JP2006160556A - Sintered material and its manufacturing method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sintered material as a biomaterial having high mechanical strength and bio-compatibility, easy to be penetrated, fixed, and grown by an osteoblast cell, etc., in its pore, and having a porous structure easy for a living body to be metabolized therein, and its manufacturing method. <P>SOLUTION: This sintered material as a biomaterial comprises a porous structure with its pore non-spherical and communicating and has a porosity of 50-90%. In this manufacturing method, a powder of an inorganic material is mixed with a polymerizable monomer, the monomer is polymerized after foaming into a porous polymer, and the porous polymer is sintered while it is kept deformed by applying stress. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a sintered body and a manufacturing method thereof, and more particularly to a sintered body as a biomaterial that can be used for artificial bones, artificial teeth, and the like, and a manufacturing method thereof.

  Artificial bones, artificial teeth, or bone or tooth replacement materials (hereinafter referred to as “bone replacement materials”) used in surgery and dentistry have sufficient mechanical strength and are non-toxic and highly compatible with living bodies. Is preferred. Furthermore, there is a need for a bone prosthesis material that has good in vivo metabolism depending on the site of use and can be naturally replaced with new bones and teeth. From this point of view, a porous bone substitute material made of a calcium phosphate compound is a component close to living bones and teeth, and is used as an excellent bone substitute material. As a bone filling material having good metabolism in vivo, a porous bone filling material obtained by mixing and sintering ceramic powder such as a calcium phosphate compound and an organic substance is known (Patent Document 1, Patent Document). 2). In these conventionally known sintered bodies for porous biomaterials, most of the formed pores tend to be independent pores depending on the pore formation method, and the adjacent pores formed are in contact with each other and are continuous. Even in such a case, the cross-sectional area of the portion where each pore communicates (hereinafter also referred to as “communication portion”) tends to be small. When the sintered body having such a pore structure is inserted into a living body, it is difficult to uniformly introduce osteoblasts and the like necessary for bone formation into each pore. Therefore, with the aim of improving the porosity connectivity, biocompatibility, etc. of the porous bone filling material, for example, a calcium phosphate porous sintered body in which the porosity, the pore diameter, the spherical pores, and the pore diameter of the communicating portion thereof are adjusted (patent document) 3) A bone prosthesis molded article (Patent Document 4) in which an organic porous material is impregnated with a ceramic raw material slurry and fired in a deformed state to have an uneven pore density is known.

Japanese Unexamined Patent Publication No. 60-16879 Japanese Patent Application Laid-Open No. 60-21773 JP 2000-302567 A JP 2002-58688 A

  However, the above-mentioned porous filling material is not sufficient in terms of improving biocompatibility and the like, and particularly in the case of a porous body produced by generating bubbles in a fluid raw material, the pore communicating portion is Although it is widened to some extent, most of the bubbles are almost spherical, and the surface area of the pores is reduced with respect to the pore volume in order to smoothly promote the establishment, growth, metabolism, bone formation, etc. of osteoblasts in the pores. It is desirable to enlarge it. On the other hand, in order to increase the surface area of the pores of the sintered body, the porosity must be significantly increased or the pore diameter must be reduced. If the porosity is increased too much, the strength of the sintered body decreases, which is not preferable as a biomaterial. If the pore diameter is too small, it becomes difficult for osteoblasts or the like to enter the pores, and metabolism in the living body becomes difficult, resulting in poor biocompatibility.

  In order to solve the above problems, the present invention has a porous structure of pores having a special shape connected by relatively large communication holes, and has mechanical strength and penetration, establishment, growth, and the like of osteoblasts into the pores. An object of the present invention is to provide a sintered body having a high metabolic compatibility and easily producing bone, and a method for producing the same.

Means for solving the problems of the present invention include:
(1) A sintered body for a biomaterial which has a porous structure in which pores are non-spherical and communicate with each other, and has a porosity of 50 to 90%.
(2) The sintered body according to (1), wherein the porosity is 60 to 80%.
(3) A sintered body in which an inorganic powder and a polymerizable monomer are mixed and foamed, the monomer is polymerized to form a porous polymer, and the porous polymer is baked while being deformed by applying stress. It is a manufacturing method.
(4) The method for producing a sintered body according to (3), wherein the stress applied to the porous polymer is compressive stress.

  Since the sintered body of the present invention has high mechanical strength and biocompatibility, most of the pores are in communication with large communication holes, and the pore shape is complicated, the pore surface area is large, and bones are contained in the pores. It is a sintered body for a biomaterial having a porous structure in which blast cells and the like are easy to enter, settle and grow, and are easily metabolized and bone-formed in vivo. Moreover, the manufacturing method of the sintered compact of this invention is a suitable manufacturing method of the said sintered compact.

  The sintered body of the present invention has a porous structure in which pores are non-spherical and communicate with each other, and has a porosity of 50 to 90%, preferably 60 to 80%. As a feature of the present invention, it is important that the pores are non-spherical. The non-spherical shape may be an elliptical sphere, a flat sphere, a polyhedron, a polygon, a half moon, a crescent, or the like, or a shape having a square or triangular cross section. Usually, when a viscous fluid such as a liquid or a slurry is made into a foam by stirring or the like, the bubbles of the porous structure become spherical. Each bubble has a substantially spherical shape, whether it is a closed bubble or a continuous bubble in which the bubbles communicate with each other. In the case of open cells, it is not a perfect sphere, but it can be regarded as a substantially spherical shape because spherical bubbles are connected. When a porous elastic body having substantially spherical pores as described above is deformed by a stress such as compression, tension or torsion, the spherical pores are also deformed. The non-spherical shape in the present invention refers to a shape like a pore generated when such a spherical pore is variously deformed by stress. This non-spherical shape only needs to be a non-spherical shape as a result, and it is not necessary to use the pore generation method as described above. In addition, the non-spherical shape of the present invention is substantially non-spherical, most of the pores are non-spherical, and conversely, most of the pores are substantially spherical. Is not included. By making the pores non-spherical in this way, the surface area of the pores can be increased even with the same porosity, and the contact area between the sintered body and the biological material such as osteoblasts can be increased to facilitate the establishment of osteoblasts and the like. It has the effect of improving metabolic suitability to the living body.

  The sintered body of the present invention has a porous structure in which these non-spherical pores communicate with each other. The communication between the pores may not be regular. Some pores may be independent, and some pores may communicate with several other pores. The porous structure that communicates is a structure that can enter the pores through which biological materials such as gas, liquid, and osteoblasts communicate from the outside of the sintered body.

  The porosity P may be calculated by a normal method. For example, the true density ρ of a sintered body having the same composition and crystal form pores as the measurement target is measured, and the apparent density ρ ′ calculated from the volume and weight of the measurement target sintered body. And the porosity P = 1−ρ ′ / ρ may be calculated. Or it is good also as a porosity by calculating | requiring as a calculated value from the ratio of the pore area in the electron micrograph of a sintered compact, and making this into an approximate value. When the porosity is 50 to 90%, preferably 60 to 80%, the strength of the sintered body can be maintained, and at the same time, the surface area becomes large and the contact area with biological materials such as osteoblasts becomes large and the metabolic suitability is improved. effective. In addition, when the porosity is within this range, there is a feature that the structure is easy to communicate between the pores.

  In such a sintered body, the communicating portion between pores, that is, the size of the communicating hole is preferably 25 μm or more, and preferably 50 μm or more. The communication holes are usually not circular but have a size distribution. Here, the size of the communication hole is a size as an average converted diameter measured by a mercury porosimeter. If the size of the communication hole is 25 μm or more, preferably 50 μm or more, biological materials such as osteoblasts are likely to enter and suitable as a biological material. Note that if the size of the communication hole is 25 μm or more, preferably 50 μm or more, the pore diameter is naturally 25 μm or more, preferably 50 μm or more. Therefore, a biological material such as osteoblasts can easily enter the entire pore. Material. Normally, it is considered that the communicating part of the open cell is the thinnest, so there is no problem as long as a biological substance or the like easily enters this part. Although there is no upper limit to the size of the communication hole, it can be manufactured up to about 8 mm, but in reality, it is often 1 mm or less. If the pore diameter and the size of the communication hole are too large, the surface area of the sintered body decreases as the strength of the sintered body decreases, and the contact area with biological materials such as osteoblasts decreases, which may reduce metabolic suitability.

The sintered body of the present invention may be made of any material, but a calcium phosphate material is suitable. For example, 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 , Ca ( One of a group of compounds consisting of 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 There is a calcium phosphate-based sintered body mainly containing two or more kinds. Some of these Ca components are selected from Sr, Ba, Mg, Fe, Al, Y, La, Na, K, Ag, Pd, Zn, Pb, Cd, H, and other rare earth elements. It may be substituted with one or more atoms. Further, a part of the (PO ₄ ) component may be substituted with one or more atomic groups selected from VO ₄ , BO ₃ , SO ₄ , CO ₃ and SiO ₄ . Further, a part of the (OH) component may be substituted with one or two or more atoms selected from F, Cl, O, CO ₃ , I and Br. As other materials, alumina, zirconia, carbon, silicon nitride, silica, titania and the like can be used. The sintered body may be a crystalline body, an amorphous body, a solid solution, or a mixture thereof.

  Although the manufacturing method of the sintered compact of the present invention is not particularly limited, a preferable manufacturing method will be described below with reference to FIG. Usually, the inorganic powder slurry is first prepared. As the raw material inorganic powder, an inorganic powder that is a raw material of the above-described material may be used. In particular, calcium phosphate powder is suitable. That is, calcium phosphate, calcium hydrogen phosphate, calcium dihydrogen phosphate, and mixtures and compounds thereof are used. A powder obtained by firing a mixture of hydroxyapatite or β-calcium phosphate at 800 ° C. is a particularly suitable raw material. There are no particular restrictions on the particle size or particle shape of the powder, as long as it is easily mixed with the slurry medium to produce a slurry.

  The slurry medium is usually water. The proportion of water is preferably reduced within a range that does not hinder foaming and polymer production described below. However, it should be noted that if the proportion of water is too small, it is difficult to produce a foam having moderately sized pores. If 10 to 200% by weight, preferably 20 to 100% by weight of water based on the raw inorganic powder is used, a desired slurry can be easily obtained. Water is added to the raw inorganic powder and stirred to obtain a uniform slurry. As the slurry medium other than water, a liquid capable of dissolving alcohol or the following monomer for polymerization may be used.

  A monomer for polymerization is added to the raw inorganic powder slurry. As the monomer, a raw material inorganic powder slurry to which the monomer is added is foamed as will be described later, and a polymer that is an elastic body or a plastically deformable molded body (referred to as a plastic body) having a porous structure communicated when polymerized. What is necessary is just to be able to form. Examples thereof include monofunctional group monomers such as acrylamide, methacrylamide, acrylic acid, methacrylic acid, acrylonitrile, and maleic acid. Among these, acrylamide and methacrylamide are preferable monomers. It is also preferable to add a polyfunctional monomer that forms a three-dimensional polymer as a crosslinking component. As the polyfunctional group monomer, methylene bisacrylamide, ethylene glycol divinyl ether, diethylene glycol divinyl ether, ethylene glycol diallyl ether, diethylene glycol diallyl ether, ethylene glycol diacrylate, ethylene glycol dimethacrylate and the like are suitable. Furthermore, a three-dimensional structure polymer can be produced by adding a crosslinking agent to the polymer. As the crosslinking agent, an epoxy compound or the like is suitable. In addition, a dispersant for improving the dispersion of the monomer, and an additive such as a catalyst for starting polymerization at a necessary time and a polymerization inhibitor may be added.

  If the monomer is difficult to polymerize with oxygen or the like, the process may be carried out in an inert gas atmosphere such as nitrogen by vacuum degassing the monomer-added raw material inorganic powder slurry. The amount of the monomer added to the raw inorganic powder slurry is not particularly limited, but it is usually desirable from the economical and firing step that the amount of the monomer is within the range where the desired polymer can be formed. Generally, the added amount of the monomer may be 1 to 50 parts by weight with respect to 100 parts by weight of the raw inorganic powder slurry.

  Next, as the foaming step, the monomer-added raw material inorganic powder slurry is stirred, or a surfactant or a foaming agent (these are collectively referred to as a foaming agent) is stirred to foam the slurry. Foaming may follow the usual slurry foaming method. Since the porosity of the polymer is determined by the degree of foaming, it is necessary to foam the polymer in consideration of this. In addition, since the porosity of the sintered body is close to the porosity after the polymer is further deformed, in the case of compressive deformation, foaming is performed particularly considering the compression. In addition, since the pore size of the polymer is almost determined by this foaming step, it is preferable to perform foaming with care. In general, if stirring is carried out for a long time, bubbles become smaller. Usually, stirring is suitably about 1 to 60 minutes. As the foaming agent, anionic, cationic, nonionic and amphoteric surfactants can be used. For example, polyoxyethylene lauryl ether, polyoxyethylene alkyl ether, polyoxyethylene nonyl phenyl ether, polyoxyethylene alkyl allyl ether, polyoxyethylene alkylamine, polyethylene glycol fatty acid ester, decaglycerin monolaurate, alkanolamide, etc. are used. I can do it.

  When foaming is completed, the monomer in the foamed slurry is polymerized. The polymerization may be performed in accordance with the normal polymerization conditions of the monomer, such as adding a polymerization initiator or adding heat, light, or radiation. Usually, it is convenient to polymerize with a polymerization initiator at room temperature. For example, a small amount of an aqueous ammonium persulfate solution may be added to the acrylamide monomer. In order to carry out the polymerization uniformly and quickly, it is advisable to stir the slurry immediately after adding the polymerization initiator to uniformly disperse the polymerization initiator. However, when the polymerization proceeds, stirring is not performed and the formation of a porous polymer molded body is awaited. The polymer molded body is cut into a desired shape. Alternatively, the foamed slurry before polymerization can be put into a container having a desired shape and polymerized to obtain a polymer molded body having a desired shape. This polymer molded body must be capable of substantially elastic deformation or plastic deformation in the subsequent polymer deformation step. In other words, when a stress for deformation is applied to the polymer molded body, the molded body is not divided and destroyed. For this purpose, it is necessary to appropriately select a monomer for polymerization and polymerization conditions.

  In the polymer deformation step, the polymer molded body is deformed by applying stress. As the stress, any stress may be used as long as it deforms the polymer molded body, such as compression, tension, shearing, twisting, bending, and composite stress thereof. Usually, it may be inserted while being compressed into a container having a smaller volume than the polymer molded body. As a result, the polymer molded body is deformed by compressive stress, and the internal pores are also deformed from spherical to non-spherical. Regarding the degree of deformation, in the case of compression, it is desirable to compress the volume to 20 to 95%, preferably 35 to 85%, more preferably 50 to 75%.

  When a deformed polymer is obtained, this is fired to produce a sintered body. The molded body is dried before firing. Note that if the drying is insufficient, cracking or abnormal deformation may occur during firing as in the case of ordinary sintered bodies. It is important to dry under conditions that do not cause deformation or cracking. Appropriate conditions may be determined depending on the size and shape of the polymer, but it is usually performed at a temperature of 90 ° C. or less over several hours to several days. In addition, if the molded body after deformation is a molded body by elastic deformation, drying and baking described below are performed while applying stress. If it is a molded body by plastic deformation, it can be dried and fired without being stressed.

  The firing step is a step of firing the raw inorganic powder to form a sintered body. At that time, the added organic substance and residual moisture including the polymer are decomposed or detached. The firing conditions may be appropriately selected depending on the amount of organic matter contained in the raw material inorganic powder and the molded body, the amount of water, and the like. Usually, the temperature may be increased from room temperature to a sintering final temperature of 800 to 1300 ° C. at about 5 to 100 ° C./hour and sintered at the sintering final temperature for about 1 to 12 hours. In addition, in a temperature range where shape deformation of the molded body is likely to occur, such as a water evaporation temperature range of about 100 ° C., an organic matter decomposition temperature range of 300 to 450 ° C., a crystal water desorption temperature range of an inorganic raw material, etc. Careful firing is required. The molded body is allowed to cool after sintering to be a good sintered body of the present invention.

Example 1
A calcium phosphate slurry was prepared by adding 67.6 g of distilled water to 170 g of calcium phosphate powder mixed at a ratio of 2 parts by weight of hydroxyapatite and 8 parts by weight of β-tricalcium phosphate and calcined at 800 ° C. In this slurry, 8.37 g of acrylamide as a monofunctional group monomer, 0.0628 g of methylenebisacrylamide as a polyfunctional group monomer, 0.39 g of diethylene glycol diallyl ether, 0.110 g of tetramethylethylenediamine as a catalyst, and Poise 532A (Kao Corporation) 2.30 g was added and vacuum degassed for 15 minutes. This deaerated slurry was placed in a nitrogen atmosphere, 3.45 g of polyoxyethylene lauryl alcohol was added as a foaming surfactant, and the mixture was stirred and foamed at room temperature for 20 minutes with a hand mixer. 1 g of ammonium peroxodisulfate aqueous solution (corresponding to 0.0265 g as ammonium peroxodisulfate) was added as a polymerization initiator to the foamed slurry, and the mixture was stirred for about 1 minute and mixed uniformly. The foamed slurry was transferred to a square container, capped and allowed to stand for 30 minutes to complete cross-linking polymerization to obtain a foam. This foam is cut into 1 cm squares to obtain compression samples.

This compression sample was inserted into a square container having a volume of 0.8 cm ^{3 in} order to compress the volume by 20%. Cover lightly and dry at 80 ° C. for 12 hours. The dried sample is heated at a constant rate to 600 ° C. in 20 hours while maintaining the shape, and is maintained for 8 hours. Thereafter, the temperature was raised to 1050 ° C. at a constant rate in 2 hours, followed by firing at 1050 ° C. for 3 hours. When firing was completed, the mixture was allowed to cool to obtain a sintered body of the present invention. The porosity, average diameter of communication holes, and relative surface area of this sintered body were measured. The results are shown in Table 1. The porosity of the sintered body was calculated from the volume and weight of the sintered body. The average diameter of the communication holes was measured by a mercury intrusion method using a mercury porosimeter. The relative surface area of the pores was measured by measuring the total perimeter of the pores in the measurement region (640 × 480 μm) of a 100-fold cross-sectional photograph of an electron microscope and using Comparative Example 1 without compression as a reference (100%). The relative perimeter of the example was calculated and used as the relative surface area. Usually, the actual surface area ratio is considered to be greater than the relative surface area (perimeter length ratio). Electron micrographs of the sintered body are shown in FIG. 3 (100 times) and FIG. 4 (30 times). FIG. 9 shows a measurement chart of the pore diameter distribution of the communication holes.

(Example 2)
A sintered body was produced in the same manner as in Example 1 except that the compression sample in Example 1 was compressed by 40% instead of 20% in volume. The porosity, average diameter of communication holes, relative surface area, and compressive strength of this sintered body were measured in the same manner as in Example 1. The results are shown in Table 1. Electron micrographs of the sintered body are shown in FIG. 1 (100 times) and FIG. 2 (30 times). FIG. 10 shows a measurement chart of pore size distribution.

(Example 3)
A sintered body was produced in the same manner as in Example 1 except that the compression sample in Example 1 was compressed by 60% instead of being compressed by 20%. The porosity, average diameter of communication holes, relative surface area, and compressive strength of this sintered body were measured in the same manner as in Example 1. The results are shown in Table 1. Electron micrographs of the sintered body are shown in FIG. 5 (100 times) and FIG. 6 (30 times). FIG. 11 shows a measurement chart of pore size distribution.

(Comparative Example 1)
The sample for compression in Example 1 was not compressed and dried and fired in the same manner as in Example 1 to produce a sintered body. The porosity, average diameter of communication holes, relative surface area, and compressive strength of this sintered body were measured in the same manner as in Example 1. The results are shown in Table 1. Electron micrographs of the sintered body are shown in FIG. 7 (100 times) and FIG. 8 (30 times). FIG. 12 shows a measurement chart of pore size distribution.

  As can be seen from the measurement results and electron micrographs, the pores of the comparative example are almost circular (spherical), and all of the pores of the examples are non-circular (nonspherical) deformed. 9 to 12 show the pore size distribution of the communicating portions of Examples 1 to 3 and Comparative Example 1, but the pore size of the communicating portion becomes smaller as the compressibility increases, but as shown in Table 1. The pore diameter peaks of the examples are almost 30 μm or more, and are large enough for invasion of osteoblasts, odontocytes and the like. In addition, the relative surface area (peripheral length ratio) of the examples increases as the compression ratio increases, indicating that the surface area increases due to deformation. Although the compressive strength of the sintered body is not described, there is no problem in use because it is 1 MPa or more.

  The sintered body of the present invention can be used as a material for artificial bones, artificial teeth or bones and teeth used in surgery and dentistry. It can be used not only for human bodies but also for animal bones and teeth. It can also be applied to a substrate for proliferation of osteoblasts, odontocytes and the like in vitro.

FIG. 1 is an electron micrograph (100 times) of the sintered body after compression to 60%. FIG. 2 is an electron micrograph (30 times) of the sintered body after compression to 60%. FIG. 3 is an electron micrograph (100 times) of the sintered body after being compressed to 80%. FIG. 4 is an electron micrograph (30 times) of the sintered body after being compressed to 80%. FIG. 5 is an electron micrograph (100 times) of the sintered body after being compressed to 40%. FIG. 6 is an electron micrograph (30 times) of the sintered body after being compressed to 40%. FIG. 7 is an electron micrograph (100 times) of a sintered body that is not compressed. FIG. 8 is an electron micrograph (30 ×) of a sintered body that is not compressed. FIG. 9 is a pore size distribution chart of the sintered body after being compressed to 40%. FIG. 10 is a pore size distribution chart of the sintered body after being compressed to 60%. FIG. 11 is a pore size distribution chart of the sintered body after being compressed to 80%. FIG. 12 is a pore size distribution chart of a sintered body that is not compressed. FIG. 13 is a block flow diagram showing a method for manufacturing a sintered body according to the present invention.

Claims (4)

  A sintered body for a biomaterial which has a porous structure in which pores are non-spherical and communicate with each other, and has a porosity of 50 to 90%.   The sintered body according to claim 1, wherein the porosity is 60 to 80%.   A method for producing a sintered body in which an inorganic powder and a polymerizable monomer are mixed and foamed, and then the monomer is polymerized to form a porous polymer, and the porous polymer is fired while being deformed by applying stress. . 4. The method for producing a sintered body according to claim 3, wherein the stress applied to the porous polymer is a compressive stress.

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