Process for producing inorganic biomaterial

The present invention relates to a process for producing an inorganic biomaterial, according to which, there can be obtained an inorganic biomaterial excellent in strength and biocompatibility, having a structure in which portions constituted by crystallized glass or crystals of calcium phosphate excellent in bioactivity are dispersed in a skeleton or matrix constituted by crystals of partially stabilized zirconia and/or alumina showing high strength. Accordingly, the inorganic biomaterial is very useful as biomaterial for artificial bones, dental implants, etc.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to a process for producing an inorganic 
biomaterial which is useful as an implant material for artificial bones, 
dental implants, etc. 
2. Description of Prior Art 
Ceramics have been attracted public attention because ceramics are 
considered to be biomaterials harmless to a living body compared with 
polymers and metallic materials. In recent years, ceramics as biomaterials 
make remarkable progress. Of ceramics, bioactive ceramics capable of 
forming a chemical bonding with bones are known. Such bioactive ceramics 
are united with a living body so that there arises no loosening problem. 
As the bioactive ceramics, there is known crystallized glass obtained by 
precipitating an apatite crystal [Ca.sub.10 (PO.sub.4).sub.6 (O.sub.0.5, 
F).sub.2 ] and a wollastonite crystal [CaSiO.sub.3 ]. However, the bending 
strength of the crystallized glass shows a value within a range of about 
120 to about 230 MPa. To improve the bending strength of the crystallized 
glass, bioactive materials such as composite crystals of bioactive 
crystallized glass and zirconia ceramics and composite crystals of 
bioactive crystallized glass and alumina ceramics have been developed 
(Japanese Patent Unexamined Publication Nos. Sho-62-231668 and 
Sho-63-82670). Those composite materials show relatively high bending 
strength in a range of from 230 to 350 MPa. However, those values are not 
yet fully satisfactory from the standpoint that the above materials are 
used in applications such as artificial bones and dental implants. 
Accordingly, the above materials are subjected to considerable restriction 
in the purpose of use thereof. 
As means for obtaining a material of higher strength, for example, Japanese 
Patent Unexamined Publication Nos. Hei-1-115360 and Hei-1-115361 disclose 
a process for producing an inorganic material comprising the steps of 
mixing glass powder having a particle size smaller than 75 .mu.m, with 
zirconia or alumina ceramic powder having a particle size smaller than 
that of the glass powder, molding the resulting mixture into a desired 
shape, sintering the glass portion of the resulting compact to crystallize 
it, and sintering the zirconia or alumina ceramic powder portion. 
The processes disclosed in the Japanese Patent Unexamined Publication Nos. 
Hei-1-115360 and Hei-1-115361 are useful in the case where the content of 
zirconia or alumina ceramic powder is large. However, the processes have 
the following disadvantages in the case where the content of zirconia or 
alumina ceramic powder is small. That is, when the glass powder is heated 
to a temperature enough to sinter the glass powder, (1) the zirconia or 
alumina ceramic powder may be enveloped in the glass being fluidized, 
and/or (2) in the positions where the glass is not fluidized well, pores 
may be formed easily in the vicinity of the interface between the glass 
and the zirconia or alumina ceramic powder. When the glass is further 
heated to a temperature enough to crystallize the glass, the fluidization 
of the glass stops to start crystallization while the states of (1) and 
(2) are kept as they are with no change. Accordingly, when the zirconia or 
alumina ceramic powder is heated to a temperature enough to sinter the 
ceramic powder, the zirconia or alumina ceramic powder cannot be sintered 
in the positions where the state of (1) exists so that a skeleton of 
zirconia or alumina ceramics having high strength cannot be formed. 
Consequently, the resulting composite material cannot show high strength. 
On the other hand, pores remain in the composite material in the positions 
where the state of (2) exists, so that the resulting composite material 
cannot show sufficiently large strength. 
Accordingly, in the processes disclosed in the Japanese Patent Unexamined 
Publication Nos. Hei-1-115360 and Hei-1-115361, the content of 
crystallized glass contributing to bioactivity must be set to be smaller 
than the content of zirconia or alumina ceramics as a reinforcement 
material. In short, bioactivity must be sacrificed. Hence, the processes 
have a disadvantage in that a considerable time is required for forming a 
chemical bonding with bones. 
As another means for improving the strength of ceramic materials, Japanese 
Patent Unexamined Publication No. Sho-64-18973 discloses a process in 
which a ceramic composite material of high strength is prepared by adding 
partially stabilized zirconia powder with a particle size of 1 .mu.m or 
less and metal fluoride powder to calcium phosphate powder, such as 
apatite powder, .beta.-tricalcium phosphate powder and the like, with a 
particle size of 1 .mu.m or less. 
FIG. 5 typically shows the result of observation, through an electron 
microscope, of the ceramic composite material disclosed in the Japanese 
Patent Unexamined Publication No. Sho-64-18973. In the drawing, metal 
fluoride is not shown because the content of metal fluoride is very small. 
As is clear from FIG. 5, the ceramic composite material has a structure in 
which fine crystals of calcium phosphate 13 with a particle size of 1 
.mu.m or less and fine crystals of partially stabilized zirconia 14 with a 
particle size of 1 .mu.m or less were mixed together at random. In 
general, zirconia and calcium phosphate are apt to react with each other. 
When the two components are mixed together at random as described above, 
the surface area where the two components are in contact with each other 
becomes so large that the two components react with each other easily. 
When calcium phosphate and partially stabilized zirconia react with each 
other as described above, calcium phosphate and partially stabilized 
zirconia form solid solutions. As this result, the amount of calcium 
phosphate is reduced so that excellent biocompatibility cannot be 
obtained. Further, partially stabilized zirconia is fully stabilized by 
reaction with calcium phosphate so that the strength and toughness of the 
ceramic composite material obtained are often unsatisfactory. 
SUMMARY OF THE INVENTION 
In order to eliminate the defect in the prior art process disclosed in the 
Japanese Patent Unexamined Publication Nos. Hei-1-115360 and Hei-1-115361, 
a first object of the present invention is to provide a process for 
producing an inorganic biomaterial which is excellent in strength and 
biocompatibility and which is composed of crystallized glass and zirconia 
and/or alumina ceramics. 
In order to eliminate the defect in the prior art process disclosed in the 
Japanese Patent Unexamined Publication No. Sho-64-18973, a second object 
of the invention is to provide a process for producing an inorganic 
biomaterial which is excellent in strength and biocompatibility and which 
is composed of calcium phosphate and zirconia and/or alumina ceramics. 
The first object of the invention has been achieved by a process for 
producing an inorganic biomaterial, which comprises: 
a first step of melting a mixture of glass raw materials and cooling it to 
thereby prepare glass containing the following components of the following 
proportions 
______________________________________ 
CaO 12 to 56% by weight 
P.sub.2 O.sub.5 1 to 27% by weight 
SiO.sub.2 22 to 50% by weight 
MgO 0 to 34% by weight 
Al.sub.2 O.sub.3 0 to 25% by weight 
______________________________________ 
in a total amount of at least 90%; 
a second step of preparing crystallized glass by heat-treating the glass 
obtained in the first step in a temperature range in which there are 
precipitated a crystal of apatite and at least one crystal of alkaline 
earth metal silicate selected from the group consisting of wollastonite, 
diopside, forsterite, akermanite and anorthite; 
a third step of preparing mixture powder by mixing the crystallized glass 
obtained by the second step with partially stabilized zirconia powder 
and/or alumina powder while grinding the crystallized glass or after 
grinding the crystallized glass; and 
a fourth step of preparing an inorganic biomaterial of a 
ceramics/crystallized glass composite by molding the mixture powder 
obtained by the third step into a desired shape and then heat-treating the 
resulting molding in a temperature range in which the partially stabilized 
zirconia and/or alumina powder is sintered. 
Hereinafter, the aforementioned process for producing an inorganic 
biomaterial is called the process according a first aspect of the present 
invention. 
The second object of the present invention has been achieved by a process 
for producing an inorganic biomaterial, which comprises: 
a first step of sintering a crystal of calcium phosphate at a temperature 
in a range of from 800.degree. to 1400.degree. C. to thereby prepare a 
calcium phosphate crystal sintered body; 
a second step of grinding the sintered body obtained in the first step to 
thereby prepare powder of the sintered body, and, at the same time of or 
after preparation of the powder of the sintered body, mixing the prepared 
powder of the sintered body with partially stabilized zirconia powder 
and/or alumina powder to thereby prepare mixture powder; and 
a third step of molding the mixture powder obtained in the second step into 
a desired shape and heat-treating the resulting molding in a temperature 
range in which the partially stabilized zirconia and/or alumina powder is 
sintered. 
Hereinafter, the process for producing an inorganic biomaterial described 
directly above is call the process according a second aspect of the 
present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The process for producing an inorganic biomaterial according to the first 
aspect of the invention will be explained successively the step by the 
step. 
The first step is of melting a mixture of glass raw materials and cooling 
it to thereby prepare glass containing the following components of the 
following proportions 
______________________________________ 
CaO 12 to 56% by weight 
P.sub.2 O.sub.5 1 to 27% by weight 
SiO.sub.2 22 to 50% by weight 
MgO 0 to 34% by weight 
Al.sub.2 O.sub.3 0 to 25% by weight 
______________________________________ 
in a total amount of at least 90%. 
The proportions of the components in the glass obtained in the first step 
are restricted quantatively as described above. The reason is as follows. 
When CaO content is less than 12%, not only the amount of the precipitated 
crystals of apatite [Ca.sub.10 (PO.sub.4).sub.6 (O.sub.0.5,F).sub.2 ] 
becomes very small but the resulting glass has a high tendency of 
devitrification. When the CaO content is more than 56%, the resulting 
glass has a high tendency of devitrification. Accordingly, the CaO content 
is restricted to fall within a range of from 12 to 56%. When the P.sub.2 
O.sub.5 content is less than 1%, the resulting glass has a high tendency 
of devitrification. When the content is more than 27%, the total amount of 
the precipitated crystals of alkaline earth metal silicates such as 
wollastonite [CaOSiO.sub.2 ], diopside [CaO MgO 2SiO.sub.2 ], forsterite 
[2MgO SiO.sub.2 ], akermanite [2CaO MgO 2SiO.sub.2 ], anorthite [CaO 
Al.sub.2 O.sub.3 2SiO.sub.2 ] and the like becomes small. Therefore, the 
P.sub.2 O.sub.5 content is restricted to 1-27 %. When the SiO.sub.2 
content is less than 22%, the total amount of the precipitated crystals of 
alkaline earth metal silicates becomes small. When the content is more 
than 50%, the resulting glass tends to be devitrified. Hence, the 
SiO.sub.2 content is restricted to 22-50%. Though MgO is not an essential 
component, it is used for precipitating crystals of diopside, forsterite 
and akermanite. When the MgO content is more than 34%, not only the amount 
of precipitated crystals of apatite becomes small but the glass tends to 
be devitrified. Therefore, the MgO content is restricted to 34% or less. 
Al.sub.2 O.sub.3 is not an essential component, either. It is used for 
precipitating crystals of anorthite. When the Al.sub.2 O.sub.3 content is 
more than 25%, not only the amount of precipitated crystals of apatite 
becomes small but the glass tends to be devitrified. Therefore, the 
Al.sub.2 O.sub.3 content is restricted to 25% or less. 
In the invention, the glass can contain, in addition to the above five 
components, at least one component selected from K.sub.2 O, Li.sub.2 O, 
Na.sub.2 O, TiO.sub.2, ZrO.sub.2, SrO, Nb.sub.2 O.sub.5, Ta.sub.2 O.sub.5, 
B.sub.2 O.sub.3, Y.sub.2 O.sub.3 and fluorine (F.sub.2) (all of which give 
no harm to human bodies) in a total amount of 10% or less. When the total 
amount of these optional components is more than 10%, the amounts of 
precipitated crystals of apatite and alkaline earth metal silicates 
(wollastonite, diopside, forsterite, akermanite, anorthite) decrease in 
some cases. Therefore, the total amount of these optional components is 
restricted to 10% or less. When the fluorine content (calculated as 
F.sub.2) is more than 5%, the resulting glass is easily devitrified. When 
the Y.sub.2 O.sub.3 content is more than 5%, the amounts of precipitated 
crystals of apatite and alkaline earth metal silicates decrease. 
Accordingly, the fluorine content and the Y.sub.2 O.sub.3 content are each 
restricted to 5% or less. 
In the first step, the glass having the aforementioned composition is 
prepared by melting a batch of glass raw materials by heating metal oxides 
per se and corresponding carbonates, phosphates, hydrates, fluorides, etc. 
to 1300.degree. C. or more and then cooling the batch rapidly. 
The second step is of preparing crystallized glass by heat-treating the 
glass obtained in the first step in a temperature range in which there are 
precipitated a crystal of apatite and at least one crystal of alkaline 
earth metal silicate selected from the group consisting of wollastonite, 
diopside, forsterite, akermanite and anorthite. When the glass obtained in 
the first step is heated from room temperature to a temperature higher 
than a glass transition point, the glass is easily fluidized to start 
sintering of the glass. When the glass is further heated, crystallization 
of the glass starts. In general, fully crystallized glass cannot be 
sintered any more even if the glass is heated again. These phenomena can 
be observed from the differential thermal analysis of glass. In general, 
the degree of sintering of the glass can be controlled by controlling the 
degree of progress of crystallization based on heat-treating temperature 
and time. In the second step, it is preferable that the glass is 
crystallized so fully as not to be sintered again. The reason is that the 
sintering property of zirconia and/or alumina ceramic powder in the fourth 
step is utilized fully. 
For example, the temperature range in which an apatite crystal and at least 
one crystal of an alkaline earth metal silicate are precipitated can be 
obtained from the differential thermal analysis of glass. That is, X-ray 
diffraction data of glass powder heat-treated at temperature with various 
heating peaks in the differential thermal analysis curve are analyzed to 
identify precipitated crystals corresponding to the heating peaks, and the 
temperature range from the start of heat generation to its completion in 
the differential thermal analysis curve is defined as the temperature 
ranges in which the crystals are precipitated. For example, the 
temperature range in which the aforementioned crystals are precipitated is 
from 750.degree. to 1260.degree. C. In the second step, crystals of 
.alpha.- or .beta.-tricalcium phosphate [Ca.sub.3 (PO.sub.4).sub.2 ], in 
addition to the aforementioned crystals, are precipitated in some cases. 
The third step is of preparing mixture powder by mixing the crystallized 
glass obtained by the second step with partially stabilized zirconia 
powder and/or alumina powder while grinding the crystallized glass or 
after grinding the crystallized glass. The grinding of the crystallized 
glass is conducted by a known means using a ball mill or the like. It is 
preferable that the particle size of the resulting crystallized glass 
powder is 500 .mu.m or less. The reason is as follows. When particles 
larger than 500 .mu.m exist in the resulting crystallized glass powder, 
the particle size of the crystallized glass powder cannot be reduced to a 
desired value of 75 .mu.m or less by mixing and grinding together with 
zirconia and/or alumina ceramic powder by using a known means using a ball 
mill or the like. The desired value of the particle size is 75 .mu.m or 
less. The reason is as follows. A crystallized glass portion having a 
larger particle size than 75 .mu.m is, in most cases, so defective that 
the mechanical strength of the finally produced inorganic biomaterial 
consisting of the ceramic/crystallized glass composite cannot be taken to 
a large value. 
Although the above description is made about the case where the 
crystallized glass is ground and then the resulting crystallized glass 
powder is mixed with zirconia and/or alumina ceramic powder, the invention 
can be applied to the case where the grinding of the crystallized glass 
and the mixing of the crystallized glass with zirconia and/or alumina 
ceramic powder may be carried out simultaneously by using a known means 
using a ball mill or the like. Also in this case, it is preferable that 
the particle size of the crystallized glass obtained is 75 .mu.m or less. 
The zirconia ceramic powder mixed into the crystallized glass in this step 
is constituted by partially stabilized zirconia. The partially stabilized 
zirconia is prepared to attain high strength and high toughness by 
utilizing the stress-induced transformation (martensitic transformation) 
of the tetragonal zirconia crystal particles ordinarily containing at 
least one component selected from Y.sub.2 O.sub.3, MgO, CaO and CeO.sub.2 
as solid solution. Accordingly, the partially stabilized zirconia has high 
strength of 1000 to 2000 MPa. By mixing .alpha.-alumina to the partially 
stabilized zirconia and sintering the resulting mixture further densely, 
zirconia-alumina composite ceramic showing very high strength of 1500 to 
2400 MPa due to the micro-crack toughening effect could be fabricated. The 
partially stabilized zirconia powder containing .alpha.-alumina can be 
used as the zirconia ceramic powder used in the process according to the 
first aspect of the invention. To stabilize zirconia partially, at least 
one member selected from the following group can be added to ZrO.sub.2. 
______________________________________ 
Y.sub.2 O.sub.3 
1.5-5 mol 
MgO 7-10 mol 
CaO 7-10 mol 
CeO.sub.2 4-15 mol 
(ZrO.sub.2 100 mol) 
______________________________________ 
In the case where .alpha.-alumina is added to the partially stabilized 
zirconia, the weight ratio of partially stabilized zirconia to 
.alpha.-alumina is preferably in a range of from 95:5 to 10:90. The reason 
is as follows. When the partially stabilized zirconia content is less than 
10%, the effect of reinforcement by utilizing the stress-induced 
transformation of zirconia is so unsatisfactory that the strength cannot 
be improved effectively. When the .alpha.-alumina content is less than 5%, 
the effect of .alpha.-alumina is very small. The more preferred range of 
the weight ratio is in a range of from 95:5 to 20:80. 
It is preferable that the zirconia powder mixed with the crystallized glass 
has a smaller particle size than that of the crystallized glass powder. 
The reason is as follows. When the particle size of the zirconia ceramic 
powder is larger than the particle size of the crystallized glass powder, 
pores are formed easily in the vicinity of the boundary between the 
zirconia particles and the crystallized glass to make it difficult to 
prepare a zirconia ceramic/crystallized glass composite of high mechanical 
strength. Zirconia ceramic fine powder with the particle size of 1 .mu.m 
or less can be obtained according to a wet method such as a 
coprecipitation method, a hydrolysis method, an alkoxide method or the 
like. Accordingly, it is desirable that zirconia powder obtained as 
described above is used. 
Although the above description is made about the case where zirconia 
ceramic powder is mixed with the crystallized glass, the invention can be 
applied to the case where zirconia ceramic powder may be replaced by 
alumina ceramic powder. In the case where alumina ceramic powder is used, 
a ceramic/crystallized glass composite having higher strength than that of 
a conventional composite produced by the conventional process can be 
produced. Alternatively, a mixture of zirconia ceramic powder and alumina 
ceramic powder may be used in this invention. 
In the conventional process disclosed in the Japanese Patent Unexamined 
Publication No. Hei-1-115360, etc., a large amount of zirconia and/or 
alumina ceramic powder must be mixed with the glass. However, in the first 
aspect of the invention, the amount of zirconia and/or alumina ceramic 
powder mixed with the crystallized glass is not restricted specifically. 
The reason is as follows. Even in the case where the amount of zirconia 
and/or alumina ceramic powder is small, there is no risk of zirconia 
and/or alumina ceramic powder surrounded by fluidized glass and there is 
no risk of generation of pores in the vicinity of the boundary between the 
glass and the zirconia and/or alumina ceramic powder. Accordingly, a 
ceramic/crystallized glass composite of high strength having a zirconia 
and/or alumina ceramic skeleton can be obtained. It is a matter of course 
that when the amount of zirconia and/or alumina ceramic powder is large, a 
ceramic/crystallized glass comosite of high strength can be obtained. 
However, when the amount of the crystallized glass is less than 5% by 
volume, the effect of addition of bioactivity by mixing with zirconia 
ceramic powder cannot be obtained in the resulting inorganic biomaterial. 
When the amount is more than 95%, on the contrary, the zirconia and/or 
alumina ceramic portion as a skeleton is so small that improvement of 
mechanical strength cannot be expected. Accordingly, the preferred range 
of the volume ratio of crystallized glass to zirconia and/or alumina 
ceramic is from 5:95 to 95:5. With respect to the material excellent in 
both bioactivity and strength, the more preferred range is from 40:60 to 
90:10. 
The fourth step is of preparing an inorganic biomaterial of a 
ceramics/crystallized glass composite by molding the mixture powder 
obtained by the third step into a desired shape and then heat-treating the 
resulting molding in a temperature range in which the partially stabilized 
zirconia and/or alumina powder is sintered. 
In this step, the mixture powder of crystallized glass powder and zirconia 
and/or alumina ceramic powder is molded into a desired shape by a known 
molding method such as dust molding, cold isostatic molding (rubber press 
molding), injection molding, extrusion molding or the like. Then, the 
resulting molding is heat-treated within the sintering temperature range 
in which the zirconia and/or alumina ceramic powder is sintered. When the 
zirconia and/or alumina ceramic powder is sintered, there is no occurrence 
of fluidization/sintering of the glass. Accordingly, a fine and strong 
ceramic/crystallized glass composite can be obtained. The temperature 
range in which the zirconia and/or alumina ceramic powder is sintered can 
be found by measuring thermal contraction while heating the molding of the 
crystallized glass/zirconia and/or alumina ceramic powder mixture at a 
constant rate. In short, the range from the start temperature of thermal 
contraction to its end is taken as the sintering temperature range. For 
example, sintering of zirconia starts from about 800.degree. C. In 
general, the temperature in which zirconia is sintered most densely is 
1300.degree. C. or more. However, when the temperature is higher than 
1500.degree. C., the crystallized glass portion is melted to generate 
pores or is made to react with zirconia ceramic powder to lose the 
bioactive function in some cases. Therefore, the preferred sintering 
temperature range is not higher than 1500.degree. C. Recently, zirconia 
ceramics capable of being sintered densely at a relatively low temperature 
of 1000.degree. to 1300.degree. C. through adding a small amount of 
transition metal oxide such as zinc oxide, manganese oxide, copper oxide, 
cobalt oxide, nickel oxide, etc. have been developed [reference be made to 
"Zirconia Ceramics 9", Uchida Rokakuho Publishing Co. Ltd., Apr. 10, 1987, 
pp 1-12]. The melting point of the crystallized glass varies according to 
its composition. Accordingly, the melting of the crystallized glass may 
start at 1300.degree. C. in some cases. The aforementioned zirconia 
ceramic powder capable of being sintered densely at a low temperature of 
1000.degree. to 1300.degree. C. is suitable to these cases. A suitable 
known method can be used as the sintering method in the fourth step. When 
hot press method or HIP (hot isostatic pressing) method is used, sintering 
is accelerated so that the number of pores is reduced and, accordingly, a 
biomaterial showing larger mechanical strength can be obtained. 
Next, the process for producing an inorganic biomaterial according to the 
second aspect of the invention will be explained successively the step by 
the step. 
In the first step of the process according to the second aspect of the 
invention, crystals of calcium phosphate are heat-treated in the 
temperature range of from 800.degree. to 1400.degree. C. to prepare a 
calcium phosphate crystal sintered body. Examples of the crystals of 
calcium phosphate subjected to heat-treatment in the first step may be 
hydroxyapatite [Ca.sub.10 (PO.sub.4).sub.6 (OH).sub.2 ], tricalcium 
phosphate [Ca.sub.3 (PO.sub.4).sub.2 ], octacalcium phosphate [Ca.sub.8 
H.sub.2 (PO.sub.4).sub.6 5H.sub.2 O], etc. These materials may be used 
singly or in combination selectively. As a method for producing crystals 
of calcium phosphate, any suitable method selected from a dry method and a 
wet method can be used. In general, the powder prepared by the wet method 
in which calcium phosphate is precipitated from an aqueous solution 
containing calcium and phosphoric acid, can be sintered more densely than 
the powder prepared by the dry method. Further, in the wet method, two or 
more kinds of calcium phosphate crystals can co-exist easily. Accordingly, 
calcium phosphate prepared by the wet method is preferably used in the 
second aspect of the invention. As described above, the heat-treating 
temperature to obtain a calcium phosphate crystal sintered body is 
restricted to a range of from 800.degree. to 1400.degree. C. The reason is 
as follows. When the temperature is lower than 800.degree. C., a dense 
sintered body cannot be obtained. When the temperature is higher than 
1400.degree. C., on the contrary, the stability of the resulting sintered 
body is reduced. 
In the second step, the calcium phosphate crystal sintered body obtained in 
the first step is ground to prepare powder. At the same time the powder is 
prepared or after the powder is prepared, the powder is mixed with 
partially stabilized zirconia and/or alumina ceramic powder. In the case 
where the grinding of the calcium phosphate crystal sintered body and the 
mixing with partially stabilized zirconia and/or alumina ceramic powder 
are carried out simultaneously, a known means such as a ball mill or the 
like can be used. Preferably, after the calcium phosphate sintered body is 
once ground to a particle size of 500 .mu.m or less by a known means such 
as a ball mill, the resulting powder is mixed with partially stabilized 
zirconia and/or alumina ceramic powder by a known means such as a ball 
mill and ground together with the zirconia and/or alumina ceramic powder. 
It is preferable that the calcium phosphate crystal sintered body obtained 
by the simultaneous grinding or the two-stage grinding has a particle size 
of 75 .mu.m or less. The reason is as follows. When the particle size of 
the calcium phosphate crystal sintered body in the finally produced 
composite ceramic biomaterial is larger than 75 .mu.m, the sintered body 
is, in most cases, so defective that the mechanically high-strength 
composite ceramic biomaterial cannot be fabricated. 
To make the particle size of the calcium phosphate crystal sintered body 
not larger than 75 .mu.m, it is desirable that the particle size of the 
calcium phosphate crystal sintered body before mixing with partially 
stabilized zirconia and/or alumina ceramic powder in the second step is 
not larger than 500 .mu.m. The reason is as follows. When particles larger 
than 500 .mu.m exist in the calcium phosphate crystal sintered body, the 
particle size cannot be reduced so sufficiently that particles of the 
calcium phosphate crystal sintered body larger than 75 .mu.m remain after 
mixing. 
The partially stabilized zirconia and/or alumina powder used in the process 
according to the first aspect of the invention can be used as they are as 
the partially stabilized zirconia and/or alumina powder to be mixed with 
the calcium phosphate crystal sintered body in the second step of the 
process according to the second aspect of the invention. Accordingly, the 
details thereof are not described here. 
According to the second aspect of the invention, a high-strength composite 
ceramic biomaterial having zirconia and/or alumina ceramics as a skeleton 
can be produced even in the case where the amount of zirconia and/or 
alumina ceramic powder used in the second step is small. Of course, a 
high-strength composite ceramic biomaterial can be produced in the case 
where the amount of zirconia and/or alumina ceramic powder is large. 
However, when the amount of the calcium phosphate crystal is less than 5% 
by volume, the effect of addition of bioactivity by mixing with zirconia 
ceramic powder cannot be obtained in the resulting inorganic biomaterial. 
When the amount is more than 95%, the zirconia and/or alumina ceramic 
portion as a skeleton is so small that improvement of mechanical strength 
cannot be expected. Accordingly, the preferred range of the volume ratio 
of calcium phosphate crystal sintered body powder to zirconia and/or 
alumina ceramic powder is from 5:95 to 95:5. With respect to the material 
excellent in both bioactivity and strength, the more preferred range is 
from 40:60 to 90:10. 
In the third step, the mixture powder obtained in the second step is molded 
into a desired shape and then the molding is sintered within the 
temperature range in which zirconia and/or alumina is sintered to thereby 
prepare a composite ceramic biomaterial. 
In the third step, the mixture powder is molded by a known molding method 
such as dust pressing, cold isostatic pressing (rubber press molding), 
injection molding, extrusion molding, or the like. The temperature range 
in which the zirconia and/or alumina ceramic powder is sintered can be 
found by measuring thermal contraction while heating the molding of the 
mixture of calcium phosphate crystal sintered body powder and zirconia 
and/or alumina ceramic powder at a constant rate. In short, the range from 
the start temperature of thermal contraction to its end is taken as the 
sintering temperature range. For example, sintering of zirconia starts 
from about 800.degree. C. In general, the temperature in which zirconia is 
sintered most densely is 1300.degree. C. or more. However, when the 
temperature is higher than 1400.degree. C., the calcium phosphate crystal 
sintered body powder is decomposed to produce pores or is made to react 
with zirconia ceramic powder to lose the bioactive function in some cases. 
Therefore, the preferred sintering temperature range is not higher than 
1400.degree. C. In the case of alumina, the preferred temperature range is 
not higher than 1500.degree. C. Recently, zirconia ceramics capable of 
being sintered densely at a relatively low temperature in a range of from 
1000.degree. to 1300.degree. C. through adding a small amount of 
transition metal oxide such as zinc oxide, manganese oxide, copper oxide, 
cobalt oxide, nickel oxide, etc. have been developed [reference be made to 
"Zirconia Ceramics 9", Uchida Rokakuho Publishing Co. Ltd., Apr. 10, 1987, 
pp 1-12]. For example, in some cases, the calcium phosphate crystal such 
as .beta.-tricalcium phosphate is transformed at a low temperature in a 
range of from 1150.degree. to 1300.degree. C. The aforementioned zirconia 
ceramic powder capable of being sintered densely at a low temperature in a 
range of from 1000.degree. to 1300.degree. C. is suitable to these cases. 
A suitable known method may be used as the heat-treating method for 
sintering. When hot press method or HIP (hot isostatic pressing) method is 
used, sintering is accelerated so that the number of pores is reduced and, 
accordingly, a biomaterial showing a larger mechanical strength can be 
obtained. 
When calcium phosphate crystal fine powder and partially stabilized 
zirconia fine powder are mixed and sintered by the conventional process 
according to the Japanese Patent Unexamined Publication No. Sho-64-18973, 
the following disadvantages arise. When the temperature reach a value in 
which calcium phosphate powder is sintered, (1) calcium phosphate is 
sintered to thereby surround the partially stabilized zirconia powder, or 
(2) reaction between calcium phosphate fine powder and zirconia fine 
powder is made easily in the boundary, so that pores are generated or the 
partially stabilized zirconia is stabilized fully in most cases. These 
phenomena occur particularly in the case where the amount of the partially 
stabilized zirconia powder is small. 
A calcium phosphate crystal such as apatite starts sintering at about 
600.degree. C. and is stable till about 1400.degree. C. The degree of 
sintering can be judged from measurement of thermal contraction of the 
calcium phosphate crystal. The stability of the crystal can be judged from 
X-ray diffraction after heat-treatment. At 600.degree. C., sintering is 
not progressed so that a dense sintered body cannot be obtained. At 
800.degree. C., a dense calcium phosphate sintered body can be obtained. 
According to the second aspect of the invention, the calcium phosphate 
crystal is sintered at the temperature range of from 800.degree. to 
1400.degree. C. in the first step, so that a dense and stable calcium 
phosphate crystal sintered body can be produced. The calcium phosphate 
crystal sintered body thus once densely sintered is not enough to sinter 
densely again even if the sintered body is ground to a particle size of 50 
.mu.m and then subjected to heat-treatment. Accordingly, the calcium 
phosphate crystal once densely sintered is not sintered again, even though 
it is treated as follows: the calcium phosphate crystal once already 
sintered is ground to prepare powder in the second step; the powder is 
mixed with zirconia powder and/or alumina powder simultaneously with or 
after the grinding thereof; the mixture is further ground to prepare 
mixture powder; and then the mixture powder is subjected to sintering in 
the third step within the temperature range in which zirconia and/or 
alumina is sintered. Therefore, the above-mentioned disadvantage of (1) 
can be eliminated. The particle size of the calcium phosphate crystal 
sintered body powder obtained by grinding is not reduced excessively. 
Therefore, the above-mentioned disadvantage of (2) can be eliminated. 
The result of observation, by using an electron microscope, of the 
inorganic biomaterial produced according to the second aspect of the 
invention is shown typically in FIGS. 3 and 4. As shown in FIG. 3 and FIG. 
4 which is an enlarged view of the circular portion IV in FIG. 3, the 
inorganic biomaterial obtained according to the second aspect of the 
invention has a plurality of first sintered portions 11A constituted by 
crystals of calcium phosphate 11a, and a plurality of second sintered 
portions 12A constituted by crystals of partially stabilized zirconia 
and/or alumina 12a, the plurality of first sintered portions being shaped 
like islands, the plurality of second sintered portions being shaped like 
an island-studded sea. In short, the plurality of first sintered portions 
11A constituted by crystals of calcium phosphate 11a excellent in 
biocompatibility are dispersed in the high-strength second sintered 
portions 12A, as a skeleton, constituted by crystals of partially 
stabilized zirconia and/or alumina 12a. Consequently, the inorganic 
biomaterial is improved in biocompatibility and strength. 
EXAMPLES 
The present invention will be described more in detail hereunder with 
respect to various Examples. However, the present invention is not limited 
to these Examples. 
Examples according to the First Aspect of the Invention 
Example 1 
Using oxides, carbonates, phosphates, hydrates, fluorides, etc. as raw 
materials, there was prepared a batch of glass materials to form glass 
containing 47.8% by weight of CaO, 44.0% by weight of SiO.sub.2, 1.5% by 
weight of MgO, 6.5% by weight of P.sub.2 O.sub.5 and 0.2% by weight of 
fluorine (F.sub.2). The batch was placed in a platinum crucible and melted 
at 1550.degree. C. for 2 hours. The melt was poured into water to prepare 
glass (the first step). The glass was dried. The dried glass was heated 
from room temperature to 1200.degree. C. at a constant rate of 3.degree. 
C./min in an electric furnace and then was kept at 1200.degree. C. for 2 
hours to thereby crystallize the glass (the second step). The crystallized 
glass was placed in a ball mill and ground to a particle size of 500 .mu.m 
or less. The crystallized glass powder obtained above and partially 
stabilized zirconia ceramic powder (mean particle diameter: 0.3 .mu.m) 
prepared by a coprecipitation method and containing 2.5 mol % of Y.sub.2 
O.sub.3 were placed in a ball mill in various ratios, wet-mixed for 
several hours while the particle size of the crystallized glass was 
reduced to 75 .mu.m or less, and then dried (the third step). Each of the 
resulting mixtures was placed in a graphite mold, heated from room 
temperature to 1300.degree. C. at a constant rate of 3.degree. C./min 
while applying pressure of 30 MPa and kept at 1300.degree. C. for 2 hours, 
by which the molding was sintered. Then, the molding was cooled to a room 
temperature in a furnace. Thus, various zirconia ceramic/crystallized 
glass composites were prepared (the fourth step). Each of the zirconia 
ceramic/crystallized glass composites had a relative density of 97% or 
more, so that the number of pores was very small. The zirconia 
ceramic/crystallized glass composites were ground and, using the resulting 
powders, the crystalline phases precipitated in the glass of each 
composite were identified according to the method of powder X-ray 
diffraction. In all the composites, crystals of apatite and wollastonite 
were precipitated. On the other hand, each composite was formed into a 
shape of a 3.times.4.times.36 mm rectangular pillar and subjected to 
three-point bending strength test according to the method of JIS R1601. 
The relationships between zirconia ceramic content (percentage by volume) 
and three-point bending strength, of the composites are shown in the curve 
1 in FIG. 1. The curve 2 in FIG. 1 shows the relationships between 
zirconia ceramic content and three-point bending strength, of inorganic 
biomaterials prepared by the conventional process disclosed in the 
Japanese Patent Unexamined Publication No. Hei-1-115360. As is clear from 
FIG. 1, the inorganic biomaterials of this Example showed higher bending 
strength than that of the conventional inorganic biomaterials and, 
particularly, the inorganic biomaterials of this Example showed higher 
strength even when the zirconia content was small. 
Example 2 
Using oxides, carbonates, phosphates, hydrates, fluorides, etc. as raw 
materials, there was prepared a batch of glass materials to form glass 
containing 47.8% by weight of CaO, 44.0% by weight of SiO.sub.2, 1.5% by 
weight of MgO, 6.5% by weight of P.sub.2 O.sub.5 and 0.2% by weight of 
fluorine (F.sub.2). The batch was placed in a platinum crucible and melted 
at 1550.degree. C. for 2 hours. The melt was poured into water to prepare 
glass (the first step). The glass was dried. The dried glass was heated 
from room temperature to 1200.degree. C. at a constant rate of 3.degree. 
C./min in an electric furnace and then was kept at 1200.degree. C. for 2 
hours to thereby crystallize the glass (the second step). The crystallized 
glass was placed in a ball mill and ground to a particle size of 500 .mu.m 
or less. The crystallized glass powder obtained above and partially 
stabilized zirconia ceramic powder (mean particle diameter: 0.3 .mu.m) 
prepared by a coprecipitation method and containing 2.5 mol % of Y.sub.2 
O.sub.3 and .alpha.-alumina in various ratios were placed in a ball mill 
in a volume ratio of 70 (crystallized glass): 30 (partially stabilized 
zirconia ceramic powder). They were wet-mixed in the ball mill for several 
hours while reducing the particle size of the crystallized glass to 75 
.mu.m or less and then dried (the third step). Each of the resulting 
mixtures was placed in a graphite mold, heated from room temperature to 
1350.degree. C. at a constant rate of 3.degree. C./min while applying 
pressure of 30 MPa and kept at 1350.degree. C. for 2 hours, by which the 
molding was crystallized and sintered. Then, the molding was cooled to a 
room temperature in a furnace. Thus, various zirconia ceramic/crystallized 
glass composites different in the .alpha.-alumina content (percentage by 
weight) of the zirconia ceramic were prepared (the fourth step). Each of 
the zirconia ceramic/crystallized glass composites had a relative density 
of 96% to 99%, so that the number of pores was very small. The zirconia 
ceramic/crystallized glass composites were ground, and, using the 
resulting powders, the crystalline phases precipitated in the glass of 
each composite were identified according to the method of powder X-ray 
diffraction. In all the composites, crystals of apatite and wollastonite 
were precipitated. On the other hand, each composite was formed into a 
shape of a 3.times.4.times.36 mm rectangular pillar and subjected to 
three-point bending strength test according to the method of JIS R1601. 
The relationships between .alpha.-alumina content (percentage by volume) 
of zirconia ceramic and three-point bending strength, of the composites 
are shown in FIG. 2. As is clear from FIG. 2, the inorganic biomaterials 
of this Example had higher bending strength than that of the conventional 
inorganic biomaterials. 
Example 3 
Using oxides, carbonates, phosphates, hydrates, fluorides, etc. as raw 
materials, a batch of glass materials was prepared. The batch was placed 
in a platinum crucible and melted at a temperature of 1450.degree. C. to 
1550.degree. C. for 2 hours. The melt was poured into water. Thus, 32 
glass samples respectively having compositions as shown in Table 1 were 
prepared (the first step). Each of the glass samples was dried. The dried 
glass sample was heated from room temperature to 1200.degree. C. at a 
constant rate of 3.degree. C./min in an electric furnace and then was kept 
at 1200.degree. C. for 2 hours to thereby crystallize the glass (the 
second step). The crystallized glass was placed in a ball mill and ground 
to a particle size of 500 .mu.m or less. The crystallized glass powder 
with the particle size of 500 .mu.m or less and partially stabilized 
zirconia ceramic powder (mean particle diameter: 0.6 .mu.m) prepared by a 
coprecipitation method and containing 2.6 mol % of Y.sub.2 O.sub.3 and 0.3 
mol % of ZnO were placed in a ball mill in a volume ratio of 70 
(crystallized glass powder): 30 (partially stabilized zirconia ceramic 
powder). They were wet-mixed in the ball mill for several hours while 
reducing the particle size of the crystallized glass to 75 .mu.m or less 
and then dried (the third step). Each of the resulting mixtures was shaped 
like a 50 mm .phi. disc by using a mold, heated in the electric furnace 
from room temperature to 1200.degree. C. at a constant rate of 3.degree. 
C./min, kept at 1200.degree. C. for 2 hours and cooled to room temperature 
in the furnace to prepare a preliminary sintered body. The preliminary 
sintered body was heated from a room temperature to 1200.degree. C. at a 
constant rate of 3.degree. C./min while applying pressure of 200 MPa in an 
atmosphere of argon gas and then kept at 1200.degree. C. for 2 hours, by 
which the compact was molded by using hot isostatic pressing (HIP). The 
molding was cooled to a room temperature in the furnace. Thus, various 
zirconia ceramic/crystallized glass composites were prepared (the fourth 
step). Each of the zirconia ceramic/crystallized glass composites had a 
relative density of 98.5% or more, so that the number of pores was very 
small. The zirconia ceramic/crystallized glass composites were ground and, 
using the resulting powders, the crystalline phases precipitated in the 
glass of each composite were identified according to the method of powder 
X-ray diffraction. In the composites, crystals as shown in Table 1 were 
precipitated. On the other hand, each composite was formed into a shape of 
a 3.times.4.times.36 mm rectangular pillar and subjected to three-point 
bending strength test according to the method of JIS R1601. 
The glass compositions, the crystalline phases precipitated in the glass of 
each composite, and the three-point bending strength is shown in Table 1. 
As is clear from Table 1, the 32 kinds of inorganic biomaterials of this 
Example containing a small quantity of zirconia showed higher bending 
strength than that of the conventional inorganic biomaterials. 
TABLE 1 
______________________________________ 
No. 1 2 3 
______________________________________ 
Glass composition 
(wt %) 
CaO 47.5 49.2 23.2 
P.sub.2 O.sub.5 
14.0 1.0 27.0 
SiO.sub.2 38.5 49.8 49.8 
Others 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Wollastonite 
Wollastonite 
Wollastonite 
in the glass Tricalcium- 
phosphate 
Bending strength 
520 520 520 
(MPa) 
______________________________________ 
No. 4 5 6 
______________________________________ 
Glass composition 
(wt %) 
CaO 55.6 44.7 36.3 
P.sub.2 O.sub.5 
22.0 16.3 16.3 
SiO.sub.2 22.4 34.2 35.4 
Others MgO 4.6 MgO 11.5 
F.sub.2 0.2 F.sub.2 
0.5 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Wollastonite 
Wollastonite 
Diopside 
in the glass Diopside 
Bending strength 
520 600 550 
(MPa) 
______________________________________ 
No. 7 8 9 
______________________________________ 
Glass composition 
(wt %) 
CaO 26.8 24.6 26.1 
P.sub.2 O.sub.5 14.1 16.0 23.0 
SiO.sub.2 34.1 28.7 29.8 
Others MgO 11.5 MgO 30.7 MgO 18.6 
Al.sub.2 O.sub. 3 
12.5 F.sub.2 
0.5 
F.sub.2 0.8 Li.sub.2 O 
2.0 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Anorthite Forsterite Akermanite 
in the glass 
Diopside Diopside Diopside 
Forsterite Tricalcium- 
Tricalcium- 
Tricalcium- 
phosphate phosphate 
phosphate 
Bending strength 
650 550 520 
(MPa) 
______________________________________ 
No. 10 11 12 
______________________________________ 
Glass composition 
(wt %) 
CaO 16.6 47.4 47.4 
P.sub.2 O.sub.5 16.2 6.2 6.2 
SiO.sub.2 37.2 42.2 42.2 
Others MgO 29.5 Y.sub.2 O.sub.3 
2.0 MgO 2.0 
F.sub.2 0.5 ZrO.sub.2 
2.0 Ta.sub.2 O.sub.5 
2.0 
F.sub.2 
0.5 F.sub.2 
0.2 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Diopside Wollastonite 
Wollastonite 
in the glass 
Forsterite 
Bending strength 
600 650 600 
(MPa) 
______________________________________ 
No. 13 14 15 
______________________________________ 
Glass composition 
(wt %) 
CaO 48.3 47.9 48.3 
P.sub.2 O.sub.5 6.3 6.3 6.3 
SiO.sub.2 43.2 42.6 43.2 
Others F.sub.2 0.2 F.sub.2 
0.2 F.sub.2 
0.2 
TiO.sub.2 
2.0 K.sub.2 O 
3.0 SrO 2.0 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Wollastonite 
Wollastonite 
Wollastonite 
in the glass 
Bending strength 
600 510 510 
(MPa) 
______________________________________ 
No. 16 17 18 
______________________________________ 
Glass composition 
(wt %) 
CaO 48.3 48.3 48.3 
P.sub.2 O.sub.5 6.3 6.3 6.3 
SiO.sub.2 43.2 43.2 43.2 
Others F.sub.2 0.2 MgO 0.2 F.sub.2 
0.2 
Nb.sub.2 O.sub.5 
2.0 Na.sub.2 O 
2.0 B.sub.2 O.sub.3 
2.0 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Wollastonite 
Wollastonite 
Wollastonite 
in the glass 
Bending strength 
510 501 520 
(MPa) 
______________________________________ 
No. 19 20 21 
______________________________________ 
Glass composition 
(wt %) 
CaO 49.3 47.8 12.0 
P.sub.2 O.sub.5 6.5 6.5 15.5 
SiO.sub.2 44.0 44.0 47.7 
Others F.sub.2 0.2 MgO 1.5 Al.sub.2 O.sub.3 
24.8 
F.sub.2 
0.2 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Wollastonite 
Wollastonite 
Anorthite 
in the glass Tricalcium- 
phosphate 
Bending strength 
550 650 620 
(MPa) 
______________________________________ 
No. 22 23 24 
______________________________________ 
Glass composition 
(wt %) 
CaO 45.0 45.0 45.0 
P.sub.2 O.sub.5 6.0 6.0 6.0 
SiO.sub.2 39.0 39.0 39.0 
Others K.sub.2 O 
9.5 Li.sub.2 O 
9.5 Na.sub.2 O 
9.5 
F.sub.2 0.5 F.sub.2 
0.5 F.sub.2 
0.5 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Wollastonite 
Wollastonite 
Wollastonite 
in the glass 
Tricalcium- 
Tricalcium- 
Tricalcium- 
phosphate phosphate phosphate 
Bending strength 
510 510 510 
(MPa) 
______________________________________ 
No. 25 26 27 
______________________________________ 
Glass composition 
(wt %) 
CaO 45.0 45.0 45.0 
P.sub.2 O.sub.5 6.0 6.0 6.0 
SiO.sub.2 39.0 39.0 39.0 
Others TiO.sub.2 
9.5 ZrO.sub.2 
9.5 SrO 9.5 
F.sub.2 0.5 F.sub.2 
0.5 F.sub.2 
0.5 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Wollastonite 
Wollastonite 
Wollastonite 
in the glass 
Tricalcium- 
Tricalcium- 
Tricalcium- 
phosphate phosphate phosphate 
Bending strength 
600 650 600 
(MPa) 
______________________________________ 
No. 28 29 30 
______________________________________ 
Glass composition 
(wt %) 
CaO 45.0 45.0 45.0 
P.sub.2 O.sub.5 6.0 6.0 6.0 
SiO.sub.2 39.0 39.0 39.0 
Others Nb.sub.2 O.sub.5 
9.5 Ta.sub.2 O.sub.5 
9.5 B.sub.2 O.sub.3 
9.5 
F.sub.2 0.5 F.sub.2 
0.5 F.sub.2 
0.5 
Crystalline phases 
Apatite Apatite Apatite 
precipitated 
Wollastonite 
Wollastonite 
Wollastonite 
in the glass 
Tricalcium- 
Tricalcium- 
Tricalcium- 
phosphate phosphate phosphate 
Bending strength 
600 580 580 
(MPa) 
______________________________________ 
No. 31 32 
______________________________________ 
Glass composition 
(wt %) 
CaO 45.0 45.0 
P.sub.2 O.sub.5 6.0 6.0 
SiO.sub.2 44.5 44.0 
Others F.sub.2 4.5 Y.sub.2 O.sub.3 
5.0 
Crystalline phases 
Apatite Apatite 
precipitated Wollastonite Wollastonite 
in the glass 
Bending strength 
620 630 
(MPa) 
______________________________________ 
(Note) In the item of "Glass composition", "F.sub.2 " is shown with a 
converted value of "F.sub.2 " of fluorine in the glass composition. 
Example 4 
Using oxides, carbonates, phosphates, hydrates, fluorides, etc. as raw 
materials, there was prepared a batch of glass materials to form glass 
containing 47.8% by weight of CaO, 44.0% by weight of SiO.sub.2, 1.5% by 
weight of MgO, 6.5% by weight of P.sub.2 O.sub.5 and 0.2% by weight of 
fluorine (F.sub.2). The batch was placed in a platinum crucible and melted 
at 1550.degree. C. for 2 hours. The melt was poured into water to prepare 
glass (the first step). The glass was dried. The dried glass was heated 
from room temperature to 1200.degree. C. at a constant rate of 3.degree. 
C./min in an electric furnace and then was kept at 1200.degree. C. for 2 
hours to thereby crystallize the glass (the second step). The crystallized 
glass was placed in a ball mill and ground to a particle size of 500 .mu.m 
or less. The crystallized glass powder obtained above and .alpha.-alumina 
ceramic powder (mean particle diameter:0.2 .mu.m) were placed in a ball 
mill in a volume ratio of 60 (crystallized glass): 40 (.alpha.-alumina 
ceramic powder). They were wet-mixed in the ball mill for several hours 
while reducing the particle size of the crystallized glass to 75 .mu.m or 
less and then dried (the third step). The molding was placed in a graphite 
mold, heated from a room temperature to 1350.degree. C. at a constant rate 
of 3.degree. C./min while applying pressure of 30 MPa and then was kept at 
1350.degree. C. for 2 hours, by which the molding was crystallized and 
sintered. Then, the molding was cooled to a room temperature in a furnace. 
Thus, an alumina ceramic/crystallized glass composite was prepared (the 
fourth step). The alumina ceramic/crystallized glass composite had a 
relative density of 96%. The alumina ceramic/crystallized glass composite 
was ground, and, using the resulting powder, the crystalline phase 
precipitated in the glass of the composite was identified according to the 
method of powder X-ray diffraction. In the composite, crystals of apatite 
and wollastonite were precipitated. On the other hand, the composite was 
formed into a shape of a 3.times.4.times.36 mm rectangular pillar and 
subjected to three-point bending strength test according to the method of 
JIS R1601. The three-point bending strength of the composite was 370 MPa. 
Examples according to the Second Aspect of the Invention 
Example 5 
An aqueous solution containing 0.5 mol/l of Ca(NO.sub.3).sub.2 and an 
aqueous solution containing 0.5 mol/l of (NH.sub.4).sub.2 HPO.sub.4 were 
made to react with each other at a temperature in a range of from 
80.degree. to 90.degree. C. for 24 hours while mixing and stirring. If 
necessary, an aqueous solution containing 0.1 mol/l of NaOH was added 
dropwise to the resulting solution to adjust pH in a range from 7 to 10. 
The precipitated product was dried, subjected to rubber press molding 
under pressure of 196 MPa, heated from a room temperature to 1300.degree. 
C. at a constant rate of 3.degree. C./min in an electric furnace and kept 
at 1300.degree. C. for 2 hours to prepare a calcium phosphate crystal 
sintered body (the first step). The sintered body was identified according 
to the method of powder X-ray diffraction. As the result of the powder 
X-ray diffraction, it was found that the sintered body consists of apatite 
and .beta.-tricalcium phosphate. The calcium phosphate crystal sintered 
body obtained in the first step was placed in a ball mill and ground to a 
particle size of 500 .mu.m or less. The calcium phosphate crystal sintered 
body powder obtained above and zirconia ceramic powder (partially 
stabilized zirconia, mean particle diameter:0.3 .mu.m) prepared by a 
coprecipitation method and containing 3 mol % of Y.sub.2 O.sub.3 were 
placed in a ball mill in various ratios. They were wet-mixed in the ball 
mill for several hours and then dried (the second step). The mixture 
obtained by the second step was placed in a graphite mold, heated from a 
room temperature to 1300.degree. C. at a constant rate of 3.degree. C./min 
while applying pressure of 30 MPa and then kept at 1300.degree. C. for 2 
hours, by which the molding was sintered. Then, the molding was cooled to 
a room temperature in a furnace. Thus, various composite ceramic 
biomaterials were prepared (the third step). 
Each of the composite ceramic biomaterials had a relative density of 97% to 
98%. Each of the composite ceramic biomaterials was observed using an 
electron microscope. As the result of the observation, each structure of 
the biomaterials was shown in FIGS. 3 and 4. Further, each composite 
ceramic biomaterial was cut and mirror polished. Then, a Vickers indenter 
was pressed into the mirror surface of each biomaterial with 9.8N for 15 
seconds. To calculate fracture toughness, the length of a crack extending 
from the pressed point was measured. The relationships between zirconia 
powder content (percentage by volume) and fracture toughness, of the 
composite ceramic biomaterials of this Example are shown in the curve a in 
FIG. 6. The curve b in FIG. 6 shows the fracture toughness of conventional 
composite ceramic biomaterials produced according to the Japanese Patent 
Unexamined Publication No. Sho-64-18973. As is clear from FIG. 6, the 
composite ceramic biomaterials of this Example had higher fracture 
toughness than those of the conventional biomaterials. 
Example 6 
An aqueous solution containing 0.5 mol/l of Ca(NO.sub.3).sub.2 and an 
aqueous solution containing 0.2 mol/l of (NH.sub.4).sub.2 HPO.sub.4 were 
made to react with each other at a temperature in a range of 80.degree. to 
90.degree. C. for 24 hours while mixing and stirring. If necessary, an 
aqueous solution containing 0.1 mol/l of NaOH was added dropwise to the 
resulting solution to adjust pH in a range from 7 to 8.5. The precipitated 
reaction product was dried, subjected to rubber press molding under 
pressure of 196 MPa, heated from a room temperature to 1300.degree. C. at 
a constant rate of 3.degree. C./min in an electric furnace and kept at 
1300.degree. C. for 2 hours to prepare a calcium phosphate crystal 
sintered body (the first step). The sintered body was identified according 
to the method of powder X-ray diffraction. As the result of the powder 
X-ray diffraction, it was found that the sintered body consists of 
apatite. The calcium phosphate crystal sintered body obtained by the first 
step was placed in a ball mill and ground to a particle size of 500 .mu.m 
or less. The calcium phosphate crystal sintered body powder obtained above 
and zirconia ceramic powder (partially stabilized zirconia, mean particle 
diameter: 0.3 .mu.m) prepared by a coprecipitation method and containing 3 
mol % of Y.sub.2 O.sub.3 and .alpha.-alumina in various ratios were placed 
in a ball mill in a volume ratio of 70 (calcium phosphate crystal sintered 
body powder): 30 (partially stabilized zirconia powder). They were 
wet-mixed in the ball mill for several hours and then dried (the second 
step). The mixture obtained by the second step was placed in a graphite 
mold, heated from a room temperature to 1350.degree. C. at a constant rate 
of 3.degree. C./min while applying pressure of 30 MPa and then kept at 
1350.degree. C. for 2 hours, by which the molding was sintered. Then, the 
molding was cooled to a room temperature in a furnace. Thus, various 
composite ceramic biomaterials were prepared (the third step). 
Each of the composite ceramic biomaterials had a relative density of 96% to 
99%. Each of the composite ceramic biomaterials was observed using an 
electron microscope. As the result of the observation, each structure of 
the biomaterials was shown in FIGS. 3 and 4. Further, each composite 
ceramic biomaterial was ground to identify precipitated crystals according 
to the method of powder X-ray diffraction. As the result of the powder 
X-ray diffraction, crystals of apatite did not change. Further, tetragonal 
crystals of zirconia, cubic crystals of zirconia and .alpha.-alumina (only 
in the niomaterial containing .alpha.-alumina) could be identified. On the 
other hand, each composite ceramic biomaterial was formed into a shape of 
a 3.times.4.times.36 mm rectangular pillar and subjected to three-point 
bending strength test according to the method of JIS R1601. The 
relationships between .alpha.-alumina content (percentage by volume) of 
zirconia ceramic and three-point bending strength, of the biomaterials are 
shown in FIG. 7. As is clear from FIG. 7, the composite ceramic 
biomaterials of this Example had higher bending strength. 
Example 7 
An aqueous solution containing 0.5 mol/l of Ca(NO.sub.3).sub.2 and an 
aqueous solution containing 0.2 mol/l of (NH.sub.4).sub.2 HPO.sub.4 were 
made to react with each other at a temperature of 80.degree. to 90.degree. 
C. for 24 hours while mixing and stirring. An aqueous solution containing 
0.1 mol/l of NaOH was added dropwise to the resulting solution to obtain 
solutions respectively adjusted to pH 6.0, 6.8, 7.0, 8.0 and 9.0. The 
precipitated reaction product was dried, subjected to rubber press molding 
under pressure of 196MPa, heated from a room temperature to 1300.degree. 
C. at a constant rate of 3.degree. C./min in an electric furnace and kept 
at 1300.degree. C. for 2 hours to prepare a calcium phosphate crystal 
sintered body (the first step). The sintered body was identified according 
to the method of powder X-ray diffraction. The result of the powder X-ray 
diffraction is shown in Table 2. 
TABLE 2 
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No. 41 42 43 
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pH at the time of 
6.0 6.8 7.0 
forming crystals of 
calcium phosphate 
Crystalline phases 
Octacalcium 
Octacalcium 
Hydroxy- 
of calcium phosphate phosphate apatite 
phosphate sintered Hydroxy- Octacalcium 
body apatite phosphate 
.beta.-tricalcium 
phosphate 
(a small 
amount) 
Bending strength 
330 350 350 
(MPa) 
Fracture toughness 
1.32 1.41 1.45 
(MPa.sqroot.m) 
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No. 44 45 
______________________________________ 
pH at the time of 
8.0 9.0 
forming crystals of 
calcium phosphate 
Crystalline phases 
Hydroxyapatite 
Hydroxyapatite 
of calcium .beta.-tricalcium 
phosphate sintered phosphate 
body 
Bending strength 
400 420 
(MPa) 
Fracture toughness 
1.77 2.01 
(MPa.sqroot.m) 
______________________________________ 
The calcium phosphate crystal sintered body was placed in a ball mill and 
ground to a particle size of 500 .mu.m or less. The calcium phosphate 
crystal sintered body powder obtained above and zirconia ceramic powder 
(partially stabilized zirconia, mean particle diameter: 0.6 .mu.m) 
prepared by a coprecipitation method and containing 2.6 mol % of Y.sub.2 
O.sub.3 and 0.3 mol % of ZnO were placed in a ball mill in a volume ratio 
of 70 (calcium phosphate crystal sintered body powder): 30 (zirconia 
powder). They were wet-mixed in the ball mill for several hours and then 
dried (second step). The mixture obtained by the second step was shaped 
like a 50 mm .phi. disk by using a mold, heated from room temperature to 
1200.degree. C. at a constant rate of 3.degree. C./min in an electric 
furnace, kept at 1200.degree. C. for 2 hours and then cooled to a room 
temperature in a furnace to prepare a preliminary sintered body. The 
preliminary sintered body was heated from a room temperature to 
1200.degree. C. at a constant rate of 3.degree. C./min while applying 
pressure of 196MPa in an atmosphere of argon gas and then kept at 
1200.degree. C. for 2 hours, by which the body was molded by using hot 
isostatic pressing (HIP). The resulting molding was cooled to a room 
temperature in the furnace. Thus, composite ceramic biomaterials were 
prepared (the third step). 
Each of the composite ceramic biomaterials had a relative density of 99% to 
99.5%. Each of the composite ceramic biomaterials was observed using an 
electron microscope. As the result of the observation, each structure of 
the biomaterials was shown in FIGS. 3 and 4. Further, fracture toughness 
was calculated in the same method as in Example 5. Further, three-point 
bending strength was measured according to the method of JIS R1601. The 
measured calcium phosphate crystal phases, three-point bending strength 
and fracture toughness are shown in Table 2. As is clear from Table 2, the 
composite ceramic biomaterials of this Example had higher bending strength 
than that of the conventional calcium phosphate/zirconia composite 
sintered body even when the zirconia content in each biomaterials of this 
Example was small. 
Example 8 
An aqueous solution containing 0.5 mol/l of Ca(NO.sub.3).sub.2 and an 
aqueous solution containing 0.5 mol/l of (NH.sub.4).sub.2 HPO.sub.4 were 
made to react with each other at a temperature in a range of from 
80.degree. to 90.degree. C. for 24 hours while mixing and stirring. If 
necessary, an aqueous solution containing 0.1 mol/l of NaOH was added 
dropwise to the resulting solution to adjust pH in a range from 7 to 10. 
The precipitated product was dried, subjected to rubber press molding 
under pressure of 196 MPa, heated from a room temperature to 1300.degree. 
C. at a constant rate of 3.degree. C./min in an electric furnace and kept 
at 1300.degree. C. for 2 hours to prepare a calcium phosphate crystal 
sintered body (the first step). The sintered body was identified according 
to the method of powder X-ray diffraction. As the result of the powder 
X-ray diffraction, it was found that the sintered body consists of apatite 
and .beta.-tricalcium phosphate. The calcium phosphate crystal sintered 
body obtained in the first step was placed in a ball mill and ground to a 
particle size of 500 .mu.m or less. The calcium phosphate crystal sintered 
body powder obtained above and .alpha.-alumina powder (mean particle 
diameter: 0.2 .mu.m) was placed in a ball mill in a volume ratio of 60 
(calcium phosphate crystal sintered body powder):40 (.alpha.-alumina 
powder). They were wet-mixed in the ball mill for several hours and then 
dried (the second step). The mixture obtained in the second step was 
placed in a graphite mold, heated from a room temperature to 1350.degree. 
C. at a constant rate of 3.degree. C./min while applying pressure of 30 
MPa and then kept at 1350.degree. C. for 2 hours, by which the mixture was 
sintered. Then, the sintered mixture was cooled to a room temperature in a 
furnace. Thus, a composite ceramic biomaterial was prepared (the third 
step). 
The composite ceramic biomaterial had a relative density of 96%. The 
composite ceramic biomaterial was observed using an electron microscope. 
As the result of the observation, the biomaterial had a structure as shown 
in FIGS. 3 and 4. Further, the composite ceramic biomaterial was formed 
into a shape of a 3.times.4.times.36 mm rectangular pillar and subjected 
to three-point bending strength test according to the method of JIS R1601. 
The three-point bending strength of the biomaterial was 270 MPa. 
As described above in detail, according to the present invention, there can 
be obtained an inorganic biomaterial excellent in strength and 
biocompatibility, having a structure in which portions constituted by 
crystallized glass or crystals of calcium phosphate excellent in 
bioactivity are dispersed in a skeleton or matrix constituted by crystals 
of partially stabilized zirconia and/or alumina showing high strength. 
Accordingly, the inorganic biomaterial is very useful as a biomaterial for 
artificial bones, dental implants, etc.