KR20120034656A - Composition for oral cavity - Google Patents

Abstract

(A) Ascorbic acid phosphate ester or salt thereof, (B) Vitamin E or derivative thereof, (C) OE average added mole number from 10 to 60 POE hardened castor oil, alkyl group C14 to 18, EO average added mole number from 5 to 8 POE alkyl ether and alkyl group containing a surfactant selected from C10-14 alkyl glucoside, and (D) nonionic fungicide, the total amount of (A), (B) and (D) is 0.2 to 1.5% by mass , (C) / ((B) + (D)) is 8-20 by mass ratio, contains (A)-(C) component, and (E) cationic fungicide, (A), (B) and The total amount of (E) component is 0.2-1.3 mass%, (C) / ((B) + (E)) is the composition for oral cavity of 8-18 in mass ratio, According to this invention, ascorbic acid phosphate ester or its Salts, vitamin E or derivatives thereof, and fungicides are stably and effectively formulated to achieve excellent prevention or improvement of periodontal disease, and are also excellent in preservation stability over time.

Description

Composition for oral cavity {COMPOSITION FOR ORAL CAVITY}

The present invention relates to an oral composition containing ascorbic acid phosphate ester or a salt thereof, exhibiting a high periodontal disease prevention or improvement effect, and excellent in storage stability over time. Among the symptoms, the effect of improving the bad breath and the increase in the amount of effusion of the pulp is especially high, and it is excellent in the storage stability of ascorbic acid phosphate ester or its salts over time, The present invention relates to a composition for oral cavity which is prevented from discoloration and excellent in appearance stability.

Periodontal disease can be counted as one of the major causes of tooth loss, and its prevention is expected to lead to the improvement of quality of life (QOL). Most of periodontal diseases are considered to be infections caused by bacteria mainly composed of anaerobic Gram-negative bacilli, and as a result, connective tissue and alveolar bone are destroyed. Clinical findings of this process include redness, swelling, bleeding, drainage and bad breath. In addition, there is a bacterium-host response between cause and effect.

In chronic periodontal disease, it is known that tissue destruction occurs by enzymes derived from a host such as collagenase while the cycle of inflammation circulates. In the tissue, the accumulation of neutrophils in the periodontal pocket, the infiltration of lymphocytes into the tooth tissue, etc. are recognized, and the enzymes which are good enzymes in the teeth affected by periodontal disease. It has been reported that plasmin is involved.

In living organisms, neutrophils have functions to sterilize bacteria and defend living organisms, but especially in chronic inflammation, they adversely affect biological tissues due to leakage of cellular components and production of excess free radicals. Thus, it is useful to prevent tissue destruction by active oxygen by using antioxidants such as ascorbic acid phosphate esters or salts thereof. It is described in, for example, Patent Document 1 and the like that blending ascorbic acid phosphate ester or a derivative thereof with an oral composition is effective for preventing periodontal disease. However, ascorbic acid phosphate ester is easy to decompose in a formulation, and there exists a problem that storage stability is not enough when water or anionic surfactant exists.

In addition, it is effective to prevent periodontal disease by promoting the blood circulation of the gingival and activating metabolism. Vitamin E (nickname; tocopherol) derivatives are effective in preventing periodontal disease because they have an antioxidant action in addition to a blood circulation promoting effect. It is described in, for example, Patent Document 2 and the like that blending a vitamin E derivative with a composition for oral cavity is effective for preventing periodontal disease. However, there is a problem that vitamin E derivatives are easy to decompose in the formulation, and it is difficult to ensure storage stability.

Moreover, in order to solubilize a useful adult vitamin E derivative in the composition for oral cavity, and to mix | blend it stably, it is common to use surfactant together. However, in this case, the micelle formed by the surfactant becomes too rigid depending on the amount of the surfactant blended, and the vitamin E derivatives contained in the micelle are not released at the target site, thereby exhibiting the effect. There is a problem that it becomes difficult.

Patent document 3 discloses that a bactericidal agent expressing an effect by directly reducing the number of bacteria in the oral cavity that causes inflammation of the tooth is effective in preventing and improving periodontal disease. However, it is common to use a surfactant to solubilize the disinfectant in the composition for oral cavity and to stably mix. However, the amount of the surfactant is used so that the micelle formed by the surfactant becomes too rigid, and the bactericide accepted in the micelle is a target site. There is a problem that it is not released from, which makes it difficult to exert its effect.

As described above, ascorbic acid esters or salts thereof, vitamin E or derivatives thereof, and fungicides are still in a stable combination in the composition for oral cavity to sufficiently exert their effects, and in particular, these components are stable at the same time. It was difficult to mix | blend and express high effect, and to make storage stability favorable also over time.

Patent document 4 abbreviates the skirt composition which mixes ascorbic acid phosphate ester salt, a vitamin E derivative, and a cationic fungicide, a vitamin E derivative, a cationic fungicide, and polyoxyethylene hardened castor oil (henceforth polyoxyethylene is POE). ) Is described, and Patent Document 5 describes a composition using a vitamin E derivative, a cationic fungicide and POE hydrogenated castor oil in combination with a non-aqueous oral composition. However, it is hard to say that the effect of preventing the periodontal disease of these compositions is sufficient, and there is no description of an average added mole number (hereinafter, referred to as EO average added mole number) of ethylene oxide of POE hardened castor oil. In addition, Patent Document 6 discloses a composition in which ascorbic acid phosphate ester salt, a vitamin E derivative, and a nonionic fungicide are used together as a coating composition for preventing caries [dental caries] containing no abrasive. The solubilization or blending stability of the derivative and the nonionic fungicide is not sufficient.

A dentifrice composition containing vitamin E or a derivative thereof, comprising ascorbic acid phosphate ester, vitamin E derivative, POE stearyl ether (EO average molar number 5), POE hardened castor oil (EO average molar number 40) and cationic fungicide. The composition which used together is described in patent document 7. However, it is difficult to say that the composition ratio of each component is appropriate, and therefore, micelles formed by the surfactant become too rigid, and vitamin E derivatives and fungicides contained in micelles are not sufficiently released from the target site. There is room for improvement in the manifestation of the effect.

Patent Document 8 describes a composition in which an ascorbic acid phosphate ester salt, a vitamin E derivative, a POE alkyl ether, and a nonionic fungicide are blended as a composition for oral cavity containing vitamin E or a derivative thereof. However, this composition is difficult to say that the blending ratio of each component, in particular, the blending ratio of POE alkyl ether to the vitamin E derivative and the nonionic fungicide is appropriate, and therefore, the stabilization of the vitamin E derivative and the nonionic fungicide is sufficient. Can not say. In addition, Patent Document 8 has no provision regarding the alkyl group portion of the POE alkyl ether, and there is a description that the ascorbic acid derivative stabilizes vitamin E. However, regarding the simultaneous stabilization of the vitamin E and ascorbic acid derivatives, Not shown.

Applicant mixes OE average added mole number 5-10 POE hardened castor oil to the composition for oral cavity containing ascorbic acid phosphate ester salt, and adjusts the composition for oral cavity which adjusted pH to 6.5-9.0 (Japanese Patent Application No. 2007-326959) No. 2009-149537). In this application, the Example 30 contains ascorbic acid phosphate ester salt, vitamin E derivative, EO average added moles 5 and 20 POE hardened castor oil, EO average added moles 7 POE cetyl ether and isopropylmethylphenol. The composition is described. However, this technique improves the oral retention and mucosal permeability of ascorbic acid phosphate ester salt by blending specific POE hardened castor oil and adjusting the pH, thereby effectively exerting the effect derived from ascorbic acid phosphate ester salt. The technical idea differs from the present invention.

In addition, in any of the techniques described herein, there is no description showing a technique for suppressing bad breath derived from periodontal disease, and the technical idea and the effect of the configuration of the present invention cannot be derived from these techniques.

Therefore, it is desired to develop a composition for oral cavity, which has the effect of preventing or improving higher periodontal disease and having excellent appearance stability represented by storage stability, separation and discoloration prevention over time.

Patent Document 1: Japanese Patent Application Laid-Open No. 2007-169201 Patent Document 2: Japanese Patent Application Laid-Open No. 2005-350483 Patent Document 3: Japanese Patent Application Laid-Open No. 2006-312588 Patent Document 4: Japanese Patent Application Laid-Open No. 2005-239654 Patent Document 5: Japanese Patent Application Laid-Open No. 2002-114656 Patent Document 6: Japanese Patent Application Laid-Open No. 2005-187333 Patent Document 7: Japanese Patent Application Laid-Open No. 2005-247786 Patent Document 8: Japanese Patent Application Laid-Open No. 2004-323488

[Non-Patent Document 1] "Considering Periodontal Disease and Whole Body Health-A Bridge to New Health Sciences", Lion Dental Hygiene Institute, Edition, Denture Medicine Press, 2004, P. 221 [Non-Patent Document 2]: "Considering Periodontal Disease and Whole Body Health-A Bridge to New Health Sciences, Lion Dental Hygiene Institute and Edition, Denture Medicine Press, 2004, P. 116"

This invention is made | formed in view of the said situation, Ascorbic acid phosphate ester or its salt, vitamin E or its derivatives, and a fungicide are stably and effectively mix | blended and achieve the outstanding prevention or improvement effect of periodontal disease, and also with time. It is an object to provide a composition for oral cavity that is excellent in storage stability.

MEANS TO SOLVE THE PROBLEM The present inventors earnestly examined in order to achieve the said objective, As a result, (A) Ascorbic acid phosphate ester or its salt, (B) Vitamin E or its derivative (s), and (C) EO average added mole number are 10- At least one surfactant selected from 60 moles of POE hardened castor oil, an alkyl group having 14 to 18 carbon atoms, an EO average added mole number of 5 to 8 moles of POE alkyl ether, and an alkyl group having 10 to 14 alkyl glucosides And a (D) nonionic fungicide or (E) cationic fungicide as a fungicide, and the composition oral composition having a corresponding range as shown below for the compounding amount and blending ratio of these components is used for periodontal disease. It confirmed that it was excellent in the prevention or improvement effect, and excellent in storage stability with time.

According to the present invention, ascorbic acid phosphate ester or a salt thereof, vitamin E or a derivative thereof, and a fungicide are stably compounded at the same time, so that the effects derived from these components are effectively expressed, and bad breath or dental meat exudates derived from periodontal disease (hereinafter, , As well as a high effect of improving the amount of GCF) and a high bactericidal effect against the periodontal disease-causing bacterium, and the prevention and improvement effect of periodontal disease is significantly improved, ascorbic acid phosphate esters or salts and vitamins E or its derivatives are stably blended for a long time at the same time, and there is no separation or discoloration with time, and it is also excellent in storage stability over time.

That is, in the present invention, the composition for oral cavity having a high periodontal disease improvement effect and excellent over time preservation stability, which could not be achieved by the prior art, can be obtained. Ascorbic acid phosphate esters or salts thereof, vitamin E or derivatives thereof, and fungicides are known to be effective in preventing or ameliorating periodontal disease, but in the present invention, as can be seen from the examples described below, the above components are combined. By blending in an appropriate compounding amount and ratio, these components act synergistically, and among the symptoms associated with periodontal disease, a high effect of improving the bad breath and an increase in the amount of GCF is exhibited, and a high bactericidal effect against the periodontal disease-causing bacteria Is also exerted. In addition, in the present invention, ascorbic acid phosphate ester or its salt and vitamin E or its derivatives remain stable even after long-term storage, so that effects derived from these components can be expressed over time and stably. Separation and discoloration do not occur in storage, and the appearance is satisfactory. Such an effect of the present invention is extraordinary, which can not be achieved when one of the essential components of the present invention is lacking, or when the blending amount or ratio of each component is inappropriate.

In addition, bad breath caused by periodontal disease is produced by gram-negative bacteria in the oral cavity. Sulfur-containing amino acids serving as substrates are supplied from GCF or blood. When suffering from periodontal disease, the amount of GCF increases, that is, bad breath occurs because the substrate of bad breath production increases (Non-Patent Document 1). In the present invention, a high periodontal disease improvement effect is exerted, and the reduction of the amount of GCF also reduces the amount of sulfur-containing amino acid, which is a substrate of bad breath production, and the sterilizing agent sterilizes bad breath acid bacteria. It is estimated that it is a factor and suppresses bad breath derived from periodontal disease. This GCF exists in the gingival or gingival meat, actively inhibits the invasion of foreign substances such as bacteria and toxins by antibody components and the like, and contributes to biological defense. Meanwhile, GCF is abbreviated as interleukin (hereinafter referred to as IL). Cytokines, such as) -1, IL-6, IL-8, etc. exist, and the relationship with periodontal disease has also been suggested (nonpatent literature 2). In the present invention, it is assumed that the periodontal disease is remarkably improved, the amount of GCF which once increased decreases, the substrate of bad breath production decreases, and the sterilizing agent sterilizes the bad breath live bacteria, which can suppress bad breath. . In addition, since the GCF amount increases when affected by periodontal disease and decreases when it improves, it is used as an index for measuring the severity and improvement of periodontal disease.

The composition of the present invention also contains (F) glycyrrhetinic acid, ε-aminocaproic acid, glycyrrhizin acid salt, tranexamic acid, sulfur white extract, and allantoin compound, by blending one or more active ingredients to prevent or improve periodontal disease. The effect is further improved, and the amount of GCF which has increased with the morbidity of periodontal disease can be reduced more effectively.

Therefore, this invention provides the following composition for oral cavity.

Claim 1;

(A) ascorbic acid phosphate ester or salt thereof,

(B) vitamin E or derivatives thereof,

(C) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 10 to 60 moles, polyoxyethylene alkyl ether having an alkyl group of 14 to 18 carbon atoms and an average added mole number of ethylene oxide of 5 to 8 moles; At least one surfactant selected from alkylglucosides having 10 to 14 carbon atoms,

(D) nonionic fungicides

Containing; (A), (B) and (D) the sum total content is 0.2-1.5 mass%, and (C) / ((B) + (D)) is 8-20 by mass ratio, It is characterized by the above-mentioned. Oral composition.

Claim 2;

(D) The composition for oral cavity of Claim 1 whose nonionic fungicide is isopropylmethylphenol or triclosan.

Claim 3;

(A) ascorbic acid phosphate ester or salt thereof,

(B) vitamin E or derivatives thereof,

(C) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 10 to 60 moles, polyoxyethylene alkyl ether having an alkyl group of 14 to 18 carbon atoms and an average added mole number of ethylene oxide of 5 to 8 moles, and an alkyl group At least one surfactant selected from alkylglucosides having 10 to 14 carbon atoms,

(E) cationic fungicide

Containing; (A), (B) and (E) the sum total content is 0.2-1.3 mass%, and (C) / ((B) + (E)) is 8-18 by mass ratio, It is characterized by the above-mentioned. Oral composition.

Claim 4;

(E) The composition for oral cavity of Claim 3 whose cationic fungicide is 1 or more types chosen from cetylpyridinium chloride, benzetonium chloride, benzalkonium chloride, chlorhexidine gluconate, and chlorhexidine hydrochloride.

Claim 5;

The sum total content of (A) component, (B) component, and (D) or (E) component is 0.2-1.0 mass%, and (C) / [(B) + ((D) or (E)) ] Is 8-15 by mass ratio, The composition for oral cavity of any one of Claims 1-4 characterized by the above-mentioned.

Claim 6;

(F) any one of claims 1 to 5, characterized in that it contains one or more selected from glycyrrhetinic acid, ε-aminocaproic acid, glycyrrhizin acid salt, tranexamic acid, sulfur white extract and allantoin. Composition for oral cavity.

The composition for oral cavity of this invention exhibits the high effect which improves especially bad breath and the increase of GCF amount among the symptoms accompanying periodontal disease, and the high bactericidal effect to the periodontal causative bacteria, and is excellent in storage stability with time. It is also excellent in appearance stability represented by separation and discoloration. Moreover, by mix | blending said (F) component, the suppression effect of a higher GCF amount increase is exhibited. Therefore, the composition for oral cavity of this invention is useful for the prevention or improvement of periodontal disease.

Hereinafter, the present invention will be described in more detail, the composition for oral cavity of the present invention as (A) ascorbic acid phosphate ester or salt thereof, (B) vitamin E or its derivatives, (C) specific surfactant, and fungicide (D) a nonionic fungicide or (E) a cationic fungicide.

(A) Ascorbic acid phosphate ester and its salt are esters of compounds, such as phosphoric acid and polyphosphoric acid, in which one or two or more of the hydroxyl groups in any of the 2nd, 3rd, 5th and 6th positions of ascorbic acid are used. Examples thereof include ascorbic acid-2-phosphate ester, ascorbic acid-3-phosphate ester, ascorbic acid-6-phosphate ester, ascorbic acid-2-polyphosphate ester, and the like. Examples of the salts include alkali metal salts such as sodium salts, potassium salts, calcium salts and magnesium salts, and alkaline earth metal salts. In particular, for use in the oral cavity and in the prevention of gingivitis, magnesium salts and sodium salts of ascorbic acid phosphate esters, that is, L-ascorbyl magnesium phosphate and L-ascorbyl sodium phosphate are suitable. Used.

Ascorbic acid phosphate esters and salts thereof are commercially available products, specifically, L-ascorbyl magnesium phosphate is digested electrician (trade name: Ascorbic acid PM), Wako Pure Chemical Industries, Ltd. (trade name: L-asphate) L-ascorbyl sodium phosphate, such as Corbyl magnesium), can be obtained from DSM Neutorishon Japan (trade name: Stay-C50), BASF Japan (trade name: L-ascorbyl sodium) Can be used.

As for the compounding quantity of ascorbic acid phosphate ester or its salt, 0.05-0.8% (mass%, the same below) of the whole composition, especially 0.1-0.5% are preferable at the point of a periodontal disease prevention effect or the preservation stability with time. If the blending amount is less than 0.05%, the effect of preventing and improving periodontal disease may not be sufficiently obtained. If the amount exceeds 0.8%, discoloration may occur over time, and irritation may occur, which may adversely affect the feeling of use.

(B) As vitamin E or a derivative thereof (hereinafter, vitamin E is abbreviated as VE), d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol or acetic acid thereof, Ester or salt with organic acids, such as nicotinic acid, succinic acid, and linolenic acid, etc. can be used. As the VE derivative, for example, acetic acid d-α-tocopherol acetate, dl-α-tocopherol acetate, nicotinic acid d-α-tocopherol, nicotinic acid dl-α-tocopherol, succinic acid d-α-tocopherol, succinic acid dl-α-tocopherol, linolenic acid d-α-tocopherol, linolenic acid dl-α-tocopherol, succinate tocopherol calcium and the like.

As vitamin E or its derivatives, physiological activity is high, and colorless to pale yellow, in particular, it does not affect the color tone or appearance of the preparations (there is almost no recognized effect, especially dl-α-tocopherol, dl-α-tocopherol acetate, nicotinic acid). dl- (alpha) -tocopherol is preferable .. VE or its derivative (s) can be mix | blended individually by 1 type or in combination of 2 or more types.

As VE or its derivatives, those conforming to the old cosmetic raw material standards (Jangwon Ki) or quasi-drug raw material standard 2006, etc. can be used, and those commonly used in cosmetics and oral compositions can be used. As VE or its derivatives, the commercial item sold from DSM Neutraltion Japan Co., Ezai Fudo Chemical Co., BASF Japan Co., etc. can be used.

As for the compounding quantity of VE or its derivative (s), 0.05-0.5%, especially 0.05-0.3% of the whole composition are preferable at the point of a periodontal disease prevention effect, or a preservation stability with time. If the blending amount is less than 0.05%, the effect of preventing and improving periodontal disease is not sufficiently obtained. If the amount exceeds 0.5%, solubilization in the formulation becomes difficult, separation, discoloration, and the like occur over time. have.

(C) component is POE alkyl ether whose EO average added mole number is 5-8 mol and C1-C18 alkyl group of an alkyl group, 10-60 mol POE average added mole number, and C10-C10 of an alkyl group One or two or more nonionic surfactants selected from alkylglucosides of 14;

As POE alkyl ether, what has a C14-18, preferably C16-18 alkyl group is preferable. When the carbon number of the alkyl group is less than 14, since the lipophilic property is low, solubilization of the oil-soluble component is insufficient, and sufficient bubbleability is not obtained. When the carbon number exceeds 18, the solubilization of the oil-soluble component is small because the size of the micelle formed is small. It becomes insufficient and also has a unique strange taste while using the formulation. Specifically, POE cetyl ether, POE myristyl ether, POE stearyl ether, etc. are mentioned as POE alkyl ether, Especially POE stearyl ether is suitable.

Moreover, EO average added mole number of POE alkyl ether is the range of 5-8 mol. If the EO average added mole number is lower than 5 moles, the solubilizing ability is insufficient, so that separation of the oil-soluble liquid component occurs in the formulation, and if it exceeds 8 moles, unique feeling-deterioration of flavor expression occurs, resulting in inferior usability.

As such POE alkyl ether, a commercial item, such as EMALEX105, 107, 605, 608, of Japan Emulsion Co., can be used.

As POE hardened castor oil, the thing of 10-60 of EO average added mole numbers can be used. For example, when used for a softener, the thing of 10-30 of EO average added mole numbers is especially preferable, and the thing of 40-60 is especially preferable when used for a mouthwash. If the EO average added mole number is less than 10 moles, the solubilizing ability of the oil-soluble component is insufficient, and especially when prepared as a softener, a rough surface at low temperatures may occur and the appearance may deteriorate. When it exceeds 60 mol, it may be inferior to the solubilizing ability of oil-soluble components, such as vitamin E or its derivative (s), a fungicide, and also a useful oil active ingredient and a fragrance | flavor ingredient, and a oil-soluble component may isolate | separate.

As such POE hardened castor oil, commercial products, such as NIKKOL HCO-10, HCO-20, HCO-30, HCO-40, HCO-50, HCO-60, can be used.

As alkyl glucoside, the C10-C14 thing of an alkyl group, Preferably the thing of 10-12 is used. If the carbon number is less than 10, sufficient foamability is not obtained. If the carbon number is more than 14, a unique strange taste or feeling occurs during use.

As such alkyl glucoside, commercial items, such as planter care 1200UP of Cognis and planter care 2000UP, can be used.

As (C) component, above-mentioned POE alkyl ether, POE hardened castor oil, or alkyl glucoside may be mix | blended, or 2 or more types chosen from POE alkyl ether, POE hardened hisashi oil, and alkyl glucoside are combined together, You may mix | blend. When using 2 or more types together, combined use of POE alkyl ether and POE hardened castor oil is preferable. In the case of a dentifrice such as a soft lubricating agent, in particular, POE alkyl ether having 16 to 18 carbon atoms and 5 to 8 moles of EO average added mole number and 10 to 30 POE hydrogenated castor oil It is preferable to use it by the ratio of 3: 7-7: 3 by mass ratio. In particular, in the case of using POE alkyl ether having 16 to 18 carbon atoms and EO addition mole number of 6 or less alkyl group, use of POE hydrogenated castor oil having 20 to 40 EO average added mole number, and less than 20 EO average added mole number When POE hardened castor oil is used, it is most preferable from the point of stability of a (B) component or suppression of isolation | separation to use together POE alkyl ether of 16-18 carbon atoms and 7-8 of EO average added mole numbers.

As for the total compounding quantity of the nonionic surfactant of (C) component, 0.5-5%, especially 0.5-3% of the whole composition are preferable at the point of the solubilization ability of an oil-soluble component, the effect expression of an oil-soluble component, and usability. If the blending amount is less than 0.5%, the oil-soluble component solubilizing ability is not sufficiently obtained, and VE or its derivatives and nonionic fungicides are not sufficiently solubilized, which may result in insufficient storage stability. When it exceeds 5%, micelles by (C) component become too rigid, and the useful ingredient of the oil-soluble substance received in micelles is not released in the oral cavity, so that sufficient periodontal disease and bad breath prevention and improvement effects cannot be obtained. In some cases, bitterness and irritation may occur, preventing the preparation of the preparation in the oral cavity for a long time. Especially in the case of a dentifrice, since many oil-soluble components, such as a fragrance | flavor, are mix | blended, it is most suitable to make a compounding quantity 1 to 3%.

Furthermore, (D) nonionic fungicide or (E) cationic fungicide is mix | blended with the composition of this invention as a fungicide.

(D) As a nonionic fungicide, isopropylmethylphenol, triclosan, a hinoki thiol, a phenol etc. are mentioned, These 1 type, or 2 or more types can be used, Especially isopropylmethyl from a point of sterilization power, a taste, etc. Phenol and triclosan are preferable. A nonionic fungicide can use a commercial item, isopropylmethylphenol can be obtained from Osaka Chemical Company (brand name: isopropylmethylphenol), and triclosan can be obtained from Chiba, Specialty Chemicals Co., Ltd. (trade name: Irugasan DP-300). .

As for the compounding quantity of a nonionic fungicide, 0.01-0.3%, especially 0.02-0.1% of the whole composition are preferable at the point of a periodontal disease prevention effect and usability. If the amount is less than 0.01%, the bactericidal effect is inferior, and the periodontal disease and bad breath improvement effect due to sterilization are not sufficiently obtained, and even if the amount exceeds 0.3%, it is not solubilized. A bitter taste may occur and a feeling may be worse.

(E) As cationic fungicides, bisguanides such as cetylpyridinium chloride, benzetonium chloride, benzalkonium chloride, and dequalinium chloride, bisguanides such as chlorhexidine gluconate and chlorhexidine hydrochloride, and alkyldiamino hydrochloride Although ethylglycine etc. are mentioned, 1 type (s) or 2 or more types of these are used, In particular, quaternary ammonium type and bisguanide type are preferable from a viewpoint of bactericidal power and taste, Among these, cetylpyridinium chloride, benzethonium chloride, Most preferred are benzalkonium chloride, chlorhexidine gluconate, and chlorhexidine hydrochloride.

A commercially available cationic fungicide can be used. Cetylpyridinium chloride is used by Wako Pure Chemical Industries, Inc. (brand name: cetylpyridinium chloride), Benzetonium chloride is Longder Japan (trade name: Hyamine 1622), and Benzalkonium chloride is Amakase Chemical Industries, Ltd. (Product Name: 10% Benzalkonium Chloride Solution), Gluconate Chlorhexidine is obtained from Sumitomo Pharmaceutical Co., Ltd. (brand name: Hibiten-gulconetto liquid), and Chlorhexidine Hydrochloride is available from Japan Sumitomo Pharmaceutical Co., Ltd. can do.

As for the compounding quantity of a cationic fungicide, 0.001 to 0.1%, especially 0.01 to 0.05% of the whole composition are preferable at the point of a periodontal disease prevention effect and usability. If the blending amount is less than 0.001%, the bactericidal effect is inferior, and the periodontal disease and bad breath improvement effect due to sterilization cannot be sufficiently obtained. If the amount exceeds 0.1%, a bitter taste or the like may worsen, or the discoloration may occur.

In this invention, the total compounding quantity of (A) ascorbic acid phosphate ester or its salt, (B) vitamin E or its derivative (s), and (D) nonionic fungicide is a composition from a periodontal disease prevention effect and an external stability. 0.2 to 1.5% of the total, particularly 0.2 to 1.0%. If the total amount is less than 0.2%, the effect of preventing periodontal disease is not sufficiently exhibited. If the total amount exceeds 1.5%, the components (A), (B) or (D) are separated over time or discoloration occurs.

In addition, the compounding ratio of (C), (B) and (D) component is (C) / ((B) + (D)) from the point of periodontal disease prevention effect, stability of (B) component, and separation suppression. The mass ratio of is 8-20, Especially the range of 8-15 is preferable. If the blending ratio is less than 8, the component (B) and the component (D) are not solubilized, so that the storage stability is insufficient, or separation occurs in the formulation, and if it exceeds 20, the micelle by the component (C) becomes too rigid. (B) component and (D) component which were taken in in micelle are not discharge | released in oral cavity, and a periodontal disease prevention effect is not fully exhibited.

In this invention, the total compounding quantity of (A) ascorbic acid phosphate ester or its salt, (B) vitamin E or its derivative (s), and (E) cationic fungicide is a composition from a periodontal disease prevention effect or an external stability. 0.2 to 1.3% of the total, particularly 0.2 to 1.0%. If the total amount is less than 0.2%, the effect of preventing periodontal disease is not sufficiently exhibited. If the total amount exceeds 1.3%, the components (A), (B) or (E) are separated over time or discoloration occurs.

In addition, the compounding ratio of (C), (B), and (E) component is (C) / ((B) + (E)) of the periodontal disease prevention effect, stability of (B) component, and external stability. The mass ratio is 8-18, especially the range of 8-15 is preferable. If the blending ratio is less than 8, since the component (B) is not solubilized, the storage stability becomes insufficient, and separation occurs in the formulation, and if it exceeds 18, the micelle by the component (C) becomes too rigid and is received in the micelle. Indented (B) component and (E) component are not released in oral cavity, and the effect derived from these components is not fully exhibited.

Especially in this invention, the sum total content of (A) component, (B) component, and (D) or (E) component is 0.2 to 1.0%, and (C) / ((B) + ((D) or When (E)) is 8-15 by mass ratio, since the prevention or improvement effect of periodontal disease improves more, and also it is excellent in storage stability with time, it is most effective.

The composition for oral cavity of this invention also mix | blends 1 type (s) or 2 or more types of active ingredients chosen from (F) glycyrrhetinic acid, (epsilon) -aminocaproic acid, glycyrrhizin acid salt, tranexamic acid, sulfur white extract, and allantoin. It is preferable. By blending the component (F), the effect of preventing and improving periodontal disease can be further improved, and as a result, the leaching of GCF associated with periodontal disease can be further suppressed. In addition, allantoin includes allantoin, allantoin hydroxyaluminum, and allantoin dihydroxyaluminum (nickname: adioxa).

A natural product or a synthetic product may be sufficient as (F) component, and a commercially available thing can be used. Specifically, glycyrrhetinic acid is Maruzen Pharmaceutical Co., Ltd. (brand name: glycyrrhetinic acid), ε-aminocapronic acid is Cheil Chemical Co., Ltd. For example, glycyrrhizin acid salt is, for example, dipotassium glycyrrhizinate is Maruzen Pharmaceutical Co., Ltd. (trade name: glycyrrhizin K2), Alps pharmaceutical industry (trade name: glycyrrhizane 2K), and tranexamic acid is the first Palmatec company (brand name: tranexamic acid), The yellowish white extract is Koshiro Pharmaceutical Co., Ltd. (brand name: yellow white extract), Iwase cospasa (brand name: Oubakurikido E), allantoin is DSM Neutorishon Japan company (brand name: allantoin), allantoin chlorohydroxy aluminum is merk company (brand name) : RonaCare Allantoin (registered trademark)) and allantoin dihydroxyaluminum are those which can be obtained from a natural fine chemical company (brand name: ALDA).

When mix | blending (F) component, the compounding quantity is 0.01-0.5%, especially 0.01-0.3% of the whole composition from a viewpoint of a periodontal disease prevention effect and usability. If the blending amount is less than 0.01%, the effect of inhibiting the increase in the amount of GCF is not satisfactorily expressed, and the improvement of the periodontal disease prevention effect may not be sufficiently obtained. If the blending amount exceeds 0.5%, a bitter taste may occur.

Dextranase can also be mix | blended with the composition for oral cavity of this invention. By combining dextranase, plaque which is one of the causes of periodontal disease can be easily decomposed and removed, and the effect of preventing and improving periodontal disease can be further enhanced.

Dextranase is an enzyme produced by the genus Ketomium, Penicillium, Aspergillus, Spicaria, Lactobacillus, Celvibrio, etc., and has a plaque degrading action. Dextranase can be obtained from the 1st three pore propama company (brand name: dextranase).

When mix | blending dextranase, the compounding quantity is 2-200 units / g, Especially 10-50 units / g are preferable at the point of a plaque decomposition effect and formulation stability. One unit of dextranase is the amount of dextranase which produces | generates free reducing sugar equivalent to 1 micromol of glucose in 1 minute when reaction is performed using dextran as a substrate. For example, when 13,000 units / g of dextranase is used, the compounding quantity is preferably 0.016 to 1.5%, particularly 0.08 to 0.38% of the whole composition. If the compounding amount is less than 2 units / g, the compounding effect, for example, sufficient plaque removal effect may not be obtained. If the compounding amount exceeds 200 units / g, discoloration of the formulation may occur.

In the oral composition of the present invention, a fluorine ion source can be further blended. By incorporating a fluorine ion source, the hemorrhoids of the root portion exposed as a result of tooth degeneration due to periodontal disease can be strengthened, and the expression or progression of hard caries can be prevented or inhibited. Can be. The root portion has a property that is easy to dissolve in acid, and therefore, it is easy to be caries. However, in the case of dry tooth, the root portion is inside the tooth, so that it does not come into contact with the acid and does not become caries. However, when toothpaste degenerates due to periodontal disease, the root portion is exposed, it contacts with acid, dissolves, and becomes caries. This is called diligent caries. In this invention, by mix | blending a fluorine ion source, the hemorrhoid of a root part strengthens and it is difficult to melt | dissolve in an acid, and it can prevent or suppress the expression or progression of hard caries.

Examples of the fluorine ion source include sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, potassium monofluorophosphate, sodium silicon fluoride, calcium silicon fluoride and the like. Although these can use 1 type (s) or 2 or more types, sodium fluoride and sodium monofluorophosphate are especially preferable at the point of taste. In addition, a fluorine ion source can be commercially available, for example, sodium fluoride can be used from sterakemipasa, sodium monofluorophosphate from Albright & Wilson, etc.

When mix | blending a fluorine ion source, the compounding quantity is 0.02 to 10.0% of the whole composition, especially 0.05 to 1.5% from a distillation caries prevention effect or solubility point is preferable. For example, 0.02 to 3.0%, in particular 0.05 to 1.5% for sodium fluoride, 0.05 to 10.0% for sodium monofluorophosphate, in particular 0.1 to 5.0%, 0.01 to 1.6% for tin fluoride, in particular Preference is given to 0.03 to 0.8%. When the compounding quantity of a fluorine ion source is less than 0.02%, satisfactory compounding effect may not be acquired, and when it exceeds 10.0%, solubilization in a formulation may become difficult.

The composition for oral cavity of this invention is a skirting agent, mouthwash, mouthwash, mouthwash, mouthwash, toothpaste, toothpaste, toothpaste, polishing skirt, foam skirt, liquid skirt, liquid skirt. It can be made into various forms, such as a tablet and chewing gum, and can be suitably prepared as a dentifrice and a mouthwash.

In this case, the composition for oral cavity can be mix | blended in addition to the said component in addition to the said component in the range which does not impair the effect of this invention, according to various formulations, and can be prepared by a conventional method. As an optional component which can be mix | blended, an abrasive | polishing agent, a humectant, a caking additive, a solvent, surfactant other than said (C) component, and also sweetener, preservative, various active ingredients, a pH adjuster, a coloring agent, a fragrance | flavor etc. can be mix | blended as needed. Can be prepared by mixing these components.

As the abrasive, silica-based abrasives such as silica gel, precipitated silica, aluminosilicate, zirconosilicate, amorphous anhydrous silicic acid, dicalcium phosphate dihydrate, dicalcium phosphate anhydride, tricalcium phosphate, tetracalcium phosphate, and eighth Calcium Phosphate, Calcium Pyrophosphate, Aluminum Hydroxide, Alumina, Titanium Dioxide, Insoluble Calcium Phosphate, Hard Calcium Carbonate, Heavy Calcium Carbonate, Magnesium Carbonate, Magnesium Triphosphate, Zeolite, Polymethylmethacrylate, Nylon Powder, Silk Powder , Cellulose powder, glocommannane, and the like.

The compounding quantity of an abrasive | polishing agent is 0 to 50% normally, and 2 to 40% is especially preferable in a dentifrice composition.

Examples of the humectant include sugar alcohols such as sorbitol, glycerin, propylene glycol, polyethylene glycol with an average molecular weight of 200 to 6000, 1,3-butylene glycol, xylitol, erythritol, lactitol, palatinose, pallatinite, trehalose and the like. And polyhydric alcohols (the compounding amount is usually 0 to 50%, particularly 5 to 45%).

As a caking additive, xanthan rubber, sodium polyacrylate, carrageenan, sodium alginate, propylene glycol alginate, carboxyvinyl polymer, trata rubber, guar rubber, hydroxypropyl guar rubber, tarago rubber, locust bean rubber, karaya rubber, queens Seed rubber, tamarind rubber, carboxymethyl cellulose sodium, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, cellulose, gellan rubber, gelatin, cardlan, gum arabic, agar, pectin, casein sodium , Polyvinyl alcohol, polyvinylpyrrolidone, pullulan, thickening silica, non-rubber, smectite, laponite, montmorillonite, bentonite, and the like (the amount is usually 0 to 5%, in particular 0.1 to 5%).

Generally as a solvent, water is used. The compounding quantity in the case of containing water is 1 to 99% normally, and is mix | blended 1-50% with a dentifrice composition normally. Lower alcohols, such as ethanol, may be mix | blended as a solvent, and the compounding quantity of lower alcohol is 0.1-30%. The total compounding quantity of a solvent is 0 to 99% normally.

As surfactant, in addition to surfactant of (C) component, another nonionic surfactant, anionic surfactant, cationic surfactant, and amphoteric surfactant can be mix | blended. Specifically, POE polyoxypropylene copolymer, sucrose fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerol fatty acid ester, POE sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE glycerin fatty acid ester, POE glycol fatty acid ester , POE alkyl ether phosphoric acid and salts thereof, POE alkyl ether sulfate, POE phytosterol and phytostanol, POE alkylphenyl ether phosphoric acid and salts thereof, POE lanolin and lanolin alcohols, POE alkylamine and fatty acid amides, POE alkylphenyl formaldehyde condensates , Nonionic surfactants such as POE polyoxypropylene alkyl ether, POE alkylphenyl ether and fatty acid ethanolamide, polyethylene glycol fatty acid ester, octyl sulfate, decyl sulfate, lauryl sulfate, myristyl sulfate, palmityl sulfate, stearyl sulfate Alkali metal salts thereof (sodium, potassium, lithium, etc.). Alkyl sulfate esters or salts thereof, such as sodium N-lauroyl sarcosine, sodium acyl sarcosine such as sodium N-myristoyl sarcosine, sodium dodecylbenzene sulfonate, hydrogenated coconut fatty acid monoglyceride mono N-acylglutamate, such as sodium sulfate, sodium laurylsulfoacetate, sodium N-palmitoylglutamate, sodium N-methyl-N-acyltaurine, sodium N-methyl-N-acylalanine, sodium α-olefinsulfonic acid, di And anionic surfactants such as sodium octyl sulfoate, cationic surfactants such as alkylammonium and alkylbenzyl ammonium salts, amphoteric surfactants such as betaine acetate, imidazolinium betaine and fatty acid amidepropyl betaine. The compounding quantity of these surfactant is 0 to 5% normally, In particular, nonionic surfactants other than (C) component may not be mix | blended, and 0% may be sufficient.

As for the compounding quantity of surfactant as said arbitrary component, the range whose total compounding quantity with surfactant of (C) component becomes 0.5 to 6% is preferable.

Examples of the sweetening agent include sodium saccharin, stevioside, stevia extract, paramethoxycinnamicaldehyde, neohespyridylhydrochalcone, peraryllatin, taumatin, sucralose, acesulfame potassium, aspartame, and the like.

As a preservative, parabens (paraoxybenzoic acid ester), such as methyl paraben, butyl paraben, and ethyl paraben, benzoic acid and its salt, salicylic acid, its ester or salt, etc. are mentioned.

As an active ingredient, the said (A), (B), (D), (E), (F) component, Furthermore, a thing other than a dextranase, a fluorine ion source, for example, ascorbic acid, its derivatives, riboflavin Pyridoxine hydrochloride, cyanocobalamin, β-carotene, ergocalciferol, menadione, ubiquinone and other vitamins, nasturtium, golden, hamamelis, cloves, chamomile, latania, myrrh, donkey, rosemary, safflower Plant extracts such as, mutanase, lysozyme, amylase, protease, lytic enzymes, enzymes such as superoxide dismutase, salts such as sodium chloride, potassium nitrate, sodium polyphosphate, carbonates, bicarbonates and sesquicarbonates, γ -Orizanol, dihydrocholesterol, α-bisabolol, azlene, methoxyethylene / maleic anhydride copolymer, trichlorocarbanilide, alanine, glycine, proline, L-arginine, L-aspartic acid sodium, trimethylglycine, copper Copper chlorophyllin Sodium gluconate, copper, zinc chloride, zinc citrate, zeolite, water-soluble inorganic phosphoric acid compounds, aluminum lactate, etc. may be added alone or in combination of two or more. The addition amount of the said active ingredient can be made an effective amount in the range which does not prevent the effect of this invention.

Examples of the pH regulator include citric acid, malic acid, lactic acid, tartaric acid, succinic acid, acetic acid, phosphoric acid, pyrophosphoric acid, copper serophosphate, various salts such as potassium salts, sodium salts and ammonium salts, sodium hydroxide, hydrochloric acid, and the like. These can be mix | blended individually by 1 type or in combination of 2 or more types so that pH of a composition may become the range of 5-9 (the compounding quantity is 0 to 2% normally).

As a colorant, Red 2, Red 3, Red 225, Red 226, Yellow 4, Yellow 5, Yellow 205, Blue 1, Blue 2, Blue 201, Blue 204, Green 3 Statutory pigments, safflower pigments, gardenia pigments, cochinyl pigments, anato pigments, iron groups, mica titanium, titanium oxide, and the like.

As perfume, peppermint oil, spearmint oil, anise oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil , Lime oil, lavender oil, rosemary oil, laurel oil, chamomile oil, caraway oil, marjoram oil, bay oil, lemon glass oil, oliganum oil, pine needle oil, neroli oil, rose oil, jasmine oil, iris concrete, absol Natural fragrances such as lute peppermint, absolutrose, orange flower, and flavorings processed by the natural fragrances (current cut, downstream cut, fractionation, liquid extraction, essence, powder fragrance, etc.) Menthol, carbon, anetol, cineol, methyl salicylate, cinnamicaldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, linalool, linalyl acetate, limonene, mentone, Menthyl acetate, N-substituted-paramentane-3-carboxamides, pinene, octylaldehyde , Citral, Plegon, Carbyl Acetate, Anisealdehyde, Ethyl Acetate, Ethyl Butyrate, Allylcyclohexanepropionate, Methyl anthranilate, Ethylmethylphenyl glycidate, Vanillin, Undecaractone, Hexaneal, Ethyl alcohol , Single-flavor flavors such as propyl alcohol, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cyclotene, furfural, trimethylpyrazine, ethyl lactate, ethylthioacetate, and strawberry flavor and apple Known for use in oral compositions such as flavors such as flavors, banana flavors, pineapple flavors, grape flavors, mango flavors, butter flavors, milk flavors, fruit mix flavors, and tropical fruit flavors A fragrance material can be used and it is not limited to the fragrance of an Example. Moreover, although a compounding quantity is not specifically limited, either, It is preferable to use said fragrance | flavor raw material 0.000001 to 1% in a formulation composition. Moreover, as a fragrance | flavor for fragrance using the said fragrance | flavor raw material, it is preferable to use 0.1 to 2.0% in formulation composition.

The composition for oral cavity of this invention is filled in containers, such as an aluminum laminate tube and tubes, such as glass vapor deposition plastic tubes, dispenser containers by mechanical or differential pressure, bottle containers, such as polyethylene terephthalate and glass, and film packaging containers, such as pillow packaging. can do.

Example

Hereinafter, although an Example, a comparative example, and a prescription example demonstrate this invention concretely, this invention is not limited to the following Example. In addition, in the following example, all compounding quantities are the mass%. As a raw material, what suited the cosmetic raw material standard or the quasi quasi-drug raw material standard except having shown in Table 1 was used. In addition, the composition of fragrance | flavor is as showing in Tables 9-15. In addition, ethylene oxide abbreviated as EO and polyoxyethylene as POE.

[Table 1]

Raw materials used to prepare oral compositions

[Example, Comparative Example]

In the common composition shown in Table 2 below, (A) to (C) component, (D) or (E) component, and further (F) component were blended in the kind and compounding quantity as shown in Tables 3-8. The dentifrice composition of the composition was degassed and mixed using the kneader, and it prepared by the daily method. The loading amount of the dentifrice composition was 5 kg. The obtained dentifrice composition was filled in the tube (A) of the material mentioned later, and the following method evaluated. The results are shown in Tables 3-8.

Tube A (manufactured by Dainippon Printing Co., Ltd.):

LDPE55 / PET12 / ℓDPE20 / white LDPE60 / EMAA20 / AL10 / EMAA30 / ℓDPE20 / ℓLDPE30 (thickness 257㎛, diameter 26mm, filling amount 50g) from outermost layer

The numerical value represents thickness (micrometer). The symbol shows as follows.

LDPE: Low Density Polyethylene

LDPE: White Low Density Polyethylene

LLDPE: Linear Low Density Polyethylene

AL: Aluminum

PET: Polyethylene Terephthalate

EMAA: Copolymer Resin of Ethylene Methacrylic Acid

Evaluation of Periodontal Disease Inhibitory Effect

Beagle dogs (4 years old, females) and four groups of four dogs were used to evaluate bad breath and GCF as indicators. After the evaluation of bad breath and measurement of the amount of GCF before the start of the test, administration was performed twice a day for 1 month, and the bad breath and the amount of GCF were evaluated. In the administration of the test preparation, 0.5 g of the test preparation was a dentifrice and 0.5 ml of the mouthwash, and the entire mouth of the beagle dog was brushed. The detail of an evaluation method is shown below.

Assessment of bad breath from periodontal disease:

Bad breath at the start of the test was evaluated in accordance with the criteria described later by five stewards, and the rating was set to S1. After the administration of the test preparation for one month, the same level of bad breath derived from periodontal disease was evaluated by five steering staff in the same manner, and the rating was set to S2. The improvement of bad breath derived from periodontal disease of each beagle dog was computed according to following Formula, and the average value of 4 beagle dogs was calculated | required.

Improvement of bad breath derived from periodontal disease = S1-S2

This average value was determined according to the criteria described later. The improvement of bad breath derived from periodontal disease was determined that the composition for oral cavity (circle) and (circle) was a composition for oral cavity which has the effect of preventing and improving periodontal disease.

<Evaluation standard of bad breath>

5: extremely strong bad breath derived from periodontal disease

4: bad breath caused by periodontal disease

3: There is slightly bad breath derived from periodontal disease

2: Bad breath derived from periodontal disease barely

1: Bad breath derived from periodontal disease (almost no

0: There is no bad breath originating from periodontal disease

<Judgement standard of bad breath>

Degree of improvement of bad breath derived from periodontal disease

◎: 3 or more and 5 or less

○: 2 or more but less than 3

△: 1 or more but less than 2

×: less than 1

Assessment of Periodontal Disease Prevention Effect Using GCF

The lower jaw 4 parts (P3, P4, M1 center, M2 centrifugal) of the beagle dog were used as the test site, and the amount of GCF was measured before and after the start of the test. In addition, the GCF was collected after the bad breath was evaluated. GCF amount was collected by inserting the GCF collection strips (PerioPaper (registered trademark), Yoshida Co., Ltd.) into the test site periodontal pocket selected at the start of the test for 30 seconds, and the GCF meter (Periotoron (registered trademark), ( Note) Yoshida). The GCF change rate was calculated according to the following formula, and the average value of four test sites of 4 beagle dogs was judged according to the criteria described later, and the periodontal disease prevention effect using the oral composition of ◎ and ○ as the index of the gingival leaching solution. Judging that there is.

% Change in GCF =

 ((GCF amount at test start-GCF amount at test end) / GCF amount at test start) x 100

<Rating of periodontal disease prevention effect>

GCF rate of change

◎: 70% or more

○: 40% or more but less than 70%

△: 20% or more but less than 40%

×: less than 20%

Evaluation of preservation stability of ascorbic acid phosphate ester or salts thereof:

The test sample was stored for 1 month in a 50 degreeC thermostat. Thereafter, the sample was left to stand at room temperature, and then used for evaluation of storage stability of ascorbic acid phosphate ester or salts thereof. The residual ratio was calculated from the initial value on the day of manufacture. All reagents were used by Kanto Chemical.

<Quantitative method>

When the test preparation is a dentifrice, 0.1 g of the product is weighed, and 10 mmol / L phosphate buffer (1.5 mmol / L potassium dihydrogen phosphate, 23.5 mmol / L potassium dihydrogen phosphate, pH8.0) is added, and ascorbic acid phosphate is added. Ester or its salt was extracted, high-speed liquid chromatography (pump: Nippon Spectrometry PU1580, autosampler: SIL-10A from Shimadzu Corporation, UV detector: SPD-6A from Shimadzu Corporation, recording device: C-R4A from Shimadzu Corporation, column thermostat: Japan Quantification was carried out using an absolute calibration curve method using spectroscopic CO-966). Mobile phase is 25mmol / l potassium dihydrogen phosphate + 5mmol / l tetrabutylammonium / acetonitrile = 91/9 mixture (volume ratio), column is about 4.6mm diameter and 150mm length stainless steel tube for 5㎛ liquid chromatograph An octadecylsilylated silica gel was charged (e.g., TSK-gel ODS-80Ts (manufactured by JR Co., Ltd.)), the column temperature was about 40 ° C, the detection wavelength was 240 nm, and the flow rate was 0.8 ml / min. In addition, in the case of a mouthwash, it diluted using 10 mmol / L phosphate buffer, and it measured on the same conditions. This result was judged according to the criteria mentioned later, and it was judged that the storage stability of ascorbic acid phosphate ester salt was ensured for the composition for oral (circle) and (circle).

Residual percentage of ascorbic acid phosphate ester or salt thereof =

 (Evaluation sample value (%) / initial value (%)) * 100

<Rating>

Evaluation of the stability of ascorbic acid phosphate ester or its salt was judged by the following reference | standards of the average of three repetitions.

Retention rate of ascorbic acid phosphate ester or salts thereof

◎: 95% or more

○: less than 95%

△: less than 90%

×: less than 80%

Assessment of preservation stability of vitamin E or its derivatives:

The test sample was preserve | saved for 1 month in the 50 degreeC thermostat. After allowing it to stand at room temperature, 10 g of the test preparation was a dentifrice or oral pasta, and the resultant was extracted with methanol, extracted with methanol, and then subjected to liquid chromatography (pump: Japanese spectroscopic PU-980, autosampler: Japanese spectroscopic AS-). 950, detector: Nippon Spectrophotometer UV-970, recording apparatus: system instrument Chromatocoder21J, column thermostat: Nippon Spectrophotometer CO-966). The measurement conditions were carried out using a column packed with a 5 µm octadecylsilylated silica gel for liquid chromatograph in a stainless steel tube having an inner diameter of 4.6 mm and a length of 15 cm. At the flow rate of minutes, it measured by the absolute calibration curve method to ultraviolet light absorption intensity (measurement wavelength 284nm). In addition, in the case of a mouthwash, it diluted using methanol and measured on the same conditions. This result was determined according to the criteria described later, and it was judged that the storage stability of the vitamin E derivative was ensured for the compositions for oral cavity (circle) and (circle).

% Residual of vitamin E or its derivatives =

 (Evaluation sample value (%) / initial value (%)) * 100

<Rating>

The stability evaluation of vitamin E or its derivative (s) judged the average value of 3 repetitions on the following references | standards.

Residual rate of vitamin E or its derivatives

◎: 95% or more

○: 90% or more but less than 95%

△: 80% or more but less than 90%

×: less than 80%

Evaluation of bactericidal power:

40 μl of the porphyromonas ginjivalis culture solution, which were cryopreserved, was used in each of 5 mg / L hemin (manufactured by Sigma) and 1 mg / L vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.). (Manufactured) and added to 4 ml of culture medium (THBHM), followed by adjusting the turbidity (OD660) = 1 at a wavelength of 660 nm to 20,000 anaerobic culture (80 vol% nitrogen, 10 vol% carbon dioxide, and 10 vol% hydrogen) at 37 ° C. Viii).

When the test formulation was a dentifrice, 40 ml of artificial saliva was added to 10 g of the composition, followed by stirring, followed by centrifugation (10,000 revolutions / minute, 10 minutes) to obtain the supernatant obtained as a sample stock solution. When the test formulation was a mouthwash, 40 ml of artificial saliva was added and diluted to 10 g of the composition to prepare a sample stock solution. After 2 ml of this sample stock solution was allowed to react with 2 ml of the bacterial solution for 30 seconds, 50 µl was aliquoted to prepare a bactericidal evaluation sample solution. The bactericidal evaluation was performed by adding a bactericidal evaluation sample solution (50 µl) to THB liquid medium (4 ml), followed by culturing (37 ° C, 8 hours), and measuring the amount of the grown bacteria by measuring turbidity (OD660) as an index. The smaller one evaluated as having obtained higher sterilizing power.

In addition, as artificial saliva, 3.73 g of potassium chloride, 0.14 g of potassium dihydrogen diphosphate, 0.15 g of calcium chloride dihydrate, and 0.02 g of magnesium chloride hexahydrate are dissolved in purified water, and the pH is adjusted to 7 with potassium hydroxide. Was adjusted to 1,000 ml.

<Criteria for Judging Power>

◎: OD660 is less than 1

○: OD660 is more than 1 and less than 1.2

△: OD660 is 1.2 or more and less than 2

×: OD660 2 or more

Evaluation of appearance stability (separation, discoloration) over time:

The test sample was stored for 1 month in a 50 degreeC thermostat. Then, the sample was left to stand at room temperature and then used for evaluation of appearance stability. When the test sample was a soft cloth, the sample was extruded about 10 cm on the pulp paper, and the presence or absence of separation and discoloration was observed and evaluated. When the test sample was a mouthwash, the container was left standing for 1 day, and then the separation and discoloration were observed and evaluated. In addition, discoloration was evaluated based on the thing which stored the test sample in the 5 degreeC thermostat. Evaluation criteria are as follows.

<Rate of separation>

◎: No separation at all

(Circle): Separation is hardly recognized.

(Triangle | delta): Separation is recognized slightly.

X: Remarkable separation is recognized.

<Rate of discoloration>

◎: discoloration is not recognized at all

(Circle): Discoloration is hardly recognized.

(Triangle | delta): Discoloration is recognized slightly.

X: Remarkable discoloration is recognized.

TABLE 2

Common composition

Table 3-1

Table 3-2

Table 4-1

Table 4-2

From the results of Tables 3 and 4, the composition for oral cavity of the present invention has an inhibitory effect of bad breath derived from periodontal disease, a periodontal disease prevention effect using GCF as an index, bactericidal power, ascorbic acid phosphate ester or salts thereof and vitamin E or It was found that the derivatives were excellent in the stability over time and the appearance stability (no separation, no discoloration), exhibited a high periodontal disease prevention or improvement effect, and were excellent in stability over time. With respect to these, when any one of (A), (B), and (D) component is lacking, or when the total compounding quantity of these components and the ratio of (C) / ((B) + (D)) are inadequate, Or when the chain length and EO addition mole number of the alkyl group of surfactant are inadequate, it is inferior to any one of said effects, and the effect of this invention was not able to be achieved. Although the comparative example 12 reproduced Example 23 of Unexamined-Japanese-Patent No. 2005-187333, the effect of this invention was not able to be achieved. In addition, the same result was obtained even if perfume B-I was used instead of perfume A.

Table 5-1

Table 5-2

[Table 6-1]

[Table 6-2]

From the results of Tables 5 and 6, the composition for oral cavity of the present invention is effective in preventing bad breath derived from periodontal disease, periodontal disease prevention effect using GCF as an index, bactericidal power, ascorbic acid phosphate ester or salt thereof and vitamin E or It was found that the derivatives were excellent in the stability over time and the appearance stability (no separation, no discoloration), exhibited a high periodontal disease prevention or improvement effect, and were excellent in stability over time. With respect to these, when any one of (A), (B), and (E) component is lacking, or when the total compounding quantity of these components and the ratio of (C) / ((B) + (E)) are inappropriate, Or when the chain length and EO average added mole number of the alkyl group of surfactant are inadequate, it is inferior to any one of said effects, and the effect of this invention was not able to be achieved. Comparative Example 25 reproduces Example 9 of JP-A-2005-247786, but the effect of the present invention cannot be achieved. In addition, the same result was obtained even if perfume B-I was used instead of perfume A.

TABLE 7

[Table 8]

From the results of Tables 7 and 8, the composition for oral cavity of the present invention was further formulated using GCF as an index by combining glycyrrhetinic acid, ε-aminocaproic acid, glycyrrhizin acid salt, tranexamic acid, sulfur white extract or allantoin compounds. It was found that the effect of preventing and improving periodontal disease improved. In addition, the same result was obtained even if perfume B-I was used instead of perfume A.

TABLE 9

TABLE 10

TABLE 11

TABLE 12

TABLE 13

[Table 14]

TABLE 15

Below, the prescription example using this invention is shown.

When the composition for oral cavity of the following composition was prepared and evaluated similarly to the above, any composition for oral cavity also has the effect of preventing the bad breath derived from periodontal disease, the periodontal disease prevention effect using GCF as an index, ascorbic acid phosphate ester, or its The storage stability of the salt, the storage stability of the vitamin E or its derivatives, bactericidal power, and appearance stability (no separation, no discoloration) were excellent. The dextranase-containing composition was also excellent in plaque removal effect and the fluorine ion source-containing composition in preventing or improving hard caries.

[Example 1] Prescription

(A) L-ascorbyl magnesium phosphate 0.3%

(B) acetic acid dl-α-tocopherol 0.1

(C) POE stearyl ether 1

 (EO average added moles 5)

(C) POE hardened castor oil 1

 (EO average added moles 20)

(D) Isopropylmethylphenol 0.05

β-glycitinic acid 0.05

Dextranase (13,000 units / g) 0.16

Sodium Fluoride 0.21

Sodium Lauryl Sulfate 1.5

Precipitated Silica 15

Thickened Silica 4

Xanthan Rubber 0.5

Carrageenan 0.5

Sodium Polyacrylate 0.2

70% sorbitan 45

Propylene Glycol 3

Sodium hydroxide 0.4

Saccharin Sodium 0.15

Titanium Oxide 0.5

Spices A 1

Blue No. 1 0.0001

Purified water                          balance

100.00% in total

                         A + B + D = 0.45%

                       C / (B + D) = 13.3

[Example 2] Prescription

(A) L-ascorbyl magnesium phosphate 0.3%

(B) acetic acid dl-α-tocopherol 0.1

(C) POE stearyl ether 1

 (EO average added moles 5)

(C) POE hardened castor oil 1

 (EO average added moles 20)

(D) Isopropylmethylphenol 0.05

β-glycitinic acid 0.05

Dextranase (13,000 units / g) 0.16

Sodium monofluorophosphate 0.73

Sodium Lauryl Sulfate 1.5

Precipitated Silica 15

Thickened Silica 4

Xanthan Rubber 0.5

Carrageenan 0.5

Sodium Polyacrylate 0.2

70% sorbitan 45

Propylene Glycol 3

Sodium hydroxide 0.4

Saccharin Sodium 0.15

Titanium Oxide 0.5

Spices A 1

Blue No. 1 0.0001

Purified water                          balance

100.00% in total

                         A + B + D = 0.45%

                       C / (B + D) = 13.3

Prescription 3

(A) L-ascorbyl magnesium phosphate 0.3%

(B) acetic acid dl-α-tocopherol 0.1

(C) POE stearyl ether 1

 (EO average added moles 5)

(C) POE hardened castor oil 1

 (EO average added moles 20)

(E) cetylpyridinium chloride 0.01

β-glycitinic acid 0.05

Dextranase (13,000 units / g) 0.16

Sodium Fluoride 0.21

Sodium Lauryl Sulfate 1.5

Precipitated Silica 15

Thickened Silica 4

Xanthan Rubber 0.5

Carrageenan 0.5

Sodium Polyacrylate 0.2

70% sorbitan 45

Propylene Glycol 3

Sodium hydroxide 0.4

Saccharin Sodium 0.15

Titanium Oxide 0.5

Spices A 1

Blue No. 1 0.0001

Purified water                          balance

100.00% in total

                         A + B + E = 0.41%

                       C / (B + E) = 12.7

[Example 4] Prescription

(A) L-ascorbyl magnesium phosphate 0.3%

(B) acetic acid dl-α-tocopherol 0.1

(C) POE stearyl ether 1

 (EO average added moles 5)

(C) POE hardened castor oil 1

 (EO average added moles 20)

(E) cetylpyridinium chloride 0.01

β-glycitinic acid 0.05

Dextranase (13,000 units / g) 0.16

Sodium monofluorophosphate 0.73

Sodium Lauryl Sulfate 1.5

Precipitated Silica 15

Thickened Silica 4

Xanthan Rubber 0.5

Carrageenan 0.5

Sodium Polyacrylate 0.2

70% sorbitan 45

Propylene Glycol 3

Sodium hydroxide 0.4

Saccharin Sodium 0.15

Titanium Oxide 0.5

Spices A 1

Blue No. 1 0.0001

Purified water                         balance

100.00% in total

                        A + B + E = 0.41%

                      C / (B + E) = 12.7

[Prescription 5] Cinnamon

(A) L-ascorbyl magnesium 0.5% phosphate

(B) acetic acid dl-α-tocopherol 0.1

(C) decylglucoside 1

(C) laurylglucoside 1

(E) cetylpyridinium chloride 0.05

Sodium Monofluorophosphate 0.7

Sodium Lauryl Sulfate 1.5

Calcium hydrogen phosphate 40

Thickened Silica 4

Xanthan Rubber 0.5

Carrageenan 0.5

Sodium Polyacrylate 0.2

70% Sorbit Liquid 20

Palatine 2

Propylene Glycol 3

Sodium hydroxide 0.4

Saccharin Sodium 0.15

Titanium Oxide 0.5

Spices A 1

Purified water                          balance

100.00% in total

                         A + B + E = 0.65%

                       C / (B + E) = 13.3

Prescription 6

(A) L-ascorbyl magnesium 0.5% phosphate

(B) acetic acid dl-α-tocopherol 0.1

(C) decylglucoside 1

(C) laurylglucoside 1

(E) cetylpyridinium chloride 0.05

Sodium Fluoride 0.21

Sodium Lauryl Sulfate 1.5

Calcium hydrogen phosphate 40

Thickened Silica 4

Xanthan Rubber 0.5

Carrageenan 0.5

Sodium Polyacrylate 0.2

70% Sorbit Liquid 20

Palatine 2

Propylene Glycol 3

Sodium hydroxide 0.4

Saccharin Sodium 0.15

Titanium Oxide 0.5

Spices A 1

Purified water                          balance

100.00% in total

                         A + B + E = 0.65%

                       C / (B + E) = 13.3

Prescription 7

(A) L-ascorbyl magnesium 0.5% phosphate

(B) acetic acid dl-α-tocopherol 0.1

(C) polyoxyethylene hardened castor oil 2

 (EO average added moles 20)

(E) Benzetonium Chloride 0.05

β-glycitinic acid 0.05

Sodium Monofluorophosphate 0.7

Sodium Lauryl Sulfate 1.5

Calcium Carbonate 40

Thickened Silica 4

Xanthan Rubber 0.5

Carrageenan 0.5

Sodium Polyacrylate 0.2

70% Sorbit Liquid 20

Erythritol 2

Propylene Glycol 3

Sodium hydroxide 0.4

Saccharin Sodium 0.15

Titanium Oxide 0.5

Spices A 1

Purified water                           balance

100.00% in total

                          A + B + E = 0.65%

                        C / (B + E) = 13.3

[Example 8] Prescription

(A) L-ascorbyl magnesium 0.5% phosphate

(B) nicotinic acid dl-α-tocopherol 0.1

(C) laurylglucoside 1

(E) cetylpyridinium chloride 0.01

β-glyciletin acid 0.2

Dextranase (13,000 units / g) 0.2

Sodium Lauryl Sulfate 0.5

Ethanol 10

Glycerin 10

Sodium hydroxide 0.4

Saccharin Sodium 0.01

Spice A 0.5

Purified water                           balance

100.00% in total

                          A + B + E = 0.61%

                        C / (B + E) = 9.1

[Example 9] Prescription

(A) L-ascorbyl magnesium 0.5% phosphate

(B) nicotinic acid dl-α-tocopherol 0.1

(C) polyoxyethylene hardened castor oil 1

 (EO average added mole 60)

(E) cetylpyridinium chloride 0.01

β-glyciletin acid 0.2

Dextranase (13,000 units / g) 0.2

Sodium Lauryl Sulfate 0.5

Ethanol 10

Glycerin 10

Sodium hydroxide 0.4

Saccharin Sodium 0.01

Spice A 0.5

Purified water                           balance

100.00% in total

                          A + B + E = 0.61%

                        C / (B + E) = 9.1

Claims (6)

(A) ascorbic acid phosphate ester or salt thereof,
(B) vitamin E or derivatives thereof,
(C) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 10 to 60 moles, polyoxyethylene alkyl ether having an alkyl group of 14 to 18 carbon atoms and an average added mole number of ethylene oxide of 5 to 8 moles; At least one surfactant selected from alkylglucosides having 10 to 14 carbon atoms,
(D) nonionic fungicides
Containing; (A), (B) and (D) the sum total content is 0.2-1.5 mass%, and (C) / ((B) + (D)) is 8-20 by mass ratio, It is characterized by the above-mentioned. Oral composition. The method of claim 1,
(D) The composition for oral cavity, characterized in that the nonionic fungicide is isopropylmethylphenol or triclosan. (A) ascorbic acid phosphate ester or salt thereof,
(B) vitamin E or derivatives thereof,
(C) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 10 to 60 moles, polyoxyethylene alkyl ether having an alkyl group of 14 to 18 carbon atoms and an average added mole number of ethylene oxide of 5 to 8 moles, and an alkyl group At least one surfactant selected from alkylglucosides having 10 to 14 carbon atoms,
(E) cationic fungicide
Containing; (A), (B) and (E) the sum total content is 0.2-1.3 mass%, and (C) / ((B) + (E)) is 8-18 by mass ratio, It is characterized by the above-mentioned. Oral composition. The method of claim 3,
(E) The composition for oral cavity in which a cationic fungicide is 1 or more types chosen from cetylpyridinium chloride, benzetonium chloride, benzalkonium chloride, chlorhexidine gluconate, and chlorhexidine hydrochloride. The method according to any one of claims 1 to 4,
The sum total content of (A) component, (B) component, and (D) or (E) component is 0.2-1.0 mass%, and (C) / [(B) + ((D) or (E)) ] Is 8 to 15 by mass ratio. The method according to any one of claims 1 to 5,
(F) Oral composition comprising at least one selected from glycyrrhetinic acid, ε-aminocaproic acid, glycyrrhizin acid salt, tranexamic acid, sulfur white extract and allantoin.