WO2013035690A1 - Porous body and method for producing porous body - Google Patents

Porous body and method for producing porous body Download PDF

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Publication number
WO2013035690A1
WO2013035690A1 PCT/JP2012/072452 JP2012072452W WO2013035690A1 WO 2013035690 A1 WO2013035690 A1 WO 2013035690A1 JP 2012072452 W JP2012072452 W JP 2012072452W WO 2013035690 A1 WO2013035690 A1 WO 2013035690A1
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porous body
slurry
spherical
pores
producing
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PCT/JP2012/072452
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French (fr)
Japanese (ja)
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智勇 松本
美知子 坂本
大助 庄司
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Hoya株式会社
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Priority to JP2013532598A priority Critical patent/JP6005046B2/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/06—Titanium or titanium alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B38/00—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof
    • C04B38/10—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof by using foaming agents or by using mechanical means, e.g. adding preformed foam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
    • C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
    • C04B2111/00836—Uses not provided for elsewhere in C04B2111/00 for medical or dental applications

Definitions

  • the degree of variation in the pore diameter of the spherical pores can be expressed by, for example, the half-value width of the pore diameter in addition to the standard deviation described above.
  • the half width is preferably 100 ⁇ m or less, and more preferably 80 ⁇ m or less.
  • this ceramic porous body is composed of an aggregate of spherical secondary particles composed of a granulated body of primary particles composed of a calcium phosphate compound.
  • the spherical pores are configured to have pores formed on the surface by the gaps between the spherical secondary particles.
  • the pores preferably have a diameter of 20 ⁇ m or less, and more preferably 10 ⁇ m or less. By setting the pore diameter within such a range, it is possible to reliably maintain the bone regeneration ability required for a ceramic porous body artificial bone.
  • Such a ceramic porous body is composed of a calcium phosphate compound having excellent biocompatibility.
  • Examples of calcium phosphate compounds include apatites such as hydroxyapatite (HAP), fluorine apatite, and carbonate apatite, dicalcium phosphate, tricalcium phosphate (TCP), tetracalcium phosphate, and octacalcium phosphate. These can be used alone or in combination of two or more. Among these calcium phosphate compounds, those having a Ca / P ratio of 1.0 to 2.0 are preferred, and those with 1.5 to 2.0 are more preferred.
  • HAP hydroxyapatite
  • TCP tricalcium phosphate
  • tetracalcium phosphate tetracalcium phosphate
  • octacalcium phosphate octacalcium phosphate.
  • the ceramic porous body has been described above among the inorganic porous bodies, but the inorganic porous body includes a porous body made of a titanium-based compound. Like the ceramic porous body, this porous body also has spherical pores. The relative porosity, the average pore diameter and standard deviation of the spherical pores, the calculation method thereof, the formed communication holes and effects, and the like are the same as those of the ceramic porous body described above.
  • the method for producing a porous body of the present invention includes the following first step and second step.
  • the first step is a step of adding a paste containing a water-soluble polymer compound and a surfactant to a slurry containing powder.
  • the second step the slurry (mixed slurry) to which the paste has been added is foamed by stirring, and then the mixed slurry is gelled and dried to obtain a dried product, and the obtained dried product Is a step of sintering.
  • these steps will be sequentially described.
  • the powder is not particularly limited, but a powder containing secondary particles having an average particle diameter of 0.5 to 80 ⁇ m composed of primary particles having an average particle diameter of 100 nm or less is preferably used. And this slurry is obtained by disperse
  • a solvent such as water may be added to the paste to adjust the viscosity.
  • water-soluble polymer compounds examples include cellulose derivatives such as methylcellulose, polysaccharides such as curdlan, synthetic polymers such as polyvinyl alcohol, polyacrylic acid, polyacrylamide, and polyvinylpyrrolidone. Of these, cellulose derivatives are preferred. Thereby, gelatinization of a slurry can be performed more reliably.
  • the paste is divided into a predetermined amount and added to the slurry a plurality of times.
  • the temperature of the paste is preferably set higher than the temperature of the slurry, and specifically, is set higher by about 10 to 20 ° C. More specifically, the temperature of the slurry is preferably about 10 to 30 ° C. The paste temperature is preferably about 30 to 40 ° C.
  • a paste containing a high-concentration water-soluble polymer compound is added to the slurry. For this reason, when the paste is added to the slurry at a normal temperature, the paste has a high viscosity, so that it becomes difficult to uniformly mix the paste into the slurry.
  • the powder is preferably 100 parts by weight, the water-soluble polymer compound is 1 to 10 parts by weight, and the surfactant is preferably 1 to 10 parts by weight. If the amount of powder added is too small, it may take more time than necessary to dry. Moreover, when there is too much addition amount of a powder, there exists a possibility that the viscosity of a slurry may become high too much and it may become difficult to generate a bubble. Moreover, when the addition amount of the water-soluble polymer compound is less than 1 part by weight, gelation of the slurry is difficult.
  • the addition amount of the water-soluble polymer compound is more than 10 parts by weight, the viscosity of the slurry is too high and foaming is difficult. Furthermore, foaming is difficult when the addition amount of the surfactant is less than 1 part by weight. Moreover, even if the addition amount of the surfactant exceeds 10 parts by weight, the effect corresponding to the addition cannot be obtained.
  • the stirring force can be obtained by [maximum output of the stirrer (W) / amount of aqueous solution (L)] ⁇ (actual rotational speed / maximum rotational speed). Further, the output of the stirrer increases in order to maintain the rotation speed as the viscosity of the slurry increases. However, when foaming to obtain a ceramic porous body having a high porosity, the slurry viscosity does not substantially change from the slurry viscosity at the time of preparation. Therefore, the effect of viscosity is virtually negligible.
  • impeller type homogenizer having such a structure
  • examples of the impeller type homogenizer having such a structure include PH91, PA92, HF93, FH94P, PD96, and HM10 manufactured by SMT.
  • an inert gas such as air, nitrogen, or argon may be injected into the slurry being stirred.
  • the stirring time depends on the stirring force, but is generally set to about 1 to 30 minutes.
  • the mixed slurry is preferably set to a liquid temperature of about 0 to 25 ° C., more preferably about 5 to 20 ° C.
  • This gelation is performed, for example, by the action of a water-soluble polymer compound such as methylcellulose by heating a slurry sufficiently foamed by stirring to 80 ° C. or higher and lower than 100 ° C.
  • a water-soluble polymer compound such as methylcellulose
  • the heating temperature is less than 80 ° C., gelation may be insufficient.
  • the heating temperature is 100 ° C. or higher, moisture boils and the formed pore structure may be destroyed.
  • the dried body (green block) is sintered to obtain a sintered body (ceramic porous body of the present invention).
  • the conditions for sintering the green block are, for example, a temperature of 1000 to 1250 ° C. and a time of 2 to 10 hours. If the sintering temperature is less than 1000 ° C., a ceramic porous body having sufficient strength cannot be obtained. When the sintering temperature is higher than 1250 ° C., when hydroxyapatite is used as the calcium phosphate compound, hydroxyapatite is decomposed into tricalcium phosphate and calcium oxide. The sintering time is appropriately set according to the sintering temperature.
  • the temperature at which the green block is sintered is set within the range of 1000 to 1150 ° C. This reliably prevents the transition from ⁇ -TCP to ⁇ -TCP.
  • a processing step for processing the dried body and / or a degreasing step for degreasing the dried body may be performed.
  • the green block since the water-soluble polymer compound contained in the green block acts as a binder, the green block has a mechanical strength that can be handled. Therefore, the dry body can be cut without being pre-baked.
  • the degreasing step can be performed by heating the green block to 300 to 900 ° C., for example. Thereby, the water-soluble polymer compound and the surfactant can be reliably removed from the green block.
  • the temperature may be gradually increased until the sintering temperature is reached.
  • the temperature is raised from room temperature to about 600 ° C. at a temperature increase rate of about 10 to 100 ° C./hour, and then the temperature is raised to a sintering temperature at a temperature increase rate of about 50 to 200 ° C./hour to maintain this temperature. Can be done.
  • the powder used in the first step is a powder composed of spherical secondary particles of a calcium phosphate compound.
  • the method for producing a porous body of the present invention uses a titanium compound as the powder. Even when a powder composed of structured particles is used, the process can be performed as described above. Thereby, the ceramic porous body comprised with titanium is obtained.
  • the conditions and effects of the first step and the second step are the same as those in the method for manufacturing the ceramic porous body described above.
  • porous body of the present invention can be used not only as an artificial biomaterial, but also as a liquid chromatography filler, a catalyst carrier, various electric / electronic materials, a nuclear reactor material, a ceramic heating element, and the like. it can.
  • methylcellulose powder was added to an aqueous solution in which 1.4 parts by weight of a surfactant (alkylbenzene sulfonic acid EDT) was added to 27 parts by weight of pure water, and a stirring defoamer (manufactured by Shinky, A paste binder was prepared by dispersing and mixing with “Awatori Nertaro ARE-250”).
  • a surfactant alkylbenzene sulfonic acid EDT
  • a slurry (mixed slurry) to which the paste-like binder is added is obtained by adding the paste-like binder prepared in the step ⁇ 2> to the slurry prepared in the step ⁇ 1>. It was. In this case, the temperatures of the slurry and the paste-like binder were 20 ° C. and 35 ° C., respectively.
  • the obtained bubble-containing slurry was gelled at 83 ° C. Then, the bubble-containing slurry was dried by maintaining the obtained gel at 83 ° C., thereby obtaining a green block (block before sintering).
  • the green block was processed into a shape of 14 mm ⁇ 14 mm ⁇ 14 mm. Thereafter, the green block was sintered at 1050 ° C. for 2 hours in the air to obtain a 10 mm ⁇ 10 mm ⁇ 10 mm sintered body composed of ⁇ -tricalcium phosphate ( ⁇ -TCP). .
  • ⁇ -TCP ⁇ -tricalcium phosphate
  • Example 2 Sintering of Example 2 composed of ⁇ -tricalcium phosphate ( ⁇ -TCP) in the same manner as in Example 1 except that the secondary particles in step ⁇ 1> were 150 parts by weight. Got the body.
  • Example 3 In the step ⁇ 1>, in place of the secondary particles having a Ca / P ratio of 1.5, secondary particles (average) consisting of granules of primary particles having an Ca / P ratio of 1.67 (average particle size: 80 nm) Particle size: 15 ⁇ m)
  • a sintered body of Example 3 composed of hydroxyapatite (HAP) was obtained in the same manner as in Example 1 except that a slurry containing 100 parts by weight was prepared.
  • step ⁇ 1> 100 parts by weight of the secondary particles were replaced with 50 parts by weight of pure titanium powder.
  • step ⁇ 2> 27 parts by weight of pure water was changed to 150 parts by weight of pure water, and methylcellulose powder 3.4. 1 part by weight of methylcellulose powder and 1.4 parts by weight of alkylbenzene sulfonic acid EDT were replaced with 0.25 part by weight of alkylbenzene sulfonic acid EDT.
  • gelation and drying were performed at 85 ° C. with a hot air dryer.
  • a sintered body of Example 4 made of titanium was obtained in the same manner as in Example 1 except that the above was performed.
  • Example 3 (Comparative Example 3)
  • a fatty acid alkanolamide-based surfactant N, N-dimethyldodecylamine oxide, “AROMOX” manufactured by Lion Co., Ltd.
  • HAP hydroxyapatite
  • the internal structure of the sintered body was measured using micro CT (SKYSCAN, “Skyscan 1172”)
  • the CT images of the upper surface (height 8 mm), middle surface (height 5 mm) and lower surface (height 2 mm) were obtained (see FIGS. 2 and 3).
  • the image analysis was performed by measuring the equivalent circle diameter of the spherical pores on Photoshop based on the photographed image result by SEM and measuring the pore diameters of the measured spherical pores. Based on the results, the average pore diameter, standard deviation, and half width of the spherical pores were determined. The results are shown in Table 2 and Table 3.
  • the average pore diameter of the spherical pores is 100 to 165 ⁇ m. And the standard deviation was 60 ⁇ m or less. Thereby, it turned out that a uniform spherical pore is obtained.
  • the average pore diameter of the spherical pores was 100 to 165 ⁇ m, and the standard deviation thereof was 60 ⁇ m or less. . Thereby, it turned out that a uniform spherical pore is obtained.
  • Example 2 the sintered bodies of Example 2 and Comparative Example 2 were respectively implanted in beagle femurs according to ISO10993-6. After 4 weeks and 13 weeks, the sintered body was removed, and a toluidine blue pathological tissue specimen was prepared. The bone regeneration ability was evaluated by image analysis of the specimen.
  • bone tissues included osteoids and mature bones. The results are shown in Table 4.
  • Example 2 and Comparative Example 2 were compared, the amount of bone regeneration was 32 times and 1.5 times at 4 and 13 weeks, respectively. Thereby, it turned out that the sintered compact of Example 2 is excellent in early bone regeneration.
  • the sintered body of each example was a porous body excellent in uniformity of spherical pores as compared with the sintered body of each comparative example. Also, due to this, it was speculated that in the sintered body of Example 2, osteoblasts and the like necessary for bone formation were able to uniformly enter the pores. Therefore, compared with the sintered body of Comparative Example 2, the ceramic porous body of the present invention can accelerate bone regeneration.
  • the porous body of the present invention has spherical pores.
  • the relative porosity of the porous body is 50% or more, the average pore diameter of the spherical pores is 100 to 165 ⁇ m, and the standard deviation of the spherical pores is 60 ⁇ m or less.

Abstract

Provided is a porous body containing a spherical pore. A relative porosity of the porous body is at least 50%, an average pore diameter of the spherical pore is between 100μm and 165μm, and a standard deviation of the spherical pore is 60μm or less. A pore content of the spherical pore with a pore diameter of at least 500μm is 1% or less. When the porous body is applied to a bone supplementing material, a cell such as an osteoblast cell may be moved smoothly, and early bone regeneration is possible. The present invention further relates to a method for producing the porous body.

Description

多孔体および多孔体の製造方法Porous body and method for producing porous body
　本発明は、多孔体および多孔体の製造方法、特に、無機多孔体および無機多孔体の製造方法に関するものである。 The present invention relates to a porous body and a method for producing the porous body, and more particularly to an inorganic porous body and a method for producing the inorganic porous body.
　近年、歯科、外科等で、人工骨、人工歯、骨類の補填等に用いられる骨補填材としては、毒性がなく、機械的強度が十分で、生体組織と親和性が高く結合しやすい多孔体が好ましく用いられている。具体的には、リン酸カルシウム系化合物で構成されたセラミックス多孔体が好ましく用いられている。 In recent years, bone substitutes used for artificial bones, artificial teeth, bones, etc. in dentistry, surgery, etc. are non-toxic, have sufficient mechanical strength, and have a high affinity with biological tissues and are easily bonded The body is preferably used. Specifically, a ceramic porous body composed of a calcium phosphate compound is preferably used.
　このようなリン酸カルシウム系化合物で構成されたセラミックス多孔体（骨補填材）の製造方法として、例えば、以下の２つの方法が知られている。第１の方法は、リン酸カルシウム系化合物で構成される原料粉末と熱分解物質とを混合し、所定の形状に成形した後、得られた成形体を加熱して熱分解物質の除去と原料粉末の焼結を行う方法（例えば、特開昭６０－２１７６３号公報参照。）である。第２の方法は、原料粉末と熱分解物質との他に、さらに起泡剤を混合し、この起泡剤により気泡を発生させた状態で、熱分解物質の除去と原料粉末の焼結を行う方法（例えば、特開２０００－３０２５６７号公報参照。）である。 For example, the following two methods are known as a method for producing a ceramic porous body (bone filler) composed of such a calcium phosphate compound. In the first method, a raw material powder composed of a calcium phosphate compound and a pyrolytic substance are mixed and molded into a predetermined shape, and then the resulting molded body is heated to remove the pyrolytic substance and This is a method of sintering (for example, see Japanese Patent Application Laid-Open No. 60-21773). In the second method, in addition to the raw material powder and the pyrolysis material, a foaming agent is further mixed, and in the state where bubbles are generated by this foaming agent, the pyrolysis material is removed and the raw material powder is sintered. This is a method to be performed (for example, see Japanese Patent Application Laid-Open No. 2000-302567).
　しかしながら、これらの製造方法では、気孔を形成するために添加した熱分解物質がほぼ均一に原料粉末と接触するとは限らないことから、形成された気孔の大部分は独立した気孔となることが多い。また、形成された気孔の気孔径のバラツキが大きい。さらに、隣り合う気孔同士が接し、これに起因して、気孔同士が連通した連通孔がたとえ形成されたとしても、連通孔の断面積が小さく、かつ、そのバラツキが大きい。 However, in these manufacturing methods, since the pyrolysis substance added to form pores does not always contact the raw material powder almost uniformly, most of the formed pores often become independent pores. . Moreover, the variation in the pore diameter of the formed pores is large. Furthermore, even if adjacent pores are in contact with each other and a communication hole in which the pores communicate with each other is formed, the cross-sectional area of the communication hole is small and the variation thereof is large.
　したがって、かかる構成の骨補填材を、生体の骨欠損部等に補填したとしても、骨生成に必要な骨芽細胞等を、気孔内に均一に侵入させることが困難である。そのため、均一な骨再生が実現できないという問題がある。 Therefore, even if the bone grafting material having such a configuration is filled in a bone defect part or the like of a living body, it is difficult to uniformly enter osteoblasts and the like necessary for bone generation into the pores. Therefore, there is a problem that uniform bone regeneration cannot be realized.
　本発明の目的は、球状をなす球状気孔が均一である多孔体、およびこの球状気孔が均一である多孔体を製造することができる多孔体の製造方法を提供することにある。 An object of the present invention is to provide a porous body in which spherical spherical pores are uniform, and a porous body manufacturing method capable of manufacturing a porous body in which the spherical pores are uniform.
　このような目的は、下記（１）～（１０）に記載の本発明により達成される。 Such an object is achieved by the present invention described in the following (1) to (10).
　（１）　球状気孔を有する多孔体であって、
　その相対気孔率が５０％以上であり、
　前記球状気孔は、その平均気孔径が１００～１６５μｍであり、かつ、その標準偏差が６０μｍ以下であることを特徴とする多孔体。 (1) A porous body having spherical pores,
Its relative porosity is 50% or more,
The porous body, wherein the spherical pores have an average pore diameter of 100 to 165 μm and a standard deviation of 60 μm or less.
　このような平均気孔径および標準偏差を有する球状気孔を備える多孔体は、均一な球状気孔を備えるものと言うことができる。 It can be said that a porous body having spherical pores having such an average pore diameter and standard deviation has uniform spherical pores.
　（２）　気孔径が５００μｍ以上の前記球状気孔の気孔含有率（気孔数基準）が１％以下である上記（１）に記載の多孔体。 (2) The porous body according to (1), wherein a pore content (based on the number of pores) of the spherical pores having a pore diameter of 500 μm or more is 1% or less.
　このように、その気孔径が極端に大きいものの含有量を小さくすることで、気孔径のバラツキ（標準偏差）がより小さくなるため、気孔径の均一性をより高めることができる。 Thus, by reducing the content of the extremely large pore diameter, the variation in the pore diameter (standard deviation) is further reduced, so that the uniformity of the pore diameter can be further increased.
　（３）　前記球状気孔同士が連通することにより形成された連通孔を有し、この連通孔の平均径が５０μｍ以上である上記（１）または（２）に記載の多孔体。 (3) The porous body according to the above (1) or (2), which has communication holes formed by communication between the spherical pores, and an average diameter of the communication holes is 50 μm or more.
　連通孔の平均径を、かかる範囲内に設定することにより、多孔体として求められる強度を維持することができる。また、多孔体を骨補填材に適用した場合、連通孔を介した球状気孔同士間の骨芽細胞等の細胞の移動が円滑に行われるため、早期の骨再生が実現可能となる。 By setting the average diameter of the communication holes within such a range, the strength required for the porous body can be maintained. In addition, when the porous body is applied to the bone grafting material, cells such as osteoblasts move smoothly between the spherical pores via the communication holes, so that early bone regeneration can be realized.
　（４）　前記多孔体は、リン酸カルシウム系化合物またはチタン系化合物で構成されている上記（１）ないし（３）のいずれかに記載の多孔体。 (4) The porous body according to any one of (1) to (3), wherein the porous body is made of a calcium phosphate compound or a titanium compound.
　（５）　当該多孔体は、前記リン酸カルシウム系化合物で構成される一次粒子の造粒体からなる球状二次粒子の集合体で構成されており、
　前記球状気孔は、その表面に、前記球状二次粒子の間隙により形成された、２０μｍ以下の細孔を有している上記（４）に記載の多孔体。 (5) The porous body is composed of an aggregate of spherical secondary particles composed of a granulated body of primary particles composed of the calcium phosphate compound,
The said spherical pore is a porous body as described in said (4) which has the pore of 20 micrometers or less formed by the space | gap of the said spherical secondary particle on the surface.
　細孔の口径を、かかる範囲内に設定することにより、セラミックス多孔体として求められる強度を確実に維持することができる。 The strength required as a ceramic porous body can be reliably maintained by setting the aperture diameter within the above range.
　（６）　上記（１）ないし（５）のいずれかに記載の多孔体の製造方法であって、
　粉体を含有するスラリーに、水溶性高分子化合物と、界面活性剤とを含有するペーストを添加して混合スラリーを得る第１の工程と、
　前記混合液スラリーを、撹拌することにより起泡させた後に、前記混合スラリーをゲル化、乾燥させて乾燥体を得、さらに前記乾燥体を焼結する第２の工程とを有することを特徴とする多孔体の製造方法。 (6) The method for producing a porous body according to any one of (1) to (5) above,
A first step of adding a paste containing a water-soluble polymer compound and a surfactant to a slurry containing powder to obtain a mixed slurry;
A second step of foaming the mixed slurry after stirring and then gelling and drying the mixed slurry to obtain a dried product, and further sintering the dried product. A method for producing a porous body.
　このように、第１の工程において、スラリーとペーストとを別個に分けて調製し、その後、これらを混合する構成とすることで、スラリーに含まれる粉体に対して、ペーストを均一に分散することができるようになる。そのため、第２の工程で得られる多孔体を、上述したような球状気孔の平均気孔径および標準偏差を有するものとすることができる。 In this way, in the first step, the slurry and the paste are separately prepared and then mixed, whereby the paste is uniformly dispersed with respect to the powder contained in the slurry. Will be able to. Therefore, the porous body obtained in the second step can have the average pore diameter and standard deviation of the spherical pores as described above.
　（７）　前記紛体は、リン酸カルシウム系化合物またはチタン系化合物で構成された粒子で構成されている上記（６）に記載の多孔体の製造方法。 (7) The method for producing a porous body according to (6), wherein the powder is composed of particles made of a calcium phosphate compound or a titanium compound.
　（８）　前記第１の工程において、前記ペーストの温度は、前記スラリーの温度よりも１０～２０℃高く設定される上記（６）または（７）に記載の多孔体の製造方法。 (8) The method for producing a porous body according to (6) or (7), wherein in the first step, the temperature of the paste is set to be 10 to 20 ° C. higher than the temperature of the slurry.
　これにより、第２の工程で得られる多孔体は、より確実に上述した球状気孔の平均気孔径および標準偏差を有するものとなる。 Thereby, the porous body obtained in the second step has the above-mentioned average pore diameter and standard deviation of the spherical pores more reliably.
　（９）　前記界面活性剤は、スルフォン酸系界面活性剤である上記（６）ないし（８）のいずれかに記載の多孔体の製造方法。 (9) The method for producing a porous body according to any one of (6) to (8), wherein the surfactant is a sulfonic acid surfactant.
　これにより、セラミックス多孔体を得た際に、このものを構成するリン酸カルシウム系化合物を、硫酸基が導入されたものとすることができる。そのため、セラミックス多孔体を骨補填材に適用した場合、骨生成の際に骨芽細胞等の細胞活性が高くなり、その結果、骨補填材における骨再生をより早期に行うことができる。 Thus, when the ceramic porous body is obtained, the calcium phosphate compound constituting the ceramic porous body can have a sulfate group introduced therein. Therefore, when a ceramic porous body is applied to a bone grafting material, cell activity such as osteoblasts is increased during bone formation, and as a result, bone regeneration in the bone grafting material can be performed earlier.
　（１０）　前記水溶性高分子化合物は、セルロース誘導体である上記（６）ないし（９）のいずれかに記載の多孔体の製造方法。 (10) The method for producing a porous body according to any one of (6) to (9), wherein the water-soluble polymer compound is a cellulose derivative.
　これにより、ペーストが添加されたスラリーのゲル化をより確実に行うことができる。 Thereby, gelation of the slurry to which the paste is added can be performed more reliably.
　本発明の多孔体であれば、球状をなす球状気孔が均一であるものと言うことができる。例えば、多孔体のうちの無機多孔体を骨補填材に適用した場合、骨芽細胞等の細胞の移動が円滑に行われるため、早期の骨再生が実現可能となる。 If it is a porous body of the present invention, it can be said that spherical spherical pores are uniform. For example, when an inorganic porous body of porous bodies is applied to a bone grafting material, cells such as osteoblasts are smoothly moved, so that early bone regeneration can be realized.
　また、本発明の多孔体の製造方法によれば、得られる多孔体を、その相対気孔率が５０％以上であり、さらに、球状気孔の平均気孔径が１００～１６５μｍであり、かつ、その標準偏差が６０μｍ以下であるものとすることができる。 Further, according to the method for producing a porous body of the present invention, the obtained porous body has a relative porosity of 50% or more, and the average pore diameter of spherical pores is 100 to 165 μm, and its standard The deviation may be 60 μm or less.
図１は、本発明のセラミックス多孔体の一例の走査顕微鏡写真である。FIG. 1 is a scanning photomicrograph of an example of the ceramic porous body of the present invention. 図２は、実施例１および比較例１の焼結体における、上面、中面および下面のＣＴ画像を示す図である。FIG. 2 is a view showing CT images of the upper surface, the middle surface, and the lower surface in the sintered bodies of Example 1 and Comparative Example 1. FIG. 図３は、実施例２および比較例２の焼結体における、上面、中面および下面のＣＴ画像を示す図である。FIG. 3 is a view showing CT images of the upper surface, the middle surface, and the lower surface in the sintered bodies of Example 2 and Comparative Example 2.
　以下、本発明の多孔体および多孔体の製造方法の好適な実施形態について詳細に説明する。 Hereinafter, preferred embodiments of the porous body and the method for producing the porous body of the present invention will be described in detail.
　ここで、本発明の多孔体は、セラミックスやチタン系化合物で構成される無機多孔体と、ポリエーテルエーテルケトン（ＰＥＥＫ）などの樹脂材料で構成される有機多孔体とを含んでいる。以下では、無機多孔体について説明する。 Here, the porous body of the present invention includes an inorganic porous body composed of ceramics or a titanium compound and an organic porous body composed of a resin material such as polyetheretherketone (PEEK). Below, an inorganic porous body is demonstrated.
　まず、本発明の無機多孔体のうち、セラミックス多孔体について詳細に説明する。 First, the ceramic porous body will be described in detail among the inorganic porous bodies of the present invention.
　図１は、本発明のセラミックス多孔体の一例の走査顕微鏡写真である。 FIG. 1 is a scanning micrograph of an example of the ceramic porous body of the present invention.
　本発明のセラミックス多孔体は、リン酸カルシウム系化合物で構成され、球状をなす球状気孔を有するものである。その相対気孔率が５０％以上であり、さらに、前記球状気孔は、その平均気孔径が１００～１６５μｍであり、かつ、その標準偏差が６０μｍ以下であることを特徴とする。 The ceramic porous body of the present invention is composed of a calcium phosphate compound and has spherical pores. The relative porosity is 50% or more, and the spherical pores have an average pore diameter of 100 to 165 μm and a standard deviation of 60 μm or less.
　このようなセラミックス多孔体は、細胞および生体組織の培養に用いる担体や、骨補填用等に好適な生体親和性を有する人工生体材料に用いることができる。 Such a ceramic porous body can be used as a carrier used for culturing cells and biological tissues, or an artificial biomaterial having biocompatibility suitable for bone replacement.
　特に、セラミックス多孔体を骨補填用の骨補填材に適用した場合、本発明では、球状気孔の平均気孔径が１００～１６５μｍであり、かつ、その標準偏差が６０μｍ以下となっており、前記球状気孔が均一なものとなっている。そのため、リン酸カルシウム系化合物で構成される粒子の塊の発生を低減することができ、前記球状気孔同士が連通することにより形成される連通孔も均一なものとなる。これにより、骨生成に必要な骨芽細胞等を、球状気孔内に均一に侵入させることができる。その結果、均一な骨再生が実現可能となる。 In particular, when a ceramic porous body is applied to a bone filling material for bone filling, in the present invention, the average pore diameter of spherical pores is 100 to 165 μm, and the standard deviation thereof is 60 μm or less, and the spherical The pores are uniform. Therefore, generation | occurrence | production of the lump of the particle | grains comprised with a calcium-phosphate type compound can be reduced, and the communicating hole formed when the said spherical pores communicate also becomes uniform. As a result, osteoblasts and the like necessary for bone generation can be uniformly introduced into the spherical pores. As a result, uniform bone regeneration can be realized.
　なお、セラミックス多孔体の相対気孔率は５０％以上であればよいが、５５％以上であるのが好ましく、６０％以上であるのがより好ましい。相対気孔率をかかる範囲内に設定することにより、前記球状気孔同士が確実に連通して連通孔が形成される。その結果、連通孔が三次元的に連通した気孔構造が形成される。相対気孔率の上限値の制限は特にないが、セラミックス多孔体の機械的強度の観点から、９５％以下であることが好ましい。 The relative porosity of the ceramic porous body may be 50% or more, but is preferably 55% or more, and more preferably 60% or more. By setting the relative porosity within such a range, the spherical pores are reliably communicated with each other to form a communication hole. As a result, a pore structure in which the communication holes communicate three-dimensionally is formed. Although there is no restriction | limiting in particular in the upper limit of a relative porosity, From a viewpoint of the mechanical strength of a ceramic porous body, it is preferable that it is 95% or less.
　また、球状気孔の平均気孔径は、１００～１６５μｍであればよいが、１２０～１５０μｍであるのが好ましく、１３０～１５０μｍであるのがより好ましい。さらに、その標準偏差は、６０μｍ以下であればよいが、５５μｍ以下であるのが好ましく、５０μｍ以下であるのがより好ましい。 The average pore diameter of the spherical pores may be 100 to 165 μm, but is preferably 120 to 150 μm, and more preferably 130 to 150 μm. Further, the standard deviation may be 60 μm or less, preferably 55 μm or less, and more preferably 50 μm or less.
　なお、球状気孔の気孔径のバラツキの程度は、上述した標準偏差の他に、例えば、気孔径の半値幅によっても表すことができる。本発明では、半値幅が１００μｍ以下であるのが好ましく、８０μｍ以下であるのがより好ましい。 It should be noted that the degree of variation in the pore diameter of the spherical pores can be expressed by, for example, the half-value width of the pore diameter in addition to the standard deviation described above. In the present invention, the half width is preferably 100 μm or less, and more preferably 80 μm or less.
　平均気孔径、標準偏差さらには半値幅をかかる範囲内に設定することにより、球状気孔がより均一なものとなっていると言え、より均一な骨再生を実現することができる。 By setting the average pore diameter, standard deviation, and half-width within such a range, it can be said that the spherical pores are more uniform, and more uniform bone regeneration can be realized.
　なお、本明細書中において、「相対気孔率」とは、セラミックス多孔体において気孔が占める割合（％）を表し、例えば、（１－W／D／V）×１００、［式中、Wは乾燥重量、Vは体積、Dは理論密度（例えば、ハイドロキシアパタイトは３．１６ｇ／ｃｍ３、β－ＴＣＰは３．０７ｇ／ｃｍ３）を表す。］の関係式より求めることができる。 In the present specification, “relative porosity” represents the ratio (%) of pores in the ceramic porous body, for example, (1−W / D / V) × 100, where W is dry weight, V is volume, D is representative of the theoretical density (e.g., hydroxyapatite 3.16g / cm 3, β-TCP is 3.07g / cm 3). ] Can be obtained from the relational expression.
　また、本明細書中において、「球状気孔」とは、図１に示すように、セラミックス多孔体において、気泡や高分子の球状ビーズ等に由来して形成された球状をなす気孔である。その気孔径は、例えば、マイクロＣＴ装置等を用いて、セラミックス多孔体の所定の部分における断面画像を取得し、その断面画像に基づいて、気孔径を測定することにより得ることができる。そして、測定された各球状気孔の気孔径から、その平均気孔径、標準偏差および半値幅を求めることができる。 In addition, in this specification, “spherical pores” are spherical pores formed from bubbles, polymer spherical beads, or the like in the ceramic porous body, as shown in FIG. The pore diameter can be obtained, for example, by obtaining a cross-sectional image of a predetermined portion of the ceramic porous body using a micro CT apparatus and measuring the pore diameter based on the cross-sectional image. And the average pore diameter, standard deviation, and half value width can be calculated | required from the measured pore diameter of each spherical pore.
　なお、球状気孔の気孔径を求めるための画像解析は、例えば、ＳＥＭ画像より気孔径を円相当径として測定して行われる。 In addition, the image analysis for obtaining the pore diameter of the spherical pore is performed by measuring the pore diameter as an equivalent circle diameter from the SEM image, for example.
　ところで、このように、球状気孔の気孔径の標準偏差は、セラミックス多孔体の所定の部分における断面画像で観察された各球状気孔の気孔径に基づいて算出される。したがって、セラミックス多孔体のある部分における断面画像から求められた標準偏差と、セラミックス多孔体の他の部分における断面画像から求められた標準偏差との差は、小さい方が気孔径のバラツキが小さいと言うことができる。具体的には、前記差が２０～５０μｍ程度であるのが好ましく、０～４０μｍ程度であるのがより好ましい。これにより、球状気孔がより均一なものとなっていると言え、より均一な骨再生を実現することができる。 By the way, as described above, the standard deviation of the pore diameter of the spherical pores is calculated based on the pore diameter of each spherical pore observed in the cross-sectional image in the predetermined portion of the ceramic porous body. Therefore, the smaller the difference between the standard deviation obtained from the cross-sectional image of a part of the ceramic porous body and the standard deviation obtained from the cross-sectional image of the other part of the ceramic porous body, the smaller the variation in pore diameter. I can say that. Specifically, the difference is preferably about 20 to 50 μm, more preferably about 0 to 40 μm. Thereby, it can be said that the spherical pores are more uniform, and more uniform bone regeneration can be realized.
　また、セラミックス多孔体では、球状気孔の気孔径が５００μｍ以上のものの気孔の含有率が１％以下であるのが好ましく、０．５％以下であるのがより好ましい。このように、その気孔径が極端に大きいものの含有率を小さくすることで、気孔径のバラツキ（標準偏差および半値幅）がより小さくなるため、気孔径の均一性をより高めることができる。なお、このような５００μｍ以上の球状気孔の含有率は、例えば、１ｃｍ３の範囲において認められる球状気孔の気孔径を測定することにより求められる。 Moreover, in the ceramic porous body, the pore content of spherical pores having a pore diameter of 500 μm or more is preferably 1% or less, and more preferably 0.5% or less. Thus, by reducing the content of those having extremely large pore diameters, the variation in pore diameters (standard deviation and full width at half maximum) becomes smaller, so that the uniformity of the pore diameters can be further increased. In addition, the content rate of such spherical pores of 500 μm or more can be obtained by measuring the pore diameter of spherical pores recognized in the range of 1 cm 3 , for example.
　さらに、このようなセラミックス多孔体では、隣り合う球状気孔同士が連通することにより、連通孔が形成される（図１参照。）。この連通孔の平均径は、５０μｍ以上であるのが好ましく、５０μｍ以上、１５０μｍ以下であるのがより好ましい。連通孔の平均径を、かかる範囲内に設定することにより、セラミックス多孔体として求められる強度を維持することができる。また、連通孔を介した球状気孔同士間の骨形成に関与する前駆細胞等の移動や栄養血管系の侵入が円滑に行われるため、早期の骨再生が実現可能となる。 Furthermore, in such a ceramic porous body, adjacent spherical pores communicate with each other to form a communication hole (see FIG. 1). The average diameter of the communication holes is preferably 50 μm or more, and more preferably 50 μm or more and 150 μm or less. By setting the average diameter of the communication holes within such a range, the strength required for the ceramic porous body can be maintained. In addition, since the migration of progenitor cells and the like involved in bone formation between the spherical pores via the communication holes and the invasion of the nutrient vascular system are smoothly performed, early bone regeneration can be realized.
　また、このセラミックス多孔体は、リン酸カルシウム系化合物で構成される一次粒子の造粒体からなる球状二次粒子の集合体で構成されている。そのため、球状気孔は、その表面に、その球状二次粒子の間隙により形成された細孔を有する構成をなしている。かかる構成のセラミックス多孔体において、この細孔は、その口径が２０μｍ以下であるのが好ましく、１０μｍ以下であるのがより好ましい。細孔の口径を、かかる範囲内に設定することにより、セラミックス多孔体人工骨として求められる骨再生能力を確実に維持することができる。 Further, this ceramic porous body is composed of an aggregate of spherical secondary particles composed of a granulated body of primary particles composed of a calcium phosphate compound. For this reason, the spherical pores are configured to have pores formed on the surface by the gaps between the spherical secondary particles. In the ceramic porous body having such a configuration, the pores preferably have a diameter of 20 μm or less, and more preferably 10 μm or less. By setting the pore diameter within such a range, it is possible to reliably maintain the bone regeneration ability required for a ceramic porous body artificial bone.
　このようなセラミックス多孔体は、上述した骨補填材として用いる場合、顆粒状をなすものが多く用いられるが、例えば、立方体、直方体、円柱およびスティック状等の形状であってもよい。 Such a ceramic porous body is often used in the form of granules when used as the above-mentioned bone grafting material, but may be in the form of, for example, a cube, a rectangular parallelepiped, a cylinder, or a stick.
　また、このようなセラミックス多孔体は、優れた生体親和性を備えているリン酸カルシウム系化合物で構成される。 Such a ceramic porous body is composed of a calcium phosphate compound having excellent biocompatibility.
　リン酸カルシウム系化合物としては、例えば、ハイドロキシアパタイト（ＨＡＰ）、フッ素アパタイト、炭酸アパタイト等のアパタイト類、リン酸二カルシウム、リン酸三カルシウム（ＴＣＰ）、リン酸四カルシウム、リン酸八カルシウム等が挙げられ、これらのうちの１種または２種以上を組み合わせて用いることができる。また、これらのリン酸カルシウム系化合物のなかでもＣａ／Ｐ比が１．０～２．０のものが好ましく、１．５～２．０のものがより好ましく用いられる。 Examples of calcium phosphate compounds include apatites such as hydroxyapatite (HAP), fluorine apatite, and carbonate apatite, dicalcium phosphate, tricalcium phosphate (TCP), tetracalcium phosphate, and octacalcium phosphate. These can be used alone or in combination of two or more. Among these calcium phosphate compounds, those having a Ca / P ratio of 1.0 to 2.0 are preferred, and those with 1.5 to 2.0 are more preferred.
　以上、無機多孔体のうち、セラミックス多孔体について説明したが、無機多孔体はチタン系化合物で構成される多孔体も含む。この多孔体もセラミックス多孔体と同様、球状気孔を有している。その相対気孔率、球状気孔の平均気孔径および標準偏差、それらの算出方法、形成される連通孔および効果などは、上述したセラミックス多孔体のものと同様である。 The ceramic porous body has been described above among the inorganic porous bodies, but the inorganic porous body includes a porous body made of a titanium-based compound. Like the ceramic porous body, this porous body also has spherical pores. The relative porosity, the average pore diameter and standard deviation of the spherical pores, the calculation method thereof, the formed communication holes and effects, and the like are the same as those of the ceramic porous body described above.
　なお、チタン系化合物としては、例えば、チタン（チタン粉末）、酸化チタン、炭化チタン、窒化チタン、塩化チタン、チタン酸バリウムなどが挙げられ、これらのうちの１種または２種以上を組み合わせて用いることができる。また、これらのチタン化合物の中でも、チタンが好ましく用いられる。 Examples of titanium compounds include titanium (titanium powder), titanium oxide, titanium carbide, titanium nitride, titanium chloride, barium titanate, and the like, and one or more of these are used in combination. be able to. Of these titanium compounds, titanium is preferably used.
　以上のような本発明の多孔体は、次のような本発明の多孔体の製造方法により製造することができる。 The porous body of the present invention as described above can be produced by the following method for producing a porous body of the present invention.
　本発明の多孔体の製造方法は、以下の第１の工程と、第２の工程とを有する。第１の工程は、粉体を含有するスラリーに、水溶性高分子化合物と、界面活性剤とを含有するペーストを添加する工程である。第２の工程は、前記ペーストが添加された前記スラリー（混合スラリー）を、撹拌することにより起泡させた後に、混合スラリーをゲル化、乾燥させて乾燥体を得、さらに得られた乾燥体を焼結する工程である。以下、これらの工程について、順次説明する。 The method for producing a porous body of the present invention includes the following first step and second step. The first step is a step of adding a paste containing a water-soluble polymer compound and a surfactant to a slurry containing powder. In the second step, the slurry (mixed slurry) to which the paste has been added is foamed by stirring, and then the mixed slurry is gelled and dried to obtain a dried product, and the obtained dried product Is a step of sintering. Hereinafter, these steps will be sequentially described.
　ここで、第１の工程で使用される紛体は、リン酸カルシウム系化合物などのセラミックスやチタン系化合物などの無機化合物で構成された粒子で構成される紛体と、ポリエーテルエーテルケトンなどの有機化合物で構成された粒子で構成される紛体を含む。以下では、第１の工程で使用される粉体として、リン酸カルシウム系化合物の球状二次粒子で構成される紛体を用いた場合を詳細に説明する。すなわち、本発明の多孔体の製造方法のうち、セラミックス多孔体の製造方法を詳細に説明する。 Here, the powder used in the first step is composed of a powder composed of particles composed of ceramics such as calcium phosphate compounds and inorganic compounds such as titanium compounds, and organic compounds such as polyether ether ketone. Containing powder composed of particles. Below, the case where the powder comprised by the spherical secondary particle | grains of a calcium-phosphate type compound is used as a powder used at a 1st process is demonstrated in detail. That is, the manufacturing method of a ceramic porous body is demonstrated in detail among the manufacturing methods of the porous body of this invention.
　［Ａ］まず、リン酸カルシウム系化合物で構成される粒子の粉体を含有するスラリーに、水溶性高分子化合物と、界面活性剤とを含有するペーストを添加する（第１の工程）。 [A] First, a paste containing a water-soluble polymer compound and a surfactant is added to a slurry containing a powder of particles composed of a calcium phosphate compound (first step).
　［Ａ－１］まず、リン酸カルシウム系化合物で構成される粒子の粉体を含有するスラリーを調製する。 [A-1] First, a slurry containing powder of particles composed of a calcium phosphate compound is prepared.
　この粉体としては、特に限定されないが、平均粒径が１００ｎｍ以下の一次粒子からなる平均粒径０．５～８０μｍの二次粒子を含む紛体が好ましく用いられる。そして、この粉体を、例えば、水等に分散することにより前記スラリーが得られる。 The powder is not particularly limited, but a powder containing secondary particles having an average particle diameter of 0.5 to 80 μm composed of primary particles having an average particle diameter of 100 nm or less is preferably used. And this slurry is obtained by disperse | distributing this powder to water etc., for example.
　［Ａ－２］次いで、水溶性高分子化合物と、界面活性剤とを含有するペースト（ペースト状をなすバインダー）を調製する。 [A-2] Next, a paste (binder that forms a paste) containing a water-soluble polymer compound and a surfactant is prepared.
　このペーストは、例えば、水溶性高分子化合物に対して、界面活性剤を所定量ずつ添加することにより得ることができる。 This paste can be obtained, for example, by adding a predetermined amount of a surfactant to a water-soluble polymer compound.
　なお、このペーストの粘度が高い場合には、水等の溶媒をペーストに添加して、その粘度を調整するようにしてもよい。 In addition, when the viscosity of this paste is high, a solvent such as water may be added to the paste to adjust the viscosity.
　水溶性高分子化合物は、その水溶性または水分散液に対して加熱等の手段を施すことによりゲル化するようなものである。ここで、水溶性または水分散液は、水溶液、コロイド溶液、エマルジョンおよび懸濁液のいずれであってもよい。 The water-soluble polymer compound is a gel that is formed by subjecting the water-soluble or aqueous dispersion to a means such as heating. Here, the water-soluble or aqueous dispersion may be any of an aqueous solution, a colloidal solution, an emulsion and a suspension.
　このような水溶性高分子化合物として、例えば、メチルセルロース等のセルロース誘導体、カードラン等の多糖類、ポリビニルアルコール、ポリアクリル酸、ポリアクリルアミド、ポリビニルピロリドン等の合成重合体等が挙げられる。中でも、セルロース誘導体が好ましい。これにより、スラリーのゲル化をより確実に行うことができる。 Examples of such water-soluble polymer compounds include cellulose derivatives such as methylcellulose, polysaccharides such as curdlan, synthetic polymers such as polyvinyl alcohol, polyacrylic acid, polyacrylamide, and polyvinylpyrrolidone. Of these, cellulose derivatives are preferred. Thereby, gelatinization of a slurry can be performed more reliably.
　また、界面活性剤は、次工程［Ｂ］において、スラリーを撹拌した際に、より微細な気泡を発生させることができるとともに、発生した気泡の消失を抑制または防止するために添加されるものである。 Further, the surfactant is added in order to suppress or prevent disappearance of the generated bubbles as well as to generate finer bubbles when the slurry is stirred in the next step [B]. is there.
　このような界面活性剤としては、特に限定されず、例えば、N,N-ジメチルドデシルアミンオキサイドのような脂肪酸アルカノールアミド系界面活性剤、アルキルベンゼンスルフォン酸ＥＤＴのようなスルフォン酸系界面活性剤等が挙げられ、これらのうちの１種または２種以上を組み合わせて用いることができる。中でも、界面活性剤は、スルフォン酸系界面活性剤であるのが好ましい。スルフォン酸系界面活性剤を用いることにより、次工程［Ｂ］において、焼結体を得た際に、このものを構成するリン酸カルシウム系化合物にスルフォン酸系界面活性剤由来の硫酸基を導入することができる。そのため、骨生成の際に骨芽細胞等の細胞活性が高くなり、その結果、骨補填材における骨再生をより早期に行うことができる。 Such a surfactant is not particularly limited, and examples thereof include fatty acid alkanolamide surfactants such as N, N-dimethyldodecylamine oxide, sulfonic acid surfactants such as alkylbenzene sulfonic acid EDT, and the like. 1 type or 2 types or more of these can be used in combination. Among these, the surfactant is preferably a sulfonic acid surfactant. In the next step [B], by using a sulfonic acid surfactant, when a sintered body is obtained, a sulfate group derived from the sulfonic acid surfactant is introduced into the calcium phosphate compound constituting the sinter. Can do. Therefore, cell activity of osteoblasts and the like increases during bone generation, and as a result, bone regeneration in the bone grafting material can be performed earlier.
　［Ａ－３］次いで、前記［Ａ－１］で調製したスラリーに、前記［Ａ－２］で調製したペーストを添加する。 [A-3] Next, the paste prepared in [A-2] is added to the slurry prepared in [A-1].
　このように、スラリーとペーストとを別個に分けて調製し、その後、これらを混合する構成とすることで、スラリー中に気泡や粉体の粒子の塊が生じることなく、スラリー（粉体）に対して、ペースト（ペースト状をなすバインダー）を均一に分散することができるようになる。そのため、次工程［Ｂ］で得られる焼結体（セラミックス多孔体）を、上述したような球状気孔の平均気孔径および標準偏差を有するものとすることができる。 In this way, the slurry and the paste are separately prepared and then mixed, and the slurry (powder) is formed without bubbles or powder particles lump in the slurry. On the other hand, the paste (binder that forms a paste) can be uniformly dispersed. Therefore, the sintered body (ceramic porous body) obtained in the next step [B] can have the average pore diameter and standard deviation of the spherical pores as described above.
　なお、この工程の際には、スラリーに対して、ペーストを所定量に分けて、複数回添加するのが好ましい。 In this step, it is preferable that the paste is divided into a predetermined amount and added to the slurry a plurality of times.
　また、ペースト（ペースト状のバインダー）の温度は、スラリーの温度よりも高く設定するのが好ましく、具体的には、１０～２０℃程度高く設定される。より具体的には、スラリーの温度は、１０～３０℃程度であるのが好ましい。また、ペーストの温度は、３０～４０℃程度であるのが好ましい。ここで、本発明では、得られるセラミックス多孔体の相対気孔率を５０％以上と高く設定する必要があるため、高濃度の水溶性高分子化合物を含むペーストがスラリーに添加される。そのため、通常の温度で、ペーストをスラリーに添加すると、ペーストが高粘度であるため、均一にスラリー中にペーストを混合することが困難となる。 Also, the temperature of the paste (paste-like binder) is preferably set higher than the temperature of the slurry, and specifically, is set higher by about 10 to 20 ° C. More specifically, the temperature of the slurry is preferably about 10 to 30 ° C. The paste temperature is preferably about 30 to 40 ° C. Here, in the present invention, since it is necessary to set the relative porosity of the obtained ceramic porous body as high as 50% or more, a paste containing a high-concentration water-soluble polymer compound is added to the slurry. For this reason, when the paste is added to the slurry at a normal temperature, the paste has a high viscosity, so that it becomes difficult to uniformly mix the paste into the slurry.
　そこで、上記のようにペーストの温度をスラリーの温度よりも高く設定することで、ペーストの低粘度化が図られ、これにより、ペーストをスラリー中により均一に混合することが可能となる。その結果、次工程［Ｂ］で得られる焼結体は、より確実に上述したような球状気孔の平均気孔径および標準偏差を有するものとなる。 Therefore, by setting the temperature of the paste higher than the temperature of the slurry as described above, the viscosity of the paste can be reduced, and thus the paste can be mixed more uniformly in the slurry. As a result, the sintered body obtained in the next step [B] has the average pore diameter and standard deviation of the spherical pores as described above more reliably.
　なお、ペーストが添加されたスラリー中において、粉体を１００重量部として、水溶性高分子化合物を１～１０重量部とし、界面活性剤を１～１０重量部とするのが好ましい。粉体の添加量が少なすぎると、乾燥のための時間に必要以上に時間を要するおそれがある。また、紛体の添加量が多すぎると、スラリーの粘度が高くなりすぎ、気泡を発生させることが困難となるおそれがある。また、水溶性高分子化合物の添加量が１重量部未満であると、スラリーのゲル化が困難である。また、水溶性高分子化合物の添加量が１０重量部超であると、スラリーの粘度が高すぎ、起泡が困難である。さらに、界面活性剤の添加量が１重量部未満であると、起泡が困難である。また、界面活性剤の添加量を１０重量部超にしても、それに見合う効果の向上が得られない。 In the slurry to which the paste is added, the powder is preferably 100 parts by weight, the water-soluble polymer compound is 1 to 10 parts by weight, and the surfactant is preferably 1 to 10 parts by weight. If the amount of powder added is too small, it may take more time than necessary to dry. Moreover, when there is too much addition amount of a powder, there exists a possibility that the viscosity of a slurry may become high too much and it may become difficult to generate a bubble. Moreover, when the addition amount of the water-soluble polymer compound is less than 1 part by weight, gelation of the slurry is difficult. Moreover, when the addition amount of the water-soluble polymer compound is more than 10 parts by weight, the viscosity of the slurry is too high and foaming is difficult. Furthermore, foaming is difficult when the addition amount of the surfactant is less than 1 part by weight. Moreover, even if the addition amount of the surfactant exceeds 10 parts by weight, the effect corresponding to the addition cannot be obtained.
　［Ｂ］次に、ペーストが添加されたスラリー（混合スラリー）を、撹拌することにより起泡させた後に、混合スラリーをゲル化／乾燥させて乾燥体を得、さらに乾燥体を焼結する（第２の工程）。 [B] Next, the slurry to which the paste has been added (mixed slurry) is foamed by stirring, and then the mixed slurry is gelled / dried to obtain a dried body, and further the dried body is sintered ( Second step).
　［Ｂ－１］まず、ペーストが添加されたスラリーを、撹拌することにより起泡させる。 [B-1] First, the slurry to which the paste has been added is foamed by stirring.
　ペーストが添加されたスラリーを攪拌すると、このスラリーが空気を巻き込み、これに起因して発泡する。 When the slurry to which the paste has been added is stirred, the slurry entrains air and foams due to this.
　この際のスラリーを撹拌する攪拌力は、特に限定されないが、５０Ｗ／Ｌ以上であるのが好ましい。攪拌力が５０Ｗ／Ｌ未満であると、粉体の種類およびその含有量等によっては、起泡が不十分となり、所望の気孔率を有するセラミックス多孔体が得られないおそれがある。 The stirring force for stirring the slurry at this time is not particularly limited, but is preferably 50 W / L or more. When the stirring force is less than 50 W / L, foaming may be insufficient depending on the type of powder and its content, and a ceramic porous body having a desired porosity may not be obtained.
　なお、攪拌力は、［攪拌機の最大出力（Ｗ）／水溶液の量（Ｌ）］×（実際の回転数／最大回転数）により求めることができる。また、攪拌機の出力は、スラリーの粘度が高くなると回転数を保つために増大する。しかし、高気孔率を有するセラミックス多孔体を得るように起泡させる場合、スラリー粘度は仕込み時のスラリー粘度から実質的に変化しない。従って、粘度の影響は実質的に無視できる。 The stirring force can be obtained by [maximum output of the stirrer (W) / amount of aqueous solution (L)] × (actual rotational speed / maximum rotational speed). Further, the output of the stirrer increases in order to maintain the rotation speed as the viscosity of the slurry increases. However, when foaming to obtain a ceramic porous body having a high porosity, the slurry viscosity does not substantially change from the slurry viscosity at the time of preparation. Therefore, the effect of viscosity is virtually negligible.
　このような攪拌力が得られる装置としては、例えば、インペラー式ホモジナイザーが挙げられる。インペラー式ホモジナイザーは本来気泡が起こらないように設計されているが、攪拌条件を５０Ｗ／Ｌ以上とすることにより、著しい気泡の発生が可能になる。また、その装置は、攪拌羽根をディスク状の羽根にするとともに、そのディスク状の羽根の外周に鋸刃状の凹凸を設け、さらに攪拌容器の内壁に邪魔板を設けた構造の攪拌装置を使用するのが好ましい。 As an apparatus capable of obtaining such a stirring force, for example, an impeller homogenizer may be mentioned. The impeller homogenizer is originally designed so as not to generate bubbles. However, when the stirring condition is 50 W / L or more, significant bubbles can be generated. In addition, the device uses a stirring device having a structure in which the stirring blade is a disk-shaped blade, a saw blade-like unevenness is provided on the outer periphery of the disk-shaped blade, and a baffle plate is provided on the inner wall of the stirring vessel. It is preferable to do this.
　このような構造を有するインペラー式ホモジナイザーは、例えば、エスエムテー社製のＰＨ９１、ＰＡ９２、ＨＦ９３、ＦＨ９４Ｐ、ＰＤ９６、ＨＭ１０等が挙げられる。さらに、上記起泡をさらに促進するために、攪拌中のスラリーに空気や、窒素、アルゴン等の不活性ガスを注入するようにしてもよい。 Examples of the impeller type homogenizer having such a structure include PH91, PA92, HF93, FH94P, PD96, and HM10 manufactured by SMT. Furthermore, in order to further promote the foaming, an inert gas such as air, nitrogen, or argon may be injected into the slurry being stirred.
　攪拌時間は、攪拌力に依存するが、一般的には、１～３０分間程度に設定される。 The stirring time depends on the stirring force, but is generally set to about 1 to 30 minutes.
　また、気泡を微細かつ均一化させるとともに安定化させるために、比較的低温で起泡を行うのが好ましい。具体的には、混合スラリーは、好ましくは０～２５℃程度、より好ましくは５～２０℃程度の液温に設定される。 In addition, it is preferable to perform foaming at a relatively low temperature in order to make the bubbles fine and uniform and to stabilize them. Specifically, the mixed slurry is preferably set to a liquid temperature of about 0 to 25 ° C., more preferably about 5 to 20 ° C.
　［Ｂ－２］次いで、発泡させたスラリー（混合スラリー）を、ゲル化した後、乾燥させて、乾燥体（グリーンブロック）を得る。 [B-2] Next, the foamed slurry (mixed slurry) is gelled and then dried to obtain a dried product (green block).
　このゲル化は、例えば、攪拌により十分に起泡したスラリーを、８０℃以上、１００℃未満に加熱することにより、メチルセルロース等の水溶性高分子化合物の作用により行われる。なお、水溶性高分子化合物の種類等によっては、加熱温度が８０℃未満であるとゲル化が不十分となるおそれがある。また、加熱温度が１００℃以上であると水分が沸騰し、形成された気孔構造が破壊されるおそれがある。 This gelation is performed, for example, by the action of a water-soluble polymer compound such as methylcellulose by heating a slurry sufficiently foamed by stirring to 80 ° C. or higher and lower than 100 ° C. Depending on the type of water-soluble polymer compound and the like, if the heating temperature is less than 80 ° C., gelation may be insufficient. In addition, when the heating temperature is 100 ° C. or higher, moisture boils and the formed pore structure may be destroyed.
　また、ゲル化した混合スラリーの乾燥は、水分が沸騰しない程度の高温（例えば、８０℃以上～１００℃未満）に混合スラリーを保持することにより行われる。 Further, the gelled mixed slurry is dried by holding the mixed slurry at a high temperature (eg, 80 ° C. to less than 100 ° C.) that does not cause moisture to boil.
　なお、ゲル化した混合スラリー（ゲル）は、乾燥によりほぼ等方的に収縮するとともに、気泡に変化は起こらない。そのため、割れ等を生ずることなく、微細かつ均一な球形の球状気孔（マクロポア）を有する強度の高い乾燥体（グリーンブロック）となる。 Note that the gelled mixed slurry (gel) shrinks almost isotropically upon drying, and the bubbles do not change. Therefore, it becomes a high-strength dry body (green block) having fine and uniform spherical pores (macropores) without causing cracks and the like.
　［Ｂ－３］次いで、乾燥体（グリーンブロック）を焼結することにより焼結体（本発明のセラミックス多孔体）を得る。 [B-3] Next, the dried body (green block) is sintered to obtain a sintered body (ceramic porous body of the present invention).
　グリーンブロックを焼結する際の条件は、例えば、１０００～１２５０℃の温度、２～１０時間の時間である。焼結温度が１０００℃未満であると、十分な強度を有するセラミックス多孔体が得られない。また、焼結温度が１２５０℃超であると、リン酸カルシウム系化合物としてハイドロキシアパタイトを用いた場合、ハイドロキシアパタイトは燐酸三カルシウムと酸化カルシウムに分解してしまう。また、焼結時間は焼結温度に応じて適宜設定される。 The conditions for sintering the green block are, for example, a temperature of 1000 to 1250 ° C. and a time of 2 to 10 hours. If the sintering temperature is less than 1000 ° C., a ceramic porous body having sufficient strength cannot be obtained. When the sintering temperature is higher than 1250 ° C., when hydroxyapatite is used as the calcium phosphate compound, hydroxyapatite is decomposed into tricalcium phosphate and calcium oxide. The sintering time is appropriately set according to the sintering temperature.
　なお、リン酸カルシウム系化合物としてβ－ＴＣＰを得たい場合、グリーンブロックを焼結する温度は、１０００～１１５０℃の範囲内に設定される。これにより、β－ＴＣＰからα－ＴＣＰへの転移が確実に防止される。 When β-TCP is to be obtained as the calcium phosphate compound, the temperature at which the green block is sintered is set within the range of 1000 to 1150 ° C. This reliably prevents the transition from β-TCP to α-TCP.
　なお、本工程［Ｂ－３］に先立って、乾燥体を加工する加工工程および／または乾燥体を脱脂する脱脂工程を施すようにしてもよい。 Prior to this step [B-3], a processing step for processing the dried body and / or a degreasing step for degreasing the dried body may be performed.
　加工工程において、グリーンブロックに含有される水溶性高分子化合物はバインダーとして作用するので、グリーンブロックはハンドリングできる機械的強度を有する。したがって、乾燥体の仮焼成を行うことなく、乾燥体のまま切削加工することができる。 In the processing step, since the water-soluble polymer compound contained in the green block acts as a binder, the green block has a mechanical strength that can be handled. Therefore, the dry body can be cut without being pre-baked.
　また、脱脂工程は、例えば、３００～９００℃に、グリーンブロックを加熱することにより行うことができる。これにより、グリーンブロックから水溶性高分子化合物および界面活性剤を確実に除去することができる。 In addition, the degreasing step can be performed by heating the green block to 300 to 900 ° C., for example. Thereby, the water-soluble polymer compound and the surfactant can be reliably removed from the green block.
　なお、脱脂工程と焼結工程とを、一括して行う場合には、焼結温度に達するまで、徐々に昇温するようにすればよい。例えば、室温から約１０～１００℃／時の昇温速度で約６００℃まで昇温し、次いで、約５０～２００℃／時の昇温速度で焼結温度まで昇温し、この温度を保持することで行うことができる。 In the case where the degreasing step and the sintering step are performed collectively, the temperature may be gradually increased until the sintering temperature is reached. For example, the temperature is raised from room temperature to about 600 ° C. at a temperature increase rate of about 10 to 100 ° C./hour, and then the temperature is raised to a sintering temperature at a temperature increase rate of about 50 to 200 ° C./hour to maintain this temperature. Can be done.
　以上、第１の工程で使用される紛体がリン酸カルシウム系化合物の球状二次粒子で構成される紛体である場合を説明したが、本発明の多孔体の製造方法は、当該紛体としてチタン系化合物で構成された粒子で構成される紛体を用いても上記のように実行することができる。これにより、チタンで構成されるセラミックス多孔体が得られる。この場合、第１工程および第２工程の条件および効果などは、上述したセラミックス多孔体の製造方法と同様である。 As described above, the case where the powder used in the first step is a powder composed of spherical secondary particles of a calcium phosphate compound has been described. However, the method for producing a porous body of the present invention uses a titanium compound as the powder. Even when a powder composed of structured particles is used, the process can be performed as described above. Thereby, the ceramic porous body comprised with titanium is obtained. In this case, the conditions and effects of the first step and the second step are the same as those in the method for manufacturing the ceramic porous body described above.
　以上、本発明の多孔体および多孔体の製造方法について説明したが、本発明は、これに限定されるものではない。 As mentioned above, although the porous body of this invention and the manufacturing method of the porous body were demonstrated, this invention is not limited to this.
　例えば、本発明の多孔体の製造方法では、任意の目的で、工程［Ａ］の前工程、工程［Ａ］と［Ｂ］との間に存在する中間工程、または工程［Ｂ］の後工程を追加するようにしてもよい。 For example, in the method for producing a porous body according to the present invention, for any purpose, a pre-step of step [A], an intermediate step existing between steps [A] and [B], or a post-step of step [B]. May be added.
　さらに、本発明の多孔体は、人工生体材料への適用のみならず、例えば、液体クロマトグラフィー用充填剤、触媒担体、各種の電気・電子材料、原子炉材料およびセラミック発熱体等として用いることもできる。 Furthermore, the porous body of the present invention can be used not only as an artificial biomaterial, but also as a liquid chromatography filler, a catalyst carrier, various electric / electronic materials, a nuclear reactor material, a ceramic heating element, and the like. it can.
　次に、本発明の具体的実施例について説明する。
　１．多孔体の製造
　（実施例１）
　＜１＞　まず、Ｃａ／Ｐ比１．５のβ－リン酸三カルシウムの一次粒子（平均粒径：１００ｎｍ）の造粒体からなる二次粒子（平均粒径：２５μｍ）１００重量部を含有するスラリーを調製した。そして、スラリーをホモジナイザー（エスエムテー社製、「ＰＡ９２」）に投入した。 Next, specific examples of the present invention will be described.
1. Production of porous body (Example 1)
<1> First, 100 parts by weight of secondary particles (average particle size: 25 μm) composed of granules of primary particles (average particle size: 100 nm) of β-tricalcium phosphate having a Ca / P ratio of 1.5 are contained. A slurry was prepared. Then, the slurry was put into a homogenizer (“PA92” manufactured by SMT Corporation).
　＜２＞　次に、純水２７重量部に界面活性剤（アルキルベンゼンスルフォン酸ＥＤＴ）１．４重量部を添加した水溶液にメチルセルロース粉体３．４重量部を加え、攪拌脱泡機（シンキー製、「あわとり練太郎ARE-250」）にて分散混合を行いペースト状バインダーを調製した。 <2> Next, 3.4 parts by weight of methylcellulose powder was added to an aqueous solution in which 1.4 parts by weight of a surfactant (alkylbenzene sulfonic acid EDT) was added to 27 parts by weight of pure water, and a stirring defoamer (manufactured by Shinky, A paste binder was prepared by dispersing and mixing with “Awatori Nertaro ARE-250”).
　＜３＞　次に、前記工程＜１＞で調製したスラリーに対して、前記工程＜２＞で調製したペースト状バインダーを添加することにより、ペースト状バインダーが添加されたスラリー（混合スラリー）を得た。なお、この際の、スラリーおよびペースト状バインダーの温度は、それぞれ、２０℃および３５℃とした。 <3> Next, a slurry (mixed slurry) to which the paste-like binder is added is obtained by adding the paste-like binder prepared in the step <2> to the slurry prepared in the step <1>. It was. In this case, the temperatures of the slurry and the paste-like binder were 20 ° C. and 35 ° C., respectively.
　＜４＞　次に、ペースト状バインダーがスラリーに完全に分散してから、起泡させた。 <4> Next, after the paste-like binder was completely dispersed in the slurry, foaming was performed.
　＜５＞　次に、得られた気泡含有スラリーを、８３℃でゲル化させた。その後、得られたゲルを８３℃に保持することで気泡含有スラリーを乾燥させ、これにより、グリーンブロック（焼結前ブロック）を得た。 <5> Next, the obtained bubble-containing slurry was gelled at 83 ° C. Then, the bubble-containing slurry was dried by maintaining the obtained gel at 83 ° C., thereby obtaining a green block (block before sintering).
　＜６＞　次に、グリーンブロックを１４ｍｍ×１４ｍｍ×１４ｍｍの形状に加工した。その後、大気中において、１０５０℃で２時間の条件でグリーンブロックを焼結することにより、β－リン酸三カルシウム（β－ＴＣＰ）で構成される１０ｍｍ×１０ｍｍ×１０ｍｍの焼結体を得た。 <6> Next, the green block was processed into a shape of 14 mm × 14 mm × 14 mm. Thereafter, the green block was sintered at 1050 ° C. for 2 hours in the air to obtain a 10 mm × 10 mm × 10 mm sintered body composed of β-tricalcium phosphate (β-TCP). .
　（実施例２）
　前記工程＜１＞における、二次粒子を１５０重量部としたこと以外は、前記実施例１と同様にして、β－リン酸三カルシウム（β－ＴＣＰ）で構成される実施例２の焼結体を得た。 (Example 2)
Sintering of Example 2 composed of β-tricalcium phosphate (β-TCP) in the same manner as in Example 1 except that the secondary particles in step <1> were 150 parts by weight. Got the body.
　（実施例３）
　前記工程＜１＞において、Ｃａ/Ｐ比１．５の二次粒子に代えて、Ｃａ/Ｐ比１．６７の一次粒子（平均粒径：８０ｎｍ）の造粒体からなる二次粒子（平均粒径：１５μｍ）１００重量部を含有するスラリーを調製したこと以外は、前記実施例１と同様にして、ハイドロキシアパタイト（ＨＡＰ）で構成される実施例３の焼結体を得た。 (Example 3)
In the step <1>, in place of the secondary particles having a Ca / P ratio of 1.5, secondary particles (average) consisting of granules of primary particles having an Ca / P ratio of 1.67 (average particle size: 80 nm) Particle size: 15 μm) A sintered body of Example 3 composed of hydroxyapatite (HAP) was obtained in the same manner as in Example 1 except that a slurry containing 100 parts by weight was prepared.
　（実施例４）
　前記工程＜１＞において、二次粒子１００重量部を純チタン粉末５０重量部に代えたこと、前記工程＜２＞において、純水２７重量部を純水１５０重量部に、メチルセルロース紛体３．４重量部をメチルセルロース紛体１重量部に、アルキルベンゼンスルフォン酸ＥＤＴ１．４重量部をアルキルベンゼンスルフォン酸ＥＤＴ０．２５重量部に代えたこと、前記工程＜５＞において、ゲル化と乾燥を熱風乾燥機で８５℃で行ったこと以外は、前記実施例１と同様にして、チタンで構成される実施例４の焼結体を得た。 (Example 4)
In step <1>, 100 parts by weight of the secondary particles were replaced with 50 parts by weight of pure titanium powder. In step <2>, 27 parts by weight of pure water was changed to 150 parts by weight of pure water, and methylcellulose powder 3.4. 1 part by weight of methylcellulose powder and 1.4 parts by weight of alkylbenzene sulfonic acid EDT were replaced with 0.25 part by weight of alkylbenzene sulfonic acid EDT. In the above step <5>, gelation and drying were performed at 85 ° C. with a hot air dryer. A sintered body of Example 4 made of titanium was obtained in the same manner as in Example 1 except that the above was performed.
　（比較例１）
　焼結体として、オスフェリオン（オリンパス社製、気孔率：７５％）１０ｍｍ×１０ｍｍ×１０ｍｍを用意した。 (Comparative Example 1)
As a sintered body, male ferion (Olympus, porosity: 75%) 10 mm × 10 mm × 10 mm was prepared.
　（比較例２）
　焼結体として、オスフェリオン６０（オリンパス社製、気孔率：６０％）１０ｍｍ×１０ｍｍ×１０ｍｍを用意した。 (Comparative Example 2)
As a sintered body, Male Ferion 60 (Olympus, porosity: 60%) 10 mm × 10 mm × 10 mm was prepared.
　（比較例３）
　前記工程＜１＞において、界面活性剤として脂肪酸アルカノールアミド系界面活性剤（N,N-ジメチルドデシルアミンオキサイド、ライオン社製、「AROMOX」）をスラリーに配合したこと、および、前記工程＜３＞において、ペースト状バインダーの温度をスラリーと同じく２０℃にしたこと以外は、前記実施例３と同様にして、ハイドロキシアパタイト（ＨＡＰ）で構成される焼結体を得た。 (Comparative Example 3)
In the step <1>, a fatty acid alkanolamide-based surfactant (N, N-dimethyldodecylamine oxide, “AROMOX” manufactured by Lion Co., Ltd.) as a surfactant was added to the slurry, and the step <3> In Example 1, a sintered body composed of hydroxyapatite (HAP) was obtained in the same manner as in Example 3 except that the temperature of the paste-like binder was 20 ° C. as in the slurry.
　２．評価
　２－１．セラミックス多孔体における気泡および塊の評価
　まず、実施例１、２の焼結体について、それぞれ、気孔率を、電子天秤（島津製作所社製）およびマイクロメータ（ミツトヨ社製）を用いて測定された焼結体の乾燥重量および体積に基づいて算出した。 2. Evaluation 2-1. Evaluation of bubbles and lumps in porous ceramic body First, the porosity of each of the sintered bodies of Examples 1 and 2 was measured using an electronic balance (manufactured by Shimadzu Corporation) and a micrometer (manufactured by Mitutoyo Corporation). Calculation was based on the dry weight and volume of the sintered body.
　さらに、実施例１、２および比較例１、２の焼結体（１０ｍｍ×１０ｍｍ×１０ｍｍ）について、それぞれ、マイクロＣＴ（SKYSCAN社製、「Skyscan 1172」）を用いて焼結体の内部構造測定を行い、上面（高さ8ｍｍ）、中面（高さ5ｍｍ）および下面（高さ2ｍｍ）のＣＴ画像を得た（図２、３参照。）。 Furthermore, for the sintered bodies of Examples 1 and 2 and Comparative Examples 1 and 2 (10 mm × 10 mm × 10 mm), the internal structure of the sintered body was measured using micro CT (SKYSCAN, “Skyscan 1172”) The CT images of the upper surface (height 8 mm), middle surface (height 5 mm) and lower surface (height 2 mm) were obtained (see FIGS. 2 and 3).
　そして、得られたＣＴ画像（実施例１、２では、２ｍｍ×２ｍｍ、比較例１、２では、２ｍｍ×２ｍｍ×２）に基づいて、ＣＴ画像中における５００μｍ以上の粒子の塊および気泡の数（含有率）を測定した。 Then, based on the obtained CT images (2 mm × 2 mm in Examples 1 and 2 and 2 mm × 2 mm × 2 in Comparative Examples 1 and 2), the number of particles and bubbles of 500 μm or more in the CT image (Content) was measured.
　なお、ＣＴ画像中における粒子の塊および気泡の数の測定は、得られた画像から手動によりカウントすることにより行った。
　その結果を、表１に示す。 Note that the number of particle lumps and bubbles in the CT image was measured by manually counting from the obtained image.
The results are shown in Table 1.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　表１から明らかなように、実施例１、２の焼結体では、５００μｍ以上の粒子の塊および気泡が、上面、中面および下面のいずれのＣＴ画像においても認められなかった。 As can be seen from Table 1, in the sintered bodies of Examples 1 and 2, a lump of particles of 500 μm or more and bubbles were not observed in any of the CT images on the upper surface, the middle surface, and the lower surface.
　これに対して、比較例１、２の焼結体では、複数個の５００μｍ以上の粒子の塊および気泡が、上面、中面および下面のいずれのＣＴ画像において認められた。 On the other hand, in the sintered bodies of Comparative Examples 1 and 2, a plurality of particles having a size of 500 μm or more and bubbles were observed in any of the CT images on the upper surface, the middle surface, and the lower surface.
　２－２．セラミックス多孔体における気孔分布の評価
　前記評価２－１で得られた実施例１、２、４および比較例１、２の焼結体における切断面をＳＥＭにより撮像し、得られた画像について、画像解析を行い、球状気孔の平均気孔径、標準偏差および半値幅をそれぞれ求めた。 2-2. Evaluation of pore distribution in porous ceramic body The cut surfaces of the sintered bodies of Examples 1, 2, and 4 and Comparative Examples 1 and 2 obtained in Evaluation 2-1 were imaged by SEM. Analysis was performed to determine the average pore diameter, standard deviation, and half-value width of each spherical pore.
　また、実施例３および比較例３の焼結体についても、実施例１、２、４および比較例１、２の焼結体と同様に、ＳＥＭ画像について、画像解析を行い、球状気孔の平均気孔径および標準偏差をそれぞれ求めた。 In addition, for the sintered bodies of Example 3 and Comparative Example 3, similarly to the sintered bodies of Examples 1, 2, 4 and Comparative Examples 1 and 2, image analysis was performed on the SEM images, and the average of spherical pores was determined. The pore diameter and standard deviation were determined respectively.
　なお、画像解析は、ＳＥＭにより、撮影した画像結果に基づいて、球状気孔の円相当径をPhotoshop上で計測し、計測された各球状気孔の気孔径を測定することにより実行された。その結果に基づいて、球状気孔の平均気孔径、標準偏差および半値幅をそれぞれ求めた。
　その結果を、表２および表３に示す。 The image analysis was performed by measuring the equivalent circle diameter of the spherical pores on Photoshop based on the photographed image result by SEM and measuring the pore diameters of the measured spherical pores. Based on the results, the average pore diameter, standard deviation, and half width of the spherical pores were determined.
The results are shown in Table 2 and Table 3.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　表２から明らかなように、β－ＴＣＰで構成される実施例１、２の焼結体およびチタンで構成される実施例４の焼結体では、その球状気孔の平均気孔径が１００～１６５μｍであり、かつ、その標準偏差が６０μｍ以下となっていた。これにより、均一な球状気孔が得られることが分かった。 As is apparent from Table 2, in the sintered bodies of Examples 1 and 2 composed of β-TCP and the sintered body of Example 4 composed of titanium, the average pore diameter of the spherical pores is 100 to 165 μm. And the standard deviation was 60 μm or less. Thereby, it turned out that a uniform spherical pore is obtained.
　これに対して、比較例１、２の焼結体では、平均気孔径および標準偏差ともに上記の範囲外となっていた。これにより、不均一な球状気孔が得られることが分かった。 In contrast, in the sintered bodies of Comparative Examples 1 and 2, both the average pore diameter and the standard deviation were outside the above ranges. Thereby, it turned out that a non-uniform spherical pore is obtained.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
　また、表３から明らかなように、ＨＡＰで構成される実施例３の焼結体では、その球状気孔の平均気孔径が１００～１６５μｍであり、かつ、その標準偏差が６０μｍ以下となっていた。これにより、均一な球状気孔が得られることが分かった。 Further, as apparent from Table 3, in the sintered body of Example 3 composed of HAP, the average pore diameter of the spherical pores was 100 to 165 μm, and the standard deviation thereof was 60 μm or less. . Thereby, it turned out that a uniform spherical pore is obtained.
　これに対して、比較例３の焼結体では、平均気孔径が１００～１６５μｍの範囲内となっているものの、標準偏差が上記の範囲外となっていた。これにより、球状気孔のバラツキが大きくなることが分かった。 In contrast, in the sintered body of Comparative Example 3, although the average pore diameter was in the range of 100 to 165 μm, the standard deviation was out of the above range. Thereby, it turned out that the variation of a spherical pore becomes large.
　２－３．セラミックス多孔体による骨再生の評価
　まず、実施例２および比較例２の焼結体を、それぞれ、ＩＳＯ１０９９３－６に従って、ビーグル犬大腿骨に埋植した。４週後および１３週後に焼結体を摘出し、トルイジンブルー病理組織標本を作製した。その標本を画像解析することにより、骨再生能を評価した。 2-3. Evaluation of Bone Regeneration with Ceramic Porous Body First, the sintered bodies of Example 2 and Comparative Example 2 were respectively implanted in beagle femurs according to ISO10993-6. After 4 weeks and 13 weeks, the sintered body was removed, and a toluidine blue pathological tissue specimen was prepared. The bone regeneration ability was evaluated by image analysis of the specimen.
　なお、本実施例では、骨組織は類骨と成熟骨を含めた。
　その結果を、表４に示す。 In this example, bone tissues included osteoids and mature bones.
The results are shown in Table 4.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
　表４から明らかなように、実施例２と比較例２とを比較すると、骨再生量は４週および１３週時点で、それぞれ３２倍および１．５倍であった。これにより、実施例２の焼結体では、早期の骨再生に優れていることが判った。 As is apparent from Table 4, when Example 2 and Comparative Example 2 were compared, the amount of bone regeneration was 32 times and 1.5 times at 4 and 13 weeks, respectively. Thereby, it turned out that the sintered compact of Example 2 is excellent in early bone regeneration.
　２－４．まとめ
　以上のことから、各実施例の焼結体は、各比較例の焼結体と比較して、球状気孔の均一性に優れた多孔体であることが判った。また、このことに起因して、実施例２の焼結体では、骨生成に必要な骨芽細胞等を、気孔内に均一に侵入させることができていると推察された。したがって、比較例２の焼結体と比較して、本発明のセラミックス多孔体は、骨再生の早期化を図ることが可能となった。 2-4. Summary From the above, it was found that the sintered body of each example was a porous body excellent in uniformity of spherical pores as compared with the sintered body of each comparative example. Also, due to this, it was speculated that in the sintered body of Example 2, osteoblasts and the like necessary for bone formation were able to uniformly enter the pores. Therefore, compared with the sintered body of Comparative Example 2, the ceramic porous body of the present invention can accelerate bone regeneration.
　本発明の多孔体は、球状気孔を有する。その多孔体の相対気孔率が５０％以上であり、前記球状気孔の平均気孔径は１００～１６５μｍであり、かつ、前記球状気孔の標準偏差は６０μｍ以下である。これにより、この多孔体を骨補填材に適用した場合、骨芽細胞等の細胞の移動が円滑に行われ、早期の骨再生が実現可能となる。また、この多孔体を製造する方法を提供する。したがって、本発明の多孔体および多孔体の製造方法は、産業上の利用可能性を有する。 The porous body of the present invention has spherical pores. The relative porosity of the porous body is 50% or more, the average pore diameter of the spherical pores is 100 to 165 μm, and the standard deviation of the spherical pores is 60 μm or less. Thereby, when this porous body is applied to a bone grafting material, cells such as osteoblasts are smoothly moved, and early bone regeneration can be realized. Moreover, the method of manufacturing this porous body is provided. Therefore, the porous body and the method for producing the porous body of the present invention have industrial applicability.

Claims (10)

  1. 　球状気孔を有する多孔体であって、
    　その相対気孔率が５０％以上であり、
    　前記球状気孔は、その平均気孔径が１００～１６５μｍであり、かつ、その標準偏差が６０μｍ以下であることを特徴とする多孔体。     A porous body having spherical pores,
    Its relative porosity is 50% or more,
    The porous body, wherein the spherical pores have an average pore diameter of 100 to 165 μm and a standard deviation of 60 μm or less.
  2. 　気孔径が５００μｍ以上の前記球状気孔の気孔含有率が１％以下である請求項１に記載の多孔体。 The porous body according to claim 1, wherein a pore content of the spherical pores having a pore diameter of 500 µm or more is 1% or less.
  3. 　前記球状気孔同士が連通することにより形成された連通孔を有し、この連通孔の平均径が５０μｍ以上である請求項１または２に記載の多孔体。 3. The porous body according to claim 1, wherein the porous body has communication holes formed by communication between the spherical pores, and an average diameter of the communication holes is 50 μm or more.
  4. 　前記多孔体は、リン酸カルシウム系化合物またはチタン系化合物で構成されている請求項１ないし３のいずれかに記載の多孔体。 The porous body according to any one of claims 1 to 3, wherein the porous body is composed of a calcium phosphate compound or a titanium compound.
  5. 　当該多孔体は、前記リン酸カルシウム系化合物で構成される一次粒子の造粒体からなる球状二次粒子の集合体で構成されており、
    　前記球状気孔は、その表面に、前記球状二次粒子の間隙により形成された、２０μｍ以下の細孔を有している請求項４に記載の多孔体。     The porous body is composed of an aggregate of spherical secondary particles composed of a granulated body of primary particles composed of the calcium phosphate compound,
    The porous body according to claim 4, wherein the spherical pores have pores of 20 μm or less formed on the surface by gaps between the spherical secondary particles.
  6. 　請求項１ないし５のいずれかに記載の多孔体の製造方法であって、
    　粉体を含有するスラリーに、水溶性高分子化合物と、界面活性剤とを含有するペーストを添加して混合スラリーを得る第１の工程と、
    　前記混合スラリーを、撹拌することにより起泡させた後に、前記混合スラリーをゲル化、乾燥させて乾燥体を得、さらに前記乾燥体を焼結する第２の工程とを有することを特徴とする多孔体の製造方法。     A method for producing a porous body according to any one of claims 1 to 5,
    A first step of adding a paste containing a water-soluble polymer compound and a surfactant to a slurry containing powder to obtain a mixed slurry;
    The mixed slurry is foamed by stirring, and then the mixed slurry is gelled and dried to obtain a dried body, and further, a second step of sintering the dried body. A method for producing a porous body.
  7. 　前記紛体は、リン酸カルシウム系化合物またはチタン系化合物で構成された粒子で構成されている請求項６に記載の多孔体の製造方法。 The method for producing a porous body according to claim 6, wherein the powder is composed of particles composed of a calcium phosphate compound or a titanium compound.
  8. 　前記第１の工程において、前記ペーストの温度は、前記スラリーの温度よりも１０～２０℃高く設定される請求項６または７に記載の多孔体の製造方法。 The method for producing a porous body according to claim 6 or 7, wherein, in the first step, the temperature of the paste is set to 10 to 20 ° C higher than the temperature of the slurry.
  9. 　前記界面活性剤は、スルフォン酸系界面活性剤である請求項６ないし８のいずれかに記載の多孔体の製造方法。 The method for producing a porous body according to any one of claims 6 to 8, wherein the surfactant is a sulfonic acid surfactant.
  10. 　前記水溶性高分子化合物は、セルロース誘導体である請求項６ないし９のいずれかに記載の多孔体の製造方法。 The method for producing a porous body according to any one of claims 6 to 9, wherein the water-soluble polymer compound is a cellulose derivative.
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WO2020008555A1 (en) * 2018-07-04 2020-01-09 オリンパス株式会社 Bone substitute and method for producing bone substitute
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JP2013079172A (en) * 2011-10-04 2013-05-02 Hoya Corp Ceramic porous body and method for producing ceramic porous body
WO2020008555A1 (en) * 2018-07-04 2020-01-09 オリンパス株式会社 Bone substitute and method for producing bone substitute
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