JPH0662408B2 - Anti-caries and anti-periodontal composition - Google Patents

Description

TECHNICAL FIELD The present invention relates to a composition effective in preventing dental caries and periodontal disease.

The anti-caries and anti-periodontal disease composition of the present invention has excellent anti-caries and anti-periodontal disease effects, and caries of infants who often eat sugar-containing beverages, especially sweets and candy. It is extremely effective in preventing periodontal disease induced by caries in adults and adults.

(Prior Art) Recent studies have revealed that the causes of dental caries and periodontal disease, which are two major diseases in the field of oral surgery, are triggered by oral bacteria.

In particular, the oral bacterium Streptococcus mutans synthesizes a sticky polysaccharide from sucrose in food and drink, and various bacteria such as Streptococcus mutans such as lactic acid bacteria and gram are synthesized in the synthesized polysaccharide. Negative bacteria) propagate and finally form plaque, which should be called the flora. Bacteria such as Streptococcus mutans produce organic acids such as lactic acid from various sugars, and the organic acids stay in dental plaque to attack the enamel layer and induce dental caries. Furthermore, it is known that gram-negative bacterial toxin in dental plaque causes periodontal disease.

Therefore, in order to prevent the occurrence of this dental caries and periodontal disease,
The most effective method is to suppress the growth of Streptococcus mutans, which is the causative agent of plaque formation.

Heretofore, in order to suppress the colonization of Streptococcus mutans in the oral cavity, a fungicide such as chlorhexidine or various kinds of antibiotics have been studied (Shigeyuki Hamada, “How Can I Make Caries?”, 1982 2 22 May, Iwanami Shinsho P125-P133).

However, these techniques do not always give satisfactory results. That is, bactericides such as chlorhexidine are highly toxic and have an unpleasant bitterness, and also have the drawback of coloring teeth and oral mucosa. In general, antibiotics and bactericides are unsuitable for long-term continuous use, indiscriminately killing oral bacteria and disrupting the balance of the indigenous flora, resulting in bacterial metaplasia. In addition, it often causes unfavorable situations, such as affecting even intestinal bacteria.

(Problems to be Solved by the Invention) The inventors of the present invention have conducted extensive studies to find a substance that exhibits a specific antibacterial action against Streptococcus mutans and is highly safe for long-term continuous use. As a result, it was found that the plants of the Camellia family, especially the polyphenol compounds contained in the tea we use for daily drinks have excellent anti-caries and anti-bacterial disease activities.

(Means for Solving Problems) The present inventors have found that tea (Camellia sinensi)
s, (L.) O. It has succeeded in obtaining a highly safe and excellent anti-caries and anti-bacterial perioperative composition containing a polyphenol compound contained in Kuntze) as an active ingredient.

The polyphenol compound of the present invention means 5 shown in Table 1 represented by the formulas (1) and (2) in the claims.
Refers to a class of catechin chloroplast compounds.

The polyphenol compound of the present invention can be obtained from an ethyl acetate-soluble fraction of tea water or an alcohol extract, but may be derived from other raw materials or a chemically synthesized product.

The typical method for preparing the polyphenol compound of the present invention is as follows.

First, tea is extracted at room temperature with a sufficient amount of water or alcohol. After extraction, the residue is separated by a known method to obtain an extract. The solvent was distilled off from the extract, water was added to the residue to dissolve it, and the mixture was partitioned using hexane, chloroform and ethyl acetate in that order, and the hexane soluble fraction, chloroform soluble fraction and ethyl acetate soluble fraction were separated. To get The distribution with hexane and chloroform in this operation can be omitted depending on the coloring and viscosity of the water or alcohol extract, but in order to increase the purity of the ethyl acetate-soluble fraction, the distribution with hexane and chloroform can be omitted. Is desirable.

As the alcohol that can be used for extraction, lower alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol and butyl alcohol are preferable from the viewpoint of operability and extraction efficiency.

Furthermore, the ethyl acetate-soluble fraction obtained above was subjected to silica gel column chromatography using chloroform-methanol (20: 1, V / V) and chloroform-methanol (10: 1, V / V) solvents. By sequentially eluting, the 6 kinds of compounds shown in Table 1 can be obtained. If necessary, it is further applied to Sephadex LH-20 and eluted with a suitable solvent such as methanol, or recycled HPLC (manufactured by Nippon Analytical Industry Co., LC-90
8, GS-320 column, solvent methanol), it is possible to obtain higher purity 6 compounds of Table 1.

This polyphenol compound is an inorganic fluorine which has been reported as an anti-cariogenic component of tea (Kenjiro Ikegaya, Food and Development,
vol122, No. 3. It is clearly different from P22), and its effect was first clarified by the present invention.

(Effect) The polyphenol compound, which is the active ingredient of the anti-caries and anti-periodontal disease composition of the present invention, showed extremely excellent results in the antibacterial test against the oral bacterium Streptococcus mutans. These effects, which are useful for the prevention of dental caries and periodontal disease, will be described in detail below with reference to test examples.

Test example Measurement of antibacterial activity 5 ml of Brain Heart Infusion (B
HI) medium was added and autoclaved at 120 ° C. for 15 minutes, and then 100 μl of a sample solution dissolved in methyl alcohol and 100 μl of a suspension of bacteria previously cultured for 24 to 48 hours were added, and the mixture was statically incubated at 37 ° C. Incubate. BHI
The sample concentration in the medium is shown in the table. Culture 24 hours and 48
The viable cell count after the lapse of time was measured on a BHI medium supplemented with 1.5% agar. For the control, only methanol was added instead of the sample solution.

Sample 1. Compound I of Table 1 2. Compound II in Table 1 3. Compound III of Table 1 4. Compound IV of Table 1 5. Compound V in Table 1 Cells used in the test 1. Streptococcus mutans
ococcus mutans MT8148) Tables 2 to 7 show the results of antibacterial tests of polyphenol compounds against Streptococcus mutans. Compounds I, II, III, IV and V all showed a growth inhibitory effect on Streptococcus mutans. The growth inhibitory concentrations of Compounds I, III and V were all 500 μg / ml, and Compound III was a lower concentration of 125 μg / ml. Since the Streptococcus mutans MT8148 strain used in the test is a serotype C bacterium that is often found in caries-infected Japanese children, the efficacy of the anticaries and anti-periodontal disease composition of the present invention is also effective. Is proven. Moreover, the polyphenol compound of the present invention is
It is derived from tea that has been used for drinking since ancient times, and its stability has already been verified from historical experience because it is contained in large amounts as a tea ingredient. Further, since it does not cause any irritation to the oral cavity and shows no harmful effects such as coloring of teeth, it is a very suitable substance to be used as a component having a caries and periodontal disease preventing effect.

Mode of Use The polyphenol compound of the present invention is preferably used as a suitable oral preparation for use as a composition for caries prevention or periodontal disease prevention. Such an oral preparation may be a liquid preparation, a solid preparation, or a semisolid preparation, and preferable preparations include a dentifrice, a mouthwash, a troche, a mouthwash, a coating liquid, chewing gum and the like.

Excipients used to make these oral formulations,
Or, the auxiliary agent may be appropriately selected from those usually used for this type of purpose according to the dosage form, and is not particularly limited, and examples thereof include lactose, starch, corn starch, magnesium stearate, and diphosphoric acid. calcium·
Dihydrate, sorbit, carboxymethyl cellulose,
Saccharin, sodium lauryl sulfate, glycerin, sodium carboxymethyl cellulose, silicic acid anhydride, gelatin, titanium dioxide, menthol, fatty acid, citric acid,
Polyethylene glycol, sodium lauroyl sarcosinate, calcium carbonate, alcohol, carrageenan,
Sodium acyl taurate, peptone, gum arabic,
Lauryl diethanolamide or the like is used.

Fluoride such as sodium fluoride, phosphorus fluoride and sodium fluorophosphate can be added to the above-mentioned preparation to further enhance the caries prevention effect, and sodium chloride can be added or a preservative, a fragrance and a coloring agent. Etc. can also be added as appropriate.

The amount of the polyphenol compound of the present invention in the oral preparation for preventing dental caries or for preventing periodontal disease thus produced varies depending on the dosage form, but is usually about 0.000 by weight.
It is preferably 1% (weight / weight) or more.

(Examples) Next, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.

[Example-1] Dentifrice [Example-2] Gargle [Example-3] Lozenge agent [Example-4] Chewing gum (Effect of the Invention) The polyphenol compound of the present invention exhibits a strong antibacterial activity against Streptococcus mutans, which is a main causative bacterium that produces dental plaque that causes dental caries and periodontal disease.

Since the raw material polyphenol compound used in the present invention is a component of tea that has been used for drinking since ancient times, its safety system is extremely high, and a large amount of its strong anti-caries and anti-periodontal disease composition should be supplied. It is considered that it is possible to contribute to the improvement of oral hygiene and of course it is extremely useful industrially.

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Claims (1)

[Claims] Claims (1) and (2) below (In the formula, R ₁ represents a hydrogen atom or a hydroxyl group, and R 1
₂ is a hydrogen atom or a 3,4,5-trihydroxybenzoyl group An anti-caries and anti-periodontal disease composition comprising a polyphenol compound represented by