JP5045933B2 - Porous tricalcium phosphate sintered body and method for producing the same - Google Patents

Description

  The present invention relates to a porous tricalcium phosphate sintered body and a method for producing the same, and more particularly to a porous tricalcium phosphate sintered body derived from β-type tricalcium phosphate calcined particles and a method for producing the same.

  Among ceramic materials, calcium phosphate ceramic materials are the main components of bones and teeth, have excellent biocompatibility, and are excellent in safety. Alternatively, it is widely used as a biomaterial such as dental cement.

  In particular, research and development of ceramic materials suitable for artificial bones that can be repaired and healed by repairing and repairing bone defects and voids due to diseases such as fractures and bone tumors and their treatment have been actively conducted in recent years. ing. Ceramic materials are already widely used in clinical settings, but the current ceramic materials are limited to the surface layer of the new bone after implantation, and because of insufficient strength, It has drawbacks such as a longer period until healing.

  Therefore, the living tissue quickly enters the interior, rapidly forms the tissue (new bone), has a practical mechanical strength, and naturally disappears in the living body and can be replaced with the new bone. Development is desired.

  As such a ceramic implant material, for example, a calcium phosphate having continuous spherical open pores in which a large number of pores are densely distributed three-dimensionally and adjacent pores communicate with each other in a skeleton wall portion that defines them. System sintered bodies have been proposed (Patent Documents 1, 2, etc.).

Further, in Patent Document 3, a sintered body having a diameter of 10 to 500 μm and having pores oriented and penetrating in one direction is a tricalcium phosphate sintered body suitable as an implant material. It is disclosed.
Japanese Patent No. 3400740 Japanese Patent No. 2597355 Japanese Patent No. 3858069

  However, in the methods according to Patent Documents 1 and 2, since the hole diameter of the communication hole formed of the continuous ball open hole is small and does not have orientation, in actual clinical practice, the induction of bone tissue (new bone) is sufficiently performed to the inside of the material. Not allowed.

  In addition, when the inventors made a trial of the method described in Patent Document 3 and formed a sintered body having pores oriented in one direction and penetrating, the method described in the document was sufficient. As a result, it was found that a bioabsorbable implant material having an orientation communication hole with a sufficient length and sufficient mechanical strength could not be obtained. It turned out that it cannot be a concrete and practical guideline for materials that can be replaced by autologous bone, where the liquid penetrates quickly into the interior.

  The present invention has been made in view of such circumstances, and an object thereof is to promptly induce bone tissue formation and to have a practical mechanical strength and to disappear naturally in a living body. An object of the present invention is to provide a porous tricalcium phosphate sintered body that can realize an implant material that can be replaced with new bone, and a method for producing the same.

In order to solve the above-mentioned problems, the present inventors conducted extensive research and as a result, completed the present invention having the following features.
That is, the present invention
(1) Porous tricalcium phosphate-based sintering having pores substantially oriented in one direction obtained by firing β-type tricalcium phosphate calcined particles having a particle size range of 0.1 to 25 μm body,
(2) The porous tricalcium phosphate-based sintered body according to (1), mainly comprising β-type tricalcium phosphate,
(3) The porosity is 40 to 90%, the first cut surface perpendicular to the orientation direction of the holes, and parallel to the first cut surface and the holes from the first cut surface The average value of the cross-sectional area per hole is 0.05 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² in both of the second cut surfaces separated by 5 mm in the orientation direction of the above (1) Or the porous tricalcium phosphate sintered body according to (2),
(4) The porous tricalcium phosphate sintered body according to (3), wherein the length of the pores in the long axis direction is 7 mm or more,
(5) The porous tricalcium phosphate sintered body according to any one of (1) to (4), which is for an implant material,
(6) Step (A): adjusting the particle size range of the β-type tricalcium phosphate calcined particles to 0.1 to 25 μm,
Step (B): A step of preparing a slurry by dispersing β-type tricalcium phosphate calcined particles in water,
Step (C): filling the slurry in a predetermined container, cooling one end of the slurry container, and freezing the slurry in one direction from the end side;
Step (D): drying the frozen slurry to obtain a molded body, and Step (E): firing the dried molded body,
Cooling the periphery of the slurry container other than the one end in the step (C) to a temperature higher than the freezing point of the slurry, a method for producing a porous tricalcium phosphate sintered body,
(7) The method according to (6) above, wherein the firing temperature in step (E) is 1000-1500 ° C., and (8) the above description (6), wherein the firing temperature in step (E) is 1000-1200 ° C. The method.

  In the present specification, the term “implant material” means “material to be embedded in a living body” regardless of medical use or dental use. Specifically, an artificial bone, an artificial tooth root, a bone filling material, Examples include bone replacement materials, bioresorbable fracture plates, sustained drug release materials, dental restoration materials, root canal filling materials, and artificial joints.

  According to the present invention, tissue fluids such as blood and bone marrow fluid can smoothly penetrate into the material, and the compressive strength in the direction (direction of tissue fluid penetration) and the bending strength in the direction perpendicular thereto are high, and the bioabsorbability is high. And a porous tricalcium phosphate sintered body particularly useful for implant materials such as artificial bones.

  Hereinafter, the porous tricalcium phosphate sintered body of the present invention will be described. In the following description, the porous tricalcium phosphate sintered body of the present invention is also referred to as “material of the present invention” or simply “material”.

  The porous tricalcium phosphate sintered body of the present invention is a substantially unidirectionally oriented void obtained by firing β-type tricalcium phosphate calcined particles having a particle size range of 0.1 to 25 μm. The main feature is that the porous body has pores. Here, “β-type tricalcium phosphate calcined particles” are substances obtained by calcining calcium-deficient apatite. When wide-angle X-ray diffraction analysis is performed, β-type tricalcium phosphate (β-TCP) is obtained. Identified.

  The porosity of the material of the present invention is preferably 40 to 90%, more preferably 50 to 90%, still more preferably 60 to 90%. If the porosity is 40% or more, a lot of blood, bone marrow fluid, etc. are impregnated in the material, so that sufficient formation of bone tissue is expected. On the other hand, if the porosity is 90% or less, the porous tricalcium phosphate sintered body can ensure the strength as an implant material.

The porosity is measured according to JIS R 1634. Specifically, it is as follows. A cylindrical test piece having a diameter of 5 mm and a height of 7.5 mm is cut out from the sintered body to be evaluated. The weight and volume of the test piece are measured, and the porosity is calculated from the following formula.
Bulk density = (weight of specimen) / (volume of specimen)
Porosity = (1−bulk density / 3.07) × 100

  FIG. 1 is a schematic view of a porous tricalcium phosphate sintered body of the present invention. In the material of the present invention, the pores 12 are oriented in one direction as shown in FIG. The void 12 is a region in the sintered body 11 where there is no ceramic material and is a space. The arrangement of the holes in one direction means that there are a plurality of holes extending in the uniaxial direction and the major axis directions of such holes are substantially aligned in one direction. More specifically, for example, more than half of the uniaxially extending holes in the sintered body, preferably 80% or more of the long axis directions of the holes are aligned within a range of, for example, an angle of 30 ° or less. . Here, the “angle” is an intersection angle of the normal projection of the long axis of the hole to an arbitrary plane.

The cross-sectional area perpendicular to the orientation direction of each hole is preferably 0.05 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² , more preferably 10 × 10 ^{−3 to} 100 × 10 ⁻³ mm ^2. It is. Within the above range, tissue fluids such as blood and bone marrow fluid can easily pass through by capillary action, and excellent tissue fluid permeability can be obtained. However, in order to achieve the object of the present invention, it is not always necessary that all the holes in the material have the cross-sectional area. In order for cells or the like contained in tissue fluid such as blood or bone marrow fluid to enter the material, the minor axis of the pores in the cross section perpendicular to the orientation direction is at least 10 μm, preferably 20 μm, more preferably 30 μm or more. Preferably there is.

  The length of the air holes in the major axis direction is preferably 7 mm or more, and more preferably 10 mm or more. The upper limit of the length is not particularly limited. If the hole has a sufficient length, the implant material can be easily obtained by cutting or the like. However, in order to achieve the object of the present invention, it is not always necessary that all the holes in the material have the above length.

In a preferred embodiment, the cross-sectional area of the holes perpendicular to the orientation direction is 0.05 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² over a length of at least 5 mm in the orientation direction, more preferably 10 × 10 ^−3. ˜100 × 10 ⁻³ mm ² . In this case, practically good penetration of blood, bone marrow fluid, etc. can be achieved over a sufficient length.

  The length of the pores in the major axis direction is determined by embedding the porous tricalcium phosphate sintered body to be measured in a resin, slicing it parallel to the orientation axis direction of the pores, and using a microscope or the like. The major axis (major axis) of the opening derived from the target hole is sequentially measured.

  In addition, the cross-sectional area of the pores is measured by embedding the porous tricalcium phosphate sintered body to be measured in a resin, slicing it perpendicular to the orientation axis direction, and observing it with a microscope, etc. The opening area derived from the holes to be measured is sequentially measured. At this time, by cutting out the material to be measured every 1 mm and measuring the opening area in each cross section, the transition of the cross-sectional area of the hole over the length direction of the hole orientation was suitable for the purpose of the present invention. Can be evaluated with accuracy.

  As described above, when the opening area of the hole is measured in the thin piece obtained by cutting out the material every 1 mm in the arrangement direction of the holes, the length of change of the opening area of the hole is 5 mm (that is, the smallest). The ratio of the maximum value to the minimum value of the opening area in the five continuous slices) is preferably within 10 times, more preferably within 5 times. In this way, when the opening area derived from the pores, that is, the cross-sectional area of the pores is less fluctuated across the orientation direction, the penetration of blood and bone marrow fluid into the material due to capillary action becomes smoother, and as an implant material preferable. Furthermore, since the ceramic layers forming the pores (walls between adjacent pores) are arranged substantially in parallel within the above range, the porous tricalcium phosphate sintered body having excellent strength Is provided.

The first cut surface perpendicular to the orientation direction of the pores of the porous tricalcium phosphate sintered body, and the orientation direction of the pores from the first cut surface parallel to the first cut surface Pay attention to the second cut surface, which is 5 mm apart. Preferably, there is an opening having an opening area of 0.05 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² in both the first cut surface and the second cut surface. If both the first cut surface and the second cut surface have an opening area and a frequency within a preferable range, it is expected that a suitable hole exists in the material. More preferably, there is an opening having an opening area of 10 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² in both the first cut surface and the second cut surface.

Preferably, the average value of the opening area of the holes is 0.05 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² in both the first cut surface and the second cut surface, and more preferably. Is 10 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² . The average value is obtained by embedding a porous tricalcium phosphate sintered body to be measured in a resin, slicing it perpendicular to the orientation axis direction, observing it with a microscope or the like, and measuring 0.7 mm square. The opening area of the holes in the range is measured, and the average value of the opening areas of the holes is obtained.

Moreover, in a particularly preferable aspect, the average value of the opening area of the holes is 0.05 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² (more than the above-described first cut surface and second cut surface. Preferably, it is 10 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² ). With this embodiment, better tissue fluid permeability can be obtained, and the mechanical strength of the material is further improved.

  As for the strength of the material of the present invention, the compressive strength in the direction parallel to the holes oriented in one direction is preferably 5 MPa or more, more preferably 10 MPa or more, and further preferably 15 MPa or more. If the compressive strength is less than 5 MPa, the mechanical strength as an implant material may be insufficient. The upper limit of the compressive strength is not particularly limited, and a compressive strength of 50 MPa or more can be realized. However, the upper limit of the compressive strength is preferably about 200 MPa or less in consideration of the strength of the bone itself of a healthy site adjacent to the affected area to be implanted. The compressive strength is measured by the following method.

[Method of measuring compressive strength]
Conforms to JIS R 1608. However, the test piece used was a cylindrical test piece having a diameter of 5 mm and a height of 7.5 mm.

The material of the present invention is a porous tricalcium phosphate sintered body obtained by sintering calcined particles of β-type tricalcium phosphate, and β-type tricalcium phosphate having a particle size range of 0.1 to 25 μm. By using calcined particles, the above-mentioned pore characteristics particularly suitable for implant materials (porosity, orientation of uniaxially oriented pores in one direction, longitudinal direction of uniaxially oriented pores) It is possible to realize a porous tricalcium phosphate sintered body having such a preferable compressive strength while having a cross-sectional area uniformity in FIG. That is, even if β-type tricalcium phosphate calcined particles are used as the raw material, if the particle size range is not adjusted to the range of 0.1 to 25 μm, the obtained sintered body is the length of the pores. The cross-sectional area uniformity in the direction is reduced and the pore length (major axis length) is not sufficiently long, and the material has a particle size range of 0.1. When using calcium deficient apatite particles that have been adjusted to a range of ˜25 μm and have not been calcined, even if the sintered body itself in which the uniaxially oriented pores are oriented in one direction cannot be formed, In the obtained sintered body, the uniformity of the cross-sectional area in the longitudinal direction of the pores is reduced, or the area of the cross section perpendicular to the orientation direction of the pores extending in the uniaxial direction (cross section perpendicular to the long axis) is 100 ×. beyond 10 ^-3 mm ^2, to obtain only the pores of large diameter Scratches, the sintered body is not obtained only having low compressive strength.

  Hereinafter, the manufacturing method of the porous tricalcium phosphate sintered body of the present invention will be described. FIG. 2 shows an example of a method for producing the porous tricalcium phosphate sintered body of the present invention. As shown in FIG. 2, the method for producing the material of the present invention includes a step of adjusting the particle size range of β-type tricalcium phosphate calcined particles to 0.1 to 25 μm (step A), and β-type triphosphate phosphate. A step of preparing a slurry by dispersing calcium calcined particles in water (step B), and a freezing step of freezing the obtained slurry from one direction (arrow direction in the drawing) to grow frosted columnar ice (step C) ), A freeze step of freeze-drying the frozen slurry to sublimate the ice to form a molded body having macropores (step D), and firing the molded body with sublimated ice by heat treatment to form the molded body It has a firing step for forming micropores in the skeleton and (Step E).

Hereinafter, each process will be described in detail.
First, β-type tricalcium phosphate calcined particles can be obtained by calcining calcium deficient apatite (raw material powder) after drying by a known drying method such as air drying or reduced pressure drying. Here, the calcium deficient apatite may be derived from natural minerals, or may be synthesized by various wet methods, dry methods and the like. Further, a part of the Ca component is one or more selected from Sr, Ba, Mg, Fe, Al, Y, La, Na, K, Ag, Pd, Zn, Pb, Cd, H, and other rare earths. May be substituted. A part of the (PO ₄ ) component may be substituted with one or more selected from VO ₄ , BO ₃ , SO ₄ , CO ₃ , SiO ₄ and the like. By performing calcination at the raw material powder stage, it is possible to suppress the formation of voids due to the crystal structure change during the main baking (step E). The calcination temperature is preferably equal to or higher than the temperature at which the crystal structure of the raw material powder is equivalent to the crystal structure of β-TCP in the wide-angle X-ray diffraction analysis and lower than the temperature at the final firing. Specifically, it is preferably 1000 ° C. or lower, more preferably 750 ° C. or higher and 1000 ° C. or lower. Although the calcination time depends on the calcination temperature, it is usually preferably about 1 to 12 hours. In the present invention, “calcination” means a heat treatment that forms a crystal structure equivalent to β-TCP and generates particles having sintering activity by firing at a temperature lower than the final firing temperature. To do.

  The β-type tricalcium phosphate obtained by calcination is pulverized by a known pulverizing and granulating means and classified by a known classifying means such as a sieve, and the β-type phosphoric acid having a particle size range of 0.1 to 25 μm. Tricalcium calcined particles are obtained (step A).

  FIG. 2 (A) schematically shows the preparation of the slurry in Step B. The slurry 21 can be prepared by dispersing β-type tricalcium phosphate calcined particles having a particle size range of 0.1 to 25 μm in water. The slurry 21 is preferably dissolved or dispersed in the additives described below.

  The β-type tricalcium phosphate calcined particles having a particle size range of 0.1 to 25 μm are well dispersed in the slurry 21. As a result, a stable slurry is obtained, and a homogeneous porous tricalcium phosphate-based calcined particle is obtained. A knot is obtained.

  For the purpose of increasing the viscosity of the slurry 21 to improve the dispersibility of the slurry and, as a result, maintaining the shape of the molded body before sintering and controlling crystal grain growth during sintering, You may use at the time of preparation. An additive will not be specifically limited if it is a compound and composition which can achieve the said objective. Preferably, the additive is an organic substance that burns during sintering. In this case, since the component derived from an additive does not remain substantially in the porous tricalcium phosphate sintered body obtained after sintering, it is excellent in safety. As such an additive, for example, those having one or more amino groups, carboxyl groups, carbonyl groups and hydroxyl groups are preferable. Specifically, monosaccharides (glucose, fructose, galactose, ribose, deoxy-ribose) are preferred. Etc.), disaccharides (maltose, cellobiose, sucrose, etc.), oligosaccharides or derivatives thereof, polysaccharides (cellulose, starch, amylopectin, chitin, chitosan, dextran, etc.) or derivatives thereof (dextran esters, etc.), polyethylene glycol, polyvinyl alcohol Gelatin, polylactic acid and the like can be mentioned, and from the viewpoint of viscosity and dispersibility of the resulting slurry, polyethylene glycol, polyvinyl alcohol, gelatin, polylactic acid, polyacrylamide and salts thereof are preferable. These additives may be used alone or in combination of two or more. In addition, you may add components other than an above-described component to the slurry 21 as needed within the range which does not inhibit the objective of this invention.

  The slurry 21 can be prepared by a known method. Typically, it is preferable that the slurry 21 is prepared by adding the β-type tricalcium phosphate calcined particles and the additive while stirring water, and the slurry 21 is defoamed. In this case, bubbles do not remain in the slurry, and as a result, it is difficult to form undesired holes (defects) due to the bubbles in the sintered body. As a method of defoaming treatment, a known method may be used, and examples thereof include a method of defoaming while stirring in vacuum, a method of defoaming by planetary kneading, and the like.

  FIG. 2B and FIG. 2C schematically represent a step of freezing the slurry in the container (step C). In step C, the slurry 21 obtained in step B is filled in a container 31, and the slurry 21 is frozen in one direction from one end side of the container 31 to obtain a porous ceramic molded body. Specific means for freezing the slurry 21 in one direction includes intensive cooling of the vicinity of one end of the container 31 to a temperature below the temperature at which the slurry 21 can be frozen. A specific apparatus for this will be described later. As a result of such freezing, frosted columnar ice grows in the molded body and is oriented in one direction. At this time, the periphery of the container 31 filled with the slurry 21 other than the one end is cooled to a temperature higher than the freezing point of the slurry 21. A white arrow in FIG. 2C schematically represents cooling the periphery of the slurry container 31 as described above.

FIG. 4 is a schematic diagram of an example of a freezing apparatus that can be used for freezing.
The slurry container 31 containing the raw material slurry is on the sample table 41, the sample table 41 is on the cooling plate 75, and the cooling plate 75 is in contact with a cooling medium 73 such as liquid nitrogen. Connected. The cooling medium 73 is contained in the cooling medium container 72. On the other hand, a cooling device 76 is provided above the slurry container 31, and a cooling medium 77 is accommodated in the cooling device 76.

  In this freezing device 71, the slurry is frozen in one direction upward from the side where the container 31 is in contact with the sample table 41. In a preferred embodiment of the present invention, one end of the slurry container is cooled to cool the periphery of the slurry container other than the end when the slurry is frozen in one direction. As a result of the cooling, the temperature at a location 1 mm away from the slurry container 31 in the direction in which the through holes are oriented is higher than the freezing point of the slurry and 15 ° C or lower, more preferably higher than the freezing point of the slurry and 10 ° C or lower, More preferably, the temperature is set to -15 to 5 ° C. Note that the freezing point of the slurry can be easily measured by using differential scanning calorimetry (DSC).

  In this way, by cooling the periphery of the slurry container to a temperature higher than the freezing point of the slurry while freezing the slurry in one direction, the columnar ice in which the water contained in the slurry is long and oriented in one direction (frost columnar ice) As a result, it is possible to obtain a porous sintered body having pores that extend in one direction and have little change in the cross-sectional area in the longitudinal direction. The freezing rate of the slurry at that time is preferably 1.0 ml / min or less, and more preferably 0.1 ml / min or less.

  The sample stage 41 is preferably made of a metal having excellent thermal conductivity, such as brass or stainless steel. In order to control the growth of frost column-shaped ice, a sample stand having a sea-island structure that is partially filled with a heat insulating material having a lower thermal conductivity than the metal plate to be formed may be used as the sample stand 41. The method for producing such a sea-island structure-like sample stage is not particularly limited, but the sample stage is formed with a groove that is a recess on the surface of the flat plate, and the groove is filled with a heat insulating material such as an epoxy resin having a low thermal conductivity. And a method of producing by curing. In addition, as a method of forming a groove that is a recess on the surface of a flat plate, a groove that is a recess is formed by pressing or etching a thermally conductive material plate such as metal by cutting. A method for forming the film can be considered.

  The cooling medium 73 is not particularly limited as long as it is a medium that can cool the end portion of the container 31 to a solidification point or less of the slurry. Specific examples include alcohol and liquid nitrogen. In order to control the cooling rate of the cooling surface and to keep the cooling temperature constant, a cooling medium may be added as appropriate.

  The container 31 is preferably formed of a heat insulating material such as vinyl chloride resin, silicone resin, fluorine resin, or styrene resin so that the slurry does not freeze from the side wall side of the container 31. The thickness of the side wall 33 of the container 31 is preferably 0.5 mm or more. In this case, it becomes difficult for the contained slurry to freeze from the portion in contact with the side wall, and the structure of ice in the form of frost columns arranged in one direction is neatly arranged.

  All three of the sample table 41, the cooling plate 75, and the heat transfer rod 74 or any two of them are preferably integrally formed of a material having excellent heat conductivity such as metal. It may be formed by joining excellent different materials. Since FIG. 4 is a schematic diagram, the diameter of the heat transfer rod 74 is not limited to the mode described in the drawing. The heat transfer rod 74 may be composed of a plurality of columnar members. If the heat transfer rod 74 is composed of a plurality of columnar members, the cooling plate 75 and the sample stage 41 can be cooled more uniformly.

  In step D, the frozen slurry is dried to obtain a molded body. Typically, the container containing the slurry is lyophilized under reduced pressure. By this operation, frost column-shaped ice is sublimated, and the portion where the ice was present becomes a hole as a sublimation mark. As a result, pores oriented in one direction are formed in the molded body. FIG. 3 is a schematic cross-sectional view of a frozen slurry (FIG. 3A) and a molded body after drying (FIG. 3B). The frozen slurry has ceramic raw material particles 51 and ice 61 arranged substantially in one direction. After drying, holes 62 are formed in the area where the ice 61 was present.

  In step E, the obtained molded body is fired to obtain a sintered body. Typically, the molded body obtained in Step D is carefully extracted from the container 31 and fired at a temperature and time suitable for the β-type tricalcium phosphate calcined particles. When firing, the mechanical strength of the obtained sintered body is suitable for embedding in the living body, that is, it can be processed at the operation site, etc., and is damaged after insertion into the living body. It is desirable to determine the conditions so as to prevent the occurrence of Such conditions can be appropriately determined in consideration of the calcining conditions of the β-type tricalcium phosphate calcined particles, the porosity of the porous body, the average pore diameter, the orientation of the pores, and the like. Although it does not specifically limit as an energy source used for baking, A heat | fever, a microwave, etc. are generally used. Generally, the firing temperature is preferably 1000 to 1500 ° C, and preferably 1050 to 1400 ° C. If the firing temperature is less than 1000 ° C., densification by sintering does not proceed sufficiently and the strength tends to be low, and if it exceeds 1500 ° C., the crystal structure of tricalcium phosphate tends not to be maintained due to melting or phase transition. It becomes. The firing time is generally about 1 to 8 hours. Here, from the viewpoint of making the sintered body of the final product more excellent in bioabsorbability, the β-TCP crystal structure of the β-type tricalcium phosphate calcined particles is probably the crystal structure of the sintered body. From this viewpoint, the firing temperature is preferably 1000 to 1200 ° C, more preferably 1000 to 1100 ° C. When the firing temperature is 1000 to 1200 ° C., the obtained sintered body is entirely composed of a β-TCP phase or becomes a eutectic in which a β-TCP phase and a very small amount of α-TCP phase are mixed, By sintering at 1100 ° C., a sintered body consisting entirely of β-TCP phase is obtained. When the firing temperature is 1250 to 1500 ° C., the β-TCP crystal structure of the β-type tricalcium phosphate calcined particles becomes α-TCP due to phase transition, and the sintered body is substantially entirely made of α-TCP. Become.

  By passing through the above process, a porous sintered body having frost column-shaped ice sublimation marks as pores is produced. This hole is a continuous hole penetrating the sintered body, preferably in one direction, in accordance with the above-mentioned sublimation mark.

The porous tricalcium phosphate sintered body of the present invention is preferably molded into a desired shape and sterilized.
The method for forming the block body is not particularly limited, and a known method may be used. Specific examples include a molding method by machining, a dry molding method, and a wet molding method. Since porous tricalcium phosphate sintered bodies are generally hard and brittle materials, conventional porous tricalcium phosphate sintered bodies with non-uniform ceramic layer thickness have extremely low machinability. It was. In the porous tricalcium phosphate sintered body of the present invention, since the pores are oriented in one direction and the pore diameter is substantially uniform as described above, the through-holes and the through-holes The thickness of the ceramic layer in between is also almost uniform. Therefore, superior machinability is exhibited as compared with the conventional porous tricalcium phosphate sintered body.

  Also, the method of forming into granules is not particularly limited, and a known method may be used. Specific examples include mechanical grinding such as a mold grinder, ball mill, jaw crusher, hammer crusher, and grinding in a mortar. Moreover, you may arrange | equalize a particle size by sieving the pulverized porous tricalcium phosphate sintered body.

  The method for sterilizing the material is not particularly limited, and a known method may be used. Specific examples include high-pressure steam sterilization (autoclave), γ-ray sterilization, EOG sterilization, and electron beam sterilization. Among them, the high-pressure steam sterilization method is widely used as the most general sterilization method.

  The porous tricalcium phosphate sintered body thus obtained has excellent biocompatibility, sufficient strength to be embedded in the living body, and bioabsorbability as described above. It is useful as a medical or dental implant material such as an artificial tooth root.

  Furthermore, for the purpose of inducing bone tissue at a higher level, bone tissues such as transforming growth factor (TGF-β1), osteoinductive factor (BMP-2), and bone morphogenetic factor (OP-1) are used. A substance having an action of promoting growth may be impregnated, adsorbed and immobilized in the porous tricalcium phosphate sintered body of the present invention.

[Measurement method of porosity]
The porosity was measured as follows. A cylindrical test piece having a diameter of 5 mm and a height of 7.5 mm is cut out from the porous tricalcium phosphate sintered body to be evaluated. The weight and volume of the test piece were measured, and the porosity was calculated from the following formula. In addition, the theoretical density in a formula is a theoretical density of the tricalcium phosphate type compound which comprises a sintered compact.
Bulk density = (weight of specimen) / (volume of specimen)
Porosity = (1-bulk density / theoretical density) × 100

[Measurement method of opening area]
The tricalcium phosphate sintered body to be measured is embedded in a resin, sliced perpendicular to the orientation axis direction, and observed with a scanning electron microscope. Were measured in order. In addition, 20 holes were selected at random, and the area of each opening (20 openings) derived from the 20 holes was measured, and the average was taken as the opening area.

[Measurement method of hole length]
The tricalcium phosphate sintered body to be measured is embedded in resin, sliced in parallel with the orientation axis direction, and observed with a scanning electron microscope to determine the major axis of the opening derived from the pores. It measured in order. In addition, ten holes were selected at random, the major axis of each of the openings derived from the ten holes (10 openings) was measured, and the average was taken as the length of the hole.

[Method of measuring compressive strength]
Conforms to JIS R 1608. However, the test piece used was a cylindrical test piece having a diameter of 5 mm and a height of 7.5 mm.

[Granularity adjustment (classification) method]
The β-type tricalcium phosphate calcined particles were pulverized with a mortar and pestle and then classified on a metal sieve having an opening of 25 or 125 μm.

[Measurement method of average particle diameter]
The calcined powder was dispersed in water, and the particle size distribution was measured by a laser diffraction method. The measurement conditions are an ultrasonic irradiation time of 10 seconds and a measurement count of 32 times. The average particle size was calculated by the following formula (Equation 1). The average particle size was calculated as 10 ^μm .

[Example 1]
Calcium-deficient apatite synthesized from calcium hydroxide and phosphoric acid is calcined at 800 ° C. for 1 hour, and then classified with a sieve having an opening of 25 μm. (Average particle diameter = 2.199 μm) was obtained. A slurry 21 in which the particles were dispersed and dissolved in distilled water together with gelatin as an additive in the composition shown in Table 1 was filled in a container 31 made of vinyl chloride resin having a diameter of 16 mm and a height of 20 mm. Ten containers 31 were arranged on a disk-shaped cooling plate 75 having a diameter of 120 mm, and cooled at a rate of 0.015 ml / min by the refrigeration apparatus 71 shown in FIG. 4 to generate frosted columnar ice in the slurry. At that time, the side surface of the refrigeration apparatus was cooled with a refrigerant so that the temperature in the vicinity of the slurry (temperature at a location 1 mm away from the slurry container 31 in the direction in which the through holes were oriented) was the temperature shown in Table 1. The frozen body thus obtained is sublimated and dried in a vacuum, and then the dried body is fired at 1100 ° C. for 6 hours, whereby a high-strength porous tricalcium phosphate system having oriented pores A sintered body was obtained. About the physical-property value, it measured by the above-mentioned method.

[Comparative Example 1]
Three-phosphate phosphate as in Example 1 except that β-type tricalcium phosphate calcined particles (average particle size: 24.028 μm) having a particle size range of 0.1 to 125 μm classified by a sieve having a mesh opening of 125 μm were used. A calcium-based sintered body was prepared and its physical property values were measured.

[Comparative Examples 2 and 3]
A porous tricalcium phosphate sintered body was prepared in the same manner as in Example 1 except that calcium-deficient apatite particles that were not calcined were used, and the physical properties thereof were measured.

  Production conditions and evaluation results of the porous tricalcium phosphate sintered bodies of the examples and comparative examples are shown in Tables 1 to 3. In Table 2, the first cut surface and the second cut surface are both perpendicular to the orientation direction of the holes, and the distance between the two cut surfaces is 5 mm.

  5 and 6 are SEM observation images of a cross section of the material of Example 1. FIG. FIG. 5 is an observation image of a cross section perpendicular to the orientation direction of vacancies, and FIG. 6 is an observation image of a cross section parallel to the orientation direction of vacancies. In FIG. 6, the presence of pores over a length of 10 mm or more can be seen.

FIG. 7 is an SEM observation image of a cross section of the material of Comparative Example 1.
Since large particles (about 30 μm or more) have settled near the bottom, the voids are occupied by the particles, and uniform voids are not formed.

FIG. 8 is an SEM observation image of a cross section of the material of Comparative Example 2.
No communication hole is formed

9 and 10 are SEM observation images of a cross section of the material of Comparative Example 3. FIG. FIG. 9 is an observation image of a cross section perpendicular to the orientation direction of vacancies, and FIG. 10 is an observation image of a cross section parallel to the orientation direction of vacancies.
Holes oriented in one direction with a large cross-sectional area are formed.

It is a schematic diagram of the porous tricalcium phosphate sintered body of the present invention. An example of the manufacturing method of the porous ceramic material of this invention is shown. It is a schematic cross section of the frozen slurry (FIG. 3A) and the molded body after drying (FIG. 3B). It is a schematic diagram of an example of the freezing apparatus which can be used for freezing. 2 is an SEM observation image of a cross section of the material of Example 1. FIG. 2 is an SEM observation image of a cross section of the material of Example 1. FIG. 3 is a SEM observation image of a cross section of the material of Comparative Example 1. 6 is a SEM observation image of a cross section of the material of Comparative Example 2. 10 is a SEM observation image of a cross section of the material of Comparative Example 3. 10 is a SEM observation image of a cross section of the material of Comparative Example 3.

Explanation of symbols

DESCRIPTION OF SYMBOLS 11 Porous tricalcium phosphate sintered body 12 Hole 21 Slurry 31 Container 41 Sample stand 51 Ceramic raw material particle 61 Ice 62 Hole

Claims (3)

Particle size range is obtained by firing the β tricalcium phosphate calcined particles 0.1～25Myuemu, substantially met porous tricalcium phosphate-based sintered body having pores unidirectionally oriented And
The porosity is 40 to 90%, the first cut surface perpendicular to the orientation direction of the pores, and the orientation direction of the pores from the first cut surface that is parallel to the first cut surface The average cross-sectional area per hole is 0.05 × 10 ^{−3 to} 100 × 10 ⁻³ mm ² in both of the second cut planes 5 mm apart from each other,
The length of the hole in the long axis direction is 7 mm or more,
A porous tricalcium phosphate sintered body, wherein the porous tricalcium phosphate sintered body has a compressive strength in a parallel direction with respect to pores oriented in one direction of 10 MPa or more . A implant material according to claim 1 Symbol placing porous tricalcium phosphate-based sintered body. Step (A): adjusting the particle size range of the β-type tricalcium phosphate calcined particles to 0.1 to 25 μm,
Step (B): A step of preparing a slurry by dispersing β-type tricalcium phosphate calcined particles in water,
Step (C): filling the slurry in a predetermined container, cooling one end of the slurry container, and freezing the slurry in one direction from the end side;
Step (D): including drying the frozen slurry to obtain a molded body, and Step (E): firing the dried molded body at 1000 to 1200 ° C.
In the step (C), the periphery of the slurry container other than the one end is cooled to a temperature higher than the freezing point of the slurry.