JP2016044163A - Oral composition and method for inhibiting oral mucosal irritation of oral composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral composition which inhibits an oral mucosal irritation by protease, and which gives an excellent oral cavity biofilm removing effect and an excellent salivation promoting effect; and to provide a method for inhibiting oral mucosal irritation of the oral composition.SOLUTION: The invention provides an oral composition containing (A) protease and (B) polyglutamic acid or a salt thereof; and a method for inhibiting oral mucosal irritation of the oral composition in which the component (B) is contained in the oral composition containing the component (A) to inhibit the oral mucosal irritation by the component (A).SELECTED DRAWING: None

Description

  The present invention relates to a protease-containing oral composition that suppresses oral mucosal irritation caused by protease and provides an excellent oral biofilm removal effect and salivary secretion promoting effect, and a method for suppressing oral mucosal irritation.

  Removal of oral biofilms formed by oral bacteria that cause oral diseases such as periodontal disease, dental caries and bad breath is not only a physical method by brushing with a toothbrush, but also in areas where the toothbrush cannot reach Chemical methods that can remove biofilms are also useful. As chemical removal methods, there have been proposed erythritol having a coaggregation-inhibiting action and a method using a glucanase such as protease, dextranase, or mutanase as an enzyme that degrades extracellular polysaccharides.

  However, among the above enzymes, proteases often have irritation to the oral mucosa, and when mixed with oral compositions, oral mucosal irritation is strongly expressed, and there is also a problem that enzyme activity tends to be inactivated. However, it is difficult to obtain an oral preparation suitable for effective use for removal of oral biofilms using protease, and it has not yet been put into practical use.

  In Patent Document 1 (Japanese Patent Publication No. 9-507481), in addition to a preparation composed of a water-soluble alkali metal tripolyphosphate, a protease is added to a composition for removing deposited coloring matter on the tooth surface. As an example, a toothpaste for whitening teeth containing papain is described, and Patent Document 2 (Japanese Patent Publication No. 2002-526029) discloses an enzyme and a modified enzyme containing a polyanionic domain. It has been proposed that it can be used in oral compositions for the prevention or removal of dental plaque, and proteases are exemplified as enzymes, but there is no specific description of compositions using proteases. In these Patent Documents 1 and 2, there is no mention of oral mucosal irritation of protease.

  Patent Document 3 (Japanese Patent Laid-Open No. 2011-126919) proposes an oral composition containing a combination of natto extract and polyoxyethylene hydrogenated castor oil, which is a natto extract with less oral mucosal irritation. Protease activity is maintained by using specific polyoxyethylene hydrogenated castor oil in combination with plaque removal effect (smooth and refreshing tooth surface after mouthwash), bad breath removal effect, and less oral mucosal irritation The dispersion removal effect on the oral biofilm was not sufficient and there was room for improvement. Note that a mouthwash containing 1% by mass of the protease (500 units / g) shown in Comparative Example 4 of Cited Document 3 has a strong oral mucosal irritation and is not suitable for use.

  On the other hand, polyglutamic acid or a salt thereof is known to have a salivary secretion promoting action, and oral compositions formulated as salivary secretion promoters are disclosed in Patent Documents 4 and 5 (International Publication No. 2005/049050, Special No. 2009-96748). However, there is no mention that polyglutamic acid or a salt thereof suppresses oral mucosal irritation derived from protease and contributes to the improvement of oral biofilm removal effect.

JP-T 9-507481 Japanese translation of PCT publication No. 2002-526029 Japanese Patent Application Laid-Open No. 2011-126819 International Publication No. 2005/049050 JP 2009-96748 A

  Accordingly, an object of the present invention is to obtain an oral composition suitable for effective use in removing oral biofilm by suppressing oral mucosal irritation of protease.

  The present invention has been made in view of the above circumstances, and provides an oral composition that suppresses oral mucosal irritation by a protease and provides an excellent oral biofilm removal effect and salivary secretion promoting effect, and an oral mucosal irritation suppression method thereof. For the purpose.

  As a result of diligent studies to achieve the above object, the present inventors have (B) polyglutamic acid or a salt thereof mixed with (B) polyglutamic acid or a salt thereof in a composition for oral cavity containing (A) protease. It was found that the composition for oral cavity, which is effective for the removal of oral biofilm, is obtained because the stimulation is suppressed, the oral biofilm is excellent in dispersion removal effect and has a high salivary secretion promoting effect.

In the present invention, the components (A) and (B) interact specifically, and surprisingly the oral mucosal irritation derived from the component (A) is reduced by the component (B), and the oral biofilm removal effect is enhanced. And the (A) component enhances the salivary secretion promoting effect derived from the (B) component, and gives the above-mentioned special effects.
That is, as shown in a comparative example described later, when a protease is added to an oral composition, oral mucosal irritation is strongly expressed and unsuitable for use, and the oral biofilm removal effect of the protease alone is not sufficient (comparison) Example 1) Furthermore, polyglutamic acid or a salt thereof has almost no oral biofilm removal effect (Comparative Example 2), and therefore, the oral biofilm removal effect of protease is enhanced by combining polyglutamic acid or a salt thereof. Despite being unthinkable, as shown in the examples below, when (A) protease and (B) polyglutamic acid or a salt thereof are used in combination, oral mucosal irritation derived from component (A) is suppressed. The feeling of use becomes good, and it is suitable for use as a preparation for oral cavity. Bacterial removal rate determined by quantifying the number of bacteria is 200% or more, and more than that, the oral biofilm removal effect is enhanced, and the saliva secretion amount cannot be increased alone (A) in combination This improves the salivary secretion promoting effect derived from the component (B).

Accordingly, the present invention provides the following oral composition and method for suppressing oral mucosal irritation.
[1]
An oral composition comprising (A) a protease and (B) polyglutamic acid or a salt thereof.
[2]
(A) The composition for oral cavity according to [1], wherein the protease is one or more selected from papain, actinidine, bromelain and nattokinase.
[3]
(A) / (b) showing the ratio between the enzyme activity (U / g) per gram of the composition of the component (A) and the blending amount (mass%) of the component (B) relative to the whole composition is 400 to 200. The composition for oral cavity according to [1] or [2], which is 1,000.
[4]
(A) The compounding quantity of component is 80-40,000 U / g as enzyme activity per 1 g of compositions, and the compounding quantity of (B) component is 0.025-5 mass% with respect to the whole composition. A composition for oral cavity according to [1], [2] or [3].
[5]
The composition for oral cavity according to any one of [1] to [4], which is liquid or paste.
[6]
(A) Oral mucosal irritation of the oral composition characterized by comprising (B) polyglutamic acid or a salt thereof in an oral composition containing a protease, and (A) inhibiting oral mucosal irritation by the protease. Suppression method.
[7]
(A) / (b) showing the ratio between the enzyme activity (U / g) per gram of the composition of the component (A) and the blending amount (mass%) of the component (B) relative to the whole composition is 400 to 200. The method for suppressing oral mucosal irritation according to [6].

  ADVANTAGE OF THE INVENTION According to this invention, the oral cavity mucosal irritation | stimulation derived from a protease is suppressed, The composition for oral cavity effective in oral biofilm removal which provides the outstanding oral biofilm removal effect and saliva secretion promotion effect can be provided.

  The present invention will be described in further detail below. The present invention is characterized in that (A) protease and (B) polyglutamic acid or a salt thereof are used in combination.

  As the component (A) protease, those derived from plants and those derived from microorganisms are preferred. Specifically, papain contained in the fruit of papaya (Carica papaya), actinidine contained in the fruit of Kiwi (Actinidia deliciosa), bromelain contained in the fruit or rhizome of the pineapple (Ananas comosus), Bacillus natto production Nattokinase, bacterial proteases belonging to the genus Aspergillus (genus Aspergillus) and the genus Bacillus (genus Bacillus). These can be used alone or in combination of two or more. Among them, papain, actinidine, bromelain, and nattokinase are preferable because they provide a high oral biofilm removal effect, and papain, actinidin, and bromelain are particularly preferable. In particular, papain is more suitable because it has a high activity per unit mass and can obtain an oral biofilm removing effect in a relatively small amount.

As protease, what has an appropriate enzyme activity according to the kind can be used.
For example, papain has an enzyme activity of 200,000 to 2,500,000 U / g, particularly 800,000 U / g, and actinidine has an enzyme activity of 9,000 to 210,000 U / g, particularly 180,000 U. / G, bromelain has an enzyme activity of 300,000 to 500,000 U / g, especially 400,000 U / g, and nattokinase has an enzyme activity of 1,000 to 20,000 U / g, especially 20,000 U. / G can be used.

  The enzyme activity value of protease can be measured according to the measuring method described in the section of papain in the Food Additives Official Document. The outline of the measurement method is to determine how much protease can digest casein by absorbance (275 nm), and the amount of enzyme that produces an amino acid corresponding to 1 μg of tyrosine per minute is defined as 1 unit (U). Is done. In nattokinase, the amount of enzyme that is measured using fibrin instead of casein and increases the absorbance (275 nm) of the resulting fibrin degradation product by 0.01 per minute is defined as 1 unit (U).

  A commercially available protease can be used as the protease. Examples of the papain include refined papain manufactured by Mitsubishi Chemical Foods Co., Ltd., papain manufactured by Godo Shusei Co., Ltd., papain Y-20 manufactured by Yakult Pharmaceutical Co., Ltd., and papain W-40 manufactured by Amano Enzyme Co., Ltd. As actinidin, such as Zactinase manufactured by BN Co., Ltd., as bromelain, bromelain manufactured by Godo Seisei Co., Ltd., etc. As nattokinase, natto bacteria culture extract NSK-SD and Daiwa Pharmaceutical Co., Ltd. There are refined natto bacteria culture NKPC and the like. Examples of proteases produced by Aspergillus sp. Include Cochlase P manufactured by Mitsubishi Chemical Foods Co., Ltd., and examples of proteases produced by Bacilli spp. Include Aroase AP-10 manufactured by Yakult Yakuhin Kogyo Co., Ltd. and Protin SD-NY10 manufactured by Amano Enzyme Co., Ltd. Can be mentioned.

  In the oral composition of the present invention, the amount of (A) protease is preferably 80 to 40,000 U / g, more preferably 400 to 40,000 U / g, particularly preferably as the enzyme activity value per gram of the composition. Is 400 to 20,000 U / g. As the blending amount of the component (A) increases, the oral biofilm removal effect increases, and when it is 80 U / g or more, a sufficient oral biofilm removal effect can be obtained, and when it is 40,000 U / g or less, Oral mucous membrane irritation does not become strong, and sufficient stimulation suppression effect is obtained.

Furthermore, the compounding quantity with respect to the whole composition of protease can be suitably adjusted according to the kind of protease, and the enzyme activity value.
For example, when protease is used as the component (A), the blending amount thereof is preferably 0.01 to 5% (mass%, the same applies hereinafter) as an 800,000 unit (U / g) product, and more preferably 0.8. It is 05 to 2.5%.
When actinidine is used as the component (A), the blending amount thereof is preferably 0.04 to 22.2%, more preferably 0.22 to 11.1% as a 180,000 unit (U / g) product. .
(A) When using bromelain as a component, as for the compounding quantity, 0.02 to 10% is preferable as a 400,000 unit (U / g) product, More preferably, it is 0.1 to 5%.
When nattokinase is used as the component (A), the blending amount thereof is preferably 0.4% or more, more preferably 2% or more as a 20,000 unit (U / g) product.

  As the polyglutamic acid or salt thereof as component (B), polyglutamic acid synthesized by a chemically known method or natural polyglutamic acid obtained as a fermentation product from various γ-polyglutamic acid producing strains such as Bacillus natto Or these salts can be used and you may use a commercial item. Among these, natural polyglutamic acid or a salt thereof is preferable from the viewpoint of blending in an oral composition, and γ-polyglutamic acid or a salt thereof that can be industrially mass-produced is most preferable. Polyglutamic acid may be D-form or L-form, and D-form and L-form may be mixed.

  Polyglutamic acid is insoluble in water, but becomes water-soluble when converted into a salt. In this case, examples of the salt of polyglutamic acid include alkali metal salts or alkaline earth metal salts such as sodium salt, potassium salt, magnesium salt, and calcium salt, ammonium salt, ethanolamine salt, basic amino acid salt, and the like. If it can be used as a composition for use, there is no particular limitation. In addition, the neutralization degree of the salt can be arbitrarily selected depending on the purpose when the 1% concentration aqueous solution is in the range of pH 1-14.

As polyglutamic acid or a salt thereof, sodium polyglutamate represented by the following formula (1) is particularly preferable.
[—NH—CH (COONa) —CH ₂ CH ₂ —CO—] _n (1)
(In the formula, n = 66 to 33,112, preferably an integer of 331 to 13,245)

  The viscosity of polyglutamic acid or a salt thereof is not particularly limited, but the viscosity of a 4% aqueous solution at 25 ° C. by a measurement method using a BL type viscometer described later is preferably 10 to 200 mPa · s, more preferably 30 to 120 mPa · s. It is the range of s. Various viscosities can be used depending on the type of product.

Viscosity Measurement Method Take 96 g of water in a 200 mL beaker and add 4.0 g of γ-polyglutamic acid or a salt thereof to the beaker with stirring with a stirrer to completely dissolve it. Next, after leaving still in a 25 degreeC thermostat for 1 hour, the viscosity after 1 minute is measured correctly using a BL type | mold viscometer.
BL type viscometer: Tokyo Keiki B type viscometer Model BL
Rotor: No. 2
Rotation speed: 60rpm
Measurement temperature: 25 ° C

  As such polyglutamic acid or a salt thereof, specifically, commercially available polyglutamic acid manufactured by Meiji Food Materials, aminopiger manufactured by Toyobo, bio-PGA manufactured by Ichimaru Falcos, cult take manufactured by Ajinomoto Co., etc. Can be used.

  In the composition for oral cavity of the present invention, the blending amount of (B) polyglutamic acid or a salt thereof is preferably 0.025 to 5%, more preferably 0.1 to 5%, particularly preferably 0. 1 to 2.5%. The greater the amount, the greater the effect of removing the oral biofilm and the effect of promoting saliva secretion, and the effect of suppressing the oral mucosal stimulation. When 0.025% or more, the effect of removing the oral biofilm, the effect of promoting saliva secretion, Oral mucosal irritation suppression effect is obtained. If it is 5% or less, the effect of removing the oral biofilm is not lowered, which is preferable.

In the present invention, when the (A) component and the (B) component are combined in combination so that the ratio of the blending amount of both components is an appropriate ratio, the oral biofilm removal effect is further enhanced, and saliva secretion The promoting effect is also improved, and oral mucosal irritation can be further suppressed, which is preferable.
In this case, the ratio of the enzyme activity (a) (U / g) per 1 g of the composition of the component (A) and the blending amount (b) (%) to the total composition of the component (B) is shown. (B) is preferably 400 to 200,000, more preferably 1,000 to 100,000, particularly 1,000 to 1,000 from the viewpoint of suitably suppressing oral mucosal irritation and obtaining a high oral biofilm removal effect. It is preferably 40,000.

Furthermore, the blending ratio of the components (A) and (B) can be adjusted as appropriate according to the type of protease and the enzyme activity value, as well as the blending amount of the protease described above with respect to the entire composition.
For example, when papain (A1) is used as the component (A), the ratio between the blending amount of the papain as an 800,000 unit (U / g) product and the blending amount of the component (B) is shown (A1) / ( B) is preferably in a mass ratio of 0.05 to 25, in particular 0.1 to 13, especially 0.1 to 5.
In the case of using actinidine (A2) as the component (A), the ratio of the amount of actinidine as a 180,000 unit (U / g) product and the amount of the component (B) is shown (A2) / (B) However, the mass ratio is preferably 0.22 to 111, particularly 0.44 to 56.
When bromelain (A3) is used as the component (A), the ratio between the blended amount of bromelain as a 400,000 unit (U / g) product and the blended amount of the component (B) is shown (A3) / (B). However, 0.1-50, especially 0.2-25 are preferable as mass ratio.
When nattokinase (A4) is used as component (A), the ratio of the amount of nattokinase as a 20,000 unit (U / g) product to the amount of component (B) is shown (A4) / (B) However, the mass ratio is preferably 2 to 1,000, particularly 4 to 500.
When the blending ratio of the component (A) and the component (B) is within the above range, the oral biofilm removing effect and the oral mucosal irritation suppressing effect are more excellent. If the ratio is too small, sufficient oral biofilm removal effect may not be obtained. If the ratio is too large, oral mucosal irritation suppression effect may be reduced and cannot be obtained satisfactorily, or saliva secretion promoting effect may not be obtained satisfactorily. There is a case.

  The oral composition of the present invention is in the form of a liquid, paste, solid, etc., in various dosage forms such as mouthwash, mouth spray, toothpaste, liquid toothpaste, liquid toothpaste, dentifrice such as a toothpaste. Although it can be prepared, it can be suitably prepared as a dentifrice such as a mouthwash, a mouth spray, a toothpaste, a liquid dentifrice, a liquid dentifrice, etc., particularly in a liquid or paste form. In this case, in addition to the above components, an appropriate component according to the dosage form can be arbitrarily blended within a range not impeding the effects of the present invention. In the dentifrice, abrasives, thickeners, binders, surfactants and, if necessary, perfumes, sweeteners, colorants, preservatives, and other active ingredients can be blended. Liquid preparations such as mouthwashes can contain wetting agents, surfactants, solvents, and if necessary, flavorings, sweeteners, preservatives, buffers, active ingredients, and the like.

  As abrasives, silica-based abrasives such as silica gel, precipitated silica, aluminosilicate, zirconosilicate, dicalcium phosphate dihydrate and anhydrous, tricalcium phosphate, tetracalcium phosphate, calcium pyrophosphate, calcium carbonate, water Examples thereof include aluminum oxide, alumina, magnesium carbonate, tribasic magnesium phosphate, zeolite, hydroxyapatite, and synthetic resin abrasive. The blending amount of the abrasive is usually 0 to 50%, particularly 2 to 40%, especially 10 to 30%.

  Examples of the thickening agent (wetting agent) include sugar alcohols such as sorbit and xylit, and polyhydric alcohols such as glycerin and propylene glycol. The blending amount is usually 5 to 50%, particularly 20 to 45%.

  As the binder, an organic or inorganic binder can be blended. Specifically, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, cellulose derivatives such as cationized cellulose, alginic acid derivatives such as sodium alginate, gums such as xanthan gum, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, Examples thereof include organic binders such as polyvinylpyrrolidone, and inorganic binders such as gelling silica and gelling aluminum silica. The compounding amount of the binder is usually 0 to 10%, and when it is blended, it is 0.1 to 10%, particularly 0.5 to 5%.

As the surfactant, generally used anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants can be used.
Examples of anionic surfactants include alkyl sulfates such as sodium lauryl sulfate, N-acyl sarcosine salts such as sodium N-lauroyl sarcosine, N-acyl glutamates, N-alkyl-N-acyl taurate salts, lauryl sulfoacetic acid Examples thereof include sodium and sodium α-olefin sulfonate.
Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester and lactose fatty acid ester, sugar alcohol fatty acid esters such as maltitol fatty acid ester and lactitol fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, monolaurin Polyglycerin fatty acid esters such as hexaglyceryl acid, hexaglyceryl monomyristate, decaglyceryl monolaurate, decaglyceryl monomyristate, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate Polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil, and polyoxyethylene lauryl ether Polyoxyethylene higher alcohol ethers, fatty acid alkanolamides, such as lauric acid diethanolamide, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene polyoxypropylene fatty acid ester, and the like. Examples of amphoteric surfactants include betaines and imidazolines.
The compounding amount of the surfactant is usually 0 to 10%, particularly 0.01 to 5%.

  As a fragrance | flavor, the well-known fragrance | flavor used normally can be mix | blended suitably. For example, 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, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie oil, Natural fragrances such as coconut oil, Iris concrete, absolute peppermint, absolute rose, orange flower, and processing of these natural fragrances (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, powdered fragrance Etc.) fragrance, menthol, carvone, a Tolu, cineol, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted paramentane-3- Carboxamide, pinene, octylaldehyde, citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allylcyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, Butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cycloten, furfural, trimethylpyrazine, ethyl lactate, ethylthioacetate Used in oral compositions such as strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor, etc. The known perfume materials can be used in combination. Moreover, although a compounding quantity is not specifically limited, It is preferable to use said fragrance | flavor raw material 0.000001 to 1% in a composition. As a fragrance | flavor for perfume using the said fragrance | flavor material, it is preferable to use 0.1 to 2% in a composition.

Examples of the sweetener include saccharin sodium, and examples of the colorant include blue No. 1, yellow No. 4, titanium dioxide and the like.
Examples of the preservative include paraoxybenzoic acid esters such as methylparaben.

  As active ingredients, known compounds that are usually blended, for example, nonionic fungicides such as isopropylmethylphenol, cationic fungicides such as cetylpyridinium chloride, tranexamic acid, epsilon aminocaproic acid, allantoin, glycyrrhetinic acid, glycyrrhizic acid, etc. Anti-inflammatory agents, enzymes other than proteases such as dextranase, mutanase, amylase, fluorides such as sodium fluoride and sodium monofluorophosphate, water-soluble phosphate compounds, copper compounds such as copper gluconate, sodium chloride, Inorganic salts such as potassium nitrate and aluminum lactate, vitamins such as ascorbic acid and tocopherol acetate, zeolite, azulene, dihydrocholesterol, chlorophyll, soft extract of thyme, thyme, ogon, clove and other plant extracts, anticalculus agent, Such as plaque prevention agents. In addition, the said active ingredient can be mix | blended in an effective amount in the range which does not prevent the effect of this invention.

  EXAMPLES Hereinafter, although an Example, a comparative example, a formulation example is shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, “%” means “% by mass” unless otherwise specified.

[Examples and Comparative Examples]
Oral compositions (mouth wash) shown in Tables 1 to 3 were prepared by a conventional method, and this was evaluated as the test liquid by the following method. The results are shown in Tables 1-3.

(1) Evaluation method of oral biofilm removal effect The oral bacteria removal effect was evaluated by the following method, and the oral biofilm removal effect was determined from the results.
The removal effect of oral bacteria was measured by the following procedure for 10 subjects.
10 mL of the test solution was placed in the mouth, and the mouthwash that was rinsed and spouted for 30 seconds was collected in a 50 mL centrifuge tube. Furthermore, 10 mL of distilled water was added to the mouth, and the mouth was rinsed and spouted for 30 seconds, and this was collected in the same centrifuge tube to obtain a mouthwash discharge liquid.
After 1 mL of the mouthwash discharge liquid thus obtained was centrifuged at 10,000 G for 10 minutes, the supernatant was discarded, and a pellet made of oral bacteria removed by the mouthwash was obtained. Oral bacterial DNA was extracted from the pellet, and the number of bacteria was quantified by a real-time PCR method (Microbiology, 148, 257-266, 2002), which was defined as the number of bacteria removed by mouthwash. In addition, according to this method, the total number of removed bacteria including dead sterilization in addition to viable bacteria can be quantified.
The removal effect of oral bacteria was calculated by calculating the ratio of the number of bacteria removed with respect to the control (bacteria removal ratio (%)), assuming that the number of bacteria removed when rinsing with physiological saline as a control was 100%. The average value was determined and judged according to the following criteria, and the oral biofilm removal effect was evaluated from the results. For the control, the number of bacteria was quantified in the same manner as described above except that physiological saline was used instead of the test solution, and this was used as the number of bacteria removed by mouthwash.
Judgment results of “◎” and “○” were considered to have a high oral biofilm removal effect and pass.
Criteria ◎: 400% ≦ average value of bacteria removal ratio ○: 200% ≦ average value of bacteria removal ratio <400%
Δ: 100% <average of bacteria removal ratio <200%
×: Average value of bacteria removal ratio ≦ 100%

(2) Evaluation method of salivary secretion promoting effect Saliva secretion amount was measured by the following procedure for 10 subjects who complained of thirst by exercising vigorously on the day before the test.
First, the mouth was rinsed with 20 mL of physiological saline for 30 seconds and discharged, and then saliva was discharged and collected in a collection container. The amount of saliva collected 30 minutes after mouthwashing was measured, and this was used as a control saliva secretion amount. Thereafter, the sample was rinsed in the same manner using the test solution, and then saliva was collected, and the amount of saliva was measured, which was defined as the amount of saliva secreted after the sample solution was rinsed.
The salivary secretion-promoting effect was obtained by calculating the increase rate (%) of the saliva secretion amount after the mouth-rinsing of the test liquid with respect to the control with respect to the control, assuming that the saliva secretion amount of each control was 100% for 10 subjects. The rate was determined and judged according to the following evaluation criteria.
The judgment results of “○” and “と し た” were considered to pass the saliva secretion promoting effect and pass.
Criteria ◎: 150% ≦ average increase rate of saliva secretion amount ○: 120% ≦ average increase rate of saliva secretion amount <150%
Δ: 100% <average rate of increase in saliva secretion <120%
×: Average increase rate of saliva secretion amount ≦ 100%

(3) Evaluation method of oral mucosal irritation suppression effect About mucosal irritation after 20 mL of test solution was rinsed for 30 seconds, 10 subjects were subjected to sensory evaluation according to the following criteria, and an average value was obtained and evaluated based on the following evaluation criteria. did.
The judgment results of 及 び and ○ were judged to pass the oral mucosal irritation suppression effect and passed.
Criterion 4: Stimulation is sufficiently suppressed and no stimulation is felt 3: Stimulation is suppressed and stimulation is hardly felt 2: Stimulation is hardly suppressed and weak stimulation is felt 1: Stimulation cannot be suppressed Evaluation criteria ◎: Average value is 3.5 or more and 4 or less ○: Average value is 3 or more and less than 3.5 △: Average value is 2 or more and less than 3 points ×: Average value is 1 More than 2 points

＊；（（Ａ）成分の組成物１ｇあたりの酵素活性（Ｕ／ｇ））／（（Ｂ）成分の組成物全体に対する配合量（％））（以下、同様。）
＊＊；口腔粘膜刺激がなく、刺激を全く感じなかった。

*; (Enzyme activity per 1 g of composition of component (A) (U / g)) / (Amount of component (B) based on the total composition (%)) (hereinafter the same)
**: No oral mucosal irritation and no irritation.

  As shown in Table 1, Comparative Example 1 containing no component (B) has a poor oral biofilm removal effect, no salivary secretion promoting effect, and strong oral mucosal irritation even when the component (A) is included. It was. Comparative Example 2 containing no component (A) has no oral biofilm removal effect and poor salivary secretion promoting effect even if component (B) is included, but oral mucosal irritation is not included because component (A) is not included. There wasn't.

Details of the raw materials used are shown below.
Component (A) Papain: Purified papain (Mitsubishi Chemical Foods, Inc., enzyme activity value 800,000 U / g
)
Bromelain: Bromelain (Godoshusei Co., Ltd., enzyme activity value 400,000 U / g)
Actinidine: Zactinase (BTN Corporation, enzyme activity value 180,000
U / g)
Nattokinase: Natto bacillus culture extract NSK-SD (National Institute for Biological Sciences, fermentation
Elementary activity value 20,000 U / g)
Component (B) Sodium polyglutamate:
Sodium γ-polyglutamate (Meiji Food Material Co., Ltd.)
The viscosity of a 4% aqueous solution at 25 ° C. measured using a BL type viscometer in the same manner as described above was 85 mPa · s.

  Next, a prescription example is shown. The raw materials used are the same as described above. Each of the following formulation examples was excellent in oral biofilm removal effect and salivation promotion effect, and oral mucosal irritation was suppressed, and the usability was also good.

[Prescription Example 1] Toothpaste (A) Papain (enzyme activity value 800,000 U / g) 0.5%
(B) Sodium γ-polyglutamate 0.5
Sodium lauryl sulfate 1.5
70% sorbite solution 40
Propylene glycol 3
Sodium alginate 0.6
Xanthan gum 0.6
Saccharin sodium 0.2
Silicic anhydride 22
Fragrance 1.2
Water balance
Total 100.0%
(A) / (b); 8,000

[Prescription Example 2] Toothpaste (A) Papain (enzyme activity value 800,000 U / g) 0.1%
(B) Sodium γ-polyglutamate 0.2
Sodium lauryl sulfate 1.3
Lauroyl sarcosine sodium 0.1
Polyoxyethylene (60) hydrogenated castor oil 0.3
70% sorbite solution 40
Propylene glycol 3
Sodium carboxymethylcellulose 1.1
Sodium polyacrylate 0.5
Saccharin sodium 0.2
Sodium fluoride 0.21
Calcium phosphate 25
Silicic anhydride 5.0
Fragrance 1.2
Water balance
Total 100.0%
(A) / (b); 4,000

Claims (7)

  An oral composition comprising (A) a protease and (B) polyglutamic acid or a salt thereof.   (A) The composition for oral cavity according to claim 1, wherein the protease is at least one selected from papain, actinidine, bromelain and nattokinase.   (A) / (b) showing the ratio between the enzyme activity (U / g) per gram of the composition of the component (A) and the blending amount (mass%) of the component (B) relative to the whole composition is 400 to 200. The composition for oral cavity according to claim 1 or 2, which is 1,000.   (A) The compounding quantity of component is 80-40,000 U / g as enzyme activity per 1 g of compositions, and the compounding quantity of (B) component is 0.025-5 mass% with respect to the whole composition. The oral composition according to claim 1, 2 or 3.   The composition for oral cavity according to any one of claims 1 to 4, which is in a liquid or paste form.   (A) Oral mucosal irritation of the oral composition characterized by comprising (B) polyglutamic acid or a salt thereof in an oral composition containing a protease, and (A) inhibiting oral mucosal irritation by the protease. Suppression method.   (A) / (b) showing the ratio between the enzyme activity (U / g) per gram of the composition of the component (A) and the blending amount (mass%) of the component (B) relative to the whole composition is 400 to 200. The method of suppressing oral mucosal irritation according to claim 6, wherein