JP2000327581A - Composition for sterilizing oral cavity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a safe composition for sterilizing the oral cavity effective in preventing dental caries and preventing and curing periodontal diseases. SOLUTION: This composition for sterilizing the oral cavity contains an extract of HOKOSSI (seeds of Psoralea corylifolia) or bakuchiol as an effective ingredient. The composition contains the effective ingredient to be 20-1000 ppm in the oral cavity. As the composition, candies, an oral cavity-cleaning agent and the like are cited. The composition can sterilize Streptococcus mutans, Streptococcus sobrinus and the like and prevent or cure diseases such as decayed teeth, periodontal diseases and the likes.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a composition for disinfecting the oral cavity, comprising as an active ingredient a sorghum extract or the active ingredient bactiol contained in the sorghum extract. The composition for disinfecting the oral cavity of the present invention has a bactericidal action against periodontopathogenic bacteria and cariogenic bacteria in dental plaque, and is used for preventing or treating the occurrence of tooth decay or periodontal disease. be able to.

[0002]

2. Description of the Related Art Dental caries and periodontal disease are diseases that lead to damage and loss of teeth and are extremely frequently observed. It is a convention of the society that these diseases are caused by bacteria resident in the oral cavity. Sugar contained in foods is derived from Streptococcus mutans, a bacterium resident in the oral cavity.
ns) and Streptococcus sobrinus
glucosyltransferase produced by sobrinus)
(GTase), insoluble polysaccharide (insoluble glucan)
Is converted to When the insoluble glucan adheres to the tooth surface, plaque, which is an aggregate of bacterial cells, is formed.
Insoluble glucan takes up these bacteria and other bacteria, or food debris, and becomes thicker plaque. Approximately 70% of plaque is a bacterium, which breaks down the carbohydrates contained in food, thereby producing organic acids such as lactic acid and causing a decrease in pH. When the pH falls below 5.4 on the tooth surface, demineralization occurs in the tooth enamel, resulting in dental caries. When the plaque layer is thin, the lactic acid generated is buffered by saliva and neutralized, but as the plaque layer becomes thicker, the lactic acid produced in the deeper layer of plaque is buffered by saliva (medium And the caries become less susceptible to caries. In addition, lactic acid bacteria such as Lactobacillus and Enterococcus as well as the above-mentioned Streptococcus mutans and Streptococcus sobrinus have been detected as bacteria that may generate an acid in dental plaque.

[0003] Bacteria in plaque and calculus and their production enzymes cause inflammation of the periodontal ligament, gingiva and alveolar bone, such as inflammation of the mucous membrane in the gingival sulcus and ulceration caused by infection with S. pyogenes. Periodontal disease develops. Porphyromonas gingivalis (Porphyromonas gingivalis) is known as a typical example of bacteria involved in this periodontal disease.
As a practical method of preventing caries and periodontal disease, tooth brushing can be mentioned. Brushing the teeth within 30 minutes after a meal can prevent caries and periodontal disease to some extent. However, it is impossible to always carry a toothpaste, and it is not always possible to brush your teeth after eating. Furthermore, plaque or cariogenic bacteria cannot be completely removed from the oral cavity by brushing. For this reason, it is required to brush the teeth regularly and continuously.

At present, various oral compositions containing an antibacterial agent that suppresses the growth of or inhibits the growth of the causative bacteria of caries (cavities) and periodontal disease are provided. ing. These are chlorhexidine, cetylpyrimidium chloride and the like, but there are cases where there is a problem in safety when considering the effect on the human body. Moreover, even with these drugs, the effect of preventing dental caries and periodontal disease may not be obtained without regular and continuous treatment.

[0005] As another method of preventing dental caries and periodontal disease,
There are methods such as not ingesting sugars assimilated by cariogenic bacteria, inhibiting GTase enzyme activity, and inhibiting bacteria from adhering to the tooth surface. Sugars that Streptococcus mutans or Streptococcus sobrinus cannot assimilate, and
Many studies on GTase activity inhibitors are said to have produced some effects. However, these do not act directly on cariogenic bacteria and periodontopathic bacteria, and are unlikely to provide a fundamental preventive effect. Also, methods for inhibiting the attachment of bacteria to the tooth surface are still being studied, and no practical examples have been found. From these facts, development of a highly safe antibacterial agent which directly acts on caries and periodontopathic bacteria and can continuously suppress growth and sterilize it is expected.

[0006]

An object of the present invention is to provide a composition for disinfecting the oral cavity which is effective in preventing caries and preventing and treating periodontal disease. In particular, it is to develop an antibacterial agent having a bactericidal action against bacteria present in dental plaque.

[0007]

The hokoshi extract is an extract from the seeds of the Dutch beet, and is listed as a manufacturing agent on the existing additive list of food additives. Also,
Bactiol is the active antimicrobial active ingredient in sorghum extract. Japanese Patent Application Laid-Open No. 10-215813 discloses that it exhibits antibacterial activity against H. pylori and Streptococcus mutans, and that it can be used as a mouthwash and a health agent. As for Streptococcus mutans, strong bactericidal activity was observed when the test was carried out using the cultured free cells.

[0008] The present invention is based on the finding that the extract of sorghum and bactiol exhibit bactericidal activity not only against various cariogenic bacteria but also periodontopathogenic bacteria, and also against bacteria in dental plaque. It was completed by discovering that it exhibits a bactericidal action effectively. Furthermore, it shows the possibility of eradication of bacteria involved in dental caries by short-term intensive treatment. Examples of the composition for disinfecting the oral cavity of the present invention include candy, confectionery, drinks, foods such as various drinks, quasi-drugs or preventive medicines such as troches and mouthwashes, and disinfectants for tooth surfaces. And the like. Moreover, the composition for oral sterilization in the present invention also includes a composition used for sterilizing toothbrushes, dentures and the like.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION As the extract of chokoshi in the present invention, a bone extract, which is a crude drug, extracted with an organic solvent can be used. For example, as described in Japanese Patent Application Laid-Open No. 5-15355, seeds of Dutch beetle (herbal medicine: osseous fat) are combined with alcohols, esters, ethers, ketones, hydrocarbons, halogenated hydrocarbons, or optionally water. , And solid-liquid separation by centrifugation or filtration. The resulting extract can be obtained by concentration or distilling off the solvent. The obtained concentrate is in the form of a paste, but may be used after further pulverized or dissolved in alcohol or the like. Further, depending on the use, purification such as decolorization or deodorization may be performed.

[0010] In addition, bakuchiol can be obtained by purifying the aforementioned sorghum extract using column chromatography or the like, and can also be produced by synthesis. This product does not dissolve in water, but can be made water-soluble by using an appropriate amount of an emulsifier, cyclodextrin or the like. The amount of Hokoshi extract or bakuchiol to be added varies depending on the duration of the treatment in the oral cavity.
It may be about 20 ppm to 1000 ppm. As a practical example for obtaining the effect of the present invention, in the case of a candy mainly composed of sugar and syrup, 500 bactiol is contained in the candy.
If you add about 2,000 ppm of sorghum extract or bakuchiol, the concentration of bakuchiol in the oral cavity will be about 50 to 20 minutes while eating candy.
Maintained at 0 ppm. When treating the tooth surface therapeutically, apply about 200 to 1000 ppm of succulent extract or bakuchiol as bakuchiol, and after 30 seconds,
The effect can be demonstrated by leaving it for about 60 seconds. Alternatively, when used as a mouthwash, if an effect is to be exerted by treatment for 20 to 30 seconds, a sorghum extract or bakuchiol having a bakuchiol concentration of about 500 to 1000 ppm may be used.

[0011] In the composition of these oral disinfecting compositions, bactiol or sorghum extract is used as a main component of the active ingredient, and other bactericides, potency enhancers, and anti-cariogenic carbohydrates are used. It does not hinder the formulation of the inhibitor or GTase. In order to more effectively exert the effect of the composition for disinfecting the oral cavity of the present invention, the thickness of the plaque is, of course, preferably thin, preferably after light brushing. In order to completely eliminate the cariogenic bacteria, it is preferable to use it several times every day from 5 to 10 days. According to the present invention, cariogenic bacteria such as Streptococcus mutans present in dental plaque are reduced in the number of viable bacteria and proliferated by treatment with a composition for oral disinfection containing a bokoshi extract or bactiol. Is late. Furthermore, by repeatedly processing,
Furthermore, the number of bacteria is reduced and the growth becomes extremely slow. Therefore, after treatment with the composition for disinfecting the oral cavity according to the present invention, the interval between toothpastes for preventing dental caries can be made longer than before.

Next, the antibacterial activity of the osteoclast extract of the present invention will be described as a test example.

[Test Example 1] (Preparation of sorghum extract) 90 kg / kg
5 L of ethanol was added thereto, and the resultant was immersed at 25 to 30 ° C for 20 hours. The immersion liquid was separated by filtration, and the filtrate was concentrated to remove the solvent. this
10 g was dissolved in 100 g of dimethyl sulfoxide and used. (Preparation of undiluted solution of bactiol)
After adding 5 L of -hexane and immersing at room temperature for 5 hours, the immersion liquid was filtered off, and the filtrate was concentrated to remove the solvent, whereby a pale brown oily substance was obtained. This was dissolved in 500 ml of n-hexane, vigorously shaken with 100 ml of a 1% potassium hydroxide solution, left for a while, and the separated potassium hydroxide layer was discarded. After repeating this operation three times, the operation of washing the n-hexane phase with 100 ml of pure water was repeated three times.

Then, after drying by adding anhydrous sodium sulfate, the mixture was concentrated to obtain about 30 g of an oily substance. This concentrate is subjected to silica gel column chromatography and silica gel
Fractionation was performed by ODS column chromatography to obtain a bakuchiol fraction. This fraction is UV-254nm on TLC,
And one spot was detected by heating after spraying with sulfuric acid and 360 nm, and a single peak was shown by gas chromatography equipped with an FID detector (flame flame ionization detector). The UV absorption spectrum and molecular weight of this fraction are based on literature values of bactiol [Tetrahedron 29, 11
99-1125 (1973): maximum absorption wavelength (ethanol solution) 260n
m, (ethanolic potassium hydroxide solution) 285 nm, molecular weight 2
56] and showed a single peak. This fraction was concentrated to obtain bactiol. This was dissolved in dimethyl sulfoxide to a concentration of 10 mg / ml and used.

In the following Test Examples 2 to 5, the concentrations of bakuchiol and sorghum extract were expressed in pure amounts. Test Example 2 shows that the sprouts extract and bakuchiol according to the present invention exhibit a bactericidal action against cariogenic bacteria and periodontopathic bacteria.

[Test Example 2] Bactericidal test for cultured cells Examination of minimum bactericidal concentration (MBC) Test method Bacterial solution obtained by culturing the strains shown in Table 1 in BHI medium for 24 hours
0.1 ml was added to 10 ml of a sterile BHI medium supplemented with 0,5,10,15,20,25,50 ppm of bactiol or 0,20,40,60,80,100 ppm of sorghum extract and added After 1 and 15 minutes, 0.1 ml of the solution was added to 10 ml of fresh BHI medium. This is 37
The culture was allowed to stand at 48 ° C for 48 hours, and the presence or absence of growth was determined by the turbidity of the medium after the culture. As a result, as shown in Table 1 and Table 2, 5-20 pp
m, or 20-60 ppm of sprouts extract, which have been sterilized by contacting for 8-15 minutes.Bactiol and sprouts extract have strong bactericidal activity against protoblastic bacteria and periodontopathogenic bacteria. found.

[0015]

[Table 1]

[0016]

[Table 2]

[0017]

[Test Example 3] Examination of sterilization time Test method Streptococcus mutans JCM5175 cultured at 37 ° C for 20 hours was inoculated 1/100 in BHI medium containing 5, 20 ppm of bactiol or 15, 60 ppm of sorghum extract. ° C,
It was left still for 0, 0.5, 1, 5, 10 minutes. Thereafter, the cells were diluted with sterile water, pour-cultured in a TGC medium containing 0.1% Tween, and the number of bacteria was measured. As a result, as shown in Table 3, the CFU decreased over time. In addition, the bacteriostatic count was significantly reduced even with a treatment time of 0.5 minutes and 1 minute, and a rapid bactericidal activity was confirmed.

[0018]

[Table 3]

Next, Test Example 4 shows that the sprouts extract and bakuchiol according to the present invention exhibit bactericidal activity against bacteria in plaque.

[Test Example 4] Sterilization test for bacteria in dental plaque Streptococcus mutans JCM5175 cultured in BHI medium at 37 ° C for 20 hours was inoculated 1/100 into BHI medium supplemented with 2% saccharose, and cultured at 37 ° C for 6 hours to artificially form plaque on the test tube wall. Formed. After gentle stirring, the culture in the test tube was discarded and washed with sterile water. Into this test tube, 100, 500, 1000 ppm bactiol and the same concentration of sucrose fatty acid ester as emulsifier, or 200, 10
10 ml of a citrate buffer having a pH of 6 containing 00,2000 ppm of a sorghum extract and the same concentration of a sucrose fatty acid ester as an emulsifier was added, followed by treatment at 37 ° C for 5 minutes. Then, in order to remove the effect of residual bactiol or sorghum extract,
Add 10 ml of sterile water with 1% Tween as an inactivator,
The plaque on the test tube wall was homogeneously dispersed by vigorous stirring and sonication. The number of surviving bacteria in this solution was determined by appropriate dilution, followed by 48 hours of pour culture in a TGC medium containing 0.1% Tween. In this test, the plaque formation before the treatment and the variance for the measurement of the bacterial count after the treatment vary greatly, and the average value of five similar tests was calculated and shown in Table 4. As a result, as shown in Table 4, Streptococcus mutans in the plaque was not completely killed, but was greatly reduced as compared with the control.

[0020]

[Table 4]

2. As a disinfectant composition, 80% of propylene glycol, 18% of purified water, 1.9% of 70% ethanol, and 0.1% (1000 ppm) of bactiol were prepared, and a disinfection test was performed on artificially formed plaque. That is, 37
Streptococcus mutans cultured for 20 hours at ℃
GS5, JC2 and Streptococcus sobrinus 6715
0.1 ml of the culture solution of BHI supplemented with 2% saccharose
10 ml of the medium was inoculated and cultured at 37 ° C. for 6 hours to form artificial plaque on the test tube wall. After gently agitating the test tube, the culture medium in the test tube was discarded, and the test tube was rinsed lightly with sterile physiological saline. To the test tube to which the artificial plaque was attached, 10 ml of the above composition using the bactiol of the present invention was added and allowed to stand. After 1 minute, discard this composition, wash 3 times with sterile physiological saline containing 0.1% Tween80, add 10 ml of sterile physiological saline, stir vigorously, homogenize, appropriately dilute, and count the number of viable bacteria did. BH count with 0.1% Tween80
This was performed by plating on an I agar medium.
As a control, the same treatment was performed using a composition prepared by using 70% ethanol instead of bactiol of the composition of the present invention. In addition, since there are variations in the tests, five tests were performed in each test, and the average value is shown in Table 5. As a result, it was confirmed that the viable bacteria were significantly reduced in all three strains.

[0022]

[Table 5]

[0023]

[Test Example 5] Repeated sterilization test against bacteria in dental plaque Streptococcus mutans cultured in BHI medium at 37 ° C for 20 hours in artificial plaque forming medium (pH 7.0) containing 2% saccharose JCM5175 was inoculated 1/100 and cultured at 37 ° C. for 6 hours to artificially form plaque on the test tube wall. After gentle stirring, the culture in the test tube was discarded and washed with sterile water. To this test tube, 10 ml of a pH 6 citrate buffer containing 200 ppm of bactiol and a sucrose fatty acid ester was added, and sterilized at 37 ° C. for 5 minutes. Washed twice (first treatment).

To the treated test tube, the above artificial plaque forming medium was added and cultured at 37 ° C. for 6 hours, and then sterilized and washed by the above-mentioned methods (second treatment).
Further, the above artificial plaque forming medium was added to the test tube,
The cells were cultured at 37 ° C. for 12 hours and subjected to the same treatment (the third treatment). After that, the test tube is cultured for 6 hours → sterilization for 5 minutes, washing treatment (fourth treatment) → culture for 6 hours → sterilization for 5 minutes, washing treatment (fifth treatment) → 12 hours culture → sterilization treatment for 5 minutes (sixth treatment) ), And at each time point
The pH was measured. After the sixth treatment, the number of surviving bacteria was measured in the same manner as in Test Example 3. As a control, 200 ppm of sucrose fatty acid ester containing no bakuchiol was added.
The same treatment was carried out with a pH 6 citrate buffer. In addition, the test and the control were performed using five test tubes, and the average value was shown. As a result, as shown in Table 6, the decrease in pH was significantly suppressed even after only one sterilization treatment, as compared with the control group without sterilization treatment. As the number of repetitions increased, the decrease in pH became smaller. When the number of surviving bacteria in the plaque was measured at the end of the sixth treatment, it was found that there was almost no bacteria. In other words, even if the concentration cannot be completely sterilized by a single sterilization treatment, there is a possibility that the bacteria can be completely eliminated by repeated sterilization treatments.

[0025]

[Table 6]

[0026]

Example 1 Production of Candy and Bactericidal Activity In the following examples, a sprouts extract was prepared in the same manner as in Test Example 1 and dissolved in 70% ethanol to a 15% concentration before use. Bactiol was prepared in the same manner as in Test Example 1 and was dissolved in 70% ethanol at a 5% concentration. Mix 120g of sugar and 120g of 70% starch syrup, heat and melt at about 150 ° C, mix, cool to about 70 ° C and stir,
2 ml of 70% ethanol containing 5% bactiol or 70% ethanol containing 15% sorghum extract
2 ml was added, mixed well, and then cooled and solidified to prepare a candy. In addition, 2 ml of 70% ethanol
The candy prepared by the addition was used as a control. 10g each of this candy
Was added to and dissolved in 100 ml of water and tested for bactericidal activity. Using Streptococcus sobrinus as an indicator bacterium, sterilization treatment was carried out by the same test method as in Test Example 3, and after 5 minutes, 10
The number of bacteria after one minute was measured. As a result, it was confirmed that the candy to which the bakuchiol or the hokoshi extract was added had bactericidal activity.

[0027]

[Table 7]

[0028]

[Example 2] Production and bactericidal activity of mouthwash Prescription Ethanol 10% Glycerin 4% Bactiol or sorghum extract 4% Glucose 10% Water 78% The mouthwash prepared by the above formulation is 10 times when used. It may be diluted to an extent, contained in the oral cavity and washed for about 30 seconds to 1 minute. The bactericidal activity was performed in the same manner as in Example 1, and the number of surviving bacteria after 30 seconds was measured. As a result, 5 × 10 ⁶ was obtained before the treatment. It was greatly reduced to 2 × 10 ¹ and 4 × 10 ¹ .

[0029]

Example 3 Production of Various Oral Sterilizing Compositions Production of Juice Fruit Juice 10% Glucose Liquid Sugar 5% Water 85% Bactiol or Hokoshi Extract 0.2% L-Ascorbic Acid 0.05%

Oral freshener 30% reduced palatinose Perfume 0.1% Sorghum extract or bakuchiol 1% Starch 68.9%

Preparation of lozenges Arabic gum 7% Sugar 30% Palatinose 40% Flavor 2% Hokoshi extract or bakuchiol 1% Water 20%

Preparation of Toothbrush Cleaning Agent Ethanol 20% Hokusoshi extract or bakuchiol 0.5% Water 79.5% By immersing a toothbrush washed with water in this solution for 1 to 5 minutes, most of the bacteria attached to the toothbrush can be removed. Sterilized.

Preparation of the drug to be applied to the tooth surface Composition: Propylene glycol 80% Purified water 18% Hokusoshi extract or bakuchiol 2% An appropriate amount of this solution is applied to the tooth surface and left for 30 seconds to several minutes. Since it can also kill bacteria in dental plaque, it can be used as a therapeutic agent. The drug can also be used as a mouthwash in dental treatment.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) A61K 31/00 631 A61K 31/00 631C 31/045 31/045 (72) Inventor Ryoichi Tsukiyama Tatsuno, Hyogo Prefecture 100-3 Tominaga, Tatsunocho F-term (reference) in Higashimaru Shoyu Co., Ltd. BA10 BA11 NA14 ZA67 ZB35 4C206 AA01 AA02 CA01 KA18 MA01 MA04 NA14 ZA67 ZB35

Claims (4)

[Claims] 1. A composition for disinfecting the oral cavity, comprising a bokchosi extract as an active ingredient. 2. A composition for the prevention and / or treatment of dental caries and / or periodontal disease, comprising an extract of Hokkosi as an active ingredient. 3. A composition for disinfecting the oral cavity, comprising bactiol as an active ingredient. 4. A composition for preventing and / or treating dental caries and / or periodontal disease, comprising a bakuchiol as an active ingredient.