U.S. patent application number 14/667704 was filed with the patent office on 2015-07-23 for miniature implanted drug delivery devices and inserter systems for introducing such devices.
The applicant listed for this patent is MICROSERT LTD.. Invention is credited to Avraham SHEKALIM.
Application Number | 20150202079 14/667704 |
Document ID | / |
Family ID | 46932006 |
Filed Date | 2015-07-23 |
United States Patent
Application |
20150202079 |
Kind Code |
A1 |
SHEKALIM; Avraham |
July 23, 2015 |
MINIATURE IMPLANTED DRUG DELIVERY DEVICES AND INSERTER SYSTEMS FOR
INTRODUCING SUCH DEVICES
Abstract
A system (10, 200) and corresponding method for introducing a
drug delivery device (18, 218) through at least part of a
biological barrier starts with the drug delivery device (18, 218)
deployed within a channel of a hollow needle (12, 212), The hollow
needle is inserted into the biological barrier and the drug
delivery device is pushed forward by a suitable plunger. The drug
delivery device is preferably anchored to the biological barrier
through a radially expanding retention arrangement (36, 36', 36a),
and is preferably filled with a liquid drug after deployment via a
filling needle (24, 222) extending within the channel of the hollow
needle (12, 212).
Inventors: |
SHEKALIM; Avraham; (Nesher,
IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
MICROSERT LTD. |
Yokneam HaMoshava |
|
IL |
|
|
Family ID: |
46932006 |
Appl. No.: |
14/667704 |
Filed: |
March 25, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14004683 |
Sep 12, 2013 |
8992503 |
|
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PCT/IB2012/051462 |
Mar 27, 2012 |
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14667704 |
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61468014 |
Mar 27, 2011 |
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Current U.S.
Class: |
604/506 ;
604/218; 604/521 |
Current CPC
Class: |
A61F 9/0017 20130101;
A61M 2205/50 20130101; A61M 5/14276 20130101; A61M 2205/3331
20130101; A61M 2205/04 20130101; F04C 2270/041 20130101; A61M
5/3297 20130101 |
International
Class: |
A61F 9/00 20060101
A61F009/00 |
Claims
1. A method for introducing a drug delivery device, the method
comprising the steps of: (a) inserting the drug delivery device via
a channel of a hollow needle through at least part of at least one
layer of a biological barrier; and (b) subsequent to said
inserting, filling the drug delivery device with a quantity of
liquid drug via a filling needle extending within the channel of
the hollow needle.
2. The method of claim 1, wherein the drug delivery device
comprises a reservoir and a proximal filling port deployed to allow
introduction of a volume of a liquid drug into said reservoir to be
released over a period of time, and wherein said inserting and
filling are performed using a system comprising: (a) a hollow
needle having a central channel and a tip, the drug delivery device
being deployed within said central channel of said hollow needle;
(b) a plunger displaceable so as to push the drug delivery device
along said central channel and beyond said tip of said hollow
needle; and (c) a liquid injection device including a filling
needle extending within said central channel of said hollow needle
for engaging said filling port so as to allow filling of said
reservoir after at least part of said reservoir has been advanced
beyond said hollow needle.
3. The method of claim 2, wherein said reservoir is an inflatable
reservoir sized for deployment within said central channel when
substantially empty and inflatable by filling with a liquid drug to
assume a deployed size greater than dimensions of said central
channel.
4. The method of claim 2, wherein said filling needle extends
through at least part of said plunger such that said filling needle
engages said filling port prior to said inserting of said drug
delivery device.
5. The method of claim 2, wherein said drug delivery device
deployed within said hollow needle, said plunger, said filling
needle and said liquid injection device pre-filled with a quantity
of a liquid drug, are preassembled into a single integrated
delivery system for implanting and filling said drug delivery
device within the body.
6. The method of claim 2, wherein said tip of said hollow needle is
a beveled tip terminating at a point for introducing said drug
delivery device into the biological barrier without formation of a
prior incision.
7. The method of claim 2, further comprising an abutment surface
surrounding at least part of said hollow needle so as to define a
depth of penetration, and wherein said plunger has a predefined
fully-advanced position, such that, after penetration of said tip
into or through the biological barrier and advancing of said
plunger, said drug delivery device extends to a predefined depth
into the body.
8. The method of claim 2, wherein said drug delivery device
includes a radially expandable retention configuration configured
to anchor said drug delivery device relative to a layer or layers
of the biological barrier.
9. The method of claim 2, wherein said drug delivery device
includes a resiliently compressible retention configuration
configured to anchor said drug delivery device relative to a layer
or layers of the biological barrier.
10. The method of claim 1, wherein the biological barrier includes
the ocular sclera.
11. A system for filling an implanted drug delivery device with a
liquid, the system comprising: (a) a syringe comprising a syringe
body for receiving a quantity of the liquid, a filling needle and a
plunger; (b) a pressure measurement arrangement associated with the
syringe for measuring a pressure of the liquid within the syringe;
and (c) a processing system comprising a processor, the processing
system being associated with said pressure measurement arrangement
so as to receive fluid pressure measurements, wherein said
processing system is configured to process said fluid pressure
measurements to monitor for at least one alarm criteria.
12. The system of claim 11, wherein said at least one alarm
criteria includes the measured pressure dropping below a threshold
minimum value.
13. The system of claim 11, wherein said at least one alarm
criteria includes the measured pressure exceeding a threshold
maximum allowed value.
14. The system of claim 11, wherein said processing system is
configured to generate a warning under conditions of said alarm
criteria.
15. The system of claim 11, further comprising a display associated
with said processor, and wherein said processing system is
configured to determine from the measured pressure a quantity of
the liquid within the drug delivery device, and to display on said
display an indication of the quantity of the liquid within the drug
delivery device.
16. A method for filling an implanted drug delivery device with a
liquid, the method comprising: (a) providing the system of claim 11
containing a quantity of the liquid; (b) inserting the filling
needle into the drug delivery device and advancing the plunger of
the syringe; and (c) monitoring an output of the processing system
for an indication of the at least one alarm condition.
17. The method of claim 16, further comprising interrupting
advancing of the plunger to allow measurement of the liquid
pressure under zero-flow conditions.
Description
FIELD AND BACKGROUND OF THE INVENTION
[0001] The present invention relates to miniature drug delivery
devices and, in particular, it concerns drug delivery devices with
particularly low flow rates, and inserter systems for introducing
such devices into the body.
[0002] It is known to provide an implantable device which delivers
a drug slowly over a period of time. This approach avoids problems
of patient compliance, and provides particular advantages where
delivery of a drug to a specific target location allows use of much
lower overall dosage than would be required for systemic delivery,
possibly avoiding undesirable side effects.
[0003] In some cases, slow drug delivery is achieved by providing a
drug is dispersed in a matrix of resorbable material and is
gradually released as the matrix breaks down in the body. Examples
of this approach may he found in U.S. Pat. Nos. 4,351,337 and
4,450,150 to Sidman. This approach typically does not achieve
highly uniform drug release rates, and is not suitable for drugs
which must be delivered in a liquid form or which have high
diffusion rates through the matrix materials.
[0004] Examples of implantable devices for delivery of liquid drugs
include, but are not limited to, U.S. Pat. Nos. 5,163,920,
4,428,397, 4,820,273, 5,061,242, 5,993,414, 6,183,461 and
5,836,935.
[0005] Certain potential applications of such devices impose
particularly demanding conditions. For example, ocular applications
pose a challenge as to how to anchor an implanted device so that it
does not drift within the internal cavity of the eye. Furthermore,
the procedure for introducing and anchoring a highly miniature drug
delivery device is difficult to perform reliably and safely.
[0006] There is therefore a need for inserter systems for
introducing and anchoring miniature drug delivery devices into a
body structure such as the eye.
SUMMARY OF THE INVENTION
[0007] The present invention is a system and method for introducing
miniature drug delivery devices. The invention also provides
various structures for such miniature drug delivery devices.
[0008] According to the teachings of an embodiment of the present
invention there is provided, a method for introducing a drug
delivery device, the method comprising the steps of: (a) inserting
the drug delivery device via a channel of a hollow needle through
at least part of at least one layer of a biological barrier; and
(b) subsequent to the inserting, filling the drug delivery device
with a quantity of liquid drug via a filling needle extending
within the channel of the hollow needle.
[0009] According to a further feature of an embodiment of the
present invention, the drug delivery device comprises a reservoir
and a proximal filling port deployed to allow introduction of a
volume of a liquid drug into the reservoir to be released over a
period of time, and wherein the inserting and filling are performed
using a system comprising: (a) a hollow needle having a central
channel and a tip, the drug delivery device being deployed within
the central channel of the hollow needle; (b) a plunger
displaceable so as to push the drug delivery device along the
central channel and beyond the tip of the hollow needle; and (c) a
liquid injection device including a filling needle extending within
the central channel of the hollow needle for engaging the filling
port so as to allow filling of the reservoir after at least part of
the reservoir has been advanced beyond the hollow needle.
[0010] According to a further feature of an embodiment of the
present invention, the reservoir is an inflatable reservoir sized
for deployment within the central channel when substantially empty
and inflatable by filling with a liquid drug to assume a deployed
size greater than dimensions of the central channel.
[0011] According to a further feature of an embodiment of the
present invention, the filling needle extends through at least part
of the plunger such that the filling needle engages the filling
port prior to the inserting of the drug delivery device.
[0012] According to a further feature Of an embodiment of the
present invention, the drug delivery device deployed within the
hollow needle, the plunger, the filling needle and the liquid
injection device pre-filled with a quantity of a liquid drug, are
preassembled into a single integrated delivery system for
implanting and filling the drug delivery device within the
body.
[0013] According to a further feature of an embodiment of the
present invention, the tip of the hollow needle is a beveled tip
terminating at a point for introducing the drug delivery device
into the biological barrier without formation of a prior
incision.
[0014] According to a further feature of an embodiment of the
present invention, there is also provided an abutment surface
surrounding at least part of the hollow needle so as to define a
depth of penetration, and wherein the plunger has a. predefined
fully-advanced position, such that, after penetration of the tip
into or through the biological barrier and advancing of the
plunger, the drug delivery device extends to a predefined depth
into the body.
[0015] According to a further feature of an embodiment of the
present invention, the drug delivery device includes a radially
expandable retention configuration configured to anchor the drug
delivery device relative to a layer or layers of the biological
barrier.
[0016] According to a further feature of an embodiment of the
present invention, the drug delivery device includes a resiliently
compressible retention configuration configured to anchor the drug
delivery device relative to a layer or layers of the biological
harrier.
[0017] According to a further feature of an embodiment of the
present invention, the biological barrier includes the ocular
sclera.
[0018] There is also provided according to the teachings of an
embodiment of the present invention, a system for filling an
implanted drug delivery device with a liquid, the system
comprising: (a) a syringe comprising a syringe body for receiving a
quantity of the liquid, a filling needle and a plunger; (b) a
pressure measurement arrangement associated with the syringe for
measuring a pressure of the liquid within the syringe; and (c) a
processing system comprising a processor, the processing system
being associated with the pressure measurement arrangement so as to
receive fluid pressure measurements, wherein the processing system
is configured to process the fluid pressure measurements to monitor
for at least one alarm criteria.
[0019] According to a further feature of an embodiment of the
present invention, the at least one alarm criteria includes the
measured pressure dropping below a threshold minimum value.
[0020] According to a further feature of an embodiment of the
present invention, the at least one alarm criteria includes the
measured pressure exceeding a threshold maximum allowed value.
[0021] According to a further feature of an embodiment of the
present invention, the processing system is configured to generate
a warning under conditions of the alarm criteria.
[0022] According to a further feature of an embodiment of the
present invention, there is also provided a display associated with
the processor, and wherein the processing system is configured to
determine from the measured pressure a quantity of the liquid
within the drug delivery device, and to display on the display an
indication of the quantity of the liquid within the drug delivery
device.
[0023] There is also provided according to the teachings of an
embodiment of the present invention, a method for filling an
implanted drug delivery device with a liquid, the method
comprising: (a) providing the aforementioned filling system
containing a quantity of the liquid; (b) inserting the filling
needle into the drug delivery device and advancing the plunger of
the syringe; and (c) monitoring an output of the processing system
for an indication of the at least one alarm condition,
[0024] According to a further feature of an embodiment of the
present invention, advancing of the plunger is interrupted, to
allow measurement of the liquid pressure under zero-flow
conditions.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] The invention is herein described, by way of example only,
with reference to the accompanying drawings, wherein:
[0026] FIG. 1A is a side view of a system, constructed and
operative according to an embodiment of the present invention, for
introducing a drug delivery device through a biological barrier,
illustrated here schematically as the surface of a human or animal
eye;
[0027] FIG. 1B is a longitudinal cross-sectional view taken through
the view of FIG. 1A;
[0028] FIG. 2 is an enlarged view of the region of FIG. 1B
designated V1;
[0029] FIGS. 3A-3C are enlarged views of a region of FIG. 1A
showing an initial state and two successive states during
preparation of the system for use;
[0030] FIGS. 4A and 4B are enlarged views of the region of FIG. 2
designated V2, and showing the relative positions of a filling
needle and the drug delivery device corresponding to the states of
FIGS. 3A and 3C, respectively;
[0031] FIGS. 5A-5C show a preferred sequence for insertion of a
hollow needle of the delivery device into or through at least one
layer of the biological barrier;
[0032] FIGS. 6A and 6B are views similar to FIGS. 3A-3C showing a
further two successive states during advancing of the drug delivery
device into or through at least one layer of the biological
barrier;
[0033] FIG. 7A is a view similar to FIG. 1B corresponding to the
state of FIG. 6B;
[0034] FIG. 7B is an enlarged view of the region of FIG. 7A
designated V11;
[0035] FIG. 8A is an enlarged view of the region of FIG. 7B
designated V12, showing the deployed drug delivery device extending
into the body;
[0036] FIG. 8B is an enlarged view of the region of FIG. 8A
designated V13, showing a first implementation of a radially
expandable retention configuration partially deployed to anchor the
drug delivery device between layers of the biological barrier;
[0037] FIG. 8C is a view similar to FIG. 8A after operation of a
filling syringe to fill an inflatable reservoir of the drug
delivery device;
[0038] FIG. 8D is a view similar to FIG. 8C after withdrawal of the
deployment system, leaving the drug delivery device anchored
between layers of the biological barrier and extending into the
body for slow release drug delivery;
[0039] FIG. 8E is a view similar to FIG. 8D illustrating a variant
implementation of an anchoring configuration for anchoring the drug
delivery device of the above embodiment in the layers of the
biological barrier;
[0040] FIG. 8F is a view similar to FIG. 8D illustrating a further
variant implementation of an anchoring configuration for anchoring
the drug delivery device of the above embodiment in the layers of
the biological barrier;
[0041] FIGS. 9A and 9B are views similar to FIGS. 4A and 4B,
respectively, illustrating a variant implementation of the drug
delivery device with an alternative implementation of the radially
expandable retention configuration;
[0042] FIGS. 10A-10D are views similar to FIGS. 8A-8D,
respectively, for the variant implementation of FIGS. 9A and
9B;
[0043] FIG. 10E is an enlarged view of the region of FIG. 10D
designated V19, illustrating the deployed state of the alternative
implementation of the radially expandable retention
configuration;
[0044] FIGS. 11A-11D are schematic longitudinal cross-sectional
views taken through a system, constructed and operative according
to an embodiment of the present invention, for introducing a drug
delivery device through a biological barrier, showing a sequence of
states during filling of a delivery system with a liquid drug in
preparation for deployment of the drug delivery device;
[0045] FIGS. 12A-12E are schematic longitudinal cross-sectional
views taken through the system of FIGS. 11A-11D, showing a sequence
of states during deployment and filling of the drug delivery
device;
[0046] FIG. 13 is a schematic representation of a device according
to an aspect of the present invention for refilling a drug delivery
device according to the present invention; and
[0047] FIGS. 14A and 14B are schematic longitudinal cross-sectional
views illustrating a retrieval system for retrieving a drug
delivery device according to the present invention, the retrieval
system being shown in an insertion state and a retrieval state,
respectively.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0048] The present invention is, according to a first aspect, a
system and method for introducing a drug delivery device into a
body. This first aspect of the invention may be implemented with a
range of drug delivery devices, particularly those having a
reservoir for storing a quantity of liquid drug for slow release.
Other aspects of the present invention relate to devices and
methods for refilling and retrieving the corresponding drug
delivery devices.
[0049] The principles and operation of systems, methods and devices
according to the present invention may be better understood with
reference to the drawings and the accompanying description.
[0050] Referring now to the drawings, FIGS. 1A-8F illustrate the
structure and operation of a first exemplary embodiment of a
system, generally designated 10, and a corresponding method for
introducing a drug delivery device through at least one layer of a
biological barrier into a body, illustrated here with reference to
a non-limiting example of the human eye 100.
[0051] In general terms, system 10 includes a hollow needle 12,
having a central channel 14 and a tip 16, and a drug delivery
device 18 comprising a reservoir for receiving a volume of a liquid
drug to be released over a period of time. Drug delivery device 18
is small relative to the overall dimensions of system 10, and is
best seen in FIGS. 4A, 4B and 8A-8D. Drug delivery device 18 is
initially deployed within central channel 14 of hollow needle 12. A
plunger 20 is displaceable within central channel 14 so as to push
the drug delivery device beyond the tip of the hollow needle. When
tip 16 of hollow needle 12 is inserted into or through a biological
barrier of a body and plunger 20 is displaced towards tip 16, drug
delivery device 18 is advanced beyond the hollow needle for
deployment within the body, as shown in FIGS. 7A-8A.
[0052] In certain particularly preferred embodiments, the reservoir
of drug delivery device 18 is an inflatable reservoir sized for
deployment within central channel 14 when substantially empty, and
inflatable by filling with a liquid drug to assume a deployed size
greater than dimensions of the central channel. Thus, when empty,
drug delivery device 18 has lateral dimensions less than the inner
diameter of channel 14, as shown in FIGS. 4A & 8A. After
filling, as shown in FIGS. 8C and 8D, the dimensions are increased
such that at least two, and typically all three, dimensions of drug
delivery device are greater than the inner diameter of channel
14.
[0053] The aforementioned approach of introducing the drug delivery
device in a collapsed state and subsequently filling it facilitates
introduction of the device via a much smaller needle canula than
would otherwise be possible. Thus, certain preferred embodiments of
the present invention employ a hollow needle 12 with internal
diameter less than 2 millimeters. In certain particularly delicate
applications such as ocular application, it may be preferred to
employ internal diameters of less than 1 millimeter, and most
preferably less than 0.5 millimeter. The deployed volume of the
drug delivery device after filling is typically at least 10 times
greater than the empty volume during deployment, thereby
facilitating controlled delivery of relatively large quantities of
drug.
[0054] According to certain particularly preferred embodiments of
the present invention, introduction of the substantially empty drug
delivery device and. filling of the device are performed
sequentially using a single deployment system, as illustrated here.
Thus, in the preferred example illustrated here, system 10 includes
a liquid injection device, such as a filling syringe 22 (visible in
FIG. 1A), linked to a tilling needle 24 (best seen in FIG. 4A).
Filling needle 24 extends within central channel 14 for engaging a
filling port 26 of drug delivery device 18, thereby allowing
filling of the reservoir after at least part of the reservoir has
been advanced beyond the hollow needle.
[0055] In the particularly preferred non-limiting example
illustrated herein, filling needle 24 is integrated with plunger 20
so that the filling needle engages the filling port prior to
advancing of the drug delivery device. In this case, according to
certain preferred implementations, the engagement of filling needle
24 with filling port 26 is performed as a preparatory step prior to
insertion of hollow needle 12 into the biological barrier. This is
illustrated here with reference to the external views of FIGS.
3A-3C, which show guided retraction of a distal tip portion 28 of
system 10 relative to a main block 30 of the deployment device. In
the implementation shown here, the length of this initial movement
is limited by a pin-and-slot inter-engagement, shown here as a pin
32 of main block 30 which is engaged in a shaped slot 34 formed in
distal tip portion 28. The resulting engagement of filling needle
24 with filling port 26 is shown in FIG. 4B.
[0056] In a particularly preferred implementation, drug delivery
device 18 is introduced and filled sequentially by a single
integrated delivery system. Thus, the delivery system includes
hollow needle 12, plunger 20, filling needle 24 and filling syringe
22, pre-filled with a quantity of a liquid drug, as illustrated in
FIG. 1B.
[0057] Turning now to additional features of the preferred
exemplary embodiment of FIGS. 1A-8F, needle tip 16 is illustrated
in the drawings as being a beveled tip which provides a sharp
point. Such an embodiment allows the entire procedure, from initial
penetration of the tissue through deployment and filling of the
drug delivery device, to be performed using the system of the
invention without prior preparation of the insertion site. It
should he noted however that alternative implementations may employ
a flat-ended or otherwise blunt hollow needle 12, and rely upon a
separately made prior incision, as is known in various other
procedures, particularly in the field of ocular procedures where a
self-sealing flap may in some cases be cut more easily with a flat
cutting tool.
[0058] In the case of a pointed needle tip, a preferred sequence
for insertion of needle tip 16 is illustrated schematically in
FIGS. 5A-5C. According to this sequence, initial penetration of
needle tip 16 is performed while the device is significantly
inclined. relative to the local perpendicular to the tissue surface
so that the needle tip penetrates through the outer tissue layers
as an oblique angle (FIG. 5B). The device is then straightened to
an upright position relative to the local tissue surface (FIG. 5C)
prior to completion of the drug delivery device insertion. Without
in any way limiting the scope of the invention, the aforementioned
angular motion is believed to generate relative lateral
displacement between the outer layers of the layered tissue. As a
result, after removal of the inserter device, elastic return of the
tissue to its original position tends to result in the penetration
openings being out of alignment, thereby providing a self-sealing
function.
[0059] Referring to FIG. 2, distal tip portion 28 preferably
provides an abutment surface 28a surrounding at least part of
hollow needle 12 so as to define a depth of penetration of the
needle. Additionally, plunger 20 has a predefined fully-advanced
position. In the example illustrated here, plunger 20 is integrated
with main block 30, which also features a forward projection 30a
configured to enter a corresponding recess 28b in the rear of
distal tip portion 28, Forward projection 30a is here shown as a
cylindrical tube and recess 28b as a corresponding cylindrical
recess. These structures define a fully advanced position of main
block 30, and hence also of plunger 20, relative to distal tip
portion 28, and also provides concentric guiding surfaces that help
to maintain alignment of the components during use. The combined
effect of the depth-limiting abutment surface 28a and the
predefined range of motion of plunger 20 is to predefine an
insertion depth to which drug delivery device 18 extends into the
body once deployed, as illustrated in FIG. 7B.
[0060] According to another aspect of certain preferred embodiments
of the present invention, drug delivery device 18 includes a
radially expandable retention configuration 36 configured to anchor
the drug delivery device within a layer, or between layers, of the
biological barrier. According to a first implementation of this
feature, as illustrated in FIGS. 8B and 8D, radially expandable
retention configuration 36 includes an expander element resiliently
biased to a size greater than the central channel and temporarily
compressed for insertion into the central channel. The expander
element is typically a C-shaped resilient partial-ring which is
squeezed closed or otherwise compressed for insertion within
central channel 14, and which returns resiliently to an oversize
diameter as it emerges from tip 16.
[0061] In the example of ocular deployment as exemplified in the
drawings, the structure of the biological barrier of eye 100 is
made up of a number of different layers, here designated
schematically as layers 102, 104 and 106, corresponding to the
conjunctiva, sclera and choroid, respectively. In this case, it is
particularly preferred that the length of hollow needle 12
projecting from abutment surface 28a is chosen to correspond
roughly to the depth of the boundary between two of the layers 104
and 106, so that expandable retention configuration 36 becomes
lodged between layers 104 and 106 when deployed. Radially
expandable retention configuration 36 then serves to anchor one end
of drug delivery device 18 between the layers after removal of the
delivery system, as shown FIG. 8D.
[0062] FIG. 8E shows a variant implementation in which the depth of
penetration is chosen such that radially expandable retention
configuration lodges itself within the thickness of the sclera
layer 104, thereby relying on the relatively high structural
strength of the sclera for positive anchoring of the device. FIG.
8F shows a further variant in which two radially expandable
retention elements 36 and 36' are spaced apart to provide
two-location anchoring, preferably corresponding to the inner and
outer surfaces of the sclera 104.
[0063] Referring parenthetically to FIGS. 9A-10E, these illustrate
an alternative implementation of a radially expandable retention
element in which the retention element includes a flexible sleeve
36a, best seen in FIGS. 10B and 10E. Flexible sleeve 36a is
deployed around an external surface of the drug delivery device
while within the hollow needle, and is made from sufficiently loose
and flexible material that it tends to become caught on surrounding
tissue as it emerges from hollow needle 12, thereby becoming
axially compressed and radially expanded (i.e., forming an outward
fold or "kink") during advancing of the drug delivery device from
the hollow needle. Hollow needle 12 is inserted through layer 102
and at least part of layer 104, so that flexible sleeve 36a does
not interact with those layers as device 18 is advanced into the
tissue. When flexible sleeve 36a starts to leave needle 12 and
encounters the tissue layer 106, the sleeve becomes caught on the
tissue and slides along the outside of the drug delivery device.
The bunching up of the sleeve material forms the aforementioned
outward fold which tends to be caught between the layers of the
biological barrier and provide the aforementioned anchoring effect.
In all other respects, the device of FIGS. 9A-10E may be
implemented in a system and method similar to those described in
FIGS. 1A-8D.
[0064] Although shown here in the context of a multi-layer
biological barrier, it should be noted that similar structures may
be used to anchor the device of the present invention relative to a
single layer barrier, or relative to other body structures, all as
will be clear to a person having ordinary skill in the art
according to the particular intended application.
[0065] Regarding drug delivery device 18 itself, this aspect of the
present invention may be implemented with a wide range of drug
delivery devices that are based on an inflatable bladder-type
reservoir for storing and slowly releasing a quantity of a liquid
drug composition or the like. A number of non-limiting examples of
suitable drug delivery devices may be found in co-pending
international application publication no. WO 2011/101833 filed Feb.
22, 2011, and related U.S. patent application Ser. No. 13/430,730,
filed 27 Mar. 2012, which do not constitute prior art. These
examples regulate flow rates for release of the liquid drug by
employing fine channels formed in facing surfaces between two parts
of the drug delivery device, preferably also provide
pressure-responsive regulation of the flow rate, or by use of a
flow path passing through a porous block which may be
biodegradable.
[0066] The operation of system 10 will now be clearly understood.
In preparation for use, distal tip portion 28 is first retracted
towards main block 30 to engage filling needle 24 with filling port
26, as illustrated in FIGS. 3A-3C and 4A-4B. Needle tip 16 is then
introduced as illustrated in FIGS. 5A-5C, or via a preformed
incision, and main block 30 is advanced as Shown in FIGS. 6A-6B to
deploy drug delivery device within the body, as shown in FIG.
7A-8A. During introduction of the device, the radially expandable
retention configuration 36 or 36a is at least partially deployed
(FIGS. 8B and 10B). The piston of filling syringe 22 is then
advanced so as to fill the reservoir of drug delivery device 18
(FIGS. 8C and 10C), and the deployment system is withdrawn, leaving
the deployed and operating drug delivery device 18 anchored between
layers of the biological barrier as shown in FIGS. 8D and 10D.
[0067] Turning now to FIGS. 11A-12E, there is shown a variant
embodiment of a system, generally designated 200 for introducing a
drug delivery device through at least one layer of a biological
barrier into a body, such as the human eye. System 200 is generally
analogous in structure and function to system 10 described
above.
[0068] Thus, in general terms, similar to system 10, system 200
includes a hollow needle 212, having a central channel 214 and a
tip 216, and a drug delivery device 218 which includes a reservoir
for receiving a volume of a liquid drug to be released over a
period of time. Drug delivery device 218 is small relative to the
overall dimensions of system 200 and is initially deployed within
central channel 214 of hollow needle 212.
[0069] One distinguishing feature of system 200 is that sequential
deployment and filling of drug delivery device 218 are effected by
a single continuous motion of a manually operated actuator 220,
thereby simplifying operation of the system, as will now be
detailed.
[0070] As seen in FIG. 11A, system 200 includes a filling needle
222 which extends through a hollow spacer 224 to a penetrating tip
226 which is initially embedded in a seal 228. The opposite end of
filling needle 222 passes through, and is integrated with, a first
piston 230 which can slide in sealing contact with the inner bore
of a syringe body 234. A second piston 232, also in sealing contact
with the inner bore of syringe body 234, is initially in close
contact with first piston 230.
[0071] Prior to use, system 200 is prepared by introduction of the
liquid drug to a storage volume defined within syringe body 234
between pistons 230 and 232. A non-limiting exemplary
implementation of this preparatory process is illustrated in FIGS.
11A-11D. In the implementation shown here, an adapter 236 includes
alignment features 238 for centering an adapter needle 240 within
the bore of syringe body 234 such that, as the adapter is inserted
as shown in FIGS. 11A and 11B, the tip of adapter needle 240
penetrates an elastomer septum of second piston 232 to reach a
small recess between the two pistons. The required quantity of drug
is then introduced via adapter 236, typically by attachment of a
standard syringe (not shown) to the rear of the adapter.
Introduction of the liquid drug forces the two pistons apart,
advancing first piston 230 to the position illustrated in FIG. 11C
to make space for the drug which occupies volume 244. This motion
of piston 230 causes a corresponding advancing of filling needle
222 so that the penetrating tip 226 emerges from seal 228 and
penetrates through the septum (not shown) of drug delivery device
218. Drug delivery device 218 is prevented from moving at this
stage by the presence of a protective cap 242 which includes an
elastomer stopper 246. Adapter 236 is then removed (FIG. 11D),
leaving system 200 ready for use.
[0072] For deployment of the drug delivery device through a
biological membrane, a manually operated actuator 220, shown here
in a preferred embodiment in the form of a plunger, is attached to
second piston 232, as illustrated in FIG. 12A, and protective cap
242 is removed, leaving the system as illustrated in FIG. 12B. Tip
216 of hollow needle 212 is then inserted into the biological
barrier, preferably in a manner similar to that described above
with reference to FIGS. 5A-5C.
[0073] Manual pressure is then applied to plunger 220 to advance it
along the body of syringe 234. Pressure applied by the plunger to
piston 232 applies pressure to the liquid drug which in turn
applies pressure to piston 230. This pressure advances piston 230,
which presses against spacer 224, thereby advancing spacer 224,
seal 228 and drug delivery device 218 along hollow needle 212 until
drug delivery device 218 is deployed in the desired position beyond
the tip of the deployment system (FIG. 12C). Thus plunger 220,
piston 232, liquid-filled volume 244, piston 230, spacer 224 and
seal 228 all function together as a compound plunger with which
filling needle 222 is integrated. Until this point, drag delivery
device 218 was prevented from inflating due to the walls of hollow
needle 212 surrounding it. After leaving the confines of hollow
needle 212, and with piston 230 reaching a stop position at the end
of the bore of syringe 234, further displacement of plunger 220 and
piston 232 forces the liquid drug from volume 244 along filling
needle 222, thereby inflating the reservoir of drug delivery device
218, as shown in FIG. 12D. Thus, both insertion of the drug
delivery device and filling of the drug delivery device with liquid
drug are both achieved sequentially by the advancing of plunger 220
unidirectionally along its range of motion. The deployment system
200 is then withdrawn, leaving drug delivery device 218 in position
for slow delivery of the drug over a period of time.
[0074] It should be noted that system 200 has been shown here
schematically, and has only been detailed to an extent necessary to
appreciate the distinctive features of this embodiment, while
numerous other features that are similar to features of the
embodiment described above have not been detailed here. For
example, drug delivery device 218 preferably features one or more
radially expandable retention elements, such as is described above
with reference to FIGS. 8A-8D, 8E, 8F or 10A-10E. Similarly, the
distal end of syringe 234 which surrounds hollow needle 212
preferably defines abutment surfaces for defining the extent of
penetration of hollow needle 212. Except where explicitly stated or
self-evident otherwise, it should be understood that features
described herein with reference to one embodiment may also be
implemented in the context of other embodiments of the present
invention.
[0075] Turning now to FIG. 13, as mentioned earlier, certain
particularly preferred embodiments of the present invention provide
an option for refilling of the drug delivery device deployed
according to the present invention in situ. Given the very small
dimensions of the drug delivery device according to certain
implementations of the present invention, there is a need to ensure
that a refilling needle has been correctly inserted through the
refilling septum of the drug delivery device, and remains correctly
inserted throughout the refilling process. There is also a need to
assess the quantity of the drug present in the reservoir so as to
ensure sufficient drug is provided without dangerously over-filling
the device. For this purpose, the present invention provides a
refilling device, generally designated 300, constructed and
operative according to a further feature of an embodiment of the
present invention. Refilling device 300 is shown here schematically
as a syringe type device including a syringe body 302 and a plunger
304 for delivering refill drug to the drug delivery device via a
refill needle 306. Additionally, device 300 includes a pressure
measurement arrangement 308 deployed for measuring the fluid
pressure within the syringe during operation, and a processing
system 310 having a processor, a data storage device and a display,
connected so as to receive the fluid pressure measurements.
Monitoring of the pressure after insertion of the device and prior
to injection of its contents provides a reliable verification that
the needle has correctly reached the elevated-pressure inner volume
of the drug storage reservoir. A known and pre-calibrated profile
mapping pressure to reservoir content may also facilitate
evaluation of the degree of filling of the reservoir during the
refilling process. Processing system 310 preferably stores a
look-up table or parametrically defined model, preferably
empirically derived, indicating the current reservoir contents as a
function of the measured pressure within the syringe under
zero-flow conditions. Processing system thus preferably translates
measured pressure into a visually displayed indication of the
current reservoir content. The processor preferably also provides a
warning function if the sensed pressure drops below the expected
value, indicating that the refill needle 306 may not be correctly
inserted into the drug delivery device or may have become
dislodged. Most preferably, the refilling device 300 also features
a safety valve, deployed for example as part of plunger 304, which
ensures release of the contained drug outside the patient in the
event that the pressure exceeds a maximum allowed threshold value
which might lead to a risk of damaging the drug delivery
device.
[0076] Turning now to FIGS. 14A and 14B, there is shown a preferred
embodiment of a retrieval device, generally designated 400, for
retrieving the drug delivery devices of the present invention.
Retrieval device 400 preferably features a fine needle 402, similar
to the refilling needles described above, which is sufficiently
fine to be inserted through the refilling port of the drug delivery
device. Inside needle 402 is a resilient wire 404 pre-formed into a
hook or otherwise curled form, but maintained in a straightened
configuration by the small diameter inner lumen of needle 402. An
actuator 406 is manually deployable to selectively advance
resilient wire 404 so as to extend beyond needle 402.
[0077] In use, needle 402 is introduced into the drug delivery
device via the refilling port while resilient wire 404 is in its
straightened state. Wire 404 is then advanced within the device,
forming its hooked or otherwise curled form within the device,
preferably so as to become anchored on or tangled around internal
features of the drug delivery device. The retrieval device can then
be removed, drawing after it the drug delivery device.
[0078] It will now be appreciated that various embodiments of the
present invention provides a number of significant advantages over
existing options in the field of implantable devices for delivering
liquid medications. hi particular, certain embodiments of the
present invention provide one or more of the following functions:
[0079] Insertion of the drug delivery device through at least part
of at least one layer of a biological barrier and anchoring of the
drug delivery device within a layer, or between layers, of the
biological barrier, where both the inserting and anchoring are
performed sequentially by use of a single deployment system. [0080]
Insertion of the drug delivery device through t least part of at
least one layer of a biological barrier and subsequent filling of
the drug delivery device with a quantity of liquid drug, wherein
both the inserting and filling are performed sequentially by use of
a single deployment system. [0081] Introduction of the drug
delivery device by a straightforward injection technique via a
needle of diameter smaller than the dimensions of the liquid
reservoir after filling. [0082] Introduction of the drug delivery
device by a deployment device which predefines the depth of
insertion, thereby facilitating consistent results without
requiring unusual skill in the deployment process.
[0083] It will be appreciated that the above descriptions are
intended only to serve as examples, and that many other embodiments
are possible within the scope of the present invention as defined
in the appended claims.
* * * * *