JP2568833B2 - Caries prevention agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to Streptococcus mutans which is greatly involved in the formation of dental caries (cavities).
ns), and has excellent antibacterial activity against oral bacteria represented by oral bacteria, and can suppress the formation of water-insoluble glucan (dextran), which is involved in oral microorganisms and causes plaque.
It relates to a caries preventive.

<Prior art> Conventionally, as agents for suppressing oral bacteria, use of bactericides such as chlorhexidine, benzalkonium chloride, butyl paraoxybenzoate, sodium benzoate and antibiotics such as penicillin and tetracycline has been known. I have.

<Problems to be Solved by the Invention> However, these known bactericides and antibiotics disrupt the bacterial balance of the natural ecosystem by stirring the oral and intestinal bacteria depending on the administration method and dosage, and have adverse effects on the human body. There was a problem that caused.

<Object of the Invention> An object of the present invention is to effectively suppress the growth of Streptococcus mutans, a cariogenic bacterium (cariogenic bacterium), and to insoluble in water-soluble glucan (dextran), which causes plaque.
An object of the present invention is to provide a caries preventive agent that is effective in suppressing formation.

<Means for Solving the Problems> According to the present invention, there is provided a caries preventive agent comprising a fatty acid obtained by hydrolysis of marine lipids as an active ingredient.

 Hereinafter, the present invention will be described in more detail.

In general, the cause of dental caries (cavities) formation is tooth
h), substrate (Substrate) and mutans bacteria (St.mutan)
s), and it is said that when these three factors are present at the same time, caries (caries) occur.

The mechanism of caries (cavities) formation (Miller theory) is that, for example, when sucrose is used as a substrate (Substrate) in sugars, this sucrose is converted into water by glucosyltransferase (enzyme) produced by mutans bacteria (St. mutans). It turns into glucan (dextran) which is insoluble and sticky, and forms plaque on the surface of the tooth (Teeth). In this plaque, it becomes anaerobic, and microorganisms such as lactic acid bacteria proliferate, fermentation proceeds, and organic acids such as lactic acid are generated to lower the pH, demineralize tooth enamel, and reduce dental caries (cavities). It is supposed to form.

The present inventors have searched for a substance that suppresses the growth of Streptococcus mutans, a cariogenic bacterium (cariogenic bacteria), and is effective in suppressing the formation of water-insoluble glucan (dextran) that causes plaque. It has been found that fatty acids obtained by hydrolysis of marine lipids are extremely effective.

As the marine lipid used in the present invention, fish oil, animal marine plankton oil, marine animal oil and seawater vegetable oil can be preferably mentioned. As fish oil, sardine oil,
Mackerel oil, horse mackerel oil, hairtail oil, tuna oil, cod oil, skipjack oil, shark oil, yellowtail oil, chili pepper oil, and the like. Oils and the like can be mentioned. Examples of marine animal oils include whale oil, seal oil, and the like.
Chlorella oil and the like can be mentioned.

Hydrolysis of marine lipids can be obtained by hydrolysis using caustic alkali, lipase and the like in a conventional manner.

Various fatty acids are contained in the fatty acids obtained by hydrolyzing the marine lipids of the present invention. As a result of intensive studies, the action of suppressing the growth of cariogenic bacteria (St. mutans) and the water-insoluble glucan (dextran) were examined. It was found that the long-chain highly unsaturated fatty acids of the ω-3 series such as icosapentaenoic acid and docosahexaenoic acid greatly contributed to the inhibitory action of the formation. The long-chain highly unsaturated fatty acid means a fatty acid having 20 or more carbon atoms per molecule and having 3 or more double bonds.

These long-chain highly unsaturated fatty acids such as icosapentaenoic acid and docosahexaenoic acid are contained in marine lipids in the form of glycerides and glycolipids, and are essential fatty acids that cannot be synthesized in the human body.

In recent years, its physiological (pharmacological) effects have been studied. Since it reduces the concentration of lipid components such as cholesterol and triglyceride in serum and suppresses platelet aggregation, it prevents adult diseases such as myocardial infarction, cerebral serum and arteriosclerosis. It is a substance that has attracted attention as a therapeutic drug.

Long-chain highly unsaturated fatty acids such as icosapentaenoic acid and docosahexaenoic acid contained in the fatty acid composition obtained by hydrolysis of the marine lipid used in the present invention are 1 to 40% by weight [Iyoda et al., 23 , 452, (1972) ; Oil chemistry, gas chromatography data, 1
978-1980] and can be used as a caries preventive agent as it is, but it is generally preferable to purify and concentrate it in order to improve the caries preventive effect.

The method for concentrating and purifying the marine lipid used in the present invention includes a method by chromatography, a method by urea adduct, a method by low-temperature solvent fractional crystallization, a method by molecular distillation, a method by liquid-liquid partition, a selective hydrolysis by lipase. It can be concentrated and purified by a known method, such as a decomposition method or a combination thereof. Hydrolysis in the same manner as described above after concentration and purification results in a concentration of long-chain highly unsaturated fatty acids such as icosapentaenoic acid and docosahexaenoic acid of 30% by weight in all fatty acids.
The above can be concentrated and purified.

Regarding the marine lipids of the present invention, various products are marketed by respective manufacturers, and any fatty acid obtained by hydrolysis of those products (lipids) can be used as the caries preventive agent of the present invention. For use as a caries preventive agent, the content of long-chain highly unsaturated fatty acids such as icosapentaenoic acid and docosahexaenoic acid is 30 wt% based on the total fatty acids.
The above products are preferred.

The problem when the caries preventive agent of the present invention is incorporated into the oral composition is that, as described above, the fatty acid obtained by hydrolysis of the marine lipid which is the caries preventive agent of the present invention has an unsaturated degree. Since it contains a fatty acid having a high content, it is liable to be oxidized, is unstable, and if the oxidation proceeds, an unpleasant odor appears and the caries prevention effect is reduced. Therefore, antioxidant addition, soft encapsulation,
It is preferable to use it after inclusion by cyclodextrin.

The caries preventive agent administration form of the present invention can be used in tablet confections, chewing gums, candies, lozenges and the like having a relatively long residence time in the oral cavity, and can also be used in oral cleansing agents such as toothpaste and mouthwash. . The compounding amount is not necessarily uniform depending on the form and type of the target product, but is 0.01 to 30% by weight, preferably 0.1 to 2% by weight in the oral composition.
In general, 0% by weight is blended, and a caries-preventing effect is effectively exhibited with this blending amount.

<Effects of the Invention> The caries preventive agent of the present invention is not only safe for the human body, but also extremely effective in preventing caries, and therefore has a high utility value.

<Formulation examples> Formulation examples of oral compositions containing the caries preventive agent of the present invention are shown below.

Formulation Example 1 A chewing gum having the following composition was prepared according to a conventional method. Ingredient % by weight Gum base 20 Calcium carbonate 1 Powdered sugar 35 Maltose 10 Fructose 10 Sugar syrup 15 Flavor 1 Sardine oil fatty acid * 0.3 Water balance 100% * Concentrated purified product containing long-chain highly unsaturated fatty acids 40wt% Formulation example-2 According to the method, a mouthwash having the following composition was produced. Fatty acids obtained by hydrolysis of Ingredient wt% ethanol 20 saccharin 0.5 Glycerin 50 sucrose Raurireto 2 Perfume 1 krill fatty * 0.5 Water balance to 100% * krill oil (concentrated purified product), the content of the long-chain highly unsaturated fatty acid 35wt % Formulation Example-3 A troche having the following composition was produced according to a conventional method. Ingredient wt% gum arabic 8 maltose 30 fructose 20 glucose 20 Perfume 1 chlorella oil fatty acid * 0.2 Water balance to 100% * content 70 wt% in concentration and purification products long-chain highly unsaturated fatty acids <Example> Next practicing the present invention embodiment Will be described in more detail.

Example 1 A sample described in Table 1 as a 5 wt% -alcohol solution was added to a liquid medium of heart infusion bouillon supplemented with 2 wt% of sucrose so as to have a concentration of 0.01 wt%, and precultured. The Streptococcus mutans strain 3125001 strain (serotype C) was cultured at 37 ° C. for 24 hours using a platinum loop. Next, the culture solution was stirred to disperse the precipitate, and the absorbance (turbidity) at 550 nm was measured to check the amount of glucan formed by the mutans bacteria. In addition, during fermentation of glucan, sugar fermentation by mutans bacteria occurred and the medium became acidic. Therefore, the pH of the culture solution was also measured. Table 1 shows the results. The amount of plaque formation was expressed as a percentage when the control (sterilized water) was taken as 100%.

As shown in Table 1, no decrease in the pH of the medium and no glucan type were observed, and it is clear that the medium is effective in suppressing the growth of mutans bacteria (St. mutans).

Example 2 For the samples in Table 1 in which no decrease in the pH of the medium and no glucan formation were observed in Example 1, Example 1 was used.
Each sample was diluted with the same medium and the same operating method as described above to conduct an antibacterial test, and the minimum effective inhibitory concentration of each substance was measured. The evaluation method (judgment method) of the lowest effective inhibitory concentration test was determined by the change in the pH of the medium and the amount of glucan formed as in Example 1. As a result of the determination, a sample in which no decrease in the pH of the medium and no formation of glucan were recognized was determined to have antibacterial activity, and the anti-mutans bacterium activity value was determined as the reciprocal of the lowest effective concentration of the test sample.

 Table 2 shows the results.

As is clear from Table 2, it is clear that all the substances of the present invention show high activity.

Claims (2)

(57) [Claims] An anti-caries agent comprising a fatty acid obtained by hydrolysis of marine lipids as an active ingredient. 2. The caries preventive agent according to claim 1, wherein said marine lipid is selected from the group consisting of fish oil, animal marine plankton oil, marine animal oil, and seawater vegetable oil.