JP2014210724A - Oral composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral composition containing a cation bactericide in which the stimulus to the oral mucosa by the cation bactericide is significantly reduced.SOLUTION: An oral composition related to the invention contains a cation bactericide and extracts derived from Juncus effusus L. var. decipens Buchen.

Description

  The present invention is effective against causative agents of oral diseases such as caries and periodontitis, and can prevent or treat oral diseases while reducing harm to the oral mucosa. It is related with the composition for use.

  Cationic fungicides such as cetylpyridinium chloride and benzethonium chloride are effective against causative bacteria of oral diseases such as caries and periodontitis, and are also incorporated in oral compositions such as mouthwashes and dentifrices. Has been. However, the cationic bactericidal agent has a problem of damaging the oral mucosa while having an excellent bactericidal action.

  The oral mucosa contains epithelial cells as well as the skin, and partly has a stratum corneum. However, most of them do not have a stratum corneum and are only covered with mucus or serum like the visceral mucosa. Therefore, when a cationic fungicide is used, epithelial cells of the oral mucosa are stimulated, sometimes causing cell damage.

  Thus, a technique for protecting the oral mucosa from the cationic fungicide contained in the oral composition is necessary, but the research is not sufficiently advanced.

  For example, Patent Document 1 discloses an oral mucosal protective agent containing trehalose as an active ingredient. However, such a protective agent is for protecting the mucous membrane in the oral cavity from irritation caused by drying, and Patent Document 1 has no description on irritation caused by a cationic fungicide.

  By the way, in Japan, rush has been used as a material for tatami mats and the throne since ancient times, and its unique fragrance stabilizes the human spirit and keeps insects away. The present inventors have found that rush powder is effective against a causative bacterium of an oral disease of a denture user, and have developed an oral composition for an antibacterial denture (Patent Document 2).

  Further, Patent Document 3 discloses a cosmetic composition containing a rush plant extract, but the rush extract is one of moisturizing plants. It is only used for the purpose. In addition, Patent Document 4 describes that an extract of rush has an ability to eliminate active oxygen, and a beverage containing the same is disclosed.

International Publication No. 2008/026310 Pamphlet International Publication No. 2011/027809 Pamphlet JP 2000-53557 A JP 2003-116499 A

  As described above, there is a possibility that the cationic bactericidal agent may harm the oral mucosa, but research on this has not progressed, and the countermeasure is not sufficient.

  Therefore, an object of the present invention is to provide an oral composition containing a cationic fungicide, in which irritation to the oral mucosa by the cationic fungicide is significantly reduced.

  The inventors of the present invention have made extensive studies to solve the above problems. As a result, the inventors found that an extract derived from rush can effectively protect the oral mucosa from irritation by the cationic fungicide, and completed the present invention.

  The composition for oral cavity according to the present invention comprises a cationic fungicide and an extract derived from rush (Juncus effusus L. var. Decipes Buchen.).

  As the extract derived from rushes blended in the composition for oral cavity according to the present invention, those extracted from rushes using water are suitable. The effect of such an extract has been experimentally confirmed by the inventors.

  Examples of the cationic fungicide to be blended in the oral composition according to the present invention include one or more selected from cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride.

  As the dosage form of the composition for oral cavity according to the present invention, a mouthwash and a dentifrice are suitable.

  Since the composition for oral cavity according to the present invention contains a cationic bactericidal agent effective against causative bacteria of oral diseases such as caries and periodontitis, it can prevent or reduce oral diseases. . In addition, the cationic bactericidal agent stimulates the oral mucosa, but this irritation is reduced by the extract derived from rush. Therefore, the composition for oral cavity according to the present invention is very useful as it can prevent or reduce oral diseases while protecting the oral mucosa.

FIG. 1 is an enlarged photograph of human gingival epithelial cells for demonstrating the effect of protecting the oral mucosa of the oral composition according to the present invention. (1) is the control, (2) is the addition of cetylpyridinium chloride (CPC), (3) and (4) are the expansion of human gingival epithelial cells when the rush extract aqueous solution is added in addition to cetylpyridinium chloride It is a photograph. FIG. 2 is an enlarged photograph of human gingival epithelial cells for demonstrating the effect of protecting the oral mucosa of the oral composition according to the present invention. (1) is a control, (2) is an enlarged photograph of human gingival epithelial cells when benzethonium chloride (BTC) is added, and (3) and (4) are magnified photographs of human gingival epithelial cells when an rush extract aqueous solution is added in addition to benzethonium chloride. is there. FIG. 3 shows lactate dehydrogenation that leaks from damaged human gingival epithelial cells when a cationic fungicide is added to human gingival epithelial cells and when an rush extract aqueous solution is added in addition to the cationic fungicide. It is a graph which shows the result of having measured the enzyme (LDH).

  The composition for oral cavity according to the present invention comprises a cationic fungicide and an extract derived from rush (Juncus effusus L. var. Decipes Buchen.).

  Cationic fungicides refer to fungicides having a cationic moiety such as a quaternary ammonium group, and are not particularly limited, and examples thereof include cetylpyridinium chloride, chlorhexidine, benzethonium chloride, benzalkonium chloride, and depotassium chloride. . Among these, one or more cationic fungicides selected from cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride are suitably used as those particularly effective for causative bacteria of oral diseases.

  What is necessary is just to adjust the compounding quantity of the cationic disinfectant in the composition for oral cavity which concerns on this invention suitably. For example, in the case of a solid preparation or a semi-solid preparation, it can be 0.001 mass% or more and 0.1 mass% or less. In the case of a liquid preparation, it can be 0.01% by mass or more and 0.5% by mass or less considering that the cationic fungicide is difficult to act. If each content is 0.001 mass% or more and 0.01 mass% or more, the bactericidal action in the oral cavity of a cationic disinfectant will be more reliably exhibited. On the other hand, if each content is too large, the unique bitterness of the cationic fungicide may be noticeable, so that it may be 0.1% by mass or less and 0.5% by mass or less, respectively. preferable. In the case of a solid preparation or a semi-solid preparation, it is more preferably 0.01% by mass or more and 0.05% by mass or less. In the case of a liquid formulation, 0.05 mass% or more and 0.2 mass% or less are more preferable.

  The composition for oral cavity which concerns on this invention contains the extract derived from a rush in addition to a cationic fungicide. The rush extract is an important component for protecting the oral mucosa from irritation caused by the cationic fungicide.

  The rush name is Juncus effusus L. var. Decites Buchen. It is a monocotyledonous plant of the order Rugbyidae, Rustaceae, Rabbit genus, Rabbit. The rush has a peculiar form in which a flower is put on the tip of a needle-like flower stem, the stem and root are in the ground, and the leaves are degenerated. In the present invention, the flower stem part of the rush is mainly used.

  In order to increase the contact area with the extraction solvent in order to increase the extraction efficiency, the rush is preferably roughly cut or pulverized, for example, after natural drying or heat drying of the flower stem part. Inside the flower stem, there is a cushioning tissue called the marrow used for the core of Japanese candles. In the present invention, such pith may be removed or used as it is.

As the extraction solvent for obtaining the extract according to the present invention, an aqueous solvent is preferably used. In the present invention, the aqueous solvent means water, a water-miscible organic solvent that is liquid at 25 ° C., and a mixture thereof. Examples of water-miscible organic solvents include C _1-4 alcohols such as methanol, ethanol, 1-propanol, 2-propanol, n-butanol, isobutanol, s-butanol and t-butanol; diethyl ether and tetrahydrofuran Examples include ether solvents: amide solvents such as dimethylformamide and dimethylacetamide; sulfoxide solvents such as dimethyl sulfoxide. As the extraction solvent, water and an aqueous alcohol solution are preferable, and water is more preferable. What is necessary is just to adjust the alcohol concentration of alcohol aqueous solution suitably. Moreover, as alcohol, _C1-2 alcohol is preferable and ethanol is more preferable.

  The kind of water used in the present invention is not particularly limited, and any of distilled water, pure water, ultrapure water, purified water, tap water, well water, and the like can be used.

  The amount of the extraction solvent used is not particularly limited and may be adjusted as appropriate. For example, with respect to a rush, it can be set to about 1 L / kg or more and 50 L / kg or less.

  Extraction temperature can also be adjusted suitably, for example, can be 10 degreeC or more and 100 degrees C or less. In addition, when extracting above the boiling point of a solvent, it is preferable to seal or pressurize an extraction container. Further, the extraction solvent may be heated to reflux. Further, the extraction temperature may be changed in stages.

  The extraction time can also be adjusted as appropriate, for example, about 2 hours or more and 20 hours or less.

  The extracted liquid mixture can be used as it is, but normal post-treatment may be performed. For example, the extraction residue and the extraction solvent are separated by filtration or centrifugation, and the separated extract is concentrated or dried using a concentrator, or by appropriately combining heat drying, reduced pressure drying, freeze drying, and the like. Also good.

  Although the usage-amount of a rush extract should just be adjusted suitably, it can be about 40 mass times or more and 200 mass times or less in a dry state with respect to a cationic fungicide, for example. If the said ratio is 40 mass times or more, irritation | stimulation of the oral mucosa by a cationic germicide can fully be suppressed, and an oral mucosa can be protected more reliably. On the other hand, when the ratio is too large, the content ratio of other components in the composition is relatively low, and there is a possibility that the respective effects cannot be sufficiently exhibited. .

  You may mix | blend a general component with the composition for oral cavity in this invention composition.

  For example, since a cationic bactericidal agent has a unique bitter taste, it is preferable to blend a fragrance such as menthol in order to reduce this. Moreover, since there are many oil-soluble fragrance | flavors, it is preferable to mix | blend surfactant. In addition, solvents such as water and ethanol according to the dosage form; medicinal components other than cationic fungicides such as xylitol, fluorine compounds, tocopherol, glycyrrhetinic acid, tranexamic acid; preservatives such as phenolic preservatives; glycerin and ethylene glycol Wetting agents such as xanthan gum and thickeners such as cellulose derivatives; sweeteners such as saccharin; abrasives such as silica gel; colorants;

  The dosage form of the oral composition according to the present invention is not particularly limited, and examples thereof include liquid oral compositions such as liquid dentifrices, mouthwashes, sprays and simulated saliva; solid oral compositions such as solid dentifrices. A semi-solid oral composition such as a dentifrice paste, periodontitis treatment ointment, oral moisturizer, and low viscosity gel.

  In any dosage form, according to the composition for oral cavity according to the present invention, the caustic fungicide suppresses the causative agent of oral disease, prevents oral disease, treats it, delays its progression, etc. can do. In addition, the extract from the rush suppresses irritation of the oral mucosa by the cationic fungicide. Therefore, the composition for oral cavity which concerns on this invention can also continue using continuously several times per day.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited by the following examples, but may be appropriately modified within a range that can meet the purpose described above and below. Of course, it is possible to implement them, and they are all included in the technical scope of the present invention.

Example 1: Preparation of rush extract liquid To 10 g of rush powder (Inada Co., Ltd., "Igusa Powder") was added 100 mL of water, heated to 60 ° C, and stirred for 5 hours. The mixture was centrifuged, and the supernatant was sterilized by filtration using a sterile filtration filter (manufactured by Sartorius, “Nitrocellulose membrane filter type 113”). Then, it concentrated 20 times using the vacuum concentration centrifuge. The obtained concentrated solution was used as a stock solution of the rush extract.

Example 2: Observation of epithelial cells RT-7 cells, a human gingival epithelial cell line, were cultured in a 24-well cell culture plate using Keratinocyte-SFM medium (manufactured by Invitrogen) in a 37 ° C, 5% CO ₂ incubator. Monolayer culture was performed. Next, cetylpyridinium chloride or benzethonium chloride was mixed in the medium in a proportion of 0.005% by mass, and the rush extract extract prepared in Example 1 was added to a 20-fold dilution or a 100-fold dilution. The treatment was performed for 3 minutes under the same conditions. Next, the medium was removed by suction, and a fresh medium (manufactured by Invitrogen, Keratinocyte-SFM medium) was added and cultured in a 37 ° C., 5% CO ₂ incubator for 24 hours. Thereafter, the cell morphology was observed and photographed under a microscope. In addition, for comparison, those cultured as they were (control) and those in which only cetylpyridinium chloride or benzethonium chloride was added to the medium were observed and photographed in the same manner. The results when cetylpyridinium chloride (CPC) is added are shown in FIG. 1, and the results when benzethonium chloride (BTC) is added are shown in FIG.

  As shown in Figs. 1 and 2, cells treated with cetylpyridinium chloride or benzethonium chloride for 3 minutes deformed into a circular shape, floated from the plate, and few normal adherent cells were observed. It was confirmed that the cells were clearly damaged. However, when the rush extract was added at the same time, few epithelial cells deformed into a circle were observed, and normal adherent epithelial cells that were hardly damaged were observed. Thus, the rush extract has been demonstrated to have an effect of protecting epithelial cells from cationic fungicides.

Example 3: LDH cytotoxicity test The LDH cytotoxicity test is a method for measuring cytotoxicity by quantifying lactate dehydrogenase (LDH) leaking from damaged cell membranes. After culturing the cells in the same manner as in Experimental Example 2, the culture supernatant was collected, and the LDH concentration released from the epithelial cells into the culture supernatant using an LDH cytotoxicity detection kit (manufactured by Cayman Chemical) Was measured. The results are shown in FIG.

  As shown in FIG. 3, when epithelial cells were treated with cetylpyridinium chloride or benzethonium chloride, the concentration of LDH released from the epithelial cells into the medium was significant (p <0) compared to the untreated control. However, when the medium contains the rush extract, the LDH concentration is significant up to the control level even when the medium contains cetylpyridinium chloride or benzethonium chloride (p <0.05). ). From these results, it is clear that the rush extract has an action of protecting the epithelial cells from the cationic fungicide.

Claims (5)

  An oral composition comprising a cationic fungicide and an extract derived from rush (Juncus effusus L. var. Decipens Buchen.).   The composition for oral cavity according to claim 1, wherein the extract derived from rush is extracted from rush using water.   The oral composition according to claim 1 or 2, wherein the cationic fungicide is at least one selected from cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride.   It is a mouthwash, The composition for oral cavity in any one of Claims 1-3.   It is a dentifrice, The composition for oral cavity in any one of Claims 1-3.