JP6061415B2 - Biomaterial ceramics comprising β-type tricalcium phosphate and method for producing the same - Google Patents

Description

  The present invention relates to a biomaterial ceramic in which a divalent anion or a tetravalent anion is substituted and dissolved in a phosphate site of β-type tricalcium phosphate.

Tricalcium phosphate [TCP; Ca ₃ (PO ₄ ) ₂ ], which is used as an alternative material for hard tissue such as medical materials, especially artificial bones, is composed of calcium ions, phosphate ions and metals in their crystal structures. It has the feature that ions are substituted and dissolved. Focusing on this feature, as an artificial aggregate in which calcium ions and cations of TCP are substituted and dissolved, zinc-containing TCP in which zinc ions (Zn ²⁺ ions) are substituted is reported in Patent Document 1 and the like.

Focusing on the substitutional solid solution of phosphate ions and anions in the TCP crystal structure for artificial aggregates in which calcium ions and metal ions are substituted and dissolved, trivalent anions with the same valence as phosphate ions As an alternative material for TCP hard tissue with ion-displaced solid solution, vanadate (VO ₄ ^3- ) ion, which is a kind of vanadium that promotes bone formation, contains vanadate ion dissolved in phosphate site in TCP structure (Solubility) TCP has been reported so far. This substitute material for hard tissue improves the sinterability of the sintered body by solid solution of VO ₄ ^3- ions, shows a fine microstructure with fine particles and few pores, improves its mechanical properties, Have the same mechanical strength.

As a calcium phosphate compound for biomaterials in which divalent anions are substituted and dissolved, an alternative material for hard tissue in which carbonate (CO ₃ ^2- ) ions are substituted and dissolved in phosphate ions in the HAp crystal structure has been reported. Non-patent literature that solid solubility of CO ₃ ^2- ion promotes solubility compared to HAp, has physical properties similar to living bones, and has good cell differentiation, proliferation and calcification ability 1 is reported.

Moreover, as a calcium phosphate compound for biomaterials in which tetravalent anions are substituted and dissolved, in addition to the above-mentioned tricalcium phosphate containing silicic acid, hydroxyapatite, which is clinically applied as an alternative material for hard tissues, like TCP Silica (SiO ₄ ^4- ) ions are substituted and dissolved at phosphate sites in the (HAp) structure, and silicate solid solution apatite is known. Although the thermal stability of the sapphire decreases, it is recognized that the firing temperature is reduced and the sinterability is improved during the preparation of the HAp sintered body. On the other hand, it has been reported from the biological viewpoint that cell adhesion, bone formation, and bone growth density are increased. Patent Document 2 also reports a silicate-containing TCP in which a silicate ion is substituted and dissolved with a phosphate ion of TCP.

JP2004-175760 JP 2008-214111 A

Iwanaga Kanji, Shibuya Toshiaki, Doi Yutaka, Moriwaki Yutaka, Iwayama Yukio, Gifu Dental Journal, 28, 90 (2001)

  However, both the zinc or silicic acid-containing TCPs are synthesized using a liquid phase method (wet method). However, in the synthesis of TCP by the wet method, since TCP is generated only with a Ca / P molar ratio = 1.50, in addition to TCP, HAp and calcium pyrophosphate are easily generated as by-products, and in addition to many experimental processes, In order to obtain only the TCP phase, strict control of experimental conditions (such as reaction temperature and pH of the reaction solution) and skilled experimental operations are required. In addition, regarding the technology of the zinc or silicic acid-containing TCP, the mechanical compatibility, which is one of the properties required for the biomaterial, has not been evaluated.

The silicate-containing TCP contains silicate ions in α-tricalcium phosphate (α-TCP) which is a high-temperature phase of TCP. However, α-tricalcium phosphate has higher solubility and lower mechanical strength than β-tricalcium phosphate (β-TCP), which is a low-temperature phase, so that its use as a biomaterial is limited. Since α-tricalcium phosphate is actually a biomaterial that easily hydrates and hardens with it, it is mainly used as the main component of calcium phosphate cement that hardens in the body. No. 2001-95913 and many others), there is no use example as an artificial bone like β-TCP. In addition, SiO ₄ ^4- ions are substituted and dissolved in HAp and α-TCP alone, but are not substituted and dissolved in β-TCP alone. In addition, materials including artificial aggregates in which divalent anions such as the above CO ₃ ^2- ion are substituted and dissolved in phosphate sites in the TCP (α-TCP and β-TCP) crystal structure have been reported so far. It has not been.

In the present invention, a divalent anion or a tetravalent anion, which cannot be dissolved in a single solution because it has a valence different from that of PO ₄ ^3- ion, was aimed to be dissolved at the PO ₄ site of β-TCP.

(1) The present invention provides a biomaterial ceramic comprising β-type tricalcium phosphate in which sulfate ions and cations for charge compensation are dissolved.

  (2) The present invention provides the biomaterial ceramic according to (1) above, wherein the cation for charge compensation is a sodium ion.

  (3) The present invention provides a biomaterial ceramic comprising β-type tricalcium phosphate in which a tetravalent anion and a cation for charge compensation are dissolved.

  (4) The present invention provides the biomaterial ceramic according to (3), wherein the tetravalent anion is a silicate ion, and the cation for charge compensation is a magnesium ion.

(5) The present invention provides a biomaterial ceramic made of β-type tricalcium phosphate in which sulfate ions and tetravalent anions are dissolved.

  (6) In the present invention, calcium oxide, diammonium hydrogen phosphate, sodium nitrate, and ammonium sulfate are wet-mixed, and then the mixing step of removing the solvent ethanol from the resulting mixture, and the mixture obtained in the mixing step, After pulverization in a solvent, a pulverization step for removing the solvent, a molding step for forming a molded body by uniaxial pressure molding of the powder obtained in the pulverization step, and firing the molded body obtained in the molding step There is provided a β-type tricalcium phosphate sintered body manufacturing method for manufacturing the β-type tricalcium phosphate sintered body according to (2) above.

  (7) The present invention includes a mixing step in which calcium ethanol, diammonium hydrogen phosphate, magnesium oxide, and silicon dioxide are wet mixed, and then the solvent ethanol is removed from the resulting mixture, and the mixture obtained in the mixing step Crushed in a solvent, and then a pulverizing step for removing the solvent, a molding step for forming a molded body by uniaxial pressure molding of the powder obtained in the pulverizing step, and a molded body obtained in the molding step. There is provided a β-type tricalcium phosphate sintered body manufacturing method for manufacturing the β-type tricalcium phosphate sintered body according to (4) above, which includes a firing step.

  The present invention clarifies that divalent or tetravalent anions having a different valence from the trivalent anion of β-TCP are dissolved in β-TCP. Not only increases the selection range of (metal) ions, but also leads to expansion of the application range as a new biomaterial for hard tissue replacement having an effect of promoting bone formation caused by solid anions.

  In the present invention, a divalent or tetravalent anion is dissolved in β-TCP in the low temperature phase, not α-TCP in the high temperature phase, using the solid phase method, which is a general method for producing tricalcium phosphate. Therefore, it does not require strict control of manufacturing conditions, skilled manufacturing methods and high-temperature processing (firing), and can be manufactured on the current tricalcium phosphate manufacturing line, so anion dissolved in a small amount of equipment investment and cost It is possible to produce β-TCP having an effect of promoting bone formation caused by the above.

Conceptual diagram showing the crystal structure of β-type tricalcium phosphate Conceptual diagram showing the columns that make up the crystal structure of β-type tricalcium phosphate Diagram showing solid solution form of monovalent metal ions Diagram showing solid solution form of divalent metal ions Process flow diagram showing the synthesis method of β-type tricalcium phosphate in which metal ions and divalent anions are dissolved. Process flow diagram showing a method for producing a sintered body made of β-type tricalcium phosphate in which metal ions and divalent anions are dissolved. Process flow diagram showing a method for producing a sintered body made of β-type tricalcium phosphate in which metal ions and divalent anions are dissolved. X-ray diffraction pattern of β-type tricalcium phosphate in which the metal ion and sulfate ion (SO ₄ ²⁻ ) in Example 1 were dissolved. It shows the d values obtained from X-ray diffraction diagram of the β-type tricalcium phosphate which solid solution of the metal ion and sulfate ion Example 1 (SO ₄ ^2-) Shows the FT-IR spectra of metal ion and sulfate ion (SO ₄ ^2-) β tricalcium phosphate in which solid solution of Example 1 Shows a lattice constant variation of the metal ion and sulfate ion (SO ₄ ^2-) β tricalcium phosphate in which solid solution of Example 1 X-ray diffraction pattern of β-type tricalcium phosphate in which the metal ion and sulfate ion (SO ₄ ²⁻ ) in Example 2 were dissolved. Shows the d values obtained from X-ray diffraction pattern of the metal ions and sulfuric acid ions (SO ₄ ^2-) β tricalcium phosphate in which solid solution of Example 2 Shows the FT-IR spectra of metal ion and sulfate ion (SO ₄ ^2-) β tricalcium phosphate in which solid solution of Example 2 Shows a lattice constant variation of the metal ion and sulfate ion (SO ₄ ^2-) β tricalcium phosphate in which solid solution of Example 2 Process flow diagram showing the synthesis method of β-type tricalcium phosphate in which metal ions and tetravalent anions are dissolved. Process flow diagram showing a method for producing a sintered body made of β-type tricalcium phosphate in which metal ions and tetravalent anions are dissolved. Process flow diagram showing a method for producing a sintered body made of β-type tricalcium phosphate in which metal ions and tetravalent anions are dissolved. X-ray diffraction pattern of β-type tricalcium phosphate in which the metal ions and silicate ions (SiO ₄ ^4- ) of Example 3 were dissolved. Shows the FT-IR spectrum of the β-type tricalcium phosphate were dissolved metal ions and silicate ions of Example 3 (SiO ₄ ^4-) Shows a lattice constant variation of the metal ions and silicate ions (SiO ₄ ^4-) β tricalcium phosphate in which solid solution of Example 3 Diagram showing solid solution form of divalent metal ions and silicate ions (SiO ₄ ^4- ) in β-TCP X-ray diffraction pattern of a β-type tricalcium phosphate sintered body in which the metal ions and silicate ions (SiO ₄ ^4- ) of Example 4 were dissolved. Shows the FT-IR spectra of metal ions and silicate ions of Example ₄ (SiO 4 ^4-) β-type solid solution tricalcium phosphate sintered body It shows a lattice constant variation of the fourth embodiment of the metal ions and silicate ions (SiO ₄ ^4-) β-type solid solution tricalcium phosphate sintered body It illustrates a volumetric shrinkage variation of metal ions and silicate ions of Example ₄ (SiO 4 ^4-) β-type solid solution tricalcium phosphate sintered body It shows the flexural strength changes in the metal ion and silicate ions (SiO ₄ ^4-) solid solution was β tricalcium phosphate sintered body of Example 4 It shows open porosity change of metal ions and silicate ions of Example ₄ (SiO 4 ^4-) β-type solid solution tricalcium phosphate sintered body It shows the bulk density changes in the metal ion and silicate ions in the Example ₄ (SiO 4 ^4-) β-type solid solution tricalcium phosphate sintered body FIG. 1 is a diagram showing the microstructure of a β-type tricalcium phosphate sintered body in which metal ions and silicate ions (SiO ₄ ^4- ) of Example 4 are solid-dissolved (1). FIG. 2 is a diagram showing the microstructure of a β-type tricalcium phosphate sintered body in which the metal ions and silicate ions (SiO ₄ ⁴⁻ ) of Example 4 are solid-dissolved (2) FIG. 3 is a diagram showing the microstructure of a β-type tricalcium phosphate sintered body in which the metal ions and silicate ions (SiO ₄ ⁴⁻ ) of Example 4 are dissolved. Figure showing the cross-section of β-type tricalcium phosphate sintered body and the state of the structure observed from the polished surface Diagram showing an example of actual crystal particle size calculation The figure which shows the average particle diameter of the beta-type tricalcium phosphate sintered compact in which the metal ion and silicate ion (SiO ₄ ^4- ) of Example 4 were dissolved.

Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In addition, this invention should not be limited to these embodiments at all, and can be implemented in various modes without departing from the gist thereof.
<< Embodiment 1 >>
<Embodiment 1: Overview>

A biomaterial ceramic composed of β-TCP in which a divalent anion and a cation for charge compensation are dissolved, and a sintered body thereof will be described.
<Embodiment 1: Configuration>

The biomaterial ceramic of the present invention is used as a replacement material for living hard tissues such as teeth and bones that have been lost or lost due to an accident or illness, and a form in which divalent anions such as sulfate ions are described later. The shape is not particularly limited as long as it is a biomaterial ceramic composed of β-TCP substituted and dissolved in PO ₄ ^3- . A sintered body such as a powder, a granule, a film, a porous body or a dense body is applicable. In addition, solid solution means that two or more kinds of elements are melted together to form a uniform solid phase as a whole, and a sintered body means a material solidified by heating at a temperature lower than the melting point.

  (1) Solid solution form

Β-TCP according to the present invention is a solution in which phosphate ion (PO ₄ ³⁻ ) in a crystal is substituted with a divalent anion such as sulfate ion. Since the mechanical strength of β-TCP is affected by its crystal structure and crystallinity (particle size, etc.), a certain amount of phosphate ion (PO ₄ ^3- ) in the crystal is replaced with a divalent anion. By melting, the mechanical strength of the biomaterial ceramic made of β-TCP is controlled.

(Properties of tricalcium phosphate)
Tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ : TCP] has three phases β, α and α ′ from low temperature. α'-TCP is stable at high temperatures from around 1450 ° C and cannot be obtained at room temperature. α-TCP undergoes phase transition to β-TCP at temperatures below 1120-1180 ° C, but exists as a metastable phase at room temperature due to the slow transition rate. It exists in nature as Whitlockite [(Ca ₁₈ (Mg, Fe) ₂ H ₂ (PO ₄ ) ₁₄ , similar to β phase)]. α-TCP and β-TCP are both bioactive materials and are used as bioceramics. These in vivo behaviors are similar to HAp, but the solubility is greater than HAp, β-TCP has a solubility of about twice that of HAp, and α-TCP is about 10 times that of HAp.

  Since β-TCP has a lower Ca / P molar ratio than HAp (Ca / P molar ratio = 1.50), β-TCP has a higher dissolution rate and resorption rate in the living body than other calcium phosphate ceramics. It is clinically applied as an artificial tooth root and bone filler to replace autogenous bone with the generation of bone. In addition, β-TCP can produce a sintered body at a temperature of 1150 ° C. or lower, which is a transition temperature to α-TCP, and does not cause decomposition or the like by such a firing process, and has water absorption. Β-TCP has the possibility of satisfying this condition because the resorption rate of the material is compatible with the bone formation rate formed in the surrounding area, and it is considered that the newly formed bone has sufficient strength. There are few materials to have.

  On the other hand, α-TCP is hydrated into HAp and hardens at that time, so it is used as a bio-cement. However, since the curing time is too long in the case of curing with water as compared with the use conditions of the biological cement, a method of adding an acid such as citric acid or polyacrylic acid as a curing agent to accelerate the curing is also used. However, when an acid is used as a biological cement, an inflammatory reaction occurs around the filling site. Therefore, a type of cement that does not use an acid or actively neutralizes the acid has been developed.

(Crystal structure of β-type tricalcium phosphate)
The space group of β-TCP is R3c and belongs to the rhombohedral system. The lattice constants are a = 1.04352 (2) nm and c = 3.74029 (5) nm in the hexagonal lattice setting. 1 and 2 show the crystal structure of β-TCP. β-TCP has two crystallographically independent A and B columns consisting of Ca and PO ₄ tetrahedra in the crystal structure (unit cell), and these two columns exist parallel to the c-axis. ing. Column A exists on the c-axis (three-fold axis) and is a repetition of P (1) -Ca (4) -Ca (5) -P (1) -hole-Ca (5). In Whitlockite, a natural mineral, Ca (4) and Ca (5) sites are replaced by other metal ions such as Mg and Fe. In addition, since the Ca (4) site has a seat occupancy of about 0.5, it has a unique crystal structure in which vacancy exists in column A. Column B is a repetition of P (2) -Ca (3) -Ca (1) -Ca (2) -P (3), but the three Ca's do not fall on a straight line but shift by 1/3. A polygonal line is formed. Tables 1 and 2 below show the ratio of each Ca ²⁺ ion site and PO ₄ ^3- ion site in the β-TCP unit cell in consideration of vacancies.

[Table 1]

[Table 2]

(Metal ion solid solution β-type tricalcium phosphate)

3 and 4 show solid solution forms of monovalent and divalent metal ions. Monovalent metal ions are dissolved in the form of 2M ^I = Ca ²⁺ ions + □ (□: vacancies) at the Ca (4) sites and vacancies, and the solid solution limit is 9.09 mol%. The ions first dissolve in the Ca (5) site up to 9.09 mol%, and when the Ca (5) site is filled with divalent metal ions, the Ca (4) site dissolves in 13.64 mol% (M ^II = Ca ^{2 + I} know).

On the other hand, it is also known that the solid solution of metal ions in β-TCP affects the β-α phase transition temperature, sinterability, mechanical strength, and solubility. Here we describe the effect of solid solution of metal ions on the solubility of β-TCP. It has been reported that the solubility of β-TCP is about twice that of HAp, but the solubility of β-TCP sintered body containing Ba ²⁺ ions as a solid solution decreases to about 1.7 times that of HAp. Compared with Mg ²⁺ ion solid solution β-TCP, the solubility is β-TCP> Mg ²⁺ ion solid solution β-TCP> Ba ²⁺ ion solid solution β-TCP> HAp. In addition, a zinc sustained-release β-TCP having a bone formation promoting action in which Zn ²⁺ ions having a pharmacological action are solid-dissolved has been prepared, and it has been reported that the solubility thereof is also reduced.

In addition, when monovalent metal ions are dissolved, the Ca ²⁺ ion elution rate is β-TCP> K ⁺ ion solid solution β-TCP> Na ⁺ ion solid solution β-TCP> Li ⁺ ion solid solution β-TCP. In particular, the dissolution rate decreases remarkably when Li ⁺ ions are dissolved, and the dissolution rate of Ca ²⁺ ions decreases even when Mg ²⁺ ions are dissolved, but it dissolves simultaneously with Na ⁺ ions. As a result, it has been clarified that the elution rate is further lowered as compared with the case where each of them dissolves alone.

In the present invention, a divalent anion that cannot be dissolved alone because it has a valence different from that of PO ₄ ³⁻ ions was dissolved in the PO ₄ site. Specifically, charge correction was performed by reducing the seat occupancy at the Ca (4) site and increasing the seat occupancy at the vacancies, and the divalent anions were dissolved. In other words, since it has been clarified that monovalent metal ions are dissolved in Ca (4) sites, Na ⁺ ions are used to form solid solutions in Ca (4) sites, and the addition of Na ⁺ ions that are dissolved The charge was corrected by reducing the amount from the solid solution limit of 9.09 mol% to create vacancies, and divalent anions were dissolved. As a result, β-TCP is a solid solution of Na ⁺ ions and Mg ²⁺ ions, which have been known to form solid solutions as monovalent and divalent metal ions, and SO ₄ ^2- ions as divalent anions. It became possible to produce.

  (3) Synthesis of divalent anion solid solution β-TCP

Synthesis of the divalent anion solid solution β-TCP according to the present invention may be either a dry method based on a solid phase reaction or a wet method based on an aqueous solution reaction according to an existing method. A dry method is preferred. For example, according to an existing method, diammonium hydrogen phosphate ((NH ₄ ) ₂ HPO ₄ ) and calcium oxide (CaO) are used as starting materials according to existing methods, and sodium nitrate ( NaNO ₃ ), magnesium oxide (MgO) as a divalent metal ion source, and ammonium sulfate ((NH ₄ ) ₂ SO ₄ ) as a divalent anion source. Each starting material is dry mixed and the resulting mixture is calcined. An example is shown in FIG. Each starting material is dry-mixed for 1 hour (S0501). This is fired under conditions of a temperature increase rate of 3 ° C./min, a firing temperature of 750 ° C., a holding time of 12 hours, and in an atmospheric atmosphere (S0502). Subsequently, dry mixing is again performed for 1 hour (S0503). Then, again, the baking rate is 3 ° C./min, the baking temperature is 800 ° C., the holding time is 5 hours, and the baking is performed in the atmosphere (S0504). β-TCP.

  The divalent anion solid solution β-TCP evaluated in Example 1 described later is synthesized by the method shown in FIG.

  (4) Sintering of divalent anion solid solution β-TCP

The divalent anion solid solution β-TCP according to the present invention may be sintered according to an existing method. An example is shown in FIG. Phosphoric acid diammonium phosphate ((NH ₄ ) ₂ HPO ₄ ) and calcium oxide (CaO) as starting materials, sodium nitrate (NaNO ₃ ), divalent metal as monovalent metal ion source Magnesium oxide (MgO) was used as the ion source, and ammonium sulfate ((NH ₄ ) ₂ SO ₄ ) was used as the divalent anion source. The above starting materials are wet-mixed with a ball mill for 48 hours (S0601). An organic solvent such as ethanol is used as the solvent. Thereafter, the solvent is removed using an evaporator or the like (S0602) (mixing step). The mixture after removal of the solvent is again put in the solvent and pulverized (S0603), and then the solvent is removed again (S0604) (pulverization step). The powder obtained here is uniaxially pressed to form a molded body (molding step) (S0605), and the molded body is fired (firing step) (S0606) to obtain a sintered body. Here, uniaxial pressure molding (S0605) pressurizes at 32 MPa for 1 minute. The mold used is 45 mm × 20 mm. Firing (S0606) is performed under conditions of a temperature increase rate of 3 ° C./min, a firing temperature of 900 ° C., a holding time of 10 hours, and in an air atmosphere.

  In addition, as shown in FIG. 7, after carrying out wet mixing with a ball mill (S0701) and removing a solvent (S0702), you may perform a calcination process (S0703). Further, the CIP molding step (S0707) may be performed after the uniaxial pressure molding (S0706). The calcination step (S0703) is performed under conditions of a temperature increase rate of 3 ° C./min, a baking temperature of 800 ° C. to 1000 ° C., a holding time of 5 hours, and in an air atmosphere. In the CIP molding step (S0707), pressure molding is performed at 200 MPa for 1 minute. In addition, since a clear difference is seen in sinterability and the mechanical strength of a sintered compact by the difference in the calcination temperature in a calcination process, these can be adjusted by performing a calcination process. Further, a more uniform sintered body can be produced by the CIP molding process.

<Embodiment 1: Effect>

  The present invention clarified that phosphate ions, which are trivalent anions of β-TCP, and divalent ions with different valences are dissolved in β-TCP. As a new biomaterial for hard tissue replacement that has not only an increased selection range, but also a solubility control of the material caused by solid anions and a bone formation promoting action, etc., the application range will be expanded.

  In the present invention, since a divalent anion is dissolved in β-TCP in a low temperature phase instead of α-TCP in a high temperature phase using a solid phase method that is a general method for producing tricalcium phosphate, Control of manufacturing conditions, skilled manufacturing methods and high temperature treatment (firing) are not required, and because it can be manufactured on the current production line of tricalcium phosphate, it is caused by anion dissolved in less equipment investment and cost It is possible to produce β-TCP having an effect of promoting bone formation.

Evaluation of β-TCP added with metal ions and sulfate ions (SO ₄ ^2- )

Tests of X-ray diffraction, FT-IR, and lattice constant change for β-TCP (hereinafter simply referred to as “sample”) added with metal ions and sulfate ions (SO ₄ ²⁻ ) prepared by the method shown in FIG. Went. In addition, the molar compounding ratio of the raw materials at the time of dry mixing of the metal ion and sulfate ion (SO ₄ ²⁻ ) -added β-TCP of this example is shown in Table 3 below, and the weight compounding example is shown in Table 4 below.

[Table 3]

[Table 4]

  (1) X-ray diffraction

  The crystal phase of the sample was identified using Rigaku RAD-2C type X-ray diffractometer. The measurement conditions are: target: CuKα monochromator, scan range (2θ): 10-60 °, scan step: 0.020 °, scan speed: 8 ° / min, tube voltage: 40 kV, tube current: 30 mA.

FIG. 8 shows an X-ray diffraction pattern of a sample prepared by changing the amount of SO ₄ ^2- ion and Na ⁺ ion added. Also, FIG. 9 shows d values of typical diffraction lines obtained from the X-ray diffraction pattern. In all samples, only the diffraction peak of β-TCP (ICDD: 09-169) was confirmed, and the obtained sample was found to be a β-TCP single phase. In addition, it was confirmed that the diffraction peak shifted to the lower angle side as the SO ₄ ^2- ion addition amount increased, and solid solution and increased lattice constant were observed.

  (2) FT-IR

Qualitative analysis was performed using a FT / IR-230 Fourier transform infrared spectrophotometer manufactured by JASCO. The measurement range is 400-4000 cm ⁻¹ and the number of integrations is 68 times. The sample is measured by the diffuse reflection method using KBr, and the mixing weight ratio of the sample and KBr is about 20 with respect to the sample 1.

FIG. 10 shows an FT-IR spectrum of a sample prepared by changing the amount of SO ₄ ^2- ion and Na ⁺ ion added. Absorption attributed to PO ₄ groups was observed in the vicinity of 945 cm ⁻¹ (ν ₁ ), 432 cm ⁻¹ (ν ₂ ), 1010 cm ⁻¹ (ν ₃ ), and 550 cm ⁻¹ (ν ₄ ). Further, solid solution as SO ₄ ^2-ionic 1130～1080Cm ^-1 attributed to SO ₄ group, since the absorption is observed near 680～610Cm ^-1 in beta-TCP with the addition of SO ₄ ^2-ions It became clear that.
Than this, confirmed that the SO ₄ ^2-ions dissolved up 14.20Mol% to beta-TCP, the added SO ₄ ^2-ions suggested that a solid solution in P site in beta-TCP structure It was done.

(3) Lattice constant

For measurement of the lattice constant, a Rigaku rotating anti-cathode X-ray diffractometer RINT-1500 was used, Si (99.99%, Mitsuwa Chemicals Co., Ltd.) was used as an internal standard sample, and β-TCP diffraction lines ( (2 0 10), (2 1 8), (2 2 0), (3 2 8), (2 0 20) and Si diffraction lines (1 1 1), (2 2 0), (3 1 Preliminary measurement was performed under the optimum conditions for 4) (1 0) and (2 0 20). The measurement was performed at a working tube voltage: 40 kV and a working tube current: 200 mA. In addition, the measured X-ray diffraction diagram was subjected to angle correction by the internal standard method using the peak top method, and the lattice constant was refined by the least square method using the following equation.

[Equation 1]

The lattice constants of samples prepared by changing the amount of SO ₄ ^2- ion addition are shown in Table 5 below, and the changes are shown in FIG. Regarding the change in lattice constant, the a-axis was almost constant and the c-axis increased linearly up to the SO ₄ ²⁻ ion addition amount of 13.99 mol%. Compared with the X-ray diffraction pattern shown in FIG. 8, samples up to the amount of SO ₄ ^2- ion addition of 13.99 mol% were β-TCP single phase, and the lattice constant change also changed linearly. Therefore, it was confirmed that SO ₄ ^2- ions were dissolved in the β-TCP structure for the added sample up to 13.99 mol%.

[Table 5]

(4) Summary

Β-TCP was prepared by adding Na ⁺ ions as monovalent metal ions, Mg ²⁺ ions as divalent metal ions, and SO ₄ ^2- ions as divalent anions, and the following was clarified. All of the obtained samples became β-TCP single phase, Ca (4) site became vacancy, SO ₄ ^2- ion was dissolved in P site so as to compensate the charge, and its solid solution limit was 14.28. It was suggested to be mol%.

Evaluation of the influence of Mg ²⁺ ions in SO ₄ ^2- ion solid solution β-TCP

Ca (4) sites and into the holes as SO ₄ ^2- ions are satisfied, SO ₄ 13.99mol% nearly ^2- ions added amount of the solid solubility limit, 0.19 mol of Na ⁺ ions amount as monovalent metal ions Β-TCP was prepared and evaluated by changing the amount of Mg ²⁺ ions added instead of Ca ²⁺ ions, which are divalent metal ions dissolved in Ca (5) sites.

(experimental method)
In the same manner as in Example 1, using CaO, (NH ₄ ) ₂ HPO ₄ , NaNO ₃ , MgO, (NH ₄ ) ₂ SO ₄ as starting materials, the SO ₄ ^2- ion addition amount is kept constant at 9.09 mol%. In addition, the Mg ²⁺ ion addition amount was changed to 0-9.09 mol% instead of Ca ²⁺ ions. Tables 6 and 7 show blending ratios and blending amounts. Moreover, the sample produced similarly to Example 1 was evaluated.

[Table 6]

[Table 7]

  (1) X-ray diffraction

FIGS. 12 and 13 show X-ray diffraction patterns and d values of samples prepared by changing the Mg ²⁺ ion addition amount. In all samples, only the diffraction peak of β-TCP (ICDD: 09-169) was confirmed, and the obtained sample was found to be a β-TCP single phase. In addition, it was confirmed that the diffraction peak shifted to the high angle side as the Mg ²⁺ ion addition amount increased.

  (2) FT-IR

FIG. 14 shows an FT-IR spectrum of a sample prepared by changing the Mg ²⁺ ion addition amount. Absorption attributed to PO ₄ groups was observed in the vicinity of 945 cm ⁻¹ (ν ₁ ), 432 cm ⁻¹ (ν ₂ ), 1010 cm ⁻¹ (ν ₃ ), and 550 cm ⁻¹ (ν ₄ ). The 1130～1080Cm ^-1 attributed to SO ₄ group was revealed that the solid solution as SO ₄ ^2-ions in the beta-TCP since the absorption is observed near 680~610cm ^-1.

(3) Lattice constant

Table 8 shows the lattice constants of samples prepared by fixing SO ₄ ^2- ions and Na ⁺ ions at 13.99 mol% and 0.19 mol%, respectively, and replacing Ca ²⁺ ions and Mg ²⁺ ions. Each is shown in FIG. Regarding the change in lattice constant, the a-axis and c-axis decreased linearly to the Mg ²⁺ ion addition amount of 9.09 mol%. Compared with the X-ray diffraction pattern shown in FIG. 12, the samples up to 9.09 mol% of Mg ²⁺ ion addition were β-TCP single phase, and the lattice constant change also changed linearly. Therefore, Mg ²⁺ ions in place of Ca ²⁺ ions for sample addition up to 9.09mol%, it was confirmed that the solid solution in beta-TCP structure.

[Table 8]

  (4) Summary

From this, it has been clarified that SO ₄ ^2- ions are dissolved at the P site in the β-TCP structure regardless of the amount of Mg ²⁺ ions added to the Ca (5) site.
<< Embodiment 2 >>
<Embodiment 2: Overview>

A biomaterial ceramic made of β-TCP in which tetravalent anions and cations for charge compensation are dissolved, and a sintered body thereof will be described.
<Embodiment 2: Configuration>

The biomaterial ceramic of the present invention is used as a replacement material for living hard tissues such as teeth and bones that have been lost or lost due to an accident or illness, and tetravalent anions such as silicate ions will be described later. The shape is not particularly limited as long as it is a biomaterial ceramic made of β-TCP substituted and dissolved with PO ₄ ^{3- in} form. A sintered body such as a powder, a granule, a film, a porous body or a dense body is applicable. In addition, solid solution means that two or more kinds of elements are melted together to form a uniform solid phase as a whole, and a sintered body means a material solidified by heating at a temperature lower than the melting point.

  (1) Solid solution form

Β-TCP according to the present invention is a solution in which phosphate ions (PO ₄ ³⁻ ) in a crystal are substituted and dissolved by tetravalent anions such as silicate ions. Since the mechanical strength of β-TCP is affected by its crystal structure and crystallinity (particle size, etc.), a certain amount of phosphate ion (PO ₄ ³⁻ ) in the crystal is replaced with a tetravalent anion. By melting, the mechanical strength of the biomaterial ceramic made of β-TCP is controlled.

  (3) Synthesis of tetravalent anion solid solution β-TCP

Synthesis of tetravalent anion solid solution β-TCP according to the present invention may be either a dry method by solid phase reaction or a wet method by aqueous solution reaction in accordance with an existing method. A dry method is preferred. For example, according to existing methods, diammonium hydrogen phosphate ((NH ₄ ) ₂ HPO ₄ ) and calcium carbonate (CaCO ₃ ) are used as starting materials and magnesium oxide as a divalent metal ion source in accordance with existing methods. (MgO), silicon dioxide (SiO ₂ ) was used as a tetravalent anion source. Here, an excessive amount of MgO was added to the vacancies in β-TCP so that Mg ²⁺ ions were dissolved, and SiO ₂ was added to correct the charge bias. Each starting material is dry mixed and the resulting mixture is calcined. An example is shown in FIG. Each starting material is dry-mixed for 1 hour (S1601). This is fired under conditions of a temperature increase rate of 3 ° C./min, a firing temperature of 1200 ° C., a holding time of 12 hours, and in an air atmosphere (S1602). Subsequently, dry mixing is again performed for 1 hour (S1603). Then, again, the firing rate is 3 ° C./min, the firing temperature is 1200 ° C., the holding time is 12 hours, and the firing is performed in the atmosphere (S1604), and the obtained fired body is a tetravalent anion solid solution according to the present invention. β-TCP.

  The tetravalent anion solid solution β-TCP evaluated in Example 3 described later is synthesized by the method shown in FIG.

  (4) Sintering of tetravalent anion solid solution β-TCP

Sintering of the tetravalent anion solid solution β-TCP according to the present invention may be performed according to an existing method. An example is shown in FIG. Diammonium hydrogen phosphate ((NH ₄ ) ₂ HPO ₄ ) and calcium carbonate (CaCO ₃ ) are used as starting materials, and magnesium oxide (MgO), tetravalent anion as a divalent metal ion source. Silicon dioxide (SiO ₂ ) was used as the ion source. The starting materials are wet mixed for 48 hours in a ball mill (S1701). An organic solvent such as ethanol is used as the solvent. Thereafter, the solvent is removed using an evaporator or the like (S1702) (mixing step). The mixture after removal of the solvent is again put in the solvent and pulverized (S1703), and then the solvent is removed again (S1704) (pulverization step). The powder obtained here is uniaxially pressed to form a molded body (molding step) (S1705), and the molded body is fired (firing step) (S1706) to obtain a sintered body. Here, uniaxial pressure molding (S1705) pressurizes at 32 MPa for 1 minute. The mold used is 45 mm × 20 mm. Firing (S1706) is performed under conditions in the air atmosphere at a heating rate of 3 ° C./min, a firing temperature of 1200 ° C., a holding time of 24 hours.

  In addition, as shown in FIG. 18, after carrying out wet mixing with a ball mill (S1801) and removing a solvent (S1802), you may perform a calcination process (S1803). Further, the CIP molding step (S1807) may be performed after the uniaxial pressure molding (S1806). The calcination step (S1803) is performed under conditions in the air atmosphere at a heating rate of 3 ° C./min, a baking temperature of 1200 ° C., a holding time of 24 hours. In the CIP molding step (S1807), pressure molding is performed at 200 MPa for 1 minute. In addition, since a clear difference is seen in sinterability and the mechanical strength of a sintered compact by the difference in the calcination temperature in a calcination process, these can be adjusted by performing a calcination process. Further, a more uniform sintered body can be produced by the CIP molding process.

  In addition, the tetravalent anion solid solution β-TCP sintered body evaluated in Example 4 to be described later is synthesized by the method shown in FIG.

<Embodiment 2: Effect>

  The present invention clarified that phosphate ions, which are trivalent anions of β-TCP, and tetravalent anions having different valences are dissolved in β-TCP. In addition to increasing the selection range of ions, the application range is expanded as a new biomaterial for hard tissue replacement having solubility control of a material caused by solid anions and promoting bone formation.

  In the present invention, a solid phase method, which is a general method for producing tricalcium phosphate, is used to make tetravalent anions form a solid solution in β-TCP in the low temperature phase instead of α-TCP in the high temperature phase. Control of manufacturing conditions, skilled manufacturing methods and high temperature treatment (firing) are not required, and because it can be manufactured on the current production line of tricalcium phosphate, it is caused by anion dissolved in less equipment investment and cost It is possible to produce β-TCP having an effect of promoting bone formation.

Evaluation of β-TCP with addition of metal ions and silicate ions (SiO ₄ ⁴⁻ )

For β-TCP (hereinafter simply referred to as “sample”) to which metal ions and silicate ions (SiO ₄ ⁴⁻ ) prepared by the method shown in FIG. 17 are added, X-ray diffraction, FT-IR, and changes in lattice constant A test was conducted. In addition, the molar compounding ratio of the raw materials at the time of dry mixing of the metal ion and the silicate ion (SiO ₄ ⁴⁻ ) -added β-TCP of this example is shown in Table 9 below, and the weight compounding example is shown in Table 10 below.

[Table 9]

[Table 10]

  (1) X-ray diffraction

  The crystal phase of the sample was identified using Rigaku RAD-2C type X-ray diffractometer. Measurement conditions are: target: Cu (Cu-Kα), scan range (2θ): 10-60 °, scan step: 0.020 °, scan speed: 8 ° / min, tube voltage: 40 kV, tube current: 30 mA, It is.

FIG. 19 shows an X-ray diffraction pattern of a sample prepared by changing the addition amount of silicate ions (SiO ₄ ⁴⁻ ) and magnesium ions (Mg ²⁺ ). From the X-ray diffraction pattern, for the samples up to 18.18 mol% Mg ²⁺ ion addition and 14.28 mol% SiO ₄ ^4- ion addition, the obtained X-ray diffraction peak coincides with the β-TCP diffraction peak, Since no by-product was produced, it was confirmed that it was a β-TCP single phase. Further, when excessive Mg ²⁺ ions and SiO ₄ ^4- ions were added, a diffraction peak of hydroxyapatite (HAp) was confirmed in addition to the X-ray diffraction peak of β-TCP.

  (2) FT-IR

Qualitative analysis was performed using a FT / IR-230 Fourier transform infrared spectrophotometer manufactured by JASCO. The measurement range is 400-4000 cm ⁻¹ and the number of integrations is 68 times. The sample is measured by the diffuse reflection method using KBr, and the mixing weight ratio of the sample and KBr is about 20 with respect to the sample 1.

FIG. 20 shows an FT-IR spectrum of a sample to which Mg ²⁺ ions and SiO ₄ ^4- ions are added simultaneously. In the spectrum of β-TCP, there are four standard vibrations belonging to the PO ₄ group around 945 cm ^-1 (ν ₁ ), 432 cm ^-1 (ν ₂ ), 1010 cm ^-1 (ν ₃ ), and 550 cm ^-1 (ν ₄ ). Admitted. Ν ₁ and ν ₃ are stretching vibrations, and ν ₂ and ν ₄ are bending vibrations. In addition, in the FT-IR spectrum of calcium pyrophosphate (Ca ₂ P ₂ O ₇ ) and hydroxyapatite (HAp) that are produced as by-products during β-TCP preparation, Ca ₂ P ₂ O ₇ near the P ₂ O due to absorption in ₇ groups 710 cm ^-1, in the case of HAp OH stretching vibration 3570cm ^-1, 633 cm ^-1 absorption attributable to OH out-of-plane deformation vibration appears in. However, from Figure 20 it could not be confirmed for the absorption of 3570cm ^-1 and 633 cm ^-1 attributable to the OH group absorption and HAp attributable to P ₂ O ₇ groups Ca ₂ P ₂ O ₇ in a molecule in the vicinity of 710 cm ^-1 It was. Further, in the spectrum of the sample to which SiO ₄ ^4- ion was added, skeletal vibration caused by SiO ₄ ^4- ion was confirmed in the vicinity of 890 cm ⁻¹ . Therefore, it became clear that β-TCP was dissolved as SiO ₄ ^4- ions.

(3) Lattice constant

For measurement of the lattice constant, a Rigaku rotating anti-cathode X-ray diffractometer RINT-1500 was used, Si (99.99%, Mitsuwa Chemicals Co., Ltd.) was used as an internal standard sample, and β-TCP diffraction lines ( (2 0 10), (2 1 8), (2 2 0), (3 2 8), (2 0 20) and Si diffraction lines (1 1 1), (2 2 0), (3 1 Preliminary measurement was performed under the optimum conditions for 4) (1 0) and (2 0 20). The measurement was performed at a working tube voltage: 40 kV and a working tube current: 200 mA. In addition, the measured X-ray diffraction diagram was subjected to angle correction by the internal standard method using the peak top method, and the lattice constant was refined by the least square method using the following equation.

[Equation 2]

Table 11 below shows the lattice constants of samples prepared by changing the addition amounts of Mg ²⁺ ions and SiO ₄ ^4- ions, and FIG. 21 shows the changes. Regarding the change in lattice constant, the a-axis increased linearly and the c-axis decreased until the Mg ²⁺ ion addition amount 18.18 mol% and the SiO ₄ ^4- ion addition amount 14.28 mol%. Thereafter, it was confirmed that the a-axis was constant and the c-axis increased. Compared with the X-ray diffraction pattern shown in FIG. 19, samples up to 18.18 mol% Mg ²⁺ ions and 14.28 mol% SiO ₄ ^4- ions are β-TCP single phase, and the lattice constant change is also It changed linearly. Therefore, it was confirmed that Mg ²⁺ ions were dissolved in β-TCP structure for the added samples up to 18.18 mol% and SiO ₄ ^4- ions up to 14.28 mol%.

[Table 11]

(4) Summary From the above results, the solid solution limit was 18.18 mol% for Mg ²⁺ ions and 14.28 mol% for SiO ₄ ^4- ions. The solid solution form is shown in FIG. Usually, divalent metal Mg ²⁺ ions is an ion replaces solid solution with Ca (4) sites (site occupancy 0.5) and Ca (5) sites Ca ²⁺ ions, the solid solubility limit and 13.64Mol% However, in order to compensate for the difference in charge between the solid solution SiO ₄ ^4- ion and PO ₄ ^3- ion, excess Mg ²⁺ ions above the solid solution limit will cause vacancies in the Ca (4) site ( also dissolves in the occupancy rate 0.5), was considered a solid solution with SiO ₄ ^4-ionic form, such as _{^{2PO 4 3- = 2SiO 4 4- +}} Mg 2+. That is, regarding the fact that Mg ²⁺ ions were dissolved in vacancies due to the charge correction of SiO ₄ ^4- ions and PO ₄ ^3- ions, as shown in Table 11, a total of 18.18 mol% was dissolved. Even so, this value confirmed the experimental results. On the other hand, with regard to SiO ₄ ^4- ions, the charge bias due to the solid solution of excess Mg ²⁺ ions occurs in the A column, so the added SiO ₄ ^4- ions are present at the P (1) site in the A column. I thought it was a solid solution. Since the ratio of P sites to all PO ₄ sites in β-TCP was 14.28 mol%, it was found that SiO ₄ ^4- ions were dissolved in all of the P sites at the solid solution limit.
Therefore, as for its solid solution form, divalent metal ions are solid-solved up to 18.18 mol% at Ca (4) site, Ca (5) site and vacancies in β-TCP, and the added amount of divalent metal ions is 13.64 mol. It was confirmed that 14.28 mol% of SiO ₄ ^4- ions were dissolved in the P site so as to correct the charge by an amount added in excess of% or more.

Evaluation of β-TCP sintered body added with metal ions and silicate ions (SiO ₄ ⁴⁻ )

For a β-TCP sintered body (hereinafter simply referred to as “sintered body sample”) to which metal ions and silicate ions (SiO ₄ ⁴⁻ ) prepared by the method shown in FIG. 18 are added, X-ray diffraction, FT -IR, lattice constant change, mechanical properties were tested. In addition, the molar compounding ratio of the raw materials in the production of the sintered body of β-TCP added with metal ions and silicate ions (SiO ₄ ⁴⁻ ) of this example is shown in Table 12 below, and an example of weight formulation is shown in Table 13 below.

[Table 12]
[Table 13]

  (1) X-ray diffraction

FIG. 23 shows an X-ray diffraction pattern of a sintered body sample produced by changing the addition amount of silicate ions (SiO ₄ ⁴⁻ ) and magnesium ions (Mg ²⁺ ). From the X-ray diffraction pattern, the sintered body with Mg ²⁺ ion addition of 18.18 mol% and SiO ₄ ^4- ion addition of 14.28 mol% is β-TCP single phase, and sintering with various ion additions beyond that Production of HAp was confirmed as a by-product from body samples.

  (2) FT-IR

FIG. 24 shows an FT-IR spectrum of a sintered body sample to which Mg ²⁺ ions and SiO ₄ ^4- ions are added simultaneously. In the spectrum of β-TCP, there are four standard vibrations belonging to the PO ₄ group around 945 cm ^-1 (ν ₁ ), 432 cm ^-1 (ν ₂ ), 1010 cm ^-1 (ν ₃ ), and 550 cm ^-1 (ν ₄ ). Admitted. Ν ₁ and ν ₃ are stretching vibrations, and ν ₂ and ν ₄ are bending vibrations. Further, in the spectrum of the sintered body sample to which SiO ₄ ^4- ion was added, skeletal vibration due to the SiO ₄ group was confirmed in the vicinity of 890 cm ⁻¹ . Therefore, it became clear that β-TCP was dissolved as SiO ₄ ^4- ions.

(3) Lattice constant

The lattice constants of the sintered body samples prepared by changing the addition amounts of Mg ²⁺ ions and SiO ₄ ^4- ions are shown in Table 14 below, and the changes are shown in FIG. The lattice constant change of the sintered body up to the Mg ²⁺ ion addition amount 18.18 mol% and the SiO ₄ ^4- ion addition amount 14.28 mol% linearly increased the a-axis and decreased the c-axis. These results are the same as the results of the powder sample prepared in Example 3. The Mg ²⁺ ions were dissolved in the β-TCP sintered body up to 18.18 mol% and SiO ₄ ^4- ions to 14.28 mol%. Reconfirmed.

[Table 14]

(4) Mechanical properties

a) Volume shrinkage change

FIG. 26 shows the volume shrinkage change with respect to various ion addition amounts calculated from the sample volume before and after firing of the sintered body produced. Volumetric shrinkage increased with increasing amounts of Mg ²⁺ ions and SiO ₄ ^4- ions, and was the solid solution limit of Mg ²⁺ ions added 18.18 mol% and SiO ₄ ^4- ions added 14.28 mol% It was confirmed that the maximum size of the sample was the most contracted before and after firing.

From this result, it was confirmed that the sintered body became dense by simultaneously dissolving Mg ²⁺ ions and SiO ₄ ^4- ions in β-TCP. Moreover, the shrinkage ratio decreased when the solid solution limit was exceeded. This was considered to be an effect produced by by-products.

b) Measurement of bending strength of sintered body

  The bending strength was measured by performing a three-point bending test under the following conditions using an autograph (AG-1, manufactured by Shimadzu Corporation) based on JIS R 1601.

Distance between fulcrums: 30mm
Crosshead speed: 0.5 mm · min ^-1
Number of sample pieces: 5 Sample piece size: 3.0 x 4.0 x 36 mm
Test temperature: Room temperature Test atmosphere: In the air Sample processing: Low-speed cutting machine (ISOMETtm, manufactured by BUEHLER) is used for sintering cutting, and polishing machine (Dialap ML-150, manufactured by Marto) is used for surface polishing. Polishing and chamfering were performed with abrasive paper # 200 and # 400.

Based on the measured maximum load of the sintered body, the bending strength was obtained from the following equation based on JIS-R-1601.

[Equation 3]

Where σ is the three-point bending strength (MPa), P is the maximum load when the specimen breaks (N), L is the distance between supporting points (mm), w is the specimen width (mm), and t is The thickness of the test piece (mm).

The bending strength change of the produced sintered body is shown in FIG. The bending strength of the solid solution limit sample with the Mg ²⁺ ion addition amount of 18.18 mol% and the SiO ₄ ^4- ion addition amount of 14.28 mol% was 31.1 MPa. It was also observed that the bending strength increased with increasing amounts of Mg ²⁺ ions and SiO ₄ ^4- ions. Therefore, we confirmed that bending strength was improved by simultaneously dissolving Mg ²⁺ ions and SiO ₄ ^4- ions in β-TCP.

c) Measurement of open porosity and bulk density by Archimedes method

The open porosity and bulk density were measured by the Archimedes method (JIS R 1634) using pure water as a solvent. The open porosity and bulk density were obtained from the following formulas.

[Equation 4]

Where W ₁ is the dry weight of the sample (g), W ₂ is the weight of the saturated sample in water (g), W ₃ is the saturated mass of the saturated sample (g), and S is the density of pure water (1.0 g cm ^-3 ).

FIG. 28 shows the change in open porosity and FIG. 29 shows the change in bulk density of the sintered body produced by changing the addition amounts of Mg ²⁺ ions and SiO ₄ ^4- ions. The open porosity decreased and the bulk density increased with increasing amounts of Mg ²⁺ ions and SiO ₄ ^4- ions. Moreover, the open porosity was the minimum and the bulk density was the maximum in the sample with the Mg ²⁺ ion addition amount of 18.18 mol% and the SiO ₄ ^4- ion addition amount of 14.28 mol%, which was the solid solution limit. Therefore, it was confirmed that a compact with a high sintering rate can be obtained by simultaneously dissolving Mg ²⁺ ions and SiO ₄ ^4- ions in β-TCP.

d) Observation of the microstructure of the sintered body

A scanning electron microscope (SEM) (VE-7800, manufactured by KEYENCE) was used to observe the microstructure of the sintered body. For sample processing, a polishing machine (Dialap ML-150, manufactured by Marto) was used, and water-resistant abrasive paper # 200, # 400, # 800, # 1500, lapping diamond fluid MM-130, and polishing diamond MM-140 were used. The samples subjected to mirror polishing were subjected to thermal etching at a heating rate of 5 ° C./min ⁻¹ , a holding time of 5 hours, and an atmospheric atmosphere at 1200 ° C. An ion sputtering apparatus (FINE CORT FC-1100, manufactured by JEOL Ltd.) was used to deposit gold (0.75 kV, 75 mA), and this was used as a microscopic sample. The measurement conditions are shown below.

Filament: W (tungsten)
Acceleration voltage: 1 to 3 kV

The microstructure of the produced sintered body is shown in FIGS. From the microstructure observation results, compared to Mg ²⁺ ion single solid solution β-TCP, the sample to which SiO ₄ ^4- ion was added had fewer pores, and the pores of the sintered body decreased as the amount of various ions added increased. Admitted. This result is consistent with the result of measuring the open porosity and bulk density. Therefore, it was clarified that the sintered compact was made dense by dissolving Mg ²⁺ ions and SiO ₄ ^4- ions.

e) Measurement of average particle size of sintered body

The average particle size of the sintered body was determined by the intercept method based on the microstructure SEM photograph. The outline of the measuring method of the average particle diameter by the intercept method is shown below. The sintered body is an aggregate of crystal grains. When the microstructure is observed using an SEM, the size of the crystal grains appears to be different depending on the cut surface as shown in FIG. is there. First, straight lines are drawn at equal intervals on the SEM photograph, and apparent crystal particle diameters (d ₁ , d ₂ , d ₃ ,...) As shown in FIG. 34 are obtained from the intersections between these straight lines and the grain boundaries. The actual particle diameter (G _true ) was calculated by multiplying this size by a statistical correction value (π / 2). The calculation formula is [G _true = dn × C], where dn is the apparent crystal particle diameter, and C is a constant (= π / 2). More than 200 crystal particles were measured per sample.

Moreover, the average particle diameter of the sintered compact calculated | required by the intercept method based on the image | photographed SEM image of the microstructure is shown in FIG. 35, respectively. As the average particle size also increased with the addition of various ions, the particle size decreased to the solid solution limit, so grain growth was achieved by simultaneously dissolving Mg ²⁺ ions and SiO ₄ ^4- ions in β-TCP. It became clear that it was suppressed, and a high-density sintered body could be produced.

(5) Summary

So far, the mechanical properties of β-TCP sintered bodies to which Mg ²⁺ ions and SiO ₄ ^4- ions were added simultaneously have been evaluated. From the above results, a compact with a high sintering rate was obtained as the amount of Mg ²⁺ ions and SiO ₄ ^4- ion solid solution increased, and the Mg ²⁺ ion addition amount 18.18 mol% and the SiO ₄ It was confirmed that the sintered body with the ^4- ion addition amount of 14.28 mol% had the highest sintering rate and was a denser sintered body. In addition, the particle size was smaller, denser and higher in bending strength than the Mg ²⁺ ion single solid solution β-TCP sintered body. Therefore, Mg ²⁺ ions and SiO ₄ ^4- ions were dissolved in β-TCP to suppress grain growth and to obtain a dense sintered body in which brittle fracture hardly occurred.

Claims (13)

  Biomaterial ceramics composed of β-type tricalcium phosphate in which sulfate ions and cations for charge compensation are dissolved.   The biomaterial ceramic according to claim 1, wherein the cation for charge compensation is a sodium ion. 14.28 mol% or less of silicate ions (however, excluding 4 mol% or less in terms of the total phosphorus atoms that should be present when phosphate ions of β-type tricalcium phosphate are to be placed ) And β-type tricalcium phosphate ceramics in which magnesium ions are dissolved as cations for charge compensation.   Biomaterial ceramics composed of β-type tricalcium phosphate in which sulfate ions and tetravalent anions are dissolved. Tetravalent anions biomaterials ceramic according to claim 4, wherein the silicate ions. A biomaterial ceramic comprising a sintered body of β-type tricalcium phosphate according to any one of claims 1 to 5 . A biomaterial ceramic as claimed in any one of 5, biomaterials ceramic properties thereof is powder. The biomaterial ceramic according to any one of claims 1 to 5 , wherein the property is a granule. The biomaterial ceramic according to any one of claims 1 to 5 , wherein the property is a film. The method for producing a biomaterial ceramic comprising β-type tricalcium phosphate according to claim 2, synthesized by dry-mixing calcium oxide, diammonium hydrogen phosphate, sodium nitrate, and ammonium sulfate, and firing the obtained mixture. . The calcium oxide and diammonium hydrogenphosphate magnesium oxide and the silicon dioxide were dry mixed, production of the resulting mixture by firing a synthesized consisting β tricalcium phosphate according to claim 3 biomaterials Ceramics Way . After wet mixing calcium oxide, diammonium hydrogen phosphate, sodium nitrate and ammonium sulfate, a mixing step of removing the solvent ethanol from the resulting mixture,
Pulverizing the mixture obtained in the mixing step in a solvent, and then removing the solvent;
A molding process for creating a molded body by uniaxial pressure molding of the powder obtained in the grinding process,
A firing step of firing the molded body obtained in the molding step;
A β-type tricalcium phosphate sintered body production method for producing the β-type tricalcium phosphate sintered body according to claim 2. After wet mixing calcium oxide, diammonium hydrogen phosphate, magnesium oxide and silicon dioxide, a mixing step of removing the solvent ethanol from the resulting mixture,
Pulverizing the mixture obtained in the mixing step in a solvent, and then removing the solvent;
A molding process for creating a molded body by uniaxial pressure molding of the powder obtained in the grinding process,
A firing step of firing the molded body obtained in the molding step;
A β-type tricalcium phosphate sintered body manufacturing method for manufacturing the β-type tricalcium phosphate sintered body according to claim 3 .