JPH10218747A - Composition containing biologically active glass and used for oral cavity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an oral cavity composition comprising biologically active glass and a specific polymer, improved in the retainability of the biologically active glass on the surface of teeth, and capable of uniformly forming the films of hydroxyapatite on the surfaces of the teeth. SOLUTION: This composition comprises biologically active glass and a polymer having adhesivity to the surfaces of teeth. The biologically active glass comprises 20-70wt.% of SiO2 and 10-60wt.% of CaO, especially preferably 30-60wt.% of SiO2 , 10-50wt.% of CaO and 0-30wt.% of Na2 O, and further optionally an inorganic compound such as P2 O5 , K2 O or TiO2 , and is contained in the composition in an amount of 0.0001-50wt.%. The polymer having the adhesivity to the surfaces of teeth can impart retainability on the surfaces of teeth to the biologically active glass, can preferably be dissolved in water, alcohols or wetting agents, and includes carboxymethylcellulose, sodium alginate and polyvinyl pyrrolidone. The polymer is added in an amount of 0.01-5wt.% based on the whole amount of the composition.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a bioactive glass-containing oral composition, and more particularly to an oral composition that uniformly forms a hydroxyapatite film on a tooth surface.

[0002]

2. Description of the Related Art Some glasses and ceramics naturally bond with living tissues, and these are called bioactive materials. Bioactive glass having bioactivity is one of them, and is already used as an artificial bone or an artificial tooth root. These bioactive glasses can be broadly classified into bioactive crystallized glasses containing crystals such as apatite and wollastonite in the glass, and ordinary bioactive glasses containing no such crystals. For example, Japanese Patent Publication No. 62-1093
No. 9 discloses a crystallized glass for artificial bone containing apatite and wollastonite crystals and a method for producing the same. The crystallized glass has excellent biocompatibility and forms a direct chemical bond with bone. It is described that it has excellent mechanical strength. Japanese Patent Application Laid-Open No. 6-30984 discloses C
In artificial bone made of glass or crystallized glass containing aO and SiO ₂ as main components, technology to prevent the strength deterioration of glass by adjusting the amount of Ca ²⁺ ions eluted by bonding hydrophobic groups to the glass surface Is disclosed. JP-A-5-31166 discloses a technique in which a metal such as titanium is coated with a bioactive glass and used as a bone replacement material. Further, Japanese Patent Application Laid-Open No. 2-255515 discloses that bioactive glass is used for bone repair materials, implantable medical instruments and equipment, medical supplies, artificial organs and the like irrespective of inorganic materials, metallic materials, and organic materials. A method for forming a bioactive apatite film similar to bone in a living body on the surface of all the materials used therein is disclosed. on the other hand,
In the field of oral preparations, it is known to form a hydroxyapatite film on the tooth surface using a calcium phosphate-based compound.For example, NaCl, KCl, MgCl ₂ and other chlorides are added to poorly soluble hydroxyapatite, A technique of coating the tooth surface by increasing the solubility in water (JP-A-56-73015) is known. Also, a technique for converting carbonate apatite into hydroxyapatite under neutral or weakly alkaline conditions (Japanese Patent Application Laid-Open No. 64-70408).
Also, a technique of converting a dentifrice composition containing a calcium salt into hydroxyapatite in the presence of water (saliva) in the oral cavity (Japanese Patent Application Laid-Open No. 7-22930) is disclosed. However, the material for forming hydroxyapatite blended in such an oral composition has short contact with the teeth and cannot uniformly coat the tooth surface in a short time, thus effectively forming hydroxyapatite and thus effective. The effect of preventing tooth decay cannot be achieved.

[0003]

The bioactive glass is a material capable of forming a hydroxyapatite film on the tooth surface. However, when incorporated in an oral composition, the bioactive glass itself stays on the tooth surface. Therefore, there is a problem that it is difficult to expect an effective formation of a hydroxyapatite film. In order to solve such a problem, the present invention
It is an object of the present invention to retain bioactive glass on the tooth surface and to effectively form hydroxyapatite on the tooth surface.

[0004]

Means for Solving the Problems The inventors of the present invention have made intensive studies to solve the above-mentioned problems, and as a result, by blending a bioactive glass and a tooth surface-adhering polymer into an oral composition, a bioactive glass was formulated. The present inventors have found that the retention of active glass on the tooth surface can be improved and a hydroxyapatite film can be uniformly formed on the tooth surface, and the present invention has been completed. That is, the present invention provides an oral composition characterized by comprising bioactive glass and a tooth surface-adhering polymer. According to the present invention, the bioactive glass stays on the tooth surface by the action of the tooth surface-adhering polymer, and effective formation of hydroxyapatite on the tooth surface can be achieved.

[0005]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The bioactive glass used in the present invention is not limited as long as it is a glass material that naturally bonds to the tooth surface, and bioactive crystallized glass containing crystals in the glass, or It may be any of the usual bioactive glasses that do not contain such crystals,
Biocrystallized glass is more preferred from the viewpoint of stability in the formulation. The composition of the bioactive glass is S
iO ₂ 20-70% by weight, preferably contains a CaO 10 to 60 wt%, in particular, a SiO ₂ 30 to 60 wt%, 10-50 wt% of CaO and Na ₂ O 0-30
It is preferred that the content be contained by weight. SiO _{2 in} glass is 20
If the content is less than 70% by weight, the affinity with the tooth surface is lowered. On the other hand, if the content is more than 70% by weight, vitrification becomes difficult. If the content of CaO in the glass is less than 10% by weight, the affinity with the tooth surface is reduced. On the other hand, if it exceeds 60% by weight, vitrification becomes difficult, which is not preferable. Na ₂ O makes the glass low-melting, but if it exceeds 30% by weight, the affinity for the tooth surface is lowered, which is not preferable.

The crystals contained in the bioactive crystallized glass used in the present invention include apatites such as wollastonite, hydroxyapatite or oxyfluoroapatite, magnesium titanate, aluminum orthophosphate, diopside and phlogopite, phlogopite and mica. One or more selected from the group consisting of mica
Those containing 1 to 80% by weight based on the whole glass are preferred. If the amount of crystals in the glass is less than 1% by weight, the effective effect of each crystal will not be exhibited, while if it exceeds 80% by weight, the apatite-forming ability is undesirably reduced. Of these crystals, wollastonite, magnesium titanate and mica increase the mechanical strength of the glass, and apatite, aluminum orthophosphate and diopside act to increase the affinity with the tooth surface.

In the composition of the present invention, one or more of these bioactive glasses are preferably used in an amount of 0.001 to 50% by weight based on the total amount of the oral composition. If the amount is less than 0.001% by weight, apatite is not formed on the tooth surface, while if it exceeds 50% by weight, the tooth surface is damaged, which is not preferable. The bioactive glass used in the present invention includes P ₂ O ₅ , K ₂ O, and Li ₂
O, TiO ₂ , Al ₂ O ₃ , MgO, B ₂ O ₃ , ZrO ₂ and F
One or more inorganic compounds selected from the group consisting of: Among these inorganic compounds, P ₂ O ₅ stabilizes the glass, K ₂ O, Li ₂ O and B ₂ O _{3 make} the glass low-melting, TiO ₂ , Al ₂ O ₃ , Mg
O, ZrO ₂ and F act to control the apatite coating rate. These inorganic compounds can be contained in an amount of 0 to 30% by weight based on the whole bioactive glass.

The bioactive glass used in the present invention is spherical,
It may have various shapes such as beads, granules, and granules, and can be produced, for example, based on a method disclosed in JP-A-60-239341. Further, as the bioactive glass, one having less than 32 mesh pass is suitably used, and 65 mesh pass is particularly preferred. When the size is 32 mesh or more, the feeling of use of the oral composition is impaired, which is not preferable.

[0009] The tooth surface-adhering polymer used in the present invention may be any polymer that imparts retention of bioactive glass on the tooth surface. For example, the polymer may be dissolved in at least one of water, alcohol, and a wetting agent. Natural or synthetic polymers. Examples of natural polymers include carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, cationized hydroxyethyl cellulose, cellulose derivatives such as cellulose acetate phthalate, alkali metal alginate such as sodium alginate, propylene glycol alginate, xanthan gum And gums such as tragacanth gum, karaya gum, gum arabic, and carrageenan, and gelatin. Examples of synthetic polymers include non-ionic polymers such as polyvinylpyrrolidone and polyvinyl alcohol, carboxyvinyl polymers, methyl vinyl ether maleate ester copolymers, anionic polymers such as sodium polyacrylate, and ethyl acrylate / methacrylic acid. And methacrylic acid copolymers such as methyl copolymers and aminoalkyl methacrylate copolymers. Among these tooth-surface-adhering polymers, particularly preferred are sodium carboxymethylcellulose, sodium alginate, carrageenan, and methyl vinyl maleate copolymer. These tooth surface-adhering polymers may be used alone or in combination of two or more, and the compounding amount is 0.01 to 5% by weight based on the total amount of the composition. If the amount is less than 0.01%, the effect of adhering the glass to the tooth surface cannot be obtained, which is not preferable. On the other hand, if the amount is 5% or more, the viscosity becomes too high, which is not preferable.

[0010] The oral composition of the present invention can be made into a formulation such as a dentifrice, gel, ointment, patch or the like according to a conventional method.
Substrates such as an abrasive, a surfactant, a flavoring agent, a wetting agent, and a sweetening agent, as well as a medicinal ingredient and the like can be appropriately compounded within a range that does not impair the effects of the invention. For example, in the case of a dentifrice, as a polishing agent, dibasic calcium phosphate dihydrate and anhydride, calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, silicic anhydride, silica gel, silicic acid Aluminum, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate, synthetic resin, and the like can be used. These abrasives may be used alone or in combination of two or more, and the compounding amount is usually 5 to 90 with respect to the total amount of the composition.
% By weight, and 5 to 60% by weight in the case of toothpaste. Examples of the surfactant include a nonionic surfactant, an anionic surfactant, and an amphoteric surfactant. Examples of the nonionic surfactant include sucrose fatty acid esters, maltose fatty acid esters, and maltitol fatty acid esters. , Maltotriitol fatty acid ester, maltotetriitol fatty acid ester, maltopentitol fatty acid ester,
Maltohexaitol fatty acid ester, maltoheptitol fatty acid ester, sorbitan fatty acid ester, lactose fatty acid ester, lactinose fatty acid ester, polyoxyethylene polyoxypropylene glycol ether, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate Polyoxyethylene sorbitan fatty acid esters, such as
Polyoxyethylene hydrogenated castor oil, polyoxyethylene fatty acid ester, fatty acid monoglyceride, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene fatty acid ester, and the like.

Examples of the anionic surfactant include water-soluble salts of higher alkyl sulfates having an alkyl group having 8 to 18 carbon atoms, such as sodium lauryl sulfate and sodium myristyl sulfate, and polyoxyethylene alkyl sulfates. , Alkyl sulfo acetate, α-olefin sulfonate, alkyl sulfosuccinic acid derivative, higher fatty acid sodium monoglyceride monosulfate, N
-Methyl-N-palmitoyl tauride salt, N-long chain acyl basic amino acid salt and the like. Examples of the amphoteric surfactant include carboxylic acid types such as betaine type, imidazolium type, imidazolium betaine type, amino acid type and amine oxide type. These surfactants may be used alone or in combination of two or more, and the compounding amount is usually 0.001 to 5% by weight based on the total amount of the composition.

Examples of the flavoring agent include 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, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, diatom oil, perilla oil, winter Examples thereof include green oil, clove oil, and eucalyptus oil. Usually, one or more of these are 0.01 to 10% by weight based on the total amount of the composition. Sweeteners include saccharin sodium, acetylpharma potassium, stevioside, neohesporidyldihydrochalcone, glycyrrhizin, perillartin, thaumatin, asparatylphenylalanine methyl ester, p-methoxycinnamic aldehyde, xylitol, maltite,
Lactit and the like can be exemplified. Further, as the pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or a chemically possible salt or sodium hydroxide thereof, and the like. The composition may be used alone or in combination of two or more so that the pH of the composition is in the range of 3 to 10. Wetting agents such as sorbitol, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, and polypropylene glycol,
They may be used alone or in combination of two or more. In addition, bactericides such as chlorhexidine gluconate, cetylpyridinium chloride, and triclosan; enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and lytic enzyme (Litec enzyme); sodium monofluorophosphate, potassium monofluorophosphate, and the like. Alkali metal monofluorophosphates, fluorides such as sodium fluoride, stannous fluoride, vitamin derivatives,
Pharmaceutical ingredients such as tranexamic acid and epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, glycyrrhizin salts, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, caropeptide, and a water-soluble inorganic phosphate compound can also be incorporated.

[0013]

Next, the present invention will be described more specifically with reference to examples and comparative examples, but the present invention is not limited to these examples. Unless otherwise specified, “%” indicates% by weight. Examples 1 to 3 and Comparative Examples 1 to 3 According to the prescription shown in Table 1, gels containing tooth-surface-adhering polymer were prepared by a conventional method (Examples 1 to 3 and Comparative Examples 1 to 3). Apply bioactive glass to an acrylic plate so that the artificial saliva becomes 0.1% in artificial saliva.
Let stand for 2 hours. The retention on the acrylic plate and the apatite conversion after 12 hours were evaluated based on the following criteria. (1) Retention: retention area of acrylic plate after 12 hours ○: 70% or more of application area stays Δ: 40 to 70% of application area stays ×: 40% or less of application area stays (2) apatite Conversion rate: When the gel is immersed in artificial saliva for 12 hours, the rate at which the glass in the formulation is converted to apatite ○: 80% or more of the glass is converted to apatite △: 40 to 80% of the glass is converted to apatite ×: 40% or less of glass was converted to apatite. Inductively coupled plasma emission analysis was used for quantification of apatite.

[0014]

[Table 1]

Example 4 Toothpaste Ingredients Content (%) Silicic anhydride 15.0 Carrageenan 2.0 Sodium benzoate 0.4 Saccharin sodium 0.1 Sodium lauryl sulfate 1.0 Sorbit 60.0 Fragrance 1.0 Water q.s. bioactive glass _{5.0 (SiO 2 / CaO / Na} 2 O: 60/20/20%) total 100.0

Comparative Example 4 Toothpaste Component Content (%) Silicic Anhydride 15.0 Sodium Benzoate 0.4 Saccharin Sodium 0.1 Sodium Lauryl Sulfate 1.0 Sorbit 60.0 Fragrance 1.0 Water Appropriate Amount Bioactivity glass _{5.0 (SiO 2 / CaO / Na} 2 O: 60/20/20%) total 100.0

Evaluation A section of about 1 × 3 mm ² was made from adult permanent tooth enamel. This section was embedded in an acrylic resin, brushed for 5 minutes using the toothpaste of Example 4 and a commercially available toothbrush, and then allowed to stand in whole saliva at 37 ° C. for 12 hours. When the adult permanent teeth were observed with a microradiograph, a hydroxyapatite film was uniformly formed on the surface of the enamel at about 5 μm.
It was recognized that a μm was formed. However, when the same operation was performed with the toothpaste of Comparative Example 4, only a hydroxyapatite film of about 2 μm was formed in 12 hours. When the same operation was performed using toothpaste having the same composition as in Example 4 except that the bioactive glass was removed, no hydroxyapatite film was formed on the enamel surface.

Examples 5 to 12 and Comparative Example 5 According to the formulation shown in Table 2, aqueous solutions containing a tooth surface-adhering polymer were prepared (Examples 5 to 12 and Comparative Example 5).
Make a section of about 3 x 3 mm ² from adult permanent tooth dentin,
This section was embedded in an acrylic resin, and the aqueous solutions of Examples 5 to 12 and Comparative Example 5 were applied.
For 24 hours. The coating amount of hydroxyapatite in the adult permanent tooth dentin was evaluated as a mineral amount (μm Vol%) by image analysis of a microradiograph obtained by X-ray irradiation.
The results are shown in Table 2.

[0019]

[Table 2] From these results, it was confirmed that the oral composition of the present invention stayed on the tooth surface and uniformly formed a hydroxyapatite film on the tooth surface.

Example 13 Toothpaste Component Content (%) Calcium phosphate 30.0 Sodium carboxymethylcellulose 1.5 Sodium benzoate 0.4 Sodium lauryl sulfate 1.0 Glycerin 20.0 Flavor 1.0 Water Appropriate amount Bioactivity Crystallized glass 10.0 (glass phase (SiO ₂ / CaO / K ₂ O: 50/40/10) 50%, apatite crystal 25%, wollastonite crystal 25%) Total 100.0

Example 14 Gel Component Content (%) Sodium Alginate 2.0 Ethyl Acrylate / Methyl Methacrylate Copolymer 2.0 Stevia 0.5 Ethanol 10.0 Water Appropriate Amount Bioactive Glass 5.0 (SiO _{2) / CaO / Na 2 O: 60/30/10} ) total 100.0

Example 15 Ointment Ingredient Component Content (%) Cationized hydroxyethylcellulose 4.0 Triacetin 12.0 Glycerin Appropriate amount Bioactive crystallized glass 10.0 (glass phase (SiO ₂ / CaO / P ₂ O ₅₎ : 50/40/10) 40%, diopsite crystal 25%, apatite crystal 35%) Total 100.0

Example 16 Liquid Toothpaste Component Content (%) Methyl vinyl ether maleic acid copolymer 2.0 Silicic anhydride 15.0 Sorbitol 60.0 Fragrance 1.0 Saccharin sodium 0.2 Water Appropriate amount Bioactive crystallized glass 10 .0 (glass phase _{(SiO 2 / CaO / B 2} O 5: 60/35/5) 70%, phlogopite crystal 30%) total 100.0

[0024]

According to the present invention, there can be provided an oral composition effective for preventing dental caries, which forms a hydroxyapatite film on the enamel surface of teeth in a short time and uniformly. The oral composition is also effective for preventing secondary caries and root caries, repairing defects such as wedge-shaped defects, alleviating hyperesthesia, and aesthetically coating tooth surfaces.

Claims (6)

[Claims] 1. An oral composition comprising a bioactive glass and a tooth surface-adhering polymer. 2. The oral composition according to claim 1, wherein the bioactive glass contains 20 to 70% by weight of SiO ₂ and 10 to 60% by weight of CaO. 3. The oral composition according to claim 1, wherein the bioactive glass is incorporated in an amount of 0.001 to 50% by weight. 4. The bioactive glass according to claim 1, comprising 30 to 60% by weight of SiO ₂ , 10 to 50% by weight of CaO and 0 to 30% by weight of Na ₂ O. Oral composition. 5. The bioactive glass further comprises P ₂ O ₅ , K ₂
O, Li ₂ O, TiO ₂ , Al ₂ O ₃ , MgO, B ₂ O ₃ , Zr
Any one of claims 1 to 4, containing one or more inorganic compounds selected from O _2, and the group consisting of F 1
The oral composition according to the above item. 6. The tooth surface-adhering polymer is soluble in water, alcohol or a wetting agent, and its compounding amount is 0.01 to 5% by weight based on the total amount of the composition. 6. The composition for oral cavity according to any one of 5).