Medicinal agent administration system

An apparatus for intraorgan administration of medicinal agents, such as, cells, growth factors, drugs and other agents under direct visualization, for example using an endoscope, by an apparatus and method which create needle channels within the target organ and deposits by injection, the medicinal agent in high concentrations at designated sites of the target organ. The device consists of a chamber having at least one retractable hollow bore needle; a reservoir for containing an injectable medicinal agent which is in communication with the needle and control means for extending and retracting the needle from and into the chamber and forcing the medicinal agent from the reservoir into the needle and injecting it into a target organ, said control means being suitable for effecting control through an endoscopic tube. Also disclosed are injection needles having side openings therein for enhanced administration of the medicinal agent to the target organ.

FIELD OF THE INVENTION 
This invention relates to a device and method for the administration of 
medicinal agents, such as, cells, growth factors, drugs and other agents 
into a designated site at a target organ under direct visualization. 
BACKGROUND OF THE INVENTION 
Current methods of drug and medicinal agent administration include oral, 
subcutaneous, intradermal, intramuscular, intravenous, intra arterial and 
transdermal approaches. They share the characteristic that they all 
utilize distribution via the circulatory system and systemic distribution. 
With these methods, therapeutic substances that are metabolized by 
circulatory factors will be rapidly degraded before reaching the target 
organ or achieving high concentration at the target site. Such methods are 
also ineffective for the delivery of cells to a specific target organ. For 
example, when using intravenous and intra arterial administration, the 
cells may become trapped in nonspecific capillary beds which can result in 
the failure of a substantial number of the cells from reaching the target 
site. If a high concentration of any therapeutic substance is required at 
a specific site, these current methods of drug delivery achieve this 
therapeutic level for the most part in a nonspecific fashion. As a result, 
concomitant high concentrations of the therapeutic substance are 
frequently observed at other organs and sites as well, resulting in 
undesirable side-effects. 
Attempts to circumvent these obstacles by passing catheters in the arterial 
circulation to the target organ cannot be accomplished when the vessel is 
occluded from atherosclerosis or if the vessel is too small in caliber. 
Administration of therapeutic substances in either the arterial or the 
venous circulation also results in much of the therapeutic agent being 
lost to the systemic circulation from dilution and potentially rapid 
degradation. This is an important concern if the target site of 
therapeutic action is in the interstitial compartment and a high 
concentration of the therapeutic agent is required for effectiveness. 
Moreover, the entire organ cannot be visualized or examined directly 
during administration. 
Recent research in growth factors, cellular transplantation, for example, 
the transplant of mature adult cells, xenograft cells, endo-secretory 
cells, genetically engineered cells, fetal cells and immune activated 
cells as well as drugs and immunotherapy, and other medicinal agents, 
suggest an important role for each of these entities in clinical medicine 
in the near future. The transition of this research into clinical 
applications will require an alternative drug delivery system other than 
the current methods. In particular, these new medicinal agents in some 
cases need to be administered directly to the tissue or organ which they 
will affect in order to maximize their medical efficacy and efficiency. 
The alternative delivery system will need to provide the ability to use 
direct target organ visualization and examination, allow for very precise 
delivery of the cells or therapeutic substances at the designated site(s), 
for example, a target organ in the body of a patient, with minimal 
systemic distribution and side-effects, and delivery of the cells and 
substances in high concentrations at the designated site(s), as well as 
ease of administration and safety for both the patient and the physician. 
Growth factors and related substances are expensive, frequently available 
only in minute quantities and oftentimes are metabolized very rapidly in 
the systemic circulation. In order for these agents to be used as 
effective therapeutic agents, they must be delivered to a specific site, 
often within a very small area, at the target organ. The level of 
concentration of the growth factor and related substances must be high to 
be effective. Contact with the circulatory system must be minimal to avoid 
rapid degradation and dilution. 
Another current approach using percutaneous single needle puncture guided 
by fluoroscopy, computer tomography scan or ultrasound is used primarily 
for diagnostic and drainage procedures. Many potential target organs are 
inaccessible by this approach. Localization is not precise enough and it 
does not provide for direct visualization and examination of the target 
organ. Furthermore, complications, such as bleeding, cannot be observed 
during the procedure. 
Convergent with the above mentioned research is the rapid development of 
minimally invasive surgery. Prior to this, any direct visualization and 
examination of internal organs are performed through a formal operation. 
This is associated with pain and discomfort for the patient, potential 
complications, hospitalization and a variable period of convalescence. 
With minimally invasive surgery, the operative procedure is performed 
through three small "keyhole" incisions using special surgical instruments 
and endoscopic techniques and equipment. With the utilization of fiber 
optics and a monitor, the minimally invasive surgical approach can provide 
direct visualization and examination of organs in the abdomen, chest and 
elsewhere. Moreover, it is accomplished with minimal pain and discomfort 
to the patient. The patient is sometimes discharged as early as the day of 
the operation. The period of convalescence is short. At the present time, 
minimally invasive procedures are used for diagnosis and for treatment of 
diseases treated previously with conventional surgical procedures. 
SUMMARY OF THE INVENTION 
We have discovered a new apparatus and method for delivering medicinal 
agents directly to target organs and tissues and which is especially 
usefull with minimally invasive procedures. Specifically, the inventive 
device is composed of a unit for holding a liquid medicinal agent and 
injection means therefor. A first portion of the unit comprises an 
enclosed chamber having first and second opposing walls. Within the 
chamber is at least one hollow bore hypodermic needle having entrance and 
exit openings. The needle is capable of being positioned substantially 
perpendicular to the first wall and is movable between a first position 
wherein the needle is fully retracted within the chamber and a second 
position wherein the needle exit opening extends exterior of the chamber 
and a sufficient portion of the needle protrudes from the chamber to allow 
it to penetrate a target organ. 
The first wall has openings which are opposite the exit openings of the 
needle when it is perpendicular to the first wall through which the needle 
can pass when moving between the first and second positions. 
The chamber may also have access means for opening and closing the openings 
in the first wall so that, if desired, when the needle is retracted in the 
first position, the chamber is completely closed, and when it is desired 
to extend the needle for injection, the openings may be uncovered to allow 
the needle to pass there through. 
A reservoir is attached to the second wall for holding a medicinal agent 
which is in injectable form. Conduits leading from the reservoir to the 
needle's entrance opening are provided for liquid communication between 
the reservoir and the needle. The reservoir also has means for moving 
liquid from the reservoir into and through the needles and out of the exit 
openings of the needles. 
Flexible control means are connected to the unit for introducing it to the 
interior of a patient's body through an endoscopic tube, and for 
positioning it adjacent a target organ or tissue be injected. This same 
control means may have means for controlling the access means to open and 
close the openings in the first wall, to move the needle between the first 
and second positions and for forcing liquid from the reservoir through the 
conduits into the needle and out of the needle exit into the target organ 
or tissue. The present invention is suitable for use in more conventions 
surgical procedures wherein access to the interior of a patient's body is 
through another type of opening in a patient's body, such as an incision 
or a bodily aperture, e.g., anus, vagina, mouth, nostril, etc. 
Accordingly, several objects and advantages of the present invention are: 
(a) to provide a delivery system for medicinal agents, including cells, 
growth factors, drugs and other therapeutic agents; 
(b) to provide a delivery system that can administer the medicinal agents 
to a specific site in a target organ or tissue; 
(c) to provide a delivery system that can administer medicinal agents to a 
target organ or tissue under direct visualization in a minimally invasive 
approach; 
(d) to provide a delivery system that can concurrently offer direct 
examination of the diseased target organ; 
(e) to provide a delivery system that can access organs directly in the 
abdomen, chest and elsewhere in the body; 
(f) to provide a delivery system that can administer medicinal agents in 
high concentration to a specific site at the target organ or tissue; 
(g) to provide a delivery system design that is flexible and may be 
adaptable to different clinical applications; 
(h) to provide a delivery system that may find clinical applications in 
transplantation, immune disorders, and diseases of the cardiovascular, 
endocrine, hepatobiliary, gastrointestinal and other organ systems; and 
(i) to provide a delivery system that can efficiently distribute a 
medicinal agent onto an extended area of an organ or tissue.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
The inventive apparatus may be configured in a range of sizes, diameters, 
and lengths depending on the clinical application and the target organ. It 
may be made of disposable or reusable materials. Generally, the apparatus 
is introduced via an access port using endoscopic devices and techniques 
into the abdomen, chest, or elsewhere in the body. One or more additional 
access ports provide access for fiberoptic cables and manipulating 
instruments for visualization, examination, retraction of adjacent organs, 
concurrent procedures, and guiding the intra organ administration system. 
Such endoscopic devices and techniques are known in the art. 
FIG. 1 depicts an embodiment of the apparatus. Additional components may be 
added, depending on the clinical requirements. As shown, the inventive 
device 100 comprises unit 102 composed of chamber 104, containing needles 
106 shown in extended form. Reservoir 108 is attached to the back of 
chamber 104. Control means 110, usually in the form of a flexible hollow 
tube is attached to unit 102 for controlling various functions from a 
position exterior of the body. This control means 110 is intended to allow 
the unit 102 to be introduced to the body interior via an endoscopic tube 
as well as to extend through an endoscopic tube and allow manipulation and 
positioning of unit 102 and needles 106 by the clinician, as well as to 
allow transference of the medicinal agent to the needles. 
The unit 102 is available in different sizes and shapes as well as other 
specifications depending on the clinical requirements. The unit is 
retractable or is connected to the control means by a pivotal mechanism 
described hereinafter. After insertion into the abdomen, chest or 
elsewhere in the body, the unit is engaged. Similarly, the needles on the 
unit are either protected by a sleeve, retractable through a spring-like 
mechanism or connected to the unit by pivotal mechanisms. These design 
considerations are made to minimize the diameter of the apparatus for 
passage through the access port and to avoid injury to adjacent organs and 
tissues. The needles may be configured in different arrays in the chamber. 
The number of needles, the length of the needles and the diameter of the 
needles are available in a variety of options. Needles are available with 
a single opening or with fenestrations at one level or multiple levels. 
This permits a variety of ways by which the cells or therapeutic 
substances are distributed within the target organ. The opening and 
fenestrations are closed during insertion into target organ and are opened 
after insertion. Puncture of the target organ by the needles may be 
achieved by either direct pressure or a spring-like mechanism in the 
cartridge. 
Referring to FIG. 2, unit 200 is composed of chamber 202 having two 
opposing walls, namely, front wall 204 and rear wall 206, connected by 
side wall 208. Reservoir 210 is attached to the rear wall 206. 
Front wall 204 has openings 212 therein. Inner plate 214 is mounted inside 
chamber 208 adjacent front wall 204 and in slidable relationship 
therewith. Inner plate 214 is slidable between a first closed position and 
a second open position with respect to front wall 204. Inner plate 214 has 
openings 216 therein, which are positioned so that they may be aligned 
with openings 212 when inner plate 214 is in the second open position. In 
the first closed position, openings 216 are out of alignment with openings 
212. Thus, in the first position, the chamber is closed because openings 
216 are completely out of alignment with openings 212. As used herein, 
"completely out of alignment" means that no part of openings 216 are 
adjacent or in alignment with openings 212. When inner plate 214 is moved 
to the second or open position, openings 216 are in complete alignment 
with openings 212, allowing needles 214 to pass through the openings and 
project exterior of the chamber as will be described hereinafter. In the 
first closed position, the contents of the chamber and the reservoir are 
protected. Inner plate 214 is slidably secured to front wall 204 by a 
mounting bracket (not shown). 
Movement of inner plate 214 between the first and second positions is 
effected by a positioning mechanism generally depicted as 220. This is 
composed of a shoulder 222 secured to front wall 204 and which protrudes 
through inner plate 214 through an elongated slot 223 such that inner 
plate 214 may slide back and forth relative to shoulder 222. 
Shoulder 224 is fixedly mounted on inner plate 214 and shoulders 222 and 
224 are connected by spring 226. When spring 226 is in the uncompressed 
state, inner plate 214 is in the first closed position such that holes 212 
an 216 are completely nonaligned. Shoulder 224 is in contact with cam 
member 228 which is rotatably mounted against shoulder 224 and may be 
turned by shaft 230. Shaft 230 may be formed in part or completely of 
flexible materials and extends exterior of chamber 202 through control 
means 110. However this is not shown in order to simplify the drawing. 
Rotation of shaft 230 in the direction of arrow A rotates cam 228 and 
moves shoulder 224 towards shoulder 222, thus compressing spring 226, 
moving inner plate 214 into the second open position and openings 216 into 
full alignment with openings 212 as depicted in FIG. 3. 
Flexible membrane 248 is of an appropriate plastic or film material which 
is both liquid, e.g., water, and gas impermeable and is secured at each 
end on side flanges 261 attached to the inner side walls of reservoir 210 
so as to divide reservoir 210 into inner and outer sub-chambers, 258 and 
259, respectively. Inner chamber is for containment of the medicinal agent 
and outer chamber 259 has an inlet 262 therein for introduction of a 
pressurized gas as described hereinafter. 
As used herein, the term "proximal" means a position on an element closer 
to the clinician and the term "distal" means a position away from the 
clinician and closer to the target. As also shown in FIG. 3, needles 218 
are positioned in alignment with openings 212 in front wall 204. Needles 
218 are hollow tubular hypodermic needles having a pointed distal opening 
250, and a proximal opening 244. Needle 218 has a flange 234 adjacent its 
proximal end 244 which, in turn, is mounted onto bar 236. Flange 234 and 
bar 236 have aligned apertures 252 therein. Upright pins 232 are secured 
to rear wall 206 and flanges 234 and bar 236 are slidably positioned onto 
pins 232 through apertures 252 so that bar 236, flanges 234 and needles 
218, may be moved back and forth along pins 232 which maintain the 
alignment of needles 218. 
The open proximal end 244 of needle 218 extends through flange 234 and bar 
236 (FIG. 4) and is attached to flexible conduit or tube 246, the other 
end of which communicates with the interior of inner sub-chamber 258. 
As shown in detail in FIGS. 3 and 4, needles 218 are moveable between two 
positions, a first in which the needles are inside chamber 202 and 
retracted from the outside and a second position wherein the needles 
protrude through apertures 216 and 212 exterior of chamber 208 for 
injection. The needles are moved between these two positions by needle 
control means indicated generally at 238. Needle control means is mounted 
through rear wall 206 and comprises a lock mechanism 256 attached to a 
control rod 242 which extends outside of rear wall 206 and through an 
appropriate endoscopic tube exterior of the body to be controlled by the 
clinician. Positioned between bar 236 and rear wall 206 is spring 240, 
which, when the needles 218 are fully retracted within the chamber, is in 
a compressed state and is held there by lock mechanism 256. When lock 
mechanism 256 is released by manipulation of rod 242, spring 240 is 
released and pushes bar 236 and, in turn, needles 218, towards front wall 
204 and through apertures 212 into the organ or tissue to be injected. 
This position of needles 218 in the extended position is shown more 
specifically in FIG. 4. As can be seen, spring 240 is in an extended 
state, bar 236 has been pushed fully forward against inner plate 214, and 
the needles 218 project through apertures 216 and 212 and are presumably 
penetrating or may be pushed into the organ or tissue to be injected. 
After penetration of needles 218 into the organ or tissue, gas pressure 
applied through conduit 260 attached to reservoir inlet 262, pushing 
membrane 248 towards rear wall 206 and forcing the medicinal agent in 
inner sub-chamber 258 into and through conduits 246 and into and out of 
needles 218 and into the organ or tissue. The amount of medicinal agent 
injected may be controlled by controlling the gas pressure applied to 
membrane 248 as well as the amount of medicinal agent initially placed in 
inner sub-chamber 258. 
After the desired amount has been injected, bar 236 may be pulled back 
towards rear wall 206 by manipulation of rod 242, and the mechanism is 
recocked so that the needles are again fully retracted to a position 
within the chamber. Shaft 230 may then be rotated so as to slide inner 
plate 214 into a position whereby apertures 212 and 216 are completely out 
of alignment, thus once again, closing off the chamber. The unit may then 
be removed from the interior of the body through the appropriate 
endoscopic tube. 
It will be appreciated that inner sub-chamber 258 will be charged with the 
medicinal agent through a port (not shown) prior to insertion of the 
device into the body and an amount of the medicinal agent will be 
introduced into conduits 246 and needles 218 to purge any air or other gas 
therein and prepare them for injection into the organ or tissue. 
FIG. 5 shows a bottom perspective view of unit 102 and in particular, shows 
the positioning of a reservoir 108 on the bottom on chamber 104. Reservoir 
108 has an elliptical donut shape with an aperture 302 in the middle to 
allow access to rear plate 206. This allows control means 110 to be 
attached to the bottom of rear plate 206. As shown, control means 110 is 
essentially a flexible tube which is sized appropriately to allow 
containment or attachment of various rods, as needed, to, for example, 
move inner plate 214 between its two positions and manipulate rod 242 of 
injection control means 238 so as to extend and retract the needles 218 
from the chamber. In the embodiment shown in FIG. 5, conduit 350 is a 
flexible tube which contains rods for these manipulations and is attached 
to control means 110 by tie 400. Additionally shown is a gas conduit 260 
which is attached to the bottom of reservoir 108 and which is further 
attached to conduit 350 and control means 110 by tie 400. Conduit 350 and 
gas conduit 260 may actually be inside conduit 110 for at least a portion 
of their length. Gas conduit 260 is also a flexible tube which extends 
through the endoscopic tube used in connection with the invention. 
As will be appreciated, it is necessary for unit 102 along with its 
pertinent conduits to fit through an endoscopic tube into the body cavity 
for placement at the tissue for organ. For this purpose, unit 102 is 
rotatably attached to an insertion rod or handle, which is not shown in 
this Figure. In particular, the rod is attached to a pin 310 which is 
secured between two posts 300 which are attached to rear wall 206. The pin 
goes through the rod or handle and device 102 may rotate about pin 310 
relative to the handle. A depression 330 in reservoir 108 is provided so 
that for insertion purposes, the device 102 may be aligned longitudinally 
with the rod in order to present a sufficiently small cross-section for 
insertion through the endoscopic tube. Once the device has been inserted 
through the tube and positioned at the organ or tissue to be injected, it 
may then be rotated so as to be positioned so that the front wall 204 can 
be pressed against the organ or tissue to be injected. 
It is also possible for the handle or rod to be the control means 110 and 
have conduit 350 and gas conduit 260 attached to it. 
FIG. 5A shows a cross-section of reservoir 108 along the lines 5A-5A' of 
FIG. 5. Control means 110 is shown in phantom to illustrate its rotatable 
positioning between plates 300. 
FIG. 6 shows in detail, a mechanism for controlling the rotation of unit 
102 relative to control means 110. Thus, control means 110 can rotate 
about pin 310 which is mounted in hole 320 of post 300. Gear 360 is 
rigidly mounted onto pin 310. A worm 380 is mounted in the handle so it 
can be rotated by a cable 390 which is within control means 110 and 
extends out through the endoscopic tube. As a result of twisting cable 
390, worm 380 rotates gear 360 and therefore the unit about the pin 310 so 
as to place the front plate 204 (not shown in FIG. 6) in the desired 
position adjacent or against the organ or tissue to be injected. As noted, 
upon initial insertion, unit 102 will be parallel to control means 110 for 
ease of insertion through the endoscopic tube. However, after insertion is 
achieved, rotation of cable 390 allows the clinician to rotate the unit 
102 about pin 310 so as to achieve the desired position. 
Also shown in FIG. 6 is a separate conduit 350 which is secured to the 
control means 110 by tie 400. Conduit 350 is routed into chamber via an 
aperture 340 which has a gas and liquid tight seal 410. 
As shown in the embodiments of FIGS. 2, 3 and 4, the needles 218 are 
conventional hypodermic needles in that the distal opening is beveled or 
pointed to allow penetration of tissue. Such a needle has only one exit 
opening at its proximate end for transference of the medicinal agent there 
through into the organ or tissue. 
We have found that in order to increase the efficiency of the distribution 
of the medicinal agent in the organ or tissue, it is desirable that the 
medicinal agent be dispensed from the needle along its length as opposed 
to only at the proximate end. For this purpose, we have discovered a new 
hypodermic needle as depicted in FIGS. 7 and 8. 
FIGS. 7 and 8 depict the hypodermic needle in accordance with the present 
invention which achieves this greater efficacy of delivery of the 
medicinal agent. Needle 600 is composed of an outer tube 602, and an inner 
tube 604. Inner tube 604 is slidably insertable into outer tube 602 and is 
rotatable relative to outer tube 602. Outer tube 602 contains 
fenestrations 606 which, as shown, are elongated and staggered along the 
length of outer tube 602. Similarly, inner tube 604 contains fenestrations 
608 having the same configuration as fenestrations 606. When inner tube 
604 is fully inserted into outer tube 602, upon rotation of the tubes 
relative to one another, fenestrations 606 and 608 come into full 
alignment. In the same manner, by rotation of inner tube 604 relative to 
outer tube 602, the fenestrations may be adjusted to be completely out of 
alignment in which case the tube is closed so that no liquid medicinal 
agent can pass therethrough. In this connection, it is noted that although 
the inner and outer tubes are slidable and rotatable in relation to each 
other, the fit between them is such that neither liquid nor gas will be 
admitted to or can travel along their interface. 
A mechanism by which the relative rotation of tubes 602 and 604 may be 
controlled is also depicted in FIGS. 7 and 8. As shown, outer tube 602 has 
at the proximal end, flange 612 having holes 614 therein for placement of 
the alignment pins, e.g., pins 232 as depicted in FIG. 3. Proximal end 626 
of the inner tube 604 extends beyond flange 612 so as to protrude 
therefrom and provide a tip for attachment of conduit 628 which is the 
same conduit 246 depicted in FIG. 3. A disk 622 having a cut-out portion 
or notch 618 is attached to inner tube 604 near its proximal end 626. 
Situated between disk 622 and proximal end 626 and mounted on inner tube 
604 is a pully member 624. String 620 is wrapped around pully 624 and is 
controlled by a mechanism (not shown) for movement of the pully. Pulling 
of the string in a given direction results in rotation of inner tube 604 
so that the fenestrations 606 and 608 may be moved into and out of 
alignment as required for injection. The control mechanism for string 620 
may be manipulated, for example, through conduit 350. Pin 616 is attached 
to flange 612 and cooperates with notch 618 to limit the relative rotation 
of the inner and outer tubes such that, in essence, the tubes can only be 
moved between their extreme positions, the first being a position in which 
the fenestrations in each tube are completely out of alignment in which 
case medicinal agent cannot be injected through the needle and a position 
where the fenestrations in each tube are completely in alignment and 
medicinal agent can be injected through the needle. 
In FIG. 7, the distal end 610 of needle 600 is closed so that medicinal 
agent cannot be dispensed from the end but rather only through 
fenestrations 606 and 608 and only when the fenestrations are in alignment 
with one another. Additionally, inner tube 604 is lugged or otherwise 
sealed at the distal end 607 at a level 611 which is even with the distal 
end of the most distal fenestration of the needle. This allows the purging 
of any air from the inner tube, when the inner tube is filled with liquid 
medicinal agent prior to use. As can be seen, when the fenestrations in 
the inner and outer tubes are in alignment with one another, liquid 
medicinal agent will be dispensed from needle 600 over a substantial 
portion of its length which allows delivery of the medicinal agent to a 
greater interior area of the organ or tissue into which the needle has 
been inserted. 
The embodiment of FIG. 8 provides an easy method of ensuring that no air 
pockets remain in the needle once the needle is filled with the medicinal 
agent. The needle in FIG. 8 is identical to the needle of FIG. 7, with the 
following exceptions: the distal end of the inner tube 604 comes to a 
point and fully fills the outer tube 602; the outer tube 602 contains a 
terminal fenestration 700 which is aligned radially with at least some of 
the outer tube's other fenestrations 608 and vents the most distal portion 
of the hollow interior of outer tube 602; and the inner tube 604 contains 
a terminal fenestration 710 which is completely out of alignment radially 
with any of the inner tube's other fenestrations 606 and vents the most 
distal portion of the hollow interior of inner tube 604. As used herein, 
"completely out of alignment radially" means that no part of inner tube 
terminal fenestration 710 is in alignment with another fenestration of 
inner tube 604, such that when inner tube terminal fenestration 710 is in 
alignment with outer tube terminal fenestration 700, none of the inner 
tube fenestrations 606 are even partially in alignment with outer tube 
fenestrations 608. The inner tube terminal fenestration must also be 
placed so as to still allow the complete closure of the needle, i.e. allow 
a rotation position of the inner tube and outer tube relative to each 
other such that no fenestrations are aligned and the medicinal agent 
cannot be injected through the needle. 
The needle of FIG. 8 is filled by rotating the inner and outer tubes 
relative to each other until the terminal fenestrations are aligned and 
applying gas pressure to the reservoir inlet 262 sufficient to fill 
conduit 246 and the needle, thereby purging the conduit and needle of all 
trapped gasses. The needle is then closed by rotating the inner and outer 
tubes relative to one another. In this position, no liquid can escape from 
the needle. At the time it is desired to inject the liquid medicinal 
agent, the inner tube is rotated such that the fenestrations 606 and 608 
are in alignment. However, fenestrations 700 and 710 are out of alignment. 
Pressure may then be applied to the reservoir and the medicinal agent will 
exit the needle along its length through fenestrations 608.