U.S. patent application number 14/801732 was filed with the patent office on 2017-01-19 for bone implant and systems that controllably releases silver.
The applicant listed for this patent is Paul E. CHIRICO, Bohdan Wolodymyr CHOPKO, Houdin DEHNAD, Robert Vincent MC CORMICK. Invention is credited to Paul E. CHIRICO, Bohdan Wolodymyr CHOPKO, Houdin DEHNAD, Robert Vincent MC CORMICK.
Application Number | 20170014607 14/801732 |
Document ID | / |
Family ID | 46048501 |
Filed Date | 2017-01-19 |
United States Patent
Application |
20170014607 |
Kind Code |
A9 |
DEHNAD; Houdin ; et
al. |
January 19, 2017 |
BONE IMPLANT AND SYSTEMS THAT CONTROLLABLY RELEASES SILVER
Abstract
Silver and/or zinc ion releasing implants, systems and method of
operating, inserting and activating/inactivating them are
described. In some variations the implant is configured as a bone
implant that includes a bone-screw or intramedullary rod like body
configured to receive a treatment cartridge having a plurality of
ion-releasing members configured as an anode that can controllably
engage with a catheter to turn galvanic release of ions on/off as
desired. These devices may be configured to release silver ions
(and/or zinc ions) above a predetermined level for a predetermined
period of time and may maintain a concentration of ions over a
relatively large volume of tissue. The ion-releasing members may be
configured to reduce or prevent implant movement.
Inventors: |
DEHNAD; Houdin; (El Granada,
CA) ; CHOPKO; Bohdan Wolodymyr; (Henderson, NV)
; CHIRICO; Paul E.; (Campbell, CA) ; MC CORMICK;
Robert Vincent; (Saratoga, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
DEHNAD; Houdin
CHOPKO; Bohdan Wolodymyr
CHIRICO; Paul E.
MC CORMICK; Robert Vincent |
El Granada
Henderson
Campbell
Saratoga |
CA
NV
CA
CA |
US
US
US
US |
|
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20150320989 A1 |
November 12, 2015 |
|
|
Family ID: |
46048501 |
Appl. No.: |
14/801732 |
Filed: |
July 16, 2015 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
13748546 |
Jan 23, 2013 |
9108051 |
|
|
14801732 |
|
|
|
|
13231219 |
Sep 13, 2011 |
8771323 |
|
|
13748546 |
|
|
|
|
13527389 |
Jun 19, 2012 |
9248254 |
|
|
13231219 |
|
|
|
|
12870082 |
Aug 27, 2010 |
8221396 |
|
|
13527389 |
|
|
|
|
61413230 |
Nov 12, 2010 |
|
|
|
61438162 |
Jan 31, 2011 |
|
|
|
61447393 |
Feb 28, 2011 |
|
|
|
61465350 |
Mar 18, 2011 |
|
|
|
61516388 |
Apr 4, 2011 |
|
|
|
61237506 |
Aug 27, 2009 |
|
|
|
61340587 |
Mar 19, 2010 |
|
|
|
61359549 |
Jun 29, 2010 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 17/686 20130101;
A61K 33/38 20130101; A61B 17/8685 20130101; A61K 33/30 20130101;
A61C 8/0012 20130101; A61B 17/864 20130101; A61B 17/7266 20130101;
A61M 37/00 20130101; A61B 17/869 20130101; A61B 17/8625 20130101;
A61C 8/0018 20130101; A61B 2017/561 20130101; A61B 17/80 20130101;
A61C 19/06 20130101; A61B 2017/00889 20130101; A61B 17/863
20130101; A61N 1/306 20130101; A61F 2/28 20130101 |
International
Class: |
A61M 37/00 20060101
A61M037/00; A61K 33/30 20060101 A61K033/30; A61K 33/38 20060101
A61K033/38; A61F 2/28 20060101 A61F002/28; A61B 17/86 20060101
A61B017/86 |
Claims
1. A method of controllably delivering silver, zinc, or silver and
zinc ions from an implant to prevent or treat infection, the method
comprising: engaging the implant with a removable silver, zinc or
silver and zinc releasing treatment cartridge, wherein the
treatment cartridge comprises a silver, zinc, or silver and zinc
anode, and wherein the implant includes a cathode comprising a
material having a higher half-cell potential than the anode,
further wherein the cathode has a greater active surface area than
the active surface area of the anode; and activating a switchable
control to initiate the galvanic release of silver, zinc or silver
and zinc from the treatment cartridge by placing the cathode in
electrical contact with the anode.
2. The method of claim 1, wherein engaging the implant comprises
coupling the removable silver, zinc or silver and zinc releasing
treatment cartridge with the implant when the implant is already
inserted into a patient.
3. The method of claim 1, further comprising placing at least a
portion of the cathode in communication with a source of oxygen at
a concentration of greater than 7.times.10.sup.-5 mol/L.
4. The method of claim 1, further comprising inserting the implant
into a patient's body.
5. The method of claim 1, further comprising inserting the implant
into a bone.
6. The method of claim 1, further comprising screwing the implant
into a subject's bone.
7. The method of claim 1, wherein activating comprises inserting
the removable silver, zinc or silver and zinc releasing treatment
cartridge into the implant so that the cathode is in electrical
contact with the anode.
8. The method of claim 1, wherein engaging comprises mating the
removable silver, zinc or silver and zinc releasing treatment
cartridge with a channel in the implant having an opening so that
the removable silver, zinc or silver and zinc releasing treatment
cartridge extends through the opening in the implant.
9. The method of claim 1, wherein engaging the implant comprises
engaging a bone-screw implant having a threaded out screw region
with the removable silver, zinc or silver and zinc releasing
treatment cartridge.
10. The method of claim 1, wherein engaging the implant comprises
extending a plurality of silver, zinc, or silver and zinc release
members forming the removable silver, zinc or silver and zinc
releasing treatment cartridge from openings in the implant
body.
11. A method of controllably delivering silver, zinc, or silver and
zinc ions from an implant, to prevent or treat infection, the
method comprising: engaging the implant with a removable silver,
zinc or silver and zinc releasing treatment cartridge, wherein the
treatment cartridge comprises a silver, zinc, or silver and zinc
anode, and wherein the implant includes a cathode comprising a
material having a higher half-cell potential than the anode; and
initiating the galvanic release of silver, zinc or silver and zinc
from the treatment cartridge by placing the cathode in electrical
contact with the anode, wherein the implant comprises a threaded
outer screw region.
12. The method of claim 11, wherein engaging the implant with the
removable treatment cartridge comprises coupling the treatment
cartridge with the implant when the implant is already inserted
into a patient.
13. The method of claim 11, wherein engaging the implant with the
removable treatment cartridge comprises coupling the treatment
cartridge with the implant before the implant is inserted into a
patient.
14. The method of claim 11, further comprising placing at least a
portion of the cathode in communication with a source of oxygen at
a concentration of greater than 7.times.10.sup.-5 mol/L.
15. The method of claim 11, further comprising inserting the
implant into a patient's body.
16. The method of claim 11, further comprising inserting the
implant into a bone.
17. The method of claim 11, wherein activating comprises inserting
the removable silver, zinc or silver and zinc releasing treatment
cartridge into the implant so that the cathode is in electrical
contact with the anode.
18. The method of claim 11, wherein engaging comprises mating the
removable silver, zinc or silver and zinc releasing treatment
cartridge with a channel in the implant so that the removable
silver, zinc or silver and zinc releasing treatment cartridge
extends through an opening in the implant.
19. The method of claim 11, wherein initiating the galvanic release
comprises activating a switchable control.
20. A method of controllably delivering silver, zinc, or silver and
zinc ions from an implant, to prevent or treat infection, the
method comprising: engaging the implant with a removable silver,
zinc or silver and zinc releasing treatment cartridge, wherein the
treatment cartridge comprises a silver, zinc, or silver and zinc
anode, and wherein the implant includes a cathode comprising a
material having a higher half-cell potential than the anode;
extending a plurality of silver, zinc, or silver and zinc release
members forming the removable silver, zinc or silver and zinc
releasing treatment cartridge from openings in the implant body;
and initiating the galvanic release of silver, zinc or silver and
zinc from the treatment cartridge by placing the cathode in
electrical contact with the anode, wherein the implant comprises a
threaded outer screw region configured for insertion into a bone.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 13/748,546, filed on Jan. 23, 2013, titled
BONE IMPLANT AND SYSTEMS THAT CONTROLLABLY RELEASES SILVER,"
Publication No. US-2013-0144204-A1, which is a divisional of U.S.
patent application Ser. No. 13/231,219, filed on Sep. 13, 2011,
titled "BONE IMPLANT AND SYSTEMS THAT CONTROLLABLY RELEASES
SILVER," now U.S. Pat. No. 8,771,323, which claims priority to the
following U.S. provisional patent applications: U.S. Provisional
Patent Application No. 61/413,230, filed on Nov. 12, 2010, and
titled "SILVER ELUTING BONE IMPLANTS AND METHODS OF USE"; U.S.
Provisional Patent Application No. 61/438,162, filed on Jan. 31,
2011, and titled "BONE SUPPORTING IMPLANTS WITH ANTIBACTERIAL
PROPERTIES"; U.S. Provisional Patent Application No. 61/447,393,
filed on Feb. 28, 2011, and titled "INTRAMEDULLARY (INTRAOSSEAL)
ROD, NAIL OR CATHETER WITH GALVANICALLY PRODUCED ANTIBACTERIAL
PROPERTIES"; U.S. Provisional Patent Application No. 61/465,350,
filed on Mar. 18, 2011, and titled "ANTIMICROBIAL IMPLANT TO
PROVIDE MECHANICAL SUPPORT FOR A BORE THAT UTILIZES A GALVANIC
POTENTIAL BETWEEN TWO OR MORE METALS TO CREATE IONS THAT ARE
GERMICIDAL AND/OR ANTIFUNGAL"; U.S. Provisional Patent Application
No. 61/516,388, filed on Apr. 4, 2011, and titled "GALVANIC
ANTIMICROBIAL BONE SCREW FOR THE TREATMENT OF DISEASED, FRACTURE OR
MISALIGNED BONE AND TO PROMOTE BONE GROWTH AND REGENERATION", each
of which is incorporated by reference in its entirety.
INCORPORATION BY REFERENCE
[0002] All publications and patent applications mentioned in this
specification are herein incorporated by reference to the same
extent as if each individual publication or patent application was
specifically and individually indicated to be incorporated by
reference.
BACKGROUND
[0003] Osteomyelitis is an infection of a bone by a microorganism
such as bacteria or fungi. Diabetes, joint replacement, trauma, and
injected drug use can lead to osteomyelitis. As people live longer,
incidences of osteomyelitis are expected to increase. To complicate
matters, an infection, such as following joint replacement surgery,
can occur long after the incision has been closed. An infection
buried in a bone can be difficult to detect; it is not visible to
the eye and taking a culture sample is difficult and painful. Once
diagnosed, antibiotics can eliminate many infections.
Unfortunately, microorganisms are developing resistances rendering
existing antibiotics useless. Reports of patients infected with
microorganisms resistant to regular and "last resort" antibiotics
are increasing in number. For these patients, there are few or no
effective options. The problem is expected to become worse as
microorganisms exchange genetic material and more species become
resistant to antibiotics. Prophylactic use of antibiotics, although
commonly done, is discouraged because it may increase antibiotic
resistance. Infection with methicillin resistant Staphylococcus
aureus (MRSA) is a significant health problem that is expected to
worsen. Additionally, microorganisms on the surface of an
artificial joint or other implanted device can cooperate to create
an impervious layer, called a biofilm. A biofilm may form a
mechanical barrier to an antibiotic.
[0004] Silver is known to be antimicrobial and has been used
(primarily as a coating) in various medical devices with limited
success. Both active (e.g., by application of electrical current)
and passive (e.g., galvanic) release of silver ions have been
proposed for use in the treatment and prevention of infection.
However, the use of silver-releasing implants have been limited
because of the difficulty in controlling and distributing the
release of silver ions as well as the difficulty in maintaining a
therapeutically relevant concentration of silver ions in an
appropriate body region. Zinc shares many of the same antimicrobial
properties of silver, but have been less commonly used, and thus
even less is known about how to control the amount and distribution
of the release of silver ions to treat and/or prevent
infection.
[0005] Thus, it would be highly desirable to provide device systems
and methods for the controlled release (particularly the controlled
galvanic release) of a high level of silver, zinc or silver and
zinc ions into the tissue for a sufficient period of time to treat
or prevent infection.
[0006] Specifically, known systems and devices that have attempted
to use ions (e.g., silver and/or zinc) to treat infection have
suffered from problems such as: insufficient amounts of ions
released (e.g., ion concentration was too low to be effective);
insufficient time for treatment (e.g., the levels of ions in the
body or body region were not sustained for a long enough period of
time); and insufficient region or volume of tissue in which the ion
concentration was elevated (e.g., the therapeutic region was too
small or limited, such as just on the surface of a device).
Further, the use of galvanic release has generally been avoided or
limited because it may effectively corrode the metals involved, and
such corrosion is generally considered an undesirable process,
particularly in a medical device.
[0007] In general, controlled release of silver and/or zinc ions
would be beneficial. Control of the release of ions may allow the
treatment of the patient to be regulated by turning the release
on/off. In general, silver coated devices do not typically allow
for the controlled release of ions. Silver coatings or
impregnations do not typically allow controlled release, because
they are always "on" (e.g., always releasing silver) to some
degree. Zinc coatings on traditional implants may suffer from the
same problem. Since release depends on the ionic concentration of
body fluids, the actual release (and therefore concentration) of
ions may be difficult to predict and control.
[0008] Therapeutically, the level of silver and/or zinc ions
released into a body is important, because it may determine how
effective the antimicrobial ions are for treating or preventing
infection. As described in greater detail below, the amount or ions
released galvanically may depend on a number of factors which have
not previously been well controlled. For example, galvanic release
may be related to the ratio of the anode to the cathode (and thus,
the driving force) as well as the level of oxygen available; given
the galvanic reaction, the level of oxygen may be particularly
important for at the cathode. Insufficient oxygen at the cathode
may be rate-limiting for galvanic release.
[0009] For example, with respect to silver, it has been reported
that a concentration of 1 mg/liter of silver ions can kill common
bacteria in a solution. Silver ions may be generated a galvanic
system with silver as the anode and platinum or other noble metal
as the cathode. However one of the challenges in designing a
galvanic system for creation of silver ion in the body that has not
been adequately addressed is the appropriate ratios of the areas of
the electrodes (e.g., anode to cathode areas) in order to create
the germicidal level of free silver ions. One challenge in
designing a galvanic system is addressing the parasitic loss of
current due to formation of silver chloride via reaction:
AgCl+e.fwdarw.Ag+Cl(-) Eo=0.222volts
[0010] We herein propose that it may be beneficial to have an area
of the cathode under common biological condition that is at least
larger than 8% of the silver area to sustain the germicidal level
of silver ions. For the purpose of this discussion, the following
assumptions have been made: for a concentration of: [H+]=10 (-7)
moles/liter; [OH-]=10 (-7) moles/liter; [O2]=5*10 (-3) moles/liter
in the capillary; [Cl-]=0.1 moles/liter. The values of the
following were also assumed (as constants or reasonable
approximations): Faraday's constant, F=96000 coulombs/mole;
diffusivity of oxygen=0.000234 cm2/sec; diffusivity of Ag+=10 (-6)
cm2/sec; diffusivity of Cl-=10 (-6) cm2/sec; R, Gas constant=8.314
J K.sup.-1 mol.sup.-1; T, temp. K; Mw of silver=108 grams/mol;
germicidal concentration of silver=10 (-5) mol/liter.
[0011] At equilibrium, for a galvanic cell it is acceptable to
assume that the two electrodes are at the same potential. Using the
Nernst equation, the equilibrium concentration of oxygen when the
silver ion is at the germicidal level may be calculated:
E=Eo-(RT/nF)ln [(Activity of products)/(activity of reactants)]
E=Eo-(0.0592/n)Log [(product)/(reactant)]
[0012] For the half cell reaction at the anode (silver electrode):
Ag.fwdarw.Ag(+)+e(-). This reaction is written as a reduction
reaction below:
Ag(+)+e(-).fwdarw.Ag Eo=0.800 volt eq. (1)
[0013] [Ag+]=1 mg/liter*(gr/1000 mg)*(1 mol/108 (Mw of Ag))=10 (-5)
Ag+mole/liter; E=0.800-(0.0592/1)log [1/(10 (-5)]. Based on this,
the resulting E=8.00-(0.0592*5)=0.504 volt.
[0014] For the cathode, the reactions are:
O.sub.2+2H.sub.2O+4e(-).fwdarw.4OH(-) Eo=0.401 volt eq. (2)
O.sub.2+4H(+)+4e(-).fwdarw.2H.sub.2O Eo=1.229 volt eq. (3)
[0015] In dilute aqueous solutions these two reactions are
equivalent. At equilibrium the potential for the two half-cell
potentials must be equal:
E=0.401-(0.0592/4)log {[OH(-)] 4/[O2]}
E(silver)=0.504=0.401-(0.0592/4)log {[10 -7] 4/[O2]}
[0016] Solving for [O.sub.2], the result is: [O.sub.2]=10 (-21)
atm. The result of this analysis is that, thermodynamically
speaking, as long as the concentration of oxygen is above 10 (-21),
the concentration of the sliver ion could remain at the presumed
germicidal level.
[0017] However, a parasitic reaction to creation of silver ions is
the formation of AgCl due to reaction of Cl- at the silver
electrode. The half-cell potential for this reaction is:
AgCl+e(-).fwdarw.Ag+Cl(-)Eo=0.222
[0018] Solving the Nernst equation for this reaction with E=0.504,
the concentration of chloride [Cl-]=2.times.10 (-5). The importance
of this reaction becomes apparent in evaluating the current needed
to compensate for the losses of current due to this reaction and
the increased in ratio of the area of the cathode to the anode.
[0019] The current density per until area requirements of the
device can be estimated by combining Fick's and Faraday equations:
the silver losses due to diffusion of silver from the device can be
calculated using the Fick's equation:
j=D[C(d)-C(c)]/d Fick's equation
[0020] The current needed to create the silver ions (A/cm2):
i=j*n*F, where, j is the mass flux, C(d) is the concentration of
the silver at the device and C(c) is concentration of silver at the
capillary bed (=0). D is the diffusion coefficient of silver (10
(-6)) cm2/sec, d is the average distance of the device from the
capillary bed (assumed to be =0.5 cm in the bone), F is Faraday's
constant (96000 col./mol), and n is the charge number.
[0021] The combination of the two equations for silver diffusion
gives:
i(Ag)=D*nF(C(d))/d
[0022] Thus:
i ( Ag ) = { 10 ( - 6 ) 1 ( 10 ( - 5 ) ) ( 96000 ) ( 5 10 ( - 3 ) )
/ 0.5 } ( 1 liter / 1000 c m 3 ) = 2 10 ( - 9 ) Amp / cm 2
##EQU00001##
[0023] The current needed to create the silver ions at the desired
concentration is approximately 2 nanoAmp/cm.sup.2. Similarly, the
current density (A/cm2) required to reduce the chloride ions from
biological level (0.1 molar) to the desired level of 2*10 (-5)
molar could be calculated. For this equation the approximate values
of the constants are D=10 (-6), d=0.1 cm. The change in the
Chloride concentration it assumed to be (0.1-2*10 (-5))=0.1. The
current needed to feed the parasitic reaction can then be
determined:
i ( cl ) = { ( 10 ( - 6 ) ) ( 1 ) ( 96000 ) ( 0.1 ) / ( 0.1 ) } ( 1
lit / 1000 cm 3 ) = 9.6 10 ( - 5 ) = 96 microAmp / Cm 2
##EQU00002##
[0024] The total anodic current needed is: i(Ag)+i
(Cl)=i(anodic)=96 microAmps/cm.sup.2. On the cathode, the reaction
limitation is the flux of oxygen form the source to the surface of
the electrode. The max i(cathodic) current could be approximated
to:
i ( O 2 ) = { 0.000324 ) ( 4 ) ( 96000 ) ( 5 10 ( - 3 ) ) / ( 0.5 )
} ( 1 lit / 1000 cm 3 ) = 1.24 10 ( - 3 ) Amps / cm 2
##EQU00003##
[0025] Since the total cathodic current must be equal to total
Anodic current:
i(cathodic)*Area of the cathode=i(anodic)*Area of Anode=>Area of
the Cathode/Area of the anode=(96*10 (-6)/(1.24*10 (-3))=0.077
[0026] This suggests that the area of the cathode must be at least
equal to 8% of that of anode.
[0027] In addition to the ratio of the cathode to the ratio of the
anode, another factor affecting the release of silver ions that has
not previously been accounted for in galvanic release of silver to
treat infection is the concentration of oxygen needed.
[0028] The concentration of the oxygen needed to power the galvanic
system is typically higher than that of the equilibrium
concentration, since the system must overcome the activation energy
of the reactions (over-potential) and supply the additional
current. In the model below we evaluated the concentration of the
oxygen needed to overcome the activation energy for the reactions.
Using the Tafel equation:
.eta.=.beta. log [i/io]
[0029] where i=current density, n=the over-potential,
13=overpotential voltage constant, and io=intrinsic current
density. For platinum, the oxygen over-potential constants are:
.beta.=0.05 volt and io=10 (-9) A/m.sup.2. Using i=9.6*10 (-5) Amp
then:
.eta.=0.05 log [9.6*10 (-5)/(10 (-9))]
.eta.=0.25 volt
[0030] Adding the over potential to the potential at the
equilibrium (0.501 volts), and the total working half-potential
needed at the cathode becomes equal to (0.501+0.25)=0.751.
[0031] Using the Nernst equation to determine the concentration of
oxygen at the cathode:
E=0.751=0.401-(0.0592/4)log {[OH(-)] 4/[O2]}
[0032] Thus, the concentration of oxygen at the electrode should be
at least 7*10 (-5) mole.
[0033] The results of this analysis show that an implanted galvanic
system would benefit from having an area of the cathode to the area
of the anode (A.sub.cathode/A.sub.anode) of greater that about 8%
and the concentration of the oxygen at the site of implant to be at
least 7*10 (-5) moles per liter, which may avoid rate-limiting
effect.
[0034] Thus, to address the problems and deficiencies in the prior
art mentioned above, described herein are systems, methods and
devices for prophylactically treating a patient to prevent an
infection and options for eliminating an existing infection,
including those untreatable by any existing treatments. Described
below are implants and methods for preventing and treating bone
infections using an implantable, controllable, and rechargeable
bone screws.
SUMMARY OF THE DISCLOSURE
[0035] The systems, devices and methods described herein may
generally be used to treat or prevent infection, including bone
infections such as osteomyelitis by the controlled release of
silver, zinc, or silver and zinc ions. In particular, the systems,
methods and devices described herein may be configured to allow
controllable galvanic release of ions (e.g., silver, zinc or silver
and zinc ions) to treat or prevent infection. Many of the
variations described herein may be used in conjunction with one or
more implants that also structurally or therapeutically support the
patient, including particularly the patient's bones.
[0036] In general, any of the implants described herein may be used
to treat bone and/or soft tissue. In some variations the implants
are bone implants specifically, and may be configured to support as
well as treat the bone. For example, the implant may be used to
secure (as a screw, nail, bolt, clamp, etc.) another member such as
a plate, rod, or the like, or the implant may itself include a
support member such as a rod, plate, etc. In some variations, the
implant is a soft tissue implant that is configured to be secured
within non-bone body structures.
[0037] Although many of the examples described herein are
illustrated describing the release of silver ions, any of the
devices, methods and systems described may be configured for the
release of zinc ions instead of, or in addition to, silver ions. It
may be beneficial to release both zinc and silver ions. In some
situations it may be beneficial to release zinc rather than silver,
or vice versa. For example, variations of the devices releasing
zinc may be used preferentially when the infection targeted is
resistant to silver. Zinc may also "corrode" faster, e.g.,
releasing ions more quickly and/or at a higher concentration than
silver, which may be avoided or exploited depending upon the
context.
[0038] Described herein are systems, devices and methods for the
controlled release of silver, zinc, or silver and zinc ions to
treat or prevent infection that may address many of the problems
identified above. For example, described herein are devices
configured for the galvanic release of ions that may be controlled
with an on/off switch mechanism. For example, in some variations
the galvanic relationship can be regulated remotely (before or
after the silver and/or zinc releasing implant has been inserted
into the body). In some variations the systems and device may be
configured so that the implant includes a separable or separate
cathode and/or anode. The anode region (e.g., silver, zinc, or
silver and zinc anode) may be placed central to the treatment
region while the cathode could be positioned in an oxygen-rich
region that may be separate from the treatment region (e.g.,
oxygenated blood). This may allow effective treatment of even
relatively anoxic regions, including bone.
[0039] The devices and systems described herein may also be
configured to regulate the effective cathode active surface area
and anode active surface area (e.g., making the cathode surface
area much larger than the effective anode surface area). For
example, the cathode active surface area may be 5% greater (e.g.,
Au/Palladium), 8% (e.g., Au/Pt), 10% (e.g., Au/Ag), etc. than the
anode surface area.
[0040] For example described herein are implants, including bone
implants, for providing antimicrobial treatment to a region of a
bone (and/or surrounding tissues) In some variations the implant
includes: an elongate cannulated body having a threaded outer
region; at least one exit channel extending from the cannulated
body and out through the threaded outer region; and one or more
silver, zinc, or silver and zinc release members configured to
extend from the cannulated body and out of the exit channel.
[0041] The ion release members may be configured as part of a
removable treatment cartridge that is configured to fit within the
cannulated body of the implant so that the one or more ion release
members extend from the cannulated body. Note, as used herein the
phrase "treat" and "treatment" may include acute and prophylactic
treatments.
[0042] In the simplest variation, the implant is configured as a
bone screw that is hollow or contains a hollow inner body region
into which a replaceable/rechargeable treatment cartridge may be
inserted and/or removed. The cartridge may be itself screwed into
the body, or it may be otherwise secured within the body. The
cartridge may include one or more (e.g., a plurality) of ion
release members extending or extendable from the cartridge and
therefore the implant. An ion release member may be configured to
release silver, zinc or silver and zinc. In general an ion release
member may be configured as an elongate member such as an arm,
wire, branch, or the like. The ion release member may be a wire
(e.g., silver wire), or it may be a coated member such as a Nitinol
or other shape-memory member, including a silver and/or zinc
coating. As mentioned, the implant (or the treatment cartridge
portion) may include a plurality of ion release members.
[0043] An implant may have one or more exit channels. In general
the exit channels may be openings from the inner hollow region
(e.g. cannulated body) of the implant through a side wall of the
implant and out, possibly in the threaded region. Thus, in some
variations the exit channel is configured to deflect the one or
more ion release members away from a long axis of the implant. For
example, the exit channel may be configured to deflect the one or
more ion release members against a thread of the outer threaded
region so that it deflects away from the implant. In some
variations a plurality of exit channels extending through the
cannulated body.
[0044] An implant may also include a guide (or guide element,
including a rail, keying, etc.) within the channel configured to
guide or direct the one or more ion release member out of the
cannulated body from the at least one exit channel. The exit
channels may be configured to allow tissue (e.g., bone) ingrowth,
which may help with stability of the device once implanted. For
example, the exit channels may be slightly oversized compared to
the ion release members, permitting or encouraging in-growth. In
some variations the exit channels may be doped or otherwise include
a tissue-growth enhancing or encouraging factor (such as a growth
factor), or may be otherwise modified to encourage tissue
growth.
[0045] In some variations the treatment cartridge may include a
silver, zinc or silver and zinc anode and the elongate body
includes a cathode, wherein the cathode has a higher redox
potential than the anode. The cathode may have an irregular
surface, or a high-surface area (e.g., per unit volume); for
example, the cathode may be formed of a foamed metal. In general
the surface area of the cathode may be substantially greater than
the surface are of the anode.
[0046] The treatment cartridge may be replaceable. For example, a
treatment cartridge may be configured to be removable from the
cannulated body of the implant in situ, without removing the body
of the implant from the device. Thus, the body of the implant may
be structurally supportive (e.g., supporting the bone) while the
silver-releasing portion may be re-charged by inserting another
(replacement) cartridge after the previous cartridge has corroded.
For example, an elongate cannulated body may be configured as bone
screw (e.g., an intramedullary bone screw).
[0047] In some variations, an implant for providing antimicrobial
treatment to a tissue includes: an elongate body having a threaded
outer screw region; an inner channel within the elongate body; a
plurality of exit channels extending from the inner channel and out
through the threaded outer screw region; and a treatment cartridge
configured to fit within the inner channel, the cartridge
comprising a plurality of ion release members configured to extend
out of the exit channels.
[0048] As mentioned, the inner channel may include a guide element
configured to direct the release members out of the exit channels.
The guide element may be a shaped channel region (e.g., keying) or
the like, configured to regulate the interaction between the
implant body and the cartridge.
[0049] Any of the variations described herein may also include a
tissue sampling feature. For example, the treatment cartridge may
comprise a sampler element configured to obtain a sample from a
patient in whom a bone implant has been implanted. A sampler
element may be a region configured to scrape, cut or otherwise
remove a sample of tissue, particularly as the cartridge is removed
from the implant. The sampled tissue may be examined for infection
or the like.
[0050] Also described herein are systems for the controllable
galvanic release of silver, zinc or silver and zinc ions from an
implant to prevent or treat infection. For example, a system may
include: a threaded implant configured to be inserted into a bone
and to hold an ion releasing treatment cartridge; a cathode on the
implant, the cathode comprising a material having a higher redox
potential than the material of the anode (e.g., silver, zinc or
silver and zinc); a treatment cartridge comprising a silver, zinc
or silver and zinc anode, wherein, when the treatment cartridge is
held by the implant, the cathode is in electrical contact with the
anode, driving the galvanic release of ions from the release
cartridge; and a switchable control configured to regulate
electrical contact between the anode and cathode.
[0051] In any of the variations described herein, the cathode may
comprise a material selected from the group consisting of:
palladium, platinum, and gold. The cathode and anode may be
configured to generate a galvanic current greater than about 0.2
.mu.amps. The treatment cartridge may include a plurality of ion
release members configured to extend from the implant when the
cartridge is engaged therewith.
[0052] As mentioned above, any of the variations described herein
may include a switchable control configured to turn on and/or off
the galvanic activity between the anode and cathode. In some
variations the switch may be configured to electrically separate
the anode and cathode preventing or limiting the galvanic reaction.
In some variations, the switchable control may be configured for
remote activation. For example, a switchable control may include a
magnet.
[0053] Also described herein are methods of controllably delivering
silver ions from an implant to prevent or treat infection. Such a
method may include the steps of: engaging an implant with a
removable ion-releasing treatment cartridge, wherein the treatment
cartridge comprises an anode (silver, zinc or silver and zinc), and
wherein the implant includes a cathode comprising a material having
a higher galvanic potential than the anode, further wherein the
cathode has a greater active surface area than the active surface
area of the anode; and activating a switchable control to initiate
the galvanic release of ions from the treatment cartridge by
placing the cathode in electrical contact with the anode.
[0054] The step of engaging the implant with the removably
treatment cartridge may include coupling the treatment cartridge
with an implant already inserted into a patient. The method may
also include the step of placing at least a portion of the cathode
in communication with a source of oxygen at a concentration of
greater than 7.times.10.sup.-5 mol/L. In some variations, the
implant may be implanted into a bone.
[0055] Also described are systems for the release of ions from an
implant to prevent or treat infection, the system including: an
implant configured to hold a silver, zinc or silver and zinc
release treatment cartridge; a removable treatment cartridge
comprising a silver, zinc or silver and zinc anode; and a cathode
comprising a material having a higher redox potential than the
anode, wherein the cathode is configured to be positioned
separately from the anode and in contact with an oxygen-rich
environment when the implant is implanted; wherein, when the
treatment cartridge is held by the implant, the cathode is in
electrical contact with the anode, driving the galvanic release of
ions from the treatment cartridge.
BRIEF DESCRIPTION OF THE DRAWINGS
[0056] FIGS. 1A-1F illustrate the general concept of galvanic
release of silver ions.
[0057] FIGS. 2A and 2B illustrate one variation of an implant as
described herein.
[0058] FIG. 3 shows another variation of an implant as described
herein.
[0059] FIG. 4 shows the implant of FIG. 3 in a deployed
configuration.
[0060] FIG. 5 is another variation of an implant.
[0061] FIG. 6 is another variation of an implant.
[0062] FIGS. 7A-7C illustrate deployment of a silver eluting bone
implant as described herein.
[0063] FIGS. 8A and 8B illustrate deployment of another silver
eluting bone implant.
[0064] FIGS. 9A and 9B show a top view of an implant in a deployed
an un-deployed configuration.
[0065] FIGS. 10A-10D illustrate variations of silver eluting bone
implants as described herein.
[0066] FIGS. 11A-11C illustrate another variation of an
implant.
[0067] FIG. 12A shows another variation of a silver-eluting implant
in a deployed and activated configuration (e.g., with silver
release members extended into the tissue) and FIG. 12B shows the
same implant in a de-activated configuration, in which the silver
release members have been withdrawn into the lumen/channel of the
implant.
[0068] FIGS. 13A and 13B illustrate two variations of silver
eluting bone implants as described.
[0069] FIG. 14 illustrates another variation of an implant
configured for use as a dental device. Similarly, FIGS. 15 and 16
illustrate variations of silver eluting bone implants configured to
treat other bone regions, including the jaw and skull (face),
respectively.
DETAILED DESCRIPTION
[0070] In some variations, the ion-releasing implants described
herein are configured as bone screws for treating a bone in need of
treatment, such as a broken or osteoporotic bone. The ions released
may be silver, zinc, or silver and zinc. Methods for treating a
tissue (including bone) are also described herein. For example, an
implant may be configured as a bone screw may align, biopsy, fuse,
and/or stabilize a bone. The screw may eliminate, prevent, or
reduce an infection, such as a bacterial, protozoan, or fungal
infection. The treatment from the screw may provide support to the
bone and may generate therapeutic silver ions to eliminate, prevent
or reduce an infection.
[0071] In general, when two metals with different redox potentials
are in electrical contact and immersed in an electrolyte, one metal
may preferentially ionize and free electrons. As the free electrons
migrate to the second metal, an electrical potential, called a
galvanic potential, is created. The process requires an electron
acceptor, such as oxygen near the second metal. When the first
metal is silver, ionic silver is released. Similarly, if the first
metal is zinc, ionic zinc is released.
[0072] The devices and systems described herein are controllable
ion-releasing systems that are configured to allow the controllable
release of ions (and particularly silver and/or zinc ions) into a
body with sufficient concentration and distribution to prevent or
treat infection in the tissue while also providing structural
support to the region and preventing migration of the device.
Various embodiments of these devices are described and illustrated,
however the general theory of operation of all of these devices may
be similar. The devices or systems may be configured as bone
implants that treat bone and surrounding tissue, by release of ions
such as silver ions.
[0073] FIGS. 1A-F describe a simple galvanic cell setup such as for
use in a body. The setup is shown treating an infection, but the
same process could be applied to healthy tissue to prevent an
infection (prophylactically). The components including a first
metal 2 (e.g., silver), second metal 4 (e.g., platinum), and
electrolytic fluid 6 (e.g., blood) are shown individually in FIGS.
1A-1C and arranged in a tissue in FIGS. 1D-1F. Electrolytic body
fluid 6 is shown bathing or contacting healthy tissue 10 as well as
infected tissue 8. When silver metal 2 contacts platinum metal 4 in
body fluid 6, it forms a galvanic cell with a silver anode and
platinum cathode. As shown in FIG. 1E, ionic silver 12 is generated
and spreads through the body fluid, killing microorganisms and
creating an infection-free zone 14 in body fluid 16 in the vicinity
of the anode. After treatment is complete, silver anode 2 may be
removed 20 leaving an infection-free body fluid 18. Alternatively,
platinum cathode 4 may be removed; alternatively both anode 2 and
cathode 4 may be removed. Although the system is described using a
silver metal anode and a platinum metal cathode, any metal with a
higher redox potential than silver may be used as the cathode. The
metal may be a noble metal, such as gold, palladium or platinum.
For purposes of illustration, the silver anode will be described as
the removable trigger for creating and stopping the galvanic
response. However, either the silver or the metal with the higher
redox potential can serve as a removable trigger (cartridge).
[0074] One embodiment of a device for controllably releasing silver
is a bone stabilization device such, such as a bone screw. A bone
stabilization device may include a support region (e.g., an
elongate rod, tube, channel, or the like) for insertion into the
bone, and an insertion engagement region (e.g., a head, shoulder,
coupling, etc.) for engaging with an insertion and or removal tool.
The insertion engagement region may be located at or near the
proximal end, and may include an opening or engagement region for
insertion and/or activation of a silver-release (e.g., galvanic
silver release) cartridge. In some variations the engagement region
includes a deployment mechanism (or contains an deployment
mechanism) for activating and/or deploying silver-releasing members
of a silver-releasing cartridge. The deployment mechanism may be
referred to as a deployment trigger. Examples of this are provided
below.
[0075] For example, a stabilization device for controllable release
of silver may be configured as a silver-releasing bone screw. In
general a silver-releasing bone screw is configured to controllably
and/or activatably release silver to prevent and/or treat
infection. A bone screw may include an elongate body (which may be
threaded or otherwise include one or more bone engagement surfaces)
and an engagement region at the proximal end configured as a head;
one or more cartridges for galvanic release may also be included to
allow the device to galvanically release silver. For example, a
bone screw according to the disclosure may have a screw rod
(elongate body) and one or more cartridges. The cartridge(s) may be
configured to insert into the screw rod, and may be configured as
an anti-infective cartridge or a biopsy cartridge or both. A bone
screw may have a platinum metal cathode and a silver metal anode.
In some variations the cathode and/or the anode (or just one or the
other) may be present on the body of the bone screw; in other
variations the cathode and/or anode (or both) may be present on a
cartridge that can be inserted and/or removed from the bone screw.
In some variations, the screw rod may be a platinum metal cathode
and the anti-infective cartridge may be a silver metal anode. The
cartridges may also include one or more anchoring, engagement,
and/or stabilization members that are configured to extend from the
bone screw and into the bone. These members may be configured as
arms, fingers, spikes, ribs, probes, struts, or the like, and may
extend from the body of the bone screw and into the tissue
(including into the bone).
[0076] For example, in some variations, the screw rod is an
elongated, cannulated (hollow), threaded rod. The rod may be
externally threaded and/or internally threaded. Internal threads
(or other guides/engagement regions) may be used to position and/or
secure a cartridge within the body. The screw rod may be sized and
elongated to fit a specific type of bone. The screw can fit any
type of bone. By way of example, the screw can be configured to fit
a femur, metatarsal, tarsal, tibia, or vertebra. Threads on the
outer surface of the screw rod may anchor the screw rod into a bone
or other body part. Thus, as mentioned, it may be threaded or may
include other externally-facing engagement regions. The screw rod
may be cannulated along its entire length, or along part of its
length. The cannulated portion may create a fluid flow path. Fluid,
such as oxygen carrying blood, may flow along the flow path and
provide oxygen to create galvanic silver ion generation by the
screw. In one example, the screw rod may be cannulated from a
proximal end to part but not all of the way to a distal end. The
screw rod may be solid along part of its distal end. The solid
distal end may be used to deflect a portion (e.g., anchoring,
engagement, and/or stabilization members) of a cartridge to be
deflected from the cannulated inside to outside the screw rod, and
may also provide additional stability and/or strength to the
elongate body.
[0077] FIG. 2A shows one variation of a bone stabilization implant
for delivering an antibiotic (e.g., silver) in a controllable
manner to a region of bone and/or surrounding tissue. In this
example the bone stabilization device is configured as a bone
anchor screw including an elongated, cannulated screw rod 22
region. Screw rod 22 has elongated body 26 and threads 24. Threads
24 are configured to penetrate a part of a bone and/or to hold the
screw in place in a bone or body region.
[0078] The screw may have a screw head 28 at a proximal end with
one or more features to aid in holding, placing and/or removing the
screw rod and for inserting and/or activating the cartridge. FIG.
2A shows one example of a screw head configured as a grippable
screw head 28. The screw head may engage an insertion device and/or
removal device. In some variations the screw may have a shaped
head, such as hexagonal head 56 shown in FIGS. 5 and 6 that can be
gripped by a wrench or other gripping tool. The feature may also be
used to hold the rod screw in place while inserting or removing a
cartridge or performing other manipulations.
[0079] The inside of the screw rod may have connection means for
connecting with or attaching an insertion tool. In one example, the
screw rod may have threads inside the screw rod (internal threads).
The internal threads may be along part or maybe along the entire
internal length of the screw rod.
[0080] The bone screw example shown in FIG. 2A includes a screw rod
with a channel or opening 30. The screw rod may have just one
channel or opening or may have more than one channel or opening.
The channels or openings may be sized and shaped to allow at least
part of a biopsy cartridge and/or anti-infective cartridge to move
outside cannulated screw rod.
[0081] The shape and pitch of the screw rod external threads may be
angled or shaped to aid or direct cartridge placement. FIG. 2A
shows screw rod external threads 24 that may aid placement of a
cartridge. The cannulated screw rod may have a port or ports (e.g.,
an opening) around the channel that is configured to guide a
portion of a biopsy element and/or anti-migration/anti-infection
element of a cartridge from inside the cannulated screw rod to
outside.
[0082] The screw rod may be made of any biocompatible material that
is sufficiently strong to be inserted into a body (bone) region.
For example, the screw may be made, at least in part, of a steel
(e.g., stainless steel), or other material. In some variations, the
screw rod is made of platinum, titanium, or stainless steel
material that is coated with platinum, palladium or gold. In
particular, the screw rod may be coated with a material or
materials that are able to create a galvanic response with silver.
The coating may be over the entire surface of the screw rod or may
be over part of the surface. The coating may be in the form of
bands. The coating material may be a noble metal that has a greater
galvanic potential than silver in a body. The noble metal may be
gold, palladium, or platinum.
[0083] The rod screw may have features to increase its surface
area. In particular, in variations in which the anode or, more
likely, the cathode is located on the surface of the screw body,
the portion of the screw body forming the cathode may have a
relatively large surface area (particularly as compared to the
opposite redox partner, e.g., anode). A larger surface area may
create a higher galvanic current for generating therapeutic silver
ions. The rod screw may comprise foamed metal on its inside
surface, outside surface, or both surfaces.
[0084] In some variations the screw or rod configured as a
stabilization device with controllable silver release may include
on ore more features to increase opportunities for contact with
body fluid. Increased contact may allow a stronger, faster, or
longer galvanic response. FIGS. 5 and 6 show examples of rod screws
50, 51 with openings 60 along body 54 in addition to openings near
threads 51. These openings may allow increased fluid flow, such as
blood flow, around and through the rod screw. Some or all of these
opening may also be configured to allow exit of one or more members
(e.g., arms, struts, etc.) from a cartridge.
[0085] Any of the devices described herein may include or be
configured for use with one or more cartridges. In general, a
cartridge is a removable/replaceable element that may be inserted
into or alongside of these support and antimicrobial devices (e.g.,
screws). As mentioned above, the cartridge may include one or more
members that are configured to be extended out of the device and
into the surrounding tissue. These members may be referred to and
configured as struts, probes, legs, arms, hooks, wires, coils,
fingers, spikes, ribs, or the like; in general they are elongate
members that may be inserted into the patient's tissue and extend
away from the body of the device. The members may therefore be
configured to help secure the device within the tissue. For
example, the members may enhance the mechanical attributes of the
device, including preventing the device from pulling out of the
tissue.
[0086] A cartridge may be referred to as an anti-infection
cartridge if it is configured to aid in the release of silver ions
from the device. For example the cartridge may include one or more
members having silver (e.g., anode) regions or configured so that
an entire member is silver releasing. In some variations the
cartridge may also be referred to as a biopsy cartridge that is
configured to remove tissue (e.g., bone, soft tissue, etc.) for
testing. In some variations the cartridge may be configured as both
an anti-infection and a biopsy cartridge.
[0087] An anti-infection cartridge may include a cathode. For
example, the cartridge may include a plurality of arms, some of
which are formed of a metal such as platinum that can react with
the silver anode to release silver. As mentioned, in some
variations the body of the implant device may include all or
portion of the cathode.
[0088] In the examples illustrated herein the treatment cartridges
are shown as separate elements that may be inserted into the
devices. For example, a cartridge may be inserted into the device
after the device (e.g., screw body) has been implanted into the
bone. Cartridges may be replaced or recharged (e.g., replacing a
portion of a cartridge such as a silver-containing member) without
removing the entire device from the patient.
[0089] In some variations the cartridge is integral with (or part
of) the implant device (e.g., screw).
[0090] The anti-infection cartridge may serve other functions in
addition to or instead of being anti-infective. For example, it may
be configured to prevent device migration. In some variations,
including those illustrated below, a plurality of member extend
from the device body (e.g., the body of the bone screw) and push
into the tissue to help anchor the device. Thus, the cartridge
member(s) may be configured to penetrate tissue, including bone. In
some variations the members are rigid/stiff member and may also
include tissue-penetrating distal regions. For example, one or more
members may be stainless steel, nickel titanium, or the like (which
may be coated with silver in some variations).
[0091] Thus, an anti-infection cartridge may comprise silver or a
silver coating, plating, or the like. The anti-infective cartridge
may be configured to be easily inserted and/or easily removed from
the cannulated device (e.g., screw). In some variations, the
cartridge has a holding end and a probe end. The holding end may be
configured to be readily held, gripped or grabbed by a hand or by a
device. By way of example, the holding end may be a loop, V shape
or U shape, or may include a grip region. The probe end may be
configured to contact a body part or a body solution. In general,
the probe end is configured as one or more members that extend from
the implant device when it is implanted. For example, the probe end
may be configured as one or more members that extend from the screw
rod. This may allow the silver ions to be directed to a particular
body region, or it may create a larger region of therapeutic silver
ions, or it may allow the cartridge to better contact or grip or
hold a body surface.
[0092] FIG. 2B shows one example of an anti-infection cartridge 32;
the proximal end may be referred to as the holding end 37, which
can be gripped by a hand or tool. The distal end of the cartridge
in this example has two probe ends that can extend out of the body
of the screw device. In FIG. 2B, the ends 33, 35 of the two members
of the cartridge 32 can be inserted into a screw rod portion of a
screw of rod for implantation into the body (bone). In this example
the body of the screw rod includes a cathode 22 along the outer
surface of the screw; the anodes on the elongate members of the
cartridge contact the cathodal surface of the screw when they are
extended from the implant. Each probe of the cartridge may have
multiple probe ends. The probe ends may be configured to contact a
portion of the bone or other tissue to hold the cartridge and bone
screw in place. The probe ends may be positioned (spread apart) to
create a larger area of effective silver ion area.
[0093] The anti-infective cartridge may be placed in contact with a
screw rod to generate a galvanic screw in variations having the
anode(s) on the cartridge and the cathode on the body of the
implant (e.g., screw). For example, FIGS. 3 and 4 illustrate
placement of an anti-infective cartridge 32 such as the one shown
in 2B in contact with a screw body such as the one shown in FIG.
2A. The cartridge arms are extended in FIG. 4. In this example the
cartridge includes two members, each formed of the twisted wires
shown. In one variation the wires are both silver wires;
alternatively one wire may be silver and the other wise stainless
steel or the like, adding column strength for insertion, such as
may be helpful for use in bone. For example, in FIG. 3 the probe
ends of the cartridge pass through the center of cannulated screw
rod 26 and may be held there until they are deployed into the
tissue. When they are deployed (e.g., after implanting the device
into the bone) the implant may include deflection/guide regions
that steer the members out of the implant and into the tissue. For
example, the threads 24 of the screw body in FIGS. 3 and 4 may
receive or guide the probe ends as they exit. As the cartridge 32
is advanced, probe ends 33 and 35 exit through openings 30 in the
screw body. As mentioned, extending the probes into the tissue may
provide mechanical resistance to inhibit unwanted removal or
movement of the probe and/or screw. In some variations the distal
end of the probes may be sharp or otherwise tissue penetrating.
[0094] A biopsy cartridge may share many similarities with an
antimicrobial cartridge as described above. For example, the biopsy
cartridge may include one or a plurality of members configured to
extend from the body of the implant device (e.g., arms, struts,
etc.). In some variations the distal ends of these members may
include one or more tissue capture elements such as a cup, hook,
scraper, basket, needle, etc. A cartridge (including a biopsy
cartridge) may also include an attachment site or coupling for a
proximal handle (e.g., a threaded region or the like). In some
variations a biopsy cartridge may be paired with an antimicrobial
cartridge and the two may be exchanged from the same implant
device. For example, the implant device (e.g., screw body) may be
inserted and an antimicrobial cartridge and a biopsy cartridge may
be alternately inserted to sample, then treat, then sample (in any
appropriate order) the bone. In some variations the members of the
biopsy device are longer (or are capable of extending to a longer
length) than the members of the antimicrobial cartridge, to sample
bone regions beyond the sites in which the members of the
antimicrobial cartridge resided. In some variations the insertion
length of the cartridge member(s) is variable, and may be selected
or modified by a user when inserting or deploying the
cartridge.
[0095] FIGS. 7A-C, 8A, 8B, 9A, and 9B describe another embodiment
of a galvanic screw system for treating or preventing infection.
These systems typically include a support device body (e.g., screw
or rod body) and one or more cartridges, as described above. A
screw system may have a collapsed or un-deployed configuration and
an expanded or deployed configuration. In some variations, toggling
between the deployed and un-deployed configurations controls the
galvanic potential. For example, in some variations, extending the
members of the cartridge including the silver anode may start the
galvanic current by placing the anode in electrical contact with
the cathode.
[0096] Additionally, because of the relatively streamlined initial
size/shape, the un-deployed configuration of the system/device can
readily be inserted into a bone in a less invasive way and expanded
into the deployed configuration once it is place, limiting any
damage or trauma to the tissue.
[0097] When the screw is in an un-deployed configuration, the
galvanic potential is essentially off. When the screw is in an
expanded position, the cathode and anode are in electrical contact
with each other and the galvanic potential is on. As the amount of
silver in the implant may be limiting, it may be useful to keep a
galvanic potential turned off when it is not needed and conserve
the potential for future use. The implant may be kept in the
collapsed (off) or partially collapsed (off) configuration for any
reason. For example, the implant may be configured to be switched
"off" (stopping the galvanic release of silver) if there is no
evidence of a current infection, but a future infection may be
expected, as might be the case in a joint implant. Joint implants
have been reported to develop infections months or years after
being implanted. By implanting one of the devices as described
herein for controllably delivering silver, but leaving galvanic
potential "off", the implant may conserve the silver for use if and
when an infection develops.
[0098] Thus the devices and systems described herein may be
configured to allow the anode to be electrically isolated from the
cathode (switching "off" the delivery of silver by the device)
until it is desired to be controllably released. For example, the
electrical connection between the anode and the cathode may depend
upon the extent to which a cartridge having members is extended
from the body of the device. In some variations, a conductive
bridge (e.g., switch) between the anode and cathode may be moveable
into and out of position to turn "on" or "off" the galvanic
reaction. This is described below in reference to FIGS. 12A-12B. In
other variations a switch is not necessary, as the anode and
cathode may be place in electrical connection by fully or partially
deploying the cartridge (e.g., the members of the cartridge); in
the un-deployed configuration the anode may be electrically
isolated from the cathode.
[0099] In some variations, the activation of the silver release
from the implant may depend upon controlling exposure of the anode
and/or cathode (which may be in electrical contact) to an
electrolytic solution. For example, the cathode and/or anode may be
retracted into the fluid-impermeable body of the device until it is
desired to release silver ions.
[0100] Note that the controllable release of silver as described
herein may also refer to the controllable distribution of silver
released into the body. In some variations the pattern of
distribution of the silver in the body may be determined in part by
the arrangement of the member in the deployed configuration. As the
members are expanded away from the body of the device (e.g., the
screw body or rod body) a much larger pattern (e.g., "cloud") of
silver ions having antimicrobial effects at a larger concentration
could be achieved than in comparison to an implant or device having
only a coating of silver, even actively released silver. In some
variations, the implant may be configured to allow control of the
extent of the deployment of the members; for example, extending the
device only partially from the body of the device as illustrated in
FIGS. 7A-8B.
[0101] FIGS. 7A-7C show a device for controllably delivering silver
ions that is configured as a screw 60; in this example, the screw
has been inserted in a bone 62 having a infected region 66. The
implant is bathed in a body fluid 64. FIGS. 7B-7C show views along
line 2B of FIG. 7A, showing the internal cannulated passage through
the elongate screw body 76. The implant is anchored in cancellous
bone 82 initially by threaded portion 78, with the rest of implant
body 76 in this example positioned within the cortical bone 80. In
this example, six members formed as anodes (silver containing
regions) are configured as ribbon coils 84 that can be rotated to
deploy them out of openings 74 on the body of the screw. The ribbon
coil 84 is held inside rod screw 60 near slots/openings 74 between
threads 78. These deployable members are part of the loaded (e.g.,
preloaded) antimicrobial cartridge 72. The cartridge may be rotated
when positioned within the screw body to deploy the members from
the screw and into the tissue. The device also includes a screw
head 68 at the proximal end and a deployment trigger 72 which is
configured as a trigger head 72 in this example. Screw head 68 has
slots 70 which can be used to insert (e.g., screw in) the screw
into the bone, and/or to hold screw body when manipulating trigger
head 72 or can be used to otherwise insert, remove, or manipulated
the screw.
[0102] In the exemplary device shown in FIGS. 7A-7C, the silver
releasing members of the cartridge may be deployed by rotating the
trigger. Referring to FIG. 7C, the trigger head 72 may be rotated
(e.g. counterclockwise), causing ribbon coils 84 to move into
position under slots 84 and to unfurl to form probes 88 that extend
from the elongate body of the screw. As the members extend from the
body, silver on the members (forming a cathode) is placed in
electrical contact with the cathode formed on the outer surface of
the screw body 76; thus the galvanic potential is on, and silver
may be released into the tissue that is bathed in the electrolyte
solution (e.g., blood). Thus, members 88 include a silver-releasing
anode that is electrically communicating with the platinum cathode
on the screw body 76. In this manner, silver ions may be released
in a region surrounding the implanted screw body, and silver ions
90 may clear infection 66 to create a clear zone 88 in tissue
around the implant.
[0103] In the example shown in FIGS. 7A-7C the device for
antimicrobial silver release may include a cartridge having the
coiled arms that can be extended from the body. In some variations,
the cartridge is integral with the body of the device. For example,
in FIGS. 7A-7C the cartridge comprises the inner rod member
connected proximally to the trigger; the cartridge includes the
coiled member wrapped around the inner rod member. The inner rod
member may be rotated within the body. In some variation the inner
rod member is permanently fixed within the body of the device. In
some variations the inner member forming the rotatable may be
removable from the body of the device. Thus, the inner member may
be recharged and/or replaced while leaving the screw within the
patient's bone.
[0104] FIGS. 8A and 8B show another variation of a device
configured as a screw similar to the one in FIG. 7A-C with tilted
slots 104 between threads 102 on rod region 100 in order to bias
ribbon coil 106 to exit the body at an angle. In general, the
device body may include one or more guides, channels, or the like
for directing the members ("ribbon coil 106") from the cartridge
(e.g., inner rod) away from the body of the device at an angle or
along a pathway. For example, in some variations the device's
threads near the distal end of the device may be used to deflect
and direct the extending members and thereby control the extent and
location of antimicrobial "cloud" surrounding the implant as the
ions are released.
[0105] FIGS. 9A and 9B show a top view of another variation of a
device configured as a screw similar to the ones shown in FIGS.
7A-8B. This variation includes more members (probes 114), which may
be distributed more tightly or specifically around the device. In
this example, the trigger head 108 is shown inside rod screw head
110. Slots 112 on screw head 110 can be used to hold the device
head 110 relative to trigger head 108 to manipulate the trigger
relative to the screw, or screw relative to the bone. In another
example, the interior surface and/or outer surface of the screw
head 110 may be shaped to engage and/or be grippable by a cannula
or other insertion/removal device during screw insertion, removal,
or repositioning. The internal shape of the proximal end of the
device may be any shape that allows an insertion/removal device to
grip the internal surface and to move (e.g. rotate) the screw. The
internal shape may be, for example, hexagonal, square, triangular,
or threaded. The internal shaping may be only in the head or may
extend through part or the entire length of the screw. Being able
to grip more than just the head of the screw may better distribute
force applied (e.g. torque) to move the screw (e.g., during
insertion, removal or repositioning) and thereby prevent the screw
from breaking, stripping, or otherwise being damaged. When the
multiple arms (probes, coils, etc.) are extended into the tissue
(e.g., bone) from within the bone implant device, these member may
(in addition to releasing silver) provided additional anchoring to
the implanted device. For example, the extended/deployed arms
provide mechanical resistance to inhibit unwanted removal or
movement of the device.
[0106] In general, the cartridges described herein can be assembled
from any materials that will allow them to be deployed from an
implanted device and release silver ions and/or remove (biopsy)
tissue. For example, FIGS. 10A-10D show a device, configured as a
screw, and a cartridge, formed from a memory shaped ribbon. FIG.
10A shows the shape of the ribbon 124 and the screw device 120. In
this example, ribbon 124 collapses to assume collapsed
configuration 126 as it's inserted into housing 120. Collapsed
ribbon 126 is pushed or turned into position so that probes 125 can
expand through slots 122.
[0107] Bones that have been subject to mechanical trauma, infection
or other forms of insult may be prone to further damage during
insertion of a bone screw. Inserting a bone screw with mechanical
properties that are closer to those of bone may reduce or prevent
further trauma. FIGS. 11A-C show a bone screw in which the
mechanical properties of the bone screw are relatively similar to
the mechanical properties of the bone, but which is still able to
generate therapeutic silver ions. In this example the elongate body
of the device 130 includes a threaded distal end region and a
proximal spring region. The device is shown in FIG. 11B and the
cartridge for use with the device is shown in FIG. 11A. FIG. 11B
shows a platinum (or platinum coated) screw with a threaded distal
end 134 and a proximal spring end 137. Screw end 134 may be
inserted into a bone by turning hex 136 with a driver. In any of
the variations described herein, an initial (e.g. pilot) passage
into the bone may be drilled or otherwise formed before implanting
the device. Stop 138 may be used to prevent the screw from being
inserted too far into the bone. Once rod screw 130 is in place, a
cartridge comprising, in this example, a silver screw or spring 132
as shown in FIG. 11A can be screwed into rod screw 130. The result
is the two springs coiled together 144 as shown in FIG. 11C. The
contact between the platinum or platinum coated coiled region of
the device body 137 and the coiled and silver or silver coated
region of the cartridge 132 is sufficient that when in the presence
of an electrolytic solution, silver ions will be released from the
implant.
[0108] Another example of a trigger or switch for controlling the
release of silver ions (e.g. for creating a device having a
controllable on/off application of silver ions) uses a magnet as
shown in FIGS. 12A-12B. In this example a control magnet is shown
outside the body, external to skin 155 while screw 152 is shown
screwed into cortical 154 and cancellous 156 regions of bone 152 in
the body. Application of external magnetic force (e.g., magnet 158)
repels or attracts a corresponding magnetic region within the
implant 160, causing it to move the cartridge 162 into or out of
position to expand probes 162 out of screw 150 or retract them into
the screw. For example, in FIG. 12B, application of external magnet
158 attracts the internal cartridge implanted with the screw,
causing it to move the cartridge 164 towards it in a contracted
position. Lateral movement of the cartridge results in extending or
retracting the members of the cartridge into and out of the screw
body, thereby turning on or off the release of silver ions from the
screw.
[0109] In use, several bone screws can be used together for larger
bones or bones otherwise requiring more support or treatment as
shown in FIGS. 13A-13B. For example, FIG. 13A shows a series of
bone screws 190 inserted through a bone plate 190 that is adjacent
to a cortical bone 194 and treating large infection 188 near
fracture 186 in femur 180. Each screw has multiple silver-releasing
members 194 extending into cancellous bone 184 to create a large
silver therapeutic area. FIG. 13B shows an alternative embodiment
in which some silver/silver coated rod screws 196 are alternating
with platinum plated or noble metal rod screws 198.
[0110] The bone screw, methods, and systems described herein may be
used with any type of bone, including long bones. FIG. 14 shows a
bone screw 202 configured to release silver ions similar to those
in FIGS. 2A-3B above, inserted into a portion of a jaw. Therapeutic
silver ions 206 are released from members 206. The screw may be
configured to attach a tooth, crown or other dental appliance. FIG.
15 shows bone screws and a plate attached to a mandible such as
might be used in a reconstructive surgery to prevent or treat
infections. FIG. 16 shows bone screws and plates used in various
bones of the jaw, face, and skull 220.
[0111] In some variations, the anti-infective cartridge includes a
lock on the cannulated screw and/or rod to hold the cartridge in
place relative to the elongate body of the device. Thus, the
cartridge may be locked in a configuration (e.g., deployed,
un-deployed, etc.) within the body of the device. The lock may be
releasable; for example, the lock may include a latch.
[0112] As mentioned above, the cartridge may be configured as a
biopsy (e.g., assay) cartridge, which may be used instead of, or in
addition to an anti-infection cartridge; in some variations the
cartridge is a combination of both anti-infective and biopsy. In
general a biopsy cartridge may be coupled to the body of the device
and used to withdraw a sample of tissue from around where the
implant has been inserted without having to remove the device
("implant") from the body. For example, in some variations, the
biopsy cartridge is inserted through the cannulated elongate body
of the device (e.g., of a screw body) and one or more members of
the cartridge extends from the elongate body, similar to the
silver-releasing members extending from the silver-release
cartridges described above, to make contact with a portion of the
body to be assayed, to obtain a biopsy (assay) sample, and to be
removed. The biopsy sample can be assayed in any way after being
removed from the patient. Thus, the biopsy cartridge may have an
expanded (deployed) form and a collapsed (un-deployed) form. The
biopsy cartridge may be expanded before obtaining a biopsy sample
and may be collapsed after obtaining a biopsy sample. Any of the
structures described in the disclosure for the anti-infective
cartridge and any of the methods described for inserting, using, or
removing the cartridge may also or instead be used for the biopsy
cartridge.
[0113] Although many of the examples described above are configured
so that the device body is configured as the cathode (e.g.,
comprising a platinum material) while the extendable members from
the cartridge are the anode material (e.g., silver or silver
coated), in some variations this configuration may be reversed. For
example, the device body (e.g., the screw body, rod body, etc.) may
be silver or silver coated and the anti-infective cartridge may
configured as the cathode, comprising a noble metal such as gold,
palladium or platinum to create a galvanic response in the body and
release silver ions.
[0114] In general, the devices may be inserted or implanted into
the body, e.g., into the bone, either before during or after
engaging a cartridge, including an anti-infective and/or biopsy
cartridge. For example, a device configured as a silver-delivering
screw may be inserted into a bone, loaded with an anti-infective
cartridge or biopsy cartridge by inserting the cartridge through
the elongate body (e.g., from the proximal end of the screw rod). A
biopsy cartridge may be inserted and removed before, after, or
instead of insertion of an anti-infective cartridge. In one
example, a biopsy cartridge is inserted through the device body,
takes a biopsy sample, and is removed before anti-infective
cartridge is inserted. In another example, an anti-infective
cartridge may be inserted, left in the body for a period of time to
create therapeutic silver ions, and removed before a biopsy
cartridge is used to remove a biopsy sample to determine an
effectiveness of anti-infective treatment. In another example, an
anti-infective cartridge may be inserted, left in the body for a
period of time to create therapeutic silver ions, and removed
before a biopsy cartridge is used to remove a biopsy sample to
determine an effectiveness of anti-infective treatment.
[0115] In another example, a first anti-infective cartridge is
placed through the device implanted in the body and one or more
anti-infective cartridges are additionally placed in the device
body, without removing the first anti-infective cartridge. The
cartridges may degrade (e.g., corrode as the silver is release) or
simply avoiding by preceding cartridges.
[0116] In another example, a first anti-infective cartridge may be
removed from an implanted device in a body and a second
anti-infective cartridge inserted. This process may be repeated.
This may be done, for example, if there is insufficient therapeutic
silver remaining on a first cartridge. The screw rod and any of the
cartridges may be left in the body for any length of time. They may
be left in for less than thirty days (e.g. a few days, a week, or
several weeks) or they may be left in for more than thirty days. In
one example, the screws may be left in permanently.
Examples
[0117] Any of the exemplary ion-releasing devices described above
may be used to treat (or prophylactically treat or prevent)
infection and/or support tissue. Exemplary methods of use are
illustrated below. These examples are intended only to illustrate
how one such implant may be operated, and is not intended to be
limiting or limited to any specific variation.
[0118] In general, the implants for controllably providing
antimicrobial treatment and support may be used to treat any
tissues of the body, but particularly bones, including the long
bones (such as the femur, tibia, radius, ulna, fibula, metacarpal,
metatarsal, phalanges, etc.), the spine, and the skull. In some
variations the device is configured for insertion into the
medullary canal of a lower extremity bone, such as a femur, tibia,
tarsal or metatarsal, for the alignment, stabilization, fixation
and bone biopsy of various types of fractures or deformities caused
by trauma, infection or disease. Examples of such fractures
include: traumatic fractures, re-fractures, non-union,
reconstruction, malunion, malalignment, pathological fractures due
to infection or disease and impending pathological fractures. The
ion controlled release systems may have silver and/or zinc coated
struts that expand out from the body of the device to form a
three-dimensional array to stabilize, minimize device migration and
form an antimicrobial barrier to reduce microbial colonization on
the external surfaces of the device.
[0119] An implant that controllably provides antimicrobial
treatment, such as a bone screw for controllably releasing silver
ions, may be used to repair a bone fracture. The bone may first be
prepared to receive the device. Pre-existing deformities may be
corrected prior to the preparation and insertion of a device such
as those described above configured as a controllable silver-ion
releasing bone screw (e.g., intramedullary or IM screw). The
anatomy of the deformity, surgeon preference, and patient
positioning may determine the appropriate approach chosen for joint
preparation and alignment.
[0120] For example, a bone implant that controllably provides
antimicrobial treatment may be use used to repair a broken ankle.
Upon properly aligning and preparing all the joint surfaces, the
ankle may be positioned for arthrodesis. The ankle may be
medizlized by thorough debridement of medial gutter facilitates
positioning in the center of the calcaneus, talus and tibia. The
ankle may then be placed in neutral dorsiflexion and symmetric
external rotation of the contralateral ankle. This position may be
maintained throughout the procedure, and may be facilitated by
provisionally placing a wire on the periphery of the ankle
joint.
[0121] Under fluoroscopic control, a 2-3 cm longitudinal incision
may be made just above the location for the bone insertion point.
After the incision is made, dissection may be continued down to the
surface of the target bone by bluntly dissecting through the soft
tissues, noting the location of neurovascular bundles. Thereafter,
the device (e.g., a controlled silver ion releasing implant or bone
screw) may be inserted. An introducing cannula can then be selected
and placed against the bone insertion point. The hand reamer may
then be used to carefully ream through the cortical bone into the
intramedullary canal. The cannula is not advanced into the bone.
The position of the hand reamer under fluoroscopy may be monitored
under fluoro periodically. The hand reamer can be removed from the
cannula.
[0122] Thereafter, the surgeon may select the proper size implant
device IM screw rod that is pre-mounted on trocar. Advance the
screw rod into the bone by turning clockwise. Periodically stop and
check under fluoroscopy the position of the screw rod with respect
to the opposite cortical side.
[0123] Finally, the trocar device may be removed from the inside of
the cannulated screw rod by turning clockwise.
[0124] In some variations, the bone implant that controllably
provides antimicrobial treatment may also be used to take a biopsy
before, during or after insertion of the implant. The implant may
be inserted into the bone as discussed above, and a bone biopsy
cartridge may be inserted through the internal cannula of the
implanted device. The proximal end of the cartridge may be grasped
direction of coupled to a handle for manipulation by a surgeon. The
distal end of the biopsy cartridge may include one or a plurality
of cupped wires that can be extended from the implant body and used
to sample the tissue. For example, one or more cupped wires may be
deployed through the ports of the body of a screw-type implant.
This may be met with some resistance from the cancellous bone.
Extension of the biopsy cup wires can be confirmed by fluoroscopy.
After deployment of the wires, the proximal end of the cartridge
may be pulled back and the wires retracted, capturing cancellous
bone for biopsy in the cups of the cartridge. The cartridge may be
removed from the rest of the implant, and placed in a sealed,
labeled laboratory infectious disease container for further
processing.
[0125] In general, the antimicrobial cartridges described herein
may be inserted and/or deployed as mentioned above. For example, a
cartridge may be removed from a foil sterile package. The cartridge
may be stored in a sealed package with an indicator to indicate if
the package integrity has been compromised. For example, the
package may include an indicating desiccant (e.g., pouch) that
visually indicated, e.g., by a line that changes red, if the
packaging has been breached and exposed to humidity.
[0126] The cartridge may be inserted into the device housing, e.g.,
the central bore or cannula within the elongate cannulated body. In
some variations the cartridge is pre-loaded into the body of the
device. The cartridge, and particularly the elongate members of the
cartridge at the distal end, may be inspected and/or aligned with
the cannulated body so that they may be extended through openings
in the body to extend from the body when implanted. The cannulated
body may include a guide, channel, keying, etc. to aid in aligning
and inserting the cartridge into the body. In some variations the
inner surface of the cannulated body is keyed (including threaded)
to guide the insertion of the cartridge; an outer surface of the
cartridge may mate with and engage the inner surface of the
cannulated body.
[0127] An insertion tool (e.g., handle) may be used to help insert
the cartridge into the elongate cannulated body of the implant. For
example, the insertion/removal tool may be an elongate rod having a
coupling and or mount its distal end region to connect to a
cartridge. In some variations the insertion/removal tool may
include an inner body region for holding the cartridge in the
collapsed/un-deployed configuration after or before it has been
connected/removed from the implant body. For example, the cartridge
may be "collapsed" by the action of the insertion tool. The distal
end of the insertion tool may include a chamber, cannula, etc. for
holding the cartridge in a collapsed configuration; the cartridge
may be pushed out of or otherwise extended from the handle into the
implant, allowing the members of the cartridge to extend through
the body of the device and into the tissue.
[0128] Thus, the distal ends of the members may be extended away
from the body of the implant and into the patient tissue so that
the members will deploy through the ports of the device. In some
variations this deployment is guided by the implant body which
deflects and/or guides the members as they are extended. For
example, the threads of an implant configured as a bone screw may
be arranged to deflect the members outward and into the tissue.
After insertion and/or deployment of the cartridge in variations
requiring it, any inserter tools may be withdrawn and proper
positioning may be confirmed using fluoroscopy.
[0129] Thereafter, the stability and operation of the device may be
verified, and the surgical access/insertion site may be closed, at
least for some amount of time. In some variations the cartridge may
be replaced/recharged into the same implant over the course of
weeks, months or years.
[0130] Once the implant has exceeded its useful life, it may be
removed from the patient or left in place. In some variations it
may be desirable to leave the implant in place so that it can
continue to provide structural support. This may be true even of
the cartridges, as any extended members that have been extended
into the tissue may continue to provide structural support even if
the source of silver ions has been exhausted.
[0131] The cartridges may be removed in many cases by reversing the
insertion process just described. In some variations the cartridge
may remain within the bone for approximately 30 days or more. The
implant may be removed with a removal device configured to couple
to the proximal end of the cartridge and/or to release the
cartridge from the device body.
[0132] In some variations a retrieval kit may be used. For example,
a retrieval kit may include a removal device (configured similarly
to an inserter). To remove the device, surgical aseptic technique
(under fluoroscopy) may be used to make a small incision directly
above the site of the previous surgery. The removal device
(cartridge retrieval device) may be inserted and attached to the
proximal end to the outer housing to stabilize it. In some
variations the retrieval device has an elongated body with a distal
end that is adapted to couple or abut the implant device body and a
second region that is configured to couple with the proximal end of
the cartridge. For example, the retrieval member may include a
central shaft having a distal end adapted to couple (e.g., screw
onto) the proximal end of the cartridge and an outer cannula
surrounding the central shaft that is configured to couple to the
proximal end of the implant device. In some variations the
retrieval device includes a proximal forceps that may be used to
couple to the inner cartridge. Such configurations (or similar
configurations) may allow sufficient leverage to remove the
extended members and withdraw the cartridge form the implant and
the body, retracting the members through the outer housing ports
and collapsing them for removal.
[0133] After removal, the cartridge may be disposed of or used to
provide biopsy material. The surgical site may be examined directly
and by fluoroscopy. If it appears that the site (and implant) would
benefit from additional anti-migration or anti-infection elements,
a new cartridge may be re-deployed for another treatment period
(e.g., 30 days) and the process repeated.
[0134] Although the illustrations described above illustrated
primarily threaded screw variations, it should be apparent that
non-treaded variations and non-screw variations are contemplated.
For example, the devices for controllable release of silver ions
described herein may be configured as nails, rods or the like.
[0135] As for additional details pertinent to the present
invention, materials and manufacturing techniques may be employed
as within the level of those with skill in the relevant art. The
same may hold true with respect to method-based aspects of the
invention in terms of additional acts commonly or logically
employed. Also, it is contemplated that any optional feature of the
inventive variations described may be set forth and claimed
independently, or in combination with any one or more of the
features described herein. Likewise, reference to a singular item,
includes the possibility that there are plural of the same items
present. More specifically, as used herein and in the appended
claims, the singular forms "a," "and," "said," and "the" include
plural referents unless the context clearly dictates otherwise. It
is further noted that the claims may be drafted to exclude any
optional element. As such, this statement is intended to serve as
antecedent basis for use of such exclusive terminology as "solely,"
"only" and the like in connection with the recitation of claim
elements, or use of a "negative" limitation. Unless defined
otherwise herein, 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. The breadth of
the present invention is not to be limited by the subject
specification, but rather only by the plain meaning of the claim
terms employed.
* * * * *