JP6011250B2 - Oral composition - Google Patents

Description

  The present invention relates to a composition for oral cavity which has an improved dental plaque removal effect by dextranase, an excellent plaque adhesion inhibiting effect, and a high caries prevention effect.

  Dextranase, a glucan-degrading enzyme, has the effect of chemically degrading dental plaque, and has been used in oral products as an active ingredient for preventing toothworms. It is an enzyme of dextranase in oral compositions. Various techniques for maintaining and stabilizing the activity and improving the effects have been proposed.

  It is known that a specific surfactant is effective for preventing the deactivation of dextranase and improving its action. In patent document 1 (Unexamined-Japanese-Patent No. 8-12543), in the composition for oral cavity containing water and an anionic surfactant by mix | blending polyglycerol fatty acid ester, fatty acid diethanolamide, and polyoxyethylene hydrogenated castor oil A technique of stabilizing and preventing the inactivation of the enzyme activity of dextranase which is easily inactivated is proposed. Patent Document 2 (Japanese Patent Laid-Open No. 10-306018) discloses the cause of caries and periodontal disease. It has been proposed that nonionic surfactants such as polyglycerin fatty acid esters are effective as agents for improving the activity of oral enzymes on plaque, which is a place for fungal activity. Patent Document 3 (Japanese Patent Application Laid-Open No. 2010-43016) proposes an oral composition for pets containing dextranase, polyglycerin fatty acid ester, green leaf alcohol and the like, which is a pasturela canis in pets such as dogs. It is disclosed that the effect of removing plaque by bacteria is excellent.

  On the other hand, it is effective to improve the retention of the dextranase enzyme in the oral cavity in order to make the degradation action due to the enzyme reaction more effective in the oral cavity. Therefore, the retention of the dextranase enzyme in the oral cavity is effective. Measures to improve have been taken. Patent Document 4 (Japanese Patent Application Laid-Open No. 2011-132139) improves the retention of dextranase in the oral cavity by combining a cationic polymer, a fatty acid amidopropyl betaine, and a cellulose derivative, thereby removing plaque. There are proposals for improved technology.

JP-A-8-12543 Japanese Patent Laid-Open No. 10-306018 JP 2010-43016 A JP 2011-132139 A

However, the effect of dextranase on plaque is not sufficient, and there is still room for improvement, and further improvement of the effect has been desired.
The present invention has been made in view of the above circumstances, and an oral composition having improved dental plaque removal effect by dextranase and having excellent dental plaque adhesion inhibiting effect and high dental caries prevention effect. The purpose is to provide.

  As a result of intensive studies to achieve the above object, the present inventors have found that (A) dextranase and (B) polyglycerin fatty acid ester, particularly glycerin, are contained in the oral composition, particularly dentifrice composition. When combined with a polyglycerin fatty acid ester in which a fatty acid having 8 to 24 carbon atoms is condensed to polyglycerin having 20 or more condensed and (C) an amphoteric surfactant, particularly coconut oil fatty acid amidopropyl betaine, It has been found that the effect of removing plaque from teeth can be improved, and an excellent effect of suppressing adhesion of plaque can be imparted. It was also found that dextranase can be stably retained over time. As a result, it was possible to provide an oral composition having a high dental caries preventive effect, which had an excellent plaque removing effect and plaque adhesion suppressing effect.

In the present invention, by blending the combined system of components (B) and (C), (A) the plaque removal effect of dextranase can be remarkably enhanced and a high plaque adhesion inhibitory effect can be imparted. ) Component alone or (C) component alone cannot be achieved. Even if the composition contains an anionic surfactant such as sodium lauryl sulfate having a strong protein denaturing action, dextranase can act stably and effectively to give the above-mentioned effects. In addition, the plaque removal force by the action improver of Patent Document 2 described above has a residual plaque rate of 89% or less, particularly 50% or less after reacting at 37 ° C. for 3 minutes. As shown in the examples below, the plaque removal rate is as high as 60% or more, further 80% or more after acting for 3 minutes at 37 ° C. and left to stand for 3 hours. The present invention, which has a special effect of being excellent in the effect of suppressing the adhesion of dirt, cannot be expected.
In the present invention, it is presumed that the combined system significantly increases the action on plaque, while maintaining the stability of dextranase, and exhibits the above effects.

Therefore, the present invention
Contains (A) dextranase, (B) one or more polyglycerol fatty acid esters selected from decaglyceryl laurate, decaglyceryl myristate and decaglyceryl oleate and (C) coconut oil fatty acid amidopropyl betaine Ri greens and, (B) content of the component 0.05 to 2% by weight, 0.1 to 5% by weight content of component (C), the mass component (B) / component (C) providing 0.02 der Ru mouth luminal cavity composition as a ratio.

  According to the present invention, dental plaque removal effect by dextranase is improved, it has an excellent plaque adhesion inhibitory effect, dextranase has good temporal stability, and has a caries prevention effect. A high oral composition can be provided.

  The present invention will be described in further detail below. The composition for oral cavity of the present invention contains (A) dextranase, (B) polyglycerin fatty acid ester, and (C) an amphoteric surfactant.

  (A) As the dextranase, dextranase obtained by a known method from a known dextranase-producing bacterium belonging to the genus Ketomium, Penicillium, Aspergillus, Spicaria, Lactobacillus, Servibrio, etc. is preferable. However, dextranase produced from other microorganisms can also be used. Commercially available products such as dextranase manufactured by Daiichi Sankyo Propharma Co., Ltd. can be used.

The blending amount of dextranase is preferably 1 to 200 units / g (U / g) in the composition, more preferably 2 to 50 units / g. In addition, 1 unit of dextranase is the amount of dextranase that produces free reducing sugar corresponding to 1 μmol of glucose per minute when an enzyme reaction is performed using dextran as a substrate.
Although dextranase can be blended in the composition with the number of units within the above range, usually, dextranase having 10,000 to 14,000 units / g is preferably used, for example, 13,000 units / g. In the case of using the above, the blending amount is preferably 0.0077 to 1.54% (mass%, the same applies hereinafter) of the entire composition.
As the amount of dextranase is increased, the effect of removing plaque and the effect of suppressing the adhesion of plaque are enhanced. However, in order to achieve the effect of the present invention satisfactorily, the blending at the above value or less is preferable.

  In the present invention, the combination of the polyglycerin fatty acid ester of the component (B) and the amphoteric surfactant of the component (C) enhances the plaque removal effect and provides an excellent plaque adhesion inhibiting effect. Is. If the component (B) or the component (C) is absent, the plaque removing power is not enhanced, and a high plaque adhesion suppressing effect cannot be obtained.

(B) As the polyglycerol fatty acid ester, a polyglycerol fatty acid ester in which a fatty acid having 8 to 24 carbon atoms is condensed to polyglycerol obtained by preferably condensing 2 to 20 glycerol can be used. Examples thereof include decaglyceryl laurate, decaglyceryl myristate, decaglyceryl oleate and the like, and one or more of these can be used. Of these, decaglyceryl laurate is preferable because of its superior effect.
Commercially available products can be used, and specifically, products manufactured by Sakamoto Pharmaceutical Co., Ltd. and products manufactured by Nikko Chemicals Co., Ltd. can be used.

  (B) 0.05-2% of the whole composition is preferable, and, as for the compounding quantity of polyglycerol fatty acid ester, More preferably, it is 0.05-1.5%. As the amount is increased, the plaque removal effect is enhanced and the plaque adhesion inhibiting effect is improved. However, 2% or less is desirable for stably maintaining dextranase and providing the plaque removal effect.

  As the amphoteric surfactant of component (C), a betaine type surfactant is used. For example, fatty acid amidopropyl betaine such as coconut oil fatty acid amidopropyl betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazo Examples thereof include alkylimidazolinium betaines such as linium betaine and alkylbetaines. These can use 1 type (s) or 2 or more types. Among these, use of fatty acid amidopropyl betaine and alkylimidazolinium betaine, particularly coconut oil fatty acid amidopropyl betaine, is preferable because it can improve the plaque removing power and improve the effect of inhibiting the adhesion of plaque.

  The amphoteric surfactant is specifically trade name as palm oil fatty acid amidopropyl betaine; trade name as TEGO Betaine CK OK (manufactured by EVONIK), 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine; Commercially available products such as Enagicol C-40H (manufactured by Lion Corporation) can be used.

  The blending amount of the amphoteric surfactant (C) is preferably from 0.1 to 5%, more preferably from 1 to 3% of the entire composition. As the amount is increased, the effect of suppressing the adhesion of plaque is enhanced and the effect of removing the plaque is improved. However, 5% or less is preferable for stably maintaining dextranase.

  In the present invention, it is preferable that the component (B) and the component (C) have an appropriate blending ratio because the plaque removing effect and the plaque adhesion inhibiting effect are more excellent, and the stability of dextranase is more excellent. The component (B) / component (C) has a mass ratio of preferably 0.01 to 20, more preferably 0.02 to 1, and still more preferably 0.05 to 0.2.

  The composition for oral cavity of the present invention is suitably prepared as a dentifrice such as a toothpaste, a liquid dentifrice, a liquid dentifrice, and a moisturized dentifrice, particularly as a toothpaste. Moreover, in addition to the said component, another well-known component can be mix | blended as needed in the range which does not prevent the effect of this invention. In the toothpaste, abrasives, binders, thickeners, surfactants, and if necessary, sweeteners, colorants, preservatives, fragrances, active ingredients and the like can be blended.

  As abrasives, silica-based abrasives such as silica gel, precipitated silica, aluminosilicate, zirconosilicate, dicalcium phosphate dihydrate and anhydrous, tricalcium phosphate, tetracalcium phosphate, tribasic magnesium phosphate, pyro Examples thereof include calcium phosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, zeolite, hydroxyapatite, and a synthetic resin abrasive. The blending amount of these abrasives is preferably 2 to 40%, particularly 10 to 30% of the entire composition.

  Examples of the thickener include sugar alcohols such as sorbit, xylite, maltite, and lactit, and polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol. The amount is usually 5 to 50%, particularly 20 to 45%.

  As the binder, an organic or inorganic binder can be blended. Specifically, cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, sodium alginate, alginic acid derivatives, gums such as xanthan gum and gum arabic, organic binders such as carrageenan and sodium polyacrylate, gels Inorganic binders such as elastogenic silica, gelled aluminum silica, bee gum, and laponite. Although the compounding quantity of a binder is adjusted with dosage form, toothpaste is 0.1 to 5% normally.

As the surfactant, an anionic surfactant, a nonionic surfactant, and a cationic surfactant can be blended as long as the effects of the present invention are not hindered.
Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, and N-acyl sarcosine salts such as sodium N-lauroyl sarcosine.
Nonionic surfactants include those other than polyglycerin fatty acid esters, such as 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, Polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan fatty acid ester such as polyoxyethylene sorbitan monostearate, polyoxyethylene fatty acid ester such as polyoxyethylene hydrogenated castor oil, polyoxyethylene higher alcohol such as polyoxyethylene lauryl ether Ethers, fatty acid alkanolamides such as lauric acid diethanolamide, polyoxyethylene polyoxypropylene copolymers, and the like are used. Examples of the cationic surfactant include alkyl ammonium and alkyl benzyl ammonium salts.
The blending amount of these surfactants is preferably 0 to 10%, particularly preferably 0.1 to 5%.
The composition of the present invention may contain an anionic surfactant, particularly an alkyl sulfate such as sodium lauryl sulfate. The amount is preferably 2% or less with respect to the whole composition. Although 0.1 to 1% is good, 0% may be sufficient. In order to maintain dextranase stably and to provide a better effect, it is desirable that the content is 2% or less based on the entire composition.

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

  Perfumes include 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 Natural fragrances such as oil, 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, powder flavor Perfume, menthol, cal , Anethole, Cineol, Methyl salicylate, Synamic aldehyde, Eugenol, 3-l-Mentoxypropane-1,2-diol, Thymol, Linalol, Linaryl acetate, Limonene, Menthone, Menthyl acetate, N-Substituted paramenthane 3-carboxamide, pinene, octyl aldehyde, 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, ethylthio For oral compositions such as single flavors such as cetate, and other flavors 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 used can be used in combination.

  Active ingredients include non-ionic fungicides such as isopropylmethylphenol, cationic fungicides such as cetylpyridinium chloride and benzalkonium chloride, anti-inflammatory agents such as tranexamic acid, epsilon aminocaproic acid, allantoin, glycyrrhetinic acid and glycyrrhizic acid , Enzymes such as amylase, protease, lysozyme, fluorides such as sodium fluoride and sodium monofluorophosphate, water-soluble phosphate compounds such as potassium salt and sodium salt of orthophosphate, condensed phosphates such as sodium polyphosphate , Copper compounds such as copper gluconate and copper chlorophyllin sodium, inorganic salts such as potassium nitrate and aluminum lactate, vitamins such as ascorbic acid and tocopherol acetate, plant extracts such as sweet potato extract, thyme, ogon and clove . 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]
Dentifrice compositions having the compositions shown in Tables 1 and 2 were prepared by a conventional method, and the obtained dentifrice composition was used as a sample and evaluated by the following method. The results are shown in Tables 1 and 2.

(I) Evaluation of plaque removal ability After culturing Sobrinas strain 6715 in 3% TSB (Tryptic Soy Broth) aqueous solution using a test tube for 24 hours, 3% TSB aqueous solution containing 1% sucrose The cells were further cultured for 24 hours, and plaques were cultured in test tubes. The test tube to which the plaque adhered was washed twice with water, 4 mL of a 3-fold diluted sample supernatant was added, and the mixture was allowed to act at 37 ° C. for exactly 3 minutes. Thereafter, it was washed with water, 4 mL of a pH 6.0, 0.1 M phosphate buffer solution was added, and the mixture was allowed to stand in a 37 ° C. constant temperature bath for 3 hours. After standing, it was washed with water, 4 mL of water was added, the plaque was crushed using an ultrasonic crusher, and the turbidity of the test tube at an absorption wavelength of 550 nm was measured using an absorptiometer (ΔT1). As a control, turbidity was measured using water instead of toothpaste supernatant (ΔT0).
The plaque removal power was evaluated based on the following criteria from the plaque removal rate calculated by the following formula.
Dental plaque removal rate (%) = (ΔT1−ΔT0) ÷ ΔT1 × 100
Evaluation criteria ◎: Plaque removal rate is 80% or more ○: Plaque removal rate is 60% or more and less than 80% △: Plaque removal rate is 20% or more and less than 60% ×: Plaque removal rate is less than 20%

(II) Evaluation of plaque adhesion inhibitory effect 8 mL of the sample supernatant (diluted 3 times) was added to the HAP pellet and immersed for 10 minutes at room temperature. Mutans (Streptococcus mutans) 10449 culture solution 8mL was added, and it anaerobically cultured at 37 degreeC for 24 hours. After washing with water, it was stained with a plaque tester 2-fold diluted solution, washed with water and air-dried, and then the color difference ΔE1 value of the pellet was measured. As a control, the color difference ΔE0 value of the pellet treated with water was measured. From these color difference values, the plaque adhesion inhibition rate was calculated according to the following formula, and the higher the plaque adhesion inhibition rate, the better the plaque adhesion inhibition effect, and the evaluation was made based on the following criteria.
Plaque adhesion inhibition rate (%) = (ΔE1−ΔE0) ÷ ΔE1 × 100
Evaluation criteria ◎: Plaque adhesion inhibition rate is 30% or more ○: Plaque adhesion inhibition rate is 15% or more and less than 30% △: Plaque adhesion inhibition rate is 10% or more and less than 15% ×: Plaque adhesion inhibition rate is 10 %Less than

(III) Evaluation of stability of dextranase 50 g of a dextranase-containing sample was filled in a 26 mm diameter laminated tube made of linear low density polyethylene and stored at 45 ° C. for 2 weeks. 0.6 g of the product was suspended in 15 mL of 0.1 M phosphate buffer, and the centrifuged supernatant was used as a test solution. 1 mL of this test solution was added to 2 mL of a 1% dextran solution, reacted in a constant temperature water bath at 40 ° C. for exactly 10 minutes, and the amount of reducing sugar produced was measured using the Somogy Nelson method. One unit of dextranase was defined as the amount of dextranase that produces free reducing sugar corresponding to 1 μmol of glucose per minute, and the average of three repetitions was evaluated according to the following criteria.
Evaluation criteria A: Dextranase remaining rate of 90% or more ○: Dextranase remaining rate of 80% or more and less than 90% Δ: Dextranase remaining rate of 60% or more and less than 80% ×: Dextranase remaining rate of less than 60%

Details of the raw materials used are shown below.
Dextranase: Dextranase, Mitsubishi Corporation Foodtech Co., Ltd. Decaglyceryl Laurate: ML-750, Sakamoto Pharmaceutical Co., Ltd. Decaglyceryl: O-1001P, Sakamoto Pharmaceutical Co., Ltd. palm oil fatty acid amidopropyl betaine:
TEGO Betaine CK OK (30% aqueous solution product), imidazolinium betaine manufactured by EVONIK:
Enadicol C-40H (2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine), manufactured by Lion Corporation

＊１：ヤシ油脂肪酸アミドプロピルベタイン液（３０％品）を使用。配合量には純分換算した値を記載（以下、同様。）。
＊２：２−アルキル−Ｎ−カルボキシメチル−Ｎ−ヒドロキシエチルイミダゾリニウムベタイン

* 1: Uses palm oil fatty acid amidopropyl betaine solution (30% product). The blending amount is a value converted into a pure content (hereinafter the same).
* 2: 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine

  A prescription example is shown below. All of these dentifrice compositions were excellent in plaque removal power, plaque adhesion inhibitory effect, and dextranase stability over time.

[Prescription Example 1]
(A) Dextranase (13,000 units / g) 0.15
(B) Decaglyceryl laurate 0.1
(C) Coconut oil fatty acid amidopropyl betaine ^{* 1} 2.0
Propylene glycol 3
Polyethylene glycol 1.0
Sodium fluoride 0.21
Sorbit 28
Xanthan gum 0.7
Sodium alginate 0.5
Silicic anhydride 25
Sodium lauryl sulfate 0.8
Xylit 1.0
Titanium oxide 0.4
Fragrance 1.3
Purified water balance
Total 100.0%
(B) component / (C) component = 0.05

[Prescription Example 2]
(A) Dextranase (13,000 units / g) 0.15
(B) Decaglyceryl laurate 0.1
(C) Coconut oil fatty acid amidopropyl betaine ^{* 1} 2.0
Propylene glycol 3
Polyethylene glycol 1.0
Sodium fluoride 0.21
Sorbit 28
Xanthan gum 0.7
Sodium alginate 0.5
Silicic anhydride 25
Sodium lauryl sulfate 0.8
Hydroxyethyl cellulose dimethyl diallylammonium chloride
0.05
Titanium oxide 0.4
Fragrance 1.3
Purified water balance
Total 100.0%
(B) component / (C) component = 0.05

[Prescription Example 3]
(A) Dextranase (13,000 units / g) 0.15
(B) Decaglyceryl laurate 0.1
(C) Coconut oil fatty acid amidopropyl betaine ^{* 1} 2.0
Propylene glycol 3
Polyethylene glycol 1.0
Sodium fluoride 0.21
Sorbit 28
Xanthan gum 0.7
Sodium alginate 0.5
Silicic anhydride 25
Sodium lauryl sulfate 0.8
Tocopherol acetate 0.10
Titanium oxide 0.4
Fragrance 1.3
Purified water balance
Total 100.0%
(B) component / (C) component = 0.05

[Prescription Example 4]
(A) Dextranase (13,000 units / g) 0.15
(B) Decaglyceryl laurate 0.1
(C) Coconut oil fatty acid amidopropyl betaine ^{* 1} 2.0
Propylene glycol 3
Polyethylene glycol 1.0
Sodium fluoride 0.21
Sorbit 28
Xanthan gum 0.7
Sodium alginate 0.5
Silicic anhydride 25
Sodium lauryl sulfate 0.8
Sodium polyphosphate 0.5
Titanium oxide 0.4
Fragrance 1.3
Purified water balance
Total 100.0%
(B) component / (C) component = 0.05

Claims (3)

Contains (A) dextranase, (B) one or more polyglycerol fatty acid esters selected from decaglyceryl laurate, decaglyceryl myristate and decaglyceryl oleate and (C) coconut oil fatty acid amidopropyl betaine Ri greens and, (B) content of the component 0.05 to 2% by weight, 0.1 to 5% by weight content of component (C), the mass component (B) / component (C) oral composition, wherein 0.02 to der Rukoto as a ratio. The composition for oral cavity according to claim 1, wherein the content of the component (A) is 1 to 200 units / g. The composition for oral cavity according to claim 1 or 2, which is a dentifrice.