JP4420662B2 - Method for producing porous calcium phosphate ceramic sintered body and molding die used therefor - Google Patents

Description

  The present invention relates to a method for producing a porous calcium phosphate ceramic sintered body and a molding die used therefor.

  Calcium phosphate ceramics such as hydroxyapatite are excellent in biocompatibility, and are used as carriers used for culturing cells, living tissues and the like, and as biomaterials such as artificial tooth roots and bone reinforcing materials. From the viewpoint of mechanical strength, the calcium phosphate ceramics are better as they are denser, but from the viewpoint of biocompatibility, they are better as they are more porous, that is, higher in porosity. For this reason, various methods such as a foaming agent addition method, a thermally decomposable resin bead addition method, a sponge resin impregnation method, and a water-soluble polymer gelation method have been proposed as methods for producing porous calcium phosphate ceramics. Yes.

  The foaming agent addition method is a method in which a foaming agent such as hydrogen peroxide is added to a slurry of hydroxyapatite and foamed to make it porous. However, there is a limit to the porosity, and there is a uniform porosity for each product lot. There is a problem that it is difficult to control the pore diameter and the porosity. The thermally decomposable resin bead addition method is, for example, a method in which a thermally decomposable resin bead is added to and mixed with a slurry of hydroxyapatite, and after molding and drying, the resin is burned off by heating to make it porous. However, since the resin beads do not shrink during drying, there is a problem that the molded body is distorted or cracked. In addition, since a large amount of resin beads are used, firing takes time and a large amount of carbon dioxide is generated. There is a problem of doing. Moreover, the porosity of the resulting porous ceramic is at most about 50%. Furthermore, the sponge resin impregnation method is widely used as a method for producing porous ceramics. However, since the porosity is defined by the porosity of the sponge, the porosity is at most about 75%, and a desired fineness is obtained. It is not possible to obtain porous calcium phosphate ceramics having various pores.

  In contrast to these methods, Patent No. 3058174 (Patent Document 1) causes foaming by stirring a slurry of ceramics and a water-soluble polymer compound, and gels by heating the foamed slurry, Disclosed is a water-soluble polymer gelation method in which air bubbles are held and dried. The porous ceramic obtained by this method is a three-dimensional communication hole formed by a gap between a spherical macropore having a pore diameter of 20 to 2000 μm derived from bubbles and a spherical secondary particle powder composed of aggregates of primary particles of ceramic raw material. And have. However, as the required level of biocompatibility for porous calcium phosphate ceramics increases, porous calcium phosphate ceramics having a higher porosity than the porous calcium phosphate ceramics obtained by the method of Patent Document 1 are required. It has become.

  Japanese Patent Laid-Open No. 2002-179478 (Patent Document 2) discloses that a slurry containing a calcium phosphate ceramic powder, a water-soluble polymer, and a nonionic surfactant is foamed by vigorous stirring, and has a high porosity. A method for obtaining a calcium phosphate ceramic sintered body is disclosed. However, this method is not sufficient in terms of production efficiency when producing biomaterials such as sheets and pellets.

  When the porous calcium phosphate ceramic sintered body is used as a sheet, pellet or the like, the sheet, pellet or the like is usually cut out from the block of the hydroxyapatite porous body with a machine. However, producing sheets, pellets and the like by this method is not only troublesome, but also has a problem that yield is poor and cost is high. Further, since the hydroxyapatite porous body is formed in a block shape, the porosity of the porous body is not improved, and it is not suitable for producing sheets, pellets and the like having a porosity of 80 to 97%.

Japanese Patent No. 3058174 JP 2002-179478 A

  Accordingly, an object of the present invention is to produce a porous calcium phosphate ceramic sintered body having a high porosity and a mold used therein, particularly a sheet-like or pellet-like porous calcium phosphate ceramic sintered body with high productivity. It is providing the manufacturing method of the porous calcium-phosphate type ceramic sintered compact which can be used, and the shaping | molding die used for it.

  As a result of diligent research in view of the above object, the present inventor has developed a slurry containing a calcium phosphate ceramic powder into a mold in which a pair of microporous resin sheets are opposed to each other via a mold. It was discovered that a porous calcium phosphate ceramic sintered body having a high porosity such as a sheet or pellet can be obtained with high productivity by injecting, gelling, and sintering after drying. I thought.

  That is, the method for producing a porous calcium phosphate ceramic sintered body of the present invention is a method for producing a porous calcium phosphate ceramic sintered body having a porosity of 80% or more, and includes (1) a calcium phosphate ceramic powder. (2) The slurry is poured into a mold formed by facing a pair of microporous resin sheets through a mold, (3) gelled, and (4) baked after drying. It is characterized by tying. It is preferable to provide a network structure on the back surface of the microporous resin sheet.

  The microporous resin sheet preferably passes air and water vapor and does not pass water as a liquid. The pore diameter of the microporous resin sheet is preferably 0.4 nm to 100 μm, and the microporous resin sheet is preferably stable at 80 to 100 ° C. Moreover, it is preferable not to densify the surface of the porous calcium phosphate ceramics after gelation and drying by using the microporous resin sheet.

  Air is preferably injected into the slurry during the foaming treatment, and an anionic or nonionic surfactant is preferably added to the slurry. As the nonionic surfactant, a fatty acid alkanolamide surfactant is preferable, and as the anionic surfactant, an alkyl ether sulfate salt is preferable. When adding air and a surfactant to the slurry, a double tube structure injection tube may be used, the anion or nonionic surfactant may be injected from the inner tube, and air may be injected from the outer tube. A water-soluble polymer compound may be added to the slurry. The temperature during the foaming treatment of the slurry is preferably maintained at 5 to 20 ° C. The slurry can be formed into a sheet or pellet to obtain a porous calcium phosphate ceramic sintered body in the form of a sheet or pellet.

  The calcium phosphate ceramic powder is preferably made of hydroxyapatite, and is preferably secondary particles having an average particle diameter of 5.0 to 100 μm made of primary particles of calcium phosphate ceramic having an average particle diameter of 100 nm or less.

  The forming die for porous calcium phosphate ceramic sintered body of the present invention has a mold for injecting slurry containing calcium phosphate ceramic powder and a pair of microporous resin sheets, and the pair of microporous resin sheets It is characterized by being made to oppose a quality resin sheet through the said formwork.

  It is preferable that a network structure is provided on the back surface of the microporous resin sheet. The mold preferably has at least one through hole whose opening is in contact with the microporous resin sheet. The mold is preferably made of silicone rubber or fluororubber so that the thickness does not change during heating. The microporous resin sheet preferably allows air and water vapor to pass therethrough and does not pass water as a liquid. The microporous resin sheet preferably has a pore diameter of 0.4 nm to 100 μm. By using such a microporous resin sheet, the slurry can be molded while retaining the moisture of the slurry, and gelled by heating. The microporous resin sheet is preferably made of a fluorine resin or a polyolefin resin.

  The method for producing a porous calcium phosphate-based ceramic sintered body of the present invention comprises the step of foaming a slurry containing calcium phosphate-based ceramic powder, and a pair of microporous resin sheets facing each other via a mold. Since the resulting dried body is sintered, a porous calcium phosphate ceramic sintered body having a high porosity can be produced with high productivity. Therefore, it is particularly suitable for the production of biological materials such as carriers and bone filling materials used for culturing cells and biological tissues.

  The mold of the porous calcium phosphate ceramic sintered body of the present invention is gelled in the mold by using a microporous resin sheet that allows air and water vapor to pass through but does not pass water as a liquid. Can do. Therefore, porous calcium phosphate ceramics having a desired shape such as a sheet shape or a pellet shape can be directly formed.

[1] Porous calcium phosphate ceramic sintered body
(1) Composition The calcium phosphate-based ceramic sintered body contains calcium phosphate-based ceramic powder having a Ca / P mass ratio of preferably 0.8 to 2.0, more preferably 1.6 to 1.7. When the Ca / P mass ratio is less than 0.8, the ratio of tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ] increases, and when it exceeds 2.0, a mixed phase with calcium oxide (CaO) is formed. A preferred example of the porous calcium phosphate ceramic sintered body to which the present invention is applied is a porous hydroxyapatite sintered body [Ca ₁₀ (PO ₄ ) _6. (OH) ₂ ].

(2) Porosity The porous calcium phosphate ceramic sintered body produced by the method of the present invention has a porosity of 80% or more. Since it has a high porosity of 80% or more, the porous calcium phosphate ceramic sintered body has an extremely high biocompatibility. The upper limit of the porosity is preferably about 97% from a practical viewpoint. A porous calcium phosphate ceramic sintered body having a porosity of more than 97% is inferior in workability and handling properties due to insufficient mechanical strength.

  The porous calcium phosphate ceramic sintered body has pores composed of communication holes. The pore diameter is preferably 5 μm to 10 mm. If the pore diameter is less than 5 μm, it becomes difficult to form cells or blood vessels, and if it exceeds 10 mm, it is difficult to obtain a stable mechanical strength, and the fluctuation range of workability and handling properties is large for each product lot. Too much. Since the pore diameter in the porous calcium phosphate ceramic sintered body is preferably uniform, most (80% or more) of the pores are preferably in the range of 50 to 500 μm.

[2] Manufacturing Method The manufacturing method of the present invention will be described in detail below by taking a porous hydroxyapatite sintered body as an example, but the present invention can also be applied to other calcium phosphate ceramic sintered bodies.

(1) Preparation of slurry Hydroxyapatite is used as the calcium phosphate ceramic powder, and a slurry containing preferably 5 to 50% by mass of hydroxyapatite powder is prepared.

(a) Hydroxyapatite powder The hydroxyapatite powder is a secondary particle having an average particle diameter of primary particles having an average particle diameter of 100 nm or less, preferably 5.0 to 100 μm, more preferably 5.0 to 30 μm. When the average particle size of the secondary particles is less than 5.0 μm, it separates from water when mixed with water, and when the average particle size of the secondary particles exceeds 100 μm, it is difficult to uniformly disperse in water. become. The hydroxyapatite powder is preferably spherical particles. When the hydroxyapatite powder is a spherical particle, the agitation of the slurry and the moldability of the porous hydroxyapatite are improved, and a particle gap is formed between the spherical particles, and a continuous pore is formed throughout. Can be obtained.

  The hydroxyapatite powder may be subjected to a calcination treatment in order to enhance the powder strength or handling properties. The calcination treatment consists of heat-treating the powder at a temperature of 700 to 850 ° C. for 4 to 10 hours. If the calcining temperature is less than 700 ° C, sufficient improvement in the strength or handling properties of the hydroxyapatite powder cannot be achieved, and if it exceeds 850 ° C, sintering starts. Decreases.

(b) Water-soluble polymer compound A water-soluble polymer compound may be added to the slurry. The water-soluble polymer compound that can be used is such that it gels by subjecting the water-soluble or aqueous dispersion to a means such as heating. Here, the water-soluble or aqueous dispersion includes all of an aqueous solution, a colloidal solution, an emulsion, and a suspension. Examples of such water-soluble polymer compounds include cellulose derivatives such as methylcellulose and carboxymethylcellulose, polysaccharides such as curdlan, synthetic polymers such as polyvinyl alcohol, polyacrylic acid, polyacrylamide, and polyvinylpyrrolidone. Methyl cellulose is preferred. In the case of polyvinyl alcohol, it can be gelled by adding boric acid or borax.

(c) Anionic or nonionic surfactant An anionic or nonionic surfactant may be added to the slurry to increase the porosity of the calcium phosphate ceramic sintered body. An anionic or nonionic surfactant is used as a surfactant that forms a large number of fine bubbles and does not lose the bubbles in the heating step for gelation. In addition, since porous hydroxyapatite is used semi-permanently in the body as a biomaterial, the anionic or nonionic surfactant to be added is not only completely burned out by sintering, but also remains such as sodium remaining after sintering. Those containing no metal ions or sulfate groups are preferred.

  Examples of such nonionic surfactants include fatty acid alkanolamides, polyoxyethylene alkyl ether carboxylates, polyoxyethylene alkyl ethers (for example, polyoxyethylene octyl phenyl ether) and the like. Examples of the anionic surfactant include alkyl sulfonates, polyoxyethylene alkyl ether sulfates, alkyl ether sulfate esters, and dodecylbenzene sulfonates. Of these, fatty acid alkanolamide surfactants (for example, N, N-dimethyldodecylamine oxide) or alkyl ether sulfates are preferred from the viewpoint of foaming properties in the presence of hydroxyapatite.

(d) Mixing ratio and concentration The mass of the slurry is 100% by mass, and the hydroxyapatite powder is preferably blended so as to be 5 to 50% by mass, more preferably 20 to 50% by mass. If the hydroxyapatite powder is less than 5% by mass, it is difficult to form the slurry into a desired shape such as a sheet or a pellet, and if it exceeds 50% by mass, it becomes difficult to disperse and the porous hydroxyapatite becomes dense. . The addition amount of the water-soluble polymer compound is preferably 1 to 5% by mass, where the mass of the slurry is 100% by mass. When the addition amount of the water-soluble polymer compound is less than 1% by mass, not only gelation is slowed but also the strength of the porous hydroxyapatite is weakened. When the addition amount of the water-soluble polymer compound is more than 5% by mass, the viscosity of the slurry is too high, foaming becomes difficult, and the porous hydroxyapatite becomes dense. The addition amount of the anionic or nonionic surfactant is preferably 0.08 to 6% by mass with respect to 100% by mass of the slurry. If it is less than 0.08% by mass, foaming is difficult, and if it exceeds 6% by mass, foaming is excessive and the strength of the porous hydroxyapatite decreases. A more preferable addition amount of the anionic or nonionic surfactant is 0.1 to 5% by mass.

(2) Foaming and gelation
(a) Foaming When the slurry having the above composition is vigorously stirred, the slurry entrains and foams. The stirring power is preferably 50 W / L or more. When the stirring force is less than 50 W / L, foaming is insufficient and porous hydroxyapatite having a desired porosity cannot be obtained. The stirring force is determined by [maximum output of the stirrer (W) / amount of aqueous solution (L)] × (actual rotational speed / maximum rotational speed). The output of the stirrer increases in order to maintain the number of revolutions as the viscosity of the slurry increases, but in the case of the present invention in which foaming is performed at a high porosity, the slurry viscosity does not substantially change from the viscosity at the time of charging. Therefore, the effect of viscosity is virtually negligible.

  The temperature of the slurry during foaming is preferably 5 to 25 ° C. If it is less than 5 ° C, the foamability is poor, and if it exceeds 25 ° C, it is difficult to generate fine bubbles.

  When foaming, air may be injected into the slurry to promote foaming of the slurry. The amount of air injected is preferably 1 to 100 ml / min, more preferably 10 to 100 ml / min. The air injection time is preferably about 10 to 120 minutes.

  Alternatively, the surfactant may not be preliminarily formulated into the slurry, and an aqueous solution of the surfactant may be injected into the slurry together with air to promote foaming. In that case, in order to generate fine bubbles, the injection tube may have a double tube structure, an aqueous surfactant solution may flow through the inner tube, and air flow through the outer tube. The air injection amount and the injection time are preferably within the above ranges, and the surfactant concentration of the surfactant aqueous solution may be about 0.1 to 35% by mass.

(b) Molding die The foamed slurry is injected into the molding die shown in FIG. The molding die 1 has a pair of microporous resin sheets 2 and a mold 3, and is formed by making the pair of microporous resin sheets 2 face each other via the mold 3. The microporous resin sheet 2 is preferably one that allows air and water vapor to pass therethrough and does not pass water as a liquid. Specifically, the pore diameter of the microporous resin sheet 2 is preferably 0.4 nm to 100 μm, and more preferably 0.1 to 100 μm. The thickness of the microporous resin sheet 2 is preferably 50 to 1000 μm. If the thickness of the microporous resin sheet is less than 50 μm, the shape cannot be maintained, and if it exceeds 1000 μm, the drying time becomes long. Since such a microporous resin sheet 2 has good air permeability and a dense film is not formed in a portion in contact with the microporous resin sheet 2, porous hydroxyapatite having a uniform pore diameter can be obtained.

  The microporous resin sheet 2 is preferably stable and flexible at 80 to 100 ° C. As a material constituting the microporous resin sheet 2, a fluorine resin such as polytetrafluoroethylene (PTFE), a polyolefin resin, or the like is preferable. Commercially available products applicable to the microporous resin sheet 2 used in the present invention include Gore-Tex (polytetrafluoroethylene, manufactured by Japan Gore-Tex Co., Ltd.), Exepol (Polyolefin resin, Mitsubishi Resin Co., Ltd.), etc. Is mentioned.

  As for the shaping | molding die 1, it is preferable that the mesh structure 4 is provided in the back surface (surface which does not oppose a slurry) of the microporous resin sheet 2 as shown in FIG. The network structure 4 preferably has good thermal conductivity in order to easily release heat. Preferable examples of the mesh structure 4 include mesh sheets, plates, and the like made of aluminum, copper, stainless steel, and the like. It is preferable that the network structure 4 has a thickness of about 100 to 1000 μm and can be ventilated not only from the top but also from the side.

  A through hole for injecting slurry is formed in the mold 3. The opening of the through hole is in contact with the microporous resin sheet 2 and is ventilated through the microporous resin sheet 2. The type of the mold 3 can be appropriately selected according to the desired shape of the molded body. For example, when producing a sheet-like porous hydroxyapatite, a form having a sheet-like through-hole formed as shown in FIG. 3 (a) may be used, and a pellet-like porous hydroxyapatite is produced. In that case, a mold having pellet-shaped through-holes may be used as shown in FIG. When porous hydroxyapatite is used as a sheet or pellet, the thickness of the mold 3 is preferably 0.1 to 10 mm, and more preferably 3 to 5 mm. The mold 3 preferably has a thickness that does not change due to heat during molding. Preferable materials constituting the mold 3 include silicone rubber, fluororubber and the like. Since the mold 3 made of these materials hardly changes in the thickness direction due to heating, the thickness of a molded body such as a sheet or a pellet can be accurately controlled.

(c) Gelation In order to gel the slurry using the mold 1 shown in FIG. 1, the microporous resin sheet 2 provided with the network structure 4 on the back is placed with the microporous resin sheet 2 facing up. Is placed on a flat plate (having a slit that can be ventilated) or the like, and the mold 3 is placed thereon. The slurry is poured into the mold 3, and the microporous resin sheet 2 provided with the network structure 4 on the back is placed on the mold 3 with the microporous resin sheet 2 on the slurry side, and further weighted (glass plate Etc.).

  When a sufficiently foamed slurry is heated to 80 ° C. or higher and lower than 100 ° C., the slurry is gelled. When the heating temperature is less than 80 ° C., gelation is insufficient, and when it is 100 ° C. or more, the water boils and the gel structure is destroyed. In the present invention, gelation and drying can be performed continuously in a mold. Although the heating time until obtaining a dry body changes with sizes of a molded object, it is about 20 to 40 hours for a block and about 10 to 20 hours for a sheet and a pellet. The gel shrinks substantially isotropically upon drying, and since there is no change in bubbles, it becomes a high-strength dry body having fine and uniform spherical macropores without causing cracks and the like.

  In the present invention, since the slurry is sandwiched between a pair of opposed microporous resin sheets 2 to be gelled, the air contained in the slurry escapes out of the mold through the microporous resin sheet 2. The moisture does not pass through the microporous resin sheet 2 and can be gelled while retaining the moisture in the slurry. Thereby, it is possible to prevent the gel structure from being broken (pore collapse) due to the volume change due to the loss of moisture, and to obtain a gelled body having a high porosity. After the gelation, the dried product can be obtained by continuing to heat the gelled product as it is, but the dried product can be obtained more efficiently by removing the gelated product from the mold and heating it.

  In the production method of the present invention, porous hydroxyapatite having a desired shape such as a sheet shape, a pellet shape, or a bead shape can be obtained directly by the above-described mold, and therefore, cutting or the like is not required. Therefore, the number of steps is small, and the yield is high because of the loss caused by processing. Moreover, the porous hydroxyapatite is easily peeled off from the microporous resin sheet 2, and the working efficiency is high.

(3) Degreasing If necessary, a degreasing treatment is performed to remove the water-soluble polymer compound and the surfactant from the porous hydroxyapatite molded into a predetermined shape. The degreasing treatment can be performed by heating to 300 to 900 ° C.

(4) Sintering The dried body is sintered at 1000-1250 ° C. for 2-10 hours. When the sintering temperature is less than 1000 ° C., a porous hydroxyapatite sintered body having sufficient strength cannot be obtained, and when it exceeds 1250 ° C., hydroxyapatite is decomposed into tricalcium phosphate and calcium oxide. What is necessary is just to set sintering time suitably according to sintering temperature. When the degreasing step is omitted, degreasing can be performed by gradually raising the temperature until the sintering temperature is reached. For example, the temperature is raised from room temperature to about 600 ° C. at a temperature increase rate of about 10 to 100 ° C./hour, and then heated to the sintering temperature at a temperature increase rate of about 50 to 200 ° C./hour and held at this temperature It is preferable to do this. Slowly cool after completion of sintering.

  The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

Example 1
367 parts by mass (100 parts by mass solids) of slurry containing hydroxyapatite spherical powder (average particle size: 15 μm) consisting of elongated primary particles (average diameter: major axis 80 nm, minor axis 15 nm), and methylcellulose ( Wako Pure Chemical Industries, Ltd., 67% by mass of a 10% by weight aqueous solution of a 2% by weight aqueous solution measured at 20 ° C. (4000 cps) and a fatty acid alkanolamide surfactant (N, N-dimethyldodecylamine oxide) , “AROMOX” (manufactured by Lion Corporation) was blended so as to be 3 parts by mass (solid content 1 part by mass). The obtained slurry was put into a homogenizer (manufactured by SMT Co., Ltd., PA92). While maintaining the slurry temperature at 15 ° C. and injecting air at 30 ml / min from the injection tube, the slurry was vigorously stirred for 20 minutes with a stirring force of 10 to 20 W / L (actual output during stirring) to cause foaming. It was.

  The bubble-containing slurry was poured into the mold shown in FIG. First, a microporous resin sheet 2 (continuous) having a thickness of 100 μm, in which a mesh-like structure 4 (a stainless mesh having a thickness of 250 μm and a mesh size of 200 μm) is provided on a flat plate having a lattice-like slit. Porous polytetrafluoroethylene, pore size 0.1-100μm, trade name: Gore-Tex, manufactured by Japan Gore-Tex Co., Ltd.) is placed with the microporous resin sheet 2 facing up. A silicone rubber mold 3 in which a through-hole of 112.5 mm × depth 5 mm was formed was installed. The slurry was poured into the through hole of the mold 3, and the microporous resin sheet 2 provided with the network structure 4 on the back was placed with the microporous resin sheet 2 on the slurry side. Further, a glass plate having a thickness of 2.5 mm was placed on the network structure 4 as a weight. The flat plate on which the mold was placed was transferred into a hot air dryer, and the slurry was heated at 83 ° C. for 0.5 hours to gel by the hot air dryer. Furthermore, the obtained gel was completely dried by holding at 83 ° C. for 12 hours to obtain a porous hydroxyapatite sheet. The porous hydroxyapatite sheet could be easily peeled off from the microporous resin sheet 2 and the surface thereof was the same porous as the inside.

  The porous hydroxyapatite sheet was heated from room temperature to 600 ° C at a heating rate of 50 ° C / hour in the atmosphere, then heated to 1200 ° C at a heating rate of 100 ° C / hour, and this temperature was maintained for 4 hours. After firing, the sample was cooled to 600 ° C. at a temperature decrease rate of 50 ° C./hour, held at this temperature for 4 hours, and then cooled to room temperature at a temperature decrease rate of 100 ° C./hour. A porous hydroxyapatite sintered body was obtained by this sintering step. The porosity of the obtained sintered body was measured. The porosity of the porous hydroxyapatite sintered body was about 90%, and most of the pores were in the range of the pore diameter of 50 to 500 μm.

Example 2
In the slurry of Example 1 excluding the fatty acid alkanolamide surfactant (N, N-dimethyldodecylamine oxide, “AROMOX”, manufactured by Lion Co., Ltd.), from the inner tube by a double tube structure injection tube A porous hydroxyapatite was produced by foaming a slurry in the same manner as in Example 1 except that 10 ml of a 30% by mass AROMOX aqueous solution (solid part 1 part by mass) was injected and air was injected from the outer tube at 30 ml / min. A sintered body was produced.

  A scanning micrograph (50 ×) of the obtained porous hydroxyapatite sintered body is shown in FIG. As can be seen from FIG. 2, the pores in the porous hydroxyapatite sintered body are uniform in size, and most of them are in the pore diameter range of 50 to 500 μm. The porosity of the porous hydroxyapatite sintered body was about 90%.

Example 3
A porous hydroxyapatite sheet was produced in the same manner as in Example 2. A pellet sintered body having a diameter of 5 mm and a thickness of 3 mm was prepared in the same manner as in Example 2 except that a puncher having an inner diameter of 7 mm was used and punched out of the obtained porous hydroxyapatite sheet. The obtained porous hydroxyapatite sintered body had a porosity of about 90% and had the same pore size as in Example 2. Table 1 shows the number and yield of pellets obtained from 100 g of hydroxyapatite.

(1) The yield was determined by the ratio (%) of the number of pellets actually obtained to the number of pellets theoretically obtained from 100 g of hydroxyapatite (theoretical value).

Example 4
The same procedure as in Example 2 was used except that the mold 3 shown in FIG. 3 (b) in which 100 through-holes having a diameter of 7 mm were formed in a silicone rubber sheet having a length of 115 mm × width of 112.5 mm × thickness of 5 mm was used. A pellet-shaped porous hydroxyapatite sintered body was produced. The obtained porous hydroxyapatite sintered body had a porosity of about 90% and had the same pore size as in Example 2.

Comparative Example 1
A slurry was prepared in the same manner as in Example 1. The obtained slurry was put into a homogenizer (manufactured by SMT Co., Ltd., PA92). While maintaining the slurry temperature at 8 ° C., the slurry was vigorously stirred for 5 minutes with a stirring force of 60 W / L (actual output during stirring) to cause foaming.

  The obtained bubble-containing slurry was poured into a mold (length 115 mm × width 112.5 mm × depth 50 mm) and heated to 83 ° C. for 2 hours to cause gelation. The obtained gel was completely dried by holding at 83 ° C. for 24 hours to obtain a green block. A sheet having a thickness of 5 mm was cut out from the green block, and a pellet was punched out using a puncher having an inner diameter of 7 mm. The pellet was sintered in the same manner as in Example 1 to prepare a sintered body of porous hydroxyapatite sintered body having a diameter of 5 mm and a thickness of 3 mm. FIG. 4 shows a scanning micrograph (60 times) of the obtained porous hydroxyapatite sintered body. It can be seen that the pores in the porous hydroxyapatite sintered body are uniform in size, and most of them are in the pore diameter range of 50 to 500 μm. The porosity of the porous hydroxyapatite sintered body was about 80%. Table 1 shows the number and yield of pellets obtained from 100 g of hydroxyapatite. The yield is 48%, and it can be seen that the productivity is inferior to that in Example 3 (yield 99%).

Comparative Example 2
A porous hydroxyapatite sintered body was produced in the same manner as in Example 1 except that a glass plate was used instead of the microporous resin sheet 2. The porous hydroxyapatite sheet obtained by foaming, gelling and drying with a mold was stuck to the glass plate and was difficult to peel off from the glass plate. Further, the surface of the porous hydroxyapatite sheet was covered with a dense film, and the pore diameter was not uniform.

It is a schematic sectional drawing which shows the shaping | molding die of the porous calcium-phosphate type ceramic sintered compact of this invention. 3 is a scanning micrograph (50 ×) of a porous hydroxyapatite sintered body obtained in Example 2. FIG. It is a plan view showing a mold used in the production method of the present invention, (a) is a mold with a sheet-like through hole formed, (b) is a mold with a pellet-shaped through hole formed It is. 2 is a scanning micrograph (60 times) of a porous hydroxyapatite sintered body obtained in Comparative Example 1. FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Mold 2 ... Microporous resin sheet 3 ... Formwork 4 ... Mesh-like structure 5 ... Weight (glass plate)

Claims (21)

A method for producing a porous calcium phosphate ceramic sintered body having a porosity of 80% or more, comprising: (1) foaming a slurry containing a calcium phosphate ceramic powder; and (2) air and water vapor And a pair of microporous resin sheets impervious to water as a liquid are injected into a mold opposite to each other through a mold, and (3) gelled, (4) sintered after drying A method for producing a porous calcium phosphate ceramic sintered body characterized by the above. The method for producing a porous calcium phosphate ceramic sintered body according to claim 1, wherein a network structure is provided on the back surface of the microporous resin sheet. The method for producing a porous calcium phosphate ceramic sintered body according to claim 1 or 2 , wherein the pore diameter of the microporous resin sheet is 0.4 nm to 100 µm. The method for producing a porous calcium phosphate ceramic sintered body according to any one of claims 1 to 3 , wherein the microporous resin sheet is stable at 80 to 100 ° C. In the manufacturing method of the porous calcium-phosphate type ceramic sintered compact in any one of Claims 1-4 , the surface of the porous calcium-phosphate type ceramic after gelatinization drying is densified by using the said microporous resin sheet. The method characterized by not letting it do. The method for producing a porous calcium phosphate ceramic sintered body according to any one of claims 1 to 5 , wherein an anionic or nonionic surfactant is added to the slurry. 7. The method for producing a porous calcium phosphate ceramic sintered body according to claim 6 , wherein a fatty acid alkanolamide surfactant or an alkyl ether sulfate ester salt is added to the slurry. The method for producing a porous calcium phosphate ceramic sintered body according to any one of claims 1 to 7 , wherein air is injected into the slurry during the foaming treatment. In the manufacturing method of the porous calcium-phosphate type ceramic sintered compact of Claim 8 , the said anion or nonionic surfactant is inject | poured from an inner tube | pipe using the injection | pouring pipe | tube structure of a double pipe | tube structure, and air is supplied from an outer pipe | tube. A method characterized by injecting. The method for producing a porous calcium phosphate ceramic sintered body according to any one of claims 1 to 9 , wherein a water-soluble polymer compound is added to the slurry. The method for producing a porous calcium phosphate ceramic sintered body according to any one of claims 1 to 10 , wherein the temperature during the foaming treatment of the slurry is maintained at 5 to 20 ° C. 12. The method for producing a porous calcium phosphate-based ceramic sintered body according to claim 1 , wherein the slurry is formed into a sheet shape or a pellet shape. 13. The method for producing a porous calcium phosphate ceramic sintered body according to any one of claims 1 to 12 , wherein the calcium phosphate ceramic powder is made of hydroxyapatite. 14. The method for producing a porous calcium phosphate-based ceramic sintered body according to claim 1 , wherein the calcium phosphate-based ceramic powder has an average particle diameter composed of primary particles of a calcium phosphate-based ceramic having an average particle diameter of 100 nm or less. A method comprising secondary particles of 5.0 to 100 μm. A mold for injecting a slurry containing calcium phosphate-based ceramic powder to perform gelation, a pair of microporous resin sheets through which a mold, air and water vapor are passed, and water as liquid is not passed And a pair of microporous resin sheets facing each other through the mold, a mold for forming a porous calcium phosphate ceramic sintered body. 16. The mold for forming a porous calcium phosphate ceramic sintered body according to claim 15 , wherein a network structure is provided on the back surface of the microporous resin sheet. 17. The molding die for porous calcium phosphate ceramics sintered body according to claim 15 or 16 , wherein the mold has at least one through hole whose opening is in contact with the microporous resin sheet. Type. 18. The mold for molding a porous calcium phosphate-based ceramic sintered body according to claim 15 , wherein the mold is made of silicone rubber or fluororubber. 19. The mold for forming a porous calcium phosphate ceramic sintered body according to claim 15 , wherein the microporous resin sheet has a pore diameter of 0.4 nm to 100 μm. 20. The molding die for porous calcium phosphate ceramics sintered body according to claim 15 , wherein the microporous resin sheet is stable at 80 to 100 ° C. 21. A mold for molding a porous calcium phosphate ceramic sintered body according to any one of claims 15 to 20 , wherein the microporous resin sheet is made of a fluororesin or a polyolefin resin.