Note: Descriptions are shown in the official language in which they were submitted.
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BIOACTIVE LOAD BEARING BONE BONDING COMPOSITIONS
FIELD OF THE INVENTION
This invention provides novel, bioactive, load
bearing, hardenable compositions, especially bone bonding
compositions. In accordance with preferred embodiments,
glass-ceramic reinforced resin matrix composites are
provided which are, at once, deliverable, shapable, and able
to adhere to metal, ceramic, and natural bone tissue.
Preferred composites of the present invention are capable of
bearing significant loads while remaining highly compatible
with natural bone tissue. The compositions of the present
invention are amenable to orthopaedic and dental uses in a
number of contexts. Novel filled composites are employed
comprised of novel inorganic fillers. Such fillers comprise
combeite. Hard, shaped bodies are also provided.
BACKGROUND OF THE INVENTION
' The need for biomaterials in orthopaedic and
dental applications has increased as the world population
ages. A significant amount of research into biomaterials
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for orthopaedic and dental uses has attempted to address the
functional criteria for orthopaedic and dental
reconstruction within the human body. The materials which
have become available for such uses have improved in recent
years. All such materials must be biocompatible, however,
and the degree of biocompatibility exhibited by materials .
which are candidates for such use is always a major concern.
Biomaterials useful for orthopaedic and dental recon-
structions must have high strength, must be able to be
immediately affixed to the situs for reconstruction, must
bond strongly to bone, and must give rise to strong, highly
resilient restorations.
Among the materials which have been used for
orthopaedic and dental restorative purposes are bone cements
based upon acrylic species such as polymethyl methacrylate
(PMMA) and related compositions. Such materials usually are
capable of convenient delivery to the site of restoration
and can be formed as to be moldable aizd to have reasonable
degrees of affinity for bony tissue. PMMA cements, however,
lack bioactivity and the ability to generate a chemical bond
to bone and new bone tissue formation. The inertness of
such restoratives leads to micromotion and fatigue over time
with attendant aseptic loosening. Additionally, the
polymerization of PMMA-based materials can give rise to
significant exothermicity which can lead to localized tissue
necrosis and inflammation. Moreover, residual methyl
methacrylate monomer can leech into surrounding tissue
leading to site inflammation and implant failure. Implants
formed from PMMA-based materials can also give rise to
particulate debris, inflammation, and failure. PMMA
polymeric structures are generally two-dimensional and
limited as to strength.
Bone grafts using bioactive glasses and calcium '
phosphates, collagen, mixtures and the like have good
biocompatibility and give rise to bone tissue formation and
incorporation in some cases. However, prior graft materials
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lack t he desired load bearing strength and are generally
technique sensitive.
Prior attempts to improve such bone grafting
material through the development of self-setting calcium
phosphate cements as well as glass ionomer bone cements have
shown promise. Both materials can be bioactive in some
cases and both can exhibit considerable strength. Glass
ionomers, in particular, have enjoyed success in dental
applications. However, most of the strengths of glass
ionome r composites is achieved by reacting a f luoro-
aluminosilicate glass with a polyalkenoic polymer matrix.
Carboxyl functionalities exist on the polymer backbone,
which functionalities chelate with ions in the surface bone
mate rial. The usual time for a surface active biomate rial
to form an inner active layer with inner tissue is from six
to eight weeks. If the material's function relies upon this
interactive biolayer rather than its inherent strength, the
required reaction time can lead to premature failure of the
material.
A number of different glasses, glas s-ceramics, and
crystalline phase materials have been used, either alone or
in combination with acrylic polymerizable species, and other.
families of polymers, for restorative purposes. These
include hydroxyapatite, fluorapatite, oxyapat ite,
Wollastonite" anorthite, calcium fluoride, agrellite,
devitrite, canasite, phlogopite,.monetite, brushite,
octocalcium phosphate, Whitlockite, tetracale ium phosphate,
cordierite, and Berlinite. Representative patents
describing such uses include U.S. Patents 3,981,736,
4,652,534, 4,643,982, 4,775,646, 5,236,458, 2,920,971,
5,336,642, and 2,920,971. Additional references include
Japanese Parent No. 87-010939 and German Patent OS
2,208,236. Other references may be found in W.F. Brown,
"Solubilities of Phosphate & Other Sparingly Soluble
Compounds," Environmental Phosphorous Handbook, Ch. 10
(1973). All of the foregoing references disclose, inter alia, prior
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restorative materials and methods and compositions which may
be included .in the compositions and methods of the
invention, as well as methods which may be employed as part
of or ancillary to the invention.
In addition to the foregoing, certain animal-
derived materials, including coral and nacre, have also been -
used in biomaterials for restorative purposes.
U.S. Patent 4,239,113 to Gross et al. reports a
pliable, moldable acrylic-based bone cement reinforced with
from 15 to 75~ by weight of a bioactive glass together with
between 1 and 10% by weight of vitreous mineral fibers. The
disclosed function of the glass fillers and fibers is to
impart mechanical strength to the acrylic matrix, however
this advantage diminishes as the fibers degrade over time in
the body. Most of the problems associated with the use of
polymethyl methacrylate still exist in the materials
disclosed by Gross.
Vuillemin et al. in Arch. Otolygol. Head Neck
Surg. Vol 113 pp..836-840 (1987) introduced different
bioactive fillers such as tricalcium phosphate and
bioceramic AZ into bisphenol-A-diglycidyl methacrylate (bis
GMA) polymerizable through the action of peroxide systems
such as benzoyl peroxide mixed with amines. Use in human
subjects for successful treatment of a right frontal sinus
and a supraorbital edge was shown in a frontobasal skull
fracture. Both examples were primarily non-load bearing,
however.
Two component, resin composites containing both
salicylates and acrylates, cured through a calcium hydroxide
cement reaction is described by Walton in U.S. Patent
4,886,843. The use of calcium hydroxide as a filler results
in Caz+ ion release for the remineralization of dental
tissues while filling tooth restorations. Adherence to '
tooth structure was shown together with maintenance of
strength and permeability for the reaction of the calcium '
hydroxide filler.
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Kokubo et al. in U.S. Patent 5,145,520 discloses a
powder-liquid mixture yielding a bioactive cement. Fine
glass powder comprising a apatite-Wollastonite glass-
- ceramic, is reacted with an aqueous solution of ammonium
phosphate. The resulting, hardening cement was employed to
. repair bone and as a dental restorative cement. The cement
was said to harden quickly to a high strength material with
no heat generation during its setting.
Sugihara et al., in U.S. Patent 5,238,491,
ZO discloses a powder-liquid hardening dental material. This
material uses tricalcium phosphate or tetracalcium phosphate
as a main constituent together with a hardening liquid
comprising of at least one inorganic acid such as acetic
acid. An addition of collagen is used to aid in
biocompatibility and hydroxyapatite formation. One
disclosed goal is biocompatibility together with chemical
bonding and space filling of adjacent tissues.
PCT document WO 93/16738 - Yamamuro et al.
describes a bioactive cement deriving from a bioactive
glass-filled resin matrix composite. The glass is a non-
alkali-containing calcium oxide-silica-Pz05-magnesium oxide-
calcium fluoride loaded into a resin matrix, bisphenol-A
glycidyl dimethacrylate, polymerized in two separate pastes,
one containing benzoyl peroxide and one N, N-dimethyl-p-
toluidine. The interaction of the fillers with the resin
was said to be significant, giving rise to a good
physiological environment for the achievement of-bioactive
composites having high strength, low heat generation, and
good bonding capability.
Saito et al., in Biomaterials Vol 15 No. 2 (1994),
used bisphenol-A glycidyl dimethacrylate together with
amine-peroxide catalyst as a resin matrix to be filled with
' hydroxyapatite granules having average size of approximately
2 micrometers. This material was said to show good strength
' 35 as a bone cement (compressive strength of 260 MPa), along
with good bioactivity and bone formation in the bonding of
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femoral condyles of rabbits after eight weeks. The cement
was also said to have a low exotherm of polymerization.
Zamora et al., in an abstract submitted for the
Spring 1995 meeting of the American Chemical Society
entitled Bioglass Reinforced Dental Composites: Thermal
Mechanical Properties, describe a heat polymerized .
bisphenol-A glycidyl dimethacrylate matrix reinforced with
BioglassT~' (described below}. It was suggested that the bis
GMA resin matrix gives significantly lower exotherms of
polymerization and polymethyl methacrylate.
Tamura et al., in Journal of Biomedical Materials
Research Vol. 29 pp 551-559 (1995), discloses the effect of
the amount of filler loading an a bioactive bone cement.
Apatite-Wollastonite glass-ceramic filler, together with a
bisphenol-A glycidyl dimethacrylate matrix resin was
employed in weight ratios of 30, 50, 70, and 80%. Animal
studies were said to show that bioactivity increases as the
bioactive filler was increased, however the mechanical
properties did not necessarily follow the same trend.
Dickens-Venz et al., in Dent. Mater. Vol. 10 pp
100-106 {1994}, report on the physical and chemical
properties of resin-reinforced calcium phosphate cements.
Meechan et al., in British Journal of Oral and
Maxillofacial Surgery Vol. 32 pp. 91-93 (1994), disclose a
pilot study analyzing the adhesion of composite resins to
bone using commercially available dental materials.
Roemer et al., in U.S. Patent 4,396,476, disclose
interpenetrating polymer networks a.n hardenable compositions
for a number of uses including the filling of teeth and
bone.
U.S. Patent, 4,369,262 - Walkowiak et al.
discloses dental materials based upon filled cross-linked
plastics together with polymerizable binders. '
U.S. Patent 4,110,184 - Dart et al. discloses
photocurable dental filling compositions based on modified,
filled acrylic polymerizable materials.
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BioglassT"" is believed to be described in U.S.
Patent 4,851,046 - Low et al. Low et al. describe a
biocompatible glass, known to those skilled in the art as
4555 bioactive glass, in particular particle size
distributions to facilitate admixture with blood for repair
of periodontal defects. Bone tissue ingrowth peripheral to
the repair is disclosed. The materials disclosed by Low et
al. are not significantly load bearing, however.
U.S. Patent 5,204,106 - Schepers et al. discloses
improved methods for forming osseous tissue from bioactive
glass such as 4555 glass. Critical particle sizes permit
osteogenesis throughout a restoration. The disclosed
compositions are not highly load bearing.'
While a number of materials have been shown to be
useful for the filling of bone and for use in restorative
dentistry, there is still a significant need for improved
materials for such uses. Thus, there remains a long-felt
need for restorative compositions comprising resin matrixes
together with bioactive fillers which have the desired
combination of delivery viscosity, setting conditions,
setting strength, and bioactivity, combined with great
overall strength and long-term compatibility with bone and
other tissue. It is also greatly desired to achieve stable,
strong, biocompatible restorations in a short time period,
shorter than the up to eight weeks which can be required
with prior materials.
It is, therefore, a principal object of the
present invention to provide improved bone restorative
materials having immediate physical strength and
biocompatibility.
A further object of the invention is to provide
load bearing bone bonding composite materials for use in
diverse restorative circumstances within the human body.
Yet another object of the invention is to provide
materials having rapid adherence to implants and bone tissue
together with the achievement of elastic moduli which are
close to the modulus of bone.
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A still further object is to achieve bone bonding
composites which can give rise to an active resin-calcium
oxide-phosphorus oxide gel layer which is capable of
enhancing the toughness and long term mechanical stability '
of restorations employing such materials.
Another object of the invention is to improve '
implant fixation in dentistry and orthopaedics through the
improved physical and physiochemcial relationship of
materials of the present invention, natural bone, and
implant materials.
A further object of the invention is to
incorporate certain drugs into the compositions hereof so as
to confer the benefits of such drugs upon the situses of
restoration employing such materials.
Still another object is to provide hardened,
shaped bodies of bioactive material for orthopaedic and
dental use.
It is also an object of the invention to provide
bone grafting materials and cements which are capable of
immediate placement together with concomitant load bearing
ability as well as ensuing bioactivity giving rise to the
formation of natural bony tissue.
Other objects will be apparent from a review of
the specification and attendant claims.
S~JNINIARY OF THE INVENTION
In accordance with the present invention,
hardenable compositions are provided comprising a
polymerizable matrix and inorganic filler. At least 10~ of
the inorganic filler comprises a combeite glass-ceramic
having a least 2~ by volume of regions of combeite together
with irregular morphology. Combeite is a mineral having
chemical composition Na4Ca3Si6016 (OH) 2 which was first reported
as a mineral from the Belgian Congo in 1957. It has now
been found that the employment of inorganic fillers in
restorative compositions, which fillers include crystallites
of combeite in a glass-ceramic structure (hence, combeite
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glass-ceramic) in accordance with the present invention
gives rise to superior orthopaedic and dental restorations.
It is preferred that the combeite glass-ceramic
. which forms some or all of the fillers of the present
invention comprise at least about 2°s by volume of combeite.
Higher percentages of combeite are more preferred and volume
percentage between 5-50~ of combeite are particularly
desired. It will be appreciated that the combeite glass-
ceramic particles of the present invention are heterogenous
in that they comprise a glassy, amorphous structure having
crystallites or regions of crystallinity of combeite
dispersed therethrough. It is preferred that these
heterogenous particles of combeite glass-ceramic have
particle sizes greater than 0.1 micron, with somewhat larger
sizes being preferred. Particle sizes between about 0.2 and
300 microns are more preferred.
In accordance with the invention, combeite glass-
ceramic particles having irregular morphologies are greatly
preferred to attain the beneficial results of the invention.
Thus, while it could be proposed to provide combeite glass-
ceramics having relatively smooth particulate forms, such
regular morphologies are not preferred. Preferred particles
may be conveniently obtained through the methods of
preparing such combeite glass ceramics as set forth in the
present invention.
In accordance with some preferred embodiments,
blends of combeite glass-ceramics may be useful. Thus, a
number of different combeite glass-ceramics can be prepared
having different properties, such as combeite crystallite
~30 size, percentage of combeite, particle sizes of the filler
and the like, and the resulting combeite glass-ceramics
blended to form fillers for restorative compositions. It is
also preferred in some cases to admix combeite.glass-ceramic
fillers in accordance with the present invention with other
fillers which are consistent with the objectives to be
obtained. Thus, a wide variety of such other fillers may be
so employed so long as at least 10~ by weight of the overall
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inorganic filler of the hardenable compositions of the
invention comprise combeite glass-ceramic.
The hardenable composition of the invention also
comprise a polymerizable matrix. A very large number of
polymerizable species have been known heretofore for use in
the formulation of restorative compositions of orthopaedics
and dentistry. While certain preferred polymerizable
species have been found to be particularly useful in the
hardenable compositions of this invention, it is to be
understood that any of the polymerizable species known to
persons of ordinary skill in the art for use in conjunction
with orthopaedic and/or dental restoration may be used
herein. In particular, a wide variety of a polymerizable
acrylic species may be employed, however those based upon
bisphenol-A, such as bisphenol-A dimethacrylate and related
species are preferred. Bisphenol-A glycidyl dimethacrylate
is especially suitable for biological restorations for all
of reasons known to persons skilled in the art and such is
preferred here.
Catalytic agents to effect polymerization are also
known to persons skilled in the art and any of those
catalytic agents and/or systems may be employed in the
present invention. In general, "heat-curable" and
photopolymerizable systems have found wide utility. Thus, a
number of peroxides, such as benzyl peroxide can be used in
°heat curable" formulations, and such is preferred for
embodiments of the present invention. Photopolymerization
is also useful, especially visible light curing.
Camphoroquinone is a well-regarded visible light curing
catalyst especially when admixed with a tertiary amine.
It is preferred that the materials of the present
invention be amenable to delivery in convenient fashion.
Exemplary methods of delivery include syringes, such as wide '
mouth syringes and spatulation. Accordingly, viscosities
for the hardenable composition of the present invention '
between about 5,000 and 75,000 centipoise is preferred.
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Still more preferred are viscosities between about 7,500 and
60,000 centipoise.
In accordance with certain embodiments of the
present invention, methods are provided for the restoration
of bony tissue. In this regard, an area of bony tissue
- requiring repair as a result of disease, injury, desired
reconfiguration, or otherwise is surgically prepared and a
composition of the present invention introduced into the
situs for the repair. The composition is caused to
polymerize through either heat or photochemistry, the wound
closed, and the restoration allowed to heal.
A major advantage of the restoration, after
polymerization, is that it has a significant, inherent
strength such that restoration of load-bearing bony situses
can be had. Improved mechanical properties of the composite
of said invention have superior static fatigue and
compressive and diametral tensile strengths. While
immobilization of the effected part will likely still be
required, the present invention permits the restoration of
many additional bony areas than heretofore. Further, since
the combeite glass-ceramic and other fillers of the present
invention are biocompatible and, indeed, bioactive,
osteogenesis occurs. This leads to bone infiltration and
replacement of the formed Ca0-P205 surface layer with
autologous bone tissue. Superior restoration ensues. It is
noteworthy to reiterate that the surface of this composite
is believed to change upon placement in physiologic
surroundings such that a chemical bond to bone and in some
cases to soft tissue can result. This is a significant
departure from commercial PMMA cements and dental
restoratives including bisGMA resins in use today.
The invention also provides methods for the
- preparation of bioactive, inorganic, particulate fillers
comprising combeite glass-ceramics. Appropriate minerals
' 35 are melted together for a time and under conditions
effective to achieve substantial homogeneity and to form a
melt. The minerals which are melted together, conven-
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tionally silica, sodium oxide, calcium carbonate, and
calcium phosphate, are blended in an amount so as to give
rise to the combeite glass-ceramics as required herein.
When a homogenous melt has been obtained, the melt is either -
cooled on an inert substrate or quenched in distilled water.
If cooled on an inert substrate, the resulting slab or body
of material is subsequently comminuted through crushing and
the like to form a particulate material. If quenched in
water, the melt forms a frit, which is easily shattered into
particles. In either event, the particles are reduced in
size as may be necessary and sorted through sieving or
otherwise. 'The particles are then selected, preferably
tested to ensure that proper size ranges, combeite content,
and other properties are present and either used alone or
blended with compatible materials to form inorganic fillers
for the production of bioactive restorative compositions. To
date no one has reported the use of this unique combeite
glass-ceramic as a bioactive filler. Furthermore, as the
combeite crystal content increases, the base glass
composition changes and becomes more reactive and bioactive.
The amount of combeite crystal can be increased in
the sample by reheating the powder to slightly above the
temperature of crystallization (Tc). which is easily
obtained from differential thermal analysis (DTA) curves.
See Figures 6a & 6b.
Figure 6a illustrates the DTA curve for 50.01 mg
of 600-1000 mm (as sieved) parent glass heated at 10°C/min in
a flowing (50cc/min) nitrogen atmosphere. The temperature
scale represents that x-axis and the y-axis is the measure
of energy released or absorded, denoting crystallization of
melting. The temperature where the onset (or begining) of
crystallization occurs is designated Tg and is found by the
conventional slope-tangent intercept method. The
temperature where to maxiumum crystallization occurs is
designated (Tc) and is similarly determined. Figure 6a
shows that for a larger particle (600-1000~m) Tg=722°C and
Tc=760°C. Where as Figure 6b, which is the DTA spectra for
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glass, run under identical conditions as Figure 6a, yields a
Tg=650°C and Tc=695°C. Anyone skilled in the art will easily
be able to find the appropriate temperature of
' crystallization for any given particle size. The initial
particle size will effect the crystallization kinetics, thus
larger particles will generally require longer times at
slightly higher temperatures.
It will be understood that the fillers in
accordance with the present methods of manufacture thereof
are not necessarily limited to use in hardenable
compositions and polymerizable matrices. Rather, such
fillers are novel per se and may be used in any composition,
either for orthopaedic restoration, dental restoration, or
otherwise. Thus, such fillers can be used in medical and
non-medical articles, such as golf balls, should the same be
desired.
Through the present processes, fillers will have
irregular morphologies rather than the smooth morphologies
which would be expected to be obtained through some other
possible techniques. Such irregularities can be
macroscopic, on the same scale as particle size, not just
microscopic.
The hardenable compositions of the present
invention may also be elaborated into hardened, shaped
bodies for a number of uses. Thus, orthopaedic appliances
such as joints, rods, pins, or screws for orthopaedic
surgery, plates, sheets, and a number of other shapes may be
formed through processing in accordance with methods known
to persons of ordinary skill in the art. Such hardened
compositions can be bioactive and can be used, preferably in
conjunction with hardenable compositions in accordance with
the present invention in the form of gels, pastes, or
fluids, in surgical techniques. Thus, a screw or pin can be
inserted into a broken bone in the same way that metal
screws and pins are currently inserted, using conventional
bone cements or restoratives in accordance with the present
invention or otherwise. The bioactivity of the present
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hardenable materials will give rise to osteogenesis with
beneficial medical or surgical results.
BRIEF DESCRIPTION OF THE DRAWINGS
Figures la and Ib respectively depict the X-ray
diffraction spectrum of 4555, base glass, which is
essentially amorphous, and combeite glass-ceramic, using
copper K-a at 35 kV and 20 mA at a step interval of 0.05°.
Figure 2a depicts a particle of combeite glass-
ceramic in accordance with one embodiment of the present
invention. A combeite glass-ceramic particle, 10 having
average dimension, 12 is shown in partial cutaway. The
particle is seen to comprise a glassy, amorphous region, 14
containing numerous crystallites, 16 of combeite.
Figure 2b is a blow up cross section of the
cutaway view of figure 2a. The amorphous regions, 14
containing the crystallites of combeite, 16 are shown, as is
an average dimension of a crystallites, 18.
Figures 3a, 3b, 3c and 3d depict shaped articles
produced from the hardenable compositions of the present
invention. The article depicted in Figure 3a is a rod or
pin which can be used in orthopaedic surgery. Figure 3b
shows a vertebral implant for spine fusion, while Figure 3c
depicts an orthopaedic screw. An endodontic "point" is
shown in Figure 3d.
Figure 4 depicts a bipolar hip replacement using
material of the invention.
Figure 5 depicts a Fourier Transformed Infrared
spectrograph (FTIR) of unreacted composite and surface
reacted composites, in an in vitro physiologic simulation
after 1 and 2 weeks at 37°C in tris-buffered simulated body
solution. The presence of Ca-Phosphate (apatite-like)
species on surface is indicated by a peak shift from 1250 to
1150 cm-1 indicative of P=0 stretch and the emergence of the
peaks at 540 cm-1 and &00 cm-'- indicative of P-0 bending.
Evidence of the composite surface change is further
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quantified by optical microscopy which reveals a whitish
coating on the surface indicative of the bioactivity of this
composite.
- Figure 6a & 6b depict the differential thermal
analysis spectra of 600 to 1000 ~.~,m and <45 ~m particles,
respectively, of the base glass (4555 glass) used in this
invention. The tangent-intercept method is easily employed
by those skilled in the art at the slope changes. This
technique yields the temperature required to achieve
crystallization and the expected rate of crystal formation.
Figure 7 depicts a schematic representation of a
composite-bone bonded interface .The extent of the calcium-
phosphate reaction layer which is also shown is determined
by the bioactive filler size, content and the reactivity of
the physiologic site.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The present invention provides hardenable
restorative compositions including inorganic fillers having,
as a constituent, combeite glass-ceramic. It has been found
that significant quantities of combeite in glass-ceramic
particles impart highly beneficial properties to restorative
compositions including such particles. In particular, good
biocompatibility, osteogenesis, radiopacity, workability,
and other properties are conferred through the use of
combeite glass-ceramic as all or part of inorganic filler
material in hardenable, restorative compositions.
Combeite, which is Na4Ca3Si6016 (OH) 2, was discovered
in 1957 in natural deposits in the Belgian Congo, as
reported by Sahama et al, Mineral. Mag. Vol. 31, No. 238,
page 503 (1957). Combeite has not been considered a
commercially significant material heretofore. It has now
been found, however, that in the preparation of certain
inorganic materials based upon "45S5" glass, some combeite
may form. Indeed, in the preparation of Biogran""
restorative composition, which is a filling material sold by
the Orthovita company of Malvern, PA for the restoration of
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osseous defects, small quantities of combeite may be formed
during the manufacturing process. This has heretofore been
considered to be an impurity, and the presence of 2~ by
volume or more of combeite in the Biogran product, as
measured by x-ray spectroscopy has been treated as a quality
control defect and cause for product rejection. Figures la &
lb show an accepted amorphous glass and a non-accepted
crystalline glass-ceramic containing combeite, respectively.
It has now been found, however, that the foregoing
"impurity" is actually highly beneficial, especially when
caused to be present in greater amounts. Thus, when
combeite crystallites are fostered in the preparation of
4555 bioactive glass, such that combeite is present in
amounts of at least about 2~ by volume and preferably more,
beneficial results are obtained. While not wishing to be
bound by theory, this benefit may be in part due to the
alteration of the base glass stoichiometry, and subsequent
reactivity and bioactivity, as the combeite crystal
formation requisitions the selected ratios of ions. The
residual amorphous content becomes increasingly higher in
phosphorous, P205 content as the combeite crystal content
increases. Improved bioactivity after crystallization is not
a priori expected as known bioactive glass-ceramics, such as
A-W glass-ceramic, have reduced bioactivity upon increased
crystallization from the parent glass.
It is now believed to be highly desirable to
permit the growth of combeite crystallites during the
preparation of particulate, inorganic filler materials for
use in biological restorations, and this may be done through
control of the conditions of time and temperature of the
formation, cooling, and optional heat treating of such
materials.
In accordance with the present invention, a blend '
of inorganic materials is prepared containing the com-
positions which will give rise to the inorganic products
desired. In particular, it is desired to select starting
minerals for the preparation of the combeite glass-ceramics
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of tYie present invention which contain the constituent
elements of the combeite and of the glass material which
will form the amorphous regions surrounding the cottibeite~
crystallites . It is greatly preferred to employ minerals
giving rise to "45S5" glass, known per se to persons of
ordinary skill in the art. U.S. Patent 5,204,106 describes
in detail how such glasses can be prepared from constituent,
inorganic materials.
The overall constitution of certain pref erred
inorganic particles in accordance with the present
invention, including both the glass portion and the
crystallites of combeite, is as follows:
Si02 from 40 to 53% by weight
NazO from 10 to 32 % by weight
P2C)5 from 0 to 12 % by weight; and
Ca0 from 10 to 32% by weight.
It is more preferred to prepare particles having overall.
compositions in accordance with the following:
Si~02 from 43 to 48% by weight
Na.20 from 15 to 30% by weight
Pz05 from 2 to 10 % by weight; and
CaC) from 15 to 30% by weight. -
As is known to persons of ordinary skill in the art, a
particularly useful overall composition for the particles of
the present invention has the formula:
Si~Jz about 45 % by weight
NazO about 24.5% by weight
PZOS about 6% by weight; and
Ca0 about 24.5% by weight.
This is the ~~omposition which is conventionally known ae~
"4555" glass . This "parent" or "base" glass has specific;
properties that are altered as a combeite crystal phase is
sequestered.
The overall constitution of other preferred inorganic
3 5 panicles in accordance with the present invention, including both the
CA 02239698 2004-09-17
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glass portion and r_he crystallites of combeite, is as follows:
SiOz from 40 to 55% by weight
Nato from l0 to 32% by weight
P205 from 4 to 12% by weight; and
Ca0 from 10 to 32% by weight.
It is also preferred to prepare particles having overall
compositions in accordance with the following:
Si02 from 42 to 48% by weight
Na20 from 14 to 28% by weight
P205 from 5 to 10% by weight; and
Ca0 from 20 to 29% by weight.
As will be understood, certain chemical
transformations occur upon heating the constituent minerals
into a melt during the course of formation of the particles of
the present invention. Thus, certain oxidation-reduction
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reactions take place during melting together with inorganic
disproportionation such that the total constituency of the
staring materials may be different from that of the product
particles. In order to prepare "4555" glass, it has been
conventionally known to employ 33.970 Si02, 30.98 NaaC03,
26.36% CaC03 and 8.68 CaHP04; (all percentages by weight). -
It will be appreciated that other formulations also give
rise to the products the present invention and that all such
formulations are within its spirit.
In accordance with preferred methods of the
present invention, appropriate inorganic starting materials
are caused to be melted under conditions of time and
temperature sufficient to effect complete disproportionation
and oxidation/reduction as may be required and to achieve
homogeneity of the melt. The melt is either then cast into
an inert form to form a mass or quenched in distilled water
to form a frit. In either case, comminution is effected '
either by crushing,, milling or otherwise, and the resulting
particles sized, heat treated as necessary to promote
crystallization, assayed for combeite content, and either
used as an inorganic filler or blended for such use.
It will be appreciated that during the processing
of the fillers of the present invention, crystallites --
small areas of crystallinity -- of combeite grow from the
melt. The resulting particles are comprised of amorphous,
glassy areas together with combeite crystallites dispersed
therethrough. Such structures are known per se as glass-
ceramics. A combeite glass-ceramic is, therefore, a glassy
material having crystallites of combeite therein. For
purposes of the present invention, the term "combeite glass-
ceramic" should be taken to mean a glass having crystallites
of combeite dispersed therethrough which material is also
possessed of properties otherwise consistent with the
results and objects to be attained hereby. Thus, it is
greatly to be preferred that such materials be biocompatible '
and capable for use as an inorganic filler in hardenable,
restorative materials for orthopaedic and dental use.
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It is possible to vary the content of combeite
crystallites in the combeite glass-ceramics in accordance
with the present invention as well as to vary the
crystallite size, and other properties. It will be
appreciated that when combeite crystallites grow from the
substantially homogeneous material of the melt, the
remaining glassy areas are depleted in composition as
regards the materials comprising the combeite. Thus, in a
combeite glass-ceramic, the glassy areas in the combeite
crystallites may not have the same composition as the
overall combeite glass-ceramic. Indeed, it is possible that
the chemical composition of the glassy portion of the
particles of the present invention varies from location to
location depending upon the relative concentration of
combeite crystals locally to those several locations. It
is, therefore, necessary to measure the overall chemical
composition of the particles of the invention, rather than
the composition of the glassy portions at localized areas
thereof. Furthermore, the original parent glass
stoichiometry has changed, creating a new and different
material, usually with measurably different properties. In
any event, it is preferred to characterize the particles, at
least in part, by what they do rather than by what they are.
Such particles are comprised of combeite and glassy areas,
and are highly biocompatible. They can give rise to
osteostimulation or osteogenesis when included as a part of
an orthopaedic or dental restoration.
As will be understood by persons skilled in the
art, crystallization to form combeite glass ceramic in
accordance with the present invention is a process involving
nucleation and crystal growth. These two parameters are
inherent to a particular system and is determined by the
kinetics of time and temperature of that system. Thus, to
alter the amount of crystallization, as represented by V~,
the volume fraction crystallized, along with the size of the
resulting crystals, time and temperature profiles are
varied. A higher temperature above the maximum temperature
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of crystallization, T°, will generally yield larger crystals
more rapidly than heating the material below T~. As will
also be appreciated by persons of ordinary skill in the art,
extending the time at temperature T~ is a simple way to
predictably increase the amount of crystal content of a
given material. The T~ temperature is easily obtained from
the change in intercept of the differential thermal analysis
curve for the material, taken in accordance with the
standard methods in the art. Figure 6a & 6b illustrate a
ZO Differential Thermal Analysis, DTA spectra for differently
sized particles. It appears from the size and position
(temperature axis) of these plots that the crystallization
can likely be maximally obtained at 700 to 800°C, depending
on the particle size. The degree of crystal nucleus
dispersion is governed by the selection of raw materials to
some extent and the level of homogeneity in processing.
Each of the nuclei around which crystal can grow generates
sensible crystals so long as the appropriate chemical
composition is available in the "neighborhood" of the
nucleus.
In short, it is well within the skill of persons
or ordinary skill in the art to vary the crystal content of
materials in accordance with the present invention and such
persons will have no difficulty in obtaining materials
having varying content of crystallites and particle
crystallite sizes.
The quenched glass after been annealing and
fragmentation can be crystallized by the controlled heating
of the glass through the transition temperature to the T°
which is defined by the tangent intercept of the exotherm
for the onset of crystallization as measured by differential
thermal analysis (see Figures 6a & 6b). This temperature
ranges from 660° to 780°C depending upon heating rate and
particle size for this composition and can be raised as high
as 1000°C for more rapid crystallization kinetics. A
preferred temperature for combeite formation is 700°C for 2-4
hours.
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Milling and classification of the glass material
after crystallization should preferably be done in a dry
mill approach. Dry ball milling, impact or puck milling are
acceptable means of comminution. Initial quenching to form a
frit by water or splat cooling is also useful, assuming the
' subsequent crystallizat;on profile is adjusted for the
different thermal history.
Preferred bioactive glass-ceramics of this
invention need not be surface treated, but up to 100% by
weight of the filler may be silanated. Silanation can be
performed by dispersing the powder into a slurry of acid,
e.g. glacial acetic, to effect catalysis of a silane
coupling agent such as (3-methacryloxypropyl-
trimethoxysilane). Preferably at 1 to 10 % by weight silane
is used.
The particles of the present invention comprising
combeite glass-ceramic, when prepared in accordance with the
methods of the present invention, have irregular
morphologies. Thus, they will be seen to have prominences,
declivities, cracks, and other irregularities or otherwise
be perceived to be "unsmooth." These irregularities are
desirable in that they impart improvements in packability of
the filler particles, and improvements in access of
biological fluid to the interior of the particles. While it
may be possible to prepare combeite glass-ceramics under
certain circumstances through techniques such as sol-gel
chemistry, which processes will give rise to relatively
"smooth" particles, such procedures and the smooth particles
they provide are not preferred.
The combeite glass-ceramic particles of the
present invention preferably comprise at least about 3% by
volume of combeite. It is more preferred that at least
about 5% by volume of the combeite glass-ceramic comprise
combeite, with at least about 10% being even more preferred.
Amounts of combeite between about 5 and 50% by volume and
preferably between about 10 and 20% by volume are still more
preferred. It will be understood that it is very difficult
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to measure the combeite content in combeite glass-ceramics
on a weight basis. It is, however, possible to closely
estimate the volume composition of combeite in combeite
glass-ceramics through photomicroscopy using known '
techniques. For example, in Introduction to Ceramics, 2nd
Ed., pg 528, John Wiley & Sons (1976), W.D. Kingery explains
certain of these optical techniques. It will be understood
that a cross-section of a particle will transect the
constituent combeite crystallites at various points and that
the transection of the combeite crystallite at or near their
midline or at a location of a wide dimension will give a
relatively large two-dimensional view of the size of that
particle. Transection at an apex will suggest that the
particle is relatively small. A statistical analysis of the
results of such an evaluation, however may be had, thus
leading to a good estimate of volume content of combeite in
combeite glass-ceramics.
The concentration of combeite in combeite glass-
ceramics may also be determined by X-ray diffraction as set
forth in BD Cullity, Elements of X-ray Diffraction, 2nd Ed.,
pp 409-419, Addison-Wesley (1978). This technique also
gives rise to an understanding of the volume fraction of a
material being studied which comprises an element or
compound in question. This may be done in number of ways
including external standardization, direct comparison, and
through use of an internal standard. The determination of
volume fraction of combeite and combeite glass-ceramics in
accordance with the present invention can be determined by
persons of ordinary skill in the art using the education,
training and experience enjoyed by such persons.
Figure lb is a depiction of an X-ray diffraction
spectrum of a combeite glass-ceramic in accordance with the
present invention. The peak positions on the X-ray
diffraction curve correspond to the d-spacing between known
planes of atoms or indices used to describe specific '
crystals. The number identifying the H, K, L or Miller
indices, correlate to numbered planes. Several specific
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planes allow determination of a particular crystal phase.
One first matches the peak positions in relative intensities
of an x-ray diffraction spectrum to be analyzed to a set of
power diffraction indices which are generally computerized
to identify a particular crystal phase. Once established,
calculations can assign specific plane numbers to specific
peaks on the x-ray diffraction pattern. Thus, for combeite,
the most pronounced planes are 204, 220, 211, 202 and 113.
It is understood that the detection limit for the
detection of particular crystals in standard x-ray
diffraction instrumentation is from 1 to 2~ by weight.
Thus, for relatively small amounts of particular crystalline
phases in materials, the limitations of the particular
instrumentation must always be kept in mind. All of the
foregoing considerations are well-known to persons of
ordinary skill in the art, however, who will have no
difficulty in determining the identity and quantitation of
combeite in materials generally in accordance with the
present invention from the foregoing discussion. Figure la
shows and XRD pattern of the amorphous parent glass prior to
combeite crystallization.
In general, it is understood that the deter-
mination of volume fractions of combeite in the particles of
the present invention can be most accurately determined
through cross-sectioning as described above. The X-ray
diffraction technique, also described above, is very
convenient and useful in approximating such volume fraction.
The preferred combeite glass-ceramic particles in
accordance with the present invention are such that at least
about 95~ by weight of said particles have particle sizes
greater than about 0.1 microns. It is preferred that at
least 95~ of such particles have particle sizes greater than
about 0.2 microns and that such particles have sizes less
than about 300 microns. In accordance with more preferred
' 35 embodiments, at least 95% of the particles have sizes less
than about 100 microns. It is still more preferred that at
least 95~ of the particles have particle sizes between about
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0.2 and 300 microns with size between about 0.2 and 100
microns being still more preferred. In accordance with
other preferred embodiments, at least 95~ of the particles,
by weight, have particles sizes between about 0.5 and 50 -
microns.
The measurement of particle sizes of the combeite '
glass-ceramics of the present invention may be done in a
number of ways. For larger particle sizes, those greater
than about 20 microns, it is convenient and customary to
determine particle sizes through the use of sieving. The
segregation of particles into size ranges through the use of
progressively finer sieves is well-known and conventional.
It is understood that a distribution of particle sizes will
be segregated through this procedure and that particles
having average sizes somewhat larger than a nominal size
may, nonetheless, pass through a sieve, especially when such
particles are irregular as is preferred in the present
invention. This is so because elongated particles may slip
through a sieve opening in a lengthwise direction. It will
accordingly be understood that particle sizes disclosed
herein are somewhat inexact for these and other reasons.
Nonetheless, it is believed that persons of ordinary skill
in the art will have no difficulty in determining
appropriate particle sizes for any particular application as
may be desired in connection with the present invention.
For particle sizes less than about 10 microns,
sieving is generally unproductive in providing size
determination. Rather, a determination of particle size
through optical means is conventionally employed. Optical
particle size counters are well-known and are readily
available, e.g. from the Horiba and MicroTrac companies.
Additionally difficulties exists in determining particle
sizes of small particles through optical means, but
resolving problems in this area is well within the skill of
persons of ordinary skill in the art.
In accordance with the present invention, it has
been conveniently chosen to require that particles have "at
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least about 95% by weight" of a particular size limitation
or size range." It is not desired that this aspect of the
invention be limited strictly by a formula, but rather by
practicality in view of the objects to be attained hereby.
Figures 2a and 2b depict a combeite glass-ceramic
particle in accordance with the present invention. In
Figure 2a, a filler particle, 10 is depicted with a cut-away
portion. In the cut-away, regions of amorphous, glassy
structure 14 are shown together with crystallites 16 of
combeite dispersed therethrough. Figure 2b is a blow-up of
a region of the cut-away view of Figure 2a depicting the
combeite crystallites in greater detail. It will be
appreciated that Figure 2b depicts a two-dimensional view, a
transection, and that the various crystallites of combeite
will be transected at various points. Thus, the dimensions
of the crystallites vary depending upon where in their
structure the transection occurs. Transection near an apex
gives a relatively small two-dimensional view, while
transection near a major access gives rise to the appearance
of a large particle. An average dimension of one
crystallite is shown by reference numeral I8. Likewise,
average dimension, 12 of the filler particle 10 is shown in
Fig. 2a.
In accordance with certain preferred embodiments
of the present invention, blends of combeite glass-ceramics
are employed. Thus, pluralities of combeite glass-ceramic
particles, e.g. those having differing combeite levels,
different particle sizes, different glass compositions, and
different particle morphologies can be blended together to
give rise to fillers having improved properties overall.
Likewise, combeite glass-ceramic particles may be blended
with other inorganic, and possibly organic filler materials
to attain certain additional benefits in accordance with the
invention. All that is required is that at least about 10%
of inorganic filler used in hardenable compositions hereof
comprise combeite glass-ceramic in accordance with the
invention.
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The powders, both bioactive, combeite glass-
ceramic, and other fillers, are preferably blended into the
resin component to achieve the desired viscosity and
strength factors. The composites are easily mixed via a Iow
speed, high sheer rotary mixer. Depending on the final
filler loading, the range of preferred viscosity values can
be 10,000 up to 65,000 centipoise (cps). Preferred ranges
for syringe delivery are 18,000 to 35,000 cps, and most
preferred, 20,000 to 30,000 cps. For p~~ty-like
consistency, the preferred viscosity range for the composite
is 25,000 to 55,000 cps, with most preferred range being
35,000 to 45,000 cps. Heat generation during fingertip
mixing of the high viscosity pastes can reduce the extremely
high viscosities and even accelerate the polymerization
mechanism.
Materials which may be included as inorganic
filler in hardenable compositions in accordance with the
present invention include silica, quartz, hydroxyapatite,
fluorapatite, oxyapatite, Wollastonite, anorthite, calcium
fluoride, agrellite, devitrite, canasite, phlogopite,
monetite, brushite, octocalcium phosphate, Whitlockite,
tetracalcium phosphate, cordierite, Berlinite and mixtures
thereof.
Among the fillers which may be admixed with the
combeite glass-ceramics of the present invention are a wide
range of inorganic glasses such as barium aluminum silicate,
lithium aluminum silicate, strontium, lanthanum, tantalum,
etc. glasses and related materials, silica, especially in
submicron sizes and other fillers as well. Silanation,
which is well known per se, may also be applied to any of
the fillers to improve the bonding thereof and their
integration into the hardenable compositions of the
invention.
Pigments, opacifiers, handling agents and other
modifications may also be included in the present
formulations and such adjuvants are conventionally admixed
with the filler components. So long as they are compatible
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with the objects of the present invention, the use of such
adjuvants is consistent with the present invention and
contemplated hereby.
' Organic filler materials which can be used in
connection with the present invention include all of those
set forth in the background of the invention section to this
application and in the references identified therein,
together with any other organic material which is consistent
with the objects of this invention.
One preferred material for inclusion herein is
inorganic material similar or identical in formula to
BiogranT'" sold by the assignee of the present invention.
This has a similar overall composition to the combeite
glass-ceramics of this invention, but has the presence of
only very minor amounts of combeite, (less than 2~ by
volume) or none at all. Such material may be admixed with
combeite glass-ceramics, and other inorganic and organic
fillers to good effect in connection with this invention.
It is preferred in some embodiments to employ particulate
fillers, such as polyacrylic particles, especially bis-GMA
polymers, crosslinked acrylic polymers, urethane-modified
polymers, and the like. In accordance with one embodiment,
interpenetrating polymer network (IPN) systems, such as are
described in U.S. Patent 4,396,476 - Romer, et al, may be
employed. It may be useful to include fibers, webs, and
other structural elements in accordance with certain
embodiments so long as the same do not deviate from the
spirit and intended scope of the present invention.
The combeite glass-ceramic filler materials of the
present invention are novel per se and may be used in any
way that an inorganic filler has been known for use
heretofore. Such uses include not only medical and dental
' uses, but also industrial use of every kind. Such filler
may, therefore, be used in polymer processing, such as the
formulation and manufacture of golf balls, filled plastics,
reinforced cements, structural, plastic elements, modified
rubbers, adhesives, paints, pigments, textiles, and as
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excipients, abrasives, fluidizing agents, catalysts, and, in
many other systems.
A principle use of the fillers of the invention
comprising combeite glass-ceramics is as part of a '
hardenable material for use in orthopaedic and dental
restorations. In this regard, a filler in accordance with '
the present invention is admixed with a polymerizable matrix
comprising a polymer system which is capable of hardening
under the influence of heat, or photochemical energy or
IO otherwise in a controlled fashion. It will be understood
that a wide variety of polymerization systems and materials
for use therein may be employed to good advantage in
connection with the present invention and all such systems
are contemplated hereby.
L5 Polymerizable resins suitable for use in the
practice of one or more embodiments of the present invention
include a wide array of ethylenically unsaturated, and other
particularly polymerizable compositions. Acrylic species
are suitable. Preferably, such resins are selected from the
20 class of acrylated polyesters. Thus, the bis-glycidyl
methacrylate adduct of bisphenol-A Ibis-GMA) and its other
acrylic counterparts are preferred. Alternatively, the
adducts of 2,2,3-trimethylhexane diisocyanate with
hydroxyethyl methacrylate, hydroxypropyl methacrylate, and
25 other hydroxyacrylic acrylic species are also preferred.
Persons of ordinary skill in the.art will appreciate that
other acrylated polyesters may also be suited for use and
that the same may be reacted with isocyanates to form
urethanes useful as polymerizable species. Thus, bis-GMA
30 may be reacted with a diisocyanate (or other isocyanate)
such as hexamethylene diisocyanate, phenylene diisocyanate
or a wide variety of other aliphatic and aromatic
diisocyanates to provide useful polymerizable species. As
disclosed in U.S. Patent 4,411,625, the adducts of bis-GMA
35 hexamethylene diisocyanate have been found to be
particularly useful for restorative purposes and the same
may be used here.
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Methyl methacrylate, ethyl methacrylate, propyl
methacrylate, and higher methacrylates, acrylates,
ethacrylates, and similar species may be employed as all or
part of the polymerizable materials of the hardenable
compositions of the present invention. It is also possible
to employ other types of polymerizable material such as
epoxide compounds, polyurethane-precursor species, and a
wide host of other materials. For example, other monomers
useful in the production of hardenable compositions of this
invention include methyl-, ethyl, isopropyl-, tert-
butyloctyl-, dodecyl-, cyclohexyl-, chloromethyl-,
tetrachloroethyl-, perfluorooctyl- hydroxyethyl-,
hydroxypropyl-, hydroxybutyl-, 3-hydroxyphenyl-, 4-
hydroxphenyl-, aminoethyl-, aminophenyl-, and thiophenyl-,
acrylate, methacrylate, ethacrylate, propacrylate,
butacrylate and chloromethacrylate, as well as the
homologous mono-acrylic acid esters of bisphenol-A,
dihydroxydiphenyl sulfone, dihydroxydiphenyl ether,
dihydroxybiphenyl, dihydroxydiphenyl sulfoxide, and 2,2
bis(4-hydroxy-2,3,5,6-tetrafluorophenyl)propane.
Polymerizable monomers capable of sustaining a
polymerization reaction such as the di-, tri-, and higher
acrylic ethylene glycol dimethacrylate, diethylene glycol
dimethacrylate, trimethylene glycol dimethacrylate, etc.;
trimethylol propane trimethacrylate, analogous acrylates,
and similar species are also useful. It is also possible to
employ mixtures of two, three, and more and more
polymerizable species to good effect.
It is known that bis-GMA-based polymerization
systems are particularly useful in restorations within the
human body. This is so for a number of well-known reasons,
including general biocompatibility, absence of significant
amounts of toxic products, compatible coefficients of
thermal expansion, ease of use, stability, and the like.
Accordingly, such materials are preferred. Bisphenol-A-
glycidyl dimethacrylate (bisGMA), either with or without
comonomeric species, is most preferred.
CA 02239698 2004-09-17
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It is generally necessary to provide catalys is for
the polymerizable species used in the hardenable
compositions of the present invention. Such catalysts are
generally of two types, heat-curing catalysts and
photopolymerization initiators. Each type is well-known and
any catalytic system known for restorative use may be
employed so long as the same is consistent with the objects
of t he invent ion .
Heat curing catalysis is generally employed in
"two-paste" systems. In such a case, a catalytic syst em is
employed such that when two components of the hardenable
composition are mixed together, the catalytic action begins,
leading to hardening. This system is familiar and can be
applied to a wide variety of polymerizable species including
many which are suitable in the present invent ion. Radi cal
initiators such as peroxides, especially benz oyl peroxide
(also called dibenzoyl peroxide) are conventional, economic,
and convenient. A stabilizer, such as butyl hydroxytoluene
is customary. Employment of co-catalysts such as dimethyl-
p-toluidine, N-N-substituted toluidine and oxylidine is
conventional. In general, one of the pastes incorporates
the radical initiator and stabilizer, general ly a peroxide _
and the other paste, the accelerator, such as an amine,
preferably toluidine. Curing is begun by mixing the two
pastes together.
Photocuring is also a useful means f or attaining
hardening of compositions in accordance with the present
invention. Thus, a photoinitiation system can be included
with the hardenable compositions and the same caused to be
activated by~exposure to actinic light of a suitable
wavelength. Both ultraviolet and visible photocuring
systems are known for use in restorative surgery and
dentistry and any such system may be employed herein.
Exemplary systems are described in U.S. Patents 4,110,184
Dart et al., 4,698,373 - Tateosian et al., 4,491,453 -
Koblitz et al., and 4,801,528 - Bennett.
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A particularly useful system employs visible light
curing, thus avoiding the potential danger inherent in
curing with ultraviolet radiation. Visible light curing has
been well-refined in the dental field, and the same may also
be applied to restorations of bony.tissues. Quinones, as
clan s, find wide utility as photochemical initiators f or
visible light sensitizing systems, preferably when the same
are admixed with tertiary amines. It is pref erred that an
alpha diketone (quinone) such as camphoroquinone or bi acetyl
be admixed with an amine reducing agent such as n-alkyl
dial kanolamine or trialkanolamine.
While the hardenable compositions of the pre sent
invention are characterized as comprising polymerizable
spec ies together with filler, including combeite glass-
ceramic, it will be understood that other mat erials may be
included in such compositions. Thus, radio-opacifying
agents, surface active agents, handling agent s, pigments,
reinforcing materials such as fibers and the like, and a
wide variety of other materials may be included so long .as
the overall objectives of the present invention are
attained.
.. Persons skilled in the art will appreciate t hat
the amount of filler used in conjunction with the
polymerizable materials of the present invent ion will depend
upon several variables including the identity of the
polymerizable resins and the fillers and the particle sires
of the fillers. It will be appreciated that for a given
resin formulation, judicious choice of filler type and
filler particle size must be made such that an appropriate
viscosity, good workability, ease of blending and eventual
biocompatibility are attained.
In practice, light curable, hardenable
compositions are provided in unitary form, e.g. they need
not be mixed just prior to use. They are applied to the
site for restoration and then exposed to visible light of a
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suitable wavelength to cause polymerization through
intermediation of the catalyst system. Light sources and
methods of applications are well known to persons of
ordinary skill in the art and the same may be employed with
the compositions of the present invention.
Thus, a composition of the present invention is '
either blended together from two ~~pastes'~ , if a thermal
curing system is selected, or is used as provided, if a
photocuring system is elected. The same is applied to a
prepared site for restoration. The restorative is then
smoothed or shaped into place and the material allowed to
harden either through the passage of time, in the case of a
thermal curing material or through application of actinic
radiation in the case of a photocuring material. After
initial polymerization and resultant hardening has occurred,
the restoration becomes relatively strong. It will be load
bearing and capable of supporting underlying and overlying
structures within the body portion thus restored.
A further aspect of the present invention is the
provision of hard, shaped bodies. Thus, the hardenable
compositions of the present invention may be shaped such as
through conventional plastic processing technology, molding,
extrusion, hand-shaping and the like, and the resulting
shaped particles hardened either through the action of heat,
photochemical energy or otherwise. It is thus, possible to
provide a whole host of shaped bodies formed from the
materials of the invention which contain combeite glass-
ceramic. These shaped bodies may be used in a wide variety
of applications, especially in surgery and dentistry, where
their properties of biocompatibility, osteogenic
stimulation, and inherent strength will be found to be
beneficial.
For example, pins, screws, or rods may be
formulated out of hardenable compositions of the invention
through conventional extrusion or molding and caused to be
hardened. These pins, screw and rods may be used wherever
conventional pins, screws, or rods used in orthopaedic
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surgery are presently employed to provide strength and
stability to injured joints, fractured bone, and otherwise.
In use, such pins, screws, and rods are inserted into a
prepared location and cemented into place. Unlike prior,
generally metallic, pins or rods, however, the materials of
the present invention are inherently biocompatible and,
indeed, osteostimulatory. This is enhanced when the cement
used to affix the object rod to the bony structure is
selected to be a hardenable composition of the present
invention as well. As will be appreciated, adjustment of
viscosity for the material to serve as a cement for the pin,
screw, or rod can make it convenient to use this system in
the repair of bony structure. The result is that the entire
repair is made using only biocompatible and, indeed,
I5 osteostimulatory material; no metal at all need be employed.
A further use of the hardened materials of the
present invention can be found in endodontics. It is
conventional to employ "points'" for the restoration of root
canals and the like. Such points are conventionally silver,
gutta percha, or certain other materials. To restore a root
canal, access to the root canal of a diseased tooth is
obtained through the enamel and dentin of the tooth and a
portion of the nervous, bony, and other tissue of the root
canal is removed through the use of a number of conventional
instruments. The actual preparation of root canals for
restoration forms no part of the.present invention and all
such aspects of the procedure are well understood by persons
skilled in the art.
A prepared root canal must then be filled.
Conventionally, this is attained by placing silver or gutta
percha "points" into the prepared canal and causing the same
to be compacted into the space to be restored. It is
important that no leakage be experienced around the apical
foramen or subsequent reinfection may occur. This process
can be traumatic to the patient and is difficult to perform
in practice.
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In accordance with the present invention,
endodontic "points" can be prepared using the hardened
compositions of the invention. These can then be inserted
into the excavated space of a root canal along with
quantities of hardenable composition in accordance with the
present invention and the same caused to harden in situ.
Substantially complete filling of the prepared root canal
space can be attained and the osteostimulatory
characteristic of the present materials can give rise to
improved biocompatibility, and integration of the
restoration into the patient's bony structure, ensuing good
results.
Figure 3A depicts a rod useful for orthopaedic
restorations as described above. Figure 3B shows a spacer
for insertion into a vertebral space during spine fusion.
Figure 3C is a screw formed from hardened composition of the
invention while Figure 3D depicts a dental point.
Composites of the present invention may be used in
a wide variety of~restorative and surgical procedures
including those involving bone tissue subject to large
forces. One example is the repair or fusion of vertebrae of
the spine. A composite material can be placed in or near
the spine via syringe delivery and caused to polymerize in
situ. The resulting, hardened material provides load-
bearing stability and micromechanical bonding to vertebrae
or other bony material. After some time in the body, tissue
and bone attachment become augmented through the biological
interfacial chemical bond that eventually forms a hydroxy
apatite biologic interfacial bond between tissue, bone, and
the composite.
Hardened materials, such as vertebral spacers of
all sizes and shapes can be prefabricated and caused to
polymerize outside the body in order to maximize design
features necessary for surgical restoration in vivo. For
example, a pre-formed and hardened vertebral spacer can be
placed into a vertebral space and affixed thereto with the
aid of wire, rods, pins, screws, or adhesives in accordance
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with the present invention or otherwise. A spinal cage
prefabricated from the material of the present invention
offers familiarity of process, stability and implementation
together with autogenous bone grafting to the end that a
number of-flexible applications for spinal and other such
restorations obtain.
The materials of the present invention can also be
employed in dentistry and orthopaedics in all of those
circumstances where polymethyl methacrylate is presently
employed. Once an implantation sight has been prepared,
syringe delivery of a low-viscosity version of composites of
the present invention can be expressed to fill the void. If
desired, an implant may be used in conjunction with
polymerizable material of the present invention, such
implant being either metal, gutta percha, ceramic, polymer,
or, indeed, a hardened material in accordance with this
invention. Subsequent setting of the polymerizable material
yields a gross restoration suitable for finishing, further
restorative application, or otherwise.
A particular advantage of the present methodology
is that after healing of the sites of the restoration or
implant, the implanted material will begin to adhere
chemically to bone tissue interface, increasing the strength
and toughness of the implant system.
The materials of the present invention are
particularly useful for repairing failed implants,
especially in dental applications. After a patient has
spent months or years in therapy directed to the
stabilization of a dental implant, it's failure is
psychologically and physically catastrophic. The use of
composite materials such as those of the present invention
permits removal of the failed implant, refilling of the
maxillary or mandibular void with bioactive composite either
in syringable or in putty form, followed by immediate
replacement of the implant. Rapid adjustment of position,
setting, and the like, together with minimal healing time is
an attractive feature of the invention. It is also possible
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to stabilize an implant which is in the process of failing
through the application of materials in accordance with the
present invention. The injection of a composite material in
accordance with this invention is particularly suited to
this application since the same bonds to tissues, metal, and
itself together with numerous other composite materials, '
thus providing tremendous flexibility for such restorations.
Materials of this invention are also particularly
suited to the repair of comminuted fractures. In such a
case, a traumatic injury has led to crushed or fragmented
bone and a non-lead bearing graft material would not be
useful for its repair. At present, the use of metal plates
and rods is the only viable option. The present invention
can be used to reassemble bone fragments since the present
materials can be formulated into putty for this purpose.
Alternatively, photocuring materials may be used to cause
tackification and curing in a short period of time thus to
facilitate the reassembly of such fractures. It is also
possible to employ hardened materials in accordance with the
present invention, or traditional metal or ceramic bones,
pins, plates, and the like for such restorations. The rapid
load bearing capability of the materials of the present
invention along with their bioactivity confer particular
advantages to the present system.
A further example of the utility of the materials
of the present invention in orthopaedics involving great
stresses and procedural difficulties involves bipolar hip
replacement or revision. In such a case, implant fixation
on the femoral stem side is simple, however, the acetabular
cup attachment is very difficult, especially in revision
cases. With the use of pins, the acetabulum can be looted
with compositions of the present invention to make up for
lost bone of the acetabulum. Immediate function is critical
to this application and the load bearing ability of the
present materials indicates it for such use. The biological
bonding of the materials of the present invention will
enhance strength and toughness in such procedures and
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prevent further absorption of existing bone. Revision
surgery for a failed bipolar hip replacement is typically an
emergency requiring deliverable, flexible, and functional
materials such as those of the present invention.
Figure 4 shows a bipolar hip replacement. The
femur, having cortical bone, 31 and spongeous bone, 32 is
implanted with a prosthesis 34, cemented in place with
composite of the invention, 33. On the acetabular side, a
femural head articulation surface, 36 is cemented to a
prepared cavity with material of the invention, 33. A high
weight polyethylene cup, 35 is used to facilitate
articulation with the head of the prosthesis. Figure 3
shows a spacer for insertion into a vertebral space during
spine fusion.
The present invention is limited solely by the
appended claims and the proposed mechanism of action is not
to be construed as limiting in any way. It is believed,
however, that the particles of combeite glass-ceramic of the
invention are particularly beneficial for biological
restorations due to their unique structure and properties.
When combeite crystallites form, the remaining glass is
depleted in some elements and enriched in others. The
residual glass matrix after combeite crystallization is high
in Ca0 and Pa05, which gives rise to a high degree of
bioactive interaction with adjacent tissue. As the volume
fraction crystallized increases, the glass phase decreases.
The nature of this dissolution creates a mineral rich
surface on the composite that allows for interdigitation of
surrounding bone tissue. The quick reaction of combeite
glass-ceramic and surface mineralization of the composite
may be self-limiting, therefore retaining the internal
strength of the composite.
The above described mechanism is qualitatively
shown in the FTIR plots in Figure 5 and schematically
illustrated in Figure 7. As the composite is placed in a
physiologic environment in vivo, the bioactive combeite
glass-ceramic filler particles react by releasing Ca+Z, and
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PO4-3 ions to the surface of the composite. The FTIR in Figure
shows how the formation of surface apatites occurs as soon
as after 1 week. Figure 7a and 7b illustrate the
interdigitated, chemically bonded layer, 42 that is believed
5 to form between the composite, 44 and the bone tissue, 40.
The metastable calcium-phosphate surface of the composite
will nucleate and provide crystal growth material for the
adjacent bone mineral. After only 1 week, the body can see a
calcium phosphate ceramic surface, not a polymer-resin
surface.
In some cases, composite surfaces on the interior
may not participate in the biological reactions and are
thus, behave as a fully strengthened composite. The
bisphenol-A glycidyl dimethacrylate (BisGMA) resin matrix
can be blended with other monomers such as triethylene
glycol dimethacrylate (TEGDMA), diurethane dimethacrylate
(DUDMA), or ethoxylated bisphenol-A-glycidyl dimethacrylate
(BisEMA). The working time and set time can easily be
adjusted with the levels of amine in one component A and the
benzoyl peroxide and butyl hydroxytoluene in the other. The
average working time desired is 3 to 6 minutes with
immediate set thereafter. Full composite strength is
preferably achieved within 1.5 to 2 hours.
The unique bioactive bone grafting composites of
this invention are suited for implant fixation and repairs
to viable tissues and bone due to their ease of delivery and
placement, low heat generation on polymerization, low
shrinkage, as well as immediate fixation, adherence, and
load bearing. The unique surface interaction leads to a
bonded bioactive surface. The synergy between the combeite
glass-ceramic filler and the resin matrix is believed to
generate a reactive bone bonding resin-gel layer that is
ultimately converted to a resin-hydroxy apatite layer. See
Figure 7.
The self limiting biologic reaction makes the '
composites of this invention are ideal for dual functioning.
Thus, it is at least bioactive on a surface while internally
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functioning as a structural composite. This dual
functioning of the present composites make them suitable for
bone fracture repair where immediate fixation and load
' bearing is critical. The lower modulus matrix affords
shapeability and transfers the stress to the higher modulus
filler. The modulus of these composites (5-50 GPa) is
closer to that of natural bone (7-20 GPa) than PMMA alone
(3-5 GPa} or metal (100-200 GPa). Having an elastic modulus
comparable to bone avoids damaging stress shielding. The
fracture toughness of the entire system is enhanced due to
the bond strength to the implant, e.g. metal and ceramic,
surfaces and to bone. The intimate surface adhesion and
chemical bonding eliminates micromotion, aseptic loosening,
and maximizes the stress transfer for optimum load bearing
characteristics.
Once in contact with the physiologic environment,
the set composite reacts with the fluids of the body. The
serum and physiologic fluids diffuse into the permeable
structure of the reinforced composite and reacts with the
bioactive phases. Similarly to surface active bioceramics,
the reactant phases transport Ca*a, and P04-3 ions to the
surface of the composite. Due to the supersaturation of the
surrounding surface fluid, the slight increase in Ph, and
the active surface silanols and other resin hydroxyls, the
entire surface of the composite and some 10 to 200
micrometers into the composite is believed to be covered
with a gel layer rich in Ca0 and PZOsas depicted
schematically in Figure 7. This diffuse layer of resin-Ca0-
P205 forms the precursor for the conversion to the bone
mineral, hydroxyapatite. The nature of the resin matrix that
allows ion migration for bioactivity also benefit drug
delivery from an incorporated medicament.
Depending on the degree of reaction of the
bioactive filler, the particle size and the filler loading,
interdigitation of surrounding structures on the partially
resorbable surface can occur. If the particle size of the
bioactive filler is relatively large, the reaction of that
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particle leaves a large channel for bone cells, macrophages,
and vascularization. On a microscale, up to 200 to 300
micrometers, interdigitation of viable bone forming tissues
can impregnate the composite surface with bone mineral. This
micromechanically and chemically bonded interface is self
limiting and strengthens as the interface crystallizes to
form bone mineral, hydroxyapatite. The time for these events
can take up to 8 weeks, but the strength of the hardened
composite allows for immediate function. Improved bonding at
the biologic interface promotes further solidification and
long term stability.
Preferred resin systems are composed of two pastes
A & B. In one embodiment, paste A resin is comprised of 40-
60% by weight bisphenol-A glycidyl dimethacrylate (BisGMA.),
10-45% by weight triethylene glycol dimethacrylate (TEGDMA},
0-40% by weight diurethane dimethacrylate (DUDMA), 0.2-3.5%
by weight N,N-dimethyl-p-toluidine or other N,N-dialkyl
anilines or N,N-dialkyl toluidines, and 0-1.5% by weight
butylhydroxytoluene (BHT) or other free radical stabilizers.
Paste B resin is comprised of 40-60% by weight bisphenol-A-
glycidyl dimethacrylate (BisGMA}, 10-45% by weight
triethyleneglycol dimethacrylate (TEGDMA), 0-40% by weight
diurethane dimethacrylate (DUDMA), 0.1-3.0% by weight
benzoyl peroxide (BPO) or other organic peroxides, and 0-2%
by weight butylhydroxytoluene (BHT} or other free radical
stabilizers.
Various combinations of amine:BPO:BHT will yield
specific working and set times. Within the composition
variables given above, the 2.25:1:0.12 ratio gives the
preferred long work time of 5 minutes and the slow set time
of 8 to 10 minutes. The more preferred 3 minutes working
time and 5 to 7 minutes set time is obtained with a
2.5:1:0.1 amine:BPO:BHT ratio. Each set character will
depend on the mass of material used, energy imparted upon
mixing, and the temperature of the body (normally 37°C) at
the implant site.
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The filler level of paste A & B can vary from 65
to 85~ by weight total filler content with the preferred
bioactive glass-ceramic (Combeite glass-ceramic, CGC)
' content ranging from ZO to 99°s by weight of that filler. It
is preferred that the particle size distribution be broad,
bimodal, or preferably trimodal, also of which being less
than about 300 micrometers, with less than 5% by weight
being sub 0.1 microns sized.
Relatively low viscosity, syringable pastes are
best suited for the filling of bony defects, fracture
repair, and implant fixation and revision. Syringable
pastes flow to fill voids, and crevices, and adhere tightly
to the surface of the bone, tissue, or implant. Flowability
can be important for tight adherence and removal of
micromotion when implant securing is being achieved. The
lack of implant motion can reduce inflammation and determine
the success of the implant system over time. Higher
viscosity pastes are desirable for larger, load bearing bone
defects and easily accessible fracture sites. A "putty" can
be manipulated, sculpted and cured in place with immediate
high strength capability. Ontological bony defects are well-
suited for highly loaded, highly bioactive composites. The
use of hand mixed pastes can also facilitate the addition of
medicaments, antibiotics, or bone growth factors.
The resulting composite has a permeable surface
and 3-dimensional network that allows the bioactive fillers
to react with the physiologic environment to form an
interdigitated, diffuse interface layer comprised of resin-
Ca0-PZOS. Thos layer is the precursor to bone mineral
adhesion and formation. The micromechanical interlocking of
bone tissue and the surface of the composite strengthens as
the chemical bonds form and Crystallize into bone mineral
(FiAp}. The degree of interdigitation and the gel layer is
controlled by the amount of bioactive filler and the
particle size distribution of that filler.
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EXAMPLE 1
Combeite Glass-Ceramic
A blend of 33.9% silica, commonly denominated
"candle quartz", 30.98% sodium carbonate, 26.36% calcium
carbonate and 8.68% calcium hydrogen phosphate (CaHP04) were
melted together in a covered, platinum crucible in a 1
kilogram batch in a Globar'"' furnace under ordinary
atmosphere at a temperature between about 1200 and 1400°C for
12 hours. The resulting homogeneous melt was cast onto a
preheated graphite plate and allowed to slowly cool to room
temperature. The slow cooling allowed for significant
surface crystallization to occur and was clearly visible as
a white material on the surface of the glass plate. The
solid body thus foxmed was crushed, comminuted in a ball-
mill, and subjected to a ball mill or jaw crusher and then
series of screens to provide size segregation.
The ensuing particulate, combeite glass-ceramic
was comprised of particles having irregular morphologies
evidencing the fracturing and comminuting processes
described above. The morphologies include jagged edges,
rough prominences, irregular declivities, and similar
structures. Combeite glass-ceramic particles were obtained
having 5-10 volume percent combeite in the form of
microcrystalline regions - crystallites - as determined by
X-ray diffraction spectroscopy. The amount of combeite in
the combeite glass-ceramics prepared in accordance with this
example can be further increased by varying the time heated
at Tc or the temperature and time held above Tc. It is, thus
possible to prepare combeite glass-ceramics in particulate
form having combeite compositions crystallites ranging from
2% to 70% by volume.
The overall composition the combeite glass-ceramic
particles produced in accordance with this method, including
both the amorphous regions and the combeite crystallites,
was found to be 45% by weight silica, 24.5% sodium oxide,
24.5 calcium oxide and 6% PZ05.
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EXAMPLE 2
Combeite Glass-Ceramic, Frit Method
The blend of silica, sodium carbonate, calcium
' carbonate and calcium hydrogen phosphate of Example 1 was
melted as before. Rather than allow the same to cool as a
body on a substrate, the melt was poured into distilled
water to yield a frit. This frit was crushed and reheated
to 700°C for 1-2 hours to give rise to particulate combeite
glass-ceramic having highly irregular surface morphologies.
The overall composition of the combeite glass-ceramic is the
same as is found in the product of Example 1, however the
combeite crystallite composition is variable. It is possible
to modify the amount of combeite in the combeite glass-
ceramic in accordance with this protocol via time,
temperature profile adjustment. Particle size ranges may
also be selected through conventional means. The
crystallization processes changes. the beginning_glassy
structure of the parent glass to yield a unique final glass-
ceramic.
EXAMPLE 3
Paste-Paste Restorative
An acrylic resin-based paste-paste bone
restorative composition is prepared including combeite
glass-ceramic in accordance with this invention. A first
component was prepared consisting of:
bisphenol-A-glycidyl 55 parts by weight
dimethacrylate (BisGMA)
triethyleneglycol 45 parts by weight
dimethacrylate (TEGDMA)
butylhydroxytoluene (BHT) 0.04 parts by weight
N,N-dimethyl-p-toluidine 1.0 parts by weight
(DMEPT)
' dihydroxyethyl-p-toluidine 1.5 parts by weight
( DHE PT )
An inorganic filler blend is prepared comprising the
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following components:
Combeite glass-ceramic 50 parts by weight
having between 2 and 5% by
volume combeite in a '
particle size less than
about 50 microns
Combeite glass-ceramic 10 parts by weight
having between 5 and 50% by
volume combeite in particle
sizes less than about 50
microns
fumed silica having 8 parts by weight
particle sizes less than
about 1 micron and treated
with 2% of chloro
trimethylsilane
barium-alumina silica glass 32 parts by weight
(available from Scientific
Pharmaceuticals, Inc. under
the trademark IF 2324)
having particle sizes less
than 50 microns
The foregoing inorganic filler material is sieved to ensure
that at least 95% by weight of the inorganic, particulate
filler is less than about 50 microns in size.
The resin blend, in the amount of 35% by weight,
is combined with the above-described filler blend, 65% by
weight, and thoroughly mixed to result in a first component
of a two-part paste restorative composition. The viscosity
of this first component is approximately 15,000 centipoise.
A second component of the two-component paste
restorative composition is prepared from resin and filler
materials as follows:
A resin composition comprising the following
materials was blended together:
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bisphenol-A-glycidyl 55 parts by weight
dimethacrylate
triethyleneglycol 45 parts by weight
dimethacrylate
butylhydroxytoluene 0.04 parts by weight
benzoyl peroxide (BPO) 1.0 parts by weight
This resin component, in the amount of approximately 35
weight percent, was blended with 65 weight percent of the
filler blend described heretofore. The resulting, second
component of the two-paste system has a viscosity of
approximately 15,000 centipoise.
The first and second components, when blended
together, undergo a peroxide-catalyzed, thermal reaction to
result in hardening of the blended composition. The initial
viscosity of the blended materials is approximately 15,000
centipoise, a viscosity which is amenable to delivery via
wi da_-mGpth cy,rrjlT~7.ge . 'fh:J,yV:?r:~~ng--time--1.8- between- abGUt- -3
cit~td
5 minutes at 22°C. After this time, substantial hardening
begins. The hardened material is fully compatible with bone
tissue and dental structures.
The composition of this example sets hard within
about 5 minutes to a load bearing, high strength form. The
composite adheres immediately to metal, forming a strong
bond, as well as adhering to the shape of a cavity being
filled. The material is highly formable, shapable and
easily delivered by a syringe delivery system. The
composite is believed to be bioactive in that, upon contact
with physiologic fluids and blood sera, there is suspected
to be a biologic interface which forms and eventually
hardens.
EXAMPLE 4
Paste-Paste Restorative
A resin formulation is prepared from the following
components:
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bisphenol-A-glycidyl 50 parts by weight
dimethacrylate
triethyleneglycol I5 parts by weight
dimethacrylate '
diurethane dimethacrylate 35 parts by weight
CAS 411 37-6-4 available '
from Rohm Tech as MHOROMER
6661-0
butylhydroxytoluene 0.04 parts by weight
N,N-dimethyl-p-toluidine 0.75 parts by weight
( DME PT }
dihydroxyethyl-p-toluidine 1.5 parts by weight
(DHEPT}
An inorganic filler blend is prepared from the
following materials:
Combeite glass-ceramic 50 parts by weight
having between 2 and 5~ by
volume combeite and
particle sizes less than
about 50 microns
Combeite glass-ceramic 5 parts by weight
particles having between 5
and 50 ~ by volume combeite
and particle sizes less
than about 50 microns
Combeite glass-ceramic 5 parts by weight
having more than 50~ by
volume combeite and
particle sizes less than
about 50 microns
silane treated fumed silica 8 parts by weight
having particle sizes less
than 1 micron
barium alumina silicate 27 parts by weight
glass having particle sizes
less than about 50 microns
dicalcium phosphate 5 parts by weight '
dihydrate
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The foregoing inorganic filler material is sized
to ensure that at least 95~ of the particles have sizes less
than about 50 microns. A first paste is prepared from 65~
of inorganic filler blend and 35~ of the foregoing resin
composition.
A second resin composition comprising:
bisphenol-A-glycidyl 50 parts by weight
dimethacrylate
triethyleneglycol 15 parts by weight
dimethacrylate
diurethane dimethacrylate 35 parts by weight
butylhydroxytoluene 0.08 parts by weight
benzoyl peroxide 1..0 parts by weight
is blended with the inorganic blend of this example such
that the resin component comprises 35~ and the filler
composition comprises 65~ by weight of the material. The
resulting composition forms a second paste capable of
catalyzing a hardening reaction.
Each of the pastes has a viscosity of
approximately 18,000 centipoise, and is suitable for syringe
delivery. When blended together, the composite has a
working time between about 5 and 8lminutes at 22°C.
It is expected that the generally higher
crystallinity of the combeite glass-ceramic of this example
gives rise to a somewhat slower bioactivity. The release of
calcium and phosphate ions is compensated for by the
addition of DCPD which give rise to a slightly overall
increase in the viscosity of the material.
EXAMPLE 5
Paste-Paste Restorative
, A resin blend is prepared from:
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bisphenol-A-glycidyl 45 parts by weight
dimethacrylate (BisGMA)
triethyleneglycol 25 parts by weight
dimethacrylate (TEGDMA)
diurethane dimethacryiate 30 parts by weight
(DUDMA)
butylhydroxytoluene (BHT) 0.06 parts by weight
N,N-dimethyl-p-toluidine
(DMEPT)
dihydroxyethyl-p-toluidine 2 parts by weight
(DHEPT)
A filler blend is prepared from:
combeite glass-ceramic 50 parts by weight
(2 < 5 % by volume
combeite)
combeite glass-ceramic 5 parts by weight
(5 < 50% by volume
combeite)
combeite glass-ceramic 0 parts by weight
(>50% by volume combeite)
silane treated fumed silica 5 parts by weight
(<1 micrometer)
silane treated Ba0-B203- 20 parts by weight
A1203-SiOa glass (<50
micrometers)
dicalcium phosphate ~20 parts by weight
dehydrate (DCPD)
All of the combeite glass-ceramic powder is less than 50
micrometers in size. A first paste having 65% by weight
filler blend is formed and found to have a low viscosity
syringe delivery.
A resin blend for a second paste was prepared
3 5 f rom
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bisphenol-A-glycidyl 45 parts by weight
dimethacrylate (BisGMA)
triethyleneglycol 25 parts by weight
dimethacrylate
(TEGDMA)
diurethane dimethacrylate 30 parts by weight
( DUDMA )
butylhydroxytoluene (BHT) 0.1 parts by weight
benzoyl peroxide (BPO) 1.0 parts by weight
The filler for this paste comprises:
Combeite glass-ceramic 50 parts by weight
(CGC) (2 < 5 % by volume
combeite)
CGC (5 < 50% by volume 5 parts by weight
combeite)
CGC (>50% by volume 0 parts by weight
combeite)
silane treated (ST) fumed 5 parts by weight
silica (<1 micrometer)
silane treated Ba0-B203- 20 parts by weight
A1203-SiOz glass (<50
micrometers)
dicalcium phosphate 20 parts by weight
dehydrate (DCPD)
All of the combeite glass-ceramic powder is less than 50
micrometers in size as measured by sieving. The filler
content of the second paste is adjusted to 65% by weight for
a syringe. The working and set time of the above composite
at room temperature (22°C) is 7 and 10 minutes, respectively.
The crystalline combeite glass-ceramic phase and the DCPD
increases the release of Ca'2 and P04-3 ions .
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EXAMPLE 6
Powder-Resin Restorative
A resin blend is prepared from:
bisphenol-A-glycidyl 45 parts by weight
dimethacrylate (BisGMA}
triethyleneglycol 25 parts by weight
dimethacrylate (TEGDMA)
diurethane dimethacrylate 30 parts by weight
(DUDMA)
butylhydroxytoluene (BHT)
N,N-dimethyl-p-toluidine 0.06 parts by weight
{ DMEPT )
dihydroxyethyl-p-toluidine 2 parts by weight
( DHE PT )
A filler blend is prepared from:
combeite glass-ceramic 50 parts by weight
(2 < 5 % by volume combeite)
combeite glass-ceramic 25 parts by weight
(5 < 50% by volume combeite)
combeite glass-ceramic 0 parts by weight
(>50% by volume combeite)
silane treated fumed silica 5 parts by weight
(<1 micrometer)
silane treated Ba0-Ba03- 20 parts by weight
A1203-SiOa glass (<50
micrometers)
benzoyl peroxide (BPO) 1.0 part by weight
All of the combeite glass-ceramic powder, which is less than
50 micrometers in size, was placed in a polyethylene jar and
placed on a roller mill to blend the powders intimately. A
first paste having 65% by weight filler blend is formed and
found to have a low viscosity syringe delivery. The set time
of the powder-resin paste is approximately 6 minutes, with
the resulting mass forming a solid shape.
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EXAMPLES 7-11
Paste-Paste Restoratives:
The following paste compositions (up to 73.5 wt% filler) were
compounded by hand and mixed by expression through a two
stage static mixer{Courtalds Aerospace, N.J. and Mixpac, Co.,
Switzerland)and allowed to set at room temperature (23°C) in
(5mm x 35mm)cylindrical molds for mechanical strength
evaluations. ISO 4049 provided the testing and mechanical
standards that were followed.
e.g. %s/t %s/t %s/t % CGC DTS CS FS
BAS Si02 CGC (MPa) (MPa) (MPa)
7 28 8.5 18.5 18.5 31 190 62
8 0 8.5 65 0 28 167 52
9 41.8 9.2 0 21.6 34 268 75
10 46 4 0 23.3 30 225 67
11 29.4 6.5 0 35.8 28 180 54
TABLE LEGEND:
%s/t BAS = silanated Ba0-B203-A1a03-SiOa glass {<20 ~,m) .
%s/t Si02 = silanated fumed silica {<1 E.cm)
%s/t CGC = silanated combeite glass-ceramic(5 < 50% by volume
combeite)
DTS = Diametral Tensile Strength {MPa)
CS = Compressive Strength (MPa)
FS = Flexural Strength (MPa)
Example 10 had additional testing: the exotherm of
polymerization was measured by Differential Scanning
Calorimetry (DSC) and only increased to 55°C for a 14 gram
sample. Other compositions, not listed in the table above ,
were measured with comparable values (ranging from 46-58 °C).
Accelerated aging as a measure of composite shelf-
life was performed by aging the composite at 45°C for 50
hours and the teeing the work and set time, as well as
mechanical strength. The acceptable deviation, which all of
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the composites met, was +/- 1 min on the work and set time
and < 10~ of the mechanical strength.
The static fatigue properties were measured on a
load controlled instron mechanical tester, at room
temperature and a cycle frequency of 5 Hz (normal for
ambulation). The maximum load to failure for over 1 million
cycles was measured. The ultimate value for example 10 was
190 MPA up to 1.6 million cycles.
Toxicology testing following ISO 10993 and FDA
guidelines was conducted on the composite of example 7. The
composite was found to be non-bacteriocidal, non-fungicidal,
non-cytotoxic (acute systemic toxicity), non-irritating
(intracutaneous reactivity), non-sensitizing (Kligman and
guinea pig), non-pyrogenic, and non-mutagenic.
Biocompatibility ,should further be realized as
the reactive apatite surface layer is formed. Confirmation of
this apatite layer formation was observed after aging several
of the above listed composites in saline or physiologic body
fluids in a 37°C environment for various periods of time. The
surface was visually and microscopically changed from a
composite color (tan) to a chalky-white. FTIR revealed this
surface to have vibration modes indicative of apatites.
