Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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BACKGROUND ~ND ~ETAILED EXPLANATION OF THE INVENTION:
The present invention relates to hydroxyapa-
tite, ceramic material comprising hydroxyapatite ceramic and a
process for preparing thereof. More in detail, the present
invention concerns a colourless and translucent ceramic material
of hydroxyapatite with a high density, a high purity and a high
thermal stability, a process for preparing the same and a com-
position useful as an implant material comprising of the ceramic
material and an organic binding material.
Hydroxyapatite is represented by the formula
Cal0(PO4)6(OH)2 or Ca5(PO4)3(OH), and is one of the inorganic
components of the hard tissues of living bodies such as bones,
teeth, etc.
The sintered material of synthetic hydroxyapatite
(hereinafter referred to as the ceramic material of '
hydroxyapatite'~-is, as has been'published, usable as an
implant material such as artificial dental root or artificial
bone closely resembling those of living bodies (for instance,
refer to Aoki and Kato, "Ceramic", 10(7): 469 (1975)), and it has
been given attention, particularly in recent years.
Naturally, it is preferable that the synthesized
ceramic material of hydroxyapatite resembles naturally occuring
hydroxyapatite in physical properties. That is, the
ceramic material of hydroxyapatite for use in living body
is-required to be colourless, to have a high density and to
be safe for living bodies.
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The purity concerning safety mentioned herein means
the physicochemical purity. In other words, the purity of the
ceramic material is determined by the facts that the material
does not contain, as far as possible, the elements other than
Ca, P or PO4, and OH which are the substantial elemental
components of hydroxyapatite; the Ca/P atomic ratio is close to
1.67 which is the theoretical value of hydroxyapatite and the
physical structure is as close as possible to that of pure
hydroxyapatite.
Among these factors, the defects in its physical
structure, if any, can be detected by the X-ray analysis, and
even in the case where its potential defects are-not possibly
detected, they may be detected cleaxly after treating the
specimen at a high temperature of about 1350C. The impurity
which is apt to be frequently contained in the product of
hydroxyapatite is whitlockite which has a lower value of Ca/P
and a different physical structure and is highly soluble in
aqueous solvent.
At any rate, the presence of these impurities and
structural defects in and of the ceramic material makes the
material coloured and eluted into within the living body to which
the material has been applied. According to thé one side of view
points, it may preferable to have an accelerated substitution of
the material with the tissues of. the living body due to the
above-mentioned elution, however, from the other side of view
- 1 ~ 6238~
points, safety, there may be unfavorable effects on the living
body due to the topical electrolyte imbalance caused by
the e]Lution and to the harmful action, etc~ of the eluted
substance itself.
Accordingly, it is strongly demanded that the
ceramic material of hydroxyapatite is highly pure as well as it is
almost colourless and in high density, and accordingly,
it is very important to offer its industrial process for preparing
such a favorable ceramic material. However, as will be
lo shown below, under present conditions, such a ceramic material
satisfying the above-mentioned demands has not been
completed yet.
A number of processes for synthesizing hydroxyapatite
have been proposed, for instance, by R.W. Mooney, et al., "Chem.
Rev.", 61:433(1961) and by Kanazawa,et al., "Xagaku no Ryoiki",
27:622(1973). However, there are ~ew disclosures which have
discussed the process for preparing a ceramic material comprising
the firi~g of the above-mentioned hydroxyapatite.
Amo~g them, Monreo reported that he has obtai~ed aceramic
material by compression-molding powdery hydroxyapatite and then
firing the thus molded material at a temperature of 1300C under
normal pressure (refer to "J. Dent. Res. n ~ 50,860(1971)).
However, since his ceramic material contains as high as 30~
by weight of whitlockite (alpha-calcium triphosphate), it cannot
be said the ceramic material of highiy pure hydroxyapatite.
The reason why the ceramic material of highly pure
1 J 62380
hydroxyapatite has not been available is considered to be the fact
that the hydroxyapatite used for making the material had not
the correct stoichiometrical composition or it had some structural
defects resulting in the by-production of whitlockite at the
time of firing, which has a different structure. In these con-
siderations, a trial has been carried out wherein the hydro-
xyapatite of the correct stoichiometric composition was synthe-
sized and then the hydroxyapatite was fired. However, the
hydroxyapatite hitherto obtained by the conventianal process for
synthesis was poor in sintering property and in thermal stabi~ity
due to its problems of purity, its own crystalline structure
and the morphological problem of its own crystalline particles.
Accordingly, the thermally stable ceramic material with a
high density and a high purity has not yet been obtained. For
instance, although the Japanese Patent Application Laying Open
No. 64199/77 o ffers a method of adding foreign-metals such as
MgO, etc. in order to improve the insufficient sintering property
of the precursor of the ceramic material having the
stoichiometrical composition of hydroxyapatite available by the
conventional synthetic process, the above-mentioned method was
based on the positive introduction of foreign elements for the
purpose o improving the sintering property of the precursor,
and accordingly, was completely different from the present
invention in its idea, as will be described later.
On the other hand, M. Jarcho used a method by Haek
(refer to Angew. Chem., 67:327 (1955) and Inorg. Synt., 7:63
1162380
(1963)) based on the following reaction:
3)2 + 3(NH4)2HPO4 ~ 4NH3 + H2O ~
S( )(P~4)3 lONH4NQ3
in which calcium nitrate is brought into reaction with diammonium
hydrogen phosphate while regulating the pH of the reaction
system at 10 to 12 with the addition of ammonia to synthesize
hydroxyapatite. The cake-like hydroxyapatite obtained by
filtrating the reaction mixture is then fired at a temperature
of 1100 to 1200C.
It was reported that a ceramic material of
hydroxyapatite having a mean size of crystals of about 0.2 to 3
microns and of 3.10 to 3.14 g/cm3 in density was obtained by
the above-mentioned procedures (refer to U.S. Pat. No. 4,097,935,
Japanese Patent ~pplications Nos. 40400/76, 94309/77 and ~J.
Material Sci.", 11:2027(1976)).
However, it was disclosed in the above-mentioned
literature that the ceramic material of hydroxyapatite was
partially decomposed to a by-product, whitlockite, in the case
where it was treated at a temperature of higher than 1250C
for more than one hour. That is, the ceramic ~aterial of
hydroxyapatite obtained by the above-mentioned procedures still
contains a structurally unstable factors, in other wordsr has
substantially structural defects, and accordingly, is poor in
thermal stability. In addition, there is a difficulty to
remove by-producing ammonium nitrate.
~ ` lJ623~
Further, as a different method for synthesizing hydroxy-
apatite, a method utilizin~ the following reaction of calcium
hydroxide with phosphoric acid has been disclosed:
( )2 3H3P04 ~ Ca5(P04)3(0H) + 9H O
The above-mentioned reaction is expected to develop
into an industrial method for producing hydroxyapatite of the
correct stoichiometric composition because of (1) not containing
any forelgn elements and (2) having only water as a by-product,
however, Mooney said in his article "Chem. Rev.", 61,433(1961)
lo that it was difficult to obtain the hydroxyapatite of stoichio-
metric composition (theoretical value of Ca/P atomic ratio of
1.67) by the above-mentioned reaction, and onl-y the hydroxyapatite
of Ca/P of 1.50 corresponding to calcium triphosphate was obtain-
able.
On the other hand, R. Wallaeys (refer to "Angew. Chem.
tParis) n ~ 7,808 (1952)) obtained the hydroxyapatite of Ca/P
atomic ratio of 1.61 to 1.67 by boiling the above-mentioned
reaction mixture after the reaction was over in order to make the
reaction proceed completely or making the reaction proceed to the
neutral point to phenolphthalein in a boiling state.
However, according to the results of trace-experiments
of the method of Wallaeys carried out by the inventors of the
present invention it was found that the dried material of filtered
cake of hydroxyapatite obtained by the Wallaeys's method was poor
in sintering property and accordingly, only a ceramic material
having a density of about 3.11 g/cm was obtained even by the
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hot-press method at a high temperature, and moreover, the thus
obtained material was coloured in blue after sintering. The
cause of colouring is not yet elucidated, however, it may be
considered to be due to some structural defects.as a ceramic
material in addition to the presence of a minute amount of im-
purities. .As mentioned above, it was clearly found that the
method of Wallaeys could not satisfy the purpose of the present
invention.
As has been described above, the publicly known ceramic
lo ~aterial of hydro~yapatite contains foreign elements for the
improvement of the sintering property of synthetic hydroxyapatite,
or has structural defects causing the poor thermal stability and
is coloured when sintered. In other words, under the present
conditions, a highly pure and highly stable ceramic material of
. a high density of hydroxyapatite suitable for application into
living bodies and its effective method for preparing thereof have
not been completed.
The inventors of the present invention, while taking
into consideration of the above-mentioned status quo, studied the
.20 relationship between the sintering property or the thermal sta-
bility of the ceramic material and the crystalline form and shape
ànd the structure of synthet.ic hydroxyapatite, and have found
that a ceramic material excellent in thermal stability, colour-
less, having a high purity and a high strength without any struc-l
tural defects which does not decompose to form whitlockite even
after heating for one hour at a temperature of 1350C is obtained
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I
11~238~
by firing a dried cake after filtration of synthetic hydroxyapa-
tite of the stoichiometric composition having a specified pro-
per~.ies, and they have arrived at the present invention.
It is an object of the present invention to provide a
filtered, dried cake of hydroxyapatite having a structure
possessing the three-dimensional order with an average opening
radius of 50 to 150 A and a pore cavity of Q.2 to 0.8 cm3/g,
said cake comprising, hydroxyapatite having an atomic ratio of
calcium to phosphorus of 1.67 to 1.6S and a dime-nsion including
lo a length of 150 to 1200 A, a width of 50 to 400 A, a ratio of
said length to said width of 3 to 10. Another object of the
invention is to provide a ceramic material comprising hydroxyapa-
tite ceramic having an atomic ratio of calcium to phosphorus of
1~67 to 1.69, an average crystal size of 4 to 20 ~, a density
Gf 3.14 to 3.16 g~cm and a thermal stability wherein whitlockite
-is not shown after said hydroxyapatite ceramic is heated for at
least one hour at a temperature of 1350C, said ceramic being
colourless or semi transparent. A further object of the inven-
tion is to provide an implant material comprising both ceramic
material of hydroxyapatite and a bonding material having a
biological acceptability to living body. A particular object of
the invention is to provide process for preparing hydroxyapatite,
comprising the steps of,
(a) converting powder calcium carbo~ate into calcium oxide
by thermal decomposing in an inert atmosphere at a tempearture of
800 to 1300 C for 0.5 to 10 hours,
(b) cooling the converted calcium oxide to a temperature
lowe hzm 500C in the inert atomosp~ere to obtain extremely
porous high reactive calcium oxide,
(c) slaking the cooled calcium oxide with water while
agitating under turbulent flow thereby to obtain fairly fine
calcium hydroxide mil~ of high purity,
(d) bxinging the obtained calcium hydrnxide into
reaction with an aqueous solution of phosphoric acid in an
inert atmosphere under turbulent flow, thereby to obtain
hydroxyapatite.
lo According to the present invention, that is, when an
aqueous emulsion of minute particles of calcium hydroxide formed
by bringing porous and minute particles of practically pure
calcium oxide into reaction with an excess amount of water is
brought into reaction with an aqueous solution of phosphoric
acid in an inert at~.osphere, a milky réaction mixture containing
the reaction product, hydroxyapatite is obtained.
After filtering the milky reaction mixture, the
separated cake is washed with water and dried to be an aggregate
of hydroxyapatite having the following properties:
Analytical value of an atomic ratio of Ca/P: 1.67 to 1.69,
Mean size of dimention of hydroxyapatite of
length : 150 to 1200 A
width : 50 to 400 A, and
ratio of lengh/width : 3 to 10.
Void: 0.2 to 0.8 cm3/g
Mean pore-radius: 50 to 150 A.
By firing the above-mentioned filtered cake,
the:aggregate of hydroxyapatite, a ceramic material
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of hydroxyapatite having the following physical properties is
obtained:
Analytical value of Ca/P : 1.67 to 1.69,
Mean crystal size : 4 to 20 microns, and
Density : 3.14 to 3.16 g/cm .
The fact that the mean crystal size of the thus obtained
material is larger than that of the conventional synthetic ceramic
material of hydroxyapatite means that the ceramic material
of the present invention is prepared from the purer raw materials
lo than those used for preparing the conventional materials. In
addition, the fact that even after firing of the aggregate of
hydroxyapatite at a temperature of 1350C for one hour, any
formation of whitlockite which is the decomposition product
of hydroxyapatite is not recognized this fact that some components
or ~tructural defect including the decomposition are not contained
therein and the aggregate is excellent in thermal stability.
The followings are the more detailed explanation of the
the present invention:
The porous and minute particles of calcium oxide for
use in the process of the present invention is obtainable by
thermally decomposing powdery calcium carbonate. As the raw
material, calcium carbonate is preferably in a high purity of
higher than 99.0%, preferably 99.8% and in a micro-fine state.
The conditions of thermal decomposition are: in an inert
atmosphere, at a temperature of 800 to 1300C, preferably 950 to
I ~62380
1200C, for 0.5 to 10 hours, preferably one to five hours. By
the clecomposition under the above-mentioned conditions, calcium
carbonate is converted to highly porous and reactive fine powder
of calcium oxide while leaving gaseous carbon dioxide free.
In this case of thermal decomposition, the milder
conditions of thermal decomposition lead to the remaining of
undecomposed calcium carbonate in the produced calcium oxide.
Not only it is difficult to remove the remaining calcium carbonate
in the produced calcium oxide, but also the remaining calcium
lo carbonate becomes to be a cause of the structural deffects and
the reduction of the thermal stability of the ceramic material
of hydroxyapatite which is one of the final products of the
present invention. In addition, in the case where the conditions
of thermal decomposition is more severe or in the case where
the product of the thermal decomposition is not cooled in an
inert atmosphere until the temperature of the product is fallen
to 500C, preferably to 200C, the porosity and the reactivity
of the thus produced calcium oxide are impaired. In this
connection, the inert atmosphere herein mentioned means the
atmosphere which does not contain any components inducing the
secondary reaction with the produced calcium oxide and calcium
hydroxide, such as gaseous carbon dioxide and ammonia.
It is effective to blow an inert gas such as nitrogen,
helium, argon, etc. into the system of thermal decomposition in
order to obtain the inert atmosphere because gasenous carbon
dioxide thus generated is successively removed from the system.
I 1 62380
The aqueous emulsion of minute particles of calcium
hydroxide of the present invention is, as mentioned above,
possibly produced by adding the above-mentioned calcium oxide
into a large amount of water in a state of high speed stirring
to provide turbulent flow under the above-mentioned inert
atmosphere. In this case, the amount of water which is mixed
with one part by weight of calcium oxide is not limited, however,
usually it is 10 to 100 parts by weight.
The above-mentioned reaction is carried out under a high
speed stirring, preferably at a relatively low temperature for
a relatively long time period and usually at 0 to 80C, preferably
0 to 50C, for 0.5 to 96 hours, preferably one to twenty four
hours.
The end point of the abo~e-mentioned reaction is
determined by X-ray diffraction analysis, wherein a part of the
reaction product is withdra~n as a specimen and the disappearance
of d200 in the X-ray diffraction pattern of the specimen is taken
as the sign of the completion of the reaction.
In addition, the mean size of particles of calcium
~o hydroxide prepared by the method of the present invention is 0.05
to 0.1 micron and it is far smaller than the mean size of calcium
hydroxide particles of one to ten microns, which are obtained
by dispersing commercial calcium hydroxide into water.
The above-mentioned emulsion of fine particles
of calcium hydroxide is the important requisite for obtaining the
1 16~380
hydroxyapatite with a favorable sintering property described
later.
The hydroxyapatite according to the present invention
is formed in a milky state by adding an aqueous solution of
phosphoric acid in an amount corresponding to Ca/P of 1.67 to
1.69 into the above-mentioned aqueous emulsion of ~inute particles
of calcium hydroxide in a state of high speed stirring under the
inert atmosphere to be brought into reaction.
In the preparation of the hydroxyapatite, it is
lo preferable that the stirring is still continued after completing
the reaction of formation of the above mentioned emulsion of
calci~m hydroxide, and the aqueous solution of phosphoric acid
is added successively into the system undér st~rring,
Phoæp~oric acid is usually made to be an aqueous one to
ten percent by weight solution and the solution is slowly added
to the above-mentioned emulsion. In this connection, the high
speed stirring referred herein means the stirring which brings
the state of the liquid in the reaction system into a turbulent
flow.
The reaction temperature is 0 to 50C. At a lower
temperature, the viscosity of the emulsion is so high
that the uniformal reaction becomes difficult, and at a
higher temperature, the sintering property of the abo~ie-mentioned
aggregate of hydroxyapatite is impaired. Thus, the reaction
temperature is an extremely important factor affecting the size
of crystals concerning the sintering property or affecting the
l 1 1 62380
easily sedimenting property which will be described later.
The reaction is usually carried out for 0.5 to 200 hours, pre-
ferably for 5 to 100 hours. The reaction mixture is highly
alkaline of pH of about 13 at an initial stage and the alkalinity
is gradually reduced to pH of 8 to 9 at the completion of the
reaction.
Although hydroxyapatite in the reaction system assumes
a milky state, it is excellent in sedimentability and easily
separable by filtration, microscopically the size of
lo the hydroxyapatite being, as has been described, usually of
50 to 400 A in width, 150 to 1200 A in length and the ratio of
length to width of 3 to 10.
m ese dimentions are clearly differ from those of the
plate-like crystal of about 200 A in width and about 200 A in
length obtained by the aforementioned reaction between calcium
nitrate and diammonium hydrogen phosphate. The easy sediment-
ability of the hydroxyapatite obtained by the process of the
present invention is considered to be due to such a size of
crystals, their shape and form and further to the state of
electric charge on the surface of the crystals. Moreover, these
factors presumably contribute the formation of the aggregate of
hydroxyapatite of the present invention, which has a favorable
sintering property.
T~e aggregate of hydroxyapatite according to the
present invention is obtained by filtering hydroxyapatite
obtained by the above-mentioned method to a water content
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I 1 ~2380
of about 0 to 2 % by weight. The thus obtained cake of aggregate
of hydroxyapatite has the following physical properties of:
said cake possessing a void ratio of 0.2 to 0.8 cm3/g and
pore radius of S0 to lS0 A, comprising hydroxyapatite having
a Ca/P atomic ratio of 1.67 to 1.69, crystal size of 50 to
400 ~ in width, lS0 to 1200 A in length, the ratio of width
~o length of 3 to 10, and these properties affect the specific
properties of the ceramic material of hydroxyapatite described
later.
lo The aggregate of hydroxyapatite according to the
present invention has a favorable sintering property and when
firined as it is, a ceramic material having an excellent
property is obtained as will be shown later.
Naturally, conventional methods for molding and
firing the aggregate are applicable in preparing the ceramic
material according to the present invention, fro instance, the
aggregate may be molded by using a metal or rubber mold and
then baked, or the aggregate may be molded and fired by a hot
press method or the molded cake can be fired under a reduced
pressure.
In addition, a ceramic material highly translucent,
highly pure, highly dense and highly stable thermally is also
available by firing under reduced pressure after pressure-molding
the aggregate of hydrioxyapatite according to the present
invention. The condition of baking are: at a temperature of
850 to 1400 C, preferably 1250 to 1400C , for o.5 to 5 hours,
preferably 1 to 3 hours. In addition, it is noticed that
1 1¢2380
the growth of the crystals of the hydroxyapatite of the
present invention during the sintering by firing is remarkably
larger than that of the conventional hydroxyapatite. Such a
property is presumably due to the above-mentioned specific
prop,erties of the aggregate of hydroxyapatite and its favorable
sintering property.
The ceramic material of hydroxyapatite prepared
according to the present invention has the following properties
of:
a) analytical Ca/P : 1.67 to 1.69,
b) mean size of crystals: 4 to 20 microns,
c) density : 3.14 to 3.16 g/cm3, and
d) thermal stability : no formation of whitlockite
is recognized after heating
for one hour at 1350C.
While the publicly known ceramic materials of
hydroxyapatite form whitlockite when heated at a temperature
of higher than 1200C or 1300C, the ceramic material according
to the present invention is extremely stable at a temperature
of higher than 1300C, and the size of crystals of the material
according to the present invention is larger than that of the
publicly known ceramic material of hydroxyapatite, the former
being clearly differentiated from the latter.
The ceramic material according to the present
invention is excellent in stability whithin the living body
presumably due to the absence of structural defects. In addition,
the ceramic material of the present invention can be prepared
2 3 8 0
by tlle successive steps of drying and firing in the order, cake
obtained by filtration of the afore-mentioned reaction solution.
: The thermal stability of the above-mentioned ceramic
material is confirmed by the determination of X-ray diffraction
pattern after sintering the material for one hour at a temperature
of 1350C.
As has been described, according to the present inven-
tion, the hydroxyapatite excellent in sintering property and
stoichiometric in composition is easily available by bringing a
lo specified calcium hydroxide into reaction with phosphoric acid
under mild conditions, and so the process of the present invention
is extremely effective as an industrial method. Moreover, the
ceramic material of hydroxyapatite obtained by the present
invention is chemically and physico-structurally pure and stable
enough to be used within living bodies and useful as an implant
material such as artificial dental roots and artificial bones.
In the next place, in the practical application of the
ceramic material of hydroxyapatite as an implant material, par-
ticularly as an artificia~ dental root material, the material
can be applied by the following method. The ceramic material
may be solely utilized for an implant material.
The implant material according to the present inventionis prepared, in consideration of its processability, easiness of
handling and mechanicai strength, by molding the mixture of the
above-mentioned hydroxyapatite of a particle size smaller than
1000 microns, preferebly 0.01 to 100 microns and an organic
l ) 1 62~8~
matrix, in a publicly known pxocess, or by impregnating the organic
matrix into the porously formulated ceramic material of the
present invention. In the process of preparing the implanting
material, it is important that the ratio of surface area of the
hydroxyapatite phase of the implant material to that of organic
matrix of the implanting material in the adhering surface to the
bone is processed to be 5 : ~5 to 70 : 30, preferably 10 : 90 to
60 : 40. In the case where the phase of hydroxyapatite occupies
more than 70% of the surface area of ~he above-mentioned adhering
lo surface, the adhesion to the natural bone is too large necessi-
tating the impairment of the natural bone when the implanted mate-
rial is to be removed. However, in the case ~there the above-
mentioned phase occupies less than 5% of the surface area of the
adhering surface, the implanted material is apt to be naturally
removed. The above-mentioned ratio has been decided in conside-
raiton of the durability and adhesiveness of the artificial
dental root.
An organic polymeric binding material is referred to
the organic matrix. As the organic material, since it is nece-
ssary to use a non-deteriorative resin for the long term implan-
tation in living body without degrading the cells of the living
body, one or a mixture of more than one substance selected from
th~ group consisting of polycondensate of bisphenol A and glycidyl
methacrylate, poly(methyl methacrylate), poly(2-hydroxyethyl
methacrylate), poly(triethyleneglycol dimethacrylate), polyethy-
lene, polysulfone resin, polyamide resin, polyester resin,
I J ~380
poly(tetrafluoroethylene), poly(vinylidene fluoride) and poly-
carbonate resin, or copolymers comprising more than one monomer
which constitute the above-mentioned polymers is pre~erable.
In addition, the ceramic material of the present
invention is used as a com~onent of t~e ~atexial usable within
living body such as the co-existent-type sintered material with
an organic substance such as cellulose, collagen, etc., the
porous material prepared by boring, the composition prepared by
impregnating an organic resin, or impregnating and polymerizing
lo an organic monomer into the porous material, the composite of
the powdery ceramic material with an organic or inorganic
matrix or their combination.
Moreover, the hydroxyapatite according to the present
invention can be used as a filling material for the chromatogra-
~phic column, other than the usé of them as the baked material.
The present invention will be further described in more
detail while referring to non-limitative examples as follows
ExAMæLE 1:
Into an electric fur~ace under a flow of gaseous nitro-
gen of a flow rate of one litre/min, 600 g of powdery calcium
carbonate of reagent grade (G.R.) were introduced and heated to a
temperature of 1000C at a rate of 3C/min. After heating for
3 hours at 1000C to decompose the material, it was cooled under
the flow of gaseous nitrogen to 200C at a rate of one litre/min tc
obtain 335 g of calcium oxide with a yield of 99.7%. It was
confirmed that the thus obtained calcium oxide did not contain
~ 1 62380
calc:Lum carbonate, by X-ray diffraction analysis. The purity
of the product determined by EDTA-method was 99.8~. According
to microscopical observation, the crystal shape of the obtained
calcium oxide was similar to that of the raw material, calcium
carbonate, and the crystal of the calcium oxide was porous.
Into a 17-litre three necked porcelain enameled tank
provided with a heater, a temperature-controller and a thermometer,
6 litres of de-aired distilled water were introduced, the atmos-
phere in the tank was substituted by nitrogen while agitating at
lo a revolution of 350 rpm. Then, 280 g (S mol) of the above-
mentioned calcium oxide were slowly added within 10 minutes, and
then made to react for 5 hours at 50C, and ~or 15 hours at room
temperature under the atmosphere of gaseous nitrogen to obtain an
emulsion o calcium hydroxide of 0.075 micron in mean particle
diameter.
In the next place, while keéping the thus obtained
emulsion at a turbulent flow by agitation of 3000 rpm, three mols
of an aqueous 3.5% solution of phosphoric acid prepared from
85% phosporic acid, were added to the emulsion wi~in 30 min,
and then the reaction was continued for 48 hours at a temperature
of 20C. After the reaction was over, the thus obtained suspen-
sion was filtered under pressure, the residue being washed with
water and dried at 150~C for 16 hours.
Thus, 497 g of the dried material of filtered cake of
hydroxyapatite were obtained and named as Specimen No. 1, the
properties of the dried material, that is, the aggregate of
~' ~
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1 ~2380
hydroxyapatite of the present invention being shown in Table 1.
EXA~PLE 2:
Another aggregate of hydroxyapatite of the present
,invention named as Specimen No. 2 was prepared by the same proce-
dure as in Example 1 except for the r'eaction condition of a tem-
perature of 40C and for 24 hours as compared to the temeperature
of 20C and for 48 hours in Example 1. The thus obtained Specimen
No. 2 showed the properties also shown in Table 1.
COMPARATIVE ELE 1:
An aqueous dispersion prepared by adding S mols of
powdery calcium hydroxide of reagent grade (G.R.), into 6 litres
of de-aired distilled water was introduced in the porcelain
enamaled tank used in Example 1, and while agitating at a revolu-
tion of 3000 rpm under the substituted nitrogen atmosphere by a
,, , flow of gaseous nitrogen, 3 mols of an aqueous 3.5% solution of
phosphoric'acid were slowly added to the dispersion. After
carrying out a reaction at a temperature of 70C for 24 hours,
. the same procedures as in Example 1 were taken to obtain an
aggregate of hydroxyapatite named as Specimen No. 3, the properties
20 of Specimen No. 3 being shown also in Table 1.
COMPARATIVE EXA~LE 2:
Another aggregate of hydroxyapatite named Specimen No. 4
was prepar~d by the following publicly well known method and its
properties were also shown in Table 1:
. Diamm,onium hydrogen phosphate ~160 g) was dissolved into
distilled water (3 litres) and an aqueous 28% ammonic solution
` I J 62380
(1700 ml) was added to the above-mentiond solution to adjust the
pH at 11 to 12. Distilled water was further added to it to
dissolve the thus precipitated diammonium hydrogen phosphate.
This solution was poured into a solution prepared by dissolving
477 g of calcium nitrate into 188 ml of distilled water adjusted
to pH of 12 by an addition of 60 ml of a concentrated aqueous
ammoniac solution and kept at a temperature of 20C under a high
speed stirring within 30 min. The mixture was further diluted
with distilled water until the whole volume arri~ed at 7.0
lo litres. After boiling the thus diluted solution for 10 min, it
was left at room temperature for 20 hours.
The thus produced gelatinous material was filtered by
Buchner's funnel under slightly reduced pressure, washed with
water while kept on the filter, and when cracks appeared on the
surface of the filtered cake, the higher vacuum was applied for
2 hours. The filtered cake was dried at 150C for 15 hours to
obtain 197 g of an aggregate of hydroxyapatite.
E~MPLE 3:
. .
Respective specimens of aggregates of hydroxyapatite
obtained by Examples 1 and 2 and Comparative Examples 1 and 2
were placed in an electric furnace and heated to a temperature of
1350C at a rate of 3~C/min. After keeping at the temperature
for one hour, it was removed from the furnace to be cooled to
room temperature. The thus obtained ceramic materials had their
respective specific properteis shown in Table 2.
Respective ceramic materials were crushed to pieces of
` 1 1 ~2380
about 5 mm in size, and after immersing the pieces into an 0.1%
aqueous solution of neutral red at room temperature for 15 hours,
the pieces were washed with water and dried to examine the colo-
ration of their respective surface of crushing. The results of
the examination showed that although no coloration was observed
on Specimens No. 1 and No. 2 of Examples 1 and 2, a coloration
was observed on Specimen No. 4 of Comparative Example 2. Since
Specimen No. 3 showed a blue colour before immersing into the
solution of the dye-staff, it could not be compared. From these
results it was clear that the ceramic material of the present
invention differs fxom the publicly known ceramic material.
EXAMæLE 4:
Twenty grams of the ag~regate of hydroxyapatite of the
present invention obtained in E~ample 1, Specimen No. 1, were
fired at a temperatue of 125~C under a reduced pressure of 10 2
mmHg for one hour, and cooled to 200C under the reduced pressure
to prepare a ceramic material. The thus prepared ceramic
material was white in colour, transparent and showed a density
of 3.16 g/cm3 which is the theoretic~l value.
EXAMPLE 5.
Sintering test was carried out on the aggregates of
hydroxyapatite of Sepcimen No. 1 of Example 1 and Specimen No. 4
of Comparative Example 2. Each 20 g of Specimens was baked at
each tempera~ure of 1200, 1250, 1300 and 1350C for one hour,
and the amount of whitlockite formed within the fired material
was determined by X-ray diffraction analysis. The results are
I 1 62380
shown in Table 3. As is seen in Table 3, the difference between
the ceramic material according to the present invention and the
publicly known ceramic material is clear.
EXAMPLE 6:
The ceramic material prepared in Example 3 from
Specimen No. 1 was pulverized and the fraction passed through a
sieve of 200 mesh was collected. The thus collected powdery
material was mixed with a 6 : 4 by weight mixture of copolymer of
bisphenol A and glycidyl methacrylate and monomeric methyl metha-
lo crylate at a volume ratio (calculated by the respective weightsand densities of both components) of 1 : 1, and after the further
addition of 0.05% by weight Gf benzoyl peroxide as a polymerizatio
initiator, the mixture was mixed to be uniform, and after pouring
into a glass tube of S mm in inner diameter and de-bubbling, a
polymerization was carried out at 80C for 2 hours on the mixture
to obtain a composition of hydroxyapatite. After processing the
co~position into a cylinder of 3.5 mm in diameter and 10 mm in
length, it was implanted into the drilled hole of the jaw-bone
of an adult dog just after the tooth extraction. The implanted
material was not naturally removed even after 3 months of im-
plantation. After 6 months of implantation, the jaw-bone of the
dog was cut off to be examined by an optical microscope and
roentgenography. It was found that the implanted part was normally
healed and a new bone-tissue was produced within the gap between
the implanted composition and the jaw-bone.
I 1 62380
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