JP2003226628A - Composition for oral cavity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To control the onset and progress of dental caries of a Lacuna fissure part by the action of a gradually released fluoride ion since particles supporting the fluoride ion supply compound is immediately penetrated into and left in the inside of Lacuna fissure part. <P>SOLUTION: The composition for the oral cavity comprises particles having 0.5-30 μm average particle diameters, caving the fluoride ion supply compound on the surfaces of the particles. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an oral composition suitable for use in the prevention of dental caries, particularly dental caries on the pit and fissure region present in molars.

[0002]

2. Description of the Related Art Milk teeth,
Not only permanent teeth, the pit and fissures on the occlusal surface of the molars are common sites for caries, and even when compared to other areas such as smooth surfaces and adjacent surfaces,
It is known that the incidence of caries is extremely high. The pit and fissure has a small inner diameter of tens of microns, and its shape is extremely complicated. As a result, the bristles of the brush cannot be reached by ordinary toothpaste, resulting in insufficient removal of plaque, which results in being susceptible to cariogenic bacteria and causing caries to occur frequently.

Further, since the pit fissure has a complicated shape as described above, it is difficult for an active ingredient such as fluoride to reach deep into the pit fissure. Conventionally, in the field of dental caries preventive dentifrice, a fluorine compound such as sodium fluoride or sodium monofluorophosphate is blended as an active ingredient. However, although it directly acts on the smooth surface and the adjacent surface to promote remineralization, the present situation is that fluoride does not act on the inside of the pit fissure due to its complicated shape.

In addition, fluoride is locally applied by fluoride varnish mainly in Northern Europe, but it is a treatment about twice a year, and fluoride is sufficiently supplied to the pit and fissure. I can't say.

The present invention has been made in view of the above circumstances, and provides a composition for oral cavity containing a fluoride ion-supplying compound, wherein the fluoride ion-supplying compound is supplied to the inside of the pit fissure for a long time. The purpose is to provide.

[0006]

Means for Solving the Problems and Modes for Carrying Out the Invention As a result of extensive studies conducted by the inventor of the present invention, the average particle size of the particles having a fluoride ion-supplying compound carried on the surface was 0.5. Fluoride that is gradually released from the particles over a long period of time because the particles immediately enter and remain inside the pit and fissure, which is a frequent site of dental caries, by incorporating particles of -30 μm into the oral composition. The inventors have found that the action of ions suppresses the occurrence and progression of caries in the pit and fissure, and has completed the present invention.

The present invention will be described in more detail below.
The composition for oral cavity of the present invention contains particles having an average particle size of 0.5 to 30 μm in which the surface of the particles carries a fluoride ion-supplying compound, and by using the composition, the pit cleft Fluoride ions are gradually supplied from the particles remaining inside for a long time, and it becomes possible to prevent caries of the pit fissure having an anatomically extremely complicated morphology.

The average particle diameter of the particles mentioned here is 0.5 to 3
It is within the range of 0 μm. If the particle size is less than 0.5 μm, the particles do not immediately enter the inside of the pit and fissure during tooth brushing, and most of them are released outside the oral cavity together with the mouthwash. Further, if the particle size exceeds 30 μm, it cannot easily enter the pit and fissure region having an inner diameter of several tens of microns and a complicated shape. Considering the residual property inside the fissure, particles having an average particle size of 3 to 20 μm are more preferable.

The particles for supporting the fluoride ions used in the present invention include calcium dihydrogen phosphate monohydrate and anhydrate, calcium monohydrogen phosphate dihydrate and anhydrate, and triphosphate tribasic. Calcium, tetracalcium phosphate, octacalcium phosphate, calcium pyrophosphate, calcium phosphate compounds such as hydroxyapatite, calcium carbonate, calcium hydroxide, calcium sulfate, alumina, aluminum hydroxide, insoluble sodium metaphosphate, magnesium monohydrogen phosphate, Inorganic particles such as magnesium phosphate, magnesium carbonate, titanium oxide, activated carbon, polymethyl methacrylate, organic particles such as crystalline cellulose, kaolinite, vermiculite, clay mineral particles such as smectite, natural rubber, polybutadiene,
Examples thereof include polymer particles such as polystyrene, polyisoprene, polyethylene and polyvinyl acetate.

Examples of the fluoride ion supplying compound include a fluorine compound composed of an alkali metal such as sodium fluoride, a fluorine compound composed of an alkaline earth metal such as magnesium fluoride and calcium fluoride, a monofluorophosphate salt, and a fluorine compound. Examples thereof include tin oxide, fluorosilicates, titanium fluoride compounds, amine fluorine compounds, and fluorine-containing amorphous materials.

The method of supporting the fluoride ion supplying compound on the particles is not particularly limited. As a supporting method, any means such as physical or chemical can be used, and the form thereof is various, such that a fluoride ion-supplying compound is adsorbed on the particles or calcium fluoride crystals are deposited on the surface. The supporting method is shown below as an example, but the present invention is not limited to the following method. Example 1: Sodium fluoride powder is dissolved in distilled water to prepare a 1.5% solution of fluorine. After heating the sodium fluoride aqueous solution to 70 to 80 ° C., the above particles (for example, calcium carbonate having an average particle diameter of 10 μm) are mixed in the liquid, and the mixture is stirred for 15 hours. After stirring, the aqueous solution is suction filtered and the calcium carbonate is dried at 40 ° C. Example 2: The above particles (for example, calcium dihydrogen phosphate monohydrate having an average particle size of 15 μm) and sodium fluoride powder are well mixed and heat-treated in an electric furnace at 200 ° C. for 48 hours. After the heat treatment, the powder is stirred in distilled water to remove excess sodium fluoride. Wash 3 times. After washing, it is dried at room temperature. Example 3: Etching the above particles (eg tricalcium phosphate with an average particle size of 30 μm) with diluted hydrofluoric acid.
After etching, it is washed with distilled water and dried at room temperature.

Although the amount of the fluoride ion-supplying compound supported is appropriately selected, the amount of fluorine contained in the fluoride ion-supplying compound is 0.5 to 70 per 100 g of the particles.
It is preferable that the treatment is carried out so as to carry 0 mg, particularly 10 to 70 mg.

The oral composition of the present invention can be used in various forms such as toothpaste, powdered toothpaste, liquid toothpaste, liquid toothpaste, gel toothpaste, etc., as well as mouthwash, chewing gum, gummies, troches and the like. It can be applied.

The optimum concentration range of the particles supporting the fluoride ion-supplying compound to be blended varies depending on the dosage form used,
It is an effective amount, and the upper limit is the range that does not impair the feeling of use, and the lower limit is the amount that can exert its use effect, depending on the dosage form. Taking a dentifrice which is a typical oral composition as an example, the concentration range of the fluoride ion supplying compound-supported particles is preferably 10 to 35% (mass percentage, the same applies hereinafter).
Is.

In the oral composition of the present invention, appropriate components can be blended depending on the kind. For example, in the case of dentifrice, an abrasive, a binder, a thickener, a surfactant, a sweetener, a preservative, a coloring agent, a fragrance, a foaming agent, and a medicinal component may be added.

As the polishing agent, the above-mentioned particles supporting a fluoride ion-supplying compound can be used, as well as calcium carbonate, calcium hydrogen phosphate / dihydrate and calcium hydrogen phosphate / anhydrous salt, calcium pyrophosphate, insoluble sodium metaphosphate, It is possible to appropriately select and use a base such as tertiary magnesium phosphate, magnesium carbonate, amorphous silica, crystalline silica, precipitated amorphous silica, zeolite, aluminosilicate, aluminum oxide, aluminum hydroxide, or resin. it can.

As the binder, carrageenan, sodium alginate, xanthan gum, pullulan, gelatin,
Carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, gum arabic, guar gum, locust bean gum, sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, montmorillonite, kaolin, hydrated silica, aluminum silicate, magnesium silicate, hectorite. It can be appropriately selected from the following.

As the thickener, propylene glycol,
One kind or two or more kinds can be appropriately selected from sorbit, xylit, glycerin, polyethylene glycol and the like.

As the surfactant, anionic surfactants such as lauryl sulfate ester salt, α-olefin sulfonate salt, N-acyl sarcosine salt, and aliphatic monoglyceride sulfate ester salt, sucrose fatty acid ester, polyoxyethylene / polyoxy are used. Propylene glycol block polymer, polyoxyethylene hydrogenated castor oil, nonionic surfactants such as fatty acid monoalkanolamides, imidazolinium betaine, alkylamide betaines, amphoteric surfactants such as amine oxides, etc. within the range that does not impair the effects of the present invention. Can be selected as appropriate.

As the sweetener, saccharin sodium,
Stevioside, neohesperidyl dihydrochalcone,
It can be appropriately selected from glycyrrhizin, perillartin, p-methoxycinnamic aldehyde, thaumatin and the like.

The preservative can be appropriately selected from sodium benzoate, methylparaben, ethylparaben, butylparaben and the like.

The fragrance can be appropriately selected from essential oils such as peppermint and spearmint, and fragrance materials such as 1-menthol, carvone, eugenol and anethole.

Further, as the medicinal component, in addition to the fluoride ion-supplying compound supported on the particles, sodium fluoride, sodium monofluorophosphate, fluorides such as tin fluoride, chlorohexidine, triclosan, cetylpyridinium chloride, etc. Antibacterial / antibacterial agents, condensed phosphates, tartar preventives such as ethanehydroxydiphosphonate, anti-inflammatory agents such as tranexamic acid and glycyrrhizin dipotassium salt, enzyme agents such as dextranase and mutanase, sodium chloride, lactic acid Astringents such as aluminium, hypersensitivity inhibitors such as potassium nitrate and strontium chloride, plaque inhibitors such as zinc citrate and gluconic acid
It can be appropriately selected and used according to the purpose within a pharmaceutically acceptable range. Further, ethanol, water or the like may be added as a dye or a solvent.

[0024]

EXAMPLES The present invention will be specifically described below by showing experimental examples, comparative examples and examples, but the present invention is not limited to the following examples.

[Experimental Example] Experimental Method The root surface of a human molar tooth was excised with a microcutter to prepare a block body of the crown including the occlusal surface. The block body was gas sterilized and the following experiment was conducted. Remineralization experiment The above block was immersed in a demineralization solution containing calcium ions and phosphate ions at a pH of 4.8, and subpit surface demineralization was performed at the pit fissure site. The block was treated for 3 minutes in the oral compositions (diluted 3-fold in distilled water) of the following Experimental Examples and Comparative Examples. The treatment was performed 3 times / day, and after the treatment, it was washed 3 times in distilled water. After washing, it was kept in artificial saliva (37 ° C.) containing calcium ions and phosphate ions and having a pH of 6.5. Two weeks later, the block body was cut with a micro cutter to prepare a slice, and the mineral loss amount ΔZ was measured from the X-ray photograph. Further, a section was similarly prepared from a block body not subjected to remineralization treatment, and the measured ΔZ was used as an initial value. The remineralization rate (%) was calculated by the following formula [ΔZ (experimental group) / ΔZ (initial)] × 100. The number of n was 3 in the initial group and 12 in each group, and the average value was calculated. The results are shown in Fig. 1.

Demineralization Inhibition Experiment Healthy blocks were treated for 3 minutes in the oral compositions (diluted 3-fold in distilled water) of the following Experimental Examples and Comparative Examples. The treatment was performed 3 times / day, and after the treatment, it was washed 3 times in distilled water. After washing, pH 4.5 including calcium ion and phosphate ion
Of artificial saliva (37 ° C.). One week later, the block body was cut with a micro cutter to prepare a slice, and the mineral loss amount ΔZ was measured from the X-ray photograph. Further, a section was similarly prepared from a block body treated with distilled water, and the measured ΔZ was used as a control. The following formula [(ΔZ (control) -ΔZ (experimental group)) / ΔZ
(Control)] × 100, and the demineralization suppression rate (%) was calculated. The n number was 2 in the control group and 10 in each group, and the average value was calculated for each. The results are shown in Figure 2.

[Experimental Example 1] Sodium fluoride 0.21% Calcium carbonate supporting a fluoride ion supplying compound ^{* 1} 35 Toxyl (registered trademark) 5 Carboxymethyl cellulose 1.5 Propylene glycol 3 Sodium lauryl sulfate 1.5 Saccharin sodium 0.05 Preservative 0.02 Perfume 1.0 Water Residual amount 100.0% * 1 Average particle size of calcium carbonate: 15 μm Fluoride ion supplying compound: Fluorine-containing amorphous Amount of fluorine contained in fluoride ion supplying compound: 15 mg

[Experimental Example 2] Sodium fluoride 0.105% Calcium carbonate supporting a fluoride ion supplying compound ^{* 2} 25 Toxyl (registered trademark) 5 Carboxymethylcellulose 1.5 Propylene glycol 3 Sodium lauryl sulfate 1.5 Saccharin sodium 0.05 Preservative 0.02 Perfume 1.0 Water Residual total 100.0% * 2 Average particle size of calcium carbonate: 15 μm Fluoride ion supply compound: Calcium fluoride Fluorine content in fluoride ion supply compound: 50 mg

[Experimental Example 3] Calcium carbonate supporting fluoride ion-supplying compound ^{* 3} 25% Toxyl (registered trademark) 5 Carboxymethyl cellulose 1.5 Propylene glycol 3 Sodium lauryl sulfate 1.5 Saccharin sodium 0.05 Preservative 0.02 Fragrance 1 Water Residual 100.0% * 3 Average particle size of calcium carbonate: 20 μm Fluoride ion supply compound: Calcium fluoride Fluoride content in fluoride ion supply compound: 40 mg

[Experimental Example 4] Sodium fluoride 0.105% Calcium monohydrogen phosphate dihydrate carrying a fluoride ion-supplying compound ^{* 4} 25 Toxyl (registered trademark) 5 Carboxymethyl cellulose 1.5 Propylene glycol 3 Lauryl sulfate Sodium 1.5 Saccharin sodium 0.05 Preservative 0.02 Perfume 1.0 Water Residual 100.0% * 4 Average particle size of calcium monohydrogen phosphate dihydrate: 15 μm Fluoride ion supply compound: Fluoride Fluorine content in calcium fluoride ion supply compound: 50 mg

[Experimental Example 5] Sodium fluoride 0.21% Aluminum hydroxide supporting a fluoride ion-supplying compound ^{* 5} 35 Toxyl (registered trademark) 5 Carboxymethyl cellulose 1.5 Propylene glycol 3 Sodium lauryl sulfate 1.5 Sodium saccharin 0. 05 Preservative 0.02 Fragrance 1.0 Water Residual 100.0% * 5 Average particle size of aluminum hydroxide: 15 μm Fluoride ion supplying compound: Fluorine-containing amorphous Amount of fluorine contained in fluoride ion supplying compound: 15 mg

Comparative Example 1 Sodium Fluoride 0.21% Silica 20 Toxyl® 2.5 Carboxymethyl Cellulose 1.5 Propylene Glycol 3 Sodium Lauryl Sulfate 1.5 Sodium Saccharin 0.05 Preservative 0.02 Perfume 1 Water balance 100.0%

Comparative Example 2 Sodium Fluoride 0.21% Calcium Carbonate 25 Toxyl (registered trademark) 5 Carboxymethyl Cellulose 1.5 Propylene Glycol 3 Sodium Lauryl Sulfate 1.5 Sodium Saccharin 0.05 Preservative 0.02 Perfume 1 Water Balance 100.0%

From the results shown in FIGS. 1 and 2, the group containing the fluoride ion-supplying compound-supporting particles (experimental example) tends to have remarkably higher remineralization rate and demineralization suppression rate than the group not containing (comparative example). there were. Further, compared with the group containing only normal sodium fluoride (Comparative Example), the group containing the fluoride ion-supplying compound-supporting particles (Experimental Example) was found to prevent caries in the pit fissures. .

Further, in the remineralization experiment, the fluoride ion-supplying compound-supporting calcium carbonate in Experiment 2 was replaced by a fluoride ion-supplying compound-supporting calcium monohydrogen phosphate dihydrate (Experimental Example 4). ) However, the remineralization rate was 72%, and the same effect as in Experimental Example 2 was obtained.
In place of the fluoride ion-supplying compound-supporting calcium carbonate of Experimental Example 1, a fluoride ion-supplying compound-supporting aluminum hydroxide was used (Experimental Example 5), and the remineralization rate was 5
It was 7%, and an effect equivalent to that of Experimental Example 1 was obtained.

Further, in the demineralization suppression experiment, a fluoride ion-supplying compound-supporting calcium carbonate was used in place of the fluoride ion-supplying compound-supporting calcium carbonate (Experimental Example 4). ) However, the demineralization suppression rate was 82%, and the same effect as in Experimental Example 2 was obtained.
When a fluoride ion-supplying compound-supporting aluminum hydroxide was used in place of the fluoride ion-supplying compound-supporting calcium carbonate of Experimental Example 1 (Experimental Example 5), the demineralization suppression rate was 6
It was 8%, and the same effect as in Experimental Example 1 was obtained.

Examples will be shown below. The average particle size of the calcium carbonate, the fluoride ion-supplying compound, and the amount of the calcium ion-supporting calcium carbonate supporting the fluoride ion-supplying compound used in the following examples are as follows. Average particle size of calcium carbonate: 15 μm Fluoride ion supply compound: Calcium fluoride Fluoride content in fluoride ion supply compound: 50
mg

[Example 1] Calcium carbonate supporting a fluoride ion-supplying compound 30% Xanthan gum 0.4 Carrageenan 0.6 Propylene glycol 3.5 Sorbitol 25 Sodium lauryl sulfate 1.5 Sodium saccharin 0.2 Sodium fluoride 0.21 Storage Charge 0.2 Perfume 1.2 Water Residual total 100.0%

[Example 2] Calcium carbonate supporting a fluoride ion supplying compound 25% Carrageenan 0.4 Sodium polyacrylate 0.6 Propylene glycol 3 Sorbitol 35 Sodium lauryl sulfate 1 Sodium saccharin 0.2 Sodium fluoride 0.21 Preservative 0.5 Perfume 1.2 Water Total 100.0%

[Example 3] Calcium carbonate supporting a fluoride ion supplying compound 35% Xanthan gum 0.3 Sodium alginate 0.9 propylene glycol 3.5 sorbitol 30 sodium lauryl sulfate 1.5 sodium saccharin 0.2 sodium fluoride 0.105 Preservative 0.2 Fragrance 1.2 Water Total 100.0%

[Example 4] Calcium carbonate supporting a fluoride ion supplying compound 30% Carrageenan 0.7 Sodium alginate 0.8 Propylene glycol 2.5 Sorbitol 30 Sodium lauryl sulfate 1.5 Sodium saccharin 0.2 Sodium fluoride 0.03 Preservative 0.2 Fragrance 1.2 Water Total 100.0%

[Example 5] Calcium carbonate supporting a fluoride ion supplying compound 15% Calcium hydrogen phosphate 20 Carrageenan 0.6 Xanthan gum 1.0 Propylene glycol 3 Sorbitol 35 Sodium lauryl sulfate 2 Sodium saccharin 0.2 Sodium monofluorophosphate 0 .8 Preservative 0.2 Perfume 1.2 Water Residual 100.0%

[Example 6] Calcium carbonate supporting fluoride ion supplying compound 20% Aluminum hydroxide 15 Sodium alginate 0.5 Carrageenan 0.4 Propylene glycol 2.5 Sorbitol 30 Sarcosinate 0.25 Sodium lauryl sulfate 0.8 Sodium saccharin 0 .3 Sodium monofluorophosphate 0.4 Preservative 0.2 Perfume 1.2 Water Residual 100.0%

[Example 7] Calcium carbonate supporting a fluoride ion-supplying compound 20% Silica 20 Toxyl (registered trademark) 2.5 Carrageenan 0.4 Sodium alginate 0.6 Polyethylene glycol 1.5 Propylene glycol 2 Sorbitol 25 Sodium lauryl sulfate 1 Saccharin sodium 0.2 Sodium fluoride 0.1 Preservative 0.2 Perfume 1.2 Water Residual 100.0%

[Example 8] Calcium carbonate supporting a fluoride ion supplying compound 30% Silica 5 Carrageenan 0.6 Sodium polyacrylate 0.5 Propylene glycol 2 Sorbitol 35 Sodium lauryl sulfate 1.5 Sodium saccharin 0.2 Hardened castor oil 1 Sodium fluoride 0.03 Preservative 0.2 Perfume 1.2 Water Residual 100.0%

[Example 9] Calcium carbonate supporting fluoride ion supplying compound 30% Toxyl (registered trademark) 5 Carboxymethyl cellulose 1.2 Propylene glycol 3 Glycerin 35 Sodium lauryl sulfate 1 Myristic acid diethanolamide 0.6 Saccharin sodium 0.2 Storage Charge 0.2 Perfume 1.2 Water Residual total 100.0%

[Example 10] Calcium carbonate supporting a fluoride ion supplying compound 35% Polyvinylpyrrolidone 0.8 Sodium alginate 0.4 Propylene glycol 2.5 Sorbitol 30 Sodium lauryl sulfate 1.5 Sodium saccharin 0.2 Sodium fluoride 21 Preservative 0.2 Perfume 1.2 Water Residual 100.0%

[Example 11] Calcium carbonate carrying a fluoride ion-supplying compound 30% Disodium hydrogen phosphate 10 Carrageenan 0.9 Propylene glycol 2.5 Sorbitol 30 Sodium lauryl sulfate 1.5 Sodium saccharin 0.2 Sodium monofluorophosphate 0.03 Preservative 0.2 Perfume 1.2 Water Residual 100.0%

[Example 12] Calcium carbonate supporting a fluoride ion-supplying compound 30% Hydroxyethyl cellulose 0.6 Carboxymethyl cellulose 0.8 Propylene glycol 2.5 Sorbitol 30 Sodium lauryl sulfate 1.5 Sodium saccharin 0.2 Sodium fluoride 0. 03 Preservative 0.2 Fragrance 1.2 Water Residual 100.0%

[0050]

EFFECTS OF THE INVENTION According to the present invention, since the fluoride ion-supplying compound-supporting particles immediately enter and remain inside the pit fissure, the action of the fluoride ions gradually released from the particles causes the pit fissure to grow. Occurrence and progress of corrosion are suppressed.

[Brief description of drawings]

FIG. 1 is a graph showing remineralization rates of samples used in Experimental Examples and Comparative Examples.

FIG. 2 is a graph showing the demineralization inhibition rate of the samples used in Experimental Examples and Comparative Examples.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Shoji Nakajima             1-3-7 Honjo, Sumida-ku, Tokyo Rio             Within the corporation F-term (reference) 4C083 AA122 AB032 AB172 AB322                       AB382 AB472 AC122 AC132                       AC582 AC792 AC862 AD042                       AD092 AD272 AD282 AD302                       AD352 BB25 CC41 EE32

Claims (2)

[Claims] 1. A composition for oral cavity, which comprises particles having an average particle size of 0.5 to 30 μm in which a fluoride ion supplying compound is carried on the surface of the particles. 2. The oral composition according to claim 1, which is used for preventing dental caries in a pit and fissure region existing in a molar.