JPH0429630B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field The present invention relates to a porous calcium phosphate compound and a method for producing the same. More specifically, the present invention relates to a porous calcium phosphate compound that is useful not only as an adsorbent or catalyst carrier but also as a filler for bone defects, and a method for producing the same.

PRIOR ART It is already known that porous bodies made of calcium phosphate compounds, such as hydroxyapatite, can be used as adsorbents, supports for catalysts, and fillers for bone defects. Conventionally, a method for manufacturing such a porous body includes adding an organic foaming agent to an aqueous slurry of an amorphous calcium phosphate compound, stirring the mixture, and forming a large number of bubbles in the slurry in advance. Powder of a calcium phosphate compound is attached to the surface of the bubbles to form a porous body, the porous body is heated to decompose and remove the organic foaming agent, and the obtained porous body is sintered to form a sintered calcium phosphate compound. A method for obtaining a compound porous body is known.

However, the conventional method described above has drawbacks such as large variations in the size of the bubbles formed depending on the type of foaming agent and the tendency for the bubbles to disappear. However, it was difficult to obtain a product having a desired porosity. In addition, the porous bodies obtained by the above-mentioned conventional method have large variations in pore size, and therefore, even if they have the same porosity, their strength varies widely. It was difficult to control the temperature so that it had the following properties.

Therefore, there has been a strong desire in the art for a calcium phosphate compound porous material having desired pore size, distribution, strength, and uniform quality, and a method for producing the same.

OBJECT OF THE INVENTION The object of the present invention is to provide a porous body of a calcium phosphate compound having pores of a desired size, excellent strength, and in which the pores communicate with the outside air through fine gaps. The purpose is to provide a manufacturing method.

Another object of the present invention is a porous body of calcium phosphate compound that can be used for in vivo bone tissue regeneration, that is, induction of new bone, other medical applications, electronic materials, genetic engineering materials, and a method for producing the same. Our goal is to provide the following.

Structure of the Invention The calcium phosphate compound porous body of the present invention is composed of a large number of sintered calcium phosphate compound needle crystals each having a length of 5 to 200 microns and is formed by cross-connecting each other. At least one pore having a pore diameter of 1 to 600 microns is formed in the porous body, and the needle-like crystals are fused to each other at their intersections by sintering, and A large number of gap spaces are formed between the acicular crystals, and the pores communicate with the outside air through these gaps.

Further, the method for producing a porous body of a calcium phosphate compound of the present invention includes a raw material powder 1 consisting of a calcium phosphate compound powder having a particle size of 1 micron or less, or a mixture of the calcium phosphate powder and a small amount of other calcium compound powder. A slurry is prepared by dispersing 5 parts by weight in 5 to 15 parts by weight of water, and the slurry is heated at 1 to 100 RPM in a closed reactor.
While stirring with a stirrer with a rotational speed of 1 to 30 to form a laminar flow with a Reynolds number (Re) of 7 to 30,
It is heated to a temperature of 50 to 100°C under 300 atmospheres, thereby forming a large number of calcium phosphate compound needle crystals with a length of 5 to 200 microns and cross-linking these large number of needle crystals to each other. forming an unsintered porous body; separating and collecting the unsintered porous body from the slurry; then sintering the unsintered porous body at a temperature of 900 to 1350°C to form the acicular crystals; and fusing them together at their points of cross-contact.

DETAILED DESCRIPTION OF THE INVENTION The porous body of the present invention is formed by cross-linking sintered needle-like crystals of a calcium phosphate compound.

The calcium phosphate compound used in the present invention is CaHPO ₄ Ca ₃ (PO ₄ ) ₂ Ca ₅ (PO ₄ ) ₃ OH Ca ₄ O (PO ₄ ) ₂ Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ CaP The main components are ₄ O ₁₁ Ca (PO ₃ ) ₂ Ca ₂ P ₂ O ₇ Ca ( _{H 2} PO ₄ ) 2.H ₂ O, and include a group of compounds called hydroxyapatite. Hydroxyapatite has the composition formula Ca ₅ (PO ₄ ) ₃ OH or
The basic component is a compound containing Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ , and a portion of the Ca component is Sr, Ba, Mg,
It may be substituted with one or more of Fe, Al, Y, La, Na, K, H, etc., and a part of the (PO ₄ ) component may be VO ₄ , BO ₃ , SO ₄ , CO ₃ , SiO ₄ The (OH) component may be partially substituted with one or more of F, Cl, O, CO ₃ and the like.

Generally, the calcium phosphate compound used in the present invention has an atomic ratio of calcium (Ca) to phosphorus (P).
Preferably within the range of 1.30 to 1.80, 1.60
Those within the range of ~1.67 are more preferable.

The porous body of the present invention is formed by a large number of sintered calcium phosphate compound needle crystals having a length of 5 to 200 microns, which intersect with each other and are entangled. At least one pore is formed with a pore size of ~600 microns, preferably 30-300 microns. Furthermore, the needle-shaped crystals are fused together at their cross-contact points by sintering. Further, a large number of gap spaces are formed between these needle-shaped crystals, and the pores can communicate with the outside air through these gaps. The interstitial space of the above-mentioned needle-like crystals preferably has a diameter of 1 to 30 microns, more preferably 1 to 20 microns.

The calcium phosphate compound needle crystals sintered in the porous body of the present invention have a length of 5 to 200 microns, and there is no particular limitation on the thickness, but it is generally 0.1 to 0.5 microns. It is preferable. If the length of the acicular crystals is less than 5 microns, a suitable porous body will not be formed and the porosity will be too small.
When the diameter is larger than 200 microns, the size of the porous body becomes too large, resulting in a disadvantage that the porosity becomes too large.

The porous body of the present invention has one or more pores with a pore diameter of 30 to 300 microns inside. The number of holes may be only one, in which case a hollow spherical unit is formed. The porous body of the present invention may have a structure in which a plurality of hollow spherical bodies are collectively connected. In this case, the plurality of pores in the porous body communicate with each other through the interstitial spaces of the needle-like crystals, and also communicate with the outside air. Generally, the hollow spherical units of the present invention have a particle size of 50 to 350 microns;
It is preferably a fine granule of 70 to 300 microns, but may be formed into granules with a particle size of 0.05 to 5 mm.
Alternatively, it may be formed into a shape and size that corresponds to the shape and size of the bone defect or void that is to be filled or prosthesized.

The porous body of the present invention generally preferably has a porosity of 30 to 90%, more preferably 40 to 70%. It is preferable that the pores in the porous body have a shape of a perfect sphere or a shape close to a true sphere, and it is preferable that the pores are uniformly distributed within the porous body.
These pores provide a living space for biologically activating bone phagocytes, bone regenerating cells, etc. when the ceramic material is implanted in a living body. Bone regeneration cells and the like very much prefer to stay in these pores, especially in the spherical pores. For this purpose, the pore diameter must be in the range of 1 to 600 microns, preferably 30 to 300 microns.
Pores with a pore diameter outside the range of 1 to 600 microns cannot provide a good living space for the cells.

When the shape of the pores is a true sphere or a sphere close to this, the resulting porous body has high mechanical strength. Therefore, when this porous body is implanted in a living body, it continues to maintain high mechanical strength until it is returned over by new bone, and fractures can be prevented during that time.

The acicular crystal interstitial spaces in the sintered porous body communicate at least the pores with the external space of the porous body, and through these passages, the bone phagocytes, bone regenerating cells, and erythrocyte body fluid etc. can freely enter the porous body, and the development of capillaries is promoted. However, when the diameter of this gap is in the range of 1 to 30 microns, preferably in the range of 1 to 20 microns, it is difficult for bone destruction cells and collagen fibers to enter the capillary void passageway in the porous body, and collagen fibers Abnormal development of bone tissue and hardening of bone tissue can be prevented. That is, in the porous body of the present invention, the acicular crystal interstitial spaces also function as a biofilter.

If the diameter of the interstitial space is smaller than 1 micron, it may be difficult for bone phagocytes, bone regenerating cells, red blood cell fluid, etc. to enter the porous body, and if it is larger than 30 microns, the intrusion of destroyed cells and collagen fibers may become difficult. This may inhibit bone regeneration and may lead to hardening of the regenerated bone tissue and surrounding tissues.

Even when the porous body of the present invention has a plurality of pores, these pores communicate with each other through the interstitial spaces between needle-like crystals. Regeneration (return over) can be promoted.

When the porous body of the present invention is implanted in a living body as a filling material or a prosthetic material, blood, body fluids, bone phagocytes, and bone regenerating cells enter through the interstitial spaces of the needle-shaped crystals, and bone proliferates in the pores. It is consumed by phagocytes, and at the same time, bone tissue is regenerated by bone regenerating cells, resulting in so-called turnover.
At this time, the interstitial spaces that communicate the pores to the external space of the porous body have a diameter of 1 to 30 microns, so bone destruction cells and collagen fibers are absorbed into the capillary-like voids within the porous body. It is difficult to enter the passageway and can prevent abnormal development of collagen fibers and their hardening. Therefore, the soft tissue of the regenerated bone will not be destroyed or hardened by collagen fibers. Therefore, the porous body of the present invention induces new bone formation and is replaced by normal bone tissue grown in vivo.

In order to produce the porous body of the present invention, raw material powder containing a calcium phosphate compound as a main component is
Metamorphoses into 200 micron needle-like crystals. This raw material powder consists of a calcium phosphate compound powder having a particle size of 1 micron or less, or a mixture of this calcium phosphate compound powder and other calcium compound powder.

The calcium phosphate compounds used in the method of the present invention are as described above, but in general, tricalcium phosphate [Ca ₃ (PO ₄ ) ₂ ], hydroxyapatite [Ca ₅
(PO ₄ )OH] and Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ are preferred, and those synthesized by a sol-gel method, filtered, washed with water, and dried are particularly preferred.

To produce the desired calcium phosphate compound,
For example, an aqueous solution containing calcium ions, or
An aqueous solution containing phosphate ions is added dropwise to the calcium compound suspension, and the reaction system is heated to a reaction temperature of 10 to 80°C.
A method of aging for 0.5 to 100 hours while adjusting the temperature and pH to 3 to 11 is known. In this case, the atomic ratio of calcium to phosphorus (Ca/P) is preferably set in the range of 1.30 to 1.80. Atomic ratio (Ca/P)
However, when the atomic ratio (Ca/P) is less than 1.30, crystalline prussiaite is produced, and when the atomic ratio (Ca/P) exceeds 1.80, CaO is produced after sintering.

The calcium phosphate compound obtained by the above synthesis process is filtered, washed with water, dried, and used as a raw material powder having a particle size of 1 micron or less.

In the method of the present invention, the calcium phosphate compound used in the raw material powder may be a normal crystalline substance,
Alternatively, it may be any one of a homomorphic solid solution, a substitutional solid solution, and an interstitial solid solution, and may also contain non-stoichiometric lattice defects.

When the calcium/phosphorus atomic ratio (Ca/P) of the calcium phosphate compound used in the raw material powder is smaller than the desired value of the atomic ratio (Ca/P) of the needle-shaped crystals to be formed, the insufficient amount of calcium is supplemented. For this purpose, powders of calcium compounds different from calcium phosphate compounds, such as calcium hydroxide, quicklime, calcium nitrate, calcium fluoride, calcium chloride, and/or calcium oxalate, are mixed with the calcium phosphate compound powder. , this mixture is used as a raw material powder.

The raw material powder is dispersed in 5 to 15 parts by weight of water, preferably distilled water or deionized water, to prepare an aqueous slurry.

In this slurry, if the amount of water is less than 5 parts by weight per 1 part by weight of the raw material powder, the growth rate of the acicular crystals of the calcium phosphate compound is slow and the formation of pores is insufficient, resulting in a clogging phenomenon. Occur. If the amount of water is more than 15 parts by weight, the size of the pores in the porous body obtained will be larger than 300 microns, and the porous body obtained by firing will have low strength and become brittle.

The obtained aqueous slurry of raw material powder is charged into a closed reactor equipped with a stirrer, for example, an autoclave, and the aqueous slurry is heated to a temperature of 50 to 100°C under a pressure of 1 to 300 atm. , 1~
Stir at a rotation speed of 100 RPM and form a laminar flow with a Reynolds number (Re) of 7 to 30. If this treatment is continued for a required period of time, for example, 1 to 100 hours, calcium phosphate compound needle crystals with a length of 5 to 200 microns will be formed from the raw material powder, and at the same time, these needle crystals will intersect (entangle) with each other. These are connected to form an unsintered porous body having at least one pore with a pore diameter of 1 to 600 microns inside. Although the formation mechanism of such porous bodies is not clear,
When needle-like crystals generated in a laminar flow move along with the laminar flow, a minute vortex is generated around the needle-like crystal, and it is thought that this vortex causes the needle-like crystals to intertwine and connect with each other. .

The steps of forming and entangling needle-shaped crystals include steps 1 to 1.
It is carried out at a temperature of 50-100℃ under 300 atmospheres. If the pressure and temperature conditions are outside the above range, the growth of needle-like crystals of the calcium phosphate compound will not proceed sufficiently.

The type of stirrer used in this step is not particularly limited, but those effective for forming a laminar flow, such as a paddle stirrer, a turbine blade stirrer, or a propeller stirrer, can be used. This stirring operation is performed at a rotation speed of 1 to 100 RPM to form a laminar flow in the slurry with a Reynozzle number (Re) of 7 to 30.
Reynolds number (Re) due to insufficient rotation speed of the stirrer
When is less than 7, the laminar flow formed is local and causes unsatisfactory growth and entanglement of needle crystals. Additionally, if the rotational speed of the stirrer is too high and the Reynolds number (Re) exceeds 30, turbulence will occur in a part of the laminar flow, making it easier to destroy the needle-shaped crystals of calcium phosphate compound that have grown. Mutual entanglement of crystals is inhibited, making it difficult to obtain a porous body having desired pores.

The formed calcium phosphate compound unsintered porous body is separated and collected from the slurry by an appropriate method such as filtration or centrifugation.

This unsintered porous body is molded as is or as needed into a molded product of desired shape and size,
At a temperature of 900 to 1350℃, for example, 0.5 to
Sintering is performed by heating for 3 hours. Through this sintering operation, the needle-like crystals are fused together at their cross-contact points, and the strength of the resulting porous body is improved, while the interstitial spaces between the needle-like crystals are maintained.

Next, the present invention will be further explained with reference to Examples.

Example 1 5 mol of special grade reagent calcium hydroxide was added to 10 mol of distilled water.
to create a calcium hydroxide slurry. This slurry was placed in a 60 4-neck enamel tank, the air in the tank was replaced with nitrogen gas, and 400 ml of a 50% by volume phosphoric acid aqueous solution was gradually added to the slurry while stirring with a stirrer at a rotation speed of 1000 RPM. Then, this mixed solution was heated at a temperature of 60° C. for 24 hours to cause a reaction. After the reaction is completed, adjust the pH of the reaction solution to 6 and adjust the atomic ratio of calcium to phosphorus (Ca/P).
An amorphous calcium phosphate compound with a value of 1.62 was obtained. This compound was dehydrated and dried. This compound has a particle size of approx.
It was a powder consisting of fine particles of 0.5 microns.

A slurry was prepared by dispersing 200 g of amorphous calcium phosphate powder in 3000 g of distilled water. This slurry is placed in an autoclave, and a turbine blade agitator is rotated at a rotation speed of 70 RPM to agitate the slurry to form a laminar flow with a Reynolds number (Re) of 10, and at the same time, the slurry in the autoclave is was heated at 80°C for 40 hours under a pressure of 100 atm. As a result, granules of unsintered porous calcium phosphate compound were formed.

This unsintered porous body was separated from the slurry and dried. This porous body was observed using a scanning electron microscope. As a result, it was found that this porous body consists of numerous needle-shaped crystals with a length of 5 to 200 microns and a thickness of 0.1 to 0.3 microns, and has pores with a pore diameter of 150 to 300 microns inside. Ta. 10 g of the dried unsintered porous body was molded into a disk shape with a diameter of 10 mm and a thickness of 5 mm under a pressure of 2 kg/cm ² . This disc-shaped porous body
Sintering was carried out at a temperature of 1200°C for 2 hours.

The obtained sintered porous body had a porosity of 48% and a porosity of 1.58 g/
It had a bulk specific gravity of ^cm2 and a compressive strength of 250Kg/ ^cm2 . When this porous body was observed with a scanning electron microscope, it was found that the pores with a pore size of 100 to 200 microns were distributed almost uniformly, the needle-shaped crystals were fused together at their cross-contact points, and the interstitial space was It had a diameter of 5-10 microns.

Example 2 Amorphous calcium phosphate compound prepared in Example 1 (Ca/P atomic ratio = 1.62, particle size approximately 0.5 micron)
and 40 g of calcium hydroxide powder (particle size: approximately 0.8 microns) were mixed, and 200 g of this mixture was dispersed in 3000 g of distilled water to prepare a slurry.

When this slurry was laminarly stirred and heated under pressure in the same manner as described in Example 1, a porous body was formed. This porous material has a length of 10 to 200 microns and a thickness of
It was formed by intertwining needle-like crystals of 0.1 to 0.3 microns, and pores of 30 to 300 microns were formed inside them.

After dehydrating and drying this porous body, it was examined by X-ray diffraction, and the needle-shaped crystals were found to be hydroxyapatite (Ca/P=1.67) with excellent crystallinity. 10 g of the porous particles were molded into a disk shape with a diameter of 10 mm and a thickness of 5 mm under a pressure of 3 kg/cm ² , and the molded body was heated at 1150° C. for 1.5 hours to sinter.

The porosity of the obtained hydroxyapatite sintered porous body was 43%, the bulk specific gravity was 1.60 g/cm ² , and the compressive strength was
It was 330Kg/ ^cm2 .

When this sintered porous body was observed with a scanning electron microscope, it was found that pores with a pore size of 60 to 200 microns were distributed almost uniformly, and the needle-like crystals were fused together at their intersections, leaving gaps between them. The diameter of the space was 5-15 microns.

Effects of the Invention The calcium phosphate compound porous body of the present invention is not only useful as an adsorbent and catalyst carrier due to its special structure, but also extremely useful as a filling material for bone defects.

Claims (1)

[Claims] Consisting of a porous body formed by cross-linking a large number of sintered calcium phosphate compound needle crystals each having a length of 15 to 200 microns, the porous body having a length of 1 to 600 microns. At least 1 with a pore size of microns
The needle-like crystals are fused to each other at their intersections by sintering, and a large number of void spaces are formed between these needle-like crystals. Through this gap,
A porous body of a calcium phosphate compound, characterized in that the pores are in communication with the outside air. 2. The porous body according to claim 1, wherein the calcium to phosphorus atomic ratio (Ca/P) in the calcium phosphate compound is within the range of 1.30 to 1.80. 3. The porous body according to claim 1, wherein the calcium phosphate compound is hydroxyapatite. 4. The porous body according to claim 1, wherein the diameter of the interstitial space between the needle crystals is within the range of 1 to 30 microns. 5. The porous body according to claim 1, wherein the porous body has a porosity of 30 to 90%. 6. The porous body according to claim 1, wherein the needle-like crystals have a thickness within a range of 0.1 to 0.5 microns. 7 Disperse 1 part by weight of a raw material powder consisting of a calcium phosphate compound powder having a particle size of 1 micron or less, or a mixture of the calcium phosphate powder and a small amount of other calcium compound powder, in 5 to 15 parts by weight of water. This slurry was heated at 1 to 100 RPM in a closed reactor.
While stirring with a stirrer with a rotational speed of
It is heated to a temperature of 50 to 100°C under 300 atmospheres, thereby forming a large number of calcium phosphate compound needle crystals with a length of 5 to 200 microns and cross-linking these large number of needle crystals to each other. forming an unsintered porous body; separating and collecting the unsintered porous body from the slurry; then sintering the unsintered porous body at a temperature of 900 to 1350°C to form the acicular crystals; are fused to each other at their cross-contact points. 8 The atomic ratio of calcium to phosphorus (Ca/P) in the calcium phosphate compound needle crystals is 1.30 to 1.30.
1.80. 9. The method according to claim 7, wherein the calcium phosphate compound needle-like crystals are made of hydroxyapatite. 10 The other calcium compound powder is at least one selected from calcium hydroxide, quicklime, calcium carbonate, calcium nitrate, calcium fluoride, calcium chloride, and calcium oxalate.
8. The method according to claim 7, wherein the powder of