U.S. patent application number 13/113717 was filed with the patent office on 2011-09-15 for universal introducer.
This patent application is currently assigned to NEOMEND, INC.. Invention is credited to Stuart D. EDWARDS, Theodore Kucklick, Ronald LAX, Theodore L. PARKER, Thomas C. Wehman.
Application Number | 20110224721 13/113717 |
Document ID | / |
Family ID | 32232872 |
Filed Date | 2011-09-15 |
United States Patent
Application |
20110224721 |
Kind Code |
A1 |
EDWARDS; Stuart D. ; et
al. |
September 15, 2011 |
Universal Introducer
Abstract
A device for introducing a catheter into a vessel through a
puncture in a vessel and for sealing the puncture. The device
includes an elongated body having a proximal end and a distal end
sized to be positioned within a tissue site which includes the
puncture. The elongated body includes a utility lumen sized to
allow a catheter to be delivered through the utility lumen. The
utility lumen is positioned within the elongated body so
positioning the elongated body within the tissue site allows a
catheter delivered through the utility lumen to enter the vessel.
The elongated body also includes a closure lumen having an entrance
port. A closure composition can be delivered through the entrance
port into the closure lumen. The closure lumen also includes an
exit port adjacent the distal end of the elongated body. The
closure composition delivered into the closure lumen can be
delivered through the exit port to the tissue site adjacent the
puncture.
Inventors: |
EDWARDS; Stuart D.; (Portola
Valley, CA) ; LAX; Ronald; (Palm City, FL) ;
PARKER; Theodore L.; (Danville, CA) ; Wehman; Thomas
C.; (Cupertino, CA) ; Kucklick; Theodore; (Los
Gatos, CA) |
Assignee: |
NEOMEND, INC.
Irvine
CA
|
Family ID: |
32232872 |
Appl. No.: |
13/113717 |
Filed: |
May 23, 2011 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11491763 |
Jul 24, 2006 |
|
|
|
13113717 |
|
|
|
|
10795955 |
Mar 8, 2004 |
7081125 |
|
|
11491763 |
|
|
|
|
09037659 |
Mar 10, 1998 |
6733515 |
|
|
10795955 |
|
|
|
|
08963408 |
Nov 3, 1997 |
6033401 |
|
|
09037659 |
|
|
|
|
60036299 |
Mar 12, 1997 |
|
|
|
Current U.S.
Class: |
606/213 |
Current CPC
Class: |
A61B 18/1482 20130101;
A61B 2017/00495 20130101; A61B 17/00491 20130101; A61B 17/3415
20130101; A61B 2017/0065 20130101; A61B 2017/00084 20130101; A61B
18/14 20130101; A61B 2017/005 20130101; A61B 17/0057 20130101; A61B
2017/3441 20130101; A61M 25/0662 20130101; A61B 2090/064 20160201;
A61B 2018/0063 20130101; A61B 2017/3492 20130101; A61B 2017/00672
20130101; A61B 2017/00637 20130101; A61B 18/1487 20130101 |
Class at
Publication: |
606/213 |
International
Class: |
A61B 17/03 20060101
A61B017/03 |
Claims
1.-5. (canceled)
6. A device for introducing a catheter through a puncture within a
vessel for sealing tissues adjacent the puncture, comprising: an
elongated body having a proximal end and a distal end sized to be
positioned within a tissue site which includes the puncture; a
membrane included at an outer surface of the elongated body and
sufficiently porous to allow a closure composition to pass through
the membrane; and a closure lumen within the elongated body, the
closure lumen having an entrance through which a closure
composition can be delivered into the closure lumen and at least
one exit port positioned on the elongated body so the closure
composition is delivered into the closure lumen can be delivered
through at least one exit port to the membrane.
7. The device of claim 6, further comprising at least one
temperature sensor positioned at the distal end of the elongated
body for detecting a temperature of closure composition adjacent
the elongated body distal end.
8. The device of claim 6, further comprising at least one
temperature sensor positioned at a side of the elongated body for
detecting a temperature of closure composition adjacent the side of
the elongated body.
9. The device of claim 6, further comprising at least one electrode
positioned at the distal end of the elongated body.
10. The device of claim 9, wherein the at least one electrode is an
RF electrode.
11. The device of claim 6, further comprising at least one
electrode included at a side of the elongated body so as to be to
be within the tissue site when the elongated body is positioned
adjacent a vessel within the tissue site.
12. The device of claim 11, wherein the at least one electrode is
an RF electrode.
13. The device of claim 6, wherein the utility lumen includes at
least one backflow valve.
14. The device of claim 6, further comprising a blood pressure
sensor positioned adjacent the distal end of the elongated
body.
15. The device of claim 6, further comprising a blood spurt
lumen.
16. The device of claim 6, further comprising a pigtail within the
utility lumen.
17. The device of claim 16, wherein the pigtail is movable within
the utility lumen.
18. The device of claim 6, further comprising a baseplate for
holding the elongated body in place within the tissue site.
19. The device of claim 18, wherein the elongated body is axially
movable relative to the baseplate.
20. The device of claim 6, wherein the distal end of the elongated
body is saddle shaped.
21. The device of claim 6, further comprising: a second closure
lumen within the elongated body having an entrance port adjacent to
the proximal end of the elongated body through which a closure
composition can be delivered into the second closure lumen; and an
exit port adjacent the distal end of the elongated body through
which the closure composition can be delivered adjacent the
puncture.
Description
RELATED APPLICATIONS
[0001] This application is a divisional of co-pending U.S.
application Ser. No. 10/795,955, filed Mar. 8, 2004, which is a
divisional of U.S. application Ser. No. 09/037,659, filed Mar. 10,
1998, now U.S. Pat. No. 6,733,515, which claims the benefit of
Provisional U.S. Application Ser. No. 60/036,299, filed Mar. 12,
1997, entitled "Universal Introducer", and which is a
continuation-in-part of U.S. application Ser. No. 08/963,408, filed
Nov. 3, 1997, entitled "Vascular Sealing Device with Microwave
Antenna," now U.S. Pat. No. 6,033,401, all of which are
incorporated herein by reference.
FIELD OF THE INVENTION
[0002] This invention relates to a wound closure device, and more
particularly to a device for delivering a catheter to a vessel
within a tissue site and closing a wound caused by the catheter
delivery.
BACKGROUND OF THE INVENTION
[0003] A wide variety of surgical procedures are performed by
introducing a catheter into a vessel. After the surgical procedure
is completed, closure of the vessel at the site where the catheter
was introduced is needed. Vessel punctures formed in the process of
performing a catheter based surgical procedure are commonly 1.5 mm
to 7.0 mm in diameter and can be larger. Closure of these punctures
is frequently complicated by anticoagulation medicine given to the
patient which interferes with the body's natural clotting
abilities.
[0004] Closure of a vessel puncture has traditionally been
performed by applying pressure to the vessel adjacent the puncture
site. This procedure requires the continuous attention of at least
one medical staff member to apply pressure to the vessel puncture
site and can take as long as 30 minutes.
[0005] Devices have been developed for effecting the closure of
vessel punctures through the application of energy. See U.S. Pat.
Nos. 5,626,601; 5,507,744; 5,415,657; and 5,002,051. Devices have
also been developed for effecting the closure of vessel punctures
through the delivery of a mechanical mechanism which mechanically
seals the puncture. See U.S. Pat. Nos. 5,441,520; 5,441,517;
5,306,254; 5,282,827; and 5,222,974. Devices have also been
developed for effecting the closure of vessel punctures through the
delivery of a composition to block the vessel puncture. See U.S.
Pat. Nos. 5,601,602; 5,591,205; 5,441,517; 5,292,332; 5,275,616;
5,192,300; and 5,156,613. Despite the various devices that have
been developed for closing vessel punctures, a need still exists
for a single device which can be used for both introducing a
catheter into a vessel and for closing the resulting wound.
SUMMARY OF THE INVENTION
[0006] The invention relates to a device for introducing a catheter
through a puncture in a vessel and for sealing the puncture. The
device includes an elongated body having a proximal end and a
distal end sized to be positioned within a tissue site which
includes the puncture. The elongated body includes a utility lumen
sized to allow delivery of a catheter through the utility lumen.
The utility lumen is positioned within the elongated body so
positioning the elongated body within the tissue site allows a
catheter delivered through the utility lumen to enter the vessel.
The elongated body also includes a closure lumen having an entrance
port. A closure composition can be delivered through the entrance
port into the closure lumen. The closure lumen also includes an
exit port adjacent the distal end of the elongated body. The
closure composition delivered into the closure lumen can be
delivered through the exit port to the tissue site adjacent the
puncture.
[0007] The invention also relates to a device for introducing a
catheter through a puncture in a vessel and for sealing tissues
adjacent the puncture. The device includes an elongated body having
a proximal end and a distal end sized to be positioned within a
tissue site which includes the puncture. A membrane is included at
an outer surface of the elongated body. The membrane is positioned
on the elongated body so the membrane is adjacent a portion of the
tissue adjacent the puncture when the elongated body is positioned
within the tissue site. The membrane is sufficiently porous to
allow a closure composition to pass through the membrane. The
closure composition can be delivered into the closure lumen through
an entrance port. The closure composition can be delivered from the
closure lumen to the membrane through at least one exit port.
[0008] The invention also relates to a system for introducing a
catheter through a puncture within a vessel and sealing the
puncture. The device includes an elongated body having a proximal
end and a distal end sized to be positioned within a tissue site
which includes the puncture. The elongated body includes a utility
lumen within the elongated body. The utility lumen is sized to
allow delivery of a catheter through the utility lumen. The utility
lumen is positioned within the elongated body so when the elongated
body is positioned within the tissue site a catheter delivered
through the utility lumen can enter the vessel. A first closure
lumen is coupled with the utility lumen. A closure composition can
be delivered into the first closure lumen through an entrance port.
The closure composition can be delivered from the first closure
lumen to the utility lumen through an exit port. The system also
includes an obturator with a structure which allows the obturator
to be at least partially positioned in the utility lumen.
Positioning the obturator within the utility lumen causes a second
closure lumen to be formed. The second closure lumen is at least
partially defined by the obturator and the utility lumen. The
second closure lumen receives the closure composition delivered
from the first closure lumen to the utility lumen and is configured
to deliver the received closure compound to the tissue site.
[0009] The invention also relates to a system for introducing a
catheter through a puncture within a vessel and for sealing the
puncture. The system includes an elongated body having a proximal
end and a distal end sized to be positioned at a tissue site which
includes the puncture. The elongated body includes a utility, lumen
and a closure lumen through which a closure composition can be
delivered to tissue at the tissue site. The system also includes a
catheter guide obturator configured to be positioned within the
utility lumen of the elongated body. The catheter guide obturator
includes a utility lumen. The utility lumen is sized to permit
delivery of a catheter through the utility lumen. The utility lumen
has a geometry which permits a catheter delivered through the
utility lumen to enter the vessel when the catheter guide obturator
is positioned within the utility lumen of the elongated body which
is positioned at the tissue site.
[0010] The invention also relates to a system for introducing a
catheter through a puncture within a vessel and for sealing the
puncture. The system includes an elongated body having a proximal
end and a distal end sized to be positioned at a tissue site which
includes the puncture. The elongated body includes a utility lumen
and a closure lumen through which a closure composition can be
delivered to tissue at the tissue site. The invention also includes
a trocar configured to be positioned within the utility lumen, the
trocar includes a sharpened tip configured to puncture the tissue
making up the tissue site.
[0011] The invention also relates to a system for introducing a
catheter through a puncture within a vessel and for sealing the
puncture. The system includes an elongated body having a proximal
end and a distal end sized to be positioned at a tissue site which
includes the puncture. The elongated body includes a utility lumen
and a closure lumen through which a closure composition can be
delivered to tissue at the tissue site. The system also includes a
sealing mold configured to be positioned within the utility lumen.
The sealing mold has a structure which causes a cavity to be formed
at the distal end of the elongated body when the sealing mold is
positioned within the utility lumen. Closure composition delivered
through the closure lumen is delivered into the cavity.
[0012] The invention also relates to a method for introducing a
catheter through a puncture within a vessel and for sealing the
puncture. The method is initiated by providing a device with an
elongated body configured to be positioned within a tissue site.
The body includes a utility lumen sized to accommodate a catheter
and at least one closure lumen. A closure composition can be
delivered through the closure lumen. The method concludes by
positioning the elongated body within the tissue site; delivering a
catheter through the utility lumen into the vessel; performing a
treatment with the catheter; withdrawing the catheter through the
utility lumen; and delivering a closure composition through the
closure lumen to the puncture.
BRIEF DESCRIPTION OF THE FIGURES
[0013] FIG. 1A is a cross section of a closure device including a
closure lumen and a utility lumen.
[0014] FIG. 1B is a sideview of a closure device according to the
present invention.
[0015] FIG. 2 is a cross section of a closure device including
sensors and energy delivery devices.
[0016] FIG. 3 is a cross section of a closure device positioned in
a tissue site. The closure device includes a catheter delivered
through a utility lumen to a vessel in the tissue site.
[0017] FIG. 4 is a cross section of the closure device of FIG. 3
after the catheter has been removed from the utility lumen.
[0018] FIG. 5 illustrates the closure of the hole in the vessel
achieved by delivering a closure composition adjacent the distal
end in combination with the delivery of energy.
[0019] FIG. 6 illustrates the closure device and the vessel after
the partial removal of the closure device from the tissue site.
[0020] FIG. 7A is a sideview of a closure device with a saddle
shaped distal end.
[0021] FIG. 7B is a sideview of a closure device with a saddle
shaped distal end.
[0022] FIG. 7C is a perspective view of the closure device shown in
FIG. 7B, illustrating the distal tip in a retracted position.
[0023] FIG. 7D is a perspective view of the closure device shown in
FIG. 7B, illustrating the distal tip in a deployed position.
[0024] FIG. 8A is a sideview of a pigtail according to the present
invention.
[0025] FIG. 8B is a topview of a pigtail according to the present
invention.
[0026] FIG. 9A illustrates a cross section of a closure device
including a utility lumen with threads on an inside of the utility
lumen. A pigtail within the utility lumen includes a head resting
on the threads.
[0027] FIG. 9B illustrates a cross section of a closure device with
a screwdriver engaging the head section of a pigtail.
[0028] FIG. 9C is a cross section of a pigtail installed within a
closure device.
[0029] FIG. 10 is a sideview of a closure device with energy and
closure composition delivered to tissue adjacent the sides of the
closure device as the closure device is retracted from the
tissue.
[0030] FIG. 11 is a sideview of a tissue site after partial
retraction of the closure device.
[0031] FIG. 12A is a cross section of a closure device with a solid
or semisolid closure composition present at the distal end of the
closure device to facilitate the closure of the vessel.
[0032] FIG. 12B illustrates the closure device of FIG. 12A with the
pigtail retracted.
[0033] FIG. 13 is a cross section of a closure device with a trocar
in place within a utility lumen.
[0034] FIG. 14 is a cross section of the closure device of FIG. 13
after the trocar has penetrated the vessel.
[0035] FIG. 15 is a cross section of a closure device with a
catheter guide obturator in place within a utility lumen.
[0036] FIG. 16 is a cross section of a closure device with a
sealing mold and curing pin in place within a utility lumen.
[0037] FIG. 17 is a cross section of a distal portion of a closure
device.
[0038] FIG. 18 is a sideview of a flapper valve.
[0039] FIG. 19 is a sideview of a closure device including an
automatic retraction device.
[0040] FIG. 20 illustrates a closure device held within a tissue
site by sutures.
[0041] FIG. 21 illustrates a closure device in place within a
tissue site. The closure device includes a catheter delivered
through a utility lumen to a vessel in the tissue site.
[0042] FIG. 22 illustrates the closure device of FIG. 21 being
withdrawn from tissue.
[0043] FIG. 23A is a longitudinal cross section of a distal end of
a closure device.
[0044] FIG. 23B is a cross section of a proximal end of a closure
device for use with an obturator.
[0045] FIG. 23C is a vertical cross-section of a distal end of a
closure device.
[0046] FIG. 24A is a cross section of an obturator for use with the
closure device illustrated in FIG. 23A.
[0047] FIG. 24B is a side view of an obturator for use with the
embodiment illustrated in FIG. 23A.
[0048] FIG. 25A is a cross section of the obturator of FIG. 24A
installed in the utility lumen of the closure device of FIG.
23A.
[0049] FIG. 25B is a cross section of the obturator of FIG. 24A
installed within the closure device of FIG. 23A and withdrawn
though the central lumen until a catch on the obturator engages a
catch channel on the closure device.
[0050] FIG. 26 is a sideview of a hollow needle penetrating a
vessel.
[0051] FIG. 27A is sideview of a guidewire threaded through the
hollow needle of FIG. 26.
[0052] FIG. 27B illustrates the needle withdrawn from the tissue
site along, the guidewire.
[0053] FIG. 28 is a cross section of a closure device. A hollow
dilator is installed within the utility lumen of the closure
device.
[0054] FIG. 29 is a cross section of the dilator and closure device
of FIG. 28 threaded over a guidewire and advanced through a tissue
site to puncture a vessel.
[0055] FIG. 30 is a cross section of the closure device of FIG. 29
withdrawn from the puncture so the distal end is adjacent the
puncture outside the vessel.
[0056] FIG. 31 is a cross section of an obturator installed within
the utility lumen of the closure device of FIG. 30.
[0057] FIG. 32 illustrates a closure composition source coupled
with the closure device of FIG. 31.
[0058] FIG. 33 illustrates closure composition delivered through a
closure lumen to a puncture.
[0059] FIG. 34 is a cross section of a tissue site after closure
composition has been introduced to the puncture and a closure
device has been completely withdrawn from the tissue site.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0060] The present invention relates to a device and method for
introducing a catheter into a vessel which is positioned within a
tissue site. An embodiment of the device includes a body with a
proximal end and a distal end which is designed to be positioned
adjacent a puncture in the vessel. The body includes a utility
lumen configured so a catheter can be delivered through the utility
lumen and the puncture into the vessel. The body can also include a
closure lumen which can be coupled with a source of fluent closure
composition. The closure composition can be delivered through the
closure lumen to the puncture.
[0061] The invention can also relate to a method for using the
device. The device is positioned within a tissue site so the distal
end of the device is adjacent a puncture in a vessel. A catheter is
passed through the utility lumen and into the vessel so a surgical
procedure can be performed using the catheter. The catheter is
withdrawn and a closure composition source is coupled with the
closure lumen. The closure composition is delivered from the
closure composition source through the closure lumen to the
puncture where it serves to bind and seal the puncture. Since the
device can be used for delivery of the catheter and sealing the
puncture, there is no need to switch devices in the tissue site. As
a result, one advantage of the present invention is a device and
method which reduces the number of necessary instruments and
accordingly the opportunity for infection.
[0062] The device can include an energy delivery device at the
distal end of the body. The energy delivery device can deliver
energy to the tissue site and closure composition which has been
delivered to the puncture. The energy can serve to increase the
polymerization/cure rate of the closure composition. Additionally,
application of energy to the tissue can promote coagulation and the
natural healing processes of the tissues within the tissue site.
The combination of these factors can increase the rate the puncture
is sealed. As a result, the device can be used to effect quick
closure of a vessel puncture.
[0063] The device can include a microporous membrane around the
outside of the body. A closure composition source can be coupled
with a second closure lumen which opens to the microporous
membrane. The closure composition can be delivered through the
second closure lumen and through the microporous membrane. The
microporous membrane provides resistance to the passage of the
closure composition and can cause the closure composition to spread
out over the microporous membrane. As a result, the closure
composition contacts at least a portion of the tissues adjacent the
puncture. Withdrawal of the device allows these tissues to contact
one another and be bound together by the closure composition. As a
result, an embodiment of the device can close the tissues adjacent
the puncture.
[0064] The device can also include energy delivery devices
positioned at the sides of the body. When closure composition is
delivered through a microporous membrane closure composition will
be delivered to tissues adjacent the puncture. The side electrodes
can deliver energy to closure composition which has been delivered
to these tissues. The energy can increases the polymerization/cure
rate of the delivered closure composition. As a result, an
embodiment of the device can promote rapid closure of tissues
adjacent the puncture.
[0065] The device can also include temperature sensors positioned
along the body. The temperature sensors can detect the temperature
of the tissues adjacent to the puncture. The signal from the
temperature sensors can be fed to a control unit. The control unit
can include logic which controls the flow of energy from the
electrode in response to the temperature of the tissue. For
instance, the flow of energy from the electrodes can be reduced
when the temperature of the tissue becomes excessively elevated. As
a result, an embodiment of the device can be used to reduce damage
to tissues within the tissue site.
[0066] FIG. 1A illustrates a device according to the present
invention. The device may be used to introduce a catheter into a
vessel through a puncture in the vessel. The device can also be
used to seal the puncture and close the tissues adjacent the
puncture. It should be noted that the functioning of the device to
close a puncture in a vessel and to close the tissues adjacent the
puncture are intended to be two separate functionalities of the
device which may both be incorporated into the device.
Alternatively, each function may be independently incorporated into
a single device of the present invention.
[0067] The device includes a body 10 for positioning within tissue.
The body 10 has lateral sides 12 which terminate in a distal end
14. The body 10 includes a utility lumen 16 through which a
catheter (not shown) may be introduced at a proximal end of the
device 18 and out through the distal end 14 of the device. Included
adjacent the distal end 14 of the utility lumen 16 is a backflow
valve 20 which reduces blood flow from the vessel through the
utility lumen 16.
[0068] Positioned within utility lumen 16 is a pigtail 22 which is
movable within the utility lumen 16. The pigtail 22 can pass
through the device distal end 14 upon deployment and into the
vessel (not shown).
[0069] The body 10 of the device also includes a closure lumen 24
for the introduction of a closure composition. The device may be
connected to a closure composition source 25 by a closure
composition port 26 coupled with the closure lumen 24. The closure
composition port 26 is illustrated as having an internal taper 28
of a configuration to accept a luer type fluid fitting. The distal
end 14 can include a reservoir 30. The closure composition can pass
from the closure composition source through the closure lumen 24
into the reservoir 30.
[0070] The device can also include an electrode 32 adjacent the
distal end 14 as well as side electrodes 32 adjacent the lateral
sides 12 of the device. The device can optionally include an
ultrasound transducer 34 adjacent the distal end 14 of the device.
In addition, the device can include temperature sensors 36 as well
as blood pressure sensors 38. The device includes a controls
attachment port 40 in energy communication with the distal and
lateral electrodes or the transducer. Similarly, the electrical
attachment port can be in communication with any sensors included
on the device. As a result, an energy source 42 and device control
unit 44 can be coupled with the device through the controls
attachment port 40. The energy source 42 can communicate energy to
the electrodes. Optionally, the control unit can include logic
which controls the amount of energy delivered from the energy
source 42 in response to the signal provided from the sensors.
[0071] The electrodes can have several configurations including,
but not limited to, ring electrodes encircling the body of the
device (FIG. 1B) or positioned at the distal end of the device
(FIG. 1B), electrodes which run the length of the body or
electrodes which act as point sources distributed about the body of
the device.
[0072] The device can include a baseplate 46 including a hole 48
through which the device may be passed. The body of the device is
movable axially along the baseplate 46. The adjustability provided
by the movable baseplate is useful for accommodating variations in
the length of device that is required to reach the artery as is
dictated by the variations in human anatomy.
[0073] The baseplate 46 can also includes openings 50. Sutures 52
can be placed through the openings 50 to attach the baseplate 46 to
the skin of a tissue site. Attaching the baseplate to the skin can
stabilize and fix the baseplate in the position selected by the
physician.
[0074] Other acceptable methods of attaching the baseplate 46 may
include use of certain adhesives, particularly pressure sensitive
materials.
[0075] FIG. 2 illustrates a device which may be used to effect the
closure of a wound in a tissue site. The device includes a body 10
with a distal end 14. Lining the lateral sides 12 of the device is
a microporous membrane 54 having a pore size of about 1-5,000 .mu.m
through which sealing media can be transmitted. The device includes
electrodes 32 and sensors 36. The electrodes 32 and sensors 36 can
be positioned between the membrane and the body or over the
membrane 54.
[0076] The body 10 includes a second closure lumen 56 coupled to a
second closure composition port 58. The second closure composition
port 58 can be coupled to a source (not shown) for a second closure
composition. The second closure lumen 56 includes a plurality of
channels 60 which permit the second closure composition to pass
from the second closure lumen 56 to the microporous membrane
54.
[0077] FIGS. 3-6 illustrate a method of using the device of FIG. 1.
FIG. 3 illustrates the baseplate 46 sutured the skin 62 at a tissue
site 64. The distal end 14 of the device is adjacent a puncture in
a vessel 66 within the tissue site 64.
[0078] The pigtail 22 is positioned within the utility lumen 16
such that the pigtail extends through the distal end 14 of the
device into the vessel 66. A catheter 68 is threaded through the
utility lumen 16 and the pigtail into the vessel 66. The catheter
can be used to perform a desired medical procedure.
[0079] FIG. 4 illustrates the device after the catheter 68 and
pigtail have been removed from the device. As illustrated, removing
the catheter and pigtail leaves a puncture 70 in the vessel 66.
Blood 72 from the puncture pushes against the distal end 14 of the
device. The backflow valve 20 reduces the flow of blood from the
vessel 66 into the utility lumen 16.
[0080] In FIG. 5 a closure composition source 25 is coupled with
the closure composition port 26. The closure composition 76 is
delivered through the closure lumen 24 to the reservoir adjacent
the puncture 70. Energy can also be delivered as illustrated by
arrows 78. Any form of energy which serves to raise the temperature
adjacent the distal end 14 may be used. Examples of types of energy
that may be used include RF, microwave, ultrasound, resistive
heating, exothermic chemical heating, electromagnetic radiation,
actinic radiation, laser, diffused laser, optical energy and
frictional heating. The energy used is preferably RF energy.
[0081] FIG. 6 illustrates the device and the vessel 66 after the
partial removal of the device from the tissue site 64. The closure
composition is delivered as the device is withdrawn to spread the
closure composition along the length of the tissue site 64. As a
result, closure of the tissues adjacent the puncture is also
effected.
[0082] FIG. 7A illustrates a preferred embodiment of the distal end
14 of the device. As illustrated, the distal end 14 is saddle
shaped 80 and surrounds a portion of the vessel 66 circumference.
Surrounding a portion of the vessel increases the area of contact
between the vessel and the distal end of the device. This increased
contact area enhances the stability of the distal end 14 relative
to the vessel 66. As a result, the opportunity for the distal end
14 to move between withdrawal of the catheter from the vessel and
delivery of the closure composition is reduced.
[0083] FIGS. 7B-7D illustrate an alternative embodiment of the
saddle shaped 80 distal end 14. The distal end 14 grips a portion
of the vessel to enhance the stability of the distal end relative
to the vessel.
[0084] FIGS. 8A and 8B illustrate an embodiment of a pigtail 22.
The pigtail 22 includes a tail portion 82 which is designed to
rotate independently of a head portion 84. The head portion 84
includes threads 86, a slot 88 and a hole 90.
[0085] The tail portion 82 can be manufactured from any flexible
and biocompatible tubing, including, but not limited to, TEFLON
tubing. The hole in the head portion 84 is aligned with the tubing
in the tail portion 82 so a catheter can pass longitudinally
through the pigtail 22. The tail portion should be bent when the
tail portion 82 is in a relaxed state.
[0086] FIGS. 9A-9C illustrate a method of deploying the pigtail 22
within the device. To install the pigtail within the device an
instrument 92 is passed through the hole 90 and tail portion 82 of
the pigtail 22. The instrument 92 is inserted into the utility
lumen 16 and through the distal end 14 of the device. The
instrument is then pushed forward until the pigtail rests on a set
of threads 94 in the device as illustrated in FIG. 9A. The device
threads 94 are sufficiently short that the tail portion 82 of the
pigtail is trapped in the backflow valve 20. The instrument 92 can
be withdrawn from the pigtail 22. The installation of the pigtail
22 in the device can occur before or after the device has been
positioned within a tissue site 64.
[0087] In FIG. 9B, the instrument is withdrawn and a screwdriver 98
is inserted into the slot 88 of the pigtail 22. The device threads
94 are complementary to the threads on the head portion 84 of the
pigtail 22. Turning the screwdriver 98 can advance or withdraw the
pigtail within the utility lumen 16. In FIG. 9C, the pigtail 22 has
been advanced until it is adjacent the backflow valve 20 and the
screwdriver 98 has been withdrawn. The tail portion returns to its
relaxed state after exiting the backflow valve 20.
[0088] FIGS. 10-11 illustrate the closure of tissue as the device
is withdrawn from the tissue site 64. In FIG. 10, a first closure
composition has been delivered to the reservoir and is accumulated
against the puncture. A second closure composition source 100 is
coupled with the second closure composition port 58. The second
closure composition is delivered through the second closure lumen
56 to the microporous membrane 54. The second closure composition
passes through the microporous membrane to the tissue adjacent the
lateral sides 12 of the device. Energy, indicated by the arrows 78
may also be delivered to the tissue site. In a preferred
embodiment, energy and the closure composition are delivered in
separate steps, optionally with the delivery of ultrasonic energy
either before during or after the delivery of energy and/or the
closure composition.
[0089] The closure composition within the second closure
composition source can be the same as or different from the first
closure composition. For instance, the first closure composition
may be directed toward closure of the vessel while the second
closure composition may be directed at closure of the tissue
adjacent the puncture.
[0090] The device may be retracted from the tissue site in a
continuous motion or in a stepwise fashion. Energy can be delivered
to the tissue site before, after or simultaneously with delivery of
closure composition. For example, a closure cycle may be used which
involves (1) delivering the closure composition; (2) delivering
energy; and (3) partially retracting the device. Other sequences
for performing these three steps, including performing one or more
of these steps at the same time is envisioned and is intended to
fall within the scope of the present invention. It is further noted
that ultrasonic energy may be delivered simultaneously with any of
these steps or in between any of these steps. FIG. 11 illustrates a
tissue site after the device has been partially retracted. The
closure composition delivered during the retraction causes a tissue
union 102.
[0091] FIGS. 12A and 12B illustrate an embodiment of the device and
a method in which a solid or semi-solid closure composition
positioned at the distal end 14 of the device can be used to
facilitate closure of the vessel 66. In FIG. 12A the closure
composition is positioned within the reservoir 30 and is pushed
aside when the pigtail 22 is delivered through the device. When the
pigtail 22 is retracted, as illustrated in FIG. 12B, the closure
composition is in position to be treated with energy to effect the
closure of the vessel 66. Although the solid or semisolid closure
composition is illustrated as being present at the device distal
end 14, it should be noted that the solid or semi-solid closure
composition may be used in combination with a fluid closure
composition delivered through the device distal end 14. Optionally,
the solid or semisolid closure composition may be used
independently of a fluid closure composition.
[0092] A variety of sensors may be used in combination with the
devices of the present invention. For example, temperature sensors
may be used to detect the temperature adjacent the distal end 14 of
the device. A temperature sensor may also be use to detect the
temperature adjacent the sides of the device. These temperature
sensors are useful for regulating the amount of energy being
delivered to the vessel 66 and tissue adjacent the device. Suitable
temperature sensors include, but are not limited to, thermocouples.
The temperature sensors can have several configurations including,
but not limited to, rings which fit around the body of the device
or point sensors distributed on the body of the device.
[0093] A pressure sensor may also be incorporated in the device,
preferably at the device distal end 14. The pressure sensor may be
used, for example, to determine when the vessel 66 has been sealed,
as signaled by a reduction in pressure adjacent the device distal
end 14.
[0094] Impedance sensors may also be employed when RF is used as
the energy in order to monitor the amount of energy being delivered
to the tissue.
[0095] FIGS. 13-17 illustrate a method of using an embodiment of a
device and its operation. In FIG. 13, a trocar 104 with a sharpened
tip 106 is placed within the utility lumen 16 of the device and is
used to puncture the skin 62, muscular tissue 108 and the vessel
66.
[0096] In FIG. 14 the trocar 104 is withdrawn and the backflow
valve 20 is closed to occlude the utility lumen 16. Closing the
utility lumen reduces the loss of blood from the vessel through the
utility lumen 16 while exchanging the trocar 104 for another device
to be positioned within the utility lumen. The flaps 110 generated
in the artery by the penetration of the trocar may partially close,
but the degree of closure or whether the flaps of the artery close
at all is not important to the function of this invention.
[0097] Referring to FIG. 15, a catheter guide obturator 112 is
placed within the utility lumen 16 of the device and moved forward
through the backflow valve 20 to enter the vessel 66. The amount of
forward movement of the device may be set (not shown) to a
predetermined distance beyond the distal end 14 of the device but
since the distal end 14 of the catheter guide obturator 112 has a
rounded end, no damage to the vessel 66 will occur if the catheter
guide obturator 112 should contact the far wall of the vessel 66.
The catheter guide obturator 112 has an internal lumen 114 that is
curved 116 near the distal end 14 to direct the catheter 68 in the
desired direction within the vessel 66. The backflow valve 20
closes the gap between the outside diameter of the catheter guide
obturator 112 and the utility lumen 16 of the device, reducing
blood loss from the vessel. In this configuration, the procedure
requiring the catheter can be performed.
[0098] In FIG. 16, the catheter 68 and catheter guide obturator 112
are withdrawn. A sealing mold 118 with a curing/ejection pin 120 is
positioned within the utility lumen 16 of the device. The position
of the sealing mold 118 and curing/ejection pin 120 are set with a
stop collar 122 as it contacts an upper flange 124 of the device. A
shallow cavity 126 is formed at the distal end 14 of the sealing
mold 118. This cavity 126 is filled with a closure composition of
the present invention which is fed from a closure composition
source 25 and passes through the closure lumen 24 to fill the
cavity 126. The filling of the cavity 126 can be assisted by
suction formed by pulling air through a port 128. This suction may
additionally be used to assist in pulling the flaps 110 of the
vessel 66 upward against the distal end 14 of the sealing mold
118.
[0099] The curing/ejection pin 120 may be constructed from an
electrically conductive material. Radio frequency energy passing
through the electrically conductive curing/ejection pin 120 to
accelerate the polymerization of the closure composition.
[0100] FIG. 17 illustrates a distal portion of an embodiment of a
device. The device includes a microporous membrane 54 applied to
the outer diameter of the device. Side electrodes 32 are positioned
at intervals along the length of the body of the device.
Alternatively the side electrodes can be a single helix shaped
electrode wound around length of the body (not shown). The side
electrodes 32 can be positioned over the membrane 54 or beneath the
membrane 54 as illustrated. A second closure lumen 56 is
incorporated into the device for delivering the closure composition
to the outer diameter of the device through the microporous
membrane 54. In this regard, the closure composition should have a
sufficiently low viscosity to allow the composition to flow through
the microporous membrane 54 and against the tissue exposed to the
device.
[0101] Upon completion of the curing/polymerization of the sealing
plug 130, the closure composition will be injected through the
second closure lumen 56 and Radio frequency energy will be applied
to the annular electrodes 32. The closure composition is preferably
of a nature that allows electrical current to flow through the
closure composition to enable heating of the composition by the
energy being delivered. After a target temperature has been
reached, the device is withdrawn. Upon withdrawal, the walls of the
tissue site 64 can close in against themselves, the bonding action
of the composition will cause adhesion and sealing of the tissue.
Additionally, the action of the energy (for example RF energy) on
the tissue for the appropriate amount of time and at the proper
temperature can promote coagulation. The combination of these
factors can provide rapid sealing of the tissue site 64.
[0102] A suitable backflow valve 20 is a flapper valve as
illustrated in FIG. 18. The flapper valve is preferably formed of
an elastomeric material such as medical grade silicone rubber. The
configuration, as illustrated by the cross sectional view, may be a
cylindrical section transitioning into a conical portion. The
conical portion has a series of slits 132 which allow various
implements to pass through the valve. The thickness of the flaps
134 and the flexibility of the elastomeric material will be
balanced to provide memory sufficient to close the opening as the
implements are withdrawn and provide a fluid seal. Blood pressure
against the outer surface of the cone will cause the flapper valve
to close more tightly.
[0103] FIG. 19 illustrates yet another embodiment of the present
invention. A removable trocar 104 is temporarily positioned in the
utility lumen of the device. The trocar has a pointed tip which can
be used for puncturing the skin, tissue and blood vessel to allow
the placement of the device into the tissue and into a femoral
artery. Closure composition port 26 provides a channel through
which the closure composition may be introduced through a closure
lumen (not shown) to microporous membrane 54. The closure lumen
allows the closure composition to pass through the microporous
membrane 54 into the tissue. As illustrated, segments of the
microporous membrane 54 are separated by side electrodes 32, the
controls attachment port 40 being for RF energy. It should be
noted, however, that the device may be adapted for delivery of
other forms of energy as described above.
[0104] The temperature sensors 36 are used to sense the temperature
adjacent the distal end 14. The temperature feedback may be pre-set
as well as adjusted during use.
[0105] In the embodiment illustrated, temperature sensors are
operatively coupled with an automated device withdrawal system 136.
The temperature sensors can activate springs 138 within a rack 140
coupled with the main member 142. The activation of the springs
causes the device to be withdrawn from the tissue site. As a
result, withdrawal of the device can be correlated with the
temperatures at various zones 144 within the tissue site. For
example, as zone one reaches a specific pre-determined temperature,
the springs become activated and the rack 140 partially withdraws
the device. As each subsequent zone meets a pre-determine
temperature, the device is withdrawn further. Suitable
pre-determined temperatures include, but are not limited to,
45-50.degree. C. This withdrawal sequence can be repeated until the
device is withdrawn through zones five, four, three, two, and one.
Closure composition can be delivered before after and during the
withdrawal of the device. As a result, the device leaves the vessel
sealed and the tissue welded together as the device is
withdrawn.
[0106] FIGS. 20-22 illustrates the use of the device of FIG. 19
where the vessel 66 is a femoral artery. FIG. 20 illustrates a
plurality of sutures holding the device in position at a tissue
site. FIG. 21 shows the catheter introduced into the femoral artery
for performance of a surgical procedure.
[0107] FIG. 22 shows the withdrawal of the catheter and the device.
During withdrawal of the device, closure composition is delivered
to the tissue site 64 through the microporous membrane and RF
energy is applied. As the temperature elevates and the closure
composition infused, the temperature sensor 36 indicates to the
spring system that the device should start to back away. As it
backs away, it seals the tissue through elevated temperature,
saline, and collagen infusion, achieving a capillary flow and
molecular bonding. The whole area is sealed as the device is
retracted. The device is then removed, and a plaster is applied to
the wound.
[0108] FIGS. 23A-23C illustrate another embodiment of the present
invention. The body 10 includes a central lumen 16 and a bloodspurt
lumen 146. A blood spurt port 148 with a shutoff valve 150 opens
into the bloodspurt lumen 146 and a closure composition port 26
opens into the utility lumen 16. At the proximal end of the body is
a stop collar 152 configured to accommodate the proximal end of an
obturator. A catch channel 154 is positioned within the proximal
end of the body 10. A first closure lumen 156 has a closure
composition port 26 through which one or more fluent closure
compositions can be delivered into the closure lumen. The first
closure lumen includes an exit port 158 through which the one or
more fluent closure composition precursors can be delivered from
the first closure lumen to the utility lumen 16.
[0109] FIGS. 24A and 24B illustrate an obturator 160 for use with
the body 10 of FIGS. 25A and 25B. The obturator 160 includes an
obturator body 162 with a distal end 164 and a proximal end 166
with an enlarged head 168. A spring biased obturator knob 170 is
positioned at the proximal end 166. The obturator knob 170 is
coupled to an internal latch 172. The latch includes a catch 174
which extends through an opening 176 in the obturator body 162.
Turning the obturator knob 170 causes the catch 174 to withdraw
through the obturator body 162. The obturator body 162 further
includes a distal electrode 178 and side electrodes 180. A
temperature sensor 36 such as a thermocouple 36 is secured within
the distal electrode 178 by potting composition. An additional
temperature sensor 36 is coupled to the inner surface of the side
electrode 180. Radiofrequency conductors and thermocouple wires
feed through the internal diameter of the obturator body 162 in a
connector cable 182.
[0110] FIGS. 25A and 25B illustrate the obturator 160 disposed
within the device body 10. In FIG. 25A the enlarged head 168 of the
obturator 160 contacts the stop collar 152 and prevents the
obturator from sliding further into the device body. The external
diameter of the obturator 160 is smaller than the diameter of the
utility lumen 16. As a result, the obturator 160 partially defines
a second closure lumen 184 between the obturator and the elongated
body. The second closure lumen is coupled with the first closure
lumen and is configured to receive closure composition delivered
through the first closure lumen. The obturator can be withdrawn
relative to the device along arrows 186 until the catch 174 engages
the catch channel 154 as illustrated in FIG. 27B.
[0111] FIGS. 26-34 illustrate operation of the device of FIG. 23.
As illustrated in FIG. 26, a hollow needle 188 is inserted through
the tissue site 64 until the vessel 66 is punctured. Location of
the needle 188 within the vessel 66 is confirmed by a blood spurt
190 from the proximal end 192 of the needle 188.
[0112] In FIG. 27A a guidewire 194 is fed through the needle 188
into the vessel 66. In FIG. 27B the needle 188 is withdrawn along
the guidewire 194 leaving the guidewire 194 in place. In FIG. 28, a
hollow dilator 196 is placed in the utility lumen 16 of the
device.
[0113] In FIG. 29, the guidewire 194 is threaded though the dilator
196 which is pushed forward along the guidewire 194 into the tissue
site 64 to dilate the puncture 70. The advancement of the device is
stopped once the distal end 14 is within the vessel 66 as indicated
by a bloodspurt from the bloodspurt lumen 146.
[0114] In FIG. 30, the dilator 196 and guidewire 194 are withdrawn
from the lumen 16. The device is withdrawn in the direction of the
arrow 198 until the distal end 14 is positioned outside the vessel
66 adjacent the puncture 70. The position of the distal end 14
outside the vessel 66 is indicated when the bloodspurt ceases. At
this stage, a catheter or other device can be fed through the
utility lumen and surgical procedures performed. Upon completion of
the procedure, the catheter and sheath are removed from the device.
A backflow valve 20 can be included at the distal end 14 to reduce
blood loss.
[0115] In FIG. 31, the obturator 160 is placed in the utility lumen
16 until the enlarged head 168 of the obturator 160 contacts the
stop collar 152 of the device. The obturator has a length such that
when the enlarged head of the obturator 160 contacts the stop
collar, the distal end 164 of the obturator 160 extends slightly
beyond the distal end 14 of the device or is flush with the distal
end 14 of the device as illustrated. Since the distal end 14 of the
device is positioned outside the vessel 66 adjacent the puncture
70, the distal end 164 of the obturator is positioned outside the
vessel 66 adjacent the puncture 70.
[0116] In FIG. 32 RF energy is applied from the distal electrode
178. The energy coagulates the blood and protein near the puncture
70. Additionally, a closure composition source 25 can be coupled to
the closure composition port 26 and closure composition applied.
The energy and closure composition create a first seal 200 at the
puncture 70.
[0117] The obturator 160 is withdrawn form the device until the
catch 174 engages the catch channel 154. As illustrated in FIG. 33,
a gap 202 is formed between the distal end 164 of the obturator 160
and the first seal 200. A closure composition source 25 is coupled
to the closure composition port 26 and closure composition 76
applied. The closure composition flows through the closure lumen
and fills in the gap 202. Radiofrequency energy can be applied from
the distal electrode 178 to accelerate the polymerization of the
closure composition. FIG. 34 illustrated the tissue site 64 after
the device is completely withdrawn. Pressure is applied at the
arrows 204 to encourage curing of the closure composition and
reduce bleeding in the tissue site 64.
[0118] The closure composition can be a fluent material that can be
hydraulically translated from a reservoir through the closure
lumen. When a microporous porous membrane is used, the viscosity of
the closure composition should be sufficiently low that the
composition can exit through pores of a microporous membrane at a
reasonable rate, preferably at least about 1 mL per minute. The
viscosity of the composition should also be sufficiently high that
the composition will remain in the vicinity of the area to be
treated with the composition for a sufficient amount of time for
energy to be delivered to the composition. Energy is preferably
applied for from 0.1 sec to 600 sec, more preferably for about 1
sec to about 20 sec. Accordingly, the composition should be
sufficiently viscous to remain adjacent the device for these
periods of time. In one embodiment, the viscosity of the fluent
closure composition is between 1 cps and about 10,000 cps,
preferably from about 20 cps to about 5,0000 cps.
[0119] Suitable closure compositions include, but are not limited
to, closure compositions composed of three components, a matrix
component, a conductivity enhancer, and a composition vehicle.
Fluent closure compositions may be a homogenous solution, a slurry,
a suspension, an emulsion, a colloid hydrocolloid, or a homogeneous
mixture.
[0120] The matrix forming component may be any biocompatible
material which can form a matrix for facilitating wound closure and
sealing upon the application of a threshold energy. Examples of
suitable classes of matrix forming components include proteins,
glycoproteins, protoeglycans, mucosaccharides and
blycoaminoglycans. The matrix forming component may include
ionizable functional groups such as carboxylic acid residues,
protonated amino groups, etc., that increase the compatibility of
the matrix forming component with water-based vehicle solvents. The
matrix forming material may also include chemical functionalities
that are reactive with themselves and each other when a threshold
energy is applied. Ultimately, thermal or light energy will speed
these so-called "cross-linking" reactions within the matrix
component and between the matrix component and tissue surfaces.
Examples of such reaction chemical functionalities are carboxy
groups, amino groups, thiol groups, disulfide groups, hydroxy
groups, ester groups, and amide groups.
[0121] When the energy source 42 used to effect the closure is RF
energy, the electrical conductivity of the fluent closure
composition is preferably such that the impedance is below 200
ohms, more preferably, below 10 ohms. Because of its innate
conductivity, water is the preferred base vehicle for the closure
composition. Additionally, many ionic conductivity enhancers are
available to allow adjustment of the overall impedance of the
fluent closure composition.
[0122] In one embodiment the vehicle is physiologic saline
solution. In principle, an aqueous vehicle may benefit from this
inclusion of a conductivity enhancer; preferred enhancers are those
that occur naturally in the body, such as sodium chloride, various
phosphate salts, salts of simple amino acids such as aspartic acid
or glutamic acid, calcium chloride, etc. The conductivity enhancer
may also function as a physiologic buffer to minimize acid or
alkaline effects. The components may be a mixture of sodium and
potassium salts at levels to mimic those typically found in the
body.
[0123] The liquid vehicle is preferably water. Relatively inert
viscosity modifiers may be included, such as polysaccharides,
poly(alkylene oxides), and material gums such as camageenan and
xanthan gum. Viscosity modifier selection and level are controlled
so as not to detrimentally affect the overall conductivity of the
fluent closure composition if RF energy is used.
[0124] Listed in Table 1 are examples of matrix components that may
be employed. Listed in Table 2 are examples of conductivity
enhancers that may be employed. Listed in Table 3 are examples of
composition vehicles that may be employed.
TABLE-US-00001 TABLE 1 Matrix Components Proteins collagen,
albumin, elastin, fibrin, laminin, algin, gelatin, fibronectin
polypeptides, e.g. glutathione Saccharides polysaccharides,
oligosaccharides, monosaccharides starch and derivatives, e.g.
amylose, amylopectin, dextrin carbohydrate materials (aldo- and
keto-derivatives of saccharides) Muco-polysaccharides N-hetero
saccharides (polymeric, oligomeric and monomeric), preferably
hexosamine derivatives N-substituted saccharide derivatives
(polymeric, oligomeric and monomeric), preferably N-acetyl
derivatives O-substituted saccharide derivatives, polymeric and
oligomeric, preferably O-sulfato derivatives (--O-- SO.sub.3H
functionality), e.g., chrondoin B sulfate, a hexosamine derivative
which has both N-acetylation and O-sulfonation Glycosaminoglycans
(GAG's, linear N-hetero polysaccharides ; e.g., heparin, heparan
sulfate, keratosulfate, dermatan, hyaluronic acid, agarose
(galactan), carrageenan) Mucoproteins and Proteoglycans
hexosamine-protein and saccharide-hexosamine- protein conjugates
chemically modified proteins, saccharides, GAG's and
mucopolysaccharides derivatives prepared by acetylation, alkylation
or sulfonation of hydroxyl, amino or carboxy functional sites, such
a acetylated or sulfonated collagen derivatives prepared by
thionylation (introducing --SO.sub.2--), sulfurization (S--), or
disulfide (--SS--) coupling Synthetic Polymer Conjugates synthetic
functional polymers covalently bonded to proteins, saccharides and
muco-polysaccharides either by direct interaction,
prefunctionalization of either synthetic polymer or natural
material or by use of a coupling agent to bond the synthetic
polymer and protein, saccharide, GAG or muco- polysaccharide
together. Examples of synthetic polymers include poly(alkylene
oxides, such as poly(ethylene oxide) (PEO), polycaprolactones,
polyanhydrides, polyorthocarbonates, polyglycolides, polylactides,
polydioxanones or co- polymers thereof. Examples of conjugates are
collagen-PEO and heparin-PEO.
TABLE-US-00002 TABLE 2 Conductivity Enhancing Materials Inorganic
ionic salts Cationic component: derived from alkaline and alkaline
earth elements, preferred cation is sodium, Na.sup.+ Anionic
component: halide, preferably chloride, phosphate
(--O--PO.sub.3.sup.-3, --O--PO.sub.4H.sup.-2,
--O--PO.sub.4H.sub.2.sup.-1), carbonate, bicarbonate Organic ionic
salts Cationic component: ammonium, derived from protonation of
lysine or arginine residues Anionic component: carboxylate, e.g.
asparate or glutamate, O-phosphate ester (--O--PO.sub.3.sup.-3,
--O--PO.sub.4H.sup.-2, --O--PO.sub.4H.sub.2.sup.-1),
(glucose-1-phosphate, glucose-6- phosphate, polysaccharide
phosphates and polyphosphates), O-sulfate ester (e.g.,
glycasoaminoglycan sulfates, such as heparan sulfate, chrondoin
sulfate)
TABLE-US-00003 TABLE 3 Composition Vehicles Water
Water-poly(alkylene oxide) mixtures, e.g. water- poly(ethylene
oxide) mixtures While the present invention is disclosed by
reference to the preferred embodiments and examples detailed above,
it is to be understood that these examples are intended in an
illustrative rather than limiting sense, as it is contemplated that
modifications will readily occur to those skilled in the art, which
modifications will be within the spirit of the invention and the
scope of the appended claims.
* * * * *