Method for manufacturing porous ceramics

Abstract

To provide a manufacturing method of porous ceramic in which uneven distribution of air pores is suppressed.SOLUTION: A manufacturing method of porous ceramic includes a formation step of forming a foam-formed body by mixing a powdery ceramic raw material, cellulose particles, and a foaming agent to generate foams, where the cellulose particles are aggregation made of dried multiple pieces of fine fibrous cellulose having an average fiber width of 1-1000 nm.SELECTED DRAWING: Figure 7

Description

[Technical Field]

[0001] This invention relates to a method for producing porous ceramics that can be used as bone graft material and the like. [Background technology]

[0002] Traditionally, ceramic materials containing calcium phosphate have attracted attention as bone graft materials. Due to their excellent biocompatibility and safety, they are used in applications such as artificial bone materials, drug-carrying materials for drug delivery systems (DDS), and scaffold materials for cell culture. Furthermore, calcium phosphate ceramic materials are also used in the treatment of bone-related diseases, such as tumors and degenerative diseases.

[0003] Thus, calcium phosphate ceramic materials are used as bone graft materials, and research and development related to them have been conducted for some time. Patent Document 1 below can be cited as an example of a document disclosing technology related to calcium phosphate ceramic materials. Patent Document 1 discloses technology related to a bioabsorbable implant characterized by being formed from bioabsorbable ceramics and having a porous structure that satisfies predetermined conditions. According to this technology, it is possible to maintain excellent bone integration ability while retaining the shape not only during the grafting procedure but also until the grafting procedure is completed, thereby maintaining high usefulness.

[0004] Another document, Patent Document 2, discloses a technology relating to artificial bone characterized by the incorporation of bone marrow cells inside porous ceramics made of β-tricalcium phosphate. This technology makes it possible to create an artificial bone material that can effectively promote bone formation, and by combining it with mechanical stimuli such as isotropy and cell growth factors such as VEGF, bone formation can be made even more reliable, thereby improving its usefulness.

[0005] Patent Document 3 discloses a porous body manufactured using cellulose nanofibers, relating to a technology for ceramics having open and closed pores. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] Japanese Patent Publication No. 2013-184878 [Patent Document 2] Japanese Patent Publication No. 2002-282285 [Patent Document 3] Japanese Patent Publication No. 2020-196649 [Overview of the project] [Problems that the invention aims to solve]

[0007] When calcium phosphate ceramic materials are used as bone graft materials, osteoconductivity becomes a crucial factor. Specifically, the material must have excellent properties for allowing osteogenic cells to migrate and settle into the material's interior through its open pores, thereby promoting bone formation.

[0008] Patent Document 3 proposes porous ceramics with numerous pores, but looking at the drawings of these porous ceramics, the pore formation surfaces appear to be angular rather than rounded. While such pore shapes are not considered a particular problem for general use in bone graft materials, they may cause problems from the perspective of bone conduction.

[0009] For example, because the stomata are formed on an angular surface, there is a possibility that dead spaces may be created where bone-forming cells cannot migrate smoothly and become stagnant.

[0010] Furthermore, while Patent Documents 1 and 2 describe press molding or foaming of ceramic raw materials to produce porous ceramics, there is a risk that the pores formed will be concentrated in the upper part of the porous ceramic.

[0011] Therefore, the main problem to be solved by the present invention is to provide a porous ceramic in which the uneven distribution of pores is suppressed.

Means for Solving the Problem

[0012] (First Aspect) The aspect for solving the above problem is as follows. It has a forming step of mixing a powdery ceramic raw material, cellulose particles, and a foaming agent and foaming them to form a foam body. The cellulose particles are those in which a large number of dried fine fibrous celluloses with an average fiber width of 1 to 1000 nm are aggregated. A method for producing porous ceramics, characterized by this. <​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​A method for producing porous ceramics according to a first embodiment.

[0018] (Seventh aspect) The total porosity is 50% to 95%, and the open porosity accounts for 55% to 99% of the total porosity. A method for producing porous ceramics according to a sixth aspect.

[0019] (Eighth aspect) The process includes a sintering step in which the bubble-forming body is sintered to obtain porous ceramics, The sintering process is carried out by raising the temperature in multiple stages and includes a high-temperature step where the temperature is maintained at 950 to 1120°C for at least 0.5 to 24 hours. A method for producing porous ceramics according to a first embodiment.

[0020] (Ninth aspect) The HLB value of the aforementioned foaming agent is 7 to 16. A method for producing porous ceramics according to a second embodiment.

[0021] (Tenth aspect) The roundness of the stomata is 0.1 or less. A method for producing porous ceramics according to a first embodiment.

[0022] The porous ceramics manufactured in this embodiment exhibit suppressed localized concentration of pores. While the exact reason for this is not entirely clear, it can likely be explained as follows: The cellulose particles used in this embodiment act as foaming aids, suppressing the bursting of bubbles. The cellulose particles used in this embodiment are aggregates of numerous dried, finely fibrous cellulose particles, and their bulk density is lower than that of the finely fibrous cellulose itself. Due to the low bulk density, the cellulose particles are less likely to settle in the liquid, and a dispersed state is maintained. Bubbles would normally rise due to buoyancy if there were no cellulose particles, but the dispersion of cellulose particles prevents them from rising. As a result, the bubbles become dispersed in a bubble-forming body, eventually dispersing throughout and suppressing localized concentration.

[0023] Furthermore, the porous ceramics manufactured according to this embodiment have the characteristic of having a small percentage of ultramicropores relative to the total pores. The reason for this is not clear, but it is presumed that ultramicro bubbles gather around cellulose particles as nuclei to form bubbles of a certain size.

[0024] Furthermore, the pores formed have a lower proportion of large-diameter and angular pores compared to porous ceramics manufactured using conventional methods. This is thought to be because the dispersion of cellulose particles suppresses the aggregation of bubbles into larger bubbles, resulting in a relatively large proportion of small-diameter pores. As the bubbles are small in diameter, they tend to be mostly rounded in shape.

[0025] As a secondary effect, porous ceramics manufactured using acylated cellulose particles have rounded pores. [Effects of the Invention]

[0026] According to the present invention, the main effect is a method for producing porous ceramics in which the uneven distribution of pore sizes is suppressed. [Brief explanation of the drawing]

[0027] [Figure 1] This figure shows an example of a structural formula of an acetylated cellulose molecular chain. [Figure 2] This is a SEM image of cellulose particles. [Figure 3] This is a SEM image of acetylated cellulose particles. [Figure 4] This diagram shows acetylated cellulose particles mixed in a liquid. [Figure 5] This diagram shows acetylated cellulose particles mixed in a liquid. [Figure 6] This diagram shows acetylated cellulose particles mixed in a liquid. [Figure 7]These are SEM images of individual pieces of porous ceramics. [Figure 8] This is a SEM image of β-TCP. [Figure 9] This is the XRD pattern of β-TCP powder. [Figure 10] This is the FT-IR spectrum of β-TCP powder. [Figure 11] This is the FT-IR spectrum of acetylated cellulose particles. [Modes for carrying out the invention]

[0028] Next, embodiments for carrying out the present invention will be described. Note that this embodiment is just one example of the present invention. The scope of the present invention is not limited to this embodiment.

[0029] The present embodiment of the method for producing porous ceramics includes, for example, a forming step of mixing powdered ceramic raw materials, cellulose particles, and a foaming agent and foaming them to form a bubble-forming body, characterized in that the cellulose particles are aggregates of many dry, fine fibrous cellulose particles having an average fiber width of 1 to 1000 nm.

[0030] While it is certainly possible to manufacture porous ceramics without cellulose particles as described above, adding cellulose particles and a foaming agent has the following effects. Generally, when foamed bubbles are left standing, they rise to the surface due to buoyancy or burst over time. When cellulose particles are included along with the ceramic raw material and foaming agent, the rising and bursting of bubbles are suppressed. This is thought to be because the cellulose particles, being dispersed in the foamed liquid, hinder the flow of bubbles, and also because the cellulose particles become part of the bubble formation surface, suppressing the disappearance of bubbles.

[0031] (Ceramic raw materials) As ceramic raw materials, one or more can be selected and used from, for example, alumina, zirconia, mullite, cordierite, titania, sialon, carbon, silicon carbide, silicon nitride, spinel, nickel aluminate, aluminum titanate, calcium phosphate, etc. However, when using porous ceramics of this form as a bone graft material, it is preferable to use calcium phosphate.

[0032] As calcium phosphate, one or more types can be selected and used from, for example, hydroxyapatite, tricalcium phosphate, dicalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcium phosphate-based glass, etc. However, the use of β-type tricalcium phosphate (β-Ca3(PO4)2) (hereinafter also simply referred to as "β-TCP") is particularly preferred.

[0033] The ceramic raw material is preferably in the form of a powder with an average particle size of 500 μm or less, and more preferably in the form of a powder with an average particle size of 10 to 500 μm.

[0034] β-TCP powder is preferably prepared by the following method. First, calcium carbonate (CaCO3) and calcium hydrogen phosphate dihydrate (CaHPO4·2H2O) are mixed with pure water using a mixer such as a ball mill or kneader. This mixing is preferably carried out for 24 to 48 hours. The pure water can be at room temperature, but it is preferable to heat it to 70 to 90°C as this facilitates the dispersion of the powder.

[0035] Next, the mixture obtained from this mixing is dried. This drying is preferably carried out at, for example, 60-70°C. Furthermore, this drying is preferably carried out for 24-48 hours.

[0036] The dried material obtained by this drying process is then pulverized. This pulverization is preferably carried out until the average particle size is, for example, 0.3 to 0.5 μm. This pulverization can be carried out using grinding equipment such as an agate mortar and pestle, an automatic mortar and pestle, a stamp mill, a dry ball mill, or a hammer mill.

[0037] Next, the pulverized material obtained from this grinding is calcined. This calcination is preferably carried out at, for example, 700-800°C. In this case, the heating rate can be, for example, 3°C / min. This calcination is preferably carried out for 8-24 hours.

[0038] The calcined material obtained from this calcination is then crushed again. This crushing is preferably carried out until the average particle size is, for example, 0.3 to 0.5 μm. This crushing is also preferably carried out using the crushing equipment described above.

[0039] As described above, powdered β-TCP is obtained.

[0040] (Fine fibrous cellulose) The cellulose particles added in the formation process of this form are formed by the aggregation of fine fibrous cellulose (also called "CNF"). Therefore, before explaining cellulose particles, we will first explain fine fibrous cellulose. As the fine fibrous cellulose, for example, multiple types of cellulose fibers with different fiber widths, cellulose fibers with a single fiber width, or cellulose fibers and aggregates of cellulose fibers can be used, and it is particularly preferable to use cellulose fibers with an average fiber width of 1 to 1000 nm. Cellulose fibers are thermally decomposable and have the property of disappearing by vaporizing when heated to the extent that the ceramic raw material sintersects.

[0041] Here, we will explain the meaning of "multiple types of cellulose fibers with different fiber widths." In this embodiment, multiple types of cellulose fibers with different fiber widths refer to cases where there are multiple types of cellulose fibers, based on the premise that cellulose fibers with an average fiber width within a predetermined range are counted as one type, and cellulose fibers with an average fiber width outside this range are counted as another type.

[0042] As raw materials for fine fibrous cellulose, one or more types can be selected and used from wood pulp made from hardwoods, softwoods, etc., non-wood pulp made from straw, bagasse, etc., recycled paper pulp (DIP) made from recycled waste paper, waste paper, etc.

[0043] However, in order to avoid the inclusion of impurities as much as possible, it is preferable to use wood pulp. As for wood pulp, one or more types can be selected and used from chemical pulps such as hardwood kraft pulp (LKP) and softwood kraft pulp (NKP), and mechanical pulp (TMP), etc. Hardwood kraft pulp may be bleached hardwood kraft pulp, unbleached hardwood kraft pulp, or semi-bleached hardwood kraft pulp. Similarly, softwood kraft pulp may be bleached softwood kraft pulp, unbleached softwood kraft pulp, or semi-bleached softwood kraft pulp. Furthermore, as mechanical pulp, one or more types can be selected and used from, for example, stone gland pulp (SGP), pressurized stone gland pulp (PGW), refiner gland pulp (RGP), chemigland pulp (CGP), thermo gland pulp (TGP), gland pulp (GP), thermomechanical pulp (TMP), chemothermetic pulp (CTMP), refiner mechanical pulp (RMP), bleached thermomechanical pulp (BTMP), etc.

[0044] (Pre-processing) Cellulose fibers can be pretreated as needed, with methods such as alkali treatment, enzyme treatment, acid treatment, oxidation treatment, and beating. Pretreatment of the pulp before defibration into fine fibrous cellulose can significantly reduce the number of defibration steps and thus reduce the energy required for defibration. However, pretreatment of cellulose fibers after defibration is also possible.

[0045] Alkaline treatment prior to defibration partially dissociates the hydroxyl groups of hemicellulose and cellulose in the pulp, causing the molecules to become anionic. This weakens intramolecular and intermolecular hydrogen bonds, promoting the dispersion of cellulose fibers during defibration.

[0046] Examples of alkalis that can be used for alkaline treatment include sodium hydroxide, lithium hydroxide, potassium hydroxide, aqueous ammonia solution, tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrabutylammonium hydroxide, and benzyltrimethylammonium hydroxide, among other organic alkalis. However, from the viewpoint of manufacturing cost, sodium hydroxide is preferred.

[0047] Enzymatic, acidic, or oxidative treatments prior to defibration can increase the water retention capacity, decrease the degree of crystallinity, and improve the homogeneity of the fine fibrous cellulose. For example, the water retention capacity of the fine fibrous cellulose is 300% or more, more preferably 350% or more. If the water retention capacity falls below 300%, the water retention capacity of the fine fibrous cellulose itself is low, and although the dewatering ability is high, the degree of cellulose refinement is low, making it difficult to obtain cellulose particles of the desired size.

[0048] On the other hand, enzymatic, acid, and oxidation treatments decompose the amorphous regions of hemicellulose and cellulose in the pulp, thereby reducing the energy required for micronization and improving the uniformity and dispersibility of the fibers. Fiber uniformity is directly related to the uniformity of cellulose particles and, consequently, the uniformity of pores. Furthermore, pretreatment increases the proportion of crystalline regions in the entire fiber, improving the dispersibility of fine fibrous cellulose. However, since pretreatment reduces the aspect ratio of fine fibrous cellulose, it is preferable to avoid excessive pretreatment.

[0049] The defibration of the raw material can be carried out by beating it using, for example, a homogenizer such as a beater, high-pressure homogenizer, or high-pressure homogenization device; a millstone-type friction machine such as a grinder or crusher; a single-screw kneader; a multi-screw kneader; a kneader refiner; or a jet mill. However, it is preferable to carry out the defibration using a refiner or a jet mill.

[0050] The defibration of the raw pulp is preferably carried out in such a way that the physical properties of the resulting fine fibrous cellulose meet the desired values ​​or evaluations shown below.

[0051] <Average fiber width> The average fiber width (average fiber diameter; average diameter of a single fiber) of the fine fibrous cellulose is 1000 nm or less, preferably 500 nm or less, more preferably 100 nm or less, and particularly preferably 50 nm or less. If the average fiber width of the fine fibrous cellulose exceeds 1000 nm, the cellulose particles formed tend to be fibrous rather than particulate, and when mixed with ceramic, the fibrous structure creates pores, making it difficult to obtain a porous material with appropriate strength. The specific surface area becomes relatively small, i.e., it has poor porous structure. The average fiber width of the fine fibrous cellulose is 1 nm or more, preferably 3 nm or more, and more preferably 10 nm or more. If the average fiber width of the fine fibrous cellulose is less than 1 nm, it has high water retention, which is related to water retention, making it difficult to obtain dry cellulose particles.

[0052] The average fiber width of fine fibrous cellulose can be adjusted, for example, by selecting the raw pulp, pre-treatment, defibration, etc.

[0053] The method for measuring the average fiber width of microfiber cellulose is as follows: First, 100 ml of an aqueous dispersion of fine fibrous cellulose with a solid content concentration of 0.01-0.1% by mass is filtered through a Teflon® membrane filter, and the solvent is replaced once with 100 ml of ethanol and three times with 20 ml of t-butanol. Next, the dispersion is freeze-dried and coated with osmium to prepare the sample. This sample is observed using an electron microscope (SEM) at a magnification of 3,000x to 30,000x depending on the width of the constituent fibers. Specifically, two diagonal lines are drawn on the observed image, and three arbitrary straight lines are drawn passing through the intersection of the diagonals. Furthermore, the width of a total of 100 fibers that intersect these three straight lines is measured visually. The median diameter of the measured values ​​is then taken as the average fiber width.

[0054] <Average fiber length> The average fiber length (average length of a single fiber) of the fine fibrous cellulose is preferably 0.01 to 1000 μm, more preferably 0.03 to 500 μm. If the average fiber length exceeds 1000 μm, the diameter of the cellulose particles formed by the aggregation of the fine fibrous cellulose becomes too large, making it easy for the pores of porous ceramics manufactured using these cellulose particles to become distorted. If the average fiber length is less than 0.01 μm, the fine fibrous cellulose may dissolve when placed in a liquid during the manufacturing process, making it difficult to form cellulose particles.

[0055] The average fiber length can be arbitrarily adjusted, for example, by selecting the raw pulp, pre-treatment, defibration, etc.

[0056] The method for measuring the average fiber length of microfiberous cellulose is the same as for the average fiber width: the length of each fiber is measured visually. The median length of the measured values ​​is taken as the average fiber length.

[0057] <Axle ratio> The axial ratio (average fiber length / average fiber width) of the fine fibrous cellulose is preferably 10 to 1,000,000, more preferably 30 to 500,000. If the axial ratio of the fine fibrous cellulose is less than 10, the cellulose is almost entirely in particle form, making it difficult to form cellulose particles. On the other hand, if the axial ratio exceeds 1,000,000, the degree of entanglement between fibers is large, making it difficult for cellulose particles to achieve the desired average particle size.

[0058] <Crystallization> The degree of crystallinity of the fine fibrous cellulose is preferably 50 or higher at the lower limit, more preferably 60 or higher, particularly preferably 70 or higher, and preferably 100 or lower at the upper limit, more preferably 95 or lower, particularly preferably 90 or lower. If the degree of crystallinity is less than 50, the entanglement of the fibers weakens due to the effects of temperature changes during drying, making it difficult to form cellulose particles of the desired particle size.

[0059] The degree of crystallinity is a value measured by X-ray diffraction in accordance with the "General Rules for X-ray Diffraction Analysis" of JIS-K0131 (1996). Note that fine fibrous cellulose contains both amorphous and crystalline portions, and the degree of crystallinity represents the proportion of the crystalline portion in the entire fine fibrous cellulose.

[0060] <Pseudo particle size distribution> The peak value in the pseudo-particle size distribution curve of fine fibrous cellulose is preferably a single peak. When there is a single peak, the uniformity of fiber length and fiber diameter of the fine fibrous cellulose is high, and entanglement among the fine fibrous cellulose particles easily occurs during the production of cellulose particles, so the produced cellulose particles do not easily unravel even when redispersed. In addition, the resulting cellulose particles have less variation in particle size.

[0061] The peak value of fine fibrous cellulose is measured in accordance with ISO-13320 (2009). More specifically, the volume-based particle size distribution in an aqueous dispersion of fine fibrous cellulose is investigated using a particle size distribution analyzer (laser diffraction / scattering particle size distribution analyzer, Seishin Corporation). The mode diameter of the fine fibrous cellulose is then measured from this distribution. This mode diameter is defined as the peak value. It is preferable that fine fibrous cellulose has a single peak in the pseudo-particle size distribution curve measured by laser diffraction in an aqueous dispersion state. Thus, fine fibrous cellulose with a single peak is preferable because it has undergone sufficient refinement and can exhibit good physical properties as fine fibrous cellulose. The peak value of the pseudo-particle size distribution of fine fibrous cellulose with a single peak is preferably 300 μm or less, more preferably 200 μm or less, and particularly preferably 100 μm or less. If the peak value exceeds 300 μm, there are relatively many large fibers, the particle size variation of the cellulose particles is large, and the cellulose particle shape tends to be non-uniform.

[0062] The peak particle size of the fine fibrous cellulose, and the median diameter of the pseudo-particle size distribution, can be adjusted, for example, by selecting the raw pulp, pretreatment, defibration, etc.

[0063] <Water retention> The water retention capacity of fine fibrous cellulose is not particularly limited, but for example, in the case of unmodified fine fibrous cellulose, it is 300% or more, more preferably 350%. The upper limit is not particularly limited, but if the water retention capacity exceeds 1000%, the water retention capacity of the fine fibrous cellulose itself is high and it has poor dewatering properties, so even if it is manufactured through a drying process, the drying time will be long and productivity will be poor. On the other hand, the lower limit of the water retention capacity of fine fibrous cellulose is not particularly limited, but if it is less than 300%, the fineness of the fine fibrous cellulose has not progressed, making it difficult to form cellulose particles, and it remains in a fibrous state, making it impossible to obtain the desired particles.

[0064] The water retention capacity of fine fibrous cellulose can be arbitrarily adjusted, for example, by selecting the raw pulp, pre-treatment, and defibration.

[0065] The water retention of the microfibrillar cellulose is a value measured in accordance with JAPAN TAPPI No.26(2000).

[0066] <Pulp viscosity> The pulp viscosity of the defibrated microfibrillar cellulose is 1 to 10 cps, more preferably 2 to 9 cps, and particularly preferably 3 to 8 cps. The pulp viscosity is the viscosity of the solution after dissolving cellulose in a copper ethylenediamine solution, and the larger the pulp viscosity, the larger the degree of polymerization of cellulose, which also affects the strength of the fiber itself.

[0067] <B-type viscosity> The B-type viscosity of the slurry (concentration 2%) obtained by dispersing the microfibrillar cellulose in water is preferably 1000 to 200000 cps, more preferably 1500 to 100000 cps, and particularly preferably 2000 to 90000 cps. When the B-type viscosity of the slurry is within the above range, mixing with the ceramic raw material, drying of the mixture, forming process, etc. become easy.

[0068] (Cellulose particles) In the present invention, the cellulose particles act as a foaming aid. Conventional porous ceramics were produced, for example, by foaming a foaming agent to obtain a foam-forming body and sintering this foam-forming body. On the other hand, in the form of the present invention, the cellulose particles act to suppress the flow and disappearance of the bubbles formed by foaming. By this action, the deviation of the distribution of the pores formed in the produced porous ceramics is reduced, and the formation of pores with extremely large diameters is suppressed, so that it is suitable for use as a bone filler.

[0069] The cellulose particles in this embodiment are formed by the drying of fine fibrous cellulose. Microscopically, some particles are formed when individual fine fibrous cellulose particles dry and aggregate (like a single thread becoming entangled within a thread), while others are formed when multiple fine fibrous cellulose particles aggregate during drying to form aggregated clumps. Since the cellulose that constitutes fine fibrous cellulose has hydroxyl groups (OH groups) and hydrogen groups (H groups), the cellulose particles containing fine fibrous cellulose also have hydroxyl groups and hydrogen groups. Hydrogen bonding between hydroxyl groups and hydrogen groups causes the fine fibrous cellulose to aggregate within or between itself, forming cellulose particles. When cellulose particles are mixed with a liquid, hydrolysis occurs, breaking the hydrogen bonds and weakening the aggregation of cellulose, resulting in partially or entirely loosened fine fibrous cellulose being dispersed in the liquid. In some cases, the aggregation between cellulose particles does not break, and the cellulose particles remain dispersed in the liquid.

[0070] A characteristic feature of the cellulose particles in this embodiment is that they have a variety of particle sizes. Specifically, statistically, the particle size distribution of the cellulose particles (or group of cellulose particles) is large, meaning that the particle size dispersion coefficient is large. Furthermore, these cellulose particles do not have excellent sphericity; each particle has irregularities, is porous, and has a different shape.

[0071] <Average particle size> Cellulose particles have an average particle diameter of 10 to 500 μm, preferably 15 to 400 μm, and more preferably 20 to 300 μm. When the average particle diameter exceeds 500 μm, a large number of pores (macropores or larger) are formed, and these pores tend to be distorted in shape. Porous ceramics with such pores have significantly lower strength and may not be suitable for use as bone graft materials. On the other hand, cellulose particles with an average particle diameter of less than 10 μm are difficult to manufacture.

[0072] The average particle diameter of the cellulose particles (the median diameter, cumulative 10% diameter, and cumulative 90% diameter described below) is a numerical value measured by a measuring device compliant with ISO-13320 (2009), specifically, a laser diffraction / scattering particle size distribution measuring device (particle size distribution) "LA-960V2" using a dry method without removing the moisture adhering to the cellulose particles.

[0073] <Specific surface area> The specific surface area of the cellulose particles is preferably 10 m 2 / g or less, more preferably 8 m 2 / g or less, still more preferably 5 m 2 / g or less. The lower limit of the specific surface area is not particularly limited, but it is 0.01 m 2 / g. When the specific surface area exceeds 10 m 2 / g, it indicates that there are many minute irregularities on the surface of the cellulose particles, and also the particles themselves are lightweight and the bulk density is low. Therefore, when mixed with a ceramic raw material, the particles are likely to be broken. On the other hand, when the specific surface area is less than 0.01 m 2 / g, there are no irregularities on the particle surface, and it is likely to become dense particles and the strength is likely to be obtained, but its production is very difficult.

[0074] The specific surface area was measured by the BET method. Specifically, a NOVA4200e manufactured by Quantachrome Instruments was used as the measuring instrument, and it was measured by the adsorption method using nitrogen gas. The test method to be complied with is JIS Z8830:2013.

[0075] <Moisture content> The moisture content of the cellulose particles is preferably 50% or less, more preferably 40%, still more preferably 30% or less. Cellulose particles with a moisture content exceeding 50% contain a lot of moisture, and even when mixed and dispersed in an oil-based dispersion medium, the dispersed state may not be maintained.

[0076] <Bulk density> The cellulose particles according to the present embodiment preferably have a bulk density of 0.1 to 1.0 g / cm 3 , more preferably a bulk density of 0.1 to 0.9 g / cm 3More preferably, the solidified bulk density is 0.1 to 0.8 g / cm³. 3 This falls within the range of 1.0 g / cm³. 3 Cellulose particles exceeding this size form aggregates where the fibers are tightly intertwined, and when added to a liquid, they may gradually begin to settle due to their own weight, meaning they do not exhibit excellent dispersibility. The bulk density of the solidified material is 0.1 g / cm³. 3 Cellulose particles smaller than a certain size are prone to disintegration in the air and have poor handling properties.

[0077] <Compression level> The following relationship [Equation 1] holds between the loosened bulk density, the compacted bulk density, and the degree of compression of the cellulose particles according to this embodiment. [Mathematics 1] (Compression degree (%)) = ((Bulk density when compressed) - (Bulk density when loosened)) / (Bulk density when compressed) × 100

[0078] The compacted and loosened bulk densities are among the parameters used in calculating Carr's fluidity index, and were measured in accordance with ASTM D6393-99 Compressibility Measurement Method. The measurement was performed using the "Multi-functional Powder Property Measuring Instrument Multi-Tester MT-02" (manufactured by Seishin Corporation).

[0079] Regarding the compressibility of the cellulose particles, it is preferable that the compressibility be 50% or less, more preferably 40% or less, and even more preferably 30%. Since the cellulose particles in this embodiment are lightweight, the voids are eliminated during the compression operation performed to measure the bulk density after measuring the loosened bulk density (i.e., the cellulose particles are densely packed together in the container by eliminating the voids formed between the cellulose particles), resulting in little change in the density of the cellulose particles themselves and making it difficult for the particle shape to collapse. On the other hand, there is no particular lower limit to the compressibility of the cellulose particles (i.e., 0%), but considering that the above-mentioned voids occur to a small extent, it may be, for example, 1% or more.

[0080] (Manufacturing) Cellulose particles can be produced using fine fibrous cellulose as a raw material by freeze-drying, vacuum drying, heat drying, spray drying, or spray freeze-drying. However, the heat drying method is particularly preferable because it allows for the production of cellulose particles in which finely divided cellulose cells are strongly bound together.

[0081] Cellulose particles are obtained by drying fine fibrous cellulose. Heat-dried cellulose particles have the property of maintaining their shape even when placed in aqueous or oil-based media because the fibers aggregate with each other. Examples of cellulose particles used in this embodiment include those obtained by drum drying and those obtained by spray drying. According to the drum drying method for producing cellulose particles, even fine fibrous cellulose with relatively high concentrations or poor fluidity can be obtained as a dried product that does not aggregate easily and is easy to disperse. One example of how cellulose particles are produced by drum drying is as follows.

[0082] Fine fibrous cellulose can be supplied to a drum dryer for drying in a slurry (aqueous dispersion) state, for example. In this case, the content of fine fibrous cellulose (absolutely dry mass%) is 1% by mass or more, preferably 1.5% by mass, and more preferably 2.0% by mass. Furthermore, the content is 10% by mass or less, preferably 7% by mass, and more preferably 5% by mass. If the content exceeds 10% by mass, the viscosity of the slurry becomes too high, making it difficult to handle. On the other hand, if the content is less than 1% by mass, a lot of energy and time is consumed to remove the water, making it uneconomical.

[0083] The drum dryer used in the drum drying process may be a known model. For example, the "John Milder JM-T" from Johnson Boiler Corporation can be used. An internal-rotation drum dryer is preferably used as the drum dryer. An internal-rotation drum dryer allows for a gentle drying process, resulting in a dried material with a relatively small specific surface area. The drying process can be carried out under atmospheric pressure.

[0084] The operating conditions for the drum dryer are such that the surface temperature of the inner surface of the drum is 80 to 200°C, preferably 90 to 190°C. At this surface temperature, a dried material with strong cohesive force can be obtained. If the surface temperature exceeds 200°C, some of the fibers of the fine fibrous cellulose may undergo thermal denaturation. On the other hand, if the surface temperature is below 80°C, not only will it take a long time to remove moisture, but the particles will have a very high moisture content. The rotation speed of the drum dryer depends on the inner diameter of the drum and the amount of slurry input, but can be, for example, between 1 rpm and 2 rpm. The drying time in the drum dryer depends on the amount of slurry input, but 1 to 60 seconds is sufficient for drying, and even if dried for longer than that, the moisture content of the dried material will not decrease further.

[0085] (Acylation) In the process of forming a bubble-forming body, cellulose particles manufactured as described above are added. The inventors of this invention have found that if the added cellulose particles are somewhat hydrophobic, the bubbles constituting the bubble-forming body are maintained for a longer period of time. This is likely because the hydrophobicity of the cellulose particles suppresses aggregation of the cellulose particles in the liquid. One method for hydrophobicizing cellulose particles is to replace the hydroxyl groups constituting the cellulose fibers of the cellulose particles with acyl groups. Cellulose particles with introduced acyl groups are less prone to aggregation than those without introduced acyl groups due to the repulsive effect.

[0086] Examples of acyl groups that can be introduced into cellulose particles include acetyl groups, propanoyl groups, propionyl groups, and benzoyl groups. Cellulose particles into which acetyl groups have been introduced are particularly preferred because they disperse easily in liquids. The suitability of the acyl group for introduction depends on the HLB value of the blowing agent, but if the HLB value of the blowing agent is between 7 and 20, it does not exhibit high hydrophilicity, and in this case, the acetyl group is preferred as a combination. With cellulose particles into which acetyl groups have been introduced, the cellulose particles and the blowing agent are appropriately dispersed in the liquid, so porous ceramics are produced in which the pores are distributed in a state where unevenness is suppressed.

[0087] The acylation of cellulose particles may be performed on the fibrous cellulose before the production of cellulose particles, or on the cellulose particles after their production. If the fibrous cellulose is acylated, it is preferable to use the acylated fibrous cellulose as a raw material to produce the cellulose particles. In the formation process, a mixture of ceramic raw material, cellulose particles, and a foaming agent (usually this mixture contains an appropriate amount of water for foaming) is obtained, in which case the cellulose particles are dispersed, but some of the cellulose particles may break down into fibrous cellulose. However, most of them do not break down and maintain the shape of the cellulose particles. Therefore, it is preferable to use acylated cellulose particles as a component of the mixture, as this allows the acylated cellulose particles to be dispersed in the mixture.

[0088] As an example of a method for acylation of cellulose particles, acetylation using acetic anhydride is shown below. Cellulose particles, acetic anhydride, and pyridine are placed in a container and heated at 100-110°C for 4-72 hours. During this time, continuous stirring is preferable as it promotes a uniform acetylation reaction. After heating, the mixture is allowed to cool, and the acetic anhydride, pyridine, and reaction by-products are removed to obtain the reaction product.

[0089] The degree of substitution (DS) of acylation (especially acetylation) is 0.05 or higher, preferably 0.05 to 2.0, and more preferably 0.06 to 1.9. The degree of substitution (DS) refers to the average number of functional groups substituted for one glucose unit in cellulose. If the degree of substitution of acylation (especially acetylation) is less than 0.05, the effect of acylation is poor. The degree of substitution of acylation can be adjusted by changing the heating temperature and heating time.

[0090] (Foaming agent) The use of foaming agents (foaming methods) is currently preferred because it has the advantage of having many empirical rules. While any surfactant can be used as the foaming agent, nonionic surfactants are particularly preferred. Specifically, one or more of the following can be selected and used: polyoxyethylene alkyl ethers, polyoxyethylene alkyl allyl ethers, polyoxyethylene alkylamines, polyethylene glycol fatty acid esters, alkanolamides, polyethylene glycol / polypropylene glycol copolymers, etc. Furthermore, ethylene oxide can be added to these nonionic surfactants to create a foaming agent.

[0091] In particular, polyoxyethylene alkyl ethers are very low in toxicity and pose little harm to the human body. Furthermore, they exhibit weak effervescence, generating numerous moderately sized bubbles, and large-diameter pores do not tend to dominate, making them suitable as porous ceramics for bone graft applications.

[0092] The HLB value of the blowing agent is 7 to 16, preferably 8 to 15, and more preferably 9 to 14. The inventors have found that when the HLB value exceeds 16, the shape of the pores does not easily become spherical. This is probably because the blowing agent is hydrophobic, which destabilizes micelle formation. On the other hand, when the HLB value is less than 7, the effect of suppressing the surface tension of water is strong, resulting in the generation of many small-diameter pores. The HLB value was calculated according to Griffaine's method.

[0093] (Formation process) The process for forming a bubble-forming body can be carried out using the following procedure, as an example: A foaming agent and cellulose particles are added to powdered ceramic raw materials, and foaming is performed to form a bubble-forming body. Adding an appropriate amount of water is recommended for foaming.

[0094] In addition to the procedure described above, the formation process can also be carried out using the following procedure. Specifically, a dispersant is added to the ceramic raw material, and the dispersant and cellulose particles are added to the ceramic raw material and mixed to form a first mixture. The foaming agent is then added to the first mixture and mixed to cause foaming and form a bubble-forming body. This procedure makes it less likely for uneven distribution of bubbles to occur. As the dispersant, one or more water-soluble polymer compounds can be selected and used from among polyacrylic acid, polyacrylic acid derivatives such as polyacrylic acid ammonium salt, and polycarboxylate ammonium.

[0095] When adding a dispersant, it is preferable to use a dispersant that has the function of dispersing both cellulose fibers and ceramic raw materials. Ammonium polyacrylate (PAA) is preferred as such a dispersant. The inventors have found that PAA can be used as a decoagulant for ceramic raw materials when a foaming agent is used for pore formation, and is also useful when cellulose fibers are used as a foaming aid.

[0096] The concentration of PAA is preferably high, preferably 10% or more by volume of the total volume of the mixture before foaming (the total volume of the aforementioned mixture with the dispersant added), more preferably 25-45% by volume, and particularly preferably 30-40% by volume. On the other hand, it is also possible to increase the amount added instead of increasing the concentration, but increasing the amount added increases the load on the subsequent drying process, requiring a longer drying time or a higher drying temperature. However, these measures make the ceramic raw material more prone to shrinkage, which can cause cracking.

[0097] On the other hand, if the PAA concentration is too high, the resulting porous ceramics tend to crumble easily.

[0098] For mixing, the ceramic raw material, cellulose particles, and dispersant are mixed together, a foaming agent is added to this mixture, and the mixture is further mixed using a mixer such as a ball mill or kneader. This mixing is preferably carried out for 5 to 10 minutes. This mixing operation is preferable if performed while applying ultrasound to promote foaming.

[0099] When cellulose particles are present in an amount of 0.01 to 0.5 parts by mass, preferably 0.05 to 0.4 parts by mass, and more preferably 0.1 to 0.4 parts by mass, per 1 part by mass of ceramic raw material, the pore shape becomes rounded, and the ratio of micropores, macropores, and ultramicropores is not extremely skewed, which is preferable. If the amount of cellulose particles exceeds 0.5 parts by mass per 1 part by mass of ceramic raw material, the contribution of the cellulose particles becomes strong, and there is a risk that a large number of bubbles with shapes other than spherical will be generated. Also, if the amount of cellulose particles is less than 0.01 parts by mass per 1 part by mass of ceramic raw material, it is difficult to obtain the effect of adding cellulose particles.

[0100] Next, the mixture obtained by this mixing may produce extremely large bubbles, so it is advisable to tap the mixture to defoam the large bubbles. After that, a bubble-forming body is formed by drying at a low temperature. The drying conditions can be as follows: The temperature is, for example, 35 to 70°C, preferably 38 to 42°C. The drying time is, for example, 2 to 5 days, preferably 3 days. In this respect, by using fine fibrous cellulose, it is possible to form micropores, macropores, and even ultramicropores, making gentle drying suitable.

[0101] (Sintering process) The bubble-forming material obtained by drying is then sintered. This sintering is carried out by heating the bubble-forming material. The heating is not particularly limited, but it is preferable to perform it in two or more stages to suppress cracking of the ceramics. For example, if the sintering process includes a constant temperature step of maintaining 950 to 1100°C for at least 0.5 to 24 hours, cracking of the porous ceramics can be suppressed.

[0102] Another example is the more preferable two-stage sintering process, consisting of low-temperature sintering and high-temperature sintering. When sintering is performed in two stages, it is preferable that the sintering is performed at a low temperature of 180-300°C (preferably 200-250°C) followed by high-temperature sintering at 800-1100°C (preferably 1000-1100°C). In this configuration, the ceramic raw material is mainly sintered at low temperature, and foaming aids such as cellulose fibers are mainly vaporized and removed at high temperature. Because the low-temperature sintering precedes the removal of the foaming aids, the ceramic raw material is reliably solidified, thus ensuring the formation of small-diameter open pores.

[0103] The low-temperature sintering time is, for example, 2 to 6 hours, preferably 3 to 5 hours. The high-temperature sintering time is, for example, 40 to 300 minutes, preferably 40 to 240 minutes. By slowly sintering at a low temperature and then rapidly removing the foaming aid at a high temperature, cracking of the ceramic raw material can be prevented as much as possible. The heating rate can be, for example, 1 to 5°C / minute.

[0104] Furthermore, sintering in four stages is preferable. When sintering is performed in four stages, the first stage is sintering at 150-200°C (preferably 160-180°C) for 2-6 hours, the second stage is sintering at 250-350°C (preferably 280-320°C) for 2-6 hours, the third stage is sintering at 350-450°C (preferably 380-420°C) for 2-6 hours, and the fourth stage is sintering at 950-1100°C (preferably 1000-1050°C) for 0.5-24 hours. Among the four-stage sintering methods, a particularly preferred method is one having the following steps: a first heating step in which the temperature is raised at 4-5°C / min to 170-190°C and maintained for 3-4 hours; a second heating step in which the temperature is raised at 4-5°C / min to 290-310°C and maintained for 3-4 hours after the first heating step; a third heating step in which the temperature is raised at 4-5°C / min to 390-410°C and maintained for 3-4 hours after the second heating step; and a fourth heating step in which the temperature is raised at 4-5°C / min to 1000-1120°C and maintained for 3-4 hours after the third heating step. In this configuration, foaming agents such as cellulose fibers are mainly vaporized and removed during the first to third stages of sintering, and ceramic raw materials are sintered during the fourth stage of sintering. By gradually increasing the temperature, bubble-building agents and other contaminants are removed, and then the ceramic raw material is sintered, ensuring the formation of large and small diameter pores.

[0105] (Porous ceramics) The porous ceramics of this form manufactured as described above have numerous pores. These pores consist of open pores that communicate with the surface of the porous ceramics and closed pores that exist inside the porous ceramics and do not communicate with the surface. Patent document, Japanese Patent Publication No. 63-40782, states that all sintered products had open pores without any closed pores. However, the inventors have found that with conventional methods (foaming methods) using a foaming agent as a foaming aid, the closed porosity can reach as high as 30%.

[0106] The porous ceramics of this form have a total porosity of 50-95%, preferably 60-90%, and more preferably 70-90%. If the total porosity exceeds 95%, it may be insufficiently strong enough to be used as a bone graft material. On the other hand, if the total porosity is less than 50%, it may be difficult to use as a scaffold for cell extension.

[0107] The open porosity of the porous ceramic in this embodiment is preferably 55% or more, more preferably 60% or more. As described above, the ceramic raw material in this embodiment has a low percentage of closed pores, so even with such a high open porosity, there is very little risk of problems arising in terms of strength.

[0108] Here, total porosity can be calculated as (total pore volume / volume of porous ceramic) × 100 (%), open porosity as (volume of open pores / volume of porous ceramic) × 100 (%), and closed porosity as (volume of closed pores / volume of porous ceramic) × 100 (%).

[0109] Furthermore, in this form of porous ceramic, the percentage of open porosity to total porosity is 55% or more, preferably 80% or more, more preferably 90% or more, and 99% or less, preferably 98.5% or less, and more preferably 98% or less. On the other hand, the percentage of closed porosity to total porosity is kept to 45% or less, more preferably 20% or less, and more preferably 10% or less. By increasing the proportion of open porosity in this way, the open porosity can be made to the same level as or higher than conventional materials without making the porosity extremely high. Therefore, there is no risk of a decrease in the strength of the porous ceramic. In this regard, for example, in the case of bone graft material, the bone graft material is filled into the bone defect, reinforces the bone defect in the initial stage until the bone defect is repaired, and is absorbed into the living bone after the bone defect has been repaired. Therefore, the strength of the bone graft material is extremely important. In addition, by increasing the open porosity in this way, it becomes possible for micro-open porosity and macro-open porosity to coexist, as will be explained next.

[0110] In this form of porous ceramic, micropores (micro-open pores and micro-closed pores) with a pore diameter of 1 μm or more and less than 20 μm, preferably 1 μm or more and less than 15 μm, and more preferably 1 μm or more and less than 10 μm, and macropores (macro-open pores and macro-closed pores) with a pore diameter exceeding the aforementioned predetermined range, coexist. By allowing micropores and macropores, particularly micro-open pores and macro-open pores, to coexist in this way, for example, when this form of porous ceramic is used as a bone graft material, it becomes a porous ceramic that can accommodate the migration and fixation of both blood vessels and cells, as well as nutrients and proteins.

[0111] The pore size of the macropores is 20 μm or more and less than 600 μm, preferably 20 μm or more and less than 500 μm, and more preferably 20 μm or more and less than 400 μm. Furthermore, ultra-macropores, which are larger in diameter than the macropores, may coexist. Ultra-macropores have a pore size of 600 μm or more.

[0112] More preferably, the porous ceramics of this embodiment have a coexistence of ultramicropores (ultramicro open pores and ultramicro closed pores) whose pore diameter is within a minute diameter range that is below the range of micropores. In this embodiment, the pores consist of ultramicropores, micropores, and macropores (which may include ultramacropores), and for example, when the porous ceramics of this embodiment are used as a bone graft material, they are more in line with the demand.

[0113] The ultra-micro pores are formed when the aforementioned cellulose particles (foaming aids) are burned away at high temperatures during the sintering process. Furthermore, the pore size of the ultra-micro pores, i.e., the small diameter range, is preferably less than 1 μm.

[0114] Macropores are thought to be bubbles formed from cellulose particles and blowing agents. Micropores are formed when bubbles created by stirring the blowing agent are sintered, while macropores are formed when large-diameter bubbles, which are formed by the coalescence of micropore-sized bubbles, are sintered. Depending on the amount of blowing agent, cellulose particles, and ceramic raw materials added, as well as the mixing and tapping of the mixture containing these, the bubbles may become small or large in diameter.

[0115] Ultramicropores are pores formed as a result of the burning away of fine fibrous cellulose during the sintering process.

[0116] This form of porous ceramic is characterized by having fewer pores with a diameter of less than 1 μm than conventional materials, and more pores with a diameter of 1 μm or more but less than 20 μm than conventional materials.

[0117] Therefore, a preferred form of porous ceramic is one in which the percentage of pores with a diameter of less than 1 μm (i.e., the total volume of pores with a diameter of less than 1 μm) in relation to the total pores (i.e., the total volume of pores) is 20 to 50%, preferably 25 to 50%, and more preferably 30 to 50%.

[0118] Furthermore, porous ceramics in which the percentage of pores with a diameter of 1 μm or more and less than 20 μm (i.e., the total volume of pores with a diameter of 1 μm or more and less than 20 μm) relative to the total pores (i.e., the total volume of all pores) is 20 to 40%, preferably 22 to 40%, and more preferably 25 to 40%, is also a preferred form.

[0119] The porous ceramics of this embodiment have an average pore diameter of 10 to 100 μm, preferably 10 to 80 μm, and more preferably 10 to 50 μm. If the porous ceramics have an average pore diameter within the above range, there are plenty of pores that can be used for the migration of osteogenic cells, and bone formation will be less hindered.

[0120] Macropores primarily serve as a good scaffold for cell extension, while micropores are involved in the penetration and immobilization of drugs and tissue fluid. Therefore, porous ceramics with a micropore-to-macropore ratio of 3:7 to 7:3, preferably 4:6 to 6:4, are preferred.

[0121] In this embodiment of porous ceramics, the pore roundness is preferably 0.2 or less, more preferably 0.15 or less, and more preferably 0.1 or less. If the roundness exceeds 0.2, it means that irregular pores are formed, which may lead to a decrease in strength in certain areas.

[0122] The porous ceramics of this form have a compressive strength of 1 MPa or more, preferably 1.5 MPa or more, more preferably 2 MPa or more, and 10 MPa or less. If the compressive strength is less than 1 MPa, handling during surgery will be poor. On the other hand, there is no particular upper limit to the compressive strength, but for example, if it is 10 MPa or less, bone formation will occur without resistance and bone defect repair will be performed smoothly, so this is preferable. The compressive strength is measured in accordance with JIS-R1608 (2003) at a crosshead speed of 0.5 mm / min.

[0123] The porous ceramics of this form, manufactured through a sintering process, are not particularly limited in shape. While it depends on the shape of the container into which the foam mixture is poured, a rectangular prism is one example. For a rectangular prism, a size of 6cm wide x 6cm deep x 3cm high is a good example. Other shapes such as cubes (e.g., 5cm per side), hexahedrons, spheres, etc., can also be provided. To obtain porous ceramics of this size, it is advisable to manufacture a large porous ceramic and then cut it to the appropriate size. Manufacturing a large piece and then cutting it into smaller pieces results in more homogenized porous ceramics.

[0124] The porous ceramics produced in this embodiment have rounded pore-forming surfaces. However, the inventors have found that if acylated cellulose particles are used as a foaming aid and the HLB value of the foaming agent is between 7 and 16, more rounded pores are more easily formed. The exact mechanism behind this is not fully understood. However, it can be inferred that the hydrophobicity of both the foaming agent and the cellulose particles is likely a contributing factor. Conventionally, the foaming agent used to produce porous ceramics was not limited by its HLB value, regardless of whether it was large or small, as long as foaming occurred. On the other hand, in the production of porous ceramics in this embodiment, the HLB value of the foaming agent is within the aforementioned range, so the foaming agent has a predetermined level of hydrophobicity. Furthermore, the cellulose particles are also hydrophobic due to acylation. Since both the foaming agent and the cellulose particles are hydrophobic, bubbles are dispersed favorably, making it difficult for them to become large in diameter and for angular bubbles to form, resulting in rounded pore-forming surfaces.

[0125] In this embodiment, the shape of the formed pores is close to spherical. However, porous ceramics produced by conventional manufacturing methods using fine fibrous cellulose as a foaming aid have shapes that deviate from spherical (for example, angular shapes, rough or polyhedral pore formation surfaces, shapes where only a part of the pore formation surface protrudes, etc.).

[0126] (Application) This form of porous ceramic can preferably be used as a bone graft material. However, in addition to being a biomaterial such as a bone graft material, it can also be used as an additive in, for example, filters, electrodes for fuel cells and gas / humidity sensors, catalyst carriers, thermal insulation materials, oral drugs, processed foods, beverages, various adsorption column materials, cosmetics, toothpaste, deodorants, odor removers, bath additives, facial cleansers, shampoos, toiletries, and other products.

[0127] (others) In this specification, open porosity is the value measured by the Archimedes method. Closed porosity is the value obtained by subtracting open porosity from total porosity, and total porosity is the value calculated using the bulk density obtained by the Archimedes method and the calculated density (theoretical density).

[0128] In this specification, "bone graft material" refers to porous ceramics used as a biological implant material for replacing bone, teeth, tooth roots, etc. [Examples]

[0129] Examples are shown below. The cellulose particles used in the examples are "ELEX®-P" manufactured by Daio Paper Corporation.

[0130] (Preparation of β-TCP powder) β-TCP powder was prepared by the following procedure. First, 0.1125 mol of calcium carbonate (99.5% purity, Wako Pure Chemical Industries, Wako Special Grade) and 0.225 mol of calcium hydrogen phosphate dihydrate (98.0% purity, Pure Special Grade) (Ca / Pmol ratio = 1.50) were added to 45 ml of pure water at 80°C, and the mixture was wet-mixed for 24 hours using a zirconia pot (Nikkatoh) and zirconia balls (Nikkatoh, 600 g of 5 mm diameter balls and 900 g of 10 mm diameter balls). Next, this mixture was dried at 70°C for 24 hours. The resulting dried material was pulverized using an agate mortar and pestle, and then calcined at 750°C for 10 hours in an air atmosphere. The heating rate was 3°C / min. The resulting calcined material was pulverized into a powder (β-TCP powder). An SEM image of this powder is shown in Figure 8.

[0131] The XRD pattern of the obtained β-TCP powder is shown in Figure 9, and the FT-IR spectrum is shown in Figure 10. From the XRD pattern, the diffraction pattern of the obtained β-TCP powder matched that of the β-TCP crystal structure. Furthermore, since the peaks seen in by-products were not observed, the obtained β-TCP powder was identified as β-TCP. From the FT-IR results, the PO present in β-TCP was identified. 4 The angular vibration is 420 cm -1 ,580cm -1 Nearby, PO4 The extension and vibration range is 800-1200cm -1 Because they were found in close proximity to each other, the obtained β-TCP powder was identified as β-TCP. <Test Example 1>

[0132] (Fabrication of porous ceramics) Procedure 1: 30 g of the obtained β-TCP powder and 2 g of (unacetylated) cellulose particles were placed in a container. 50 mL of a 30% ammonium polyacrylate (PAA, Wako Grade 1) aqueous solution was added, and the mixture was stirred for 5 minutes with a hand mixer while applying ultrasonic waves to ensure uniform dispersion. The ultrasonic waves were applied by immersing the container in an ultrasonic water bath (manufactured by AS ONE). Then, 4 mL of foaming agent was added to the container and stirred for 5 minutes to produce a foam. The foaming agent was a nonionic surfactant, polyoxyethylene alkyl ether (R-O-(CH2CH2O)5-H (R is C 12 ~C 14 The alkyl group (BT-5, manufactured by Nikkol) was used.

[0133] Procedure 2: The obtained foam was poured into a square container (60 mm long x 60 mm wide), tapped to a height of 30 mm, and then dried. The drying conditions were as follows: the tapped foam was left at 40°C for 48 hours, and then at 70°C for 24 hours to obtain a bubble-forming body (dried body). The obtained dried body was sintered. The sintering process was carried out in multiple stages, specifically as follows: In the first stage, the temperature was raised at a rate of 5°C / min to 180°C and maintained at this temperature for 4 hours. Next, the temperature was raised at 5°C / min to 300°C and maintained at this temperature for 4 hours. Furthermore, the temperature was raised at 5°C / min to 400°C and maintained at this temperature for 4 hours. In addition, the temperature was raised at 5°C / min to 1000°C and maintained at this temperature for 4 hours. After that, it was allowed to cool to obtain porous ceramics (Test Example 1).

[0134] <Test Example 2> (Acetylation treatment) For every 1 g of cellulose particles, 40 mL of acetic anhydride (special grade, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) and 2 mL of pyridine (grade 1, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were used. These were placed in a container (beaker), covered with aluminum foil, and stirred at 100°C for a predetermined time (4 hours). The stirred mixture was then washed with acetone and filtered by suction using filter paper (5C grade, manufactured by Toyo Filter Paper Co., Ltd.) to allow the acetic anhydride, pyridine, and by-products to pass through, obtaining the residue. This residue was dried at 70°C for 8 hours, then allowed to cool to room temperature. This was used as the preparation sample for FT-IR spectral measurement and scanning electron microscopy (SEM) observation. The FT-IR spectral measurement results of this sample are shown in Figure 11, and the SEM image is shown in Figure 3.

[0135] Based on the FT-IR spectral measurement results, the prepared sample was found to be 3700 cm⁻¹. -1 From 3000cm -1 A waveform originating from the stretching vibration of OH is present in the vicinity at 2950 cm². -1 From 2850cm -1 Waveforms originating from the stretching vibrations of CH were observed in the vicinity. Cellulose structure can be inferred from these waveforms. Also, 1740 cm -1 A waveform originating from the stretching vibration of the C=O group in the acetyl group is present nearby at 1230 cm². -1 Waveforms originating from the stretching vibration of CO were observed in the vicinity. From these waveforms, the prepared sample was identified as cellulose particles containing acetyl groups (acetylated cellulose particles). The degree of substitution of these acetylated cellulose particles was 0.1.

[0136] (Fabrication of porous ceramics) Porous ceramics (Test Example 2) were prepared using the same procedure as in Test Example 1, except that acetylated cellulose particles were used as the cellulose particles.

[0137] <Test Example 3> (Acetylation treatment) The acetylation treatment in Test Example 3 was carried out using the same procedure as in Test Example 2, except that the time required for stirring (predetermined time) was 24 hours. The acetylated cellulose particles had a degree of substitution of 0.15.

[0138] (Fabrication of porous ceramics) Porous ceramics (Test Example 3) were prepared using the same procedure as in Test Example 1, except that acetylated cellulose particles were used as the cellulose particles.

[0139] <Reference example 1> The porous ceramics in Reference Example 1 were fabricated without the addition of cellulose particles.

[0140] (Fabrication of porous ceramics) The porous ceramic (Reference Example 1) was prepared using the same procedure as in Test Example 1, except that cellulose particles were not added to the porous ceramic preparation procedure.

[0141] <Reference example 2> The porous ceramics in Reference Example 2 were prepared by adding a slurry of fine fibrous cellulose instead of cellulose particles.

[0142] (Fabrication of porous ceramics) Porous ceramics (Reference Example 2) were prepared using the same procedure as in Test Example 1, except that 0.9 g (oven-dry mass) of fine fibrous cellulose slurry ("ELEX®-S" manufactured by Daio Paper Corporation) was added instead of 2 g of cellulose particles in the preparation procedure for porous ceramics in Test Example 1.

[0143] As shown in Figure 11, the estimated degree of acetyl group substitution obtained from the FT-IR spectrum revealed that the longer the stirring time (the predetermined time mentioned above), the greater the peak intensity.

[0144] The formulations for each test example and each reference example are shown in Table 1.

[0145] [Table 1]

[0146] <Experiment 1: SEM Image Observation> A rectangular porous ceramic was obtained using the procedure described above. The porous ceramic was cut horizontally using a horizontal plane passing through points that divide the height into three equal parts, resulting in three pieces (top, middle, and bottom from top to bottom). SEM images of each of the porous ceramics are shown in Figure 7.

[0147] For example, in Test Example 1, the stomata were uniformly distributed across the upper, middle, and lower lobes, and no bias towards the upper lobe was observed. The same can be said for Test Examples 2 and 3.

[0148] <Test 2: Bubble retention performance test> Next, a bubble retention performance test was conducted. The foaming agent was a nonionic surfactant polyoxyethylene alkyl ether (R-O-(CH2CH2O)5-H (R is C 12 ~C 14 The alkyl group (BT-5, manufactured by Nikkol) was used. <Test Example 4> 30 g of the β-TCP powder obtained above and 5 g of (unacetylated) cellulose particles were placed in a container. 50 mL of a 10% ammonium polyacrylate (PAA, Wako Grade 1) aqueous solution was added, and the mixture was stirred with a hand mixer for 5 minutes while applying ultrasound to ensure uniform dispersion. The ultrasound was applied by immersing the container in an ultrasonic bath (manufactured by AS ONE). Subsequently, 4 mL of foaming agent was added to the container and stirred for 5 minutes to produce a foam. The entire volume of this foam was placed in a graduated cylinder and allowed to stand. The height of the bubbles was measured over time (0 minutes, 60 minutes). This is referred to as Test Example 4.

[0149] <Test Example 5> 30 g of the β-TCP powder obtained above and 5 g of acetylated cellulose particles with a degree of substitution of 0.1 were placed in a container. 50 mL of a 10% ammonium polyacrylate (PAA, Wako Grade 1) aqueous solution was added, and the mixture was stirred for 5 minutes with a hand mixer while applying ultrasound to ensure uniform dispersion. The ultrasound was applied by immersing the container in an ultrasonic bath (manufactured by AS ONE). Subsequently, 4 mL of foaming agent was added to the container and stirred for 5 minutes to produce a foam. The entire volume of this foam was placed in a graduated cylinder and allowed to stand. The height of the bubbles was measured over time (0 minutes, 60 minutes). This is designated as Test Example 5.

[0150] <Reference example 3> 30 g of the β-TCP powder obtained above was placed in a container, to which 50 mL of a 10% ammonium polyacrylate (PAA, Wako Grade 1) aqueous solution was added. The mixture was then stirred for 5 minutes with a hand mixer while applying ultrasound to ensure uniform dispersion. The ultrasound was applied by immersing the container in an ultrasonic bath (manufactured by AS ONE). Subsequently, 4 mL of foaming agent was added to the container and stirred for 5 minutes to produce a foam. The entire volume of this foam was placed in a graduated cylinder and allowed to stand. The height of the bubbles was measured over time (0 minutes, 60 minutes). This is referred to as Reference Example 3.

[0151] The bubble retention performance test measures the height of the foam placed in a graduated cylinder after a predetermined time has elapsed, and expresses the degree to which the foam is maintained as an index called the bubble retention rate. The bubble retention rate can be calculated using the following formula. (Bubble retention rate (%)) = (Height of foam after 60 minutes (mm)) / (Height of foam after 0 minutes (mm)) × 100

[0152] The results of the bubble retention performance test are shown in Table 3. Test Examples 4 and 5 showed higher bubble retention rates compared to Reference Example 3.

[0153] [Table 3]

[0154] <Test 3: Distributed Performance Test> We conducted tests on the dispersibility of cellulose particles. Test 3-1: Regarding unacetylated cellulose particles Unacetylated cellulose particles were mixed in a clear bottle containing water and mesitylene and left to stand until the phase flow subsided. As a result, the mixture separated into two phases: an aqueous phase (lower phase) and a mesitylene phase (upper phase), with the cellulose particles settling at the bottom of the aqueous phase. In addition, unacetylated cellulose particles were mixed in a clear bottle containing water and chloroform and left to stand until the phase flow subsided. As a result, the mixture separated into two phases: an aqueous phase (upper phase) and a chloroform phase (lower phase), with the cellulose particles remaining at the interface between the aqueous and chloroform phases. These results are shown in Figure 5.

[0155] Test 3-2: Regarding acetylated cellulose particles (degree of substitution 0.10) Acetylated cellulose particles were mixed in a clear bottle containing water and mesitylene and left to stand until the phase flow subsided. As a result, the mixture separated into two phases: an aqueous phase (lower phase) and a mesitylene phase (upper phase), with the cellulose particles dispersed in the mesitylene phase. Similarly, acetylated cellulose particles were mixed in a clear bottle containing water and chloroform and left to stand until the phase flow subsided. As a result, the mixture separated into two phases: an aqueous phase (upper phase) and a chloroform phase (lower phase), with the cellulose particles remaining at the interface between the aqueous and chloroform phases. These results are shown in Figure 6.

[0156] Test 3-3: Regarding the slurry of fine fibrous cellulose (ELEX®-S) A slurry of fine fibrous cellulose was mixed with water and mesitylene in a clear bottle and left to stand until the phase flow subsided. As a result, it separated into two phases: an aqueous phase (lower phase) and a mesitylene phase (upper phase), with the fine fibrous cellulose dispersed in the aqueous phase. Similarly, a slurry of fine fibrous cellulose was mixed with water and chloroform in a clear bottle and left to stand until the phase flow subsided. As a result, it separated into two phases: an aqueous phase (upper phase) and a chloroform phase (lower phase), with the fine fibrous cellulose dispersed in the aqueous phase. These results are shown in Figure 4.

[0157] While fine fibrous cellulose showed high dispersibility in the aqueous phase, unacetylated cellulose particles and acetylated cellulose particles were difficult to disperse in the aqueous phase.

[0158] <Test 4: Measurement of pore size distribution> The pore size distribution of porous ceramics was measured. The results are shown in Table 2. In Table 2, "pore size less than 1 μm" refers to the percentage of the total volume of pores with a pore size of less than 1 μm relative to the total volume of all pores. "Pore size 1 μm or more and less than 20 μm" refers to the percentage of the total volume of pores with a pore size of 1 μm or more and less than 20 μm relative to the total volume of all pores. "Pore size 20 μm or more and less than 600 μm" refers to the percentage of the total volume of pores with a pore size of 20 μm or more and less than 600 μm relative to the total volume of all pores. "Pore size 600 μm or more" refers to the percentage of the total volume of pores with a pore size of 600 μm or more relative to the total volume of all pores.

[0159] Test Examples 1 and 2 have a larger average pore size compared to Reference Examples 1 and 2. Furthermore, pores smaller than 1 μm are less prevalent in Test Examples 1 and 2 than in Reference Examples 1 and 2. Additionally, pores between 1 μm and 20 μm are more prevalent in Test Examples 1 and 2 than in Reference Examples 1 and 2. The pore size distribution was measured using the "Allpore V9620" from Micromeritex.

[0160] [Table 2]

[0161] <Test 4: Roundness, compressive strength, bulk density, porosity> For test examples and reference examples, the roundness of pores, the compressive strength of porous ceramics, the bulk density of porous ceramics, and the porosity of porous ceramics were measured. The method for measuring roundness is as follows: Ten pores in the range of pore size from 50 to 400 μm were randomly selected from SEM images (50x magnification). For each selected pore, the longest diameter (major axis) and the shortest diameter (minor axis) were measured, and the ratio of the major axis to the minor axis was calculated. Then, the major axis was normalized to 1, and the length of the minor axis (normalized minor axis) was calculated from this ratio. This was done for all 10 points. The average value of the normalized minor axes of the 10 points thus calculated was found. The roundness was calculated using the following formula. (Roundness) = (1 - Mean value of normalized minor axis) / 2 The closer the roundness is to 0, the closer the pore is to being perfectly round.

[0162] Compressive strength was measured using porous ceramics processed to a size of 6 mm (length) x 6 mm (width) x 9 mm (height). [Industrial applicability]

[0163] This invention can be used as a porous ceramic that can be used as a bone graft material or the like.

Claims

1. The process includes a forming step of mixing powdered ceramic raw materials, cellulose particles, and a foaming agent to create a foamed body, The cellulose particles are composed of numerous aggregates of dry, fine fibrous cellulose with an average fiber width of 1 to 1000 nm. A method for producing porous ceramics characterized by the following:

2. The aforementioned fine fibrous cellulose is obtained by introducing acyl groups into cellulose fibers. A method for producing porous ceramics according to claim 1.

3. The cellulose particles have an average particle diameter of 10 to 500 μm and a compacted bulk density of 0.1 to 1.0 g / cm³. ３ This is what it will be. A method for producing porous ceramics according to claim 1.

4. The cellulose particles mentioned above are obtained by heating and drying. A method for producing porous ceramics according to claim 1.

5. The porous ceramic has a compressive strength of 1 to 10 MPa. A method for producing porous ceramics according to claim 1.

6. The cellulose particles are added in an amount of 0.01 to 0.5 parts by mass per 1 part by mass of the ceramic raw material. A method for producing porous ceramics according to claim 1.

7. The total porosity is 50% to 95%, and the open porosity accounts for 55% to 99% of the total porosity. A method for producing porous ceramics according to claim 6.

8. The process includes a sintering step in which the bubble-forming body is sintered to obtain porous ceramics, The sintering process is carried out by raising the temperature in multiple stages and includes a constant temperature step of maintaining a temperature of 950 to 1100°C for at least 0.5 to 24 hours. A method for producing porous ceramics according to claim 1.

9. The HLB value of the aforementioned foaming agent is 7 to 16. A method for producing porous ceramics according to claim 2.

10. The roundness of the stomata is 0.1 or less. A method for producing porous ceramics according to claim 1.

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