JP2003089641A - Obligate anaerobic bacteria inhibitor and composition for inhibiting obligate anaerobes - Google Patents

Abstract

(57) [Solution] An obligate anaerobic bacterium inhibitor that specifically inhibits the growth of obligate anaerobic bacteria, comprising (1) vitamin B group compounds, derivatives thereof and / or related compounds. (2) Gocahi, Shushakon, Ryukid, Seiko or an extract thereof, (3) A pigment selected from the group consisting of cochineal pigment, cacao pigment, gardenia blue pigment, Benikouji pigment, grape skin pigment, (1) to ( At least one of 3)
A composition for preventing or treating obligate anaerobic bacteria and active anaerobic bacteria comprising more than one species as an active ingredient, wherein the obligate anaerobic bacteria inhibitor is an active ingredient A composition for suppressing obligate anaerobic bacteria, comprising: [Effects] According to the present invention, obligate anaerobic bacteria such as the oral cavity, such as periodontal bacteria, without degrading the balance of the resident bacterial flora that works to maintain a healthy flora such as the oral cavity. It became possible to specifically suppress the main causative bacteria such as diseases and bad breath.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an obligate anaerobic bacterium inhibitor that specifically suppresses the growth of an obligate anaerobic bacterium, and an obligate anaerobic bacterium inhibitor. The present invention relates to a composition for suppressing obligate anaerobic bacteria, which prevents or treats diseases caused by infection and proliferation.

[0002]

2. Description of the Related Art It is said that more than 300 kinds of bacteria live in the human oral cavity. In human dental plaques (plaques) with healthy periodontal tissues, gram-positive facultative anaerobes are usually the majority, but when periodontal disease progresses, such as Porphyromonas gingivalis. Due to the increase in Gram-negative obligate anaerobes, these bacteria are regarded as promising bacteria as the cause of periodontal disease. Also,
The main causative bacteria of bad breath include Fusobacterium nucleatum, which is also a Gram-negative obligate anaerobic bacterium, and Bayonera spp.

Based on the above findings, attempts have been made to apply bactericidal agents or antibacterial substances that suppress the growth of these pathogenic bacteria as a means for preventing or treating periodontal disease and halitosis. For example, it has been conventionally practiced to incorporate an antibiotic such as tetracycline or minocycline or a bactericide such as chlorhexidine or cetylpyridinium chloride into an oral composition.

[0004] However, while antibiotics have a strong action, they have strong side effects, and it has been pointed out that resistant bacteria to these antibiotics may appear, so that they cannot be used on a daily basis. Since other antibacterial agents have a fairly broad antibacterial spectrum, if they are used at high concentrations, they may disturb the normal bacterial flora in the oral cavity and cause bacterial symptomatosis, while at low concentrations, they cause There has been a problem that a sufficient effect against bacteria cannot be obtained.

From such a viewpoint, various applications of plant extracts and fragrance components having a relatively mild action have been studied as an antibacterial substance which can be used on a daily basis. However, these antibacterial substances also do not exert an effect specifically against only a specific causative bacterium, and thus the above-mentioned fundamental problems of the bactericidal / antibacterial agents have not been avoided. .

[0006]

The present invention has been made in view of the above circumstances, and is an obligate anaerobe which is considered to be a main causative bacterium of so-called adult dental diseases (or oral defects) such as periodontal disease and halitosis. To provide an antibacterial substance that has both a high effect of suppressing growth specifically against sex bacteria and a high safety of not affecting other indigenous bacteria in the oral cavity. With the goal. Further, by using an antibacterial substance that specifically acts against obligate anaerobic bacteria, a composition effective for preventing or treating adult dental diseases (or oral defects) such as periodontal disease and halitosis, Furthermore, diseases other than the oral cavity caused by obligately anaerobic bacteria, for example, tetanus involving Clostridium spp., Food poisoning, gas gangrene, acne involving Propionibacterium spp., Etc. It is an object of the present invention to provide a composition for suppressing an obligate anaerobic bacterium, which is a composition used in a wide range of applications such as the skin diseases described above and various diseases involving spirochete.

[0007]

Means for Solving the Problems and Modes for Carrying Out the Invention As a result of intensive research to solve the above problems, the present inventor has hitherto not been known to have a bactericidal / antibacterial action. 1) Vitamin B group compounds, derivatives or analogs thereof, 2) Gokahi (five skins), Shushakon (Zhu sand roots), Ryukid (Liu Yihu), Seiko (Soba), or a plant selected from them. 3) Cochineal pigment (carminic acid pigment), cacao pigment (cocoa pigment), gardenia blue pigment, Benikouji pigment (Monascus pigment), grape skin pigment (Grape skin pigment) are surprisingly facultative anaerobic Although it does not affect the growth of bacteria and aerobic bacteria at all and does not show antibacterial action against them, it suppresses the growth of obligately anaerobic bacteria specifically, and Against It found to have specifically only antibacterial activity, leading to completion of the present invention.

[0008] To briefly explain the technical idea of the present invention, the present inventor has diligently studied the action mechanism of a drug having an antibacterial activity specifically against an obligate anaerobic bacterium, and as a result, It was found that it is important for the drug to have an effect of suppressing the reduction in redox potential caused. The effect of suppressing the reduction of the redox potential, in other words, the effect of causing oxidation in a biological reaction, is undesired for the bacteria in the intracellular body of the obligate anaerobic bacterium that is weak in oxygen (that is, is considered to be weak in oxidation). It is presumed that it causes a reaction and inhibits the growth of bacteria.

On the basis of such knowledge, the present inventor has found that the substances which have been used in humans and have high safety, that is, vitamins, plants such as crude drugs or their extracts, and food additives are used. As a result of screening the inhibitory effect of reduction of redox potential on hundreds of kinds of substances such as pigments, vitamin B such as vitamin B ₁ , vitamin B ₂ , vitamin B ₅ , vitamin B ₆ and vitamin B ₁₂ Group compound, Gokahi (Chinese name: Gokaskin) [Scientific name: Acanthopanax
gracistylus] (similarly below), Shuchacon (red sand root) [Ardisia cr
enata], Ryukido [Artemis]
ia anomala], seikou (soba) [Arte
or a plant extract thereof, as well as cochineal pigments (also known as carminic acid pigments, the same applies hereinafter), cacao pigments (cocoa pigments), gardenia blue pigments, Benikozi pigments (Monascus pigments), grape skin pigments (Grape skin pigments) The present invention has been completed by finding that pigments such as edible acid, enocyanine) are effective.

That is, the present invention is an obligate anaerobic bacterium inhibitor which specifically suppresses the growth of obligate anaerobic bacterium, which comprises
Group 3 Group 1: Vitamin B group compounds, derivatives of these or analogues of vitamin B group compounds, Group 2: Gokahi (five skins), Shushakon (Zhu sand root), Ryukid (Liu Yihu), Seiko (seisaku). Or an extract thereof, Group 3: One selected from the group consisting of cochineal pigments (carminic acid pigments), cacao pigments (cocoa pigments), gardenia blue pigments, Benikouji pigments (Monascus pigments), grape skin pigments (Grape skin pigments) Or, an obligate anaerobic bacterium inhibitor characterized by containing two or more kinds of active ingredients, and an obligate anaerobic bacterium inhibitor characterized by containing the obligate anaerobic bacterium inhibitor as an active ingredient A composition for use is provided.

The present invention will be described in more detail below. In the present invention, the obligately anaerobic bacterium means that it grows vigorously under anoxic conditions and cannot grow under the condition of oxygen, that is, under normal atmospheric oxygen partial pressure (about 0.2 atm), and dies. It refers to a group of bacteria that end up. Specifically, for example, in the oral cavity, black pigment-producing anaerobic bacilli (Bacteroides,
Porphyromonas, Prevotella), Fusobacterium, Bayonella, Peptococcus, Peptostreptococcus, Treponema, etc. belong to this group. Other than in the oral cavity, Clostridium spp., Propionibacterium spp., Spirochete and the like belong to this category.

The obligate anaerobic bacterium inhibitor of the present invention is
It shows a growth inhibitory action only against the obligate anaerobic bacterium, and does not show an antibacterial action against facultative anaerobic bacterium and aerobic bacterium. Specifically, Actinomyces
It does not show an antibacterial action against indigenous bacteria in the oral cavity such as Neslandii, Streptococcus sanguis, Streptococcus salivarius, Streptococcus mitis, Escherichia coli, and intestinal bacteria.

The obligate anaerobic bacterium inhibitor of the present invention comprises 1) a vitamin B group compound, a derivative thereof or a compound related to the vitamin B group compound, 2) a specific plant or its extract, 3) a specific pigment One type or two or more types are used as active ingredients.

As the vitamin B group compound of 1) above,
One or more selected from the group consisting of vitamin B _1's , vitamin B _2's , vitamin B _5's , vitamin B _6's and vitamin B _12's are suitable. More specifically, thiamine (thiamine hydrochloride, thiamine nitrate), bisthiamine nitrate, thiamine dicetyl sulfate ester salt, fursultiamine hydrochloride,
Vitamin B ₁ such as octothiamine and benfotiamine
, Riboflavin, sodium riboflavin phosphate, riboflavin butyrate and other vitamin B ₂ species, calcium pantothenate, sodium pantothenate and other vitamin B ₅
, Pyridoxine (pyridoxine hydrochloride), pyridoxal (pyridoxal phosphate), pyridoxamine and other vitamin B ₆ classes, cyanocobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate and other vitamin B ₁₂
And the like. In addition, examples of the derivative or related compound of the vitamin B group compound include dibenzoylthiamine hydrochloride, thiamine acetyl sulfate, pyridoxine-3,4-dipalmitate, pyridoxine-3,4-dilaurate hydrochloride, and the like.

As the vitamin B group compound used in the present invention, vitamins contained in various natural products can be used as they are, but vitamins industrially produced as raw materials for medicines and foods are also suitable. Available. Also,
In the composition of the present invention, the vitamin B group compound, a derivative thereof or a related compound may be blended alone, but
Two or more kinds of the above vitamin B depending on the usage form of the composition
It is more preferable to combine a group compound, a derivative thereof or a related compound in an appropriate combination.

Further, as the specific plant of the above 2), there is Gokahi (Chinese name: Wakaka skin) [Scientific name: Acanthhopan
ax gracistylus] (the same shall apply hereinafter), Shuchacon (red sand root) [Ardisia cr
enata], Ryukido [Artemis]
ia anomala], seikou (soba) [Arte
misia apiacea] is used, and these plant extracts are particularly preferably used.

As the plant group of the present invention, use is made of the whole plant or a part thereof, such as xylem, heartwood, bark, stem, branch, leaf, root, seed, fruit and flower. You can

The plant extract may be an extract or a product obtained by separating and purifying from an extract. In the case of an extract, the plant can be obtained by drying or pulverizing the plant as it is, or by subjecting the residue obtained by steam distillation to solvent extraction, and if the extraction solvent is nontoxic in use, the extract can be used as it is. Alternatively, it may be used as a diluting solution diluted with an appropriate solvent, or may be used as a concentrated extract, a dry powder by freeze-drying, or a paste prepared.

Examples of the solvent used for obtaining the above plant extract include commonly used organic solvents such as methanol, ethanol, butanol, hexane, heptane, cyclohexane, ethyl acetate and acetone, or water. These 1 type can be used individually or in mixture of 2 or more types. Among these solvents, methanol, ethanol and water are particularly preferable. The extraction treatment can be carried out by a conventional method at a temperature of usually about 3 to 100 ° C.

In addition to solvent extraction, an extract obtained by supercritical extraction in which carbon dioxide gas is in a supercritical state can be used as well. At this time, hexane, ethanol or the like can be used as an extraction aid.

Separation and purification of the active ingredient from the extract can be carried out by purifying the extract by column chromatography, liquid chromatography or the like.

The dye 3) used in the present invention is a cochineal dye (also known as a carminic acid dye, the same applies hereinafter), a cocoa dye (cocoa dye), a gardenia blue dye, a red beetle dye (monascus dye), and a grape skin dye (grape). Skin pigment, enocyanine). It is possible to use the pigment contained in each natural product as it is or to use the pigment extracted from the natural product, but pigments industrially produced as raw materials for food additives can also be suitably used.

For example, for cochineal dyes, "Carmine Red K" (manufactured by Kiriya Kagaku), "Red Color TH-C"
(Manufactured by Hasegawa Fragrance), the cocoa dye is "Choco Color 61
0P "(manufactured by Glico Nutrition Food)," Chocolate Color T "
"H" (manufactured by Hasegawa Fragrance), "Cutina Blue Color 1250P" (manufactured by Glico Nutrition Foods) for Gardenia Blue Dye, "Techno Color Blue P" (manufactured by Mitsubishi Kagaku Foods), "Red NY-M300" (Japanese Chlorophyll) Made),
"Rubiruka SP" (manufactured by Mitsubishi Kagaku Foods), "grape color BC-120" (manufactured by Kiriya Chemical Co., Ltd.), "grape color P" (manufactured by Yaegaki Hakko Giken Co., Ltd.) can be used as the grape skin pigment.

The obligate anaerobic bacterium inhibitor of the present invention includes the above 1
~ One or two or more kinds selected from 3 groups are contained as an active ingredient, but the composition ratio may be only for each group or may be for all groups.

The obligate anaerobic bacterium inhibitor of the present invention is a drug,
By mixing other drugs used in quasi-drugs and the like and pharmaceutically acceptable base materials or foods within the range that does not impair the effects of the present invention, obligate anaerobic bacteria may cause Oral diseases such as periodontal disease and bad breath, diseases other than the oral cavity, for example, tetanus involving Clostridium spp., Food poisoning, gas gangrene, skin diseases such as acne involving Propionibacterium spp., The composition for suppressing an obligate anaerobic bacterium can be used for treating or preventing various diseases associated with spirochete.

The composition for suppressing an obligate anaerobic bacterium of the present invention has various forms as an oral composition, a food composition, a skin external composition, and a pharmaceutical composition, depending on its use form or purpose. Can be prepared into a dosage form. As the form of the oral cavity composition, for example, powder toothpaste, toothpaste, liquid toothpaste, liquid toothpaste, mouthwash, troche, oral pasta agent, gel and the like can be formulated. Examples of the form of the food composition include troches, tablets, capsules, granules, powders, chewing gum, candies, gummy candies, and the like.

A particularly preferred use form of the composition of the present invention is to specifically suppress the obligate anaerobic bacterium which causes periodontal disease and bad breath to infect the oral cavity, and to suppress these oral diseases. To use as a composition for the oral cavity for preventing or treating.

The compounding amount of the obligate anaerobic bacterium inhibitor in the composition of the present invention can be appropriately selected depending on the use form or purpose of use, but it inhibits or suppresses the growth of the obligate anaerobic bacterium. It is necessary to include as much obligate anaerobic bacterium inhibitor as possible. Basically, it is desirable that the concentration is about 1 to 10000 times the MIC based on the minimum inhibitory concentration (MIC) against the obligately anaerobic bacterium described below. More specifically, the composition is usually A blending amount of 0.001 to 5% (mass%, the same applies below), preferably 0.01 to 5%, and more preferably 0.05 to 2% is desirable with respect to the total mass.

The components other than the above-mentioned obligate anaerobic bacterium inhibitor to be added to the composition of the present invention are, as described above, appropriately used depending on the dosage form as long as they do not impair the effects of the present invention. Ingredients may be added, and as such an ingredient, for example, an abrasive, a thickener, a binder, a surfactant, a sweetener, an antiseptic, when prepared as an oral composition such as dentifrice. Examples include agents, fragrances, coloring agents, various active ingredients, and the like.

The method of using the composition of the present invention is not particularly limited, and the use form of the composition and the usual dose of the dosage form can be used by a conventional method.

[0031]

EXAMPLES The present invention will be described in more detail below by showing Examples and Comparative Examples, but the present invention is not limited to these Examples.

[Examples 1 to 14 and Comparative Examples 1 to 3] The antibacterial activity of the obligate anaerobic bacterium inhibitor of the present invention and other agents against various bacteria was measured by the following method.

(1) Test strain a) Obligate anaerobic bacterium (harmful bacterium associated with periodontal disease and halitosis in the oral cavity) (i) Porphyromonas gingivalis (Porphy)
romanas gingivalis) 381 [P. g. (Ii) Prevotella Intermedia (Prevot
ella intermedia) ATCC 49046
[P. i. Abbreviated] (iii) Prevotera Nigresense (Prevote
lla nigrescens) ATCC 33563
[P. n. (Iv) Fusobacterium nucleatum (Fusob)
bacterium nucleatum) ATCC23
726 [hereinafter, F. n. Abbreviated] (v) Bayonella Atipika (Veillonell)
a atypica) ATCC 17744 [hereinafter, referred to as V.
a. Abbreviated]

B) Facultative anaerobic bacteria (indigenous bacteria and intestinal bacteria that live in the oral cavity) (vi) Actinomyces neslandii (Acti)
nomyces naeslundii) T14V [hereinafter referred to as A. n. Abbreviated] (vii) Streptococcus sanguis
ptococcus sanguis) ATCC105
56 [hereinafter, S. san. Abbreviated] (viii) Streptococcus salivarius (St
reptococcus salivarus) ATC
C13419 [hereinafter, S. sal. (Ix) Streptococcus mitis (Strept
ococcus mitis) ATCC 49456 [S. m. Abbreviation] (x) Escherichia coli
E. coli) ATCC 8739 [hereinafter referred to as E. c. Abbreviated]

(2) Test Drugs (Oliotropic Anaerobic Bacterial Inhibitors of Examples 1 to 14 and Drugs of Comparative Examples 1 to 3) Example 1: 0.1 M Thiamine Hydrochloride (Vitamin B ₁ Hydrochloride) Example 2 : 0.1 M sodium riboflavin phosphate (vitamin B ₂ phosphate) Example 3: 0.1 M calcium pantothenate (vitamin B ₅ ) Example 4: 0.1 M pyridoxine hydrochloride (vitamin B ₆ ) Example 5:10 mM Cyanocobalamin (Vitamin B ₁₂ ) Example 6: 1% (10000 ppm) Gokahi (root bark) hot water extract Example 7: 1% (10000 ppm) Shushakon (whole grass) hot water extract Example 8: 1% (10000 ppm) ) Ryukydo (whole grass) hot water extract Example 9: 1% (10000 ppm) Gypsophila (whole grass)
Hot water extract Example 10: 1% (10000 ppm) cochineal dye (Carmine Red K: manufactured by Kiriya Kagaku) Example 11: 1% (10000 ppm) cocoa dye (Choco Color 610P: manufactured by Glico Nutrition Food) Example 12: 1 % (10000 ppm) Gardenia blue pigment (Cutina blue color 1250P: Glyco nutritive food product) Example 13: 1% (10000 ppm) Benikouji pigment (Red NY-M300: Nippon Chlorophyll) Example 14: 1% (10000 ppm) grape skin Dye (Grape Color BC-120: manufactured by Kiriya Chemical)

Comparative Example 1: 0.1 M Sodium Ascorbate (Vitamin C) Comparative Example 2: 0.1 M Cetylpyridinium Chloride (CPC) Comparative Example 3: 10 mM Chlorhexidine Gluconate (CH)
X)

Each test drug prepared at the above-mentioned concentration was 0.2
It was sterilized by filtration with a 2 μm membrane filter.

The extracts used in Examples 6 to 9 were prepared by the following method. That is, 10
The extract was extracted by adding twice the amount of water and boiling at 100 ° C. for 3 hours. This operation was repeated 3 times for extraction, and the resulting extract for 3 times was freeze-dried to obtain a hot water extract. The yield was about 10% to 20%.

(3) Medium preparation 3% TODD HEWIT BROTH (DIFCO
A medium containing 5 μg / ml hemin and 0.5 μg / ml menadione was used as a basic medium. The test drug was serially diluted 4-fold with sterile distilled water, and the drug at each concentration was added to the basal medium.

[0040] (4) the laboratory procedures the liquid medium 4ml with the addition of agents for each concentration, culture approximately 10 test strain in advance overnight preculture ⁶
The cells were added at a concentration of cells / ml and cultured anaerobically at 37 ° C for 3 days. After culturing, change the turbidity of the culture solution to 655 nm.
The minimum concentration of the test drug that completely inhibited bacterial growth was expressed as MIC. The results were expressed as MIC (mM) for vitamins with known molecular weights (Table 1), and MIC (ppm) for other plant extracts and pigments (Table 2).

[0041]

[Table 1]

[0042]

[Table 2]

As is clear from the results in Table 1, the obligate anaerobic bacterium inhibitor (Vitamin B group compound) of the present invention has no effect on the growth of facultative anaerobic bacteria. It showed a growth inhibitory effect against obligate anaerobes. On the other hand, sodium ascorbate (vitamin C), which was tested as a comparative example, has no growth inhibitory effect against any bacteria, and the fungicides cetylpyridinium chloride and chlorhexidine gluconate are It showed a strong growth inhibitory effect on bacteria. Also,
Among the vitamin B group compounds, especially sodium riboflavin phosphate (vitamin B ₂ phosphate) shows a growth inhibitory action against obligate anaerobic bacteria even at a relatively low concentration,
MIC against obligate anaerobes and M against facultative anaerobes
Since the ratio with IC is 100 to 1000 times or more,
It was confirmed that the utility as the obligate anaerobic bacterium inhibitor of the present invention is extremely high.

The results in Table 2 also show that the obligate anaerobic bacterium inhibitor (plant extract and pigments) of the present invention exerts almost no effect on the growth of facultative anaerobes, although It was revealed that it shows a growth inhibitory effect on sexual anaerobes. These obligate anaerobic bacterium inhibitors also show MIC against obligate anaerobes and MI against facultative anaerobes.
Since the ratio with C is about 100 to 1000 times, it was confirmed that the utility as an obligate anaerobic bacterium inhibitor is extremely high.

Next, an obligate anaerobic bacterium inhibitor that acts specifically on the obligate anaerobic bacterium is added to prevent or prevent adult dental diseases (or oral defects) such as periodontal disease and halitosis. A composition for controlling obligately anaerobic bacteria effective for treatment was prepared as follows.

Example 15 Toothpaste Mass% Riboflavin Sodium Phosphate 0.5 Aluminum Hydroxide 45.0 Sorbit 30.0 Sodium Lauryl Sulfate 0.8 Sodium Alginate 0.6 Sodium Saccharin 0.1 Gelatin 0.2 Lauric Acid Diethanolamide 1.6 Propylene glycol 5.0 Fragrance 0.3 Lauroyl sarcosine sodium 0.4 Sodium monofluorophosphate 0.75 Purified water Residual amount 100.0

Example 16 Toothpaste Mass% Thiamine Hydrochloride 0.2 Sodium Riboflavin Phosphate 0.2 Calcium Carbonate 45.0 Sorbit 24.0 Sodium Lauryl Sulfate 1.3 Carrageenan 0.7 Sodium Alginate 0.3 Sodium Saccharin 0 .1 Gelatin 0.2 Lauric acid diethanolamide 0.8 Propylene glycol 4.0 Perfume 1.0 Lauroyl sarcosine sodium 0.4 Sodium monofluorophosphate 0.75 Purified water Residual total 100.0

Example 17 Toothpaste Mass% Calcium Pantothenate 1.0 Pyridoxine Hydrochloride 0.5 Cyanocobalamin 0.5 Dibasic Calcium Phosphate Dihydrate 50.0 Sodium Lauryl Sulfate 1.0 Carrageenan 0.6 Xanthan Gum 0 .3 Saccharin sodium 0.1 Gelatin 0.2 Lauric acid diethanolamide 1.0 Propylene glycol 4.0 Perfume 1.0 Lauroyl sarcosine sodium 0.4 Sodium monofluorophosphate 0.5 Glycerin 0.5 Purified water Residual total 100 .0

Example 18 Toothpaste Mass% Riboflavin Sodium Phosphate 1.0 Silica 20.0 Sorbitt 60.0 Sodium Lauryl Sulfate 0.9 Sodium Saccharin 0.15 Gelatin 0.3 Diethanolamide Laurate 1.5 Propylene Glycol 5.0 Perfume 1.5 Lauroyl sarcosine sodium 0.5 Sodium fluoride 0.2 Xanthan gum 0.5 Polyethylene glycol # 4000 0.5 Purified water Residual total 100.0

Example 19 Toothpaste Mass% Thiamine Hydrochloride 0.5 Sodium Pantothenate 1.0 Pyridoxine Hydrochloride 0.5 Modified Aluminum Hydroxide 50.0 Sodium Lauryl Sulfate 1.5 Carrageenan 0.5 Saccharin Sodium 0.14 Propylene glycol 5.0 Perfume 1.3 Myristoyl sarcosine sodium 0.3 Sodium monofluorophosphate 0.5 Glycerin 20.0 Silica anhydride 5.0 Titanium oxide 0.5 Carboxymethylcellulose sodium 0.1 Purified water Residual total 100 .0

Example 20 Toothpaste Mass% Thiamine Hydrochloride 0.5 Sodium Riboflavin Phosphate 0.2 Pyridoxine Hydrochloride 0.5 Silica Anhydride 20.0 Sodium Polyacrylate 0.5 Xanthan Gum 0.5 Propylene Glycol 5. 0 70% sorbit solution 20.0 Saccharin sodium 0.1 Sodium benzoate 0.3 Sodium lauryl sulfate 1.5 Perfume 1.0 Purified water Residual amount 100.0

Example 21 Liquid Toothpaste Mass% Riboflavin Sodium Phosphate 0.5 Pyridoxine Hydrochloride 0.5 Precipitable Silica 20.0 Butyl Paraoxybenzoate 0.01 Xanthan Gum 0.2 Sodium Polyacrylate 0.15 Propylene Glycol 2.0 Sorbit 35.0 Glycerin 25.0 Saccharin sodium 0.1 Perfume 1.0 Sodium lauryl sulfate 1.5 Decaglyceryl monolaurate 4.0 Purified water Residual total 100.0

Example 22 Mouthwash Mass% Thiamine hydrochloride 0.5 Sodium phosphate riboflavin 0.3 Sodium pantothenate 1.0 Pyridoxine hydrochloride 0.5 Denatured ethanol 1.6 Polyoxyethylene hydrogenated castor oil 2.0 Citric acid 0.01 Trisodium citrate 0.3 Perfume 0.5 Sodium lauroyl sarcosine 0.1 Sodium fluoride 0.08 Glycerin 10.0 DL-alanine 1.0 Purified water Residual total 100.0

Example 23 Mouthwash Mass% Riboflavin Sodium Phosphate 0.5 Pyridoxine Hydrochloride 1.0 Ethanol 10.0 Glycerin 10.0 P. O. E (60) hydrogenated castor oil 5.0 saccharin sodium 0.7 sodium benzoate 0.1 fragrance 1.0 purified water balance 100.0

Example 24 Troche Mass% Thiamine Hydrochloride 0.2 Riboflavin Sodium Phosphate 0.05 Pyridoxine Hydrochloride 0.2 Cyanocobalamin 0.5 Arabic Gum 6.0 Fragrance 1.0 Sodium Monofluorophosphate 0.05 Lauroyl Sarcosine sodium 0.01 Glucose 36.0 Palatinose 36.0 Purified water Residual total 100.0

Example 25 Troche Mass% Thiamine Nitrate 0.2 Sodium Riboflavin Phosphate 0.1 Pyridoxine Hydrochloride 0.2 Lactose 97.0 P.I. O. E (60) Monostearate 0.2 Sodium lauryl sulfate 0.05 Stevia extract 0.2 Methyl salicylate 0.2 Isoeugenol 0.05 Perfume 0.02 Hydroxyethyl cellulose Residual 100.0

Example 26 Tablet Mass% Thiamine hydrochloride 0.2 Riboflavin sodium phosphate 0.5 Calcium pantothenate 1.0 Pyridoxine hydrochloride 0.2 Cyanocobalamin 0.5 Xylitol 40.0 Polydextrose 7.0 Sugar ester 2 0.0 Fragrance 1.0 Palatinose Balance 100.0

Example 27 Chewing Gum Mass% Thiamine Hydrochloride 0.2 Riboflavin Sodium Phosphate 0.3 Calcium Pantothenate 1.0 Pyridoxine Hydrochloride 0.2 Gum Base 20.0 Fragrance 1.0 Sodium Monofluorophosphate 0.1 Lauroyl sarcosine sodium 0.01 Calcium carbonate 2.0 Syringe 15.0 Powdered sugar 58.0 Purified water Residual 100.0

Example 28 Oral Pasta Agent Mass% Fursultiamine Hydrochloride 1.0 Riboflavin Butyrate 2.0 Cetanol 10.0 Squalane 20.0 Precipitable Silica 5.0 P. O. E (40) hydrogenated castor oil 0.1 sorbitan monooleate 1.0 sodium lauryl sulfate 0.2 glycyrrhetinic acid 0.1 saccharin sodium 0.6 ε-aminocaproic acid 0.5 ethyl salicylate 0.2 isoeugenol 0.1 Mentone 0.05 Perfume 0.6 Purified water Residual total 100.0

Example 29 Oral Gel Mass% Thiamine Hydrochloride 1.0 Riboflavin Sodium Phosphate 1.0 Carboxymethyl Cellulose 0.2 Glycerin 40.0 Perfume 0.6 Purified Water Residual Total 100.0

Example 30 Toothpaste Mass% Riboflavin Sodium Phosphate 1.0 Shushacon (whole grass) hot water extract 0.5 Grape skin pigment (Grape Color BC-120: manufactured by Kiriya Chemical Co., Ltd.) 0.05 Calcium carbonate (Average particle size = 0.5 μm) 40.0 Pyrogenic silica (Average particle size = 10 μm) 2.0 Sodium polyacrylate (Polymerization degree = 15000) 0.5 Carrageenan (MW = 500,000) 0.5 Propylene Glycol 3.0 Glycerin 30.0 Ethyl paraoxybenzoate 0.1 Propyl paraoxybenzoate 0.1 Sodium saccharin 0.2 Sodium monofluorophosphate 0.76 Sodium lauryl sulphate 1.4 Sodium lauroylsarcosine 0.1 Perfume 1. 0 Purified water Residual total 100.0

Example 31 Toothpaste Mass% Calcium Pantothenate 1.0 Ryukydo (whole grass) hot water extract 1.0 Seiko (whole grass) hot water extract 0.5 Cochineal dye (Carmine Red K: Kiriya) 0.1) Calcium hydrogen phosphate dihydrate (average particle size = 10 µm) 45.0 Silicic anhydride (average particle size = 10 µm) 2.0 Sodium carboxymethylcellulose (MW = 300,000) 1.0 Carrageenan (MW = 500,000) 0.1 Propylene glycol 3.0 60% sorbit solution 25.0 Methyl paraoxybenzoate 0.2 Sodium benzoate 0.5 Sodium saccharin 0.2 Sodium monofluorophosphate 0.73 Tranexamic acid 0 .05 Isopropylmethylphenol 0.1 Sodium lauryl sulfate 1.2 Lauroylza Sarcosine sodium 0.3 Perfume 1.0 Purified water balance Total 100.0

[Example 32] Toothpaste mass% Thiamine hydrochloride 0.5 Pyridoxine hydrochloride 0.5 Shushakon (whole grass) hot water extract 0.2 Gokahi (root bark) hot water extract 0.2 Cacao pigment (chocolate) Color 610P: Glyconutrient food products) 0.05 Modified aluminum hydroxide 50.0 Sodium lauryl sulfate 1.5 Carrageenan 0.5 Xanthan gum 0.5 Sodium saccharin 0.14 Propylene glycol 5.0 Perfume 1.3 Myristoyl sarcosine sodium 0.3 Sodium fluoride 0.5 Glycerin 20.0 Silica anhydride 5.0 Titanium oxide 0.5 Sodium carboxymethylcellulose 0.1 Dextranase (1 million units / g) 0.2 Mutanase (500,000 units / g) ) 0.04 Purified water Residual total 100.0

Example 33 Liquid Toothpaste Mass% Thiamine Hydrochloride 0.5 Cyanocobalamin 0.2 Ryukid (whole grass) Hot Water Extract 1.0 Gardenia Blue Pigment (Cutina Blue Color 1250P: Glico Nutrition Food) 0.5 Silica 18.0 Sorbit 52.0 Sodium lauryl sulfate 1.0 Saccharin sodium 0.1 Gelatin 0.2 Lauric acid diethanolamide 1.2 Propylene glycol 2.0 Perfume 1.1 Menthol 0.3 Palmitoyl sarcosine sodium 0.4 Fluor Sodium chloride 0.2 Glycerin 18.0 Xanthan gum 0.1 Decaglyceryl laurate 0.5 Sodium sulfate (anhydrous) 0.3 Dextranase (1 million units / g) 0.1 Mutanase (500,000 units / g) 0 .05 purified water balance total 100 0

Example 34 Liquid Toothpaste Mass% Riboflavin Sodium Phosphate 0.5 Gokahi (root bark) Hot Water Extract 0.2 Seiko (whole grass) Hot Water Extract 0.2 Benjioji pigment (Red NY-M300 : Made of Nippon chlorophyll) 0.1 Aluminum hydroxide 25.0 Sodium polyacrylate (Polymerization degree = 15000) 0.1 Sodium carboxymethyl cellulose (MW = 300,000) 0.2 Propylene glycol 2.0 Solbit 15.0 Glycerin 40 0.0 Saccharin sodium 0.1 Fragrance 1.0 Sodium lauryl sulfate 1.5 Decaglyceryl monolaurate 1.0 Purified water Residual total 100.0

Example 35 Foaming Toothpaste Mass% Sodium Pantothenate 1.0 Pyridoxine Hydrochloride 0.5 Ryukid (whole grass) hot water extract 2.0 Cochineal dye (Carmine Red K: manufactured by Kiriya Kagaku) 0.5 Sodium lauryl sulfate 0.2 P. O. E (60) hydrogenated castor oil 1.0 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine 0.06 glycerin (85%) 10.0 propylene glycol 1.0 xanthan gum 0.1 polyvinylpyrrolidone 0 .5 Xylitol 1.0 Citric acid 0.08 Sodium citrate 0.2 Sodium benzoate 0.3 Methylparaben 0.2 Perfume 0.5 Purified water Residual total 100.0

[Example 36] Mouthwash Mass% Thiamine hydrochloride 0.2 Pyridoxal phosphate 0.5 Cyanocobalamin 0.2 Shushacon (whole grass) hot water extract 0.2 Gardenia blue pigment (Cutina blue color 1250P: glyco (Nutrient food products) 0.2 Citric acid 0.1 Sodium citrate 0.1 Ethanol 0.5 Sorbit solution (70%) 10.0 Polyoxyethylene hydrogenated castor oil 2.0 Perfume 0.3 Aspartame 1.0 Benzoic acid Sodium 0.3 Methyl paraoxybenzoate 0.1 Dextranase (1 million units / g) 0.3 Mutanase (500,000 units / g) 0.02 Purified water Residual amount 100.0

Example 37 Mouthwash Mass% Riboflavin Sodium Phosphate 0.1 Calcium Pantothenate 0.2 Ginseng (whole grass) hot water extract 0.2 Grape skin pigment (Grape Color BC-120: manufactured by Kiriya Chemical Co., Ltd.) ) 0.05 90% ethanol 20.0 polyoxyethylene (80 mol) sorbitan monotaurate 0.5 perfume 1.2 l-menthol 0.3 sodium monofluorophosphate 0.15 lauroyl sarcosine sodium 0.1 purified Water balance 100.0

Example 38 Oral Cooling Agent Mass% Fursultiamine Hydrochloride 0.1 Shushacon (Root) 70% Ethanol Extract 0.2 Benzioji Dye (Red NY-M300: Made by Nippon Chlorophyll) 0.05 Ethanol 50. 0 glycerin 15.0 P.O. O. E (60) hydrogenated castor oil 3.0 l-menthol 1.0 fragrance 0.3 purified water balance 100.0

Example 39 Chewing Gum Mass% Thiamine Hydrochloride 0.2 Calcium Pantothenate 1.0 Gokahi (Root Bark) Hot Water Extract 0.2 Cacao Dye (Choco Color 610P: Glico Nutrition Food) 0.5 Gum Base 20.0 Fragrance 0.7 l-Menthol 0.3 Sodium monofluorophosphate 0.1 Lauroyl sarcosine sodium 0.01 Calcium carbonate 2.0 Syringe 15.0 Powdered sugar 58.0 Dextranase (1 million units / g) 0.1 Mutanase (500,000 units / g) 0.01 Purified water Residual amount 100.0

Example 40 Oral Pasta Agent Mass% Octothiamine 0.5 Riboflavin Butyrate 1.0 Shushacon (root) 70% Ethanol Extract 0.2 Ginseng (whole grass) 70% Ethanol Extract 0.5 Cochineal Dye (Carmine Red K: manufactured by Kiriya Kagaku) 0.2 Cetanol 10.0 Squalane 20.0 Precipitable silica 5.0 P.I. O. E (40) hydrogenated castor oil 0.1 sorbitan monooleate 1.0 sodium lauryl sulfate 0.2 glycyrrhetinic acid 0.1 sodium saccharin 0.5 0.5 ε-aminocaproic acid 0.5 ethyl salicylate 0.2 isoeugenol 0.1 Mentone 0.05 Fragrance 0.5 Purified water Residual total 100.0

[0072]

The obligate anaerobic bacterium inhibitor of the present invention has no effect on the growth of facultative anaerobic bacteria, and therefore it is a resident bacterium having a function of maintaining a healthy flora in the oral cavity and the like. It is possible to specifically suppress obligate anaerobic bacteria which are harmful bacteria in the oral cavity, for example, main causative bacteria such as periodontal disease and halitosis, without disturbing the balance of the flora.

Further, the composition for inhibiting an obligate anaerobic bacterium of the present invention containing the above-mentioned obligate anaerobic bacterium inhibitor as an active ingredient,
For example, by using it as a composition for oral cavity, it becomes a composition effective for preventing or treating adult dental diseases (or oral defects) such as periodontal disease and halitosis, and also for diseases other than oral cavity , For example, tetanus associated with Clostridium spp., Food poisoning, gas gangrene, skin diseases such as acne associated with Propionibacterium spp., Obligate anaerobes such as various diseases associated with spirochetes It is useful as a food composition, an external composition for skin, a pharmaceutical composition, etc. used for preventing or treating diseases caused by

Front page continuation (51) Int.Cl. ⁷ identification code FI theme code (reference) A61K 7/28 A61K 7/28 31/4415 31/4415 31/51 31/51 31/525 31/525 31/714 31 / 714 35/64 35/64 35/70 35/70 35/78 35/78 C M T X A61P 1/02 A61P 1/02 17/00 101 17/00 101 31/04 31/04 F term (reference) ) 4C083 AA031 AA032 AA071 AA072 AA111 AA112 AB172 AB222 AB242 AB292 AB322 AB352 AB472 AC022 AC072 AC102 AC122 AC132 AC302 AC312 AC402 AC422 AC432 AC442 AC472 AC482 AC582 AD622 AD5322 AD4722 AD072 AD072 AD072 AD072 AD072 AD072 AD072 AD092 AD631 AD632 BB22 BB41 BB48 BB55 CC41 DD08 DD15 DD16 DD21 DD22 DD23 DD31 DD41 EE07 EE33 EE34 4C086 AA01 AA02 BC18 BC83 CB09 DA39 MA03 MA04 MA10 MA13 MA17 MA22 MA23 CA28 A01 A02 A11 A02 A35 A10 A11 A02 A35 A10 A11 A11 A02 A35 A90 A11 A11 A02 A35 A87 A11 A02 A35 A90 A11 A02 MA02 MA13 MA17 MA22 MA23 MA28 MA35 MA36 MA41 MA47 MA52 MA57 MA63 NA14 ZA67 ZA90 ZB35 4C088 AB12 AB14 AB16 AB2 9 AB56 AC01 AC03 AC04 AC05 AC06 AC11 AD09 AD19 BA09 BA10 BA11 CA02 CA05 CA06 CA07 CA09 CA10 CA14 MA08 MA13 MA17 MA22 MA23 MA28 MA35 MA36 MA41 MA52 MA57 MA63 NA14 ZA67 ZA90 ZB35 4C206 AA01 AA02 GA05 GA36 MA03 MA04 MA37 MA42 MA14 MA17 MA17 MA33 MA55 MA56 MA61 MA67 MA72 MA77 MA83 NA14 ZA67 ZA90 ZB35

Claims (3)

[Claims] 1. An obligate anaerobic bacterium inhibitor that specifically suppresses the growth of obligate anaerobic bacteria, wherein the following groups 1-3 groups and 1 group: vitamin B group compounds, derivatives thereof or vitamin B group compounds. Related compounds, Group 2: Gokahi (five skins), Shushakon (Zhu Sand Root), Ryukido (Liu Yihu), Seiko (green soba) or its extract, Group 3: Cochineal pigment (carminic acid pigment), cocoa pigment (Cocoa pigment), Gardenia blue pigment, Benjioji pigment (Monascus pigment), Grape skin pigment (Grape skin pigment), One or two or more selected from Bacterial inhibitor. 2. The vitamin B group compound of the above-mentioned group 1 is vitamin B ₁ , vitamin B ₂ , vitamin B ₅ , vitamin B ₆ or vitamin B ₁₂ compounds. An obligate anaerobic bacterium inhibitor. 3. A composition for preventing or treating a disease or the like caused by an obligate anaerobic bacterium, which comprises the obligate anaerobic bacterium inhibitor according to claim 1 or 2 as an active ingredient. A composition for suppressing an obligate anaerobic bacterium, which is characterized in that: