JP2001097835A - Dental caries inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a dental caries inhibitor which contains, as an active ingredient, a material available at a low cost, safe for the human body, capable of being safely added to an oral care composition, such as a mouth wash solution, and further capable of being added to food and drink. SOLUTION: This dental caries inhibitor contains an extract from at least one kind of herb selected from the group consisting of Scutellaria baicalensis Georgi, Glycyrrhiza glabura Linne, Coptis japonica Makino and Curcuma zedoaria Roscoe as the active ingredient. The inhibitor preferably contains an extract from the root of the above herb. The oral care composition is prepared by the use of the inhibitor.

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-carious agent containing an extract extracted from a plant, particularly a plant root, as an active ingredient.

[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 compounded in an oral composition such as a mouthwash or a dentifrice, and which can also be compounded in food and drink. is there. The third object of the present invention is to suppress the formation of plaque,
An object of the present invention is to provide an anti-caries agent useful for preventing oral diseases such as halitosis, periodontal disease, gingivitis and alveolar pyorrhea.

[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. However , a solvent extract of plants such as Scutellaria, licorice, spinach or spinach used as a crude drug, especially the roots of these plants, the action of significantly preventing S. mutans and S. sobrinus from adhering to teeth. In addition to confirming its effectiveness as an anti-cariogenic agent, it has been found that the action is due to the antibacterial action of the plant extract against the above bacteria. 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, an extract of a plant such as Scutellaria, Scutellaria, Spinach, or Radish, in particular, an extract of the root thereof.

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-caries agent of the present invention, licorice ( Glycyrrhiza uralensis Fisher, Glyc
yrrhiza glabura Linne, leguminous genus or other congeners ( Leguminosae ), Scutellaria ( Scutellar )
ia baicalensis Georgi, Labiataceae
ae )), spinach ( Coptis japonica Makino ( Ranunculaceae )) or other congener plants ( Ranunculacea
e)), zedoary (Curcuma zedoaria Roscoe, solvent extract is used Zingiberaceae Curcuma (Zingiberaceae)), especially liquorice or other same genus plant roots and stolons, roots Scutellaria roots preferably excluding pericytes ( In the following, solvent extracts of rhizomes of spinach or other congener plants, and rhizomes of gyuthus are preferably used. The roots or rhizomes of the above plants are defined as crude drugs in the Pharmacopoeia.

[0008] These roots or rhizomes may be subjected to an extraction operation as they are or as crushed materials, or may be subjected to an extraction operation as a pulverized powder if necessary 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,
Water, alcohol such as ethanol or 20-40% by weight
A hydrated alcohol solution such as an aqueous ethanol solution can be used.

As an extraction method, a generally used method can be adopted. Although not limited, for example, a method of immersing roots or rhizomes (as is or coarse powder, finely chopped) or their dried and crushed materials (such as powder) in a solvent by cold immersion, digestion, etc., while 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. Further, the extract is purified by a commonly used purification method, for example, a countercurrent distribution method or liquid chromatography, etc., using a fraction having glucosyltransferase inhibitory activity or S. mutans.
It is also possible to obtain, purify, and use a fraction having an antibacterial action against bacteria or S. sobrinus (growth suppression, growth suppression, etc.). Furthermore, in the present invention, for example, the solvent extract obtained as described above can be used as a dried plant extract by ordinary means such as drying under reduced pressure and freeze drying.

These solvent extracts of liquorice, sycamore, spinach and zedoary are commercially available as liquorice extract or licorice extract, sycamore extract, spinach extract or gajutsu extract, respectively. Therefore, in the present invention, they can be used simply.

The anti-caries agent of the present invention contains the above-mentioned solvent extract of plant roots as an active ingredient, and is blended as a component of various oral compositions such as foods, quasi-drugs, and pharmaceuticals. By suppressing the growth or proliferation of S. mutans bacteria or S. sobrinus bacteria causing caries,
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 concentration of the anti-caries agent of the present invention to be applied should be appropriately determined in consideration of factors such as the type of oral composition, the effective concentration of extracts of licorice, orange gourd, cucurbits or burdock, and dilution in the mouth. Can be. As a suitable concentration, licorice extract (1 g / m
In the case of l), 0.05 per 100% by weight of the oral composition
In the range of 10 to 10% by weight, especially 0.2 to 5% by weight, in the case of the extract of Orgon (1 g / ml in terms of dry matter of Orgon).
In the range of 05 to 10% by weight, particularly 0.4 to 5% by weight, in the case of a spinach extract (1 g / ml in terms of dry spinach),
In the range of 0.005 to 10% by weight, especially 0.02 to 5% by weight per 100% by weight of the composition for oral cavity, and 0.1 to 5% by weight in the case of a germ extract (1 g / ml in terms of dried gugets).
The range may be 10% by weight, especially 1 to 5% by weight.

The anti-cariogenic agent of the present invention is an antibacterial agent against S. mutans or S. sobrinus, or a tooth of such a bacterium, as another component, as long as the effect of the present invention is not impaired. Anti-adhesion agent to surface or anti-GT
An anti-caries agent such as an ase agent, or a component such as an anti-inflammatory agent may be combined and compounded.

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 Examples> Test Example 1 Ougon extract (a) Inhibition test of plaque (bacteria) adhesion The anti-cariogenic effect of the Ougon extract was evaluated by a plaque (fungus) adhesion inhibition 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 (sterilized test tube with a lid), and mixed with pentagon extract (containing 6 g / ml in dry pentagon component) at various concentration ratios. The tube was tilted at 30 ° and incubated at 37 ° C. for 18 hours.

[0024] The extract of pentagon was prepared by treating a crushed pentagon specified in Japanese Pharmacopoeia as follows. That is, 150 L of ordinary water prescribed by the Japanese Pharmacopoeia is added to 30 kg of the crushed oregon crushed material, leached at about 90 ° C. for 3 hours, and then subjected to warm filtration using cotton, and the obtained filtrate is decompressed at 60 ° C. or lower. It was concentrated to obtain about 5 kg of a soft extract. 1 ml of the obtained extract was equivalent to about 6 g of the original gougon (dry matter).

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). Place the above 1 in an empty test tube with the plaque (fungus) attached to the inner surface of the test tube.
3 ml of BHI medium containing 3% sucrose was added, and the mixture was stirred with a vortex mixer to wash and elute a part of the plaque (bacteria) deposit on the inner surface of the test tube. Was decanted into a 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 according to the following formula, and the plaque (bacterium) adhesion-suppressing action of the Orgonum extract was evaluated based on the adhesion rate (%).

[0025]

(Equation 1)

The results are shown in Table 1. As a control, the plaque (bacteria) adhesion rate when the experiment was performed in the same manner as described above without adding the pentagon extract to the test tube (concentration of the pentagon extract: 0 μl / 3 ml), and the pentagon extract as a comparative example Table 1 also shows the plaque (bacteria) adhesion rate when a similar experiment was performed using a flow extract obtained by extracting a root of a corn ( Angelica acutiloba Kitagawa) with a 30% ethanol leachate.

[0027]

[Table 1]

[0028] (ii) subjected to plaque (bacteria) adhering inhibition tests in the same manner as above (i) the plaque against Streptococcus sobrinus bacteria (bacteria) adhering inhibition Streptococcus sobrinus bacteria 6715 strain (serotype g), Scutellaria baicalensis The plaque (bacteria) adhesion inhibitory effect of the extract was evaluated. Table 2 shows the results.

[0029]

[Table 2]

From the above results, it was found that the extract of Hagfish had a significantly superior plaque (bacteria) adhesion-inhibiting effect and was an effective anti-carious agent.

(B) Antibacterial test -MIC (minimum inhibitory concentration) test- Streptococcus mutans strain MT8148 (serotype c) and Streptococcus sobrinus strain 6715 (serotype g) were used as test strains for MIC test (microplate method). Was used to examine the antibacterial properties of the extract.

Specifically, first, an extract of gongon (containing 6 g / ml in terms of dry gongon component) was added to a BHI medium prepared in the same manner as in the above (a) to a concentration of 50 μl / 3 ml. Was used as a test sample solution. 4
A × 6 24-well microplate was prepared, 1 ml of BHI medium was added to all wells, and 1 ml of the test sample solution was added to the three wells in the lower three rows at the left end (25 μl / 3m).
l). After each well was mixed well, 1 ml of the solution in each well was transferred to the right row well (12.5 μl / 3 ml) and the same procedure was repeated to repeat 25, 12.5, 6.3, 3.1, 1.6 and 0.8.
Each dilution series of μl / 3 ml was prepared. Each pre-cultured test strain was added to each well except the bottom row of the dilution series. This was cultured overnight at 37 ° C., and the presence or absence of bacterial growth was visually checked while comparing the top row and the bottom row. The concentration of the gougon extract in the wells where no bacterial growth was observed is the minimum inhibitory concentration (MIC).

As a result, Streptococcus terrestris
ococcus mutans and Streptococcus sobrinus were all inhibited from growing, and the minimum inhibitory concentration (MIC) of the extract of Ogon to these bacteria was 25 μm.
1/3 ml. From this, it was found that the extract of Hagfish had an antibacterial effect on each of the above bacteria.

From the above results, it has been found that the extract of pentagon has significantly excellent plaque adhesion inhibitory activity and is an effective anti-carious agent.

Test Example 2 Licorice extract (a) Inhibition test on plaque (bacteria) adhesion The anti-cariogenic effect of the liquorice extract was determined by examining Test Example 1 (a).
In the same manner as in (i) and (ii), the plaque (bacteria) adhesion inhibition test was evaluated. It was prepared by a dipping method using an aqueous solution as a leaching agent. Specifically, for 20 kg of licorice shreds, 10
0 L of a 30% aqueous ethanol solution was added, and the mixture was left at room temperature for 4 days or more with occasional stirring to be leached, and then subjected to centrifugal filtration using cotton. The obtained leachate is further added to 60
Concentration under reduced pressure to about 16 L below ℃ (vacuum about 200
mmHg) and add the Japanese Pharmacopoeia “absolute ethanol”
L, left for 2 days, and filtered under pressure using diatomaceous earth to obtain a clear liquid. 1 ml of the obtained extract corresponded to 1 g of original liquorice (dry matter).

(I) an effect of inhibiting plaque (fungus) adhesion to Streptococcus mutans bacteria, and (ii) Streptococcus sobri
Tables 3 and 4 show the results showing the plaque (bacteria) adhesion inhibitory effect on the Nus bacteria, respectively. In addition, about the plaque (fungus) adhesion inhibitory effect with respect to S. mutans bacteria, the result of the same test using a corn extract in place of a licorice extract is also shown as a comparative example.

[0037]

[Table 3]

[0038]

[Table 4]

From the above results, it was found that the liquorice extract has a plaque (bacteria) adhesion inhibitory action and is an effective anti-carious agent.

[0040] (b) Streptococcus mutans bacteria and Strept antibacterial test licorice extract
The antibacterial activity against ococcus sobrinus was tested in the above Test Example 1.
The evaluation was performed by the MIC test in the same manner as (b).

As a result, Streptococcus elegans extract
The growth of both ococcus mutans and Streptococcus sobrinus is inhibited, and the minimum inhibitory concentration (MIC) of the licorice extract against these bacteria is 6.3.
μl / 3 ml. This indicates that the licorice extract has an antibacterial effect on each of the above bacteria.

Test Example 3 Antioxidant (a) Antiplaque (Bacterial) Adhesion Inhibition Test The anticariogenic action of the extract was measured using the test example 1 (a).
In the same manner as (i) and (ii), the plaque (bacterium) adhesion inhibition test was evaluated. The spinach extract was 30% based on 1 kg of the shredded “ouren” specified in the Japanese Pharmacopoeia as a raw material.
Using an aqueous solution of ethanol as a leaching agent,
It was prepared according to the method specified in the general rules of formulation and liquid extract. Specifically, an appropriate amount of a 30% aqueous ethanol solution was added to 1 kg of a slice of spinach, mixed well, and allowed to stand at room temperature for about 2 hours in a closed container. This is packed into a leacher as tightly as possible. After opening the lower opening of the leacher, gradually add a 30% aqueous ethanol solution from above until the crude drug is covered. When the leachate begins to drip, close the lower opening and seal. After leaving at room temperature for 2 to 3 days, the leachate was allowed to flow out at a rate of 0.5 to 1 mL per minute. The first obtained 8.5 L was separately stored as a first leachate, and a second leachate was further added to the leachate to continue the outflow to obtain a second leachate. 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 then filtered to obtain a clear solution. 1 ml of the obtained extract corresponded to 1 g of raw spinach (dry matter).

(I) an inhibitory effect on plaque (bacteria) adhesion to Streptococcus mutans bacteria, and (ii) Streptococcus sobri
Tables 5 and 6 show the results showing the plaque (bacteria) adhesion inhibitory effect on the Nus bacteria, respectively. The plaque (bacteria) adhesion inhibitory effect on S. mutans bacteria is also shown as a comparative example, in which the same test was carried out using a corn extract instead of an orange extract.

[0044]

[Table 5]

[0045]

[Table 6]

From the above results, it was found that the spinach extract has a significantly excellent plaque (bacteria) adhesion inhibitory action and is an effective anti-carious agent.

(B) Antibacterial test Streptococcus mutans and Streptococcus mutans in spinach extract
The antibacterial activity against ococcus sobrinus was tested in the above Test Example 1.
The evaluation was performed by the MIC test in the same manner as (b). As a result, due to the spinach extract, S. mutans bacteria and S. mutans .
The growth of all S. sobrinus bacteria was inhibited, and the minimum inhibitory concentration (MIC) of the spinach extract was 3.1 μl / 3 ml for S. mutans bacteria and 1 for S. sobrinus bacteria.
2.5 μl / 3 ml. This indicates that the spinach extract has an antibacterial effect on each of the above-mentioned bacteria.

Test Example 4 Gadget Extract (a) Plaque (Bacterial) Adhesion Inhibition Test
In the same manner as (i) and (ii), the plaque (bacterium) adhesion was evaluated by performing a plaque (bacteria) adhesion inhibition test. As a raw material, a 30% aqueous ethanol solution was used as a leaching agent and prepared as a soft extract according to the method specified in the Japanese Pharmacopoeia, General Rules for Preparations, and Liquid Extract (Gaduz Flow Extract 1.2).
5 kg). 1 ml of the obtained extract was equivalent to 20 g of the original gadget (dried product).

(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. The plaque (bacteria) adhesion inhibitory effect on S. mutans bacteria is also shown as a comparative example, in which the results of a similar test were carried out using a corn extract instead of a gull extract.

[0050]

[Table 7]

[0051]

[Table 8]

From the above results, it was found that the extract of Gadget has a significantly excellent plaque (bacteria) adhesion inhibitory action and is an effective anti-carious agent.

(B) Antibacterial test Strepto
The antibacterial activity against Coccus mutans and Streptococcus sobrinus was measured in the same manner as in Test Example 1 (b).
It was evaluated by an IC test. As a result, the growth of both S. mutans and S. sobrinus was inhibited by the gutttu extract, and the minimum growth inhibitory concentration (MIC) of the gutttu extract against these bacteria was 25 μl / 3 ml.
Met. From this, it was found that the extract of zedoary had an antibacterial effect on each of the above bacteria.

<Examples> Examples of application of the anti-caries agent of the present invention will be described below 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]

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 Benzotonium Chloride 0.10 Methyl Salicylate 0.10 Saccharin 0.20 Perfume 0.25 Liquorice Extract 0.50 Water Residue Total 100.00 In the above Examples 1 to 10, each of the above-mentioned formulations was prepared in the same manner, except that each of the extract of Japanese radish, the extract of orange and the extract of syrup were used instead of the extract of licorice.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 1/02 A61P 1/02 // A23G 3/00 101 A23G 3/00 101 3/30 3/30 ( 72) Inventor: Noriko Yoshii 3-13-35, Mitsujinaminami, Yodogawa-ku, Osaka, Osaka Prefecture F-term (reference) 4B014 GB06 GB07 GB08 GB09 GB13 GB17 GE03 GK12 GL03 GP01 4C083 AA072 AA111 AA112 AA122 AB032 AB222 AB282 AB322 AC022 AC072 AC102 AC122 AC132 AC302 AC312 AC342 AC432 AC442 AC482 AC642 AC692 AC782 AC862 AD212 AD222 AD272 AD302 AD352 AD412 AD432 CC41 DD15 DD21 DD22 DD27 EE32 EE33 4C088 AB32 AB38 AB60 AB81 AC11 BA08 CA05 CA06 CA07 MA57 NA15 ZA67 ZA67 ZA67

Claims (3)

[Claims] 1. An anti-cariogenic agent comprising as an active ingredient an extract of at least one plant selected from the group consisting of Scutellaria, Licorice, Radish and Radish. 2. An anti-cariogenic agent comprising, as an active ingredient, an extract of at least one plant root selected from the group consisting of a gourd root, a licorice root, a spinach root and a sage root. 3. An oral composition comprising the anti-caries agent according to claim 1 or 2.