JP4662294B1 - Oral preparation - Google Patents

Abstract

【Task】
Excellent dentinal tubule sealing, improved tooth acid resistance and remineralization ability, can be treated in a short time with simple operation, safe and aesthetic, caries prevention and initial caries Provided are a therapeutic agent, an agent for preventing and / or treating dentine hypersensitivity, and an agent for oral cavity suitable for an agent for backing of a cavity forming tooth surface, and a kit for preparing the oral agent.
[Solution]
An oral preparation comprising a liquid (A) in which fluoroaluminosilicate glass fine particles are dispersed and an acidic aqueous solution (B) of an oxalic acid compound.
[Selection figure] None

Description

The present invention relates to an oral preparation capable of performing dental treatment such as caries prevention and initial caries treatment, and prevention and / or treatment of dentin hypersensitivity with a short required treatment time.
More specifically, by depositing fine particles on the tooth surface in a short time with a simple operation of applying a liquid preparation, (1) imparting acid resistance to the tooth, and (2) remineralizing the tooth. The present invention relates to an oral preparation having a function of accelerating the action, and (3) sealing a sensitive dentin (open dentinal tubule).

From the outside, the crown is composed of a three-layer structure of enamel, dentin, and pulp.
Enamel is a hard and highly insoluble layer composed mainly of hydroxyapatite. However, when exposed to an acidic medium caused by the glycolytic action of food residues by oral bacteria, elution of phosphate ions and calcium ions occurs. (Decalcification) is promoted, and as a primary lesion of caries, vitiligo (white spot) is generated and develops into so-called caries.
As one method for preventing caries, fluorine coating is known. In other words, when a tooth is treated with a fluorine ion source, hydroxyapatite is converted to fluoroapatite, acid resistance is imparted, elution (decalcification) of phosphate ions and calcium ions is suppressed, and hydroxyapatite is produced (re-lime) It is well known that it has the effect of promoting the conversion of dental caries. For example, a caries preventive treatment method in which a fluoride preparation containing a fluoride ion source is applied to the tooth surface is widely used.
A preparation generally used in the dental medical field as the fluoride preparation is a phosphoric acid acidic fluorine solution (hereinafter referred to as “APF”). The tooth is decalcified by the acid, and the eluted calcium ions react with the fluorine ions to form calcium fluoride on the tooth surface. However, the problem with APF treatment is that it is highly exposed to saliva in the oral cavity and there is a high possibility that the effect will not be fully manifested. For this reason, it takes 4 minutes of holding time with APF applied to the teeth, and after that, it is necessary to prohibit eating and drinking for 30 minutes or more. It was. Moreover, it is known that calcium fluoride deposited on the tooth surface is eluted in saliva in a decalcified (acidic) environment and has a poor remineralization promoting effect.

In addition, oral compositions containing a calcium ion source, a phosphate ion source, calcium phosphate and the like in addition to a fluorine ion source have been reported. By precipitating calcium fluoride and calcium phosphate simultaneously on the tooth surface, elution into saliva is prevented in a decalcified (acidic) environment, and a remineralization promoting effect is expected.

Furthermore, it is said that a glass ionomer cement, which is a kind of dental cement, can be expected to have a tooth strengthening action by fluorine contained as a glass component. Glass ionomer cement is widely used for caries cavity filling, crowns, inlays, bridges and orthodontic brackets because of its excellent biocompatibility, adhesion, and aesthetics. When exposed to moisture such as, the curing reaction is inhibited and the final physical properties are lowered. In addition, since the polished surface after curing is rough and the film thickness is thick, there are disadvantages such as inferior touch and aesthetics. Among them, a glass ionomer having a specific gravity of 2.4 to 4.0, an average particle size of 0.02 to 4 μm, and a BET specific surface area of 2.5 to 6.0 m ² / g as a method for improving the roughness of the polished surface and the film thickness. It has been proposed to use cement powder (Patent Document 1). However, as a specific example, only an average particle size of 2.0 to 2.2 μm and a maximum particle size of 3.49 to 3.95 μm are shown. As in the same document, dental glass ionomer cement powder is kneaded with a dedicated cement solution at the time of use, like cement for building materials, and itself used as a liquid agent. Is not envisaged and no examples have been reported.

In addition to caries, dentinal hypersensitivity is one that complains of severe pain in dental practice. As described above, the dental crown is composed of three layers of enamel, dentin, and dental pulp, and dentinal tubules run through the entire dentin. Dentine hypersensitivity is often caused when a dentinal tubule covered with enamel or gingiva is opened for some reason. For example, if dentinal tubules are exposed or opened due to caries, use of dental preparations containing abrasives, wear due to bleaching for aesthetic purposes, or gingival retraction due to aging, cold water or Scratch stimulation causes temporary but severe pain.
Although the pathogenesis of dentin hypersensitivity has not been fully elucidated, hydrodynamic theory is considered promising. The hydrodynamic theory is a theory that various stimulation forms applied to the dentin cause fluid movement in the dentinal tubule and excite nerve fibers on the pulp side.

Therefore, a treatment that inhibits the movement of dentinal tubule fluid is effective in improving the sensitivity of dentinal perception, for example, as exemplified by the application of a varnish containing a resin and a solvent for sealing teeth. It has been reported that dentin hypersensitivity is reduced or eliminated by blocking dentinal tubules.
Dentine hypersensitivity treatments include the following: (1) Treatment method for sealing dentinal tubules: Resin, strontium chloride, silver diamine diamine, HY material, sodium fluoride solution, sodium fluoride-containing pasta, calcium hydroxide agent, iontophoresis, etc. in addition to potassium oxalate (Non-patent document 1), (2) Treatment with exposed dentin coating: cement, paraform combination dressing, etc. (3) Repair of defect: glass ionomer cement, adhesive resin, etc. (4) Sedation of pulp nerve (5) Tooth pulp extraction therapy, such as taking anti-inflammatory analgesics and soft laser irradiation.

Of these, the glass ionomer cement and adhesive resin (3), which have adhesiveness to the tooth structure, form a strong film and are difficult to remove. Therefore, it is possible to apply periodontal regeneration therapy on the root surface. It is not preferable when there is a property.
(4) has only a temporary effect, and (5) completely removes the pulp, that is, the nerve, thereby removing the blood vessel together with the nerve, eliminating pain but sacrificing the tooth.
(1) and (2) are treatments that do not sacrifice the pulp and teeth, and are effective when there is no large defect. However, some cements (2) have a low pH, so care must be taken when selecting them. The paraform-containing dressing has an action of fixing the dental pulp by its component paraformaldehyde, but is not safe for application in the oral cavity. Among (1), 2% sodium fluoride (neutral) is usually used as the sodium fluoride solution and the sodium fluoride-containing pasta, but since the dentinal tubules are not blocked, the effect of suppressing hypersensitivity is extremely weak. Calcium hydroxide is effective when used for the purpose of protecting the pulp, but its effect on normal dentin hypersensitivity such as cold water pain is extremely weak. The ion introduction method is a method in which an ion tray is impregnated with a 2% sodium fluoride solution (neutral), and fluorine is actively taken in by passing an electric current, which requires an expensive fluorine ion introduction device.
Furthermore, since (1) and (2) only apply a material containing an effective ingredient to the tooth surface, the effect is often temporary.
If the particle diameter of the material is smaller than the diameter of the dentinal tubule and a two-liquid reaction occurs in the dentinal tubule and a reaction product (precipitate) of fine particles is generated in a short time, the dentinal tubule can be closed. Further, if such fine particles uniformly cover the dentin surface and block the dentinal tubules, stimulation to the dentinal tubules is blocked and a great therapeutic effect can be expected. For that purpose, it is necessary to devise the physical properties of the material, but it is difficult to say that the conventional material has been sufficiently improved in that respect.
The HY material (trade name: HYC) is a mixed powder of tannin, zinc fluoride, strontium fluoride and zinc oxide. Although suppression of hypersensitivity by the astringent action of tannin and prevention of dental caries by fluoride are expected, there is a problem in operability because it hardens instantly when it comes into contact with water. In addition, the cured product has a drawback that it is colored blackish in the oral cavity.
The fluorinated diamine silver preparation (trade name: Saphoride) is easy to apply on the tooth surface and remains on the tooth surface for a long time. It is excellent in treating hypersensitivity and preventing secondary caries. The teeth are colored black like a black tooth, and there is a fatal problem in aesthetics, and its application is limited.
With regard to (3), for example, the tooth neck that is not covered with enamel is likely to be worn by the toothbrush, and the dentinal tubule is opened at the worn portion, and hypersensitivity is likely to occur. Even in other cases in which such dentinal tubules are opened, by cutting the tooth at the site and filling it with cement, adhesive resin, or the like, it is possible to treat the hypersensitivity simultaneously with the repair of the defect. However, since the feature of dentin of hypersensitivity is that no caries (soft dentin) is observed, a treatment method that avoids healthy tooth cutting is required.

For this reason, the most promising method for treating dentin hypersensitivity is oxalate, and about 2% oxalic acid can be easily used as a liquid preparation. Salt (alkali metal salt or ammonium salt) aqueous solution (Patent Document 2) and two-part set (Patent Document 3) of 30% potassium oxalate aqueous solution and 3% potassium hydrogen oxalate aqueous solution (Patent Document 3) Dentin of OP Laboratories Hypersensitivity treatment (Dentin
An aqueous solution (Patent Document 4) consisting of 1.5 to 10.0% by weight of potassium oxalate dihydrate and having a pH of 2.0 to 4.0 (Patent Document 4) is used as dental dentist of Phoenix Dental, USA. Although it has been clinically applied as a material for suppressing quality of hypersensitivity (Super Seal), they do not all have a remineralization or secondary caries prevention effect.

It is desirable that the treatment for dentine hypersensitivity is applied to the tooth surface during dental treatment and can be washed with water after several tens of seconds, and the treatment should be completed in a short time. It is desirable to have a caries prevention and treatment effect. Furthermore, if there is no aesthetic problem, it can be expected as a material applicable to a wide range of cases.
Furthermore, it is also desired that the mixed solution penetrates into the dentinal tubules and the initial carious lesion and generates a nanoparticle precipitate in a short time, and that the precipitate contains a fluorine compound that can be expected to be calcified. However, no material that satisfies these conditions has been reported yet.
Also proposed is a dental composition for dentin hypersensitivity containing aqueous polymer emulsion particles that react with calcium compounds at a particle size smaller than the dentinal tubule size to form an aggregate larger than the dentinal tubule size. (Patent Document 5) does not provide remineralization or secondary caries prevention effect.
Induced pain may occur due to temperature stimulation after cavity formation or dental prosthesis placement. In some cases, such as when the caries is progressing, deep cavities are formed that reach close to the pulp, and evoked pain is often seen despite treatment. To avoid this, the cavity surface near the pulp is covered with calcium hydroxide or glass ionomer cement. However, calcium hydroxide has a high protective effect on the pulp, but does not adhere to the tooth and is easy to fall off. Therefore, it must be covered with another cement on the calcium hydroxide layer. It is complicated. Glass ionomer cement has problems as described above.

JP-A-11-180815 US Pat. No. 4,057,621 U.S. Pat. No. 4,538,990 Japanese Patent No. 3851777 Japanese Patent No. 3502390

Dental Journal Vol. 34, No. 2, pp. 223-229, August 1991

As described above, only fluorinated diamine silver is the only one that exhibits both the functions of hypersensitivity suppression and caries prevention so far, but the deposited part of the tooth is colored black. There was a fatal problem with aesthetics.
The treatment with acidic fluorine for preventing dental caries has a problem that it is inconvenient for both dentists and patients because the retention time (about 4 minutes) after application for moisture prevention is long.

  Therefore, the problem to be solved by the present invention is excellent in sealing ability of dentinal tubules, and has the ability to improve acid resistance and remineralization (caries prevention and initial caries treatment) of teeth, and can be performed in a short time with simple operation. (10-20 seconds), safe and aesthetically pleasing caries prevention and early caries treatment, dentine hypersensitivity prevention and / or treatment, and cavity on the cavity surface An object of the present invention is to provide an oral preparation suitable for a layer preparation.

As a result of diligent research, the present inventors have dispersed fluoroaluminosilicate glass, which has been used as a conventional powder, in water in the form of fine particles, whereby a stable dispersion can be obtained without causing precipitation. This is mixed with a separately prepared oxalic acid aqueous solution at the time of use and applied to the tooth surface, and the caries or dentin exposed part is composed of silicate oxalate containing calcium oxalate and calcium fluoride. By forming fine particle precipitates, adjusting the pH of the mixture to ensure fine particle precipitation on the tooth surface, these enable remineralization or occlusion of dentinal tubules The present invention was completed.
At this time, pH at the time of treating the tooth surface is particularly important, and in the initial stage of treatment (after 10 seconds of mixing), Ca ions due to tooth decalcification are used, so the working fluid, that is, fluoroaluminosilicate glass fine particles The solution obtained by mixing the solution (A) in which the oxalic acid compound is dispersed with the acidic aqueous solution (B) of the oxalic acid compound has a pH of 0.5 to 4 capable of decalcification of the tooth, and calcium oxalate at the end of the treatment. And it controls so that it may gradually change to pH 2-5 vicinity where calcium fluoride precipitates.

The present invention comprises a liquid (A) in which fluoroaluminosilicate glass fine particles are dispersed and an acidic oxalic acid compound aqueous solution (B), and in particular, caries prevention and early caries treatment agent, dentin hypersensitivity prevention and The present invention provides an oral preparation suitable for a therapeutic agent and an agent for lining a cavity forming tooth surface.
The fluoroaluminosilicate glass fine particles contain, as constituent elements, a total of 1 at least one selected from Si: 5 to 25% by mass, Al: 5 to 35% by mass, F: 1 to 25% by mass, and Na, K, and Mg. In addition, it may contain 10% by mass or more, and other constituent elements may include alkaline earth metals such as Ca, Sr, and Ba, or metal elements such as Zr, La, Y, and Ti.
The fluoroaluminosilicate glass fine particles are those having a 50% particle size (D50) of 1 μm or less and a 90% particle size (D90) of 2.5 μm or less, as measured from the small diameter side in the volume-based particle size distribution. Preferably, D50 is 0.5 μm, and D90 is 2 μm or less.
The pH of the liquid (A) in which the fluoroaluminosilicate glass fine particles are dispersed is 6 to 12, the pH of the acidic aqueous solution (B) of the oxalic acid compound is 0.5 to 3, and (A) and (B) The pH after 10 seconds of mixing of the mixed solution is preferably 0.5-4.
Examples of oxalic acid compounds include oxalic acid, sodium hydrogen oxalate, disodium oxalate, potassium hydrogen oxalate, dipotassium oxalate, lithium hydrogen oxalate, dilithium oxalate, ammonium hydrogen oxalate, and diammonium oxalate. Etc. Of these, oxalic acid and potassium hydrogen oxalate are preferred.

In the present invention, the principle of remineralization is estimated as follows.
That is, Ca ions eluted by tooth decalcification with oxalic acid precipitate calcium oxalate on the tooth surface. At the same time, these Ca ions react with fluorine ions eluted from the fluoroaluminosilicate glass fine particles to precipitate calcium fluoride. The fluoroaluminosilicate glass fine particles after elution of fluorine ions precipitate silicate / oxalate by reaction with oxalic acid. According to the inventor's electron microscope observation, these precipitates form a mixed layer of fine particles (about 0.01 to 1.0 μm) on the tooth surface, but appropriately control the pH of the liquid when applied to the tooth surface. By doing so, the formed precipitate firmly adheres to the tooth surface. That is, at the initial stage of the tooth surface treatment (after 10 seconds of mixing), a low pH is set to 0.5 to 4 to decalcify the tooth substance, and calcium oxalate and calcium fluoride are precipitated at the end of the treatment. Therefore, the pH is gradually changed from the initial stage to the final stage of treatment so that the pH is around 2 to 5. By remineralizing the demineralized tooth by the fine particle deposit formed in this way, and entering and sealing into the exposed dentinal tubule, it becomes possible to cure the hypersensitivity symptom. .

Conventionally, fluoroaluminosilicate glass has been used in the form of powder in dental preparations. However, it takes time and effort to mix it with a liquid agent each time it is used, and the particle size is large, and the touch and aesthetics are inferior. As a result, a dispersion obtained by pulverizing this to a particle size having a particle size (D90) of 2 μm or less and dispersing it in water can be stored very stably, and the conventional solid (powder) / Liquid / liquid mixed coating can be used instead of liquid mixed coating. Since the mixing operation for liquid-liquid mixing is easy and the glass powder is uniformly dispersed as fine particles, the reaction at the time of application is fast, and the deposition is completed in a short time without requiring a holding time.
That is, precipitates of fine particles (reaction product calcium fluoride, calcium oxalate, silicate, oxalate) generated on the tooth surface by a simple operation of application of the mixed solution protect the carious portion, Causes remineralization. In addition, it penetrates into the dentinal tubule and deposits reaction products (calcium fluoride, calcium oxalate, silicate, oxalate) in the tubule to seal the exposed dentinal tubule. It can be used as a therapeutic agent for dentine hypersensitivity that is large and has immediate effect and excellent durability. Further, the precipitate is not easily removed by brushing or the like. Therefore, the present invention makes it possible to efficiently incorporate a large amount of fluoride into a tooth with a short treatment, and at the same time, it is difficult to treat with a conventional cement material. Caries prevention and initial caries treatment agent, dentin hypersensitivity prevention and / or treatment agent, and agent for backing layer of cavity forming tooth surface by depositing fine particle deposit on desired site such as ash surface Can be used as

As a method for preventing dental caries, (1) by imparting acid resistance to teeth, the components constituting the teeth are made difficult to dissolve in acids that directly cause cavity, and (2) remineralization action on teeth. By promoting the above, it is possible to supplement more of the dissolved tooth components.
By applying the liquid mixture according to the present invention to teeth, it is possible to supply fluorine ions and Ca ions to form fine calcium fluoride, calcium oxalate and silicate oxalate on the tooth surface. It becomes. In addition, by simultaneously forming calcium fluoride and calcium oxalate in the silicate / oxalate layer, calcium fluoride does not elute even in a decalcified (acidic) environment and is taken into the tooth (fluoro Apatite formation) can improve the acid resistance of teeth and promote remineralization. A notable advantage of the present invention is a reduction in the time required for tooth surface application treatment. The treatment time of the present invention is 10 to 30 seconds, which is a short time of 1/10 or less compared with the conventional product, and can be washed with water after application. The burden on dentists and patients (especially children) is greatly reduced, as there is no need for the retention time for 4 minutes at the time of application, and the limitation of gargle and eating and drinking over several tens of minutes after application. Therefore, the usability as an oral preparation can be greatly improved.
Therefore, the oral preparation according to the present invention makes it possible to obtain a high caries prevention and initial caries treatment effect as well as a dentine hypersensitivity suppressing effect.

Further, when the caries progresses, the softened dentin is removed, the cavity is formed, and repair is performed with a filling or a prosthesis. At that time, the mixed liquid of the present invention is applied to the cavity wall, thereby It can suppress the progress of further caries as well as prevent caries. There may be temporary hypersensitivity due to physical stimulation during cutting. Induced pain hypersensitivity also occurs when healthy dentin covering the pulp becomes thin by cutting. By using the product of the present invention, it is also useful as an agent for the back layer of the cavity forming tooth surface, which has the effect of preventing / treating dentine hypersensitivity after cutting.
The material of the present invention is very useful as an agent for the back layer, such that it can be applied in a short period of time, such as being applied to the tooth surface during dental practice and being washed with water after several tens of seconds. The filling procedure can be performed immediately after the back layer is completed, and an impression can be taken for the dental prosthesis immediately after the back layer. Moreover, the effect is not only suppressing hypersensitivity but also preventing and treating secondary caries. Furthermore, it is an oral preparation that is excellent in aesthetics and can be expected as a material applicable to a wide range of cases. In other words, it exhibits not only an excellent effect in the prevention and / or treatment of general dentin hypersensitivity and initial caries, but also a wide range of suppression of hypersensitivity that develops after basic periodontal treatment and secondary caries prevention effect. (Periodontal disease field), suppression of hypersensitivity on the inlay and crown forming surface and secondary caries prevention effect (dental prosthesis field), root caries treatment (dental preservation field), vitiligo teeth around orthodontic brackets It has become possible to apply to a wide range of cases, such as treatment (orthodontic field) without removing (enamel initial caries).

It is the figure which showed the time-dependent change of pH after mixing A liquid and B liquid.

In the present invention, the fluoroaluminosilicate glass is composed of at least one selected from Si: 5 to 25% by mass, Al: 5 to 35% by mass, F: 1 to 25% by mass, and Na, K, and Mg as constituent elements. In addition, 1 to 10 mass% in total may be included, and as other constituent elements, alkaline earth metals such as Ca, Sr, and Ba, or metal elements such as Zr, La, Y, and Ti may be included.
Fluoroaluminosilicate glass is a chemical and light curable glass ionomer cement product (for example, Fuji I (GC Corporation), High Bond Glass Ionomer CX (Matsukaze Corporation), Tokuyama Iono for filling, sealant and bonding applications Glass used in Tight F (manufactured by Tokuyama Dental Co., Ltd.) and the like, and glass having a composition shown in JP-A Nos. 11-180815 and 2002-60342 may be used. Use glass obtained by mixing appropriate amounts of compounds such as silicon oxide, aluminum oxide, calcium phosphate, aluminum phosphate, sodium fluoride, sodium monofluorophosphate, tin fluoride, etc. May be.

  In the present invention, the fluoroaluminosilicate glass is pulverized to a mean particle diameter (D50) of about 2 to 5 μm in a volume-based particle size distribution by a normal pulverizer such as a ball mill or a jet mill, and this is further wet-pulverized. Finely pulverize by a pulverizer such as a disperser (bead mill) to obtain a 90% particle diameter (D90) of 2 μm or less measured from the small diameter side in the volume-based particle size distribution. When the particle size is larger than 2.5 μm, the dispersibility is lowered, and not only aggregation and precipitation are likely to occur during storage, but also large particles adhere to the application tooth surface during use, so that reliable dentinal tubules The obstruction effect, remineralization, and secondary caries prevention effect cannot be obtained.

Fluoroaluminosilicate glass powder is added in a medium solution such as water at a ratio of 0.5% to 45% by weight, preferably 1% to 30% by weight, more preferably 5% to 20% by weight. A stable dispersion of fluoroaluminosilicate glass fine particles (hereinafter referred to as “liquid A”) can be obtained by pulverizing with a pulverizing apparatus such as a bead mill. When the amount of fluoroaluminosilicate glass particles is less than 0.5% by mass, the concentration of the fluoroaluminosilicate glass particles becomes too low, and when mixed and applied with an acidic aqueous solution of an oxalic acid compound (hereinafter referred to as “B solution”). If the amount of precipitation of calcium fluoride or the like is insufficient and the amount is more than 45% by mass, the viscosity of the liquid A is so high that it is difficult to use.
The medium solution is preferably water, but for the purpose of improving the stability of the solution A, a water-soluble solvent such as propylene glycol or polyethylene glycol which is not affected by washing with water when the tooth surface is applied may be added.

  Liquid A is adjusted to pH 6 to 12, preferably 6.5 to 10.5, depending on the constituent elements of the glass, but it can also be adjusted by adding a pH adjuster such as hydrogen oxalate or hydrogen sulfate during the preparation of the dispersion. Can be adjusted. The dispersion of the fluoroaluminosilicate glass fine particles may further include a dispersant such as hexametaphosphate and polyphosphate, and a fluorine ion such as sodium fluoride or stannous fluoride, as long as the dispersion stability is not impaired. Feed materials and the like may be added.

  In the present invention, the solution B is prepared by dissolving an oxalic acid compound in water to prepare an acidic aqueous solution. However, even if one or more acidic oxalic acid compounds are added to water, An acid aqueous solution containing 0.5 mass% to 15 mass%, preferably 1 to 10 mass%, of the oxalate ion may be added.

In the present invention, when the solution A having a pH of 6 to 12 and the solution B having a pH of 0.5 to 3 are mixed, the pH after mixing of the mixed solution is preferably 0.5 to 4. Within this range, calcium ions contained in the tooth can be efficiently precipitated in a short time as calcium oxalate, calcium fluoride, silicate oxalate, and fixed on the tooth surface. As a result, the amount of fluorine taken into the tooth increases, and fluoride is adsorbed on the tooth as calcium fluoride. When the pH of the mixed solution is lower than 0.5, there is a risk of excessive decalcification of the tooth, and calcium fluoride dissolves and the fluorine uptake amount decreases. A pH higher than 4 is not preferable because the reaction between oxalic acid and glass and tooth becomes slow, and a long time is required to obtain a precipitate.

In the present invention, liquid A and liquid B are mixed in appropriate amounts at the time of use, and immediately applied and held on the treatment site (carious site, dentin hypersensitive region) or cavity forming tooth surface for 10 to 30 seconds. As a result, a film made of fine deposits of silicate and oxalate containing calcium fluoride and calcium oxalate is formed. Moreover, the application to a tooth surface can also apply | coat A liquid and B liquid to a tooth surface separately, and can also mix on a tooth surface.
As a commercial preparation, the liquid A and the liquid B of the present invention may each be a separate package, or may be a package as a kit in which the liquid A and the liquid B are combined.

Hereinafter, the present invention will be described in more detail with reference to examples and comparative examples, but the present invention is not limited to these examples. In the following examples, “%” indicates “% by mass”.

[Example 1] (1) Preparation of dispersion of fluoroaluminosilicate glass fine particles (A ₁ liquid)
SiO ₂ : 25.8 g, Al ₂ O ₃ : 20.9 g, CaF ₂ : 17.8 g, La ₂ O ₃ : 16.4 g, Ca ₂ (H ₂ PO ₄ ) ₂ : 9.43 g, Na ₂ CO ₃ : 15.9 g, CaO: 0.50 g was sufficiently mixed and stirred in a mortar, and the resulting batch was placed in a porcelain crucible and heated to 1100 ° C. at a rate of about 7 ° C./min. In an electric furnace. did. After mooring for 5 hours, the melt was poured into water and quenched to obtain glass. The obtained glass was pulverized with a ball mill (wet) to obtain fluoroaluminosilicate glass powder (a ₁ ) having an average particle size (D50) of 3.2 μm in a volume-based particle size distribution. The fluoroaluminosilicate glass powder (a ₁ ) was purified at a concentration of 15% using a wet pulverizer / disperser (bead mill: Nanogetter DMR110 manufactured by Ashizawa Finetech) at a peripheral speed of 10 m / s. (Used beads: ZrO ₂ 0.2 mm) for 90 minutes, average particle size (D50) in volume-based particle size distribution (D50) 0.38 μm, particle size at 90% position measured from the smaller diameter side (D90) in the same particle size distribution. dispersion of fluoroaluminosilicate glass particles of 77μm to (a ₁ solution) was obtained. The pH of the glass dispersion _{(A 1} solution) was 8.6.
(2) Preparation of oxalic acid aqueous solution (B ₁ solution) Oxalic acid was dissolved in purified water to obtain an aqueous solution (B ₁ solution) of 6.9% oxalic acid (pH: 0.88).

[Example 2] (1) Preparation of dispersion (A ₂ liquid) of fluoroaluminosilicate glass fine particles
CaF ₂ : 51.5 g, CaO: 16.3 g, SiO ₂ : 12.1 g, Al ₂ (HPO ₄ ) ₃ : 8.26 g, Al ₂ O ₃ : 7.23 g, Na ₂ AlF ₆ : 4.52 g The mixture was sufficiently mixed and stirred in a mortar, and the resulting batch was placed in a porcelain crucible and heated to 1100 ° C. at a temperature increase rate of about 5 ° C./min. In an electric furnace. After mooring for 5 hours, the melt was poured into water and quenched to obtain glass. The obtained glass was pulverized with a dry jet mill to obtain a fluoroaluminosilicate glass powder (a ₂ ) having an average particle size (D50) of 2.4 μm in a volume-based particle size distribution. This fluoroaluminosilicate glass powder (a ₂ ) was treated for 90 minutes at a peripheral speed of 10-15 m / s (beads used: ZrO ₂ 0.3 mm) at a concentration of 13% using a bead mill as in Example 1. Volume Dispersion liquid of fluoroaluminosilicate glass fine particles having an average particle diameter (D50) of 0.42 μm in the standard particle size distribution and a 90% particle diameter (D90) of 1.27 μm measured from the smaller diameter side in the same particle size distribution (A ₂ liquid) ) The pH of the glass dispersion _{(A 2} solution) was 10.2.
(2) Preparation of oxalic acid aqueous solution (B ₂ solution) 8 g of oxalic acid and 1 g of potassium nitrate were dissolved in purified water to obtain 100 g of an aqueous solution (B ₂ solution) (pH: 0.56).

Preparation of Example 3 (1) Dispersion of fluoroaluminosilicate glass particles _{(A 3} solution)
SiO ₂ : 40.3 g, Al ₂ O ₃ : 33.8 g, Na ₂ CO ₃ : 15.5 g, Al ₂ (HPO ₄ ) ₃ : 7.77 g, Na ₂ AlF ₆ : 5.31 g, ZrO ₂ : 2 .82 g, La ₂ O ₃ : 0.24 g, Y ₂ O ₃ : 0.79 g were used to prepare a glass in the same procedure as in Example 1, and the average particle size (D50) in the volume-based particle size distribution. An 8 μm fluoroaluminosilicate glass powder (a ₃ ) was obtained. This fluoroaluminosilicate glass powder (a ₃ ) was bead-milled at a concentration of 10% in the same manner as in Example 1, the average particle size (D50) in the volume-based particle size distribution was 0.33 μm, and from the smaller diameter side in the same particle size distribution. particle size of the measured 90% position (D90) was obtained dispersion of fluoroaluminosilicate glass particles of 1.44μm to _{(a 3} solution). The pH of the glass dispersion (A ₃ ) was 7.3.
(2) Preparation of aqueous oxalic acid solution (B ₃ solution) 1.76 g of potassium hydrogen oxalate was dissolved in purified water, 1.24 g of 70% nitric acid was added, and then purified water was added to make 100 g (B ₃ solution). (PH: 0.89) was obtained.

Preparation of Example 4 (1) Dispersion of fluoroaluminosilicate glass particles _{(A 4} solution)
_{SiO 2: 29.1g, CaF 2:} 20.5g, Al 2 O 3: 13.3g, CaO: 12.1g, MgO: 10.2g, Na 2 AlF 6: 9.35g, KHCO 3: 6.82g , Ca ₂ (H ₂ PO ₄ ) ₂ : 2.38 g, a glass was prepared by the same procedure as in Example 2, and a fluoroaluminosilicate glass having an average particle size (D50) of 2.2 μm in the volume-based particle size distribution A powder (a ₄ ) was obtained. This fluoroaluminosilicate glass powder (a ₄ ) was bead-milled at a concentration of 18% in the same manner as in Example 1, the average particle size (D50) in the volume-based particle size distribution was 0.31 μm, and the same particle size distribution from the smaller diameter side. particle size of the measured 90% position (D90) was obtained dispersion of fluoroaluminosilicate glass particles of 1.11μm to _{(a 4} solution). The pH of the glass dispersion _{(A 4} solution) was 8.0.
(2) Preparation of oxalic acid aqueous solution (B ₄ solution) Oxalic acid was dissolved in purified water to obtain an aqueous solution (B ₄ solution) of 6.9% oxalic acid (pH: 0.88).

Preparation of Example 5 (1) Dispersion of fluoroaluminosilicate glass particles (A ₅ solution)
SiO ₂ : 22.6 g, ZrO ₂ : 18.4 g, Al ₂ O ₃ : 17.3 g, La ₂ O ₃ : 15.7 g, SrCO ₃ : 13.8 g, Na ₂ HPO ₄ : 3.48 g, CaO: 3.24 g, K ₂ HPO ₄ : 3.16 g, Al ₂ (HPO ₄ ) ₃ : 2.89 g, CaF ₂ : 2.37 g, Y ₂ O ₃ : 1.58 g Glass was prepared according to the procedure to obtain fluoroaluminosilicate glass powder (a ₅ ) having an average particle size (D50) of 6.2 μm in the volume-based particle size distribution. This fluoroaluminosilicate glass powder (a ₅ ) was bead-milled at a concentration of 10% in the same manner as in Example 1 and the average particle size (D50) in the volume-based particle size distribution was 0.43 μm. particle size of the measured 90% position (D90) was obtained dispersion of fluoroaluminosilicate glass particles of 1.94μm to _{(a 5} solution). The pH of the glass dispersion _{(A 5} solution) was 6.8.
(2) was dissolved preparation oxalate dipotassium 4.1g of oxalic acid aqueous solution (B ₅ liquid) in purified water, aqueous solution with 100g added purified water after addition of 70% nitric acid 2.2 g _{(B 5} liquid) (PH: 1.84) was obtained.

[Example 6] Sealing effect of dentinal tubules (1) Preparation of pseudo-hypersensitive dentin To remove the enamel from the front teeth extracted from the bovine and open the dentinal tubules assuming hypersensitivity, a 15% EDTA aqueous solution (pH 7. 2) for 1 minute. Hereinafter, this is called pseudo-hypersensitive dentin.
(2) Experimental method The liquid A and the liquid B described in each example were mixed with the pseudo-hypersensitive dentin at a sampling ratio described in Table 1. The time required for the mixing operation was 10 seconds. Immediately after that, after applying the moisture-proof and dried tooth surface with a microbrush so as to be rubbed for 20 to 30 seconds, the tooth surface was washed with water and dried, and the treatment surface was visually checked for coloring of the tooth surface. . The change in pH of the mixed solution was measured until 2 minutes after separately mixing (FIG. 1). Next, the treated surface of this sample and the fractured surface perpendicularly broken with mycel and mallet were observed with a field emission scanning electron microscope (JSM-7000F, manufactured by JEOL Ltd.), and from the 500 times observed image of the treated surface. The dentinal tubule occlusion rate (number of occluded dentinal tubules in the observed image / percentage of the number of dentinal tubules in the observed image) was determined. At the same time, elemental analysis of precipitates on the treated surface was performed by energy dispersive X-ray spectroscopy (EDS). A similar experiment was performed on comparative examples as shown in Table 2. Comparative Example 1 was carried out in the same manner as in Example 1 except that the particle diameter of the fluoroaluminosilicate glass fine particles was changed to those of 3.34 μm (D50) and 6.63 μm (D90) in Example 1. Although Examples 2-4 were implemented with respect to the composition as described in patent document 1, patent document 2, and patent document 3, respectively, the processing method at this time was performed by the method as described in each patent document.

(3) Evaluation Regarding the mixed solution of each Example, the pH after mixing for 10 seconds is pH 0.5 to 4 suitable for decalcification of the tooth as shown in Table 1, but gradually increases after mixing, 30 seconds after mixing, it was confirmed that the pH was 2 to 5 suitable for the precipitation of Ca salt (FIG. 1). At this time, the liquid A of Examples 1 to 5 was rich in dispersion stability and had no problem during use, whereas the liquid component of Comparative Example 1 had a powder component precipitated during use, which was a problem in use. However, it was forcibly shaken during the test.
As a result of observation of each treated surface with an electron microscope, in the treatments of Examples 1 to 5 and Comparative Examples 2 to 4, the dentinal tubule openings were all blocked with preparation-derived aggregates or precipitates, and high ivory While the tubule occlusion rate was shown, in Comparative Example 1, the dentinal tubule occlusion rate was low because of the large precipitate formed on the tooth surface. In addition, as for the particle size of the deposit which precipitated by the process with the liquid mixture shown in Examples 1-5, according to an electron microscope observation, the particle size in a glass dispersion liquid (A liquid) is 0.01-1.0 micrometer. Reflected well, the treated surface was completely covered with precipitates of this size. According to the observation of the fractured surface, in the treatments of Examples 1 to 5, precipitation of dentinal tubule obstructions was observed at a depth of about 10 μm.
By energy dispersive X-ray spectroscopy (EDS), Si, Al and other glass-derived elements were confirmed by elemental analysis of precipitates on the treated surface by the treatment of Examples 1 to 5, and in the glass dispersion liquid (A liquid) It was confirmed that this was a reaction product of oxalic acid.

[Example 7] Evaluation of efficacy against dentin hypersensitivity during periodontal treatment (1) Method
20 patients with gingival retraction caused by basic periodontal treatment and complaining of hypersensitivity to air and cold water due to root surface exposure were rubbed for 20 seconds using the prescription solution of Example 1 for 20 seconds. After applying and washing with water, the reaction to the cold stimulus by the air syringe (subject's subjective symptoms) was determined. The air syringe was 1 cm away from the affected tooth and air was blown for 3 seconds.
(2) Results After receiving the treatment for 20 seconds with the product of the present invention (Example 1), most of the patients with dentinal hypersensitivity symptoms (19 out of 20) no longer experience cold pain-induced pain, Dentin hypersensitivity symptoms disappeared.
From this result, it was demonstrated that the composition of Example 1 according to the present invention has a high improvement effect on dentin hypersensitivity.

[Example 8] Acid resistance test (1) Method The effect of application of fluoride on the remineralization of enamel initial caries samples can be observed in situ using the QUANTITATIVE Light-induced Fluorescence (QLF) method. It has been known. (Journal of Oral Hygiene 57 (1), 2-12, 2007)
The A ₁ solution and the B ₁ solution of Example 1 were mixed for 10 seconds, applied to the bovine anterior tooth enamel surface for 20 seconds, washed with water, dried, and then decalcified with a 0.1 M (0.92%) lactate buffer solution for 12 hours. Later, the QLF method (measurement device: Quantitative Light-Fluorescence (trade name: QLF-TM, Inspector Dental)
Measurement by Care BV (hereinafter also referred to as QLF) was performed to calculate the ΔF value. Similarly, the compositions of Comparative Examples 2 to 4 were applied as described in Table 2, and ΔF values were calculated. The ΔF value takes a negative value, and the larger the absolute value, the stronger the decalcification, which is a parameter that is said to correlate with the decalcification depth of the initial caries lesion.
(2) Results The ΔF value in the formulation of Example 1 was −0.8, whereas the ΔF values in the compositions of Comparative Examples 2 to 4 were −12.2, −10.0, and −15. 2. It was confirmed that significant acid resistance was imparted compared to the conventional technology.

By applying the mixed liquid of the dispersion (A) and the aqueous solution (B) according to the present invention to the teeth, a large amount of fluoride can be efficiently taken into the teeth in a short treatment, and high acid resistance is imparted. High dentinal hypersensitivity due to the effect of occluding the dentinal tubules by the fine particles of calcium fluoride, calcium oxalate and silicate oxalate, which can promote remineralization and prevent secondary dental caries Can be prevented.

Claims (7)

An oral preparation comprising a mixed solution of a liquid (A) in which fluoroaluminosilicate glass fine particles are dispersed and an acidic aqueous solution (B) of an oxalic acid compound. The oral preparation according to claim 1, wherein the fluoroaluminosilicate glass fine particles have a particle diameter (D90) at a 90% position measured from the small diameter side in the volume-based particle size distribution of 2 µm or less. The fluoroaluminosilicate glass fine particles contain, as constituent elements, a total of at least one selected from Si: 5 to 25 mass%, Al: 5 to 35 mass%, F: 1 to 25 mass%, and Na, K and Mg. The oral preparation of Claim 1 or 2 containing 10 mass%. The oral preparation according to any one of claims 1 to 3, wherein the oral preparation is a caries prevention and / or initial caries treatment agent. The oral preparation according to any one of claims 1 to 3, wherein the oral preparation is an agent for preventing and / or treating dentine hypersensitivity. The oral preparation according to any one of claims 1 to 3, wherein the oral preparation is an agent for the back layer of the cavity forming tooth surface. The preparation kit for oral preparation according to any one of claims 1 to 6, comprising a combination of a liquid (A) in which fluoroaluminosilicate glass fine particles are dispersed and an acidic aqueous solution (B) of an oxalic acid compound. .

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