JP5665280B2 - Oral composition - Google Patents

Description

  The present invention relates to a composition for oral cavity, which contains an extract of a plant of the genus Rubiaceae and two or more cationic fungicides and can effectively exert the bactericidal effect of the cationic fungicide.

  It is known that oral symptoms and diseases such as caries (decayed teeth), bad breath, periodontal disease, gingivitis, and alveolar pyorrhea are caused by dental plaque. For example, the caries generation mechanism is considered as follows. In other words, bacteria such as lactic acid bacteria and mutans streptococci adhere to the pecyl layer on the surface of the teeth and adhere to food-derived sucrose by the action of glucosyltransferase (hereinafter referred to as “GTase”) secreted by the bacteria. Dental plaque is formed by denaturing the polysaccharide and firmly adhering to the tooth surface while growing. The bacteria contained in the plaque metabolize the saccharide, and the acid produced as a metabolite decalcifies the tooth enamel surface, thereby causing caries.

  Today, it is considered effective to inhibit the formation of plaque by inhibiting the action of GTase as one measure for preventing oral symptoms and diseases caused by dental plaque. Therefore, in recent years, substances having a GTase inhibitory action have been vigorously developed, and various plant extracts having a GTase inhibitory action have been reported (for example, see Patent Documents 1 and 2). On the other hand, many plant extracts that have been reported to have a GTase inhibitory action cannot be put to practical use because the GTase inhibitory action is not sufficient. However, it is known that the extract of the genus Ranaaceae is superior in GTase inhibitory action and can effectively exhibit plaque formation inhibitory effect in the oral cavity. (See Patent Document 2).

  Oral diseases and symptoms caused by dental plaque involve cariogenic bacteria and periodontal disease bacteria in the oral cavity. These oral bacteria are sterilized to clean the oral cavity. It is also important to prevent oral symptoms and diseases. Conventionally, bactericides have been used to sterilize oral bacteria. In particular, cationic bactericides such as quaternary ammonium salt bactericides and pyridinium salt bactericides are effective in a wide range of antibacterial spectrum, immediate effect, and low concentration. Widely used.

  Therefore, for the development of an oral composition that effectively exhibits both plaque formation inhibitory effect and bactericidal effect, it is considered effective to add a cationic bactericidal agent together with an extract of the genus Acrobaceae evening primrose. It is done.

Japanese Patent Laid-Open No. 4-95020 JP 2006-306844 A

  The inventors of the present invention have studied an oral composition containing an extract of the genus Ranunculaceae and a cationic bactericidal agent. When a cationic bactericidal agent is used in combination to improve the bactericidal effect, the present inventors have unexpectedly found that In addition, the present inventors have found a new finding that the cationic fungicide becomes unstable and cannot fully enjoy the original bactericidal effect. Therefore, it is indispensable to solve the above-mentioned problems in the development of a composition for oral cavity containing an extract of the genus Ranunculaceae and a cationic fungicide.

  Therefore, the present invention includes an extract of the genus Rabbitaceae and a cationic fungicide, but the cationic fungicide can be stably present, effectively preventing both plaque formation and sufficient bactericidal effect. It aims at providing the composition for oral cavity which can be made to show.

  The inventors of the present invention have made extensive studies to solve the above-mentioned problems. Surprisingly, in addition to the extract of the plant of the genus Rabbitaceae and two or more kinds of cationic fungicides, carbon number 2- By blending 3 lower alcohols and / or polyhydric alcohols at a predetermined ratio, it is possible to stabilize the cationic bactericidal agent in the oral composition and effectively exert its bactericidal effect. I found out that The present invention has been completed by further studies based on this finding.

That is, this invention provides the composition for oral cavity of the following aspect:
Item 1. (A) An extract of the genus Oenothera spp., (B) at least two cationic fungicides, and (C) at least one selected from the group consisting of C2-C3 lower alcohols and polyhydric alcohols Including alcoholic solvents,
An oral composition, wherein the component (C) satisfies a ratio of 30 ml or more per 1 g of the component (A).
Item 2. Item 2. The oral composition according to Item 1, comprising at least two cationic fungicides selected from the group consisting of a quaternary ammonium salt fungicide and a pyridinium salt fungicide as the component (B).
Item 3. Item 3. The oral composition according to Item 1 or 2, which contains at least one quaternary ammonium salt fungicide and at least one pyridinium salt fungicide as the component (B).
Item 4. Item 4. The oral cavity composition according to any one of Items 1 to 3, comprising at least one lower alcohol having 2-3 carbon atoms and at least one polyhydric alcohol as the component (C).
Item 5. Item 5. The component (B) includes at least one quaternary ammonium salt fungicide selected from the group consisting of benzalkonium chloride and benzethonium chloride, and cetylpyridinium chloride. Oral composition.
Item 6. Item 6. The oral composition according to any one of Items 1 to 5, wherein the blending ratio of the component (A) is 0.01 to 50 w / v%.
Item 7. The component (C) is at least one selected from the group consisting of ethanol, isopropanol, glycerin, monopropylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol having a weight average molecular weight of 200 to 600. Item 7. The oral composition according to any one of Items 1 to 6.
Item 8. Item 8. The composition for oral cavity according to any one of Items 1 to 7, wherein the component (A) is an extract of seeds of the plant of the genus Ranunculaceae.
Item 9. Item 9. The oral composition according to any one of Items 1 to 8, which is a mouthwash or a liquid dentifrice.

  According to the composition for oral cavity of the present invention, it contains a cationic fungicide together with an extract of the genus Rubiaceae, a cationic fungicide, and has a plaque formation inhibitory effect based on the extract of the genus Rhizopus sp. Both the bactericidal effects based on can be effectively exhibited. Therefore, the composition for oral cavity of the present invention is useful for prevention of oral diseases and symptoms caused by plaque formation and oral bacteria.

In Test Example 1, the results of collecting the recovery rate of cetylpyridinium chloride measured from each oral composition for each solvent used are shown. In Test Example 1, the results of collecting the recovery rate of benzalkonium chloride measured from each oral composition for each solvent used are shown. In Test Example 2, the results of collecting the recovery rate of cetylpyridinium chloride measured from each oral composition for each solvent used are shown. In Fig. 3, "Eta + PG" is when ethanol and monopropylene glycol are used as solvents; "Eta + BG" is when ethanol and 1,3-butylene glycol are used as solvents; "PG + BG" is as a solvent The cases where monopropylene glycol and 1,3-butylene glycol are used are shown respectively. In Test Example 2, the results of collecting the recovery rate of benzalkonium chloride measured from each oral composition for each solvent used are shown. In Fig. 4, "Eta + PG" is when ethanol and monopropylene glycol are used as solvents; "Eta + BG" is when ethanol and 1,3-butylene glycol are used as solvents; "PG + BG" is as a solvent The cases where monopropylene glycol and 1,3-butylene glycol are used are shown respectively. In the comparative test example 1, the result which put together the collection | recovery rate of the cetyl pyridinium chloride measured from each composition for oral cavity for every solvent used is shown.

  In the present specification, the unit “w / v%” represents the blending weight (g) per 100 ml of the composition, and the unit “v / v%” represents the blending volume (ml) per 100 ml of the composition.

  The composition for oral cavity of the present invention comprises (A) an extract of the genus Oenothera spp., (B) at least two cationic fungicides, and (C) an alcohol solvent, and the (C) alcohol The blending ratio of the system solvent satisfies a predetermined range. Hereinafter, the composition for oral cavity of the present invention will be described in detail.

(A) Extract of the genus Oenothera spp., The composition for oral cavity of the present invention contains an extract of the genus Oenothera spp. (Hereinafter sometimes simply referred to as component (A)) as a GTase inhibitor. To do.

There are no particular restrictions on the plant belonging to the genus Rabbitaceae , but examples include Oenothera biennis , Oenothera striata , Oenothera erythrosepala , and Oenothera laciniata . Of these, the evening primrose is preferable.

  The extract of the genus Oenothera spp. Is not limited as long as it is extracted from the whole plant of the plant or a part of the plant such as seeds, roots, stems, leaves, and florets. Extracted from plant seeds.

  Moreover, a polar solvent is mentioned as a preferable extraction solvent used for the extraction of the extract of the Rabbitaceae evening primrose plant. Examples of such a polar solvent include water; lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propanol, isopropyl alcohol, and butanol; polyhydric alcohols such as 1,3-butylene glycol, glycerin, and polyethylene glycol; Examples include acetone; ethyl ether; ethyl acetate; methyl acetate. These extraction solvents may be used alone or in combination of two or more. The extraction solvent is preferably water, a lower alcohol having 1 to 5 carbon atoms, and a mixed liquid of water having a lower alcohol having 1 to 5 carbon atoms and water; more preferably water, ethanol, and a mixed liquid of ethanol and water; Is a mixture of ethanol and water. When a mixed solution of lower alcohol having 1 to 5 carbon atoms and water is used as the extraction solvent, the content ratio of the lower alcohol to the total weight of the mixed solution is, for example, 0.0001 to 99.9% by weight, preferably Is a ratio of 40 to 99.9% by weight, more preferably 50 to 90% by weight.

  The extract of the genus Rhizophoraceae is obtained by extracting the plant part to be extracted as it is or after drying, shredded, crushed, pressed, boiled or fermented with the above extraction solvent. It is done. As the extraction method, a commonly used extraction method for plant extracts can be employed, and specifically, immersion methods such as cold immersion and digestion; a method of stirring under heating; or a percolation method, etc. Is exemplified.

  In addition, prior to extraction of the plant of the genus Ranunculaceae with an extraction solvent, as a pretreatment, a depolarization treatment is performed in advance by using a nonpolar organic solvent such as a pressing method or hexane, and an extra portion is removed from the plant during the extraction treatment. It is desirable to prevent the extraction of fresh lipids.

  The extract of the plant of the genus Rubiaceae obtained by the above extraction method is in a liquid state, and in the present invention, the extract may be used in a liquid state, and if necessary, subjected to treatment such as concentration and drying. It may be used as a concentrate or a dry product. Further, after concentration or drying, the concentrated or dried product may be used after being purified by washing with an insoluble solvent, or may be used by further dissolving or suspending it in an appropriate solvent. It is also possible to obtain and purify a fraction having GTase inhibitory activity using the obtained extract using a conventional purification method such as a countercurrent distribution method or liquid chromatography. .

  In addition, for convenience, a commercially available extract may be used as an extract of the plant belonging to the genus Pinaceae. Specific examples of commercially available extracts of the genus Rhizopus genus are evening primrose extract-P (manufactured by Oriza Yuka Co., Ltd.), evening primrose extract-PC (manufactured by Oriza Yuka Co., Ltd.), and evening primrose extract. -WSPS (manufactured by Oriza Oil & Chemical Co., Ltd.), evening primrose extract-PH (manufactured by Oriza Oil & Chemical Co., Ltd.), evening primrose extract-WSPH (manufactured by Oriza Oil & Chemical Co., Ltd.), evening primrose extract-LC (manufactured by Oriza Oil & Chemical Co., Ltd.), Examples include Luna White B (Ichimaru Falcos Co., Ltd.). All of the extracts of the genus Ranunculaceae exemplified here are extracts produced from the seeds of evening primrose.

  In the oral composition of the present invention, the blending ratio of the component (A) is not particularly limited and can be appropriately set according to the form of the oral composition, but the component (A) From the viewpoint of effectively exerting the plaque formation inhibitory effect based on the GTase inhibitory action, the component (A) is 0.001 w / v% or more, preferably 0.01 to 50 w /% per total amount of the oral composition. It is desirable that it is contained at a blending ratio of v%, more preferably 0.05 to 10 w / v%. The unit “w / v%” of the blending ratio of the component (A) shown here is a blending ratio in terms of the dry weight of the extract of the genus Acrobaceae.

(B) Cationic fungicide The composition for oral cavity of the present invention contains at least two kinds of cationic fungicides (hereinafter sometimes simply referred to as component (B)). In the composition for oral cavity of the present invention, the bactericidal effect can be effectively exhibited even in the presence of the component (A) by using two or more kinds of cationic fungicides in combination. The cationic fungicide used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, but it is a quaternary ammonium salt fungicide, pyridinium salt fungicide, bisbiguanide. Examples include bactericides and the like. Specific examples of the quaternary ammonium salt fungicide include benzalkonium chloride, benzethonium chloride, dimethylethylbenzylammonium chloride, didecyldimethylammonium chloride, didecyldimethylammonium adipate, didecyldimethylammonium gluconate, Examples include decyl monomethylhydroxyethylammonium adipate, didecyldimethylammonium propionate, didecylmonomethylhydroxyethylammonium sulfonate, decalinium chloride and the like. Specific examples of the pyridinium salt fungicide include cetylpyridinium chloride. Specific examples of the bisbiguanide fungicide include chlorhexidine hydrochloride, chlorhexidine acetate, chlorhexidine gluconate and the like.

  About the combination aspect of 2 or more types of cationic fungicides mix | blended in the composition for oral cavity of this invention, it does not restrict | limit in particular, It sets suitably according to the use and form of an oral composition. Specific examples of the combination of two or more kinds of cationic fungicides include, for example, a combination of at least one quaternary ammonium salt fungicide and at least one pyridinium salt fungicide, and at least two kinds of fourth fungicides. A combination of a quaternary ammonium salt fungicide and a combination of at least two pyridinium salt fungicides. Among these combinations, from the viewpoint of improving the bactericidal effect against oral bacteria, a combination of at least one quaternary ammonium salt fungicide and at least one pyridinium salt fungicide is more preferable. May include benzalkonium chloride or a combination of zenzetonium chloride and cetylpyridinium chloride. In particular, a combination of a quaternary ammonium salt fungicide and a pyridinium salt fungicide (especially a combination of benzalkonium chloride or benzethonium chloride and cetylpyridinium chloride) can be used even in the presence of an extract of the genus Acanthaceae. Further, the stabilization of the cationic fungicide can be further improved, and the bactericidal effect can be more effectively exhibited.

  As the component (B), when a quaternary ammonium salt fungicide and a pyridinium salt fungicide are used in combination, the mixing ratio is not particularly limited, but as an example, a quaternary ammonium salt Examples of the fungicide: pyridinium salt fungicide are 100: 10 to 10000, preferably 100: 50 to 5000, and more preferably 100: 100 to 1000 by weight.

  In the oral composition of the present invention, the blending ratio of the component (B) is not particularly limited and can be appropriately set according to the form of the oral composition, but the component (B) From the viewpoint of effectively exerting the bactericidal effect of (B) component per total amount of the oral composition, the total amount (that is, the total amount of two or more cationic bactericides) is 0.0005 to 1 w / It is desirable that it is contained at a blending ratio of v%, preferably 0.001 to 0.5 w / v%, more preferably 0.01 to 0.25 w / v%.

  In the composition for oral cavity of the present invention, the ratio of the component (B) to the component (A) is appropriately set within the range satisfying the blending ratio of the component (A) and the component (B) described above. As an example, the component (B) is 0.00002 to 1000 parts by weight, preferably 0.00002 to 50 parts by weight, more preferably 0.001 to 5 parts by weight, per 1 part by weight (in terms of dry weight) of the component (A). Is mentioned.

(C) Alcohol-based solvent The oral composition of the present invention comprises at least one alcohol-based solvent selected from the group consisting of lower alcohols and polyhydric alcohols having 2 to 3 carbon atoms (hereinafter simply referred to as component (C)). In some cases). By selecting the above components among the alcohol-based solvents, it is possible to stabilize the component (B) and to effectively exhibit the bactericidal effect based on the component (B).

  Specific examples of the lower alcohol having 2-3 carbons used as the component (C) include ethanol, n-propanol, and isopropanol. Specific examples of the polyhydric alcohol used as the component (C) include glycerin, monopropylene glycol, dipropylene glycol, 1,3-butylene glycol, hexylene glycol, diethylene glycol, and a weight average molecular weight of 50. -2000 (preferably 100-1000, more preferably 200-600) polyethylene glycol and the like are exemplified. Among these, from the viewpoint of further stabilizing the component (B), ethanol, isopropanol, glycerin, monopropylene glycol, dipropylene glycol, 1,3-butylene glycol, and a weight average molecular weight of 200 to 600 are preferable. Examples include polyethylene glycol.

  These alcohol solvents may be used alone or in combination of two or more.

  In addition, when two or more alcohol solvents are used as the component (C), the combination mode is not particularly limited, but at least one kind of the component (B) is further improved from the viewpoint of further improving the stability of the component (B). A combination of a lower alcohol having 2-3 carbon atoms and at least one polyhydric alcohol; preferably a combination of ethanol and at least one of propylene glycol and 1,3-butylene glycol is exemplified. When the lower alcohol having 2-3 carbon atoms and the polyhydric alcohol are used in combination as the component (C), the mixing ratio is not particularly limited, but as an example, the total amount of the lower alcohol having 2-3 carbons is 100 wt. The total amount of polyhydric alcohol per part is 10 to 1000 parts by weight, preferably 20 to 500 parts by weight, and more preferably 50 to 200 parts by weight.

  In the composition for oral cavity of the present invention, the component (A) and the component (C) satisfy the ratio that the component (C) is 30 ml or more per 1 g of the component (A) (in terms of dry weight). By blending the component (C) at such a ratio, the component (B) can be stabilized even in the presence of the component (A), and the bactericidal effect based on the component (B) can be effectively exhibited. become. In the composition for oral cavity of the present invention, from the viewpoint of more effectively expressing the bactericidal effect of the component (B), the component (C) is preferably 30 to 8000 ml per 1 g of the component (A) (in terms of dry weight). Preferably 40-2000 ml is mentioned.

  In the composition for oral cavity of the present invention, the blending ratio of the component (C) is appropriately set within the range satisfying the blending ratio of the component (A) and the ratio of the component (C) to the component (A). However, as an example, 0.02-99 v / v%, preferably 0.3-80 v / v%, more preferably 2-60 v / v% per total amount of the oral composition.

Other compounding components In addition to the components (A) to (C), the composition for oral cavity of the present invention includes other antibacterial agents and other GTase inhibitors within the range that does not impair the effects of the present invention. You may mix | blend a substance in combination. By using these antibacterial agents and GTase inhibitors in combination, the anti-cariogenic effect based on the component (A), the plaque formation inhibitory effect, or the bactericidal effect based on the component (B) should be additively or synergistically enhanced. You can also. Examples of such antibacterial agents include sorbic acid, hinokitiol, isopropylmethylphenol, triclosan, potassium iodide and the like. Other GTase inhibitors include, for example, Vitis plant extracts, dextranase, mutanase, sodium monofluorophosphate, sodium fluoride, stannous fluoride, tastein, tannins , Ellagic acid, polyphenol, oolong tea extract, green tea extract, assembly, Taiso, fennel, glaze, gentian, senso, rye gall, yellow ream and the like.

  Moreover, in addition to the said component, the composition for oral cavity of this invention can also mix | blend the component normally used for the composition for oral cavity as needed in the range which does not impair the effect of this invention. Examples of such components include abrasives, binders, thickeners, foaming agents, fragrances, flavoring agents, sweeteners, preservatives, anti-inflammatory agents, disinfectants, other antibacterial agents, pigments, and thickeners. , Buffers, surfactants, pH adjusters, antioxidants, and the like.

  Furthermore, the composition for oral cavity of the present invention can contain a pharmaceutically acceptable carrier according to the preparation form. For example, when the dosage form of the composition for oral cavity of the present invention is made liquid, water such as purified water, ion-exchanged water, ultrapure water, tap water or the like may be used as a carrier.

Method for Producing Oral Composition The oral composition of the present invention can be produced by mixing a predetermined amount of components (A) to (C) and, if necessary, a predetermined amount of other components. In the production of the oral composition of the present invention, the mixing order of each compounding component is not particularly limited, but in order to stabilize the components (A) and (B) during preparation of the oral composition In addition, it is desirable to mix the components (A) and (B) in the presence of the component (C).

Use, form of oral composition The oral composition of the present invention is applied to the oral cavity to inhibit plaque formation based on the GTase inhibitory action of component (A), and sterilization based on component (B) Since the effect can be exhibited effectively, it can be used for the purpose of preventing oral diseases and symptoms such as caries, bad breath, periodontal disease, and alveolar pus leakage. In particular, the composition for oral cavity of the present invention has an excellent anti-cariogenic effect and is suitable for use for the purpose of preventing caries.

  In addition, the composition for oral cavity of the present invention is a liquid dentifrice, toothpaste, moisturizing dentifrice, mouth freshener (mouse spray, etc.), oral paste, mouthwash (mouth wash), mouth rinse, gargle. It is provided as an oral preparation in the form of an agent, gingival massage cream and the like. Among these, Preferably, liquid oral agents, such as a liquid dentifrice, a mouth freshener, a mouthwash, mouth rinse, a mouthwash, etc. are mentioned, More preferably, a liquid dentifrice and a mouthwash are mentioned.

Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited thereto.
Test example 1
The following tests were conducted on the effect of the type and concentration of the solvent used on the stability of the cationic fungicide in an oral composition containing an evening primrose extract and two cationic fungicides. . First, an oral composition was prepared according to the formulation shown in Table 1. Specifically, after mixing the solvent and water shown in Table 2, an evening primrose extract was added, and finally a cationic bactericidal agent was mixed to prepare an oral composition.

About each obtained composition for oral cavity, the density | concentration of the cationic microbicide was measured by HPLC. HPLC measurement conditions are as follows.
Standard solution: An aqueous solution in which a cationic disinfectant is diluted stepwise with water so as to have the same concentration as that of each oral composition.
Sample pretreatment: Insoluble components were removed by centrifugation and filter filtration.
Injection volume: 10 μl
Column: A stainless steel tube having an inner diameter of 4.6 mm and a length of 15 cm was packed with octadecylsilylated silica gel for liquid chromatography having a particle size of 5 μm.
Column temperature: constant temperature around 40 ° C
Mobile phase: Mixture of acetonitrile and 0.3 mol / l ammonium chloride (volume ratio 3: 2)
Flow rate: 1.6ml / min
Detection conditions: An ultraviolet absorptiometer was used (measurement wavelength: cetylpyridinium chloride: 258 nm, benzalkonium chloride: 210 nm, benzethonium chloride: 210 nm).

  The concentration ratio of the cationic fungicide actually measured by the HPLC measurement was calculated as a recovery rate (%), with the concentration of the blended cationic fungicide being 100. The results are shown in FIG. 1 (measurement result of cetylpyridinium chloride) and 2 (measurement result of benzalkonium chloride). As a result, when the lower alcohol or polyhydric alcohol having 2 to 3 carbon atoms is used as the solvent and the solvent is set to a ratio of 30 ml or more per 1 g of the evening primrose extract, the bactericidal effect of the cationic fungicide It was confirmed that the cationic bactericidal agent was stably present in the oral composition to the extent that can be effectively produced. On the other hand, when using a solvent other than a C2-C3 lower alcohol and a polyhydric alcohol, and using a C2-C3 lower alcohol or a polyhydric alcohol, and per 1 g of evening primrose extract, When the solvent was set at 10 ml, it was revealed that the cationic bactericidal agent did not exist stably from the oral composition, and the bactericidal effect based on the bactericidal agent could not be fully enjoyed. In particular, when a solvent other than a C2-C3 lower alcohol or polyhydric alcohol was used, no cationic fungicide could be detected in the oral composition at any solvent concentration.

Test example 2
The following test was conducted to determine how the combination of solvents used affects the stability of the cationic fungicide in an oral composition containing an evening primrose extract and two cationic fungicides. First, oral compositions were prepared according to the formulations shown in Tables 3 and 4. Specifically, after mixing an alcohol solvent and water, an evening primrose extract was added, and finally a cationic disinfectant was mixed to prepare an oral composition.

  About each obtained composition for oral cavity, it carried out similarly to Test Example 1, and measured the density | concentration of the cationic germicide by HPLC. The concentration ratio of the cationic fungicide actually measured was calculated as a recovery rate (%), with the concentration of the blended cationic fungicide being 100. The results are shown in FIGS. 3 (measurement results of cetylpyridinium chloride) and 4 (measurement results of benzalkonium chloride). Also in this result, as in Test Example 1, two or more kinds of ethanol, monopropylene glycol, and 1,3-butylene glycol were combined, and the total amount of the solvent was set to a ratio of 30 ml or more per gram of evening primrose extract. In some cases, it was confirmed that the cationic fungicide was stably present in the oral composition. In particular, when ethanol was combined with monopropylene glycol or 1,3-butylene glycol, a higher proportion of cationic fungicide was detected. From the above results, it becomes clear that it is effective to further improve the bactericidal effect of the cationic bactericidal agent by using a combination of a C2-C3 lower alcohol and a polyhydric alcohol as a solvent. It was.

Test example 3
The following tests were conducted on the effect of the combination of the cationic fungicide used on the oral composition containing the evening primrose extract and two cationic fungicides on the stability of the cationic fungicide. It was. First, an oral composition was prepared according to the formulation shown in Table 5. Specifically, after mixing an alcohol solvent and water, an evening primrose extract was added, and finally a cationic disinfectant was mixed to prepare an oral composition.

  About each obtained composition for oral cavity, it carried out similarly to Test Example 1, and measured the density | concentration of the cationic germicide by HPLC. The concentration ratio of the cationic fungicide actually measured was calculated as a recovery rate (%), with the concentration of the blended cationic fungicide being 100. The results are also shown in Table 5. From this result, even when benzethonium chloride is used as one of the two types of cationic fungicides, the cationic fungicide can be stably added to the oral composition as in Test Example 1-2. It was confirmed that it could be present. In particular, Examples 1 and 2 showed a significantly higher recovery rate of two types of cationic fungicides than Example 3, so that the fourth and fourth types of cationic fungicides were No. 4 It has also been clarified that these cationic fungicides can be further stabilized in the oral composition by using a combination of a quaternary ammonium salt fungicide and a pyridinium salt fungicide.

Comparative Test Example 1
The following tests were conducted on the effects of the use of a single cationic fungicide on the stability of the cationic fungicide in an oral composition containing an evening primrose extract and a cationic fungicide. went. First, an oral composition was prepared according to the formulation shown in Table 6. Specifically, after mixing the solvent shown in Table 2 and water, an evening primrose extract was added, and finally cetylpyridinium chloride was mixed to prepare an oral composition.

  About each obtained composition for oral cavity, the density | concentration of cetyl pyridinium chloride was measured by HPLC similarly to Test Example 1. The concentration ratio of cetylpyridinium chloride actually measured was calculated as the recovery rate (%), with the concentration of the blended cetylpyridinium chloride being 100. The obtained results are shown in FIG. As is clear from FIG. 5, when cetylpyridinium chloride was used alone as the cationic fungicide, the cationic fungicide could not be present stably at any concentration of any solvent. From the above results, the stabilizing effect in the composition for oral cavity of the cationic fungicide shown in Test Example 1-3 is a characteristic obtained when two or more kinds of cationic fungicides are used. It became clear that it was an effect.

Test example 4
The above formulation D (solvent is isopropanol; cetylpyridinium chloride recovery rate 100%, benzalkonium chloride recovery rate 100%) and the above comparative formulation 1 (cetylpyridinium chloride recovery rate 0%, benzalkonium chloride recovery rate 0%) The following bactericidal effects were evaluated for the oral compositions. First, a medium (10-fold diluted solution) was prepared by adding 1 ml of a test sample (composition for oral cavity) to 9 ml of brain heart infusion (BHI) liquid medium. Next, a 10-fold diluted solution was mixed with an equal amount of BHI liquid medium to prepare a 20-fold diluted solution. A two-step dilution series (10, 20, 40, 80, 160, 320, 640, and 1280 times) was prepared by the same procedure, and 0.5 ml was added to each well of a 48-well microplate. 10 μl of a suspension of Streptococcus mutans strain MT8148 cultured overnight in a BHI liquid medium was added to each well of the plate and left to stand at 37 ° C. for 24 hours. It was confirmed. As a control, the above and the bactericidal effect were also evaluated for an aqueous solution containing 0.05 w / v% cetylpyridinium chloride and 0.01 w / v% benzalkonium chloride.

  The results are shown in Table 7. As shown in Table 7, the oral composition having a 100% recovery rate of the cationic fungicide showed a bactericidal effect equivalent to that of the control, whereas the oral composition having a 0% recovery rate of the cationic fungicide. The composition did not have a bactericidal effect. That is, from the above results, it was confirmed that, in Test Examples 1-3 and Comparative Test Example 1 described above, the rate of recovery of the evaluated cationic bactericides was correlated with the bactericidal effect exhibited by the oral composition.

Test Example 5
As evening primrose extract, evening primrose extract-WSPS (manufactured by Oriza Oil Chemical Co., Ltd.), evening primrose extract-PH (manufactured by Oriza Oil Chemical Co., Ltd.), evening primrose extract-WSPH (manufactured by Oriza Oil Chemical Co., Ltd.), evening primrose extract-LC (Oriza oil) When the same test as the above-described Test Example 1-4 was performed using Yuka Kagaku Co., Ltd.) and Luna White B (Ichimaru Falcos Co., Ltd.), the result of the same tendency as the above-mentioned Test Example 1-4 Obtained.

Claims (8)

(A) an extract of the genus Oenaceae, (B) at least two cationic fungicides selected from the group consisting of quaternary ammonium salt fungicides and pyridinium salt fungicides, and (C) carbon Including at least one alcohol solvent selected from the group consisting of lower alcohol and polyhydric alcohol of formula 2-3,
An oral composition, wherein the component (C) satisfies a ratio of 30 ml or more per 1 g of the component (A). The composition for oral cavity according to claim 1 , comprising at least one quaternary ammonium salt fungicide and at least one pyridinium salt fungicide as the component (B). The composition for oral cavity of Claim 1 or 2 containing at least 1 type of C2-C3 lower alcohol and at least 1 type of polyhydric alcohol as said (C) component. As the component (B), at least one quaternary ammonium salt-based fungicide is selected from the group consisting of benzalkonium chloride and benzethonium chloride, including cetyl pyridinium chloride, to any one of claims 1 to 3 The composition for oral cavity of description. The composition for oral cavity in any one of Claims 1 thru | or 4 whose compounding ratio of the said (A) component is 0.01-50 w / v% or more. The component (C) is at least one selected from the group consisting of ethanol, isopropanol, glycerin, monopropylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol having a weight average molecular weight of 200 to 600. The composition for oral cavity in any one of Claims 1 thru | or 5 . The composition for oral cavity according to any one of claims 1 to 6 , wherein the component (A) is an extract of the seeds of the genus Rhizopus. The composition for oral cavity according to any one of claims 1 to 7 , which is a mouthwash or a liquid dentifrice.

Images