mouth, no discomfort or irritation was felt at all. [Example 3] Using the mixture No. 3 in Table 4 as a target, the effective growth-inhibiting concentration against P. myutans was determined.
The effective growth-inhibiting concentration of this product was 1/8000 (anti-Myutans activity value 8000). Even when a 5% alcohol solution of this product was added to a 10% sucrose solution at a ratio of 1/8000 of the above-mentioned mixture and put into the mouth, no discomfort or irritation was felt at all. [Example 4] The mixture No. 4 in Table 4 was investigated for its effective growth inhibitory concentration against Myutans bacteria, and the effective growth inhibitory concentration was 1/7000 (anti-Myutans activity value 7000). It was hot. This mixture has a herbal lemon flavor and contains 5%
Even when an alcoholic solution was added to a 10% sucrose solution at a ratio of 1/7000 of the above mixture and the mixture was put into the mouth, no discomfort or irritation was felt at all. [Example 5] The mixture No. 5 in Table 4 was investigated for its effective growth inhibitory concentration against Myutans bacteria, and the effective growth inhibitory concentration was 1/6000 (anti-Myutans activity value 6000). It was hot. This mixture has a herbal lemon flavor and contains 5%
Even when an alcoholic solution was added to a 10% sucrose solution so that the above mixture contained at a ratio of 1/6000 and the mixture was put into the mouth, no discomfort or irritation was felt at all.

Claims (1)

[Claims] 1. The following active ingredients include (A) and (B)
At least one of the component and (C) component is contained,
and the content of component (A) above is 0.01% by weight based on the total
An anti-caries composition characterized by having the following properties. (A) Hinokitiol. (B) _C3 - _C18 carboxylic acid. (C) _C9 - _C14 lactone.