JP2004284898A - Calcium phosphate porous body and method of manufacturing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a versatile use porous body having high mechanical strength, excellent user-friendliness, secondary workability and large effective surface area. <P>SOLUTION: The calcium phosphate porous body has uniform three dimensional continuous through holes in which the ratio of the volume of fine pores having 10-100 μm fine pore diameter in the fine pore diameter distribution to the whole fine pore volume is ≥80% and the size of the skeleton forming the fine pores is 1-10 μm. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【００４７】
【発明の効果】
本発明によるリン酸カルシウム多孔体は、前述の特製に起因して、例えば、骨、細胞および血管等の侵入が可能な機能的な空間を有すると共に、均一な細孔構造を有するために、機械的特性に優れ、二次加工が簡便である。従って、本発明によるリン酸カルシウム多孔体は、例えば、骨形成材料等の生体補填材料として有用なだけでなく、空気浄化フィルターや廃水処理などの環境浄化材料および断熱材などの建築材料等としても有用である。
また、本発明によれば、上記の特性を有するリン酸カルシウム多孔体を注型によって製造することができるので、複雑な形状を有するリン酸カルシウム多孔体を容易に得ることができる。
【図面の簡単な説明】
【図１】実施例１で得られたリン酸カルシウム多孔体の破断面の走査型電子顕微鏡写真である。図１（ｂ）は図１（ａ）の拡大写真である。
【図２】実施例１で得られたリン酸カルシウム多孔体の細孔径分布を示すグラフである。
【図３】比較例１で得られたリン酸カルシウム多孔体の破断面の走査型電子顕微鏡写真である。図３（ｂ）は図３（ａ）の拡大写真である。
【図４】比較例１で得られたリン酸カルシウム多孔体の細孔径分布を示すグラフである。
【図５】骨形成試験における埋植部位のＸ線ＣＴ断層写真である。図５（ａ）は実施例１で得られた多孔体を使用した場合の写真であり、図５（ｂ）は、比較例１で得られた多孔体を使用した場合の写真である。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a novel porous calcium phosphate material and a method for producing the same.
More specifically, the present invention provides a ratio [(V / Va) × 100 of the volume (V) of pores having pore diameters in the range of 10 to 100 μm in the pore diameter distribution in the total pore volume (Va). ] Has a uniform continuous three-dimensional through-hole of 80 vol% or more, and the size of the skeleton forming the pore is in the range of 1 to 10 µm, and a method for producing the same.
[0002]
[Prior art]
Calcium phosphate is a major component of living hard tissues that make up vertebrate bones and teeth. Therefore, it is attracting attention as a material having excellent biocompatibility, and its use as a bioreinforcing material such as an artificial bone, an artificial tooth, an artificial root, and a bone filler has been promoted. In particular, since the calcium phosphate porous body has a large contact area between the tissue in the living body and the calcium phosphate material, it can construct a structure entangled with the bone tissue in the living body and can be processed in an operating room or the like. It has been considered suitable.
[0003]
The prior art relating to this type of porous body and a method for preparing the porous body is exemplified below:
(1) A plate-like structure-type calcium phosphate compound having an opening obtained by dropping phosphoric acid in an aqueous suspension of calcium carbonate in the presence of a third substance capable of forming a complex (see Patent Document 1);
(2) Calcium phosphate having a relative density of 35 to 80% by compressing a powder of calcium phosphate ceramics under a pressure of 5 to 50 MPa and heating the compact to 650 to 900 ° C. by applying a pulse voltage. Method for producing a porous ceramic body (see Patent Document 2),
(3) A surface-modified bone replacement member formed by filling a mixture of CM chitin and calcium phosphate granules in the space of a three-dimensional porous body made of a non-absorbable material for a living body such as a wire mesh or a bead combination, and the like. Manufacturing method (see Patent Document 3),
(4) a porous bone filling material comprising a calcium phosphate compound in which pores have a certain direction and communicate along the direction (see Patent Document 4);
[0004]
(5) From a calcium phosphate ceramic porous body having spherical open pores having a pore diameter of 10 to 100 μm and an open porosity of 40 to 80%, and from 20 to 60% by weight of a spherical pore forming material and 80 to 40% by weight of a calcium phosphate ceramic. A green body formed by compression molding and firing the green body at 800 to 1400 ° C. (see Patent Document 5).
(6) A bioreinforcement member obtained by forming holes of 100 to 1000 μm in a green sheet of a ceramic material, stacking the green sheets so that the holes communicate with each other, and firing the stacked body (Patent Document 6) reference),
(7) Three-dimensional gelatinous calcium phosphate precipitate (molar ratio of calcium to phosphorus: 1.45 to 1.75) obtained by reacting calcium ions and phosphate ions in an aqueous medium (pH: 8 or more) Placing in a porous organic material having a network structure, drying the gelatinous calcium phosphate precipitate to form a granular calcium phosphate molded product in the pores of the porous material, and then removing the organic porous material A method for producing a granular calcium phosphate molded article containing (see Patent Document 7),
[0005]
(8) A ceramic substrate is placed in contact with or in proximity to a porous body in which one to three layers of a thermally decomposable substance are three-dimensionally connected in the thickness direction, and the gap between the two and the porous body is A method for producing a ceramic implant material, which comprises heating and firing these composites after filling with a slurry of ceramic powder of the same quality as the ceramic substrate (see Patent Document 8);
(9) A product obtained by reacting a starting material containing a calcium compound and a phosphoric acid compound that generates a gas by a chemical reaction is subjected to pressure molding by a hydrothermal hot press method, and calcium phosphate obtained by calcining the molded body is obtained. Porous ceramics (see Patent Document 9), and
(10) a step of adding an aqueous solution of deflocculant to crystalline calcium phosphate fine powder and mixing the mixture; a step of preparing a porous fluid having continuous fine pores by adding a foaming agent to the mixed solution; Subjecting the porous fluid to a drying treatment to produce a porous body having a calcium phosphate skeleton, and heating the porous body to decompose and eliminate the deflocculant and the foaming agent and fire the calcium phosphate porous body. A method for producing a porous calcium phosphate including a tying step (see Patent Document 10).
[0006]
The conventional calcium phosphate porous material is mainly produced by curing a slurry of a calcium phosphate material containing bubbles using a foaming agent, or by firing the slurry. For example, Patent Document 9 discloses a method for producing a porous body using a method of generating a gas by a chemical reaction. In the case of this method, gas is generated uniformly (that is, the pore diameter is made uniform). ), It is difficult to obtain only a porous body having nonuniform pores of 0.01 to 500 µm.
Patent Document 10 discloses a method of producing a porous body by foaming with a foaming agent. In the case of this production method, the obtained porous body has a pore size of 0.05 to 1.3 mm. There is a problem that a porous body having fine pores cannot be manufactured.
[0007]
As described above, in the case of a method for producing a porous body using a foaming agent, it is difficult to control the formation of pores, so that not only the formed pore structure becomes irregular, but also the strength of the obtained porous body is low. Problem. Furthermore, since the pore diameter of such a porous body is not uniform, there is a problem that when the porous body is used as a biomaterial, a high effect cannot be obtained in constructing an entangled structure with bone tissue.
[0008]
In view of these problems, there has been proposed a method of impregnating a slurry comprising calcium phosphate, a water-soluble organic compound and water with an organic material having a water-insoluble three-dimensional network structure, such as polyurethane, in order to achieve a uniform pore structure. (See Patent Document 11). However, according to this method, in addition to uniform continuous pores formed by the decomposition of the water-soluble organic compound, a porous material having a large number of pores of 100 μm or more formed by the decomposition of an organic substance having a water-insoluble three-dimensional network structure. The porous body has a problem that the compressive strength is low and the handling is inferior.
[0009]
[Patent Document 1]
JP-A-2000-128513
[Patent Document 2]
JP-A-11-035379
[Patent Document 3]
JP-A-11-276510
[Patent Document 4]
JP-A-7-123994
[Patent Document 5]
JP-A-5-208877
[Patent Document 6]
JP-A-8-173463
[Patent Document 7]
Japanese Patent Publication No. 8-29992
[Patent Document 8]
Japanese Patent No. 2759147
[Patent Document 9]
Japanese Patent Publication No. 7-10747
[Patent Document 10]
Patent No. 2597355
[Patent Document 11]
JP-A-2002-274968
[0010]
[Problems to be solved by the invention]
The present invention solves the above-mentioned problems in the art, and is a porous body having high mechanical strength, excellent handling simplicity and secondary workability, and a very large effective surface area. The object of the present invention is to provide a porous material that is also useful as a biomaterial, an environmental purification material such as an air purification filter and wastewater treatment, and a building material such as a heat insulating material.
[0011]
[Means for Solving the Problems]
That is, in the present invention, the ratio [(V / Va) × 100] of the volume (V) of the pores having pore diameters in the range of 10 to 100 μm in the total pore volume (Va) in the pore diameter distribution is determined. The present invention relates to a porous calcium phosphate having a uniform three-dimensional continuous through-hole of not less than 80 vol% and a size of a skeleton forming the pore is in a range of 1 to 10 μm, and a method for producing the porous calcium phosphate. .
[0012]
BEST MODE FOR CARRYING OUT THE INVENTION
Since the pores of the calcium phosphate porous body according to the present invention are three-dimensional continuous through-holes, they can be continuously brought into contact with gas or liquid. In the porous calcium phosphate according to the present invention, the ratio of the volume (V) of the pores having a diameter in the pore diameter distribution of 10 to 100 μm, preferably 20 to 80 μm in the total pore volume (Va) [( V / Va) × 100] is at least 80 vol%, preferably at least 90 vol%. When the ratio is less than 80 vol% (for example, when the volume of pores having a diameter of 100 μm or more in the pore diameter distribution increases), mechanical properties decrease, and the handling becomes less convenient. When pores smaller than 10 .mu.m increase, there arises a problem that the porous body does not effectively act on invasion of bone or cells.
[0013]
The pore size of the porous calcium phosphate according to the present invention can be measured using, for example, a scanning electron microscope or an optical stereo microscope, and the pore size distribution can be quantified by, for example, a mercury intrusion method. The amount of continuous pores in the porous calcium phosphate according to the present invention can be evaluated, for example, by measuring the air permeability.
[0014]
The size of the skeleton forming the pores of the porous calcium phosphate according to the present invention is in the range of 1 to 10 μm, preferably 3 to 8 μm in order to maintain the strength of the porous body and secure an effective surface area. When the size of the skeleton is smaller than 1 μm, the strength is reduced, so that the operation at the time of insertion into the defective portion becomes difficult. On the other hand, if the size of the skeleton is larger than 10 μm, the porosity is relatively reduced, so that the skeleton cannot function sufficiently as a scaffold for bone tissue regeneration.
The size (thickness) of the skeleton of the porous calcium phosphate according to the present invention can be measured using, for example, a scanning electron microscope or an optical stereo microscope.
[0015]
The porous calcium phosphate according to the present invention preferably has a porosity in the range of 40 to 90%, preferably 50 to 80%, from the viewpoint of maintaining the strength of the porous body and securing the effective surface area. When the porosity is higher than 90%, the mechanical properties of the porous body are reduced, and when the porosity is lower than 40%, it becomes difficult to secure a sufficient effective surface area. For example, when the porous body is used as a medical material, a material for environmental purification, or the like, the effective surface area becomes insufficient.
[0016]
As a method for measuring the porosity of the porous calcium phosphate according to the present invention, a method of calculating from the volume and weight of the porous body and the true specific gravity of calcium phosphate and filling the liquid having a known specific gravity into the pores of the porous body, A method of calculating from the weight of the porous body before and after that is exemplified, but the porosity of the porous body can also be obtained by using a mercury intrusion method utilizing the latter principle.
The specific surface area as an index of the effective surface area of the porous body may be determined by an adsorption method based on the amount of molecules or ions having a known occupied area on the surface of the porous body. Examples of the method include a transmission method determined from permeability and an immersion heat method determined from a calorific value when the porous body is immersed in a liquid.
[0017]
A preferred method for producing the above-described porous calcium phosphate according to the present invention is a method comprising casting an aqueous slurry containing calcium phosphate, a water-soluble organic compound and water into a heat-resistant container, and subjecting the aqueous slurry to a baking treatment. .
[0018]
Examples of the calcium phosphate used in the method for producing the porous calcium phosphate according to the present invention include α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, hydroxyapatite, octacalcium phosphate, calcium orthophosphate, amorphous calcium phosphate and Calcium phosphate glass is exemplified, but β-tricalcium phosphate and α-tricalcium phosphate are particularly preferred because of their excellent bioabsorbability.
In addition, these calcium phosphate components may be used as a composite, particularly as a mixture of two or more, if desired.
As the above-mentioned calcium phosphate component, those produced naturally can be used, but a product synthesized from a phosphoric acid-containing aqueous solution and a calcium-containing aqueous solution by a wet method, and a heat treatment of a raw material for producing calcium phosphate by a dry method at a high temperature. Or a product synthesized by reacting a raw material for producing calcium phosphate by a gas phase method.
[0019]
Examples of the water-soluble organic compound used in the method for producing the porous calcium phosphate according to the present invention include water-soluble saccharides (for example, glucose, maltose, sucrose, trehalose, starch, carboxymethylcellulose, carboxymethyl starch, alginic acid, hyaluronic acid, Dextran and chitosan, etc.), water-soluble proteins (eg, albumin, collagen, casein, lysozyme, globulin, etc.), and water-soluble polymer compounds (eg, polyacrylic acid, polymethacrylic acid, polyacrylamide, polymethacrylamide, polyvinyl alcohol) And polyvinylpyrrolidone, etc.), and water-soluble polysaccharides such as starch, carboxymethyl cellulose, carboxymethyl starch, and alginic acid are particularly preferable.
[0020]
The proportion of calcium phosphate and water-soluble organic compound used in preparing the above aqueous slurry is usually such that the weight percentage of the latter in the mixture of calcium phosphate and water-soluble organic compound is in the range of 10 to 70 wt%. Adjustment is preferred. If the used amount of the water-soluble organic compound is higher than 70 wt%, the porosity of the obtained calcium phosphate becomes too high and the mechanical properties are lowered. If the used amount is lower than 10 wt%, the porosity becomes low. Is too low to function sufficiently as a scaffold for bone tissue regeneration, which is not preferable.
[0021]
In preparing the above-mentioned aqueous slurry, it is desirable to use calcium phosphate in a powder state, and preferably a powder having a particle size of 0.01 to 10 μm, particularly 0.1 to 5 μm. The particle size of the water-soluble organic compound is not particularly limited. For example, when starch is used, powder having a particle size of 10 to 100 μm substantially equal to the pore diameter of the obtained calcium phosphate porous material, that is, potato starch It is preferable to use
[0022]
The weight ratio of water / powder (a mixture of calcium phosphate and a water-soluble organic compound) during preparation of the aqueous slurry is generally adjusted to 0.5 to 1.5. When the weight ratio is less than 0.5, the fluidity of the aqueous slurry is low, and the workability at the time of casting is deteriorated. When the weight ratio is more than 1.5, the process from molding to firing is performed. It is not preferable because sedimentation of the powder occurs during the process and an uneven porous body having a high porosity on the surface is obtained.
[0023]
The firing temperature of the aqueous slurry prepared as described above is such that the calcium phosphate in the slurry sinters, the water-soluble organic compounds disappear, and the crystal structure and amorphous structure of the target calcium phosphate are stable. The temperature is not particularly limited, but is preferably in the range of 500 to 1700 ° C. In a particularly preferred embodiment of such a calcination treatment, the calcination treatment is performed in two stages, that is, the aqueous slurry is calcined in the range of 500 to 1,000 ° C. to eliminate the water-soluble organic compound (degreasing). The obtained fired product is fired in the range of 500 to 1700 ° C. to stabilize the crystal structure of calcium phosphate in two stages.
[0024]
The heating rate in the above-mentioned firing step depends on the kind of the calcium phosphate and the water-soluble organic compound to be used, the firing temperature and the like, and is not particularly limited, but is usually 1 to 10 ° C / min, preferably 2 to 6 ° C. / Min. If the heating rate is too fast, the decomposition of the water-soluble organic compound occurs at once, resulting in a non-uniform pore size distribution.On the contrary, if the heating rate is too slow, it takes time to manufacture. However, there is a problem in terms of simplicity of manufacture.
[0025]
Further, the calcination time in the above calcination step also depends on the type of the calcium phosphate and the water-soluble organic compound to be used, the calcination temperature and the like, and is not particularly limited, but is usually 5 to 50 hours, preferably 10 to 36 hours. is there. If the firing time is excessively long, thermal decomposition or particle growth occurs, and the strength of the porous body decreases. Conversely, if the calcination time is too short, the densification is insufficient, so that the strength also decreases.
[0026]
Note that the above-described firing step is usually performed in the air, but may be performed in another atmosphere, for example, Ar or N 2.₂And O₂Or the like.
[0027]
ADVANTAGE OF THE INVENTION According to the said manufacturing method by this invention, the fine pore diameter in a fine pore diameter distribution is in the range of 10-100 micrometers, and the calcium phosphate porous body which has a uniform three-dimensional continuous through-hole can be obtained. In order to efficiently achieve high protein adsorption characteristics, ion exchange characteristics, cell affinity and irritation using a smaller amount of calcium phosphate, it is advantageous to increase the area in contact with the surrounding gas or liquid per unit volume. is there. Furthermore, since the calcium phosphate porous body has continuous pores that allow the flow of gas and liquid, and the pore diameter is in the range of 10 to 100 μm, the inside of the pores includes, for example, proliferating cells and contaminant gas. Therefore, the porous body according to the present invention is very useful as a material for artificial bone, a material for environmental purification, and the like.
[0028]
As described above, as for the functionality of the porous body, as the area in contact with the surrounding gas or liquid increases, the number of sites that can react increases, and for example, high efficiency in biocompatibility and environmental purification can be achieved. When the pore volume of the porous body is 70 vol%, assuming that the average pore diameter is 10 μm and all the pores are continuous, a cube of 1.0 cm × 1.0 cm × 1.0 cm is assumed. The surface area of the porous body is at least about 0.28m²Becomes Further, assuming that the average pore diameter is 100 μm and all the pores are continuous, the surface area of the porous body in the cube is about 0.028 m²Becomes That is, as the pore diameter becomes smaller, the surface area per unit volume of the porous body becomes larger, so even with such a difference, a difference of 10 times or more in the amount of adsorbed protein and the amount of ion exchange on the calcium phosphate surface is obtained. Occurs. This is the case where it is assumed that the continuous pores are connected by one, and when three-dimensional continuous pores (that is, continuous through holes) are formed, the difference becomes larger.
[0029]
Further, if all the pores are continuous, the gas or liquid to be treated can freely flow inside the porous body, and not only the contact area becomes large, but also as long as the supply of the gas or liquid continues. The effect that the reaction or the like on the surface is maintained can be obtained. On the other hand, in the case of closed pores in which pores are not continuous, a surface reaction with gas or liquid does not occur (here, closed pore means pores (pores) inside the skeleton without contact with the outside world. ). In the case of a bottle-shaped pore that is opened on one side only, it is difficult to continuously supply the surrounding liquid or gas, so that a continuous surface reaction cannot be expected. Therefore, the point that the pores are continuous is a very important element in, for example, a medical material or an environment purification material that involves the adsorption of proteins, organic molecules, and inorganic molecules. The utility is extremely high.
[0030]
In the synthesis of a porous body by sintering, when a powder having a particle size of 1 to 10 μm is used as a powder for producing a green body, there is a high possibility that pores existing between the particles will remain in the sintered sample. . In this case, when the size of the skeleton after sintering is 100 μm or more, closed pores of 10 μm or less remain inside the skeleton structure. The closed pores do not contribute to protein adsorption or reaction due to contact with gas or liquid necessary for environmental purification. Therefore, in order to prepare a high-performance porous body suitable for the above-mentioned applications, it is necessary to avoid pores remaining inside the skeleton. Making the skeleton diameter very small is a very effective technique for increasing the number of pores per unit volume and at the same time avoiding the residual closed pores. Furthermore, in order to improve the mechanical properties at the same porosity, it is important to make the pore size distribution as uniform as possible, and it is particularly effective to reduce the abundance of coarse pores of 100 μm or more.
[0031]
The porous calcium phosphate according to the present invention can be used as it is as a bioreplacement material such as an osteogenic material, but it is used by covering the inner wall of the pore with a protein such as alginic acid, chitosan, or cellulose, collagen, or albumin. Alternatively, these polysaccharides or proteins may be used by filling the pores. In addition, a drug, a growth factor, or the like may be used as it is, or may be used after being coated, or may be used by being added to, included in, or bound to a polysaccharide or protein to be filled in a porous body.
[0032]
Drugs used in combination with the calcium phosphate porous material according to the present invention include calcitonin, parathyroid hormone, retinoic acid, ascorbic acid, vitamin D and bisphosphonate, etc. Antibacterial agents such as disinfectants are exemplified.
[0033]
The growth factors used in combination with the calcium phosphate porous material according to the present invention include bone morphogenetic proteins (Bone morphogenetic protein), tumor growth factor-β, osteopontin, basic fibroblast growth factor and insulin-like growth factor, etc. Growth factors and the like.
[0034]
The porous calcium phosphate according to the present invention may be subjected to sterilization before use. Sterilization methods include methods described in the Japanese Pharmacopoeia, namely, dry heat sterilization at 180 ° C for 2 hours, wet heat steam sterilization at 121 ° C for 20 minutes, ethylene oxide gas sterilization, and gamma ray sterilization. Is exemplified.
[0035]
Since the porous calcium phosphate according to the present invention has communicating pores and a very large surface area, bacteria, viruses, pollen, dust, CO₂, NO_X, SO_XIt is extremely useful in use as an air purification filter for removing ozone and the like, and as an environmental purification material such as wastewater treatment used for removing heavy metal and light metal ions, organic matter, bacteria and the like in water. The calcium phosphate porous material according to the present invention can be used as it is as an environment-purifying material. However, the inner wall of the pores can be polysaccharides (eg, alginic acid, chitosan, cellulose, etc.) or polymer compounds (eg, nylon, polyvinyl chloride, polyethylene). , Polypropylene, polyurethane, polyester, etc.) and then used as an environmental purification material.
[0036]
The porous calcium phosphate according to the present invention has characteristics such as high porosity, low toxicity, and nonflammability, and thus is useful as a building material such as a heat insulating material. In this case as well, the porous calcium phosphate according to the present invention can be used as it is as a building material, but the inner walls of the pores are formed of polysaccharides (eg, alginic acid, chitosan, cellulose, etc.) or high molecular compounds (eg, nylon, Vinyl, polyethylene, polypropylene, polyurethane, polyester, etc.), and then used as a building material.
[0037]
【Example】
Hereinafter, the present invention will be described more specifically with reference to examples. However, these examples are for illustratively describing the present invention, and the present invention is not limited to these examples.
[0038]
Examples 1-3
Table 1 shows β-tricalcium phosphate [product of Nacalai Tesque; code 069-30] and potato starch [product of Nacalai Tesque; code 321-28 (particle size: about 50 μm)]. The starch content was placed in a ball mill so that the indicated starch content [= weight of potato starch / (weight of tricalcium phosphate + weight of potato starch) × 100 (%)], and these components were mixed for 1 hour without using a medium. An aqueous slurry was prepared by adding 35 g of pure water to 40 g of the obtained mixed powder and sufficiently stirring. The viscosities at 25 ° C. of the aqueous slurries having starch contents of 50% by weight, 25% by weight and 10% by weight were 700 mPa · s, 1200 mPa · s and 1300 mPa · s, respectively. Each aqueous slurry was poured into an alumina crucible and dried at 60 ° C. for about 12 hours. Then, the crucible was moved into a muffle furnace, and the furnace was heated to 1000 ° C. at a rate of temperature increase of 5 ° C./min and fired. The treatment was performed at this temperature for 3 hours. Next, after the crucible was cooled to room temperature, it was transferred into a high-temperature electric furnace, the furnace was heated to 1400 ° C. at a rate of temperature increase of 5 ° C./min, and a firing treatment was performed at this temperature for 12 hours.
[0039]
FIG. 1 shows a scanning electron micrograph of a fracture surface of a calcium phosphate porous material prepared from an aqueous slurry having a starch content of 50% by weight. FIG. 1B is an enlarged photograph of FIG. As is clear from FIG. 1, the obtained calcium phosphate porous body has uniform pores in the range of 10 to 100 μm and uniform skeletons in the range of 1 to 10 μm.
[0040]
The porosity, average pore diameter and pore size distribution of the obtained calcium phosphate porous body were measured by a mercury intrusion method, and the results are shown in FIG. 2 (pore size distribution) and Table 1 (porosity and average pore diameter). Show.
Further, Vh was calculated using the following equation as an index indicating the uniformity of the pore diameter distribution, and the results are shown in Table 1.
Vh (vol%) = [V (cc) / Va (cc)] × 100
In the formula, V indicates the volume of pores having a diameter of 10 to 100 μm, and Va indicates the volume of all pores. Vh is 88 to 93 vol%, which indicates that the obtained porous body has a uniform pore size distribution.
Furthermore, the compressive strength of the obtained calcium phosphate porous body was measured according to a conventional method, and the results are shown in Table 1.
[0041]
Comparative Example 1
20 g of β-tricalcium phosphate (a product of Nacalai Tesque; code 069-30) and 20 g of potato starch (a product of Nacalai Tesque; code 321-28) were put into a ball mill, and without using a medium. These components were mixed for 1 hour, 35 g of pure water was added to the obtained mixture, and the mixture was sufficiently stirred to prepare an aqueous slurry. The viscosity at 23 ° C. of the aqueous slurry was 700 mPa · s.
[0042]
The aqueous slurry was sufficiently impregnated with a polyurethane "body sponge" (a product of Myna). After confirming that the slurry was uniformly impregnated, the body sponge was dried at 60 ° C. for about 12 hours, then transferred into a muffle furnace, and heated to 1000 ° C. at a rate of 5 ° C./min. Heating and baking were performed at this temperature for 3 hours. Next, after cooling the body sponge to room temperature, the body sponge was transferred into a high-temperature electric furnace, and the furnace was heated to 1400 ° C. at a rate of temperature increase of 5 ° C./min, and a firing treatment was performed at this temperature for 12 hours.
[0043]
FIG. 3 shows a scanning electron micrograph of the fracture surface of the obtained calcium phosphate porous body. FIG. 3B is an enlarged photograph of FIG. As is clear from FIG. 3A, in the porous body, coarse pores of 200 μm coexist in addition to uniform pores in the range of 10 to 100 μm.
FIG. 4 shows the pore size distribution of the calcium phosphate porous body. In FIG. 4, another peak is observed near 150 μm, which indicates that the pore size distribution of the porous body is not uniform. This is considered to be due to pores formed by the disappearance of the urethane sponge skeleton supporting the slurry.
Further, the porosity, average pore diameter, Vh and compressive strength of the porous calcium phosphate were measured in the same manner as in Examples 1 to 3, and the results are shown in Table 1. Vh indicating the uniformity of the pore size distribution is lower (71 vol%) than in the example, and the compressive strength is 1/5 of that in the example. This is considered to be due to the presence of coarse pores.
[0044]
Bone formation test
The calcium phosphate porous bodies obtained in Example 1 and Comparative Example 1 were subjected to secondary processing into test pieces having a diameter of 4 mm and a length of 10 mm, and these test pieces were implanted in a hole formed in the tibia of a rabbit. . Regarding the workability at the time of secondary processing, the porous body obtained in Example 1 was good, but in the case of the porous body obtained in Comparative Example 1, when the sample was cut into a desired size, There was a problem that some were missing. Also, regarding the handleability at the time of implantation, the porous body obtained in Example 1 has a higher compressive strength than the porous body obtained in Comparative Example 1, so that the insertion operation into the defective portion is easier. there were.
[0045]
FIG. 5 shows an X-ray CT tomographic image of the implanted site one month later. FIG. 5A is an X-ray CT tomogram when the porous body obtained in Example 1 is used, and FIG. 5B is an X-ray CT tomogram when the porous body obtained in Comparative Example 1 is used. It is a line CT tomogram. As is clear from FIG. 5, in each case where the calcium phosphate porous bodies obtained in Example 1 and Comparative Example 1 were used, the remaining amount of the porous body was slight, and bone tissue was mostly contained in the defect. However, when the porous body obtained in Example 1 was used, it was found that the bone density of the defect was higher and the repair effect was high.
[0046]
[Table 1]

[0047]
【The invention's effect】
The calcium phosphate porous body according to the present invention has a functional space capable of invading bones, cells, blood vessels, and the like, and has a uniform pore structure. And secondary processing is easy. Therefore, the porous calcium phosphate according to the present invention is useful not only as a bioreplacement material such as an osteogenic material, but also as an environmental purification material such as an air purification filter and wastewater treatment and a building material such as a heat insulating material. is there.
Further, according to the present invention, a calcium phosphate porous body having the above-described properties can be produced by casting, so that a calcium phosphate porous body having a complicated shape can be easily obtained.
[Brief description of the drawings]
FIG. 1 is a scanning electron micrograph of a fractured surface of a porous calcium phosphate obtained in Example 1. FIG. 1B is an enlarged photograph of FIG.
FIG. 2 is a graph showing the pore size distribution of the porous calcium phosphate obtained in Example 1.
FIG. 3 is a scanning electron micrograph of a fracture surface of the porous calcium phosphate obtained in Comparative Example 1. FIG. 3B is an enlarged photograph of FIG.
FIG. 4 is a graph showing the pore size distribution of the calcium phosphate porous body obtained in Comparative Example 1.
FIG. 5 is an X-ray CT tomogram of an implanted part in an osteogenesis test. FIG. 5A is a photograph when the porous body obtained in Example 1 is used, and FIG. 5B is a photograph when the porous body obtained in Comparative Example 1 is used.

Claims (9)

Uniform in which the ratio [(V / Va) × 100] of the volume (V) of the pores having a pore diameter in the range of 10 to 100 μm to the total pore volume (Va) in the pore diameter distribution is 80 vol% or more. A porous calcium phosphate, characterized in that it has three-dimensional continuous through-holes, and the size of the skeleton forming the pores is in the range of 1 to 10 μm. The porous calcium phosphate according to claim 1, wherein the porosity is in a range of 40 to 90%. The calcium phosphate is α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, hydroxyapatite, octacalcium phosphate, calcium orthophosphate, amorphous calcium phosphate or calcium phosphate glass, or a mixture of two or more of these. 3. The porous calcium phosphate according to claim 1 or claim 2. A method for producing a porous calcium phosphate, comprising casting an aqueous slurry containing calcium phosphate, a water-soluble organic compound and water into a heat-resistant mold and subjecting the slurry to a baking treatment. The method according to claim 4, wherein the calcination treatment is performed at 500C to 1700C. The calcium phosphate is α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, hydroxyapatite, octacalcium phosphate, calcium orthophosphate, amorphous calcium phosphate or calcium phosphate glass, or a mixture of two or more of these. The method according to claim 4. The method according to any one of claims 4 to 6, wherein the water-soluble organic compound is a saccharide, a protein, polyacrylic acid or polyvinyl alcohol, or a mixture of two or more thereof. The weight percentage of the water-soluble organic compound in the mixture of calcium phosphate and the water-soluble organic compound is in the range of 10 to 70 wt%, and the weight ratio of water / powder (the mixture) at the time of preparing the slurry is 0.5 to 1. The method according to any one of claims 4 to 7, which is 5. The method according to any one of claims 4 to 8, wherein the baking treatment is performed in two stages: a baking treatment at 500 to 1000C and a baking treatment at 500 to 1700C.

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