U.S. patent application number 10/628147 was filed with the patent office on 2004-02-05 for reverse phase connective tissue repair composition.
This patent application is currently assigned to GenSci OrthoBiologics, Inc.. Invention is credited to Clokie, Cameron M.L..
Application Number | 20040022858 10/628147 |
Document ID | / |
Family ID | 25446457 |
Filed Date | 2004-02-05 |
United States Patent
Application |
20040022858 |
Kind Code |
A1 |
Clokie, Cameron M.L. |
February 5, 2004 |
Reverse phase connective tissue repair composition
Abstract
A biocompatible connective tissue repair composition which
comprises a therapeutic material and a carrier comprising a means
for achieving reverse phase characteristics, and methods for using
said composition. The therapeutic material can be demineralized
bone powder, and the carrier can be a poloxamer such as poloxamer
407.
Inventors: |
Clokie, Cameron M.L.;
(Rancho Palos Verdes, CA) |
Correspondence
Address: |
Janelle D. Waack
HOWREY SIMON ARNOLD & WHITE, LLP
750 Bering Drive
Houston
TX
77057
US
|
Assignee: |
GenSci OrthoBiologics, Inc.
|
Family ID: |
25446457 |
Appl. No.: |
10/628147 |
Filed: |
July 28, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10628147 |
Jul 28, 2003 |
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09939898 |
Aug 27, 2001 |
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6623748 |
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09939898 |
Aug 27, 2001 |
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08922068 |
Sep 2, 1997 |
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6309659 |
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Current U.S.
Class: |
424/486 ;
424/549 |
Current CPC
Class: |
A61L 27/3645 20130101;
A61L 27/3608 20130101; A61P 19/04 20180101; A61L 2430/02 20130101;
A61L 27/227 20130101; A61L 27/365 20130101; A61L 27/3683 20130101;
A61L 27/3687 20130101 |
Class at
Publication: |
424/486 ;
424/549 |
International
Class: |
A61K 035/32; A61K
009/14 |
Claims
What is claimed is:
1. A biocompatible connective tissue repair composition comprising:
demineralized bone powder, and, a carrier comprising a liquid
poloxamer solution or a solid poloxamer dissolved in a solvent,
whereby said carrier achieves reverse phase characteristics when
mixed with the demineralized bone powder.
2. The composition of claim 1, whereby the carrier causes the
composition to be substantially liquid at 0.degree. C., and
substantially solid at 35.degree. C.
3. The composition of claim 1 which has a first viscosity at
0.degree. C., and a second viscosity at 35.degree. C., wherein the
second viscosity is at least twice as great as the first
viscosity.
4. The composition of claim 1, wherein carrier comprises a solid
poloxamer dissolved in a solvent, and the poloxamer is poloxamer
407.
5. The composition of claim 4 wherein the solvent is sterile
water.
6. The composition of claim 5 wherein 25 weight percent of the
poloxamer 407 is dissolved in 75 weight percent of the sterile
water.
7. The composition of claim 1, wherein 30 weight percent of the
bone powder is dispersed in 70 weight percent of the carrier.
8. The composition of claim 1, wherein 50 weight percent of the
bone powder is dispersed in 50 weight percent of the carrier.
9. The composition of claim 1 wherein the-bone powder comprises
particles with a median length to a median thickness ratio of about
1.742:1, a mean length of 0.25-1 mm (250-1,000 microns), and a mean
thickness of about 0.5 mm (500 microns).
10. A biocompatible connective tissue repair composition
comprising: a therapeutic material, and, a carrier comprising a
means for achieving reverse phase characteristics.
11. The composition of claim 10, wherein the therapeutic material
is osteoinductive, osteoconductive, or osteoinductive and
osteoconductive.
12. The composition of claim 10, wherein the therapeutic material
is alloplastic, xenogeneic, allogeneic, or autogenic.
13. The composition of claim 10, whereby the means for achieving
reverse phase characteristics causes the composition to be
substantially liquid at 0.degree. C., and substantially solid at
35.degree. C.
14. The composition of claim 10 which has a first viscosity at
0.degree. C., and a second viscosity at 35.degree. C., wherein the
second viscosity is at least twice as great as the first
viscosity.
15. The composition of claim 10, wherein the means for achieving
reverse phase characteristics comprises a poloxamer.
16. The composition of claim 15, wherein the means for achieving
reverse phase characteristics comprises poloxamer 407.
17. The composition of claim 10, wherein the means for achieving
reverse phase characteristics comprises a block copolymer.
18. The composition of claim 17, wherein the means for achieving
reverse phase characteristics comprises a poly(oxyalkylene) block
copolymer.
19. The composition of claim 18, wherein the means for achieving
reverse phase characteristics comprises a
poly(oxyethylene)-poly(oxypropylene)-po- ly(oxyethylene) triblock
copolymer.
20. The composition of claim 19, wherein the triblock copolymer
comprises a formula: 3
21. The composition of claim 17, wherein the block copolymer is a
solid and is dissolved in a biocompatible solvent.
22. The composition of claim 21, wherein the biocompatible solvent
is sterile water.
23. The composition of claim 21, wherein 30 weight percent of the
therapeutic material is dispersed in 70 weight percent of the
carrier.
24. The composition of claim 21, wherein 50 weight percent of the
therapeutic material is dispersed in 50 weight percent of the
carrier.
25. The composition of claim 10 wherein the therapeutic material
comprises bone powder, and the bone powder comprises particles with
a median length to a median thickness ratio of about 1.742:1, a
mean length of 0.25-1 mm (250-1,000 microns), and a mean thickness
of about 0.5 mm (500 microns).
26. A method to facilitate the development of bone tissue, said
method comprising: providing the composition of claim 10; and,
placing the composition in a bony defect of a mammal.
27. The method of claim 26, further comprising a step of placing a
prosthetic object in the bony defect.
28. The method of claim 27, wherein the composition coats a portion
of the prosthetic object, and the step of placing the composition
and the step of placing a prosthetic object are contemporaneous.
Description
FIELD OF THE INVENTION
[0001] This invention concerns prosthetic materials. More
particularly, it concerns a biocompatible material that exhibits
reverse phase behavior.
BACKGROUND ART
[0002] Osteogenic bone repair materials are known in the art. These
materials contain an osteogenic material, such as demineralized
bone powder in a carrier, such-as glycerol. See, e.g., U.S. Pat.
No. 5,290,558, issued Mar. 1, 1994 to O'Leary et al., and U.S. Pat.
No. 5,284,655, issued Feb. 8, 1994 to Bogdansky et al.
[0003] The carrier of the bone material in the art is a liquid,
having a viscosity generally somewhere between runny to paste-like.
"Runny" bone repair compositions have the advantage of being
relatively easy to apply to and fill a bone defect, however, they
are disadvantageous in that the material also tends to readily flow
from the defect site. Conversely, bone repair compositions with a
"paste-like" consistency are harder to apply to a defect, yet tend
to remain positioned at the defect once applied. Additionally, when
any of the bone repair compositions in the art are placed in vivo
and become warmed, they become even less viscous; the decease in
viscosity is due to the addition of thermal energy to the
composition.
[0004] Accordingly, there is a need for a bone repair composition
that is easy to apply to a defect site, and which remains
positioned at the site once placed at the site.
DISCLOSURE OF THE INVENTION
[0005] Disclosed is a biocompatible composition to facilitate
repair of connective tissues. The composition can comprise
demineralized bone powder, and, a carrier comprising a means for
achieving reverse phase thermodynamic characteristics when mixed
with the bone powder. The composition can be substantially liquid
at 0.degree. C., and substantially more viscous at 35.degree. C.,
such that the composition has a consistency like that of paste
floor wax or like solid shoe wax. The means for achieving reverse
phase characteristics can comprise a block copolymer, such as a
poly(oxyalkylene) block copolymer, which can be a
poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) triblock
copolymer. The triblock copolymer can be a compound of the formula:
1
[0006] The means for achieving reverse phase characteristics
comprises a poloxamer, such as poloxamer 407. The block copolymer
can be a solid dissolved in a biocompatible solvent such as sterile
water.
[0007] Preferably, the composition comprises a carrier of 25 weight
percent of a block copolymer dissolved in 75 weight percent of a
biocompatible solvent. To vary the consistency of the composition,
the weight percentage of demineralized bone powder or other solid
can be varied relative to the weight percentage of the carrier in
the composition. For example, a paste-like form of the composition
comprises 50 weight percent of bone powder and 50 weight percent of
a carrier solution. A gel-like embodiment of the composition
comprises 70 weight percent of bone powder and 30 weight percent of
a carrier solution.
[0008] The bone powder of the composition can comprise particles
with a median length to a median thickness ratio of about 1.742:1,
a mean length of 0.25-1 mm (250-1,000 microns), and a mean
thickness of about 0.5 mm (500 microns).
[0009] Also disclosed is a method to facilitate the development of
bone tissue, said method comprising: providing a biocompatible
connective tissue repair composition comprising demineralized bone
powder, and, a carrier comprising a means for achieving reverse
phase thermodynamic characteristics when mixed with the bone
powder; and, placing the composition in a bony defect of a mammal.
A prosthetic object can also be placed in the bony defect. The
method can also comprise coating a portion of the prosthetic object
with the biocompatible composition, and in this embodiment the step
of placing the composition and the step of placing a prosthetic
object can be contemporaneous.
MODES FOR CARRYING OUT INVENTION
[0010] Definitions
[0011] By "reverse phase" or "reverse thermal behavior" is intended
a material that exhibits a physical property of becoming more
viscous or solidified upon addition of thermal energy. It is
believed that the solidification occurs by a mechanism other than
that due to evaporation and corresponding loss of liquid.
[0012] As used herein, "ambient temperature" is 25.degree. C., plus
or minus 5.degree. C.
[0013] As used herein, "body temperature" is 37.degree. C., plus or
minus 5.degree. C.
[0014] As used herein, a "bony defect" or "bone defect site" is
bony environment of a mammal which comprises some viable bone
tissue. The defect can be congenital, caused by trauma, or caused
by disease.
[0015] "Osteoinductive" materials cause undifferentiated cells to
differenitiate into a committed bone cell lines.
[0016] "Osteoinductive" materials provide support for cells of a
bone cell lineage, e.g., permitting cells of a bone cell lineage to
grow along or through a matrix or lattice.
[0017] Preferred Modes
[0018] In a preferred embodiment, the composition of the present
invention is a flowable liquid when applied to a bony defect,
whereupon the composition becomes increasingly solidified or
viscous as it warms to ambient and is further solidified as it
warms to body temperature. Upon being warmed to body temperature, a
preferred composition of the invention is a solid or highly viscous
fluid. The reverse phase compositions in accordance with the
invention are significantly different in principle from bone repair
materials in the art, and do not function in the same way.
[0019] The composition comprises a therapeutic material for
treating one or more connective tissues; and, a carrier. The
therapeutic material can be a material to facilitate repair of
connective tissues, i.e., a "connective tissue repair material."
The carrier achieves reverse phase characteristics when mixed with
the therapeutic material.
[0020] The therapeutic material can be a material that is
osteoinductive, osteoconductive, or a material that is
osteoinductive and osteoconductive. The therapeutic material can be
xenogeneic, allogeneic, or autogenic. The therapeutic material can
be alloplastic. As appreciated by one of ordinary skill in the art,
the therapeutic material can comprise combinations of various
therapeutic materials.
[0021] Examples of osteoinductive material include but are not
limited to bone powder (mineralized or demineralized), tissue
growth factor beta (TGF-.beta.) types 1 through 13, bone
morphogenetic protein (BMP) types 1 through 15, or combinations
thereof.
[0022] Examples of therapeutic materials that are osteoconductive
include but are not limited to xenogeneic bone (mineralized or
demineralized); the xenogeneic bone can also be subjected to
deproteination. Presently preferred xenogeneic source are porcine
and bovine.
[0023] Therapeutic materials that are osteoinductive and
osteoconductive include particulate human allograft, e.g., of
demineralized bone.
[0024] Examples of alloplastic materials comprise gypsum, coralline
hydroxyapatite, synthetic hydroxyapatite, calcium carbonate,
calcium phosphate, calcium sulfate, biodegradable polymeric
materials, or combinations thereof.
[0025] A presently preferred composition comprises demineralized
osteogenic bone powder in a carrier; the composition can be applied
to a bone defect site to induce new bone growth. This composition
of the present invention comprises demineralized bone particles or
granules (referred to here-in as "demineralized bone powder") in an
inert biocompatible carrier.
[0026] In a preferred embodiment, the particles/granules have a
median length to median thickness ratio about 1.742:1, a mean
length of 0.25-1 mm (250-1,000 microns) and a mean thickness of
about 0.5 mm (500 microns).
[0027] The presently preferred biocompatible carrier of the
composition of the invention is a material that confers reverse
phase thermodynamic properties on the composition. The use of
PLURONIC.RTM. F127 as a component of an osteointegration promoting
composition is set forth in U.S. Pat. No. 5,503,558, issued Apr. 2,
1996 to the inventor herein, Cameron C. L. Clokie; and in PCT
International Publication No. WO 95/13099. In a presently preferred
embodiment, the carrier comprises a polymer marketed by BASF
(Parsipanny, N.J.) as PLURONIC.RTM. F127. PLURONIC.RTM. F127 is a
poly(oxyalkylene) block copolymer; more specifically, a
poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)
poly(oxyethylene) triblock copolymer; it is a member of a class of
compounds called poloxamers. (Schmolka, "A Review of Block Polymer
Surfactants" J. Am. Oil Chemists Soc. 54:110-116 (1977)). Several
members of the poloxamer family exhibit reverse phase thermodynamic
characteristics. PLURONIC.RTM. F127 is also known by the name
"poloxamer 407." (Schmolka, "A Comparison of Block Polymer
Surfactant Gels" J. Am. Oil Chemist Soc. 68:206-209 (1991)).
PLURONIC.RTM. F127 has an average molecular weight of approximately
12,500. (Schmolka, "A Comparison of Block Polymer Surfactant Gels"
J. Am. Oil Chemist Soc. 68:206209 (1991)) The structure of the
PLURONIC.RTM. F127 polymer is depicted as follows: 2
[0028] In preferred embodiments of a composition of the present
invention, the carrier is a liquid diluted in a solvent or is a
solid dissolved in a solvent. In one embodiment, PLURONIC.RTM. F127
is dissolved in a solvent such as sterile water. The PLURONIC.RTM.
F127 carrier is vastly different in size, molecular weight, and
chemical structure than carriers in the art. The carrier is also
substantially different in terms of its functional properties than
any carrier of a bone repair material in the art.
[0029] The proposed composition has a unique physical property,
being flowable at refrigerated temperatures and increasingly
solidified at elevated temperatures, such as ambient and body
temperatures. This property is referred to in the art as "reverse
phase" or "reverse thermal behavior". Due to the reverse phase
property of the proposed composition, the composition is generally
manufactured at refrigerated temperatures, such as 5.degree. C.
Manufacturing is done at refrigerated temperatures to enhance
mixing of the components of the composition, since the proposed
composition comprising an aqueous solution of PLURONIC.RTM. F127
begins to become more viscous at ambient temperature, and is
increasingly viscous and solidified at body temperature. Generally,
a composition of the invention will be twice as viscous at
35.degree. C. as it is at 0.degree. C.
[0030] For example, the preferred PLURONIC.RTM. F127 carrier in the
composition of the present invention (when dissolved in an
appropriate amount of sterile water), has the unique property of
being a liquid at ambient temperature and increasingly solidified,
then solid at elevated temperature, absent the effects of
evaporation and concomitant loss of water. This property is called
"reverse phase" or "reverse thermal behavior" because it is the
exact opposite of the thermodynamic properties exhibited by
standard carriers.
[0031] It is believed that the reverse phase property is due; at
least in part, to the fact that PLURONIC.RTM. F127 is composed of
discrete blocks of both hydrophilic (i.e., oxyethylene) and
hydrophobic (i.e., oxypropylene) subunits. (See e.g., Schmolka, "A
Comparison of Block Polymer Surfactant Gels" J. Am. Oil Chemist
Soc. 68:206-209 (1991)).
[0032] In contrast, standard carriers, as well as all liquids,
manifest the typical physical property of becoming increasingly
flowable upon addition of thermal energy, such as occurs when the
liquid is heated to body temperature. However, the preferred
carrier in a composition of the present invention becomes less
flowable as energy is added to it either by heating or by
shaking.
[0033] The unique reverse phase thermodynamic properties of the
composition of the present invention allow the product to function
in a substantially different, and preferred manner relative to
other flowable bone repair products. When applied to a bone defect
site, the reverse phase property of the preferred carrier provides
support characteristics for the composition which are substantially
different than the characteristics of standard carriers. Enhanced
support is provided by the composition of the invention. The
preferred PLURONIC.RTM. F127 carrier of the composition of the
present invention helps to provide support characteristics which
are unlike those of any standard carrier. This is because the
composition is flowable at ambient temperature and can thus readily
be applied to a bony defect site, but it becomes increasingly
viscous and solidified once it is warmed at the site. The
solidification of the composition of the present invention achieves
several; beneficial effects. When solidified, the composition does
not flow away from the defect site, and the solidified product
immediately augments and facilitates structural support at the
defect. Also, since the osteogenic composition of the invention is
initially liquid, it readily fills a defect, then becomes
solidified and achieves enhanced osteogenesis. Moreover, with
preferred compositions of the invention, comprising a sterile
aqueous solution of PLURONIC.RTM. F127 as carrier and demineralized
bone powder, the carrier will resorb or dissolve after about three
days, leaving the osteogenic bone powder at the bone defect site.
It is believed to be advantageous that the carrier dissolves as
this then allows for enhanced ingrowth of connective or vascular
tissues.
[0034] In a composition of the invention, the weight percentages of
the therapeutic material and the carrier can each be varied. For
example, the weight percent of the therapeutic material can vary
between about 20 to 80 weight percent of the composition, and the
weight percent of the carrier can vary between about 20 to 80
weight percent of the composition. Furthermore one or more
additional components can be present in a composition of the
invention, such as antibiotics, analgesic, anti-inflammatory
agents, or agents to promote development of connective or
circulatory system tissues.
EXAMPLES
Example 1
[0035] To obtain a composition having a gel-like consistency, the
composition comprised 70 weight percent of a solution of
PLURONIC.RTM. F127 and 30 weight percent of bone powder. In this
example, the carrier comprised 25 weight percent of PLURONIC.RTM.
F127 powder dissolved in 75 weight percent sterile water.
[0036] A composition of the invention is available as DynaGraft.TM.
Gel (GenSci Regeneration Laboratories, Inc., Irvine, Calif.); this
product is a composition comprising demineralized allograft bone
from a single donor mixed with an inert preservative and a
biocompatible carrier. The composition has a "gel" consistency and
is provided in a sterile, single patient use package.
[0037] The tissues used in the bone repair composition are
recovered by United States tissue banks, from carefully screened
donors, according to standards established by the American
Association of Tissue Banks. All such tissues meet stringent
specifications during donor screening and laboratory testing in
order to reduce the risk of transmitting any infectious
disease.
[0038] For example, each donor is tested and found to be negative
for (at a minimum): hepatitis B surface antigen, human
immunodeficiency virus 1 and 2 antibodies, HTLV-1 antibody,
hepatitis C virus antibody, and syphilis. The tests were performed
by a CLIA approved laboratory utilizing FDA-licensed test kits. The
medical and social history of the donor revealed no risk factors
for, or clinical evidence of, HIV or hepatitis infection.
[0039] This biocompatible composition in accordance with the
invention was produced under environmentally controlled conditions
using stringent cleaning, preservation, and sterilization
procedures. All steps are rigorously quality controlled in
accordance with accepted methodologies in the art.
[0040] DynaGraft.TM. Gel is indicated for use in surgical
procedures in which osteogenesis, calcification or bony fusion is
needed to achieve or enhance the quality of the final result.
Accordingly, DynaGraft.TM. Gel can be used in a variety of
orthopedic, reconstructive, and dental bone grafting procedures.
DynaGraft.TM. Gel may be used alone as a bone graft in cases in
which the graft is not intended to provide weight bearing support
or dimensional integrity to the graft site. If the graft is
intended to be weight bearing, the composition should be used with
appropriate fixation. DynaGraft.TM. Gel can, therefore, be used as
a complement to musculoskeletal implants such as joint replacement
prostheses, intraoral implants, and internal and external fixation
devices for procedures in which demineralized freeze-dried bone
allograft would be used.
[0041] The composition is sterilized by a targeted 2.5 megarads of
electron beam irradiation as terminal sterilization. When
implanting the composition, sterile technique should be maintained
to minimize the risk of post-operative complications. Use of the
composition is contraindicated when there is active or latent
infection at or near the surgical site.
[0042] The composition should be stored long-term in a clean, dry
place at room temperature. It should be kept out of direct sunlight
and should not be frozen. DynaGraft.TM. Gel does not require
rehydration prior to use.
[0043] The packaging of all DynaGraft.TM. implant compositions has
been specially designed to provide ease of use within the surgical
field. For example, the composition can be packaged within syringes
that are kept sterile within one or more foil containers.
DynaGraft.TM. Gel is supplied in 1.0 cc, 5 cc, and 10 cc
syringes.
[0044] To use the composition packaged in syringes within foil
containers, the packaging is opened by peeling open the outer foil
and, using sterile technique, transferring the entire inner package
to the sterile field. The inner package is then opened and the
syringe removed. Immediately before use, a protective cap which
covers the tip of the syringe is removed. The composition is then
extruded by pushing on the syringe plunger to deliver the desired
volume. Appropriate placement and/or fixation are critical factors
in the avoidance of potentially adverse effects on product service
life.
[0045] Accordingly, the DynaGraft.TM. Gel is bacteriologically
sterile during the stated shelf life in an unopened and undamaged
package. The product must be used before the expiration date.
Unused product should be properly discarded.
Example 2
[0046] To obtain a composition having a paste-like consistency, the
composition comprised 50 weight percent of a solution of
PLURONIC.RTM. F127 and 50 weight percent of bone powder. In this
example, the carrier comprised 25 weight percent of PLURONIC.RTM.
F127 powder dissolved in 75 weight percent sterile water.
[0047] A composition of the invention is available as DynaGraft.TM.
Putty (GenSci Regeneration Laboratories, Inc., Irvine, Calif.);
this product is a composition comprising demineralized allograft
bone from a single donor mixed with an inert preservative and a
biocompatible carrier. The composition has a "putty-like"
consistency and is provided in a sterile, single patient use
package.
[0048] The tissues used in the bone repair composition are
recovered by United States tissue banks, from carefully screened
donors, according to standards established by the American
Association of Tissue Banks. All such tissues meet stringent
specifications during donor screening and laboratory testing in
order to reduce the risk of transmitting any infectious
disease.
[0049] For example, each donor is tested and found to be negative
for (at a minimum): hepatitis B surface antigen, human
immunodeficiency virus 1 and 2 antibodies, HTLV-1 antibody,
hepatitis C virus antibody, and syphilis. The tests were performed
by a CLIA approved laboratory utilizing FDA-licensed test kits. The
medical and social history of the donor revealed no risk factors
for, or clinical evidence of, HIV or hepatitis infection.
[0050] This biocompatible composition in accordance with the
invention was produced under environmentally controlled conditions
using stringent cleaning, preservation, and sterilization
procedures. All steps are rigorously quality controlled in
accordance with accepted methodologies in the art.
[0051] DynaGraft.TM. Putty is indicated for use in surgical
procedures in which osteogenesis, calcification or bony fusion is
needed to achieve or enhance the quality of the final result.
Accordingly, DynaGraft.TM. Putty can be used in a variety of
orthopedic, reconstructive, and dental bone grafting procedures.
DynaGraft.TM. Putty may be used alone as a bone graft in cases in
which the graft is not intended to provide weight bearing support
or dimensional integrity to the graft site. If the graft is
intended to be weight bearing, the composition should be used with
appropriate fixation. DynaGraft.TM. Putty can, therefore, be used
as a complement to musculoskeletal implants such as joint
replacement prostheses, intraoral implants, and internal and
external fixation devices for procedures in which demineralized
freeze-dried bone allograft would be used.
[0052] The composition is sterilized by a targeted 2.5 megarads of
electron beam irradiation as terminal sterilization. When
implanting the composition, sterile technique should be maintained
to minimize the risk of post-operative complications. Use of the
composition is contraindicated when there is active or latent
infection at or near the surgical site.
[0053] The composition should be stored long-term in a clean, dry
place at room temperature. It should be kept out of direct sunlight
and should not be frozen. DynaGraft.TM. Putty does not require
rehydration prior to use.
[0054] The packaging of all DynaGraft.TM. implant compositions has
been specially designed to provide ease of use within the surgical
field. For example, the composition can be packaged within jars
that are kept sterile within one or more foil containers.
DynaGraft.TM. Putty Gel is supplied in 2.5 cc, 5 cc, and 10 cc
jars.
[0055] To use the composition packaged in jars within foil
containers, the packaging is opened by peeling open the outer foil
and, using sterile technique, transferring the entire inner package
to the sterile field. The inner package is then opened and the jar
and a spatula are removed. The jar lid is opened in a sterile
manner and composition putty is removed with the spatula or other
hand-held instrument.
[0056] Appropriate placement of the composition and/or fixation are
critical factors in the avoidance of potentially adverse effects on
product service life.
[0057] Accordingly, the DynaGraft.TM. Putty is bacteriologically
sterile during the stated shelf life in an unopened and undamaged
package. The product must be used before the expiration date.
Unused product should be properly discarded.
[0058] Closing
[0059] It must be noted that as used herein and in the appended
claims, the singular forms "a," "and," and "the" include plural
referents unless the context clearly dictates otherwise. Thus, for
example, reference to "a formulation" includes mixtures of
different formulations and reference to "the method of treatment"
includes reference to equivalent steps and methods known to those
skilled in the art, and so forth.
[0060] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Although
any methods and materials similar to or equivalent to those
described herein can be used in the practice or testing of the
invention, the preferred methods and materials are now described.
All publications mentioned herein are fully incorporated herein by
reference.
* * * * *