Implant material composition, preparation thereof as well as uses thereof and implant product obtainable therefrom

The invention relates to an implant material composition, its preparation, and its use for restoring bone tissue in a human or animal body. The composition comprises a particulate biocompatible bone tissue substitute material distributed in a bioacceptable mixture of (a) a water-based liquid, (b) a monoglyceride, and optionally (c) a triglyceride. The ingredients (a), (b) and (c) form an L2-phase or a lamellary liquid crystalline phase, and are present in such proportions within said phases that they are capable of being transformed into a cubic liquid crystalline phase or a reversed hexagonal liquid crystalline phase when contacted with an aqueous liquid. The phase conversion imparts to the composition such a high viscosity that it functions as an implant material as defined.

Technical Field 
The present invention relates to the field of implant materials for 
restoring bone tissues in humans or animals. More specifically the 
invention relates to a new, easily and consistently applicable implant 
material composition, to a method of preparing said composition, to uses 
of the same as well as to an implant product obtainable from said 
composition. 
BACKGROUND OF THE INVENTION 
The implantation of materials of different types in the human or animal 
body in order to replace bone portions which have been worn out or which 
have deteriorated due to diseases of other reasons is steadily increasing. 
In order to eliminate the risk of having immunological diseases different 
synthetic materials have come into use within this technical field. As 
examples of suitable materials used for said purpose there can be 
mentioned a metal like titanium and minerals and ceramics such as 
high-purity alumina, tricalcium phosphate and calcium aluminate. In the 
absence of risks of immunological diseases fragments from natural bone may 
also be considered in this respect. Especially preferred materials are, 
however, materials having a chemical composition and crystal structure 
similar to those of the materials that are built up by the living 
organism, such as calcium hydroxyapatite. One synthetic material of this 
type which has come into use for restoring bone tissue is the 
polycrystalline mineral calcium hydroxyapatite and particularly the 
non-resorbable type thereof which has the formula Ca.sub.10 
(PO.sub.4).sub.6 (OH).sub.2 and which is also one of the main constituents 
of the bones in the body wherein the organic matrix of the bone tissue is 
received. Said material serves as a "climb structure" for bone tissue and 
prevents connective tissues from growing into the region of the bone which 
has been destroyed and is to be restored. 
Calcium hydroxyapatite of the above-mentioned formula is manufactured by 
Asahi Optical Co., Ltd., Tokyo, Japan, and is marketed under the trade 
mark AERAM.RTM., which may be registered in some or all of the 
designated states. The material is available as performed pieces, such as 
tooth roots, bones for the middle ear and elements for brain surgery and 
also as a raw material in the form of blocks, which can be worked by 
sawing, milling and boring and which are of different shapes and 
porosities, and as a particulate material in the form of granules, i.e. 
particles of regular or irregular shapes, the sizes of which are of the 
orders from 0.1 mm to some millimeters. The blocks are used for large 
implants, preferably after having been properly shaped, and the granules 
are used for filling bone cavities as well as in combination with said 
blocks. Thus, since calcium hydroxyapatite is a hard and brittle material 
as most ceramics are, it is difficult to impart to the blocks the exact 
shapes needed for the actual implantations, by cutting or otherwise 
working the blocks, and therefore said granules are used in combination 
with the shape block pieces to fill out gaps or spaces existing between 
the shaped block pieces and the surrounding intact bone tissues. 
In most cases the above-mentioned granules or particles are mixed with 
blood or a physiological saline solution in order to obtain a mass that is 
easier to apply to the desired site of the bone and to eliminate surface 
tension phenomena when applying said granules or particles to the bone. A 
major drawback to this material or technique is, however, that such a mass 
is not easily properly confined within the bone cavity referred to. 
Furthermore, when the mass has been applied to the bone, blood that may 
come from adjacent bleeding portions of the body or any other secreted 
body fluid will dilute the particulate mass and may even carry away the 
material from the site of application. 
The primary object of the present invention is to overcome last-mentioned 
drawbacks and to provide an implant material which can be easily and 
consistently applied to the desired site of action, i.e. where the bone 
tissue restoration is to be made. More specifically, this means that the 
new implant material according to the present invention is capable of 
resisting dilution and any forces tending to carry away the material from 
the place of application. 
These advantages with the present invention will be explained more in 
detail below as will also other objects of the invention as well as 
additional advantages therewith. 
SUMMARY OF THE INVENTION 
The primary object of the invention referred to above is achieved according 
to a general aspect thereof by providing an implant material composition 
for restoring bone tissues in a human or animal body, which composition 
essentially comprises or consists of a solid biocompatible bone tissue 
substitute material distributed in a bioacceptable mixture of (a) a 
water-based liquid, and (b) a monoglyceride or a vegetable or animal oil 
containing such a monoglyceride, and optionally (c) a triglyceride or a 
vegetable or animal oil containing such a triglyceride, where said 
ingredients (a), (b) and optionally (c) are present in the form of an 
L2-phase or a lamellary liquid crystalline phase, and where said 
ingredients are present in such proportions that said L2 or said lamellary 
phase is capable of being transformed into a cubic liquid crystalline 
phase or a reversed hexagonal liquid crystalline phase when coming into 
contact with or being contacted with an aqueous liquid. 
According to one embodiment of the invention, an implant material for 
restoring bone tissue is provided comprising a particulate biocompatible 
non-organic bone tissue substitute and a mixture of an aqueous liquid and 
a monoglyceride, which material remains in the liquid phase below a 
predetermined temperature. 
The invention also relates to a method of preparing the above-identified 
implant material composition. Said method essentially comprises forming 
the L2 or lamellary liquid crystalline phase of said ingredients (a), (b) 
and optionally (c), and then distributing the bone tissue substitute 
material therein. According to one embodiment then, a method for preparing 
the implant material for restoring bone tissue comprises the steps of 
mixing a particulate biocompatible non-organic bone tissue substitute with 
a mixture of an aqueous liquid and monoglyceride which remains in the 
liquid phase below a predetermined temperature. 
Moreover, the present invention provides a method of restoring lost bone 
tissue in a bone of a human or animal body, which comprises applying the 
implant material composition as defined above to the surface of any bone 
or bone cavity where lost bone tissue is to be restored and allowing said 
composition to come into contact and/or contacting the same with an 
aqueous liquid in such an amount that said composition will be transformed 
or converted into the corresponding cubic liquid crystalline phase or the 
corresponding reversed hexagonal liquid crystalline phase. 
According to one embodiment, the procedure for restoring lost bone tissue 
in a bone in a human or animal body comprises the steps of applying to the 
surface of the bone an implanted material of low viscosity comprising a 
particulate biocompatible non-organic bone tissue substitute, and a 
mixture of an aqueous liquid and a monoglyceride remaining in the liquid 
phase below a predetermined temperature, said application being below the 
predetermined temperature, and then bringing said implant material into 
contact with the aqueous liquid to change the phase of the material to a 
cubic liquid phase. The material thus forms a well confined plastic mass 
of high viscosity. 
The invention also related to the composition as defined above, as to all 
preferable embodiments thereof, for use as an implant material composition 
for restoring bone tissue in a human or animal body. 
Furthermore, the invention relates to the use of the above-mentioned 
composition for the manufacture of a product or preparation to be used as 
an implant material for restoring bone tissue in a human or animal body. 
All preferable embodiments described above in connection with the implant 
material composition are equally applicable to this aspect of the 
invention. 
Finally, the invention also provides the restored implant bone tissue 
product per se, i.e. the product that is obtainable or obtained by contact 
between the implant material composition as defined above with an aqueous 
liquid, said product being in the state of a cubic liquid crystalline 
phase or a reversed hexagonal liquid crystalline line phase. All 
preferable embodiments disclosed above are applicable also to this aspect 
of the invention. 
As was mentioned above, the major advantage of the present invention is 
that the handling of the bone substitute material will be considerable 
facilitated and that particles thereof are prevented from escaping from 
the application site. If this would happen the particles could cause 
irritation or complication at other places of the body. 
Another advantage in connection with the invention is that the composition 
can be sterilized and can be stored in closed packages without any changes 
of properties. 
Other advantages could be gathered from the present specification or should 
be obvious to a person skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION 
The biocompatible bone tissue substitute material used according to the 
present invention generally is the same bone tissue substitute material 
that has been previously used within this technical field, as was 
mentioned above when describing the background of the invention. Thus, 
said material generally is a non-organic material in any particulate form, 
e.g. granular form. Moreover, it is biocompatible in the general sense of 
said term. 
In other words the general, known principles as to the choices of 
biocompatible bone tissue substitute materials can be utilized when 
performing the present invention, but according to a preferably embodiment 
of the invention, said bone tissue substitute material is selected from 
the group consisting of a mineral, ceramic or metal. 
Preferable embodiments of minerals or ceramics are calcium hydroxyapatite, 
alumina, tricalcium phosphate and calcium aluminate, while the dominating 
and preferable metal is titanium. 
Especially preferably is calcium hydroxyapatite, particularly the 
non-resorbable type thereof which has the formula Ca.sub.10 
(PO.sub.3).sub.6 (OH).sub.2. The main reason therefor is that said 
compound or mineral is a natural and major constituent of the bones in the 
body wherein the organic matrix of the bone tissue is received. 
The bone tissue substitute material is distributed in a mixture of the 
above-mentioned ingredients (a) and (b), optionally also in the presence 
of (c), which mixture forms an L2-phase or a lamellary liquid crystalline 
phase. In this context the term "distributed" should be interpreted in a 
broad sense and generally means spread out in any manner throughout said 
L2 or lamellary liquid crystalline phase. Expressed in other ways the bone 
tissue substitute material can be said to be dispersed or slurried in any 
of the two phases referred to. 
A major feature of this aspect of the invention thus is that the 
ingredients (a), (b) and optionally (c) (when present) are present in such 
amounts or proportions and conditions that they form an L2-phase or a 
lamellary liquid crystalline phase. In this context, it should be noted 
that said expressions "L2-phase" and "lamellary liquid crystalline phase", 
respectively, are well known to a person skilled in the art and that any 
more detailed descriptions thereof should not be needed. Rather, 
information thereabout can be found in the technical literature, and 
especially with reference to the nature of the L2-phase, reference is made 
to PCT publication WO 88/00059 and the literature mentioned therein. Thus, 
although said PCT publication discloses the use of an L2-phase for a 
completely different purpose, the principles and information found therein 
with reference to the L2-phase and also with reference to the lamellary 
liquid crystalline phase are equally applicable to said phases in 
connection with the present invention. For instance, said PCT publication 
discloses that the exact composition of the L2-phase or the lamellary 
liquid crystalline phase can be found in the prior art, e.g. from a 
ternary phase diagram. An example of such a phase diagram is also shown in 
the publication. 
From such a diagram it can also be gathered that the L2-phase is a liquid 
single-phase with water-aggregates in a hydrocarbon-continuous medium. 
From the above-mentioned it can also be gathered that the mixture forming 
said L2-phase or lamellary liquid crystalline phase can be a binary system 
of (a) and (b) only, or alternatively, a ternary system where ingredient 
(c) is also present. In both cases, however, the exact compositions to 
have the desired phases can easily be determined by a person skilled in 
the art, e.g. by means of a ternary diagram of the type referred to. 
However, for the purposes of the present invention it is not sufficient to 
provide such proportions between the ingredients (a), (b) and optionally 
(c) that said L2-or lamellary phase is obtained. According to another 
important feature of the invention, the proportions between the 
ingredients present also have to be selected properly such that the 
composition obtained is within such specific regions or domains of the 
L2-phase or lamellary liquid crystalline phase that when the composition 
is in contact with or is contacted with an aqueous liquid it has to be 
capable of being transformed into the cubic liquid crystalline phase or 
the reversed hexagonal liquid crystalline phase. Also these two phases are 
well known to a person skilled in the art and therefor further information 
in this respect can be obtained from the prior art. PCT publication No. 
W088/00059 referred to above gives some information also in this context, 
but especially with reference to the cubic liquid crystalline phase 
reference is made to European Patent specification No. 126,751. This 
European Patent specification discloses the use of the cubic liquid 
crystalline phase for completely different purposes, but as was mentioned 
in connection with the PCT publication, said European Patent specification 
is rather detailed as to the nature of the cubic liquid crystalline phase 
or the reversed hexagonal liquid crystalline phase, which details are 
equally applicable per se to the present invention. 
Thus, it can be gathered that the exact composition for which a cubic 
liquid crystalline phase or a reversed hexagonal liquid crystalline phase 
is obtained is easily determined by the skilled artisan in a manner known 
per se, e.g. from a ternary phase diagram. From such a phase diagram one 
can also easily see where the starting compositions of the L2-phase or the 
lamellary liquid crystalline phase have to be to obtain the corresponding 
cubic liquid crystalline phase or reversed hexagonal liquid crystalline 
phase by mere addition of water or other aqueous liquid. 
The basic principle of the present invention and which is utilized for the 
specific purposes defined herein, which is not in any way disclosed or 
suggested in any prior art known by us, is that the starting L2-phase or 
lamellary crystalline phase has the ability to change at a constant 
temperature its state from a liquid condition to a gel-like structure 
having high viscosity, solely by swelling in the water-based liquid. By 
mixing the bone tissue substitute material with the mixture forming said 
L2 or lamellary liquid crystalline phase the bone tissue substitute 
material will form together with any of said two phases a toothpaste-like 
mass or similar mass of a relatively low viscosity, which can easily be 
applied to a bone cavity or to a bone with an implant body mounted therein 
or thereupon by smearing the mass onto the surface of said bone or the 
surface of said bone and said implant, respectively. The viscosity of the 
mass will then be temporarily increased due to the increased temperature 
at the application site, but when the mass will come into contact with 
body fluid, such as blood or the humidity from soft tissue, or any other 
aqueous liquid, it will harden in a very short time, generally in a few 
seconds, to form a moldable well-confined plastic body. This sudden change 
in the viscosity of the implant material composition is due to the 
formation of the cubic liquid crystalline phase or the reversed hexagonal 
liquid crystalline phase when the material referred to is brought into 
contact with any body fluid or any other liquid present on or supplied to 
the site of application of the material, said material being a precursor 
for the formation of the cubic liquid crystalline phase or the reversed 
hexagonal liquid crystalline phase. In other words the phase conversion 
referred to is utilized in a completely new manner and for a completely 
new purpose, by which the previously known disadvantages within this 
specific technical field can be reduced or more or less completely 
eliminated. 
In addition to the fact that the mixture of (a), (b) and optionally (c) 
should of course be bioacceptable, i.e., must not cause any significant 
side effects in contact with living cells or organisms, it could be added 
that generally the viscosity considerations as to the different phases 
refer to temperatures at or around normal body temperatures, as the 
composition is intended for use in contact with the body. This generally 
means that the viscosity of the starting phase as well as that of the 
transformed phase should be selected, preferably by choice of materials, 
so as to be proper, i.e. liquid, below a temperature of about 40.degree. 
C. for the intended purpose. More specifically this means that preferable 
embodiments of the three ingredients (a), (b) and (c) are as follows. 
The water-based liquid (a) is any liquid wherein water is the major or 
dominating part. This means that pure water or an isotonic salt solution 
is preferably utilized, but if advisable for any reason, any aqueous body 
fluid or other aqueous liquid may be used. 
The monoglyceride (b), which can be used in the form of one single 
monoglyceride or as a mixture thereof, generally is a monoglyceride of an 
unsaturated fatty acid. Preferably said unsaturated fatty acid is an 
unsaturated C.sub.16 -C.sub.22 -fatty acid. An especially preferably 
embodiment thereof is a C.sub.18 -fatty acid, particularly monoolein. Said 
monoolein, which is the glyceride of oleic acid, is preferably utilized in 
the form of 1-monoolein or a mixture of 1-monoolein and 2-monoolein, said 
mixture preferably being an equilibrium mixture thereof. However, often it 
is not necessary to utilize the monoglyceride per se. Instead any 
vegetable or animal product containing the same, such as vegetable or 
animal oil containing the desired monoglyceride, can be used, which may 
even by a preferred embodiment. 
The triglyceride when used as ingredient (c) generally is a triglyceride of 
an unsaturated fatty acid. As in connection with the monoglyceride, said 
triglyceride is preferably a triglyceride of an unsaturated C.sub.16 
-C.sub.22 -fatty acid, more preferably a C.sub.18 -fatty acid. The 
triglyceride may not have to be utilized as such, but rather it may be 
preferable to use any natural product containing the same, such as any 
vegetable or animal oil containing the desired triglyceride. A preferable 
example of such a natural product is soybean oil. Furthermore, mixtures of 
triglycerides may be utilized if desired. 
Although the specific ratios between the ingredients of the mixture of (a), 
(b) and (c) (if present) are individually determined for each specific 
case, e.g. from a ternary phase diagram, preferable embodiments with 
reference to such compositions, mainly for viscosity reasons, are the 
following. 
A preferable weight ratio of monoglyceride (b) to water-based liquid (a) is 
within the range of about 97:3-85:15, a range of about 97:3-95:5 being 
especially preferable in many cases. 
Especially in a case where a ternary system is used, preferable weight 
percentages of the ingredients, based on the total weight of (a)+(b)+(c), 
are about 2-15 percent of the water-based liquid (a), about 80-98 percent 
of the monoglyceride (b), and about 0-12 percent of the triglyceride (c). 
A preferable range of (a) is within 2-8%, especially 3-5%, while a 
preferable range of (b) is 85-98% or 80-90%. If present, (c) is preferably 
used within the range of 2-12%. A specific, interesting weight ratio 
within the above-mentioned range is about 5:85:10, i.e. expressed as 
(a):(b):(c). 
Generally, although the bone tissue substitute material may be a minor 
volume constituent, the volume ratio of bone tissue substitute material to 
the total of (a) plus (b) plus (c) (when present) is within the range of 
1:1-5:1, a range of about 1:1-3:1 being especially preferable for many 
applications. The optimum ratio, especially in the case of calcium 
hydroxyapatite, is around 3:1 by volume. 
If the monoglyceride or triglyceride is not in the liquid state at the 
temperature where said L2 or lamellary liquid crystalline phase is formed, 
any one thereof is generally melted before the water-based liquid is added 
thereto. 
As concerns the conditions for forming an L2 or lamellary liquid 
crystalline phase, reference is made to the prior art, and with reference 
to the distribution of the bone tissue substitute material therein, 
reference is made to the specification above. Thus, any suitable method of 
distributing a solid material in a phase of the type referred to can be 
utilized. 
The preferable embodiments described above in connection wit the implant 
material composition are equally applicable to the method according to the 
invention of preparing said composition. 
The starting L2 or lamellary liquid crystalline phase is preferably chosen 
so as to have a viscosity which enables the use of a conventional one-way 
syringe, the low viscosity implant material being received by the syringe 
and being ejected therefrom to the region of the bone where the mass is to 
be applied. 
Irrespective of the method of application, however, the applied composition 
changes its phase to a cubic liquid crystalline phase or a reversed 
hexagonal liquid phase in contact with the aqueous liquid as defined 
above, a well-confined plastic mass of high viscosity being formed at the 
site of application. 
After said phase conversion, the applied material may be given the final 
form at the application site by a plastic working of the material. The 
implant material can also be fixed by being covered with surrounding soft 
tissue which is closed by suturing. 
Although the method just referred to has been described and will be more 
specifically described below as a method of shaping the implant product at 
the ultimate site of application, it is also within the scope of the 
invention to make a preshaping of the product outside the body in any 
suitable mode by bringing the implant material composition into contact 
with the water-based liquid and then making the final shaping and fixing 
in the desired bone cavity. 
The preferable embodiments described above in connection with the implant 
material composition are equally applicable to the method of restoring 
lost bone tissue just described. 
The invention will now be described with reference to the accompanying 
drawings, which show non-limiting embodiments of the invention only. 
An ideal monoglyceride for use in connection with the present invention is 
oleic acid, inter alia because it is not easily oxidized, which might 
cause formation of toxic substances. Reference is made to the diagram 
shown in FIG. 1, which is a phase diagram for a mixture of monoolein and 
water indicating the relationship between temperature and water content 
related to the existence of the phase wherein the monoolein-water mixture 
is liquid and the phase wherein the monoolein-water mixture has a gel-like 
structure with high viscosity. If the water phase contains salts of 
physiological concentrations or proteins from the blood or lymph system, 
the diagram will not be changed. 
Thus, starting from monoolein having a water content of about 4% (weight by 
weight) the phase is liquid in the temperature range from about 20.degree. 
to 40.degree. C., i.e. below the body temperature (about 36.degree. C). 
This phase is indicated as L2 because the water molecules thereof form a 
reversed micellular structure. After swelling in contact with water or any 
other aqueous liquid, such as blood or the humidity of soft tissue, the 
viscous phase D ("D" stands for diamond glitter, which is the water canal 
structure of the phase) will be obtained, which is the cubic liquid 
crystalline phase. The other phases shown in FIG. 1 are: L.sub..alpha. 
=lamellary liquid crystalline phase; H.sub.II =reversed hexagonal liquid 
crystalline phase; and G=gyroid, which is also a cubic liquid crystalline 
phase. 
An implant material of the D phase of monoolein in soft tissue and in bone 
tissue has been found to be perfectly biocompatible therewith and to cause 
no changes of inflammatory character. Probably this is due to the fact 
that monoolein is present in the body and will be exchanged with esterases 
(lipases) in the normal lipid metabolism. Another favorable factor 
probably is that the cubic structure is identical with the lipid structure 
of biological membranes, i.e. a bimolecular layer with the polar group 
facing outwardly towards the water medium. 
In order to obtain the favorable liquid L2 phase at about room temperature, 
the water content of the monoolein-water mixture should preferably be 
within the range of from about 3.5 to 4% (weight by weight). Thus, such a 
liquid L2 phase has been found to be especially preferable as it imparts 
ideal consistence conditions to the implant material. However, higher 
water contents are also possible for this specific case, as then the 
lamellar liquid crystalline phase will be formed, which phase is also of 
such a viscosity that it is useful in accordance with the present 
invention. 
In FIG. 2 there is shown a plate 10 obtained from a block of calcium 
hydroxyapatite, which plate is located and suitably fixed in an opening 11 
of a scull portion 12. The implant material composition can be applied to 
the plate and the surrounding region of the scull indicated by hatching at 
13 by dispensing the low viscosity implant material composition from a 
syringe wherein it has been stored, and the composition is then smeared 
out at least in the region 13. 
When the composition is contacted with the scull, the viscosity thereof may 
decrease due to a temperature rise but when the composition comes into 
contact with any body fluid, such as blood, the viscosity thereof will 
increase in a few seconds so as to form a well confined mass of high 
viscosity which can still be plastically worked at the site of application 
so as to impart to the material the desired shape and to provide a smooth 
and tight transition between the plate and the surrounding bone of the 
scull. Thus, by means of the implant material, applied inaccuracies are 
equalized between the plate 10 and the edges of the opening 11 due to 
difficulties to accurately work the hard and brittle calcium 
hydroxyapatite blocks to the exact form of the opening. 
The applied implant material may be fixed in the intended position by 
covering the scull and the implant region by means of surrounding soft 
tissue which is then closed by suturing. 
FIG. 3 shows a phase diagram for one useful composition according to the 
invention, i.e. sunflower oil monoglyceride/soy bean oil 
triglyceride/water composition at 40.degree. C. and 90.degree. C. 
The two-phase regions and three-phase triangles are marked at 40.degree. C. 
only. The meanings of the symbols are: L2, isotropic "oily" solutions; C, 
cubic liquid crystalline phase; D, lamellary liquid crystalline phase; and 
F, reversed hexagonal liquid crystalline phase. In other words, the 
starting implant material composition according to the invention is within 
the part of the L2- or D-phase where addition of water or aqueous liquid 
will give a composition (and a phase conversion) within any of the C-or 
F-phases, respectively. 
The invention will also be more specifically described by means of the 
following non-limiting examples. 
EXAMPLE 1 
Monoolein is heated to a temperature just above the melting point thereof 
(36.degree. C.) and not above 40.degree. C. When the monoolein is 
completely melted a physiological saline solution of the same temperature 
(just below 40.degree. C.) is added so as to obtain a weight ratio of 
monoolein:water of 96.2:3.8. 
The resulting L2 phase is allowed to cool to room temperature and then 
granules of calcium hydroxyapatite (AERAM.RTM.) are added, with 
stirring, said addition being made to a volume ratio of calcium 
hydroxyapatite:L2 solution of 3:1. 
The implant material composition thus obtained as a toothpaste-like 
consistency and can be stored in closed packages, e.g. a one-way syringe, 
at a temperature ranging from about 0.degree. C. to 40.degree. C. without 
any changes of properties. When the composition is to be used, a 
temperature within the range of from 20.degree. C. to 35.degree. C. should 
be imparted thereto. In this context it should be noted that a rise of 
temperature will mean a lowering of the viscosity. 
When applied to a bone cavity the composition sucks up body fluid and/or 
blood into the structure and a dramatic increase of viscosity is obtained 
due to the conversion of the L2 phase into a cubic liquid crystalline 
phase which ultimately gets saturated. The mixture is stiff but still 
moldable. 
EXAMPLE 2 
As in Example 1, monoolein is heated just over the melting point thereof 
(36.degree. C.). Soybean oil is added to the melted monoolein and then a 
physiological saline solution is added thereto, the weight ratio of 
monoolein/soybean oil/water being 85:10:5. 
After cooling of the resulting L2 phase to room temperature, granules of 
calcium hydroxyapatite (AERAM.RTM.) are added thereto as in Example 1 
to a ratio of calcium hydroxyapatite/L2-solution of 3:1 by volume. The 
composition thus obtained has a lower viscosity than the composition 
obtained according to Example 1, and the viscosity thereof will be further 
reduced by adding more soybean oil. 
The composition behaves in a manner similar to that of the composition 
described in Example 1 when applied to bone in a human or animal body, 
that is, a phase conversion to the cubic phase is obtained. 
EXAMPLE 3 
As in the previous examples, monoolein is heated just above the melting 
point thereof (36.degree. C.). A physiological saline solution is added 
thereto, the weight ratio of monoolein:water being 86:14. 
After cooling the L2 phase thus obtained to room temperature, granules of 
the same calcium hydroxyapatite as in Examples 1 and 2 are added to a 
volume ratio of calcium hydroxyapatite:L2 phase of 2:1. The composition 
obtained has a lower viscosity than the one prepared in Example 1, but 
higher than that prepared in Example 2. 
When applied to a bone cavity the composition sucks up body fluid and/or 
blood and the ultimate water content thereof increases to about 39% of the 
total weight when the cubic phase is saturated. During the phase 
conversion the viscosity increases dramatically to a stiff but still 
formable mixture. The time for said phase conversion depends on the body 
volume of the mixture, but generally it is of the order of 10-60 seconds 
for a volume of 1 cm.sup.3. 
The present invention may be embodied in other specific forms without 
departing from the spirit or essential attributes thereof and, 
accordingly, reference should be made to the appended claims, rather than 
to the foregoing specification, as indicating the scope of the invention.