Intra-extravascular drug delivery catheter and method

A drug delivery catheter is provided which includes a catheter comprised of an elongated tubular shaft with an inner lumen and a vessel puncturing element which is housed in the lumen. The puncturing element has a retracted position such that it will not be in contact with the vessel wall as the catheter is guided through the vasculature. The puncturing element also has a puncturing position where it protrudes radially outward of the catheter shaft and engages and punctures the vessel wall. The catheter is first inserted into the vessel to be treated and the puncturing element is positioned at the site in the vessel to be treated. The puncturing element is then moved to its puncturing position and the inner surface of the vessel wall is punctured. A drug is then delivered through the puncture. The drug may be delivered into either the vessel wall itself or to the outside of the vessel wall.

BACKGROUND OF THE INVENTION 
The present invention relates to a drug delivery device and method for 
delivering a drug agent to a vessel or vessel-like lumen in the body. More 
particularly, the present invention relates to a drug delivery device and 
method wherein the drug agent is delivered to the vessel wall or to the 
outside of the vessel wall. 
Obstructive atherosclerotic disease is a serious health problem facing our 
society today. This disease is the result of the deposit of fatty 
substances and cells and connective tissue on the interior of the walls of 
the arteries. The build-up or accumulation of such deposits results in a 
narrowing of the inside diameter of the artery which in turn restricts the 
blood flow through the artery. This disease, wherein the opening or lumen 
of the artery is narrowed, is known as atherosclerosis and the 
accumulation is known as a lesion. 
One commonly used procedure for treating an obstruction caused by 
atherosclerosis is a procedure known as coronary artery bypass graft 
surgery ("bypass surgery"). Although bypass surgery has been used with 
moderate success in the treatment of atherosclerosis, it is invasive and 
traumatic to the patient. 
One less invasive and traumatic procedure developed more recently is 
coronary angioplasty. Coronary angioplasty, and angioplasty in general, is 
a procedure in which a balloon is positioned in the inside of the artery 
at the site of the accumulation or lesion and inflated in order to dilate 
the atherosclerotic lesion and thus open the restricted area of the 
artery. In order to advance the balloon to the lesion, the balloon is 
attached to the distal end of a small diameter catheter, which includes 
means for inflating the balloon from the other end of the catheter. The 
catheter is maneuvered or "steered" through the patient's vessels to the 
site of the lesion with the balloon in an un-inflated form. When the 
un-inflated balloon is properly positioned at the lesion, the balloon is 
then inflated to dilate the restricted area. 
While angioplasty has been relatively successful in treating coronary 
artery disease, restenosis of the treated site often occurs approximately 
3 to 6 months following the procedure. It is believed that the primary 
factor in developing restenosis is the healing that takes place after the 
injury caused by the intervention of balloon dilation procedure. The 
restenosis has close analogy to scar formation following vascular surgery 
in that the histologic result has a similar morphology. The histologic 
response is called myointimal hyperplasia. The process of myointimal 
hyperplasia consists of the migration of smooth muscle cells through the 
internal elastic lamina into the vessel lumen where they then proliferate. 
The net result is a thickening of the vessel wall. Over time, this 
thickening re-occludes or re-stenoses the vessel to a point where it is 
clinically significant. That is, the blood flow through the vessel is 
diminished to a rate similar to the rate before the angioplasty procedure. 
The occurrence of this seems to happen approximately 30-35% of the time 
following an angioplasty to that specific site in coronary arteries. 
Several alternative procedures have been attempted to try to affect the 
occurrence or rate of the restenosis following intervention to the lesion 
site in the coronary artery. These procedures have included the use of 
lasers, mechanical atherectomy devices, heated balloons, and metal 
implantable stents. While each of these procedures has shown some success 
in dealing with the initial lesion, all have the similar problem of 
restenosis at a similar or even greater occurrence. Current estimates of 
restenosis of the lesion site using these alternative procedures ranges 
between 40-50%. The time frame of restenosis of all of these is generally 
from 3-6 months after the procedure. 
Therefore, it appears that this re-stenotic healing lesion area is 
independent of the type of interventional procedure used. Rather, it is a 
physiologic response to any type of injury brought to that lesion site. 
Because of this intervention independent physiologic response, it is felt 
by many physicians that potentially the best way to deal with restenosis 
would be by a pharmacologic means, such as a drug agent, targeted at the 
biochemical events that take place after injury. 
To date, most pharmacologic trials involve either an oral or intravenously 
injected drug that is delivered throughout the whole body in hopes of 
trying to effect this small site in the arteries. This type of 
pharmacologic treatment is known as a "systemic treatment." Some agents 
that have been tried in human clinicals include: heparin, calcium channel 
blockers, angiotensin converting enzyme inhibitors, Omega-3 fatty acids, 
and growth peptides. Other agents that may not have been tried in 
clinicals but are of interest include thromboxane synthetase inhibitor, 
serotonin, growth factor inhibitors, growth factor analogs such as 
angiopeptin, antagonists, HMGCoA reductase inhibitors, platelet derived 
growth factor, inflammatory cell factors, platelet aggregation inhibitors, 
and thrombin inhibitors such as hirudin or its analogs. 
The indication for use of most of these has been either in vitro-cell 
culture studies or animal studies. These studies have shown some effect on 
the smooth muscle cell proliferation and migration which are major 
components of the myointimal hyperplasia that takes place in the 
restenotic lesion. However, none of the systemic drug delivery human 
trials to date has shown a major effect on the occurrence of restenosis. 
Even though none of these agents have been completely successful in the 
in-vivo human clinical trials, it is still generally felt that one of 
these agents or some other new agent, if delivered locally and site 
specifically to the lesion, would still be able to reduce the 
proliferative response. One of the problems with systemic techniques is 
the inability to deliver a high enough concentration of the agent locally 
at the lesion in order to effect the physiologic response. In the in-vitro 
and in-vivo animal studies which have shown some success, a high 
concentration of the agent was used. Thus, it is believed that if the 
agent was delivered specifically to the site as opposed to systemically, 
the agent may be delivered at a high enough concentration to truly effect 
the physiologic response. 
The reason many of these agents have not been used in a higher 
concentration in-vivo in humans is that many of the agents may exhibit 
undesirable side effects. Thus, if a high concentration of the agents is 
given systemically, they may have unwanted physiologic effects. Therefore, 
if the drug can be given with high concentrations locally to the vessel 
wall while minimizing the systemic amount of drug, the desired result of 
modulating the restenotic growth while preventing any unwanted systemic 
effects may be achieved. 
There are other ways known to date in trying to create a site specific 
local delivery of drug to a site. One approach presently contemplated is 
the use of a perforated or sweating balloon. For example, a drug delivery 
device is disclosed by Wolinsky, H., et al. in the article entitled, Use 
of a Perforated Balloon Catheter to Deliver Concentrated Heparin Into the 
Wall of a Normal Canine Artery, 15 JACC 475 (Feb. 1990). This device is a 
percutaneous transluminal coronary angioplasty (PTCA) balloon with several 
microholes in the balloon for delivery of an agent during balloon 
dilatation. The drug is incorporated into the same fluid which is used to 
inflate the balloon. 
A disadvantage of available devices, such as the one disclosed by Wolinsky 
et al., is that these devices cause a substantial blockage of blood flow 
in the subject vessel during the procedure. Thus, such devices may only be 
used for the fairly short time frame (typically, from one to two minutes), 
similar to the time frame of the actual angioplasty dilatation. 
Other available drug delivery devices are disclosed, for example, in U.S. 
Pat. No. 4,824,436 (Wolinsky) and U.S. Pat. No. 4,636,195 (Wolinsky). 
These devices are directed to a dual occlusion catheter in which a balloon 
is inflated proximally and distally of the accumulation or lesion creating 
a space for infusion of a drug. This dual balloon catheter creates a space 
for infusion of drug separate from the blood flow. This device, however, 
also can only be used for a short period of time because it occludes blood 
flow. 
In these types of devices where a balloon is inflated inside the vessel, 
some means for providing perfusion through the catheter itself becomes 
important. It is necessary in such devices that the device provide a large 
latitude in time over which the agent could be delivered. Devices which 
occlude blood flow may not provide the necessary latitude. Because the 
basic research into the biochemistry and physiologic events indicate that 
the initial events begin immediately after injury and continue intensely 
for several hours, it is desirable for the drug delivery system to allow 
drug delivery for several hours to a day or two beginning immediately 
after intervention. This research also points out that the initial events 
subsequently create a cascade of events that ultimately lead to intimal 
thickening. While these accumulations or lesions do not become apparent 
for several months, it is felt that if these initial events can be 
modulated, blocked, or even accelerated, then the subsequent cascade can 
be altered and a diminished overall thickening could be achieved. 
Some devices have been designed which permit localized delivery of a drug 
agent while providing enhanced perfusion capabilities. For example, the 
drug delivery catheter disclosed in co-pending U.S. patent application 
Ser. No. 07/740,045 filed on Aug. 2, 1991, commonly assigned to the 
Assignee of the present application, provides an inflatable perfusion 
lumen which provides significantly more perfusion area than previous drug 
delivery devices. The disclosed catheter and method also provides drug 
delivery pockets on the outer periphery of the perfusion lumen. The 
pockets allow the drug agent to be delivered site specifically for 
extended periods of time. 
All of the drug delivery devices discussed above, however, require that the 
device remain in the vessel while the drug agent is being administered. It 
would be desirable to have a technique for delivering a drug agent locally 
without the need for the drug delivery device to remain in the vessel. 
To this end, some techniques have been proposed wherein a drug is delivered 
by a surgical procedure where a drug agent is delivered to the outside of 
a vessel to be treated. Studies have shown that during administration by 
implanting a controlled release device which surrounds the vessel 
(periarterial drug administration) using drugs such as 
heparin-ethylenevinyl acetate significantly inhibited restenosis in an 
arterial injury model. See for example, Edelman et al., Proc. Natl. Acad. 
Sci. U.S.A., 87, 3773 (1990); and Edelman et al., J. Clin. Invest., 39, 65 
(1992). In these types of procedures, access to the vessel is obtained by 
surgically cutting to the desired location in the vessel. Then the drug 
agent is maintained at the desired location by wrapping a band or cuff 
around the vessel with the agent being loaded into the band or cuff. 
Although periarterial drug administration has shown some initial success 
in an animal model, this procedure used for delivering the implant has the 
obvious disadvantage of being very invasive. 
Therefore, it is desirable to have a drug delivery device capable of 
providing the necessary blood flow to the heart while the drug agent is 
being administered, which can be removed after the drug agent has been 
delivered and which is substantially less invasive than presently proposed 
techniques. 
Such a device may also be extremely desirable in other procedures where a 
drug is to be delivered to a specific site in a vessel. For example, drug 
delivery devices may be useful in procedures where a drug or agent is used 
to dissolve the stenosis in an effort to avoid the use of angioplasty or 
atherectomy procedures altogether or to deliver a thrombolytic agent to 
dissolve a clot at the lesion site Such a device may also be useful in the 
treatment of various disorders involving other vessels or vessel-like 
lumens in the body. 
It will be recognized from this discussion that there is a need for a 
generic type of drug delivery system which emphasizes physician control 
over the device and agent. The device should have flexibility as to the 
agent that is to be delivered and should be capable of delivering any 
number of agents (either separately or at the same time), or possibly also 
allow a change in the protocol of the delivery. It should also be flexible 
with respect to the time frame over which these agents would be delivered. 
It would also be desirable to have a device which can be removed from the 
vessel while the drug remains in place at the desired location. 
Therefore, it is a primary object of the present invention to provide a 
device and method which can contain a relatively high concentration of a 
drug agent in a selected portion of a vessel, such as a blood vessel. 
It is another object of the present invention to provide a device which can 
be removed after the agent has been delivered while the drug remains at 
the desired site. 
It is a still further object of this invention to provide a device which is 
flexible as to the drug and the number of drugs or combination of 
therapeutic agents which can be delivered as well as the time frame over 
which they can be delivered. 
SUMMARY OF THE INVENTION 
To achieve these and other objects, the present invention provides a new 
and unique drug delivery catheter and method which may be inserted into a 
vessel, such as a blood vessel. The drug delivery technique of the present 
invention includes a catheter which comprises an elongated tubular shaft 
with an inner lumen and a vessel puncturing element which is housed in the 
lumen. The puncturing element has a retracted position such that it will 
not be in contact with the vessel wall as the catheter is guided through 
the vasculature. The inner wall that defines the lumen acts as a restraint 
that retains and holds the puncturing element in its retracted position. 
The puncturing element also has a puncturing position where it protrudes 
outwardly of the catheter shaft and engages and punctures the vessel wall. 
The puncturing element is configured such that it moves to the puncturing 
position when the restraint provided by the inner wall of the lumen is no 
longer being applied. 
First, the catheter is inserted into the area to be treated. The puncturing 
element is then moved to its puncturing position and the inner surface of 
the vessel wall is punctured. A drug agent is then delivered through the 
puncture in the wall. The drug agent may be delivered either into the 
vessel wall itself or outside of the vessel wall. Thus, the drug will 
remain at a treatment site and diffuse, preferably in a time released 
manner to the treatment area. The drug will remain at the delivered site 
even after the drug delivery catheter has been removed from the vessel. 
In a preferred embodiment, the puncturing element comprises a needle which 
also functions as a tube to deliver the drug. 
In a preferred embodiment, the techniques of the present invention involves 
the implantation of a biodegradable material loaded with the drug agent in 
close proximity to the extravascular side of the vessel where the implant 
will remain and release the drug agent over a period of time. 
The present invention provides a device and method for drug delivery in 
relatively high concentrations and which can be used in a relatively 
flexible time frame depending on the particular form of the drug being 
delivered. 
Additional objects, advantages and novel features of the invention will be 
set forth in part in the description which follows and in part will become 
apparent to those skilled in the art upon examination of the following or 
may be learn by practice of the invention. The objects and advantages of 
the invention may be obtained by means of the combinations particularly 
pointed out in the appended claims.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Referring now specifically to FIGS. 1-5, a preferred embodiment of the drug 
delivery catheter 20 of the present invention is illustrated. The drug 
deliver catheter comprises a tubular catheter shaft 21 which has a 
proximal end, connected to a manifold 32, and a distal end. The distal end 
of the catheter 20 is intended to be inserted into and placed at the 
treatment site in the vessel 23. The catheter shaft may be made of any 
suitable material such as a metallic tube (commonly known in the art as a 
hypotube), a polymer material, or polypropylene. An exemplary dimension 
for the shaft is a 4F (.apprxeq.0.053") but for coronary applications a 
size of 8F or smaller will be suitable. An exemplary length for the 
catheter shaft 21 is 51" but for coronary applications lengths from 15" to 
60" are suitable. 
Referring to FIG. 4, the catheter shaft 21 includes a first lumen 24 and a 
second lumen 26. The first lumen 24 is used to house and guide the vessel 
puncturing element of the drug delivery catheter 20. The second lumen 26 
is used to house a guidewire or fixed wire 28 in order to advance the 
catheter to the desired location in a manner known in the art. In an 
exemplary embodiment, the first lumen 24 is "D" shaped and has a height 
h.sub.L1 of about 0.022" and a width W.sub.L1 of about 0.042" and the 
second lumen 26 has a height h.sub.L2 of about 0.016" and a width W.sub.L2 
of about 0.023". 
In the illustrated embodiment, the vessel puncturing device comprises a 
needle 22 which is bent at its distal end to define a short U-shaped 
portion. When the needle 22 is bent into this U-shape, it is in a 
retracted position. The bent needle 22 is positioned inside the first 
lumen 24 of the catheter shaft 21 such that the catheter 21 acts as a 
restraint holding the bent needle 22 in its retracted position. The bent 
tip 22a of the needle 22 defines the puncturing element. The needle 
defines a tube through which the drug agent may be delivered. Thus, with 
this preferred embodiment, the needle 22 functions as both the puncturing 
element as well as the drug delivery means. Preferably, the needle 22 is 
joined to a thicker tube 25 which may be bonded to another slightly larger 
tube. In an exemplary embodiment the needle 22 is a sharpened hypotube 
with an OD of 0.008" and an ID of 0.004". The needle 22 is bonded using 
cyanoacrylate to a polyamide tube 25 with an OD of 0.018" and an ID of 
0.016" and a length of about 10". The tube 25 is in turn bonded using 
cyanoacrylate to a hypotube having an OD of 0.014" and an ID of 0.007" and 
a length of about 3.5'. 
The needle 22 is comprised of a material which will provide a certain 
degree of opening force when the tip 22a is bent towards a position 
parallel with the catheter shaft 21. The amount of opening force will also 
depend on the angle .phi. of the bend and the length L of the tip 22a. In 
an exemplary embodiment, the needle 22 is a stainless steel hypotube with 
an angle .phi. in the completely opened or relaxed position being about 
30.degree. and the length L of the tip 22a being about 6 mm. Suitable 
materials for the needle or hypotube include spring steel, stainless 
steel, titanium, nitenol, a polymer or copolymer or some combination of 
these materials. The ID of the needle 22 may vary from less than 0.001" to 
about 0.131" and have OD from-smaller than 35 gauge to about 6 gauge. 
Exemplary OD's for the needle 22 for coronary applications are from 30 to 
36 gauge. 
As illustrated in FIG. 6, the point of the tip 22a is preferably beveled at 
an angle .theta. for varied cutting effects. In an exemplary embodiment, 
the angle .theta. is about 25.degree.. Patterns may also be formed on the 
sharpened end of the needle tip 22a to optimize its cutting or puncturing 
properties. 
It will also be recognized that the lumen of the needle 22 may have various 
shapes. In an exemplary embodiment, the shape of the needle lumen is 
round, but the needle lumen may also be oval, rhomboid, trapezoidal, 
triangular, or rectangular. 
Although only a single needle is illustrated in this embodiment, the drug 
delivery catheter 20 may comprise a multitude of needles. 
Manifold 32 comprises an external body which has a port communicating with 
the guidewire lumen 26 for the introduction of the guidewire 28 through 
the catheter 20. The manifold 32 also includes an actuator which 
communicates with the needle 22 in such a way that a fluid can be 
delivered through the lumen in the needle 22. The actuator may comprise 
for example a syringe 33 which may be used to infuse the fluid into the 
needle 22. A suitable syringe is a standard luer lock 5 cc syringe 
available from Becton Dickinson. The infusion may also be accomplished by 
other methods such as an infusion pump or gravity. 
Referring to FIG. 16, a manifold 32 includes the actuating element. The 
manifold 32 includes a manifold body 50 with grooves 51. A mating member 
58 includes ribs 52 which slide into the grooves 51. The needle 22 (not 
shown in FIG. 16) is bonded to the end 54 of the member 58. A lock 56 
formed of members 56a and 56b bonded together locks the body 50 to the 
engaging member 58 as the lock 56 is rotated. Thus, the needle 22 will 
move as the member 58 is moved and then is locked in the desired position. 
As illustrated best in FIGS. 3 and 6, the catheter shaft 22 includes a 
window 30 near its distal end. When the distal tip 22a of the needle 22 is 
positioned such that it is distal of the distal portion of the window 30 
(FIG. 2), the needle tip 22a is bent and housed completely within the 
catheter shaft 21 thus defining a retracted position for the puncturing 
element. As the needle 22 is pulled in a direction toward the proximal end 
of the catheter 20, the tip 22a of the needle 22 will begin to protrude 
radially outwardly and outside the perimeter of the catheter shaft 21 
through the window 30. As the tip of the needle tip 22a protrudes 
outwardly, it will move until it engages the inner surface of the vessel 
wall 23. Upon further movement of the proximal end of the needle 22 in the 
proximal direction, the needle tip 22a will puncture the vessel wall 23 as 
illustrated in FIG. 3. 
As illustrated in FIGS. 2, 3 and 6, the present invention may also include 
a trolley which is used to guide the needle 22 back into the window 30 
when the needle 22 is advanced forward to move the needle 22 to its 
retracted position. In the illustrated embodiment, the trolley includes a 
wire loop 34 which surrounds the needle 22 and a plug 36 to which the wire 
loop 34 is attached. The plug 36 may be, for example, tubing filled with 
an adhesive. The wire loop 34 may be attached to the plug 36 by bonding or 
any other suitable method. The plug 36 and loop 34 can move freely in the 
axial direction in the inner lumen 24 of the catheter shaft 21. The plug 
36 may also serve as a cam to inhibit rotation of the needle 22. 
The location of the window 30 will be determined by the specific use 
contemplated for the device. In an exemplary embodiment used for coronary 
applications, the window 30 will be 3 mm long and disposed about 20 mm 
from the distal tip of the catheter 20. It will be recognized, of course, 
that the window size and location may vary for other applications such as 
peripheral applications. 
As illustrated in FIGS. 7 and 8, the catheter 20 of the present invention 
may also include a plurality of cams 38 which act as anti-rotation means 
for the needle 22. The cams 38 may be bonded, to the hypotube and spaced 
at suitable distances apart. A suitable bond for the cams is 
cyanoacrylate. In the illustrated embodiment, the cams 38 are D-shaped and 
have a width of approximately 0.0418", a height of approximately 0.0223", 
a length of approximately 0.0844" and an inner aperture for the hypotube 
needle 22 having a diameter of approximately 0.019". These cams 38 may be 
made of a material such as platinum or PTFE or a combination of a polymer 
and metals. With such materials, the cams 38 may aid in the visualization 
of the movement of the needle tip 22a on a fluoroscope. 
It will be recognized by those skilled in the art that other suitable 
anti-rotation means may be employed. For example, the needle 22 and lumen 
24 may be provided with mating gears. FIG. 15 illustrates an embodiment 
where a gear 60 is bonded to the needle 22 and a mating gear 62 is formed 
in the tube 61. 
It will also be possible to coat the inner diameter and outer diameter of 
the various tubes with materials such as teflon, silicone, or HPC to 
reduce friction between the sliding elements. 
Referring now to FIG. 11, the catheter of the present device may also 
include an opening gauge which is comprised of a plurality of markers 64 
disposed on the hypotube 22 and a marker 66 on the catheter shaft 21. 
These markers may be made of a material such as platinum and bonded to the 
respective tubes. In this manner, the markers may be used to gauge the 
degree to which the tip 22a of the needle has opened and penetrated the 
vessel. It will be recognized that the plurality of markers may be 
disposed on the catheter shaft 21 and a single marker on the needle 22. 
FIGS. 9 and 10 illustrate another preferred embodiment of the invention 
which includes an inflatable balloon 38. The balloon 38 is used to enable 
controlled placement/penetration of the needle 22. The balloon 38 is 
placed distally of the window 30 in the illustrated embodiment. It will be 
recognized, of course, that the balloon 38 may also be placed proximal of 
the window 30. This balloon 38 will stabilize or hold the shaft 21 at the 
desired position in the vessel as the needle 22 is retracted and opened to 
its puncturing position. The balloon 38 may also serve as a means for 
inducing hemostasis in the site of the puncture or it may be used for 
dilatation before, during, or after the delivery of the drug. It will be 
recognized that the balloon 38 may also be used to perform PTCA or similar 
procedures. 
For the embodiment illustrated in FIGS. 9 and 10 which comprises the 
balloon 38, a third lumen is provided for inflating the balloon 38. FIG. 
10 shows a cross-section of the catheter shaft which includes lumens 40, 
42, and 44. These lumens 40, 42 and 44 may be used for a guide wire lumen, 
a lumen for the needle 22, and an inflation lumen for the balloon 38, 
respectively. 
It is also possible that the device may be coated with a material which 
will make the needle 20 detectable or enhance its detectability by 
intravascular ultrasound. The location of the components of the delivery 
apparatus can then be determined with respect to one another via the use 
off a separate intravascular ultrasound probe, or a probe which is a 
component of the device itself. This will allow the physician to monitor 
the position of the needle as it enters its target site. It will also be 
recognized that the device may be coated with a material which will enable 
or enhance its visualization by methods such as MRI, CT scanning, X-Ray, 
Gamma camera imaging, or PET scanning. 
The drug delivery catheter 20 of the present invention is used to deliver 
drugs to the desired treatment site as follows. The catheter 20 is guided 
to the site which is to be treated under fluoroscopy using standard PTCA 
guiding catheter and guidewire techniques. The catheter 20 is advanced 
such that the window 30 is placed at the particular site where the drug is 
to be delivered. The hypotube 22 is then pulled back such that the needle 
tip 22a exits radially outward from the window 30 and is inserted into the 
vessel wall 23. The needle tip 22a is then moved further radially outward 
until the tip 22a is at the desired location. The needle may be positioned 
to deliver the drug: between the inner and out surfaces of the vessel wall 
23; to the adventitial side or outer surface of the vessel wall 23; or 
between the tissue 27 surrounding the vessel wall 23 and the outer surface 
of the vessel wall 23. The drug agent is then infused into the desired 
location using the syringe 33 attached to the manifold 32. Since the 
catheter does not block the flow of blood, the infusion may take place 
over almost any desired period of time. After the infusion is complete, 
the hypotube 22 is pushed forward to remove the needle tip 22a from the 
vessel wall 23 and to place the needle tip 22a into place within the 
distal tip of the catheter 20 parallel to the catheter shaft 21. 
The illustrated embodiments uses a needle which is in a retrograde 
position. Since the needle is angled in this retrograde path, it is 
protected from being filled with flowing blood and causing dissection, and 
allowing the track to clot. It will, however, be recognized by those 
skilled in the art that other positions are possible. For example, the 
needle may protrude directly radially outward or may even project in a 
forward direction toward the distal end of the catheter 20. 
FIGS. 12 and 13 show another embodiment of the drug delivery catheter of 
the present invention. In this embodiment, the needle 72 is moved to the 
puncturing position to puncture the wall of the vessel 78 (shown in FIG. 
13) by means of an inflatable balloon 76. Inflation fluid is provided 
through an inflation port 74. When the window 70 has been positioned at 
the desired location, the balloon is inflated until the needle has 
puncture the wall. 
FIG. 14 shows another embodiment where the needle 72 is moved by means of 
fluid pressure being applied to a flexible flap 82 through a port 80. The 
drug being administered itself may take various forms. For example, the 
drug may be delivered in the form of a polymeric rod or spike loaded with 
a drug which will be implanted next to the area which is to be treated. In 
this form, the rod or spike would be preloaded into the tip 22a of the 
needle 20 and would be ejected from the needle 20 as fluid pressure is 
applied by means of the syringe 38 to the other end of the needle 20. The 
catheter 20 may also be used to inject microcapsules loaded with the drug 
which will be placed in close proximity to the area to be treated. The 
catheter may also be used to deliver an emulsion of liposomes loaded with 
the drug which will be placed in close proximity of the area to be 
treated. 
In these embodiments where the drug is encapsulated or loaded in a 
biodegradable material, the implants will remain and release the drug 
agent over a selected period of time after the catheter has been removed 
from the vessel. The device, however, can also be used to deliver the 
drugs in fluid for in high concentration between the outer wall of the 
vessel being treated and fatty tissue which surrounds the vessel. A list 
of potential drugs which may be used with the present invention is 
provided below in Table 1. 
TABLE 1 
______________________________________ 
A Thrombolytic A fragment of a 
glycoprotein 
An Anti-thrombotic 
A recombinant glycoprotein 
An Anti-proliferative 
A fragment of a 
recombinant glycoprotein 
An Anti-platelet A Carbohydrate or a 
fragment thereof 
A Protein An Antiarrhythmic 
A Peptide A beta blocker 
A fragment of a A calcium channel blocker 
recombinant 
peptide/protein 
A fragment of a non- 
A vasodilator 
recombinant 
peptide/protein 
Genetic material A vasoconstrictor 
A recombinant An inorganic ion or 
peptide/protein mixture thereof 
A glycoprotein 
______________________________________ 
Other steps may be used to further enhance the treatment provided by the 
present invention. For example, the needle can be heated or cooled to 
enhance the performance of the device. The catheter can be used to deliver 
and activate hot or cold activated drugs. 
The needle can also be made to vibrate at various frequencies to enhance 
the performance of the device (i.e. to optimize drug delivery). For 
example, the catheter can be used to deliver and activate sonically 
activated drugs. 
It is also conceivable that the device may have a conduction path for the 
conduction, transfer or passage of light such that the device will deliver 
a predetermined wave length of light to a specific portion of the vessel 
or body cavity, the vessel wall, or to a specific portion of the 
adventitia. The light may then be used to deliver and activate 
light-activated drugs. The catheter can be used to deliver a substance 
which will carry the energy of light through wave lengths and/or energy 
transitions or which will deliver a substance which will carry energy 
through wave lengths and/or energy transitions. 
The device can also have selectively or non-selectively magnetized elements 
or can be used to induce an electric charge or induce a magnetic field in 
a selected area. The device can then be used to deliver and activate 
electrically-activated drugs. 
Other uses for the catheter of the present invention are the delivery of a 
matrix to the exterior of a body lumen or cavity to structurally reinforce 
the area. A drug may be impregnated in this matrix and delivered 
coincidentally. The device may also be used to deliver a material that can 
be hardened in the wall or on the adventitial side. The hardened material 
may be used to form an extravascular stent or an intravascular stent 
depending on the precise delivery location. 
The device may also be used to remove substances by using a vacuum in the 
needle lumen (microsuction). 
Therefore, the device of the present invention provides a new and novel 
apparatus and technique which can be used to deliver drugs or other 
materials in close proximity to the extravascular side of a vessel. In 
addition to providing treatment for coronary disease, the present 
invention may be used to treat other disorders involving lumens or 
lumen-like vessels in the body such as prostatitis, the delivery of cancer 
chemotherapeutics, and the site specific delivery of controlled release 
antibiotics for the treatment of pericarditis, myocarditis, or 
endocarditis. 
The present invention may also be used for delivering agents to the 
myocardium which have cardioprotective effects on myocardium exposed to a 
global or sub-global ischemic insult i.e. induced cardiologia during an 
"open heart" operation in which it is necessary to stop the heart and put 
the patient on cardiopulmonary bypass. Possible agents to be delivered 
include heat-shock proteins, hormones, ATP and its biochemical precursors, 
glucose or other metabolic carbohydrates. The treatment can allow the 
heart to recover function quicker after re-perfusion by reducing the 
"myocardial stunning" that occurs due to global ischemia. 
The foregoing description of the preferred embodiments of the present 
invention has been presented for purposes of illustration and description. 
The disclosed embodiments are not intended to be exhaustive or to limit 
the invention to the precise forms disclosed, and obviously many 
modifications and variations are possible in light of the above teachings. 
It is intended that the scope of the invention be defined by the following 
claims, including all equivalent.