U.S. patent application number 16/046525 was filed with the patent office on 2018-12-27 for drug delivery apparatus.
This patent application is currently assigned to RENISHAW (IRELAND) LIMITED. The applicant listed for this patent is RENISHAW (IRELAND) LIMITED. Invention is credited to Steven Streatfield GILL, David Roberts MCMURTRY, Maxwell Roy WOOLLEY.
Application Number | 20180369555 16/046525 |
Document ID | / |
Family ID | 45896737 |
Filed Date | 2018-12-27 |
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United States Patent
Application |
20180369555 |
Kind Code |
A1 |
WOOLLEY; Maxwell Roy ; et
al. |
December 27, 2018 |
DRUG DELIVERY APPARATUS
Abstract
Percutaneous access apparatus is described that comprises a
percutaneous fluid access device having an extracorporeal portion,
one or more ports accessible from the extracorporeal portion and a
septum for sealing each port. A connector device comprising one or
more hollow needles is attachable to the percutaneous fluid access
device. The apparatus also includes an attachment mechanism for
attaching the connector device to the extracorporeal portion and an
actuation mechanism that, after the connector device has been
attached to the extracorporeal portion, can be used to drive the
one or more hollow needles through the septum to establish fluid
communication between the one or more hollow needles and the one or
more ports. The apparatus may be used for neurosurgery
applications.
Inventors: |
WOOLLEY; Maxwell Roy;
(Bristol, GB) ; MCMURTRY; David Roberts;
(Stancombe, GB) ; GILL; Steven Streatfield;
(Bristol, GB) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
RENISHAW (IRELAND) LIMITED |
Swords |
|
IE |
|
|
Assignee: |
RENISHAW (IRELAND) LIMITED
Swords
IE
|
Family ID: |
45896737 |
Appl. No.: |
16/046525 |
Filed: |
July 26, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14374362 |
Jul 24, 2014 |
10086187 |
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PCT/EP2013/052458 |
Feb 7, 2013 |
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16046525 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 2039/0282 20130101;
A61M 39/04 20130101; A61M 39/105 20130101; A61M 2039/0288 20130101;
A61M 2210/0693 20130101; A61M 39/1011 20130101; A61M 2039/0205
20130101; A61M 2039/009 20130101; A61M 2039/1033 20130101; A61B
17/3403 20130101; A61M 2039/0264 20130101; A61M 39/0247 20130101;
A61M 39/10 20130101; A61M 2039/0261 20130101; A61M 2039/0276
20130101; A61M 2039/1044 20130101; A61M 2039/027 20130101; A61M
2039/0081 20130101; A61M 2039/042 20130101; A61M 2039/025
20130101 |
International
Class: |
A61M 39/02 20060101
A61M039/02 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 7, 2012 |
GB |
1202091.3 |
Claims
1-15. (canceled)
16. A fluid connector device for providing a fluidic connection
with a percutaneous fluid access device having a plurality of
ports, the fluid connector device comprising: a connector body
having a first axis; a plurality of hollow needles, each hollow
needle of the plurality of hollow needles having a longitudinal
axis that is aligned to be substantially parallel to the first
axis; and at least one needle guide configured to enable the
plurality of hollow needles to be translated back and forth
relative to the connector body along the first axis.
17. A fluid connector device according to claim 16, comprising a
needle holder for holding the plurality of needles.
18. A fluid connector device according to claim 17, wherein the at
least one needle guide comprises an axial alignment channel formed
within the connector body for guiding the needle holder back and
forth along the first axis.
19. A fluid connector device according to claim 16, wherein the at
least one needle guide is detachable from the connector body.
20. A fluid connector device according to claim 16, comprising an
actuation mechanism to drive the plurality of hollow needles back
and forth along the first axis.
21. A fluid connector device according to claim 20, wherein at
least part of the actuation mechanism is detachable from the
connector body.
22. A fluid connector device according to claim 16, comprising an
attachment mechanism configured to secure the fluid connector
device to an extracorporeal portion of the associated percutaneous
fluid access device.
23. A fluid connector device according to claim 22, wherein the
attachment mechanism is configured to provide repeatable alignment
of the connector body with the extracorporeal portion of the
associated percutaneous fluid access device
24. A fluid connector device according to claim 23, wherein the
associated percutaneous fluid access device comprises a plurality
of ports and the attachment mechanism allows a repeatable alignment
of each hollow needle with a predetermined one of the ports.
25. A fluid connector device according to claim 22, wherein the
attachment mechanism comprises an indicator to indicate that the
fluid connector device has been securely attached to the
extracorporeal portion.
26. A fluid connector device according to claim 22, comprising an
actuation mechanism to drive the plurality of hollow needles back
and forth along the first axis, wherein the actuation mechanism is
configured to drive the needles into engagement with the associated
percutaneous fluid access device after the fluid connector device
has been secured to the extracorporeal portion by the attachment
mechanism.
27. A fluid connector device according to claim 16, wherein the
plurality of hollow needles comprises at least four hollow
needles.
28. A neurosurgical fluid delivery apparatus comprising a
percutaneous fluid access device having a plurality of ports and a
fluid connector device for providing a fluidic connection with the
plurality of ports of the percutaneous fluid access device, wherein
the fluid connector device comprises: a connector body having a
first axis; a plurality of hollow needles, each hollow needle of
the plurality of hollow needles having a longitudinal axis that is
aligned to be substantially parallel to the first axis; and at
least one needle guide configured to enable the plurality of hollow
needles to be translated back and forth relative to the connector
body along the first axis.
29. An apparatus according to claim 28, wherein the plurality of
ports comprises at least one septum having a septum surface and the
apparatus is configured such that, whilst the fluidic connection is
being established between the fluid connector device and the
percutaneous fluid access device, the first axis of the connector
body is substantially perpendicular to the plane containing the
septum.
30. An apparatus according to claim 28, comprising an attachment
mechanism configured to secure the fluid connector device to an
extracorporeal portion of the percutaneous fluid access device.
31. An apparatus according to claim 30, wherein the attachment
mechanism allows repeatable alignment of each hollow needle of the
plurality of hollow needles with a predetermined one of the
plurality of ports.
32. An apparatus according to claim 28, further comprising at least
one catheter connectable to the percutaneous fluid access
device.
33. A method for delivering fluid to the central nervous system
using a fluid connector device comprising: a connector body having
a first axis, a plurality of hollow needles, each hollow needle of
the plurality of hollow needles having a longitudinal axis that is
aligned to be substantially parallel to the first axis, and at
least one needle guide configured to enable the plurality of hollow
needles to be translated back and forth relative to the connector
body along the first axis, the method comprising the steps of: (i)
connecting the fluid connector device to a percutaneous fluid
access device implanted in a subject to thereby establish a fluidic
connection with the percutaneous fluid access device; and (ii)
passing fluid to the percutaneous fluid access device via the fluid
connector device.
34. A method according to claim 33, wherein the implanted
percutaneous fluid access device is in fluid communication with at
least one catheter and step (ii) comprises delivering fluid to the
central nervous system via the at least one catheter.
35. A method according to claim 34, wherein the fluid delivered in
step (ii) comprises a therapeutic agent for the treatment of a
neurological disease.
Description
[0001] This application is a continuation application of U.S.
patent application Ser. No. 14/374,362 filed Jul. 24, 2014, which
is in turn a U.S. National Stage of International Application No.
PCT/EP2013/052458, filed Feb. 7, 2013, which claims the benefit of
British Patent Application No. 1202091.3 filed Feb. 7, 2012. The
disclosure of the prior applications is hereby incorporated by
reference herein in their entirety.
[0002] The present invention relates to medical apparatus and in
particular to the various components of an apparatus for delivering
fluids, such as drugs, to different parts of the human or animal
body. In one aspect, the present invention relates to a
percutaneous access apparatus that may form part of a drug delivery
apparatus for delivering therapeutic agent to the brain.
[0003] The drug treatment of a number of neuro-degenerative
disorders, hereditary neurological disorders, brain tumours and
other diseases of the nervous system are compromised by the
presence of the blood brain barrier which prevents the transfer of
drugs from the vascular system or cerebrospinal fluid into the
brain substance. Examples of drugs which do not adequately cross
the blood brain barrier include protein molecules such as
neurotrophins, monoclonal antibodies, viral particles for delivery
of gene therapy, as well as a number of cytotoxic drugs for the
treatment of tumours. It has been described previously how such
drugs can be delivered to the brain by direct infusion into the
parenchyma via one or more indwelling catheter. For example, a
guide tube and catheter system is described in U.S. Pat. No.
6,609,020. A catheter with a small external diameter that can be
precisely positioned in the brain is described in WO2003/077785.
Percutaneous access ports have also been described in WO2008/062173
and WO2011/098769.
[0004] According to a first aspect of the present invention, there
is provided percutaneous access apparatus, comprising a
percutaneous fluid access device comprising an extracorporeal
portion, one or more ports accessible from the extracorporeal
portion and a septum for sealing each port, and a connector device
comprising one or more hollow needles, wherein the apparatus
includes an attachment mechanism for attaching the connector device
to the extracorporeal portion and an actuation mechanism that,
after the connector device has been attached to the extracorporeal
portion, can be used to drive the one or more hollow needles
through the septum to establish fluid communication between the one
or more hollow needles and the one or more ports.
[0005] The first aspect of the present invention thus relates to
percutaneous access apparatus. The apparatus comprises two main
components. Firstly, there is the percutaneous fluid access device
that may be implanted within the subject. The percutaneous fluid
access device comprises an extracorporeal portion (i.e. a part of
the device that is located outside of, and protrudes from, the
body), one or more ports that are accessible from the
extracorporeal portion and a septum for sealing each port.
Secondly, a connector device is provided that comprises one or more
hollow needles. The connector device, which remains outside of the
body, can be connected to external fluid pumps or the like and can
also be connected to the percutaneous fluid access device whenever
fluid access is required.
[0006] The percutaneous access apparatus includes an attachment
mechanism for attaching (i.e. securing) the connector device to the
extracorporeal portion. As explained in more detail below, this
attachment mechanism preferably allows the connector device and
extracorporeal portion to be locked or placed together in a precise
and repeatable relative position. An actuation mechanism is also
provided that, after the connector device has been attached to the
extracorporeal portion, can be used to drive the one or more hollow
needles through the septum to establish fluid communication between
the one or more hollow needles and the one or more ports. The
actuation mechanism, which is also described in more detail below,
is preferably manually activated by rotation of a knurled hub or
the like.
[0007] The present invention thus establishes fluid communication
between the connector device and extracorporeal portion of the
percutaneous fluid access device in two stages. The connector
device is firstly attached to the extracorporeal portion of the
percutaneous fluid delivery device (i.e. secured or fixed to the
extracorporeal portion without a fluidic link being established).
After attachment, the actuation mechanism can be used to drive the
tips of the hollow needles through the septum and thus establish a
fluidic link with the associated ports. This arrangement has the
advantage that correct alignment of the connector device with the
ports of the percutaneous fluid access device is provided before
the hollow needles engage the septum. Preferably, the hollow
needles are aligned with an accuracy better than 0.2 mm, more
preferably better than 0.1 mm and even more preferably better than
0.05 mm. This reduces the risk of the hollow needles being damaged
(e.g. bent) or damaging the septum during attachment/removal.
Furthermore, the hollow needles pierce the septum in the same place
each time the fluid connection is established thereby increasing
the lifetime of the septum. The present invention, in one
embodiment, can also protect the clinician from a sharps risk by
only extending the hollow needles after engagement of the connector
device with the extracorporeal portion. A more robust and reliable
percutaneous access apparatus is thereby provided.
[0008] The percutaneous access apparatus of the present invention
has a variety of different applications. It can, for example, be
used to deliver fluid to one or more locations within the brain
parenchyma via suitably implanted catheters. Delivery of
therapeutics, contrast agents and other fluids can be achieved
intermittently through re-accessing the percutaneous fluid access
device, which is conveniently situated in/on the skull of the
subject. The apparatus could, for example, be used to deliver drugs
for indications such as Parkinson's disease, Alzheimer's, oncology
and other neurological diseases. The drug can be used for chronic,
sub-chronic and acute delivery of therapeutics to the patient. It
should also be noted that the apparatus is not only suitable for
human use but could also be used for animals.
[0009] Advantageously, the attachment mechanism includes a first
set of features on the extracorporeal portion. A second set of
features are preferably provided on the connector device. The first
and second sets of features conveniently provide, when engaged,
accurate alignment of the connector device with the extracorporeal
portion. In a preferred embodiment, the attachment mechanism
provides a kinematic or pseudo-kinematic connection between the
extracorporeal portion and the connector device. Providing such a
kinematic or pseudo-kinematic connection, in which each of the six
degrees of freedom of motion between the two bodies is constrained
by a single point of contact, ensures accurate and repeatable
alignment of the extracorporeal portion and the connector device.
For example, the first set of features may include a vertical
groove, a horizontal groove and a conical recess. The second set of
features may include three spaced apart balls. Engagement of the
balls with the grooves and recess can provide such high accuracy,
kinematic, alignment. One or more macro-alignment features may also
be provided to ensure correct general or macro alignment of the
first and second sets of features. The ability to provide
repeatable alignment between the extracorporeal portion and the
connector device is advantageous because it means that the correct
alignment of the one or more hollow needles with the one or more
ports can be ensured.
[0010] After the actuation mechanism has been used to drive the one
or more hollow needles of the connector device into the one or more
ports, at least part of the attachment mechanism and/or at least
part of the actuation mechanism may be detached. For example, the
attachment mechanism may comprise a protruding guide element along
which the connector device is driven by the actuation mechanism.
After the fluid connection has been established, this guide element
may be detached. This allows, for example, a longer guide element
to be used whilst establishing the fluid link (e.g. to make
establishment of such a fluidic link easier for medical personnel)
but for such a guide element to be removed during fluid infusion
(e.g. for patient comfort/convenience). Similarly, the actuation
mechanism may include a mechanism for driving the connector device
toward the port(s) of the percutaneous fluid access device that can
be detached after the necessary fluidic link has been
established.
[0011] The apparatus may comprise one hollow needle and one port;
i.e. single channel percutaneous access apparatus may be provided.
Advantageously, the apparatus comprises a plurality of hollow
needles and a plurality of ports. Preferably, the same number of
hollow needles and ports are provided. In this manner, a plurality
of separate fluid pathways may be provided through the percutaneous
access apparatus. For example, the percutaneous access apparatus
may provide at least two, at least three, at least four or at least
five separate fluid pathways (e.g. it may comprise at least two, at
least three, at least four or at least five hollow needles and
ports). In a preferred embodiment, four separate fluid pathways
(e.g. four needles and four ports) are provided.
[0012] If multiple ports and hollow needles are provided, the
attachment mechanism preferably allows repeatable, preferably
unique, alignment of each hollow needle with a predetermined one of
the ports. In other words, it is preferred that the extracorporeal
portion and the connector device can only be connected together in
a single relative orientation. This ensures that the same hollow
needle always enters the same port and hence reduces the risk of
incorrect fluid connections being established. This is particularly
important if different volumes, or different therapeutic agents,
are to be delivered to different target sites.
[0013] Conveniently, the attachment mechanism comprises a locking
device for releasably locking the connector device to the
extracorporeal portion. In other words, the connector device may be
securely locked to the extracorporeal portion (e.g. during fluid
delivery). The extracorporeal portion may comprise the locking
device. Advantageously, the connector device comprises the locking
device. Providing the locking device as part of the connector
device allows the profile and size of the extracorporeal portion to
be minimised.
[0014] The skilled person would appreciate the numerous ways to
implement a compact and reliable locking device. Advantageously,
the locking device comprises a screw and a hinged engagement
member. Tightening the screw may be used to deflect the hinged
engagement member into contact with the extracorporeal portion
thereby locking the connector device to the extracorporeal portion.
Preferably, the hinge acts as a spring so that releasing the screw
causes disengagement (i.e. it unlocks the connector device from the
extracorporeal portion).
[0015] The attachment mechanism preferably includes an indicator to
indicate that the connector device has been securely attached to
the extracorporeal portion of the percutaneous fluid access device.
This indicator ensures that the user knows when the connector
device has been properly attached and hence that it is possible to
use the actuation mechanism to drive the needles into the septa.
The indicator may be an indicator of any type. For example, it may
be a sensory indicator such as a visual or tactile indicator.
[0016] Advantageously, the connector device comprises a needle
holder for holding the one or more hollow needles. Each hollow
needle may comprise an aperture at its tip. Preferably, each needle
comprises a (solid) sharp tip and an aperture in its side wall. The
needle holder is preferably movable relative to the rest of the
connector device (e.g. it can be moved within the housing or body
of the connector device). When the connector device is attached to
the extracorporeal portion, the needle holder is preferably
moveable relative to the extracorporeal portion. This allows the
hollow needles to be moved into engagement with the ports.
[0017] The needle holder may be located in, and more preferably is
retained within, an axial alignment channel defined by (e.g. formed
within) the connector device. Preferably, the longitudinal axis of
the axial alignment channel is, when the connector device is
attached to the percutaneous fluid access device, substantially
perpendicular to the septum. Advantageously, the needle holder can
be translated back and forth along the axial alignment channel. In
such an arrangement, the longitudinal axes of the one or more
hollow needles of the needle holder are preferably aligned with the
axis of the alignment channel. In this manner, translation of the
needle holder along the alignment channel towards the
extracorporeal surface can drive the one or more needles through
the septum into the one or more ports.
[0018] The actuation mechanism may be used to drive the needle
holder back and forth along the alignment channel. The actuation
mechanism may comprise an elongate shaft with the needle holder
attached to its distal end. The elongate shaft may then be used to
push the needle holder along the alignment channel until the hollow
needles pierce the septum and enter the ports. A stop may be
provided in the connector device to set the depth of needle
penetration into the ports. In a preferred embodiment, the needle
holder is attached to the distal end of a threaded shaft. The
threaded shaft is also preferably retained in the threaded channel
through a rotatable knurled hub. Preferably, rotation of the
knurled hub causes translation of the threaded shaft and hence
moves the needle holder back and forth along the alignment channel.
Advantageously, the connector device also comprises a retaining hub
or connector base. The retaining hub may be held stationary (e.g.
using one hand) whilst the knurled hub is rotated (e.g. using the
other hand) thereby preventing significant torque being applied to
the interface between the bone and the percutaneous fluid access
device. The hollow needles are thus brought into engagement with
the septum from a direction substantially normal to the septum
surface thereby minimising the risk of damage to components of the
apparatus. Although manually operated actuation mechanisms are
described above, it should be noted that automated (e.g.
electrical) actuation mechanisms could be alternatively be
provided.
[0019] The percutaneous fluid access device preferably comprises a
subcutaneous base portion. The subcutaneous base portion is, when
implanted, preferably located below the outer surface of the skin.
The one or more ports preferably extend through the subcutaneous
base portion. Advantageously, the subcutaneous base portion
comprises one or more port outlets. Each of these one or more port
outlets may be connected, or connectable, to one or more implanted
catheters. The port outlets may comprise multiple single lumen
tubes or a multi-lumen tube. The fluid pathways (e.g. tubes) may
exit the device at between 70-110 degrees to the longitudinal axis
of the device (e.g. from an approximately perpendicular direction).
The tubes thus preferably exit the device from the side and not
from beneath the device; the tube can thus exit the device in the
bone level.
[0020] Advantageously, the channels through the percutaneous fluid
access device have a low dead volume. This maximises the
therapeutic delivery during re-accesses as inert fluid rests in the
system between infusions. Preferably, the dead volume of each
channel is less than 500 microlitres, more preferably less than 250
microlitres, more preferably less than 100 microlitres and more
preferably less than 50 microlitres.
[0021] The percutaneous fluid access device preferably comprises a
subcutaneous base portion that is at least partially insertable
into a complementary recess formed in a bone. The percutaneous
fluid access device is thus preferably a bone anchored percutaneous
fluid access device. Preferably, the percutaneous fluid access
device is not a skin anchored device. Advantageously, the
subcutaneous base portion also comprises one or more features (e.g.
annular circumferential features such as ribs) for gripping the
internal surface of such a complementary recess thereby directly
anchoring the subcutaneous base portion to the bone. The
percutaneous fluid access device may thus be retained in bone
through an interference or press fit; this maximises retention of
the subcutaneous base portion after implantation.
[0022] The subcutaneous base portion may comprise a rough surface
to encourage rapid osseointegration. Similarly, the percutaneous
portion of the device (i.e. the part in contact with the skin) may
comprise a roughened region to promote dermal integration (e.g. the
tissue around the percutaneous portion of the device will heal to
the device and/or to the periosteal layer thereby providing a
healed seal around the device to minimise infection and/or
rejection). Although not essential, additional coatings such as
Hydroxyappetite could be used to provide a roughened coating to
accelerate and strengthen dermal attachment and/or
osseointegration. The percutaneous portion may also include a
smooth (e.g. polished or coated) region located above the roughened
region to which the skin adheres. The smooth portion inhibits
tissue in-growth and can be kept clean, thereby reducing the risk
of infection of the underlying dermis. Preferably, the percutaneous
fluid access device is arranged to be anchored to a recess formed
in the skull. Further details of a bone anchored percutaneous fluid
access device are described in WO2011/098769.
[0023] The percutaneous fluid access device may be formed using a
variety of manufacturing techniques. The device could also be
manufactured from a range of different materials. For example, the
device could be formed from a ceramic (e.g. Zirconia) and/or PEEK
if use in MRI sensitive environments is required. Advantageously,
manufacture of the percutaneous fluid access device comprises using
a selective melting (e.g. selective laser melting) technique in
which components of the device are formed by selectively melting
powdered material (e.g. powdered metal). Such techniques are also
termed rapid manufacturing or printing. The device may thus
comprise printed or cast titanium. In a preferred embodiment, a
flared tube is provided within the main body of the device; this
tubing is retained during injection moulding. Advantageously, the
percutaneous fluid access device is implanted after it has been
fully assembled. In other words, all the constituent parts of the
percutaneous fluid access device are preferably combined prior to
implantation.
[0024] The percutaneous fluid access device may comprise a
plurality of ports and separate septa may be provided for the
different ports. Advantageously, the percutaneous fluid access
device comprises a plurality of ports and a single septum is
provided to cover each of the plurality of port. Preferably, the
single septum can be accessed and removed via the extracorporeal
portion of the percutaneous fluid access device. Conveniently, the
septum is compressed and retained using a press fit, an
interference fit or a snap fit cap. A filter unit may also be
provided as part of percutaneous access apparatus; e.g. a filter
could be provided underneath the septum allowing it to be replaced
if the septum was removed.
[0025] The invention also extends to a kit comprising the
percutaneous access apparatus and at least one implantable catheter
device. The kit may also include a guide tube. The kit may also
include at least one bacterial and/or air filter. The percutaneous
access apparatus may be used for any medical purpose. Preferably,
the percutaneous access apparatus is used for neurosurgical
purposes. Although the apparatus is mainly described for delivering
fluid, it should be noted that the apparatus is also suitable for
collecting (aspirating) fluid from the body. The cross-sectional
area of the fluid channel through each component of the kit may be
substantially the same.
[0026] According to a further aspect of the invention, there is
provided a connector device for attachment to a percutaneous fluid
access device, comprising; one or more hollow needles, an
attachment mechanism for attaching the connector device to the
extracorporeal portion of an associated percutaneous fluid access
device, and an actuation mechanism for driving the one or more
hollow needles towards an attached percutaneous fluid access
device. The attachment mechanism and/or the actuation mechanism may
be fully integrated within the connector device. At least part of
the attachment mechanism may be removable from the connector
device. At least part of the actuation mechanism may be removable
from the connector device. In this manner, some or all of the
attachment mechanism and/or the actuation mechanism may be detached
from the connector device after the required fluidic connection(s)
with the percutaneous fluid access device has been established.
[0027] The actuation mechanism of the connector device thus allows,
after the connector device has been secured to the extracorporeal
portion, the hollow needles to be driven through the septum of the
attached percutaneous fluid access device to establish fluid
communication with the ports of the percutaneous fluid access
device. The connector device may include any of the features
described above.
[0028] According to a further aspect of the invention, there is
provided a connector device attachable to a port via a kinematic or
pseudo-kinematic interface. The kinematic or pseudo-kinematic
interface ensures accurate alignment of the connector device and
the port. The port may be a percutaneous port (e.g. a percutaneous
fluid access device as described above).
[0029] According to a further aspect of the present invention, a
guide device is provided for attachment to a percutaneous fluid
access device. The guide device may be directly or indirectly
attachable to the percutaneous fluid access device. The guide
device may, for example, be directly or indirectly attached to the
extracorporeal surface of a percutaneous fluid access device as
described herein. If directly attached, the guide device may
include features for engaging corresponding features of the
extracorporeal surface of the percutaneous fluid access device. The
guide device may thus be directly attachable to the extracorporeal
surface via a kinematic or pseudo-kinematic interface as described
above. If indirectly attached, the guide device may be attached
(optionally via a kinematic or pseudo-kinematic interface) to one
or more components that are in turn attached (optionally via a
kinematic or pseudo-kinematic interface) to the extracorporeal
surface of the percutaneous fluid access device.
[0030] The guide device is preferably arranged to guide a connector
device into engagement with the percutaneous fluid access device.
The connector device may comprise one or more hollow needles, as
described above. The percutaneous fluid access device may comprise
one or more ports for receiving such needles, as also described
above. The guide device may thus act to guide the connector device
as it is brought into engagement with the percutaneous fluid access
device. In particular, the guide device preferably guides the one
or more hollow needles of the connector device into engagement with
the one or more ports of the percutaneous fluid access device. It
should be noted that such a guide device may be used with an
actuation mechanism as described elsewhere herein or the connector
device may simply be pushed by hand into engagement with the
percutaneous fluid access device to establish the fluidic link(s)
(optionally using a rod or other element that can be attached to
the connector device). Preferably, the guide device can be detached
after the fluidic connection is established between the connector
device and the percutaneous fluid access device. The guide device
may thus be used during connector device attachment but removed
before any subsequent infusions. The guide device may include an
elongate protruding channel along which the connector device can be
passed. The guide device may protrude further from the percutaneous
fluid access device than the connector device. For example, the
guide device may be at least 3 cm, at least 5 cm or at least 10 cm
long.
[0031] According to a further aspect of the present invention,
there is provided a percutaneous fluid access device comprising an
extracorporeal portion, one or more ports accessible from the
extracorporeal portion and a septum for sealing each port. The
extracorporeal portion may comprise a kinematic or pseudo-kinematic
interface for an associated connector device. Advantageously, the
percutaneous fluid access device comprises a subcutaneous portion
(the portion underneath the skin that can include the part anchored
to the bone recess) and a percutaneous portion (i.e. a part that
passes through the skin). Conveniently, the percutaneous fluid
access device includes an increase in cross-sectional from the
subcutaneous portion. In other words, the percutaneous fluid access
device preferably increases in cross-sectional area (e.g. diameter)
with distance from the skin surface. The percutaneous portion may
thus be tapered. For example, it may comprise a tapered cone.
Preferably, the angle of the taper (from the skin surface normal)
is greater than 5.degree., or greater than 10.degree., or greater
than 15.degree.. Preferably, the angle of the taper is less than
40.degree., or less than 35.degree., or less than 30.degree. or
less than 25.degree.. Such an outwardly tapered profile stops
tissue overgrowth of the device after implantation.
[0032] The invention also extends to a method of neurosurgery, the
method comprising the step of implanting at least part of the above
percutaneous access apparatus. Catheter, tubing and other
components may also be implanted. The implanted apparatus may be
used to deliver therapeutic agent to the central nervous
system.
[0033] According to a further aspect of the invention, fluid
storage apparatus for medical use is provided, the apparatus
comprising a length of tubing having a first end and a second end,
a first sealable connector portion being provided at the first end
and a second sealable connector portion being provided at the
second end, wherein the volume of fluid that can be stored within
the apparatus is known.
[0034] Fluid storage apparatus is thus provided that allows a
precise volume of fluid (e.g. a fluid or infusate optionally
comprising a therapeutic agent) to be stored. In use, the
therapeutic agent is loaded into the tubing and the ends of the
tubing are sealed. A quantity of fluid can thus be stored in the
apparatus that is equal to the internal volume of the fluid storage
apparatus; the internal volume being the internal volume of the
tubing plus any internal volume of the first and second connector
portions.
[0035] The fluid storage apparatus has a number of advantages. For
example the volume of fluid contained with the storage apparatus
can be defined with a greater resolution than a typical syringe
thereby providing improved control over the amount of fluid
delivered to a subject. Furthermore, the fluid storage apparatus
can be readily inserted in the fluid line between a fluid pump and
a catheter implanted in the patient. A precise amount of fluid can
be delivered and almost no residual fluid will remain in the
delivery system; i.e. there is no substantial fluid mixing and all
the stored fluid is pushed from the fluid storage apparatus to the
catheter for delivery to the target site. Although the fluid
storage apparatus is highly suited to neurological applications
where small and precisely known quantities of therapeutic agent are
delivered, it should be recognised that the apparatus is suitable
for any medical application.
[0036] The fluid storage apparatus has a number of advantages. For
example, it may be loaded by a pharmacist in a clean environment
thereby reducing the chance of an error being made on the ward.
There is also no need to provide Y-connectors as part of the drug
delivery system (Y-connectors typically having a large dead volume)
and also a reduced chance of bubbles entering the system. The fluid
storage apparatus also allows for the safe storage and transport of
drug; this is especially advantageous when using cytotoxic
(chemotherapy) drugs or the like.
[0037] As mentioned above, the volume of fluid that can be stored
within the apparatus is known. This knowledge may arise from
measuring the internal volume of the apparatus or by theoretically
predicting the volume (e.g. from design data). Preferably, the
internal volume of the apparatus is known with an accuracy of
better than 10%, more preferably better than 5% and even more
preferably better than 1%. In a preferred embodiment, the internal
volume of the apparatus is known with an accuracy of between 2% and
3%.
[0038] Advantageously, the cross-section area of the fluid pathway
through the fluid storage apparatus (including the first and second
sealable connector portions) is substantially constant. It is also
preferred that the cross-section area is small. For example, it is
preferred that the cross-sectional area has a internal diameter
less than 1 mm, more preferably less than 0.9 mm and more
preferably less than 0.8 mm. In a preferred embodiment, an internal
diameter of 0.7 mm is provided. The provision of a small,
optionally substantially constant, cross-sectional area through the
apparatus reduces fluid mixing and the chance of pockets of fluid
being bypassed. A line of fluid can thus be pushed down connected
tubing towards a catheter.
[0039] The first and second sealable connector portions may be
provided by any suitable connector portion. For example, stop-cocks
or needleless septa may be provided. Preferably, the first and
second sealable connector portions have a low dead volume (e.g. a
dead volume of less than 50 .mu.l); i.e. there is only a very small
volume in which fluid mixing can occur. Advantageously, one or both
of the first and second sealable connector portions comprise a
self-sealing connector portion. In other words, the sealable
connector portions preferably remain sealed when they are not
connected to a complementary connector portion. Preferably, the
first and second connector portions are both of the same
design.
[0040] In a preferred embodiment, each self-sealing connector
portion includes a septum. The septum seals the lumen of the length
of tubing, thereby ensuring stored fluid is retained therein. Each
self-sealing connector portion may also include a twist-lock
member. Such a twist lock member is preferably arranged to engage a
complementary twist lock member, thereby enabling connection with
an associated connector portion by a twist lock action. A
complementary fluid connector portion may also be provided (e.g.
affixed to the end of associated tubing) that comprising a
complementary twist lock member and a lumen, a hollow needle being
retained in and protruding from the aperture at the end of the
lumen. Engaging the self-sealing connector portion with the
complementary fluid connector portion using a twist lock action
thus causes the hollow needle of the complementary fluid connector
portion to pierce the septum of the self-sealing fluid connector
portion thereby establishing a fluid link. The self-sealing
connector portion and the complementary fluid connector portion may
include internal cylindrical tubes that are dimensioned to slide
within one another when the twist lock connection is being
established. The internal cylindrical tubes may thus provide
relative alignment of the self-sealing connector portion and the
complementary fluid connector prior to the needle piercing the
septum. This ensures the needle penetrates the septum from the
required direction (e.g. perpendicular to the surface normal) and
that the septum is pierced in the same location each time a
connection is made. Such connectors may, for example, be provided
as a modified Luer connector. Further details of such connectors
are outlined below.
[0041] A complementary fluid connector portion may also be provided
that is unattached to a tube or is attached to an open ended tube.
This may be used to open or vent the first sealable connector
portion whilst the apparatus is being filled with fluid via a
complementary connector portion that is attached to the second
sealable connector portion. A filling tube (e.g. attached to a
syringe or pump) may also be provided that comprises a
complementary fluid connector portion at its distal end. The
filling tube may then be connected to the second sealable connector
portion to enable the apparatus to be filled with fluid.
[0042] Advantageously, the internal volume of the apparatus is
selected to equal to the volume of therapeutic agent to be
delivered to a patient. The apparatus may thus be fabricated to
have a certain internal volume that equals a volume of therapeutic
agent to be delivered. Alternatively, the apparatus may be made to
have a certain internal volume and the required dosage of
therapeutic agent may be provided in a volume of fluid that matches
the internal volume of the apparatus.
[0043] Conveniently, the apparatus comprises a marking and/or label
that indicates the internal volume of the apparatus. For example, a
label could be affixed to the apparatus, and/or a marking could be
applied to the apparatus and/or a part of the apparatus (e.g. the
connector portions) could be colour coded to indicate the internal
volume.
[0044] Advantageously, a therapeutic agent is contained within the
length of tubing. In other words, the invention extends to the
apparatus in combination with the therapeutic agent stored therein.
The volume of therapeutic agent stored in the apparatus is then
known. The therapeutic agent may be suitable for delivery the
central nervous system. In particular, the therapeutic agent may be
for direct infusion into the brain via an intracranial catheter.
The therapeutic agent may comprise a protein or virus; such agents
can be easily damaged under high pressure (e.g. as found in a
syringe) and hence the present apparatus can protect such
therapeutic agents from accidental damage. The therapeutic agent
may comprise a neurotrophic factor, such as GDNF.
[0045] The length of tubing may be of any type. The tubing may
comprise fused silica or FEP. Preferably, the length of tubing
comprises plastic. The plastic may be flexible. It is preferred
that the tubing is of a medical grade. Advantageously, the tubing
and is long-term compatible with the therapeutic agent being
stored.
[0046] According to a further aspect of the invention, fluid
delivery apparatus is provided that includes fluid storage
apparatus as described above. The fluid delivery apparatus may also
comprise an implantable catheter. The fluid delivery apparatus may
also comprise an outlet tube from a fluid delivery device (such as
a syringe pump). Advantageously, the outlet tube of the fluid
delivery device is connectable to the implantable catheter via the
fluid storage apparatus. In other words, the fluid storage
apparatus can be inserted in the fluid pathway between the outlet
tube of the pump and the implantable catheter. There may be a
direct connection between the fluid storage apparatus and the
catheter and/or the outlet tube. Alternatively, the fluid delivery
apparatus may also include additional intermediate components (such
as percutaneous access apparatus, hubs, additional supply tubing,
filters etc) in the fluid pathway.
[0047] In use, the fluid (e.g. therapeutic agent) stored by the
fluid storage apparatus is pushed or flushed from the fluid storage
apparatus by the flow of fluid from the pump to the catheter. The
arrangement provides in-line delivery of the therapeutic agent with
minimal fluid mixing. The fluid dispensed by the pump can also be
an inert or buffer fluid (e.g. saline or artificial CSF) meaning
that the pump does not contain the therapeutic agent and can thus
be reused to deliver a different therapeutic agent without having
to be flushed clean. There is also no need to have two pumps per
delivery line (e.g. one for buffer and one for the therapeutic
agent). The various tubes of the fluid delivery apparatus may all
be linked by low dead volume fluid connectors, for example of the
type described in more detail below. Preferably, the
cross-sectional area (e.g. the diameter) of the fluid pathway from
the pump to the catheter tip is substantially constant.
[0048] The present invention also extends to a fluid storage kit
that comprises a plurality of fluid storage apparatus of the type
described above. In particular, the plurality of fluid storage
apparatus preferably includes fluid storage apparatus for storing
different known volumes of fluid. In other words, a kit containing
a plurality of fluid storage apparatus having different storage
volumes can be provided. The fluid storage apparatus of most
appropriate volume may then be selected (e.g. by a pharmacist) to
store a prescribed volume of therapeutic agent.
[0049] According to a further aspect of the invention, a fluid
storage vessel is provided that comprises a length of tubing
containing a defined dosage of therapeutic agent, the length of
tubing being sealed at each end. The seal may be provided by a
connector portion.
[0050] According to a further aspect of the invention, a fluid
storage vessel is provided that comprises a length of tubing
containing a defined volume of liquid comprising a therapeutic
agent, the length of tubing being sealed at each end. The seal may
be provided by a connector portion.
[0051] According to a further aspect of the invention, there is
provided a method for storing a preset volume of fluid comprising a
required dosage of therapeutic agent, the method comprising the
steps of selecting a length of tubing having a volume equal to the
preset volume of fluid, loading the fluid into the length of tubing
and sealing each end of the length of tubing. The step of sealing
each end of the length of tubing may comprise providing or using
fluid connector portions at each end of the length of tubing to
seal the tube. Such fluid connector portions may advantageously
comprise septum seals. The step of selecting a length of tubing
having a volume equal to the preset volume of fluid may comprise
selecting an appropriate length of tubing from a kit containing
lengths of tubing of different lengths. The step of selecting a
length of tubing having a volume equal to the preset volume of
fluid may alternatively comprise cutting a length of tubing to the
required length.
[0052] According to a further aspect of the invention, there is
provided a method for dispensing a predetermined dosage of
therapeutic agent to a subject. The method comprises the step of
connecting a fluid dispensing pump to an implanted catheter via one
or more fluid delivery tubes, wherein the method further comprises
the step of locating a storage tube in the fluid path from the pump
to the catheter, the storage tube containing a known volume of
therapeutic agent for delivery to the subject.
[0053] According to a further aspect of the invention, there is
provided a first fluid connector portion comprising a first twist
lock member and a lumen, wherein a septum is provided for sealing
the lumen. The lumen may be in fluid communication with an attached
tube. The provision of the septum means the first fluid connector
portion is self-sealing (i.e. it provides a fluid seal when not
connected to a complementary connector portion). This makes it
particularly suitable for inclusion in fluid storage apparatus of
the type described above.
[0054] According to a further aspect of the invention, there is
provided a second fluid connector portion comprising a second twist
lock member and a lumen, wherein a hollow needle is retained in and
protrudes from the aperture at the end of the lumen. The lumen may
be in fluid communication with an attached tube. Preferably, the
needle has a sharp (pointed) tip. Preferably the needle comprises
an aperture in its side wall that is in fluid communication with
the lumen of the needle. Providing a side aperture prevents coring
during septum penetration. Preferably, the aperture is adjacent the
tip. The lumen of the hollow needle may have an outer diameter
substantially equal to the internal diameter of the lumen. The
lumen of the second fluid connector portion may have an internal
diameter substantially equal to the internal diameter of an
attached tube. The lumen of the second fluid connector portion may
have a diameter of less than 1 mm, more preferably less than 0.9 mm
and more preferably less than 0.8 mm. The needle may have an outer
diameter of less than 1 mm, more preferably less than 0.8 mm and
more preferably less than 0.6 mm. In a preferred embodiment, the
needle may have an outer diameter of 0.5 mm and the lumen of the
second fluid connector portion (and optionally the first fluid
connector portion) may have an internal diameter of 0.7 mm.
[0055] The second fluid connector portion is preferably arranged to
connect to the first fluid connection portion described above. The
lumen of the second fluid connector portion may have the same
internal diameter as the lumen of the first fluid connector
portion.
[0056] The first fluid connector portion may comprise a first
internal cylindrical tube co-axial with the lumen thereof. The
second fluid connector portion may comprise a second internal
cylindrical tube co-axial with the lumen thereof. The first and
second internal cylindrical tubes may have different dimensions so
that one tube can slide into the lumen of the other tube. For
example, the first internal cylindrical tube may be dimensioned to
fit within the lumen of the second internal cylindrical tube. The
first and second internal cylindrical tubes may be arranged to
slide into engagement with one another when the twist lock
connection is being established. The first and second internal
cylindrical tubes may thus provide relative alignment of the first
and second fluid connector portions during twist-lock attachment.
This can provide alignment of the needle and the septum. In
particular, this arrangement ensures that the needle penetrates the
septum from the required direction (e.g. perpendicular to the
surface normal) and that the septum is pierced in the same location
each time a fluid connection is made. The first and second internal
cylindrical tubes can also provide control over how far the hollow
needle penetrates the septum. If the hollow needle comprises a
fluid aperture in its sidewall, the depth of insertion can be set
so that, during attachment, the part of the needle comprising the
fluid aperture passes through the septum and the aperture is
located adjacent the septum. In this way, the dead volume of the
system is minimised.
[0057] The present invention also extends to a fluid connector that
comprises a first fluid connector portion and a second fluid
connector portion as described above. The first and second twist
lock members of the first and second fluid connector portions are
preferably arranged to co-operate to provide a twist lock
connection between the first and second fluid connector portions.
The first twist lock member may comprise a male Luer lock
arrangement. The second twist lock member may comprise a female
Luer lock arrangement. Engaging the first fluid connector portion
and the second fluid connector portion using a twist lock action
preferably causes the hollow needle of the second fluid connector
portion to pierce the septum of the first fluid connector portion.
A fluid link between the lumens of the first and second connector
portions (and hence between two lengths of tubing) can thus be
established. It should also be noted that the second fluid
connector portion can also establish a fluid link with a connector
portion that does not include a septum.
[0058] Connectors of the above described type are particularly
advantageous because they have a low dead volume. This means they
are especially suited to neurological applications where relatively
small amounts of fluid (e.g. hundreds of microlitres) are
dispensed.
[0059] The present invention also extends to apparatus for delivery
of fluid to the brain via one or more intracranial catheters, the
apparatus also comprising one or more the following; a percutaneous
access apparatus, a connector device, a fluid storage apparatus, a
fluid delivery apparatus; and fluid connectors. External drug
deliver pumps (e.g. syringe pumps) may also be provided.
Advantageously, the apparatus has a low dead volume.
[0060] The invention will now be described, by way of example only,
with reference to the accompanying drawings in which;
[0061] FIG. 1 shows a drug delivery system of the present
invention,
[0062] FIGS. 2A and 2B show in more detail the implanted catheters
and guide tubes of FIG. 1,
[0063] FIGS. 3A, 3B and 3C show the percutaneous port and the
connector device respectively of the percutaneous access apparatus
shown in FIG. 1,
[0064] FIGS. 4A and 4B show in more detail the guide member of the
connector device of FIG. 3B,
[0065] FIG. 5 shows in more detail the needle holding member of the
connector device of FIG. 3B,
[0066] FIGS. 6A, 6B, 6C and 6D show how the connector device is
secured to the percutaneous port,
[0067] FIGS. 7A and 7B illustrate how turning the knurled ring of
the connector device forces the needles of the needle holding
member through the septa of the percutaneous port,
[0068] FIGS. 8A and 8B are cross-sectional views of the
illustrations of FIGS. 7A and 7B respectively,
[0069] FIG. 9 illustrates a drug storage tube,
[0070] FIGS. 10A and 10B show modified Luer connectors,
[0071] FIG. 11 shows the Luer connnectors of FIGS. 10A and 10B
aligned relative to one another,
[0072] FIG. 12 shows the Luer connnectors of FIGS. 10A and 10B
connected to one another, and
[0073] FIGS. 13A and 13B show alternative embodiments of the
connector device.
[0074] Referring to FIG. 1, an overview of the apparatus for
delivering fluid to the brain is illustrated when implanted in a
subject.
[0075] The apparatus comprises four fine catheters 2, each catheter
being inserted into the brain via a previously implanted guide tube
4 (although it should be noted that only two of these are shown in
FIG. 1). Suitable stereotactic insertion apparatus and methods have
been described elsewhere previously, for example see U.S. Pat. No.
7,329,262 for details of a stereoguide based catheter insertion
procedure. Supply tubing 6 runs from each catheter 2 to a hub 8.
The hub 8 is connected by a length of multi-lumen tubing 10 to
percutaneous access apparatus 12. The catheters 2, guide tubes 4,
supply tubing 6, hub 8 and multi-lumen tubing 10 are all
subcutaneously implantable (i.e. buried beneath the skin of the
patient).
[0076] The percutaneous access apparatus 12 comprises a
percutaneous fluid access device that is anchored directly to the
skull of the patient. The percutaneous fluid access device
comprises an extracorporeal portion to which an associated
connector device is releasably attached. The percutaneous access
apparatus 12 thus enables a fluidic link to the implanted catheters
2 to be established when required. In particular, the arrangement
provides a separate, isolated, fluidic pathway to each catheter 2.
More details about the percutaneous access apparatus 12 are
provided below.
[0077] Outside of the body, the connector device of the
percutaneous access apparatus 12 is linked to four external supply
tubes 14. Each supply tube 14 includes an in-line bacterial and/or
air filter 16. A four channel syringe pump 18 (which may comprise
four separate single channel syringe pumps) is also provided. An
outlet tube 20 from each channel of the syringe pump 18 is linked
to one of the external supply tubes 14 via a drug storage tube 22.
As will be explained in more detail below, each drug storage tube
22 is preloaded with a desired volume of therapeutic agent allowing
the syringe pump 18 to be loaded with an inert solution (e.g.
saline or artificial CSF). Fluidic connections between the drug
storage tube 22 and the outlet tubes 20 and supply tubes 14 are
made using low dead volume Luer lock connectors 24 of the type
described in more detail below.
[0078] In use, the catheters 2, guide tubes 4, supply tubing 6, hub
8 and multi-lumen tubing 10 are all subcutaneously implanted in the
subject (i.e. the skin flap 23 showed in a raised position in FIG.
1 is folded down and sutured in place). The percutaneous fluid
access device of the percutaneous access apparatus 12 is also
secured in place (e.g. attached to the skull and left protruding
through the scalp) thereby providing the required fluid connection
as and when required. These components are preferably suitable for
long term implantation within a subject.
[0079] For example, they may be designed to remain implanted for
months or years. When delivery of therapeutic agent is required,
the connector device is attached to the percutaneous fluid access
device. The supply tubes 14 (pre-primed with inert fluid) are then
connected to the syringe pump via drug storage tubes 22 that
contain the required dosage of therapeutic agent that is to be
delivered. Each channel of the syringe pump is arranged to expel
inert fluid (saline, artificial CSF etc) thereby pushing the
therapeutic agent through the apparatus and expelling it from the
tips of each catheter 2. The rate of fluid flow can be precisely
controlled using the syringe pump 18 and the amount of therapeutic
agent can be precisely set by defining the volume of the drug
storage tubes 22. It is possible for fluid delivery to be
continuous or intermittent. Fluid may also be delivered through
all, or just some, of the catheters in parallel and/or it may be
delivered sequentially through a sub-set of one or more catheters
in turn. The precise delivery protocol can be set by a
clinician.
[0080] Turning to FIGS. 2a and 2b, the fine catheter 2 and guide
tube 4 of the apparatus described with reference to FIG. 1 are
illustrated in more detail.
[0081] The guide tube 4 comprises an elongate tube 62 having a head
64 at its proximal end. The head 64 has a screw thread formation 66
on its outer surface that allows it to be secured to a burr hole
formed in the skull by a press-fit action. The catheter 2 comprises
a length of fine tubing for insertion into the lumen of the guide
tube. The distal end or tip of the fine tubing of the catheter 2
extends beyond the distal end of the elongate tube 62 when inserted
therein and comprises a hole for dispensing fluid. A hub 56 is
provided at the proximal end of the fine tubing of the catheter 2.
Further details of such a guide tube and catheter combination are
outlined in WO2003/077785.
[0082] Referring to FIGS. 3A, 3B and 3C, the percutaneous access
apparatus 12 of FIG. 1 is illustrated. FIGS. 3A and 3B illustrate
the percutaneous fluid access device 100 that is implanted in the
subject and FIG. 3C shows the external connector device 130 that
attaches to the percutaneous fluid access device 100 whenever fluid
delivery is required.
[0083] Referring to FIGS. 3A and 3B, the percutaneous fluid access
device 100 comprises a subcutaneous portion 102, a percutaneous
portion 104 and an extracorporeal portion 106.
[0084] The subcutaneous portion 102 is substantially cylindrical
with protruding ribs 108 that enable secure attachment of the
device to a hole formed in the skull via an interference or press
fit. The external surface of the subcutaneous portion 102 is also
roughened to promote osseointegration after implantation. The ribs
108 have an inclined surface that is at an angle .theta. of between
15 and 35 degrees to the longitudinal axis; this helps retain the
device securely in place after implantation.
[0085] The percutaneous portion 104 (which can also be termed a
transcutaneous portion) is the part of the device that passes
through the skin. The surface of the percutaneous portion 104 is
also roughened to promote skin in-growth after implantation thereby
reducing the risk of infection. The percutaneous portion 104 is
conical (i.e. it increases in diameter from skin surface) with an
angle from the vertical of between 5 and 40 degrees.
[0086] The extracorporeal portion 106 is the part of the device
that protrudes above the outer surface of the dermis. The
extracorporeal portion 106 thus has a smooth surface to prevent
tissue in-growth; such a smooth surface also allows it to be easily
cleaned thereby reducing the chance of bacterial retention.
[0087] The extracorporeal portion 106 has a substantially
cylindrical outer surface with a conical recess 109 and two
v-shaped grooves 110 spaced apart around its circumference. A
macro-alignment feature 112 is also provided. The conical recess
109 and grooves 110 act as very precise (kinematic) location
features for the associated connector device, whilst the
macro-alignment feature 112 ensures the connector device is in the
approximately correctly orientation prior to attachment. Further
details of the connector device are provided below.
[0088] As shown in the cross-sectional views of FIG. 3B, the
percutaneous fluid access device 100 comprises four ports 120. Each
port 120 is in fluid communication with a lumen of the multi-lumen
supply tube 6. The supply tube 6 exits the subcutaneous portion 102
from its side and, when implanted, runs a short distance in a
channel formed in the bone. The four ports 120 are accessible from
the extracorporeal portion via a septum 122. In particular, each
port 120 comprises an elongate channel having an axis substantially
parallel to the longitudinal axis of the device. A single septum
122 that is accessible from the extracorporeal portion seals the
end of the channel of all four ports. During fluid delivery, hollow
needles of the connector device pierce the septum, enter the
channels and thereby provide the required fluid communication with
each port. In the absence of an attached connector device, the
septum seal provides a fluid seal for all ports that prevents
leakage of fluid or ingress of unwanted material (e.g. bacteria
etc). FIG. 3B also shows in dashed outline the location of the
dermal layer 121 and underlying bone 123 when the device is
implanted.
[0089] FIG. 3C shows the connector device 130 for attachment to the
percutaneous fluid access device 100. The connector device 130
comprises a connector base 131 having an attachment mechanism for
securing the connector device 130 to the percutaneous fluid access
device 100 in a precisely define relative position. The connector
device 130 also includes a needle holder 134 attached to the end of
a shaft 136. The shaft 136 has an external thread that engages a
corresponding internal thread of a knurled portion 138. The needle
holder 134 is located within a guide channel inside the connector
base 131 and rotation of the knurled portion 138 relative to the
connector base 131 drives the needle holder 134 back and forth
along the channel. After the connector base 131 has been attached
to the percutaneous fluid access device 100 by the attachment
mechanism 132, the knurled portion 138 can be rotated to drive the
hollow needles held by the needle holder 134 through the septum of
the percutaneous fluid access device 100 thereby establishing the
required fluid communication. The supply tubes 16 connected to the
needles of the needle holder 134 are also shown. More details of
the various components of the percutaneous fluid access apparatus
are provided below.
[0090] Referring to FIGS. 4a and 4b, the attachment mechanism of
the connector base 131 mentioned with reference to FIG. 3c is
illustrated.
[0091] FIG. 4A shows a top-down view of the connector base 131 of
the connector device 130. As explained above, the connector base
131 is configured to be releaseably attachable to the percutaneous
fluid access device 100. The connector base 131 has a generally
cylindrical outermost surface with a fluted slot 146 formed along
one side and an internal lip 148 at the lower end. The inner walls
of the connector base 131 are generally cylindrical and define a
guide channel 154 along which an associated needle holder 134 (not
shown) can slide. The connector base 131 also includes an
attachment mechanism 132 that comprises two fixed balls 150 and
152. A floating ball member 154 comprising a third ball 155 is
carried by a hinge 156 (not shown in FIG. 4A). A macro-alignment
feature in the form of a v-shaped slot 158 is formed in the
internal lip 148.
[0092] FIG. 4B is a sectional view of the connector base 131 along
the line A-A shown in FIG. 4A. The hinge 156 carrying the floating
ball member 154 is shown. An elongate aperture 160 having an
internal screw thread is also provided adjacent the hinge 156 and
ball member 154. The elongate aperture 160 is arranged so that the
tip of a screw (not shown) inserted through the aperture will
protrude from the aperture and engage the floating ball member 154.
Tightening the screw thus deflects the floating ball member 154
(i.e. it pivots at the hinge 156) thereby moving the ball toward
the centre of the connector base. This allows the connector base
131 to be locked onto the percutaneous fluid access device 100 when
required. The floating ball member 154 springs back when the screw
is removed, thereby allowing the connector base 131 to be removed
from the percutaneous fluid access device 100.
[0093] Moreover, the relative positions of the connector base 131
and percutaneous fluid access device 100 are defined by the
engagement of the three ball of the connector base (i.e. the two
fixed balls 150 and 152 and the third ball 155) with the grooves
110 of the percutaneous fluid access device 100. This arrangement,
which is typically called a kinematic connection or kinematic
joint, provides a highly repeatable mechanical linkage in which the
six points of contact between the balls and grooves constrain the
six degrees of freedom of movement between the connector base 131
and percutaneous fluid access device 100. This precise alignment
ensures the hollow needles of the needle holder 134 (not shown) are
correctly positioned relative to the ports of the percutaneous
fluid access device 100.
[0094] It should be noted that, instead of the hinge 156 and
floating ball member 154 arrangement shown in FIGS. 4A and 4A,
various alternative arrangements could be implemented. For example,
the tip of the screw could comprise a ball that directly engages a
feature (e.g. groove) of the percutaneous fluid access device. A
cam and lever arrangement could also be used instead of a screw to
bias the floating ball member into contact with the percutaneous
fluid access device.
[0095] Referring to FIG. 5, there is provided an exploded view of
the connector device 130. The connector base 131 is arranged to
receive a needle holder 134. The needle holder 134 comprises a
substantially flat, keyhole shaped, supporting member 180. Four
hollow needles 182 project perpendicularly from the flat surface of
the supporting member. The four hollows needles 182 are spaced
apart in a configuration that matches the arrangement of the ports
of the percutaneous fluid access device 100. The needle holder 134
is also shaped to fit within, and slide along, the guide channel
154 of the connector base 131 that is described above. The needle
holder 134 also includes four internal channels that provide
separate fluidic channels between the lumens of the four hollow
needles 182 and the four supply tubes 14. The screw threaded shaft
136 attached to the needle holder 134 is held by the threaded inner
surface of the knurled portion 138. A lip 183 protruding from the
connector base 131 secured the knurled portion 138 to the base
131.
[0096] Referring to FIGS. 6a to 6d, the procedure for locking the
connector device 130 to the percutaneous fluid access device 100 is
illustrated.
[0097] FIG. 6a shows the connector device 130, a screw 190 and a
percutaneous fluid access device 100. FIGS. 6b and 6c show how the
connector base 131 of the connector device 130 can be located on
the percutaneous fluid access device 100. FIG. 6d shows the screw
190 inserted into the elongate aperture 160 of the connector base
131 and tightened so that the three ball of the connector base
(i.e. the two fixed balls 150 and 152 and the third ball 155 shown
in FIGS. 4a and 4b) firmly engage the recess 109 and grooves 110 of
the percutaneous fluid access device 100. The connector device 130
is thus locked to the percutaneous fluid access device 100
(although no fluid linkage has yet been established).
[0098] Referring to FIGS. 7A, 7B, 8A and 8B, the procedure for
establishing a fluid connection is illustrated. FIGS. 7A and 8A
show the configuration of the connector device 130 after it has
been locked to the percutaneous fluid access device 100. The hollow
needles 182 of the needle holder 134 are positioned above the
septum 122 in alignment with the respective channels of the ports
120. The connector base 131 is held in one hand whilst the other
hand rotates the knurled portion 138 of the connector device 130 in
an anticlockwise direction thereby driving the shaft 136 and needle
holder 134 along the guide channel inside the connector base 131.
As shown in FIGS. 7B and 8B this translational motion of the needle
holder along the guide channel causes the four hollow needles 182
to pierce the septum 122 and enter the four ports 120. Holding the
connector base 131 ensures no torque is applied to the device-bone
connection. In this manner, the four separate fluid pathways
through the percutaneous access apparatus 12 are established.
[0099] Once the required fluid delivery has occurred, the knurled
portion 138 can be rotated in a clockwise direction to withdraw the
four hollow needles 182 back through the septum 122. The connector
device 130 can then be unlocked from the percutaneous fluid access
device 100 by removing the screw 190.
[0100] If required, the various components of the fluid delivery
system can be MRI compatible.
[0101] Referring to FIG. 9, a drug storage tube 22 of the type
described above is illustrated. The function of each drug storage
tube 22 is to store the required volume of therapeutic agent that
is to be dispensed through the associated catheter.
[0102] The drug storage tube 22 comprises a length of single lumen
tubing 248 having a first end that terminates at a first fluid
connector portion 250 and second end that terminates at a second
fluid connector portion 252. The first and second fluid connector
portions 250 and 252 are self-sealing connector portions that can
mate with a complementary connector portion to establish a fluid
link. For example, the first and second fluid connector portions
250 and 252 may be provided by a modified male Luer lock based
connector portion of the type described in more detail below with
reference to FIG. 10B.
[0103] The volume of the drug storage tube 22, including the dead
volume of the first and second connector portions, is pre-selected
to match the desired volume of fluid that is to be dispensed. In
particular, the length of the single lumen tubing is pre-selected
so that the internal volume of the drug storage tube 22 (including
the dead volume of the connector portions) equals a desired value.
In one example, the drug storage tube 22 may be pre-loaded with the
desired volume (e.g. 300 .mu.l.+-.6 .mu.l) of GDNF. Once connected
to an apparatus as shown in FIG. 1, the therapeutic agent can be
pushed through the drug storage tube 22 by the flow of inert liquid
from the pump and delivered to the patient.
[0104] A kit of drug storage tubes may also be provided. Each drug
storage tube may comprise a certain, different, pre-defined volume.
The required drug storage tube may then be selected and loaded with
the appropriate drug as required. The procedure of loading the drug
storage tube may be performed, for example, by a pharmacist.
[0105] FIGS. 10A and 10B illustrate a pair of mating Luer lock
connectors that have been modified so as to have a low dead volume.
Such connectors are suitable for applications, such as dispensing
fluid to the brain, where low dead volumes are required due to the
relatively low volumes of fluid being delivered. Preferably, the
fluid path through the pair of connectors has a small and/or
substantially invariant cross-sectional area. For example, the
diameter of the fluid path may be about 0.7 mm. FIG. 10A shows a
female Luer connector 300 in which a hollow needle 302 has been
attached to the end of the lumen 304. The hollow needle 302 has a
sharp tip 306 and a fluid aperture 308.
[0106] FIG. 10B shows a male Luer connector 310 in which a septum
312 has been inserted near the end of the lumen 314. The inclusion
of the septum 312 in the male Luer connector 310 provides a fluid
seal in the absence of an associated female Luer and also minimises
the dead volume of the male Luer connector 310.
[0107] FIG. 11 shows the female Luer connector 300 aligned with the
male Luer connector 310 prior to connection. FIG. 12 shows the male
and female Luer connectors after engagement by a twisting action.
In particular, the septum 312 of the male Luer connector 310 is
pierced by the needle 302 of the female Luer connector 300 thereby
providing a fluidic connection. The aperture 308 of the needle 302
is located a small distance d from the septum.
[0108] FIG. 13 shows an alternative connector device 430 suitable
for attachment to the percutaneous fluid access device 100. The
connector device 430 includes a connector base 432 that can be
locked to the percutaneous fluid access device 100 in the manner
described with reference to FIGS. 4a and 4b above. An additional
guide device 434 is provided that can be secured to the connector
base 432 after the base has been locked to the percutaneous fluid
access device 100. A needle holder 436 is attached to the end of an
elongate shaft 438 by a screw thread. The needle holder 436 and
elongate shaft 438 may then be inserted into the channel of the
additional guide device 434 and pushed along the channel until the
hollow needles 440 of the needle holder engage and pierce the
septum of the attached percutaneous fluid access device 100. The
additional guide device thus ensures the needles are guided into
contact with the septum from the required direction thereby
reducing the risk of the septum being damaged. The additional guide
device 434 may be detached from the connector base 432 after the
fluidic connection has been established.
[0109] It should be remembered that the above are merely examples
of the various aspects of the present invention.
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