U.S. patent application number 10/336459 was filed with the patent office on 2003-07-17 for drug delivery device.
This patent application is currently assigned to Elan Pharma International Limited. Invention is credited to Azoulay, Avi, Brodeur, Craig, Cabiri, Oz, Daily, David, Davidson, Diana, Lavi, Gilad, Rozanowich, Mario, Sahar, Miki, Shor, Eran, Stern, Jacob, Tsals, Izrail.
Application Number | 20030135159 10/336459 |
Document ID | / |
Family ID | 24307007 |
Filed Date | 2003-07-17 |
United States Patent
Application |
20030135159 |
Kind Code |
A1 |
Daily, David ; et
al. |
July 17, 2003 |
Drug delivery device
Abstract
A drug delivery device having a housing having an internal
reservoir in communication with a drug delivery outlet via a fluid
path. An expandable chamber disposed adjacent to the reservoir
forces drug from the reservoir to the outlet when supplied with a
gas. A flow regulating chamber, in communication with the fluid
path, is capable of volumetric changes in response to temperature
and/or pressure changes. An increase in the volume of the flow
regulating chamber increases flow resistance to the outlet and
thereby counteracts the corresponding increase in delivery rate
resulting from the expansion of the expandable chamber due to the
same volumetric changes in response to temperature and/or pressure.
In a preferred embodiment, an electrical circuit has a current
stabilizing element in electrical communication with an
electrolytic cell which supplies the gas. A throttling device
maintains a higher pressure in the device to reduce possible
clogging of the fluid path. In a preferred embodiment, the drug
delivery device is packaged to insulate the device from atmospheric
pressure and humidity.
Inventors: |
Daily, David; (Herzliya,
IL) ; Cabiri, Oz; (Macabim, IL) ; Rozanowich,
Mario; (Ezer, IL) ; Sahar, Miki; (Ramat
Hasharon, IL) ; Stern, Jacob; (Shoam, IL) ;
Davidson, Diana; (Framingham, MA) ; Tsals,
Izrail; (Sudbury, MA) ; Lavi, Gilad; (Holon,
IL) ; Azoulay, Avi; (Ashdod, IL) ; Shor,
Eran; (Moshav Bitzaron, IL) ; Brodeur, Craig;
(Marlborough, MA) |
Correspondence
Address: |
CAESAR, RIVISE, BERNSTEIN, COHEN & POKOTILOW, LTD.
ATTN: ELAN
12TH FLOOR, SEVEN PENN CENTER
1635 MARKET STREET
PHILADELPHIA
PA
19103-2212
US
|
Assignee: |
Elan Pharma International
Limited
WIL House Shannon Business Park
Shannon Claire County
IE
|
Family ID: |
24307007 |
Appl. No.: |
10/336459 |
Filed: |
January 3, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10336459 |
Jan 3, 2003 |
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09577033 |
May 23, 2000 |
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6530900 |
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09577033 |
May 23, 2000 |
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09072875 |
May 5, 1998 |
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6186982 |
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60045745 |
May 6, 1997 |
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Current U.S.
Class: |
604/141 |
Current CPC
Class: |
A61M 5/14593 20130101;
A61M 2005/14204 20130101; A61M 5/16877 20130101; A61M 2005/14252
20130101; A61M 5/155 20130101; A61M 2206/22 20130101; A61M
2005/14264 20130101; A61M 2005/1426 20130101; A61M 5/14248
20130101 |
Class at
Publication: |
604/141 |
International
Class: |
A61M 037/00 |
Claims
What is claimed is:
1. A drug delivery device comprising: a housing having an internal
chamber; an elastomeric diaphragm within said internal chamber for
defining an internal drug reservoir chamber and an expandable gas
chamber which forms a pair of variable area chambers; a gas
generator for expanding the area of said expandable gas chamber and
decreasing the area of said internal drug reservoir; a lumen having
an inlet and an outlet; a fluid path defined between said internal
drug reservoir and said lumen input; a flow regulator, in
communication with said fluid path, for effecting volumetric
changes in response to ambient condition changes, said flow
regulator comprising a chamber filled with fixed volume of air and
a flexible chamber surface that opens or closes said lumen inlet
based on a pressure differential between said fluid path and said
internal drug reservoir chamber; and means for maintaining a
specific flow rate of drug delivery, said means for maintaining a
specific flow rate comprising an electrical circuit that controls
said gas generator.
2. The drug delivery device of claim 1 wherein said lumen is a
needle and said flexible chamber surface is a diaphragm.
3. The drug delivery device of claim 2 wherein said gas generator
generates a sufficient gas pressure to drive the drug through said
fluid path and to deform said diaphragm to allow said drug to flow
through said needle and prevent a bolus delivery of drug that may
be caused by an occlusion in said needle.
4. A drug delivery device comprising: a housing having an internal
chamber; an elastomeric diaphragm within said internal chamber for
defining an internal drug reservoir chamber and an expandable gas
chamber which form. a pair of variable area chambers; a gas
generator for expanding the area of said expandable gas chamber and
decreasing the area of said internal reservoir; a drug delivery
outlet; a fluid path defined between said internal reservoir and
said drug delivery outlet; a flow regulator, in communication with
said fluid path, for effecting volumetric changes in response to
ambient condition changes; and means for maintaining a specific
flow rate of drug delivery, said means for maintaining a specific
flow rate comprising: an electrical circuit that controls said gas
generator; and an electrical switch, coupled to said electrical
circuit, that which controls power to said electrical circuit, said
electrical switch being is controlled by the pressure differential
between said expandable gas chamber and a third chamber filled with
a predetermined volume of gas.
5. The drug delivery device of claim 4 wherein said electrical
switch comprises a conductive lever that interfaces with a
conductive membrane which forms a surface of said third chamber
filled with said predetermined volume of gas, said lever either
contacting, or not contacting, said membrane which can flex
depending on the pressure differential between said expandable gas
chamber and said third chamber, to open or close said switch.
6. The drug delivery device of claim 4 wherein said electrical
switch cannot be closed, once opened, said switch comprising: an
isolator membrane that forms a flexible surface of said third
chamber; a conductive thread that runs along said flexible surface;
and said conductive thread conveying power to said electrical
circuit whenever the pressure in said expandable gas chamber is
less than the pressure in said third chamber, said conductive
thread severing whenever the pressure in said expandable gas
chamber exceeds the pressure in said third chamber, thereby
terminating power to said electrical circuit.
7. The drug delivery device of claim 4 wherein said electrical
switch comprises: a channel having a first end exposed to said
expandable gas chamber and a second end exposed to said third
chamber; a pair of electrodes across the width of said channel; a
conductive metal droplet that can move inside said chamber; and
wherein whenever the pressure in said expandable gas chamber is
less than the pressure in said third chamber, said conductive metal
droplet electrically couples said pair of electrodes together and
whenever the pressure in said expandable gas chamber exceeds the
pressure in said third chamber, said conductive meal droplet is
driven out of contact with said pair of electrodes.
8. The drug delivery device of claim 7 wherein said conductive
metal droplet comprises mercury.
9. A method of controlling the rate of drug delivery, said method
comprising the steps of: providing a drug delivery device having a
housing including an internal chamber and an elastomeric diaphragm
within said internal chamber for defining an internal drug
reservoir chamber and an expandable gas chamber that form a pair of
variable area chambers; expanding the area of the expandable gas
chamber and decreasing the area of the internal area by generating
a gas in an electrolytic cell controlled by an electrical circuit
to drive the drug out of said reservoir at a specific flow rate;
and altering the flow which is in communication with the fluid path
between the internal reservoir and a needle outlet in response to
ambient condition changes by valving a needle input and requiring
that the driven drug pressure required to open the valve be equal
to, or greater than, ambient pressure.
10. A method of preventing a bolus delivery of drug from a drug
delivery device, said method comprising the steps of: providing a
drug delivery device having a housing including an internal chamber
and an elastomeric diaphragm within said internal chamber for
defining an internal drug reservoir chamber and an expandable gas
chamber that form a pair of variable area chambers; expanding the
area of the expandable gas chamber and decreasing the area of the
internal area by generating a gas in an electrolytic cell
controlled by an electrical circuit to drive the drug out of said
reservoir at a specific flow rate; and altering the flow which is
in communication with the fluid path between the internal reservoir
and a needle outlet by valving a needle input and requiring that
the driven drug pressure required to open the valve be greater than
back pressure created by an occlusion of said needle.
11. A method of preventing a bolus delivery of drug from a drug
delivery device, said method comprising the steps of: providing a
drug delivery device having a housing including an internal chamber
and an elastomeric diaphragm within said internal chamber for
defining an internal drug reservoir chamber and an expandable gas
chamber that form a pair of variable area chambers; expanding the
area of the expandable gas chamber and decreasing the area of the
internal area by generating a gas in an electrolytic cell
controlled by an electrical circuit to drive the drug out of said
reservoir at a specific flow rate; and de-activating said
generation of gas by sensing a pressure differential between said
expandable gas chamber and a reference gas chamber wherein the
pressure in said expandable gas chamber exceeds the pressure in
said reference gas chamber.
12. The method of claim 11 further comprising the step of
re-activating said generation of gas whenever the pressure in said
expandable gas chamber is less than the pressure in said reference
gas chamber.
13. A drug delivery device comprising: a housing having an internal
chamber; an elastomeric diaphragm within said internal chamber for
defining an internal drug reservoir chamber and an expandable gas
chamber which form a pair of variable area chambers; an
electrolytic cell controlled by an electrical circuit which
generates a gas for expanding the area of the expandable gas
chamber and decreasing the area of said internal reservoir; a drug
delivery outlet; a fluid path defined between said internal
reservoir and said drug delivery outlet; a flow regulator, in
communication with said fluid path, for effecting volumetric
changes in response to ambient condition changes; and a visual drug
quantity indicator carried by said housing.
14. The drug delivery device of claim 13 wherein said elastomeric
diaphragm comprises a color and wherein said visual drug quantity
indicator comprises a window having a transparent portion and a
portion having the color of said elastomeric diaphragm and wherein
the color appearing in said window informs a user of the quantity
of drug in said device.
15. The drug delivery device of claim 13 further comprising a
visual usage indicator indicating proper usage of said device.
16. The drug delivery device of claim 15 wherein said visual usage
indicator comprises a component which is to be hidden when properly
installed on the user's body, said component including a color that
can only be seen by the user if said device is installed
improperly.
17. The drug delivery device of claim 15 wherein said visual usage
indicator comprises a component which is to be removed prior to
activating said device, said component including a color that
alerts the user to remove said component before said device can be
activated.
18. The drug delivery device of claim 13 wherein said electrolytic
cell is covered by a foil cover.
19. The drug delivery device of claim 18 further comprising an
activation mechanism having an electrical contact and a puncturing
device for puncturing said foil cover of said electrolytic
cell.
20. A method of controlling the rate of drug delivery comprising
the steps of: providing a drug delivery device having a housing
including an internal chamber and an elastomeric diaphragm within
said internal chamber for defining an internal drug reservoir
chamber and an expandable gas chamber that form a pair of variable
area chambers; expanding the area of the expandable gas chamber and
decreasing the area of the internal area by generating a gas in an
electrolytic cell controlled by an electrical circuit; altering the
flow which is in communication with the fluid path between the
internal reservoir and a drug delivery outlet in response to
ambient condition changes; and controlling residual air volume,
material permeability, material properties of plastic material in
said device and said membrane seal.
21. A method of controlling the rate of drug delivery comprising
the steps of: providing a drug delivery device having a housing
including an internal chamber and an elastomeric diaphragm within
said internal chamber for defining an internal drug reservoir
chamber and an expandable gas chamber that form a pair of variable
area chambers; expanding the area of the expandable gas chamber and
decreasing the area of the internal area by generating a gas in an
electrolytic cell controlled by an electrical circuit; altering the
flow which is in communication with the fluid path between the
internal reservoir and a drug delivery outlet in response to
ambient condition changes; and packaging said drug delivery system
to insulate said device from environmental conditions.
22. The method of claim 21 wherein one of said environmental
conditions is atmospheric pressure.
23. The method of claim 21 wherein one of said environmental
conditions is humidity.
24. A method of controlling the rate of drug delivery comprising
the steps of: providing a drug delivery device having a housing
including an internal chamber and an elastomeric diaphragm within
said internal chamber for defining an internal drug reservoir
chamber and an expandable gas chamber that form a pair of variable
area chambers; expanding the area of the expandable gas chamber and
decreasing the area of the internal area by generating a gas in an
electrolytic cell controlled by an electrical circuit; altering the
flow which is in communication with the fluid path between the
internal reservoir and a drug delivery outlet in response to
ambient condition changes; and including an insertion device for
accommodating design tolerances.
25. The method of claim 24 wherein said insertion device comprises
foam.
26. A drug delivery device comprising: a housing having an internal
chamber; providing a drug delivery device having a housing
including an internal chamber and an elastomeric diaphragm within
said internal chamber for defining an internal drug reservoir
chamber and an expandable gas chamber that form a pair of variable
area chambers; a gas generator having an electrolytic cell and an
electrical circuit, said gas generator providing gas at a
controllable rate into said expandable gas chamber; said electrical
circuit having a current stabilizing element in electrical
communication with said electrolytic cell; a drug delivery outlet;
and a fluid path defined between said internal reservoir and said
drug delivery outlet and said reservoir.
27. The drug delivery device of claim 26 further comprising a flow
regulator, in communication with said fluid path, for effecting
volumetric changes in response to ambient condition changes.
28. The drug delivery device of claim 26 wherein said drug delivery
outlet comprises a tube extending from said housing.
29. The drug delivery device of claim 28 wherein said tubing is
coupled to said housing at an outlet port having a luer
connection.
30. The drug delivery device of claim 29 further comprising an
epidural needle.
31. The drug delivery device of claim 24 wherein said drug delivery
outlet comprises a needle extending from said housing for
penetration of the skin of a subject.
32. The drug delivery device of claim 31 further comprising a
displaceable cover that is coupled to said housing such that
displacement of said housing relative to said cover when said cover
has been applied to the skin of a subject causes said delivery
needle to penetrate the skin of the subject.
33. The drug delivery device of claim 32 wherein said displaceable
cover is displaceable relative to said housing between a first
position in which said needle is concealed from the exterior of
said device, a second position in which said delivery needle
protrudes from said device for penetration of the skin, and wherein
said device further comprises means for locking said device in said
first position after a single reciprocation of said device from
said first position to said second position and back to said first
position.
34. The drug delivery device of claim 33 further comprising a
visual usage indicator indicating proper usage of said device.
35. The drug delivery device of claim 34 wherein said visual usage
indicator comprises a component which is to be hidden when properly
installed on the user's body, said component including a color that
can only be seen by the user if said device is installed
improperly.
36. The drug delivery device of claim 34 wherein said visual usage
indicator comprises a component which is to be removed prior to
activating said device, said component including a color that
alerts the user to remove said component before said device can be
activated.
37. The drug delivery device of claim 33 wherein movement of said
cover relative to said housing is initially prevented by a
removable locking member.
38. The drug delivery device of claim 37 wherein the presence of
said removable locking member also prevents said means for
providing a gas from being actuated.
39. The drug delivery device of claim 27 wherein said flow
regulator includes a member having a cavity and a flow diaphragm
defining a closed space, said member being movable in said flow
path.
40. The drug delivery device of claim 27 wherein said flow
regulating chamber includes a member having a cavity and a flow
diaphragm defining a closed space, said member being rigid relative
to said flow path.
41. The drug delivery device of claim 38 further comprising
packaging of said drug delivery device to insulate said device from
environmental conditions.
42. The drug delivery device of claim 41 wherein one of said
environmental conditions is atmospheric pressure.
43. The drug delivery device of claim 41 wherein one of said
environmental conditions is humidity.
44. The drug delivery device of claim 26 further comprising a
visual drug quantity indicator and wherein said elastomeric
diaphragm comprises a color, said visual drug quantity indicator
comprising a window having a transparent portion and a portion
having the color of said elastomeric diaphragm and wherein the
color appearing in said window informs a user of the quantity of
drug in said device.
45. The drug delivery device of claim 44 wherein said drug delivery
outlet comprises the outlet of a needle having an inlet, said drug
delivery device further comprising a flow regulator, in
communication with said fluid path, for effecting volumetric
changes in response to ambient condition changes, said flow
regulator comprising a chamber filled with a fixed volume of air
and a flexible chamber surface that opens or closes said needle
inlet based on a pressure differential between said fluid path and
said internal drug reservoir chamber.
46. The drug delivery device of claim 45 wherein said current
stabilizing element has at least a pair of resistors in series.
47. The drug delivery device of claim 46 further comprising a
pressure sensitive mechanism that detects increased pressure in
said internal chamber and prevents a pressure build-up.
48. The drug delivery device of claim 47 wherein said electrolytic
cell is covered by a foil cover.
49. The drug delivery device of claim 49 further comprising an
activation mechanism including an electrical contact and a
puncturing device for puncturing said foil cover of said
electrolytic cell.
50. The drug delivery device of claim 49 further comprising a
visual usage indicator for indicating proper usage of said device.
Description
RELATED APPLICATION(S)
[0001] This application is a divisional of U.S. Ser. No. 09/577,033
filed on May 23, 2000, which is a continuation-in-part of U.S. Ser.
No. 09/072,875 filed on May 5, 1998 which claims priority to U.S.
Provisional Application No. 60/045,745 filed May 6, 1997, and all
of whose entire disclosures are incorporated herein by
reference.
BACKGROUND OF THE INVENTION
[0002] A wide range of subcutaneous drug delivery devices are known
in which a drug is stored in an expandable-contractible reservoir.
In such devices, the drug is delivered from the reservoir by
forcing the reservoir to contract. (The term "subcutaneous" as used
herein includes subcutaneous, intradermal and intravenous.)
[0003] Such devices can be filled in the factory or can be filled
by the pharmacist, physician or patient immediately prior to use.
In the former case it may be difficult to provide the required drug
stability in the device since the drug will be stored in the
reservoir for a shelf life of from several months to a number of
years. In the latter case, it is difficult to ensure that the drug
has completely filled the reservoir, i.e. that the reservoir and
fluid path do not contain any air bubbles. In general, this
requires priming the device by filling it in a certain orientation
which ensures that the air bubbles are pushed ahead of the drug,
such as with the filling inlet at the bottom and the delivery
outlet at the top (to allow the bubbles of air to rise during
filling).
[0004] A further problem associated with subcutaneous drug delivery
devices is that in many cases gas generation is used to compress
the reservoir. While it may be possible to ensure a constant or a
controllably varying rate of gas generation (for example by passing
a constant current through an electrolytic cell), this does not
ensure a constant rate of drug delivery.
[0005] The amount of compression of the reservoir (and thus the
rate of delivery of drug) depends on the amount by which the volume
of the gas generation chamber expands. The behavior of an ideal gas
is governed by the equation PV=nRT, in which the volume of gas, V,
is proportional to the number of moles of gas, n, and the
temperature, T, and inversely proportional to the pressure, P.
[0006] An electrolytic cell working at constant current will
generate a constant number of moles of gas per unit time. However,
changes in the temperature of the gas and in the atmospheric
pressure exerted on the gas will cause the volume to vary. Even if
the temperature of the device remains constant, the fact that
atmospheric pressure drops by approximately 3% for every increase
in altitude of 300 m means that the delivery rate will vary
substantially between a location at sea level and a higher altitude
location (for example, Denver, Colo. is approximately 1 mile or 1.6
kilometers above sea level, so atmospheric pressure will be
approximately 17% lower on average than at sea level). Similarly,
normal changes in atmospheric pressure due to the weather cause the
delivery rate of this type of device to vary.
[0007] For devices which employ a needle to penetrate the skin
there is a danger that after use the device may accidentally infect
the patient or others if not properly disposed of. WO 95/13838
discloses an intradermal device of this type having a displaceable
cover which is moved between a first position in which the needle
is retracted before use and a second position in which the needle
is exposed during use. Removal of the device from the skin causes
the cover to return to the first position in which the needle is
again retracted before disposal. However, this device does not
include a locking mechanism in the assembly for locking the device
prior to use to minimize accidental contact with the needle and/or
accidental actuation of the device that may occur during shipping
and/or storage.
[0008] When filling a drug delivery device, the conventional method
is to use a syringe, which carries the risk of accidental injury.
The present invention has as a further aim the improvement of
safety when syringes are used. The present invention also aims to
decrease the possibilities that the needle could become exposed by
accident before or after use, for example, by a child playing with
the device if not properly disposed of. Clearly given the risks
associated with infectious diseases, particularly those carried by
blood, any possibility of accidental infection must be minimized to
the utmost and preferably eliminated entirely.
[0009] Our International Application No. PCT/IE 96/00059 discloses
a medicament delivery device having a filling mechanism integral
within the housing which receives a cylindrical cartridge (or
"vial") sealed by a sliding stopper. When the cartridge is pushed
into the filling mechanism, a hollow needle in the filling
mechanism penetrates the stopper and establishes communication
between the interior of the cartridge and the device's internal
reservoir. Continued movement of the cartridge into the filling
mechanism causes the stopper to slide into the cartridge and act as
a piston to pump the medicament from the cartridge into the
reservoir. While this mechanism overcomes some of the disadvantages
of using a syringe, it also makes the device bulkier.
[0010] Thus, there is a need to provide a subcutaneous drug
delivery device having an improved filling mechanism which
facilitates filling the device in an orientation-independent
manner.
[0011] There is a further need to provide a filling system that is
less bulky.
[0012] There is still a further need to provide a filling system
that maintains the needles within the system in a recessed fashion
so as to minimize the risk of injury associated with needles.
[0013] There is yet a further need to provide a device which
operates at a substantially constant delivery rate independently of
the ambient atmospheric pressure.
[0014] There is a further need to provide a drug delivery device in
which the needle is retracted from the housing surface before and
after use so as to minimize injury due to accidental contact with
the needle.
[0015] There is yet a further need to provide a device having
improved adhesion to the skin, i.e. for which there is less
likelihood that the device will become detached during use.
SUMMARY OF THE INVENTION
[0016] The present invention overcomes these and other
disadvantages associated with prior art drug delivery devices and
filling systems. Stated generally, the present invention provides
for a drug delivery device having a housing that has an internal
reservoir and an expandable chamber disposed relative to the
reservoir. The device also has a drug delivery needle extending
from the housing for penetration of the skin of a subject. The
needle has an outlet for drug delivery. The drug delivery device of
the present invention further includes a fluid path defined between
the delivery needle outlet and the reservoir and means for
providing a gas at a controllable rate into the expandable chamber.
The device also includes a flow regulating chamber, in
communication with the fluid path, which is capable of volumetric
changes in response to temperature and/or pressure changes.
[0017] By calibrating the degree of increase or decrease in flow
resistance, it is possible to compensate for differences occurring
in the rate of delivery which arise because of pressure- or
temperature-induced differences in the volume of a given mass of
gas in the expandable chamber. Thus, if the ambient atmospheric
pressure drops, the gas in the expandable chamber will tend to
expand and thereby force more drug from the reservoir. This will
however be counteracted by the flow regulating chamber which will
increase flow resistance along the fluid path and thereby
counteract the increased flow rate arising from the effect of the
tendency for the expandable chamber to expand.
[0018] Preferably, the expandable chamber causes contraction of the
reservoir in use. Further, preferably, the flow regulating chamber
alters the drug delivery rate by varying the flow resistance
between the reservoir and the outlet. Preferably, the flow
regulating chamber is associated with a blocking member which upon
expansion of the flow regulating chamber moves within the fluid
path so as to restrict the flow of drug.
[0019] Further, preferably, the blocking member comprises a
formation provided on a displaceable member which at least
partially bounds the flow regulating chamber, the formation being
disposed adjacent to an inlet of a conduit forming part of the
fluid path, such that restriction of the fluid path occurs when the
blocking member is moved into the inlet of the conduit. By having a
suitably shaped and sized formation relative to the inlet, it is
possible to precisely vary the flow resistance of the conduit, and
thereby precisely control the delivery rate notwithstanding changes
in ambient temperature and/or pressure.
[0020] Suitably, the shape of the blocking member is adapted to cut
off the fluid path completely with a predetermined degree of
expansion of the flow regulating chamber. Alternatively, the
formation can be shaped such that the fluid path is never entirely
cut off.
[0021] In preferred embodiments of the invention, a displaceable
cover is connected to the housing such that displacement of the
housing relative to the cover when the cover has been applied to
the skin of a subject causes the delivery needle to penetrate the
skin of the subject. Such a displaceable cover is suitable for
concealing the needle before and after application to the skin of a
subject, which prevents injury and reduces the possibility of
contamination of the needle.
[0022] In another aspect of the invention the expandable chamber is
provided with a release valve operatively connected to the
displaceable cover such that the movement of the housing relative
to the cover controls the closing of the valve and thereby the
sealing of the expandable chamber. This feature is not dependent on
the existence of the flow regulating chamber.
[0023] The valve enables the device to be supplied with the
displaceable member positioned such that the volume of the (empty)
reservoir is minimized and that of the expandable chamber
maximized. Thus, the reservoir can be of substantially zero volume
initially, with no entrapped air volume. The device can then be
primed or loaded by filling the reservoir, for example using a
syringe- or cartridge-based filling mechanism. As the reservoir is
filled, the displaceable member moves to expand the reservoir and
thereby contract the expandable chamber. The valve allows the air
or other gas in the expandable chamber to be exhausted into the
atmosphere.
[0024] The device can then be applied to the skin of the user. When
the device is applied the housing moves relative to the cover which
is applied to the skin, not only does the needle penetrate the
skin, but also (because the valve is operatively connected to the
cover) the valve is closed to seal the expandable chamber. If the
valve remained open then gas supplied into the expandable chamber
would be free to escape and delivery would not be effected. While
it would be possible for the user to close the valve manually, this
would clearly leave open the possibility of error. Instead, by
connecting the valve operatively to the cover, it is possible to
ensure that the valve is always closed when the device is applied
to the skin.
[0025] Preferably the valve comprises two components one of which
is connected to the cover and the other of which is connected to
the expandable chamber, such that relative movement of the housing
towards the cover causes the valve to close.
[0026] The invention includes a displaceable cover that is
displaceable relative to the housing between a first position in
which the needle is concealed from the exterior of the device, and
a second position in which the delivery needle protrudes from the
device for penetration of the skin. A further aspect of the present
invention comprises means for locking the device in the first
position after a single reciprocation of the device from the first
position to the second position and back to the first position.
[0027] The displaceable cover is an advantageous feature since it
solves a problem unaddressed by prior art devices. Our prior art
device has a locking mechanism to lock the housing in place after
use and keep the needle concealed. However, there is no mechanism
to prevent premature activation prior to intended use that may
cause the needle to protrude accidentally thereby giving rise to
injury. According to the present invention, however, the locking
means engages automatically when the cover and housing are
reciprocated relative to one another, i.e. the housing and cover
are moved relative to one another to cause the needle to protrude
when the device is applied to the skin. This relative movement is
reversed when the device is removed thereby concealing the needle
but also engaging the locking means to prevent the needle from
being exposed again by accident.
[0028] In a preferred embodiment, the locking means comprises a
mechanical latch which is brought into operation by the
reciprocation. Further, it is preferred that the latch comprises a
pair of elements mounted on the cover and the housing respectively.
It is preferred that the elements be shaped such that they can have
two relative configurations when the cover is in the first position
relative to the housing. It is preferred the elements have a first
movable configuration in which the elements are mutually movable,
and a second locked configuration in which the elements are
prevented from mutual movement. It is also preferred that the
reciprocation of the cover and the housing causes the elements to
pass from the first movable configuration, through an intermediate
configuration when the cover is in the second position relative to
the housing, and then to the second locked configuration, thereby
preventing any further movement of the cover relative to the
housing.
[0029] In preferred embodiments illustrated further below, one of
the elements is provided with a recess which is adapted to receive
a projection on the other of the elements, the recess and the
projection being spaced apart from one another in the movable
configuration, and being in engagement with one another in the
locked configuration.
[0030] These embodiments are preferred because while they are
mechanically simple and easy to make, their very simplicity
provides fewer opportunities for malfunction.
[0031] In a preferred embodiment of the present invention, movement
of the cover relative to the housing is initially prevented by a
removable locking member. This feature helps to prevent accidental
injury occurring because the needle is only exposed when the
housing is moved relative to the cover, i.e. only after the user
has specifically removed the removable locking member. The presence
of the removable locking member also prevents the means for
providing a gas from being actuated. This prevents the device from
being exhausted by accidental switching on at an incorrect time. In
a preferred embodiment of the present invention, the removable
locking member comprises a laminar member inserted between the
cover and the housing.
[0032] In a further aspect of the invention, the surface of the
housing from which the needle extends or the surface of the
displaceable cover, if present, is of a concave cross-section. When
the device has been applied to the skin of a subject, removal of
the device is resisted because the cover conforms more closely to
the skin. In prior art devices, it has been found that retention on
the skin of the user is problematic because of adhesive failure,
for example. Using a concave surface causes the device to be
retained more effectively by adhesive means.
[0033] With prior art devices the lower surface tends to be peeled
away from the skin more easily as the edges of the device can be
detached relatively easily. Where a concave lower surface is used
the edges tend to remain in contact with the skin and removing the
device is thus more difficult. In effect a shear force is required
rather than a simple peeling, and this assists in preventing
accidental removal. This feature is not dependent on the existence
of the other aspects of the invention.
[0034] In a modified device according to the invention, the needle
extends from the lower surface of the housing is replaced by a tube
extending from the housing. The tube is adapted for carrying a drug
delivery needle. Such a device is preferred for intravenous
delivery of a drug as the needle carried on the end of the tube can
be accurately located in a suitable vein. The needle may be
integral with the tube or supplied separately.
[0035] In a further preferred feature of the present invention, the
drug reservoir is separated from the expandable chamber by a
diaphragm. The diaphragm exhibits bistable behavior such that in
one stable state the reservoir is full and in the other stable
state the reservoir is empty. The diaphragm is shaped to minimize
the energy required in the transition between the stable states. In
a preferred embodiment of the present invention, the diaphragm is
in the form of a body having a peripheral lip connected to a
substantially flat central section by a flexible annular section.
The flexible annular section assumes a substantially frusta-conical
cross-section in one of the states and assuming an arcuate curved
cross-section in the other state.
[0036] Preferably, the means for providing a gas comprises an
electrical circuit in which any transistors are bipolar transistors
having a gain of not less than 500, such that the circuit can be
irradiated by ionizing radiation without destroying the
circuit.
[0037] This type of transistor has been found to be advantageous as
it enables the device to be sterilized using gamma radiation with
the electronic components intact. While a certain loss of
performance results from the irradiation, the high gain transistor
still has an adequate gain after irradiation to operate reliably.
It is preferred that the current gain of the or each transistor is
not less than 750. For example, a transistor having a rated current
gain of 800 has been found to give an excellent performance after
irradiation, despite the fact that irradiation lowers the current
gain characteristics of the transistor by a factor of ten or more.
The initial high gain compensates for the subsequent reduction
arising from irradiation. The fact that the effects of irradiation
can be predicted means that the performance after irradiation is
reliable.
[0038] It is also preferred that the circuit further include a
reference component across which a fixed potential drop is
measurable. The reference component is essentially unchanged by the
ionizing radiation. If a reference voltage is used which is not
affected by the irradiation process, then the operation of the
other components in the circuit may be determined by this reference
voltage. For example, while the current gain of a group of
transistors may vary individually when a batch is irradiated, each
such transistor can be used to make an identically functioning
amplifier if the output current of the amplifier is matched against
a given reference component.
[0039] Light emitting diodes (LEDs) have been found to be affected
less than other standard components when irradiated by gamma
radiation. Thus, the reference component of the preferred
embodiment comprises a light-emitting diode. Gallium arsenide
(GaAs) LEDs are virtually unaffected by gamma rays. Thus, it is
preferred that the light emitting diode employs gallium arsenide as
a semiconductor.
[0040] In a further aspect, the present invention provides for a
subcutaneous drug delivery kit including a drug delivery device as
described above. The device is provided with a filling mechanism
associated with the reservoir. The filling mechanism includes means
for receiving a filling adapter. The filling adapter includes a
body which is adapted to accommodate a drug cartridge. The body has
means for engaging the adapter-receiving means of the drug delivery
device at one end thereof, means for receiving a cartridge at the
other end thereof, and transfer means for transferring a liquid
from a cartridge to the filling mechanism of the device as the
cartridge is emptied. The adapter-receiving means and the
corresponding engaging means provided on the adapter together
constitute a releasable locking mechanism which holds the adapter
in place on the device once engaged. The locking mechanism is
disengaged by the cartridge when the cartridge is emptied within
the adapter.
[0041] The kit according to the invention is advantageous because
it eliminates the need for a bulky filling mechanism which
accommodates the cartridge within the device, and instead employs
an adapter which is releasable from the device so as to enable the
filled device to be less bulky than prior art cartridge-based
devices.
[0042] Furthermore, the locking mechanism employed is only
disengaged when the cartridge has been completely emptied, i.e.,
the rubber stopper within the cartridge is pushed to the bottom. If
the cartridge used is of a type which will empty when the stopper
is pushed to the bottom, this feature ensures accurate loading of
the reservoir, i.e. it is not possible to easily remove the device
before the reservoir is filled with the correct dose of
medicament.
[0043] Suitably, the transfer means comprises a hollow double-ended
needle, one end of which is associated with the engaging means such
that it communicates with the filling mechanism when the adapter is
engaged with the device, and the other end of which is associated
with the cartridge receiving means such that it communicates with
the interior of a cartridge having a penetrable stopper when such a
cartridge is received by the adapter.
[0044] Such a hollow double ended needle can be replaced by a pair
of needles which are connected by a conduit, such as a moulded
conduit running through the body of the adapter and having a needle
mounted at either end such that it is functionally equivalent to a
double ended needle. Preferably, both ends of the needle are
disposed within the body of the adapter such that they are recessed
from the exterior of the body when the adapter is disengaged from
the device. This arrangement is preferable for safety reasons, as
it allows the adapter to be disposed of without fear of accidental
injury occurring from casual handling of the adapter.
[0045] In a preferred embodiment, the releasable locking mechanism
comprises a pair of locking members provided on the adapter
receiving means and the corresponding engaging means, respectively.
One of the locking members is movable between a locking position
and a disengaging position. The movable locking member is disposed
relative to the body such that, in use, when a cartridge is emptied
within the body, the movable locking member is moved from the
locking position to the disengaging position under the action of
the cartridge.
[0046] Where a substantially cylindrical cartridge is employed, the
body can receive the cartridge within a passage having a diameter
sufficient to completely accommodate the cartridge. However, the
end of the passage is of slightly narrower diameter on account of a
projection provided on the movable locking member. Thus, when the
cartridge completely emptied by pushing the stopper to the bottom,
it contacts the movable locking member and pushes it out of the
way, thereby disengaging the locking mechanism.
[0047] Suitably, the movable locking member is resiliently biased
towards the locking position. Preferably, the movable locking
member is a latch which automatically locks the adapter and device
to one another when engaged together. It is preferred that the
cartridge is emptied by moving the penetrable stopper against the
adapter
[0048] The present invention further provides a subcutaneous drug
delivery kit including a device according to any preceding claim
further comprising a filling mechanism associated with the
reservoir, the filling mechanism comprising means for receiving a
filling adapter as defined herein and a filling adapter. The
filling adapter has a body adapted to receive a syringe. The body
has means for engagement with the adapter-receiving means of the
device at one end thereof, syringe-receiving means at the other end
thereof and transfer means for transferring a liquid from the
syringe to the filling mechanism of the device as the syringe is
emptied. The transfer means includes a conduit associated with the
syringe receiving means, the conduit leads to a needle which is
associated with the engagement means and is disposed within the
body of the filling adapter.
[0049] It is preferred that the needle disposed within the body of
the filling adapter is recessed from the exterior of the body when
the adapter is disengaged from the device. It is also preferred
that the adapter receive the syringe without a needle. Since the
needle on the adapter is recessed from the exterior of the adapter
body and the syringe has no needle when filling, a conventional
syringe (minus needle) can be used to fill the device without any
risk of accidental injury.
[0050] A further aspect of the present invention provides a method
of filling a drug delivery device. The method includes providing a
drug delivery device having a drug reservoir. The reservoir is
associated with a filling mechanism having filling adapter
receiving means. The method further includes providing a filling
adapter having a first end for engagement with the adapter
receiving means, and a second end for receiving a syringe and
causing the filling adapter receiving means to receive the filling
adapter. The method further includes causing the second end of the
filling adapter to receive a syringe having liquid stored therein
and a needle, and providing a conduit for communication between the
liquid stored within the syringe and the first end of the filling
adapter. The method of filling further includes emptying the
syringe and concurrently transferring the liquid from the syringe
to the device via the conduit. In yet further aspects, the
invention provides a filling adapter as defined above and a
diaphragm as defined above.
[0051] In a preferred embodiment of the present invention, the
electrical circuit used to provide gas to the expandable chamber
includes a high voltage supply, such as, for example, between one
and three batteries and current stabilizing elements, such as, for
example, two resistors connected in series. The electrical circuit
of this preferred embodiment simplifies the electrical circuit and
stabilizes the current supplied to the electrolytic cell without
using components such as transistors which are sensitive to gamma
radiation used for sterilization.
[0052] Another aspect of a preferred embodiment of the drug
delivery system of the present invention includes an occlusion
prevention mechanism. Further, it is not desirable that the
delivery rate of the drug delivery device be altitude dependent. An
element, such as, for example, a valve in the drug delivery device,
creates a constant high, back pressure within the gas chamber,
minimizing or preferably preventing the formation of boli of
drugs.
[0053] In a preferred embodiment of the present invention, an
optical window, such as, for example, a ring like structure,
provides a more accurate assessment of the quantity of drug
delivered or alternatively, the quantity of drug remaining in the
drug reservoir. The embodiment makes use of the principle of light
reflected from the elastomeric membrane or diaphragm containing the
drug. When the drug reservoir is approximately full, the optical
window appears black as the elastomeric membrane is extended away
from the housing as the drug fills it. However, when the drug
reservoir is approximately empty, the optical window appears blue
in color, for example, as the elastomeric membrane is proximate to
the housing as drug delivery is close to completion.
[0054] Further, in a preferred embodiment, the subcutaneous drug
delivery device includes a pressure sensitive mechanism for
preventing a rapid injection of a drug to a user. For example, the
pressure sensitive mechanism can include a switch that forms a part
of the electrical circuit which controls the power supply to a gas
generating portion of the drug delivery device. The switch can
include different preferred components to complete the circuit,
such as one including a conductive membrane and a conductive lever,
or alternatively, electrodes and a droplet of mercury. The
electrical circuit is completed as long as the pressure in the gas
generating portion is less than the pressure within a chamber.
[0055] In another preferred embodiment, the drug delivery system in
accordance with the present invention includes a visual indicator
to indicate proper application and operation to a user. The
indicator can be, for example, a color marking system. The color
marking system can be used to indicate to a user components of the
system which should be removed from the system prior to use.
[0056] Another preferred embodiment of the drug delivery system of
the present invention includes an insert, for example, a foam
insert that receives the internal components of the device and
accommodates design tolerances. The insert maintains an accurate
internal volume so that upon assembly, the volume of the internal
housing, and thus the drug reservoir, is within an accurate
range.
[0057] In a preferred embodiment, the drug delivery system of the
present invention includes an activation mechanism, such as, for
example, an activation lever to initiate gas generation in the
expandable chamber which in turn controls the delivery of the drug
from the device. The activation mechanism also includes a
puncturing device and an electrical contact. In operation, upon
depression, the puncturing device punctures the foil cover of the
electrolytic cell, thereby allowing the chemical ingredients to
release gas for expanding the expandable chamber. As a result, the
proximate drug reservoir is compressed and drug delivery is
initiated.
[0058] Another preferred embodiment of the drug delivery system
relates to controlling the rate of delivery which is controlled by
several parameters. The parameters include, but are not limited to,
circuit current, residual air volume, material permeability,
material properties of plastic material in device, and membrane
seal. For example, the permeability of the drug delivery system
components, such as the permeability of the materials used in the
base affects the delivery rate of the drugs delivered. thus,
materials such as, for example, PET that minimizes or preferably
prevents the permeation of the gases generated in the device, for
example, hydrogen is used. By minimizing the permeability of the
gases of the expandable chamber, a constant delivery rate can be
maintained. As the diffusion rate of the gases controls the
delivery rate of the drug, material changes can control the
delivery rate of drugs.
[0059] Another aspect of the present invention includes packaging
of the drug delivery system to insulate the system from storage and
use in different altitudes. In particular, the electrolyte in the
electrolytic cell used to generate gas in the expandable chamber is
affected by environmental conditions. Further, the performance of
the barometric pressure valve can be affected by the environmental
conditions as it relies on a reference pressure of a fixed amount
of the air. At high altitudes, air from the reference cell can
diffuse out of the device due to expansion. of the air. In a
preferred embodiment, by hermetically packaging the device, the
barometric pressure valve has only one position, that is, it is a
stationary valve as the pressure inside the device is constant.
[0060] Thus, it is an object of the present invention to provide a
subcutaneous drug delivery device having an improved filling
mechanism which facilitates filling the device in an
orientation-independent manner.
[0061] It is a further object of the present invention to provide a
filling system that is less bulky.
[0062] It is still a further object of the present invention to
provide a filling system that maintains the needles within the
system in a recessed fashion so as to minimize the risk of injury
associated with needles.
[0063] It is yet a further object of the present invention to
provide a device which operates at a substantially constant
delivery rate independently of the ambient atmospheric
pressure.
[0064] It is even yet a further object of the present invention to
provide a drug delivery device in which the needle is retracted
from the housing surface before and after use so as to minimize
injury due to accidental contact with the needle.
[0065] It is yet a further object of the present invention to
provide a device having improved adhesion to the skin, i.e. for
which there is less likelihood that the device will become detached
during use.
[0066] Other objects, features and advantages of the present
invention will be apparent upon reading the following specification
taken in conjunction with the drawings and appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0067] The foregoing and other objects, features and advantages of
the invention will be apparent from the following more particular
description of preferred embodiments of the invention, as
illustrated in the accompanying drawings in which like reference
characters refer to the same parts throughout the different views.
The drawings are not necessarily to scale, emphasis instead being
placed upon illustrating the principles of the invention.
[0068] FIG. 1 is a sectional side view of a first embodiment of
drug delivery device according to the present invention;
[0069] FIG. 2 is an exploded perspective view of the flow
regulating chamber and needle assembly of the first embodiment of
the device of FIG. 1;
[0070] FIG. 3 is an enlarged sectional side view of the flow
regulating chamber and needle assembly of the first embodiment of
the device of FIG. 1;
[0071] FIGS. 4-6 are sectional side views of a second embodiment of
drug delivery device according to the invention, shown before,
during and after use, respectively;
[0072] FIGS. 7-9 are enlarged perspective views of the locking
mechanism of the device of FIGS. 4-6, shown before, during and
after use, respectively;
[0073] FIGS. 10A, 10B and 10C are schematic elevations of a first
alternative embodiment of a locking mechanism, shown before, during
and after use, respectively;
[0074] FIGS. 10D is a perspective view of the locking mechanism as
shown in FIG. 10A;
[0075] FIGS. 11A, 11B and 11C are schematic elevations of a second
alternative embodiment of a locking mechanism, shown before, during
and after use, respectively;
[0076] FIG. 11D is a perspective view of the locking mechanism as
shown in FIG. 11A;
[0077] FIGS. 12A, 12B and 12C are schematic elevations of a third
alternative embodiment of a locking mechanism, shown before, during
and after use, respectively;
[0078] FIG. 12D is a perspective view of the locking mechanism as
shown in FIG. 12A;
[0079] FIGS. 13A, 13B and 13C are schematic elevations of a fourth
alternative embodiment of a locking mechanism, shown before, during
and after use, respectively;
[0080] FIG. 13D is a side elevation of the locking mechanism as
shown in FIG. 13A;
[0081] FIG. 13E is a perspective view of the locking mechanism as
shown in FIG. 13A;
[0082] FIGS. 14 and 15 are sectional elevations of a third
embodiment of drug delivery device according to the invention,
shown before and during use, respectively;
[0083] FIG. 16 is a partially cut away perspective view of the
lower part of the housing on the device of FIGS. 14 and 15,
including various components housed therein;
[0084] FIG. 17 is an exploded perspective view of the electrolytic
cell used in the embodiment of FIGS. 14 and 15;
[0085] FIG. 18 is a sectional side view of the electrolytic cell
used in the embodiment of FIGS. 14 and 15;
[0086] FIGS. 19 and 20 are sectional side views of a fourth
embodiment of drug delivery device according to the invention,
shown before and during use, respectively;
[0087] FIG. 21 is a sectional plan view of a drug delivery kit
comprising the first embodiment of FIG. 1, a filling adapter and a
medicament cartridge;
[0088] FIG. 22 is a perspective view of a subassembly used in the
adapter shown in FIG. 21;
[0089] FIGS. 23 and 24 are sectional side views of the drug
delivery kit of FIG. 21, shown during and after filling of the
device, respectively;
[0090] FIGS. 25 and 26 are sectional side views of fifth and sixth
embodiments, respectively, of drug delivery device according to the
invention;
[0091] FIGS. 27 and 28 are sectional side views of a diaphragm
suitable for use in a device according to the invention;
[0092] FIG. 29 is a diagram of an electronic controller circuit
suitable for use in a device according to the invention;
[0093] FIGS. 30 and 31 are perspective views of the top side and
underside, respectively, of a displaceable cover from a device
according to the invention;
[0094] FIG. 32A schematically illustrates a preferred embodiment of
an electrical circuit for an electrolytic cell in a drug delivery
device in accordance with the present invention;
[0095] FIG. 32B graphically illustrates the current profile of the
electrolytic cell shown in FIG. 32A in accordance with the present
invention;
[0096] FIGS. 33A-33F illustrate both schematically and graphically,
an embodiment of a drug delivery device which can be compromised by
an occlusion;
[0097] FIGS. 34A and 34B schematically and graphically illustrate a
preferred embodiment of a drug delivery device having an occlusion
prevention mechanism in accordance with the present invention;
[0098] FIG. 35 schematically illustrates a preferred embodiment of
the drug delivery device in accordance with the present
invention;
[0099] FIGS. 36A-36C schematically illustrate the changes in the
drug reservoir of a drug delivery device in accordance with the
present invention;
[0100] FIG. 37A is a perspective view of a printed circuit board
with a pressure sensitive mechanism;
[0101] FIGS. 37B and 37C schematically illustrate a preferred
embodiment of a pressure sensitive mechanism of FIG. 37A included
in a drug delivery device in accordance with the present
invention;
[0102] FIG. 37D is a schematic illustration of an electrical
circuit for the drug delivery system incorporating elements of FIG.
32A and FIG. 37A.
[0103] FIGS. 38A and 38B schematically illustrate another preferred
embodiment of a pressure sensitive mechanism included in a drug
delivery device in accordance with the present invention;
[0104] FIG. 39A is a perspective view of a pressure sensitive
mechanism, with portions broken away on a printed circuit
board;
[0105] FIGS. 39B and 39C schematically illustrate the preferred
embodiment of a pressure sensitive mechanism of FIG. 39A included
in a drug delivery device in accordance with the present
invention;
[0106] FIG. 40 schematically illustrates a preferred embodiment of
a drug delivery device including an insert in accordance with the
present invention;
[0107] FIGS. 41A and 41B illustrates a preferred embodiment of a
drug delivery device including an activation lever in accordance
with the present invention;
[0108] FIG. 42 graphically illustrates the delivery of drugs using
a preferred embodiment of the drug delivery device which controls
residual air volume in accordance with the present invention;
[0109] FIG. 43 graphically illustrates the delivery of drugs using
a preferred embodiment of the drug delivery device which controls
the system permeability in accordance with the present
invention;
[0110] FIG. 44A illustrates a full assembly of the drug delivery
device including a stationary barometric pressure valve in
accordance with the present invention;
[0111] FIG. 44B is an enlarged sectional view of the stationary
valve of FIG. 44A;
[0112] FIG. 45 illustrates a preferred embodiment of the packaging
used for the drug delivery device in accordance with the present
invention;
[0113] FIG. 46 illustrates an alternate embodiment of packaging
used for the drug delivery device in accordance with the present
invention;
[0114] FIGS. 47A-47C illustrate another embodiment of packaging
used for the drug delivery device in accordance with the present
invention;
[0115] FIG. 48 is a sectional side view of an alternative
embodiment of a drug delivery device;
[0116] FIG. 49 is a sectional side view of an alternative
embodiment of a drug delivery device;
[0117] FIG. 50A is a sectional side view of the alternative
embodiment of the drug delivery device of FIG. 48 with the luer
connection on to be an epidural needle; and
[0118] FIG. 50B is a sectional side view of the alternative
embodiment of the drug delivery device of FIG. 48 with the luer
connection to an epidural needle with a hydrophobic membrane and a
hydrofoil membrane.
DETAILED DESCRIPTION OF THE INVENTION
[0119] Referring now in more detail to the drawings, in which like
numerals refer to like parts throughout the several view, FIG. 1
indicates a subcutaneous drug delivery device 10 according to the
invention.
[0120] A housing 11 defines a reservoir 12 which is partially
bounded by an elastomeric diaphragm 13 which allows the reservoir
to expand and contract. The diaphragm 13 also bounds an expandable
chamber 14 such that expansion of the expandable chamber causes the
reservoir 12 to contract and vice versa. In FIG. 1, the reservoir
12 is at full volume and contains a drug, while the expandable
chamber 14 is at minimum volume.
[0121] A circuit board 15 having an electrolytic cell 48 mounted
thereon (explained in greater detail below) is mounted in the lower
part 16 of the housing 11. In use, the electrolytic cell 48 feeds a
gas into the expandable chamber 14 via an aperture 17 in a
supporting member 18.
[0122] The reservoir 12 is provided with an inlet 19 which is in
communication with a filling mechanism 20 (explained in greater
detail below). A delivery needle 21 provided with an outlet 22 is
in communication with the reservoir 12 via a fluid path 23 which is
indicated by arrows. The fluid path 23 passes around an air-filled
flow-regulating chamber 35 which comprises a top member 24, annular
member 25 and flow diaphragm 26. The fluid path 23 also passes via
a needle holder 27 to the needle 21. The inlet 19 to the needle 21
is partially restricted by a projection 28 on the flow diaphragm
26, such that any upward movement of the projection 28 reduces
resistance to flow and any downward movement of the projection
increases flow resistance.
[0123] Referring additionally to FIG. 2, the flow regulating
chamber 35 can be seen in exploded view. Annular member 25 receives
the flow diaphragm 26, and top member 24 and the three components
fit together to form an airtight chamber 36 which is positioned
above the needle holder 27. The inlet 19 in the needle holder 27
leading to the needle 21 can be clearly seen on the top surface of
the needle holder. Projection 28 extends into the inlet 19.
[0124] Further features of device 10 which can be seen in FIG. 1
are a displaceable cover 29 attached to the housing 11 by a hinge
30. The movement of the displaceable cover 29 between the position
shown in FIG. 1 (wherein the needle 21 protrudes through the
displaceable cover) and a position in which the needle 21 is
substantially concealed by the displaceable cover 29 (as shown in
FIG. 4), is controlled by a locking mechanism indicated generally
at 31 and explained in greater detail below.
[0125] In use, the displaceable cover 29 is affixed to the skin
using an adhesive coating 29' provided on the surface thereof
distal from the housing ("the underside"). The displaceable cover
29 has a concave shape when viewed from the underside. This shape
is advantageous because if a flat or convex surface is provided,
the edges of the cover 29 will be more easily peeled away from the
skin by accident, i.e. the use of a convex surface is less likely
to have protruding edges, and the force required to peel the device
away is a shear force rather than a simple peeling force.
[0126] The housing 11 is covered by a protective top cover 32 which
can provide a more aesthetically pleasing appearance to the device,
as well as one which is ergonomically more advantageous for the
user. An aperture in protective top cover 32, indicated at 33,
allows a transparent portion 34 of the housing 11 to be seen,
thereby allowing the user to visually check the reservoir to see
whether drug is present. The protective top cover 32 also protects
the housing 11 and its component parts if the device 10 is
mishandled or dropped.
[0127] The flow regulating chamber 35 is shown in greater detail in
FIG. 3 and comprises the top member 24, the annular member 25, and
the flow diaphragm 26, as explained above. The construction ensures
that the airtight space 36 exists in the interior of the chamber
35. A fluid path between the reservoir and the needle (FIG. 1) is
shown with heavy arrows. As can be seen, projection 28 on the flow
diaphragm 26 extends into the inlet 37 in the needle holder 27
leading to the needle 21. The fluid has to push up on the flow
diaphragm 26 in order to reach the needle 21. Little force is
required to do this, as the air in the chamber 36 is
compressible.
[0128] However, if the ambient atmospheric pressure drops, for
example due to an increase in altitude, the fixed mass of air in
the chamber 36 tends to expand (since for ideal gases at fixed
temperature the product of pressure and volume is a constant). This
makes it more difficult for fluid to flow past the flow diaphragm
26 into needle holder 27 and would thus tend to cause a decrease in
the rate of delivery of drug.
[0129] The fact that the drug is being driven by a gas-filled
expandable chamber 14, however, means that the expandable chamber
tends also to increase in volume due to this increase in altitude,
and the effect of an increase in expandable chamber volume is to
speed up the rate of delivery.
[0130] Therefore, by calibrating the flow regulating chamber 35
correctly, barometric changes which would otherwise tend to
increase or decrease the rate of delivery of drug are counteracted
by the corresponding increase or decrease in the amount of flow
resistance exerted by the flow regulating chamber, thereby allowing
a constant delivery rate to be maintained. It will be appreciated
that changes in temperature which would cause the gas in the
expandable chamber to expand or contract are also counteracted in
the same way.
[0131] A further feature of the device of FIGS. 1-3 is an o-ring 38
located on displaceable cover 29 (see FIG. 1). The o-ring 38 forms
a seal with needle holder 27 and thereby assists in protecting the
puncture point of the needle 21 into the skin of the user from
contact with soap, water, perspiration or other contaminates. If
water or other liquid contacts the needle 21, the needle 21 may act
as a switch and allow water to be drawn into the puncture. However,
adhesive 29' on the displaceable cover 29 prevents water from
reaching the needle 21 via the underside of the cover, and the
o-ring 38 prevents water from reaching the needle via the upper
side of displaceable cover. Top member 24, annular member 25, flow
diaphragm 26 and needle holder 27 and all other parts in the fluid
pathway are preferably made of a polycarbon material. Polycarbon
materials are essentially inert and will not react with the liquid
drug. Moreover, the polycarbon material withstands gamma radiation
without degradation of any properties.
[0132] FIGS. 4, 5, and 6 show a device similar to that of FIG. 1
before, during and after use, respectively. The device, indicated
generally at 50, differs slightly from the FIG. 1 device and
accordingly different reference numerals are used in relative to
FIG. 1. The device 50 is shown in FIG. 4 with the needle 51
concealed by the displaceable cover 52 because the displaceable
cover 52 is displaced relative to the housing 53 about the hinge
54. A removable tab 55 prevents the displaceable cover 52 from
being moved towards housing 53, as will be described further below.
The underside 56 of the displaceable cover 52 is coated with a
contact adhesive 56, and during storage, the adhesive is protected
by a release liner.
[0133] When the release liner is removed, the adhesive-coated
underside 56 is pressed against the skin to ensure good adhesion
(the concave surface assists in obtaining good adhesion) and the
tab 55 is removed. The housing 53 is then pushed towards the skin
and the needle 51 penetrates the skin as the displaceable cover 52
and housing 53 move together about hinge 54, leading to the
configuration shown in FIG. 5.
[0134] A start button is pressed to activate a gas generating
electrolytic cell 57. As gas is generated, a diaphragm 58 is pushed
upwards to drive a liquid drug from the reservoir 59 (which was
filled before use via inlet 60) and thereby force the drug through
a fluid path 61 around the flow regulating chamber 62 (as explained
above in relation to FIGS. 1-3) and to the patient via the delivery
needle 51.
[0135] When delivery has been completed, the diaphragm 58 will have
moved up such that the space occupied by the reservoir 59 at the
beginning of delivery (see FIGS. 4 and 5) is now occupied by the
expandable chamber 14 (see FIG. 6), since the expansion of the
expandable chamber causes contraction of the reservoir.
[0136] The device 50 is removed from the skin by pulling upwards on
the upper protective cover 63 (FIG. 6). This causes the needle 51
to be retracted behind the displaceable cover 52 once again because
the adhesive force holding the displaceable cover 52 against the
skin is greater than the force exerted by the locking mechanism 64
(explained in greater detail below). Once the needle 51 is
retracted in this way, the locking mechanism 64 holds the
displaceable cover 52 permanently in the position shown in FIG. 6,
i.e. away from the housing 53 with the needle 51 concealed. FIG. 7
shows locking mechanism 64 in greater detail, with the protective
top cover 63 removed for illustrative purposes. The locking
mechanism 64 is illustrated before use, i.e. when the displaceable
cover is positioned as shown in FIG. 4. In other words, there is a
gap between the housing 53 and the displaceable cover 52, and the
needle 51 (FIG. 4) is recessed in this gap and thereby concealed by
the displaceable cover 52. A projection 65 mounted on the front of
housing 53 is positioned at the upper end of a slot 66. The slot 66
has an enlarged portion 67 at the lower end and is provided with
wedge projections 68, 69 at the exterior surface of the upper
portion thereof. The slot 66 is formed in a member 70 which is
attached to displaceable cover 52 by connecting arms 72 which allow
a slight degree of flexibility. A widened rib is provided on the
projection 65, and the width of this rib is greater than that of
the upper portion of the slot 66. The member 70 is biased slightly
against this rib.
[0137] The removable tab 55 (see FIG. 4) is positioned so as to
engage wings 71 and prevent them from moving towards the cover 52.
This effectively prevents the entire housing 53 from being moved
towards the cover 52 and prevents the device from being activated
prematurely. When the tab 55 is removed, as shown in FIG. 7, the
displaceable cover 52 can be snapped towards the housing 53 by
pressing down on the housing. This results in the locking mechanism
adopting the configuration shown in FIG. 8, wherein the projection
65 has moved to the lower end of the slot 66, allowing a lipped
member 73 to pass through the enlarged portion 67 at the lower end
of slot 66. This allows a member 70, which was biased in the
direction of projection 65, to relax. The sides of the lipped
member 73 rest against the member 70.
[0138] When delivery is complete and the housing 53 is lifted away
from the displaceable cover 52, this disengages the lips of the
lipped member 73 from resting against member 70 and again moves the
projection 65 to the upper end of the slot 66. However, the lipped
member 73 passes over the wedge projections 68, and 69, as shown in
FIG. 9. When this happens, the wedge projections 68, and 69 catch
the lipped member 73 and prevent it from moving back down. This
effectively locks the locking mechanism 64 permanently in the
configuration shown in FIG. 9, thereby concealing the needle 51
permanently from view and making the device 50 safe for
disposal.
[0139] An additional feature of the device of FIGS. 4-8 relative to
that of FIG. 1 can be seen with reference to FIGS. 4-6. A pair of
projections 74 grip the flow regulating chamber 62 before use to
block the path between the reservoir 59 and the needle 51 before
use (FIG. 4). When gas generation begins, the pressure of liquid in
the reservoir 59 forces the flow regulating chamber 62 downwards
relative to the projections 74. The projections 74 are resilient
and move together when the flow regulating chamber 62 moves
downwards. In this position the projections 74 hold flow regulating
chamber 62 in a fixed position both during delivery (FIG. 5), and
when the device is removed from the skin (FIG. 6). Thus, after
delivery, accidental leakage of medicament from the needle 51 (e.g.
due to gravity) is prevented by the fixed position of the flow
regulating chamber 62 and no gas being generated to create a higher
pressure than within the flow regulating chamber 62 to lift the
projection which seals the inlet to the needle.
[0140] A further feature of the embodiment of FIGS. 4-6 is an
annular elastomeric inwardly extending lip 75 which seals the skin
at the point of entry of the needle 51 in the same manner as the
o-ring 38 in the FIG. 1 embodiment. This feature reduces the danger
of infection due to wicking by the needle of unwanted substances
into the skin.
[0141] Four alternative embodiments of different locking mechanisms
according to the invention are shown in FIGS. 10A-10D, 11A-11D,
12A-12D, and 13A-13E. In each case the mechanism is shown
schematically in "pre-use" (A), "in-use" (B) and "post-use" (C)
configurations as well as in one or two perspective views (D/E).
The mechanism can in each case be moved from position A to position
B and from position B to position C with little difficulty
(although generally some resistance is present to prevent
spontaneous or accidental movement), but once in position C, the
mechanism is effectively locked permanently and is no longer
capable of operation.
[0142] The first alternative embodiment of a locking mechanism
comprises a resilient arm and related assembly and is shown in
FIGS. 10A-10D. In FIG. 10A the locking mechanism is indicated
generally at 80 and comprises a biasing member 81 and a resilient
strut 82 mounted on a housing 83, and the resilient arm 84 and a
post 85 mounted on a displaceable cover 86.
[0143] The resilient arm 84 is flexibly hinged at the base thereof
87. When the housing 83 is pushed towards the displaceable cover
86, the biasing member 81 pushes the resilient arm 84 against the
post 85. The resilient arm 84 and post 85 are mutually shaped to
allow the arm 84 to pass over the top of the post 85, where it
latches (see FIG. 10B) and is prevented from returning to the
position shown in FIG. 10A.
[0144] In passing over the top of the post 85, the arm 84 acts
against the resilient strut 82, momentarily bending the strut 82
away from the biasing member 81. Although when the arm 84 has
passed fully over the top of the post 85 the strut 82 has returned
to its relaxed (straight) position (FIG. 10B).
[0145] When (after use) the housing 83 is pulled away from the
displaceable cover 86, this causes the strut 82 to again be bent
away from biasing member 81 (because arm 84 which is now locked in
place by post 85 impedes the path of strut 82). However, when the
end 88 of strut 82 has cleared the arm 84, it springs back into
position, past a projection 89 on arm 84 (see FIG. 10C). In fact,
strut 82 latches behind projection 89, preventing the strut from
moving back to the position shown in FIG. 10B, and thereby
permanently locking the mechanism 80 in the FIG. 10C
configuration.
[0146] The perspective view in FIG. 10D shows the mechanism in the
position illustrated in FIG. 10A. An additional feature visible in
FIG. 10D is a snap mechanism comprising an arm 90 depending from
either side of the housing 83. A raised protuberance 91 on the
inner surface of each arm 90 acts against a sloped surface 92 on
the displaceable cover 86 to provide resistance to movement. The
effect of the snap mechanism is to add further resistance to any
unintended relative movement between the housing 83 and the
displaceable cover 86. A further effect is that the movement of the
housing 83 relative to the cover 86 between the configurations of
FIGS. 10A and 10B, and the configurations of FIGS. 10B and 10C, is
extremely rapid, causing the penetration of the needle into the
skin and the removal of the needle from the skin to be quick and
painless.
[0147] The second alternative embodiment of a locking mechanism of
the present invention comprises an inverted V-shaped assembly and
is shown in FIGS. 11A-11D. In FIG. 11A the locking mechanism is
indicated generally at 100 and comprises a member 101 resiliently
mounted on a housing 102, and a pin 103 supported in a frame 104
mounted on a displaceable cover 105. The member 101 has an inverted
V-shape slot 106 therein. The slot 106 has an outer slot portion
107 connected at the upper end thereof to an inner slot portion
108, and a dividing member 109 between the outer and inner slot
portions 107, 108 below the upper ends.
[0148] In moving from the "pre-use" position to the "in-use"
position, the (fixed) pin 103 moves up the outer slot 107, acting
against the dividing member 109 until it springs past the dividing
member 109 at the top of the outer slot. In the position shown in
FIG. 11B, the pin 103 is located above the top of the inner slot
108.
[0149] When the housing 102 is subsequently pulled away from the
displaceable cover 105 (moving from FIG. 11B to FIG. 11C, the pin
moves down inner slot 108, acting against the dividing member 109
to push the member 101 sideways. When the position shown in FIG.
11C is reached, the pin 103 locates a recess 110 (see FIG. 11B) in
the lower end of inner slot 108, which allows the member 101 to
relax slightly but still keeping a certain degree of stress on the
member 101 by holding it away from the equilibrium position
relative to the housing 102. In this way, the pin 103 latches into
the recess 110 and locks the mechanism 100 permanently in the
"post-use" configuration. In FIG. 11D, the mechanism 100 can be
seen in the "pre-use" configuration, with the member 101, housing
102, pin 103, frame 104, and displaceable cover 105 visible.
[0150] The third alternative embodiment of a locking mechanism of
the present invention comprises generally a rotatable pawl assembly
and is shown in FIGS. 12A-12D. The mechanism, indicated generally
at 120, comprises a rotatable pawl 121 mounted on the displaceable
cover 122 and which is rotated by an arm 123 in moving from the
"pre-use" to "in-use" positions (FIGS. 12A and 12B, respectively).
When the rotatable pawl 121 reaches the "in-use" position, a recess
124 (FIG. 12A) receives a projection 125 located on a resilient
portion 126 of the displaceable cover 122, providing a degree of
resistance to further movement.
[0151] In moving from the FIGS. 12A to 12B positions, the rotatable
pawl 121 acts against a flexible strut 127 depending from the
housing 128. When the rotatable pawl 121 is in the FIG. 12B
position, further clockwise rotation of the pawl is prevented by
the arm 123.
[0152] When the housing 128 is lifted (moving from FIGS. 12B to
12C), the strut 127 acts against a projection 129 urging the
rotatable member 121 in a clockwise direction, but the arm 123
prevents such rotation. As the housing reaches the FIG. 12C
position, the strut 127 springs past the projection 129 to sit in a
recess above the projection 129, and the arm 123 clears the upper
corner of the rotatable pawl 121. When in this configuration, the
arm 123 prevents any counter-clockwise rotation of the rotatable
pawl 121, while the strut 127 prevents any clockwise rotation
thereby locking the rotatable pawl 121 in position and preventing
any further downward movement of the housing 128 towards
displaceable cover 122.
[0153] The fourth alternative embodiment of a locking mechanism of
the present invention comprises generally a flexible post assembly
as shown in FIGS. 13A-13E. In FIG. 13A the locking mechanism is
indicated generally at 130 and comprises a vertical flexible post
131 (see FIGS. 13D and 13E) mounted on the displaceable cover 132
and having a projection 133 extending therefrom towards a sloped
surface 134 on the housing 135.
[0154] A slot 136 in surface 134 connects two apertures, namely a
lower aperture 137 (see FIG. 13B) which is of smaller diameter than
the widest part of projection 133, and an upper aperture 138 which
is of larger diameter than the widest part of projection 133.
[0155] In the "pre-use" position, projection 133 is positioned at
the lower aperture. As the housing moves towards the "in-use"
position (FIG. 13B) the flexible arm 131 is bent back until the
projection 133 reaches the upper aperture 138 whereupon it springs
back into position as the projection 133 moves through the upper
aperture 138. In moving to the "post-use" position, the projection
133 is constrained by the slot 136 and the arm 131 is bent forward
until the projection 133 reaches the lower aperture 137 which
provides a recess for the projection 133 to spring back into (but
not through). Because the arm 131 remains bent forward slightly,
this effectively traps the projection 133 in the lower aperture 137
and thereby holds the mechanism permanently in the "post-use"
configuration, as shown in FIG. 13C.
[0156] In FIG. 14 there is another drug delivery device 140
according to the invention similar in many respects to the
embodiments previously described. The device 140 has a protective
upper cover 141, a housing 142, a displaceable cover 143, a
delivery needle 144, a flow regulating chamber 145 and a three
position locking mechanism 146.
[0157] The internal space of the drug delivery device 140 of FIG.
14 defines an expandable chamber 147 when the diaphragm 148 is in
the position shown or a reservoir when the diaphragm is in the
position shown in dotted outline at 149. The expandable chamber 147
is initially air filled (FIG. 14 shows the device in the pre-use
configuration before medicament has been loaded). Thus, the
reservoir is substantially of zero volume. The expandable chamber
147 communicates with the atmosphere via an open valve 150.
[0158] When liquid drug is loaded into the reservoir via a fill,
the diaphragm 148 moves downwards to position 149, with the
reservoir filling with air and the expandable chamber 147 being
emptied as the volume thereof decreases. Because the expandable
chamber 147 is in communication with the atmosphere, the air
initially filling the chamber 147 is exhausted into the atmosphere
via the valve 150 without any necessity for action on the part of
the user.
[0159] Furthermore, because the reservoir is initially of
substantially zero volume, it does not require filling in any
particular orientation. While prior art devices have required
careful loading in order to ensure that all air bubbles are vented
from the drug supply before delivery begins, the only air in the
drug path of the device of FIG. 14 is in the short, narrow portion
of the device between the reservoir and the needle 144. Thus, when
drug enters the reservoir it immediately pushes the small amount of
air ahead of it through the narrow space towards the needle 144,
irrespective of the orientation of the device 140. By filling with
the drug until a drop of the drug appears on the end of the needle
144 one can be sure that no air remains in the fluid path.
[0160] When the device 140 has been filled with drug, the diaphragm
148 is at the position shown at 149, and the valve 150 is open.
However, when the displaceable cover 143 is applied to the skin,
and the housing is pushed downwards, the valve 150 is closed and
the closing of the valve actuates a switch 151 to begin generation
of gas by an electrolytic cell 152 (described in more detail
below).
[0161] The device 140 is then in the "in-use" position shown in
FIG. 15, with reservoir 147 filled with drug, the diaphragm 148 in
position 149, valve 150 and switch 151 closed, and electrolytic
cell 152 actuated to generate a gas and hence begin delivery of
drug from reservoir to the patient through delivery needle 144.
[0162] Valve 150 is closed by a connecting member 153 which is
connected to displaceable cover 143. When displaceable cover 143
moves towards housing 142, connecting member 153 fits into a valve
150 and pushes it home to seal the expandable chamber 147 (the area
below diaphragm 149) from the atmosphere. When a gas is generated
by the electrolytic cell 152, it pressurizes the reservoir 147.
[0163] A coloured plastic member 154 forming part of locking
mechanism 146 protrudes through an aperture 155 in the protective
upper cover 141 when the device 140 is in the position as shown in
FIG. 15. The coloured member 154 visually indicates that the device
140 has been actuated.
[0164] FIG. 16 is a detail view of the lower section 156 of the
housing 142 (see FIG. 15). The lower section 156 houses a battery
157 and an electrolytic cell 158, both mounted on a printed circuit
board (PCB) 159. The PCB 159 can be provided with controlling
circuitry as required in order, for example, to vary the rate of
delivery, stop delivery if the rate of gas generation is too high,
or control the operation of the device 140 in any other way
required. In the embodiment shown, the device 140 is a disposable
single-rate device which does not require advanced controlling
circuitry, but more sophisticated devices are of course within the
scope of the invention.
[0165] A cylindrical outlet 160 is formed in section 156, and this
provides a valve seat for the valve 150. When the valve 150 is
pushed upwards into an outlet 160 it makes an airtight seal, as
shown in FIG. 15. A recess 161 in the valve 150 tightly
accommodates the connecting member 153 (FIG. 15), and the force
used to push the housing 142 down onto displaceable cover 143 as
described above is sufficient to jam the connecting member 153 into
the valve 150. This design enables the device 140 to be removed
from the skin by pulling housing 142 away from displaceable cover
143 to the "post-use" position, causing the connecting member 153
(which is permanently mounted on displaceable cover 143 and at this
stage jammed into valve 150 also) to pull the valve 150 down and
out of outlet 160 so as to open the valve. Using this design, if
the reservoir 147 is not empty when the device 140 is removed, and
if gas generation continues, then the gas will escape through
outlet 160 rather than driving further drug through the needle
144.
[0166] As described above, when the valve 150 is closed, it
actuates a switch 151 (see FIG. 15) which comprises a fixed contact
162 and a rocking contact 163. This completes a circuit to connect
a battery 157 to an electrolytic cell 158. When the valve 150 is
pulled downwards as the device 140 is removed from the skin, the
switch 151 should automatically disconnect because of the
resilience of rocking contact 163 which pivots about a fulcrum 164.
Thus, the opening of the valve 150 is generally a redundant feature
and is important as a safety feature if the switch 151 does not
automatically disconnect (leading to an unwanted continuation of
delivery or, if the reservoir 147 is already empty, to a build up
of gas pressure inside the device 140).
[0167] The electrolytic cell 158 comprises (see also FIGS. 17 and
18) a body 165 defining an internal space 166 for an electrolyte
and through which a pair of electrodes 167 pass, each electrode
being connected to a terminal of battery 157 (FIG. 16). The
internal space 166 is enclosed above and below by a pair of
hydrophobic filters 168 and 169. These filters 168 and 69 retain
the electrolyte but allow gas generated in the cell 158 to be
released to the expandable chamber 147. The hydrophobic filters 168
and 169 are positioned on the body 165 such that gas will transfer
out of the gas generator irrespective of the orientation. The top
and bottom of the body 165 is provided with a seating 170. The
filters 168 and 169 are placed in the seating 170 above and below
the body 165 and are sealed in place. In a preferred embodiment,
the body 165 is an injected molded high density poly ethylene
(HDPE) to minimize permabilty.
[0168] The cell 158 is then sealed above and below by aluminum foil
layers 171 and 172. A connecting cell 174 sealed at both ends by
foil layers 171 and 172 enables gas passing through the hydrophobic
filters 168 and 169 to be released, once the top foil layer 171 has
been pierced. A gap adjacent to the seating 170, enables gas
escaping through hydrophobic filters 168 and 169 to reach the
connecting cell 174. The foil layer 171 is pierced by a spike 175
carried on rocking contact 163 (see FIG. 16). Thus, when the device
140 is actuated, the foil layer 171 is pierced to unseal the cell
158. A hydrophobic filter 176 (see FIG. 17) is also carried in the
body 165 to enable the cell 158 to be filled with electrolyte by
injection.
[0169] In FIGS. 19 and 20, a further embodiment 180 of the
invention is shown. This embodiment differs from the embodiment of
FIGS. 14-18 only in that the valve member 181 is not held by the
displaceable cover 182 when the device 180 is removed from the skin
after use. However, the valve 181 nevertheless achieves the primary
purpose of allowing the internal space 183 to be occupied entirely
by the expandable chamber when received by the user, with the
diaphragm 184 moving to the position shown at 185 when the device
180 is loaded with medicament. This means that no air bubbles can
be entrapped in the reservoir during filling, and the reservoir can
thus be filled quickly and easily. The valve 181 closes
automatically when the housing 186 is pressed towards the
displaceable cover 182 (see FIG. 20).
[0170] FIG. 21 shows a device 190 according to the invention which
is identical to the device of FIG. 1, together with a filling
adapter 191 and a drug-containing cartridge 192. Cartridge 192 is
cylindrical in shape, closed at one end 193 thereof and sealed at
the other end 194 by an elastomeric stopper 195 which is fittably
mounted in the cartridge 192. Because the cartridge's liquid-filled
internal space 196 is sealed, the stopper 195 is prevented by the
incompressible nature of the liquid from moving in either
direction.
[0171] The adapter 191 has a housing 197 in which a cannula
subassembly 198 is mounted. The subassembly 198 (see FIG. 22)
includes a plastic body 199 moulded in two halves 200,201, which
when assembled together clamp a double-ended hollow needle or
cannula 202 in place.
[0172] A device 190 is provided with a socket 203 for receiving the
adapter 191. A cylindrical projection 204 on the end of the adapter
191 is designed to fit into the socket 203, and also to conceal the
cannula 202 to prevent injury before and after the adapter 191 is
mounted on the device 190. A self-sealing penetrable plug 205
mounted in the socket 203 leads to a conduit 206 and an inlet for
the reservoir (see inlet 19 in FIG. 1). A subassembly 198 is
mounted in a channel 207 of the adapter 191 such that it can be
pushed inward until a shoulder 208 meets the end of the structure
209 defining the channel 207. At this point, the cannula 202 will
penetrate the plug 205 enabling communication between the cannula
202 and the reservoir of device 190. In use, a cartridge 192 is
pushed into the adapter 191, whereby a stopper 195 causes the
subassembly 198 to be pushed inwards and the cannula 202 to
penetrate the plug 205. Since the subassembly 198 can move no
further inward, further pushing of the cartridge 192 into the
adapter 191 causes cannula 202 to penetrate stopper 195, thus
putting drugfilled space 196 in indirect communication with the
reservoir of device 190.
[0173] The stopper 195 is then held by subassembly 198, further
pushing of the cartridge 192 inwards causes the stopper 195 (which
remains stationary) to move relative to the cartridge 192 (which is
progressively accommodated in the interior of adapter 191), with a
consequent emptying of the contents of the cartridge 192 through
the cannula 202 into the reservoir of device 190.
[0174] This is illustrated best in FIG. 23, which shows a sectional
view of the components shown in sectional plan view in FIG. 21,
after the cartridge 192 has been pushed most of the way home into
adapter 191. It can be seen that at this point, the stopper 195
(penetrated by cannula 202 which also penetrates plug 205) has
almost reached the end 203 of cartridge 192.
[0175] The adapter 191 is not only held by the fit of the
projection 204 into the socket 203, but also by a releasable
locking mechanism 210. The releasable locking mechanism comprises
210 an aperture 211 on the device 190 and a resilient catch 212 on
the adapter 191 which is biased into the position shown in FIG. 23
so as to hold the adapter firmly in place on device. Preferably the
adapter 191 and the device 190 are sold together in kit form,
optionally with the adapter already mounted on the device.
[0176] When the cartridge 192 is pushed fully home it acts on a
sloped section 213 of wall 214 of adapter 191 so as to push
resilient catch 212, which is an extension of wall 214, downwards.
This disengages the locking mechanism 210, allowing the adapter 191
to be removed from the device 190.
[0177] FIG. 24 shows the kit after the cartridge 192 has disengaged
the catch 212 allowing it to be withdrawn from the aperture 211.
This permits the adapter 191 to be removed from the device 190 by
pulling the projection 204 from the socket 203 whereupon the plug
205 seals itself and thereby isolates the reservoir of the
device.
[0178] Because the catch 212 is only disengaged when the cartridge
192 is fully emptied (i.e. when the stopper is pushed to the closed
end 193 of the cartridge 192), one can ensure that the reservoir is
loaded with exactly the correct amount of drug every time, thereby
eliminating human error and making the kit more suitable for home
administration.
[0179] Furthermore, because both ends of the cannula 202 at all
times are concealed, the adapter 191 can be safely disposed of
without risk of injury. The adapter 191 allows the drug to be
transferred to the reservoir with sterility ensured, since the user
does not at any time handle any of the components in the fluid
path.
[0180] FIG. 25 shows another alternative embodiment of the device
according to the invention, indicated generally at 220. This
embodiment differs from previous ones in that instead of a needle
extending directly from the housing 221, a tube 222 extends from
the housing 221 and carries a connector 223 thereon to which a
needle may be affixed before use. This device 220 is particularly
suitable for intravenous drug delivery because the tube 222 allows
the needle to be accurately positioned in a vein.
[0181] FIG. 26 shows an alternative intravenous embodiment,
indicated generally at 230. In this embodiment the displaceable
lower cover has been omitted and the device is actuated by a
contact switch 231 positioned on the underside of the housing 232.
When the device is applied to the skin, the switch 231 is pressed
inwards (to the position shown in FIG. 26), thereby closing an
electrical circuit and actuating a gas generating electrolytic cell
233 in the manner previously described. As the snap action provided
by previously described devices is not required to cause a needle
to penetrate the skin, the cover can be omitted without interfering
with other functions of the device.
[0182] FIG. 27 shows the elastomeric diaphragm 240 utilized in the
above-described devices according to the invention. The diaphragm
240 can also be used in other drug delivery devices according to
the invention. The diaphragm 240 is shown in FIG. 27 in its relaxed
position, as it would be when the reservoir is empty (see FIG. 6,
for example). In this configuration the diaphragm 240 substantially
has the form of a truncated cone having a sloped portion 241
surrounding a flat portion 242, with a lip 243 surrounding sloped
portion 241 (lip 243 is used to attach diaphragm 240 to the housing
of a drug delivery device).
[0183] FIG. 28 shows the diaphragm 240 in the configuration in
which the reservoir is full (see FIG. 1, for example). In this
configuration, the central portion 242 is still flat, and the
surrounding portion 241 has an arcuate curved cross-section, in the
form of a substantially inverted U shape.
[0184] The diaphragm 240 is bistable, such that it is stable in
either the FIG. 27 or the FIG. 28 configuration. However, a
particular advantage has been found to result from the fact that in
moving from the reservoir full (FIG. 28) configuration to the
reservoir empty (FIG. 27) configuration, very little energy is
needed.
[0185] Unlike many bistable arrangements, only minimal force is
required to move between the stable configurations. In many
bistable arrangements a substantial amount of energy is required to
move from one configuration to a midpoint, at which the amount of
stored energy is relatively high, following which the stored energy
is released to complete the transition. The diaphragm 240, rather
than flipping between configurations, makes a smooth transition.
However, in contrast to a completely pliable body, which cannot be
depended on to exert force uniformly, the diaphragm 240 will behave
dependably since it is constrained in its movement between
configurations. This means that a predictable manner of movement is
combined with a minimal expenditure of energy in actually effecting
the transition between bistable configurations.
[0186] The elastomeric diaphragm 240 (and others shown in
alternative embodiments) and the flow diaphragm 26 of the flow
regulating chamber 35 are elastomers. There are two preferred
sources for this material. One is a bromobutyl compound made by
Vernay Laboratories, Inc. of Yellow Springs, Ohio (material number:
VL 911N7). The second is an ethyl propylene diene monomer ("EPDM")
material number Bryant 85055, made by Bryant Rubber.
[0187] There are several advantages in using these two materials.
First, the material has a low durometer, which enables the material
to remain soft. Moreover, it enables the diaphragm to keep air out
and deflect from one stable position to the other with little
energy. In addition, these elastomers provide a long shelf life.
Another advantage is the ability to withstand gamma radiation
without degradation of properties. As stated above, gamma radiation
is used in some sterilization procedures. The ability of these
materials to withstand gamma radiation is very important as these
materials will be assembled in the device and sterilized. An
additional advantage of using these materials is their lack of
toxicity.
[0188] FIG. 29 shows a circuit diagram of a controlling circuit
particularly useful or a drug delivery device according to the
invention. In the circuit 250, all symbols have their normal
meanings within the art. The components shown are a battery B1, a
switch S1 (activated by applying the device to the body), fixed
resistors R1-R6 and R9-R10, variable resistors R7 and R8, a
capacitor C1, transistors Q2-Q6, measurement terminals TP1 and TP2,
a light emitting diode LED, and a load U1 which represents the
electrolytic cell or other gas generating means. Reference numeral
251 denotes a section of the circuit 250 which functions as a
current driver, and reference numeral 252 denotes a section of the
circuit 250 which functions as an error circuit.
[0189] The current through the electrolytic cell Ul determines the
potential drop across variable the resistance comprising resistors
R7 and R8 (which may be adjusted to calibrate the device or set the
delivery rate). This potential drop is compared by the error
circuit with the potential drop across a reference resistor R1,
which itself depends on the voltage drop across the LED. The value
of resistor R1 is chosen to provide a potential drop equal to the
drop measured across the resistors R7 and R8 when the correct
current is flowing through the cell U1.
[0190] If the potential drop across the resistors R7 and R8 is
lower than the constant potential measured across the resistor R1,
indicating that the current through the cell U1 is too low (e.g.
because of fading battery power, changes in the internal resistance
of electrolytic cell U1 as the reactants are consumed, etc.), the
error circuit 252 forces the driver 251 to increase the current
flow to the correct value. In practice, the error circuit 252
continually ensures that the current does not deviate from the
correct value by constant feedback operation.
[0191] Each of the transistors in the circuit 250 is a
silicon-based bipolar transistor. The advantage of using bipolar
transistors in particular is that they have been discovered to
surprisingly withstand gamma radiation to a far greater extent than
other types of transistors. The use of silicon as semiconductor is
not essential but this material is currently less expensive than
many other semiconductors. It has been found that by employing a
circuit in which the or each transistor is a bipolar transistor,
the circuit and hence the entire device can be subjected to intense
gamma irradiation as a means of sterilizing the device after
manufacture. Conventional integrated circuits are destroyed by the
intense radiation required to sterilize a device quickly.
[0192] For example, a dose of 2.5 Mrad (25 kJ/kg) of gamma
radiation may be required to sterilize a device. In trying to
design a circuit which would withstand such harsh conditions we
consulted data regarding the electronic components used in space
missions, such as the U.S. Space Shuttle missions. It was found
that the same degree of radiation resistance was not required
because the absorbed dose measured on the Space Shuttle averages
approximately 0.4-0.5 Mrad.
[0193] As a rule, all electronic components will undergo a degree
of degradation when subjected to irradiation. However, by selecting
components which are resistant to irradiation as far as possible
and whose performance can be predicted after receiving a given dose
of radiation, it is possible to design a circuit which will
withstand intense gamma radiation and still function in a
predictable manner.
[0194] In particular, by using a bipolar transistor with a high
current gain (e.g. a current gain of at least 600 but preferably
800 or more) the drop in current gain exhibited after irradiation
can be compensated for in advance. This drop in gain can be of the
order of a tenfold drop or more, but can be predicted well in
advance. Furthermore, by using current values which are
sufficiently low, the drop in voltage at the silicon junction of
the transistor occurring as a result of the irradiation only
slightly affects performance.
[0195] A further advantage is gained using a circuit which employs
a light emitting diode as a basis for the reference voltage used in
the error correction circuit, since the LED reference source is not
affected by the gamma radiation. The LED used is a gallium arsenide
(GaAs) based LED which has been found to provide particularly good
resistance to gamma radiation.
[0196] In summary, the components and circuit employed have been
found to be suitable for gamma irradiation, following which they
give a well predictable performance in use. This enables the
manufacture to be completed more efficiently, with the assembled
device sterilizable by gamma radiation.
[0197] FIG. 30 is a perspective view of the top side of a
displaceable cover 160 forming part of a device according to the
invention. FIG. 31 is a perspective view of the underside of cover
160. Such a cover is described generally above in relation to the
embodiment of FIGS. 4-8, for example.
[0198] The cover 160 is provided with formations 161 forming part
of a locking mechanism as described above, with an aperture 162
through which a delivery needle protrudes in use. The cover 160
also has hinge formations 163 which enable the cover to be
displaced relative to the housing between first and second
positions as previously described.
[0199] The cover 160 is shaped to improve retention of the device
against the skin: thus. the top side 164 (FIG. 30) is convex, and
the underside 165 (FIG. 31) from which the needle protrudes in use
is concave. Accordingly, when the device has been applied to the
skin of a subject removal of the device is resisted because the
cover 160 conforms more closely to the skin. It is less likely that
the device will peel from the skin without a conscious effort by
the user since there is a lower likelihood of the periphery of the
cover being detached from the skin.
[0200] FIG. 32A schematically illustrates an alternative preferred
embodiment of an electrical circuit 250 within a subcutaneous drug
delivery device. The circuit 250 replaces the entire circuitry of
FIG. 29. In order to provide a constant rate of drug delivery, the
delivery system 254 requires a constant current. This electrical
circuit stabilizes the current supplied to the electrolytic cell
without using components such as transistors which are sensitive to
gamma radiation during sterilization. Gamma radiation is a standard
method of sterilization of medical devices. A constant current
supplied to the electrolytic cell results in a volume of gas which
provides a desired constant delivery rate. The circuit uses a
higher voltage than the previous embodiments along with current
stabilizing resistive elements, such as, for example, resistors in
series. FIG. 32A shows an electrical circuit 250 having a pair of
batteries 253 coupled to a drug delivery system 254 by a current
stabilizer 256. The batteries 253 in the electrical circuit 250 can
include, for example, but is not limited to, between one and three
batteries, having voltages of, for example, 1.5 or 3V. FIG. 32A
illustrates an embodiment having two batteries 253. The current
stabilizer 256 can calibrate the electrical circuit 250 to provide
an appropriate current for the subcutaneous drug delivery device.
The electrical circuit 250 can also include a switch 255.
[0201] In the alternative embodiment described in the preceding
paragraph, the current stabilizer 256 can use a single resistor or
alternatively as shown in FIG. 32A, the current stabilizer 256
includes two resistors 260 connected in series. In a preferred
embodiment, the two resistors 260 have identical resistance values.
The use of multiple resistors 260 can reduce the current charge as
a result of accidental short circuiting of a resistor. The maximal
delivery rate of the delivery system 254 with a short circuit
condition at one resistor can only be twice the nominal rate. A
change of battery voltage and a change of resistance of the
electrical circuit 250 can change the current profile at the
circuit 250. In one embodiment, it is possible to control the
current profile by selecting the voltage and number of batteries
used in the circuit 250. In a preferred embodiment, the current
profile 257 is constant over time, as illustrated in FIG. 32B.
[0202] The subcutaneous drug delivery device can also include an
occlusion prevention mechanism. FIGS. 33A-33F schematically
illustrate a drug delivery system in which an undesired delivery of
a bolus of a medicament can occur. FIG. 33A schematically shows a
delivery device 262 having a gas chamber 264, a drug chamber 266, a
flexible diaphragm 265, and a needle 270. There is a lower risk of
bolus delivery if the back pressure in the gas chamber 264 is
constant. The gas is produced at a constant rate by the gas
generator. As the gas is produced, the drug within the drug chamber
can flow constantly to keep equal pressure within the device 262.
FIG. 33B shows the linear relationship of drug delivery over
time.
[0203] FIG. 33C shows an occlusion 268 occurring in needle 270 of
the delivery device 262. Once occluded, the pressure in the gas
chamber 264 will rise as the gas generator continues to produce gas
and the drug within the drug chamber 266 does not flow. FIG. 33D
illustrates that an occlusion can result in the reduction or
termination of delivery of the drug over time. The pressure in the
gas chamber 264 can reach a high enough level to overcome and
remove the occlusion. Once the occlusion is removed, the drug
within the drug chamber 264 can flow rapidly until back pressure in
the gas chamber 264 and the pressure in the drug chamber 266
equalize, therein creating a bolus delivery of the drug.
[0204] FIGS. 33E and 33F illustrate the relationship between drug
delivery and time, as the occlusion is removed and the pressures
equilibrate. The size of the bolus can depend on the time duration
of the occlusion and the nominal flow rate without the occlusion
(Volume bolus=Time occlusion*Flow rate). The occlusion time
duration depends upon the gas generation rate and the volume of the
gas within the gas chamber 264. The longer the time the
subcutaneous drug delivery device worked before the occlusion, the
bigger the volume of the gas in the chamber 264, the longer the
time needed to rise to the pressure to remove the occlusion 268,
the larger the bolus. FIG. 33F shows a graphical representation of
the rapid flow of a drug delivery system as an occlusion is removed
from a needle and the pressure equalizes.
[0205] FIG. 34A shows a bolus prevention mechanism 272 within a
drug delivery device 262 created by forming a constant, relatively
high pressure level in the drug reservoir. In a preferred
embodiment, the mechanism 272 is a valve 274. The use of a valve
274 can create a constant high pressure 276 within the gas chamber
264, while maintaining a low pressure 278 within the needle 270 of
the delivery device 262. The high back pressure 276 and the low
pressure 278 within the needle 270 can prevent occlusions from
clogging the delivery device 262 for lengthy periods of time,
therefore minimizing or preferably preventing the formation and
delivery of boli. As long as the high back pressure 276 is higher
than the pressure needed to deliver the drugs subcutaneously, the
flow of the drug will not be adversely affected. FIG. 34B shows a
graphical representation of the steady delivery of drugs over time
created by the use of a bolus prevention mechanism within the drug
delivery device of the present invention.
[0206] A preferred embodiment of the subcutaneous drug delivery
device 282 can also include an optical window 280, shown in FIG.
35, which indicates to a user when delivery of a drug contained
within the device 282 is complete. The drug is typically contained
between the plastic housing and the elastomeric membrane or
diaphragm that moves away from the housing as the drug fills the
reservoir. When the drug delivery device does not contain the drug,
the elastomeric membrane is proximate to the housing. The optical
window 280 is located on the housing. When the membrane is
proximate to the housing, the optical effect of the direct
reflection of light from the elastomeric membrane results in
clearly visible membrane color, for example, blue. However, when
the reservoir is full, the light is diffused in the drug chamber
results in the appearance of the black color. In a preferred
embodiment, the optical window 280 is a circular structure which
allows light to enter and includes a pair of opaque sections 284
matching the membrane color and a transparent annular ring section
286 which allows the light to enter. The ring-like structure
provides a more accurate assessment of the quantity of drug
delivered. FIGS. 36A-36C show changes to the optical path through
the window during drug delivery which indicate to a user the amount
of fluid in the reservoir of the drug delivery device.
[0207] FIG. 36A illustrates a drug reservoir 290 bounded by a
diaphragm 288 and a reservoir housing element 292. The reservoir
housing element 292 has the drug window 280 which includes both the
opaque section 284 and the transparent section 286. In a preferred
embodiment, the color of the colored section 284 and the diaphragm
288 are the same, for example, both the colored section 284 and the
diaphragm 288 are light blue in color. At the onset of drug
delivery, the drug reservoir 290 can be full of a medication to be
delivered to a patient. When the reservoir 290 is full, the
transparent section 286 of the optical window 280 appears as a
different color to that of the colored section 284 and the
diaphragm 288. In one embodiment, the transparent section 286 will
appear as black.
[0208] FIG. 36B illustrates a drug reservoir 290 after drug
delivery has been partially completed. At this stage of drug
delivery, the diaphragm 288 can partially contact the optical
window 280 and can block a portion of the transparent section 286.
Such a blockage optically changes the appearance of a portion of
the transparent section 286, that is, instead of appearing black,
it appears as the same color as the colored section 284. Such a
change in color indicates to a user that drug delivery is partially
completed.
[0209] FIG. 36C illustrates a drug reservoir 290 after drug
delivery has been completed. At this stage of drug delivery, the
diaphragm 288 can completely contact the optical window 280 and can
block the entire transparent section 286. The contact of the
diaphragm 288 against the transparent section 286 can optically
change the appearance of the color of the transparent section 286,
that is, instead of appearing black, the diaphragm becomes visible.
A complete change in color of the transparent section 286 can
indicate to a user the end of drug delivery.
[0210] In another preferred embodiment, the drug delivery system
can include an optical indicator to indicate proper application and
operation to a user. The indicator can be, for example, a color
marking system. The color marking system can be used to indicate to
a user components of the drug delivery system which should be
removed from the system prior to use. The color marking system can
also indicate to the user whether or not the drug delivery system
has been applied correctly or is operational. In a preferred
embodiment, the color marking is, for example, yellow in color. The
color marking can be applied directly to components of the drug
delivery system or can be applied in the form of a colored
label.
[0211] In one embodiment, the filling adaptor or syringe adaptor of
the subcutaneous drug delivery device can have yellow labeling
attached thereon to indicate to a user that the adaptor should be
removed before activating the delivery device. In another
embodiment, the base of the delivery device can be produced (for
example, dye in the plastic) with a color which contrasts with the
color of the cover. During use, the cover of the delivery device
can be hingedly moved towards the base and covers all but a small
portion at the base. The disappearance of the contrastingly colored
base can indicate to a user that the drug delivery device has been
correctly applied and activated. Generally, when the drug delivery
device is correctly applied and started, none of the parts of the
device, which include color marking or color labeling, can be
visible to the user.
[0212] In another preferred embodiment, the subcutaneous drug
delivery device can include a pressure sensitive mechanism, such as
in FIG. 37A, for preventing bolus delivery or rapid injection of a
drug into the user. A switch 300 can prevent a rapid injection of
drug to a user as a result of an increase in pressure in the drug
delivery device. The switch 300 can help to avoid an increase in
pressure within the drug delivery device caused by blockage of the
needle. The switch 300 can form part of a circuit 250, as shown in
FIG. 32A, which controls the power supply to a gas generating
portion of the drug delivery device.
[0213] One embodiment of the switch 300 is shown in FIGS. 37A-37C.
In this embodiment, the switch 300, which is part of a circuit 308,
is made from a conductive membrane 302 and a conductive lever 306
is located on the printed circuit board 159, as seen in FIG. 37A.
The switch 300 has a chamber 304 which is sealed by the conductive
membrane 302 as seen in FIGS. 37B and 37C. The chamber 304 contains
an accurate amount of gas, such as, for example, air, and can be
made of a solid material whose volume is not affected by pressure
and is non conductive electrically, referred to as a solid
isolator. The membrane 302 has a raised annular portion to allow
the membrane to flex depending on the pressure differential between
the chamber 304 and the expandable chamber 14. The lever 306 is
designed to rest upon the membrane 302 during operation. When the
conductive lever 306 contacts the conductive membrane 302, the
circuit 308 can be closed, thereby allowing the gas generating
portion of the device to operate 310. As long as the pressure
within the gas generating portion of the delivery system is lower
than the pressure within the chamber 304, the lever 306 can contact
the membrane 302.
[0214] In the event that the pressure within the drug reservoir
increases, such as caused by a blockage in the needle, the pressure
within the gas generating portion can increase to a higher level
than the pressure within the chamber 304. In the event pressure
within the drug reservoir and the expandable chamber 14 increases,
the pressure within the chamber 304 is lower relative to the
expandable chamber 14 and the membrane 302 is pushed away from
contact with the lever 306, as shown in FIG. 37B. As a result, the
lever 306 is no longer in electrical contact with the membrane 304
and the circuit opens, thus shutting off power to the gas
generating portion of the device. This, in turn, stops any pressure
build-up and potential for a boli delivery. The conductive membrane
or lever can be made from aluminum or copper, for example.
[0215] FIG. 37D illustrates circuit 308 as part of circuit 256
which was shown in FIG. 32A. The switch 300 is in series with
switch 255. Both switches 255 and 300 must be closed to generate
gas. Switch 300 is normally closed and switch 255 is closed to
start the gas generation. As indicated above, switch 300 only opens
if the pressure increases to a current level, such as due to a
blockage.
[0216] FIGS. 38A and 38B illustrate an alternative embodiment of a
pressure sensitive mechanism 300. In this embodiment, the switch
300 includes an isolator membrane 314, mounted above a chamber 304,
and a conductive thread 316 combined with the membrane 314. As long
as the pressure within the gas generating portion is lower than the
pressure within the chamber 304, the thread will remain intact,
thereby completing the circuit for the gas generator, which remains
in an on position 310. In the event of an increase in pressure in
the drug reservoir, as shown in FIG. 38B, the gas generating
portion can increase to a higher level than the pressure within the
chamber 304. The pressure differential can cause the membrane 314
to sink into the chamber 304, thereby severing the thread 316. Such
a break can open the circuit 308, thereby preventing the gas
generator from producing gas 312 and preventing an increase in
pressure in the drug reservoir. In contrast to the previous
embodiment, once the circuit is open the circuit cannot be closed
again, i.e. once the membrane is depressed the thread is
severed.
[0217] FIGS. 39A-39C illustrate another preferred embodiment of a
pressure sensitive switch 300. FIG. 39A is an enlarged perspective
view of the switch 300 with portions broken away. FIGS. 39B and 39C
are schematics of the switch 300. In this embodiment, the switch
300 is formed from a pair of electrodes 318, extending into a
capsule 319. Each electrode 318 connected to the circuit 308
contacts a droplet of mercury 320 located in a channel which opens
onto a large chamber 304. The droplet 320 of mercury maintains the
current between contacts as long as the pressure in the gas
generating portion is less than the pressure within the chamber
304. Such a contact can close the circuit 308, thereby allowing the
gas generator to operate 310. Under a high enough pressure in the
drug reservoir, as shown in FIG. 39B, the pressure in the chamber
304 can be lower than the pressure within the gas generating
portion of the delivery device, thereby causing the mercury droplet
320 to move towards the chamber 304 and away from the electrodes
318. The mercury droplet responds to the relative pressure between
the gas generating portion and the chamber 304. Such a movement
opens the circuit 308, thereby preventing the gas generator from
producing gas and increasing the pressure in the drug
reservoir.
[0218] While both the first embodiment, FIGS. 37A-37D, and the
third embodiment, FIGS. 39A-39C, have the capability to have the
switch 300 closed again if the pressure equalizes, it is
contemplated that the pressure will not decrease and therefore once
the switch is open, it will remain open and the power to the gas
generator will not be restored.
[0219] Another preferred embodiment of the subcutaneous drug
delivery system includes a mechanism which reduces tolerances and
thus errors during manufacture of the device. During manufacture,
certain components need to have a particular tolerance. When the
device is assembled, if the tolerances of each component are
significant, the volume of the internal housing may be outside of a
specified desired range. Thus, an insert, for example, a foam
insert that receives the internal components of the device,
maintains an accurate internal volume so that upon assembly, the
volume of the internal housing, and thus, the drug reservoir is
within an accurate range.
[0220] A subcutaneous drug delivery device 322 is shown in FIG. 40.
The device 322 can have a cover 324 and a base 326 and can house an
inner component 328. The device 322 can also have an internal
volume 330 between the cover 324 and the inner component 328.
During manufacture of the device, the base 326, cover 324, and
inner components 328 need to be manufactured within certain
tolerances. Due to the tolerances of the components, the internal
volume 330 can be outside of a specific range. To eliminate any
variability due to tolerances, an insert 332 can be used to
maintain the precise drug reservoir 12 necessary within the device
322. The insert 332 forces the inner component 328 toward the cover
324 of the delivery device 322. This eliminates assembly tolerance
errors during manufacturing and can get the internal volume 330 of
the device 322 within an accurate and acceptable range. The
internal air volume 330 includes the internal chamber which defines
the reservoir 12 and the expandable chamber 14, and air volume
between components and below the expandable chamber 14, which is
referred to as a dead air volume. Dead air can also be defined as
residual air below the diaphragm after the primming. In one
embodiment, the insert 332 is a flexible material. In a preferred
embodiment, the insert 332 is closed foam; the air pockets or
bubbles are sealed so not forming a part of the dead air. The
internal volume 330 of the device 322 can be used as a drug
reservoir.
[0221] In another embodiment, the drug delivery device 336 can
include an activation lever 334, as shown in FIGS. 41A and 41B to
initiate gas generation in the expandable chamber which in turn
controls the delivery of the drug from the device. The activation
lever 334 includes a puncturing device 340 and an electrical
contact 342. The drug delivery device 336 includes an electrolytic
cell 338 mounted next to the activation lever 334. On the printed
circuit board, the electrolytic cell 338 has a foil cover, for
example, aluminum foil, to preserve chemical ingredients within the
cell 338. Without the foil, the electrolyte water content could
evaporate during storage affecting the performance of the device
336. The activation lever 334 can be mounted to the drug delivery
device by a pivot 344. Upon depression, the puncturing device 340
of the activation lever 334 can puncture the foil cover of the
electrolytic cell 338, thereby allowing the gases generated by the
cell operation to escape and to expand the expandable gas chamber
and thereby compressing the drug reservoir of the delivery device
336. Also upon depression of the activation lever 334, the
electrical contact 342 on the lever 334 engages a contact 346 on
the printed circuit board of the device 336 which starts the
delivery of the drug. The contact 342 on the lever 334 engages the
two contact 346 on the delivery device 336 moving one of the
contacts 346 into engagement with the other contact 346 for an
indefinite time period.
[0222] In a preferred embodiment, the lever 334 can be made from a
plastic material. A plastic lever 334 can be economically produced
using an injection molding technique, for example. The plastic
lever 334 can be secured to the pivot 344 by a snap fit and thereby
not require soldering. The plastic lever 334 can be manufactured
such that the lever does not bend when forming an electrical
contact with the drug delivery device 336 or when puncturing the
foil on the electrolytic cell 338.
[0223] Another embodiment of the drug delivery system relates to
controlling the rate of delivery by parameters such as, for
example, residual air volume, base permeability, membrane seal and
membrane permeability. In particular, with regards to the residual
air volume, an air space can be created within a drug delivery
system by providing a cavity for air, for example. Such an air
space can be considered as a residual or dead air volume and can
have an effect on the drug delivery rate. The larger a residual air
volume, the greater the effect on delivery rate. For example, the
expansion of the air volume because of a temperature increase can
create a bolus effect in the device delivery. Residual air volume
can be controlled by design characteristics of the geometry of the
inner parts of the device. A high residual air volume within the
device can add a delivery period between the activation of the drug
delivery system and the actual start of drug delivery.
[0224] FIG. 42 illustrates a graph of a delivery 350 of drugs
through a drug delivery system under normal or low residual air
volume conditions and delivery 352 under high residual air volume
conditions. The drugs delivered under high residual air volume
conditions are delayed 354 between the activation of the system and
the start of drug delivery. By altering the residual air volume
within the delivery system by changing the design characteristics,
the delay can be reduced or eliminated within the system.
[0225] Another embodiment of the drug delivery system relates to
controlling the material characteristics of the device components,
such as, for example, the permeability of the system which in turn
affects the delivery rate of the drug. Permeability can be
controlled, for example, by both changing the geometery of the
inner components of the delivery system and by changing the
materials used to manufacture the system. By lowering the
permeability of the delivery system, less gas can diffuse out from
the system. With less gas leaving the system, the variance in
delivery rate can be lowered or eliminated. By minimizing the
permeability to gases of the expandable chamber, a constant
delivery rate of the drug can be maintained.
[0226] For example, by using PET plastic, the gas leak rate or
permeability is minimized. Alternatively, a highly permeable
material can allow a large amount of gas to diffuse out of the drug
delivery system which can reduce the drug delivery rate. FIG. 43
illustrates a graph of delivery 356 of drugs for a low permeability
system and delivery 358 for high permeability system. As shown, a
high permeability yields a higher delivery rate at the onset of
delivery 359 and a lower rate of delivery 360 as time goes on,
compared to a delivery system having a normal permeability 356.
[0227] Packaging of a drug delivery device can be an important
factor relating to the practical storage and use of the device at
different altitudes and humidities. For example, proper packaging
of the device can extend the storage period of the device, without
an appreciable affect on the device performed. Proper packaging can
also prevent environmental affects, such as, the diffusion of water
from the electrolyte that provides for the gas generation from the
drug delivery device without additional protection, internal to the
device.
[0228] In a preferred embodiment, a hermetic packaging for a drug
delivery system achieves extended shelf conditions and simplifies
the barometric pressure valve and the electrolytic cell of the
system.
[0229] In a previous embodiment, the drug delivery system was
packaged using a blister and a Tyvek lid to maintain sterility and
protect the device during a two year shelf life. In this
embodiment, the Tyvek lid is gas permeable when exposed to
atmospheric conditions, such as, for example, non-controlled
pressure and humidity conditions. With this type of packaging,
issues can arise as to the maintenance of barometric pressure valve
performance and the prevention of drug evaporation from the
delivery system. To maintain the desired performance of the
barometric pressure valve of the delivery device, the valve has two
positions. In one position, the storage position, the valve
membrane can move. In another position, the working position, the
valve builds pressure against the drug delivery system needle. In
order to prevent evaporation of the electrolyte, the electrolytic
cell can be fully protected by aluminum foil. Further, the foil
seal requires the use of an activation lever. Pinching of this foil
around the cell is required for system operation.
[0230] In the preferred embodiment, the blister and Tyvek lid
packaging can be replaced by a hermetically sealed packaging. By
changing the packaging, the issues of valve position and adverse
environmental impact, such as, for example, diffusion can be solved
without any internal feature protection.
[0231] Referring to FIG. 44A, an alternative drug delivery system
362 is shown with a stationary valve 368. The drug delivery system
362 is shown without the displaceable cover 143, such as shown in
FIGS. 14 and 15. The internal space of the drug delivery device 362
of FIG. 44A defines an expandable chamber 147 when the diaphragm
148 is in the position shown or a reservoir when the diaphragm is
in the position shown in dotted outline at 149. The device 362 has
a switch 151 which is engaged by a valve 150, such as seen in FIGS.
14-16, to close the switch to activate the process.
[0232] In contrast to the air-filled flow-regulating chamber 35 or
145 of FIGS. 1-3, 14, and 15, in which the chamber 35 moved with
the flow of fluid (the drug) both above and below the chamber, the
stationary valve 368 does not move. The stationary valve 368 has an
airtight chamber 370 sealed by a flow diaphragm 372, similar to the
airtight chamber 36 and diaphragm 26 of FIG. 3. However, another
distinction is that the flow diaphragm 372 of this embodiment does
not have a projection which is received in the inlet associated
with the needle such as in some of the previous embodiments.
[0233] In contrast, referring to FIG. 44B, the flow diaphragm 372
has a flat circular portion 374 for sealing the top of the needle
376. The drug flows through a port 378 from the reservoir to an
annular chamber 380 underlying the flow diaphragm 372. The pressure
in the reservoir and the annular chamber 380 is equal to the
pressure inside the controlled volume, the airtight chamber 370,
therein stressing/flexing the flow diaphragm 372 and opening the
entrance to the needle 376. In this embodiment, the valve can
become a stationary valve, more accurate and with longer shelf life
in extreme conditions. The aluminum protective liner and the
pincher mechanism are no longer needed for the cell
functioning.
[0234] The packaging is illustrated in FIG. 45. The drug delivery
system 362 can be enclosed between a foil layer 364 and a
non-permeable blister 366 to maintain internal pressure despite
environmental parameter changes, such as pressure and temperature.
The blister is a semi-rigid package with an aluminum cover or low
permeability plastic welded at its bottom. The drug delivery device
is inserted into the cavity. The blister is made of PET. The cover
is made of aluminum foil 38 micron with 2 micron of H.S.C. for the
welding. The leak through the materials due to relative pressure at
the storage time, designed to effect less than permitted by the
drug delivery system specification. The surface area of the package
is about 0.034 m.sup.2 with an average thickness of 0.3 mm, with a
permeability factor of about 0.4. Given these dimensions, the
pressure in the device is calculated to decrease up to about 3% in
two years. The foil layer 364 can be, for example, an aluminum
foil.
[0235] Over-pressurization of the package during manufacturing can
provide a longer shelf life as there is more time for the air to
leak before getting to the minimum required pressure, and thus
adding shelf life.
[0236] In an alternative embodiment for packaging a drug delivery
device, a secondary packaging device can be used with a primary gas
permeable packaging, such as a blister and Tyvek lid, to extend the
storage life of the device. The use of secondary packaging can
increase the shelf life of a delivery device without altering the
drug delivery rate.
[0237] In a preferred embodiment, the secondary packaging device
380 can be a cylindrical container 382, as shown in FIG. 46. The
cylindrical container 382 can be an aluminum or tin can, for
example. In an embodiment, the container 382 can hold either four
delivery device packages 384, as shown in FIG. 46, or can hold more
delivery device packages 384. Prior to storing the drug delivery
packages 384 within the container 382, in one embodiment, the drug
delivery device can be packaged between a blister and a Tyvek lid
and then sterilized.
[0238] FIGS. 47A-47C illustrate an alternative embodiment for a
secondary packaging device 380. In this embodiment, as shown, the
secondary packaging device is a rectangular container 386. The
rectangular container 386 can have a cover portion 390 and a base
portion 388 where the base portion 388 can be used for storage of
drug delivery packages 384. FIG. 47A shows an embodiment of the
cover portion 390 in a closed position while FIG. 47B shows an
embodiment of the cover portion 390 in an open position where the
cover 390 can completely disconnect from the base portion 388. In
an alternate embodiment, the cover portion 390 can be hingedly
attached to the base portion 388.
[0239] The rectangular container 386, in one embodiment, can be
designed to hold up to four drug delivery devices 384, as shown in
FIG. 47B. In another embodiment, the container 386 can be sized to
hold a single delivery device 384, as shown in FIG. 47C. A
limitation to the use of the container 386 holding four delivery
devices 384 can include using the fourth, or last, device within
opening the container 386. For a container 386 holding up to four
delivery devices, the dimensions of the container can be about 240
mm.times.148 mm.times.70 mm. For a container 386 holding a single
delivery device, the dimensions of the container can be about 120
mm.times.110 mm.times.35 mm. The container 386 can be made from a
plastic material. The container 386 can include aluminum foil
covered with, for example, polyethylene lamination to close the
packaging using heat.
[0240] FIG. 48 shows an alternative embodiment of the drug delivery
device indicated generally at 400. The delivery system is adapted
for epidural, intraterial and intrathecial administration. Instead
of a hypodermic needle extending directly from a housing 402, a
tube 404 extends from a barometric pressure valve 406 to a location
on the housing 402. A catheter 410 is secured by a collet gripper
408 to connect to the tube 404.
[0241] An alternative embodiment drug delivery device 412 of FIG.
49 has a piece of tubing 414 from an epidural needle 416 connected
directly to a tube 418 located within the housing 402. The tube 418
extends from the barometric valve 406.
[0242] FIG. 50A shows a drug delivery device 420 with a luer 422
for attaching a tubing 424 from an epidural needle 416. A tube 404
extends from the barometric valve 406 to the luer 422.
[0243] FIG. 50B shows the drug delivery device 420 with the luer
422. The tubing 424 from the epidural needle 416 attaches to the
luer 422. The epidural needle set has a hydrophilic membrane 428
for filtration.
[0244] It is further appreciated that the present invention may be
used to deliver a number of drugs. The term "drug" used herein
includes but is not limited to peptides or proteins, hormones,
analgesics, anti-migraine agents, anti-coagulant agents, narcotic
antagonists, cleating agents, anti-anginal agents, chemotherapy
agents, sedatives, antineoplastics, prostaglandins and antidiuretic
agents.
[0245] Typical drugs include peptides, proteins or hormones such as
insulin, calcitonin, calcitonin gene regulating protein, atrial
natriuretic protein, colony stimulating factor, betaseron,
erythrogpoietin (EPO), interferons such as a,b or g interferon,
somatropin, somatotropin, somastostatin, insulin-like growth factor
(somatomedins), luteinizing hormone releasing hormone (LHRH),
tissue plasminogen activator (TPA), growth hormone releasing
hormone (GHRH), oxytocin, estradiol, growth hormones, leuprolide
acetate, factor VM, interleukins such as interleukin-2, and
analogues thereof; analgesics such as fentanyl, sufentanil,
butorphanol, buprenorpbine, levorphanol, morphine, hydromorphone,
hydrocodone, oxymorphone, methadone, lidocaine, bupivacaine,
diclofenac, naproxen, paverin, and analogues thereof; anti-migraine
agents such as sumatriptan, ergot alkaloids, and analogues thereof;
anti-coagulant agents such as heparin, hirudin, and analogues
thereof; anti-emetic agents such as scopolamine, ondansetron,
domperidone, metocloprarnide, and analogues thereof; cardiovascular
agents, anti-hypertensive agents and vasodilators such as
diltiazem, clonidine, nifedipine, varapmil,
isosorbide-5-mononitrate, organic nitrates, agents used in
treatment of heart disorders, and analogues thereof; sedatives such
as benzodiazepines, phenothiozines, and analogues thereof;
chelating agents such as deferoxamine, and analogues thereof;
anti-diuretic agents such as desmopressin, vasopressin, and
analogues thereof; anti-anginal agents such as nitroglycerine, and
analogues thereof; anti-neoplastics such as fluorouracil,
bleomycin, and analogues thereof; prostaglandins and analogues
thereof; and chemotherapy agents such as vincristine, and analogues
thereof.
[0246] While this invention has been particularly shown and
described with references to preferred embodiments thereof, it will
be understood by those skilled in the art that various changes in
form and details may be made therein without departing from the
scope of the invention encompassed by the appended claims.
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