JP3114359B2 - Anti-caries and anti-periodontal agents - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an anti-cariogenic and anti-periodontal agent containing ε-poly-L-lysine, an oral composition, an anti-cariogenic and anti-periodontal food and drink, and the like.

[0002]

BACKGROUND OF THE INVENTION Periodontal diseases such as periodontitis and alveolar pyorrhea and caries are affected by many people, and the morbidity particularly in adults continues to increase. Causes of caries are mainly due to Bacteroides mutans ( Bacteroides).
s mutans ) and the cause of periodontal disease are mainly due to Bacteroides gingivalis ( Bactero).
ides gingivalis ) and Actinobacillus actinomycetemcomitans ( Actinobaci)
llus actinomycetemcomitan
s ), Actinomyces visco- sus ( Actino
myces viscos ) and the like. For the prevention and treatment of these diseases,
It is considered that suppressing the growth of the causative pathogen is the most effective means. Conventionally, antibiotics or synthetic bactericides have been mainly used for this purpose.

[0003]

[Problems to be Solved by the Invention] The continuous use of conventional antibiotics and synthetic bactericides for a long period of time for the prevention and treatment described above may cause side effects such as effects on intestinal bacteria, There is a problem that is not always safe in daily use. Accordingly, an object of the present invention is to provide an anti-caries and anti-dental agent which has an antibacterial action against caries or periodontal disease pathogens, and which has a high safety without affecting intestinal bacteria by long-term use for prevention. To provide perioperative agents. According to the present invention, ε-poly-L-
It has been found that ricin or a salt thereof inhibits the growth of caries or periodontal disease pathogens, shows low toxicity to intestinal bacteria, and is effective as an anti-cariogenic and anti-periodontal agent.

[0004]

The present invention has the following arrangement. An anti-cariogenic and anti-periodontal agent comprising ε-poly-L-lysine or a salt thereof as an active ingredient.

The configuration and effect of the present invention will be described in detail below. The anti-cariogenic and anti-periodontal agent of the present invention comprises ε-poly-L
-The antibacterial effect of lysine suppresses the growth of caries or periodontal disease-causing bacteria, and the safety of ε-poly-L-lysine does not affect intestinal bacteria and is excellent in safety. .

The ε-poly-L-lysine used in the present invention is
For example, ε-poly-L- described in JP-A-59-20359
A lysine-producing bacterium, Streptomyces albras subsp. Lysinopolymeras, belonging to the genus Streptomyces, is cultured, and ε-poly- is obtained from the resulting culture.
It is obtained by separating and collecting L-lysine.

L-lysine is an amino acid having two amino groups in one molecule, and poly-L-lysine obtained therefrom is generally α-poly-L-lysine having an amino group at the α-position and a carboxyl group bonded thereto. And ε-poly-L-lysine in which an amino group at the ε-position and a carboxyl group are bonded. In the present invention, a method using ε-poly-L-lysine obtained by the above production method is used. It has a high antibacterial effect against caries or periodontal disease-causing bacteria, and is also desirable in terms of safety.

In the present invention, ε-poly-L-lysine can be used in a free form. However, inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, or acetic acid, propionic acid, fumaric acid, malic acid, It can also be used in the form of a salt of an organic acid such as citric acid. ε-poly-L-lysine, whether in free form or in the form of a salt with the above-mentioned inorganic or organic acids, has essentially no difference in its effect as an anti-cariogenic and anti-periodontal agent.

In the present invention, ε-poly-L-lysine or a salt thereof can be used alone or in combination with other known antibacterial agents in oral compositions, medicines, etc., and applied in the oral cavity. . Further, depending on the type of the oral composition (eg, dentifrice, ointment, troche, chewing gum, etc.), carriers, auxiliary agents and the like usually used in the composition can be appropriately selected and used in combination. These carriers, auxiliaries, etc.
Although not particularly limited, particularly preferred are, for example, dibasic calcium phosphate, glycerin, vinyl acetate resin, sorbitol, mannitol, saccharin, white petrolatum, polyethylene glycol, silicic anhydride, calcium carbonate, sodium lauryl sulfate, magnesium stearate, and paraoxybenzoate. Sodium acid, talc, hydroxypropyl cellulose, carboxymethyl cellulose, liquid paraffin, ethanol and the like.

In the present invention, enzymes such as dextranase, mutanase, sorbic acid, hinokitiol, alkylglycine, allantoin, tranexamic acid, vitamin E, azulene, indomethacin, and anti-inflammatory agents can also be used.

The amount of ε-poly-L-lysine or a salt thereof used in the present invention varies depending on the form of the oral composition or drug, the site of application, the method of application, the number of applications, and the like. Can vary widely depending on
For example, when blended in an oral composition, it is desirable to blend ε-poly-L-lysine in an amount of 0.001 to 10% by weight, particularly 0.005 to 5% by weight, based on the total amount of the components.

[0012]

According to the present invention, .epsilon.-poly-L-lysine is used as a cariogenic bacteria Bacteroides mutans and a periodontal disease bacteria Bacteroides gingivalis and Actinobacillus actinomycetemecomi. Since it has strong antibacterial activity against Tance and Actinomyces viscosus, it is suitable as an anti-caries and anti-periodontal agent. Further, ε-poly-L-lysine is a highly safe substance that is a food additive, has no effect on the intestinal flora, and has high safety that can be used for a long period of time.

[0013]

Hereinafter, the present invention will be described based on examples.
The present invention is not limited to these. Example 1 As a sample, ε-poly-L-lysine was dissolved in sterilized water, and T
Odd-Hewitt medium (Difco) was aseptically added. This was inoculated with Bacteroides mutans, the main causative bacterium of caries, and the MIC (minimum inhibitory concentration: μg / ml) for ε-poly-L-lysine was 37.
After culturing at 24 ° C. for 24 hours, the measurement was performed. For the control, 0.9% saline was added instead of the sample. As a result, ε-poly-
M for L-lysine Bacteroides mutans
IC was 25 μg / ml.

Example 2 As a sample, ε-poly-L-lysine hydrochloride was dissolved in sterile water, and a Todd-Hewitt medium (Difco) was used.
Was added aseptically. This was inoculated with Bacteroides mutans, the main causative organism of caries, and ε-poly-L-
MIC (minimum inhibitory concentration: μ
g / ml) was measured after culturing at 37 ° C. for 24 hours. For the control, 0.9% saline was added instead of the sample. As a result, the MIC of ε-poly-L-lysine hydrochloride against Bacteroides mutans was 25 μg / ml.

Example 3 As a sample, ε-poly-L-lysine was dissolved in sterilized water and added aseptically to a basal medium shown in Table 1. This was inoculated with Bacteroides gingivalis, Actinobacillus actinomycetemcomitans and Actinomyces viscosus, which are the main causative bacteria of periodontal disease, and ε-poly-L-
MIC against lysine (minimum inhibitory concentration: μg / m
1) was measured after culturing at 37 ° C. for 24 hours. For the control, 0.9% saline was added instead of the sample. The results are shown in Table 1.

Example 4 As a sample, ε-poly-L-lysine hydrochloride was dissolved in sterilized water and added aseptically to a basal medium shown in Table 2. This was inoculated with Bacteroides gingivalis, Actinobacillus actinomycetemcomitans and Actinomyces viscosus, which are the main causative bacteria of periodontal disease, and MIC against ε-poly-L-lysine (minimum inhibitory concentration: μ).
g / ml) was measured after culturing at 37 ° C. for 24 hours. For the control, 0.9% saline was added instead of the sample. The results are shown in Table 2.

Example 5 Effect on intestinal bacterial flora SD rats (male, 7 weeks old, average body weight: 138.0 ± 1.2)
g; 6 mice in each group), and ε-poly-L-lysine 0.4
Weight% added compound feed and ε-poly-L as control
After oral administration of 16 g / day of a compound feed without addition of lysine for 7 days, intestinal flora in cecal contents was searched. The measurement of the number of intestinal bacteria was performed by culturing the target bacterium using the medium shown in Table 3, recording the shape and the number of the grown colonies, and performing gram staining on each of them to perform gram staining. Bacterial groups were determined by cell morphology. The results are shown in Table 4. The numerical values were shown as logarithmic values and standard deviations of the number of each bacterial group per 1 g of cecal contents. As a result, ε−
It was confirmed that oral administration of poly-L-lysine had no effect on intestinal flora.

In the following, examples of the composition of the present invention containing ε-poly-L-lysine as an active ingredient are shown, but the present invention is not limited to the following examples. Formulation Example 1. Dentifrice 50% by weight of dibasic calcium phosphate Glycerin 20 Sodium lauryl sulfate 1 Sodium carboxymethyl cellulose 1 Saccharin sodium 0.1 Sodium parahydroxybenzoate 0.1 ε-Poly-L-lysine 0.1 Fragrance 0.5 Ethanol 5 Purified water Remaining amount 100.0% by weight in total

Formulation Example 2 Mouthwash Ethanol 20% by weight Saccharin sodium 0.05 Sodium monofluorophosphate 0.1 Sucrose palmitate 0.5 ε-poly-L-lysine 0.05 Fragrance 1 Purified water Remaining 100.0% by weight in total

Formulation Example 3 Chewing gum gum base 20% by weight calcium carbonate 2 starch syrup 15 powdered sugar 30 maltose 10 fructose 10 ε-poly-L-lysine 0.01 fragrance 1 purified water remaining 100.0% by weight in total

Formulation Example 4 Lozenge Polyethylene glycol 6000 2% by weight Silicic anhydride 1 Magnesium stearate 0.6 Talc 0.3 Hydroxypropylcellulose 0.7 ε-Poly-L-lysine 0.01 Mannit Remaining amount 100.0% by weight in total

[Table 1]

[Table 2]

[Table 3]

[Table 4]

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Claims (2)

(57) [Claims] 1. An anti-cariogenic and anti-periodontal agent comprising ε-poly-L-lysine or a salt thereof as an active ingredient. 2. The method according to claim 1, wherein the salt of ε-poly-L-lysine is at least one selected from hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, propionic acid, fumaric acid, malic acid and citric acid. The anti-caries and anti-periodontal agent according to claim 1.