JP2001302476A - Dentifrice composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a dentifrice composition containing a specific kind of silica and preferably a specific binder and having >=pH 8.0 and therefore having significant prophylactic/therapeutic effect on periodontosis even in the case of low dose content of ascorbic acid compound(s). SOLUTION: This dentifrice composition is characterized by containing at least one compound selected from ascorbic acid and derivatives thereof and >=5 mass % of silica <=100 m2/g or >=500 m2/g in BET specific surface area, and being >=pH 8.0.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a dentifrice composition further improved in the prevention and treatment of periodontal disease by ascorbic acid or an ascorbic acid derivative.

[0002]

2. Description of the Related Art Ascorbic acid is known to play an important role in the expression of various enzyme activities in living organisms and to have various physiological activities. In particular, it acts as a coenzyme for prolyl and lysyl hydroxylase and is said to be essential for collagen synthesis.

[0003] In recent years, antioxidant vitamins that eliminate excess active oxygen produced in a living body and protect living tissues from oxygen damage have attracted attention, and are known to have various physiological activities. . For this reason, it is also useful for the prevention and treatment of gingivitis and periodontitis, and ascorbic acid or ascorbic acid derivatives (hereinafter referred to as ascorbic acids)
Is known to be incorporated into oral compositions such as dentifrices. For example, ascorbic acid phosphates (JP-A-62-96408 and JP-A-62-273910) and ascorbic acid sulfates (JP-A-3-29.
No. 4227) and higher fatty acid esters of ascorbic acid (Japanese Patent Laid-Open No. 157417/1995).

[0004] However, if a sufficient amount of the ascorbic acid derivative is incorporated into the composition, problems such as coloration and discoloration of the composition occur, making it difficult to incorporate an effective amount into the oral composition. It is. For this reason, JP-A-63-141921, JP-A-2-292210, JP-A-2-292221, and 4-173727.
Japanese Patent Application Publication No. JP-A-2002-115139 discloses means for solving this problem by blending a coloring and discoloration inhibitor.

On the other hand, a low dose of ascorbic acid which does not cause a problem such as coloring of the composition does not sufficiently exhibit its physiological activity. Therefore, Japanese Patent Application Laid-Open No. Hei 7-351563 discloses a method in which a specific fatty acid is formulated. In addition, a composition which has a periodontal disease prevention / treatment effect is proposed.

However, coloring of ascorbic acids,
Incorporation of various additives for the purpose of suppressing discoloration or for expressing physiological activity causes a decrease in feeling of use and the like, and in an ascorbic acid-containing oral composition containing no specific additive, a physiologically active agent is used. There is a demand for the development of a means for sufficiently expressing the above.

[0007] The present invention has been made to solve the above problems, and a dentifrice composition having a high prophylactic and therapeutic effect on periodontal disease even at a low dose of ascorbic acid which does not cause problems such as coloring and discoloration. The purpose is to provide things.

[0008]

Means for Solving the Problems and Embodiments of the Invention As a result of various studies to achieve the above object, the present inventor has found that even in a dentifrice composition containing a low dose of ascorbic acid, the BET method is used. Mixing silica having a specific surface area of 100 m ² / g or less or 500 m ² / g or more and adjusting the pH of the whole composition to 8.0 or more, more preferably carboxymethyl cellulose, polyacrylic acid, xanthan gum, carrageenan, It has been found that by combining one or more alginic acids or salts thereof, an excellent effect of preventing and treating periodontal disease can be obtained.

Conventionally, Japanese Patent Application Laid-Open No. 4-173727 discloses that the pH of a composition is adjusted to 7 to 10 to improve coloring and the like.
Although it has already been disclosed that the pH is in the range of 9 or more, when the pH of the composition is adjusted to 8.0 or more and the specific silica and the specific binder are mixed, a low dose can be obtained. It has not been shown that the physiological activity of ascorbic acids is sufficiently expressed.

Hereinafter, the present invention will be described in more detail. The dentifrice composition of the present invention contains ascorbic acid or an ascorbic acid derivative as an active ingredient.

Here, the ascorbic acid derivative to be incorporated in the dentifrice composition of the present invention includes
One in which one or two or more of the hydroxyl groups at the 3, 5, and 6 positions are phosphoric acid, polyphosphoric acid, sulfuric acid, or an ester of a pharmaceutically acceptable compound can be used. For example, ascorbic acid-2-phosphate, ascorbic acid-
3-phosphate, ascorbic acid-6-phosphate, ascorbic acid-2-polyphosphate, ascorbic acid-2-sulfate, ascorbic acid-2-
Palmitic acid ester, ascorbic acid-6-palmitic acid ester, ascorbic acid-2-stearic acid ester, ascorbic acid-6-stearic acid ester, ascorbic acid-2,6-dibutyl ester, ascorbic acid-2,6-dipalmitin Acid esters and the like,
2-O-galactopyranosyl ascorbic acid;
Derivatives such as O-galactopyranosyl ascorbic acid, 6-O-galactopyranosyl ascorbic acid, 2-O-glucosyl ascorbic acid, and 3-O-glucosyl ascorbic acid can also be suitably used. In addition, examples of such salts include sodium salt, potassium salt, calcium salt, magnesium salt and the like.

These ascorbic acid and ascorbic acid derivatives can be used alone or in combination of two or more, but a derivative in which the hydroxyl group at the 2- or 3-position of ascorbic acid is preferably used.

Further, the compounding amount is low, that is, 1.5% (% by mass, the same applies hereinafter) or less, particularly preferably 0.001 to 1.0% of the whole composition from the problem of coloring and the like.

In the present invention, the specific periodontal disease preventing / treating effects of the above-mentioned ascorbic acids can be effectively exhibited by blending a specific silica and preferably a specific binder.

Here, the specific silica has a specific surface area of 100 m ² / g or less, preferably from 1 to ² , according to the BET method.
100 m ² / g, more preferably 5 to 100 m ² / g, and 500 meters ² / g or more, preferably 500~850m ² /
g, more preferably 500 to 750 m ² / g, and one of these can be used alone or in combination of two or more. In this case, the particle size of the silica is appropriately selected, but the average particle size is 0.1 to 100 μm.
m, especially 1 to 50 μm, is preferably used. As the silica, ignitable silica, precipitated silica and the like can be used as long as the above specific surface area is satisfied, and those obtained by a known production method can be used. Further, aluminosilicate, zirconosilicate and the like, Al, Zr, etc. 10% or less, especially 1
% Or less. Commercial products can be used as such silica.

The amount of the silica is at least 5%, preferably 5 to 30%, more preferably 5 to 30% of the whole composition from the viewpoint of sufficiently exhibiting the effects of ascorbic acids.
Desirably, it is about 20%.

The specific binder used in the present invention is preferably carboxymethylcellulose, polyacrylic acid, xanthan gum, carrageenan, alginic acid or salts thereof, and these binders may be used alone or in combination of two or more. Can be used. In the case of carboxymethyl cellulose, those having a degree of etherification of at least 0.85 can be suitably used. The amount of the binder is preferably 0.1 to 5%, more preferably 0.5 to 3% of the whole composition.

In the present invention, the effect of the above ascorbic acids can be efficiently reduced by adjusting the pH of the whole composition to 8.0 or higher, preferably 8.0 to 11.0, more preferably 8.0 to 10. Can be expressed. In this case, when the pH is less than 8.0, the expression of the physiological activity of ascorbic acids is weak. If the pH is too high, harmful effects may be caused to the oral mucosa. For pH adjustment, generally used pH adjusters can be used, but sodium hydroxide and potassium hydroxide can be preferably used, and water-soluble citrate, phosphate, and carbonate can be used. , Bicarbonate and the like can also be preferably used.

The dentifrice composition of the present invention can be made into a dentifrice such as toothpaste, liquid toothpaste, powdered toothpaste and the like. In this case, in the dentifrice composition of the present invention, in addition to the above-mentioned components, various base components used in a normal dentifrice composition, for example, abrasives, thickeners, sweeteners, flavors, and the like are contained in a usual amount. May be blended.

As the polishing agent, the above-mentioned silica can be used. In addition, calcium hydrogen phosphate dihydrate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, aluminum silicate, insoluble sodium metaphosphate , Tribasic magnesium phosphate,
One or more of magnesium carbonate, calcium sulfate, bentonite, zirconium silicate, polymethyl methacrylate, and other synthetic resins may be blended within a range that does not impair the effects of the present invention.

Examples of the binder include, in addition to the binders described above, cellulose derivatives such as methylcellulose and hydroxyethylcellulose; alginic acid derivatives such as propylene glycol alginate; gums such as gellan gum, tragacanth gum and gum karaya; polyvinyl alcohol; One or more kinds such as a synthetic binder such as a polymer and an inorganic binder such as veegum and laponite may be blended.

As humectants, glycerin, sorbit, propylene glycol, polyethylene glycol,
One or more polyhydric alcohols such as xylitol, maltitol and lactitol may be blended.

As the surfactant, an anionic surfactant such as sodium lauryl sulfate, a nonionic surfactant such as decaglyceryl laurate and diethanolamide myristate, and an amphoteric surfactant such as betaine can be blended. .

As the fragrance component, menthol, anethole, carvone, eugenol, n-decyl alcohol,
Flavors such as citronellol, α-terpineol, cineol, linalool, ethyl linalool, crocodile, thymol, peppermint oil, spearmint oil, wintergreen oil, clove oil, eucalyptus oil and the like can be used alone or in combination. Furthermore, sweeteners such as saccharin sodium, perillartin, thaumatin and the like can be added.

The present invention also includes a cationic fungicide such as chlorhexidine, benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, decalinium chloride, a phenolic compound such as triclosan, hinokitiol, biosol, dextranase, and mutanase. , Lysozyme, amylase, protease, lytic enzyme, SO
Enzymes such as D, alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon aminocaproic acid, allantoin, dihydrocole Known vitamins such as stanols, glycyrrhizic acids, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, xylitol, zinc chloride, water-soluble inorganic phosphate compounds, vitamin A, vitamin B group, vitamin E, and derivatives thereof. One or more active ingredients can be blended.

[0026]

The dentifrice composition of the present invention reduces ascorbic acids by using the above specific silica, more preferably the above specific binder, and adjusting the pH of the composition to 8.0 or more. Even a composition containing a dose has a high effect on the prevention and treatment of periodontal disease.

[0027]

EXAMPLES Hereinafter, the present invention will be described in detail with reference to experimental examples and examples, but the present invention is not limited to the following examples.

Experimental Example 1 The buccal mucosa of a Syrian hamster (8 weeks old, male) was excised, washed thoroughly with physiological saline, and then filled with a known amount of physiological saline and a 1.5 cm diameter Franz type diffusion. Attached to the cell. Prepare the toothpaste (test dentifrice) described below, dilute 5-fold with physiological saline,
3 ml was applied to the attached mucosa. The sample and the physiological saline in the lower layer were stirred at a constant speed in a water bath at 35 ° C., and after 30 minutes, the total amount of ascorbic acids permeating into the lower layer was quantified by HPLC under the following conditions to determine the amount of mucosal absorption. Table 1 shows the results. Apparatus: Shimadzu LC-10A High Performance Liquid Chromatograph Column: STR-ODSII Eluent: 20 mM, KH ₂ PO _4.5 mM, tetrabutylammonium sulfate hydrochloride: acetonitrile (90:10), pH 3.0 Column temperature: 40 ° C. Detector: UV 254 nm test dentifrice aluminum hydroxide 30.0% silica Compounding amount shown in Table 1 Sorvitol 25.0 sodium carboxymethylcellulose 1.0 sucrose monopalmitate 1.0 sodium lauryl sulfate 1.5 sodium saccharin 0.2 Ethanol 0.1 Sodium benzoate 0.1 Ascorbic acid sulfate dipotassium salt 0.05 Ascorbic acid phosphate ester magnesium salt 0.1 Disodium phosphate proper amount Trisodium citrate proper amount Fragrance 1.0 water balance 100.0% pH table pH shown in

[0029]

[Table 1]

[Experimental Example 2] Toothpaste (test dentifrice) described below was prepared and diluted 5-fold with physiological saline, and the mucosal absorbability to hamster buccal mucosa was compared as in Experimental Example 1. Table 2 shows the results. Test dentifrice Silica shown in Table 2 25.0% Sorbit 25.0 Glycerin 25.0 Polyvinylpyrrolidone 1.0 Lauroyl polyglycerin ester 1.0 Polyoxyethylene (60) 0.5 Sorbitan monolaurate Saccharin sodium 0.2 Paraoxy Ethyl benzoate 0.1 Chlorhexidine hydrochloride 0.1 Ascorbic acid phosphate sodium salt 0.05 Disodium phosphate Appropriate amount Fragrance 1.0 Water Residual 100.0% pH pH shown in Table 2

[0031]

[Table 2]

[Experimental Example 3] An experimental example 1 was prepared using a test dentifrice (pH adjusted to about 8.5) prepared based on the following composition.
In the same manner as in the above, the mucosal absorbability to the hamster buccal mucosa was compared. Table 3 shows the results and details of the composition. Test dentifrice silica (specific surface area 30 m ² / g, average particle size 18 μm) 10.0% Binder 1.0 Sorbite 45.0 Sodium lauryl sulfate 1.0 Saccharin sodium 0.2 Ascorbic acid-2-phosphate magnesium Salt 0.2 Fragrance 1.0 pH adjuster Appropriate amount of water Balance 100.0%

[0033]

[Table 3]

[Experimental Example 4] Experimental gingivitis suppression experiment of a beagle dog Example of the present invention silica (specific surface area 30 m ² / g, average particle size 7.5 μm) 8.0% silica (specific surface area 700 m ² / g, average particle size) 10.0 sorbit 20.0 sodium carboxymethyl cellulose 1.2 (degree of etherification 1.50) sodium lauryl sulfate 1.5 magnesium ascorbic acid phosphate 0.5 perfume 1.0 purified water balance 100. 0% pH 8.61

The above composition was prepared by a usual production method. As a comparative example, a specific surface area of 300 m
² / g of silica was used, the binder was methylcellulose, and the pH was not adjusted (6.98). Also,
Bases were prepared by removing ascorbic acid phosphate magnesium salt from the present invention examples and comparative examples.

The test was performed using male and female beagle dogs (four in each group) using a total of six teeth P2 to P4 on the left and right lower jaws. That is, healthy gingiva was established by continuing brushing twice a day for 8 weeks after scaling the target tooth. afterwards,
Gingivitis is induced by stopping all oral cleaning, and at the same time, the drug of the present invention or comparative example is applied to one jaw and the base is applied to the other jaw twice a day at the periphery of the target tooth. Min, then washed with tap water. At 2 weeks and 4 weeks after the induction of gingivitis, the gingivitis index of the target site was measured, and the gingivitis inhibition rate with respect to the base was calculated. Table 4 shows the results.

[0037]

[Table 4]

From the results shown in Tables 1 to 4, ascorbic acid derivatives have specific silica and preferably specific viscosity such as carboxymethylcellulose having a degree of etherification of 0.85 or more, carrageenan, xanthan gum, sodium alginate and sodium polyacrylate. It was recognized that the effect of ascorbic acids was enhanced by adding a binder and adjusting the pH to 8.0 or more.

Hereinafter, examples will be described. [Example 1] Toothpaste silica (specific surface area: about 30 m ² / g, average particle size: 7.5 μm) 25.0% sorbitol 25.0 propylene glycol 3.0 sodium saccharin 0.2 sodium lauryl sulfate 1.5 sodium carboxymethylcellulose 1.0 (Degree of etherification: 0.85) Magnesium ascorbic acid phosphate ester 0.2 Ethanol 0.1 Sodium benzoate 0.1 Fragrance 1.0 pH adjuster Appropriate amount of water Residue 100.0% pH 8.54

Example 2 Toothpaste Silica (specific surface area: about 700 m ² / g, average particle size: 5 μm) 25.0% sorbitol 20.0 glycerin 20.0 polyethylene glycol 4.0 carboxymethylcellulose sodium 0.6 (ether Degree of conversion 1.05) Sodium carboxymethylcellulose 0.5 (Degree of etherification 2.80) Sodium lauryl sulfate 1.2 Sodium phosphate ascorbate 0.2 Fragrance 0.8 pH adjuster Appropriate amount of water Residue 100.0% pH 9.27

Example 3 Toothpaste Silica (specific surface area: about 30 m ² / g, average particle diameter: 16 μm) 10.0% Silica (specific surface area: about 700 m ² / g, average particle diameter: 8 μm) 8.0 Titanium oxide 1 2.0 Sorvit 20.0 Xanthan gum 0.3 Sodium polyacrylate 0.5 Sucrose monopalmitate 1.0 Sodium lauryl sulfate 1.5 2-O-α-glucosyl-L-ascorbic acid 0.2 Chlorhexidine hydrochloride 0 .1 Ethyl paraoxybenzoate 0.1 Sodium saccharin 0.1 Fragrance 1.0 pH adjuster Appropriate amount of water Residue 100.0% pH 8.65

Example 4 Toothpaste Aluminum hydroxide 45.0% silica (specific surface area: 70 to 100 m ² / g, 5.0 average particle size: 10 μm) Sorbitol 25.0 sodium carboxymethylcellulose 1.0 (degree of etherification: 1 .85) Sucrose monopalmitate 1.0 Sodium lauryl sulfate 1.5 Saccharin sodium 0.2 Ethanol 0.1 Sodium benzoate 0.1 Ascorbic acid phosphate magnesium salt 0.1 Ascorbic acid palmitate sodium salt 0. 2 Tranexamic acid 0.08 Fragrance 1.0 pH adjuster Appropriate amount of water Residue 100.0% pH 9.45

Example 5 Toothpaste Precipitable silica (specific surface area: 30 to 50 m ² / g, 20.0% average particle size: 8 μm) Sorvit 25.0 glycerin 25.0 sodium carboxymethylcellulose 0.7 (degree of etherification: 1 .05) Carrageenan 0.5 Sodium lauryl sulfate 1.0 Polyoxyethylene (60 mol) 0.2 Sorbitan monolaurate Saccharin sodium 0.2 Ethyl parahydroxybenzoate 0.1 Chlorhexidine hydrochloride 0.1 Ascorbic acid phosphate derivative 0.3 Perfume 1.0 pH adjuster Appropriate amount of water Residual 100.0% pH 8.82

Example 6 Toothpaste Calcium Carbonate 40.0% Silica (Specific Surface Area 700 m ² / g, Average Particle Size 2 μm) 8.0 Sorbit 25.0 Sodium Lauryl Sulfate 1.5 Carboxymethyl Cellulose Sodium 0.6 (Ether Degree of chemical conversion 0.85) Carrageenan 0.5 Sodium saccharin 0.1 Sodium monofluorophosphate 0.5 Propylene glycol 5.0 Ascorbic acid phosphate sodium salt 0.2 Glycyrrhetinic acid 0.05 Fragrance 1.0 pH adjuster Suitable amount Water balance 100.0% pH 9.45

Example 7 Toothpaste Silica (Specific surface area about 630 m ² / g, average particle size 3.5 μm) 10.0% Silica (Specific surface area 50-70 m ² / g, 10.0 Average particle size 13 μm) Xanthan gum 0.5 Sodium alginate 0.3 Sorbite 65.0 Sodium lauroyl sarcosine 0.3 Sodium lauryl sulfate 1.0 Saccharin sodium 0.2 Magnesium phosphate ascorbate 0.2 Fragrance 1.0 pH adjuster Suitable amount of water Balance 100 0.0% pH 8.55

[0046] [Example 8] Toothpaste silica (specific surface area 10~40m ² / g, 13.0% average particle size 8 [mu] m) silica (specific surface area of about 700m ² / g, average particle size 5 [mu] m) 8.0 Sorbitol 45. 0 Glycerin 18.0 Sodium lauryl sulfate 1.0 Sodium carboxymethyl cellulose 0.5 (degree of etherification 1.05) Sodium carboxymethyl cellulose 0.4 (degree of etherification 1.85) Sodium saccharin 0.1 Gelatin 0.2 Diethanolamine laurate C 1.0 1.0 Propylene glycol 2.0 Ascorbic acid palmitate derivative 0.05 Ascorbic acid phosphate derivative 0.1 Perfume 1.0 pH adjuster Appropriate amount of water Residue 100.0% pH 8.45

Example 9 Toothpaste Aluminosilicate 10.0% Zirconosilicate 10.0 Silica (specific surface area: about 630 m ² / g, average particle size 3.5 μm) 5.0 Titanium dioxide 0.5 Xanthan gum 8 Sodium alginate 0.4 Polyethylene glycol 400 2.5 70% sorbite solution 35.0 Methyl parahydroxybenzoate 0.1 Sodium monofluorophosphate 0.73 Ascorbic acid 0.04 Ascorbic acid phosphate sodium salt 0.15 Triclosan 0.3 Glycyrrhetinic acid 0.1 Sodium pyrophosphate 2.0 Sodium lauryl sulfate 1.5 Fragrance 1.0 pH adjuster Appropriate amount of water Residue 100.0% pH 9.17

Example 10 Toothpaste Calcium hydrogen phosphate anhydrate 20.0% Calcium hydrogen phosphate dihydrate 20.0 Silica (specific surface area: about 70 m ² / g, average particle size: 10 μm) 0 Sodium carboxymethylcellulose 0.4 (degree of etherification 1.0) Sodium carboxymethylcellulose 0.3 (degree of etherification 1.3) Propylene glycol 3.0 70% sorbite liquid 25.0 Methyl parahydroxybenzoate 0.1 Benzoic acid Sodium 0.2 Saccharin sodium 0.2 Sodium monofluorophosphate 0.6 Sodium fluoride 0.04 Sodium tripolyphosphate 1.0 Sodium lauryl sulfate 0.8 Lauroyl sarcosine sodium 0.4 Ascorbic acid phosphate magnesium salt 0.2 Fragrance 1.0 pH adjustment Agent appropriate amount water balance 100.0% pH 8.58

Example 11 Liquid Dentifrice Precipitable Silica (Specific Surface Area 70 m ² / g, 18.0% Average Particle Size 10 μm) Propylene Glycol 2.0 60% Sorbitol Solution 20.0 Glycerin 24.0 Sodium Polyacrylate 0.1 Xanthan gum 0.2 Sodium lauryl sulfate 1.5 Polyglycerin fatty acid ester 1.6 Methyl parahydroxybenzoate 0.12 Butyl paraoxybenzoate 0.01 Sodium saccharin 0.1 Sodium fluoride 0.5 Xylitol 12.0 Ascorbic acid Phosphate magnesium salt 0.5 Perfume 1.0 pH adjuster Appropriate amount of water Residue 100.0% pH 8.23

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C083 AB171 AB172 AB222 AB242 AB282 AB292 AB322 AB372 AB472 AC102 AC122 AC132 AC302 AC312 AC422 AC442 AC482 AC622 AC642 AC662 AC742 AC782 AC812 AC862 AD042 AD072 AD091 AD092 AD222 AD262 AD271 AD272 AD301 AD302 AD351 AD352 AD641 AD642 CC41 DD22 DD23 DD27 EE33

Claims (2)

[Claims] 1. A composition comprising silica containing one or more compounds selected from ascorbic acid or an ascorbic acid derivative and having a specific surface area by BET method of 100 m ² / g or less or 500 m ² / g or more. A dentifrice composition containing 5% by mass or more of the whole and making the pH of the whole composition 8.0 or more. 2. The dentifrice composition according to claim 1, wherein one or more selected from carboxymethylcellulose, polyacrylic acid, xanthan gum, carrageenan, alginic acid and salts thereof are blended.