U.S. patent application number 12/575638 was filed with the patent office on 2010-03-25 for disc annulus closure.
This patent application is currently assigned to Promethean Surgical Devices, LLC. Invention is credited to Robert M. Arcangeli, Michael T. Milbocker, Jeffrey A. Wilson.
Application Number | 20100076486 12/575638 |
Document ID | / |
Family ID | 40002656 |
Filed Date | 2010-03-25 |
United States Patent
Application |
20100076486 |
Kind Code |
A1 |
Wilson; Jeffrey A. ; et
al. |
March 25, 2010 |
DISC ANNULUS CLOSURE
Abstract
Disclosed herein are methods for treating a defect in a spinal
disc nuclear space, comprising: (a) creating an opening by open,
percutaneous or laparoscopic techniques to access the defect in the
nuclear space; (b) removing a desired amount of tissue from the
nuclear space; (c) positioning a delivery catheter through the
opening; (d) fluidically isolating the nuclear space by blocking
the opening with a blocking component of the catheter; (e)
delivering an in-situ curable liquid material through a lumen of
the catheter to the nuclear space; and (f) maintaining the
isolating until the liquid material has cured. Also disclosed are
treatment systems and materials for prostheses.
Inventors: |
Wilson; Jeffrey A.;
(Wrentham, MA) ; Milbocker; Michael T.;
(Holliston, MA) ; Arcangeli; Robert M.;
(Westborough, MA) |
Correspondence
Address: |
RISSMAN HENDRICKS & OLIVERIO, LLP
100 Cambridge Street, Suite 2101
BOSTON
MA
02114
US
|
Assignee: |
Promethean Surgical Devices,
LLC
East Hartford
CT
|
Family ID: |
40002656 |
Appl. No.: |
12/575638 |
Filed: |
October 8, 2009 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12152389 |
May 14, 2008 |
|
|
|
12575638 |
|
|
|
|
60931407 |
May 22, 2007 |
|
|
|
60930064 |
May 14, 2007 |
|
|
|
60930104 |
May 14, 2007 |
|
|
|
Current U.S.
Class: |
606/214 |
Current CPC
Class: |
A61F 2002/3092 20130101;
A61F 2002/30733 20130101; A61F 2002/444 20130101; A61F 2002/30069
20130101; A61F 2/442 20130101; A61F 2002/30586 20130101 |
Class at
Publication: |
606/214 |
International
Class: |
A61B 17/03 20060101
A61B017/03 |
Claims
1. A method for treating a defect in a spinal disc nuclear space,
comprising: (a) creating an opening by open, percutaneous or
laparoscopic techniques to access the defect in the nuclear space;
(b) removing a desired amount of tissue from the nuclear space; (c)
positioning a delivery catheter through the opening; (d)
fluidically isolating the nuclear space by blocking the opening
with a blocking component of the catheter; (e) delivering an
in-situ curable liquid material through a lumen of the catheter to
the nuclear space; and (f) maintaining the isolating until the
liquid material has cured.
2. The method of claim 1, further comprising: (g) removing the
blocking component and the delivery catheter; and (h) closing the
opening.
3. The method of claim 1, where the treating comprises one or more
of: (i) augmenting or replacing the nucleus pulposus; (ii)
reinforcing a wall of the annulus fibrosus; (iii) removing and
sealing herniated or bulging portions of a disc; and (iv) closing a
defect in the annulus pulposus.
4. The method of claim 1, wherein the removing in (b) comprises
removing one of (i) a portion of the nucleus pulposus, (ii) all of
the nucleus pulposus, or (iii) a portion or all of the nucleus
pulposus and a portion or all of the inner layers of the annulus
fibrosus.
5. The method of claim 1, wherein the blocking component comprises
an expandable balloon surrounding the catheter.
6. The method of claim 1, wherein the blocking component comprises
an elastic collar surrounding the catheter.
7. The method of claim 1, wherein after (e) a second in-situ
curable liquid material is delivered over or into said first cured
material, to achieve a desired pressure in the nuclear space.
8. The method of claim 1, wherein the blocking component isolates
the tissues surrounding the opening in the annulus from the liquid
implant placed in the nuclear space to provide for the unobstructed
growth of the annulus into the space created by the opening.
9. The method of claim 1, wherein the blocking component is tapered
distally such that a wider part of the blocking component projects
into the nuclear space with a diameter greater than the diameter of
the opening in the annulus.
10. The method of claim 1, wherein the blocking component has a
tissue engaging surface to prevent slippage.
11. The method of claim 1, wherein the curable liquid material is
delivered under pressure sufficient to increase the distance
between vertebral endplates adjacent to a treated nucleus.
12. The method of claim 11, wherein a lumen in the delivery
catheter allows for evacuation of gas from the nuclear space as
liquid implant is injected.
13. The method of claim 1, wherein a disposable lumen is placed
inside the delivery catheter lumen to allow for multiple injections
of liquid implant without repositioning the blocking component of
the delivery catheter.
14. The method of claim 1, wherein the delivering of the curable
liquid material in (d) comprises: a first application that coats
and seals an inner surface of the annulus fibrosus; and a second
application to fill the nuclear space.
15. The method of claim 15, wherein the second application
pressurizes the nuclear space.
16. The method of claim 1, wherein the curable liquid material
foams while it cures and produces a pressure inside the nuclear
space independent of the pressure of the delivering.
17. The method of claim 1, wherein the curable liquid material
foams and incorporates any air pockets remaining in the nuclear
space to provide substantially complete contact between the inner
surface of the annulus and the cured implant.
18. The method of claim 1, wherein after (b), a sheet is interposed
between the nuclear space and the blocking component to provide
increased strength to the cured liquid implant after it has
cured.
19. The method of claim 18, wherein the sheet is a mesh.
20. The method of claim 18, wherein the sheet comprises a cured
liquid implant.
21. The method of claim 18, wherein the sheet has a conical cross
section.
22. The method of claim 1, wherein the curable liquid material
comprises: a polyurethane prepolymer comprising a polymeric polyol
end-capped with diisocayanate, and a low molecular weight
polyisocyanate.
23. The method of claim 22, wherein the polymeric polyol comprises
polyethylene oxide and polypropylene oxide.
24. The method of claim 23, wherein the polymeric polyol comprises
polyethylene oxide in an amount ranging from 70 to 90% by weight
and polypropylene oxide in an amount ranging from 10 to 30% by
weight.
25. The method of claim 22, wherein the polymeric polyol comprises
75% polyethylene oxide and 25% polypropylene oxide.
26. The method of claim 22, wherein the polyurethane prepolymer is
a trifunctional polyol capped with diisocyanate, the trifunctional
polyol being formed by trimerizing polymeric diols with trimethylol
propane.
27. The method of claim 22, the polyurethane prepolymer has a
molecular weight ranging from 4500 D to 5500 D.
28. The method of claim 22, the low molecular weight polyisocyanate
has a molecular weight of 1000 D or less.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of and claims priority
under 35 U.S.C. .sctn.120 to U.S. Ser. No. 12/152,389, filed May
14, 2008, and claims the benefit of priority under 35 U.S.C.
.sctn.119(e) to U.S. Provisional Application Nos. 60/931,407, filed
May 22, 2007, 60/930,064, filed May 14, 2007 and 60/930,104, filed
May 14, 2007, the disclosures of which are incorporated herein by
reference.
FIELD OF THE INVENTION
[0002] This disclosure relates to methods and devices for modifying
intervertebral disc tissue, spaces, and structure. Also disclosed
are methods and devices disclosed relate to the localization of an
in situ forming nucleus replacement prosthetic, while it is fluid
and not fully cured, using open and minimally invasive techniques.
The devices for localizing the in situ curing implant are
catheter-based, and adapt their cross section to occlude the otomy
to the disc nucleus while providing for catheter delivery of the
fluid implant.
BACKGROUND OF THE INVENTION
[0003] Intervertebral disc abnormalities are common in the
population and cause considerable pain, particularly if they affect
adjacent nerves. Disc abnormalities result from trauma, wear,
metabolic disorders and the aging process and include degenerative
discs, localized tears or fissures in the annulus fibrosus,
localized disc herniations with contained or escaped extrusions,
and chronic, circumferential bulging discs. Disc fissures occur as
a degeneration of fibrous components of the annulus fibrosus.
Rather minor activities such as sneezing, bending or simple
attrition can tear degenerated annulus fibers and create a fissure.
The fissures may be further complicated by extrusion of nucleus
pulposus material into or beyond the annulus fibrosus. Difficulties
can still present even when there is no visible extrusion, due to
biochemicals within the disc irritating surrounding structures and
nerves.
[0004] A contained disc herniation is not associated with free
nucleus fragments migrating to the spinal canal. However, a
contained disc herniation can still protrude and irritate
surrounding structures, for example by applying pressure to spinal
nerves. Escaped nucleus pulposus can chemically irritate neural
structures. Current treatment methods include reduction of pressure
on the annulus by removing some of the interior nucleus pulposus
material by percutaneous nucleotomy. See, for example, Kambin U.S.
Pat. No. 4,573,448. Complications include disc space infection,
nerve root injury, hematoma formation, instability of the adjacent
vertebrae and collapse of the disc from decrease in height. It has
been proposed to treat weakening due to nucleus pulposus deficiency
by inserting preformed hydrogel implants. See, Ray U.S. Pat. Nos.
4,772,287; 4,904,260 and, 5,562,736 and Bao U.S. Pat. No.
5,192,326.
[0005] More recently, delivery of in situ curing liquids to form a
solid prosthetic in the nucleus of a disc have been disclosed. The
fluid form of these implants enables access to the spine in a
minimally invasive manner, and includes procedures for restoring
structural integrity to vertebral bodies. See Scribner U.S. Pat.
Nos. 6,241,734 and 6,280,456; Reiley U.S. Pat. Nos. 6,248,110 and
6,235,043; Boucher U.S. Pat. Nos. 6,607,554 and Bhatnagar
6,395,007. Methods of repairing the spinal disc or portions thereof
are disclosed in Cauthern U.S. Pat. No. 6,592,625, Haldimann U.S.
Pat. No. 6,428,576, Trieu U.S. Pat. No. 6,620,196 and Milner U.S.
Pat. No. 6,187,048.
[0006] There are a variety of injectable biomaterials disclosed in
issued patents including: cross-linkable silk elastin copolymer
disclosed in Stedronsky U.S. Pat. No. 6,423,333, Capello U.S. Pat.
No. 6,380,154, Ferrari U.S. Pat. No. 6,355,776, Stedronsky U.S.
Pat. No. 6,258,872, Ferrari U.S. Pat. No. 6,184,348, Ferrari U.S.
Pat. No. 6,140,072; Stedronsky U.S. Pat. No. 6,033,654; Ferrari
U.S. Pat. No. 6,018,030; Stedronsky U.S. Pat. No. 6,015,474;
Ferrari U.S. Pat. No. 5,830,713; Stedronsky U.S. Pat. No.
5,817,303; Donofrio U.S. Pat. No. 5,808,012; Capello U.S. Pat. No.
5,773,577; Capello U.S. Pat. No. 5,773,249; Ferrari U.S. Pat. No.
5,770,697; Stedronsky U.S. Pat. No. 5,760,004; Donofrio U.S. Pat.
No. 5,723,588; Ferrari U.S. Pat. No. 5,641,648; Capello U.S. Pat.
No. 5,235,041; protein hydrogel described in Morse U.S. Pat. No.
5,318,524; Morse U.S. Pat. No. 5,259,971; Morse U.S. Pat. No.
5,219,328; polyurethane-filled balloons disclosed in Bao U.S. Pat.
No. 7,077,865; Bao U.S. Pat. No. 7,001,431; Felt U.S. Pat. No.
6,306,177; Felt U.S. Pat. No. 6,248,131; Bao U.S. Pat. No.
6,224,630; collagen-PEG disclosed in Olsen U.S. Pat. No. 6,428,978;
Olsen U.S. Pat. No. 6,413,742; Rhee U.S. Pat. No. 6,323,278;
Wallace U.S. Pat. No. 6,312,725; Sierra U.S. Pat. No. 6,277,394;
Rhee U.S. Pat. No. 6,166,130; Berg U.S. Pat. No. 6,165,489; Simonyi
U.S. Pat. No. 6,123,687; Berg U.S. Pat. No. 6,111,165; Sierra U.S.
Pat. No. 6,110,484; Prior U.S. Pat. No. 6,096,309; Rhee U.S. Pat.
No. 6,051,648; Esposito U.S. Pat. No. 5,997,811; Berg U.S. Pat. No.
5,962,648; Rhee U.S. Pat. No. 5,936,035; Rhee U.S. Pat. No.
5,874,500; chitosan disclosed in Chemte U.S. Pat. No. 6,344,488;
other polymers discussed in Boyd U.S. Pat. No. 7,004,945; Collins
U.S. publication 2006/0004326; Collins U.S. publication
2006/0009851; Milner U.S. Pat. No. 6,187,048; Daniell U.S. Pat. No.
6,004,782; Urry U.S. Pat. No. 5,064,430; Urry U.S. Pat. No.
4,898,962; Urry U.S. Pat. No. 4,870,055; Urry U.S. Pat. No.
4,783,523; Urry U.S. Pat. No. 4,589,882; Urry U.S. Pat. No.
4,500,700; Urry U.S. Pat. No. 4,474,851; Urry U.S. Pat. No.
4,187,852; Urry U.S. Pat. No. 4,132,746.
[0007] Delivery of an in situ forming prosthetic to the nuclear
space requires constructing a passageway into the nucleus and
removal of the nucleus fibrosus, in total or in part. The
passageway is usually made through the annulus, especially when
part of the annulus should be removed to correct a pathological
condition. Whether the passageway is through the annulus or
elsewhere, for example, through the vertebral body, there is a risk
of the formed nucleus prosthetic extruding through the passageway.
Nucleus prosthetic extrusion can affect the surrounding nerves
adversely. Methods of blocking a passageway made through the
annulus are disclosed in Lambrecht U.S. Pat. No. 6,425,919,
Lambrecht, et al. U.S. Pat. No. 6,482,235, Lambrecht, et al. U.S.
Pat. No. 6,508,839, Cauthen U.S. Pat. No. 6,592,625, Lambrecht, et
al. U.S. Pat. No. 6,821,276 and Lambrecht et al. U.S. Pat. No.
6,883,520. Other methods of preventing nucleus prosthetic extrusion
include enclosing the prosthetic entirely inside of an enveloping
sheath and are disclosed in Ray, et al. U.S. Pat. No. 4,904,260,
Bao, et al. U.S. Pat. No. 5,192,326, Kuslich U.S. Pat. No.
5,549,679, Stalcup, et al. U.S. Pat. No. 6,332,894, Wardlaw U.S.
Pat. No. 6,402,784, Weber, et al. U.S. Pat. No. 6,533,818, and
Reuter, et al. U.S. Pat. No. 6,805,715. Still other methods of
preventing nuclear prosthetic extrusion include delivering a
preformed prosthetic in a reduced state, which when introduced into
the body increases in volume. These methods and devices are
disclosed in Ray, et al. U.S. Pat. No. 6,602,291, Stoy, et al. U.S.
Pat. No. 6,726,721, and Li, et al. U.S. Pat. No. 6,764,514.
[0008] None of the techniques or devices and associated methods of
their use described above are entirely satisfactory from either a
biocompatibility or efficacy perspective, for localization of an in
situ curing liquid nucleus implant. Accordingly, there remains a
need for the development of treatment methods and devices for
implanting spinal disc prostheses.
SUMMARY OF THE INVENTION
[0009] One embodiment provides a method for treating a defect in a
spinal disc nuclear space, comprising:
[0010] (a) creating an opening by open, percutaneous or
laparoscopic techniques to access the defect in the nuclear
space;
[0011] (b) removing a desired amount of tissue from the nuclear
space;
[0012] (c) positioning a delivery catheter through the opening;
[0013] (d) fluidically isolating the nuclear space by blocking the
opening with a blocking component of the catheter;
[0014] (e) delivering an in-situ curable liquid material through a
lumen of the catheter to the nuclear space; and
[0015] (f) maintaining the isolating until the liquid material has
cured.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] Various embodiments of the invention will be understood from
the following description, the appended claims and the accompanying
drawings, in which:
[0017] FIG. 1 is a superior cross sectional anatomical view of a
cervical disc and vertebra; and
[0018] FIG. 2 is a schematic view of an introducer and an
embodiment of a delivery catheter having a balloon as a blocking
component, in which solid lines illustrate the position of the
instrument in the absence of bending forces and dotted lines
indicate the position of the distal portion of the instruments
under bending forces applied to the intradiscal section of the
instrument;
[0019] FIG. 3 is a schematic view of another embodiment of a
delivery catheter in which the blocking component comprises an
elastic collar;
[0020] FIG. 4A is a schematic view of a guidewire introduced into
the nuclear disc space;
[0021] FIG. 4B is a schematic view of a cannula fitted with an
obturator introduced into the nuclear disc space;
[0022] FIG. 4C is a schematic view of a shaver blade introduced
into the lumen of the cannula of FIG. 4B;
[0023] FIG. 4CD is a schematic view of a delivery catheter
introduced into the lumen of the cannula of FIG. 4B; and
[0024] FIG. 5 is a schematic view of a cannula moved distally in
the annulus such that the delivery catheter is deployed in contact
with the annulus tissue.
DETAILED DESCRIPTION
[0025] One embodiment provides a device for delivering an in situ
curing liquid nucleus implant intended to replace or augment the
natural disc nucleus space. The disc nucleus space includes the
nucleus pulposus and the adjacent tissues, including the vertebral
endplates and inner layers of the disc annulus. Curing with respect
to the liquid nucleus implant refers to a phase change of the
implant from liquid to solid. The treatment involves delivery of an
in situ polymerizing tissue adhesive into the treatment area of the
nucleus or nuclear space. The treatment further involves a means
for preventing migration of the liquid implant after it has been
delivered and before it has fully cured. The delivery aspects of
the device are not intended to remain in the body after the implant
has been delivered and cured.
[0026] One embodiment provides a method for treating a defect in a
spinal disc nuclear space, comprising:
[0027] (a) creating an opening by open, percutaneous or
laparoscopic techniques to access the defect in the nuclear
space;
[0028] (b) removing a desired amount of tissue from the nuclear
space;
[0029] (c) positioning a delivery catheter through the opening;
[0030] (d) fluidically isolating the nuclear space by blocking the
opening with a blocking component of the catheter;
[0031] (e) delivering an in-situ curable liquid material through a
lumen of the catheter to the nuclear space; and
[0032] (f) maintaining the isolating until the liquid material has
cured.
[0033] In one embodiment, the removing in (b) comprises removing
one of (i) a portion of the nucleus pulposus, (ii) all of the
nucleus pulposus, or (iii) a portion or all of the nucleus pulposus
and a portion or all of the inner layers of the annulus
fibrosus.
[0034] In one embodiment, the device or delivery catheter comprises
a lumen, typically of minimal cross section, but sufficiently large
to deliver the liquid nucleus implant by conventional methods.
Conventional methods include a syringe or similar liquid dispensing
device that is either mechanically pressurized or manually
pressurized sufficiently to deliver the liquid nucleus implant to
the treatment site before the liquid implant has cured. In one
embodiment, the delivery lumen, conventionally a catheter, is
fitted with a syringe-type connection, such as a luer
connection.
[0035] In one embodiment, the delivery catheter comprises a
blocking component that sealably interfaces with the access hole
made through bone or the disc annulus. In one embodiment, the
blocking component is inflatable, e.g., a balloon surrounding a
catheter, where the catheter possesses at least one lumen for
delivery of the liquid nucleus implant and a least one lumen for
controllably inflating the balloon.
[0036] In another embodiment, where the blocking aspect is an
elastic collar made to expand by compression along the delivery
catheter only one lumen is required.
[0037] In one embodiment, the treatment method comprises two or
more applications of in-situ curable liquid material. The delivery
lumen may be suitably sized to allow a tube to be inserted in the
delivery lumen to act as a disposable delivery lumen to be removed
after a first delivery of liquid material has cured and to be
subsequently replaced by an additional disposable delivery lumen to
enable a second delivery of liquid implant. This process can be
repeated for as many applications of liquid material desired.
[0038] In one embodiment, the proximal and distal ends of the
blocking component may be marked with radio-opaque features or
other marker suitable for enabling a medical professional to
position the blocking aspect relative to a vertebral feature. In
another embodiment, a set of proximal and distal markers suitable
for positioning the blocking component in the nucleus annulus
provides the proximal end flush with the inner surface of the
annulus or on the margin of a cleared region of nucleus.
[0039] In one embodiment, the treating comprises one or more
of:
[0040] (i) augmenting or replacing the nucleus pulposus;
[0041] (ii) reinforcing a wall of the annulus fibrosus;
[0042] (iii) removing and sealing herniated or bulging portions of
a disc; and
[0043] (iv) closing a defect in the annulus pulposus.
[0044] One embodiment provides techniques employing the in situ
curing liquid nucleus implant delivery device for modifying the
disc annulus, vertebral endplates and/or nucleus to restore nuclear
integrity. Open and minimally invasive surgical methods can be used
to treat disc abnormalities at locations previously not accessible
via percutaneous approaches, and without substantial destruction of
the disc and/or surrounding tissue. The treatment entails delivery
of in-situ curable liquid material to select locations within the
disc, including delivery to the location of an annular fissure, the
location of a nuclectomy, or the location of an annulus herniation.
In one embodiment, the surgical methods disclosed herein involve
producing an access to the nucleus pulposus, and delivering an in
situ phase-changing liquid to repair the annulus, endplates and/or
nucleus.
[0045] Establishing the access to the nucleus pulposus may involve
a positioning means comprising a needle or guidewire which is
directed to a treatment site in the disc, guiding a cutting device
to the site where the positioning means is located so as to make an
access through the annulus or bone, and delivering along the
positioning means an operational port through which the delivery
catheter might be deployed. In the case of access through the disc
annulus, the operational port may accommodate a conically
terminated stylet suitable for delivering the operational port in a
minimally disruptive manner to a site within the disc. Once
positioned, the conically terminated stylet is removed and a
portion or all of the nucleus pulposus may be removed by
conventional means through this port. Once a sufficient quantity of
nucleus is removed the delivery catheter is positioned within the
operational port such that when the blocking means is deployed,
liquid nucleus implant may be injected into the created nuclear
space such that the implant material is prevented from traversing
the operational port.
[0046] In one embodiment, the delivery catheter does not require a
second lumen for removal of the displaced gas where the implant
foams and encapsulates the air at an elevated pressure.
Alternatively, an overflow or gas displacement port situated in
either the operational port or the delivery catheter may be
employed in the design. Once the liquid implant is cured the
catheter and operational port may be removed from the body leaving
the cut surfaces of the annulus free from implant material and thus
disposed to grow together through the natural healing process.
[0047] In a further embodiment, it is contemplated that the in-situ
curing nucleus implant may be introduced into the nucleus (which
may be previously evacuated by nucleotomy) to form a reinforced
nucleus implant in-situ. Additional nucleus implant may be
introduced at the same time or subsequent to curing of the initial
insertion by removing the delivery catheter only and repositioning
a fresh delivery catheter in the operational port.
[0048] In another embodiment, the method further comprises:
[0049] (g) removing the blocking component and the delivery
catheter; and
[0050] (h) closing the opening.
[0051] In one embodiment, the proposed methods generally involve
one or more of the following steps: [0052] 1. Creating an opening
by open, percutaneous posterior-lateral, retroperitoneal, or
anterior laparoscopic method. Accessing a desired portion of spinal
disc region through an operational port can occur in a minimally
invasive manner and under the assistance of a guide wire. The
surgical approach selected may vary depending upon the portion of
the spinal disc segment to be treated. [0053] 2. Optionally,
removing diseased or degenerated tissue while minimizing removal of
healthy tissue while (e.g. removing bulging portions of the annulus
fibrosis, or nucleus pulposis, removal of osteophytes, etc.) [0054]
3. Positioning a delivery catheter through the opening. The
positioning can comprise placing the operational port in the disc
annulus by means of insertion of a conical stylet into the
operational port, advancing the operational port into the disc
annulus, removal of the conical stylet, and insertion of a delivery
catheter. [0055] 4. Fluidically isolating the nuclear space by
blocking the opening with a blocking component of the catheter,
(actuation of the blocking means). [0056] 5. Delivering an in-situ
curable liquid material (e.g., a polymerizing nucleus implant)
through a lumen of the delivery catheter and into the nuclear
space. The delivering can comprise replacing all or a portion of
the disc nucleus (which may have previously been removed during the
same or prior surgery) with the in-situ curable liquid
(polymerizing fluid). [0057] 6. Maintaining the isolating until the
liquid material/implant has cured. Upon curing, the method can
comprise removing the delivery catheter by deactuation of the
blocking means, retracting the operational port or optionally
introducing another delivery catheter for a second delivery of
liquid polymer and repeating the above steps until suitable
replacement and augmentation of the disc nucleus is achieved.
[0058] 7. Retracting the operational port from the disc annulus,
stopping just outside the disc annulus and optionally providing a
closure means to the otomy (i.e., the surgically created opening)
of the disc annulus and finally removing the operational port from
the body. [0059] 8. Closing any openings created to gain access to
the spine.
[0060] In addition to the method, there is provided an in-situ
curable liquid material (a liquid nucleus implant) sufficient to
provide the therapeutic effect of strengthening and/or filling the
intervertebral space and preventing extrusion of the polymerized
prosthetic. A variety of in-situ polymerizing liquids may be used,
both adhesive and non-adhesive. In one embodiment, the in-situ
polymerizing liquid is a single-component polyisocyanate based
adhesive as described in U.S. Pat. Nos. 6,254,327, 6,296,607, U.S.
provisional patent application Ser. No. 60/557,314, and U.S. Pub.
Nos. 2003/0135238 and 2005/0215748, the disclosures of which are
incorporated herein by reference in its entirety.
[0061] Another embodiment provides a device that has a distal end
fitted with a detachable bag that is inserted into the disc and
accesses the posterior, posterior lateral and the posterior medial
regions of the inner wall of the annulus fibrosus in order to
repair an annular fissure at such a location by filling the bag
with adhesive.
[0062] The present invention generally provides methods and
apparatus for treating intervertebral disc disorders by delivering
a liquid nucleus implant through a delivery catheter to the spinal
disc space. The liquid implant can be delivered within the disc
nucleus to repair or replace the nucleus through a delivery
catheter containing a blocking component to contain or prevent
escape of extrusions. The liquid nucleus implant and delivery
catheter may also be used to create a disc nucleus implant in-situ.
In one embodiment, the methods and devices are used to deliver and
reinforce a single-part in-situ polymerizing nucleus implant to
accomplish the desired surgical results.
[0063] In one embodiment, a liquid in situ curing agent is
delivered via a delivery catheter with a blocking component for
fluidically isolating, accessing, and delivering an in-situ curing
agent to a location in an intervertebral disc having an annulus
fibrosus, the annulus having an inner wall. Additionally, certain
embodiments can be used with any of a variety of insertional
apparatus to provide proximity to the disc, such as insertional
apparatus known in the art as "introducers". In one embodiment, the
delivery catheter comprises a lumen that fits snuggly to the inner
surface of the introducer and provides sufficient frictional
retaining and blocking force to remain localized in the introducer
during injection of the liquid nucleus implant. An introducer has
an internal lumen with a distal opening at a terminus of the
introducer to allow insertion/manipulation of the operational parts
of the delivery catheter in the interior of a disc.
[0064] In one embodiment, the blocking component isolates the
tissues surrounding the opening in the annulus from the liquid
implant placed in the nuclear space to provide for the unobstructed
growth of the annulus into the space created by the opening. In one
embodiment, the inner wall of the annulus fibrosus can include the
young wall comprised primarily of fibrous material as well as the
transition zone, which includes both fibrous material and amorphous
colloidal gels.
[0065] In one embodiment, after the removing in (b), a sheet is
interposed between the nuclear space and the blocking component to
provide increased strength to the cured liquid implant after it has
cured. Exemplary sheets include those described in U.S. Pat. No.
7,044,982 and U.S. Pub. Nos. 2006/0233852, the disclosure of which
is incorporated herein by reference.
[0066] The relevant anatomy is illustrated in FIG. 1, which
illustrates a cross sectional view of the anatomy of a vertebra and
associated disc. Structures of a typical cervical vertebra
(superior aspect) are shown in FIG. 1: 104--amina; 106--spinal
cord; 108--dorsal root of spinal nerve; 114--ventral root of spinal
nerve; 118--intervertebral disc; 120--nucleus pulposus;
122--annulus fibrosus; 124--anterior longitudinal ligament;
126--vertebral body; 128--pedicle; 130--vertebral artery;
132--vertebral veins; 134--superior articular facet; 136--posterior
lateral portion of the annulus; 138--posterior medial portion of
the annulus; 140--vertebral plate, and 142--spinous process. In
FIG. 1, one side of the intervertebral disc 118 is not shown so
that the anterior vertebral body 126 can be seen.
Liquid Nucleus Implants
[0067] One embodiment provides methods for use of a liquid nucleus
implant to repair defects in a disc, including repair of the
annulus and/or filling of a nuclear space. Regarding the nucleus
implant, a liquid material is introduced into the intervertebral
space to improve the function of the disc tissues and fluids
contained therein. In one embodiment, the liquid nucleus implant
has a low viscosity and is capable of delivery through a small
diameter needle, cannula or catheter, for example through a typical
catheter having an inner diameter ranging from 3.5 to 5 mm (but
smaller diameter devices can be used if viscosity is sufficiently
low.) Low viscosity can be useful in one or more of the following:
1) ease of delivery, 2) timely delivery, 3) prevention of delayed
pressure transference from source to the target tissue site, and 4)
permits sensing of resistance feedback by the operator to determine
appropriate delivery volumes.
[0068] In one embodiment, the viscosity of the curable liquid
material is less than 1000 cp, such as an implant viscosity of less
than 200 cp. In another embodiment, the viscosity ranges from 100
cp to 1000 cp. In one embodiment, the viscosity limit of 1000 cp is
satisfied when prepolymer is mixed with water in the ratio of 70:30
or less, and 60:40 or less for the 200 cp limit.
[0069] In one embodiment, the liquid nucleus implant is a
single-component, self-curing adhesive that polymerizes in-situ
forming internal cross links as well as bonds to surrounding tissue
and bone. A single-component implant is one in which the
composition of the implant is substantially the same during all
phases of delivery; and, specifically is not an implant that has
more than one tissue reactive component. A single-component implant
may be mixed with one or more dilutive agents to aid in implant
delivery provided the ratio of diluent to active component is not
critical to the curing of the implant. An implant component is any
combination of chemical species that can be stored at room
temperature without substantial chemical change and remain
homogenous in combination. For example, sodium chloride and water
when mixed form an implant component commonly known as saline.
Specifically, a single-component implant may be a mixture of any
number of implant components provided only one is tissue reactive.
A tissue reactive implant component is any implant component with a
tissue biocompatibility as assessed by ISO 10993 different from
that of physiologic saline.
[0070] In one embodiment, the single-component in-situ curable
liquid material comprises a prepolymer An example of a
single-component in situ polymerizing implant is one in which
polymerization of the prepolymer, which can be a tissue reactive
component, is initiated either by aqueous fluids present in the
tissue or by addition of physiological saline or other inert
medicinal solution before delivery to the target site. In one
embodiment, the polymerization of a single-component implant does
not require the addition of cross linkers, catalysts, chain
extenders, or complementary components of an adhesive composition.
In one embodiment, cross linking and tissue bonding is mediated
either by aqueous fluids present in the tissue, or by premixing of
the adhesive with physiological saline or other medicinal saline
solution at the time of administration. The polymerization time of
adhesives is variable, and can be in the range of about 30 seconds
to 30 minutes or more, depending on the application. Exemplary
prepolymers are described in U.S. Pat. No. 6,254,327, and U.S. Pub.
Nos. 2003-0135238 and US 2004-0068078, the disclosures of which are
incorporated herein by reference.
[0071] Polymerization time can be adjusted by selection of
properties and components of the liquid nucleus implant. In one
embodiment, the tissue reactive single component is a liquid
comprising a polyisocyanate-capped polyol, typically macromolecular
in size, having a mean molecular weight of about 1000 Daltons or
more, more typically at least about 4000 Daltons, and yet more
typically in a range of about 4500 D to about 10,000 D, depending
on application. Higher molecular weight macromers may be of use in
adhesives having great pliability (and lower tensile strength). In
another embodiment, the liquid nucleus implant further comprises a
low-molecular weight polyisocyanate, for example with a molecular
weight less than about 1000 D. This may comprise the polyisocyanate
used to cap the polyols. This low molecular weight polyisocyanate
may be present in an amount ranging from 1% to 5% of the
composition. The capped polyol can be multifunctional, and
typically at least partially trifunctional or higher. The polyol
may be any of various biocompatible substances such as polyethylene
oxide, polypropylene oxide, polyethylene glycol, and copolymers of
these. In one embodiment, the polyol has about 10% to about 30% by
weight propylene oxide subunits, and the rest ethylene oxide.
[0072] In one embodiment, the polyisocyanate is typically
difunctional. In one embodiment, the composition is a fast reacting
formulation comprising an aromatic diisocyanate such as toluene
diisocyanate. In another embodiment, the low reacting formulations
comprise an aliphatic diisocyanate such as isophorone diisocyanate.
The polymerization time can be adjusted by selection of appropriate
molecular weight polyols. The higher molecular weight polyols
produce lower viscosity capped reaction products and faster
reacting solutions. Combinations of the above species are
considered to comprise a single component when they are stable and
remain homogenous while stored at room temperature.
[0073] The tissue reactive component of a single-component in situ
curing implant is typically called a prepolymer. The cure times of
a prepolymer achieved using the approaches described above depend,
in part, on controlling one or more of the rate of water diffusion
into the prepolymer, the rate of isocyanate to amine conversion,
and the activity of the isocyanate-functionalized ends. There are
various non-tissue-reactive additions to the prepolymer that can be
made at the time of application to speed prepolymer curing. For
example, when water is added to the prepolymer just before
application, the cure time dependence on water diffusion is
reduced. Generally, addition of water in volumetric ratios of
approximately 1:1 volumetric ratio with the prepolymer maximally
reduces cure time. When additional water is added, such as 4:1
volumetric ratio of water to prepolymer, the cure time increases
from its fastest mixed cure time because the polymer density
decreases. Similarly, when using higher concentrations of
prepolymer, such at 80% or more by volume, the cure time increases
from its fastest cure time because the water availability
decreases. However, all mixtures with water, from 1% up to about
95% by volume, cure faster than application of prepolymer placed
directly on tissue.
[0074] In one embodiment, cure times can span as long as 1 hour and
as short as 30 seconds, although longer cure times are possible. In
general, access will have been made to the implantation site, and
preparation of the implantation site completed before the liquid
implant is prepared. In one embodiment, the liquid implant is
prepared by mixing between two syringes bridged by a
female-to-female luer lok connection prepolymer in one syringe and
saline or other suitable aqueous solution in the other syringe. In
one embodiment, the hydrophilic nature of the prepolymer achieves
homogenous mixing in approximately 10 mix cycles for mix ratios of
10-90% prepolymer. In one embodiment, all implant ratios are
homogenous after 20 mix cycles. In one embodiment, the fastest cure
time are achieved where the mix ratio is approximately 1:1.
However, the cure time does not differ by more than 100% for all
mix ratios.
[0075] The surgeon typically requires a cure time long enough to
mix and inject the liquid implant and short enough to provide for
in situ curing within a few minutes after implantation. In one
embodiment, the cure time ranges from 1 to 10 minutes, such as from
3 to 5 minutes. In one embodiment, the cure time halves for every
10 degree centigrade increase in mixture temperature. The typical
difference between body temperature and room temperature is about
10.degree. C. Often, there is a decrease in cure time once the
liquid implant is injected in the body.
[0076] The first action of water with an isocyanate capped
prepolymer is to convert some of the active isocyanate ends on the
isocyanate capped polyol and some of the active isocyanate ends on
the free isocyanate to amine groups. Amine groups react with other
isocyanate groups to cause rapid chain extension and eventual
crosslinking. Therefore, reduced cure times can also be achieved by
substituting some or all of the water admixture with aqueous
amines. However, in the case of the admixture of tissue reactive
amines such a mixture is no longer considered a single-component
implant.
[0077] In one embodiment, the prepolymer is an aromatic isocyanate
made by end capping a deionized, dried polyalkylene diol with
toluene diisocyanate (TDI), and then reacting the end-capped diol
with a deionized dried triol. In one embodiment, the diol is a
polyethylene glycol/polypropylene glycol co-polymer (random, block
or graft), with EO (ethylene oxide) and PO (propylene oxide) in
weight ratios ranging from about 95:5 to about 25:75, e.g., about
75% EO and 25% PO. An exemplary triol is trimethylol propane (TMP).
An exemplary composition is the reaction product of from about 25%
to 35% TDI, from about 65% to 75% diol (75% EO: 25% PO) and from
about 1% to about 8% TMP. In one embodiment, the composition is the
reaction product of about 30% TDI, about 70% of the 75:25 diol, and
about 1% to about 2% TMP. The prepolymer can have a mean molecular
weight of 4500 to 5500 Dalton.
[0078] These prepolymers can have the added advantage of being
water-soluble. Their water solubility enables them to be injected
into tissue to polymerize the tissue; or, alternatively or
additionally to solidify as gels to stabilize tissue or structures.
The prepolymer acts as a self-sealing fluid when injected into body
cavities.
[0079] Isocyanate-capped polyols, while suitable, are not the sole
adhesives or in situ curing non-adhesive compositions that can be
used. In one embodiment, the adhesive is hydrophilic and
water-soluble before being crosslinked. This hydrophilicity can
enable the adhesive to be injected into tissue to polymerize in
contact with, and bond to, the tissue, as adhesive and/or as local
bulking agent to fill gaps or fissures, or to stabilize implants.
The adhesive can act as a self-sealing fluid when injected into
cavities or gaps. Once cured in situ, the hydrophilic adhesive can
absorb fluid from the tissue, forming a structure that will be at
least somewhat gel-like in character. The cured adhesive can swell
to a controlled extent, exerting a controlled amount of local
pressure. The tensile properties of the cured adhesive can be
adjusted so that the adhesive, like the native tissues of the
annulus or of the nucleus, deforms under pressure while exerting a
restorative force on the surrounding structures. Hence, the
adhesive-tissue composite tends to return to its original shape and
location after movement of the spine and is characteristically
elastic. These properties can be controlled by the composition of
the adhesive, or by providing a controlled degree of dilution with
saline at the time of administration. This is in contrast with
rigid materials, which tend to fracture rather than yield, and to
flowable media, which have no tendency to return to their original
shape after relaxation of stress. In particular, hydrophobic
adhesives tend to become rigid, favoring fracture of the cured
adhesive at the surface of the tissue or implant. They also tend
not to bond to tissue, which is highly hydrophilic.
[0080] In situ polymerization of a liquid nucleus implant can
comprise two phase changes. The first phase change is the
conversion of the liquid implant into an elastic solid, e.g., a
relatively low modulus gel. In one embodiment, the gel modulus
ranges from 0.5 to 20 MPa, from 0.5 to 10 MPa, from 0.5 to 5 MPa,
from 1 to 5 MPa, from 1 to 3 MPa, or from 1.5 and 3 MPa. The
suitability of the implant modulus is somewhat dependent upon the
size of the otomy (surgically created opening) made in the annulus
or vertebral body in order to deliver the liquid implant. The
larger the otomy, the higher is the minimum acceptable modulus. The
minimum acceptable modulus is also determined by the extent of
tissue bonding achieved by the implant curing, the higher the bond
strength the lower the minimum acceptable modulus.
[0081] The second phase change is the conversion of part of the
liquid implant into a gas phase, which when released and entrapped
during curing results in an elastic gel foam. In one embodiment,
the ratio of gas phase to gel phase volume is 10 to 0.1, e.g., 5 to
0.5, or 3 to 1. The gas phase component of the curing implant can
ensure intimate contact between implant and surrounding tissue, and
specifically the reduction or elimination of air pockets or the
need for elaborate venting aspects of the delivery means to
accomplish the same.
[0082] The uncured liquid implant can be polymeric in nature, as
opposed to being a low molecular weight monomer before curing, such
as a cyanoacrylate. A number of known polymers are potentially
useful in the synthesis of suitable adhesive prepolymers. The
polymers can be hydrophilic, for example, sufficiently hydrophilic
to swell in water. A suitable range of swelling can be, at
atmospheric pressure, between from 5% to about 100%, and more
typically is from about 5% to about 30%. In one embodiment, the
prepolymers are sufficiently hydrophilic to have substantial
solubility in water, such as, for instance, 1 g/l or more, e.g., 10
g/l or more, or 100 g/l or more.
[0083] The cured implant may be stable in the body, or may degrade
in the body to smaller, excretable molecules ("degradable"). A wide
variety of linkages are known to be unstable in the body. These
include, without limitation, esters of hydroxy acids, particularly
alpha and beta hydroxy carboxylic acids; esters of alpha and beta
amino acids; carboxylic acid anhydrides; phosphorous esters; and
certain types of urethane linkages. In one embodiment, the cured
implant is stable in the body for prolonged periods, as the fibrous
materials of the annulus have very limited self-repair
capabilities, and the nucleus has virtually none. However, if
methods are found to enhance natural biological repair of the
nucleus or annulus, then degradable adhesives or fillers could be
used.
[0084] The prepolymers can also have reactive groups covalently
attached to them, or part of the backbone. The reactive groups are
suitable for reaction with tissue, and for crosslinking in the
presence of water or components of bodily fluids, for example water
and protein. Suitable groups include isocyanate, isothiocyanate,
anhydrides and cyclic imines (e.g., N-hydroxy succinimide,
maleimide, maleic anhydride), sulfhydryl, phenolic, polyphenolic,
and polyhydroxyl aromatic, and acrylic or lower alkyl acrylic acids
or esters. Such reactive groups are most commonly bonded to a
preformed polymer through suitable linking_groups in the polymer.
Commonly found linking_groups include, without limitation, amines,
hydroxyls, sulfhydryls, double bonds, carboxyls, aldehydes, and
ketone groups. Of these groups, aliphatic hydroxyls are among the
most widely used.
[0085] Thus, suitable base polymers include poly(alkyl)acrylic
acids and polyhydroxyalkyl acrylates, polysaccharides, proteins,
polyols, including polyetherpolyols, polyvinyl alcohol, and
polyvinylpyrrolidone, and these same structures with amine or
sulfur equivalents, such as polyethyleneimine, aminosugar polymers,
polyalkylamine substituted polyethers, and others. Any of these
polymers can be substituted with two or three reactive groups, as
is required to form a crosslinkable polymer. When there are many
substitutable linking groups, as with polysaccharides, only a few
of the substitutable groups (here, mostly hydroxyls) should be
substituted, and the derivatized polymer will have a somewhat
random substitution. In one embodiment, the hydrophilic polymer
will have only a few substitutable linking groups. Polyether
polyols grown on glycol or amine starters will typically have
reactive groups only at the end of the polyether chains, allowing
for detailed control of stoichiometry. Such polymers can be used.
In one embodiment, the base polymer is a polymer of ethylene
glycol, or a copolymer of ethylene glycol with one or more of
propylene glycol, butylene glycol, trimethylene glycol,
tetramethylene glycol, and isomers thereof, wherein the ratio of
ethylene glycol to the higher alkanediol in the polymer is
sufficient to provide substantial water solubility at room or body
temperature. Such polymer substrates can be synthesized by known
methods. More typically, preformed polyetherpolyols are purchased,
optionally in a prequalified medical grade, from any of numerous
catalogs or manufacturers.
[0086] In one embodiment, the prepolymer comprises a
polyisocyanate-capped polymeric polyol and a small amount of free
poly isocyanate. Such materials and their synthesis are described
in detail in U.S. Pat. No. 6,524,327, the disclosure of which is
incorporated herein by reference. The small amount of excess
polyisocyanate, typically of molecular weight less than about 1000
Daltons, maximizes the reactivity of the polyols, and by directly
and rapidly reacting with tissue, promotes bonding of the adhesive
to tissue. Typically the small isocyanate contains up to about 3%
of the number of active isocyanate groups on the polymer. The small
isocyanate may be all or part low molecular weight capped diol. The
capped polyol is multifunctional, and typically is trifunctional or
tetrafunctional, or a mixture of trifunctional and/or
tetrafunctional with difunctional. The polyol can be at least in
part a polyether polyol as described above.
[0087] The polyisocyanate is typically difunctional, but tri- or
tetrafunctional, or star, forms of isocyanate are known and can be
useful. Branching (tri- or tetra-functionality) may be provided by
a trifunctional polymer, or by providing a tri- or tetrafunctional
low molecular weight polyol, such as glycerol, erthyritol or
isomer, or trimethylolpropane (TMP). Fast reacting formulations use
an aromatic diisocyanate such as toluene diisocyanate. Slow
reacting formulations use an aliphatic diisocyanate such as
isophorone diisocyanate. Many additional diisocyanates are
potentially useful. Some are listed in U.S. Pat. No. 6,524,327, and
these and others are found in chemical catalogs, for example from
Aldrich Chemical. Alternatively, the polymerization time can be
adjusted by selecting appropriate molecular weight polyols. The
higher molecular weight polyols produce lower viscosity capped
reaction products and slower reacting solutions. However, at any
molecular weight of the polyol(s), the reaction rate is most
significantly determined by the reactivity of the functional end
group attached to the polyol.
[0088] In one embodiment, the prepolymer is liquid at room
temperature (ca. 20.degree. C.) and body temperature (ca.
37.degree. C.), for ease of administration and of mixture with
additives, etc. The prepolymer is stable in storage at room
temperature, when protected from moisture and light.
[0089] The prepolymer may be supplemented by the addition, during
manufacture or at the time of administration, of ancillary
materials. These may include reinforcing materials, drugs, volume
or osmotic pressure controlling materials, and visggggggualization
aids for optical, fluoroscopic ultrasound or other visualization of
fill locations. Reinforcing materials may include particulate
materials, fibers, flocks, meshes, and other conventionally used
reinforcers. These can be commercial materials approved for in vivo
medical use. Visualization materials include a wide variety of
materials known in the art, such as, among others, small particles
of metals or their oxides, salts or compounds for fluoroscopy,
gas-filled particles for ultrasound, and dyes or reflecting
particles for optical techniques.
[0090] Osmotic properties can be adjusted for immediate or
long-term effects. In one embodiment, the polyether polyol
isocyanates have little ionic charge either before or after
polymerization. However, in some situations, as described below, it
is desirable to have a controlled degree of swelling in water after
curing. This can be controlled in part by the ratio of ethylene
glycol to other polyols in the formulation. It can also be adjusted
by adding charged groups to the formulation. A simple method is to
add charged polymers or charged small molecules to the adhesive at
the time of application, for example dissolved in an aqueous
solution. Charged polymers, such as polyacrylic acids, will react
poorly with the isocyanates, but will tend to be trapped in the
polymerized matrix. They will tend to increase the swelling of the
cured material. In turn, this would allow the use of higher
proportions of non-ethylene glycol monomers in the polyols.
Alternatively, charge could be introduced by addition of hydroxy
carboxylic acids, such as lactic acid, or tartaric acid, during
synthesis or during administration. Added polymers could instead be
polyamines, but, to avoid rapid polymerization, should be tertiary
or quaternary amines or other amine types that will not react with
isocyanate. A method of increasing swelling is to incorporate
higher concentration of diffusible ions, such as soluble
salts--e.g., sodium chloride--into the adhesive at the time of
application. The salt will attract water into the adhesive
polymers; after polymerization, the salt will diffuse away and the
gel will remain expanded.
[0091] The prepolymer can be adjusted in several ways to optimize
its post-cure properties for the particular situation. In one
embodiment, a method of adjustment of properties is dilution of the
polymer with water, saline, or other aqueous solution. A typical
dilution would be in the range of 5% or less (volume of saline in
liquid polymer), for formation of dense, high-tensile, low-swelling
deposits, up to about 95% (19 vol. saline/vol. polymer) for readily
swelling, highly compliant deposits or bonds. In formulation,
allowance should be made for the amount of water that will flow
into the adhesive from the tissue during reaction. This will
usually be relatively small for bulk deposits, but is of more
concern for thin adhesive layers. In thin layers, fast-curing
compositions can be used, such as compositions with a higher
proportion of aromatic diisocyanates. In general, dilution will
reduce the tensile strength and the modulus. The amount of dilution
will tend to be different depending on whether the modulus or
tensile strength is to match that of the annulus (higher) or the
nucleus (lower).
[0092] Various non-reactive ingredients can be added to the polymer
solution either in the prepolymer or in the aqueous solution to
alter the hydrogel mechanical properties, e.g., tensile strength,
elasticity and bubble size. Inert particulate such as tantalum
powder will result in bubble nucleation and a finer bubble size,
increase the modulus of the hydrogel, and make the hydrogel radio
opaque. Emulsifiers can be added to increase mix homogeneity,
reduce bubble size, and provide a higher elongation at break. It is
possible to use the same diol used to construct the prepolymer as
an emulsifier. Alternatively, a higher or lower molecular weight
diol may be used. The ratio of EO/PO can be altered to increased
mixability, or pure forms of EO or PO can be used.
[0093] Other adjustable factors include the molecular weight of the
polymer, and its degree of branching; and its hydrophilicity, which
is a function of the particular polyol or polyols used in the
formulation. In addition, additives, as described above, can also
influence these properties.
Compositions
[0094] One embodiment provides a liquid preparation for use in
medicine, and its uses therein. The liquid preparation contains a
reactive polymer, which comprises a "base polymer" or "backbone
polymer", reactive groups on the backbone polymer, and a slight
excess of "free" (low molecular weight) polyreactive molecules. The
liquid composition is prepared by a method requiring no catalysts
and essentially no solvent. The reactive liquid polymer is
self-curing when applied to tissue, by absorption of water and
other reactive molecules from the tissue. The cured polymer is used
to seal tissue to tissue, or to devices; to apply a protective
coating to tissue; to form an implant within or upon tissue; to
deliver drugs. The cured polymer is optionally provided with
biodegradable groups, and has a controllable degree of swelling in
bodily fluids.
Backbone Polymers
[0095] The backbone polymer will comprise a polymeric segment, of
molecular weight about 500 D or more, e.g., about 1000 to about
10,000 D, or up to about 15 kD or 20 kD. The backbone polymer will
contain groups that can be easily derivatized ("capped") to form
the final reactive group. Such groups can be alcohols or amines, or
optionally sulfhydryls or phenolic groups. Examples include
polymers such as a polymeric polyol, or optionally a polymeric
polyamine or polyamine/polyol. In one embodiment, the polyols are
polyether polyols, such as polyalkylene oxides (PAOs), which may be
formed of one or more species of alkylene oxide. The PAO, when
comprising more than one species of alkylene oxide, may be a
random, block or graft polymer, or a polymer combining these modes,
or a mixture of PAO polymers with different properties. Exemplary
alkylene oxides are ethylene oxide and propylene oxide. Other
oxiranes may also be used, including butylene oxide. PAOs are
typically made by polymerization onto a starter molecule, such as a
low molecular weight alcohol or amine, e.g., a polyol. Starting
molecules with two, three, four or more derivatizable alcohols or
other derivatizable groups can be used. The multi-armed PAOs
obtained from such starters will typically have one arm for each
group on the starter. PAOs with two, three or four terminal groups
can be used. Mixtures of PAOs or other backbone polymers, having
variable numbers of arms and/or variation in other properties, are
contemplated.
[0096] Common polyols useful as starters are aliphatic or
substituted aliphatic molecules containing a minimum of 2 hydroxyl
or other groups per molecule. Since a liquid end product is
desired, the starters can be of low molecular weight containing
less than 8 hydroxyl or other groups. Suitable alcohols include,
for illustration and without limitation, adonitol, arabitol,
butanediol, 1,2,3-butanetriol, dipentaerythritol, dulcitol,
erythritol, ethylene glycol, propylene glycol, diethylene glycol,
glycerol, hexanediol, iditol, mannitol, pentaerythritol, sorbitol,
sucrose, triethanolamine, trimethylolethane, trimethylolpropane.
Small molecules of similar structures containing amines,
sulfhydryls and phenols, or other groups readily reactive with
isocyanates, are also useable.
[0097] The PAO, or other backbone polymer, may optionally
incorporate non-PAO groups in a random, block or graft manner. In
particular, non-PAO groups are optionally used to provide
biodegradability and/or absorbability to the final polymer. Groups
providing biodegradability are well known. They include hydroxy
carboxylic acids, aliphatic carbonates, 1,4-dioxane-2-one
(p-dioxanone), and anhydrides. The hydroxy carboxylic acids may be
present as the acid or as a lactone or cyclic dimmer, and include,
among others, lactide and lactic acid, glycolide and glycolic acid,
epsilon-caprolactone, gamma-butyrolactone, and delta-valerolactone.
Amino acids, nucleic acids, carbohydrates and oligomers thereof can
be used to provide biodegradability. Methods for making polymers
containing these groups are well known, and include, among others
reaction of lactone forms directly with hydroxyl groups (or amine
groups), condensation reactions such as esterification driven by
water removal, and reaction of activated forms, such as acyl
halides. The esterification process involves heating the acid under
reflux with the polyol until the acid and hydroxyl groups form the
desired ester links. The higher molecular weight acids are lower in
reactivity and may require a catalyst making them less
desirable.
[0098] The backbone polymers may also or in addition carry amino
groups, which can likewise be functionalized by polyisocyanates.
Thus, the diamine derivative of a polyethylene glycol could be
used. Low molecular weight segments of amine containing monomers
could be used, such as oligolysine, oligoethylene amine, or
oligochitosan. Low molecular weight linking agents, as described
below, could have hydroxyl functionality, amine functionality, or
both. Use of amines will impart charge to the polymerized matrix,
because the reaction product of an amine with an isocyanate is
generally a secondary or tertiary amine, which may be positively
charged in physiological solutions. Likewise, carboxyl, sulfate,
and phosphate groups, which are generally not reactive with
isocyanates, could introduce negative charge if desired. A
consideration in selecting base polymers, particularly other than
PAOs or others that react only at the ends, is that the process of
adding the reactive groups necessarily requires adding reactive
groups to every alcohol, amine, sulfhydryl, phenol, etc. found on
the base polymer. This can substantially change the properties,
particulaly the solubility properties, of the polymer after
activation.
Reactive Groups
[0099] The base or backbone polymer is then activated by capping
with low molecular weight (LMW) reactive groups. In one embodiment,
the polymer is capped with one or more LMW polyisocyanates
(LMW-PIC), which are small molecules, typically with molecular
weight below about 1000 D, more typically below about 500 D,
containing two or more reactive isocyanate groups attached to each
hydroxyl, amine, etc of the base molecule. After reaction of the
LMW-PIC with the backbone, each capable group of the backbone
polymer has been reacted with one of the isocyanate groups of the
LMW-PIC, leaving one or more reactive isocyanates bonded to the
backbone polymer via the PIC. The LMW-PIC are themselves formed by
conjugation of their alcohols, amines, etc. with suitable
precursors to form the isocyanate groups. Starting molecules may
include any of those mentioned above as starting molecules for
forming PAOs, and may also include derivatives of aromatic groups,
such as toluene, benzene, naphthalene, etc. Exemplary LMW-PIC for
activating the polymer are di-isocyanates, e.g., particular toluene
diisocyanate (TDI) and isophorone diisocyanate, both commercially
available. When a diisocyanate is reacted with a capable group on
the base polymer, one of the added isocyanates is used to bind the
diisocyanate molecule to the polymer, leaving the other isocyanate
group bound to the polymer and ready to react. As long as the
backbone polymers have on average more than two capable groups
(hydroxyl, amine, etc.), the resulting composition will be
crosslinkable.
[0100] A wide variety of isocyanates are potentially usable as
LMW-PICS. Suitable isocyanates include 9,10-anthracene
diisocyanate, 1,4-anthracenediisocyanate, benzidine diisocyanate,
4,4'-biphenylene diisocyanate, 4-bromo-1,3-phenylene diisocyanate,
4-chloro-1,3-phenylene diisocyanate, cumene-2,4-diisocyanate,
cyclohexylene-1,2-diisocyanate, cyclohexylene-1,4-diisocyanate,
1,4-cyclohexylene diisocyanate, 1,10-decamethylene diisocyanate,
3,3' dichloro-4,4'biphenylene diisocyanate,
4,4'diisocyanatodibenzyl, 2,4-diisocyanatostilbene,
2,6-diisocyanatobenzfuran, 2,4-dimethyl-1,3-phenylene diisocyanate,
5,6-dimethyl-1,3-phenylene diisocyanate, 4,6-dimethyl-1,3-phenylene
diisocyanate, 3,3'-dimethyl-4,4'diisocyanatodiphenylmethane,
2,6-dimethyl-4,4'-diisocyanatodiphenyl,
3,3'-dimethoxy-4,4'-diisocyanatodiphenyl,
2,4-diisocyantodiphenylether, 4,4'-diisocyantodiphenylether,
3,3'-diphenyl-4,4'-biphenylene diisocyanate, 4,4'-diphenylmethane
diisocyanate, 4-ethoxy-1,3-phenylene diisocyanate, ethylene
diisocyanate, ethylidene diisocyanate, 2,5-fluorenediisocyanate,
1,6-hexamethylene diisocyanate, isophorone diisocyanate, lysine
diisocyanate, 4-methoxy-1,3-phenylene diisocyanate, methylene
dicyclohexyl diisocyanate, m-phenylene diisocyanate,
1,5-naphthalene diisocyanate, 1,8-naphthalene diisocyanate,
polymeric 4,4'-diphenylmethane diisocyanate, p-phenylene
diisocyanate, 4,4',4''-triphenylmethane triisocyanate,
propylene-1,2-diisocyanate; p-tetramethyl xylene diisocyanate,
1,4-tetramethylene diisocyanate, toluene diisocyanate,
2,4,6-toluene triisocyanate, trifunctional trimer (isocyanurate) of
isophorone diisocyanate, trifunctional biuret of hexamethylene
diisocyanate, and trifunctional trimer (isocyanurate) of
hexamethylene diisocyanate.
[0101] In general, aliphatic isocyanates will have longer cure
times than aromatic isocyanates, and selection among the various
available materials will be guided in part by the desired curing
time in vivo. In addition, commercial availability in grades
suitable for medical use will also be considered, as will cost.
Toluene diisocyanate (TDI) and isophorone diisocyanate (IPDI) can
be used. The reactive chemical functionality of the liquid implants
can be isocyanate, but may alternatively or in addition be
isothiocyanate, to which all of the above considerations will
apply.
Physical Properties
[0102] The polymerizable materials are typically liquids at or near
body temperature (i.e., below about 45 deg. C.), and can be liquid
at room temperature, ca. 20-25 deg. C., or below. The liquids are
optionally carriers of solids. The solids may be biodegradable or
absorbable. The liquid polymerizable materials are characterized by
polymerizing upon contact with tissue, without requiring addition
of other materials, and without requiring pretreatment of the
tissue, other than removing any liquid present on the surface(s) to
be treated. A related property of the polymerizable materials is
that they are stable for at least 1 year when stored at room
temperature (ca. 20-25 degrees C.) in the absence of water vapor.
This is because the material has been designed so that both the
reaction that polymerizes the polymers, and the reactions that
optionally allow the polymer to degrade, both require water to
proceed.
[0103] In contrast to previous formulations, the polymeric
polyisocyanates contain a low residual level of low molecular
weight (LMW) polyisocyanates (PIC). For example, the final
concentration of LMW-PIC isocyanate groups in the formulation,
expressed as the equivalent molarity of isocyanate groups attached
to LMW compounds, is normally less than about 1 mM (i.e., 1 mEq),
e.g., less than about 0.5 mEq and or less than about 0.4 mEq. In
one embodiment, the level of LMW isocyanate groups is finite and
detectable, for example greater than about 0.05 mEq, or greater
than about 0.1 mEq. In one embodiment, a low but finite level of
LMW-PIC molecules tends to promote adherence between the applied
polymer formulation and the tissue being treated. However,
decreased levels of LMW-PIC may tend to decrease tissue irritation
during application and cure of the liquid polymer preparation. In
one embodiment, the range of about 1 mEq to about 0.05 mEq is
approximately optimal. In situations requiring tissue adherence in
the presence of biological fluid, or in adherence to difficult
tissues, greater levels of LMW-PIC isocyanate groups may be
used.
Swellability
[0104] The active prepolymers may form intertwined polymer chains
after reaction that may change their intertwined geometry under
action by fluids within the body. In particular, one or more
components may cause the formed polymeric material, whether as
coating, adhesive, or solid, to swell. Swelling may have several
consequences, and can be controlled. In one mode, swelling can lead
to subsequent break-up (physical disintegration) of an implant or
other final form, rendering the entire implant absorbable. Or, one
or more of the components may dissolve in the body rendering the
remaining components absorbable. (Dissolvable materials could be
added as solids, or as nonreactive polymers diluting the reactive
components.) Or, one or more components may be biodegradable
rendering the remaining components absorbable. For example, liquids
containing a polyethylene/polypropylene random coblock polyol
capped with polyisocyanate are capable of forming elastic gels with
water content as high as 90%. When these polyethylene/polypropylene
polyols are esterified with a carboxylic acid and reacted with a
trifunctional molecule such as trimethylolpropane, or alternatively
when the trifunctional molecule is esterified and reacted with
diols of polyethylene/polypropylene, useful activated polyols are
formed. These polyols, when end capped with a polyisocyanate are
capable of forming gels or solids in a living organism that
decrease in volume and strength over time.
[0105] However, the ratio of propylene oxide to ethylene oxide can
be varied, and the two monomers can be polymerized into block
copolymers, random copolymers, or graft copolymers. These types are
commercially available. While the ethylene oxide groups tend to
absorb water, and so to swell the crosslinked material formed in
the body, the propylene oxide groups are less hydrophilic, and tend
to prevent swelling in aqueous fluids. Thus, the degree of swelling
of the polymerized material in water can be controlled by the
design of the reactive polymers. Another route of swelling control
is by incorporation of non-PAO groups, such as aliphatic or
aromatic esters, into the polymer (as, or in addition to, esters
used to confer degradability.)
[0106] The prepolymer can be formed by capping the polyols (as
backbone polymer) with polyisocyanate, preferably a diisocyanate.
However, suitable isocyanates have the form R(NCO).sub.x, where x
is 2 to 4 and R is an organic group. Another approach to creating
an in situ polymerizing liquid that biodegrades in the body is to
graft the polyol onto a biodegradable center. Suitable polymers for
inclusion as center molecules are described in U.S. Pat. No.
4,838,267. They include alkylene oxalates, dioxepanone,
epsilon-caprolactone, glycolide, glycolic acid, lactide, lactic
acid, p-dioxanone, trimethylene carbonate, trimethylene dimethylene
carbonate and combinations of these.
[0107] The center molecule may be a chain, a branched structure, or
a star structure. Suitable star structures are described in U.S.
Pat. No. 5,578,662. Isocyanate capped alkylene oxide can be reacted
with these molecules to form one or more extended chains. The ends
of these chains can therefore participate in crosslinking with
other centers or bond to tissue.
[0108] Center molecules such as those listed above will form rigid
solids upon polymerization. Therefore, it is generally more useful
to ensure at least 80% alkylene oxide is in the final polymerized
structure. Furthermore, the alkylene oxide should be comprised of
at least 70% ethylene oxide.
[0109] These criteria ensure that the polymerized product is
flexible enough to prevent stress localization and associated
tissue bond failure. Furthermore, star molecules in general will
not be preferred since they contain numerous branches. More
numerous branching of the center molecule is associated with higher
liquid viscosity. Furthermore, highly branched prepolymers will
form polymerized products more slowly and with higher modulus. For
example, U.S. Pat. No. 5,578,662 quotes a cross-linking reaction
time of 5 minutes to 72 hours. Both of these characteristics are
undesirable when the prepolymer is intended as a surgical adhesive
or sealant.
Absorbable Compositions and Particulate Additives
[0110] Absorbable prepolymer systems can be composed of
discontinuous (solid) and continuous (liquid) parts. The solid part
may be absorbable or may not be absorbable. One of the simplest
forms of an absorbable implant is one that mechanically breaks into
small pieces without appreciable chemical modification. Fracture of
an implant can be seeded or propagated by the placement of hard
centers in the polymer during formation.
[0111] Mixing the liquid polymer with calcium triphosphate
particles will after exposure to fluids or tissue polymerize into
an elastic solid containing an inelastic particulate. Movement of
the surrounding tissue will deform the elastic implant. Since the
particulate cannot deform, stress will localize around these
centers and cracks will begin to propagate from these centers. In
this way, the rate of disintegration and size of the disintegrated
parts can be controlled by varying the particulate size, the
modulus of the formed continuous polymer, and the density
distribution of the particulate.
[0112] Non-absorbable solids are well known and include, as
examples and without limitation, calcium triphosphate, calcium
hydroxylapatite, carbon, silicone, Teflon, polyurethane, acrylic
and mixture of these. Absorbable solids are well known and include,
as examples and without limitation, glycolic acid, glycolide,
lactic acid, lactide, dioxanone, epsilon-caprolactone, trimethylene
carbonate, hydroxybutyrate, hydroxyvalerate, polyanhydrides, and
mixtures of these.
[0113] Other absorbable prepolymer liquids can be composed of two
continuous mechanically mixed parts. For example, one part may be
absorbable and the other not. Consequently, the absorption of one
part results in the mechanical disintegration or weakening of the
implant. Absorbable components may include liquid forms of
cellulose ether, collagen, hyaluronic acid, polyglycolic acid,
glycolide and others known in the art.
Exemplary Polymeric Structures
[0114] There are several ways in which the above-recited steps can
be used to obtain a liquid reactive polymer system. In a simple
system, a polymeric polyol with a number of end groups on average
greater than two is treated with a slight excess of a LMW-PIC, such
as toluene diisocyanate. The reaction product is formed under
nitrogen with mild heating, preferably by the addition of the
LMW-PIC to the polymer. The product is then packaged under
nitrogen, typically with no intermediate purification.
[0115] In one embodiment, the biodegradable polyol composition
includes a trifunctional hydroxy acid ester (e.g., several lactide
groups successively esterified onto a trifunctional starting
material, such as trimethylolpropane, or glycerol). This is then
mixed with a linear activated polyoxyethylene glycol system, in
which the PEG is first capped with a slight excess of a LMW-PIC,
such as toluene diisocyanate. Then the activated polymer is formed
by mixing together the activated polyoxyethylene glycol and the
lactate-triol. Each lactate triol binds three of the activated PEG
molecules, yielding a prepolymer with three active isocyanates at
the end of the PEG segments, and with the PEG segments bonded
together through degradable lactate groups. In the formed implant,
the lactate ester bonds gradually degrade in the presence of water,
leaving essentially linear PEG chains that are free to dissolve or
degrade. Interestingly, in this system, increasing the percentage
of degradable crosslinker increases rigidity, swell and solvation
resistance in the formed polymer.
[0116] Other polyol systems include hydroxy acid esterified linear
polyether and polyester polyols optionally blended with a low
molecular weight diol. Similarly, polyester and polyether triols
esterified with hydroxy acid are useful. Other polyol systems
include the use of triol forming components such as
trimethylolpropane to form polyols having three arms of linear
polyether chains.
Delivery Devices and Methods
[0117] In one embodiment, the delivery device possesses a blocking
component for preventing liquid implant from escaping from the
nuclear region of a vertebral disc and preferably prevents liquid
implant from coating a portion or all of the otomy made to access
the nuclear region. The delivery device can be used in combination
with a hollow fixed instrument that guides the operational
instruments to a selected location in or adjacent to an annular
fissure, or other site in the spine in need of repair. The
described procedures address minimally invasive use, but can be
used in open surgeries. A detailed description of an entire
apparatus or series of apparatuses for each instance should not be
necessary to enable those skilled in the art to make a device for
the treatment methods disclosed herein, since some of the
individual components are conventional. The methods can be
accomplished with endoscopic instruments, automated surgical
systems, or any system with structural parts that function as set
forth herein.
[0118] Delivery Device
[0119] In one embodiment, a device for delivering the liquid
nucleus implant to the site is an injector. An example of a
suitable delivery device 610 is shown in a schematic way (not to
scale) in FIG. 2. The device illustrated is constructed in the same
general manner as an intravascular catheter, although it may be
considerably shorter in overall length. FIG. 2 shows the handle
611, which holds a catheter-like compound tube 614, which in this
embodiment encloses an injection lumen 620 terminating at distal
tip 616, and an inflation lumen 617 terminating in encircling
balloon 618. The injection lumen connects to a port 607 near to or
within the handle 611 for connecting a polymer source 615, which as
illustrated can be a syringe, but could instead be a pump. The
balloon 618 and tube 614, when being introduced into the patient,
passes through the lumen 613 of an introducer 612. The balloon 618
can be arranged in a collapsed state to facilitate the introduction
into lumen 613. The introducer 612 can be as simple as a hollow
tube. An introducer can comprise a hollow tube device 612 or a
combination of a simple exterior cannula 612 that fits around a
tapered obturator 619. A hollow tube is placed through skin and
tissue to provide access into the annulus fibrosus. More complex
variations exist in percutaneous instruments designed for other
parts of the body and can be applied to design of instruments
intended for disc repairs. The distal end 621 of the introducer
will typically be inserted into tissue until it lies at a location
into which the prosthetic is to be formed. A suitable outer
diameter for the tube portion 612 is in the range of 5 to 12 mm. In
the illustrated embodiment, the diameter of the collapsed balloon
618 is less than the inner diameter of the tube portion 613.
[0120] In one embodiment, the blocking component is tapered
distally such that a wider part of the blocking component projects
into the nuclear space with a diameter greater than the diameter of
the opening in the annulus.
[0121] In one embodiment, the pressure and/or delivery volume of
the liquid implant is controlled. Control of injection can be
provided by placing a pressure transducer in a suitable location.
With pumps, a pressure sensor can be placed on or in the tube, or
at the tip. With a syringe, a pressure-sensitive pad can be placed
on the proximal end of the plunger, as well as on the tube or in
the tip. A pressure sensor can be coupled to a display, or a gauge,
and/or can be coupled to a microprocessor for automatic or
semiautomatic control. In the later case, the variance of pressure
with time can be used to help decide when injection has been
sufficient.
[0122] The delivery device described above uses a balloon to be
inflated in a cannula 612 or a surgically formed otomy to provide a
barrier to implant loss during injection of the liquid nucleus
implant into the disc nuclear region. The balloon is inflated by
attaching an air source 608 to a port 609 located on the
catheter-like compound tube 614. Alternatively, the blocking means
may be any mechanically distensible interface that forms a seal
between it and a cannula or surgically formed passageway. An
example of an alternative blocking means is illustrated in FIG. 3.
In this instance, the blocking means 622 replaces the balloon 618
of FIG. 2. The inflation lumen 617 of FIG. 2 is replaced by wire
lumen 623. Inside wire lumen 623 is wire 624 attached to actuation
hub 625. When actuation hub 625 is turn axially the wire 624 is
drawn into the hub. The detailed mechanics for achieving this wire
retraction are known in the art. Blocking means 622 is comprised of
an elastic material with outer diameter less than the inner
diameter 613 of the cannula 612 of FIG. 2. Blocking means 622
possesses a concentric axially aligned hole 626 of inner diameter
equal to the outer diameter of catheter 614. The blocking means 622
resides on the delivery catheter 614 as shown in FIG. 3. The
blocking means 622 is held in place by stationary hub 627 and
actuation hub 628. A slot 629 in tube 614 allows wire 624 to pull
actuation hub 628 toward actuation hub 625. The actuation hub 625
is rotatable on catheter 614 such that when tension is placed on
wire 624 the blocking means 622 compresses and increases in outer
diameter.
[0123] In one embodiment, the blocking means 622 prevents liquid
implant from leaving the injection site. The proximal end of the
blocking component can be flush with the inner layers of the
annulus. To accomplish this the catheter 614 may be marked for
imagining during fluoroscopy to indicate the proximal and distal
ends of the blocking means. In another embodiment, the blocking
component has a tissue engaging surface to prevent slippage.
[0124] In the use of some liquid nucleus implants, primarily those
that are not foaming, in one embodiment a third lumen is provided
in the delivery catheter to allow for the passage of displaced air
as the nuclear space is filled with implant.
[0125] In the application of multiple injections the inflation
lumen 617 may be filled with a disposable lumen that can be removed
after a first application of liquid implant without repositioning
the blocking means and inflation lumen 617. In this case, the
disposable lumen can be extended beyond the catheter tip 616 to
provide a first small application of liquid implant to coat the
inner surface of the annulus, such a disposable lumen can be
flexible to contour to and spread evenly liquid implant upon the
inner surface of the annulus.
Methods
[0126] There are two common approaches to a vertebral disc. The
posterior approach is generally an open procedure, where access to
the disc does not require a cannula or tube through which surgical
procedures are performed. The contra-lateral approach is generally
a percutaneous approach where access to the disc requires a cannula
or tube through which surgical procedures are performed. The
methods associated with each of these approaches are different, but
both approaches use the delivery catheters disclosed herein.
[0127] The proximal approach is used when the disc annulus has
large defects or the disc is impinging on the spinal cord. In this
case the outer dimension of the balloon when inflated should exceed
the expected inner diameter of the otomy to be made in the disc
annulus so that a sealed interface can be formed between balloon
and annulus. The diameter of the balloon will typically be between
5 and 12 mm. The balloon may have a rigid maximum diameter when
inflated or may be elastic. The balloon shape may be dumbbell in
axial cross section to help localize it in the otomy of the
annulus.
[0128] The procedural steps are as follows: 1) surgically expose
the portion of the disc annulus to be treated, 2) create an otomy
in the annulus sufficient to allow for removal of part or all of
the disc nucleus to prevent further loss of disc nucleus in the
case of an annulus defect and to reduce pressure on the annulus in
the case of a herniated disc, 3) insert the delivery catheter so
that the blocking means is flush with the excavated inner surface
of the nucleus/annulus interface, 4) actuate the blocking means so
that the delivery catheter is localized in the annulus, 5) begin
injecting nucleus implant to a desired volume or pressure, 6) hold
assembly in place until the implant has cured, and 7) deactuate the
blocking means and remove the delivery catheter. Generally the
otomy will be left open so that the annulus may heal and seal the
implant within the disc.
[0129] The contra-lateral approach is generally a percutaneous
approach. It is used when the annulus has a normal shape and
generally when a nuclectomy is performed. In the diagnostic phase
leading up to the decision to place a nucleus implant first the
integrity of the annulus is assessed. This is done by placing an
anchoring guidewire through the annulus wall into the nucleus of
the disc so that various diagnostic and treatment procedures may be
performed. The guidewire may be employed in directing an injection
needle for delivering an indicator solution to the nucleus to
assess leakage outside the annulus from the nucleus. Alternatively
the guidewire may be employed in directing means for creating an
otomy in the annulus and subsequent removal of nucleus.
[0130] In the contra-lateral procedure described here, the
guidewire is further employed to deliver a cannula. In FIG. 4A,
cranial view, a guidewire 710 is position in the nuclear area 711
of a disc 712. The nuclear area may include part of the disc
annulus 713. FIG. 4B shows a cannula 714 fitted with an obturator
715 with a central axial bore 716. The distal end of the guidewire
710 is placed into the bore 716 and the cannula/obturator assembly
is advanced along the guidewire 710. The proximal end of the
obturator 715 is tapered such that it easily enters the disc
annulus 713 with a minimal disruption of tissue. The annulus 713
may be prepared for this operation by placing a slit cut in the
annulus centered on the guidewire. Under fluoroscopy the cannula
714 is advanced into the annulus until its proximal end is flush
with the outer layers of the disc nucleus 711. The outer diameter
of the cannula 714 is preferably 5 mm. The obturator 715 is removed
and a 4.5 mm shaver blade 719 is introduced into the lumen 718 of
the cannula 714 as pictured in FIG. 4C. The nucleus is then removed
to a therapeutic degree and the evacuated space washed of loose
debris. The delivery catheter 614 is introduced into the lumen 718
of the cannula 714 as shown in FIG. 4D. The proximal end of the
catheter is positioned flush with the periphery of the evacuated
space of the nucleus and the blocking means 720 actuated. If the
blocking means is a balloon as shown in FIG. 4D, then a stop-cock
721 is attached to inflation port 722 and to the open end of the
stopcock is connected to a syringe 723 loaded with either air or
liquid. The balloon is inflated by positioning the valve of the
stop-cock so that pressure applied to the syringe 723 delivers
fluid volume to the balloon. When the proper volume of fluid is
delivered or an appropriate pressure achieved the valve of the
stop-cock is closed fixing the balloon 720 in a deployed position.
The syringe 724 containing the single-part liquid implant is
attached to the delivery catheter via luer connection 725. The
delivery catheter is primed by depressing the plunger of syringe
724 to a specified volume position 726 indicated on the syringe.
The medical professional may optionally release the catheter
balloon and subsequently re-inflate to allow for the volume
displaced by priming the catheter to be released from the nucleus
of the disc 711. Then liquid implant from syringe 724 is injected
into the nuclear space 711 until a specified volume or pressure is
achieved. The dispensing syringe 724 may optionally have a pressure
sensing device 727. After a specified period of time the balloon
720 is deflated and the delivery catheter 614 removed. A plurality
of delivery catheters may be deployed in this manner to fills
regions left unfilled, or to build pressure in the nuclear space
711 by injecting liquid implant inside of an already formed implant
volume. This may optionally be performed by a piercing needle
placed in the center of a formed implant, and additional liquid
implant dispensed into this center. The liquid implant delivered in
this manner would not require a blocking mechanism since the formed
implant provides the blocking.
[0131] Optionally, the cannula 714 may be moved distally in the
annulus as depicted in FIG. 5, such that the delivery catheter 614
may be deployed in contact with the annulus tissue 713 and inflated
there to provide blockage.
* * * * *