U.S. patent application number 11/087490 was filed with the patent office on 2005-07-28 for hydraulic reducer for injector.
Invention is credited to Holmes, David R., Schwartz, Robert S., Van Tassel, Robert A..
Application Number | 20050165354 11/087490 |
Document ID | / |
Family ID | 27403421 |
Filed Date | 2005-07-28 |
United States Patent
Application |
20050165354 |
Kind Code |
A1 |
Schwartz, Robert S. ; et
al. |
July 28, 2005 |
HYDRAULIC REDUCER FOR INJECTOR
Abstract
A medical device is provided having a needle or a catheter,
insertable into a living body, which defines a plurality of holes
in fluid communication with a central lumen. The holes may be of
various patterns located and angled to create a desired injectate
cloud pattern when an injectate is forced through the central lumen
and through the plurality of holes. One embodiment provides various
designs including a moveable sheath or stylet used to selectively
occlude one or more of the holes while in use, thereby providing an
operating physician a way to manipulate the cloud pattern anytime
during the introduction of the injectate. A reducer may be used in
conjunction with these needles which provides an increased degree
of control when injecting very small quantities of fluid.
Inventors: |
Schwartz, Robert S.;
(Excelsior, MN) ; Van Tassel, Robert A.;
(Excelsior, MN) ; Holmes, David R.; (Excelsior,
MN) |
Correspondence
Address: |
Attn: James W. Inskeep
INSKEEP INTELLECTUAL PROPERTY GROUP, INC.
Suite 205
1225 W 190th Street
Gardena
CA
90248
US
|
Family ID: |
27403421 |
Appl. No.: |
11/087490 |
Filed: |
March 22, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11087490 |
Mar 22, 2005 |
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09967681 |
Sep 28, 2001 |
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60295701 |
Jun 4, 2001 |
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60283799 |
Apr 13, 2001 |
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Current U.S.
Class: |
604/152 |
Current CPC
Class: |
A61B 2017/00247
20130101; A61M 2025/0008 20130101; A61M 5/3291 20130101; A61M
2005/3123 20130101; A61M 2025/0091 20130101; A61B 17/3478 20130101;
A61M 2005/14513 20130101; A61M 2025/0079 20130101; A61M 5/158
20130101; A61M 2025/0057 20130101; A61B 2018/00392 20130101; A61M
5/16813 20130101; A61M 5/14546 20130101; A61M 2025/0081
20130101 |
Class at
Publication: |
604/152 |
International
Class: |
A61M 001/00 |
Claims
What is claimed is:
1. An in-line volumetric reducer useable to advance a predetermined
volume of liquid to an open end of a fluid-delivery catheter
comprising: a rigid housing defining: a proximal opening attachable
to a distal end of a hydraulic pressure line, said line having a
proximal end in fluid communication with a plunger, whereby said
proximal opening is in fluid communication with said pressure line
when attached thereto; a first inner chamber extending distally
from said proximal opening and having a predetermined,
substantially uniform, cross-sectional area along a predetermined
linear axis; a distal opening attachable to a proximal end of a
catheter such that said distal opening is in fluid communication
with said catheter when attached thereto; and, a second inner
chamber extending proximally from said distal opening and having a
predetermined, substantially uniform cross-sectional area along a
predetermined linear axis, wherein said cross-sectional area of
said second inner chamber is smaller than said cross-sectional area
of said first inner chamber; a piston assembly including: a first
piston operably disposed within said first inner chamber and having
a proximal side and a distal side, said first piston forming a
substantially liquid-tight seal with said rigid housing such that
pressurized liquid on said proximal side of said first piston is
not able to pass around said first piston to said distal side of
said first piston; and, a second piston operably disposed within
said second inner chamber and having a proximal side and a distal
side, said second piston forming a substantially liquid-tight seal
with said rigid housing such that liquid on said distal side of
said second piston is not able to pass around said second piston to
said proximal side of said second piston; wherein said first piston
is operably attached to said second piston such that when said
first piston is moved linearly a predetermined distance, said
second piston moves linearly an equal distance to said
predetermined distance.
2. The reducer of claim 1 wherein said first piston is rigidly
connected to said second piston.
3. The reducer of claim 1 wherein said housing is constructed and
arranged such that a portion of said housing that defines said
first inner chamber is integral with a portion of said housing that
defines said second inner chamber and said housing further defines
at least one vent constructed and arranged to allow a fluid to
escape from said first inner chamber when said first piston is
moved distally.
4. The reducer of claim 1 wherein said predetermined second chamber
linear axis is aligned with said predetermined first chamber linear
axis.
5. The reducer of claim 1 further comprising a stop extending
inwardly from said housing constructed and arranged to limit said
predetermined linear distance which said pistons may move.
6. The reducer of claim 1 wherein said housing further defines a
threaded connector surrounding said proximal opening connectable to
a complimentarily threaded fitting on said distal end of said
hydraulic pressure line.
7. The reducer of claim 1 wherein said housing further defines a
threaded connector surrounding said distal opening connectable to a
complimentarily threaded fitting on said proximal end of said
catheter.
8. The reducer of claim 1 wherein said housing further defines a
luer lock connector surrounding said proximal opening connectable
to a complimentary connector on said distal end of said hydraulic
pressure line.
9. The reducer of claim 1 wherein said housing further defines a
luer lock connector surrounding said distal opening connectable to
a complimentary connector on said proximal end of said
catheter.
10. The reducer of claim 1 further comprising a base plate to which
said first cylinder is operably attached and to which said second
cylinder is operably attached, said base plate fixing said first
cylinder and said second cylinder relative to each other.
11. The reducer of claim 1 further comprising a bleed valve
operably attached to said second cylinder and useable to vent air
therefrom.
12. The reducer of claim 1 further comprising a vial attachment
port operably attached to said second cylinder, and in fluid
communication therewith, constructed and arranged to receive a vial
of medicament.
13. An in-line volumetric reducer useable to advance a
predetermined volume of liquid to an open end of a fluid delivery
lumen comprising: a first cylinder having a proximal end defining a
proximal opening and a distal end defining a distal opening; a
second cylinder having a proximal end defining a proximal opening
and a distal end defining a distal opening, said second cylinder
having a smaller diameter than said first cylinder; a first piston
operably disposed in said first cylinder; a second piston operably
disposed in said second cylinder; wherein said first cylinder
distal end is operably connected to said second cylinder proximal
end; wherein said first piston is operably connected with said
second piston such that when said first piston travels a
predetermined distance within said first cylinder, said second
piston travels a distance within said second cylinder which is
substantially equal to said predetermined distance.
14. The reducer of claim 13 wherein said first cylinder distal end
is integral with said second cylinder proximal end and said first
cylinder further defines at least one vent constructed and arranged
to allow a fluid to escape from inside said first cylinder when
said first piston is moved distally.
15. The reducer of claim 13 wherein said first cylinder comprises a
stop extending inwardly constructed and arranged to limit said
predetermined linear distance which said pistons may travel.
16. The reducer of claim 13 wherein said second cylinder is
removably attachable to said first cylinder.
17. The reducer of claim 16 wherein said first piston comprises a
distal end and a member extending distally from said distal end and
constructed and arranged to abut against a proximal end of said
second piston when said second cylinder is attached to said first
cylinder.
18. The reducer of claim 16 wherein said second piston comprises a
proximal end and a member extending proximally from said proximal
end and constructed and arranged to abut against a distal end of
said first piston when said second cylinder is attached to said
first cylinder.
19. A method of releasing a predetermined output volume from an
output of a lumen of a catheter for a given input volume introduced
to an input of said lumen comprising: providing a flow reducer in
line with said catheter between said input and said output, said
reducer having a first piston distal said input and a second piston
proximal said output, said first piston constructed and arranged
such that when said first piston travels a predetermined distance,
said second piston travels a distance substantially equal to said
predetermined distance, said first piston having a first diameter
and said second piston having a second diameter; filling that
portion of said catheter which extends from said second piston to
said output with a desired output fluid; injecting a predetermined
amount of input fluid into said catheter input, thereby moving said
first piston a predetermined distance and second piston a distance
substantially equal to said predetermined distance; thereby causing
said predetermined output volume of output fluid to exit said
catheter output, said output volume equal to the squared ratio of
the second diameter to the first diameter.
20. A method of injecting a predetermined quantity of injectate
comprising: providing a catheter having a proximal end attached to
a supply of pressurized fluid and a distal end in fluid
communication with a first component operably containing a first
piston; attaching a second component to a distal end of the first
component, the second component operably containing a second piston
which is constructed and arranged to move with the first piston,
said second piston having a smaller cross sectional area than the
first piston, said second component defining a chamber on a distal
side of said second piston containing said predetermined quantity
of injectate, said second component having a distal end which is
operably attached to a hypodermic device; forcing a predetermined
quantity of said pressurized fluid through said catheter to cause
said first piston and said second piston to move a predetermined
linear distance in a distal direction, thereby forcing said
predetermined quantity of injectate out of said hypodermic
device.
21. An in-line volumetric amplifier useable to advance a
predetermined volume of liquid to an open end of a fluid delivery
lumen comprising: a first cylinder having a proximal end defining a
proximal opening and a distal end defining a distal opening; a
second cylinder having a proximal end defining a proximal opening
and a distal end defining a distal opening, said second cylinder
having a larger diameter than said first cylinder; a first piston
operably disposed in said first cylinder; a second piston operably
disposed in said second cylinder; wherein said first cylinder
distal end is operably connected to said second cylinder proximal
end; wherein said first piston is operably connected with said
second piston such that when said first piston travels a
predetermined distance within said first cylinder, said second
piston travels a distance within said second cylinder which is
substantially equal to said predetermined distance.
23. A method of introducing precise amounts of medical substance
into a human comprising: providing an injecting device containing
fluid; providing a hydraulic reducer; providing said medical
substance at an output end of said hydraulic reducer; connecting
said injecting device to said hydraulic reducer; urging a volume
fluid out of said injecting device into a hydraulic reducer such
that a volume of medical substance urged out of said reducer to
said human is a fraction of said volume of fluid urged into said
hydraulic reducer;
24. A device for deliverying precise amounts of a medical fluid to
a human comprising: injector device having a working fluid and an
outlet; a reducing device having an inlet connected to said outlet
of said injector device, said reducing device having an outlet in
fluid communication with a human; said medical fluid disposed in
said reducing device at said outlet; said reducing device having a
reduction element movable according to an introduction of working
fluid into said reducing device, said movement of said reduction
element causing a discharge of medical substance from said outlet
of said reducing device, said discharge being a fraction in volume
of a volume of said working fluid introduced into said reducing
device.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to previously filed U.S.
Provisional Application entitled "Syringe System", Ser. No.
60/295,701, filed on Jun. 4, 2001 and U.S. Provisional Application
entitled "Passive Hydraulic Volume Reduction Device", Ser. No.
60/283,799, filed on Apr. 13, 2001.
BACKGROUND OF THE INVENTION
[0002] The present invention pertains generally to instruments used
to inject medicaments or other materials into a body wall, tissue,
chamber, or vessel. More particularly, a syringe system is provided
that is capable of injecting, manually or automatically, precisely
measured quantities of liquids into a body. A plurality of needle
designs are included for creating advantageously shaped or diffused
clouds, streams, or jets of medicament, contrast agents or other
liquids.
[0003] The direct introduction of a drug, compound, contrast agent,
biologically active peptide, gene, gene vector, protein, or cells
for therapy, into the tissues or cells of a patient can have
significant therapeutic value. Injection has long been a popular,
relatively non-invasive means for the direct introduction of
various medicaments and other fluids and is becoming more popular
as a means for non-invasive delivery of pharmaceutical preparations
of peptides because it minimizes tissue trauma. Injection is also a
practical delivery strategy for angiogenesis.
[0004] Angiogenesis is defined as the growth of new blood vessels.
It is an important natural process occurring in the body, both in
health and in disease. It occurs in the healthy body for healing
wounds and for restoring blood flow to tissues after injury or
insult. It can be affected by angiogenic growth factors such as
VEGF (vascular endothelial growth factor) and Fibroblast Growth
Factor (acidic or basic). Endothelial and vascular smooth muscle
cells, and myocardial cells have low mitotic activity in normal
adult coronary arteries and heart muscle. However, during growth
and development, and under conditions of ischemia, hypoxia,
inflammation or other stresses, these cells may begin to migrate
and divide, especially in the microcirculation. This eventually
results in the development of new intramuscular blood vessels.
Naturally occurring endothelial growth factors with angiogenic
potency, like FGF and VEGF, can induce angiogenesis by stimulating
endothelial cell growth, differentiation and migration.
[0005] The delivery strategy of angiogenesis is a major issue
limiting its widespread use. A number of strategies have been
attempted but none have proven as practical as the
transendomyocardial injection. Other approaches have certain
disadvantages that make them less desirable. Intracoronary
infusions, injection of angiogenic factors into the blood stream in
the coronary arteries, while minimally invasive, cause systemic
exposure to growth factors, which can have undesirable effects
elsewhere in the body. In addition, intracoronary infusions cause
little uptake of factors by the myocardium. Intrapericardial
injections, injection of factors into the sac surrounding the
heart, have potential to be used as a reservoir for continual
delivery, but many receiving the treatment have also received CABG
and no longer possess an intact pericardium. Also the procedure to
make the injection is very difficult due to the anatomy of the
pericardium. The transepicardial injection, injection directly into
myocardium from the outside, requires open-chest surgery although
there is potentially a thoracoscopic method, which is less
invasive. The problems of the above approaches for delivery leave
transendomyocardial injection as the approach that most reliably
delivers the factors without waste of factors, open-chest surgery,
or systemic exposure.
[0006] However, there are several problems with the current
procedure of intramyocardial injection using a standard needle with
a single end hole. First, a significant amount of material often
exits the needle and leaves the myocardium retrogradely via the
needle puncture tract. This phenomenon is hereafter referred to as
"backflow". This is a serious problem in that the
angiogenesis-promoting factors are extremely expensive and if they
are not introduced into the target area, they do not serve their
desired function. Additionally, systemic exposure could produce
problems such a hypotension, as the drug may interact with other
areas of the body.
[0007] Another problem with the current procedure has to do with
poor distribution of the factors. Convincing evidence has been
observed that a traditional needle has a poor distribution of
factors to the heart during injection. It is apparent, therefore,
that there is a need for diffusionary needle having multiple holes
which provides a greater and more controllable distribution of
injectate in the area of injection.
[0008] Furthermore, the above identified problem pertaining to poor
distribution of the factors may also be attributed to a vacuum
effect created in the myocardial area when the needle is removed.
This vacuum effect may draw injectate from the surrounding tissue
back into the track formed by the needle. This effect may be
lessened by providing a needle design whereby the outside surface
of the needle prevents a seal from forming between the surface of
the needle and the surrounding tissue. A diffusionary needle having
multiple holes formed in the outer surface, a needle with a scored
outer surface, or a combination of the two reduces this effect.
[0009] Not necessarily specific to angiogenesis, traditional
injection methods and devices have failed to give the operating
physician an acceptable degree of control over the size, shape and
distribution of the injectate cloud. Conventional needle designs
deliver the injectate to a single target site, thereby depositing
an often higher than desired concentration of injectate, which must
distribute itself naturally. In the case of certain peptides and
pharmaceuticals, a high deposit concentration is potentially toxic
if the concentration is sufficient to produce a biological response
to the injected agent.
[0010] More specifically, traditional needles define an inner lumen
leading from a reservoir, such as a syringe, to an opening in a
distal, sharpened point. Once the tip of the needle has reached a
target site, a physician or machine forces injectate through the
opening. Control is achieved only by varying the rate at which the
fluid is forced through the needle. In the case of a manually
operated syringe, control is an imprecise matter of dexterity and
muscle control. The resulting cloud of injectate at the injection
site has a shape largely controlled by the density of the
surrounding tissue and the flow rate of the stream leaving the
needle. Moreover, as the partial pressure of injectate at the
needle tip becomes high, there is a tendency for the injectate to
follow the needle as it is withdrawn, thereby leaving the target
site.
[0011] Accordingly, there continues to be a need in the art for new
and better needles and injection systems, or devices suitable for
injection of controlled amounts of therapeutic or diagnostic
substances without substantial loss of injectate and without
substantial damage to tissue, even during repeat injections.
[0012] There is a particular need for needles that are adapted for
attachment to various types of catheters for such controlled
delivery of therapeutic substances at remote locations within the
body.
[0013] There is also a need for a method and a device which
significantly yet controllably reduces the minimum quantity of
injectate which a manual or automatic syringe may deliver.
[0014] Further, there is a need for an injection system that
provides control over the stream or streams of injectate leaving
the needle or a catheter. More specifically, there is a need for a
needle or catheter which gives the operator the ability to
manipulate the resulting cloud of injectate while the fluid is
flowing from the needle, without having to move the needle
longitudinally or transversely and risk causing injury to the
target site.
[0015] Summarily, there is a need for an injection device that
gives control over the concentration, pattern, and location of the
deposition of an injectate.
BRIEF SUMMARY OF THE INVENTION
[0016] Generally, the present invention overcomes many of the
problems in the art by providing a medical device capable of
creating a cloud of injectate, in tissue, having a predetermined
shape, size and concentration. The device includes a needle system
having at least one elongate member with a plurality of holes
constructed and arranged to create the desired cloud shape when
injectate is forced therethrough. Preferably two elongate,
telescopically related members act together to create a desired
cloud shape. There is also a provision for an in-line hydraulic
reducer assembly which allows an easily controlled, relatively
large volume of liquid to be used to provide the injecting force
necessary to deliver an extremely small injection into body
tissue.
[0017] The reducer and needle of the present invention can be
adapted for attachment to such instruments as a manual or automatic
syringe, or adapted for attachment to a controlled pressure
source.
[0018] In another embodiment according to the present invention,
there are provided assemblage(s) useful for injecting a medicament
into a remote location of subject in need thereof. The assemblage
comprises a needle with a sharp distal point, with or without a
flow-through lumen, and a catheter with a diffusing distal portion
attached to the distal end of the needle. Preferably, the distal
end of the catheter has a plurality of holes constructed and
arranged for delivery of an injectate over a relatively large area.
This catheter is optimally coupled with a substantially solid
needle such that the injectate exits through the holes in the
catheter. Alternatively the distal end of the catheter is
constructed of a porous polymer. Uses for this catheter are
numerous but a particularly important example is the intravenous
delivery of a contrast agent, or for use in high magnetic fields
such as produced by magnetic resonance imaging methods. The
remainder of the catheter is non-porous to assure that the
medicament will be delivered only to tissue in contact with the
porous or hole-defining portion of the catheter.
[0019] The needle and/or assemblage are ideally suited for
injecting, into tissue, medicaments containing nucleic acid
encoding a therapeutic agent (or living cells containing such
nucleic acid). For example, the needle (when attached to an
appropriate catheter) or assemblage can be used to inject
medicament(s) into the wall of a beating heart or other internal
organ, without substantial loss of the medicament at the surface of
the body wall and without substantial damage to tissue at the
injection site caused by injectate.
[0020] One embodiment of the present invention particularly suited
for injecting medicaments into fibrous tissue, such as the
myocardium, provides a method of injecting fluid comprising
developing an optimal pressure wave which acts to prepare the
tissue for injectate reception prior to delivery of an operative
dose. The pressure waveform includes an initial pressure spike
which tenderizes and somewhat separates the tissue, thereby
creating receiving "planes" in the tissue that provide areas of
lower resistance to injectate reception. After the initial pressure
wave, an operative dose of the injectate is delivered at a pressure
which is less than the initial spike. Additional subsequent spikes
may be included in the waveform if necessary to maintain these
planes or open new, additional planes.
[0021] In other embodiments of the present invention, there are
provided other methods for injecting a medicament into tissue of a
subject. One injection method comprises inserting the distal
portion of the needle into the tissue of the subject and causing a
stream of injectate to form a cloud of a predetermined shape and
size in the surrounding tissue. The cloud shape and size are
determined not only by the arrangement and angles of the holes in
the needle, but also the amount of force used to deliver the
injectate. By varying the pressure, a physician can advantageously
utilize the turbulent flow patterns created within the needle which
necessarily vary with pressure. Thus, not only the size of the
cloud is altered by delivering an injectate at various pressures,
the cloud shape changes as well.
[0022] Controlling the flow of injectate through the needle also
allows the physician to control the concentration of injectate at
the target site. With a given size and distribution of exit holes,
driving injectate into the needle at a predetermined pressure will
force it out of the needle and into the tissue in a corresponding,
predictable, distribution pattern. More specifically, each flow
rate through a given needle with a predetermined hole pattern will
cause the fluid to interact with the hole size and the tissue in a
unique manner to provide a predetermined cloud pattern. The total
volume of distribution of the injectate, divided by the absolute
amount of injectate delivered, will fix the injectate concentration
of injectate in the target tissue at distances from the needle.
This is true for drugs, proteins, viral or other particles, or cell
delivery (e.g. stem cells, myocardial cells, or any other living
cells, etc). Thus, not only can the pattern of inject be
controlled, the concentration of injectate is readily controlled.
Injection through such a needle with holes has two dependent
variables: pressure and flow rate. Pressure and flow rate at any
point along the interior of the needle by the holes and exit of
injectate from the needle. The total volume is an independent
variable, and so governs absolute concentration.
[0023] Additional control and flexibility is obtained by
manipulating the stream as it is being introduced into the tissue.
As introduced above, the present invention provides a plurality of
sheath designs either outside or inside the needle, including
sheaths defining openings in their side walls which are useable to
alter or occlude the cloud patterns during operation. It is
envisioned that either the sheath, or the needle-like member
telescopically received by the sheath, could be sharpened to
provide the piercing ability necessary to introduce the device into
a body. For example, a sharpened sheath having a plurality of holes
constructed and arranged to create a desired cloud pattern is
provided in one embodiment. A stylet is telescopically or slideably
received by the sharpened sheath which is sized to occlude holes as
it passes thereunder. The stylet defines its own inner lumen which
allows the injectate to flow through the stylet and out the holes.
Rotation of the sheath relative to the needle and its holes will
effect this change.
[0024] It can be seen that variations on this stylet arrangement
can produce varying effects. For instance, if the stylet has solid
side walls and an opening on its distal end, leading to the lumen,
then the stylet will allow the injectate to flow freely through the
stylet and out the holes of the sheath when the stylet is in a
position proximally displaced from the most proximal holes. In this
position the resulting cloud will achieve its maximum length. As
the stylet is moved in a distal direction, it begins to occlude the
holes, beginning with those holes most proximal and eventually
occluding all of the holes when the stylet achieves a distal
position. The cloud, thus, may be shortened during operation from
the cloud's proximal extent.
[0025] Another embodiment provides a stylet with an opening or
window defined in its side wall. If this stylet further has a
closed distal end wall, the resulting effect is quite different. In
the proximal position, no injectate will be able to escape the
stylet and no cloud will result. As the stylet is advanced in a
distal direction, the window will begin to align with certain
holes. A cloud will thus begin to form at a proximal end and
advance distally. If the window is elongate, injectate will
continue to flow from the more proximal holes as the stylet is
advanced distally. Therefore, more injectate will have flowed from
the proximal holes than from the distal holes during the course of
stylet travel. The resulting cloud will have a tear drop shape or
frustoconical shape. If the window is only defined on one side of
the stylet, the cloud will have more of a wedge shape. If the
window is not elongate, rather it is long enough to open a one or
only a few holes at a time, the proximal holes will become
reoccluded as the distal holes become unobstructed and a ribbon
cloud will result. Additional flexibility is achieved by combining
similar variations of a needle with a plurality of holes and a
surrounding sheath defining a window.
[0026] Similarly, rotational relative movement between the sheath
and the member can be used to provide even more cloud formations.
For example, a sheath having an angled window, such that the window
forms either a spiral around the sheath or a window of distally
increasing or decreasing width, disposed over a needle with a
linear arrangement of holes, will provide rotational control to an
operating physician over the resulting cloud size and shape. As the
sheath rotates over the holes, different holes will be uncovered
and covered and the cloud will change shape, size and location.
This embodiment may provide less tissue trauma than a linearly
moving sheath.
[0027] It can thus be seen that there are a variety of combinations
of hole patterns and window or opening shapes that can act in
concert to produce a large number of cloud shapes, all of which are
considered within the scope of this invention. Moreover, the needle
itself, and its hole pattern, may be a functional device
independent of the need for a sheath.
[0028] These various injection devices may be particularly useful
in fighting coronary artery disease. Coronary artery disease (CAD)
remains the leading killer in America of both men and women,
responsible for nearly half a million deaths a year. It is
estimated that every twenty-nine seconds an American will suffer
from a coronary event and every minute someone will die from one.
People suffering from coronary artery disease exhibit many levels
of its development. In earlier stages, angioplasty can be performed
to temporarily fix the problem. However in later stages, extremely
invasive procedures such as coronary artery bypass graft (CABG)
surgery must be performed to insure survival of the patient.
Approximately 30% of patients in need of CABG will not be able to
receive the treatment due to a lack of availability of the
necessary veins to perform the graft. Angiogenesis, the formation
of new vessels, has been demonstrated conclusively in a variety of
animal models, as well as in patients with CAD. Mentioned above, as
the field of therapeutic coronary angiogenesis has matured from
basic investigations to clinical trials, the need for a minimally
invasive and effective delivery strategy has come into focus.
[0029] The present invention provides a minimally invasive
treatment involving angiogenesis-inducing factors introduced to an
ischemic heart by way of the diffusionary, multi-holed, needle on a
catheter. The development of the needle of the present invention is
an important step in developing a delivery strategy that will
distribute growth factors or gene vectors to the border regions
between ischemic and nonischemic areas. These growth factors can
induce the endothelial cells to reperfuse ischemic areas of the
heart. Studies have shown that intramyocardial injections, direct
injections into the heart, provide the most specific delivery to
the myocardium. However, injections made with a traditional end
hole needle have proved ill suited for the task of distributing and
retaining the angiogenic factors within the myocardium. The needles
of the present invention are designed to deliver the drug more
successfully than a standard needle.
[0030] In still another embodiment, the present invention provides
an in-line volumetric reducer useable to advance a predetermined
volume of liquid to an open end of a fluid delivery lumen. The
reducer comprises a first cylinder having a proximal end defining a
proximal opening and a distal end defining a distal opening. A
second cylinder is operably associated with the first cylinder and
has a proximal end defining a proximal opening and a distal end
defining a distal opening. The second cylinder has a smaller
diameter than the first cylinder. Operably disposed within the
first and second cylinders, are first and second pistons,
respectively. The first and second pistons are operably connected
such that when the first piston travels a predetermined linear
distance within the first respective cylinder, the second piston
moves the same distance within the second cylinder. Insofar as the
second cylinder is smaller than the first cylinder, the quantity of
fluid pushed therefrom, when the piston is moved, is substantially
smaller than the quantity of fluid used to push the first piston
over the predetermined distance.
[0031] If the flow through the reducer is reversed, it acts as a
flow amplifier. Specifically, a small amount of fluid entering the
second cylinder and moving the second piston will result in the
first piston expelling a larger amount of fluid from the first
cylinder. Of course, doing so will result in a significant pressure
drop across the device and may require significant input pressure,
depending on the disparity in size between the first and second
pistons.
[0032] One embodiment of the reducer provides a rigid connection
fixing the first piston to the second piston. The cylinders are
also fixed relative to each other such that the pistons are
slideable relative to the cylinders. For example, a base plate may
be provided for mounting the cylinders in axial alignment with each
other. A connecting rod integrally connecting the pistons follows
an axis of symmetry from one cylinder to the other cylinder.
[0033] Another embodiment of the reducer provides an integral
connection between the distal end of the first cylinder and the
proximal end of the second cylinder. This connection may include a
wall spanning the difference in diameters between the two
cylinders. To prevent a hydraulic lock, a vent is provided, either
in this wall or in the distal end of the first cylinder. A stop is
provided to prevent the piston from moving past the vent. The
integral connection allows the first piston to be used to pull the
second piston in a proximal direction. This would be advantageous
when using the reducer for either aspiration of very small amounts
of fluid, or for using the reducer to draw medicament from a vial
attachable to the second chamber of the reducer. Such a draw could
also be taken from a vial in the more traditional sense by
inserting the end of a standard hypodermic needle into the vial and
pulling the second piston proximally a predetermined distance.
Additionally a bleed air valve may be provided to permit air
bubbles to escape from the catheter prior to injection.
[0034] Another embodiment provides a second cylinder which is
removably attachable to the first cylinder. This is advantageous
because it allows precisely measured medicaments and other
injectates to be packaged within the second cylinder. The first
piston of this embodiment may have a member, such as a rod,
extending distally from the distal side of the piston, which is
constructed and arranged to abut the second piston of the
attachable second cylinder and push thereon during operation.
Alternatively, the member could extend proximally from the
proximate side of the second piston for abutment against the distal
side of the first piston.
[0035] In yet another embodiment, a first cylinder is provided
which may be integral or an attachable to an automatic injection
machine or syringe. A plurality of second cylinders are selectably
indexable to become operatively associated with the first cylinder,
giving a physician a wide range of reduction or amplification
ratios from which to choose. An indexing motor may be associated
with a rotatable or linearly moveable magazine of second cylinders
such that software loaded into the automatic syringe may determine
the appropriate second cylinder for a given desired injection
volume and flow rate. This embodiment vastly increases the
operating range of the automatic syringe device.
[0036] In operation, the method of providing a predetermined output
volume from a lumen of a catheter for a given input volume
comprises providing such a flow reducer in line with a catheter
between the input and the output of the catheter. If the second
cylinder is not prepackaged with medicament, it is necessary to
fill the second cylinder, distal of the second piston, and the
catheter extending distally therefrom, with the medicament or
injectate. A predetermined amount of input fluid is then injected
into the input side of the catheter, thereby moving the first
piston a predetermined distance and causing the second piston to
move a distance substantially equal to the predetermined distance.
Doing so results in causing an amount of injectate to exit the
catheter output, such as the end of a diffusing or cloud creating
needle, which is equal to the ratio of the second piston area to
the first piston area.
[0037] One skilled in the art would realize that the shape of the
cylinders and pistons is a design consideration only and the
present invention could be practiced using a variety of
alternatively shaped vessels and pistons.
[0038] One skilled in the art will also realize that the needles,
sheaths, catheters and reducers of the present invention provide a
great deal of control to the operating physician. This control is
further improved by the use of automatic injection devices, such as
that introduced above and described in more detail herein.
Additionally, it is envisioned that hand-held automatic injection
devices be provided by the present invention and used with the
various needle, catheter, and reducer embodiments described herein
and defined by the scope of the claims. These hand-held injectors
control flow rate of injectate and may be electrically powered, or
powered, for example, by compressed air or a carbon dioxide gas
cylinder, using gas pressure to force a piston for fluid injection,
or mechanically powered by mechanisms such as a spring. The gas is
preferably pressurized in a chamber to a fixed pressure, which when
released advances the driving piston a given distance within a
given time, forcing injectate from the needle. Thus, a fixed
pressure flow relation is created that is used to drive the
injectate into the tissue. Alternatively, other methods of
energizing the piston are possible, such as a wound-spring. Such a
system would provide controls to set volume of injection and
injection flow rate.
[0039] It is a particular object of the present invention to
provide devices and methods useful for simultaneously injecting a
medicament from multiple orifices along an injection course, rather
than delivering a bolus injection, as is the case with traditional
hypodermic needles.
[0040] The applications of this technology are numerous and not
meant to be limited by the descriptions herein as will be readily
appreciated by those skilled in the art. For example, the teachings
herein could be used for injecting brain malignancy (primary or
metastatic), or for cellular therapy where it is important to place
living cells at specific points in the body. The embodiments herein
could also be used to deliver high concentrations of chemotherapy
to gain a higher therapeutic ratio than would otherwise be possible
with systemic injection. Additionally, local anesthesia could be
more effectively delivered to an area of a predetermined size using
a quantity more representative of the size of the area to be
numbed. This is in contrast to injecting a concentration high
enough to eventually diffuse and numb the desired area. Similarly,
steroids could more effectively be delivered into joints using the
same principles. Insulin could be injected with this mechanism, as
could low molecular weight heparin or other potent anticoagulants,
high concentrations of which can cause tissue damage, fibrosis, or
bleeding.
[0041] Additionally, it is envisioned that the needles of the
present invention be fitted with tissue grabbing hooks such as
those presently used when a needle is intended to remain in a
patient for extended periods and it is desired that the tissue grow
around the needle and anchor it in place. In other words, the
teachings herein of multiple holes and placement thereof could be
adapted to various present needle designs.
BRIEF DESCRIPTION OF THE DRAWINGS
[0042] FIG. 1 is a schematic drawing showing an exploded view of
the invention needle with weeping tip and a catheter to which it
attaches;
[0043] FIG. 2 is a schematic drawing showing the invention needle
with the electrical connector for attachment to an
electrocardiogram;
[0044] FIG. 3 is a schematic drawing showing the invention
assemblage comprising a catheter and a needle, wherein the porous
or hole pattern in the distal portion is located in the flexible
catheter;
[0045] FIG. 4 is a perspective view of the reducer of the present
invention;
[0046] FIG. 5 is a perspective view of an alternative embodiment of
the reducer of the present invention;
[0047] FIG. 6 is a side elevation of an elongate member of the
present invention;
[0048] FIG. 7 is a side elevation of an alternative elongate member
of the present invention;
[0049] FIG. 8 is a front perspective view of an elongate member of
the present invention producing a shaped injectate cloud;
[0050] FIG. 9 is a front perspective view of an elongate member of
the present invention producing an alternatively shaped injectate
cloud;
[0051] FIG. 10 is a sectional side elevation of a portion of an
elongate member showing a distally, perpendicularly and proximally
angled holes leading from the central lumen of the member, whereby
the direction of holes diffuse the injectate in space, within the
desired pattern;
[0052] FIG. 11 is a side elevation of a preferred embodiment of the
present invention;
[0053] FIG. 12 is a side elevation of a preferred embodiment of the
present invention whereby part of the elongate member is cut away
to show the detail of the stylet;
[0054] FIG. 13 is a side elevation of a preferred embodiment of the
present invention whereby part of the elongate member is cut away
to show the detail of the stylet;
[0055] FIG. 14 is a perspective view of a key of the present
invention;
[0056] FIG. 15 is a side elevation of a preferred embodiment of the
present invention whereby part of the elongate member is cut away
to show the detail of the stylet;
[0057] FIG. 16 is a side elevation of a preferred embodiment of the
present invention whereby a rotatably sheath is operably disposed
over the elongate member;
[0058] FIG. 17 is an embodiment of the elongate member of the
present invention having scored marks thereon;
[0059] FIG. 18 is a pressure versus time graph of a preferred
pressure waveform of the present invention;
[0060] FIG. 19 is a side elevation view of a needle having holes
constructed and arranged to form a tear drop cloud pattern;
[0061] FIG. 20 is a side elevation view of a needle having holes
constructed and arranged to form a spiral ribbon cloud pattern;
[0062] FIG. 21 is a sectional side elevation of a portion of an
elongate member showing a distally, perpendicularly and proximally
angled holes leading from the central lumen of the member, whereby
the direction of holes concentrate the injectate in space, within
the desired pattern;
[0063] FIG. 22 is a side elevation of a needle having holes
constructed and arranged to form a cloud in the shape of a
disk;
[0064] FIG. 23 is a side elevation of a needle having holes
constructed and arranged to form a cloud in the shape of a
sphere;
[0065] FIG. 24 is a perspective view of a preferred embodiment of
the reducer of the present invention;
[0066] FIG. 25 is a perspective view of another preferred
embodiment of the reducer of the present invention; and,
[0067] FIG. 26 is a preferred embodiment of a catheter of the
present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0068] The present invention overcomes many of the problems in the
art by providing a needle and/or a catheter having a plurality of
holes formed therethrough for micro or diffused injection of
injectates, such as medicaments, living cells, contrast agents, or
any liquid, into a body surface. The invention needle comprises a
nonporous hollow needle shaft having a proximal end adapted to mate
with an injection instrument, a porous or hole-based distal portion
in fluid-tight connection to the needle shaft, and a point that is
open, closed, or has a solid partial plug. The distal portion of
the invention needle is adapted to cause a liquid injectate to
weep, ooze, or form any desired 3-dimensional pattern therefrom
multidirectionally under injection pressure with the distal portion
and point of the needle are inserted into a tissue, chamber, or
blood vessel. Typically, the length of the porous distal portion of
the needle is determined by its intended use (e.g., whether
intended for injecting medicament into a blood vessel or into a
kidney, and the like). Alternatively, a solid needle is provided
which is operatively attached to a catheter having a plurality of
holes formed therethrough for introducing an injectate into a lumen
in vivo over a relatively large area, thereby avoiding a point of
high concentration. The needle or catheter could similarly be
advantageously used for aspiration as the presence of a plurality
of holes provides a low resistance fluid flow.
[0069] The invention needle with weeping tip can be adapted for
attachment to such instruments as a syringe, or controlled pressure
injector through a nonporous catheter. The assemblage of the needle
and catheter is preferably steerable. For example, the needle can
be attached to the distal tip of a steerable catheter (i.e.,
comprising a steering mechanism at the handle for controlling
deflection of the distal tip section of the catheter shaft), some
of which are known in the art for injection of medicaments into a
remote body cavity or organ wall. Alternatively, the needle can be
attached to a catheter with a porous distal portion and then the
combination can be introduced into a steerable guidance catheter,
such as is used in such techniques as angioplasty, angiogenic
therapy such as angiogenic gene or protein injection,
transmyocardial revascularization (TMR), percutaneous
transmyocardial revascularization (PTMR), and the like, to direct
the needle and catheter to the appropriate site for injection of a
medicament. Guidance catheters suitable for use in the invention
assemblages and methods are commercially available, for example
from such vendors as Eclipse Technologies (Sunnyvale, Calif.) and
CardioGenesis Corp. (Sunnyvale, Calif.).
[0070] In another embodiment according to the present invention,
the distal portion of the needle is adapted with holes sized to
create decreasing hydraulic impedance on injectate moving
therethrough toward the point to cause a substantially uniform flow
rate of injectate from the needle along with length thereof. The
decrease in hydraulic impedance to injectate outflow can be of any
type, for example, linear, exponential, Gaussian, and the like, and
with a gradient in either longitudinal direction. The sharp point
of the invention needle can be open, closed, or fitted with a solid
partial plug to prevent the injectate from exiting as a single jet.
If the point of the needle is open, the rate of flow from the open
point can also be controlled by adjustment of the hydraulic
impedance along the length of the distal portion of the needle to
prevent the rate of fluid flow at the tip from substantially
exceeding the rate of fluid flow along the porous portion adjacent
to the point of the needle, as can be the hole size in the end of
the needle
[0071] Alternatively, the point of the needle can be open, but
restricted by a solid partial plug so that the distal tip of the
needle is designed to operate similarly to the tip of a garden
nozzle wherein the solid partial plug cooperates with the open tip
to restrict exit of fluid, thereby preventing exit of the fluid as
a single jet.
[0072] The proximal end of the invention needle shaft is provided
with a connector, such as a flange, hub, or the like, as is known
in the art, for removable attachment of the needle to an
instrument, such as a syringe or a catheter. The instrument serves
as a reservoir or conduit for the fluid medicament. Therefore, the
connector is such that there is fluid communication between the
needle and the instrument. In use, the invention needle is mounted
on the distal tip of the instrument, which is adapted to apply or
transmit pressure to the medicament within the nonporous hollow
shaft of the needle.
[0073] The holes may be formed in the needle using a cutting laser
and techniques known in the art to punch holes into the needle
segment (i.e. by a process of laser etching). The holes generally
are, but need not be, circular. Also, the holes may taper in either
direction from inside the needle to outside the needle. This will
permit flow modification as the injectate exits the needle. The
holes may be drilled in any direction to point fluid exit in
directions making any arbitrary 3-dimensional pattern. The holes
thus need not be perpendicular to the longitudinal axis of the
needle.
[0074] In the embodiment of the invention illustrated in FIG. 1
herein, needle 2 has a nonporous hollow needle shaft, a porous
distal portion 6 having inter-connecting pores and a closed sharp
tip 8. Injectate 12 oozes from the pores in the distal portion
under injection pressure. The sharp tip 8 of needle 2 is closed so
that no injectate flows from the point of the needle. The proximal
end of needle 2 is fitted with flange 10 for removable attachment
to a catheter. The distal end of catheter 16, which has at least
one open lumen 14 for passage of injectate into needle 2 attaches
to the proximal end of needle 2. In other embodiments, a hub for
mating with a syringe is substituted for the flange at the proximal
end of the needle.
[0075] In another embodiment according to the present invention,
the invention needle further comprises one or more sensor
connectors for electrical attachment to an electrocardiogram. The
electrocardiogram can be used to determine contact between the
needle tip and the tissue, or if multiple electrodes are present,
to determine the depth of penetration. In the embodiment shown in
FIG. 2, the exterior of the needle shaft (not visible in this
FIGURE) is coated with an insulator 18 and the connector 19 is
attached directly to the proximal end (uncoated) of the needle
shaft. Electrical lead 20 can be threaded down the lumen of a
catheter for attachment to an electrocardiogram. Multiple leads can
also be used in order to determine depth of the needle. In this
configuration, the electrocardiogram is recorded from all leads.
The larger signal is present from those ECG leads that are
intramyocardial. Alternatively, the connector can be attached to
the interior of the tip of the needle and catheter for attachment
to an electrocardiogram. In this embodiment the needle itself acts
as the electrode for the electrocardiogram and can be used for
monopolar sensing of electrical currents or impedance within the
heart, brain, nerves, proximal arteries, and the like. For
monopolar sensing a return electrode can be provided by placing an
ECG pad in electrical connection with the electrocardiogram on the
exterior of the patient, for example on the exterior of the chest
wall. It is also contemplated within the scope of the invention
that a second electrode or sensor connector can be attached to the
needle, for example to the exterior of the needle, spaced apart
from the first electrode by at least about 0.5 mm, so as to provide
two electrodes for sensing electrical currents within a subject's
bodily organs. Multiple connectors can be used, and bipolar or
multipolar electrical impedance sensed in this manner between/among
the multiplicity of electrodes.
[0076] It is also possible that an electrode permanently implanted
in a subject, such as belongs to a pacemaker, can be used as the
return lead for remote bipolar sensing.
[0077] The advantages of using the invention needles to perform
sensing are several. For example, for injection into a muscle or
other organ that has electrical impulses running through it, an
electrogram sensor attached to the invention needle can be used to
confirm contact of the needle tip or proper insertion of the needle
into the body wall of interest (e.g., the wall of a beating heart)
before injection of the medicament into a treatment site. The depth
of needle insertion into the tissue is determined by an array of
electrodes. Those of skill in the art will realize that the
invention needle having attached electrocardiogram sensor can also
be used to judge whether such a prospective injection site is
electrically active or not (i.e., whether the tissue is dead,
hibernating due to lack of oxygen, or alive), and the like.
[0078] As with the needle described above, the size, and/or number,
or density of holes in the catheter of the invention assemblage can
be selected to create any desired gradient of injectate along the
course of the injection path. For example, the size, and/or number
or density of pores or holes can decrease along the length of the
catheter moving towards the connection with the needle to allow for
a substantially uniform rate of injectate flow along with length of
the catheter. In this configuration, therefore, once the needle is
used to thread the porous portion of the catheter through the
tissue to be treated, a substantially uniform rate of fluid
injection into surrounding tissues can be obtained along the
injection course. Alternatively, or in conjunction with such a
porosity gradient, the porous distal portion can also have a
decreasing interior diameter along its length moving from the
proximal end towards the connection with the needle to accomplish
the same goal.
[0079] FIG. 3 herein illustrates the invention assemblage 22.
Non-porous needle 24 with a closed tip is attached to the distal
end of flexible catheter 26, which has a porous distal portion 28.
Injectate 30 flows from the pores or holes in the flexible distal
portion 28 of catheter 26.
[0080] As used herein, the terms "medicament(s)" and "injectate(s)"
include all types of liquid substances (e.g., including solutions
and suspensions) that have a beneficial therapeutic or diagnostic
effects and use. Non-limiting examples of medicaments suitable for
use in the invention methods include biologically active agents,
such as small molecule drugs, proteinaceous substances,
polynucleotides or nucleic acids (e.g. heterologous DNA, or RNA)
and vectors (such as virus), liposomes, living cells including
recombinant or bone marrow cells, and the like, containing such
nucleic acids or polynucleotides, as well as liquid preparations or
formulations thereof. Diagnostic injection of contrast or other
diagnostic agents is also an additional application.
[0081] FIG. 4 illustrates an embodiment of a preferred reduction
device or reducer 40 of the present invention which is useful to
control the amount of medicament or injectate that is delivered to
the patient. Reducer 40 preferably includes a housing 42 which is
constructed and arranged to form a proximal first chamber 44 and a
distal second chamber 46 which has a smaller cross sectional area
than that of the first chamber 44. A first piston 48 is slideably
disposed within the first chamber 44 and a second piston 50 is
slideably disposed within the second chamber 46.
[0082] The housing 42 defines a proximal opening 52 at the proximal
end of the first chamber 44 which is attachable to a catheter. As
used herein, the term "proximal" refers to the upstream side or
operator/machine side whereas the term "distal" refers to the
downstream or patient side of a component. The housing 42 also
defines a distal opening 54 at the distal end of the second chamber
46 which is also attachable or integral to a catheter or needle. It
is envisioned that the proximal and distal ends of the housing 42
could be attachable to catheters using threaded connections, luer
locks, quick connections, friction fittings, or any suitable
mechanism.
[0083] It can be seen that the first piston 48 is operably
connected to the second piston 50 such that when the first piston
48 is moved a predetermined distance distally, the second piston 50
also moves. The embodiment in FIG. 4 uses a rod 51, which is
integral with both the first piston 48 and the second piston 50.
Because of the disparity in sizes of the respective pistons, and
because the distances they move are the same, a hydraulic reducer
is created. For any given input volume, the output volume is
reduced by a ratio of the cross-sectional area of the second piston
50 divided by the cross-sectional area of the first piston 48. This
is advantageous when it is desired to deliver a microinjection
either manually, or using an automatic injection device such as
that taught by U.S. Pat. No. 6,099,502, issued Aug. 8, 2000 to
Duchon et al. Vents 53 are located in the distal end of the first
chamber or cylinder 44 to allow air to escape as the first piston
48 is advanced distally. Without vents 53, a hydraulic lock would
be created. A stop 55 is also provided to prevent the first piston
48 from traveling too far in a distal direction. Though shown in
FIG. 4 as an annular ring, the stop 55 could be one or more
inwardly extending protuberances, rods or similar formations
extending distally from the first piston 48, or proximally from the
end wall of the first cylinder 44, or even a similar arrangement
associated with the second piston 50. It is important to prevent
the first piston 48 from traveling distally past any vents 53 which
may be formed in the side of the housing 42 because the pressurized
fluid used to move the first piston 48 would leak through the vents
53.
[0084] Another preferred embodiment of the reducer 40 is shown in
FIG. 5. The housing 42 comprises two detachable components 42a and
42b. Component 42a defines the first cylinder 44 and component 42b
defines the second cylinder 46. The first piston (not shown) is
operably disposed within the first cylinder 44 and a rod 51 is
integral with the first piston and extends distally therefrom. The
second component 42b operably houses the second piston (not shown).
The second component is preferably integral with a needle or
catheter and contains a predetermined quantity of injectate which
is packaged therewith. When the components 42a and 42b are
connected, such as with the threaded connector 57 shown in the
FIGURE, the distal end of the rod or plunger 51 abuts against the
proximal side of the second piston, acting thereon during operation
in the same manner as described above and shown in FIG. 4. Once the
injectate has been administered, the needle may be removed from the
patient and the second component 42b may be detached from component
42a and discarded. The first piston may be proximally withdrawn and
the first component may be used again in conjunction with a new
second component 42b. Though the rod 51 could be effectively
integral with the proximal side of the second piston and abut
against the first piston when components 42a and 42b are operably
connected, this may result in accidental movement of the second
piston while the second component 42b is being handled prior to
use.
[0085] Yet another embodiment of the reducer 40 is shown in FIG.
24. The first cylinder 44 is provided which may be integral or an
attachable to an automatic injection machine or syringe. A
plurality of second cylinders 46, each having different diameters,
are selectably indexable to become operatively associated with the
first cylinder 44, giving a physician a wide range of reduction or
amplification ratios to choose from. An indexing motor 136 may be
associated with a rotatable or linearly moveable magazine 130 of
second cylinders 46 such that software loaded into the automatic
syringe may determine the appropriate second cylinder 46 for a
given desired injection volume and flow rate. The embodiment shown
provides a magazine 130 of second cylinders 46 each containing a
piston (not shown) for interaction with the first piston 48 in the
manner described above. The magazine 130 comprises a housing 132
which carries the second cylinders 46 and is rotatable around a
pivot pin 134. This embodiment vastly increases the operating range
of the automatic syringe device.
[0086] Still another embodiment of the reducer 40 is shown in FIG.
25. The first cylinder 44 and the second cylinder 46 are rigidly
mounted to a base 150 via a plurality of mounting brackets 152.
This arrangement fixes the first cylinder 44 relative to the second
cylinder 46. The connecting rod 51 rigidly connects the first
piston 48 to the second piston 50. The base plate 150 and mounting
brackets 152 obviate a need for a vent to prevent a hydraulic lock
as a housing is not necessary between the first cylinder 46 and the
second cylinder 46.
[0087] The advantage of the reducer, when used manually, arises
when the catheter attached to the proximal opening has a smaller
diameter or cross section than that of the first chamber 44. This
arrangement not only reduces the volume of injectate forced from
the needle for a given volume of fluid introduced into the first
chamber 44, it also reduces the linear distance the piston 48 or 50
moves compared to the distance a physician moves an input piston or
syringe.
[0088] For example, assume the first chamber 44 has a
cross-sectional area of 10.sup.-4 m.sup.2, the second chamber 46
has a cross-sectional area of 10.sup.-5 m.sup.2, and the catheter
attached to the proximal opening 52 of the first chamber 44 also
has a cross-sectional area of 10.sup.-5 m.sup.2. Filling the
catheter with a driving fluid and placing a syringe into the
proximate end of the catheter for use in pushing fluid into the
first chamber 44 will give the operating physician a great deal of
control. If the physician pushes the syringe into the catheter 1
cm, there will be 10.sup.-7 m.sup.3 or 0.1 ml of fluid injected
into the first chamber 44. This will cause the first piston 48 to
move 10.sup.-7 m.sup.3/10.sup.-4 m.sup.2=10.sup.-3 m or 1 mm. In
other words, there is a linear reduction equal to the area of the
input syringe divided by the area of the first piston 48, in this
case, a 10 to 1 reduction.
[0089] Continuing with this example, the movement of the first
piston 48 a distance of 10.sup.-3 m, which is equal to the movement
of the second piston 50, causes the second piston 50 to force
(10.sup.-3 m)(10.sup.-5 m.sup.2)=10.sup.-8 m.sup.3 or 0.01 ml of
injectate to exit the to 1 reduction in volume injected. If two
such reducers are connected in series, the reduction multiplies,
becoming a 100 to 1 reduction.
[0090] This reducer 40 is particularly advantageous when used in
conjunction with an automatic injection machine. These machines are
expensive and only the most recent models are capable of measuring
and delivering microinjections. The reducer 40 of the present
invention allows both models to perform microinjections. This
obviates the need to replace an expensive machine with an even more
expensive machine.
[0091] These machines typically require an operator to enter a
desired injectate volume into a computerized control board. The
control board then calculates the linear distance that an automated
piston should travel to force the desired volume of injectate or
similar liquid through a catheter, and can do so with precise
pressure control. However, with many machines, especially older
models, there is a lower limit on the injectate volume that may be
entered, making microinjections impossible. The reducer 40 makes
microinjections with these machines possible.
[0092] Using the reducer 40 not only allows the machine to deliver
smaller amounts of injectate than previously possible, it
bifurcates the catheter into a hydraulic side feeding the first
chamber 44 and an injectate side, downstream of the second chamber
46. This allows the use of water or similar, preferably
incompressible and inexpensive, fluid to be used to force the
expensive injectate into the patient.
[0093] Notably, that portion of the catheter between the patient
and the reducer catheter must be filled with the desired injectate
and free of air bubbles prior to operating the machine to avoid
forcing gas bubbles into the recipient. A bleed valve 41 is
preferably provided which is attached to the second chamber 46 for
venting air therefrom. Additionally, a connection 43 may be
provided so that a vial of medicament may be drawn from by the
second piston 50. The connection 43 may be integral with or
separate from bleed valve 41.
[0094] In addition to the weeping needles and reducers described
above, it is also desired to be able to create a cloud of injectate
or medicament in vivo. This cloud can be shaped to target a
specifically shaped tumor or other spatial pattern, or provide a
relatively uniform area of delivery of such injectates as steroids
or local anesthetics. In order to create such a cloud, it may be
desired to allow the injectate to flow from the needle at a higher
rate such that a stream is produced, thereby propelling the
injectate into the surrounding tissues. Attention is now directed
to the remaining FIGURES which show just a few of the envisioned
arrangements.
[0095] FIG. 6 shows an elongate member 60 having a sharpened tip 62
at its distal end and defining a central lumen 64 and a plurality
of holes 66 extending through the side wall of the member 60 to the
central lumen 64. The sharpened tip 62 is shown as defining a small
end hole 68 extending through to the central lumen 64, but could
have more open, or could be closed depending on the desired cloud
shape. It is understood that the components and holes of the
present embodiments could be any size suitable to the intended
uses. End holes 68 having diameters on the order of 0.002-0.008"
have been particularly effective.
[0096] It can be seen that holes 66 increase in diameter toward the
distal end. This creates a pressure gradient which results in a
relatively uniform cloud shape. As injectate is forced through the
needle-like member 60, a pressure drop is felt across each hole 66
as some of the injectate is lost. Increasing the size of the holes
66 in relation to their proximally adjacent neighboring holes 66
accounts for this pressure drop and maintains a relatively constant
flow rate by increasing the size of the stream through each
subsequent hole 66. On the other hand, if it is desired to create a
cloud which has a larger proximal end and a smaller distal end,
holes 66 of a relatively uniform diameter can be used. Altering the
size, shape, density, angle of drilling will permit any arbitrary
shape of injectate deposition.
[0097] FIG. 7 shows an elongate member 60 having a closed tip 62
and a plurality of holes 66 which are positioned to wrap around the
member 60 to form a spiral. Like all of the holes 66, they lead
into the central lumen 64. The resulting cloud shape formed when
using this embodiment of the elongate member 60 is a helical
ribbon. An example of a cloud having a ribbon shape is shown in
FIG. 20. Positive results have been obtained using 23 and 25.5
gauge needles having spaces between the holes 66 of approximately
0.01". This shape has been combined with one or more end holes 68
of 0.0047".
[0098] FIGS. 8 and 9 show diagrammatic depictions of resulting
cloud shapes for respectively given hole patterns. The hole pattern
in FIG. 8 is a single line of holes 66 extending down one side of
the member 60. The holes 66 increase in diameter as they approach
the tip 62 in order to create a relatively uniform flow rate
through each hole. The resulting cloud shape is roughly a cylinder,
shown in FIG. 8 in phantom lines and given the number 68 for
clarity. It can be seen that the cloud 68 has a central axis which
is roughly parallel to but laterally offset from the central axis
70 of the member 60.
[0099] FIG. 9 shows another cloud shape or pattern 72. The holes 66
in the member 60 are, again, increasing in diameter as they
approach the distal tip 62. However, these holes 66 are constructed
and arranged in a relatively uniform pattern around side wall of
the member 60. The cloud pattern 72 results in a cylinder which is
relatively concentric with the member 60.
[0100] It is now clear to one skilled in the art that an infinite
number of cloud patterns can be achieved by following the teachings
of the present invention and varying the size and locations of the
holes 66 along the length of the member 60. For example, if it is
desired to project a cloud of injectate in a distal or proximal
direction, relative to the placement of the hole 66 from which the
cloud is being projected, the hole 66 may be formed in the member
60 such that it has a central axis 74 which forms an acute or
obtuse angle a to the central axis 70 of the member 60. FIG. 10
shows such a configuration. The cloud 75 created is somewhat
conical as it is created by a single hole 66. As seen in FIG. 10,
it may be possible to create a large cloud with a relatively short
member 60 by combining holes 66 having axes 74a and 74c with obtuse
and acute angles .alpha. to the central axis 70 with a hole 66b
having an axis 74b which is perpendicular to the central axis 70.
The resulting clouds 75a, 75b, and 75c combine to create a cloud 75
which is large given the relatively close proximity of the holes
66a, 66b and 66c.
[0101] Alternatively, it may be desired to focus more than one
stream of injectate at a common target site, thereby increasing the
concentration of injectate at the site. FIG. 21 shows three holes
66 angled such that their streams are aimed to converge on a
specific target site, thereby forming a very concentrated cloud of
injectate 75. Notably, the holes 66 may be shaped to focus, or
diffuse, more efficiently by tapering the sides of the holes such
that the diameter of the hole increases or decreases as it extends
from the inner lumen to the outer surface of the needle or
catheter.
[0102] More versatility is achieved when the member 60 is coupled
with a flow manipulating device such as a sheath or a stylet. FIGS.
11-16 show various embodiments where the flow from member 60 is can
be altered during use by the use of such a flow manipulating
device.
[0103] FIG. 11 depicts a sharpened member 60 which has a sheath 76
slideably disposed over the member 60. The inner dimensions of the
sheath 76 closely match the outer dimensions of the member 60 such
that when the sheath 76 over one of the holes 66, the hole is
occluded and substantially no injectate is allowed to flow
therefrom. It can be seen that sheath 76 is slideable from a
proximal position 78, whereby an open distal end 80 of the sheath
76 is proximally displaced from the holes 66, to a distal position
82 whereby the distal end 80 is distally displaced from the most
distal hole 66. Preferably, the open distal end 80 is defined by a
tapered section 81, thereby preventing damage to surrounding tissue
when the sheath 76 is slid distally. If a solid sheath 76 is used,
all of the holes 66 will by occluded when the sheath 76 is in the
distal position 82. Alternatively, as is shown in FIG. 11, one or
more openings 84 may be defined by the sheath 76. The opening 84
may be sized to allow fluid to flow from a predetermined number of
holes 66 while some or all of the other holes 66 remain
occluded.
[0104] FIG. 12 shows an alternative embodiment wherein two pieces
are used in combination to manipulate flow patterns during use.
Member 60 has a closed sharpened tip 62 and a plurality of holes
66. A stylet 90 is slideably received within the central lumen 64
of the member 60. The stylet 90 comprises a distal end 92 and its
own inner lumen 94 through which fluid may be introduced to the
elongate member 60. The stylet 90 also comprises at least one
opening 96 defined either by its side wall 98 or by its distal end
92. An elongate opening 96 extends relatively parallel to the
central axis of the stylet 90. Again, the stylet 90, like the
aforementioned sheath 76, is moveable from a proximal position 100
to a distal position 102. In the proximal position 100, the distal
end 92 of the stylet 90 is proximally displaced from the distal
most hole 66. In the distal position 102, the distal end 92 of the
stylet 90 is distally displaced from the distal most hole 66.
Moving the stylet 90 from the proximal position 100 to the distal
position 102 will have widely varying effects on the resulting
cloud shape based on the position, size, and shape of the opening
96. This will be demonstrated in more detail below.
[0105] The stylet 90 has an outer diameter which is substantially
equal to the inner diameter of the central lumen 64 of the elongate
member 60. This ensures that fluid does not leak from the opening
96 until the opening 96 is in line with one of the plurality of
holes 66. Looking at FIG. 12, given the shape and size of the
opening 96 and the locations of the holes 66, it can be seen that
when the stylet 90 is in the proximal position 100, the elongate
opening 96 is proximally displaced from the hole 66 so that no
fluid is allowed to flow therethrough. As the stylet 90 is advanced
from the proximal position 100 to the distal position 102, the
elongate opening 96 begins to uncover the plurality of holes 66 and
a cloud shape begins to result. The cloud grows in length distally
as the stylet 90 is advanced until the stylet 90 achieves the
distal position 102 whereby all of the plurality of holes 66 are
uncovered and emitting fluid or injectate.
[0106] FIG. 13 shows a different arrangement which will have a
drastically different effect. It can be seen that the stylet 90 of
this embodiment defines no holes in the side wall 98, but that the
central lumen 94 passes through the stylet to an opening 96 in the
distal end 92. In this arrangement, when the stylet 90 is in the
proximal position 100, whereby the distal end 92 is proximally
displaced from the proximal most hole 66, fluid is allowed to flow
through the stylet 90 and all of the plurality of holes 66. As the
stylet is advanced to the distal position 102, the holes become
occluded by the side wall 98 of the stylet 90. Once the stylet 90
achieves the distal position 102, all of the plurality of holes 66
are covered or occluded. FIG. 13 shows an embodiment, similarly
shown in FIG. 6, where distal openings 68 may be defined by the
elongate member 60. Therefore, when the stylet 90 achieves the
distal position 102, fluid is still allowed to pass through the
hole 68. However, if it is desired to prevent all fluid from
flowing through elongate member 60 when the stylet has achieved the
distal position 102, the sharpened tip 62 may be solid so that the
stylet 90 would not allow any fluid to flow through the elongate
member 60 when it achieves the distal position 102.
[0107] Some configurations, such as that shown in FIG. 12, require
that the shaped opening 96 is aligned with the plurality of holes
66. In other words, if the stylet were to be rotated in one
direction or another, the elongate opening 96 may not align with
any of the plurality of holes 66 and therefore would not function.
It may be desired to provide a key 100 which protrudes from the
side wall 98 of the stylet 90 and aligns with a slot 102 defined by
the elongate member 60. Alternatively, it may be desired to
controllably allow both longitudinal and rotational relative
movement between the member 60 and the stylet 90 or sheath 76. To
provide more control, a frictional threading (not shown) may be
provided between the two.
[0108] FIGS. 15 and 16 show how a twisting motion of stylet 90 can
be used advantageously. FIG. 15 shows a stylet 90 having an opening
96 defined by its side wall 98 which increases in width toward its
distal end 92. When used with an elongate member 60 having a line
of holes 66, the stylet 90 can be twisted to increase the number of
holes 66 that become aligned with the opening 96. This stylet 90
may operably remain in a most distal position, as shown. The stylet
90 is shown in a position whereby the opening 96 is angularly
displaced from the plurality of holes 66. However, if the stylet
were rotated in a direction as indicated by arrow 104, the distal
most hole 66 would be the first to be opened followed quickly by
the adjacent holes in a proximal direction until all of the holes
66 were open. This configuration gives a physician a great deal of
control as to the number of holes 66 that are allowed to emit
injectate.
[0109] FIG. 16 shows how this twisting arrangement may be
incorporated on an elongate member-sheath configuration as was
described above. It can be seen that an elongate member 60 is
provided with a sharpened tip 62 and a sheath 76 rotatably disposed
thereon. Sheath 76 defines an opening 84 which has a wider proximal
end and a narrower distal end. A plurality of holes 66 is shown in
phantom beneath the sheath 76. As the sheath 76 is rotated relative
to the member 60 in a direction as indicated by arrow 106, the
opening 84 begins to uncover the holes 66 starting with the
proximate-most hole and eventually uncovering all of the holes 66.
Indicator marks 108 are shown at the proximal end of the sheath 76.
The indicator marks 108, used in conjunction with a position arrow
110, indicate to the physician how many holes 66 are uncovered. A
similar indicator 114 is shown in FIG. 14 which is configured for
one of the sliding embodiments shown herein. The markings on the
stylet 98 indicate the number of holes 66 which remain open or
closed, depending on the configuration of the stylet 98.
Alternatively, it is envisioned to provide radiopaque markers (not
shown) on the needle itself such that the needle could be
visualized and its position ascertained in vivo.
[0110] One skilled in the art will quickly realize that the
flexibility provided by various shaped opening and variously placed
holes 66 will allow an infinite number of variations in order to
achieve any desired cloud shape or sequence of hole uncoverings as
one member is slid or rotated against another member to uncover or
occlude desired holes.
[0111] One problem which has not been addressed involves back
pressure caused by adjacent tissue into which fluid is being
injected. This is especially cumbersome at low injection flow
rates. In order to provide more space for injectate to flow,
thereby reducing back pressure, scoring 112 may be provided on the
outer surface of the elongate member 60 adjacent the holes 66. This
is seen in FIG. 17.
[0112] FIG. 18 shows a graph of a pressure waveform 120 which may
be used to further enhance the perfusion of an injectate into a
fibrous tissue such as the myocardium. An initial pressure spike
122 is provided which is of sufficient force, such as 50 to 300
mmHg but not limited thereto, to pretreat or prepare the tissue for
injectate reception. In other words, the hydraulic pressure of
fluid exiting from the needle will locally raise the tissue
pressure where the needle holes are located. By controlling the
pressure of the needle, tissue pressure can be controlled. This is
important because tissue pressure may be used to determine where
the injectate flows into the tissue. For example, a rapid increase
in myocardial tissue may separate the muscle bundles from the
connective stromal tissue, so that fluid flows selectively into the
interstitial regions rather than the cellular areas. The waveform
120, having at least one spike 122 followed by a lower pressure
level 124, can create such an effect. It may be desired to provide
a subsequent spike 122, as shown, to reopen or separate the muscle
bundles if necessary.
[0113] It is noted that, though the various embodiments described
above place an emphasis on the use of a needle at the distal end of
the devices, the various principles taught herein also apply to a
catheter without a needle. Thus, the term elongate member 60 has
been used to encompass needles, catheters, and similar
lumen-defining elongate devices suitable for use in the body. A
specific example of an elongate member 60 without a needle is shown
in FIG. 26. Provided is a flexible, catheter-style elongate member
60 comprising a generally conical or somewhat pointed tip 62 at its
distal end and defining a central lumen 64 and a plurality of holes
66 extending through the side wall of the member 60 to the central
lumen 64. The tip may or may not include a small hole 66.
[0114] In a preferred embodiment, the tip 62 is constructed of a
soft durometer plastic which accommodates a guidewire 140 passing
therethrough. The plastic is chosen such that when the member 60 is
in a desired position, the guidewire 140 may be removed and the
plastic seals itself, thereby leaving a substantially solid tip
62.
[0115] Also shown in FIG. 26 is an embodiment whereby the elongate
member 60 is a catheter or similar device of substantial length,
such as between 10 and 70 centimeters, or any length suitable for
use in vivo, with holes 66 occurring over substantially the entire
length. Such an embodiment is particularly useful for operations
involve blood clots in longer blood vessels such as those found in
the legs.
[0116] In a related embodiment, the invention method comprises
inserting the distal portion of the invention needle into an
interior body wall or tissue of the subject and applying sufficient
pressure to a liquid medicament in fluid communication with the
distal portion of the needle to expel a therapeutic amount of the
medicament such that the medicament weeps multidirectionally from
the pores in the distal portion thereof into the interior body wall
or tissue without substantial leakage or loss of the medicament at
the surface of the body wall. The body wall can be located within a
natural body cavity or any opening.
[0117] The invention method utilizing the needle with weeping tip
is particularly useful for injection of medicaments into the wall
of an interior organ that is subject to motion during the injection
procedure, for example, the wall of a beating heart of adjacent
arterial walls during electrophysiologic testing, transmyocardial
revascularization, and the like. Additional internal organs subject
to movement into which injections can be made using the invention
methods include the stomach, esophagus, gallbladder, liver, bowel,
kidney, lung, and the like.
[0118] The embodiment utilizing a weeping, or porous needle is more
thoroughly described in U.S. patent application Ser. No.
09/468,689, filed Dec. 20, 1999 and Ser. No. 09/829,022, filed Apr.
9, 2001, and is incorporated by reference herein.
[0119] Furthermore, in order to determine if a multi-holed needle
would better distribute the angiogenic factors, the flow patterns
of the diffusionary needle have been analyzed and the findings used
to develop a method for determining the optimal design given
experimentally defined flow velocities. The optimal design for
angiogenic applications involves a constant flow of angiogenic
fluid along the porous length of the needle, thereby providing an
even factor distribution.
[0120] Multiple holes on the shaft of the needle proved effective
in improving the distribution of the injectate (a contrast agent
was used for analysis purposes) but had shortcomings in that the
holes did not deliver the material equally to the area around the
holed section of the needle. A conclusion was made that this was
due to at least two problems: a small and uneven distribution of
holes on the shaft of the needle and an unequal flow through the
holes on the needle depending on their relative locations. A
mathematical analysis was performed to determine the validity of
this conclusion.
[0121] The analysis applied to a needle having a closed distal end
and holes located only along the shaft near the distal end of the
needle. Generally, a pressure drop through any constant inner
diameter tube is characterized by Poiseuille's equation: 1 P x = -
128 Q d 4 ( 1 )
[0122] where P is pressure, x is the distance along the holed
section of the needle, .mu. is viscosity, Q is flow, and d is the
inner diameter of the tube or needle. Additionally, because the
tube is porous, flow constantly decreases down the porous or holed
section of the tube. Assuming that the holes on the side of the
tube are arranged in such a manner that the porous section is
equally porous along the entire length, the pressure drop through
the porous tube becomes: 2 P x = - 128 Q d 4 ( 1 - x l ) ( 2 )
[0123] wherein l is the length of the porous section of the needle.
Pressure, as a function of distance, x, becomes: 3 p o p P = - 128
Q d 4 0 x ( 1 - x l ) x ( 3 ) P ( x ) = P o - 128 Q d 4 ( x - x 2 2
l ) ( 4 )
[0124] Equation 4 then gives the pressure drop along the porous
section of a tube, or the section of the needle with holes along
the shaft. Assuming that the flow from the porous section of the
needle is constant and equal along the length, l, of the porous
section, the velocity, v, of the fluid flowing out of the hole can
be calculated using Torricelli's formula, which is Bemoulli's
equation simplified to apply to a draining tank:
v=C.sub.viscous{square root}{square root over (2gH)} (5)
[0125] where C.sub.visous is a coefficient accounting for
frictional losses, g is gravity, and H is the height of the
draining tank. This draining tank formula can be manipulated to
apply to fluid being forced through a needle by acknowledging that:
4 P = gH or gH = P ( 6 )
[0126] so that the velocity, v, of flow through a hole can be
represented by: 5 v = C viscous 2 P . ( 7 )
[0127] Knowing the velocity, v, of fluid flowing through a hole,
the flow rate, q, through a cross-section of porous material, such
as that of the needle, is calculated as:
q=C.sub.contraction.nu.A or q=C.sub.contraction.nu.(n.pi.r.sup.2)
(8)
[0128] where q is cross-sectional flow, A is the area of the
hole(s), n is the number of holes at the particular cross-section
(number of holes per unit length), r is the radius of the hole(s),
and C.sub.contraction is a contraction coefficient account for a
fluid jet's tendency to contract or curve from the sharp orifice,
or hole edge.
[0129] The cross-sectional flow, q, then becomes: 6 q = C
contraction C viscous 2 P ( n r 2 ) . ( 9 )
[0130] One can define a discharge coefficient C.sub.discharge as
the product of the C.sub.contraction and C.sub.viscous.
[0131] Assuming that flow from the needle at any given
cross-sectional area is constant throughout the length of the holed
portion of the needle, then:
ql=Q (10).
[0132] Rearranging and combining Equations 7, 9, and 10 provides: 7
n = Q r 2 lC discharge 2 P ( 11 )
[0133] In so far as pressure, P, has been defined as a function of
distance in Equation 4, the number of holes, n, as a function of
distance for a desired flow rate can be represented by: 8 n ( x ) =
Q r 2 lC discharge 2 [ P o - 128 Q d 4 ( x - x 2 2 l ) ] ( 12 )
[0134] Equation 9 then gives the concentration of holes at
positions along the porous section of the needle needed to obtain
constant and equal flow along the entire holed portion of the
needle. An alternative method of obtaining this equal and constant
flow is to keep hole concentration constant and just change the
size of the holes as a function of position. Simply rearranging
Equation 9 and solving for radius, r, as a function of distance
provides: 9 r ( x ) = Q n lC discharge 2 [ P o - 128 Q d 4 ( x - x
2 2 l ) ] . ( 13 )
[0135] Thus, it is shown that the net exit of injectate as a
function of length along the needle can be controlled by varying
the size of holes or by utilizing a differing density of the same
sized hole along the length of the needle/catheter. This variation
in hole density can create any pattern of injectate also, as
previously disclosed. Such a pattern of hole density can be used
primarily to cause a constant injectate per unit of needle length.
With additional variations, the pattern can be adjusted to create
any desired injectate pattern around the needle. The outcome of
this design is to permit concentration control of the
injectate.
[0136] The mathematical findings were applied to a specific
embodiment of the present invention in order to obtain the
following results:
[0137] The specific embodiment used a flow rate, Q, of 1.5
cm.sup.3/s, an inner diameter, d, of 0.04064 cm, which is the inner
diameter of a 22-gauge needle, and porous length, l, of 1 cm. Given
the low molecular weight of proteins and genes suspended in saline
solution, viscosity, .mu., and density, .rho., of the angiogenic
fluid was approximated to that of water at 40.degree. C. The hole
radius, r, was set at 25 microns, which is the lower limit of the
hole size that a laser can create. This hole size was selected
because it represents the lower limit and, therefore, larger
pressures would be needed to force the same amount of fluid through
it, thereby creating larger maximum velocities through the holes.
The viscous coefficient, C.sub.viscous, which accounts for
frictional losses was assumed to be 0.95, a 5% loss. The
contraction coefficient, C.sub.contract, for a sharp edged orifice
is 0.61, therefore the discharge coefficient, C.sub.discharge is
0.58.
[0138] The ideal design or placement of the optimal number of holes
in the optimal position is dependent on the desired maximum
velocity leaving the holes. It is clear, from equations 4 and 7,
that the pressure before the beginning of the porous section of the
needle, P.sub.o, will be determined by the desired velocity, v.
P.sub.o is then related to the pressure at the pump required to
generate this ideal velocity for a given flow rate by Poiseuille's
law. The linear pressure drop along the catheter, although small
because of the small diameter of the catheter, must be taken into
account when programming into the power injector.
[0139] Plot 1 shows the number of holes per centimeter at
one-millimeter intervals along the length of the porous section of
the needle for four different maximum velocities. This plot is an
example of a determination of the optimal design for four given
values of
[0140] Vmax:
[0141] An additional consideration when designing the optimal
needle is that if the pressure is too low, the number of holes
required to maintain constant flow may exceed the number of holes
that can fit on the needle without creating the risk that the
needle could break off in the patient. In order to maintain the
structural integrity of the needle, the porosity is kept under 20%.
By requiring two diameters of steel for every 1 hole diameter, the
geometric maximum number of holes per centimeter for a 22-gauge
needle with 50 micron diameter holes is 560. Looking at Plot 1,
Vmax=400 cm/s exceeds the geometric limit and therefore cannot be
considered a viable design.
[0142] Plot 2 shows that if pressure exceeds 7.3 psi, the number of
holes per centimeter not only decreases, but becomes constant over
the length of the porous section:
[0143] Recalling Equation 13, hole arrangement or concentration as
a function of position could be held constant and hole size could
be varied. Though manufacturing costs may decrease if hole size is
kept constant, as shown above, there are many embodiments where
hole location is crucial, such as those involving strategic
occlusion.
[0144] Therefore, using Equation 13 and keeping the remaining
variables the same, the number of holes per centimeter is fixed,
for purposes of this analysis, at 160. The results, though more
difficult to notice, show that an increase in radius of the hole
size is necessary to maintain constant flow, as show in Plot 3. As
was the case above, when the number of holes varied, Plot 3 shows
that increasing the pressure beyond a value of 145 psi produces a
constant radius of holes. Again geometric constraints must be
considered.
[0145] While the invention has been described in detail with
reference to certain preferred embodiments thereof, it will be
understood that modifications and variations are within the spirit
and scope of that which is described and claimed.
1 1. TABLE OF REFERENCES Total Page and line Element(s) Reference
count locations flange 10 1 Page 13 line 13 proximal position 100 6
Page 24 line 8 Page 24 line 9 Page 24 line 12 Page 24 line 19 Page
24 line 21 Page 24 line 29 position 102 10 Page 24 line 9 Page 24
line 10 Page 24 line 12 Page 24 line 22 Page 24 line 24 Page 25
line 2 Page 25 line 3 Page 25 line 6 Page 25 line 8 Page 25 line 9
distal position 102 10 Page 24 line 9 Page 24 line 10 Page 24 line
12 Page 24 line 21 Page 24 line 24 Page 25 line 1 Page 25 line 3
Page 25 line 5 Page 25 line 8 Page 25 line 9 arrow 104 1 Page 25
line 23 arrow 106 1 Page 26 line 3 indicator marks 108 2 Page 26
line 5 Page 26 line 6 position arrow 110 1 Page 26 line 6 scoring
112 1 Page 26 line 18 Injectate 12 1 Page 14 line 5 lumen 14 1 Page
14 line 8 catheter 16 1 Page 14 line 8 insulator 18 1 Page 14 line
16 connector 19 1 Page 14 line 16 needle 2 6 Page 14 line 3 Page 14
line 6 Page 14 line 7 Page 14 line 9 Page 14 line 9 Page 16 line 24
lead 20 1 Page 14 line 17 assemblage 22 1 Page 16 line 24 needle 24
1 Page 16 line 24 catheter 26 2 Page 16 line 25 Page 16 line 27
distal portion 28 2 Page 16 line 26 Page 16 line 26 Injectate 30 1
Page 16 line 26 housing 42 6 Page 18 line 24 Page 19 line 1 Page 19
line 4 Page 19 line 6 Page 19 line 26 Page 19 line 28 Component 42a
2 Page 19 line 29 Page 20 line 9 component 42b 5 Page 19 line 30
Page 20 line 2 Page 20 line 9 Page 20 line 11 Page 20 line 14 first
chamber 44 11 Page 18 line 25 Page 18 line 26 Page 18 line 27 Page
19 line 1 Page 20 line 16 Page 20 line 18 Page 20 line 21 Page 20
line 23 Page 20 line 25 Page 20 line 27 Page 21 line 19 second
chamber 46 5 Page 18 line 25 Page 18 line 28 Page 19 line 5 Page 20
line 21 Page 21 line 19 first piston 48 13 Page 18 line 26 Page 19
line 9 Page 19 line 10 Page 19 line 12 Page 19 line 15 Page 19 line
19 Page 19 line 20 Page 19 line 23 Page 19 line 25 Page 19 line 26
Page 20 line 27 Page 20 line 29 Page 21 line 1 rod 51 3 Page 19
line 11 Page 20 line 1 Page 20 line 11 proximal opening 52 2 Page
19 line 1 Page 20 line 22 Vents 53 4 Page 19 line 18 Page 19 line
19 Page 19 line 25 Page 19 line 27 distal opening 54 1 Page 19 line
4 stop 55 2 Page 19 line 20 Page 19 line 22 connector 57 1 Page 20
line 5 distal portion 6 1 Page 14 line 4 elongate member 60 12 Page
22 line 1 Page 22 line 14 Page 22 line 17 Page 24 line 5 Page 24
line 16 Page 25 line 5 Page 25 line 7 Page 25 line 9 Page 25 line
15 Page 25 line 18 Page 25 line 28 Page 26 line 18 tip 62 8 Page 22
line 1 Page 22 line 3 Page 22 line 14 Page 22 line 21 Page 22 line
26 Page 24 line 2 Page 25 line 8 Page 25 line 29 lumen 64 6 Page 22
line 2 Page 22 line 3 Page 22 line 4 Page 22 line 16 Page 24 line 3
Page 24 line 16 holes 66 40 Page 22 line 2 Page 22 line 6 Page 22
line 9 Page 22 line 10 Page 22 line 13 Page 22 line 14 Page 22 line
15 Page 22 line 19 Page 22 line 20 Page 22 line 25 Page 22 line 26
Page 23 line 3 Page 23 line 9 Page 23 line 13 Page 23 line 20 Page
23 line 23 Page 23 line 25 Page 23 line 27 Page 23 line 28 Page 24
line 3 Page 24 line 17 Page 24 line 19 Page 24 line 22 Page 24 line
24 Page 25 line 1 Page 25 line 3 Page 25 line 11 Page 25 line 13
Page 25 line 19 Page 25 line 19 Page 25 line 22 Page 25 line 25
Page 25 line 26 Page 26 line 2 Page 26 line 4 Page 26 line 5 Page
26 line 7 Page 26 line 9 Page 26 line 12 Page 26 line 19 hole 66 12
Page 22 line 8 Page 22 line 11 Page 23 line 5 Page 23 line 5 Page
23 line 8 Page 23 line 10 Page 23 line 24 Page 24 line 10 Page 24
line 11 Page 24 line 20 Page 24 line 30 Page 25 line 23 cloud 68 1
Page 22 line 23 central axis 70 4 Page 22 line 24 Page 23 line 6
Page 23 line 10 Page 23 line 11 cloud pattern 72 1 Page 22 line 28
central axis 74 1 Page 23 line 6 cloud 75 2 Page 23 line 7 Page 23
line 12 sheath 76 14 Page 23 line 18 Page 23 line 19 Page 23 line
20 Page 23 line 22 Page 23 line 23 Page 23 line 24 Page 23 line 25
Page 23 line 26 Page 24 line 8 Page 25 line 29 Page 26 line 1 Page
26 line 2 Page 26 line 2 Page 26 line 6 proximal position 78 1 Page
23 line 22 tip 8 2 Page 14 line 5 Page 14 line 6 distal end 80 2
Page 23 line 22 Page 23 line 23 distal position 82 2 Page 23 line
23 Page 23 line 25 openings 84 1 Page 23 line 26 opening 84 3 Page
23 line 27 Page 26 line 1 Page 26 line 3 stylet 90 26 Page 24 line
3 Page 24 line 4 Page 24 line 5 Page 24 line 7 Page 24 line 8 Page
24 line 9 Page 24 line 11 Page 24 line 11 Page 24 line 15 Page 24
line 19 Page 24 line 21 Page 24 line 23 Page 24 line 24 Page 24
line 27 Page 24 line 29 Page 25 line 1 Page 25 line 2 Page 25 line
2 Page 25 line 5 Page 25 line 8 Page 25 line 14 Page 25 line 16
Page 25 line 17 Page 25 line 19 Page 25 line 20 Page 25 line 21
distal end 92 7 Page 24 line 4 Page 24 line 6 Page 24 line 9 Page
24 line 10 Page 24 line 28 Page 24 line 29 Page 25 line 18 inner
lumen 94 1 Page 24 line 4 opening 96 14 Page 24 line 6 Page 24 line
7 Page 24 line 13 Page 24 line 17 Page 24 line 17 Page 24 line 18
Page 24 line 20 Page 24 line 22 Page 24 line 28 Page 25 line 11
Page 25 line 12 Page 25 line 17 Page 25 line 20 Page 25 line 22
side wall 98 5 Page 24 line 6 Page 24 line 27 Page 25 line 2 Page
25 line 14 Page 25 line 17
* * * * *