JPH1017449A - Composition for hyperesthesia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition for hyperesthesia, containing hydroxyapatite, tricalcium phosphate, etc., having a specific particle diameter, capable of effectively preventing and treating the dentin hyperesthesia and useful for reinforcing the peripheries of dentin. SOLUTION: This composition for hyperesthesia contains hydroxyapatite, tricalcium phosphate, an antibacterial hydroxyapatite or an antibacterial tricalcium phosphate which has a particle diameter of 1.0-5.0μm, preferably 1.0-2.0μm. The antibacterial hydroxyapatite and/or the antibacterial tricalcium phosphate are obtained by allowing the hydroxyapatite and/or the tricalcium phosphate to adsorb and carry at least one metal selected from among silver, zinc and copper. The further addition of collagen exhibits synergistic effects for preventing and treating the dentin hyperesthesia. The composition for the hyperesthesia has good safety, does not color teeth, is excellent in touch and is long in the sustainability of the effect.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for hypersensitivity useful for effectively preventing and treating dentin hypersensitivity of teeth and for strengthening the periphery of dentin.

[0002]

2. Description of the Related Art It is believed that sharp electric shocks of teeth are caused by stimulating the nerves of the dentin of a tooth when a cold object, a hot object, a sweet object or a sour object is ingested. . The dentin of a tooth is penetrated by a large number of dentinal tubules, and a tissue fluid is contained in the dentinal tubules. This dental pain is caused by externally stimulated tissue fluid in the dentin tubules when exposed to dentin, stimulating sensory nerves near the boundary between the pulp and dentin It is believed that. This irritation is caused by anything that moves tissue fluid in the dentinal tubules,
Thermal stimuli, stimuli that produce a change in sweetness, sourness, or osmotic pressure will all cause dentin pain.
Therefore, pain is caused during eating, drinking, brushing with a toothbrush, or exercising, which considerably impairs daily life. Dentin hypersensitivity includes cervical hypersensitivity due to loss of enamel or cementum due to tooth abrasion or dental caries due to inappropriate brushing with a toothbrush, and root surface perception due to gingival degeneration due to incorrect brushing I have hypersensitivity. In recent years, the aging of the population and the increasing movement to preserve myelinated teeth have led to an increase in dentin hypersensitivity due to gingival degeneration and root exposure.

[0003] Many of the current treatments for dentin hypersensitivity are aimed at preventing the migration of intradentin solution. Methods of blocking external stimuli with drugs include (1) a method of mechanically coating the surface of exposed dentin or clogging dentinal tubules, and (2) promoting calcification in dentinal tubules and sealing the tubules. And (3) denaturing and coagulating odontoblasts. (1) Filling of glass ionomer cement, coating of silicon or resin, coating of potassium oxalate, etc. (2) Zinc chloride, paraform, strontium chloride coating, etc. (3)
Includes application of sodium fluoride. Dentifrices containing a drug useful for such dentin hypersensitivity have been studied and developed. This is because a method for treating dentin hypersensitivity with a dentifrice has many advantageous aspects, such as easy treatment in daily life. In addition, although irritating pain is a concern, exposure of dentin not only increases the frequency of root caries, but also avoids brushing, which can cause or worsen periodontal disease. Cannot be missed.

[0004] Examples of dentifrices suitable for hypersensitivity include dentifrices containing aluminum lactate and aluminum fluoride (Takeshi Uchida et al., Kodaigaku 7; 152-158, 197).
5), strontium chloride-containing dentifrice (Shoji Uchida et al., Nihon Periodon 22; 468-491, 1980), aluminum compound-containing dentifrice (Tetsuya Nakamura et al., Japanese Dental Review 5)
35; 263-269, 1987), a dentifrice containing aluminum lactate (Eikichi Yoneda et al., Nichihobo 33: 1070-1).
077, 1990), dentifrice containing zinc sulfate and aluminum chloride (Watari Hori et al., Japanese Dental Review 568; 237-24)
3, 1990), and dentifrice containing potassium nitrate (Toshihiko Nagata et al., Nikkei Periodon 34; 465-471, 1992).

[0005]

However, these dentifrices have drawbacks such as irritation to the pulp and gums, coloring of the teeth, non-persistence of the effects and insufficient effects. Satisfactory ones have not been obtained.
Further, not only the tooth surface but also the gums are considerably damaged by friction due to the brushing, and dentin and cementum are not as strong as enamel, so they are more easily worn than enamel and are more susceptible to erosion by acid. Therefore, if hyperesthesia is observed, it is necessary to not only treat but also protect the root. However, none of these dentifrices has a root protecting effect.

[0006]

Means for Solving the Problems To achieve the above object, the present inventors have a high preventive and therapeutic effect on dentin hypersensitivity, and have excellent dental root caries and therapeutic effects. As a result of intensive research to obtain a composition for the disease, hydroxyapatite, antibacterial hydroxyapatite,
A composition for hyperesthesia having a preventive effect on dentin hypersensitivity and an excellent therapeutic effect by using granules having a particle size of tricalcium phosphate or antibacterial tricalcium phosphate of from 1.0 μm to 5.0 μm. I found that I could get something.

It has also been found that the combination of these compositions with collagen has a synergistic effect on the prevention and treatment of dentin hypersensitivity, and that the composition for hypersensitivity has good safety. It has been found that it has good properties, does not color teeth, and is excellent in feeling of use, and has a long lasting effect, and has completed the present invention.

[0008] It is already known that hydroxyapatite is filled in microscopic defects in enamel to remineralize and has an effect of preventing dental caries ("Caries preventive effect of hydroxyapatite-containing dentifrice," Mizuo Kani Dental Journal Vol. 39, No. 6, June 1994). It also discloses that collagen relieves oral mucosal irritation and improves taste (see JP-A-60-48919) and protects gingiva and teeth (see JP-A-61-17508). . However, hydroxyapatite or tricalcium phosphate with a particle size of 1.0 μm to 5.0 μm blocks and calcifies the dentinal tubules, adsorbs and protects the cement and dentin, and furthermore, the collagen is bound to the above-mentioned hydroxyapatite and phosphorus. It has not yet been proposed that the combined use with tricalcium acid further blocks and calcifies the dentinal tubules, adsorbs and protects them on cement and dentin, and exhibits an excellent effect on hyperesthesia. The antibacterial hydroxyapatite and / or antibacterial tricalcium phosphate is obtained by adsorbing and supporting at least one metal ion selected from silver, zinc, and copper on hydroxyapatite and / or tricalcium phosphate. The use of hydroxyapatite and antibacterial tricalcium phosphate not only exhibits the above-mentioned effects of hydroxyapatite and tricalcium phosphate, but also protects the tooth surface from bacteria due to their antibacterial properties, thereby enhancing their effects.

The content of hydroxyapatite, tricalcium phosphate, antibacterial hydroxyapatite, or antibacterial tricalcium phosphate contained in the oral composition of the present invention is preferably 0.1% or more. If the content is less than 0.1%, it becomes difficult for apatite to come into contact with the demineralized portions of the teeth and the dentinal tubules, so that the effect of the present invention cannot be sufficiently obtained. Hydroxyapatite, tricalcium phosphate, antibacterial hydroxyapatite, or antibacterial tricalcium phosphate are effective when the particle diameter is in the range of 1.0 to 5.0 μm, preferably 1.0 to 2.0 μm. . Even if a particle diameter outside this range is used, the particle diameter is too small or too large for the dentinal tubule, so that the dentinal tubule cannot be closed, and the effect of treating hyperesthesia is low. In addition, collagen to be blended may be insoluble or soluble,
The compounding amount is 0.1 to 10.0%, preferably 0.1 to 5.0%, based on the total weight.

The oral composition of the present invention contains the above-mentioned hydroxyapatite, tricalcium phosphate, antibacterial hydroxyapatite, antibacterial tricalcium phosphate, and collagen together with other components according to a conventional method,
It is prepared in the form of toothpastes, liquid dentifrices, powdered dentifrices and the like. The intraoral composition of the present invention contains additives other than essential components, such as abrasives, wetting agents, surfactants, flavors, sweeteners and preservatives, and various active ingredients. Can be used as appropriate within a pharmaceutically acceptable range. Specific examples of these components are shown below. Abrasives: calcium carbonate, calcium pyrophosphate, calcium phosphate, silicic anhydride, aluminum silicate, aluminum hydroxide, calcium hydrogen phosphate and the like. Wetting agents; glycerin, sorbitol, propylene glycol, polyethylene glycol, dipropylene glycol, maltitol and the like. Surfactants: alkyl sulfates, alkyl benzene sulfonates, sucrose fatty acid esters, sodium lauryl sulfate and the like. Thickeners: hydroxyethylcellulose, sodium carboxymethylcellulose, carrageenan, carboxyvinyl polymer, sodium polyacrylate, chitansan gum, etc. Preservatives: sodium benzoate, methyl parapen, paraoxybenzoate, alkyldiaminoethyl glycine hydrochloride and the like. Sweeteners: saccharin sodium, xylitol, stevioside, etc. Flavors: menthol, orange oil, spearmint oil, peppermint oil, lemon oil, eucalyptus oil, methyl salicylate, etc. Other components: allantoin, tocopherol acetate, isopropylphenol, β-glycyrrhetinic acid, triclosan, chlorhexidine, dextranase, chlorophyll, flavonoid, tranexamsan, hinokitiol, and the like.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to Examples 1 to 13 showing disclosure examples of the present invention and Examples 14 to 15 showing examples using the dentifrice composition of the present invention. The present invention is not limited to the following examples. In addition, all% in each example are weight%.

Example 1 Toothpaste Composition Calcium Carbonate 29.0% Hydroxyapatite 1.0 Glycerin 25.0 Propylene Glycol 10.0 Polyethylene Glycol 6.0 Sodium Lauryl Sulfate 0.5 Hydroxyethyl Cellulose 1.0 Sorbitol Aqueous solution (70% concentration) 0.2 Methyl parapen 0.1 Menthol 0.5 Water 26.7 Total 100.0

[Example 2] Toothpaste composition Silica anhydride 37.0% Hydroxyapatite 5.0 Glycerin 20.0 Propylene glycol 9.0 Sodium lauryl sulfate 0.5 Hydroxyethyl cellulose 1.0 Sorbitol aqueous solution (70% Concentration) 1.7 Methyl parapen 0.1 Menthol 0.8 Water 24.9 Total 100.0

Example 3 Toothpaste Composition Calcium Hydrogen Phosphate 20.0% Hydroxyapatite 10.0 Glycerin 20.0 Propylene Glycol 10.0 Polyethylene Glycol 5.0 Sodium Lauryl Sulfate 0.8 Hydroxyethyl Cellulose 0.8 5 Collagen 0.1 Methyl parapen 0.1 Sorbitol aqueous solution (70% concentration) 3.3 Water 30.2 Total 100.0

Example 4 Toothpaste Composition Aluminum Hydroxide 11.0% Hydroxyapatite 35.0 Glycerin 21.8 Propylene Glycol 5.0 Sodium Lauryl Sulfate 1.6 Sodium Benzoate 0.1 Sorbitol Aqueous Solution (70 % Concentration) 4.5 Water 21.0 Total 100.0

Example 5 Toothpaste Composition Tricalcium Phosphate 17.0% Hydroxyapatite 17.0 Silicic Anhydride 12.7 Glycerin 11.0 Propylene Glycol 10.0 Sodium Lauryl Sulfate 1.0 Butyl Parapen 0 .2 Sorbitol aqueous solution (70% concentration) 5.0 Water 26.1 Total 100.0

Example 6 Toothpaste Composition Calcium Carbonate 35.0% Tricalcium Phosphate 0.1 Glycerin 20.0 Sodium Lauryl Sulfate 1.0 Hydroxyethyl Cellulose 1.0 Paraoxybenzoate 0.1 Spearmint 0 .5 Sorbitol aqueous solution (70% concentration) 6.7 Collagen 10.0 Water 25.6 Total 100.0

Example 7 Toothpaste Composition Silica Anhydride 11.0% Tricalcium Phosphate 5.0 Glycerin 22.0 Propylene Glycol 2.0 Sodium Lauryl Sulfate 1.0 Carboxymethyl Cellulose 1.2 Carrageenan 0.2 8 Methyl parapen 0.1 Menthol 0.6 Sorbitol aqueous solution (70% concentration) 16.7 Water 39.6 Total 100.0

Example 8 Toothpaste Composition Calcium hydrogen phosphate 20.0% Tricalcium phosphate 14.0 Glycerin 19.6 Propylene glycol 10.0 Sodium lauryl sulfate 1.0 Carrageenan 0.4 Paraoxybenzoic acid Ester 0.1 Spearmint 0.6 Sorbitol aqueous solution (70% concentration) 8.4 Water 25.9 Total 100.0

Example 9 Toothpaste composition Tricalcium phosphate 20.0% Calcium hydrogen phosphate 20.0 Glycerin 27.0 Polyethylene glycol 3.0 Sodium lauryl sulfate 1.0 Kitansan gum 0.5 Collagen 1. 0 Methyl parapen 0.1 Menthol 0.5 Sorbitol aqueous solution (70% concentration) 10.7 Water 16.2 Total 100.0

Example 10 Toothpaste Composition Tricalcium phosphate 35.0% Aluminum hydroxide 10.0 Glycerin 20.0 Propylene glycol 5.0 Sodium lauryl sulfate 1.0 Carrageenan 0.3 Methyl parapen 0.1 Menthol 0.6 Sorbitol aqueous solution (70% concentration) 2.0 Water 26.0 Total 100.0

Example 11 Liquid Dentifrice Composition Hydroxyapatite 0.1% Ethyl Alcohol 10.0 Sodium Lauryl Sulfate 1.0 Glycerin 2.0 Menthol 0.4 Sorbitol Aqueous Solution (70% Concentration) 16.5 Collagen 0 .1 Water 69.9 Total 100.0

Example 12 Toothpaste Composition Containing Antibacterial Hydroxyapatite (1) Production of Antibacterial Hydroxyapatite 10.0 g of hydroxyapatite was added to 100 ml of distilled water.
Add 0.2 g of silver nitrate and stir. The product was thoroughly washed with distilled water and dried to obtain an antibacterial hydroxyapatite containing about 1% of silver.

(2) Production of toothpaste composition The toothpaste composition having the following composition was obtained using the above-mentioned antibacterial hydroxyapatite. Calcium carbonate 29.0% Antibacterial hydroxyapatite 1.0 Glycerin 25.0 Propylene glycol 10.0 Polyethylene glycol 6.0 Sodium lauryl sulfate 0.5 Hydroxyethylcellulose 1.0 Sorbitol aqueous solution (70% concentration) 0.2 Methyl parapen 0 .1 Menthol 0.5 Water 26.7 Total 100.0

Example 13 Toothpaste composition containing antibacterial tricalcium phosphate (1) Production of antibacterial tricalcium phosphate 50.0 g of tricalcium phosphate and 1.0 g of copper nitrate in 500 ml of distilled water 6.9 g of zinc nitrate are added and stirred. The product is washed well with distilled water and dried, copper is about 0.5% and zinc is about 3.
An antibacterial tricalcium phosphate containing 0% was obtained.

(2) Production of toothpaste composition A toothpaste composition having the following composition was obtained using the above-mentioned antibacterial tricalcium phosphate. Calcium hydrogen phosphate 20.0% Antibacterial tricalcium phosphate 14.0 Glycerin 19.6 Propylene glycol 10.0 Sodium lauryl sulfate 1.0 Carrageenan 0.4 Paraoxybenzoic acid ester 0.1 Spearmint 0.6 Sorbitol aqueous solution ( 8.4 water 25.9 total 100.0

[Example 14] Adhesion effect test on dentinal tubules (1) In case of using hydroxyapatite Using the dentifrice of Example 2, an adhesion effect test on dentinal tubules was performed. The lower molars of the human lower teeth were used as the test teeth. Model trimmer on the lingual enamel surface was removed and # 4 under water injection
It was polished with a 00, # 600 emery paper so as to have a smooth ivory surface. After polishing the surface, it was immersed in a demineralized liquid (0.1 M lactic acid, 500 mg / l hydroxyapatite, adjusted to pH 4.8) and left at 37 ° C. for 30 hours. After being washed with distilled water, it was dried to obtain test teeth.

For comparison, the particle diameter is less than 1.0 μm,
55.0 μm (average particle size: 2.0 μm), a dentifrice having a composition of dentifrice 2 was prepared using hydroxyapatite powder having a particle size of more than 5.0 μm, and using dentifrice and artificial saliva,
A slurry containing 10% by weight of the dentifrice was prepared. The test teeth were left in the slurry at 37 ° C. for 10 hours. After washing with distilled water, it was dried at room temperature, and the dentin surface was gold-coated according to a conventional method, and observed with a scanning electron microscope (SEM).

FIGS. 1 and 2 show photographs of surface observation. FIG.
(A) is an SEM observation photograph result when the same dentifrice (blank) as in Example 2 was used without containing hydroxyapatite and other compositions. The pores on the surface are ivory tubules. FIG. 1b shows the experimental results when the dentifrice of Example 2 using a hydroxyapatite powder of less than 1.0 μm was used. From this photograph, it was found that the hydroxyapatite of less than 1.0 μm had a dentinal tubule. It turned out that the blockade had not progressed much. FIG. 1c shows 1.0-5.0 μm.
m (average particle size: 2.0 μm), using dentifrice of hydroxyapatite powder. The dentinal tubules on the surface are blocked, and the dentin surface is uniformly and densely covered with the hydroxyapatite deposit. I knew it was there.

FIG. 2A shows a case where a hydroxyapatite powder having a size of 5.0 μm or more is used. FIG. 2B shows 1.0 to 5.
The experimental results obtained when a dentifrice containing 1.0% collagen added to the dentifrice of Example 2 using hydroxyapatite powder of 0 μm (average particle size of 2.0 μm) were obtained. When a combination of 5.0 μm hydroxyapatite powder and collagen was blended, dentinal tubules were best closed.

(2) Using Tricalcium Phosphate Using the dentifrice of Example 8, a test similar to the test described above was conducted. 3 and 4 show photographs of surface observation after the test. FIG. 3A is a SEM observation photograph result when the same dentifrice (blank) as in Example 8 was used without containing tricalcium phosphate and other compositions. The pores on the surface are ivory tubules. FIG. 3B shows the experimental results when the dentifrice of Example 8 using tricalcium phosphate powder having a particle size of less than 1.0 μm was used. It was found that ivory tubules were hardly blocked. FIG. 3 c shows 1.0 to 5.0 μm.
m (average particle size: 2.0 μm), using dentifrice of powdered tricalcium phosphate. The exposed portion of the dentinal tubules on the surface was almost restored, and the surface of the dentin was deposited with tricalcium phosphate. Was covered with.

FIG. 4A shows the case where a powder of tricalcium phosphate having a particle size of 5.0 μm or more is used, but the blockage of the dentinal tubules hardly progresses. FIG. 4B shows 1.0 to 5.0.
The experimental result when 5.0% collagen was used in the dentifrice of Example 8 using tricalcium phosphate powder having an average particle size of 2.0 μm was 1.0 to 5.0 μm. The best results were obtained when the tricalcium phosphate powder and collagen were combined and blended.

[Example 15] Evaluation of effectiveness for hyperesthesia (1) In case of using hydroxyapatite Brushing twice or more with dentifrice disclosed in Example 2 for 30 subjects At random. Using 120 teeth of these subjects as test teeth, the response to air gun stimulation, water gun stimulation, and abrasion stimulation at 1 month before use and for 1 week, 2 weeks and 1 month after use was evaluated by applying the following test scores. In addition, hydroxyapatite having a particle diameter of 1.0 to 5.0 μm was used. Score Evaluation criteria 0 ……… No pain 1 ……… Pain 2 ……… Strong pain Table 1 summarizes the obtained test scores and fluctuations in the scores.
It is. That is, it was found that the use of the present dentifrice effectively works against irritation.

[0034]

[Table 1]

(2) Use of Tricalcium Phosphate Thirty subjects were randomly brushed at least twice a day with the dentifrice disclosed in Example 8. Using 120 teeth of those subjects as test teeth, the response to air gun stimulation, water gun stimulation, and abrasion stimulation at 1 month, 2 weeks and 1 month before and after use was evaluated by applying the same test score as described above. The results are shown in Table 2. Note that 1.
Tricalcium phosphate with a particle size of 0-5.0 μm was used.

[0036]

[Table 2]

From the results of Examples 14 and 15, the particle diameter was 1.
Hydroxyapatite of 0 μm to 5.0 μm and tricalcium phosphate are effective for dentin hypersensitivity, and it has been shown that hydroxyapatite and collagen are more effective when used in combination with collagen. .

[0038]

According to the present invention, it is possible to obtain a composition for hyperesthesia having an excellent effect of effectively preventing and treating dentin hyperesthesia and strengthening the periphery of dentin.

[Brief description of the drawings]

FIG. 1 (a) is a micrograph (× 2000) of a tooth tissue when a dentifrice (blank) containing no hydroxyapatite is used. FIG. 1 (b)
Micrograph (× 20) of dentin tissue when using a dentifrice using a hydroxyapatite powder of less than 1.0 μm
00). FIG. 1C is a photomicrograph (× 2000) of the dentin tissue when a dentifrice using a hydroxyapatite powder of 1.0 μm to 5.0 μm was used.

FIG. 2 (a) is a micrograph (× 2000) of a tooth tissue when a dentifrice using a hydroxyapatite powder of 5.0 μm or more is used. FIG. 2 (b)
Is a micrograph (× 2000) of a dentin tissue when collagen is added to a dentifrice using a hydroxyapatite powder of 1.0 μm to 5.0 μm.

FIG. 3 (a) is a photomicrograph (× 2000) of dentin tissue when a dentifrice (blank) not containing tricalcium phosphate was used. (B) of FIG.
It is a microscope picture (x2000) of a dentin tissue when using a dentifrice using tricalcium phosphate powder of less than μm. FIG. 3C shows phosphoric acid 3 of 1.0 μm to 5.0 μm.
It is a microscope picture (x2000) of a dentin tissue at the time of using a dentifrice using calcium powder.

FIG. 4 (a) is a photomicrograph (× 2000) of a tooth tissue when a dentifrice using tricalcium phosphate powder of 5.0 μm or more was used. (B) of FIG.
It is a micrograph (x2000) of a dentin tissue when collagen is added to a dentifrice using tricalcium phosphate powder of 1.0 μm to 5.0 μm.

Claims (5)

[Claims] 1. A composition for hyperesthesia characterized by using at least hydroxyapatite having a particle size of 1.0 μm to 5.0 μm. 2. A composition for hypersensitivity, characterized in that at least tricalcium phosphate having a particle size of 1.0 μm to 5.0 μm is used. 3. The composition for hypersensitivity according to claim 1, wherein the composition contains 0.1 to 10.0% of collagen. 4. The composition according to claim 1, wherein the hydroxyapatite carries one or more metal ions selected from the group consisting of silver, zinc and copper. 5. The composition for hypersensitivity according to claim 2, wherein the tricalcium phosphate carries one or more metal ions selected from the group consisting of silver, zinc, and copper.