JPS6090880A - Calcium phosphate porous body and manufacture - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

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.

BACKGROUND OF THE INVENTION 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 involves adding an organic foaming agent to an aqueous slurry of an amorphous calcium phosphate compound.
This mixture is stirred to form a large number of bubbles in the slurry in advance, powder of a calcium compound is attached to the surface of the bubbles to form a porous body, and this porous body is heated to generate organic foam. A method of obtaining a sintered calcium phosphate compound porous body by decomposing and removing the agent and sintering the obtained 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 with a desired porosity.

In addition, the porous bodies obtained by the conventional method described above have large variations in pore size, and therefore, even if they have the same porosity, their strength varies widely. [3]
Met.

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

OBJECTS OF THE INVENTION An 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 voids; The purpose is to provide a manufacturing method.

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

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 2 QQ 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 crystals are fused to each other at their intersections by sintering, and the needle crystals are fused to each other at their intersections by sintering. A large number of gap spaces are formed between the 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. Part by weight is dispersed in 5 to 15 parts by weight of water to prepare a slurry, and this slurry is stirred in a closed reactor with a stirrer having a rotation speed of 1 to 11001P to obtain the Reynolds number (Re).
This is heated under 1 to 300 atmospheres while forming a laminar flow of 5 [l! Heating to a temperature of ~100C, thereby forming a large number of calcium phosphate compound needle crystals with a length of 5 to 200 microns, and cross-linking these large numbers of needle crystals to each other to form a green porous body. , separating and collecting the green porous body from the slurry, and then sintering the green porous body at a temperature of 900 to 1350 C to bring the needle-shaped crystals together at their cross-contact points. Fii! I! 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 01LHPC! 4 aas (PO4) 2 oas (po4) 3 oa Ca40 (PO4) 2 0a, O (PO4) 6 (OH) 2 0aP401゜aa (po5)2 0a2P207 0a (H2PO4) 21H2゜ etc. are the main components, Includes a group of compounds called hydroxyapatites. Hydroxyapatite has the composition formula oa5(PO4)30I (or 0a1o(
The basic component is a compound having PO4)6(OH)2, and a portion of the Oa acid component is Sr, Ba, Mg
.

1! o, A4 Y, I+a, Na, K, H, etc. may be substituted with one or more types, and (po4)
Some of the components are VO4, BO3, SO2,00,,S
It may be substituted with one or more types such as iO4, and further,
A part of the (OH) component may be substituted with one or more of a, at, o, oo3, etc.

Generally, the calcium phosphate compound used in the present invention has an atomic ratio of calcium (Oa) to phosphorus (P) of 1.30 to
It is preferably within the range of 1.80, and 1.60 to 1
．． Those within the range of 67 are more preferable.

The porous body of the present invention has a length of 5 to 200 microns,
It is formed by a large number of sintered calcium phosphate compound needle crystals intersecting and entangling each other, and the porous body has pores with a diameter of 1 to 600 microns, preferably 30 to 300 microns. At least one pore is formed. Moreover, the needle-like crystals are fused together at their cross-contact points by sintering. Further, a large number of gap spaces are formed between these needle-like 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 phosphorescent calcium compound needle-shaped crystals sintered in the porous body of the present invention have a length of 5 to 200 μm, and there is no particular limitation on the thickness, but it is generally 0.5 μm in length.
Preferably it is between 1 and 0.5 microns. If the length of the needle crystal is less than 5 microns, there is a disadvantage that a suitable porous body will not be formed and the porosity will be too small. In this case, the dimensions of the porous body become 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
Fine granules of 550 microns, preferably 70-300 microns, but may be formed into granules with a particle size of 0.05-511 m, or the shape of the bone defect or void to be filled or prosthesized. It may be molded into a shape and size corresponding to the dimensions.

The porous body of the present invention is generally! It is preferable to have a porosity of 10 to 90%, more preferably 40 to 70%. The pores in the porous body preferably have a pearl shape or a shape similar to a pearl, and are preferably uniformly distributed within the porous body. These pores provide a living space for biologically activating bone cells, bone regenerating cells, etc. when the ceramic material is implanted in a living body. Bone regeneration #ll cells and the like very much like to stay in these pores, especially spherical pores. For this purpose, the pore diameter needs to 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 hole 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 space in the sintered porous body at least communicates the pores with the external space of the porous body, and through these passages, the bone cells, 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 osteoclastic cells and collagen fibers to enter the capillary-like void passageway in the porous body. , can prevent abnormal development of collagen fibers and hardening of bone tissue. 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 above-mentioned gap space is smaller than 1 micron, it may be difficult for bone cells, bone regenerating cells, red blood cell body fluid, etc. to enter the porous body, and if it is larger than 30 microns, broken cells and collagen fibers may enter the porous body. This inhibits bone regeneration, and also inhibits regenerated bone tissue and
This may lead to hardening of the tissue in the vicinity.

Even when the porous body of the present invention has a plurality of pores, these pores are connected to each other through the acicular crystal interstitial spaces. ) can be promoted.

When the porous body of the present invention was implanted in a living body as a filler or a filler material, blood, body fluids, bone cells, and bone regenerating cells entered through the interstitial spaces of the needle-shaped crystals and proliferated in the pores. It is consumed by bone cells, and at the same time, bone tissue is regenerated by bone cells, resulting in a so-called turnover.

At this time, since the interstitial space communicating the pores toward the external space of the porous body has a diameter of 1 to 30 microns, 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, a raw material powder containing a calcium phosphate compound as a main component is transformed into needle-shaped crystals having a length of 5 to 200 microns. 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 compound used in the method of the present invention is as described above, but in general, tricalcium phosphate (aa, (
po4)2), hydroxyapatite [0a5(PO4
)01i] and a a , o (P O4) , s
(on) 2 is preferred, and in particular, one synthesized by a sol-gel method, filtered, washed with water, and dried is preferred.

To produce the desired calcium phosphate compound, e.g.
An aqueous solution containing phosphate ions is added dropwise to an aqueous solution containing calcium ions or a suspension of a calcium compound, and the reaction system is aged for 0.5 to 100 hours while adjusting the reaction temperature to 10 to 80 Us and pH 3 to 11. There are known ways to do this. In this case, the atomic ratio of calcium to phosphorus (Cα/
P) is preferably set in the range of 1.30 to 1.80. When the atomic ratio (Cα/P) is less than 1.30, crystalline brushite is produced, and the atomic ratio (Oc
When L/P) exceeds 1.80, a disadvantage arises in that OaO is generated 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 crystal, or may be any of a isomorphic solid solution, a substitutional solid solution, and an interstitial solid solution. It may contain lattice defects.

When the calcium/phosphorus atomic ratio (0α/P) of the calcium phosphate compound used in the raw material powder is smaller than the desired value of the atomic ratio (0α/P) of the needle-like crystals to be formed, the insufficient amount of calcium is captured. 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 per 1 part by weight, preferably distilled water or deionized water,
An aqueous slurry is prepared.

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 an agitator, such as an autoclave, and the slurry is heated for 1 hour.
The aqueous slurry was stirred at a rotational speed of 1 to 11001 P while heating to a temperature of 50 to 100 C under a pressure of ~300 atm and then subjected to Reynolds'I! I(Re)7~3
A laminar flow of 0 is formed. The time required for this process, e.g.
If it continues for 1 to 100 hours, the length will be 5 to 200 mm from the raw material powder.
Micron needle-like crystals of calcium phosphate compound are formed, and these needle-like crystals are cross-connected (intertwined) with each other and have a microorganism inside which has at least one pore with a pore size of 1 to 600 microns. Form a sintered porous body. The mechanism of formation of such a porous body is not clear, but 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 this vortex causes the needle-like crystal to move freely. It is thought that the crystals are intertwined and connected to each other.

The formation and entangling process of needle-like crystals is carried out at a temperature of 50-100C under 1-600 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 rotational speed of 1 to 100 Rp'M, and the slurry has a Reynolds number (Re) of 7 to 30.
form a laminar flow.

When the rotational speed of the keyaki stirrer is insufficient and the Reynolds number (Re) is less than 7, the laminar flow formed is local and causes unsatisfactory growth and entanglement of needle crystals.

In addition, the rotation speed of the stirrer is too high and Reynolds 1f ((Re
) is larger than 30, turbulent flow occurs in a part of the laminar flow, the grown acicular crystals of phosphorus and calcium compounds are easily destroyed, and mutual entanglement of these acicular crystals is inhibited, resulting in the formation of the desired empty space. It becomes difficult to obtain a porous body having pores.

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

This unsintered porous body can be used as is, or as necessary,
Molded into a molded product of desired shape and dimensions, and then heated to 900~
Sintering is performed at a temperature of 1350 t:' for, for example, 05 to 3 hours. Through this sintering operation, the needle-shaped crystals are fused together at their cross-contact points, and the strength of the resulting porous body is improved, while the interstitial spaces of the needle-shaped crystals are maintained as they are.

Next, the present invention will be further explained by examples.

Example 1 A calcium hydroxide slurry was prepared by dispersing 5 moles of special grade reagent calcium hydroxide in 101 parts of distilled water. This slurry was put into a 60-e four tank made of enamel, the air in the tank was replaced with nitrogen gas, and the slurry was heated to 11,000 RP.
While stirring with a stirrer at a rotational speed of
The reaction was carried out by heating at a temperature of 0C for 24 hours. After the reaction is complete,
The pH of the reaction solution was adjusted to 6 to obtain an amorphous calcium phosphate compound having an atomic ratio of calcium to phosphorus (0α/P) of 1.62. This compound was dehydrated and dried.

This compound was a powder consisting of fine particles with a particle size of about 0.5 microns.

A slurry was prepared by dispersing 2001 amorphous calcium phosphate powder in 30001 distilled water. Put this slurry into an autoclave and turn the turbine blade agitator to 7QRPM.
The slurry was stirred by rotating at a rotational speed of 10 to form a laminar flow with a Reynolds number (Re) of 10, and the slurry in the autoclave was heated at 80C under a pressure of 100 atm for 40 hours. . 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, this porous body consists of numerous needle-like crystals with a length of 5 to 2 mm and a thickness of 0.1 to 0.3 mm,
It was found that the inside had pores with a pore diameter of 150 to 300 microns. Dried unsintered porous body 10?
was molded into a disk shape with a diameter of 10 cm and a thickness of 5+wi under a pressure of 2 kl/cd. 1200t of this disc-shaped porous body:'
It was sintered at a temperature of 2 hours.

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

Example 2 Amorphous calcium phosphate compound prepared in Example 1 (O
α/P atomic ratio = 1.62, particle size approximately 0.5 mm)
1602 and calcium hydroxide powder (particle size approximately 0.8 microns) 402, this mixture 200? was dispersed in distilled water 30005F 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 body was formed by intertwining needle-like crystals with a length of 10 to 200 microns and a thickness of 0.1 to 0.3 microns, and pores of 30 to 300 microns were formed inside the porous body.

After dehydrating and drying this porous body, it was examined by X-ray diffraction, and it was found that the needle-shaped crystals were hydroxyapatite with excellent crystallinity (Cα/p=1.67).

This porous particle 10f! was molded into a disk shape with a diameter of 1011% and a thickness of 5IIIl under a pressure of 3 ky/ct/I, and this molded body was sintered by heating at 1150 t:' for 1.5 hours.

The porosity of the obtained hydroxyapatite sintered porous body was 4
3%, bulk specific gravity is 1.60 P/cd, compressive strength is 55
It was 0 kl/cd.

When this sintered porous body was observed with a scanning electron microscope,
Holes with a pore diameter of 60 to 200 microns! The needle-like crystals were uniformly distributed, and the needle-like crystals were fused to each other at their intersections, and the diameter of the interstitial space was 5 to 15 mm.

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.

patent applicant Sumitomo Cement Co., Ltd. Shigeru Yamanouchi patent application agent Patent Attorney Akira Aoki Patent attorney Kazuyuki Nishidate Patent attorney Akira Yamaguchi Patent attorney Masaya Nishiyama

Claims (1)

[Scope of Claims] It consists 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 micrometers. At least one hole having a pore diameter of 600 mm is formed, and the needle-like crystals are fused to each other at their intersections by sintering, and the needle-like crystals are fused to each other at their intersections. A porous body of a calcium phosphate compound, characterized in that a large number of gap spaces are formed between the pores, and the pores communicate with the outside air through the gaps. 2. The porous body according to claim 1, wherein the calcium phosphate compound has an atomic ratio of calcium to phosphorus (0α/P) of 1.30 to 1.80. 6. The porous body according to claim 1, wherein the a-acid calcium 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 the range of 0.1 to 0.5 microns. 7. 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 above calcium phosphate powder and a small amount of other calcium compound powder is mixed with 5 to 15 parts by weight of water. This slurry was stirred in a closed reactor with a stirrer having a rotation speed of 1 to 1100 RP to obtain a Reynozzle number (Re) of 7.
This is heated to a turbidity of 50-100C under 1-300 atmospheres while forming a laminar flow of ~30C, thereby
A large number of calcium phosphate compound needle crystals of ~200 microns are formed, and these large numbers of needle crystals are cross-connected to each other to form an unsintered porous body, and the unsintered porous body is separated and captured from the slurry. and then sintering the green porous body at a temperature of 900-1350C to fuse the needle-like crystals together at their cross-contact points. Production method. 8. The atomic ratio of calcium to phosphorus (0α/P) in the calcium phosphate compound needle crystals is 1.30 to 1.
80. The method of claim 7 within the range of 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 a powder of at least one member selected from calcium hydroxide, quicklime, calcium carbonate, calcium nitrate, calcium fluoride, calcium chloride, and acetic calcium. The method described in scope item 7.