JP2964182B2 - Dentin hypersensitivity treatment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a therapeutic agent for dentin hypersensitivity which can treat and prevent dental dentin hypersensitivity.

[0002]

BACKGROUND OF THE INVENTION Dentin hypersensitivity is a disease in which pain is induced by cold water or abrasion stimuli when dentine is exposed for various reasons. In recent years, with the aging of society, gingival regression and periodontal disease have been increasing, making this disease more and more clinically important. At present, the theory of hydrodynamics is considered to be the cause of hyperesthesia. That is, the stimulus propagates through the dentinal tubule, and stimulates nerves distributed in the dental pulp or dentin to induce pain. To suppress such dentin hypersensitivity and relieve pain, physically or chemically block dentin tubules, which are sensory conduction,
It is said that the protein in the tubule should be fixed.

[0003] Therapeutic agents used for dentin hypersensitivity
Are used in clinical settings and after-sales services at home.
A. Some are used for prevention. The former includes
Application of sodium iodide solution (Yoshida et al.
173, 39 (1959)), zinc ion introduction method (Inoue
Masaomi, Journal of the Japanese Society of Dental Conservation,1, 1 (1958)), salt
Of strontium fluoride (Yoshio Murakami, Review of Japanese Dentistry,3
28, 36 (1970)), coating of silver ammonium fluoride
Cloth (Masao Aono et al., Journal of the Japanese Society of Conservative Dentistry,10, 31 (1
967)) and application of F-Vanish (Masashi Miura et al., Mouth
Journal of the Japan Society of Cavity Hygiene,28, 301 (1978)).
And the latter include strontium chloride-containing dentifrices (Shoji Uchida
Et al., Journal of the Japanese Society of Periodontology,23, 486 (1980)),
Sodium citrate-containing dentifrice (JF Collin)
set. al. , J. et al. Periodontol,5
5, 720 (1984)), toothpaste containing aluminum lactate
(Eikichi Yoneda et al., Journal of the Japanese Society of Conservative Dentistry,33, 1070
(1990)).

[0004]

However, the above-mentioned therapeutic agents have disadvantages such as coloring of teeth, irritation to pulp and gums, poor taste, and insufficient safety and effect. It was not yet satisfactory. Accordingly, an object of the present invention is to provide a therapeutic agent which does not have such disadvantages and exhibits excellent therapeutic and preventive effects on dentin.

[0005]

Under such circumstances, the present inventors have developed a dentin perception that can treat and prevent hypersensitivity to dentine by narrowing or occluding dentin tubules in the dentin. As a result of intensive studies to find a therapeutic agent for hypersensitivity, a specific zinc colloid or zinc salt prepared using a polyol phosphate ester or the like is free from the above-mentioned drawbacks and exhibits excellent dentin hypersensitivity treatment and prevention effects. That is, the present invention has been completed.

That is, the present invention provides the following component (A) and / or
Or (B) a colloid of zinc hydroxide and / or zinc oxide obtained by mixing (A) (a) a water-soluble zinc salt and (b) a polyol phosphate ester and / or a salt thereof in an aqueous medium. (B) A therapeutic agent for hypersensitivity to dentin, comprising a zinc salt of a polyol phosphate ester.

The water-soluble zinc salt (a) as a raw material of the component (A) used in the present invention includes, for example, zinc halides such as zinc chloride and zinc bromide; inorganic zinc salts such as zinc sulfate and zinc nitrate; Examples thereof include organic zinc salts such as zinc, zinc lactate, zinc aspartate, and zinc citrate. Of these, zinc chloride, zinc sulfate, and zinc nitrate are preferable.

[0008] Examples of the polyol phosphate ester of the component (b) include phosphate esters of monosaccharides, oligosaccharides, polysaccharides and polyols. For example, glucose-1-phosphate, glucose-6-phosphate, mannose-phosphate. 6-phosphate, galactose-6-phosphate, fructose-6-phosphate, glucose-1,6-diphosphate, fructose-
1,6-diphosphate, α-glycerophosphate, β-glycerophosphate, sucrose phosphate, ascorbic phosphate, sorbitol phosphate, phosphorylated polyglycerin, phosphorylated polyethylene glycol, phosphorylated starch, and the like, and salts thereof. Examples thereof include salts of alkali metals, alkaline earth metals, amines, amino acids and the like, and are preferably glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate. Acid, α-
Examples include glycerophosphate, β-glycerophosphate, ascorbic phosphate, sucrose phosphate, sorbitol phosphate, phosphorylated polyglycerin, phosphorylated polyethylene glycol, and salts thereof.

The colloid of the component (A) used in the present invention is produced by mixing the components (a) and (b) in an aqueous medium. As the aqueous medium used herein, water is particularly preferable, and an organic solvent such as an alcohol can be mixed and used as long as the reaction is not hindered. The mixing method is not particularly limited. For example, the component (a) may be mixed with the aqueous solution of the component (b), or the component (b) may be mixed with the aqueous solution of the component (a). The components (a) and (b)
After converting each of the components into an aqueous solution, they may be mixed,
After mixing these, water may be added and dissolved.

The mixing ratio of the component (a) and the component (b) is not particularly limited.
It is preferably at least 5 moles, particularly preferably at least equimolar. Also,
The pH of the solution obtained by mixing the components (a) and (b) is from 1 to 1.
It is preferably 0, especially 4 to 10, more preferably 6 to 8. pH
Is less than 1, the desired colloid cannot be obtained.
If it exceeds 300, aggregation of colloid particles is likely to occur, and it is difficult to obtain a stable colloid. The pH of the mixed solution can be adjusted using an appropriate acid or base. The temperature and other conditions are not particularly limited, and may be set as appropriate. The obtained colloid can be isolated by removing the solvent using a method such as ultracentrifugation or freeze-drying. The particle size of the colloid produced by the above method is usually 1 to 100 nm.

The colloid formed by this reaction is a zinc hydroxide colloid, a zinc oxide colloid, or a mixture thereof. Although the details of the colloid formation reaction are not clear, the zinc salt of the component (a) is hydrolyzed in an aqueous medium to form hydroxides and / or oxides of these zincs, and the component (b) It is considered that a stable colloid is formed by performing some action.

The colloid particles are generally very fine, and the particle diameter may be about 10 nm. Therefore, when homogeneous colloids are produced at an appropriate blending ratio and blending operation conditions, these can be made into a transparent solution.

As the polyol phosphate ester which is a raw material of the zinc salt of the polyol phosphate component (B) used in the present invention, those mentioned in (B) of the component (A) can be used.

The zinc salt of the polyol phosphate ester as the component (B) can be prepared by a conventional method such as a neutralization method and a salt exchange method. Examples of the preparation method include (1) a method in which an alkali metal salt of a polyol phosphate is prepared using a cation exchange resin or the like to prepare an acid form of the polyol phosphoric acid, and then neutralized with hydroxide or zinc oxide; (3) a method in which an alkali metal salt of an ester and zinc chloride are mixed and salt-exchanged for desalting; (3) a water-insoluble water solution of BaSO ₄ or CaSO ₄ which is obtained by mixing a Ba phosphate or Ca salt of a polyol phosphate with zinc sulfate; And the like.

The therapeutic agent for hypersensitivity to dentin of the present invention comprises (A)
The component alone, the component (B) alone, or both may be used in combination. The compounding amount is 0.01 to 10% by weight as the zinc content when only the component (A) is used, and 0.01 to 20% by weight as the zinc content when only the component (B) is used, and the components (A) and (B) are used together. In this case, the zinc content is preferably 0.01 to 20% by weight.

The therapeutic agent for dentin hypersensitivity of the present invention may contain various known components depending on its form. Examples thereof include known dentin hypersensitivity therapeutic agents such as sodium fluoride, silver ammonium fluoride, F-Vanish, strontium chloride, citric acid, and aluminum lactate; glycerin, sorbite, propylene glycol, 1,3-butylene glycol , Ethylene glycol, polyethylene glycol, polypropylene glycol, xylitol, maltite, lactit and the like; carboxymethylcellulose and salts thereof; methylcellulose, hydroxyethylcellulose, carrageenan, sodium polyacrylate, hydroxypropylcellulose, sodium carboxymethylhydroxyethylcellulose, sodium alginate , Alginate propylene glycol ester, xanthan gum, tragacanth gum, karaya gum,
Binders such as arabic gum, polyvinyl alcohol, polyvinylpyrrolidone, veegum, laponite; dentin enhancers such as sodium monofluorophosphate, tin fluoride, sodium fluoride; fungicides such as salts of chlorhexidine, cetylpyridinium chloride; PH adjusters such as sodium phosphate; enzymes such as dextranase, amylase, protease, lysozyme, and mutanase; sodium chloride, hinokitiol, ε-aminocaproic acid, tranexamic acid, allantoins, tocopherols, dihydrocholesterol, glycyrrhetinic acid, Glycyrrhizic acid and salts thereof; glycerophosphate, chlorophyll, water-soluble inorganic phosphate compounds, azulene, chamomile, Toki, Kawayumi, crude drugs and other anti-inflammatory agents and blood circulation promoters; lauryl sulfate, myristyl sulfate, α- Les fin sulfonate,
N-acyl amino acid salts, acyl monoglyceride sulfates,
Soap, fatty acid monoglyceride, fatty acid monoalkanolamide, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, alkyl glycoside, imidazolinium betaine, alkyl betaine,
Surfactants such as alkylamidobetaine, sulfobetaine, and amine oxide; sweeteners such as saccharin sodium, stevioside, thaumatin, asparatylphenylalanine methyl ester; parahydroxybenzoic acid;
Preservatives such as ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate and sodium benzoate; coloring agents and pigments such as titanium dioxide; 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, crocodile, thymol, anise oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, cinnamon oil, perilla oil,
Flavors such as winter green oil, clove oil and eucalyptus oil can be mentioned.

[0017]

Industrial Applicability The present invention provides a therapeutic agent for hypersensitivity to dentin comprising a zinc-containing colloid and / or a zinc salt of a polyol phosphate which is stable in a wide pH range. This drug shows extremely excellent dentin hypersensitivity therapeutic effect and imparts high safety, and is extremely useful clinically. For example, zinc (zinc chloride) alone has the effect of preventing hypersensitivity to dentin, which fixes proteins present in the sensory pathway or remaining dentin blast cell processes and removes pain, but does not stimulate the gingiva or pulp. Limited in use due to strong. On the other hand, this agent not only has a similar effect of preventing dentin hypersensitivity but also has low irritation and excellent safety, so that it can be used for a wide range of oral products or drugs. In addition, the present composition does not only treat hypersensitivity,
By using it constantly, it is possible to effectively prevent the appearance of hyperesthesia.

[0018]

Next, the present invention will be described with reference to examples, but the present invention is not limited to these examples. Example 1 Glucose-1-phosphate was used as a polyol phosphate ester. First, 5.7 g (15 mmol) of glucose-1-phosphate disodium tetrahydrate was dissolved in 50 ml of ion-exchanged water, and 1.0 g (7.3 mmol) of zinc chloride was added and mixed. After adjusting the pH to 7.5 with a 1N sodium hydroxide solution, the solution was adjusted to 100 g to prepare a zinc colloid aqueous solution (0.5% by weight as Zn content). Glucose-6 instead of glucose-1-phosphate disodium salt
Using phosphoric acid, glycerophosphoric acid, fructose-1,6-diphosphoric acid, sucrose phosphoric acid, and sodium salt of phosphorylated polyethylene glycol, and similarly using each of the aqueous zinc colloid solutions (0.5% by weight as Zn content) Was prepared. Each of the tooth sections from which the dentinal tubules were exposed by polishing the cervical portion of the freshly extracted tooth and phosphoric acid treatment was immersed for 5 minutes in each of 10 ml of the aqueous zinc colloid solution obtained as described above. Then, after washing with the same amount of ion-exchanged water for 5 minutes and drying, a scanning electron microscope (SEM)
As a result, it was found that the dentinal tubules were narrowed or blocked.

Example 2 Glucose-1-phosphate disodium salt tetrahydrate
4 g (30 mmol) was dissolved in 200 ml of ion-exchanged water. This is treated with a cation exchange resin (Dowex 50W-X).
8, Dow Chemical Company) (300 ml) was passed through a column filled with 300 ml to prepare glucose-1-phosphate (acid form). To this, 3.0 g (30 mmol) of zinc hydroxide was added, and after neutralization,
8. Dry to give glucose-1-zinc phosphate monohydrate 9.
8 g (28.7 mmol) were obtained. Instead of glucose-1-phosphate disodium salt, glucose-6-phosphate,
Using each of glycerophosphoric acid, fructose-1,6-diphosphoric acid, sucrose phosphoric acid and phosphorylated polyethylene glycol, a zinc salt was obtained in the same manner as described above.

The zinc salts obtained above were each dissolved in ion-exchanged water to prepare a zinc salt aqueous solution having a Zn content of 0.5% by weight. Each tooth section in which the dentinal tubule was exposed by polishing the cervical part of the freshly extracted tooth and then phosphoric acid treatment was immersed in 10 ml of this solution for 5 minutes. Then use the same amount of ion-exchanged water for 5
After washing and drying for a minute, observation with a scanning electron microscope (SEM) revealed that the dentinal tubules were narrowed or clogged.

Example 3 A sponge piece was impregnated with each of the six aqueous colloidal zinc solutions (pH: 2.1% by weight) prepared at pH 7.5 prepared in Example 1 and the tooth dentition of a patient complaining of hypersensitivity symptoms As a result of thinly applying the sponge to the surface of the substance, the hypersensitivity symptom of the patient disappeared with any of the aqueous solutions, and the condition was maintained for one month or more.

Example 4 20 ml of each of the pH 7.5 zinc colloid aqueous solutions (0.5 wt% in terms of Zn content) prepared in Example 1 were applied to the surface of the tooth dentin of a patient complaining of hyperesthesia for 30 seconds. As a result of the gargle, the hypersensitivity symptom of the patient disappeared in any of the aqueous solutions.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int.Cl. ⁶ , DB name) A61K 33/30 A61K 6/00 CA (STN)

Claims (3)

(57) [Claims] 1. The following component (A) and / or component (B): mixing (A) (a) a water-soluble zinc salt and (b) a polyol phosphate ester and / or a salt thereof in an aqueous medium. (B) a zinc salt of a polyol phosphoric acid ester, comprising a zinc colloid of zinc hydroxide and / or zinc oxide obtained by the above method. 2. The therapeutic agent for dentin hypersensitivity according to claim 1, wherein the pH of the aqueous medium obtained by mixing the component (A) and the component (B) in the component (A) is 4 to 10. 3. The polyol phosphate ester used in the component (A) and / or the component (B) is glucose-1-phosphate, glucose-6-phosphate, mannose-6-phosphate, galactose-6-phosphate. Acid, fructose-6-phosphate, glucose-1,6-diphosphate, fructose-
One or two selected from the group consisting of 1,6-diphosphate, α-glycerophosphate, β-glycerophosphate, ascorbate phosphate, sucrose phosphate, sorbitol phosphate, phosphorylated polyglycerin and phosphorylated polyethylene glycol The therapeutic agent for dentin hypersensitivity according to claim 1 or 2, which is at least one species.