U.S. patent application number 10/005673 was filed with the patent office on 2002-08-22 for porous sintered body of calcium phosphate-based ceramic and method for producing same.
This patent application is currently assigned to ASAHI KOGAKU KOGYO KABUSHIKI KAISHA. Invention is credited to Matsumoto, Toshio.
Application Number | 20020114938 10/005673 |
Document ID | / |
Family ID | 18842958 |
Filed Date | 2002-08-22 |
United States Patent
Application |
20020114938 |
Kind Code |
A1 |
Matsumoto, Toshio |
August 22, 2002 |
Porous sintered body of calcium phosphate-based ceramic and method
for producing same
Abstract
A porous sintered body of a calcium phosphate-based ceramic
having a porosity of 80% or more. The porous sintered body is
produced by a method comprising the steps of: (1) preparing a
slurry comprising a calcium phosphate-based ceramic powder, a
water-soluble high molecular compound and a nonionic surface active
agent; (2) stirring the slurry vigorously to froth the slurry; (3)
solidifying the frothed slurry into a gel; and (4) drying and
sintering the gel.
Inventors: |
Matsumoto, Toshio; (Tokyo,
JP) |
Correspondence
Address: |
GREENBLUM & BERNSTEIN, P.L.C.
1941 ROLAND CLARKE PLACE
RESTON
VA
20191
US
|
Assignee: |
ASAHI KOGAKU KOGYO KABUSHIKI
KAISHA
Tokyo
JP
|
Family ID: |
18842958 |
Appl. No.: |
10/005673 |
Filed: |
December 7, 2001 |
Current U.S.
Class: |
428/307.3 ;
428/315.5; 501/123; 501/80 |
Current CPC
Class: |
C04B 38/10 20130101;
Y10T 428/249953 20150401; Y10T 428/249978 20150401; C04B 38/10
20130101; C04B 35/447 20130101; Y10T 428/249956 20150401; C04B
35/447 20130101; C04B 38/0045 20130101; C04B 38/0074 20130101; C04B
38/0054 20130101 |
Class at
Publication: |
428/307.3 ;
428/315.5; 501/80; 501/123 |
International
Class: |
B32B 003/26; B32B
003/06; B32B 003/00; C04B 038/00; C04B 035/03 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 7, 2000 |
JP |
2000-373600 |
Claims
What is claimed is:
1. A porous sintered body of a calcium phosphate-based ceramic
having a porosity of 80% or more.
2. The porous sintered body according to claim 1, wherein said
porous sintered body has an average pore-diameter of 5 to 1500
.mu.m.
3. The porous sintered body according to claim 1, wherein a weight
ratio of Ca/P in said calcium phosphate-based ceramic is 1.6 to
1.7.
4. The porous sintered body according to claim 1, wherein said
calcium phosphate-based ceramic is hydroxyapatite.
5. A method for producing a porous sintered body of a calcium
phosphate-based ceramic having a porosity of 80% or more, wherein
said method comprises the steps of: (1) preparing a slurry
comprising a calcium phosphate-based ceramic powder, a
water-soluble high molecular compound and a nonionic surface active
agent; (2) stirring said slurry vigorously to froth said slurry;
(3) solidifying the frothed slurry into a gel; and (4) drying and
sintering said gel.
6. The method for producing a porous sintered body according to
claim 5, wherein said calcium phosphate-based ceramic powder is a
secondary particle having an average particle diameter of 0.5 to 80
.mu.m prepared from a primary particle having an average particle
diameter of 100 nm or less.
7. The method for producing a porous sintered body according to
claim 5, wherein said water-soluble high molecular compound is a
cellulose derivative.
8. The method for producing a porous sintered body according to
claim 5, wherein said nonionic surface active agent is a fatty acid
alkanolamide surface active agent.
9. The method for producing a porous sintered body according to
claim 5, wherein 1 to 10 part by weight of said water-soluble high
molecular compound and 1 to 10 part by weight of said nonionic
surface active agent are used with 100 parts by weight of said
calcium phosphate-based ceramic powder.
10. The method for producing a porous sintered body according to
claim 5, wherein a weight ratio of the total of said calcium
phosphate-based ceramic powder, said water-soluble high molecular
compound and said nonionic surface active agent is 20 to 50 weight
% based on 100 weight % of said slurry.
11. The method for producing a porous sintered body according to
claim 5, wherein said slurry is stirred under a stirring condition
of 50 W/L or more to froth said slurry.
12. The method for producing a porous sintered body according to
claim 5, wherein said slurry is stirred at 5 to 20.degree. C. to
froth said slurry.
13. The method for producing a porous sintered body according to
claim 5, wherein said nonionic surface active agent is free of a
metal ion and a sulfate group.
14. The method for producing a porous sintered body according to
claim 5, wherein said slurry is stirred while passing a gas through
said slurry to froth said slurry.
15. The method for producing a porous sintered body according to
claim 5, wherein said calcium phosphate-based ceramic is
hydroxyapatite.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to a porous sintered body of a
calcium phosphate-based ceramic and a method for producing the
porous sintered body. The porous sintered body is useful as a
carrier for cultivation of cells or biological tissues and as a
biocompatible artificial material suitable for filling a defective
part of a bone, etc., and further, the porous sintered body is
excellent in mechanical strength and machinability to be usable as
a filler for a liquid chromatography, a catalyst-carrier, an
electric or electronic material, a nuclear reactor material, a
ceramic heating element, etc.
[0002] Calcium phosphate-based ceramic such as hydroxyapatite has
an excellent biocompatibility to have been used as a carrier for
cultivation of cells or biological tissues, a biomaterial such as
an artificial dental root and a bone-reinforcing material, etc. It
is preferred that the calcium phosphate-based ceramic is compact
from the viewpoint of a mechanical strength. However, it is
preferred that the calcium phosphate-based ceramic is porous, thus,
that a porosity of the calcium phosphate-based ceramic is as high
as possible from the viewpoint of a biocompatibility. Therefore,
various methods have been proposed to produce the porous calcium
phosphate-based ceramic, for example, frother methods, pyrolytic
resin beads methods, spongy resin impregnation methods,
water-soluble high molecular compound gelation methods, etc.
[0003] In the frother methods, to a slurry of hydroxyapatite, etc.
is added a frother such as hydrogen peroxide water to froth the
slurry, thereby increasing the porosity of the calcium
phosphate-based ceramic. However, there is a limit in the porosity,
and it is difficult to control an average pore-diameter and the
porosity regularly in every lot in the frother methods. In the
pyrolytic resin beads methods, pyrolytic resin beads are added to a
slurry of hydroxyapatite, etc., mixed and formed therewith, and the
resultant formed body is heated to burn down the pyrolytic resin
beads, thereby producing the porous calcium phosphate-based
ceramic. However, the pyrolytic resin beads methods are
disadvantageous in that the formed body is often warped or cracked
because the pyrolytic resin beads are not constricted in a drying
process. Further, a large quantity of the pyrolytic resin beads is
used in the methods, whereby long period of time is required in
sintering and a large quantity of carbon dioxide gas is unavoidably
provided. Furthermore, the porosity of the porous calcium
phosphate-based ceramic produced by the pyrolytic resin beads
methods is approximately equal to but no more than 50%. The spongy
resin impregnation methods have been widely used to produce the
porous calcium phosphate-based ceramic, the porosity of the porous
calcium phosphate-based ceramic produced thereby depends on a
porosity of the spongy resin to be approximately 75% at most.
Therefore, the porous calcium phosphate-based ceramic having
desired minute pores cannot be produced by the spongy resin
impregnation methods.
[0004] In the water-soluble high molecular compound gelation
methods, a slurry comprising a ceramic and a water-soluble high
molecular compound is stirred to froth the slurry, the frothed
slurry is heated for gelation, and the resultant gel containing air
babbles is dried to provide a porous ceramic as disclosed in
Japanese Patent No. 3058174. The porous ceramic produced by a
method described in Japanese Patent No. 3058174 has spherical
macro-pores resulting from the air babbles having a pore diameter
of 20 to 2000 .mu.m and three dimensional passing-through pores
formed by gaps between spherical secondary particles composed of an
aggregate of primary particles of the ceramic raw material.
However, under a circumstances where the porous calcium
phosphate-based ceramic have been required to be further improved
in the biocompatibility, there has been increasing need for the
porous calcium phosphate-based ceramic having a further high
porosity.
OBJECT AND SUMMARY OF THE INVENTION
[0005] Accordingly, an object of the present invention is to
provide a porous sintered body of a calcium phosphate-based ceramic
that has a porosity higher than that of conventional calcium
phosphate-based ceramic, and a method for producing the porous
sintered body.
[0006] As a result of intense research in view of the above object,
the inventor has found that a porous sintered body of a calcium
phosphate-based ceramic superior in high porosity to conventional
calcium phosphate-based ceramic can be obtained by adding a
nonionic surface active agent to a slurry comprising a calcium
phosphate-based ceramic powder and a water-soluble high molecular
compound and by stirring the slurry vigorously. The present
invention has been accomplished by the finding.
[0007] Thus, a porous sintered body of a calcium phosphate-based
ceramic according to the present invention has a porosity of 80% or
more.
[0008] The porous sintered body of the calcium phosphate-based
ceramic according to the present invention preferably has an
average pore-diameter of 5 to 1500 .mu.m. A weight ratio of Ca/P in
the calcium phosphate-based ceramic is preferably 1.6 to 1.7. A
preferred embodiment of the porous sintered body is a porous
sintered hydroxyapatite.
[0009] A method of the present invention for producing a porous
sintered body of a calcium phosphate-based ceramic having a
porosity of 80% or more comprises the steps of: (1) preparing a
slurry comprising a calcium phosphate-based ceramic powder, a
water-soluble high molecular compound and a nonionic surface active
agent; (2) stirring the slurry vigorously to froth the slurry; (3)
solidifying the frothed slurry into a gel; and (4) drying and
sintering the gel.
[0010] The calcium phosphate-based ceramic powder is preferably a
secondary particle having an average particle diameter of 0.5 to 80
.mu.m derived from a primary particle having an average particle
diameter of 100 nm or less. The water-soluble high molecular
compound is preferably a cellulose derivative such as
methylcellulose, carboxymethylcellulose, etc. Further, the nonionic
surface active agent is preferably a fatty acid alkanolamide
surface active agent.
[0011] It is preferred that the slurry has a composition where 1 to
10 part by weight of the water-soluble high molecular compound and
1 to 10 part by weight of the nonionic surface active agent are
used with 100 parts by weight of the calcium phosphate-based
ceramic powder. A weight ratio of the total of the calcium
phosphate-based ceramic powder, the water-soluble high molecular
compound and the nonionic surface active agent is preferably 20 to
50 weight % based on 100 weight % of the slurry.
[0012] The slurry is preferably stirred under a stirring condition
of 50 W/L or more to froth the slurry. Further, it is preferable
that the slurry is stirred while passing a gas through the slurry
to froth the slurry, examples of the gas including air, nitrogen
gas, inert gases such as argon gas, etc. The slurry is preferably
stirred at 5 to 20.degree. C. to froth the slurry. Furthermore, it
is preferred that the nonionic surface active agent is free of a
metal ion and a sulfate group.
[0013] The method of the present invention is particularly
preferably used for producing the porous sintered
hydroxyapatite.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is a scanning microscope photograph with a
magnification of .times.60 of a porous sintered hydroxyapatite body
produced in Example 1.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] [1] Porous Sintered Body of Calcium Phosphate-Based
Ceramic
[0016] (1) Composition
[0017] In a porous sintered body of a calcium phosphate-based
ceramic according to the present invention, a weight ratio of Ca/P
is preferably 1.6 to 1.7. When the weight ratio of Ca/P is less
than 1.6, the calcium phosphate-based ceramic has a multi-phase
structure containing tricalcium phosphate Ca.sub.3(PO.sub.4).sub.2.
On the other hand, the weight ratio of more than 1.7 results in a
multi-phase structure containing calcium oxide CaO. An preferred
example of the porous sintered body of the present invention is a
porous sintered hydroxyapatite
Ca.sub.10(PO.sub.4).sub.6.(OH).sub.2.
[0018] (2) Porosity
[0019] The porous sintered body of the calcium phosphate-based
ceramic according to the present invention has a porosity of 80% or
more. The porous sintered body having such a high porosity is
achieved by the following method of the present invention for the
first time. The porous sintered body has a high porosity to exhibit
a remarkably high biocompatibility. The porosity is preferably less
than approximately 95% from the viewpoint of practical use. If the
porosity exceeds 95%, the porous sintered body is insufficient in a
mechanical strength to be poor in workability and handling
ability.
[0020] An average pore-diameter of the porous sintered body of the
calcium phosphate-based ceramic is preferably 5 to 1500 .mu.m. When
the average pore-diameter is less than 5 .mu.m, cells or blood
vessels can hardly impregnate into the porous sintered body. On the
other hand, when the average pore-diameter is more than 1500 .mu.m,
it is difficult to control the mechanical strength of the porous
sintered body regularly so that the workability and the handling
ability vary excessively in every lot. Pores in the porous sintered
body preferably have a uniform pore-diameter, thus, it is
particularly preferable that 80% or more of the pores have a
diameter of 50 to 500 .mu.m.
[0021] [2] Production Method
[0022] Explanations will be made for a method of the present
invention in detail below taking production of a porous sintered
hydroxyapatite body for instance, however, the scope of the present
invention is not restricted thereby and the method can be similarly
applied to other sintered bodies of calcium phosphate-based
ceramic.
[0023] (1) Preparation of Slurry
[0024] A slurry comprising a hydroxyapatite powder, a water-soluble
high molecular compound and a nonionic surface active agent is
prepared.
[0025] (a) Hydroxyapatite Powder
[0026] The hydroxyapatite powder is preferably a secondary particle
having an average particle diameter of 0.5 to 80 .mu.m derived from
a primary particle having an average particle diameter of 100 nm or
less. The hydroxyapatite powder is preferably spherical from the
viewpoint of improving stir of the slurry and formability of a
porous hydroxyapatite green block.
[0027] It is preferred that the hydroxyapatite powder is subjected
to a burning treatment to obtain powder strength sufficient for
vigorous stirring. The burning treatment may be achieved by heating
the hydroxyapatite powder at 700 to 850.degree. C. for 4 to 10
hours. The burning temperature of less than 700.degree. C. results
in insufficient increase of the strength of the hydroxyapatite
powder. When the burning temperature is higher than 850.degree. C.,
the hydroxyapatite powder is sintered, whereby grain growth takes
place and powdering is needed after the burning treatment.
[0028] (b) Water-Soluble High Molecular Compound
[0029] The water-soluble high molecular compound used in this
invention acts to change an aqueous liquid containing this compound
into a gel state. The aqueous liquid is solidified into a gel by
heating, etc. The water-soluble high molecular compound may be such
that cannot be completely dissolved in water, and the aqueous
liquid may be a solution, a dispersion, a colloidal solution, an
emulsion or a suspension. Examples of the water-soluble high
molecular compound include: cellulose derivatives such as
methylcellulose and carboxymethylcellulose; polysaccharides such as
curdlan; synthetic polymers such as polyvinylalcohol, poly(acrylic
acid), polyacrylamide and polyvinylpyrrolidone; etc. Among them,
preferred are cellulose derivatives, and particularly preferred is
methylcellulose. An aqueous liquid of polyvinylalcohol may be
changed into a gel by adding boric acid or borax.
[0030] (c) Nonionic Surface Active Agent
[0031] The nonionic surface active agent forms a lot of minute air
babbles when the slurry is vigorously stirred, and acts to prevent
the air babbles from breaking in the heating step for the gelation.
In the case where the porous sintered hydroxyapatite body according
to the present invention is semipermanently used in vivo as a
biomaterial, it is preferable that the nonionic surface active
agent is completely burnt down by sintering, thus, it is preferable
that the nonionic surface active agent do not contain a metal ion
such as sodium ion or a sulfate group, which are still existent
after sintering.
[0032] Examples of the nonionic surface active agent used in the
present invention include fatty acid alkanolamides,
poly(oxyethylene alkyl ether carboxylates), poly(oxyethylene alkyl
ethers) such as poly(oxyethylene octyl phenyl ether), etc. Among
them, preferred are the fatty acid alkanolamide surface active
agents such as N,N-dimethyldodecylamine oxide from the viewpoint of
frothing properties in the presence of hydroxyapatite.
[0033] (d) Weight Ratio of Contents
[0034] The slurry preferably contains 1 to 10 part by weight of the
water-soluble high molecular compound, 1 to 10 part by weight of
the nonionic surface active agent and 100 parts by weight of the
hydroxyapatite powder. When the weight ratio of the hydroxyapatite
powder is too small in the slurry, relatively long period of time
is needed in drying the gel. On the other hand, too large amount of
the hydroxyapatite powder results in high viscosity slurry so that
it becomes difficult to froth the slurry. Further, gelation of the
slurry is difficult when the weight ratio of the water-soluble high
molecular compound is less than 1 part by weight to 100 parts by
weight of the hydroxyapatite powder, and more than 10 parts by
weight of the water-soluble high molecular compound results in high
viscosity slurry so that it becomes difficult to froth the slurry.
More preferred weight ratio of the water-soluble high molecular
compound is 1 to 5 part by weight based on 100 parts by weight of
the hydroxyapatite powder. Furthermore, it is difficult to froth
the slurry when the weight ratio of the nonionic surface active
agent is less than 1 part by weight to 100 parts by weight of the
hydroxyapatite powder, and further improved effects of the nonionic
surface active agent is not obtained if it is used in an excess
amount of more than 10 parts by weight. More preferred weight ratio
of the nonionic surface active agent is 1 to 5 part by weight based
on 100 parts by weight of the hydroxyapatite powder.
[0035] A weight ratio of the total of the hydroxyapatite powder,
the water-soluble high molecular compound and the nonionic surface
active agent is preferably 20 to 50 weight % in 100 weight % of the
slurry. When the weight ratio is less then 20 weight %, too long
period of time is required in drying after gelation and the gel is
often crushed after drying, failing to maintain the porous
structure. On the other hand, when the weight ratio is more then 50
weight %, the viscosity of the slurry is too high, whereby it
becomes difficult to froth the slurry by stirring. The weight ratio
is more preferably 25 to 40 weight %.
[0036] (2) Frothing
[0037] The slurry froths while catching air when the
above-mentioned slurry is stirred vigorously. The slurry is
preferably stirred under a stirring condition of 50 W/L or more to
froth. If the stirring condition is less then 50 W/L, the slurry is
not sufficiently frothed so that the porous hydroxyapatite having a
desired porosity cannot be produced. Incidentally, the stirring
condition means "[maximum output of stirring apparatus (W)/amount
of slurry (L)].times.(actual rotational frequency/maximum
rotational frequency)". When the viscosity of the slurry is
increased, the output of the stirring apparatus is generally
increased to maintain a predetermined rotational frequency. In the
present invention, the slurry is frothed such that the porosity of
the sintered hydroxyapatite body is remarkably increased and the
viscosity of the slurry is not substantially changed since the
preparation thereof, whereby the effect of the viscosity may be
substantially disregarded.
[0038] As the stirring apparatus providing the above stirring
condition, an impeller-type homogenizer may be used. Although the
impeller-type homogenizer is generally designed not to froth the
slurry, etc., the slurry can be remarkably frothed if the stirring
condition is 50 W/L or more. Further, a stirring apparatus
preferably used in the present invention is such that has a
structure where a stirring blade is in shape of a disk, saw
blade-like convexoconcave is provided at a circumference part of
the stirring blade, and a baffle plate is disposed on the inner
wall of a stirring chamber. Examples of the impeller-type
homogenizer having such a structure include PH91, PA92, HF93,
FH94P, PD96 and HM10 manufactured by SMT Co., Ltd., etc. Further,
it is preferable that the slurry is stirred while passing a gas
therethrough to promote frothing, examples of the gas including
air, nitrogen gas, inert gases such as argon gas, etc.
[0039] Stirring period, which is depends on the stirring condition,
may be approximately 1 to 30 minute. It is preferable that stirring
temperature (temperature of the slurry) is relatively low to make
the air babbles minute, uniform and stable, and specifically, the
stirring temperature is preferably approximately 0 to 25.degree.
C., particularly preferably 5 to 20.degree. C.
[0040] The frothed slurry is preferably cast by a mold having a
flexible water-resisting film at the inner wall thereof. In this
case, the flexible water-resisting film is peeled off from the mold
with shrinkage of the ceramic while drying, whereby the ceramic is
prevented from deformation of a surface in contact with the mold or
cracking of an inner portion to provide the dried body with
excellent quality.
[0041] (3) Gelation
[0042] When the slurry that is sufficiently frothed by stirring is
heated, the water-soluble high molecular compound such as
methylcellulose acts to change the slurry into a gel. The heating
temperature is generally in the range of 80.degree. C. to less than
100.degree. C. Less than 80.degree. C. of the heating temperature
results in insufficient gelation, and water in the slurry boils to
destruct the gel structure when the heating temperature is
100.degree. C. or more.
[0043] (4) Drying
[0044] The gel is preferably dried at a high temperature such that
water in the gel do not boils, for example, the temperature may be
in the range of 80.degree. C. to less than 100.degree. C. The gel
is isotropicaly shrunk by drying, the air babbles being not
changed, whereby the dried body (green block) that is high in
strength and has minute, uniform, spherical macro-pores is provided
without cracking.
[0045] (5) Cutting
[0046] Because the water-soluble high molecular compound in the
green block acts as a binder, the green block has a mechanical
strength sufficient for handling. Thus, the dried green block can
be cut or worked into a desired shape without provisional burning
treatment.
[0047] (6) Degreasing
[0048] The green block cut into a predetermined shape may be
subjected to a degreasing treatment to remove the water-soluble
high molecular compound and the nonionic surface active agent
therefrom if necessary. The green block may be degreased by heating
at 300 to 900.degree. C.
[0049] (7) Sintering
[0050] The green block is generally sintered at 1000 to
1250.degree. C. for 2 to 10 hours. When the sintering temperature
is less than 1000.degree. C., the resultant porous sintered
hydroxyapatite body is insufficient in strength. On the other hand,
when the sintering temperature is more than 1250.degree. C.,
hydroxyapatite is decomposed into tricalcium phosphate and calcium
oxide. Sintering period may be appropriately selected in accordance
with the sintering temperature. In the case where the degreasing
treatment is not carried out, the green block may be gradually
heated to the sintering temperature so that the green block is
subjected to both of degreasing and sintering. For example, it is
preferable that the green block is gradually heated from room
temperature to approximately 600.degree. C. at a heating rate of
approximately 10 to 100.degree. C./hour, it is then heated to the
sintering temperature at a heating rate of approximately 50 to
200.degree. C./hour, and the sintering temperature is maintained.
The green block may be subjected to annealing or slow cooling after
sintering.
EXAMPLES
[0051] The present invention will be explained in further detail by
the following examples without intention of restricting the scope
of the present invention defined by the claims attached hereto.
Example 1
[0052] 120 parts by weight of spherical hydroxyapatite powder
having an average diameter of 10 .mu.m, which is composed of long
thin primary particles having an average particle diameter of 78 nm
in the major axis and 23 nm in the minor axis; 320 parts by weight
of an aqueous solution containing 1 weight % of methylcellulose
manufactured by Wako Pure Chemical Industries, Ltd., an aqueous
solution containing 2 weight % of the methylcellulose exhibiting a
viscosity of 4000 cps at 20.degree. C.; and 10 parts by weight
(solid content) of N,N-dimethyldodecylamine oxide "AROMOX"
manufactured by LION CORPORATION used as a fatty acid alkanolamide
surface active agent were mixed to prepare a slurry. The slurry was
put into a homogenizer "PA92" manufactured by SMT Co., Ltd. Then,
the slurry was vigorously stirred for 5 minutes under a stirring
condition of 60 W/L (actual output in the stirring process) while
maintaining the temperature of the slurry at 8.degree. C. to froth
the slurry.
[0053] The resultant slurry that contained air babbles was put into
a mold and heated at 83.degree. C. for 2 hours to provide a gel.
The gel was then completely dried at 83.degree. C. to produce a
green block.
[0054] The green block was cut into a shape of 30 mm.times.15
mm.times.10 mm, heated from room temperature to 600.degree. C. at a
heating rate of 50.degree. C./hour in the air, heated to
1200.degree. C. at a heating rate of 100.degree. C./hour, sintered
at 1200.degree. C. for 4 hours, cooled down to 600.degree. C. at a
cooling rate of 50.degree. C./hour, maintained at 600.degree. C.
for 4 hours, and cooled down to room temperature at a cooling rate
of 100.degree. C./hour, to produce a porous sintered hydroxyapatite
body according to Example 1.
[0055] Porosity of the resulting porous sintered hydroxyapatite
body was measured. The result was shown in Table 1 with a
composition of raw materials in the slurry. Further, a scanning
microscope photograph with a magnification of .times.60 of the
porous sintered hydroxyapatite body was shown in FIG. 1. As shown
in FIG. 1, pores in the porous sintered hydroxyapatite body of
Example 1 were uniform in size, most of them having a pore diameter
of 50 to 500 .mu.m.
Example 2
[0056] A porous sintered hydroxyapatite body according to Example 2
was produced in the same manner as Example 1 except that the slurry
was vigorously stirred while passing nitrogen gas therethrough from
a pipe disposed on bottom of the homogenizer to froth the slurry.
Porosity of the resulting porous sintered hydroxyapatite body was
measured. The result was shown in Table 1 with a composition of raw
materials in the slurry.
Comparative Example 1
[0057] A porous sintered hydroxyapatite body according to
Comparative Example 1 was produced in the same manner as Example 1
except that 140 parts by weight of the hydroxyapatite powder used
in Example 1 was added to 240 parts by weight of an aqueous
solution containing 1 weight % of methylcellulose having a
temperature of 20.degree. C. to prepare a slurry and that this
slurry was stirred for 15 minutes under a stirring condition of 5.5
W/L (actual output in the stirring process) by "KENMIX mixer"
manufactured by Aicohsha Manufacturing Co., Ltd. to froth the
slurry before gelation. Porosity of the resulting porous sintered
hydroxyapatite body was measured. The result was shown in Table 1
with a composition of raw materials in the slurry.
1 TABLE 1 Composition (Part by Weight) Surface Active
Hydroxyapatite Methylcellulose Agent Porosity Ex. No. Powder
Aqueous Solution (AROMOX) (%) Ex. 1 120 320 10 85.6 Ex. 2 120 320
10 93.2 Comp. Ex. 1 140 240 -- 70.3
[0058] As shown in Table 1, the porous sintered hydroxyapatite
bodies of Examples 1 and 2 were produced by the method according to
the present invention comprising the steps of adding the nonionic
surface active agent to the slurry and frothing the slurry under
the vigorous stirring condition to exhibit porosity remarkably
higher than that of the porous sintered hydroxyapatite body of
Comparative Example 1 produced under the stirring condition of 5.5
W/L without the nonionic surface active agent. The porous sintered
hydroxyapatite body of Example 2, which was produced by a method
using nitrogen gas in the frothing process, was further excellent
in porosity as compared with Example 1.
Examples 3 and 4
[0059] Porous sintered hydroxyapatite bodies according to Examples
3 and 4 were produced in the same manner as Example 1 except that a
homogenizer "HM10" manufactured by SMT Co., Ltd. was used instead
of the homogenizer "PA92" and that a slurry having a composition
shown in Table 2 was stirred under conditions shown in Table 2 to
froth the slurry, respectively. Incidentally, "Actual Output of
Stirring Apparatus" in Table 2 corresponded to the stirring
condition. Further, porosity of each porous sintered hydroxyapatite
bodies was measured. The results were shown in Table 2.
Comparative Example 2
[0060] A porous sintered hydroxyapatite body according to
Comparative Example 2 was produced in the same manner as Example 1
except that the nonionic surface active agent was not used, that
the "KENMIX mixer" was used instead of the homogenizer "PA92" and
that a slurry having a composition shown in Table 2 was stirred
under conditions shown in Table 2 to froth the slurry. Further,
porosity of the resulting porous sintered hydroxyapatite body was
measured. The result was shown in Table 2.
2 TABLE 2 Ex. 3 Ex. 4 Comp. Ex. 2 Methylcellulose 4000 g 2000 g
1975 g 1% Aqueous Solution Hydroxyapatite 1600 g 800 g 850 g Powder
Surface Active AROMOX 40 g AROMOX 20 g -- Agent Stirring Apparatus
HM10 HM10 KENMIX Rotational 3000 rpm 4000 rpm 150 rpm Frequency
Stirring Period 10 minutes 10 minutes 10 minutes Maximum Output of
750 W 750 W 650 W Stirring Apparatus 188 W/L 375 W/L 329 W/L Actual
Output of 62.5 W/L 166.7 W/L 5.5 W/L Stirring Apparatus Porosity
80.3% 86.2% 40.0%
[0061] As shown in table 2, the porous sintered hydroxyapatite
bodies of Examples 3 and 4 according to the present invention
exhibited porosity of 80% or more in contrast with the porous
sintered hydroxyapatite body of Comparative Example 2 exhibiting a
low porosity of 40%.
Example 5
[0062] Porous sintered hydroxyapatite bodies were produced in the
same manner as Example 1 except for changing the above slurry used
in Example 1 to such that was prepared by mixing 120 parts by
weight of spherical hydroxyapatite powder used in Example 1; 240
parts by weight of an aqueous solution containing 1 weight % of
methylcellulose used in Example 1; and 2.4 parts by weight (solid
content) of a surface active agent shown in Table 3, respectively.
Porosity of each porous sintered hydroxyapatite bodies was
measured. The results were shown in Table 4.
3TABLE 3 Surface Active Agent Trade Frothing Compound Name Ionicity
Properties Residue Manufacturer N,N-Dimethyldodecyl AROMOX Nonionic
Very (a) Lion Corporation amine oxide Good Poly(oxyethylene Triton
Nonionic Good (a) Wako Pure Chemical octyl phenyl ether) X100
Industries, Ltd. Lauric sulfuric acid TEALS Nonionic Very (b) Nikko
Chemicals triethanolamine Good Co., Ltd. Poly(oxyethylene POELA
Nonionic Good (a) Nikko Chemicals laurylamine) Co., Ltd.
Poly(oxyethylene EMULGEN Anionic Good (a) Kao Corporation
alkylcarboxylic acid) LS110 Poly(oxyethylene EMULGEN Anionic Good
(a) Kao Corporation alkylcarboxylic acid) 420 (a): Both of a metal
ion and a sulfate group were not exist and only pyrolyzed residue
of C, H, O, N, etc. was still existent in the porous sintered
hydroxyapatite body after sintering. (b): A metal ion and/or a
sulfate group was still existent in the porous sintered
hydroxyapatite body after sintering.
[0063]
4 TABLE 4 Surface Active Agent Trade Name Ionicity Porosity AROMOX
Nonionic 91.0 Triton X100 Nonionic 88.2 TEALS Nonionic 85.6 POELA
Nonionic 80.7 EMULGEN LS110 Anionic 73.9 EMULGEN 420 Anionic
63.0
[0064] As shown in Table 4, the porous sintered hydroxyapatite
bodies of the present invention produced from the slurry comprising
the nonionic surface active agent had a high porosity of 80% or
more, though the comparative porous sintered hydroxyapatite bodies
produced from the slurry comprising the anionic surface active
agent exhibited a low porosity. Further, in the case of using
lauric sulfuric acid triethanolamine "TEALS" as the nonionic
surface active agent, sulfate group was still existent in the
porous sintered hydroxyapatite body after sintering though the
frothing properties was remarkably excellent.
[0065] As described in detail above, a porous sintered body of a
calcium phosphate-based ceramic according to the present invention
has a porosity higher than that of conventional calcium
phosphate-based ceramic to be excellent in biocompatibility,
thereby being useful as a biomaterial. Further, the porous sintered
body is excellent in a mechanical strength and a machinability to
be usable as a filler for a liquid chromatography, a
catalyst-carrier, an electric or electronic material, a nuclear
reactor material, a ceramic heating element, etc.
[0066] In a method for producing such a porous sintered body
according to the present invention, a nonionic surface active agent
is added to a high viscosity slurry comprising a ceramic powder and
a water-soluble high molecular compound and the slurry is stirred
remarkably vigorously, whereby the porous sintered body having a
high porosity can be effectively produced with minute, uniform
pores. Furthermore, in the method of the present invention, the
intermediate gel is isotropicaly shrunk by drying so that the dried
body is provided without cracking to provide the porous sintered
body of the calcium phosphate-based ceramic with ease. The present
disclosure relates to subject matter contained in Japanese Patent
Application No. 2000-373600 (filed on Dec. 7, 2000) which is
expressly incorporated herein by reference in its entirety.
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