U.S. patent application number 14/102155 was filed with the patent office on 2014-04-10 for bone cement with adapted mechanical properties.
This patent application is currently assigned to DePuy Synthes Products, LLC. The applicant listed for this patent is DePuy Synthes Products, LLC. Invention is credited to Andreas Boger, Elliott Gruskin, Andrea Montali, Kurtis Wheeler.
Application Number | 20140100297 14/102155 |
Document ID | / |
Family ID | 39738977 |
Filed Date | 2014-04-10 |
United States Patent
Application |
20140100297 |
Kind Code |
A1 |
Gruskin; Elliott ; et
al. |
April 10, 2014 |
Bone Cement With Adapted Mechanical Properties
Abstract
A bone cement is shown that includes a monomer, and a
non-reactive substance that is fully miscible with the monomer. A
resulting cured bone cement exhibits desirable properties such as
modification in a stiffness of the material. Modified properties
such a stiffness can be tailored to match bone properties and
reduce an occurrence of fractures adjacent to a region repaired
with bone cement. One example includes adjacent vertebral body
fractures in vertebroplasty procedures.
Inventors: |
Gruskin; Elliott; (West
Chester, PA) ; Boger; Andreas; (Burgoberbach, DE)
; Montali; Andrea; (Oberdorf, CH) ; Wheeler;
Kurtis; (Oberdorf, CH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
DePuy Synthes Products, LLC |
Raynham |
MA |
US |
|
|
Assignee: |
DePuy Synthes Products, LLC
Raynham
MA
|
Family ID: |
39738977 |
Appl. No.: |
14/102155 |
Filed: |
December 10, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12529562 |
Sep 2, 2009 |
8618188 |
|
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PCT/US2008/002811 |
Feb 29, 2008 |
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14102155 |
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60904673 |
Mar 2, 2007 |
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60967052 |
Aug 31, 2007 |
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Current U.S.
Class: |
521/128 ;
523/116; 523/117 |
Current CPC
Class: |
A61L 24/0036 20130101;
A61L 24/06 20130101; A61L 24/0084 20130101; A61L 24/0094 20130101;
A61L 24/06 20130101; C08L 33/12 20130101; A61L 2430/02
20130101 |
Class at
Publication: |
521/128 ;
523/116; 523/117 |
International
Class: |
A61L 24/00 20060101
A61L024/00 |
Claims
1. A method of forming bone cement, comprising: identifying a
mechanical property of bone; forming a fluid phase, comprising
mixing a monomer and a polymerizing agent; adding a powder phase to
the fluid phase; and adding a miscible substance to the fluid phase
in an amount sufficient to substantially match a mechanical
property of the bone cement to the identified mechanical property
of bone.
2. The method of claim 1, wherein the substance comprises an amount
between 20% and 60% of the fluid phase.
3. The method of claim 1, wherein the substance comprises an amount
between 30% and 60% of the fluid phase.
4. The method of claim 1, wherein the substance comprises an amount
between 30% and 50% of the fluid phase.
5. The method of claim 1, wherein the substance comprises an amount
between 20% and 45% of the fluid phase.
6. The method of claim 1, wherein the substance comprises an amount
of between 20% and 30% of the fluid phase.
7. The method of claim 1, wherein the substance comprises an amount
of about 25% of a total liquid component.
8. The method of claim 1, further including adding a radiopaque
agent to the fluid phase.
9. The method of claim 1, wherein the powder phase comprises poly
methyl methacrylate (PMMA) powder.
10. The method of claim 1, wherein the powder phase comprises
hydroxyapatite powder.
11. The method of claim 1, wherein the miscible substance does not
react with the powder phase.
12. The method of claim 1, wherein the substance creates a
microporous structure in the bone cement.
13. The method of claim 1, wherein the monomer comprises methyl
methacrylate (MMA) monomer, and the miscible substance comprises
n-methyl-pyrrolidone (NMP).
14. The method of claim 1, wherein the monomer comprises methyl
methacrylate (MMA) monomer, and the miscible substance comprises
dimethyl-sulfoxide (DMSO).
15. The method of claim 1, wherein the monomer comprises methyl
methacrylate (MMA) monomer, and the miscible substance comprises
polyethylene glycol (PEG).
16. The method of claim 1, wherein the monomer comprises methyl
methacrylate (MMA) monomer, and the miscible substance comprises
cellulose or cellulose derivate.
17. The method of claim 1, wherein the monomer comprises methyl
methacrylate (MMA) monomer, and the miscible substance comprises
NMP, DMSO, polyethylene glycol (PEG), cellulose, cellulose derivate
or any combination thereof.
18. The method of claim 1, wherein the bone is osteoporotic
bone.
19. The bone cement according to claim 1, wherein an elastic
modulus of the bone cement is between 50 MPa and 2000 MPa.
20. The bone cement according to claim 1, wherein an elastic
modulus of the bone cement is between 300 MPa and 1500 MPa.
21. The bone cement according to claim 1, wherein an elastic
modulus of the bone cement is between 500 MPa and 1200 MPa.
22. The bone cement according to claim 1, wherein an elastic
modulus of the bone cement is between 100 MPa and 1000 MPa.
23. The bone cement according to claim 1, wherein a yield strength
of the bone cement is between 30 MPa and 100 MPa.
24. The bone cement according to claim 1, wherein a yield strength
of the bone cement is between 40 MPa and 80 MPa.
25. The bone cement according to claim 1, wherein the bone cement
has a Young's modulus that matches osteoporotic bone.
26. The bone cement according to claim 1, wherein the miscible
substance is added to reduce elastic modulus, yield strength, or
both, of the bone cement.
Description
RELATED APPLICATION
[0001] This patent application is a divisional application of U.S.
application Ser. No. 12/529,562, filed Sep. 2, 2009, which is a
U.S. National Stage filing of International Patent Application
Serial No. PCT/US2008/002811, filed Feb. 29, 2008, which claims
benefit to U.S. Provisional Patent Application Ser. No. 60/904,673,
filed Mar. 2, 2007, and to U.S. Provisional Patent Application Ser.
No. 60/967,052, filed Aug. 31, 2007. The applications are
incorporated herein by reference in their entireties.
BACKGROUND
[0002] Vertebral compression fractures in osteoporotic patients are
typically treated by a surgical procedure known as vertebroplasty.
In this procedure the fractured vertebral body is augmented with a
bone cement. The bone cement polymerizes and hardens upon injection
into the vertebral body and stabilizes the fracture. Pain relief
for the patient is usually immediate and vertebroplasty procedures
are characterized by a high rate of success.
[0003] Typically, bone cement is prepared directly prior to
injection by mixing bone-cement powder (e.g.,
poly-methyl-methacrylate (PMMA)), a liquid monomer (e.g.,
methyl-methacrylate monomer (MMA)), an x-ray contrast agent (e.g.,
barium sulfate), and an activator of the polymerization reaction
(e.g., N,N-dimethyl-p-toluidine) to form a fluid mixture. Other
additives including but not limited to stabilizers, drugs, fillers,
dyes and fibers may also be included in the bone cement. Since the
components react upon mixing, immediately leading to the
polymerization, the components of bone cement must be kept separate
from each other until the user is ready to form the desired bone
cement. Once mixed, the user must work very quickly because the
bone cement sets and hardens rapidly.
[0004] Other examples of bone cement compositions and/or their uses
are discussed in U.S. Pat. No. 7,138,442; U.S. Pat. No. 7,160,932;
U.S. Pat. No. 7,014,633; U.S. Pat. No. 6,752,863; U.S. Pat. No.
6,020,396; U.S. Pat. No. 5,902,839; U.S. Pat. No. 4,910,259; U.S.
Pat. No. 5,276,070; U.S. Pat. No. 5,795,922; U.S. Pat. No.
5,650,108; U.S. Pat. No. 6,984,063; U.S. Pat. No. 4,588,583; U.S.
Pat. No. 4,902,728; U.S. Pat. No. 5,797,873; U.S. Pat. No.
6,160,033; and EP 0 701 824, the disclosures of which are herein
incorporated by reference.
[0005] The elastic moduli of typical PMMA bone cements lie around
2-4 GPa, while the elastic modulus of osteoporotic cancellous bone
lies in the range of 0.1-0.5 GPa. This mismatch in stiffness is
generally perceived as favoring the subsequent fracturing of the
vertebral bodies that are adjacent to the augmented vertebral
body.
[0006] It is therefore an object of the invention to obtain a bone
cement with a reduced stiffness that is adapted to the stiffness of
the surrounding bone. This is thought to be an efficient way to
reduce the risk of adjacent vertebral body fractures after the
augmentation of vertebral bodies.
[0007] Reduction of the stiffness by introducing non-miscible
phases, such as aqueous components, into the PMMA upon
polymerization is well known and has been described before. This
leads to a macroporous structure with reduced stiffness.
SUMMARY OF THE INVENTION
[0008] The invention relates to a bone cement including a monomer
and a substance that is substantially miscible with the monomer and
substantially does not contribute to a polymerization reaction. In
one embodiment of the invention, the substance is
N-methyl-pyrrolidone. In another embodiment, the substance is
dimethyl-sulfoxide (DMSO). In another embodiment, the substance is
polyethylene glycolide (PEG). In another embodiment, the substance
is cellulose and cellulose derivates. In another embodiment, the
substance is a mixture or blend of the mentioned substances or
other, comparable substances. In another embodiment, the substance
reduces a crosslink density of the bone cement. In another
embodiment, the substance creates a microporous structure in the
bone cement. In another embodiment, the bone cement further
includes polymerization of the monomer. In another embodiment, a
portion of the monomer in substituted by the substance during
polymerization. In another embodiment, substitution of the monomer
by the substance yields a decrease in the stiffness of the bone
cement.
[0009] The invention also relates to a bone cement including
methyl-methacrylate and N-methyl-pyrrolidone. In one embodiment of
the invention the volume percentage of the methyl-methacrylate
which is substituted by NMP, DMSO, PEG or other analogous
substances lies in the range of 20%-60%. One specific example
includes a volume percentage substitution of 25%. The volume of MMA
can be substituted by either one of the pure substances mentioned
above or by a mixture of these substances. In another embodiment of
the invention, a stiffness of the bone cement is between about 100
MPa to about 2000 MPa. In another embodiment of the invention, a
stiffness of the bone cement is between about 100 MPa to about 1500
MPa. In another embodiment of the invention, a stiffness of the
bone cement is between about 500 MPa to about 1200 MPa. In another
embodiment of the invention, a yield strength of the bone cement is
from about 30 MPa to about 100 MPa. In another embodiment of the
invention, a yield strength of the bone cement is from about 30 MPa
to about 80 MPa.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 is a graph showing the stiffness and yield strength
of bone cements according to an embodiment of the present
invention;
[0011] FIG. 2 is a graph showing the hardening behavior of bone
cements in accordance with an embodiment of the present
invention.
DETAILED DESCRIPTION
[0012] The present invention relates to a polymer bone cement or a
derivative thereof having improved mechanical properties that is
adapted to bone or osteoporotic bone. In one embodiment of the
invention, the polymer bone cement is PMMA. The improved mechanical
properties are achieved by adding a fully miscible solvent that
does not react with the PMMA to the reactive MMA monomer. By doing
so, the crosslink density of the material and the stiffness can be
reduced.
[0013] The present invention is based on using a substance that is
fully miscible with the monomer and is, therefore, molecularly
dissolved in the PMMA after polymerization. However, due to its
non-reactivity, this leads to a reduction in the final crosslink
density and/or to a material with a microporous structure and,
therefore, the stiffness of the material is reduced. After
implantation and full polymerization of the material, the
crosslink-lowering substance may be gradually substituted by body
fluids.
[0014] This concept was tested by substituting different amounts of
the reactive monomer with N-methyl-pyrrolidone (NMP), which does
not contribute to the polymerization reaction. Subsequent
mechanical testing of PMMA samples produced in this way showed a
reduction in stiffness greater than about 50% in some
embodiments.
[0015] The described effect of lowering the stiffness of the
material can be obtained with any solvent that is miscible with the
monomer of PMMA but does not contribute to the polymerization
reaction. Another example of such of a solvent is
Dimethyl-sulfoxide (DMSO). In other embodiments, a range of other
solvents can also be envisioned. In another embodiment, substances
such as PEG, cellulose, cellulose derivates or mixtures thereof can
be added.
[0016] Furthermore, the present concept is not limited to PMMA
cements, it can be applied to a wide variety of derivatives of
PMMA, e.g. modifications in which Styrene groups are built into the
polymer backbone. The same concept also applies to cements that are
not based on the acrylate chemistry.
[0017] A material as described above, with mechanical properties
adapted to those of e.g. osteoporotic bone can be used in any
indication, where bone needs to be augmented, e.g. the proximal
femur, the proximal humerus, long bones, vertebral bodies or the
like.
[0018] As shown by the data in Table 1, the bone cements according
to embodiments of the present invention that include NMP exhibit a
decrease in stiffness when compared to the bone cement without NMP.
The decrease in stiffness occurs as a result of the substitution of
some of MMA monomer by NMP. According to some embodiments, by
substituting a part of the reactive liquid MMA monomer with
non-reactive organic solvent NMP during polymerization, the
crosslink density in the final material was lowered and therefore
the stiffness of the material was reduced. In other embodiments,
the NMP can act as a pore forming phase, resulting in bone cement
having a microporous structure. As discussed above, a decrease in
stiffness is an efficient way to reduce the risk of adjacent
vertebral body fractures in vertebroplasty procedures.
[0019] In some embodiments, the bone cements including NMP
demonstrate an increase in hardening time. That is, the time for
the bone cement to set and harden is longer for the cements having
an NMP component. In some embodiments, an increase in handling time
allows for greater working time for the user, which can increase
the safety of surgical procedures.
[0020] In addition to the reduced stiffness, another property which
is influenced by the mentioned modification is the maximum
polymerization temperature of the exothermic polymerization of
PMMA. Typically, polymerization of the PMMA can generate enough
heat and increase the temperature of the bone cement to such a
degree as to cause tissue necrosis. Because the bone cements of the
present invention includes a lower content of monomer (MMA), which
is the component that generates the heat during the polymerization
reaction, the maximum polymerization temperature can be lowered.
This is particularly advantageous because tissue necrosis may be
reduced or avoided when the bone cement of the present invention is
used, which allows for the use of the bone cement in areas of the
body which are particularly sensitive to heat. For example, bone
necrosis or other tissue necrosis can be a substantial problem
during cranial reconstruction where the bone cement may contact the
dura mater, due to the delicacy of the tissues and bone structures.
Use of a bone cement having reduced heat generation is therefore
particularly desirable in these areas.
[0021] Another advantage of the bone cements of the present
invention is the potential reduction in the toxicity of the
composition. Bone cement monomers, including methyl methacrylate,
give off toxic vapors which can be irritating to the eyes and
respiratory system. Furthermore, acrylate monomers can irritate the
skin, and contact with minute concentrations can cause
sensitization. Therefore, since the bone cement of the present
invention uses a lower amount of monomer, the potential for the
above problems to occur while using the bone cement of the present
invention may be reduced.
[0022] In some embodiments of the present invention, the bone
cement can be useful for vertebroplasty. The mentioned properties
of hardening behavior, mechanical and thermal properties especially
increasing of the handling time (more time for the surgeon and
therefore more safety), lowering the stiffness (avoiding the
mechanical property mismatch of the bone to the cement) and
reducing the polymerization temperature (reduce tissue necrosis)
are important properties for cement used in vertebroplasty. It is
possible, that all of these requirements could be achieved by
substituting some of the MMA monomer with NMP.
EXAMPLE
[0023] The following example was carried out using commercial PMMA
cement Vertecem. Vertecem is a fast setting, radiopaque acrylic
bone cement for use in percutaneous vertebroplasty. The fluid phase
is composed of 97.6% methyl-methacrylate (MMA), 2.4%
N,N-dimethyl-p-toluidine as activator and very small quantities (20
ppm) of hydroquinones as stabilizer. The polymer powder is composed
of 64.4% PMMA, 0.6% benzoyl peroxide which initiates the
polymerization, 25% barium sulfate as radiopaque agent and 10%
hydroxyapatite.
[0024] The fluid MMA monomer phase was partly substituted by NMP
organic solvent by different amounts. NMP is totally miscible with
the MMA monomer fluid. The amounts of MMA, and NMP, and PMMA used
in the different compositions are listed in Table 1.
TABLE-US-00001 TABLE 1 Sample MMA/ NMP/ PMMA Stiffness/ Yield
strength/ Name ml ml powder/g MPa Average MPa Average 0% 10 0 21
2384 78 20% 8 2 21 1838 86 30% 7 3 21 752 52 50% 5 5 21 456 37 60%
4 6 21 320 24
[0025] The MMA monomer and NMP was premixed to form a fluid
mixture. Subsequently the fluid mixture was mixed with the PMMA
powder to form a paste. To prepare the samples for mechanical
testing, the paste was filled into cylindrical Teflon.RTM. molds
(20 mm height, 6 mm diameter). The hardened cylinders were then
removed from the mold, sawed and ground to the length of 12 mm,
these dimensions correspond to the requirements of standard ISO
5833. After storing the samples in water for 6 days at room
temperature they were submitted for mechanical compression testing
according to standard ISO 5833. The elastic modulus and yield
strength were determined according to the mentioned standard and
presented in FIG. 1. Results are shown in FIG. 1, illustrating
trends versus percent of MMA that is substituted by NMP.
[0026] For the investigation of the hardening behavior of the
cement compositions, 3 ml of the mixed bone cement were placed in a
rotational rheometer with a custom designed double gap measurement
system and rheological data were recorded directly to a computer
for 24 portions of cement. The real (fluid-like) part of complex
viscosity vs. time data are presented in FIG. 2.
* * * * *