Glass composition, sustained release composition, medical composition, and dental composition

Abstract

This glass composition contains gallium and phosphorus, contains at least one selected from alkali metals, calcium, and strontium, and contains aluminum in an amount of 0%-3.8% by mass in terms of oxide.

Description

Glass compositions, sustained-release compositions, medical compositions, and dental compositions

[0001] This disclosure relates to glass compositions, sustained-release compositions, medical compositions, and dental compositions.

[0002] Sustained-release glass that releases functional ions has been known for some time. For example, there are technologies that use inorganic glass particles that release phosphorus ions and calcium ions into water as granular soil modifiers, technologies that use potassium glass as fertilizer, technologies that use antibacterial glass that elutes silver ions in resin molded products, technologies that use bioglass in medical applications such as bone repair materials and medical implants, and technologies that use ion-sustained-release glass in deodorant compositions (see Patent Documents 1 to 6).

[0003] Japanese Patent Publication No. 2000-41482, Japanese Patent Publication No. 2007-308322, Japanese Patent No. 6604499, Japanese Patent No. 6622416, Japanese Patent Publication No. 2020-535881, International Publication No. 2019 / 189851

[0004] Conventional sustained-release glass may lose its ability to control its release properties when used in environments with inconsistent acidity, as the acidity changes.

[0005] The objective of this disclosure is to provide a glass composition that yields glass that is poorly soluble in acidic regions and readily soluble in neutral regions, even in environments where the acidity changes between neutral and acidic regions.

[0006] A glass composition according to one aspect of the present disclosure contains gallium and phosphorus, at least one selected from alkali metals, calcium, and strontium, and contains aluminum in an oxide equivalent of 0% by mass or more and 3.8% by mass or less.

[0007] According to one aspect of this disclosure, it is possible to provide a glass composition that yields glass that is poorly soluble in acidic regions and readily soluble in neutral regions, even in environments where the acidity changes between neutral and acidic regions.

[0008] The embodiments of this disclosure will be described in detail below.

[0009] <Glass Composition>The glass composition according to this embodiment contains gallium and phosphorus, contains at least one selected from alkali metals, calcium, and strontium, and contains aluminum in an amount of 0% by mass or more and 3.8% by mass or less in terms of oxide.

[0010] In this specification, the form of the glass constituting the glass composition is not limited to the amorphous form, and includes the crystalline form or the form in which the amorphous and crystalline forms are mixed. Further, the glass includes glass ceramics in which a part is composed of glass.

[0011] The form of the glass is preferably powder. The size of the glass powder is preferably 0.01 μm or more and 100 μm or less in terms of median diameter, more preferably 0.02 μm or more and 50 μm or less, and even more preferably 0.03 μm or more and 30 μm or less. In this specification, the median diameter indicates the particle diameter (D50) at which the volume-based cumulative distribution measured by the laser diffraction / scattering method is 50%. When the size of the glass powder is 0.01 μm or more and 100 μm or less in terms of median diameter, the sustained release property of the glass can be exhibited.

[0012] Gallium (Ga) may exist in the glass composition in the state of gallium oxide (gallium oxide (Ga ２ O ３ )). By blending gallium into the glass composition, it is easy to obtain a glass that does not dissolve too much in the acidic range and is easily soluble in the neutral range.

[0013] The content of gallium (Ga) is preferably 5% by mass or more and 45% by mass or less in terms of oxide in the glass composition, more preferably 10% by mass or more and 40% by mass or less, and even more preferably 15% by mass or more and 38% by mass or less. When the content of Ga is 5% by mass or more, it is easy to obtain a glass that does not dissolve too much in the acidic range and is easily soluble in the neutral range. When it is 45% by mass or less, the melting temperature of the glass decreases, and it is easy to obtain the glass.

[0014] Phosphorus (P) is, in the glass composition, phosphorus oxide (phosphorus oxide (P ２ O ５It can exist in the state of )). By blending phosphorus into the glass composition, phosphorus plays a role in forming a network in the glass. Further, since the glass composition contains phosphorus, phosphate ions (PO4 ３－ released from the glass can impart an effect of preventing dental hard tissue remineralization and dental caries, for example, when the glass composition is used in the oral cavity.

[0015] The content of phosphorus (P) is preferably 40% by mass or more and 80% by mass or less in terms of oxide conversion in the glass composition, more preferably 45% by mass or more and 75% by mass or less, and still more preferably 50% by mass or more and 70% by mass or less. When the content of P is 40% by mass or more, it becomes easier to obtain glass. When it is 80% by mass or less, more other components can be contained, and the handling during the production of glass is improved.

[0016] Alkali metals can exist in the state of oxides of alkali metals in the glass composition. By blending alkali metals into the glass composition, the melting temperature of the glass can be lowered, and further the solubility of the glass can be increased.

[0017] Alkali metals are lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), which are metal elements belonging to Group 1 in the periodic table. Among these, Na and K are preferable in that they can lower the melting temperature of the glass and further increase the solubility of the glass. When the alkali metal is Na, it can exist in the state of sodium oxide (sodium oxide (Na ２ O)) in the glass composition.

[0018] The content of alkali metals is preferably 0% by mass or more and 30% by mass or less in terms of oxide conversion in the glass composition, more preferably 0% by mass or more and 25% by mass or less, and still more preferably 0% by mass or more and 20% by mass or less. When the content of alkali metals is 0% by mass or more and 30% by mass or less, it becomes easier to obtain a glass that does not dissolve too much when the acidity is low.

[0019] Calcium (Ca) can exist in the glass composition in the form of calcium oxide (calcium oxide (CaO)). By incorporating calcium into the glass composition, calcium ions (Ca ２＋ ) released from the glass can exert an acid resistance effect, an effect of suppressing dental enamel demineralization, and a bone formation promoting effect.

[0020] The content of calcium (Ca) in the glass composition is preferably 0% by mass or more and 30% by mass or less in terms of oxide, more preferably 0% by mass or more and 25% by mass or less, and even more preferably 5% by mass or more and 20% by mass or less. When the content of Ca is 0% by mass or more and 30% by mass or less, an acid resistance effect, an effect of suppressing dental enamel demineralization, and a bone formation promoting effect can be imparted, the melting temperature of the glass can be lowered, and the solubility of the glass can be further increased, making it easier to obtain a glass that does not dissolve too much in the acidic range.

[0021] Strontium (Sr) can exist in the glass composition in the form of strontium oxide (strontium oxide (SrO)). By incorporating strontium into the glass composition, strontium ions (Sr ２＋ ) released from the glass can impart an acid resistance effect and a bone formation promoting effect.

[0022] The content of strontium (Sr) in the glass composition is preferably 0% by mass or more and 30% by mass or less in terms of oxide, more preferably 0% by mass or more and 25% by mass or less, and even more preferably 5% by mass or more and 20% by mass or less. When the content of Sr is 0% by mass or more and 30% by mass or less, an acid resistance effect and a bone formation promoting effect can be imparted, and it becomes easier to obtain a glass that does not dissolve too much in the acidic range.

[0023] Aluminum (Al) can exist in the glass composition in the form of aluminum oxide (aluminum oxide (Al ２ O ３ )). By incorporating aluminum into the glass composition, the chemical resistance of the glass can be improved and the stability as a glass can be enhanced.

[0024] The aluminum (Al) content in the glass composition is 0% to 3.8% by mass, more preferably 0% to 3.6% by mass, and even more preferably 0% to 3.4% by mass, in terms of oxide. When the Al content is 0% to 3.8% by mass, it is easier to obtain glass that does not dissolve excessively in acidic conditions.

[0025] The glass composition according to this embodiment preferably further contains fluorine (F). Fluorine (F) may exist in the glass composition as fluoride or fluoride salt. By incorporating fluorine into the glass composition, the demineralization inhibitory effect and antibacterial effect of the glass are improved.

[0026] The fluorine (F) content in the glass composition is 0% to 20% by mass, more preferably 0% to 15% by mass, and even more preferably 0% to 10% by mass, in terms of oxide. When the F content is 0% by mass or more, the demineralization inhibitory effect and antibacterial effect of the glass can be obtained, and when it is 20% by mass or less, the glass is easier to obtain.

[0027] Furthermore, the glass composition of this embodiment may contain other elements such as silver (Ag), copper (Cu), zinc (Zn), and boron (B), as long as they do not impair the purpose of this disclosure.

[0028] The glass composition of this embodiment preferably does not contain silicon (Si). Here, "does not contain" means that silicon is not actively added to the glass composition, but this does not exclude the possibility of silicon being mixed in as an unavoidable component such as an impurity during the manufacturing process. Because the glass composition does not contain silicon, the melting point of the glass is less likely to rise, so the melting temperature of the glass can be lowered, making it easier to obtain glass.

[0029] As described above, the glass composition of this embodiment contains Ga, P, and at least one selected from alkali metals, Ca, and Sr, and contains Al in an oxide equivalent of 0% to 3.8% by mass, so that the solubility in the neutral range is greater than the solubility in the acidic range. In this specification, the neutral range refers to a pH range greater than 6.5 and less than 8, and the acidic range refers to a pH range of 6.5 or less.

[0030] Furthermore, the dissolution rate is calculated by immersing the material in a predetermined buffer solution and following the formula (1) below. Dissolution rate (%) = [(Weight before immersion) - (Weight after immersion)] × 100 / Weight before immersion ... (1)

[0031] Generally, glass dissolves more easily in acidic conditions than in neutral conditions. If too much glass dissolves in acidic conditions, a large amount of glass will be consumed in those conditions, which can lead to a decrease in the amount of ions released in neutral conditions and a shortened lifespan of the ion release capacity. For example, when using a glass composition in the oral cavity, it is desirable for a large amount of calcium (Ca) to be released in neutral conditions to efficiently promote remineralization. Releasing a large amount of calcium in acidic conditions is inefficient as it does not contribute much to remineralization or bone formation.

[0032] In contrast, the glass composition of this embodiment has a higher solubility in the neutral range than in the acidic range. As a result, even in environments where the acidity changes between the neutral and acidic ranges, a glass is obtained that is difficult to dissolve in the acidic range and easily dissolves in the neutral range. Therefore, in such a glass, sustained release is suppressed in the acidic range and promoted in the neutral range. In this specification, sustained release refers to the property of a component dissolving and being gradually released in an ionic state.

[0033] As a result, for example, the sustained release properties of the glass can be controlled so that the glass is less likely to dissolve when the acidity in the oral cavity becomes acidic after a meal, and more likely to dissolve when the acidity in the oral cavity returns to a neutral range.

[0034] In the glass composition of this embodiment, the pH in the neutral range is 7.5, the pH in the acidic range is 4.5, and the ratio of the solubility at pH 7.5 to the solubility at pH 4.5 is preferably 1.4 or higher, more preferably 1.6 or higher, and even more preferably 1.8 or higher. When the ratio of the solubility at pH 7.5 to the solubility at pH 4.5 is 1.4 or higher, a glass is obtained that is less soluble in the acidic range and more soluble in the neutral range.

[0035] Furthermore, in the glass composition of this embodiment, the pH in the neutral range is 7.5, the pH in the acidic range is 5.5, and the ratio of the solubility at pH 7.5 to the solubility at pH 5.5 is preferably 1.4 or higher, more preferably 1.45 or higher, and even more preferably 1.5 or higher. When the ratio of the solubility at pH 7.5 to the solubility at pH 4.5 is 1.4 or higher, a glass can be obtained that is less soluble in the acidic range and more soluble in the neutral range.

[0036] <Sustained-Release Composition> The sustained-release composition according to this embodiment includes the glass composition of this embodiment described above. Specifically, the sustained-release composition of this embodiment contains gallium and phosphorus, at least one selected from alkali metals, calcium, and strontium, and aluminum in an oxide equivalent of 0% by mass or more and 3.8% by mass or less. In this specification, a sustained-release composition means a composition in which the components dissolve and are gradually released in an ionic state.

[0037] In the sustained-release composition according to this embodiment, the same effects as the glass composition of this embodiment can be obtained by including such a glass composition. Specifically, the sustained-release composition of this embodiment contains glass that is difficult to dissolve in the acidic range and easy to dissolve in the neutral range, even in environments where the acidity changes between the neutral and acidic ranges. Therefore, sustained release can be suppressed in the acidic range and promoted in the neutral range. As a result, by using such a sustained-release composition in the oral cavity, for example, the sustained release of the glass can be controlled so that the glass is difficult to dissolve when the acidity in the oral cavity becomes acidic after a meal, and easy to dissolve when the acidity in the oral cavity returns to the neutral range.

[0038] The applications of the sustained-release composition are not particularly limited and include, for example, resins, coatings, soil conditioners, fertilizers, electronic materials, bone grafts, biomaterials, medical materials, and dental materials.

[0039] <Medical Composition> The medical composition according to this embodiment includes the sustained-release composition of this embodiment described above. Specifically, the glass composition contained in the sustained-release composition of the medical composition according to this embodiment contains gallium and phosphorus, at least one selected from alkali metals, calcium and strontium, and aluminum in an oxide equivalent of 0% by mass or more and 3.8% by mass or less. In this specification, a medical composition refers to a composition used for medical purposes.

[0040] In the medical composition according to this embodiment, the same effects as the glass composition of this embodiment can be obtained by including a sustained-release composition containing such a glass composition. Specifically, the medical composition of this embodiment contains glass that is difficult to dissolve in the acidic range and easy to dissolve in the neutral range, even in environments where the acidity changes between the neutral and acidic ranges. Therefore, sustained release can be suppressed in the acidic range and promoted in the neutral range. As a result, by using such a medical composition, for example, the sustained release of glass can be controlled so that the glass is difficult to dissolve when the acidity in the body becomes acidic in response to changes in acidity in bone destruction, bone formation, skin regeneration, etc., and easy to dissolve when the acidity in the body returns to the neutral range.

[0041] The uses of the medical composition are not particularly limited and include, for example, bone graft materials and artificial dermis.

[0042] <Dental Composition> The dental composition according to this embodiment includes the sustained-release composition of this embodiment described above. Specifically, the dental composition of this embodiment contains a glass composition that contains gallium and phosphorus, at least one selected from alkali metals, calcium, and strontium, and aluminum in an oxide equivalent of 0% by mass or more and 3.8% by mass or less. In this specification, "dental composition" refers to a composition used in dental applications.

[0043] In the dental composition according to this embodiment, the inclusion of a sustained-release composition containing such a glass composition provides the same effects as the glass composition of this embodiment. Specifically, the dental composition of this embodiment contains glass that is less soluble in acidic environments and more soluble in neutral environments, even in environments where the acidity changes between neutral and acidic ranges. Therefore, sustained release can be suppressed in acidic environments and promoted in neutral environments. As a result, by using such a dental composition in the oral cavity, the sustained release of the glass can be controlled such that, for example, the glass is less soluble when the acidity in the oral cavity becomes acidic after a meal, and more soluble when the acidity in the oral cavity returns to a neutral range.

[0044] The uses of dental compositions are not particularly limited and include, for example, dental cements, dental adhesives, temporary dental fillings, temporary dental fixatives, dental primers, dental coatings, root coverings, dental composite resins, dental hard resins, dental cutting resin materials, temporary dental restoratives, dental fillings, pulp capping materials, denture base materials, artificial teeth, and toothpastes.

[0045] The present disclosure will be further explained below with reference to examples. Various tests and evaluations will be carried out according to the methods described below. In the following, unitless numerical values, "%", or "parts" are based on mass unless otherwise specified.

[0046] <Preparation of Glass Powder> The raw materials were weighed, mixed in a Teflon beaker, and after the water was evaporated, the mixture was placed in a platinum crucible and melted at a predetermined temperature for 1 hour. The melt was then cooled by an iron press. This was then ground in a ball mill for 30 minutes (ethanol wet grinding, 40 mm alumina balls, 100 rpm), and then ground again in a ball mill for 30 minutes (ethanol wet grinding, 5 mm alumina balls, 100 rpm). After that, the glass powder was recovered by centrifugation, and the remaining ethanol was removed by vacuum drying (-0.1 MPa, 40°C) to obtain the glass powder.

[0047] <Particle Size Distribution of Glass Powder> The obtained glass powder was dispersed in ethanol, and the particle size distribution was measured using a laser diffraction / scattering particle size analyzer (Partica LA-960V2, Horiba, Ltd.). It was confirmed that the D(50) of all glass powders was in the range of 10 ± 2 μm.

[0048] <Composition of Glass Powder> The composition of the glass powder was determined by analyzing it using a fluorescent X-ray analyzer (Rigaku Corporation, ZSX Primus IV). Tables 1 and 2 show the composition of the glass powder (unit: mass%).

[0049] <Dissolution Rate> 50 mg of glass powder was immersed in 10 mL of pH 4.5 acetic acid-sodium acetate buffer, 10 mL of pH 5.5 acetic acid-sodium acetate buffer, and 10 mL of pH 7.5 hydroxyethylpiperazine ethanesulfonic acid (HEPES) buffer, respectively. The mixture was stored at 37°C, then filtered through a 0.2 μm syringe filter. The filtered glass was dried with the syringe filter at 60°C for 48 hours. The weights of the syringe filter and glass were then measured, and the dissolution rates at pH 4.5, pH 5.5, and pH 7.5 were calculated according to the following formula (1). The calculation results are shown in Tables 1 and 2. Dissolution rate (%) = [(Weight before immersion) - (Weight after immersion)] × 100 / Weight before immersion ... (1)

[0050] <Dissolution Ratio> The ratio of the dissolution rate at pH 4.5 to the dissolution rate at pH 7.5 (dissolution rate at pH 7.5 / dissolution rate at pH 4.5) and the ratio of the dissolution rate at pH 5.5 to the dissolution rate at pH 7.5 (dissolution rate at pH 7.5 / dissolution rate at pH 5.5) were calculated from the dissolution rates at pH 4.5, pH 5.5, and pH 7.5. A ratio of 1.4 or higher for the dissolution rate at pH 7.5 / dissolution rate at pH 4.5 was evaluated as good, and a ratio below 1.4 was evaluated as poor. Similarly, a ratio of 1.4 or higher for the dissolution rate at pH 7.5 / dissolution rate at pH 5.5 was evaluated as good, and a ratio below 1.4 was evaluated as poor.

[0051] Examples and comparative examples will be described below.

[0052] [Example 1] Phosphorus pentoxide (P ２ O ５) 56.1 parts, calcium oxide (CaO) 11.2 parts, gallium oxide (Ga ２ O ３ Glass containing 32.7 parts of [the substance] was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 1.

[0053] [Example 2] Phosphorus pentoxide (P ２ O ５ ) 66.0 parts, calcium oxide (CaO) 15.9 parts, gallium oxide (Ga ２ O ３ Glass containing 18.1 parts of the substance was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 1.

[0054] [Example 3] Phosphorus pentoxide (P ２ O ５ ) 58.0 parts, calcium oxide (CaO) 7.0 parts, strontium oxide (SrO) 13.9 parts, gallium oxide (Ga ２ O ３ Glass containing 21.1 parts of the substance was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 1.

[0055] [Example 4] Phosphorus pentoxide (P ２ O ５ ) 53.8 parts, strontium oxide (SrO) 26.1 parts, gallium oxide (Ga ２ O ３ Glass containing 20.1 parts of the substance was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 1.

[0056] [Example 5] Phosphorus pentoxide (P ２ O ５ ) 64.3 parts, sodium oxide (Na ２ O) 13.4 parts, gallium oxide (Ga ２ O ３ ) 19.7 parts, aluminum oxide (Al ２ O ３ Glass containing 2.6 parts of the substance was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 1.

[0057] [Example 6] Phosphorus pentoxide (P ２ O ５ ) 64.7 parts, sodium oxide (Na ２ O) 13.6 parts, gallium oxide (Ga２ O ３ ) 18.4 parts, aluminum oxide (Al ２ O ３ Glass containing 3.3 parts of the substance was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 1.

[0058] [Example 7] Phosphorus pentoxide (P ２ O ５ ) 54.2 parts, calcium oxide (CaO) 8.3 parts, gallium oxide (Ga ２ O ３ Glass containing 37.5 parts of [the substance] was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 1.

[0059] [Example 8] 64.2 parts phosphorus pentoxide (P2O5), 11.4 parts strontium oxide (SrO), gallium oxide (Ga ２ O ３ Glass containing 24.4 parts of [the substance] was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 1.

[0060] [Comparative Example 1] Phosphorus pentoxide (P ２ O ５ ) 58.6 parts, calcium oxide (CaO) 22.7 parts, strontium oxide (SrO) 15.2 parts, aluminum oxide (Al ２ O ３ Glass containing 2.7 parts of fluorine (F) and 0.8 parts of fluorine (F) was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 2.

[0061] [Comparative Example 2] Phosphorus pentoxide (P ２ O ５ Glass containing 59.3 parts of ) , 23.6 parts of calcium oxide (CaO), 16.2 parts of strontium oxide (SrO), and 0.9 parts of fluorine (F) was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 2.

[0062] [Comparative Example 3] Phosphorus pentoxide (P ２ O ５ ) 63.2 parts, calcium oxide (CaO) 15.5 parts, gallium oxide (Ga ２ O ３ ) 16.7 parts, aluminum oxide (Al ２ O ３Glass containing 4.6 parts of the substance was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 2.

[0063] [Comparative Example 4] Phosphorus pentoxide (P ２ O ５ ) 68.4 parts, calcium oxide (CaO) 17.3 parts, aluminum oxide (Al ２ O ３ Glass containing 14.3 parts of the substance was prepared and evaluated. The composition of the glass and the evaluation results are shown in Table 2.

[0064]

[0065]

[0066] Table 1 shows that in Examples 1 to 8, the glass containing gallium (Ga) and phosphorus (P), and further containing one or more of sodium (Na), calcium (Ca), and strontium (Sr), and further containing aluminum (Al) in an oxide equivalent of 0% to 3.8% by mass, was found to be poorly soluble in acidic ranges and readily soluble in neutral ranges.

[0067] On the other hand, Table 2 shows that, compared to Examples 1 to 8, the glass containing gallium (Ga) and / or aluminum (Al) in an oxide equivalent of more than 3.8% by mass was found to be more easily dissolved in acidic conditions.

[0068] Based on the above, it can be said that a glass containing gallium and phosphorus, further containing at least one selected from alkali metals, calcium, and strontium, and further containing aluminum in an oxide equivalent of 0% to 3.8% by mass, is difficult to dissolve in acidic and neutral environments, even when the acidity changes between neutral and acidic ranges.

[0069] Although embodiments of this disclosure have been described above, this disclosure is not limited to any particular embodiment, and various modifications and changes are possible within the scope of the invention as described in the claims.

[0070] This application claims priority based on Japanese Patent Application No. 2024-166690, filed on 25 September 2024, the entire contents of which are incorporated herein by reference.

Claims

1. A glass composition containing gallium and phosphorus, at least one selected from alkali metals, calcium, and strontium, and aluminum in an oxide equivalent of 0% by mass or more and 3.8% by mass or less.

2. The glass composition according to claim 1, wherein the solubility in the neutral range is greater than the solubility in the acidic range.

3. The glass composition according to claim 2, wherein the pH of the neutral range is 7.5, the pH of the acidic range is 4.5, and the ratio of the solubility at pH 7.5 to the solubility at pH 4.5 is 1.4 or more.

4. The glass composition according to claim 2, wherein the pH of the neutral range is 7.5, the pH of the acidic range is 5.5, and the ratio of the solubility at pH 7.5 to the solubility at pH 5.5 is 1.4 or more.

5. A sustained-release composition comprising the glass composition according to any one of claims 1 to 4.

6. A medical composition comprising the sustained-release composition described in claim 5.

7. A dental composition comprising the sustained-release composition described in claim 5.

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