JP2001089386A - Anti-dental caries agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an anti-dental caries agent that is inexpensively available and includes the substances safe to human bodies as active ingredients and further provide an anti-teeth-decaying agent that permits not only oral compositions, for example, a mouth-washing solution, to be formulated, but also can be formulated to foods and beverages as an food additive. SOLUTION: The objective anti-dental caries agent comprises, as an active ingredient, at least one extract from the whole glass bodies or the whole leaves selected from the group consisting of barrenwort, (Epimedium grandiflorum), beefsteak plant (Perilla frutescens crispa), ginkgo (Ginkgo biloba), Engelhardtia chrysolepis and bark of hamamelis (Hamamelis virginiana), particularly the extract from the fruits or the seeds is used as the active ingredient. An oral composition including the anti-dental caries agent is provided.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an anti-carious agent. More specifically, the present invention relates to an anti-cariogenic agent containing, as an active ingredient, an extract extracted from whole plants or leaves of plants.

[0002]

2. Description of the Related Art Caries are generally called caries, and the causes thereof are considered as follows. Naturally, certain kinds of bacteria are adsorbed on teeth due to the interaction between the glycoprotein, which is a component in saliva, and the cell surface substance of bacteria resident in the oral cavity. This bacterium is a glucosyltransferase (hereinafter referred to as "G"), which is an enzyme secreted outside the cells.
Tase ”. ), Food-derived sucrose is denatured into a sticky polysaccharide, and adheres more firmly to the tooth surface. This is generally called plaque, and the attached bacteria metabolize sugars in the plaque and generate an acid as a metabolite thereof.
The acid demineralizes the enamel surface of the tooth and promotes dental caries. It is said that plaque causes not only caries, but also bad breath, and depending on its progress, periodontal disease, gingivitis, and even alveolar pyorrhea.

[0003]

An object of the present invention is to provide an anti-cariogenic agent which is available at a low cost and contains a substance which is safe for the human body as an active ingredient. A second object of the present invention is to provide an anti-cariogenic agent comprising, as an active ingredient, a substance which can be safely blended into an oral composition such as a mouthwash or a dentifrice, and which can be blended into food or drink as a food additive. It is to provide. A third object of the present invention is to provide an anti-cariogenic agent which is useful for preventing oral diseases such as bad breath, periodontal disease, gingivitis and alveolar pyorrhea by suppressing the formation of plaque. It is.

[0004]

SUMMARY OF THE INVENTION In view of the above circumstances, the present inventor has conducted intensive studies day and night in search of an anti-cariogenic agent which is suitable for prevention of dental caries and periodontal disease and which is safe for the human body. where, extract of Epimedium leaf and stem of which is also used as a food ingredient (whole plant), as well as perilla, ginkgo, yellow杞又the leaf extract of hamamelis, S. mutans bacteria and S. sobrinu
It was found that it had an effect of significantly preventing s bacteria from adhering to teeth, and was confirmed to be effective as an anti-cariogenic agent.
The present invention has been completed based on such findings.

[0005] That is, the present invention is an anti-cariogenic agent containing, as an active ingredient, at least one kind of whole plant or leaf solvent extract selected from the group consisting of epimedium, perilla, ginkgo, Huanggang and Hamamelis. .

The present invention is also an oral composition (including food and drink) containing the above-mentioned anti-carious agent.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION As an active ingredient of the anti-carious agent of the present invention, epimedium ( Epimedium grandtiorum Morren, Epimedium of Berberidaceae), perilla ( Perilla f. )
rutescens var. acuta Kudo, Shisoka Perilla spp.), ginkgo (Ginkgo biloba L. ginkgo family ginkgo spp.), Ki杞(Engelhardtia Chrysdepis Hance, walnut family) and witch hazel (Hamamelis virginiana Linuaeus, witch hazel family witch hazel (Hamamelis) spp.) A solvent extract of leaves, preferably a solvent extract of whole plants including stems in addition to leaves, is suitably used. In addition, perilla includes perilla or other closely related plants (for example, chili menjiso, catamenjiso, chirimencatameniso, etc.), and in the present invention, it is defined in the Japanese Pharmacopoeia as soybean (soybean leaf, perilla leaf). Can be used.

[0008] The whole plant or leaf of these plants may be subjected to an extraction operation as it is or as a crushed product, or may be subjected to an extraction operation, if necessary, as a crushed powder after drying.

Examples of the extraction solvent include water, lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol and butanol; lower alkyl esters such as ethyl acetate; ethylene glycol, butylene glycol, propylene glycol, glycerin and the like. Other known organic solvents such as glycols; other polar solvents such as ethyl ether, acetone and acetic acid; hydrocarbons such as benzene and hexane; and nonpolar solvents such as ethers such as ether and petroleum ether. These solvents may be used alone or in combination of two or more. For example, in the case of a raw material having a high fat content, an appropriate amount of water can be added to an organic solvent as needed to be used as a water-containing organic solvent. In the present invention, preferably,
An alcohol such as ethanol or a hydroalcoholic solution such as an aqueous solution of 20 to 30% by weight of ethanol can be used.

As an extraction method, a generally used method can be adopted. Although there is no limitation, for example, a method of immersing whole grass or leaves (as is or coarse powder, finely chopped material) or their dried and crushed materials (such as powder) in a solvent by cold immersion, digestion, etc., heating and stirring Extraction and filtration are performed to obtain an extract, or percolation. The obtained extract may be used after removal of solids by filtration or centrifugation as necessary, depending on the mode of use, or may be used as it is, or may be partially concentrated or dried by evaporating the solvent. .
After concentration or drying, the concentrated or dried product may be washed with an insoluble solvent and purified for use, or it may be further dissolved or suspended in a suitable solvent for use. In addition, a fraction having glucosyltransferase inhibitory activity can be obtained and purified from the extract using a conventional purification method, for example, a countercurrent distribution method or liquid chromatography, and used. Further, in the present invention, for example, the solvent extract obtained as described above,
It can also be used as a dried plant extract by ordinary means such as drying under reduced pressure and freeze drying.

The whole plant extract of Epimedium is used as a pharmaceutical raw material such as epimedium extract, extract, etc .; The whole plant extract of Hamamelis is used as a raw material for cosmetics such as Hamamelis extract; and the extraction of perilla, ginkgo and Huangqi The products are all sold commercially as food additives (for food ingredients). Therefore, they can be used simply in the present invention.

The anti-carious agent of the present invention contains an extract of the whole plant or leaf of the above-mentioned plant as an active ingredient, and is used as an ingredient of various oral compositions such as foods, quasi-drugs, and pharmaceuticals. By being blended, it can be effectively used to prevent the formation of plaque in the oral cavity. Here, the oral composition includes both those that are taken orally, such as food and drink, and those that are used in the oral cavity, such as toothpaste and mouthwash.

Specific examples of the oral composition include various foods such as troches, chewing gums, candy, gummy candy, chocolate, juice, etc .; dentifrice (paste, liquid, powder solid), mouth spray such as mouse spray, etc. Pharmaceutical or quasi-drugs such as fresheners, chewing agents, lozenges, oral pasta, gargles, syrups; dentifrices
Oral cosmetics such as mouthwash and mouth rinse can be mentioned. Preferably, foods such as troches, chewing gums and candy, and mouthwashes such as dentifrices, mouthwashes and mouth rinses can be mentioned.

[0014] These forms and dosage forms are not particularly limited, and can be arbitrarily determined according to the type.

The application concentration of the anti-carious agent of the present invention is determined by the type of the oral composition, the effective concentration of the whole plant or leaf extract of the above plant,
It can be appropriately selected and determined in consideration of factors such as dilution in the mouth. As a suitable concentration, in the case of epimedium whole plant extract (1 g / ml in terms of epimedium dry matter), 1 to 10% by weight, especially 3 to 10% by weight per 100% by weight of the composition for oral cavity
A range of 5% by weight can be mentioned. In addition, in the case of a perilla leaf extract (1 g / ml in terms of perilla dried product), 1 to 10% by weight, particularly 3 to 5% by weight per 100% by weight of the oral composition
Ginkgo leaf extract (1 ginkgo dry matter equivalent)
g / ml), 1 to 10% by weight, especially 3 to 5% by weight
Range, and yellow ginger leaf extract (1 g / m
1) in the case of 0.005 to 10% by weight, in particular 0.05 to 10% by weight
In the case of hamamelis leaf extract (1 g / ml in terms of dried hamamelis), the range is 0.1 to 10% by weight, particularly 0.5 to 5% by weight.

The anti-cariogenic agent of the present invention is known or may be known in the future as an antibacterial agent against S. mutans or S. sobrinus , as long as the effects of the present invention are not impaired. Anti-adhesion agent to surface or anti-GTas
It can also be compounded in combination with components such as anti-caries agents such as e-agents or anti-inflammatory agents.

The anti-caries agent of the present invention can be used in combination with a component usually blended in the oral composition, depending on the type of the oral composition to be applied.

For example, in the case of toothpaste, abrasives such as dibasic calcium phosphate, calcium carbonate, insoluble sodium metaphosphate, amorphous silica and aluminum oxide; carboxymethylcellulose, hydroxyethylcellulose, alginate, carrageenan, gum arabic, polyvinyl alcohol, etc. Binders such as polyethylene glycol, sorbitol, glycerin, propylene glycol;
Sodium lauryl sulfate, sodium dodecylbenzene sulfonate, hydrogenated coconut fatty acid sodium monoglyceride monosulfate, sodium lauryl sulfoacetate,
Foaming agents such as sodium N-lauroyl sarcosinate, N-acyl glutamate, sucrose fatty acid esters and the like can be mentioned. Further, flavoring agents such as menthol and flavoring or sweetening agents, preservatives and the like which are usually used therefor can be used. Can be blended. In the case of mouthwashes such as mouthwashes and foods such as chewing gum, conventional ingredients can be used in combination. In addition, as a sweetener combined and used, those with low or no caries are preferable, and for example, D-xylose, xylitol, saccharin sodium, aspartame, trehalose and the like can be suitably mentioned.

Further, the anti-caries agent of the present invention includes lysozyme chloride, lytic enzyme, dextranase, mutanase, chlorhexidine, sorbic acid, alexidine, hinokitiol, cetylpyridinium, alkylglycine, alkyldiaminoethylglycine salt, monofluorophosphate Sodium, sodium fluoride, stannous fluoride, water-soluble primary or secondary phosphate, quaternary ammonium compound,
It can be used in combination with components such as sodium chloride.

[0020]

The present invention will be described in more detail with reference to the following Test Examples and Examples, which should not be construed as limiting the present invention. Test Example (1) Plaque (Bacterial) Adhesion Inhibition Test (a) Ginkgo biloba leaf extract The anti-cariogenic effect of the Ginkgo biloba leaf extract was evaluated by the plaque (bacterium) adhesion suppression test described below. In addition, plaque (fungus)
The adhesion test was performed using a glass test tube instead of the tooth surface.

[0021] The (i) Streptococcus mutans plaque against bacteria (bacteria) adhesion prevention effect First, overnight cultures 30μl of Streptococcus mutans bacteria MT8148 strain brain heart infusion liquid medium containing (serotype c) (BHI medium) It was added to 3 ml of BHI medium containing 1% sucrose (sterile test tube with a lid), and the extract of ginkgo biloba (containing 1 g / ml in terms of dry ginkgo biloba component) (hereinafter referred to as “Ginkgo biloba”) The extract was mixed at various concentration ratios, and the test tube was incubated at 37 ° C. for 18 hours while tilted at 30 °.

Ginkgo biloba extract was prepared as follows. That is, 10 kg of dried ginkgo leaves
Was thoroughly mixed with 40 L of a 30% aqueous ethanol solution, allowed to stand at room temperature for 3 days, and then subjected to gravity filtration.
A 30% aqueous solution of ethanol was added, the mixture was allowed to stand for 2 days, and filtered naturally. The filtrate obtained by such an operation is combined at 60 ° C.
After concentration under reduced pressure, ethanol was added to bring the total amount to 10
As L, it was left for 2 days and filtered with diatomaceous earth. 1 ml of the obtained extract was equivalent to 1 g of original ginkgo leaves (dry matter).

Next, after culturing for 18 hours, the test tube was slowly rotated three times while keeping the angle of 30 °, and the culture solution was slowly decanted into an empty test tube (sample 1). 3 ml of the above-mentioned 1% sucrose-containing BHI medium is placed in an empty test tube having plaque (fungi) adhered to the inside surface of the test tube, and the mixture is stirred with a vortex mixer to attach plaque (fungus) on the inside surface of the test tube. A part of the kimono was washed and eluted, and the culture solution containing the plaque (bacteria) eluate was decanted into an empty test tube (sample 2). Then, 3 ml of 1% sucrose-containing BHI medium was again added to the obtained plaque (bacteria) attached test tube, the plaque (bacteria) firmly adhered to the inner surface of the test tube was scraped off with a spatula, and the solution was sampled. It was set to 3. Note that, of the above operations, the vortex stirring operation is based on the assumption that the mouth is rinsed. That is, Sample 2 reflects the amount of plaque (bacterium) that can be obtained by rinsing the mouth, and Sample 3 reflects the amount of plaque (bacterium) that cannot be obtained by rinsing the mouth.

Further, the amount of plaque (bacteria) contained in each sample solution was determined by measuring the turbidity (OD: absorbance 550 nm) of the solution. Next, the plaque (bacteria) adhesion rate was determined from the turbidity of the solution by the following formula, and the plaque (bacterium) adhesion suppression effect of the ginkgo biloba leaf extract was evaluated based on the adhesion rate (%).

[0025]

(Equation 1)

In the formula, OD ₅₅₀ is the absorbance of the ginkgo leaf extract itself (550) based on the OD ₅₅₀ values of Samples 1 to 3.
nm) is shown. Table 1 shows the results.

As a control, a ginkgo biloba leaf extract was not added to a test tube (ginkgo biloba leaf extract concentration: 0 μm).
l / 3ml) Plaque (bacteria) adhesion rate when the experiment was performed in the same manner as above, and instead of ginkgo biloba leaf extract as a comparative example,
Table 1 also shows the plaque (bacteria) adhesion rate when a similar experiment was carried out using leaves of Eucommia ulmoides Oliver extracted in the same manner.

[0028]

[Table 1]

(Ii) Inhibitory effect of plaque (bacteria) adhesion on Streptococcus sobrinus bacteria The plaque (fungus) adhesion suppression test was also performed on Streptococcus sobrinus strain 6715 (serotype g) in the same manner as in (i) above. The plaque (bacteria) adhesion inhibitory effect of the extract was evaluated. Table 2 shows the results.

[0030]

[Table 2]

From the above results, it was found that Ginkgo biloba leaf extract has an effect of inhibiting plaque (bacteria) adhesion and is an effective anti-carious agent.

(B) Perilla leaf extract The anti-cariogenic effect of the perilla leaf extract was determined by comparing (a) (i) and (ii)
In the same manner as described above, plaque (bacteria) adhesion inhibition test was performed, and the perilla leaf extract was prepared using 10 kg of finely divided pieces of Japanese soybean soybean “Soyo” as a raw material and a 30% aqueous ethanol solution as a leaching agent. It was prepared as follows according to the Japanese Pharmacopoeia, the general rules for preparations, and the method for producing a liquid extract. That is, 10 kg of the Japanese pharmacopoeia "Soyo" shreds were used for the first leaching agent (3
(0% ethanol aqueous solution), and allowed to stand at room temperature for about 2 hours in a sealed state. Pack this as tightly as possible into a leachate, open the lower mouth of the leacher, and gradually add a second leachate (30% aqueous ethanol) from above until the crude drug is covered.
Was added, and when the leachate began to drip, the lower opening was closed and sealed, and allowed to stand at room temperature for 3 days, after which the leachate was allowed to flow out at a rate of 15 to 20 mL per minute. 8.5 L of the initially obtained leachate was separately stored as a first leachate, and the leachate was further added with a second leachate to continue the outflow to obtain about 10 L of a second leachate. Then
The second leachate is concentrated under reduced pressure at 65 ° C. or
Combine with the leachate and add 30% aqueous ethanol
After standing for 2 days as L, the mixture was filtered using filter paper.
1 ml of the obtained extract is the original perilla (dry) (dry matter) 1
g.

(I) an inhibitory effect on plaque (fungus) adhesion to Streptococcus mutans bacteria, and (ii) a Streptococcus sobri.
Tables 3 and 4 show the results showing the plaque (bacteria) adhesion inhibitory effect on the Nus bacteria, respectively.

[0034]

[Table 3]

[0035]

[Table 4]

From the above results, it was found that the perilla leaf extract exhibited an effect of inhibiting plaque (bacteria) adhesion and was an effective anti-carious agent.

(C) Epimedium extract The anti-cariogenic effect of Epimedium extract was determined by (a) (i) and
In the same manner as in (ii), evaluation was performed by performing a plaque (bacteria) adhesion inhibition test.

The epimedium extract was prepared from epimedium ( Epimedium macrenthum mor)
dec Decnt.) and the stems and leaves of similar plants of the same genus were collected and dried in the summer and dried in 1 kg. It was prepared as follows according to the pharmacopoeia, general rules for preparations, and the method for producing a liquid extract. That is, 1 kg of the epimedium leaf and stem was mixed well with the first leaching agent (aqueous 25% ethanol solution) and allowed to stand in a closed state at room temperature for 2 days. This is packed tightly in the brewer, and the lower mouth of the brewer is opened.
Add a leaching agent (25% aqueous ethanol solution), and when the leaching solution starts to drip, close the lower mouth and seal, leave it at room temperature for 2 to 3 days, and then flow out the leaching solution at a rate of 0.5 to 1 mL per minute I let it. 850 mL obtained first was separately stored as a first leaching solution, and a second leaching agent was further added to the leaching solution to continue the outflow, thereby obtaining a second leaching solution. Next, the second leaching solution was concentrated and combined with the first leaching solution, the second leaching agent was added to 10 L, the mixture was allowed to stand for 2 days, and the supernatant was taken. 1 ml of the obtained extract was equivalent to 1 g of raw epimedium (dry matter).

(I) an inhibitory effect on plaque (bacteria) adhesion to Streptococcus mutans bacteria, and (ii) a Streptococcus sobri
Tables 5 and 6 show the results showing the plaque (bacteria) adhesion inhibitory effect on the Nus bacteria, respectively.

[0040]

[Table 5]

[0041]

[Table 6]

From the above results, it was found that the extract containing at least the leaves of Epimedium had a plaque (fungus) adhesion inhibitory effect and was an effective anti-carious agent.

(D) Huang Gia extract The anti-cariogenic effect of the Huang Gia extract was evaluated by performing a plaque (bacteria) adhesion inhibition test in the same manner as in (a) (i) and (ii) above. .

Incidentally, the yellowish extract was prepared as follows. That is, the dried yellow leaf is thoroughly mixed with a water-containing ethanol solution, allowed to stand at room temperature for 3 days, and then naturally filtered.
An aqueous ethanol solution was further added to the residue, and the mixture was allowed to stand for 2 days, followed by gravity filtration. The filtrates obtained by such an operation were combined and concentrated under reduced pressure at a temperature of 60 ° C. or lower, and ethanol was added to make the total volume 10 L, and the mixture was allowed to stand for 2 days and filtered. 1 ml of the obtained extract corresponded to 1 g of leaves (dried material) of the original yellow cabbage.

(I) an inhibitory effect on plaque (fungus) adhesion to Streptococcus mutans bacteria, and (ii) Streptococcus sobri
Tables 7 and 8 show the results showing the plaque (bacteria) adhesion inhibitory effect on the Nus bacteria, respectively.

[0046]

[Table 7]

[0047]

[Table 8]

From the above results, the yellowish extract was found to be plaque (fungi)
It has an antiadhesive effect and was found to be an effective anti-carious agent.

(E) Hamamelis leaf extract The anti-cariogenic effect of Hamamelis leaf extract was evaluated by performing a plaque (fungus) adhesion inhibition test in the same manner as in (a) (i) and (ii) above. .

The Hamamelis leaf extract was prepared as follows. That is, Hamamelis virgin
iara L.) 10 kg leaves are cut into small pieces and 50 v / v%
About 50 L of 1,3-butylene glycol at room temperature
After soaking for 10 days, the solution is filtered. 7
The mixture was left to stand for 10 days to ripen, and the deposits and precipitates generated in this step were removed by filtration, and at the same time, 50 V / v% of 1,3-butylene glycol was added to adjust to 50 L. 1 ml of the obtained extract was equivalent to 1 g of raw Hamamelis (dried product).

(I) a plaque (fungus) adhesion inhibitory effect on Streptococcus mutans bacteria, and (ii) Streptococcus sobri
Tables 9 and 10 show the results showing the plaque (bacteria) adhesion inhibitory effect on the Nus bacteria, respectively.

[0052]

[Table 9]

[0053]

[Table 10]

From the above results, it was found that the Hamamelis leaf extract has an effect of inhibiting plaque (bacteria) adhesion and is an effective anti-carious agent. Examples Hereinafter, application examples of the anti-caries agent of the present invention will be described as examples. The unit of each prescription means part by weight unless otherwise specified.

[0055]

Example 3 Sugar-Coated Tablet A mouthwash was prepared by coating 200 parts by weight of a tablet portion with 130 parts by weight of a sugar-coated portion.

[0057]

[0058]

[0059]

[0060]

[0061]

[0062]

Example 10 Oral Pasta Liquid Paraffin 13.00 Cetanol 10.00 Glycerin 25.00 Sorbitan Monopalmitate 0.60 Polyoxyethylene Sorbitan Monostearate 5.00 Sodium Lauryl Sulfate 0.10 Methyl Benzotonium Chloride 0.10 Methyl Salicylate 0.10 Saccharin 0.20 Fragrance 0.25 Epidermal Extract 3.00 Water Residue Total 100.00 In Examples 1 to 10, instead of Epimedium extract, perilla leaf extract, Ginkgo leaf extract, Yellow leaf extract, and Hamamelis leaf extract, each of the above formulations was similarly used. Prepared.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor: Shoko Yoshii 3-13-35, Mitsujinaminami, Yodogawa-ku, Osaka-shi, Osaka F-term (reference) 4C083 AA111 AA112 AA122 AB222 AB282 AB292 AB322 AB472 AC012 AC022 AC072 AC102 AC122 AC132 AC302 AC312 AC402 AC432 AC442 AC472 AC482 AC542 AC582 AC692 AC782 AC862 AD212 AD222 AD272 AD302 AD352 AD412 CC41 DD11 DD15 DD22 DD23 DD27 EE31 EE32 4C088 AB02 AB12 AB38 AB63 AB99 AC01 AC05 BA08 BA09 BA10 MA07 NA14 Z

Claims (2)

[Claims] 1. An anti-cariogenic agent comprising as an active ingredient at least one solvent extract of a whole plant or leaf selected from the group consisting of epimedium, perilla, ginkgo, yellow ginkgo, and hamamelis. 2. An oral composition comprising the anti-cariogenic agent according to claim 1.