阅读说明：本技术 碳酸钙烧结体及其制造方法、以及植骨材料 (Calcium carbonate sintered body, method for producing same, and bone graft material ) 是由 鹈沼英郎 古泽利武 梅本奖大 田近正彦 于 2020-03-09 设计创作，主要内容包括：本发明提供一种不使用烧结助剂也能够得到良好的烧结体的碳酸钙烧结体的制造方法。该方法的特征在于,包括：将碳酸钙压缩成型,制造成型体的工序；通过在温度500℃以下的条件下对上述成型体进行加热,除去上述成型体中所含的有机成分的工序；和通过在碳酸气气氛且温度450℃以上的条件下将上述成型体烧结,得到碳酸钙烧结体的工序。(The invention provides a method for producing a calcium carbonate sintered body, which can obtain a good sintered body without using a sintering aid. The method is characterized by comprising the following steps: a step of producing a molded body by compression molding calcium carbonate; removing the organic component contained in the molded body by heating the molded body at a temperature of 500 ℃ or lower; and a step of obtaining a calcium carbonate sintered body by sintering the molded body in a carbonic acid gas atmosphere at a temperature of 450 ℃ or higher.)

1. A calcium carbonate sintered body characterized by:

contains 99.5 mass% or more of calcium carbonate, has an average particle diameter of 0.1 to 20 μm in a particle diameter distribution measured by a scanning electron microscope, has a Vickers hardness of 50HV1.0 or more, and has a relative density of 90% or more.

2. The sintered calcium carbonate body according to claim 1, wherein:

contains 99.7 mass% or more of calcium carbonate.

3. A method for producing a calcium carbonate sintered body, comprising:

a step of producing a molded body by compression molding calcium carbonate; removing an organic component contained in the molded body by heating the molded body at a temperature of 500 ℃ or lower; and a step of obtaining a calcium carbonate sintered body by sintering the molded body in a carbonic acid gas atmosphere at a temperature of 500 ℃ or higher.

4. The method for producing a sintered calcium carbonate body according to claim 3, wherein:

the heating of the molded article at a temperature of 500 ℃ or less is performed in an oxygen atmosphere.

5. The method for producing a sintered calcium carbonate body as claimed in claim 3 or 4, wherein: the calcium carbonate has an average particle diameter of 0.05 to 0.30 [ mu ] m and a BET specific surface area of 5m in a particle size distribution measured by a transmission electron microscope²/g～25m²/g。

6. The method for producing a sintered calcium carbonate body according to any one of claims 3 to 5, wherein:

the purity of the calcium carbonate is 99.9 mass% or more.

7. A porous sintered calcium carbonate body, characterized in that:

contains 95 mass% or more of calcium carbonate, has a porosity of 10% or more, and has a whiteness of 85 or more.

8. The porous sintered body of calcium carbonate according to claim 7, wherein:

contains 99 mass% or more of calcium carbonate.

9. The porous sintered body of calcium carbonate according to claim 7 or 8, characterized in that:

communication holes are formed to the outside of the sintered body.

10. A method for producing a porous sintered calcium carbonate body, comprising:

a step for preparing a dispersion liquid containing calcium carbonate; adding a foaming agent to the dispersion, and then stirring and foaming the dispersion to prepare a foam; a step of removing an organic component contained in the foam by heating the foam at a temperature of 500 ℃ or lower; and a step for obtaining a porous sintered body of calcium carbonate by sintering the foam in a carbonic acid gas atmosphere at a temperature of 450 ℃ or higher.

11. The method for producing a porous sintered body of calcium carbonate according to claim 10, characterized in that:

heating of the foam at a temperature of 500 ℃ or less is performed in an oxygen atmosphere.

12. The method for producing a porous sintered body of calcium carbonate according to claim 10 or 11, characterized in that:

the dispersion liquid contains 20 vol% or more of the calcium carbonate.

13. A bone grafting material, characterized by:

the calcium carbonate sintered body according to claim 1 or 2 or the porous calcium carbonate sintered body according to any one of claims 7 to 9 is contained in an amount of 70 wt% or more in terms of calcium carbonate as a whole.

14. A bone grafting material, characterized by:

the calcium carbonate sintered body according to claim 1 or 2 or the calcium carbonate porous sintered body according to any one of claims 7 to 9 is coated on a part or all of the surface.

15. A growing nucleus for cultured pearls is characterized in that:

the calcium carbonate sintered body according to claim 1 or 2 or the porous calcium carbonate sintered body according to any one of claims 7 to 9 is contained in an amount of 70 wt% or more in terms of calcium carbonate as a whole.

16. A water purifying agent is characterized in that:

the calcium carbonate sintered body according to claim 1 or 2 or the porous calcium carbonate sintered body according to any one of claims 7 to 9 is contained in an amount of 70 wt% or more in terms of calcium carbonate as a whole.

Technical Field

The present invention relates to a calcium carbonate sintered body and a method for producing the same, a porous calcium carbonate sintered body and a method for producing the same, a bone graft material using the calcium carbonate sintered body or the porous calcium carbonate sintered body, a growth nucleus of a cultured pearl, and a water purification agent.

Background

The calcium carbonate sintered compact is expected to be applied to a material (artificial bone) for filling a bone defect and promoting bone regeneration, a material for embedding a nucleus in mother shell as an artificial nucleus for pearl culture, a water purifier for adsorbing fluorine, phosphorus, and the like, and various methods for producing the same have been studied. In a conventional method for producing a calcium carbonate sintered body, a mixture of calcium carbonate and a sintering aid is generally formed into a molded body by hydrostatic pressing, and the molded body is sintered in a carbonic acid gas atmosphere to produce the calcium carbonate sintered body (patent document 1 and non-patent document 1).

Documents of the prior art

Patent document

Patent document 1: japanese laid-open patent publication No. 2007-254240

Non-patent document

Non-patent document 1: du sacrifice of clever, etc. "influence of starting Material in sintering of calcium carbonate" the gist of lecture of academic Association of inorganic Material Association Vol.105th P.46-47 (2002.11.14)

Disclosure of Invention

Technical problem to be solved by the invention

In recent years, the use of calcium carbonate in artificial bones and the like as bone graft materials has been studied.

However, in the conventional method for producing a calcium carbonate sintered body, since a sintering aid needs to be used as described above, it is difficult to reduce the content of impurities. Therefore, the present invention may not be used for biological applications such as bone graft materials.

In addition, in the conventional method for producing a porous sintered calcium carbonate body, the obtained porous sintered calcium carbonate body may be colored.

In addition, in the method for producing a high-purity calcium carbonate sintered body which does not require the use of a sintering aid, the density may not be sufficiently increased, and a good sintered body may not be obtained.

The invention aims to provide a method for producing a calcium carbonate sintered body, a method for producing a porous calcium carbonate sintered body, a bone grafting material using the calcium carbonate sintered body or the porous calcium carbonate sintered body, a growth nucleus of a cultured pearl, and a water purifier, which can obtain a good sintered body without using a sintering aid.

Technical solution for solving technical problem

The calcium carbonate sintered body of the present invention is characterized in that: contains 99.5 mass% or more of calcium carbonate, has an average particle diameter of 0.1 to 20 μm in a particle diameter distribution measured by a scanning electron microscope, has a Vickers hardness of 50HV1.0 or more, and has a relative density of 90% or more.

The calcium carbonate sintered body of the present invention preferably contains 99.7 mass% or more of calcium carbonate.

The method for producing a calcium carbonate sintered body of the present invention preferably includes: a step of producing a molded body by compression molding calcium carbonate; removing the organic component contained in the molded body by heating the molded body at a temperature of 500 ℃ or lower; and a step of obtaining a calcium carbonate sintered body by sintering the molded body in a carbonic acid gas atmosphere at a temperature of 500 ℃ or higher.

In the method for producing a calcium carbonate sintered body of the present invention, the molded body is preferably heated at a temperature of 500 ℃ or lower in an oxygen atmosphere.

In the method for producing a calcium carbonate sintered body of the present invention, the calcium carbonate preferably has an average particle diameter of 0.05 to 0.30 μm and a BET specific surface area of 5m in a particle size distribution measured by a transmission electron microscope²/g～25m²/g。

In the method for producing a calcium carbonate sintered body of the present invention, the purity of the calcium carbonate is preferably 99.9 mass% or more.

The porous sintered calcium carbonate body is characterized by containing 95 mass% or more of calcium carbonate, having a porosity of 10% or more, and having a whiteness of 85 or more.

The porous sintered calcium carbonate body of the present invention preferably contains 99 mass% or more of calcium carbonate.

The porous sintered calcium carbonate body of the present invention is preferably formed with communicating pores extending to the outside of the sintered body.

The method for producing a porous sintered calcium carbonate body of the present invention is characterized by comprising: a step for preparing a dispersion liquid containing calcium carbonate; adding a foaming agent to the dispersion, and then stirring and foaming the mixture to prepare a foam; a step of removing the organic component contained in the foam by heating the foam at a temperature of 500 ℃ or lower; and a step of obtaining a porous sintered body of calcium carbonate by sintering the foam in a carbonic acid gas atmosphere at a temperature of 450 ℃ or higher.

In the method for producing a porous sintered calcium carbonate body of the present invention, the foam is preferably heated at a temperature of 500 ℃ or lower in an oxygen atmosphere.

In the method for producing a porous sintered body of calcium carbonate according to the present invention, the dispersion preferably contains 20 vol% or more of the calcium carbonate.

The bone graft material of the present invention is characterized by containing 70 wt% or more of the whole of the calcium carbonate sintered body constituted according to the present invention or the calcium carbonate porous sintered body constituted according to the present invention in terms of calcium carbonate.

The bone graft material of the present invention is characterized in that a part or the whole of the surface is coated with the calcium carbonate sintered body constituted according to the present invention or the calcium carbonate porous sintered body constituted according to the present invention.

The growing core of a cultured pearl of the present invention is characterized by containing 70 wt% or more of the calcium carbonate sintered body according to the present invention or the calcium carbonate porous sintered body according to the present invention as a whole in terms of calcium carbonate.

The water purifying agent of the present invention is characterized by containing 70% by weight or more of the calcium carbonate sintered body or the calcium carbonate porous sintered body according to the present invention in terms of calcium carbonate as a whole.

ADVANTAGEOUS EFFECTS OF INVENTION

The method for producing a calcium carbonate sintered body and the method for producing a porous calcium carbonate sintered body according to the present invention can produce a good sintered body without using a sintering aid.

The calcium carbonate sintered body of the present invention has a low impurity content and can be used for biological applications and the like. The calcium carbonate sintered body of the present invention also has an improved density and an improved strength.

The porous sintered calcium carbonate body of the present invention has a low impurity content and can be used for biological applications and the like. Further, the whiteness of the porous sintered calcium carbonate body of the present invention is also improved.

The bone grafting material of the present invention has a low impurity content and an improved biological safety.

The growing nucleus of the cultured pearl of the present invention is easy to handle and has a size larger than that of the shell of the natural shell mainly used at present, and can be produced in large quantities.

The water purifying agent of the present invention is free from fear of disintegration in water by sintering, and is improved in usability and operability.

Drawings

Fig. 1 is a graph showing the relative density when only the sintering temperature was changed under the conditions of example 2.

FIG. 2 is a scanning electron micrograph showing a calcium carbonate sintered body obtained by main sintering at a sintering temperature of 600 ℃ for 1 hour at a magnification of 30000 times.

FIG. 3 is a scanning electron micrograph showing a magnification of 10000 times of a sintered calcium carbonate body obtained by main sintering at a sintering temperature of 650 ℃ for 1 hour.

FIG. 4 is a scanning electron micrograph showing a magnification of 5000 times that of a calcium carbonate sintered body obtained by main sintering at a sintering temperature of 700 ℃ for 1 hour.

FIG. 5 is a scanning electron micrograph showing a sintered calcium carbonate body obtained by main sintering at a sintering temperature of 800 ℃ for 1 hour at a magnification of 1000.

FIG. 6 is a photograph showing the appearance of an observation sample prepared by embedding the calcium carbonate porous sintered body particles of example 4 in the skull bone of a male rat.

FIG. 7 is a photograph showing the appearance of an observation sample prepared by embedding β -TCP artificial bone particles of comparative example 4 in the skull bone of a male rat.

Fig. 8 is a graph showing the calculation results of the area ratios of the new bone, the embedding material, and the fibrous structure in the observation samples of example 4 and comparative example 4.

Detailed Description

Hereinafter, preferred embodiments will be described. However, the following embodiments are merely examples, and the present invention is not limited to the following embodiments.

[ method for producing sintered calcium carbonate ]

The method for producing a calcium carbonate sintered body of the present invention comprises: a step of producing a molded body by compression molding calcium carbonate; removing organic components contained in the molded body by heating the molded body at a temperature of 500 ℃ or lower; and a step of obtaining a calcium carbonate sintered body by sintering the molded body in a carbonic acid gas atmosphere at a temperature of 450 ℃ or higher.

(calcium carbonate)

The calcium carbonate used in the present invention preferably has an average particle diameter (D) in a particle size distribution as measured by observation with a transmission electron microscope₅₀) Is in the range of 0.05 to 0.50. mu.m, more preferably in the range of 0.05 to 0.30. mu.m, still more preferably in the range of 0.08 to 0.30. mu.m, and particularly preferably in the range of 0.10 to 0.25. mu.m. By making the average particle diameter (D)₅₀) Within such a range, a molded body having a higher density can be produced, and a calcium carbonate sintered body having a higher density can be produced. The particle size distribution obtained by the observation with a transmission electron microscope can be determined by measuring 1000 or more calcium carbonates to be measured by the observation with a transmission electron microscope.

The calcium carbonate used in the present invention can be produced, for example, by a generally known carbonation method in which a carbonic acid gas is blown into lime milk to react with the lime milk. Especially for the average particle diameter (D)₅₀) Particles having a particle size of more than 0.1 μm can be produced by the production method of Japanese patent No. 0995926.

The BET specific surface area of the calcium carbonate used in the present invention is preferably 5m²/g～25m²G, more preferably 7m²/g～20m²(iv)/g, more preferably 8m²/g～15m²(ii) in terms of/g. When the BET specific surface area is in the above range, the sinterability of the calcium carbonate can be further improved. Therefore, a calcium carbonate sintered body having a higher density can be produced.

The purity of the calcium carbonate used in the present invention is preferably 99.0% by mass or more, more preferably 99.5% by mass or more, and still more preferably 99.6% by mass or more.

In the present invention, high-purity calcium carbonate having a purity of 99.7 mass% or more can be used. By using high-purity calcium carbonate, it is possible to use it more suitably for biological applications requiring biological safety. Further, the amount of the sintering aid added during sintering can be further reduced. The purity of calcium carbonate is more preferably 99.8% by mass or more, still more preferably 99.9% by mass or more, and particularly preferably 99.95% by mass or more. Such high-purity calcium carbonate can be produced by, for example, the method disclosed in japanese patent laid-open publication No. 2012-240872.

The upper limit of the purity of calcium carbonate is not particularly limited, but is usually 99.9999 mass%.

By using calcium carbonate having a high purity, the sintering temperature can be lowered as compared with the case of using calcium carbonate having a low purity.

(molded body)

In the present invention, a calcium carbonate powder is compression-molded to produce a molded article. The compression molding is preferably single screw molding. According to the present invention, a calcium carbonate sintered body having a high density can be produced by using a molded body obtained by single-screw molding. However, in the present invention, the molded article may be produced by other known molding methods such as hydrostatic press molding, doctor blade molding, and cast molding, without being limited to single screw molding.

In the present invention, the relative density of the molded article is preferably 50% or more, more preferably 55% or more, and further preferably 58% or more. The relative density of the molded article is the bulk density of the molded article divided by the theoretical density of calcium carbonate (2.711 g/cm)³) And the resulting value. The bulk density of the molded article can be measured by the archimedes method described later. The molded article preferably has a relative density of 196.1MPa (2000 kgf/cm)²) The molding pressure of (a) is a value obtained when single screw press molding is performed. By setting the relative density in the above range, a calcium carbonate sintered body having a higher density can be obtained.

(removal of organic component)

In the present invention, the molded article is heated at a temperature of 500 ℃ or lower. The molded article is preferably heated at 300 to 500 ℃. Although the above heating may be performed in air, it is preferably performed in an oxygen atmosphere. The "oxygen atmosphere" refers to an atmosphere containing oxygen at a concentration higher than the oxygen partial pressure concentration in the atmosphere (about 20%). The concentration of oxygen (general gas) specified in the high-pressure gas security method is 99.7%, and the method (flow rate is not particularly limited) of flowing the oxygen into the furnace is the simplest.

The heating time may be, for example, 2 to 24 hours.

The temperature rise rate during heating may be set in the range of 2 ℃/min to 20 ℃/min. By the heating, the organic component contained in the molded article can be removed. Examples of the organic component contained in the molded article include lubricants used in molding. By removing the thermally deteriorated organic component and the carbonized organic component, discoloration of the obtained calcium carbonate sintered body can be suppressed. Therefore, the whiteness of the obtained calcium carbonate sintered body can be improved.

(production of calcium carbonate sintered body)

In the present invention, the molded article is sintered in a carbonic acid gas atmosphere at a temperature of 500 ℃ or higher. The molded article is preferably sintered at 500 to 950 ℃. The carbonic acid gas atmosphere refers to an atmosphere in which a partial pressure of carbonic acid gas is maintained so that calcium carbonate is not decomposed into calcium oxide. Specifically, as an example, the calculation is performed using thermodynamic equilibrium calculation and state diagram creation software "CaTCalc" (product of industrial technology integration research) of the institute of material design technology, ltd, and is shown in fig. 3 of "japanese patent application laid-open No. 2015-166075" in the patent document. Thus, it is only necessary to set the partial pressure of carbon dioxide to 0.3 atm or more when the sintering temperature is 800 ℃.

When high-purity calcium carbonate having a purity of 99.7 mass% or more is used, the sintering temperature is preferably 500 to 800 ℃, and more preferably 650 to 800 ℃. When the sintering temperature is too low, the sintering may not be sufficiently performed, and the density may not be increased. When the sintering temperature is too high, the obtained sintered body may be cracked.

On the other hand, when calcium carbonate having a purity of less than 99.7 mass% is used, the sintering temperature is preferably 800 to 900 ℃. When the sintering temperature is too low, the sintering may not be sufficiently performed, and the density may not be increased. When the sintering temperature is too high, the obtained sintered body may swell.

The sintering time is not particularly limited, and is preferably 1 to 10 hours, more preferably 1 to 3 hours. If the sintering time is too short, the sintering may not be sufficiently performed, and the density may not be increased. When the sintering time is too long, the obtained sintered body may be cracked or swelled.

The temperature rise rate during sintering is preferably in the range of 2 ℃/min to 20 ℃/min. This can further suppress cracking of the obtained sintered body and swelling of the sintered body.

In the present invention, the amount of the sintering aid required for sintering can be reduced by performing sintering in the above-described atmosphere. Further, a good calcium carbonate sintered body can be obtained without using a sintering aid. Therefore, even when calcium carbonate having a purity of less than 99.7 mass% is used, a calcium carbonate sintered body having a higher purity can be obtained. Further, by performing sintering in the above atmosphere, a good sintered body can be obtained, and the density of the obtained sintered body can be increased.

(sintering aid)

According to the present invention, the amount of the sintering aid required for sintering can be reduced by performing sintering in the above-described atmosphere. Further, a sintered body of calcium carbonate can be produced without using a sintering aid. Therefore, according to the present invention, the content of calcium carbonate in the sintered body can be increased, and a calcium carbonate sintered body with higher purity can be produced.

However, a sintering aid may be used as needed. Examples of the sintering aid include a sintering aid containing a carbonate of at least 2 of lithium, sodium, and potassium and having a melting point of 600 ℃. The melting point of the sintering aid is preferably 550 ℃ or lower, more preferably 530 ℃ or lower, and still more preferably in the range of 450 to 520 ℃. When the melting point of the sintering aid is in the above range, the calcium carbonate sintered body can be produced by firing at a lower temperature. When added to calcium carbonate for use in sintering, the calcium carbonate can sufficiently function as a sintering aid because the actual melting point is lower than the above-mentioned temperature. The sintering aid is preferably a mixture of potassium carbonate and lithium carbonate. The melting point of the sintering aid can be determined from, for example, a phase diagram, or can be measured by Differential Thermal Analysis (DTA).

In addition, as the sintering aid, a mixture of potassium fluoride, lithium fluoride, and sodium fluoride may also be used. Such mixtures are also preferably mixtures having the melting point ranges mentioned above. Examples of such a sintering aid include a mixture having a composition range of 10 to 60 mol% of potassium fluoride, 30 to 60 mol% of lithium fluoride, and 0 to 30 mol% of sodium fluoride. By setting the range as described above, the calcium carbonate sintered body can be produced by firing at a lower temperature and having a higher density.

When a sintering aid is used, the sintering aid is preferably mixed with calcium carbonate to prepare a mixture so that the content of the sintering aid in the mixture of calcium carbonate and sintering aid becomes 1.5% by mass or less, more preferably 1.0% by mass or less, and still more preferably 0.7% by mass or less. When the content ratio of the sintering aid is too large, the purity and density of the calcium carbonate sintered body may not be improved.

[ calcium carbonate sintered body ]

In the present invention, the purity of the calcium carbonate sintered body is preferably 99.5% by mass or more, more preferably 99.7% by mass or more, more preferably 99.8% by mass or more, more preferably 99.9% by mass or more, further preferably 99.95% by mass or more, and particularly preferably 99.99% by mass or more. This makes it possible to use the calcium carbonate sintered body for biological applications and the like. The upper limit of the purity of the calcium carbonate sintered body is not particularly limited, but is generally 99.9999 mass%.

The relative density of the calcium carbonate sintered body is preferably 90% or more, more preferably 95% or more, more preferably 97% or more, further preferably 98% or more, and particularly preferably 99% or more. The upper limit of the relative density of the calcium carbonate sintered body is not particularly limited, but is generally 99.9%.

The calcium carbonate sintered body of the present invention has an average particle diameter (D) in a particle diameter distribution measured by observation with a scanning electron microscope₅₀) In the range of 0.1 to 20 μm. Average particle diameter (D) in the particle diameter distribution measured by observation with a scanning electron microscope₅₀) Preferably in the range of 0.2 to 15 μm, more preferably in the range of 0.3 to 10 μm, and still more preferably in the range of 0.5 to 5 μm. Measured by observation with a scanning electron microscopeThe particle size distribution of (b) is preferably obtained by measuring the size of 100 or more particles constituting the sintered body from an observation image of the calcium carbonate sintered body to be measured by a scanning electron microscope. In this case, the particle size of the broken surface of the sintered body is preferably measured, but the particle size may be measured and converted to a particle size of 1.5 times.

In the present invention, the Vickers hardness of the calcium carbonate sintered body is 50HV1.0 or more. The Vickers hardness of the calcium carbonate sintered body is preferably 90HV1.0 or more, and more preferably 100HV1.0 or more.

The vickers hardness can be measured by the method described in the hardness test method of JIS R1610 fine ceramics.

The calcium carbonate sintered body of the present invention has an improved purity, and thus can be suitably used for biological applications such as artificial bone as a bone graft material. Furthermore, the calcium carbonate sintered body can be suitably used as a growth nucleus for cultured pearls or a water purifying agent.

[ method for producing porous sintered calcium carbonate ]

The method for producing a porous sintered calcium carbonate body of the present invention comprises: a step for preparing a dispersion liquid containing calcium carbonate; adding a foaming agent to the dispersion, and then stirring and foaming the mixture to prepare a foam; a step of removing the organic component contained in the foam by heating the foam at a temperature of 500 ℃ or lower; and a step of obtaining a porous sintered body of calcium carbonate by sintering the foam in a carbonic acid gas atmosphere at a temperature of 450 ℃ or higher.

(calcium carbonate)

As the calcium carbonate, the calcium carbonate described above in the production of the calcium carbonate sintered body can be used. In the production of the porous sintered calcium carbonate body, calcium carbonate having high purity can be used more suitably for biological applications requiring biological safety. When the sintering aid is used, the same kind and content of the sintering aid as described above can be used.

(foaming agent)

Examples of the foaming agent used in the present invention include alkyl sulfate salts such as triethanolamine lauryl sulfate, polyoxyethylene alkyl ether sulfate salts, polyoxyethylene alkyl ether acetate salts, and alkyl polyglucosides.

(excipients)

In the present invention, an excipient may be added to the dispersion. By adding the excipient, the strength of the cells in the dispersed foam after foaming is improved, and the shape of the foam can be stabilized. Examples of the excipient include starch, dextrin, polyvinyl alcohol, polypropylene glycol, pectin, alginic acid, and sodium salt of carboxyl cellulose.

(gelling agent)

In the present invention, a gelling agent may be contained in the dispersion. By containing the gelling agent, the strength of the cells in the dispersed foam after foaming is further improved, and the shape of the foam can be stabilized. Examples of the gelling agent include polysaccharides such as methylcellulose and alkali water-soluble polymers of isobutylene-maleic anhydride copolymers.

The content of the gelling agent in the dispersion is preferably in the range of 0.1 to 5 parts by mass, and more preferably in the range of 0.5 to 3 parts by mass, based on 100 parts by mass of calcium carbonate. When the content of the gelling agent is too small, the strength of the cells in the foam may not be improved, and the shape of the foam may not be stabilized. When the content of the gelling agent is too large, the above-mentioned effect proportional to the content may not be obtained.

(Dispersion liquid)

In the present invention, it is preferable to disperse calcium carbonate in a dispersion medium such as water using a device having a strong stirring force such as a disperser, a mixer, or a ball mill while slowly adding calcium carbonate to the dispersion medium. Generally, the content of calcium carbonate in the dispersion is preferably 30 to 70% by mass. In this case, a polymer surfactant such as polyacrylate may be added as a dispersant as needed in an amount of about 0 to 3 parts by mass per 100 parts by mass of calcium carbonate.

(preparation of foam)

In the present invention, a foaming agent is added to the dispersion, and then the mixture is stirred and foamed to produce a foam. The foaming agent is preferably added so that the concentration of the foaming agent in the dispersion liquid becomes about 0.01 to 5% by mass. The stirring is preferably performed using a hand mixer, a disperser, or the like. The temperature of the dispersion may be increased by stirring, and therefore the dispersion may be stirred while being cooled as necessary.

(removal of organic component in foam)

In the present invention, the above foam is heated at a temperature of 500 ℃ or lower. The foam is preferably heated at a temperature of 300 to 500 ℃. Although the above heating may be performed in air, it is preferably performed in an oxygen atmosphere. The "oxygen atmosphere" mentioned above means an atmosphere containing oxygen at a concentration higher than the oxygen partial pressure concentration (about 20%) in the atmosphere. The concentration of oxygen (general gas) specified in the high-pressure gas security method is 99.7%, and the method (flow rate is not particularly limited) of circulating the oxygen in the furnace is the simplest.

The heating time may be, for example, 2 to 24 hours.

The temperature rise rate during heating may be set in the range of 2 ℃/min to 20 ℃/min. By the heating, the organic component contained in the foam can be removed. Examples of the organic component contained in the foam include a foaming agent, an excipient, a gelling agent, and a dispersing agent. By removing the thermally deteriorated organic component and the carbonized organic component, discoloration of the obtained porous sintered calcium carbonate body can be suppressed. Therefore, the whiteness of the obtained calcium carbonate porous sintered body can be improved. Further, the mechanical strength of the obtained porous sintered calcium carbonate body can be improved.

(sintering of foam)

In the present invention, the foam is sintered in a carbonic acid gas atmosphere at a temperature of 450 ℃ or higher. The foam is preferably sintered in a carbonic acid gas atmosphere at a temperature of 450 to 950 ℃. The carbonic acid gas atmosphere refers to an atmosphere in which a partial pressure of carbonic acid gas is maintained so that calcium carbonate is not decomposed into calcium oxide. Specifically, as an example, the calculation is performed using thermodynamic equilibrium calculation and state diagram creation software "CaTCalc" (product of industrial technology integration research) of the institute of material design technology, ltd, and is shown in fig. 3 of "japanese patent application laid-open No. 2015-166075" in the patent document. Thus, it is only necessary to set the partial pressure of carbon dioxide to 0.3 atm or more when the sintering temperature is 800 ℃.

When high-purity calcium carbonate having a purity of 99.7 mass% or more is used, the sintering temperature is preferably 500 to 800 ℃, and more preferably 650 to 800 ℃. When the sintering temperature is too low, the sintering may not be sufficiently performed, and the density may not be increased. When the sintering temperature is too high, cracks may occur in the obtained porous sintered body.

On the other hand, when calcium carbonate having a purity of less than 99.7 mass% is used, the sintering temperature is preferably 800 to 900 ℃. When the sintering temperature is too low, the sintering may not be sufficiently performed. When the sintering temperature is too high, the obtained porous sintered body may swell.

The sintering time is not particularly limited, and is preferably 1 to 12 hours, and more preferably 1 to 3 hours. If the sintering time is too short, the sintering may not be sufficiently performed. When the sintering time is too long, the obtained sintered body may be cracked or the porous sintered body may be swollen.

The temperature increase rate during sintering is preferably in the range of 2 ℃/min to 20 ℃/min. This can further suppress the occurrence of cracks in the obtained porous sintered body and the occurrence of swelling in the porous sintered body.

In the present invention, the amount of the sintering aid required for sintering can be reduced by performing sintering in the above-described atmosphere. Further, a good porous sintered body of calcium carbonate can be obtained without using a sintering aid. Therefore, even when calcium carbonate having a purity of less than 99.7 mass% is used, a calcium carbonate porous sintered body having a higher purity can be obtained. Further, by sintering in the above atmosphere, a favorable porous sintered body can be obtained.

[ porous sintered calcium carbonate ]

The purity of the porous sintered calcium carbonate body of the present invention is 95 mass% or more. The purity of the calcium carbonate porous sintered body is preferably 99% by mass or more, more preferably 99.5% by mass or more, more preferably 99.7% by mass or more, more preferably 99.8% by mass or more, more preferably 99.9% by mass or more, further preferably 99.95% by mass or more, and particularly preferably 99.99% by mass or more. This makes it possible to use the porous sintered calcium carbonate body for biological applications and the like. The upper limit of the purity of the porous sintered calcium carbonate body is not particularly limited, but is usually 99.9999 mass%.

The porosity of the porous sintered calcium carbonate body is 10 vol% or more. The upper limit of the porosity of the porous sintered calcium carbonate body is not particularly limited, but is usually 95 vol%. Although the bioabsorbable property in the case of using the material for artificial bone as a bone graft material can be improved by increasing the porosity, the strength is lowered, and therefore, the material is preferably used by being adjusted to an appropriate porosity according to the use and condition.

In the present invention, the whiteness of the porous sintered calcium carbonate body is 85 or more. The whiteness of the porous sintered calcium carbonate body is preferably 90 or more. The upper limit of the whiteness of the porous sintered calcium carbonate body is not particularly limited, and may be, for example, 100.

The whiteness degree can be measured by a whiteness meter, a spectrophotometer, or the like. The basic principle of measurement is to irradiate the surface of a sample uniformly filled in a cell with light whose wavelength is limited to a certain range by a specific filter, and to compare the amount of reflection in the 45-degree direction at that time with the amount of reflection of a standard white plate.

The high-purity calcium carbonate porous sintered body of the present invention is preferably formed with communication holes extending to the outside of the sintered body. This makes it possible to easily contact the calcium carbonate inside the porous sintered body with the external atmosphere. Therefore, for example, the present invention can be more suitably used for biological applications.

The porous sintered calcium carbonate compact of the present invention has an improved purity, and therefore can be suitably used for biological applications such as artificial bone as a bone graft material. In addition, the calcium carbonate porous sintered body can also be suitably used for growing nuclei of cultured pearls or a water purifying agent.

[ bone graft materials, etc. ]

The bone graft material of the present invention contains 70 wt% or more of the above calcium carbonate sintered body of the present invention or the above calcium carbonate porous sintered body of the present invention in terms of calcium carbonate. The bone graft material of the present invention is coated on a part or the whole of the surface with the above calcium carbonate sintered body of the present invention or the above calcium carbonate porous sintered body of the present invention. Therefore, the content of impurities is small, and the biological safety is improved. Also, the mechanical strength and bone forming ability are excellent.

The growing nuclei of the cultured pearls of the present invention contain 70 wt% or more of the above-described sintered calcium carbonate of the present invention or the above-described porous sintered calcium carbonate of the present invention in terms of calcium carbonate.

The water purifying agent of the present invention contains 70% by weight or more of the above-mentioned sintered calcium carbonate of the present invention or the above-mentioned porous sintered calcium carbonate of the present invention as a whole in terms of calcium carbonate.

Examples

Specific examples according to the present invention will be described below, but the present invention is not limited to these examples.

< production of calcium carbonate sintered body >

< example 1 >

(calcium carbonate)

The purity was 99 mass% and the average particle diameter (D) was used₅₀)0.15 μm, BET specific surface area 15m²Per gram of calcium carbonate. The purity was derived by a difference method. Specifically, the amount of impurities in a measurement detection solution in which a sample having a known mass is dissolved is measured using an inductively coupled plasma luminescence analyzer, the sum of the obtained results is regarded as the impurity content, and the impurity content is subtracted from the whole to obtain a value as the purity.

Regarding the average particle diameter (D)₅₀) The calcium carbonate particles to be measured were measured for their particle diameters of 1500 by observation with a transmission electron microscope, and the particle diameter distribution was determined.

The BET specific surface area was measured by the 1-point method using FlowSorb 2200 manufactured by Shimadzu corporation.

The calcium carbonate sintered body was produced by using the calcium carbonate described above in the following manner.

(preparation of molded article)

A small amount of ethanol was added to calcium carbonate and wet-mixed to form a raw material powder. The raw material powder was put into a cylindrical mold and single-screw press-molded using a press machine. At 98MPa (1000 kgf/cm)²) Is pre-press-molded at the molding pressure of (1) for 1 minute, and then is subjected to a pressure of 196.1MPa (2000 kgf/cm)²) The molding pressure of (3) was subjected to press molding for 1 minute.

(heating and firing of molded article)

The obtained molded article was heated at 5 ℃ per minute to 500 ℃ in an air atmosphere (oxygen concentration: 21%), and the temperature was maintained for 12 hours to remove organic components. After cooling, the temperature was raised to the sintering temperature (800 ℃ C.) at the same rate of temperature rise in a carbonic acid gas atmosphere (carbon dioxide concentration 100%), and after the temperature rise, main sintering was carried out for 1 hour to obtain a calcium carbonate sintered body.

(measurement of relative Density of calcium carbonate sintered body)

Determination of bulk Density ρ of calcium carbonate sintered body by Archimedes method_b[g/cm³]The resulting bulk density was divided by the theoretical density of calcium carbonate (2.711 g/cm)³) The relative density was determined. The bulk density of the calcium carbonate sintered body was determined as follows. First, the dry weight W of a sample of a calcium carbonate sintered body was measured₁The sample was left to stand in the boiled paraffin for about 10 minutes, and then taken out and cooled to normal temperature. Measuring the weight W of the sample containing paraffin after cooling₂. Then, the weight W in water of the sample was measured₃The bulk density ρ of the sample was determined by the following equation_b. The relative density of the calcium carbonate sintered body is shown in table 1.

Bulk density ρ_b[g/cm³]＝W₁ρ_W/(W₂－W₃)

ρ_W: density of water [ g/cm³]

W₁: dry weight of sample [ g]

W₂: weight of sample containing Paraffin [ g ]]

W₃: test forWeight in Water [ g ] of sample]

(measurement of average particle diameter of calcium carbonate sintered body)

The average particle size of the calcium carbonate sintered body was determined from the particle size distribution by measuring 150 particle sizes of calcium carbonate particles to be measured by observation with a scanning electron microscope.

(measurement of purity of calcium carbonate sintered body)

The purity of the calcium carbonate sintered body was derived by the difference method described above.

The purity of the calcium carbonate sintered body is shown in table 1.

< example 2 >

The purity was 99.9 mass% and the average particle diameter (D) was used₅₀)0.1 μm, BET specific surface area 18m²Per gram of calcium carbonate. The molded article obtained in the same manner as in example 1 was heated at 5 ℃ per minute to 500 ℃ in an air atmosphere (oxygen concentration 21%), and the temperature was maintained for 12 hours to remove organic components. After cooling, the temperature was raised to the sintering temperature (700 ℃) at the same rate of temperature rise in a carbonic acid gas atmosphere (carbon dioxide concentration 100%), and after the temperature rise, main sintering was carried out for 1 hour to obtain a calcium carbonate sintered body. The relative density, average particle diameter and purity of the calcium carbonate sintered body are shown in table 1.

Fig. 1 is a graph showing the relative density when only the sintering temperature was changed under the conditions of example 2. For comparison, fig. 1 also shows relative densities before sintering. From FIG. 1, it is understood that the relative density at the sintering temperature of 650 to 800 ℃ is about 95% or more.

FIG. 2 is a scanning electron micrograph showing a calcium carbonate sintered body obtained by main sintering at a sintering temperature of 600 ℃ for 1 hour at a magnification of 30000 times. FIG. 3 is a scanning electron micrograph showing a magnification of 10000 times of a sintered calcium carbonate body obtained by main sintering at a sintering temperature of 650 ℃ for 1 hour. FIG. 4 is a scanning electron micrograph showing a magnification of 5000 times that of a calcium carbonate sintered body obtained by main sintering at a sintering temperature of 700 ℃ for 1 hour. FIG. 5 is a scanning electron micrograph showing a sintered calcium carbonate body obtained by main sintering at a sintering temperature of 800 ℃ for 1 hour at a magnification of 1000.

It is clear that while good calcium carbonate sintered bodies are obtained in fig. 2 to 4, particles excessively grow and cracks are slightly generated in fig. 5.

< comparative example 1 >

The calcium carbonate of example 1 and the sintering aid were mixed so that the content of the sintering aid became 0.6 mass%, and the mixed powder was put into a polyethylene bottle together with an appropriate amount of zirconium beads and dry-blended at once to form a raw material powder. Further, as the sintering aid, a mixture of potassium fluoride, lithium fluoride, and sodium fluoride is used. The mixing ratio was 40: 49: 11 in terms of molar ratio. The melting point (eutectic temperature) of the mixture was 463 ℃. The molded article obtained in the same manner as in example 1 was heated at 5 ℃ per minute to 400 ℃ in an air atmosphere (oxygen concentration 21%) except that the raw material powder was used, and the temperature was maintained for 12 hours after the temperature rise. After cooling, the temperature was raised to the sintering temperature (480 ℃) at the same rate in the air atmosphere (carbon dioxide concentration: 0.03%), and main sintering was carried out for 3 hours after the temperature rise to obtain a calcium carbonate sintered body. The relative density and purity of the calcium carbonate sintered body are shown in table 1.

< comparative example 2 >

The molded body obtained in the same manner as in example 2 was heated at 10 ℃ per minute to 500 ℃ in an air atmosphere (oxygen concentration 21%), and the temperature was raised and maintained for 12 hours to perform main sintering, thereby obtaining a calcium carbonate sintered body. The relative density, average particle diameter and purity of the calcium carbonate sintered body are shown in table 1.

< example 3 >

2.4 parts by mass of methylcellulose and 11.0 parts by mass of the specific polycarboxylic acid type polymeric surfactant (4.4 parts by mass of solid matter) were mixed in advance with 238 parts by mass of ion-exchanged water using a homogenizer, and 434 parts by mass of the calcium carbonate of example 1 was dispersed in the obtained dispersion medium to obtain a dispersion liquid. Methylcellulose is used as a gelling agent, and a special polycarboxylic acid type high molecular surfactant is used as a dispersing agent. The obtained dispersion was stirred at 1000rpm for 10 minutes by a hand mixer to foam, thereby producing a foam. The foam was placed in a mold made of paper, the mold was transferred to a hot air dryer, and the foam was heated at 80 ℃ for 0.5 hour in the hot air dryer to gel the foam. The gelled foam was heated at 80 ℃ for 12 hours, thereby obtaining a dried foam. The resulting dried foam was heated to 500 ℃ in an oxygen atmosphere (oxygen concentration: 100%) at a heating rate of 5 ℃/min, and after heating, degreasing and sintering were carried out for 12 hours. The whiteness of the obtained calcium carbonate porous sintered body is shown in table 1. Furthermore, the whiteness degree was evaluated by a spectrophotometer < comparative example 3 >

The dried foam produced by the method of example 3 was heated to a temperature (400 ℃) in an air atmosphere (oxygen concentration 21%) at a heating rate of 5 ℃/min, and was degreased for 10 hours after the heating. Subsequently, the temperature was raised from 400 ℃ to the firing temperature (510 ℃) at the same rate of temperature rise, and after the temperature rise, the main firing was carried out for 3 hours, and then the resultant was cooled to room temperature at a rate of 10 ℃/min, to obtain a porous sintered body of calcium carbonate. The whiteness of the obtained calcium carbonate porous sintered body is shown in table 1.

< example 4 >

The dried foam produced by the method of example 3 was pulverized into granules having a diameter of about 1mm to 2mm, heated to 500 ℃ at a heating rate of 5 ℃/min under an oxygen atmosphere (oxygen concentration 100%), degreased for 12 hours after heating, cooled, heated to a sintering temperature (800 ℃) at the same heating rate under a carbonic acid atmosphere (carbon dioxide concentration 100%), and subjected to main sintering for 1 hour after heating, to obtain porous sintered calcium carbonate granules. The obtained calcium carbonate porous sintered body particles were embedded in the approximately central portion of the anterior skull of 11-week-old male rats by trepanning (trepan) with a 5mm diameter at the opening 1. The day of implantation was taken as the first day, and the skull bone was collected at the time of 3 weeks (21 days). The surrounding soft tissue was removed, fixed in 10% neutral buffered formalin, stored, delimed with formic acid, embedded in paraffin, sliced, and stained with hematoxylin-eosin to obtain an observation sample. Fig. 6 shows how the sample is observed. The embedded material, fibrous tissue and new bone were confirmed in the observation sample. In the hematoxylin-eosin staining, the fibrous tissue, the embedded material, and the new bone are light red, white, and deep red, respectively, and thus each part of the observation sample can be distinguished.

In addition, the area ratios of the new bone, the embedding material, and the fibrous tissue in the observation sample were calculated for 6 specimens implanted under the same conditions, and the calculation results are shown in fig. 8. Then, the area ratio (%) is calculated by enlarging the photograph shown in fig. 6 to obtain the areas of the new bone, the embedding material, and the fibrous tissue, and calculating the ratio of the areas of the new bone, the embedding material, and the fibrous tissue to the sum of the areas of the new bone, the embedding material, and the fibrous tissue. The area of each region is obtained by labeling each region with a drawing tool and binarizing the labeled region with ImageJ.

< comparative example 4 >

In the same manner as in example 4, commercially available β -TCP artificial bone particles were embedded in the skull bone of male rats to prepare observation samples. Fig. 7 shows how the sample is observed. Fig. 8 shows the calculation results of the area ratios of the new bone, the embedding material, and the fibrous structure in the observation sample. This was compared with the results of example 4 using Wilcoxon rank sum test, and as a result, with respect to new bone, at a significance level of 0.01, example 4 was higher; for the embedded material, at a significance level of 0.05, comparative example 4 was higher; no significant difference was seen with respect to fibrous tissue. From the comparison, the particles embedded in example 4 are considered to be a material that is absorbed quickly in vivo, because the degree of bone regeneration in vivo is higher than that of conventional artificial bone products.

[ Table 1]