U.S. patent application number 14/213855 was filed with the patent office on 2014-09-18 for implantable medical devices comprising bio-degradable alloys with enhanced degradation rates.
This patent application is currently assigned to Bio DG, Inc.. The applicant listed for this patent is Bio DG, Inc.. Invention is credited to Paul JABLONSKI, Herbert RADISCH.
Application Number | 20140271768 14/213855 |
Document ID | / |
Family ID | 51528021 |
Filed Date | 2014-09-18 |
United States Patent
Application |
20140271768 |
Kind Code |
A1 |
RADISCH; Herbert ; et
al. |
September 18, 2014 |
IMPLANTABLE MEDICAL DEVICES COMPRISING BIO-DEGRADABLE ALLOYS WITH
ENHANCED DEGRADATION RATES
Abstract
The invention provides medical devices comprising high-strength
alloys which degrade over time in the body of a human or animal, at
controlled degradation rates, without generating emboli and which
have enhanced degradation due to the presence of a halogen
component. In one embodiment the alloy is formed into a bone
fixation device such as an anchor, screw, plate, support or rod. In
another embodiment the alloy is formed into a tissue fastening
device such as staple. In yet another embodiment, the alloy is
formed into a dental implant or a stent.
Inventors: |
RADISCH; Herbert; (San
Diego, CA) ; JABLONSKI; Paul; (San Diego,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Bio DG, Inc. |
San Diego |
CA |
US |
|
|
Assignee: |
Bio DG, Inc.
San Diego
CA
|
Family ID: |
51528021 |
Appl. No.: |
14/213855 |
Filed: |
March 14, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61785531 |
Mar 14, 2013 |
|
|
|
Current U.S.
Class: |
424/422 ;
420/127; 420/72; 420/8; 428/586 |
Current CPC
Class: |
A61L 31/148 20130101;
A61C 8/0012 20130101; Y10T 428/12292 20150115; A61L 31/16 20130101;
A61L 27/042 20130101; A61L 31/022 20130101 |
Class at
Publication: |
424/422 ;
428/586; 420/8; 420/72; 420/127 |
International
Class: |
A61L 27/04 20060101
A61L027/04; A61C 8/00 20060101 A61C008/00 |
Claims
1. An implantable medical device comprising a biodegradable alloy,
wherein the alloy is iron based and comprises an iron reactive
component, wherein the alloy reacts with a bodily fluid when it is
in contact with the fluid and wherein the degradation rate of the
alloy when implanted in a biological subject is faster than the
degradation rate of an alloy having the same composition as the
said alloy except the absence of the iron reactive component.
2. The implantable medical device of claim 1, wherein the iron
reactive component has a boiling point above the melting
temperature of an alloy having the same composition as the said
alloy in claim 1 except the absence of the iron reactive
component.
3. The implantable medical device of claim 1, wherein the iron
reactive component is a halogen component.
4. The implantable medical device of claim 3, wherein the halogen
component is selected from chloride, fluoride, bromide and
iodide.
5. The implantable medical device of claim 3, wherein the halogen
component is chloride or fluoride.
6. The implantable medical device of claim 3, wherein the halogen
component is provided as a salt.
7. The implantable medical device of claim 3, wherein the halogen
component is selected from sodium fluoride, sodium chloride, copper
chloride, copper fluoride, magnesium chloride, silver chloride,
calcium chloride, calcium fluoride and iron chloride.
8. The implantable medical device of claim 1, wherein the iron
reactive component is in a salt form with a boiling temperature of
at least about 1600.degree. C., at least about 1650.degree. C., at
least about 1700.degree. C., at least about 1750.degree. C., at
least about 1800.degree. C., at least about 1850.degree. C., at
least about 1900.degree. C., at least about 1950.degree. C., or at
least about 2000.degree. C.
9. The implantable medical device of claim 3, wherein the halogen
component is chlorine.
10. The implantable device of claim 1, wherein the iron reactive
component is equally dispersed within the alloy.
11. The implantable device of claim 1, wherein the iron reactive
component is dispersed on the surface of the alloy.
12. The implantable medical device of claim 1, wherein the device
degrades at a rate of about 1-2 mg per day per square inch when
placed in purified water.
13. The implantable medical device of claim 1, wherein the average
grain size is about 0.5 microns to about 5.0 microns.
14. The implantable medical device of claim 1, wherein the average
grain size is stable at minimum recrystallization temperature of
about 0.55 times the absolute melting temperature of the alloy.
15. The implantable medical device of claim 1, wherein the
implantable device is a bone screw, bone anchor, tissue staple,
craniomaxillofacial reconstruction plate, fastener, reconstructive
dental implant, or stent.
16. The implantable medical device of claim 1, wherein the alloy
comprises an austenite promoting component and a corrosion
resisting component.
17. The implantable medical device of claim 1, wherein the alloy
contains between about 20% to 40% manganese.
18. The implantable medical device of claim 1, wherein the alloy
contains less than about 0.3% niobium.
19. The implantable medical device of claim 1, wherein the alloy
contains less than about 1% carbon.
20. The implantable medical device of claim 1, wherein the
biodegradable alloy comprises manganese and niobium.
21. The implantable medical device of claim 1, wherein the
biodegradable alloy comprises at least about 0.01% to about 0.1%
non-metallic element.
22. The implantable medical device of claim 1, wherein the
biodegradable alloy comprises at least about 0.01% to about 0.1%
carbon.
23. The implantable medical device of claim 1, wherein the device
is coated with a therapeutic agent.
24. The implantable medical device of claim 1, wherein the device
is coated with a biodegradable hydrogel.
25. The implantable medical device of claim 1, wherein the device
comprises a geometry that maximizes the surface to mass ratio.
26. The implantable medical device of claim 1, wherein the device
comprises a hollow opening or passageway.
27. The implantable medical device of claim 1, wherein the
concentration of the iron reactive component in the alloy is
between about 1 ppm to about 500 ppm, between about 10 ppm to about
300 ppm, or between about 50 ppm to about 150 ppm.
28. The implantable medical device of claim 1, wherein the
concentration of the iron reactive component in the alloy is about
200 ppm,
29. An implantable medical device of claim 1, wherein the
biodegradable alloy is formed by: adding a gaseous iron reactive
component during the melting process.
30. The implantable medical device of claim 29, wherein the gaseous
iron reactive component has a partial pressure of at least about
0.1 tor, at least about 0.2 tor, at least about 0.5 tor, at least
about 0.8 tor, at least about 1 tor, at least about 2 tor, at least
about 5 tor, at least about 10 tor, at least about 50 for or at
least about 100 tor.
31. The implantable medical device of claim 29, the iron reactive
component is a halogen component.
32. The implantable medical device of claim 31, wherein the halogen
component is chlorine.
33. The implantable medical device of claim 29, wherein the gaseous
iron reactive component was added to mix with argon gas.
34. The implantable medical device of claim 33, wherein the argon
gas has a partial pressure of at least about 10 tor, at least about
20 tor, at least about 50 tor, at least about 80 tor, at least
about 100 tor, at least about 150 tor, at least about 200 tor, at
least about 250 tor, at least about 300 tor, or at least about 500
tor.
35. A method of controlling the degradation rate of an implantable
medical device of claim 1 comprising a step of: modulating the
concentration of the iron reactive component in the alloy.
36. The method of claim 35, wherein the concentration of the iron
reactive component in the alloy is between about 1 ppm to about 500
ppm, between about 10 ppm to about 300 ppm, or between about 50 ppm
to about 150 ppm.
37. The method of claim 35, wherein the concentration of the iron
reactive component in the alloy is about 200 ppm.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of priority to U.S.
Provisional Application No. 61/785,531, filed on Mar. 14, 2013, the
contents of which are hereby incorporated by reference in their
entireties for all purposes.
FIELD OF THE INVENTION
[0002] The present invention relates to biodegradable materials
useful for manufacturing implantable medical devices, specifically
biodegradable compositions comprising iron reactive component
containing metal alloys that can provide high strength when first
implanted and are gradually eroded and replaced with body
tissue.
BACKGROUND OF THE INVENTION
[0003] Medical devices meant for temporary or semi-permanent
implant are often made from stainless steel. Stainless steel is
strong, has a great deal of load bearing capability, is reasonably
inert in the body, does not dissolve in bodily fluids, and is
durable, lasting for many years, if not decades. Long lasting
medical implants, however, are not always desirable. Many devices
for fixing bones become problematic once the bone has healed,
requiring removal by means of subsequent surgery. Similarly, short
term devices such as tissue staples have to be removed after the
tissue has healed, which limits their use internally.
[0004] Attempts to generate biodegradable materials have
traditionally focused on polymeric compositions. One example is
described in U.S. Pat. No. 5,932,459, which is directed to a
biodegradable amphiphilic polymer. Another example is described in
U.S. Pat. No. 6,368,356, which is directed to biodegradable
polymeric hydrogels for use in medical devices. Biodegradable
materials for use in bone fixation have been described in U.S. Pat.
No. 5,425,769, which is directed to CaSO.sub.4 fibrous collagen
mixtures. And U.S. Pat. No. 7,268,205 describes the use of
biodegradable polyhydroxyalkanoates in making bone fasteners such
as screws. However, none of the biodegradable polymeric materials
developed to date have demonstrated sufficient strength to perform
suitably when substantial loads must be carried by the material,
when the material is required to plastically deform during
implantation, or when any of the other native characteristic of
metal are required from the material. For example, the
polyhydroxyalkanoate compositions described in U.S. Pat. No.
7,268,205 do not have sufficient strength on their own to bear
weight and must be augmented by temporary fixation of bone
segments. In addition, biodegradable polymeric materials tend to
lose strength far more quickly than they degrade, because the
portions of the material under stress tend to be more reactive,
causing preferential dissolution and breakdown at load-bearing
regions.
[0005] Metals, particularly steels, are thus preferred for the
construction of many medical implants. The performance
characteristics of steel closely match the mechanical requirements
of many load bearing medical devices. Although ordinary steel
compounds, unlike stainless steel, will degrade in biological
fluids, they are not suitable for use in biodegradable implantable
medical devices. This is because ordinary steels do not degrade in
a predictable fashion, as one molecule or group of molecules at a
time, which can be easily disposed of by the body. Rather, because
of their large-grain structures, ordinary steels tend to break down
by first degrading at grain boundaries, causing fissures and
separations in the medical device, followed by rapid loss of
strength and integrity and particulation. Particulation of the
medical device is extremely dangerous because it allows small
pieces of the device to leave the area of implantation and become
lodged in other tissues, where they can cause serious injury
including organ failure, heart attack and stroke. The use of
ordinary steels in implantable medical devices is also complicated
by the fact that ordinary steels typically contain alloying
elements that are toxic when released in the body.
[0006] There remains a need in the field to develop additional
implantable medical devices that have desirable characteristics
associated with steel but which are also biodegradable.
SUMMARY OF THE INVENTION
[0007] The invention is based, in part, on the discovery that
certain metal alloys having an iron reactive component will
biodegrade over time without forming emboli. The invention is also
based, in part, on the discovery that certain metal alloys having,
e.g., an iron reactive component containing alloy which reacts with
a bodily fluid when it is in contact with the fluid degrades with a
degradation rate that is faster when implanted in a biological
subject than the degradation rate of an alloy having the same
composition except that the alloy does not contain an iron reactive
component. Such alloys are useful for making biodegradable,
implantable medical devices.
[0008] In some embodiments, the implantable medical device of the
present invention comprises a biodegradable alloy, wherein the
alloy is iron based and comprises an iron reactive component,
wherein the alloy reacts with a bodily fluid when it is in contact
with the fluid and wherein the degradation rate of the alloy when
implanted in a biological subject is faster than the degradation
rate of an alloy having the same composition as the said alloy
except the absence of the iron reactive component.
[0009] In some embodiments, the iron reactive component has a
boiling point above the melting temperature of an alloy having the
same composition except the absence of the iron reactive
component.
[0010] In some embodiments, the iron reactive component is a
halogen component. In some embodiments, the halogen component is
provided as a salt. In some embodiments, the halogen component is
selected from sodium fluoride, sodium chloride, copper chloride,
copper fluoride, magnesium chloride, silver chloride, calcium
chloride, calcium fluoride and iron chloride.
[0011] In some embodiments, the halogen component is selected from
chloride, fluoride, bromide and iodide. In some embodiments, the
halogen component is chloride or fluoride.
[0012] In some embodiments, the iron reactive component is in a
salt form with a boiling temperature of at least about 1600.degree.
C., at least about 1650.degree. C., at least about 1700.degree. C.,
at least about 1750.degree. C., at least about 1800.degree. C., at
least about 1850.degree. C., at least about 1900.degree. C., at
least about 1950.degree. C., or at least about 2000.degree. C.
[0013] In some embodiments, the halogen component is halogen. In
some embodiments, the halogen is chlorine.
[0014] In some embodiments, the iron reactive component is equally
dispersed within the alloy.
[0015] In some embodiments, the iron reactive component is
dispersed on the surface of the alloy.
[0016] In some embodiments, the implantable medical device of the
present invention degrades at a rate of about 1-2 mg per day per
square inch when placed in purified water.
[0017] In some embodiments, the average grain size is about 0.5
microns to about 5.0 microns. In some embodiments, the average
grain size is stable at minimum recrystallization temperature of
about 0.55 times the absolute melting temperature of the alloy.
[0018] In some embodiments, the implantable medical device is a
bone screw, bone anchor, tissue staple, craniomaxillofacial
reconstruction plate, fastener, reconstructive dental implant, or
stent.
[0019] In some embodiments, the alloy comprises an austenite
promoting component and a corrosion resisting component.
[0020] In some embodiments, the alloy contains between about 20% to
40% manganese. In some embodiments, the biodegradable alloy
comprises manganese and niobium. In some embodiments, the alloy
contains less than about 0.3% niobium. In some embodiments, the
alloy contains less than about 1% carbon. In some embodiments, the
biodegradable alloy comprises at least about 0.01% to about 0.1%
non-metallic element. In some embodiments, the biodegradable alloy
comprises at least about 0.01% to about 0.1% carbon.
[0021] In some embodiments, the implantable medical device is
coated with a therapeutic agent.
[0022] In some embodiments, the implantable medical device is
coated with a biodegradable hydrogel.
[0023] In some embodiments, the implantable medical device
comprises a geometry that maximizes the surface to mass ratio.
[0024] In some embodiments, the implantable medical device
comprises a hollow opening or passageway.
[0025] In some embodiments, the biodegradable alloy is formed by
adding a gaseous iron reactive component during the melting
process.
[0026] In some embodiments, the gaseous iron reactive component has
a partial pressure of at least about 0.1 tor, at least about 0.2
tor, at least about 0.5 tor, at least about 0.8 tor, at least about
1 tor, at least about 2 tor, at least about 5 tor, at least about
10 tor, at least about 50 for or at least about 100 tor.
[0027] In some embodiments, the iron reactive component is a
halogen component. In some embodiments, the halogen component is
chlorine.
[0028] In some embodiments, the gaseous iron reactive component was
added to mix with argon gas. In some embodiments, the argon gas has
a partial pressure of at least about 10 tor, at least about 20 tor,
at least about 50 tor, at least about 80 tor, at least about 100
tor, at least about 150 tor, at least about 200 tor, at least about
250 tor, at least about 300 tor, or at least about 500 tor.
[0029] The invention and additional embodiments thereof will be set
forth in greater detail in the detailed description that
follows.
[0030] Accordingly to some embodiments of the present invention,
provided is a method of controlling the degradation rate of an
implantable medical device, comprising a step of modulating the
concentration of the iron reactive component in the alloy.
DETAILED DESCRIPTION OF THE INVENTION
[0031] As used herein, the term "percentage" when used to refer to
the amount of an element in an alloy means a weight-based
percentage. "Weighted percentages" of corrosion resisting and
austenite promoting components, however, are calculated in a manner
such that the weighted percentages do not necessarily correspond to
the actual weight-based percentages.
[0032] The present invention is based, in part, on the discovery
that certain metal alloys having, e.g., an iron reactive component
containing alloy which reacts with a bodily fluid when it is in
contact with the fluid degrades with a degradation rate that is
faster when implanted in a biological subject than the degradation
rate of an alloy having the same composition except that the alloy
does not contain an iron reactive component. In some embodiments
the alloys of the present invention have, for example, a
fine-grain, substantially austenite structure that will biodegrade
over time without forming emboli and that when these alloys contain
an iron reactive component the degradation rate in human or animal
body is enhanced. These austenite alloys exhibit little or no
magnetic susceptibility and low magnetic permeability and can be
made non-toxic and/or non-allergenic by controlling the amounts of
various metals (e.g., chromium and nickel) incorporated into the
alloys. In some embodiments the alloys of the present invention
have, for example, a substantially martensite structure will
biodegrade over time without forming emboli and that when these
alloys contain an iron reactive component the degradation rate in
human or animal body is enhanced. These martensite alloys can also
be made non-toxic and/or non-allergenic by controlling the amounts
of various metals (e.g., chromium and nickel) incorporated into the
alloys. The alloys described herein may be incorporated into a
variety of implantable medical devices that are used to heal the
body of a subject (e.g., a human or other animal), but become
unnecessary once the subject is healed. The alloys of the present
invention can be used, for example, to make biodegradable,
implantable medical devices that require high strength, such as
bone fasteners for weight-bearing bones. The alloys can also be
used to make biodegradable, implantable medical devices that
require ductility, such as surgical staples for tissue
fixation.
[0033] One object of the present invention is to provide medical
devices for temporary implantation in the body of a subject (e.g.,
a human or animal subject), wherein the devices are made using a
biodegradable alloy comprising an iron reactive component. The
biodegradable alloy comprising an iron reactive component is one
that is not a stainless steel, but instead undergoes reactions
involving normal body chemistry to biodegrade or bio-absorb over
time and will be removed by normal body processes. It is another
object of the invention to provide implantable medical devices made
using a biodegradable iron reactive component containing alloy that
is non-toxic and/or non-allergenic as it is degrading and being
processed by the body. It is yet another object of the invention to
provide implantable medical devices made using a biodegradable
alloy comprising an iron reactive component that has little or no
magnetic susceptibility and low magnetic permeability and does not
distort MRI images.
[0034] The iron reactive component can be added to the alloy by a
variety of means known in the art. In some embodiments, the iron
reactive component is capable of being equally dispersed throughout
the alloy. In some embodiments, the iron reactive component is
equally dispersed throughout the alloy.
[0035] In some embodiments, an iron reactive component is added at
the time of melting of an alloy mixture or at anytime during the
melting process. For example, the iron reactive component can be
added later in the melting process, prior to the melt being poured
into a mold. The iron reactive component can also be dispersed on
the surface of the alloy. Such alloys can be generated by a variety
of methods known in the art, including for example ion
implantation. Ion implantation is well known and involves the
process by which ions of a material are accelerated in an
electrical field and impacted onto a solid surface, such as for
example an alloy of the present invention. In some embodiments, the
iron reactive component is dispersed on the surface of the alloy.
In some embodiments, the iron reactive component is applied to the
exterior surface of the alloy. In some embodiments, the iron
reactive component is added to the alloy by methods of
ion-implanting. (See, e.g., Hamm, Robert W.; Hamm, Marianne E.,
Industrial Accelerators and Their Applications. World Scientific
(2012).) An iron reactive component of the present invention can
include any component which provides for an enhanced alloy
degradation rate when the alloy comprising the iron reactive
component is exposed to a biological environment (i.e., implanted
in a biological subject), as compared to the same alloy absent the
iron reactive component. In some embodiments, the alloy comprises
more than one iron reactive component.
[0036] According to one aspect of the present invention, small
amounts of iron reactive components are useful for controlling the
biodegradation rate of suitable alloys. In some embodiments, the
concentration of the iron reactive component in the alloy is
between about 0.1 ppm to about 1000 ppm, between about 0.1 ppm to
about 800 ppm, between about 0.1 ppm to about 600 ppm, between
about 0.1 ppm to about 400 ppm, between about 0.1 ppm to about 300
ppm, between about 0.1 ppm to about 250 ppm, between about 0.1 ppm
to 200 ppm, between about 0.1 ppm to about 150 ppm, between about
0.1 ppm to about 100 ppm, between about 0.1 ppm to about 75 ppm,
between about 0.1 ppm to about 50 ppm, between about 0.1 ppm to
about 25 ppm or between about 0.1 ppm to about 10 ppm. In some
embodiments, the concentration of the iron reactive component in
the alloy is between about 1 ppm to 500 ppm, between about 10 ppm
to about 300 ppm, or between about 50 ppm to about 150 ppm.
[0037] In some embodiments, the iron reactive component is stable
at temperatures greater than or equal to the melting point of the
alloy in the absence of the iron reactive component. In some
embodiments, the iron reactive component is provided as a salt with
a boiling temperature of at least about 1600.degree. C., at least
about 1650.degree. C., at least about 1700.degree. C., at least
about 1750.degree. C., at least about 1800.degree. C., at least
about 1850.degree. C., at least about 1900.degree. C., at least
about 1950.degree. C., or at least about 2000.degree. C.
[0038] In some embodiments, the iron reactive component is provided
as a gas during the fabrication process with a total or partial
pressure of at least about 0.1 tor, at least about 0.2 tor, at
least about 0.5 tor, at least about 0.8 tor, at least about 1 tor,
at least about 2 tor, at least about 5 tor, at least about 10 tor,
at least about 50 for or at least about 100 tor.
[0039] In some embodiments, the iron reactive component is a
halogen component. Halogen components of the present invention
include halogens and/or the salt forms such as chloride, fluoride,
bromide and iodide. In some embodiments, the halogen component is
chlorine. In some embodiments, the halogen component is chloride or
fluoride. In some embodiments the halogen component is chloride. In
some embodiments the halogen component is fluoride. In some
embodiments, the halogen component is stable at temperatures
greater than or equal to the melting point of the alloy. In some
embodiments, the alloy containing the iron reactive component
comprises more than one halogen component.
[0040] In some embodiments, the iron reactive component is halogen
containing salt. The halogen component can be provided to the alloy
mixture as a salt during the process of generating the alloy. In
some embodiments, the halogen containing salt is selected from
sodium fluoride, sodium chloride, copper chloride, copper fluoride,
silver chloride, calcium chloride, calcium fluoride and iron
chloride. In some embodiments, mixtures of salts can be
employed.
[0041] In some embodiments, a halogen containing salt is added to
the alloy mixture at the time of melting or at anytime during the
melting process. Any halogen containing salt with a boiling
temperature greater than the melting temperature of the alloy can
be used with the methods of the present invention. In some
embodiments, the halogen component is provided as a salt with a
boiling temperature of at least about 1600.degree. C., at least
about 1650.degree. C., at least about 1700.degree. C., at least
about 1750.degree. C., at least about 1800.degree. C., at least
about 1850.degree. C., at least about 1900.degree. C., at least
about 1950.degree. C., or at least about 2000.degree. C. In some
embodiments, the halogen component is stable at temperatures
greater than or equal to the melting point of the alloy. In some
embodiments, more than one halogen component can be employed.
[0042] Additionally or alternatively, a gaseous iron reactive
component can be used during the process of generating the alloy.
In some embodiments, the halogen component is chlorine gas. In some
embodiments, the halogen component is provided as a gas with a
total or partial pressure greater than or equal to about 0.1 tor,
about 0.2 tor, about 0.5 tor, about 0.8 tor, about 1 tor, about 2
tor, about 5 tor, about 10 tor, about 50 for or about 100 tor. In
some embodiments, the total or partial pressure of the halogen
component is a range of about 0.1 for to about 100 tor, about 0.5
for to about 50 tor, or about 1 to about 5 tor.
[0043] In some embodiments, mixtures of gases can be employed.
Without being bound to any particular theory, it is contemplated
that the amount of the iron reactive component can be fine tuned by
controlling a partial pressure of the iron reactive component with
or without additional gases. In some embodiments, an inert gas such
as argon can be provided in a mixture with one or more halogen
gases. In some embodiments, the argon gas has a partial pressure of
at least about 10 tor, at least about 20 tor, at least about 50
tor, at least about 80 tor, at least about 100 tor, at least about
150 tor, at least about 200 tor, at least about 250 tor, at least
about 300 tor, or at least about 500 tor. As demonstrated in
Example 2, approximately 1 for of chlorine can be added into 200
for of argon during the melt process.
[0044] In some embodiments, the concentration of the halogen
component in the alloy is between about 0.1 ppm to about 500 ppm,
between about 0.1 ppm to about 400 ppm, between about 0.1 to about
300 ppm, between about 0.1 to about 250 ppm, between about 0.1 to
about 200 ppm, between about 0.1 ppm to about 150 ppm, between
about 0.1 to about 100 ppm, between about 0.1 ppm to about 75 ppm,
between about 0.1 ppm to about 50 ppm, between about 0.1 to about
25 ppm or between about 0.1 ppm to about 10 ppm. In some
embodiments, the halogen component in the alloy comprises between
about 0.1 ppm to about 100 ppm.
[0045] Accordingly, in one aspect, the invention provides
implantable medical devices comprising a biodegradable alloy that
dissolves from its exterior surface. As used herein, the term
"alloy" means a mixture of chemical elements comprising two or more
metallic elements. Biodegradable alloys suitable for making
implantable medical devices of the invention can be, for example,
iron alloys (e.g., steels). In certain embodiments, the iron alloys
comprise about 55% to about 65%, about 57.5% to about 67.5%, about
60% to about 70%, about 62.5% to about 72.5%, about 65% to about
75%, about 67.5% to about 77.5%, about 70% to about 80%, about
72.5% to about 82.5%, or about 75% to about 85% iron. The iron
alloys further comprise one or more non-iron metallic elements. The
one or more non-iron metallic elements can include, for example,
transition metals, such as manganese, cobalt, nickel, chromium,
molybdenum, tungsten, tantalum, niobium, titanium, zirconium,
hafnium, platinum, palladium, iridium, rhenium, osmium, rhodium,
etc., or non-transition metals, such as aluminum. In some
embodiments, the iron alloys comprise at least two non-iron
metallic elements. The at least two non-iron elements can be
present in an amount of at least about 0.5% (e.g., at least about
1.0%, about 1.5%, about 2.0%, about 2.5%, about 3.0%, about 4.0%,
about 5.0%, or more). In certain embodiments, the iron alloys
comprise at least two non-iron metallic elements, wherein each of
said at least two non-iron elements is present in an amount of at
least about 0.5%, and wherein the total amount of said at least two
elements is at least about 15% (e.g., at least about 17.5%, about
20%, about 22.5%, about 25%, about 27.5%, about 30%, about 32.5%,
about 35%, about 37.5%, or about 40%). The biodegradable alloys can
also comprise one or more non-metallic elements. Suitable
non-metallic elements include, for example, carbon, nitrogen, and
silicon. In certain embodiments, the iron alloys comprise at least
about 0.01% (e.g., about 0.01% to about 0.10%, about 0.05% to about
0.15%, about 0.10% to about 0.20%, about 0.15% to about 0.25%, or
about 0.20% to about 0.30%) of at least one non-metallic
element.
[0046] Biodegradable alloys suitable for use in the implantable
medical devices of the invention are designed to degrade from the
outside inward, such that they maintain their strength for a
greater portion of their life and do not particulate or embolize.
Without intending to be bound by theory, it is believed that this
is accomplished by providing an alloy structure that either has no
appreciable reactive grain boundaries, forcing degradation to take
place at the surface molecular layer, or by providing a very fine
grain alloy that acts as a homogeneous, grain free material. In
certain embodiments, the rate of dissolution from an exterior
surface of a suitable biodegradable alloy is substantially uniform
at each point of the exterior surface. As used herein in this
context, "substantially uniform" means that the rate of dissolution
from a particular point on an exterior surface is +/-10% of the
rate of dissolution at any other point on the same exterior
surface. As persons skilled in the art will appreciate, the type of
"exterior surface" contemplated in these embodiments is one that is
smooth and continuous (i.e., substantially planar, concave, convex,
or the like) and does not include sharp edges or similar such
discontinuities, as those are locations where the rate of
dissolution is likely to be much higher. A "substantially" planar,
concave, or convex surface is a surface that is planar, concave,
convex, or the like and does not contain any bumps, ridges, or
grooves that rise above or sink below the surface by more than 0.5
mm.
[0047] Steel alloys have iron as their primary constituent.
Depending upon a combination of (i) the elements alloyed with the
iron and (ii) the historical working of the alloy, steels can have
different structural forms, such as ferrite, austenite, martensite,
cementite, pearlite, and bainite. In some instances, steels having
the same composition can have different structures. For example,
martensite steel is a form of high tensile steel that can be
derived from austenite steel. By heating austenite steel to between
1750.degree. F. and 1950.degree. F., and then rapidly cooling it to
below the martensite transition temperature, the face centered
cubic structure of the austenite steel will reorient into a body
centered tetragonal martensite structure, and the martensite
structure will freeze into place. Martensite steel does not have
appreciable grain boundaries, and thus provides no primary
dissolution path to the interior of the steel. The result is a slow
dissolution from the outside, without the formation of emboli.
Metallurgical examination of martensitic material will show
"pre-austenitic grain boundaries," places where the austenite grain
boundaries once existed, but these are nonreactive traces of the
former structure.
[0048] Accordingly, in certain embodiments, the biodegradable
implantable medical devices of the invention comprise an alloy
containing an iron reactive component (e.g., an iron alloy) having
a substantially martensite structure. As used herein, the term
"substantially martensite structure" means an alloy having at least
90% martensite structure. In certain embodiments, the alloy has at
least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.8%,
99.9% or more martensite structure.
[0049] The martensite alloy can have the composition of any alloy
described herein. For example, in certain embodiments, the
martensite alloy is formed from an austenite alloy described
herein. In certain embodiments, the martensite alloy comprises
carbon, chromium, nickel, molybdenum, cobalt, or a combination
thereof. For example, in certain embodiments, the martensite alloy
comprises (i) carbon, (ii) chromium and/or molybdenum, and (iii)
nickel and/or cobalt. In certain embodiments, the martensite alloy
comprises about 0.01% to about 0.15%, about 0.05% to about 0.20%,
about 0.10% to about 0.25%, about 0.01% to about 0.05%, about 0.05%
to about 0.10%, about 0.10% to about 0.15%, or about 0.15% to about
0.20% carbon. In certain embodiments, the martensite alloy
comprises about 0.1% to about 6.0%, about 1.0% to about 3.0%, about
2.0% to about 4.0%, about 3.0% to about 5.0%, or about 4.0% to
about 6.0% chromium. In certain embodiments, the martensite alloy
comprises about 0.1% to about 6.0%, about 0.5% to about 2.5%, about
1.0% to about 3.0%, about 1.5% to about 3.5%, about 2.0% to about
4.0%, about 2.5% to about 4.5%, about 3.0% to about 5.0%, about
3.5% to about 5.5%, or about 4.0% to about 6.0% molybdenum. In
certain embodiments, the martensite alloy comprises about 5.0% to
about 9%, about 6.0% to about 10%, about 7.0% to about 11%, about
8.0% to about 12%, about 9.0% to about 13%, about 10% to about 14%,
or about 11% to about 15% nickel. In certain embodiments, the
martensite alloy comprises about 5.0% to about 10%, about 7.5% to
about 12.5%, about 10% to about 15%, about 12.5% to about 17.5%, or
about 15% to about 20% cobalt.
[0050] In certain embodiments, the martensite alloy contains about
2.0% to about 6.0%, about 3.0% to about 7.0%, about 3.5% to about
7.5%, about 4.0% to about 8.0%, about 4.5% to about 8.5%, or about
5.0% to about 9.0% of a corrosion resisting component. In certain
embodiments, the martensite alloy contains about 2.5%, about 3.0%,
about 3.5%, about 4.0%, about 4.5%, about 5.0%, about 5.5%, or
about 6.0% of a corrosion resisting component. In certain
embodiments, the corrosion resisting component is calculated as a
sum of the percentages of corrosion resisting elements (e.g.,
chromium, molybdenum, tungsten, tantalum, niobium, titanium,
zirconium, hafnium, etc.) in the alloy. In other embodiments, the
corrosion resisting component is calculated as a weighted sum of
the corrosion resisting elements in the alloy. In certain
embodiments, individual elements in the weighted sum are weighted
according to their corrosion resisting efficacy, as compared to
chromium. In certain embodiments, the weighted % corrosion
resisting component is determined according to the formula: %
chromium+% molybdenum+% tungsten+0.5*(% tantalum+% niobium)+2*(%
titanium+% zirconium+% hafnium).
[0051] In certain embodiments, the martensite alloy contains at
least about 10%, about 15%, about 18%, about 20%, about 22%, or
about 24% of a austenite promoting component. For example, in
certain embodiments, the martensite alloy contains about 10% to
about 20%, about 15% to about 25%, about 20% to about 30%, about
25% to about 35%, about 30% to about 40% of an austenite promoting
component. In certain embodiments, the martensite alloy comprises
about 22%, about 23%, about 24%, about 25%, about 26%, about 27%,
or about 28% of an austenite promoting component. In certain
embodiments, the austenite promoting component is calculated as a
sum of the percentages of austenite promoting elements (e.g.,
nickel, manganese, cobalt, platinum, palladium, iridium, aluminum,
carbon, nitrogen, silicon, etc.) in the alloy. In other
embodiments, the austenite promoting component is calculated as a
weighted sum of all the austenite promoting elements in the alloy.
In certain embodiments, individual elements in the weighted sum are
weighted according to their austenite promoting efficacy, as
compared to nickel. In certain embodiments, the weighted %
austenite promoting component is calculated according to the
formula: % nickel+% platinum+% palladium+% iridium+0.5*(%
manganese+% cobalt)+30*(% carbon+% nitrogen).
[0052] In certain embodiments, the martensite alloy comprises about
2.0% to about 4.0%, about 3.0% to about 5.0%, or about 4.0% to
about 6.0% of a corrosion resisting component, and about 10% to
about 20%, about 15% to about 25%, about 20% to about 30%, about
25% to about 35%, or about 30% to about 40% of an austenite
promoting component. For example, in certain embodiments, the
martensite alloy comprises about 3.0% to about 5.0% of a corrosion
resisting component and about 20% to about 30% of an austenite
promoting component. In certain embodiments, the corrosion
resisting and austenite promoting components are calculated as sums
of the percentages of corrosion resisting and austenite promoting
elements, respectively. In other embodiments, the corrosion
resisting and austenite promoting components are calculated as
weighted sums of the corrosion resisting and austenite promoting
elements, respectively.
[0053] While martensite alloys have the desirable characteristic of
lacking grain boundaries, austenite alloys are particularly useful
for medical implants because of their low magnetic susceptibility,
which can be useful where the alloy is exposed to a strong magnetic
field. It is desirable for medical implants to have low magnetic
susceptibility because they may be used in patients that would have
future need of Magnetic Resonance Imaging (MRI), which utilizes
very high magnetic fields. A magnetic reactive alloy in a strong
magnetic field can experience heating, causing local tissue stress
and damage to tissue surrounding the implant. Magnetic reactive
implants also distort MRI images, making them unreadable. In
addition, austenite alloys can provide certain mechanical benefits,
since they undergo larger plastic deformations between their
elastic limit (yield point) and ultimate failure, as compared to
martensite alloys. For example, whereas a martensite alloy may have
a maximum elongation of about 16% to 20%, an austenite alloy can
have a maximum elongation of about 50% to 60%.
[0054] Thus, in certain embodiments, the biodegradable implantable
medical devices of the invention comprise an iron reactive
component containing alloy (e.g., an iron alloy) having a
substantially austenite structure. As used herein, the term
"substantially austenite structure" means at least 85% austenite
structure. In certain embodiments, the alloy has at least 88%, 90%,
91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.8%, 99.9% or
more austenite structure. In certain embodiments, the austenite
alloy has substantially no martensite or ferrite structure. As used
herein, the term "substantially no martensite or ferrite structure"
means less than 5% (e.g., less than 4%, 3%, 2%, 1%, 0.5%, 0.2%,
0.1%, or 0.05%) martensite or ferrite structure. In certain
embodiments, the austenite alloy is characterized by a maximum
elongation of about 40% to about 65% (e.g., about 50% to about
60%).
[0055] Austenitic steels have grains with defined boundaries of
irregular shape. Since austenite is a face centered cubic
structure, the grains tend to be cubic when viewed perpendicular to
a major lattice plane. In austenite alloys having either very low
carbon or very low chromium, it is possible to create a structure
with a fine grain size (e.g., about 0.5 to about 5.0 microns on a
side). A cubic austenite grain of 2.5 microns has a total surface
area of 37.5 square microns and a volume of 15.625 cubic microns,
for a surface to volume ratio of 2.4.mu..sup.-1 and a total mass of
0.12 micrograms. Because of the extremely small mass of the grain,
the grain material reacts as quickly as the grain boundary material
when placed in a biological environment, allowing the alloy to shed
material from the outside. This, in turn, prevents weakening of the
material bulk along grain boundaries and grain separation from the
material bulk of the alloy. As the size of grains increase,
however, the ratio of surface to volume decreases. Each grain
becomes bigger, taking longer to be absorbed, making it more likely
that dissolution will take place along grain boundaries,
penetrating deeper into the alloy's material bulk and thereby
reducing the strength of the alloy.
[0056] The rate of biodegradation of iron reactive component
containing alloys of the present invention can be further altered
by controlling the grain size and surface to volume ratio of the
individual grains. As the grain size increases, with a commensurate
decrease in the surface-to-volume ratio, biodegradation progresses
faster toward the center of the device, increasing the total
biodegradation rate. However, too large a grain size can cause
separation of grains and adverse effects.
[0057] In some embodiments the alloy containing the iron reactive
component is an austenite alloy. In certain embodiments, the
austenite alloy has an average grain size of about 0.5 microns to
about 20 microns on each side. For example, in certain embodiments,
the average grain size is about 0.5 microns to about 5.0 microns,
about 2.5 microns to about 7.5 microns, about 5.0 microns to about
10 microns, about 7.5 microns to about 12.5 microns, about 10
microns to about 15 microns, about 12.5 microns to about 17.5
microns, or about 15 microns to about 20 microns on each side. In
certain embodiments, the average grain size is about 0.5 to about
3.0 microns, or about 1.0 micron to about 2.0 microns on each side.
In certain embodiments, the austenite alloy has a structure wherein
the surface to volume ratio of individual grains is, on average,
greater than 0.1.mu..sup.-1. For example, in certain embodiments,
the surface to volume ratio of individual grains is, on average,
greater than 0.2.mu..sup.-1, 0.3.mu..sup.-1, 0.4.mu..sup.-1,
0.5.mu..sup.-1, 0.6.mu..sup.-1, 0.7.mu..sup.-1, 0.8.mu..sup.-1,
0.9.mu..sup.-1, 1.0.mu..sup.-1, 1.5.mu..sup.-1, 2.0.mu..sup.-1,
2.5.mu..sup.-1, 3.0.mu..sup.-1, 3.5.mu..sup.-1, 4.0.mu..sup.-1,
4.5.mu..sup.-1, 5.0.mu..sup.-1, 6.0.mu..sup.-1, 7.0.mu..sup.-1,
8.0.mu..sup.-1, 9.0.mu..sup.-1, 10.0.mu..sup.-1, 11.0.mu..sup.-1,
12.0.mu..sup.-1, 13.0.mu..sup.-1, 14.0.mu..sup.-1, 15.0.mu..sup.-1,
or more.
[0058] Austenite grain sizes of about 0.5 microns to about 20
microns can be achieved by successive cycles of mechanical working
to break down the alloy, followed by thermal recrystallization. The
mechanical working of materials, whether done at cold temperatures
(i.e. room temperature to 200.degree. C.) or at elevated
temperatures, causes strain-induced disruption of the crystal
structure, by physically forcing the alloy into a new shape. The
most common method of mechanical working of metals is by reducing
the thickness of a sheet of metal between two high pressure rolls,
causing the exiting material to be substantially thinner (e.g.,
20%-60% thinner) than the original thickness. Other methods such as
drawing can also be employed. The process of mechanically working
metals breaks down larger, contiguous lattice units into different
structures. More importantly, it stores substantial strain-induced
energy into distorted lattice members, by straining lattice
structure distances to higher energy arrangements. Subsequent
low-temperature recrystallization, which takes place at about 0.35
to about 0.55 times the absolute melting temperature of the alloy,
allows the lattice structure to undergo rearrangements to a lower
energy condition, without changes to overall macro dimensions. To
accommodate lattice rearrangement without gross changes in
dimensions, the size of individual lattice sub-units, or grains, is
reduced, releasing substantial strain energy by breaking the
lattice into smaller sub-units, and producing a finer grain
structure. The process of mechanical working followed by
recrystallization can be repeated serially, producing finer and
finer grains.
[0059] In certain embodiments, the austenite alloy comprises
carbon. For example, in certain embodiments, the alloy comprises
about 0.01% to about 0.10%, about 0.02% to about 0.12%, about 0.05%
to about 0.15%, about 0.07% to about 0.17%, about 0.10% to about
0.20%, about 0.12% to about 0.22%, or about 0.15% to about 0.25%
carbon. In certain embodiments, the austenite alloy comprises one
or more (e.g., two or more) elements selected from the list
consisting of nickel, cobalt, aluminum, and manganese. In certain
embodiments, the alloy comprises about 2.0% to about 6.0%, about
3.0% to about 7.0%, about 4.0% to about 8.0%, or about 5.0% to
about 9.0% nickel. In other embodiments, the alloy comprises
substantially no nickel. In certain embodiments, the alloy
comprises about 10% to about 20%, about 15% to about 20%, about 15%
to about 25%, about 18% to about 23%, about 20% to about 25%, or
about 20% to about 30% cobalt. In certain embodiments, the alloy
comprises less than about 5.0% (e.g., less than about 4.5%, about
4.0%, about 3.5%, about 3.0%, or about 2.5%) manganese. In certain
embodiments, the alloy comprises about 0.5% to about 1.5%, about
1.0% to about 2.0%, or about 1.5% to about 2.5% manganese. In other
embodiments, the alloy comprises about 1.0% to about 8.0%, about
6.0% to about 10%, about 8.0% to about 12%, or about 10% to about
14% manganese. In other embodiments, the alloy comprises about 10%
to about 50%, about 15% to about 45%, about 20% to about 40%, about
25% to about 35%, or about 25% to about 30% manganese. In certain
embodiments, the austenite alloy comprises one or more (e.g., two
or more) elements selected from the list consisting of chromium,
molybdenum, and tantalum. In certain embodiments, the alloy
comprises about 0.5% to about 1.5%, about 1.0% to about 2.0%, about
1.5% to about 2.5%, or about 2.0% to about 3.0% chromium. In other
embodiments, the alloy comprises substantially no chromium. In
certain embodiments, the alloy comprises about 0.5% to about 1.5%,
about 1.0% to about 2.0%, about 1.5% to about 2.5%, or about 2.0%
to about 3.0% molybdenum. In certain embodiments, the alloy
comprises about 1.0% to about 3.0%, about 2.0% to about 4.0%, about
3.0% to about 5.0%, or about 4.0% to about 6.0% tantalum. In
certain embodiments, the austenite alloy comprises (i) carbon, (ii)
at least two elements selected from the list consisting of nickel,
cobalt, aluminum, and manganese, and (iii) at least two elements
selected from the list consisting of chromium, molybdenum, and
tantalum.
[0060] Aside from the pattern of dissolution, the rate of
dissolution and the release of potentially toxic elements needs to
be controlled in alloys used to make implantable medical devices of
the invention. The particular elements used to make up an alloy
help determine the physical and chemical properties of the
resulting alloy. For example, adding small amounts of carbon to
iron changes the structure of the iron, creating steel that is
greatly increased in hardness and strength, while changing the
plasticity relative to iron. Similarly, stainless steels are
fabricated by adding elements to the iron that decrease corrosion
(i.e., corrosion resisting components), such as chromium and
molybdenum. A stainless steel that resists corrosion in a
biological system can contain, for example, 18% chromium and 1%
molybdenum. Titanium, niobium, tantalum, vanadium, tungsten,
zirconium, and hafnium likewise provide a protective effect that
slows down the rate of degradation of steel in a biologic
system.
[0061] A stainless steel that does not break down in the intended
biological system is typically not suitable for use in a
biodegradable implant. Thus, alloys having large quantities of
corrosion resisting elements, such as chromium, molybdenum,
titanium, and tantalum, usually cannot be used to make
biodegradable implantable medical devices of the invention.
However, small quantities of such corrosion resisting elements are
useful for controlling the biodegradation rate of suitable alloys.
Accordingly, in certain embodiments, an alloy useful for making a
biodegradable implantable medical device of the invention (e.g., an
austenite alloy) contains at least about 0.5%, about 1.0%, about
1.5%, about 2.0%, about 2.5%, about 3.0%, or about 3.5%, but less
than about 15%, about 12%, about 11%, about 10%, about 9.0%, about
8.0% or about 7.0% of a corrosion resisting component. For example,
in certain embodiments, the alloy contains about 1.0% to about
7.0%, about 2.0% to about 8.0%, or about 3.0% to about 9.0% of a
corrosion resisting component. In certain embodiments, the alloy
(e.g., austenite alloy) contains about 3.0%, about 3.5%, about
4.0%, about 4.5%, about 5.0%, about 5.5%, about 6.0%, about 6.5%,
or about 7.0% of a corrosion resisting component. In certain
embodiments, the corrosion resisting component is calculated as a
sum of the percentages of corrosion resisting elements (e.g.,
chromium, molybdenum, tungsten, tantalum, niobium, titanium,
zirconium, hafnium, etc.) in the alloy. In other embodiments, the
corrosion resisting component is a weighted sum of all the
corrosion resisting elements in the alloy. For example, in certain
embodiments, individual elements in the weighted sum are weighted
according to their corrosion resisting efficacy, as compared to
chromium. In certain embodiments, the weighted % corrosion
resisting component is determined according to the formula: %
chromium+% molybdenum+% tungsten+0.5*(% tantalum+% niobium)+2*(%
titanium+% zirconium+% hafnium).
[0062] Corrosion resisting elements, such as chromium and
molybdenum, are ferrite promoting and tend to cause steel to form a
ferritic structure. To overcome such ferrite promotion and achieve
an austenite structure, austenite promoting elements can be added
to the alloy. Austenite promoting elements include, for example,
nickel, manganese, cobalt, platinum, palladium, iridium, aluminum,
carbon, nitrogen, and silicon. Accordingly, in certain embodiments,
an alloy (e.g., an austenite alloy) useful for making an
implantable medical device of the invention contains an austenite
promoting component. In certain embodiments, the alloy contains
about 10% to about 20%, about 15% to about 25%, about 20% to about
30%, about 25% to about 35%, or about 30% to about 40% of an
austenite promoting component. In certain embodiments, the alloy
contains at least about 10%, about 12%, about 14%, about 16%, about
18%, about 20%, about 22%, about 24%, about 26%, about 28%, or
about 30% of an austenite promoting component. In certain
embodiments, the austenite promoting component is calculated as a
sum of the percentages of austenite promoting elements (e.g.,
nickel, cobalt, manganese, platinum, palladium, iridium, aluminum,
carbon, nitrogen, silicon, etc.) in the alloy. In other
embodiments, the austenite promoting component is a weighted sum of
the austenite promoting elements in the alloy. In certain
embodiments, individual elements in the weighted sum are weighted
according to their austenite promoting efficacy, as compared to
nickel. In certain embodiments, the weighted % austenite promoting
component is calculated according to the formula: % nickel+%
platinum+% palladium+% iridium+0.5*(% manganese+% cobalt)+30*(%
carbon+% nitrogen). In certain embodiments, the alloy contains a
weighted % austenite promoting component of about 15% to about 25%
(e.g., about 16%, about 17%, about 18%, about 19%, about 20%, about
21%, about 22%, about 23%, about 24%, or about 25%). In certain
embodiments, the alloy contains an unweighted % austenite promoting
component of about 25% to about 35% (e.g., about 28%, about 29%,
about 30%, about 31%, about 32%, about 33%, about 34%, or about
35%).
[0063] In certain embodiments, an iron reactive component
containing alloy (e.g., an austenite alloy containing an iron
reactive component) useful for making an implantable medical device
of the invention contains less than about 5.0% (e.g., about 0.1% to
about 2.5%, about 0.5% to about 3.0%, about 1.0% to about 3.5%,
about 1.5% to about 4.0%, or about 2.0% to about 4.5%) of platinum,
iridium, and osmium, either individually or in total. In certain
embodiments, the alloy contains substantially no platinum,
palladium, or iridium. As used herein, "substantially no" platinum,
palladium, or iridium means that the alloy contains less than 0.1%
of platinum, palladium, or iridium. In certain embodiments, the
alloy contains substantially no platinum, palladium, and iridium.
In certain embodiments, the alloys contain less than about 0.05%,
or about 0.01% of each of platinum, palladium, or iridium. In
certain embodiments, the alloys contain less than about 0.05%, or
less than about 0.01%, of each of platinum, palladium, and iridium.
In other embodiments, the total amount of platinum, iridium, and
osmium in the alloy is about 5.0% or greater, and the alloy further
comprises at least one additional metal element other than iron,
manganese, platinum, iridium, and osmium (e.g., at least about 0.5%
or more of said at least one additional metal element). In certain
embodiments, the at least one addition metal element is a corrosion
resisting element (e.g., chromium, molybdenum, tungsten, titanium,
tantalum, niobium, zirconium, or hafnium) or a austenite promoting
element selected from the group consisting of nickel, cobalt, and
aluminum.
[0064] Biodegradable iron reactive component containing alloys
implanted in a human or animal body need to be relatively non-toxic
because all of the elements in the alloys will eventually be
dissolved into body fluids. Nickel is often used to stabilize an
austenitic crystal structure. However, many people have nickel
allergies and cannot tolerate nickel ions in their systems. Having
nickel as part of a biodegradable alloy guarantees that all of the
nickel in the alloy will eventually be absorbed by the host's body,
which can cause complications in a nickel sensitive individual.
Likewise, chromium, cobalt, and vanadium have some toxicity in the
human body, and should be minimized in a biodegradable alloy.
Accordingly, in certain embodiments, an alloy useful for making a
biodegradable implantable medical device of the invention (e.g., an
austenite alloy) contains less than about 9.0%, about 8.0%, about
7.0%, about 6.0%, about 5.0%, about 4.0%, about 3.0%, about 2.5%,
about 2.0%, about 1.5%, about 1.0%, or about 0.5% of each of
nickel, vanadium, chromium, and cobalt. In certain embodiments, the
alloy contains substantially no nickel. As used here, the phrase
"substantially no nickel" means that the alloy contains 0.1% or
less nickel. In certain embodiments, the alloy contains less than
about 0.05%, less than about 0.02%, or less than about 0.01%
nickel. In certain embodiments, the alloy contains substantially no
vanadium. As used here, the phrase "substantially no vanadium"
means that the alloy contains 0.1% or less vanadium. In certain
embodiments, the alloy contains less than about 0.05%, less than
about 0.02%, or less than about 0.01% vanadium. In certain
embodiments, the alloy contains less than about 4.0% chromium
(e.g., less than about 3.0%, about 2.0%, or about 1.5%). In certain
embodiments, the alloy contains substantially no chromium. As used
here, the phrase "substantially no" chromium means that the alloy
contains 0.1% or less chromium. In certain embodiments, the alloy
contains less than about 0.05%, less than about 0.02%, or less than
about 0.01% chromium. In certain embodiments, the alloy contains
less than about 6.0% (e.g., less than about 5.0%, about 4.0%, about
3.0%, about 2.0%, or about 1.0%) cobalt.
[0065] To remove or minimize toxic elements from the alloys used to
created the biodegradable implantable medical devices of the
invention, the toxic elements can be replaced with non-toxic
counterparts. For example, since nickel is used as an austenite
promoting element, it can be replaced with other austenite
promoting elements, such as manganese, cobalt, platinum, palladium,
iridium, aluminum, carbon, nitrogen, and silicon. Similarly, since
chromium is used as a corrosion resisting element, it can be
replaced with other corrosion resisting elements, such as
molybdenum, tungsten, titanium, tantalum, niobium, zirconium, and
hafnium. However, not all alloy substitutions are equivalent. For a
corrosion resisting effect, molybdenum is as effective as chromium,
while niobium and tantalum are only half as effective as chromium,
and titanium is twice as effective as chromium. For austenite
promoting effect, manganese and cobalt are only half as effective
as nickel, while carbon is 30 times more effective than nickel, and
nitrogen is 25-30 times more effective than nickel. Accordingly, in
certain embodiments, a biodegradable alloy is rendered
non-allergenic or less allergenic by replacing one part of nickel
with two parts manganese, one part of manganese and one part of
cobalt, or two parts of cobalt. In other embodiments, a
biodegradable alloy is rendered non-toxic or less toxic by
replacing one part of chromium with one part of molybdenum, half a
part of titanium, or two parts of tantalum or niobium. In some
embodiments, the total percentage of manganese is from about 10% to
about 50%, about 15% to about 45%, or about 20% to about 40%, about
25% to about 35%, or about 25% to about 30%, or about 30%. In
certain embodiments, the total percentage of nickel, cobalt and
manganese is from about 10% to about 50%, about 15% to about 45%,
or about 20% to about 40%, about 25% to about 35%, or about 25% to
about 30%, wherein the percentage of nickel is less than about
9.0%, about 8.0%, about 7.0%, about 6.0%, about 5.0%, about 4.0%,
or about 3.0%. In other embodiments, the total percentage of
chromium and molybdenum is from about 1.0% to about 7.0%, about
2.0% to about 8.0%, about 3.0% to about 9.0%, or about 4.0% to
about 10%, wherein the amount of chromium is less than about 2.0%,
about 1.5%, about 1.0%, or about 0.5%.
[0066] Additional elements that can be included in alloys useful
for making biodegradable, implantable medical devices of the
invention include rhodium, rhenium, and osmium. In certain
embodiments, the amount of rhodium, rhenium, or osmium in the alloy
is less than about 5.0% (e.g., about 0.1% to about 2.5%, about 0.5%
to about 3.0%, about 1.0% to about 3.5%, about 1.5% to about 4.0%,
or about 2.0% to about 4.5%). In certain embodiments, there is
substantially no rhodium, rhenium, or osmium in the alloy. As used
herein, "substantially no" rhodium, rhenium, or osmium means that
the alloy contains less than about 0.1% of rhodium, rhenium, or
osmium. In certain embodiments, there is substantially no rhodium,
rhenium, and osmium in the alloy. In certain embodiments, the alloy
contains less than about 0.05%, or less than about 0.01%, of
rhodium, rhenium, or osmium. In certain embodiments, the alloy
contains less than about 0.05%, or less than about 0.01%, of each
of rhodium, rhenium, and osmium.
[0067] In certain embodiments, when one or more elements selected
from the group consisting of platinum, palladium, iridium, rhodium,
rhenium, and osmium is present in an alloy useful for making
biodegradable, implantable medical devices of the invention, the
amount of manganese in the alloy is less than about 5.0% (e.g.,
less than about 4.5%, about 4.0%, about 3.5%, about 3.0%, or about
2.5%). In other embodiments, when one or more elements selected
from the group consisting of platinum, palladium, iridium, rhenium,
rubidium, and osmium is present in the alloy and the amount of
manganese in the alloy is about 5.0% or greater (e.g., about 5.0%
to about 30%), then the alloy further comprises at least one
additional metal element. In certain embodiments, the at least one
addition metal element is a corrosion resisting element (e.g.,
chromium, molybdenum, tungsten, titanium, tantalum, niobium,
zirconium, or hafnium) or a austenite promoting element selected
from the group consisting of nickel, cobalt, and aluminum.
[0068] In certain embodiments, alloys useful for making
biodegradable, implantable medical devices of the invention contain
substantially no rubidium or phosphorus. As used herein,
"substantially no" rubidium or phosphorus means less than 0.1% of
rubidium of phosphorus. In certain embodiments, the alloys contain
substantially none rubidium and phosphorus. In certain embodiments,
the alloys contain less than about 0.05%, or less than about 0.01%,
of rubidium or phosphorus. In certain embodiments, the alloys
contain less than about 0.05%, or less than about 0.01%, of each of
rubidium and phosphorus.
[0069] In certain embodiments, the present invention provides
biodegradable implantable medical devices comprising a range of
biodegradable alloys (e.g., austenitic alloys) that are acceptably
non-allergenic, non-toxic, has little or no magnetic susceptibility
and low magnetic permeability, and provide a useful range of
degradation rates. The following are exemplary boundaries defining
alloys useful in the biodegradable implantable medical devices of
the present invention: [0070] an iron reactive component; [0071]
substantially no nickel; [0072] substantially no vanadium; [0073]
less than about 6.0% chromium; [0074] less than about 10% cobalt;
[0075] a corrosion resisting component of less than about 10%
(e.g., about 0.5% to about 10%); and [0076] an austenite promoting
component of at least about 10% (e.g., about 10% to about 40%).
[0077] In certain embodiments, the present invention provides
biodegradable implantable medical devices comprising a range of
biodegradable alloys (e.g., austenitic alloys) that are acceptably
non-allergenic, non-toxic, has little or no magnetic susceptibility
and low magnetic permeability, and provide a useful range of
degradation rates. The following are exemplary boundaries defining
alloys useful in the biodegradable implantable medical devices of
the present invention: [0078] an iron reactive component; [0079]
28%-30% manganese; [0080] 0.07%-0.09% carbon; [0081] 0.18%-0.22%
Niobium; [0082] a corrosion resisting component of less than about
10% (e.g., about 0.5% to about 10%); and [0083] an austenite
promoting component of at least about 10% (e.g., about 10% to about
40%).
[0084] In certain embodiments, the present invention provides
biodegradable implantable medical devices comprising a range of
biodegradable alloys (e.g., austenitic alloys) that are acceptably
non-allergenic, non-toxic, has little or no magnetic susceptibility
and low magnetic permeability, and provide a useful range of
degradation rates. The following are exemplary boundaries defining
alloys useful in the biodegradable implantable medical devices of
the present invention: [0085] an iron reactive component; [0086]
28%-30% manganese; [0087] 0.18%-0.22% niobium; [0088] <0.01%
carbon; [0089] a corrosion resisting component of less than about
10% (e.g., about 0.5% to about 10%); and [0090] an austenite
promoting component of at least about 10% (e.g., about 10% to about
40%).
[0091] In certain embodiments, the present invention provides
biodegradable implantable medical devices comprising a range of
biodegradable alloys (e.g., austenitic alloys) that are acceptably
non-allergenic, non-toxic, has little or no magnetic susceptibility
and low magnetic permeability, and provide a useful range of
degradation rates. The following are exemplary boundaries defining
alloys useful in the biodegradable implantable medical devices of
the present invention: [0092] an iron reactive component; [0093]
28-30% manganese; [0094] 0.07-0.09% carbon; [0095] a corrosion
resisting component of less than about 10% (e.g., about 0.5% to
about 10%); and [0096] an austenite promoting component of at least
about 10% (e.g., about 10% to about 40%).
[0097] In certain embodiments, the alloys contain about 55% to
about 80% iron. For example, in certain embodiments, the alloys
contain about 55% to about 65%, about 60% to about 70%, about 65%
to about 75%, about 70% to about 80% iron. In certain embodiments,
the amount of chromium is less than about 4.0% and the amount of
cobalt is less than about 6.0%. In certain embodiments, the amount
of chromium is less than about 2.0% and the amount of cobalt is
less than about 4.0%. In certain embodiments, the corrosion
resisting component is less than about 8.0% (e.g., about 0.5% to
about 8.0%) and the austenite promoting component is greater than
about 12%. In certain embodiments, the corrosion resisting
component is less than less than about 7.0% (e.g., about 0.5% to
about 7.0%) and the austenite promoting component is greater than
about 14%. In certain embodiments, the corrosion resisting
component is less than about 6.0% (e.g., about 0.5% to about 6.0%)
and the austenite promoting component is greater than about 16%. In
certain embodiments, the corrosion resisting and austenite
promoting components are calculated as sums of the percentages of
corrosion resisting and austenite promoting elements, respectively.
In other embodiments, the corrosion resisting and austenite
promoting components are calculated as weighted sums of the
corrosion resisting and austenite promoting elements, respectively.
In certain embodiments, the weighted % corrosion resisting
component is determined according to the formula: % chromium+%
molybdenum+tungsten+0.5*(% tantalum+% niobium)+2*(% titanium+%
zirconium+% hafnium). In certain embodiments, the weighted %
austenite promoting component is calculated according to the
formula: % nickel+% platinum+% palladium+% iridium+0.5*(%
manganese+% cobalt)+30*(% carbon+% nitrogen). In certain
embodiments, the alloys contain less than about 5.0% manganese
(e.g., less than about 4.5%, about 4.0%, about 3.5%, about 3.0%, or
about 2.5%). In certain embodiments, the alloys contain one or more
elements selected from the group consisting of platinum, palladium,
iridium, rhodium, rhenium, and osmium. In certain embodiments, the
alloys contain about 0.5% to about 5.0% of one or more elements
selected from the group consisting of platinum, palladium, iridium,
rhodium, rhenium, and osmium. In certain embodiments, the alloys
contain substantially none of the elements selected from the group
consisting of platinum, palladium, iridium, rhodium, rhenium, and
osmium. In certain embodiments, the alloys contain substantially
none of the elements selected from the group consisting of rubidium
and phosphorus.
[0098] The biodegradation rate of the implantable medical devices
of the present invention is enhanced by the presence of the iron
reactive component in the alloy. As such, the incorporation of a
halogen component into the alloy of an implantable medical device
provides a novel method for enhancing biodegradation. In some
embodiments, the alloy containing the iron reactive component
reacts with a bodily fluid when it is in contact with the fluid. In
some embodiments, the degradation rate of the alloy comprising the
iron reactive component when implanted in a biological subject is
faster than the degradation rate of an alloy having the same
composition as except the iron reactive component is absent. In
some embodiments, the implantable medical devices of the present
invention have a degradation rate of about 1-100 mg per day per
square inch, about 1-50 mg per day per square inch, about 1-20 mg
per day per square inch, about 1-10 mg per day per square inch,
about 1-5 mg per day per square inch, or about 1-1.5 mg per day per
square inch when placed in pure water or a solution that does not
contain a halogen component. In some embodiments, the implantable
medical devices of the present invention have a degradation rate of
about 1-2 mg per day per square inch when placed in pure water or a
solution that does not contain a halogen component. In some
embodiments, the implantable medical devices of the present
invention have a degradation rate of about 1.2 and 1.4 mg per day
per square inch. The degradation rate of biodegradable materials in
a human or animal body is a function of the environment surrounding
the implantable medical device.
[0099] In embodiments where the iron reactive component is a
halogen component, the degradation of the biodegradable material in
an environment containing a halogen is faster than in an
environment with lower concentrations of halogen or lacking a
halogen (i.e., a halogen poor or absent environment). Halogens in
the environment speed the degradation of the implantable medical
device, but do not become part of the degradation products, which
include oxides, phosphates and carbonates. The biodegradation rate
is further enhanced by the presence of a halogen in the solution in
which the implantable medical device is immersed. In some
embodiments, the biodegradation rate is enhanced by the presence of
the halogen component in the alloy. In some embodiments, the
biodegradation rate is enhanced by the presence of the halogen
component on the exterior of the implantable medical device.
[0100] The degradation of an entire implant is an additionally a
function of the mass of the implant as compared to its surface
area. Implants come in many different sizes and shapes. A typical
coronary stent, for example, weighs 0.0186 grams and has a surface
area of 0.1584 square-inches. At a degradation rate of 1
mg/square-inch/day, a coronary stent would loose 50% of its mass in
30 days. In comparison, a 12 mm long cannulated bone screw weighs
0.5235 g and has a surface area of 0.6565 square-inches. At the
same degradation rate of 1 mg/square-inch/day, the cannulated screw
will loose half of its mass in 363 days. Thus, as persons skilled
in the art will readily appreciate, it is desirable to have
biodegradable alloys that have a range of degradation rates to
accommodate the variety of implants used in the body of a
subject.
[0101] In addition, the biodegradation rate of the implantable
medical devices of the present invention are significantly
influenced by the transport characteristics of the surrounding
tissue. For example, the biodegradation rate of an implant placed
into bone, where transport to the rest of the body is limited by
the lack of fluid flow, would be slower than a vascular stent
device that is exposed to flowing blood. Similarly, a biodegradable
device embedded in tissue would have slower degradation rate than a
device exposed to flowing blood, albeit a faster degradation rate
than if the device was embedded in bone. Moreover, different ends
of a medical device could experience different rates of degradation
if, for example, one end is located in bone and the other end is
located in tissue or blood. Modulation of biodegradation rates
based on the location of the device and ultimate device
requirements is thus desirable.
[0102] In order to control the dissolution rate of a medical device
independent of the geometric shape changes that occur as the device
degrades, several techniques have been developed. The first method
to alter the dissolution profile of a metallic device is to alter
the geometry of the device such that large changes in surface area
are neutralized. For example, the surface to mass ratio can be
increased or maximized. A substantially cylindrical device, which
would lose surface area linearly with the loss of diameter as the
device degrades, could have a concentric hole drilled through the
center of the device. The resulting cavity would cause a
compensating increase in surface area as alloy was dissolved from
the luminal surface of the device. As a result, the change in
surface area as the device degrades over time--and thus the change
in rate of degradation--would be minimized or eliminated. A similar
strategy of creating a luminal space (e.g., a luminal space that
has a shape similar to the outer surface of the device) could be
implemented with essentially any type of medical device.
[0103] Because biodegradation rates are partially a function of
exposure to bodily fluid flow, biodegradation rates can be modified
by coating (e.g., all or part of) the biodegradable implantable
medical device with a substance that protects the alloy surface.
For example, biodegradable hydrogels, such as disclosed in U.S.
Pat. No. 6,368,356, could be used to retard exposure of any parts
of a device exposed to mobile bodily fluids, thereby retard
dissolution and transport of metal ions away from the device.
Alternatively, medical devices can be constructed with two or more
different alloys described herein, wherein parts of the device that
are exposed to mobile bodily fluids are made from more corrosion
resistant alloys (i.e., alloys comprising higher amounts of a
corrosion resisting component), while parts of the device imbedded
in bone or tissue are made from less corrosion resistant alloys. In
certain embodiments, the different parts of the device can be made
entirely from different alloys. In other embodiments, parts of the
device exposed to mobile bodily fluids can have a thin layer or
coating of an alloy that is more corrosion resistant than the alloy
used to make the bulk of the device.
[0104] It is frequently desirable to incorporate bioactive agents
(e.g., drugs) on implantable medical devices. For example, U.S.
Pat. No. 6,649,631 claims a drug for the promotion of bone growth
which can be used with orthopedic implants. Bioactive agents may be
incorporated directly on the surface of an implantable medical
device of the invention. For example, the agents can be mixed with
a polymeric coating, such as a hydrogel of U.S. Pat. No. 6,368,356,
and the polymeric coating can be applied to the surface of the
device. Alternatively, the bioactive agents can be loaded into
cavities or pores in the medical devices which act as depots such
that the agents are slowly released over time. The pores can be on
the surface of the medical devices, allowing for relatively quick
release of the drugs, or part of the gross structure of the alloy
used to make the medical device, such that bioactive agents are
released gradually during most or all of the useful life of the
device. The bioactive agents can be, e.g., peptides, nucleic acids,
hormones, chemical drugs, or other biological agents, useful for
enhancing the healing process.
[0105] As persons skilled in the art will readily recognize, there
are a wide array of implantable medical devices that can be made
using the alloys disclosed herein. In certain embodiments, the
implantable medical device is a high tensile bone anchor (e.g., for
the repair of separated bone segments). In other embodiments, the
implantable medical device is a high tensile bone screw (e.g., for
fastening fractured bone segments). In other embodiments, the
implantable medical device is a high strength bone immobilization
device (e.g., for large bones). In other embodiments, the
implantable medical device is a staple for fastening tissue. In
other embodiments, the implantable medical device is a
craniomaxillofacial reconstruction plate or fastener. In other
embodiments, the implantable medical device is a dental implant
(e.g., a reconstructive dental implant). In still other
embodiments, the implantable medical device is a stent (e.g., for
maintaining the lumen of an opening in an organ of an animal
body).
[0106] Powdered metal technologies are well known to the medical
device community. Bone fasteners having complex shapes are
fabricated by high pressure molding of a powdered metal in a
carrier, followed by high temperature sintering to bind the metal
particles together and remove the residual carrier. Powdered metal
devices are typically fabricated from nonreactive metals such as
316LS stainless steel. The porosity of the finished device is
partially a function of the metal particle size used to fabricate
the part. Because the metal particles are much larger and
structurally independent of the grains in the metal's crystal
structure, metal particles (and devices made from such particles)
can be made from alloys of any grain size. Thus, biodegradable
implantable medical devices of the invention can be fabricated from
powders made from any of the alloys described herein. The porosity
resulting from the powdered-metal manufacturing technique, can be
exploited, for example, by filling the pores of the medical devices
with biodegradable polymers. The polymers can be used to retard the
biodegradation rates of all or part of the implanted device, and/or
mixed with bioactive agents (e.g., drugs) that enhance the healing
of the tissue surrounding the device. If the porosity of the
powdered metal device is filled with a drug, the drug will be
delivered as it becomes exposed by the degradation of the device,
thereby providing drug to the tissue site as long as the device
remains present and biodegrading.
[0107] In certain embodiments, the implantable medical device is
designed for implantation into a human. In other embodiments, the
implantable medical device is designed for implantation into a pet
(e.g., a dog, a cat). In other embodiments, the implantable medical
device is designed for implantation into a farm animal (e.g., a
cow, a horse, a sheep, a pig, etc.). In still other embodiments,
the implantable medical device is designed for implantation into a
zoo animal.
[0108] In another aspect, the invention provides a container
containing an implantable medical device of the invention. In
certain embodiments, the container is a packaging container, such
as a box (e.g., a box for storing, selling, or shipping the
device). In certain embodiments, the container further comprises an
instruction (e.g., for using the implantable medical device for a
medical procedure).
[0109] All publications, patent applications, and issued patents
cited in this specification are herein incorporated by reference as
if each individual publication, patent application, or issued
patent were specifically and individually indicated to be
incorporated by reference in its entirety.
[0110] The following examples are intended to illustrate, but not
to limit, the invention in any manner, shape, or form, either
explicitly or implicitly. While the specific alloys described
exemplify alloys that could be used in implantable medical devices
of the invention, persons skilled in the art will be able to
readily identify other suitable alloys in light of the present
specification. Although the foregoing invention has been described
in some detail by way of illustration and example for purposes of
clarity of understanding, it will be readily apparent to one of
ordinary skill in the art in light of the teachings of this
invention that certain changes and modifications may be made
thereto without departing from the spirit or scope of the appended
claims. The following examples are provided by way of illustration
only and not by way of limitation. Those of skill in the art will
readily recognize a variety of non-critical parameters that could
be changed or modified to yield essentially similar results.
EXAMPLES
Example 1
[0111] Background: Biodegradable metal systems have been developed
for use in cardiovascular, orthopedic, surgical and other
applications. The advantage of biodegradable metals are that they
have high strength and are dissolved by the body and excreted over
time until they are completely eliminated from the body. These
materials are extremely useful where an implant is needed for a
short period of time, such as for bone fixation or artery repair,
and can have negative impacts after healing has take place at the
implant site. Stents can cause a stenotic lesion if left in place
long after they no longer serve a function and bone fixation
devices can cause long term discomfort and are frequently removed
after they are no longer required. An example of a biodegradable
metal system is U.S. Pat. No. 8,246,762 which discloses
biodegradable metals for implant that degrade from the surface and
consequently do not lose bulk properties of the non-degraded
portion of the implant.
[0112] The degradation performance of biodegradable materials in a
human or animal body is a function of the environment surrounding
the implant. The degradation of the biodegradable material in an
environment containing sodium or potassium chloride is faster than
in a sodium or potassium chloride poor environment. Chloride in the
environment speeds the degradation but does not become part of the
degradation products, which are normally oxides, phosphates and
carbonates. Degradation in areas directly exposed to a flow of body
fluid, such as blood, bile, bone marrow or lymph, is faster than
material imbedded in tissue or bone, where the flow of fluids
required for the degradation reactions are transported across
cellular membranes to the implant. As more fluid and chloride are
transported to the site of the implant, the biodegradation becomes
faster and degraded material can be transported away from the site
more quickly.
[0113] One such material is an iron alloy that contains 28%
Manganese, 0.2% niobium, 0.08% carbon and the balance iron. When
placed in a solution of saline 0.9% sodium chloride in water
(normal saline), the material degrades at a rate of 1.2 mg per day
per square inch of surface. A sample of the material 0.69 inches
long by 0.39 inches wide by 0.025 inches thick was placed in
purified water for 123 days. The sample lost 0.7 mg per day per
square inch of surface, approximately half of the saline
degradation rate. When implanted in the body and surrounded by
tissue or bone, the degradation of the material is dependent on the
amount and content of the bodily fluid transported to and away from
the implant site and degradation is slowed. However, if the
chloride content at the implant surface can be increased, the
degradation rate can be increased.
[0114] Disclosure: It has been found that the degradation profile
of iron based metals can be altered by including materials that are
reactive with iron based alloys into the alloy at the time it is
made or added to the surface of the alloy after it is final formed.
Iron based alloys react with chloride ions in solution as is
demonstrated by increased degradation of alloys in saline solution
as compared with purified water. Some body fluids can become
chloride deficient. Adding chloride to the alloy causes the
chloride located at the surface or the alloy to react with the
alloy when it comes in contact with a fluid regardless of the fluid
composition. In addition, the chloride at the surface of the alloy
upsets the osmotic equilibrium at the site causing an increase in
fluid migrating to the site. It is not just chloride ion that
increases the degradation of iron based compounds, the other
halogens such as fluoride and iodide and bromide have the same
effect.
[0115] Adding halogens to an alloy can be accomplished by adding
small amounts of halogen compounds, which have boiling points above
the melting temperature of the alloy mix at the time it is melted.
In some embodiments, the halogen compound is stable on heating to
alloying temperatures and capable of being dispersed in the alloy
without appreciable segregating at the grain boundaries. Examples
of useful compounds are sodium fluoride, sodium chloride, copper
chloride, silver chloride, calcium chloride and iron chloride.
[0116] Four ingots of approximately 28% manganese, 0.2% niobium,
0.08% carbon and the balance iron were fabricated with the addition
of 100 ppm of chloride from one of sodium chloride, calcium
chloride, sodium fluoride and copper chloride salts. The fabricated
ingots were hot worked and cold rolled to approximately 0.025
inches thick. Samples of each ingot were placed in purified water
with no chloride or fluoride present and experienced degradation
rates of between 1.2 and 1.4 mg per day per square inch of
sample--essentially the expected degradation rate in saline of the
base material without the addition of a chloride source.
[0117] Alternatively, a halogen may be applied to the exterior
surface of an alloy or an implant fabricated from an alloy by
ion-implanting the surface with a halogen such as chlorine or
fluorine. Ion-implanting is a well understood process that is
practiced on large scale to modify the chemical structure and
properties of semiconductors and metals. By ion-implanting a
halogen onto the surface structure of a metal, the reaction at the
surface can be moderated and because the halogen is not consumed by
the degradation products, it is available to continue the
degradation process as long as it is not transported away from the
site.
[0118] Samples of an alloy consisting of 28% manganese, 0.2%
niobium, 0.08% carbon and the balance iron was electropolished,
fastened to a silicon wafer and the surface successfully implanted
with 10.sup.15 molecules of chlorine at an accelerating voltage of
100 kev. The experiment was repeated with fluorine. Each sample had
one side implanted with either a chlorine and fluorine and the
reverse side was left as native alloy. The samples were placed in
distilled water and examined twice daily. The halogen implanted
surface began to degrade in one day while the native surface took
several days.
Example 2
[0119] Fabrication of a biodegradable material with enhanced
degradation rates may be facilitated through the use of a partial
pressure of a gaseous reactive component during the fabrication
process. For example, a procedure for the initial fabrication of a
metal alloy is to place some or all of the desired components of
the alloy into the crucible of a vacuum induction furnace, evacuate
the furnace and melt the components under vacuum and/or with a
partial pressure of argon. Without being bound to any particular
theory, it is recognized in the present invention a partial
pressure of argon can be used to minimize evaporative loss of the
desired components and to prevent metal plasma forming in the
furnace chamber which would cause damage to the furnace. After the
alloy is fully melted and mixed, it is poured into a mold and
cooled.
[0120] In some embodiments, it is desirable to add the some
components of the metal alloy at a later stage of the melting
process. To add components to the melt they are contained
separately in an addition chamber and released into the crucible at
the appropriate time. The reactive components of this invention in
some embodiments can be added later in the melting process, prior
to the melt being poured into the mold. In some embodiments, the
amount of reactive component in the melt can be better controlled
by using a partial pressure of the reactive component in the vacuum
chamber surrounding the melt. The partial pressure of the reactive
component can have a chemical activity approximately equal to the
chemical activity of the reactive component in the melt. The
partial pressure of the reactive component can either be used to
replace the partial pressure of argon or be added to the partial
pressure of argon. The latter would provide a higher total pressure
surrounding the melt and would further reduce loss by
evaporation.
[0121] An example of this procedure is the melting of the main
alloy components of Iron, Manganese, Niobium and carbon under
vacuum followed by the addition of a partial pressure of 200 for
argon. At the appropriate time in the melt process, the partial
pressure in the chamber is increased with the addition of
approximately 1 for chlorine gas and the reactive chloride salts
are released into the melt from the addition chamber. The melt is
allowed to mix and poured into the mold for cooling.
[0122] Although the invention has been described with reference to
the presently preferred embodiments, it should be understood that
various changes and modifications, as would be obvious to one
skilled in the art, can be made without departing from the spirit
of the invention. Accordingly, the invention is limited only by the
following claims.
* * * * *