JPH0692829A - Oral composition - Google Patents

Abstract

(57) [Summary] [Object] The present invention provides a composition for oral cavity, which is effective in preventing halitosis, effective in preventing periodontal disease, and highly safe. The present invention has the formula: A composition for oral cavity containing a coumarin derivative and a benzylidene phthalide derivative represented by:

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for oral cavity which has excellent effects of preventing bad breath and periodontal disease.

[0002]

2. Description of the Related Art Various bacteria are present in the oral cavity, and obligately anaerobic Gram-negative bacilli occupy most of them due to progression of periodontitis and the like. Among them, Fusobacterium Nukuretsumu (Fusobacterium nucleatum) is to produce indole, hydrogen sulfide. Bacteroides melaninogenicus is a bacterium that is detected at a high rate from the lesion of periodontal disease, and produces proteolytic enzymes such as collagenase, and produces indole and hydrogen sulfide. These two types of bacteria are considered to be one of the causative bacteria of halitosis and periodontal disease. Therefore, suppressing the growth of these bacteria is effective in preventing halitosis and preventing periodontal disease.

On the other hand, armature ( Hydrangeae macrophyll
a Seringe ver. thunbergii MAKINO) is used as a sweetener in beverages and as a corrigent in home remedies. It is known that filozultin and hydrangenol are one of the compositions contained in armature.

Regarding the bioactivity studies of phyllozultin and hydrangenol, it has been reported that phyllozultin has antibacterial activity against Escherichia coli and Staphylococcus aureus, and antifungal activity of phyllozultin and hydrangenol.
The effects on bad breath and periodontal disease-causing bacteria are not known.

[0005]

In recent years, substances that suppress the growth of bacteria that cause halitosis and periodontal disease have been attracting attention as halitosis removers and periodontal disease preventives. Although chlorhexidine and cetylpyridinium have already been used as antibacterial agents for synthetic drugs, safer and more effective drugs are desired.

The present invention provides a composition for the oral cavity, which is effective in preventing halitosis, highly effective in preventing periodontal disease, and highly safe.

[0007]

[Means for Solving the Problems] The inventors of the present invention have sought the raw material for natural products, and as a result of diligent studies on various natural product extracts, as a result, specific components such as phyllozultin and hydrangenol contained in armatures have been found. However, it was found that even when used in a small amount, it exerts an excellent antibacterial action, and is effective in preventing halitosis and preventing periodontal disease, and thus the present invention has been accomplished.

That is, the present invention has the formula:

[0009]

[Chemical 2]

There is provided an oral composition containing a coumarin derivative represented by: The above-mentioned coumarin derivative (I) can be obtained from an armature extract in the form of a single substance or a mixture.

The armature extract is an extract such as a soft extract, a flow extract or a tincture, and is prepared by a usual method in accordance with the "12th Revised Japanese Pharmacopoeia" General Rule of Formulation ". For example, the method for preparing a soft extract is exemplified below. The armature is impregnated with the extraction solvent and filtered to obtain a filtrate. For the residue, the above cold soaking and filtration are repeated 2-3 times. The obtained filtrates are combined, the extraction solvent is distilled off and concentrated to obtain an extract.
In addition, it is preferable to occasionally stir during cold immersion.

Examples of the extraction solvent include water, alcohols such as methanol and ethanol, ethyl acetate, acetone, and a mixture thereof, with preference given to hydrous acetone. The amount of the extraction solvent used is 2 to 10 parts by weight, preferably 4 to 5 parts by weight, relative to 1 part by weight of the raw material. If it is less than 2 parts by weight, the extract is not sufficiently extracted, and if it is more than 10 parts by weight, the extraction effect is not improved and it is economically disadvantageous.

In the case of cold immersion extraction, the extraction temperature and temperature are 5 to 40 ° C., preferably 15 to 25 ° C., and 1 to 5 days, preferably 2 to 3 days. In case of heat extraction, 4
From 0 ° C to around the boiling point of the extraction solvent, preferably 70
At -80 ° C, it is 30 minutes to 3 hours, preferably 1 to 2 hours.

The concentration operation may be carried out under normal pressure or reduced pressure, but it is preferable that the concentration temperature is 40 ° C. or lower. The coumarin derivative may be used in the extraction mixture, but may be isolated if desired. For isolation, first extract with an organic solvent such as lower alkyl ketone, lower alcohol, lower fatty acid ester, lower aliphatic ether, etc., and then concentrate the extract on column chromatography using silica gel, alumina, etc. as an adsorbent. It can be done by attaching.

As the lower alkyl ketone, for example, acetone and methyl ethyl ketone are used, as the lower alcohol, for example, methanol, ethanol and the like, and as the lower fatty acid ester, for example, ethyl ether, isopropyl ether and the like are used. An example of extraction and separation from armature is shown in the embodiment. Basically, the above-mentioned extraction is suitable, but other separation means may be used, or those separation means may be combined.

Illustrating the above-mentioned isolated compound,

[0017]

[Chemical 3]

[0018]

[Chemical 4]

[0019]

[Chemical 5]

In the present invention, the oral composition is a troche, a tablet, a pill, a candy, a drink, a chewing gum, a jelly, a mouthwash, an oral pasta, a toothpaste, a moistened toothpaste, a powdered toothpaste and the like.

The amount of the armature extract or the above-mentioned 6 components added to the oral composition is 0.00 based on the total solid content.
It is preferably 1 to 20% by weight, and particularly preferably 0.003 to 10% by weight. More preferably 0.005 to 5% by weight
It is to mix.

The oral composition of the present invention may contain appropriate components depending on the type. For example, in the case of troches, excipients such as glucose, lactose, sucrose, gum arabic, crystalline cellulose, binders such as sodium carboxymethyl cellulose, disintegrants such as starch and carboxymethyl cellulose calcium, magnesium stearate, sucrose. A lubricant such as a fatty acid ester, a saccharin sodium, a sweetener such as glycyrrhizinic acid, a flavoring agent and the like are mixed, and the mixture is prepared by a conventional method. Further, in tablets, pills, candy, drinks, and the like, components suitable for the properties of the product are appropriately mixed.

Further, the oral composition of the present invention includes natural chlorophyllin sodium, iron chlorophin sodium,
Active ingredients such as lecithin, lysozyme chloride, and l-menthol can also be blended.

[0024]

The oral composition according to the present invention has an excellent halitosis-preventing effect and a periodontal disease-preventing effect by incorporating the coumarin derivative (I).

[0025]

EXAMPLES The present invention will be described in more detail by way of examples. The invention should not be construed as limited to these examples.

Extraction and separation from armatures 5 kg of armatures were heat-extracted with 5 volumes of methanol to obtain a methanol extract (950 g) by a conventional method. The methanol extract was dissolved in water and partitioned and extracted with ethyl acetate. Silica gel chromatography [(chloroform / methanol) and (chloroform /
Methanol / water)], then medium pressure reverse phase chromatography
By separating and purifying with [(60% methanol) and Sephadex LH-20 (methanol)], 12 kinds of compounds including 6 kinds of the products of the present invention were obtained.

Antibacterial test Freeze-preserved strain (Bacteroides melaninogenium
( Bacteroides melaninogenicus ) IID891, Fusobacterium nucleatum
GIFFU 4637) was thawed and subcultured in GAM semi-fluid high-layer medium (Nissui Pharmaceutical Co., Ltd.), and after culturing at 37 ° C. for 24 hours, GA
It was subcultured in M broth medium (Nissui Pharmaceutical Co., Ltd.) and anaerobically cultured at 37 ° C. for 24 hours (BBL gas back system). After culturing,
The absorbance was adjusted to about 0.3 (610 nm) to obtain a test bacterial solution.

1000 μl of the test bacterial solution was placed in a microtube, the sample was added, and the mixture was stirred and then contacted at 37 ° C. for 10 minutes. 100 μl of this solution was inoculated into GAM broth medium and anaerobically cultivated at 37 ° C. for 24 hours, and then the presence or absence of bacteria was determined to determine the minimum inhibitory concentration (minimum inhibitor
tory concentration (MIC) was determined. First result
The results are shown in Table 2 and Table 2.

[0029]

[Table 1]

As shown in Table 1, Stevia, which is a sweetener,
Aspartame showed no effect at 200 ppm, while the armature methanol extract showed effect at 50 ppm.

[0031]

[Table 2]

As shown in Table 2, it was found that each ingredient containing armature exhibited an antibacterial action, and in particular, phyllozultin and hydrangenol had an activity close to that of chlorhexidine hydrochloride which is an antibacterial agent.

Toxicity test Each group of 10 male ddy mice was given water and feed ad libitum, and the extract and 6 kinds of ingredients used in the antibacterial test
Toxicity test was conducted by daily administration for 1 week at a dose of 0 mg / kg. As a result of observing the mice for one week, there were no deaths and no symptoms of intoxication were observed at all, which proves that the drug of the present invention has no toxicity.

Formulation examples are shown below. All% are weight%
Indicates.

Formulation Example 1: Pills

Formulation Example 2: Lozenge armature water extract 15.0 Maltosyl cyclodextrin 10.0 Corn starch 6.0 Glucose 44.0 Phyllozultin 0.01 (or hydrangenol, HS-A HS-B, HS-) C, HS-D, HS-E, HS-F) Gelatin 3.0 Perfume 0.2 Mintca 3.8 Time 2.0 Anhydrous calcium hydrogen phosphate 15.0 Sucrose fatty acid ester 1.0 Total 100.0

Formulation Example 3: Candy armature acetone extract 10.0 Maltosyl cyclodextrin 14.0 Granulose 40.0 Water candy 34.9 Taste 1.0 Fragrance 0.1 Total 100.0

Formulation Example 4: Drinking Agent Amacha Hydrous Ethanol Extract 5.0 Maltosyl Cyclodextrin 5.0 Fructose Glucose Liquid Sugar 5.0 Honey 5.0 Dipotassium Phosphate 0.3 Perfume 0.1 Synthetic Preservative 0.1 01 Purified water 79.59 Total 100.0

Formulation Example 5: Chewing gum Amateur water extract 5.0 β-Cyclodextrin 5.0 Gum base 40.0 Calcium carbonate 2.0 Water syrup 15.0 Powdered sugar 27.49 Peppermint oil 0.2 Dextranase 0.01 Mint powder 0.3 Anhydrous disodium phosphate 5.0 Total 100.0

Formulation Example 6: Mouthwash Amacha water-containing ethanol extract 5.0 Maltosyl cyclodextrin 5.0 Ethanol 20.0 Hydrogenenol 0.05 (or phyllozultin, HS-A, HS-B, HS-) C, HS-D, HS-E, HS-F) Perfume 1.5 Sodium monofluorophosphate 0.1 Chlorhexidine gluconate 0.01 Lauryl diethanol amide 0.3 End of time 0.1 Glycyrrhizinate 0.1 Allantoin 0.1 Dipotassium Phosphate 0.3 Water Residual Total 100.0

Formulation Example 7: Toothpaste Amacha hydrated acetone extract 2.0 Dibasic calcium phosphate, dihydrate 40.0 Sorbito 10.0 Glycerin 5.0 Rhidium lauryl sulphate 2.0 Carboxymethylcellulose sodium 1.0 Philozrutin 0 .01 (or hydrangenol, HS-A, HS-B, HS-C, HS-D, HS-E, HS-F) Sodium chloride 2.0 Perfume 1.0 Water Residual total 100.0

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[Procedure amendment]

[Submission date] June 18, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0012

[Correction method] Change

[Correction content]

Examples of the extraction solvent include water, alcohols such as methanol and ethanol, ethyl acetate, acetone, and mixtures thereof, with preference given to methanol or ethanol. The amount of the extraction solvent used is 2 to 10 parts by weight, preferably 4 to 5 parts by weight, relative to 1 part by weight of the raw material. If it is less than 2 parts by weight, the extract is not sufficiently extracted, and if it is more than 10 parts by weight, the extraction effect is not improved and it is economically disadvantageous.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0018

[Correction method] Change

[Correction content]

[0018]

[Chemical 4]

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0019

[Correction method] Change

[Correction content]

[0019]

[Chemical 5]

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Joji Yamahara 1-1-30 Tamatsukuri, Chuo-ku, Osaka-shi, Osaka Inside Morishita Jintan Co., Ltd.

Claims (1)

[Claims] 1. The formula: A composition for oral cavity containing a coumarin derivative and a benzylidene phthalide derivative represented by: