JPH0663119A - Bone defective part and void art filling calcium phosphase porous granule and manufacture thereof - Google Patents

Abstract

PURPOSE:To provide bone defective part and void part filling calcium phosphate porous granule and a manufacture thereof which can fill up a defective part and a void part of a bone without a surgical operation and enables the whole of a filling part and the new bone to be united in one body in a short period of time. CONSTITUTION:A calcium phosphate compound synthesized by a wet method is calcinated at 500-800 deg.C and then ground to obtain easily sintering fine crystal with the average particle diameter of 0.01-100mum and with the specific surface area of 5-50m<2>/g. After that, the crystal is granulated into spherical particles of 10-100mum, and then burnt at 800-1100 deg.C to obtain substantially spherical sintered porous granule which has the average pore size of 0.1-1.0mum, 70% or more pores having capillary communicating pores of the pore size 0.5-2.0 times as large as the average pore size, the porosity of 20-90% and the average granule diameter of 10-100mum, 5mum or less being 10% or less.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a calcium phosphate-based porous granule for filling a bone defect portion and a void portion and a method for producing the same, and can fill a bone defect portion and a void portion without particularly performing an incision operation. Further, the present invention relates to a calcium phosphate-based porous granule for filling a bone defect portion and a void portion, which enables rapid integration of the whole filling portion and new bone after filling, and an advantageous production method thereof.

[0002]

BACKGROUND ART A calcium phosphate compound has been conventionally used as a medical material, for example, as a substitute material or a filling material for bones, tooth roots and the like, since it has a good affinity with living bodies.

In particular, when such a calcium phosphate compound is used as a filling material for a bone defect or void, the structure and function of the bone tissue defect or the like is promptly restored or restored. There is a need for the rapid production of new bone so that the new bone and such filler material can be integrated in a short period of time for recovery.

Therefore, various proposals have been made in order to satisfy such requirements, for example, JP-A-60-
Japanese Patent No. 16879 discloses a sintered porous body of a calcium phosphate compound having a large number of pore diameters of 1 to 600 μm and capillary pores having a diameter of 1 to 30 μm which communicate with each other. In the sintered porous body of this calcium phosphate compound, through the pores and voids, osteoblasts and the like which are bone-forming components, in the porous body,
It allows them to freely enter and activates such osteoblasts by providing a good living space in such pores,
Therefore, it is intended to promptly generate new bone.

Further, in Japanese Patent Laid-Open No. 56-166843, the bone-forming component is easily infiltrated, and it is from 0.05 to 3.0.
A porous body of a calcium phosphate compound having a pore size of 0 mm and pores having a substantially three-dimensional network structure has been proposed. That is, in the porous body of this calcium phosphate compound, when the pores are formed as described above, the bone-forming component is promptly filled in the entire pores when the bone defect is filled. Fill up, so
It aims to accelerate the formation of new bone.

However, in each of the porous bodies of the calcium phosphate compound disclosed in those publications, in each case, pores having a pore diameter that allows osteoblasts and the like which are osteogenic components to freely enter are formed. However, in order to fill such a porous body into a bone defect or void, it is necessary to perform an incision operation. , To the patient,
It is an extremely heavy burden.

In addition, since the porous body of the calcium phosphate compound has a large particle size, the volume of the space between the particles of the porous body is large in the filling portion, and thus the space between the porous body and the porous body of the calcium phosphate compound is large. On the other hand, it takes a long time for the generated new bone tissue to be filled, and eventually, there is a problem that the integration between the entire filling site including such a gap and the generated new bone is prolonged. Was also inherent.

[0008]

The present invention has been made in view of the above circumstances, and a problem to be solved by the present invention is to fill a bone defect or a void without performing any incision surgery. Further, it is possible to provide a calcium phosphate-based porous granule for filling a bone defect portion and a void portion, in which the whole filling portion and the new bone can be integrated in a short time after such filling, and a method for producing the same. There is something to do.

[0009]

In order to solve the above problems, the present invention is characterized in that it is a sintered porous granule having a substantially spherical shape of a calcium phosphate compound. Has vertical and horizontal capillary vent holes with an average pore diameter of 0.1 to 1.0 μm
And 70% or more of the pores have 0.5 of the average pore diameter.
Porosity is 2 to 2.0 times, and porosity is 2
Average granule diameter in the range of 0-90% is 10-100μ
m is 5 μm or less, and the content of the granules of 5 μm or less is 10% or less.

In the present invention, the calcium phosphate compound synthesized by the wet method is calcined at a temperature of 500 to 800 ° C. and then pulverized to have an average particle diameter of 0.01 to 1.00 μm.
m, specific surface area: 5 to 50 m ² / g, to make easily sinterable fine crystals, and then obtain the obtained fine crystals in an amount of 10 to 100 μm.
A feature is also a method for producing a calcium phosphate-based porous granule for filling a bone defect portion and a void portion, which is granulated into spherical particles of m and then fired at a temperature of 800 to 1100 ° C.

In the present invention, the granulation is carried out by spray-drying a slurry having a concentration of 5 to 60% of the fine crystals to obtain the desired bone defect and void filling calcium phosphate. The method of producing the porous porous granules will be advantageously adopted.

[0012]

[Concrete composition] By the way, in the calcium phosphate-based porous granules for filling bone defects and voids, osteoblasts are fixed to the outer peripheral surface of the granules by a predetermined chemical reaction. When the osteoblasts enter into the pores, the osteoblasts are firmly fixed in the pores in the same manner, and the new bone and the porous granules thus produced are integrated. It was thought that the incarnation would be accelerated. Therefore, as clearly shown in the above-mentioned publications, etc., in a porous body having fine pores in which osteoblasts cannot enter, it may be It was said that the unification would be prolonged.

However, after various investigations by the present inventors, osteoblasts have a large number of fine cell projections having a diameter of about 0.2 μm on the surface thereof, and these cell projections are Invasion into the pores of such porous granules, binding with the porous granules, and further, in the pores, cell projections are joined to each other to firmly adhere to the inside of the pores and With respect to the porous granules, it plays the role of anchoring and has a function of firmly fixing the both, and therefore, even if the osteoblasts are not allowed to enter the pores of the porous granules, If only the cell protrusions are allowed to enter the pores, in addition to the chemical reaction as described above, the anchoring action of the cell protrusions allows the osteoblasts and the porous granules to be more firmly fixed. , As a result, the new bone and the porous granules are produced that is made to integrate in a short period of time, it became apparent.

Therefore, in the calcium phosphate-based porous granules for filling a bone defect portion and a void portion according to the present invention, osteoblast cell projections from the surface of the granule to the capillary continuous ventilation holes extending vertically and horizontally inward. Is designed to be easy and efficient.

That is, in such calcium phosphate-based porous granules, the average diameter of the capillary continuous vents is 0.1 to 1.0 μm. If the average pore size is smaller than 0.1 μm, the penetration of such cell projections into the pores is hindered.
If it is larger than m, it may be necessary to fill the growth of cell projections in the pores.
It takes a long period of time, and the integration of the generated new bone and the porous granules will be prolonged.

Moreover, in such a capillary continuous vent hole, 70% or more of the pores have a pore diameter within the range of 0.5 to 2.0 times the average pore diameter as described above. There must be. This is because, when the porosity is less than 70%, the cell protrusions are prevented from entering the inside of the granule, or the growth of new bone is prolonged.

The calcium phosphate-based porous granules according to the present invention must have a porosity of 20 to 90%. If the porosity is less than 20%, the penetration of osteoblast cell projections into the inside of the porous granules through the pores will be insufficient, and the adhesion strength between the porous granules and the new bone tissue will be low, The period until the two are integrated will be prolonged. On the other hand, when the porosity is more than 90%, the strength of the porous granules is too low, and the strength of the tissue after being integrated with the generated new bone is lowered, resulting in a sufficient healing effect. There is a problem that you can not expect it.

In the case of such fine pores, the diameter of the granules can be made extremely small. However, the calcium phosphate-based porous material according to the present invention for filling bone defects and voids. In the granules, the average granule diameter is 10 to 100 μm, and the content of the granules of 5 μm or less is 10% or less. If the average particle diameter is less than 10 μm or the content of granules of 5 μm or less is more than 10%, such fine porous granules penetrate into the capillaries around the filling site. If the average granule diameter exceeds 100 μm, the effect that can be achieved by reducing the granule diameter is effectively enjoyed. Because you won't get it.

As described above, the calcium phosphate-based porous granules for filling bone defects and voids according to the present invention are
Since it has an extremely small granule diameter, and has a substantially spherical shape and good fluidity,
When filling a bone defect or void, it is possible to directly inject and fill the filling site from outside the skin tissue with a syringe, etc., and therefore, an incision operation for the muscle tissue around the filling site. Is completely unnecessary, and the burden on the patient can be greatly reduced.

In addition, the calcium phosphate-based porous granules for filling bone defects and voids have a significantly smaller granule diameter than conventional fillers for bone defects and voids. , The volume of the gaps between the particles of the porous granules can be efficiently reduced, and new bones can be quickly filled into the gaps, and the cell projections of osteoblasts can be infiltrated. Since the average pore diameter of the capillary continuous vents is also much smaller than that of the conventional material, the new bone tissue generated by the invasion of cell projections can be filled in the pores in a shorter period of time and the inside of the filling site can be filled. The whole of the bone can be quickly filled with new bone, so that the entire filling site and the new bone tissue can be integrated in a short period of time.

By the way, the calcium phosphate-based porous granules for filling the bone defect portion and the void portion, which exert the excellent characteristics as described above, are manufactured as follows.

First, as the starting material, a calcium phosphate compound synthesized by a conventionally known wet method is used. Further, as this calcium phosphate compound, since new bone is rapidly produced, for example, Ca ₃ (P
O ₄ ) ₂ , Ca ₄ (PO ₄ ) ₂ O and the like are preferably calcium phosphate compounds having a Ca / P molar ratio within the range of 1.5 to 2.0, and more preferably Ca ₁₀ (PO ₄ ) ₆ (O
H) ₂ is a hydroxyapatite having a Ca / P molar ratio of 1.67, and in particular, by using this, the generation of new bone can be promoted even more advantageously. In addition, in those calcium phosphate compounds, unless their excellent biocompatibility is impaired,
The existence of foreign ions does not matter.

Then, the calcium phosphate compound as the starting material is calcined within a temperature range of 500 ° C. to 800 ° C. to obtain a bulk calcined product. The calcination temperature is 500 ° C.
If it is lower than this, crystal grain growth hardly progresses, and there is no point in performing calcination treatment, and if the calcination temperature is higher than 800 ° C,
On the contrary, the crystal grains grow too much, which makes it difficult to produce the porous granules having the desired properties.

Next, the block-like calcined material thus obtained has an average particle size of 0.01 to 1.00 μm (specific surface area of 50 to 5).
(corresponding to m ² / g) is pulverized by a conventional method to obtain fine particles having easily crystallizable fine crystals.
As the pulverization treatment method, either a dry pulverization method or a wet pulverization method can be adopted. However, in the case where the average particle diameter of the fine particles obtained by pulverization is smaller than 0.01 μm, Since it is almost the same as the average particle size, there is no point in calcination, and the average particle size is 1.00 μm.
If it exceeds, there is a problem that the sinterability of such fine particles is lowered.

Subsequently, the fine particles obtained as described above are granulated, but the finally obtained calcium phosphate-based porous granules for filling bone defects and voids are
In order to have an average granule diameter of 10 to 100 μm and have a substantially spherical shape, and thereby to exhibit the above-mentioned excellent characteristics,
It must be granulated into spherical particles of 100 μm.

In the method of the present invention, such granulation is advantageously carried out by spray drying a slurry having a concentration of 5 to 60% of the fine particles. That is, in the fine particles obtained by crushing as described above, pure water or the like was added to the dry powdery fine particles obtained by the dry pulverization method, and the slurry fine particles obtained by the wet pulverization method were Pure water or the like is added or dehydration is performed to prepare a slurry having a concentration of 5 to 60%, and the slurry is granulated by spray drying to obtain substantially spherical dry granules. To get.
Here, if the slurry concentration is less than 5%, the average particle size of the obtained granulated particles will be too small, and the amount of granules obtained per unit time will be too small to be industrially practical. If it exceeds, there is a problem that the particle size of the obtained granulated particles becomes large. Therefore, by carrying out the granulation as described above, it is possible to easily and efficiently obtain the dry granules having an appropriate particle size, a relatively narrow particle size distribution, and a substantially spherical shape. .

The granulated particles thus obtained are subjected to a sizing treatment, if necessary, and then 800-110.
A firing operation is carried out at a temperature of 0 ° C. and sintering is performed to obtain the desired calcium phosphate-based porous granules for filling bone defects and voids. In addition, in this firing, 80
When the firing is performed at a temperature lower than 0 ° C., the granulated particles hardly sinter, and the fired product obtained has poor mechanical strength.
When firing is performed at a temperature higher than 100 ° C., crystal grain growth proceeds rapidly and the obtained sintered body becomes dense,
The porosity will be significantly reduced.

[0028]

EXAMPLES Some examples of the present invention will be shown below to clarify the present invention in more detail. However, the present invention is not limited by the description of such examples. Needless to say, it is not something to receive. In addition to the following embodiments, the present invention is not limited to the above specific description, and various changes and modifications are made based on the knowledge of those skilled in the art without departing from the spirit of the present invention. It is to be understood that improvements, etc. can be added.

Example 1 First, 40% of calcium oxide was added in a nitrogen gas stream.
0.7 g was added to 8.7 l of decarbonated water, and then stirred for 20 hours to prepare a calcium hydroxide slurry. Then, the obtained calcium hydroxide slurry is treated at 60 ° C.
The solution is heated to 1 mol / l of a phosphoric acid aqueous solution at a rate of 250 ml / hr, and the total amount is 4470 ml.
It was dripped until it became. And at this time, at the same time, p
As a H buffer solution, tris (hydroxymethyl) aminomethane having a concentration of 1 mol / l was added at an appropriate time to maintain the pH of the slurry at 7.0 to 7.5.
It was aged for a week to generate a calcium phosphate compound.
During this aging, the total amount of tris (hydroxymethyl) aminomethane added was 1000 ml.

The calcium phosphate compound thus synthesized was dehydrated by suction filtration, dried at 110 ° C. for 24 hours, and then crushed to obtain a calcium phosphate compound powder. In addition, when the powder of the calcium phosphate compound was sampled and chemical analysis was performed,
The Ca / P composition ratio was 1.67, and it was confirmed from the X-ray powder diffraction pattern that the calcium phosphate compound was hydroxyapatite.

The synthetic hydroxyapatite powder was calcined at 700 ° C. for 3 hours to obtain a bulk calcined product of synthetic hydroxyapatite. Then, the thus obtained massive calcined product is put into a resin pot mill, and pure water is further added thereto and wet-ground for 10 hours to obtain an average particle size of 0.29 μm and a specific surface area of 33 m ² / g. ,
A slurry of synthetic hydroxyapatite in which fine particles having easily sinterable fine crystals were dispersed at a concentration of 40% was prepared.

Subsequently, the slurry thus prepared was sprayed with a spray dryer at a slurry flow rate of 5
Spray drying was carried out under the conditions of 0 ml / min, hot air inlet temperature 200 ° C. and atomizer rotation speed 8000 rpm to obtain spherical dry granules. Then, the dried granules are passed through an 80-mesh screen, and the dried granules that have passed through the screen are calcined at 1000 ° C. for 3 hours to obtain the desired calcium phosphate-based porous granules for filling bone defects and voids. A sample 1 was obtained.

Then, the sample 1 thus obtained was observed with a scanning electron microscope (SEM). The SEM
The photographs are shown in FIGS. 1 and 2. As is clear from FIG. 1 and FIG. 2, the sample 1 is a sintered porous granule having a spherical shape, and has capillary communication holes extending vertically and horizontally from the surface of the granule to the inside. It is recognized that

Further, in this sample 1, when the granule diameter was measured by the dry sieving method, the average granule diameter was 3
At 9 μm, the content of granules of 5 μm or less was found to be 5%, and when the pore diameter was measured with a mercury porosimeter, the average pore diameter was 0.2 μm, and more than 70% of the pores were found. , 0.8 to 1. of the average pore diameter.
It was found to have a pore size in the double range. Furthermore, when the porosity of the porous granules was determined, it was 46.
It was 8%.

Next, the sample 1 consisting of the calcium phosphate-based porous granules for filling the bone defect portion and the void portion is injected into and filled in the bone marrow of the rabbit femur with a syringe to generate new bone thereafter. The progress was observed with a transmission electron microscope. Then, one week after the injection and filling of the porous granules,
It was observed that the porous granules were surrounded by 3 to 4 osteoblasts, respectively, and the cell projections extending from the surface of the osteoblasts entered the pores of the porous granules. In addition, at that time, no rejection reaction against foreign matter was observed at the filling site. Upon continuous observation, new bone rapidly grew, and 8 weeks after injection and filling, the porous granules were completely incorporated into the new bone formed around the porous granules, and the entire filling site was It was confirmed that they were integrated with the generated new bone.

Example 2 In the same manner as in Example 1, a slurry of synthetic hydroxyapatite having an average particle diameter of 0.34 μm, a specific surface area of 21 m ² / g and a concentration of 50% was prepared. Then, with respect to this slurry, using a spray dryer, the slurry flow rate:
Spray drying was carried out under the conditions of 60 ml / min, hot air inlet temperature: 200 ° C., atomizer rotation speed: 5500 rpm to obtain spherical dry granules. Then, the dried granules are passed through an 80-mesh screen, and the dried granules that have passed through the screen are calcined at 1000 ° C. for 3 hours to obtain a target calcium defect-based porous granule for filling bone defect and voids, Sample 2. Obtained.

Then, the sample 2 thus obtained was observed by SEM in the same manner as in Example 1. As a result, the sample 2 was a sintered porous granule having a spherical shape, and from the surface of the granule, It was confirmed that it had a capillary vent hole extending vertically and horizontally inside.

Also in this sample 2, the granule diameter and the pore diameter were measured in the same manner as in Example 1. The average granule diameter was 78 μm, and the content of granules having a particle diameter of 5 μm or less was 1
%, And the average pore diameter is 0.2 μm, 70%
It was confirmed that the above pores had a pore diameter in the range of 0.8 to 1.2 times the average pore diameter. Furthermore, the porosity of the porous granules was determined and found to be 45.1%.

Next, a sample 2 consisting of the calcium phosphate-based porous granules for filling the bone defect portion and the void portion was prepared as in Example 1.
Similarly to the above, the bone marrow of the rabbit femur was injected and filled with a syringe, and the subsequent generation process of new bone was observed with a transmission electron microscope. After the injection and filling of the porous granules, the same progress as in Example 1 was shown, and 1 week later, the injection and filling of the porous granules into the pores of the osteoblasts caused cell protrusions. Invasion was confirmed, and 8 weeks later, it was confirmed that the entire filling site was integrated with the generated new bone.

Comparative Example 1 In the same manner as in Example 1, a slurry of synthetic hydroxyapatite having an average particle diameter of 0.25 μm, a specific surface area of 39 m ² / g and a concentration of 4% was prepared. Then, using a spray dryer, a slurry flow rate of 30 is applied to this slurry.
Spray drying was carried out under the conditions of ml / min, hot air inlet temperature of 200 ° C., and atomizer rotation speed of 10,000 rpm. Then, the fine dry granules collected in the receiver under the cyclone were fired at 1000 ° C. for 3 hours to obtain Sample 3 as fine sintered granules.

Then, the sample 3 thus obtained was observed by SEM in the same manner as in Example 1. As a result, the sample 3 was a sintered porous granule having a spherical shape. It was confirmed that it had a capillary vent hole extending vertically and horizontally inside.

Also in this sample 3, the granule diameter and the pore diameter were measured in the same manner as in Example 1. The average granule diameter was 8 μm and the content of granules of 5 μm or less was 37%. It was found that the average pore diameter was 0.2 μm and 70% or more of the pores had a pore diameter in the range of 0.8 to 1.2 times the average pore diameter. Furthermore, the porosity of the porous granules was determined to be 47.0%.

Next, as in Example 1, the sample 3 composed of the fine calcium phosphate-based porous granules was injected and filled in the bone marrow of the rabbit femur with a syringe. Approximately 1 minute later, some dyspnea symptoms were observed in the rabbits. It is considered that this is because the injected and filled porous granules penetrated into the capillaries through the opening of the capillaries around the filling site and further into the lungs.

Comparative Example 2 The spherical dry granules obtained in Example 2 were passed through an 80 mesh sieve, and the dried granules passing through the sieve were calcined at 1150 ° C. for 3 hours to obtain a sintered granule, Sample 4. It was

Then, the sample 4 thus obtained was observed by SEM in the same manner as in Example 1. The SEM photographs are shown in FIGS. 3 and 4. As is clear from FIGS. 3 and 4, the sample 4 had a spherical shape, but almost no pores were observed.

Also in this sample 4, the granule diameter and the pore diameter were measured in the same manner as in Example 1. The average granule diameter was 73 μm, and the content of granules of 5 μm or less was 3%. It was found that the average pore diameter was 0.2 μm and 70% or more of the pores had a pore diameter in the range of 0.8 to 1.2 times the average pore diameter. Furthermore, the porosity of the porous granules was determined to be 3.7%.

Next, as in Example 1, the sample 4 composed of the densified calcium phosphate-based sintered granules was injected into and filled in the bone marrow of the rabbit femur with a syringe, and thereafter, new bone was prepared. The generation process was observed with a transmission electron microscope.
Then, eight weeks after injecting and filling the sintered granules, it was observed that the generated new bones surrounded the sintered granules, but the pores slightly contained in the sintered granules were observed. No invasion of osteoblast cell processes into the cells was confirmed. Therefore, it is presumed that osteoblasts are fixed to the sintered granules only by chemical bonds, and therefore, the fixing strength is low, and the sintered granules to be injected and filled are generated. It is easily inferred that the integration with new bone will be prolonged.

[0048]

As is apparent from the above description, the calcium phosphate-based porous granules for filling bone defects and voids according to the present invention have an extremely small granule diameter and have a substantially spherical shape. Since it has good fluidity, it can be directly injected into the filling site with a syringe or the like from the outside of the skin tissue when the bone defect or void is filled, and the filling site Incision surgery for surrounding muscle tissue and the like is no longer necessary, and the burden on the patient can be greatly reduced.

Since the calcium phosphate-based porous granules for filling the bone defect portion and the void portion are extremely fine as compared with the conventional bone defect portion and the void portion filler,
In the filling part, the volume of the gap between the particles of the porous granules can be made as small as possible, and the new bone can be quickly filled into the gap, and the capillary communication that it has. Since the pores are also very small in diameter, new bone tissue generated by the invasion of cell projections can be filled in the pores in a short period of time, thereby generating new bone. Filling of the entire filling site can be advantageously accelerated as compared with the conventional bone filling material, so that the period required for integrating the entire filling site and the new bone tissue can be shortened extremely efficiently. It was possible to be punished.

Moreover, in the calcium phosphate-based porous granules for filling bone defects and voids according to the present invention, the content of ultrafine granules is limited to a predetermined amount or less. The fine granules injected and filled in the living body can be prevented from invading the capillaries, and the safety for the living body can be advantageously ensured.

Further, according to the method of the present invention, the calcium phosphate-based porous granules for filling bone defects and voids, which exhibit such excellent characteristics, can be advantageously obtained, and further, in the granulation operation thereof, By adopting the method of spray-drying a slurry having a predetermined concentration and granulating, the desired calcium phosphate-based porous granules can be easily and efficiently produced.

[Brief description of drawings]

FIG. 1 is a scanning electron micrograph of calcium phosphate-based porous granules for filling bone defects and voids obtained in Example 1: Sample 1, with a magnification of 5000 times.

FIG. 2 is a scanning electron micrograph of calcium phosphate-based porous granules for filling bone defects and voids obtained in Example 1, which is a scanning electron micrograph with a magnification of 20000 times.

3 is a scanning electron micrograph of calcium phosphate-based sintered granules: sample 4, obtained in Comparative Example 2.
The magnification is 5000 times.

FIG. 4 is a scanning electron micrograph of calcium phosphate-based sintered granules: sample 4, obtained in Comparative Example 2,
The magnifying power is 20000 times.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Hideo Sakano, Hideo Sakano, 11-11 Tsukisan-cho, Minato-ku, Nagoya, Aichi Prefecture, STC Ceramics Laboratory Co., Ltd. (72) Inventor Hajime Saito Aichi, Aichi 7-1409 Higashiyama, Nisshin-cho, Gunma (72) Inventor Shigero Niwa 2-1213, Goshikinen, Nisshin-cho, Aichi-gun, Aichi Prefecture 4E

Claims (3)

[Claims] 1. A sintered porous granule having a substantially spherical shape of a calcium phosphate compound, which has capillary continuous pores extending longitudinally and laterally from the surface of the granule to the inside thereof, and has an average pore diameter of 0.1. Average granules having a porosity in the range of 20 to 90% and having a porosity in the range of 0.5 to 2.0 times the average pore size and 70% or more of the pores. A calcium phosphate-based porous granule for filling a bone defect portion and a void portion, which has a diameter of 10 to 100 μm and a content of granules of 5 μm or less is 10% or less. 2. A calcium phosphate compound synthesized by a wet method is calcined at a temperature of 500 to 800 ° C. and then pulverized to have an average particle diameter: 0.01 to 1.00 μm and a specific surface area:
It is characterized in that it is made into easily sinterable fine crystals of 5 to 50 m ² / g, and then the obtained fine crystals are granulated into spherical particles of 10 to 100 μm, and then fired at a temperature of 800 to 1100 ° C. And a method for producing a calcium phosphate-based porous granule for filling a bone defect portion and a void portion. 3. The granulation is 5 to 60% of the fine crystals.
The method for producing a calcium phosphate-based porous granule for filling a bone defect portion and a void portion according to claim 2, which is carried out by spray-drying a slurry having a concentration.