JPH0692860A - Therapeutic agent for hypersthesia - Google Patents

Abstract

PURPOSE:To obtain a lightly usable therapeutic agent for hyperesthesia of the dentin, having excellent obliterating effects on dentinal tubules and improving effects on acid resistance without any damaging properties such as coloring. CONSTITUTION:This therapeutic agent for hyperesthesia comprises (A) one or two or more water-soluble phosphoric acid compounds selected from the group consisting of (i) phosphoric acid esters having a 6-20C alkyl group which may be substituted with a fluorine atom, (b) phosphoric acid ester-modified silicones and (c) phosphoric acid ester (meth)acrylate-based polymers and (B) water-insoluble noncalcium-based powder having 0.01-2mum average particle diameter in amounts so as to provide (1/1) to (1/50) weight ratio of the ingredients [(A)/(B)].

Description

Detailed Description of the Invention

[0001]

The present invention relates to a therapeutic agent for hyperesthesia, more specifically, it contains a specific water-soluble phosphoric acid compound and a non-calcium powder having a specific particle size in a specific compounding ratio, and is excellent. The present invention relates to a therapeutic agent for hypersensitivity, which has an effect of obstructing dentinal tubules and an effect of improving acid resistance of dentin, and is effective in treating and preventing hypersensitivity of dentin.

[0002]

2. Description of the Related Art Hypersensitivity of dentin is caused by acid etc. acting on the dentin of the tooth, elution of lime and opening of dentinal tubules, and the liquid entering the dentin is subjected to heat and physical force and It stimulates all nerves and causes pain. Therefore, for treatment and prevention, it is necessary to block dentinal tubules or improve acid resistance of dentin.

Conventionally used drugs for treating hypersensitivity are silver diamine difluoride, silver nitrate, strontium chloride, stannous fluoride, sodium fluoride, aluminum fluoride, aluminum lactate, zinc chloride and water. There are compounds such as calcium oxide, paraformaldehyde and formaldehyde. Among these, the silver compound is excellent in the blocking property of the dentinal tubule, but has a remarkable coloring property and has a drawback that it is not suitable for general use.
In addition, it cannot be said that sufficient effects have been obtained for other compounds.

Further, other treatment methods for hypersensitivity include resin filling, laser treatment or extraction, and root canal filling. These treatment methods are specialized by dentists. However, there is a problem that it cannot be easily performed.

[0005]

Therefore, it is desired to develop a therapeutic agent for hypersensitivity which is effective for treating and preventing hypersensitivity of dentin, can be easily used, and is harmless due to coloring and the like. It was

[0006]

Under these circumstances, the inventors of the present invention have conducted diligent research and, as a result, have found that a specific water-soluble phosphate compound and a water-insoluble non-calcium-based powder having a specific particle size have a specific ratio. The inventors have found that the above problems can be solved by using the above method, and completed the present invention.

That is, the present invention comprises the following components (A) and (B): (A) (a) 6 carbon atoms which may be substituted by a fluorine atom.
To one or two or more water-soluble phosphoric acid compounds selected from the group consisting of phosphoric acid ester having 20 to 20 alkyl groups, (b) phosphoric acid ester modified silicone, and (c) phosphoric acid ester (meth) acrylate-based polymer, (B) a water-insoluble non-calcium-based powder having an average particle diameter of 0.01 to 2 μm, in a weight ratio of (A) / (B) = 1/1 to 1/50. The present invention provides a therapeutic agent for hyperesthesia.

Since the water-soluble phosphate compound of the component (A) in the present invention is a surfactant, it has a foaming power and a solubilizing power by itself, and the taste of foods and drinks after use is low and mild. Since it has the property of not changing, it can be easily used as a main activator. Furthermore, since it has a phosphate group, it has a property of forming a hydrophobic film with high adsorptivity on the tooth surface and high acid resistance, and when it gets into the dentinal tubule, saliva and dentinal tubule By forming a salt with calcium ions on the surface of the liquid or dentin, it becomes a powder that is practically insoluble in water, so it is fixed in the dentinal tubule, and the dentinal tubule is closed to prevent nerve stimulation of the tooth surface. It has the property.
Therefore, even if it is used a few times, it is highly effective in treating and preventing hypersensitivity and has little harm. The term “substantially insoluble in water” means that purified water at pH 7 and 25 ° C.
When 10g of powder is added to 0g and mixed by stirring, 95%
It means that the above powder remains without being dissolved.

The component (A) in the present invention includes (a) a phosphoric acid ester having an alkyl group having 6 to 20 carbon atoms which may be substituted by a fluorine atom, (b) a phosphoric acid ester modified silicone, and (c) phosphorus. One or two or more selected from the group consisting of acid ester (meth) acrylate-based polymers, and of these, phosphoric acid having an alkyl group having 6 to 20 carbon atoms which may be substituted with a fluorine atom. Examples of the ester (hereinafter, abbreviated as “alkyl phosphate ester”) (a) include monoalkyl phosphate ester or mono (perfluoroalkyl) phosphate ester represented by the following general formula (1).

[0010]

[Chemical 4]

[Wherein R ¹ represents an alkyl group having 6 to 20 carbon atoms or a perfluoroalkyl group, and M ¹ and M ² are the same or different and each is a hydrogen atom, ammonium, alkylamine, alkanolamine or basic amino acid. Indicates]

In formula (1), R ¹ has 6 to 20 carbon atoms.
Examples of the alkyl group include hexyl group, octyl group, 2-
Examples thereof include an ethylhexyl group, a decyl group, a dodecyl group, a tetradecyl group, a hexadecyl group, and an octadecyl group. Examples of the perfluoroalkyl group include groups in which a hydrogen atom of the above alkyl group is substituted with a fluorine atom. Among these alkyl groups, an alkyl group having 8 to 16 carbon atoms, particularly an alkyl group having 10 to 14 carbon atoms is preferable, and a perfluoroalkyl group is an alkyl group having 8 to 16 carbon atoms, particularly an alkyl group having 10 to 14 carbon atoms, Fluorine substitution degree is 10
100%, especially 60 to 100% is preferable. Further, as the alkylamine of M ¹ or M ² , methylamine, ethylamine, propylamine, butylamine,
Examples include trimethylamine and triethylamine, examples of the alkanolamine include monoethanolamine, diethanolamine, triethanolamine, and the like, and examples of the basic amino acid include arginine, lysine, and the like.

Of the compounds represented by the general formula (1), those in which R ¹ is a perfluoroalkyl group can further enhance the hydrophobicity and acid resistance of the adsorption coating on the tooth surface.

Monoalkyl phosphate or mono (perfluoroalkyl) represented by the general formula (1).
The phosphoric acid ester can be obtained by, for example, hydrolyzing a monoalkyl phosphorodichloridate obtained by reacting phosphorus oxychloride with a corresponding aliphatic alcohol.

The phosphoric acid ester-modified silicone (b) has the following general formula (2), (3) or (4):
The polymer represented by

[0016]

[Chemical 5]

[In the formula, X represents a divalent hydrocarbon group having 1 to 10 carbon atoms, M ³ and M ⁴ are the same or different and represent a hydrogen atom, ammonium, alkylamine, alkanolamine or basic amino acid. , M and n each represent a positive number]

In the general formula (2), (3) or (4), X is a hydrocarbon group having 1 to 10 carbon atoms, preferably an alkylene group, particularly preferably an ethylene group or a trimethylene group. The alkylamine, alkanolamine and basic amino acid of M ³ and M ⁴ are the same as those mentioned above. Further, in the expressions (2) and (3), m and n are preferably m / n = 1/100 to 100/1, particularly preferably 1/20 to 60/1, and at this time m + n
Is 10 or more, especially 10 to 1000, especially 10 to 20
It is preferably 0.

Further, as the phosphoric acid ester (meth) acrylate polymer (c) in the present invention, a polymer having a constitutional unit represented by the following general formula (5) can be used.

[0020]

[Chemical 6]

[In the formula, R ² represents a hydrogen atom or a methyl group, R ³ represents a hydrocarbon group having 4 to 20 carbon atoms, M ⁵ represents a hydrogen atom, an alkali metal atom, ammonium, an alkylamine or an alkanolamine. And p is 0 or 1.]

This polymer may be a homopolymer composed of the constitutional unit represented by the general formula (5), or a copolymer having another monomer as the constitutional unit in addition to the constitutional unit represented by the general formula (5). , And the binding mode may be block or random. Particularly preferred are those having a pentamer or higher oligomer of the constitutional unit represented by the general formula (5) and having a molecular weight in the range of 10 to 5,000,000, particularly 10,000 to 1,500,000, and particularly 10,000 to 200,000. is there.

In the general formula (5), the hydrocarbon group having 4 to 20 carbon atoms represented by R ³ is butyl group, hexyl group, octyl group, 2-ethylhexyl group, decyl group,
Examples thereof include dodecyl group, tetradecyl group, hexadecyl group, octadecyl group, etc., examples of the alkali metal atom represented by M ⁵ include sodium, potassium, lithium, etc., and examples of the alkylamine and alkanolamine are the same as above. Is mentioned.

The polymer may be produced by any method, for example, JP-A-62-15.
By using the method described in Japanese Patent Publication No. 210 (a novel polymer containing a phosphoric acid residue and a method for producing the same, Wakatsuki et al.), And with regard to a copolymer having a structural unit represented by the general formula (5), The method described in JP-A No. 62-15214 (manufacturing method of copolymer, Wakatsuki et al.) Can be used. That is, the general formula (6)

[0025]

[Chemical 7]

A monomer represented by the formula [wherein R ² , R ³ , M ⁵ and p have the same meaning as described above], or this monomer and another vinyl monomer are radical polymerization initiators. By polymerizing in the presence of, a phosphoric acid ester polymer relating to the polymer can be obtained.

The vinyl monomer as a partner monomer for copolymerization with the phosphoric acid group-containing monomer represented by the formula (6) may be any copolymerizable monomer, for example, anionic monomer. Examples of the monomer include (meth) acrylic acid, crotonic acid, vinylbenzoic acid, vinylsulfonic acid, styrenesulfonic acid, 3-acrylamido-2,2-dimethylpropane-1-sulfonic acid, and vinyltoluenesulfonic acid. Unsaturated monobasic acids, unsaturated dibasic acids such as maleic acid and fumaric acid, and monoesters thereof, and monomers having a carboxylic acid or sulfonic acid group such as maleic anhydride, and also cations. Examples of the polymerizable monomer include vinyl pyridine, monovinyl pyridines such as 2-methyl-5-vinyl pyridine, N, N-dimethylaminostyrene, N, N-dimethyl. Styrenes having a dialkylamino group such as ruaminomethylstyrene, esters of a (meth) acrylic acid having a dialkylamino group such as N, N-dimethylaminoethyl (meth) acrylate and N, N-diethylaminopropyl (meth) acrylate Kind, N
(Meth) acrylamides having a dialkylamino group such as-(N ', N'-dimethylaminoethyl) (meth) acrylamide and N- (N', N'-diethylaminopropyl) (meth) acrylamide, (meth) allyl Examples include unsaturated amines such as dimethylamine, (meth) acryloyloxyethyltrimethylammonium chloride, and ammonium salts having an unsaturated group such as (meth) acrylamidopropyltrimethylammonium chloride. (Meth) acrylic acid alkyl ester (alkyl group is linear or branched and has 1 to 18 carbon atoms), glyceryl (meth) acrylate, polyethylene glycol (meth) acrylate, glycidyl (meth) acrylate, allyl glycidyl ether,
Vinyl acetate, acrylonitrile, styrene, alkyl-substituted styrene (alkyl group having 1 to 18 carbon atoms), (meth)
Examples thereof include acrylamide and vinylpyrrolidone. It is also possible to use two or more types of these copolymerization partner monomers as a mixture.

In the therapeutic agent for hyperesthesia of the present invention, the compounding amount of the water-soluble phosphate compound as the above-mentioned component (A) is 0.1 to 0.1.
50% by weight (hereinafter referred to simply as%), especially 0.5 to 5%
Is preferred.

In the therapeutic agent for hyperesthesia of the present invention,
The water-insoluble non-calcium-based powder as the component (B) has an effect of blocking the dentin tubules and an effect of improving acid resistance of dentin. In the present invention, the non-calcium-based powder means a powder having a structure having no calcium atom in the molecule.

As the water-insoluble non-calcium powder as the component (B), both organic and inorganic powders can be used as long as they have high acid resistance, and aluminum hydroxide is particularly preferable. , Alumina, silicic acid anhydride,
Examples include inert non-calcium-based inorganic powders such as hydrous silicic acid and synthetic aluminum silicate. In addition, water-insoluble bactericidal agents, anti-inflammatory agents, tooth strengthening agents, powders of medicinal agents such as enzymes can also be used as the component (B). The particle size of the component (B) is required to be 0.01 to 2 μm,
It is preferably from 0.1 to 1.5 μm, particularly preferably from 0.1 to 1 μm. If the particle size is less than 0.01 μm, the blocking effect of the dentinal tubules will be reduced, and if the particle size exceeds 5 μm, the dentinal tubule diameter will be 1 to 5 μm. It cannot penetrate into the dentinal tubules enough to obtain the blocking effect. The particle size was measured by the laser scattering method.

Water-insoluble non-calcium powder (B)
As the above, by using the composite powder of the above-mentioned inert non-calcium-based inorganic powder and the medicinal agent, a therapeutic effect on diseases other than hyperesthesia can be obtained. Here, the composite powder means a powder in which an inert non-calcium-based inorganic powder and a drug are mixed in advance and weakly integrated by an adsorption phenomenon or the like.

The medicinal agent used for the composite powder is, for example, sodium monofluorophosphate which is a tooth strengthening agent,
Water-soluble fluorides such as tin fluoride and sodium fluoride are mentioned, and by using them, the acid resistance of teeth can be further improved.

Other medicinal agents used in the composite powder include, for example, chlorhexidine salts, triclosan, cetylpyridinium chloride, thymoles, benzalkonium chloride, zinc chloride and other bactericides; sodium phosphate and other pH. Regulators; enzymes such as dextranase, amylase, protease, lysozyme, mutanase; sodium chloride, hinokitiol, ε-aminocaproic acid, tranexamic acid, allantoins, tocopherols, octylphthalide, nicotinic acid esters, dihydrocholesterol, Glycyrrhetinic acid, glycyrrhizinic acid and salts thereof, glycerophosphate, chlorophyll, water-soluble inorganic phosphate compound, azulene, chamomile, assembly, toki, Kawayumi, anti-inflammatory agents such as crude drugs, blood circulation promoters, etc. ,these By using
Highly effective for caries and periodontal diseases.

In the therapeutic agent for hyperesthesia of the present invention,
The blending amount of the water-insoluble non-calcium powder as the component (B) is 5
-60% is preferable.

Further, in the therapeutic agent for hyperesthesia of the present invention, the above-mentioned components (A) and (B) are in a weight ratio of (A) /
(B) = 1/1 to 1/50, preferably 1/7 to 1/4
It is blended in such an amount that it becomes zero. When the value of (A) / (B) exceeds 1/1, the component (B) does not sufficiently enter the dentinal tubule, and when the value of (A) / (B) is less than 1/50, the component (B) is Even if the ivory tubules are blocked, they are not fixed by the component (A) and immediately come off.

The therapeutic agent for hypersensitivity of the present invention can be produced by a conventional method, and is used by applying it to the tooth surface or brushing with a toothbrush. In addition, as for the physical properties, since powder does not enter the dentinal tubules when brushing or applying unless the viscosity is to some extent, the liquid form is not suitable and the viscosity is 30
It is preferably in the form of a paste of 0 to 40,000 cps.

Further, the therapeutic agent for hyperesthesia of the present invention may contain various known ingredients depending on its form. For example, in addition to tooth strengthening agents and drug agents such as the above-mentioned water-soluble fluorides, glycerin, sorbit, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltite, lactit, etc. Wetting agent; carboxymethyl cellulose and its salts, methyl cellulose, hydroxyethyl cellulose, carrageenan, sodium polyacrylate, hydroxypropyl cellulose, carboxymethyl hydroxyethyl cellulose sodium, sodium alginate, propylene glycol alginate ester, xanthan gum, tragacanth gum, karaya gum, arabic gum, polyvinyl alcohol, Binders such as polyvinylpyrrolidone, veegum and laponite; saccharin Thorium, stevioside,
Sweeteners such as thaumatin, aspartyl phenylalanine methyl ester; preservatives such as p-hydroxybenzoic acid, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-pydroxybenzoate, sodium benzoate; titanium dioxide, etc. Colorants and pigments of peppermint oil, spearmint oil, menthol, carvone,
Anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineol, linalool, ethyl linalool, vanillin, thymol, anise oil, lemon oil, orange Oil, sage oil, rosemary oil, cinnamon oil, pimento oil, laurel oil, perilla oil, winter green oil,
Fragrances such as clove oil and eucalyptus oil can be appropriately used. Further, conventionally used activators such as lauryl sulfate, myristyl sulfate, α-olefin sulfonate, N-acyl amino acid salt, acyl monoglyceride sulfate, fatty acid monoglyceride, fatty acid monoalkanolamide, polyoxyethylene sorbitan fatty acid ester. , Pooxyethylene hydrogenated castor oil, alkyl glycoside, imidazolinium betaine, alkyl betaine,
Alkylamidobetaine, sulfobetaine, amine oxide sugar glycerin ester and the like can also be used in combination.

The amount of the medicinal agent such as water-soluble fluoride used is 0.
An amount of 01 to 5%, particularly 0.1 to 0.5% is preferable. In addition, when a water-soluble fluoride is blended, the pH of the acidic region tends to be better than that of the neutral region in the adsorption of the water-soluble fluoride on the tooth surface. Since the amount of incorporation into the body also increases, it is preferable to adjust the hypersensitivity pH of the present invention to 7 or less and to a range that is not harmful to the teeth, and particularly preferably pH 4 to 7.

[0039]

EFFECTS OF THE INVENTION The therapeutic agent for hyperesthesia of the present invention has an excellent dentinal tubule occlusion effect and an effect of improving acid resistance of dentin, is not harmful due to coloring, etc., and can be easily used. It is extremely useful for treating and preventing dentin hypersensitivity.

[0040]

The present invention will be further described with reference to examples, but the present invention is not limited thereto.

Example 1 A dentifrice having the following composition was prepared by a conventional method, and a test for occluded dentinal tubules was conducted according to the following method. Table 2 shows the test results of the compound A in the composition and the dentinal tubule blocking effect.

[0042]

(Table 1) (Composition) Aluminum hydroxide (average particle size 1 μm) 40.0% Sorbitol liquid 35.0 Propylene glycol 5.0 Polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 2.0 Sodium benzoate 0. 2 Saccharin sodium 0.1 Sodium monofluorophosphate 0.7 Silicic anhydride (Average particle size 2 μm) 7.5 Compound A 1.5 Hydroxyethyl cellulose 0.8 10% Sodium hydroxide 1.5 Perfume 0.9 Purified water balance 100.0%

(Test method) A sample is prepared by exposing the dentin of a healthy human tooth by cutting. A sample was decalcified with a 0.5% phosphoric acid aqueous solution at room temperature for 30 minutes and then immersed in artificial saliva for 1 day, and used for the experiment. 0.5g for toothbrush
The toothpaste was removed, the sample was brushed for 3 minutes, then brushed with running water for 3 minutes, washed, and immersed in artificial saliva for 1 hour. The sample was dried and the surface of the sample was observed with a scanning electron microscope to examine the occlusal property of the dentinal tubule.

The determination of the results was made by ◯ when 80% or more of the dentinal tubules were occluded, and Δ when 50% or more and less than 80% of the dentin tubules were occluded. The case where the blockage was less than 50% was designated as x.

[0045]

[Table 2]

Further, the same test of dentinal tubule occlusion effect was conducted on a commercial product which is said to be effective against hyperesthesia. The results are shown in Table 3.

[0047]

[Table 3]

Example 2 Using the product 1 of the present invention and the commercially available products 1 and 2 in Example 1,
The amount of aluminum on the surface of the sample obtained by the same method as in Example 1 was analyzed using EPMA (EDX).

As a result, it was not possible to quantify the sample surface because the sample surface was not a uniform plane and density, but it was observed that a large amount of aluminum was localized in the dentinal tubule in the product 1 of the present invention.
However, Aluminum was not detected in the commercial product 1. Further, in the commercial product 2, although aluminum was detected, the absolute amount thereof was less than half that of the product of the present invention, and localization to the dentinal tubule portion could not be observed.

Example 3 A dentifrice having the following composition was produced by a conventional method.

[0051]

(Table 4) (Composition) Aluminum hydroxide (average particle size: 0.5 μm) 25.0% Solbit solution 40.0 Propylene glycol 5.0 Polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 2.0 Sodium benzoate 0.2 sodium saccharin 0.1 sodium monofluorophosphate 0.7 silicic acid anhydride (average particle size 2 μm) 7.5 monoalkylphosphoric acid (carbon number of alkyl group = 12) 1.5 hydroxyethyl cellulose 1.5 10% water Sodium oxide 1.5 Zinc chloride 0.1 Perfume 0.9 Purified water Balance 100.0%

Example 4 A dentifrice having the following composition was produced by a conventional method.

[0053]

(Table 5) (Composition) Aluminum hydroxide (average particle size 2 μm) 30.0% Solbit solution 35.0 Propylene glycol 5.0 Polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 2.0 Sodium benzoate 0. 2 Saccharin sodium 0.1 Sodium monofluorophosphate 0.7 Silicic anhydride (Average particle size 2 μm) 5.0 Monoalkyl phosphoric acid (alkyl group carbon number = 14) 1.5 Hydroxyethyl cellulose 0.8 Glycyrrhetinic acid 0.1 Fragrance 0.9 Purified water Balance 100.0%

Example 5 A dentifrice having the following composition was produced by a conventional method.

[0055]

[Table 6] (Composition) Aluminum hydroxide (average particle size 1 μm) 45.0% Solbit solution 25.0 Propylene glycol 5.0 Polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 2.0 Sodium benzoate 0. 2 Sodium saccharin 0.1 Sodium monofluorophosphate 0.7 Silicic anhydride (Average particle size 2 μm) 3.0 Monoalkylphosphoric acid (carbon number of alkyl group = 16) 1.5 Hydroxyethyl cellulose 0.8 10% Sodium hydroxide 1.5 Glycyrrhetinic acid 0.1 Triclosan 0.1 Perfume 0.9 Purified water Balance 100.0%

Example 6 A dentifrice having the following composition was produced by a conventional method.

[0057]

Table 7 (Composition) Alumina (average particle size 0.5 μm) 30.0% sorbit solution 35.0 propylene glycol 5.0 polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 2.0 sodium benzoate 2 Saccharin sodium 0.1 Sodium monofluorophosphate 0.7 Silicic anhydride (Average particle size 2 μm) 7.5 Monoalkylphosphoric acid (Number of carbon atoms in alkyl group = 10) 1.5 Hydroxyethyl cellulose 1.5 10% Sodium hydroxide 1.5 Zinc chloride 0.1 Perfume 0.9 Purified water Balance 100.0%

Example 7 A dentifrice having the following composition was produced by a conventional method.

[0059]

(Table 8) (Composition) Alumina (average particle size 1 μm) 15.0% Solbit solution 35.0 Propylene glycol 5.0 Polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 2.0 Sodium benzoate 0.2 Saccharin sodium 0.1 sodium monofluorophosphate 0.7 silicic anhydride (average particle size 2 μm) 10.0 monoalkylphosphoric acid (carbon number of alkyl group = 8) 2.0 hydroxyethyl cellulose 1.0 10% sodium hydroxide 1. 5 Glycyrrhetinic acid 0.1 Triclosan 0.1 Perfume 0.9 Purified water Balance 100.0%

Example 8 A dentifrice having the following composition was produced by a conventional method.

[0061]

(Table 9) (Composition) Hydrous silicic acid (average particle size 1.5 μm) 30.0% sorbit solution 30.0 Glycerin 5.0 Polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 3.0 Sodium benzoate 0 .2 sodium saccharin 0.1 sodium fluoride 0.2 silicic acid anhydride (average particle size 2 μm) 15.0 monofluoroalkylphosphoric acid (in the general formula (1), R ¹ ═C ₁₀ F ₂₁ —CH ₂ CH ₂ — , M ¹ = M ² = H) 1.5 Carboxymethyl cellulose 1.0 Zinc chloride 0.1 Perfume 0.9 Purified water Balance 100.0%

Example 9 A dentifrice having the following composition was produced by a conventional method.

[0063]

(Table 10) (Composition) Aluminum hydroxide (average particle size 1 μm) 15.0% Solbit solution 35.0 Propylene glycol 5.0 Polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 2.0 Sodium benzoate 0. 2 Sodium saccharin 0.1 Sodium monofluorophosphate 0.7 Silicic anhydride (Average particle size 2 μm) 7.5 Phosphoric acid ester modified silicone ^{* 5} 2.0 Sodium lauryl sulfate 1.0 Hydroxyethyl cellulose 1.0 Glycyrrhetinic acid 0. 1 triclosan 0.1 perfume 0.9 purified water balance 100.0% * 5: in formula _{(2), X = -CH 2} CH 2 -, m / n ≒ 2
/ 1, m + n = 15 , M 3 = Na, M 4 = H

Example 10 A dentifrice having the following composition was produced by a conventional method.

[0065]

[Table 11] (Composition) Aluminum hydroxide (average particle size: 1.5 μm) 30.0% Solbit solution 35.0 Propylene glycol 5.0 Polyethylene glycol (PEG600, manufactured by Shoei Pharmaceutical Co., Ltd.) 2.0 Sodium benzoate 0.2 Sodium saccharin 0.1 Sodium monofluorophosphate 0.7 Silicic anhydride (Average particle size 2 μm) 5.0 Sodium lauryl sulfate 1.5 Phosphoric acid ester (meth) acrylate polymer ^{* 6} 1.0 Glycyrrhetinic acid 0 1 Fragrance 0.9 Purified water Balance 100.0% * 6: In the general formula (5), R ² = CH ₃ , R ³ = C ₁₂ H ₂₅ ,
M ⁵ = Na, molecular weight = 76000

Example 11 A hydrous silicic acid powder (average particle size: 1.5 μm) was stirred with an aqueous solution of chlorhexidine hydrochloride to adjust the adsorption amount of chlorhexidine hydrochloride to 1000 ppm to obtain a drug-containing powder. A dentifrice having the composition shown in Table 12 below was produced using this, and the dentinal tubule occlusion effect was tested in the same manner as in Example 1 and the amount of chlorhexidine hydrochloride remaining in the sample was determined according to the following method. These results are shown in Table 1.
3 shows.

[0067]

[Table 12]

(Test Method) A healthy human tooth was cut to expose the fresh surface of dentin as a sample. Create a window on the surface of the material so that the area is uniform. The toothbrush was taken with 0.5 g of dentifrice, and the sample was brushed for 3 minutes, washed with running water for 30 seconds, and immersed in artificial saliva for 10 minutes. This sample is a solvent (acetonitrile / water / SDS)
System) and quantified chlorhexidine hydrochloride by HPLC.

[0069]

[Table 13]

Example 12 A dentifrice having the following composition was produced by a conventional method.

[Table 14] (Composition) Drug-containing powder (average particle size: 1.5 μm, hydrous silicic acid containing 0.1% of chlorhexidine hydrochloride) 20.0% sorbit solution 35.0 propylene glycol 5.0 polyethylene glycol (PEG600, Shoei) Yakuhin Co., Ltd. 2.0 Sodium benzoate 0.2 Sodium saccharin 0.1 Silicic anhydride (average particle size 1.5 μm) 7.5 Sodium fluoride 0.2 Monoalkylphosphoric acid (C = 14) 1. 5 Hydroxyethyl cellulose 1.5 10% Sodium hydroxide 1.5 Perfume 0.9 Purified water Balance 100.0%

Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location A61K 33/08 8314-4C

Claims (7)

[Claims] 1. The following components (A) and (B): (A) (a) 6 carbon atoms which may be substituted by a fluorine atom.
To one or two or more water-soluble phosphoric acid compounds selected from the group consisting of phosphoric acid ester having 20 to 20 alkyl groups, (b) phosphoric acid ester modified silicone, and (c) phosphoric acid ester (meth) acrylate-based polymer, (B) a water-insoluble non-calcium-based powder having an average particle diameter of 0.01 to 2 μm, in a weight ratio of (A) / (B) = 1/1 to 1/50. A therapeutic agent for hyperesthesia. 2. A phosphoric acid ester (a) having an alkyl group having 6 to 20 carbon atoms which may be substituted with a fluorine atom is represented by the following general formula (1): [In the formula, R ¹ represents an alkyl group having 6 to 20 carbon atoms or a perfluoroalkyl group, and M ¹ and M ² are the same or different and represent a hydrogen atom, ammonium, alkylamine, alkanolamine or basic amino acid] The therapeutic agent for hyperesthesia according to claim 1, which is a monoalkyl phosphate ester or a mono (perfluoroalkyl) phosphate ester represented by: 3. A phosphate ester-modified silicone (b) has the following general formula (2), (3) or (4): [In the formula, X represents a divalent hydrocarbon group having 1 to 10 carbon atoms, M ³ and M ⁴ are the same or different and represent a hydrogen atom, ammonium, alkylamine, alkanolamine or basic amino acid, m and n is a positive number]
The therapeutic agent for hyperesthesia according to claim 1, which is a polymer represented by: 4. A phosphoric acid ester (meth) acrylate polymer (c) is represented by the following general formula (5): [In the formula, R ² represents a hydrogen atom or a methyl group, R ³ represents a hydrocarbon group having 4 to 20 carbon atoms, M ⁵ represents a hydrogen atom, an alkali metal atom, ammonium, an alkylamine or an alkanolamine, p is 0 or 1], The therapeutic agent for hyperesthesia according to claim 1, which is a polymer having a constitutional unit represented by the formula: 5. The water-insoluble non-calcium-based powder (B) is an inert non-calcium-based inorganic powder selected from aluminum hydroxide, alumina, silicic acid anhydride, hydrous silicic acid and synthetic aluminum silicate. The therapeutic agent for hyperesthesia according to 1. 6. The therapeutic agent for hyperesthesia according to claim 1, which further comprises a pharmaceutically acceptable water-soluble fluoride. 7. The therapeutic agent for hyperesthesia according to claim 1, wherein the water-insoluble non-calcium powder (B) is a composite powder of an inert non-calcium inorganic powder and a drug.