JP7031253B2 - Toothpaste composition - Google Patents

Description

The present invention relates to an isopropylmethylphenol-containing dentifrice composition, which has an antibacterial effect on oral bacteria for a long period of time and is suitable for prevention or suppression of dental caries and periodontal disease.

In order to kill oral bacteria that cause oral diseases such as caries and periodontal disease, use an oral composition such as a dentifrice containing a bactericidal agent or an antibacterial agent, and go to bed as a preferable preventive measure. It is widely known that it is recommended to brush the teeth before, but it is difficult to completely kill the pathogenic bacteria in the oral cavity. In particular, the oral cavity during sleep is maintained at a temperature and humidity at which bacteria can easily grow, so that the number of bacteria in the oral cavity tends to increase dramatically overnight. Therefore, for example, it is considered effective if the dentifrice is brushed before going to bed and the antibacterial effect is maintained even after sleeping overnight and even when waking up. It is hard to say, and a dentifrice composition capable of obtaining an antibacterial effect that lasts for a long time, for example, sleeping overnight and even when waking up, has been desired.

Various techniques for improving the action of oral bactericides and antibacterial agents have been proposed. For example, as a non-ionic bactericidal agent, isopropylmethylphenol has a biofilm penetrating bactericidal action, and in order to improve its bactericidal activity, a specific fragrance component and an anionic surfactant acyltaurine salt, a specific sugar alcohol, or the like are used. The blended dentifrice composition has been proposed in Patent Documents 1 and 2 (Japanese Patent Laid-Open Nos. 2011-98916 and 2011-98918), but the sustainability of bactericidal activity is not mentioned and is unknown. be. Further, Patent Document 3 (Patent No. 5568876) proposes a demineralization inhibitor in which isopropylmethylphenol and arabitol are used in combination, and may be incorporated into an oral composition such as a mouthwash together with a surfactant. Is disclosed.

On the other hand, it can be applied to the prevention of dental caries and bad breath due to its antibacterial action as well as the improvement of usability of tea extract such as green tea as a compounding component of the oral composition. It is disclosed in Japanese Patent No. 222419, Japanese Patent No. 5067529, Japanese Patent Application Laid-Open No. 2006-199661, International Publication No. 2013/100089), but does not mention the sustainability of the antibacterial effect.

Japanese Unexamined Patent Publication No. 2011-98916 Japanese Unexamined Patent Publication No. 2011-98918 Japanese Patent No. 5568876 Japanese Unexamined Patent Publication No. 11-22419 Japanese Patent No. 5067529 Japanese Unexamined Patent Publication No. 2006-199661 International Publication No. 2013/100089

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a dentifrice composition in which an antibacterial effect against oral bacteria is maintained for a long period of time.

As a result of diligent studies to achieve the above object, the present inventor combined isopropylmethylphenol among oral disinfectants with a specific anionic surfactant and cha extract to make an oral composition, especially a dentifrice. When blended in the agent composition, the sustainability of the antibacterial effect is remarkably improved, the antibacterial effect that lasts for a long time immediately after brushing the teeth can be imparted, and the irritation and dislike are suppressed and the usability is improved. I found out. That is, according to the present invention, the dentifrice composition containing (A) isopropylmethylphenol, (B) α-olefin sulfonate, and (C) cha extract has a long-term antibacterial effect on oral bacteria. We have found that it can be sustained for a long time and can be given a mild and tasty feeling of use, and have led to the present invention.

More specifically, the antibacterial effect of the oral antibacterial agent is not sufficiently sustained, and the antibacterial effect of Cha Extract is weak and persistent. On the other hand, surfactants such as anionic surfactants, which are general-purpose components of dentifrice compositions, are generally known to have a cleaning action and a certain degree of antibacterial effect, but depending on the surfactant. It was not possible to give a satisfactory antibacterial effect. However, in the present invention, when combined with the components (A), (B) and (C), surprisingly, the three act synergistically to deal with oral bacteria, especially pathogenic bacteria such as periodontal disease. The sustainability of the antibacterial effect was remarkably improved, and an excellent antibacterial effect that lasted for a long time immediately after brushing the teeth could be imparted. In addition, although the component (A) has a unique sarcasm and the component (B) has a unique stimulus and bitterness, when the three are combined, these components unexpectedly interact with each other to achieve the above-mentioned sarcasm. It was also possible to sufficiently suppress irritation and give a good feeling of use. Therefore, according to the present invention, it is possible to continuously antibacterialize oral bacteria that cause oral diseases such as dental caries and periodontal disease for a long period of time, and effectively prevent or suppress them.
In the present invention, the combination of the components (A), (B) and (C) gives a specific and special action and effect as an antibacterial agent for the oral cavity, and the action and effect, particularly the sustainability of the antibacterial effect, is As is clear from the results of the comparative examples described later, the lack of any of the components (A), (B) or (C) was inferior (Comparative Examples 2 to 5). In this case, if the component (A) is not blended, the durability of the antibacterial effect (after 8 hours) is inferior even if the antibacterial agents triclosan and the components (B) and (C) are blended (Comparative Example). 3) If the components (B) are not blended, the components (A) and (C) are blended, and even if the anionic surfactant sodium lauryl sulfate is blended, the antibacterial effect is sustained (8). After hours) was inferior (Comparative Example 4).

Therefore, the present invention provides the following dentifrice composition.
[1]
(A) Isopropylmethylphenol,
A dentifrice composition comprising (B) α-olefin sulfonate and (C) cha extract.
[2]
It contains 0.001 to 0.1% by mass of the component (A), 0.1 to 2% by mass of the component (B), and 0.0007 to 0.01% by mass of the pure extract of the component (C) [1]. ] The dentifrice composition according to.
[3]
The dentifrice composition according to [1] or [2], which is a dentifrice.

According to the present invention, it is possible to provide a dentifrice composition that has an antibacterial effect on oral bacteria for a long period of time and has a good usability. Since the antibacterial effect of the dentifrice composition of the present invention is maintained even after use, it is more effective by preventing the increase of oral bacteria that cause oral diseases such as dental caries and periodontal disease for a long period of time. It is possible to prevent or suppress oral diseases such as dental caries and periodontal disease in a targeted and effective manner.

Hereinafter, the present invention will be described in more detail. The dentifrice composition of the present invention contains (A) isopropylmethylphenol, (B) α-olefin sulfonate and (C) cha extract.

(A) Isopropylmethylphenol is an antibacterial agent, and the blending amount thereof is preferably 0.001 to 0.1% (mass%, the same applies hereinafter) of the entire composition, and more preferably 0.01 to 0.06. %. When the blending amount is 0.001% or more, a sufficient antibacterial effect is exhibited, and when it is 0.1% or less, the peculiar sarcasm due to itself is sufficiently suppressed.

When the (B) α-olefin sulfonate is used in combination with the (C) cha extract, it acts as an agent for improving the sustainability of the antibacterial action of the component (A) and also as an agent for suppressing the sarcasm of the component (A). It works.
(B) As the α-olefin sulfonic acid salt, an alkali metal salt such as sodium or potassium of the α-olefin sulfonic acid having 10 to 16 carbon atoms, particularly 14 to 16 carbon atoms can be used. An α-olefin sulfonate having 14 carbon atoms, particularly a sodium salt (generic name; sodium tetradecene sulfonate) is preferable.
For these, commercially available products that can be used for oral preparations, for example, trade name "K Liporan PJ-400CJ" manufactured by Lion Specialty Chemicals Co., Ltd. can be used.

The blending amount of the α-olefin sulfonate (B) is preferably 0.1 to 2%, more preferably 0.3 to 1% of the total composition. When the blending amount is 0.1% or more, a long-lasting antibacterial effect can be sufficiently obtained. When it is 2% or less, irritation and bitterness due to itself are sufficiently suppressed, and a hypoallergenic feeling of use is obtained.

(C) Cha extract acts as a long-lasting agent for the antibacterial action of the component (A) when used in combination with the component (B), and also suppresses the sarcasm of the component (A) and the irritation of the component (B). Also works as.
As the cha extract, a commercially available product or a product obtained by a known method can be used.
Specifically, green tea can be used as the raw material. A hydrophilic solvent can be used as the extraction solvent, and examples thereof include water, lower monohydric alcohols such as ethanol and propanol, and polyhydric alcohols such as 1,3-butylene glycol and propylene glycol. A solvent or a mixed solvent of two or more kinds can be used. Normal methods can be used for extraction conditions and post-processing.
Examples of commercially available products include green tea extract (“Wa ism”, manufactured by Maruzen Pharmaceuticals Co., Ltd.) and the like.

The blending amount of the cha extract (C) is preferably 0.0007 to 0.01%, more preferably 0.001 to 0.005%, as the pure extract content excluding the solvent. When the blending amount is 0.0007% or more, a long-lasting antibacterial effect can be sufficiently obtained, and when it is 0.01% or less, deterioration of taste (sarcasm) can be prevented and a good usability can be maintained.

In the present invention, the blending ratio of the component (B) or the component (C) to the component (A), or the blending ratio of the component (B) and the component (C) is not particularly limited, but each of the above-mentioned components is not particularly limited. It can be set within a range that satisfies the blending amount of.

The dentifrice composition of the present invention can be prepared by a usual method as a dentifrice, a liquid dentifrice such as a liquid dentifrice, a dentifrice, and the like, and is particularly suitable as a dentifrice. Further, in addition to the above-mentioned components, other known components can be blended, if necessary, within a range that does not interfere with the effects of the present invention. For example, in dentifrices, abrasives, wetting agents, binders, surfactants other than the component (B), and if necessary, coloring agents, sweeteners, preservatives, fragrances, components other than the components (A) and (C) It may contain active ingredients and the like. The blending amount of these may be a normal amount as long as the effect of the present invention is not impaired.

Examples of the abrasive include silica-based abrasives such as precipitate silica, aluminosilicate and zirconosilicate, calcium phosphate-based compounds, calcium carbonate, and synthetic resin-based abrasives, and silica-based abrasives are particularly preferable. The blending amount of the abrasive is usually 2 to 50%, particularly 10 to 30%.

Examples of the wetting agent include sugar alcohols such as sorbitol and xylit, and polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol having an average molecular weight of 160 to 400 (average molecular weight described in the non-medicinal product raw material standard 2006). The blending amount of the wetting agent is usually 5 to 50%, particularly 10 to 30%.

As the binder, an organic or inorganic binder can be blended. Specifically, cellulose derivatives such as sodium carboxymethyl cellulose, methyl cellulose and hydroxymethyl cellulose, arginic acid derivatives such as propylene glycol alginate, gums such as xanthan gum, organic binders such as carrageenan, polyvinyl alcohol and sodium polyacrylate, and gelation. Examples thereof include inorganic binders such as thickening silica such as sex silica and gelling aluminum silica.
The blending amount of the binder is usually 0.1 to 10%, particularly 0.1 to 5%. In the present invention, the blending of the organic binder and the inorganic binder is preferable, the blending amount of the organic binder is 5% or less, particularly 3% or less, and the blending amount of the inorganic binder is 5% or less. Especially, 2% or less is good.

As the surfactant, an anionic surfactant other than the component (B), a nonionic surfactant, a cationic surfactant, and an amphoteric surfactant can be blended.
Examples of the anionic surfactant include alkyl sulfates such as lauryl sulfate.
Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, sugar alcohol fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil and the like. Examples thereof include polyoxyethylene fatty acid ester, polyoxyethylene higher alcohol ether, and fatty acid alkanolamide.
Examples of the cationic surfactant include an alkylammonium type and an alkylbenzylammonium salt. Examples of the amphoteric tenside include an acetate betaine type such as alkyl betaine and fatty acid amide propyl betaine, a betaine type such as alkyl imidazolinium betaine, an imidazoline type, and an imidazolium betaine type.
The blending amount of the surfactant is usually 0 to 10%, particularly 0.1 to 5%.
The preferable blending amount of the anionic surfactant other than the component (B), particularly lauryl sulfate, is 1 to 5%, particularly 1 to 3%. The preferable blending amount of the nonionic surfactant is 0 to 2%.

Examples of the colorant include Blue No. 1, Yellow No. 4, Titanium Dioxide and the like. Examples of the sweetener include saccharin sodium and the like.
Examples of the preservative include paraoxybenzoic acid esters such as methylparaben and butylparaben, benzoic acid or salts thereof and the like.

Fragrances include peppermint oil, sparemint oil, anis oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamon oil, coriander oil, mandarin oil, Lime oil, lavender oil, rosemary oil, laurel oil, camomill oil, caraway oil, majorum oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie Natural fragrances such as oil, yuzu oil, iris concrete, absolute peppermint, absolute rose, orange flower, and processing of these natural fragrances (front reservoir cut, rear reservoir cut, distilling, liquid extraction, essence, powder fragrance) Perfume, menthol, carboxylic, anator, cineole, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-mentoxypropane-1,2-diol, timole, linalol, linalyl acetate, limonene, menton , Menthylacetate, N-substituted-paramentan-3-carboxamide, pinen, octylaldehyde, citral, pregon, calbea acetate, anisaldehyde, ethylacetate, ethylbutyrate, allylcyclohexanepropionate, methylanthranilate, ethylmethyl Single flavors such as phenylglycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethylsulfide, cycloten, furfural, trimethylpyrazine, ethyllactate, ethylthioacetate, as well as strawberry flavor, apple flavor, banana flavor. , Peppermint flavor, Grape flavor, Mango flavor, Butter flavor, Milk flavor, Fruit mix flavor, Tropical fruit flavor, etc., can be used in combination with known fragrance materials used in dentifrice compositions. It is not limited to the fragrances described in the examples.
The blending amount of the fragrance is not particularly limited, but it is preferable to use 0.000001 to 1% of the above fragrance material in the composition, and the fragrance for fragrance using the above fragrance material is 0. It is preferable to use 1 to 2%.

The active ingredient is known as a medicinal ingredient for the oral cavity, for example, a cationic bactericidal agent such as cetylpyridinium chloride, an anti-inflammatory agent such as tranexamic acid and allantin, and a fluorine-containing compound such as sodium fluoride and sodium monofluorophosphate. , Enzymes, plant extracts, anti-dental agents, anti-plaque agents and the like. These can be blended in an effective amount.

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following,% indicates mass% unless otherwise specified.

[Examples, comparative examples]
Toothpaste compositions (dentifrices) having the compositions shown in Tables 1 to 3 were prepared by a conventional method and evaluated by the following method. The results are also shown in the table.

(1) Evaluation method of antibacterial effect immediately after application and persistence of antibacterial effect (after 8 hours)-1
(1-1) Preparation of model biofilm 4 hours with human non-irritating saliva obtained by filtering a hydroxyapatite (HA) plate (manufactured by Asahi Optical Co., Ltd.) having a diameter of 7 mm and a thickness of 3.5 mm with a 0.45 μm filter. The treated product was used as a model biofilm preparation carrier. The culture solution is 5 mg / L of hemin (manufactured by Sigma) and 1 mg / L of vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.) in a solution prepared by dissolving 30 g of trypticase soybros (manufactured by Difco) in 1 L of purified water. Was added.
As the oral bacteria, Streptococcus mutans ATCC25175 strain, Streptococcus sanguinis ATCC10556 strain, Actinomyces naeslandy ATCC51655 strain, Fuzobacterium nucleotam ATCC10953 strain, and Bayonera palbra ATCC1745 strains were used, respectively, and 5 strains thereof were used. Inoculate the above-mentioned culture solution to 10 ⁷ cfu / mL (colony forming units), and together with a saliva-treated HA carrier at 37 ° C. under anaerobic conditions (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) 2 Continuous culture was carried out for a week (the replacement rate of the culture solution was 10 vol%), and a model biofilm containing 5 bacterial species was formed on the surface of the HA carrier.

(1-2) Evaluation method of antibacterial effect immediately after application The formed model biofilm is centrifuged after adding twice the mass of artificial saliva ^* to the evaluation agent (toothpaste composition to be evaluated), dispersing it, and then centrifuging it. Qing) Soaked in 2 mL for 3 minutes and washed 6 times with 1 mL of sterile saline. Then, by sonication (200 μA, 10 seconds) in 4 mL of sterile saline, the model biofilm was dispersed in sterile saline, and 50 μL was smeared on a Bacteroides agar plate until colonies could be confirmed with the naked eye. Anaerobic culture (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) was performed. The number of grown colonies was counted, the number of remaining viable bacteria (cfu) was determined, and the determination was made according to the following criteria.
*; Artificial saliva composition (solvent; water, pH 6.5)
CaCl ₂ 2.2 mmol / L
KH ₂ PO ₄ 2.2 mmol / L
Acetic acid 0.1 mol / L
Collagenase derived from Clostridium collagenase (Type 1A, manufactured by Sigma) 1.0 unit / mL
<Evaluation criteria>
⊚: cfu is less than 10 ⁶ ○: cfu is 10 ⁶ or more and less than 10 ⁷ ×: cfu is 10 ⁷ or more

(1-3) Method for evaluating the persistence of antibacterial effect (after 8 hours) The formed model biofilm was added to 2 mL of the evaluation agent (toothpaste composition supernatant obtained in the same manner as in (1-2)). The cells were soaked for 3 minutes, washed 6 times with 1 mL of sterile physiological saline, and then anaerobically cultured at 37 ° C. for 8 hours. After culturing, the model biofilm is dispersed in sterile saline by ultrasonic treatment (200 μA, 10 seconds) in 4 mL of sterile saline, and 50 μL is smeared on a Bacteroides agar plate, and colonies can be confirmed with the naked eye. Up to anaerobic culture (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen). The number of grown colonies was counted, the number of remaining viable bacteria (cfu) was determined, and the determination was made according to the following criteria.
<Evaluation criteria>
⊚: cfu is less than 10 ⁷ ○: cfu is 10 ⁷ or more and less than 10 ⁸ ×: cfu is 10 ⁸ or more

(2) Evaluation method of usability (hypoallergenicity) Evaluation was made by a sensory test using 10 expert panelists. 1 g of the dentifrice composition was placed on a toothbrush and brushed for 3 minutes in the same manner as usual, and the irritation to the tongue and oral mucosa felt during use was judged according to the following score criteria.
<Score criteria>
4 points: No stimulus at all 3 points: Almost no stimulus 2 points: Slightly stimulating 1 point: Stimulated The score results of 10 people are averaged and the usability (hypoallergenicity) is evaluated according to the following evaluation criteria. did. It was judged that the dentifrice composition having no irritation was the one in which the evaluations of ⊚ and ○ were ensured.
<Evaluation criteria>
⊚: 3.5 points or more and 4.0 points or less ○: 3.0 points or more and less than 3.5 points △: 2.0 points or more and less than 3.0 points ×: less than 2.0 points

(3) Evaluation method of usability (no sarcasm) Evaluation was made by a sensory test using 10 expert panelists. 1 g of the dentifrice composition was placed on a toothbrush and brushed for 3 minutes in the same manner as usual, and the sarcasm felt during use was judged according to the following scoring criteria.
<Score criteria>
4 points: No sarcasm 3 points: Almost no sarcasm 2 points: Slightly sarcasm 1 point: Has sarcasm The score results of 10 people are averaged and the usability (no sarcasm) is evaluated according to the following evaluation criteria. did. It was judged that the dentifrice composition having no sarcasm was one in which the evaluations of ⊚ and ○ were ensured.
<Evaluation criteria>
⊚: 3.5 points or more and 4.0 points or less ○: 3.0 points or more and less than 3.5 points △: 2.0 points or more and less than 3.0 points ×: less than 2.0 points

Details of the main raw materials used are shown below.
(A) Isopropylmethylphenol (4-isopropyl-3-methylphenol, manufactured by Osaka Kasei Co., Ltd.)
(B) Sodium α-olefin sulfonate (manufactured by Lion Corporation)
(C) Cha extract ("Wa ism", manufactured by Maruzen Pharmaceuticals Co., Ltd., extract content 0.2%, extraction solvent: 50% butylene glycol aqueous solution)
Triclosan (comparative product) (Ilgasan, manufactured by Ciba Specialty Chemicals Co., Ltd.)
The blending amount of (C) cha extract in the table is the pure amount of the extract.

In addition, the following tests were carried out on the dentifrice compositions of Examples 1 and Comparative Examples 4 and 5. The results are shown in Table 4.

(4) Evaluation method of antibacterial effect immediately after brushing teeth and sustainability of antibacterial effect (after 8 hours)-2
The antibacterial effect on oral bacteria was evaluated by measuring the number of oral bacteria in human saliva.
Subjects were randomly divided into two groups of 15 each (I; dentifrice group, II; water brushing group (control)).
Oral cleaning after lunch was stopped for each subject, and saliva before bedtime was collected without brushing teeth (initial saliva sample A). In addition, the subject placed 1 g of the dentifrice composition on a toothbrush, brushed the teeth for 3 minutes in the same manner as usual, and collected saliva immediately after that (immediately after saliva sample B). Further, after going to bed for 8 hours, saliva was collected (saliva sample C after 8 hours). The collected saliva samples were diluted, anaerobically cultured, and then the number of oral bacteria (Log (cfu / mL)) was measured. The numbers of oral bacteria in the samples A, B, and C were defined as a, b, and c, respectively. In the water brushing group (control group), saliva samples A, B, and C were collected in the same manner as above except that water was immersed in a toothbrush without using the dentifrice composition.
Regarding the measurement results, the average value of the rate of increase in the number of oral bacteria (immediately after; b / a × 100 (%), 8 hours later; c / a × 100 (%)) with respect to the initial value for each group was obtained, and the evaluation shown below was performed. Each was judged based on the criteria, and the antibacterial effect immediately after brushing and the sustainability of the antibacterial effect after a long time (8 hours) after brushing were evaluated.
<Evaluation criteria>
⊚: Increase rate of oral bacteria in the dentifrice group is less than 25% compared to the control group ○: Increase rate of oral bacteria in the dentifrice group is 25% or more and less than 50% compared to the control group ×: Oral cavity in the dentifrice group Bacterial count increase rate is 50% or more compared to the control group

Claims (3)

(A) Isopropylmethylphenol,
A dentifrice composition comprising (B) α-olefin sulfonate and (C) cha extract. Claimed to contain 0.001 to 0.1% by mass of the component (A), 0.1 to 2% by mass of the component (B), and 0.0007 to 0.01% by mass of the pure extract of the component (C). 1. The dentifrice composition according to 1. The dentifrice composition according to claim 1 or 2, which is a dentifrice.