JP3873085B2 - Calcium phosphate porous sintered body and method for producing the same - Google Patents

Description

[0002]
[Technical field to which the invention belongs]
[0003]
  The present invention relates to a calcium phosphate-based porous sintered body that can be used as a bone or tooth replacement material, a restoration material, a drug sustained-release base material, a culture vessel or induction vessel for bone or cartilage tissue, and a method for producing the same. Relates to a calcium phosphate-based porous sintered body having a porous structure having excellent properties such as affinity to a living body, cell penetration required for bone formation, and strength, and a method for producing the same.
[Prior art]
[0004]
  As a material used for artificial bones, artificial teeth, bones, etc. in dentistry, brain surgery, plastic surgery, orthopedic surgery, etc. (hereinafter referred to as `` bone replacement material ''), it is not toxic and has sufficient mechanical strength. It is preferable to have a high affinity with a living tissue and easily bind to the living tissue, and which naturally disappears in the living body and can be naturally replaced with new bone.
[0005]
  From such a viewpoint, a bone grafting material having a porous structure made of a calcium phosphate compound is used.
[0006]
  As a method for manufacturing a bone grafting material having a porous structure, a raw material powder and a pyrolytic substance are mixed, formed into a predetermined shape, and then heated to remove the pyrolytic substance and sinter the raw powder. (Japanese Patent Laid-Open Nos. 60-21863 and 60-16879).
[0007]
  However, in these conventionally known production methods, the pyrolysis substance added to form pores does not always come into uniform contact, and therefore, most of the formed pores tend to be independent pores. Further, even if the formed adjacent pores are in contact with each other and are continuous, the cross-sectional area of the portion where each pore communicates (hereinafter referred to as “communication portion” or “communication portion”) becomes small. With such a pore structure, it is difficult to evenly infiltrate cells (osteoblasts and the like) necessary for bone formation into each pore even if they are compensated in the living body.
[0008]
  Therefore, for the purpose of increasing the cross-sectional area of the communicating portion, the surface of the flammable spherical particles is coated with a binder, the aggregate of the particles is stored in a mold and pressed, and the surface portion of each particle and its surroundings After contacting and fixing the surface of other particles arranged adjacent to each other, the gap portion existing between the particles is filled with the slurry in which the calcium phosphate powder is suspended, dried, and solidified. A method is known in which flammable spherical particles and binder are thermally decomposed and removed by heating, and then sintered (Japanese Patent Laid-Open No. 7-291759).
[0009]
  The porous bone substitute material manufactured by this method has a sufficient cross-sectional area of the communication portion.
[0010]
  However, in the method of contacting and fixing flammable spherical particles by pressurization, the pressure to be applied is limited, and the destruction of the porous structure due to springback has been considered for the time being, but the flammability fixed at the time of drying In spite of almost no dimensional change of the spherical particles, large shrinkage occurs when moisture is removed from the slurry and the filling state of the powder is changed. Therefore, the skeleton part constituting the porous body is likely to be broken. The problem is not considered.
  Further, the fixed combustible spherical particles undergo a large thermal expansion in the process of temperature rise until the fixed combustible spherical particles are thermally decomposed and removed, but constitute a porous body made of a raw material powder filler. The thermal expansion does not occur so much in the skeleton portion, and therefore the difference in thermal expansion becomes large, and as a result, the problem that the skeleton portion constituting the porous body easily breaks is not considered.
[0011]
  Furthermore, the problem that a large amount of gas is generated when the combustible spherical particles and the binder are thermally decomposed, cannot escape to the outside, and the pressure causes cracks in the porous body is not considered.
[0012]
  Therefore, it is difficult for such a conventional method to exhibit sufficient mechanical strength.
[Problems to be solved by the invention]
[0013]
  The present invention has been made to solve the above-mentioned problems of the prior art, has sufficient mechanical strength, high biocompatibility, most of the pores are uniformly connected, and bone buds in most of the pores. An object of the present invention is to provide a calcium phosphate porous sintered body having a porous structure into which cells and the like easily enter, and a method for producing the same.
[Means for Solving the Problems]
[0014]
  The solving means of the present invention is as follows.12The calcium phosphate porous sintered body described in 1) and a method for producing the same.
DETAILED DESCRIPTION OF THE INVENTION
[0015]
  In the calcium phosphate porous sintered body according to the present invention, substantially spherical pores communicate with almost the entire porous sintered body. Its porosity is 50% or more85% Or less (preferably 50 to 70%). And the average diameter of the communication part between pores is 35 micrometers or more (preferably 35-70 micrometers). The pore diameter is in the range of 80 μm or more and smaller than 150 μm (preferably 80 to 140 μm). The three-point bending strength is 5 MPa or more (preferably 10 MPa or more).
[0016]
  In particular, among the three conditions of porosity of 50 to 70%, pore diameter of 80 to 140 μm, and three-point bending strength of 10 Mp or more, two conditions are more preferably satisfied at the same time, and it is particularly preferable that all three conditions are satisfied. The reason is that the strength is improved and the range that can be used as a bone grafting material is widened, and the pore diameter is reduced, so that the drug is easily released as a drug sustained-release base material for a long period of time.
[0017]
  Measuring method of porosity
  The porosity of the calcium phosphate porous sintered body is measured by the following method. A sintered body having the same composition as the calcium phosphate porous sintered body of the object to be measured is prepared in advance, and measured using a true density meter to determine the true density (ρ *). The calcium phosphate porous sintered body of the object to be measured is processed into a rectangular parallelepiped or a cylinder, its dimensions are measured, and the volume is obtained by calculation. Further, the weight is measured, and the density (ρ) is obtained by dividing the weight by the volume. Using these values, the porosity (P) is calculated by the following equation.
[0018]
  P = 1-ρ / ρ *
  Further, the calcium phosphate porous sintered body is embedded in a resin, polished and observed with a microscope or the like, and the area of the pore portion (Ap) and the area of the portion measured by image analysis (the area of the pore portion ( Am). Using these values, the porosity (P) is calculated by the following equation.
[0019]
  P = Ap / Am
  Measuring method of pore diameter
  The pore diameter of the calcium phosphate porous sintered body is measured by the following method. A calcium phosphate-based porous sintered body is embedded in a resin, polished, and observed with a microscope or the like, and a substantially spherical pore area is obtained by image analysis. Here, the number of pores to be measured is preferably as high as possible. However, in general, measurement may be performed for 300 or more pores. The pore area required here is a cross section in a plane passing through a part of a substantially spherical pore, and is not the diameter of the pore, so that three-dimensional correction is performed.
[0020]
  The Johnson-Saltkov method is used as the correction method. In the Johnson-Saltkov method, the pore size distribution is obtained directly from the observed pore area, and the average pore size is calculated as the pore size that accounts for 50% of the total pore volume in the cumulative pore volume distribution. To do.
[0021]
  Since the calcium phosphate porous sintered body of the present invention has the above-described structural characteristics, it has sufficient mechanical strength, has high affinity with living tissue, and is easily lost in vivo. However, it has the characteristic that it can be naturally replaced with new bone.
[0022]
  In addition, when used as a drug sustained-release base, it has a large number of pores that can sufficiently hold the drug, and a communication part between the pores that is effective for gradually releasing the drug, and Possesses enough strength.
[0023]
  Here, the porosity is 50% or more85Describe the reason why the percentage is less than or equal to%.
[0024]
  When the porosity is less than 50%, the cross-sectional area of the communication portion formed between adjacent pores becomes small, or when there are too many independent pores and used as a bone filling material, the calcium phosphate of the present invention It becomes difficult to take in a sufficient amount of osteoblasts and the like inside the porous sintered body, and when used as a drug sustained-release base, it is difficult to secure pores that can sufficiently hold the drug. The porosity is preferably 55% or more.
[0025]
  If the porosity exceeds 90%, the strength of the calcium phosphate porous sintered body is significantly reduced. The porosity is preferably 85% or less. In particular, when the strength is increased or the substrate for sustained release is used, 70% or less is preferable.
[0026]
  Moreover, the reason why the average diameter of the communication part between the pores is set to 35 μm or more is that if it is less than 35 μm, the cell invasion necessary for bone formation cannot be obtained. The upper limit of the average diameter of the communication part between the pores is not particularly limited. The average diameter of the communication part is preferably 50 μm or more.
[0027]
  In addition, the average diameter of the communication part between pores is measured by the mercury intrusion method. If the mercury intrusion method cannot be applied because the diameter of the communication part is too large, the cross-sectional part of the porous sintered body is observed with a microscope, the diameter of the communication part is observed, and the average diameter of the communication part between the pores Is calculated as an area average diameter.
  The reason why the pore diameter of the calcium phosphate-based porous sintered body is set to 80 μm or more is that when it is less than 80 μm, it is difficult to set the average diameter of the communication portion between the pores to 35 μm or more. The upper limit of the pore diameter is in a range smaller than 150 μm. Pore diameter can also be implemented. A preferable pore diameter is 80 to 140 μm. Especially preferably, it is 80-120 micrometers.
[0028]
  The reason why the three-point bending strength of the calcium phosphate porous sintered body is set to 5 MPa or more is that the mechanical strength is insufficient in the desired use of the calcium phosphate porous sintered body of the present invention if it is less than 5 MPa. is there. The upper limit of the three-point bending strength is not particularly limited, but a strength of about 50 MPa can be implemented.
[0029]
  In a preferred calcium phosphate sintered body according to the present invention, the calcium phosphate porous sintered body is composed of a calcium phosphate sintered body in which the skeleton portion is densified, and the surface portion has fine irregularities or calcium phosphate porous sintered body. It has a layer consisting of a knot. As a result, the specific surface area of the calcium phosphate porous sintered body is 0.1 m.²/ G or more.
[0030]
  When the calcium phosphate porous sintered body is used for applications such as a bone grafting material, it is common to adsorb a drug that aids bone formation. At that time, in order to obtain a sufficient amount of adsorption, the specific surface area is 0.1 m 2 / g or more (particularly 0.2 m²/ G or more). From this point of view, the calcium phosphate-based porous sintered body is composed of a dense calcium phosphate-based sintered body, and the surface portion of the layer is composed of moderately fine irregularities or a calcium phosphate-based porous sintered body. Have. Such a structure of the surface portion increases the specific surface area, but does not cause a significant decrease in strength. Therefore, a good bone filling material can be obtained.
[0031]
  In addition, in the case of bone prosthetic materials, if there are fine irregularities (including pores) on the surface of the skeleton part of the calcium phosphate porous sintered body, osteoclasts and osteoblasts are easily attached to them. As a result, it naturally disappears in the living body and is easily replaced with new bone. When the surface of the skeleton part of the calcium phosphate porous sintered body has a moderately fine unevenness or a layer made of a calcium phosphate based porous sintered body, the fine unevenness effectively functions for the supplementary bone. The upper limit of the specific surface area is not particularly limited, but 100 m²A specific surface area of about / g can also be implemented.
[0032]
  The calcium phosphate porous sintered body is, for example, CaHPO._Four, Ca_Three(PO_Four)₂, Ca_Five(PO_Four)_ThreeOH, Ca_FourO (PO_Four)₂, Ca_Ten(PO_Four)₆(OH)₂, CaP_FourO₁₁, Ca (PO_Three)₂, Ca₂P₂O₇, Ca (H₂PO_Four)₂, Ca₂P₂O₇, Ca (H₂PO_Four)₂・ H₂It is a porous sintered body mainly composed of O or the like, and includes a porous sintered body made of a group of compounds called calcium phosphate.
[0033]
  In addition, a group of compounds called calcium phosphate constituting the calcium phosphate-based porous sintered body includes a part of the Ca component such that Sr, Ba, Mg, Fe, Al, Y, La, Na, K , Ag, Pd, Zn, Pb, Cd, H, and other rare earths may be substituted. Also, (PO_Four) Part of the component is VO_Four, BO_Three, SO_Four, CO_Three, SiO_FourIt may be substituted with one or more selected from the above. Furthermore, a part of the (OH) component is F, Cl, O, CO_Three, I, Br may be substituted with one or more selected from.
[0034]
  In addition, a group of compounds called calcium phosphate may be any of the same type solid solution, substitution type solid solution, and interstitial type solid solution in addition to a normal crystal, and includes non-stoichiometric defects. It may be a thing.
[0035]
  The aforementioned calcium phosphate porous sintered body is provided by a method for producing a calcium phosphate porous sintered body described later.
[0036]
  For example, a suitable example of such a production method includes a step of preparing a slurry in which a calcium phosphate powder and an organic substance that can be cured by crosslinking polymerization are dispersed or dissolved in a solvent, and a foaming agent is added to the slurry and stirred. And / or foaming to a predetermined volume by introducing a gas to form a foamed slurry, and adding and mixing a crosslinking agent and / or a crosslinking initiator to the foamed slurry, introducing the mixture into a mold, and crosslinking It includes a step of curing by polymerization to form a molded body, and a step of drying and sintering the molded body. In addition, you may add a dispersing agent, a foam stabilizer, a thickener, etc. in the above-mentioned slurry.
[0037]
  As the organic material that can be cured by cross-linking polymerization, it is possible to use polyvinyl alcohol, methyl methacrylate, methyl cellulose, and other materials having various cross-linking polymerization properties. In particular, a polymer having a linear, branched, or block form containing an amino group is rich in cationic properties, can contribute to the dispersion of the raw material powder, and can produce a good slurry. It is preferable because a good cross-linked polymer can be obtained in combination.
[0038]
  Any crosslinking agent can be used as long as it crosslinks the selected crosslinked polymerizable substance. In particular, when an organic substance having an amino group such as polyacrylamide, polyethyleneimine, polypropyleneimine or the like is used, it is sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, pentaerythritol polyglycidyl ether, diester. It is preferable to use an epoxy compound having two or more epoxy groups, such as glycerol polyglycidyl ether, glycerol polyglycidyl ether, polymethylolpropane polyglycidyl ether.
[0039]
  As the foaming agent, anionic, cationic, amphoteric, and nonionic surfactants can be used. However, when an organic substance having an amino group such as polyacrylamide, polyethyleneimine, propyleneimine or the like is selected as an organic substance having a crosslinkable polymer, an anionic surfactant should be used. If used, due to the difference in ionicity, an ion complex may be formed and the foaming operation may be difficult. In this case, it is not desirable to use an anionic surfactant.
[0040]
  The calcium phosphate-based porous sintered body is composed of a calcium phosphate-based sintered body in which the skeleton portion is densified, and the surface portion has a layer made of fine irregularities or a calcium phosphate-based porous sintered body. The specific surface area of the bonded body is 0.1m²A calcium phosphate porous sintered body having a weight of at least / g can be produced by the method described below.
[0041]
  For example, the surface of the skeleton portion of the calcium phosphate-based porous sintered body made of a densified calcium phosphate-based sintered body is etched with acid to provide fine irregularities on the surface of the skeleton portion. The surface of the skeleton portion of the densified calcium phosphate sintered body is subjected to etching with an acid, and the grain boundary portion is dissolved. As a result, fine irregularities are formed on the surface of the skeleton portion. As the acid used for etching, various acids can be used in addition to hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, citric acid and the like. Further, the pH of the etching solution is not particularly specified. Since the etching rate varies depending on the acid type and concentration, the conditions are adjusted. However, in the method described here, if the etching is excessive, the strength of the calcium phosphate-based porous sintered body is reduced, so it depends on the size of the crystal particles constituting the calcium phosphate-based porous sintered body, 0.3 m when the crystal particle size is 1 μm²/ G or less is desirable.
[0042]
  It is preferable to employ the following etching method as a method for producing the calcium phosphate porous sintered body. That is, it is preferable that the etching step with an acid comprises a step of circulating the acid in the pores of the calcium phosphate porous sintered body installed so as to block the channel in the acid channel. When the calcium phosphate porous sintered body is immersed in an acid, the surface of the porous sintered body is significantly etched, but the etching inside the porous sintered body does not progress so much. If it is adopted, it is easy to uniformly etch the inside of the calcium phosphate porous sintered body.
[0043]
    It is further desirable to provide a step of removing acid components adsorbed and remaining on the surface after acid etching by thoroughly washing away the acid by passing ion exchange water or the like and further performing heat treatment after drying.
[0044]
  In another preferred embodiment of the method for producing a calcium phosphate porous sintered body, a slurry containing a calcium phosphate powder is newly attached to the surface of the skeleton portion of the calcium phosphate porous sintered body, dried and sintered. . In this way, the calcium phosphate-based sintered body layer is provided on the surface of the skeleton portion of the calcium phosphate-based porous sintered body. The newly provided layer of the calcium phosphate-based sintered body varies depending on the composition of the calcium phosphate-based powder, but can be made porous or dense depending on the sintering temperature. In the case of a porous material, since a dense skeleton portion is included therein, a layer made of a calcium phosphate-based porous sintered body can be provided on the surface of the skeleton portion without causing a decrease in strength. The specific surface area of the calcium phosphate porous sintered body can be increased. In the case of a dense material, the slurry is less likely to adhere to the communicating portion having an edge shape, so that the cross-sectional shape of the calcium phosphate porous sintered body is close to a circle. For this reason, it is possible to improve the mechanical strength without significantly reducing the average diameter of the communicating portion.
[0045]
  The calcium phosphate powder is, for example, CaHPO._Four, Ca_Three(PO_Four)₂, Ca_Five(PO_Four)_ThreeOH, Ca_FourO (PO_Four)₂, Ca_Ten(PO_Four)₆(OH)₂, CaP_FourO₁₁, Ca (PO_Three)₂, Ca₂P₂O₇, Ca (H₂PO_Four)₂, Ca₂P₂O₇, Ca (H₂PO_Four)₂・ H₂It is a powder mainly composed of O or the like, and includes a powder made of a group of compounds called calcium phosphate.
[0046]
  Further, this calcium phosphate powder is constituted. One group of compounds referred to as calcium phosphate has a portion of its Ca component comprising Sr, Ba, Mg, Fe, Al, Y, La, Na, K, Ag, Pd, Zn, Pb, Cd, H, and These may be substituted with one or more selected from other rare earths. In addition, a part of the (PO4) component is VO_Four, BO_Three, SO_Four, CO_Three, SiO_FourIt may be substituted with one or more selected from Furthermore, a part of the (OH) component is F, Cl, O, CO_Three, I, Br may be substituted with one or more selected from.
[0047]
  The group of compounds called calcium phosphate may be any of the same type solid solution, substitution type solid solution, and interstitial type solid solution in addition to the usual crystal, and it contains non-stoichiometric defects. There may be.
[0048]
  In addition, it is also possible to adsorb | suck the chemical | medical agent which accelerates | stimulates bone formation, and the chemical | medical agent with another effect to the surface part of the calcium-phosphate type porous sintered compact by this invention. Furthermore, it is possible to include a drug that promotes bone formation or a drug having other effects in the pores.
[0049]
  Further, the surface portion of the calcium phosphate porous sintered body according to the present invention can be used by being coated with an organic substance having a high biocompatibility including a protein such as collagen.
[0050]
  Furthermore, the biodegradation characteristics of the calcium phosphate porous sintered body of the present invention can be achieved by controlling the crystal particles constituting the skeleton of the calcium phosphate porous sintered body or by depositing carbonate ions or the like at the boundaries between the particles. It is possible to control. For example, biodegradation properties can be imparted that gradually degrade over a period required for bone formation, often between 2 months and 5 years.
[0051]
  In one preferred form of the production method of the present invention, first, a slurry in which a calcium phosphate powder and an organic substance that can be cured by cross-linking polymerization are dispersed or dissolved in a solvent is prepared. Here, the raw material powder is dispersed using a ball mill or the like, and an organic substance that can be cured by cross-linking polymerization is dispersed or dissolved in a solvent to form a slurry. A foaming agent is added to the slurry and foamed to a predetermined volume by stirring and / or introducing gas to obtain a foamed slurry. Next, a crosslinking agent and / or a crosslinking initiator is added to the foamed slurry, mixed, introduced into a mold, and cured by crosslinking polymerization to obtain a molded body. After foaming and before loss of fluidity due to cross-linking polymerization, discharge of raw material powder and solvent from the contact part between adjacent foams toward the triple point (lung part) and four points (vertex part) between the foams Around the time when the slurry loses fluidity, the liquid film at the contact portion is broken, and a communication portion between the pores is formed.
[0052]
  This molded body is dried and sintered to form a calcium phosphate porous sintered body. In that case, it is desirable to perform drying under humidification. This is to prevent the occurrence of cracks due to a dimensional difference between the inside and outside of the molded body due to a rapid decrease in moisture. Sintering is preferably performed at 800 ° C. or higher and 1300 ° C. or lower.
[0053]
  In order to allow communication between pores to occur evenly throughout the calcium phosphate porous sintered body of the present invention, the porosity is preferably 50% or more. The condition that the pores communicate uniformly is the percolation phenomenon, and the number of communicating portions increases dramatically from a certain porosity. However, when the porosity is 50% or more, the entire calcium phosphate porous sintered body is stably communicated. Easy to make it happen evenly.
[0054]
  The porosity of the calcium phosphate-based porous sintered body is mainly determined by the amount of gas introduced into the slurry, shrinkage due to drying, and shrinkage due to sintering. The porosity of the sintered material can be controlled by the amount of gas introduced into the slurry.
[0055]
  The pore diameter of the calcium phosphate porous sintered body can be controlled by the type and concentration of the surfactant added as a foaming agent, the viscoelasticity of the slurry, and the time until the foamy slurry loses fluidity due to cross-linking polymerization. .
[0056]
  Therefore, according to the method for producing a calcium phosphate porous sintered body according to the present invention, a bone filling material capable of evenly invading osteoblasts and the like into pores when filled in a living body is easily produced. be able to.
【Example】
[0057]
  Hereinafter, the present invention will be described specifically by way of examples.
[0058]
  Example 1
  First, 100 parts by weight of hydroxyapatite powder as a raw material powder, 80 parts by weight of ion-exchanged water as a solvent, and 12 parts by weight of polyethyleneimine (solid content 60%, number average molecule 8000 to 10500) as an organic substance having a crosslinking polymerization property are used. Then, they were mixed with a ball mill for 24 hours to prepare a slurry. The slurry having the above composition was weighed into containers of 288 g (Example 1-1), 224 g (Example 1-2), and 160 g (Example 1-3), respectively, and polyoxyethylene lauryl ether ( 1.2 g, 0.9 g and 0.7 g of nonionic surfactant) are added and 300 cm each by mechanical stirring.^ThreeFoamed until it became a foamy slurry. To this, 6.0 g, 4.7 g, and 3.3 g of an epoxy compound (sorbitol polyglycidyl ether) as a cross-linking agent were added, stirred sufficiently, introduced into the mold, allowed to stand, and cross-linked by polymerization. The mold was removed when the strength was developed to such an extent that the fluidity was lost and handling was possible. After demolding, it was sufficiently dried using a humidifying dryer and a dryer, and sintered at 1200 ° C.
[0059]
  The thus obtained hydroxyapatite porous sintered body has a porosity of 55%, 65%, and 75%, respectively, and an average pore diameter of 100 μm, 120 μm, and 140 μm, respectively. They were 38 μm, 42 μm, and 50 μm. In addition, the three-point bending strengths were 20 MPa, 15 MPa, and 9 MPa, respectively, and had sufficient strength for use as a bone substitute material.
[0060]
  When the specific surface area of the sample of Example 1-3 was measured by the BET one-point method, it was 0.10 m.²/ G.
[0061]
  Example 2
  The hydroxyapatite porous sintered body produced by the method of Example 1-3 was installed so as to block the flow in the flow path, and dilute hydrochloric acid adjusted to pH 5.5 was added in this flow path to the hydroxyapatite. 1cm porous body²Per 50cm^ThreeFor 5 hours at a flow rate of / min. The hydroxyapatite porous sintered body was dried at 100 ° C. and then heat-treated at 1000 ° C.
[0062]
  When this sample was observed with an SEM, crystals of about 1 μm were observed on the surface of the dense skeleton portion of the hydroxyapatite porous sintered body. The grain boundary around the crystal was etched to a depth of about 1 μm.
[0063]
  This hydroxyapatite porous sintered body had a porosity of 75%, an average pore diameter of 140 μm, and an average diameter of the communicating portion of 55 μm. Further, the three-point bending strength was 8 MPa, and the strength was sufficient for use as a bone filling material.
[0064]
  When the specific surface area of this sample was measured by the BET single point method, it was 0.20 m.²/ G.
  In this way, the specific surface area could be increased by providing a fine concavo-convex structure on the surface of the dense skeleton portion of the hydroxyapatite porous sintered body without causing a significant decrease in strength due to acid etching. .
[0065]
  Example 3
  Using 50 g of hydroxyapatite powder as a raw material powder, 100 g of ion-exchanged water as a solvent, and 1 g of polyethyleneimine (solid content 60%, number average molecular weight 8000 to 10500) as a binder, they are mixed in a ball mill for 5 hours to obtain a slurry. Produced.
[0066]
  The hydroxide apatite porous sintered body produced by the method of Example 1-3 was immersed in this slurry, and the excess slurry was drained. Then, the slurry was further drained by air blow and dried.
[0067]
  This process was repeated three times to prepare a hydroxyapatite powder compact adhered to the surface of the skeleton portion of the hydroxyapatite porous sintered body.
[0068]
  When sintered at 1200 ° C., the porosity was 70%, the average pore diameter was 140 μm, and the average diameter of the communicating portion was 46 μm. Further, the three-point bending strength was 13 MPa, and the strength was sufficient for use as a bone filling material.
[0069]
  When the skeleton portion of this sample was observed by SEM, a dense layer of a hydroxyapatite sintered body newly added to the surface of the skeleton portion was observed.
[0070]
  By such a method, a calcium phosphate porous sintered body with higher strength could be created without greatly changing the mechanism structure of Example 1.
[0071]
  Example 4
  Hydroxyapatite powder 50g as raw material powder, ion exchange water 100g as solvent, polyethyleneimine (solid content 60%, number average molecular weight 8000-10500) 1g as a binder, they are mixed for 5 hours with a ball mill, and slurry is obtained. Produced.
[0072]
  In this slurry, the hydroxyapatite porous sintered body produced by the method of Example 1-3 was immersed, and the excess slurry was drained. Then, the slurry was further drained by air blow and dried.
[0073]
  This process was repeated three times to prepare a hydroxyapatite powder compact adhered to the surface of the skeleton portion of the hydroxyapatite porous sintered body.
[0074]
  When sintered at 1000 ° C., the porosity was 72%, the average pore diameter was 140 μm, and the average diameter of the communicating portion was 48 μm. Further, the three-point bending strength was 9 MPa, and the strength was sufficient for use as a bone filling material.
[0075]
  When the cross section of the skeleton portion of this sample was observed with an SEM, a porous hydroxyapatite sintered body layer newly formed on the surface of the skeleton portion was observed.
[0076]
  When the specific surface area of this sample was measured by the BET 1-point method, 0.5 m²/ G.
[0077]
  Thus, by providing a layer of a porous apatite sintered body on the surface of the skeleton portion of the hydroxyapatite porous sintered body, the strength of the hydroxyapatite porous sintered body is reduced without causing a decrease in strength. The specific surface area could be increased.
[0078]
  In the artificial aggregate composed of the calcium phosphate porous sintered bodies of Examples 1 to 4 described above, pores connected to each other by communication portions having a sufficient cross-sectional area are distributed throughout. Therefore, this artificial bone material can sufficiently invade osteoblasts and the like in vivo to form new bone.
[0079]
  In addition, conditions, such as each raw material, its addition amount, sintering, are not restricted to what was specifically described in Examples 1-4.
【The invention's effect】
[0080]
  In the artificial bone composed of the calcium phosphate porous sintered body of the present invention, pores connected to each other by communication portions having a sufficient cross-sectional area are distributed throughout. Therefore, this artificial bone material can sufficiently invade osteoblasts and the like in vivo to form new bone.
[0081]
  In addition, the calcium phosphate porous sintered body of the present invention has pores having high porosity and communicating with each other, and can increase the specific surface area of the calcium phosphate porous sintered body. Useful as a release substrate.
[0082]
  The calcium phosphate porous sintered body of the present invention has pores and communication holes that can substitute for the role of the Volkmann tube for invasion of blood vessels found in living bones and the Habers tube necessary for nutritional component supplementation. Therefore, as a tissue induction container for guiding bone tissue, cartilage tissue, etc. in and around the material in vivo, and tissue for culturing bone tissue, cartilage tissue, etc. in the material in vitro It can be used as a culture container.
[0083]
  Furthermore, it is possible to carry out supplementation of the affected area by using the calcium phosphate porous sintered body of the present invention, which is induced inside the living body or tissue-cultured outside the living body.
[0084]
  According to the method for producing a calcium phosphate porous sintered body of the present invention, the aforementioned calcium phosphate porous sintered body of the present invention can be easily produced.

Claims (12)

In a calcium phosphate-based sintered body having a porous structure, the sintered body has a porosity of 50% or more and 85 % or less, and substantially spherical pores communicate with each other over the entire area. The diameter is 35 μm or more, the pore diameter is 80 μm or more and smaller than 150 μm, the three-point bending strength of the sintered body is 5 MPa or more, the skeleton part of the sintered body is densified, and the pores are The foamed slurry is added to the slurry and stirred to form a foamed slurry, which is formed into a molded body by cross-linking polymerization, and the sintered body is formed by cross-linking polymerization. calcium phosphate porous sintered body, characterized in that is obtained by sintering. The calcium phosphate-based porous sintered body consists of a calcium phosphate-based sintered body in which the skeleton part is densified, and the surface part of the skeleton part has a layer consisting of fine irregularities or a calcium phosphate-based porous sintered body. The calcium phosphate porous sintered body according to claim 1, wherein the specific surface area of the porous sintered body is 0.1 m ² / g or more. The calcium phosphate porous sintered body is CaHPO ₄ , Ca ₃ (PO ₄ ) ₂ , Ca ₅ (PO ₄ ) ₃ OH, Ca ₄ O (PO ₄ ) ₂ , Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ , 1 composed of CaP ₄ O ₁₁ , Ca (PO ₃ ) ₂ , Ca ₂ P ₂ O ₇ , Ca (H ₂ PO ₄ ) ₂ , Ca ₂ P ₂ O ₇ , Ca (H ₂ PO ₄ ) ₂ .H ₂ O The calcium phosphate porous sintered body according to claim 1 or 2, wherein one or more of the compounds of the group is a main component. A part of the component of Ca 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. Further, a part of the (PO ₄ ) component can be substituted with one or more selected from VO ₄ , BO ₃ , SO ₄ , CO ₃ , and SiO ₄ , and (OH) 4. The calcium phosphate porous sintered body according to claim ₃ , wherein a part of the component can be substituted with one or more selected from F, Cl, O, CO ₃ , I, and Br.   The calcium phosphate-based porous sintered body is made of calcium phosphate and is any of a crystal, an isomorphous solid solution, a substitutional solid solution, and an interstitial solid solution, and may contain non-stoichiometric defects. Item 3. The calcium phosphate porous sintered body according to Item 1 or 2. 2. The method for producing a calcium phosphate porous sintered body according to claim 1, wherein a step of preparing a slurry in which a calcium phosphate powder and an organic substance curable by cross-linking polymerization are dispersed or dissolved in a solvent, and foaming in the slurry A step of foaming to a predetermined volume by adding an agent and / or stirring and / or introducing gas into a foamed slurry, and adding and / or mixing a crosslinking agent and / or a crosslinking initiator to the foamed slurry And a step of introducing into a mold and curing by cross-linking polymerization to form a molded body, and a step of drying and sintering the molded body, and the porosity is 50% or more and 85% or less. and the average diameter of the communicating portion is 35μm or more, smaller than 150μm in pore diameter of 80μm or more, is 5MPa or more bending strength three-point, that the skeletal portion is densified Method for producing a calcium phosphate porous sintered body, characterized.   The organic material that can be cured by cross-linking polymerization is a polymer having a linear, branched, or block form containing an amino group of polyacrylamide, polyethyleneimine, or polypropyleneimine, and the cross-linking agent is sorbitol polyglycidyl ether , An epoxy compound having two or more epoxy groups of polyglycerol polyglycidyl ether, pentaerythritol polyglycidyl ether, diglycerol polyglycidyl ether, glycerol polyglycidyl ether, or polymethylolpropane polyglycidyl ether Item 7. A method for producing a calcium phosphate porous sintered body according to Item 6.   The method for producing a calcium phosphate porous sintered body according to claim 6 or 7, wherein the surface of the skeleton part of the calcium phosphate porous sintered body is etched with an acid to provide fine irregularities on the surface of the skeleton part. .   9. The calcium phosphate according to claim 8, wherein the acid etching step comprises a step of circulating an acid in the pores of the calcium phosphate porous sintered body installed so as to block the channel in the acid channel. Of manufacturing a porous sintered body. Calcium phosphate powders are CaHPO ₄ , Ca ₃ (PO ₄ ) ₂ , Ca ₅ (PO ₄ ) ₃ OH, Ca ₄ O (PO ₄ ) ₂ , Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ , CaP ₄ O _11. A group of compounds consisting of Ca (PO ₃ ) ₂ , Ca ₂ P ₂ O ₇ , Ca (H ₂ PO ₄ ) ₂ , Ca ₂ P ₂ O ₇ , Ca (H ₂ PO ₄ ) ₂ .H ₂ O The method for producing a calcium phosphate-based porous sintered body according to any one of claims 6 to 9 , wherein one or more kinds are mainly contained. A part of the component of Ca 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. Further, a part of the (PO4) component can be substituted with one or more selected from VO ₄ , BO ₃ , SO ₄ , CO ₃ , SiO ₄ , and (OH) The method for producing a calcium phosphate porous sintered body according to claim 10 , wherein a part of the components can be substituted with one or more selected from F, Cl, O, CO ₃ , I, and Br. .   The calcium phosphate powder is made of calcium phosphate, and is any of a crystal, an isomorphous solid solution, a substitutional solid solution, and an interstitial solid solution, and may contain non-stoichiometric defects. The manufacturing method of the calcium-phosphate type porous sintered compact of any one of these.