U.S. patent application number 11/355000 was filed with the patent office on 2007-08-16 for drug delivery device.
Invention is credited to Pankaj Modi.
Application Number | 20070191780 11/355000 |
Document ID | / |
Family ID | 38371151 |
Filed Date | 2007-08-16 |
United States Patent
Application |
20070191780 |
Kind Code |
A1 |
Modi; Pankaj |
August 16, 2007 |
Drug delivery device
Abstract
A novel device and method for intradermal delivery of an active
agent is provided. The device comprises a housing which contains a
reservoir chamber. A flexible reservoir containing the active agent
is placed in the chamber. Upon pressure on an actuator the active
agents is delivered via a hollow needle to the skin.
Inventors: |
Modi; Pankaj; (Ancaster,
CA) |
Correspondence
Address: |
GOWLING, LAFLEUR HENDERSON LLP
ONE MAIN STREET WEST
HAMILTON
ON
L8P 4Z5
CA
|
Family ID: |
38371151 |
Appl. No.: |
11/355000 |
Filed: |
February 16, 2006 |
Current U.S.
Class: |
604/187 |
Current CPC
Class: |
A61M 5/282 20130101;
A61M 2005/3247 20130101; A61M 5/288 20130101; A61M 37/00 20130101;
A61M 5/3129 20130101; A61M 5/3287 20130101; A61M 5/286 20130101;
A61M 2207/00 20130101; A61M 5/002 20130101; A61M 5/326 20130101;
A61M 2205/6081 20130101; A61M 5/2425 20130101; A61M 5/46 20130101;
A61M 5/31525 20130101; A61M 2005/3143 20130101 |
Class at
Publication: |
604/187 |
International
Class: |
A61M 5/00 20060101
A61M005/00 |
Claims
1. A reservoir for carrying an active agent, said reservoir
comprising a fillable bladder of thermoplastic material.
2. A reservoir according to claim 1, wherein the reservoir is color
coded to a specific drug.
3. A reservoir according to claim 1, wherein the bladder has a
capacity of about 0.2 to 10 ml.
4. A reservoir according to claim 3, wherein the bladder has a
capacity of about 0.3 to 6 ml.
5. A reservoir according to claim 4, wherein the bladder has a
capacity of about 0.5 to 3 ml.
6. A method of manufacturing a reservoir as defined in claim 1,
comprising the steps of: i. providing at least one sheet having a
depression formed therein and facing that sheet with a second
sheet.
7. A method according to claim 6, further comprising the steps of:
i. filling the bubble with a fluid drug; and ii. sealing the
bubble.
8. A device for delivery of a fluid drug to an animal, said device
comprising: i. a housing having an upper end and a lower end, said
lower end having an aperture therein and said upper end being
associated with an actuator; ii. a reservoir chamber disposed
within the housing and operatively linked to the actuator, said
reservoir chamber comprising a base and wall(s); iii. a flexible
reservoir, filled with the fluid drug, disposed within the
reservoir chamber; and iv. a needle mounted so as to transverse the
base of said chamber such that a back of the needle is in
communication with the chamber and a tip of the needle extends in
the housing below the chamber.
9. A device according to claim 8, wherein the reservoir chamber is
located at a predetermined distance from the lower end of the
housing whereby abutment of the base of the chamber to the lower
end of the housing acts as a stop to provide a predetermined length
of travel of the needle through the aperture when the actuator is
activated.
10. A device according to claim 9, wherein the length of travel of
the needle is from about 0.5 mm to about 10 mm.
11. A device according to claim 9, wherein the length of travel of
the needle is from about 1.5 mm to about 8 mm.
12. A device according to claim 9, wherein the length of travel of
the needle is from about 3 mm to about 8 mm.
13. A device according to claim 8 wherein the actuator is a plunger
comprising a plunger rod having an activation flange at one end and
a stopper at the other end.
14. A device according to claim 8 further comprising biasing means
to retain the needle with the housing in the absence of pressure on
the drive mechanism.
15. A device according to claim 14 wherein the biasing means
comprises an air bladder.
16. A device according to claim 14 wherein the biasing means
comprises a spring.
17. A device according to claim 16 wherein the spring is disposed
below the base of the reservoir chamber.
18. A device according to claim 16, wherein the spring is
associated with the actuator.
19. A device according to claim 8 further including a piercable
septum covering said aperture.
20. A method of administering a fluid drug through the skin of an
animal, said method comprising: i. providing a device as defined in
claim 8; ii. applying the lower surface of the device to the skin;
iii. exerting pressure on the drive mechanism thereby lowering the
reservoir chamber and causing the needle tip to travel through the
aperture and into the skin a predetermined distance; and iv.
applying continued pressure on the drive mechanism to cause the
upper end of the needle to pierce the reservoir and the contents of
the reservoir to flow through the needle into the skin.
21. A method according to claim 20 wherein the tip of needle is
limited to travel a depth of 1.5 to 8 mm.
22. A method according to claim 20 wherein the needle travel is
from about 1.5 to 3 mm.
23. A method according to claim 20 wherein the needle travel is
from about 3 to 5 mm.
24. A method according to claim 20 wherein the needle travel is
from about 5 to 8 mm.
25. A method according to claim 20 further comprising the step of
retracting the needle back into the housing after use.
26. A method according to claim 25 whereby the step of retracting
is done by biasing means automatically upon release of pressure on
the drive mechanism.
27. A device for delivering an active agent to the skin, said
device comprising: i. a housing; ii. a reservoir chamber releasably
positioned in said housing, said reservoir chamber adapted to
receive a reservoir containing the active agent; iii. at least one
needle having an upper opening and a lower opening defining a
cannula transversing the base of the reservoir chamber; and iv.
actuator means for moving said chamber downward within said
housing.
28. A device according to claim 27, wherein said reservoir chamber
further comprises latch means for retaining said chamber in an
upward position in the housing, said latch means adapted for
release upon downward pressure on the actuator.
29. A device according to claim 28, wherein said latch means
includes a tab and notch for connection to the actuator.
30. A device according to claim 29, wherein said actuator includes
at least one notch for receiving a tab on said latch means.
31. A device according to claim 29, wherein said actuator includes
an upper notch and a lower notch.
32. A device according to claim 29, wherein said upper notch
receives said tab to lock said needle in a retracted position.
Description
FIELD OF INVENTION
[0001] The present invention relates to drug delivery devices and
methods of delivering a drug intradermally. In particular, the
present invention relates to intradermal delivery of a liquid
drug.
BACKGROUND OF THE INVENTION
[0002] There has long been a desire to deliver drugs intradermally.
The skin comprises two layers, the outer or upper surface called
the epidermis, and the internal surface referred to as the dermis.
The epidermis does not contain any blood vessels and it is
dependent on the underlying dermis for nutrient delivery and waste
disposal via diffusion. The inner layer, the dermis, is composed of
two layers, the more superficial papillary dermis and the deeper
reticular dermis. The papillary dermis is thinner and consists
primarily of loose connective tissue containing small capillaries,
elastic fibers, reticular fibers and some collagen. The deeper
reticular dermis consists of a thicker connective tissue containing
larger blood vessels, interlaced elastic fibers and core spindles
of collagen fibers arranged in layers parallel to the surface. The
reticular layer also contains many antigen-presenting cells,
fibroblasts, mast cells, nerve endings, and lymphatics. Because of
the high amount of blood vessels, lymphatics and antigen presenting
cells in the dermis, this is an ideal site for delivery of drugs
and/or antigens.
[0003] A major problem, however, with intradermal delivery is the
difficulty in precisely delivering the drug into the dermal layer.
Generally, the outer layer, the epidermis, has a thickness of about
0.05 to 2 mm and the dermis has a thickness between about 1.5 and 4
mm. Thus, to deliver an agent to the dermis, the needle must
penetrate the skin to a depth of no more than 5 mm, preferably
between about 2 and 4 mm. It is very difficult to control an
injection to this shallow depth. For certain types of injection,
such as the Mantoux test for tuberculosis, a fine gauge needle is
inserted at a 45.degree. angle to try and get the agent into the
dermis.
[0004] Several efforts have been made to try and find reliable ways
of delivering agents to the dermis. For example, United States
Patent Application No. 2005/0124967 is directed to a method for
directly delivering a high molecular weight substance into an
intradermal space within mammalian skin comprising administering
the substance through at lease one hollow needle having an outlet
with an exposed height between 0 and 1 mm, said outlet being
inserted into the skin to a depth of between 0.3 mm and 2 mm, such
that delivery of the substance occurs at a depth between 0.3 mm and
2 mm and a microneedle for intradermal injection of a high
molecular weight pharmaceutical substance, wherein the microneedle
has a length and outlet selected for its suitability for
specifically delivering the substance into the dermis.
[0005] U.S. Pat. No. 5,527,288 discloses an intradermal drug
delivery device for delivering a liquid drug to a subject via the
subject's skin, comprising a housing having a lower surface for
application to the skin of the subject; means for affixing the
housing in position with the lower surface in contact with the
subject's skin; and a drug reservoir within the housing. The
reservoir is in the form of an expansible-contractible chamber
which is expanded when filled with the drug and which can be
contracted to dispense the drug therefrom. A single hollow needle
is associated with the drug reservoir and extends through the lower
surface, having an inner end communicating with the drug reservoir
and an outer end projecting outwards a sufficient distance so as to
penetrate through the epidermis and into the dermis when the
housing is pressed against the skin. The device also includes means
for actively discharging the drug from the reservoir to the
subject's skin via the needle.
[0006] U.S. Pat. No. 6,689,118 is directed to a method of making an
intradermal injection into the skin of an animal to obtain systemic
delivery or to induce an immune response. The method comprises
providing a drug delivery device including a needle cannula having
a forward needle tip and a needle cannula being in fluid
communication with a substance contained in said drug delivery
device; inserting the needle tip into the skin of an animal and
engaging the surface of the skin with a skin engaging surface of a
limiter portion such that the skin engaging surface of the limiter
portion limits penetration of the needle Up into the dermis layer
of the skin of the animal; and expelling the substance from the
drug deliver device through the needle tip into the skin of the
animal to expose the injected substance to the microcirculatory
blood vasculature and the lymphatic plexuses.
[0007] U.S. Pat. No. 6,569,143 is directed to another related
method of making an intradermal injection comprising providing a
drug delivery device; inserting a needle tip into the skin of an
animal whereby penetration of the needle Up is limited to the
dermis layer of the skin of the animal; and expelling the substance
from said drug delivery device through the needle tip into the skin
of the animal.
[0008] U.S. Pat. No. 5,997,501 describes an intradermal drug
delivery device for the delivery of at least one drug to a subject
via the subject's skin. The device comprises a housing having a
lower surface; a drug reservoir located with the housing; a cover
that is adjustable engaged with the housing from a first extended
position to a second retracted position such that the cover is
proximal to the lower surface of the housing when the cover is
retracted and the cover is distal to the lower surface of the
housing when the cover is extended; means for affixing the cover in
position with the lower surface of the housing in contact with the
subject's skin; a single hollow needle fixed to the cover and
having a first end in communication with the drug reservoir and a
second end projecting outwards no further than the lower surface of
the housing when the cover is extended, and to penetrate through
the epidermis and into the dermis when the cover is retracted; and
means for actively discharging the drug from the reservoir to the
subject's skin via the needle.
[0009] Although multiple efforts have been made to try and provide
a device for intradermal delivery, many of the prior art devices
are expensive to manufacture or can only be used for one drug. In
spite of all the efforts made to provide a method and/or device for
intradermal delivery, there remained a need for a reliable,
single-use, disposable device for intradermal delivery.
SUMMARY OF THE INVENTION
[0010] Many people consider an injection (at best) unpleasant and
(at worst) a painful encounter, no matter how well the nurse or
doctor administers the shot This is because most shots are given
subcutaneously or intramuscularly, reaching deep enough into the
skin to hit nerves. Part of the skin's job is to sense danger in
the environment through nerve cells, and it is richly endowed with
these cells--a single square inch of skin contains approximately
1,300 nerve endings. Since most injections are given subcutaneously
or intramuscularly, thereby delivering drugs to be absorbed into
the blood vessels, the needle generally strikes nerves and causes
pain along the way. The device of the present invention is based on
a unique technology that allows a liquid pharmaceutical formulation
to be delivered into the skin of the patients through a fine needle
without the significant pain experienced by regular injection
needles. The drug is injected into the layers of the skin, avoiding
the pinching of the nerves. This reduces pain significantly or
eliminates it totally in many cases thus improving the acceptance
and compliance to treat many diseases like diabetes.
[0011] The present invention addresses the problems of the prior
art by providing a novel type of reservoir for a drug and a
delivery device for delivering the drug from the reservoir to a
specific depth of skin. A method of preparing the drug reservoir
and a method of delivering a fluid drug are also provided.
[0012] In one aspect of the invention a reservoir for carrying an
active agent is provided. The reservoir comprises a fillable
bladder having flexible walls that can be sealed.
[0013] A method of manufacturing such a reservoir is also provided.
In one embodiment, the method comprises the steps of: opposing two
layers of thermoplastic film; heating the film; applying a vacuum
mold to the outer surface of each layer of film to form a bubble;
and allowing the film to cool.
[0014] In another embodiment, the method comprises preparing a
sheet of thermoplastic material having a series of wells or
depressions as fillable reservoirs. A top sheet is then applied to
seal the reservoirs.
[0015] A method of filling the reservoir is also provided and
comprises filling the bladder with a fluid drug; and sealing the
reservoir.
[0016] In another aspect of the invention, a device for delivery of
a fluid drug to an animal is provided. The term "animal" is used
herein to include both human and non-human animals. The devices and
methods of the invention are applicable for both human and
veterinary use. The device comprises a housing having an upper end
and a lower end, the lower end having an aperture therein and the
upper end being adapted to receive a drive actuator. A reservoir
chamber is disposed within the housing and operatively linked to
the drive actuator. The reservoir chamber has a base and wall(s).
The wall may be a continuous circular wall or a connected set of
walls. Within the reservoir chamber, there is a flexible reservoir
filled with the fluid drug. A microneedle is mounted on the base so
as to transverse the base of the chamber such that the top of the
needle is in communication with the chamber and the tip of the
needle extends in the housing below the chamber.
[0017] In a preferred embodiment, the reservoir chamber is located
at a predetermined distance from the lower end of the housing
whereby abutment of the base of the chamber to the lower end of the
housing acts as a stop to provide a predetermined length of travel
of the needle through the aperture when the drive mechanism or
actuator is activated. The length of travel is optimally set to
deliver the drug intradermally. The device also preferably includes
biasing means to maintain the reservoir chamber in the upper
position within the housing, in the absence of pressure on the
actuator thus retaining the needle tip inside the housing.
[0018] In another embodiment of the invention, the device includes
a lower housing and an upper housing that fits over the lower
housing. In this embodiment, the upper housing is continuous with
the actuator that causes the reservoir to descend and contact the
needle end.
[0019] In yet another aspect of the invention, a method of
administering a fluid drug through the skin of an animal is
provided. The method comprises providing a device as defined above;
applying the lower surface of the device to the skin; exerting
pressure on the drive mechanism thereby lowering the reservoir
chamber and causing the needle tip to travel through the aperture
and into the skin a predetermined distance; and applying continued
pressure on the actuator to cause the upper end of the needle to
pierce the reservoir and continuing to apply pressure so that all
the contents of the reservoir flow through the needle into the
skin.
[0020] This summary of the invention does not necessarily describe
all features of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] These and other features of the invention will become more
apparent from the following description in which reference is made
to the appended drawings wherein:
[0022] FIGS. 1A to 1G illustrate the steps in the manufacture of a
drug reservoir according to the present invention;
[0023] FIGS. 2A to 2J Illustrate the operation of one embodiment of
a delivery device of the invention;
[0024] FIGS. 3A and 3B illustrate another embodiment of a delivery
device; and;
[0025] FIGS. 4A to 4C illustrate yet another embodiment of a
delivery device.
DETAILED DESCRIPTION
[0026] The following description is of preferred embodiments.
[0027] In one aspect of the present invention a novel type of drug
reservoir is provided. The drug reservoir comprises a fillable
bladder. The reservoir is formed between two layers of plastic
film. The two layers can be formed from two sheets or from one
sheet folded in half. When two sheets are used, the sheets may
comprise the same material, thickness, etc. or they may be two
different types of sheets.
[0028] The present invention provides for a drug delivery device
incorporating a disposable reservoir. The device may be provided as
a single-use, disposable device or a multi-use device. The device
comprises a housing that has an upper end and a lower end. As used
herein, the term "upper" is used to refer to the surface furthest
away from an individual skin and the term "lower" is used to refer
to the part of the device that contacts a patient's skin. An
actuator is mounted at the top of the housing. The actuator is used
to activate a drive mechanism. One example of a drive mechanism is
a plunger that travels up and down within the housing. A reservoir
chamber is slideably mounted within the housing. The reservoir
chamber holds a reservoir filled with a liquid. The reservoir
chamber is operatively linked to the drive mechanism. The reservoir
chamber has a micro needle mounted on the lower surface of the
chamber. When the plunger is depressed, the reservoir housing
travels downward within the housing until it stops when the bottom
of the reservoir housing hits the bottom of the outer housing.
[0029] A process for the manufacture of one embodiment of the
reservoir is shown in FIGS. 1A-G. In FIG. 1A, a sheet of
thermoplastic material 10 is folded in half to provide a first
surface 12 and a second surface 14. Referring to FIG. 1B, the sheet
10 is folded so that the first surface and the second surface
overlap each other. Then the sheet is heated to soften the film.
FIG. 1C illustrates a mold 18 applied to each of the surfaces 12,
14. The mold for each side may be of similar or different shapes.
As a vacuum is applied to the mold halves, a bubble 20 is formed
and at the same time the boundary 22 of the reservoir shape is
sealed. A vertical path 24 is left open for filling of the
reservoir. As shown in FIG. 1D, the mold halves 18 are removed and
the sheet 10 including the bubbles 20 are cooled to room
temperature. The filling process is demonstrated in FIG. 1E. The
film is preferably oriented with the vertical path 24 open at the
top for filling to avoid the formation of air pockets during the
filling process. A fine dispensing nozzle 26 is inserted into the
vertical path 24 and a controlled amount of drug 27 is inserted
into the reservoir. The open end 30 of the vertical path 24 is then
heat sealed as shown in FIG. 1F. The bubble shaped reservoir 20 can
then be trimmed as shown in FIG. 1G from the remaining sheets of
plastic film or the bubble shapes can be partially trimmed and the
bubbles can be stored in a roll format.
[0030] In another embodiment, the reservoir is formed by preparing
a sheet of material having a series of wells or depressions. The
wells are filled with a drug and then an upper sheet is applied to
cover and seal the open end of the wells. In both embodiments the
reservoir comprises a fillable, sealable bladder of thermoplastic
material.
[0031] Various colors and shapes of reservoirs can be used for
different drugs. For example, a round, blue bubble may indicate
that the reservoir contains insulin and a square pink bubble may
indicate a DPT vaccine. The reservoir of the present invention can
be used to store many different kinds of active agents. Color
coding can be used to identify the agent and/or dose strength.
[0032] The present invention also provides a device and method for
delivery of the drug stored in the reservoir to an animal,
preferably a human. The device comprises an outer housing. The
outer housing can be made of any durable material, preferably a
hard plastic. The outer housing can take various shapes, e.g. it
can be round, oval, hexagonal, square etc. The outer housing can
incorporate various colours to identify the agent and/or dose
strength. The outer housing defines an internal chamber that
includes an open top at the upper end and a base having an aperture
at the lower end. A reservoir chamber is fitted inside the housing.
The reservoir chamber is adapted to receive a disposable reservoir
such as that described above. A microneedle is mounted in the
bottom platform of the reservoir chamber with its upper (non-skin
contacting) end protruding upward and just below the reservoir and
the skin-contacting tip extending beyond the bottom of the chamber.
The reservoir chamber frictionally engages the internal wall(s) of
the housing. A drug reservoir or bubble is contained within the
reservoir chamber. A drive actuator is operatively linked to the
reservoir chamber. The drive actuator may include a flexible dome
or an upper casing. The reservoir chamber typically comprises an
open upper end, an internal chamber to hold the reservoir and a
base platform with the needle mounted so that it transects the
base. A retraction mechanism such as a vacuum bulb or a spring is
also optionally included.
[0033] In use, the delivery device is placed on the skin with the
lower end of the housing touching the skin. The drive mechanism is
then actuated to drive the reservoir chamber downwards until the
base platform of the reservoir chamber hits the base of the
housing. This causes the needle to exit through the aperture in the
base of the housing a predetermined distance and enter into the
skin to a predetermined depth. Further downward pressure on the
plunger compresses the drug filled reservoir and causes it to be
pierced by the upper end of the needle. This puts the cannula of
the needle in fluid communication with the contents of the
reservoir and as the downward pressure continues until the tip of
the plunger bottoms on the base platform of the reservoir chamber,
the contents of the reservoir are passed through the cannula of the
needle to the skin of an animal or human subject. When the pressure
on the drive mechanism is released, retraction means cause the
needle to be retracted back into the housing for disposal.
[0034] One preferred embodiment of the device and its operation is
shown in FIGS. 2A-J. The device 50 comprises housing 52. The
housing has an open upper end 54 and a bottom base 56 defining an
interior chamber 58 that optionally includes a spring. The bottom
base comprises an aperture 60. The interior of the housing is
adapted to receive a reservoir chamber 62. The reservoir chamber
comprises a base 64 and a surrounding wall 66 extending upwards
from the base defining a chamber 62 with an open top 68. A filled
reservoir body 70 is located in the reservoir chamber.
[0035] A single hollow needle 72 is associated with the reservoir
chamber 62. The needle 72 extends through the base 64 of the
chamber 62 and has a cannula with an upper end 74 communicating
with the interior 75 of the reservoir chamber and a lower end 78
projecting out of the chamber and down a predetermined distance.
The open top 68 of the reservoir chamber is adapted to receive an
actuator 80. In the illustrated embodiment, the actuator comprises
a plunger 82 having an activation flange 84 at one end and a
stopper 86 at the other end. In the initial position of the device
as provided and as shown in FIGS. 2A and 2B, the base 64 of the
reservoir chamber 62 is held at a predetermined distance from the
interior surface 88 of the base 56 of the housing by at least one
releasable latch 90 which retains the chamber in position by the
interaction of the latch 90 with a latch retainer 92. The latch 90
includes a notch 91.
[0036] In one preferred embodiment an upper housing 96 encases the
plunger 80.
[0037] It is clearly apparent that the distance the needle travels
can be varied depending on the desired application and on the
bubble position and the length of the needle. For example, the
device can be adapted to have the needle travel a distance between
about 0.5 mm to about 10 mm. Thus, the device of the invention can
be adapted for intradermal, subcutaneous or intramuscular
injections. The needle preferably travels from about 3 mm to 8 mm.
The needle gauge is preferably 25 to 84 gauge although different
gauge needles can be used.
[0038] The operation of the device is illustrated sequentially in
FIGS. 2A to 2J. FIGS. 2A and 28 illustrate the device in the
initial state as described above. Referring now to FIGS. 2C and 2D
for use, the base 56 of the housing 52 is placed against the skin.
When pressure is exerted on the actuator 80, the latch 90 is
released from the retainer 92. The actuator 80 is connected to the
reservoir chamber 62 via a notch 100 and tab 102 connector and the
reservoir chamber will be forced down until the base 64 of the
reservoir chamber 62 hits the interior surface 88 of the housing
base 56 and the chamber is stopped from any further downward
movement. By adjusting the relative sizes and positions of the
components, the length of the travel of the needle through the
aperture into the skin can be tightly controlled. The distance that
the needle extends is about 0.5 to 10 mm, preferably 0.5 to 5 mm,
more preferably from about 3 mm to about 5 mm, even more preferably
from about 1.5 to 3 mm. The outer layer of skin, the epidermis
typically has a thickness of about 0.5 to 2 mm. and the inner
layer, the dermis, has a thickness of about 1.5 to 3 mm. The dermis
comprises two layers, the papillary layer and the reticular layer.
The reticular layer contains many blood vessels and lymph vessels,
making it a desirable area for delivery of active agents. Below the
dermis is the subcutaneous layer and then muscle. In a preferred
embodiment, the distance that the tip of the needle can extend
beyond the lower outer surface of the housing is selected to be
optimum for insertion in the dermis or subcutaneous layer. As the
reservoir chamber 62, carrying the needle 72 descends, the lower
tip of the needle 78 exits the aperture 60. The downward travel of
the reservoir chamber 62 is limited when the base 64 of the chamber
contacts the base 56 of the housing. In this way the travel of the
needle through the aperture 60 is also limited so as to limit the
depth of penetration of the needle into the skin. The components of
the device have been configured so that the distance that the
bottom of the chamber travels is translated into a predetermined
travel for the needle through the aperture in the bottom of the
housing to provide a certain skin penetration.
[0039] Referring now to FIGS. 2E and 2F, as continued pressure is
applied to the actuator 80, the tab 102 is released from the notch
100 and the plunger 82 descends within the reservoir chamber
forcing the filled reservoir 70 downwards until it contacts the
base 64 of the reservoir chamber 62. As the actuator 80 exerts
pressure on the reservoir 70, the reservoir 70 contacts the upper
end 74 of the needle 72 and is punctured. The cannula of the needle
72 is now in fluid communication with the contents of the
reservoir.
[0040] Referring now to FIGS. 2G and 2H, continued pressure on the
actuator 80 compresses the reservoir 70 and forces all the contents
to flow through the needle 72 and into the patient. The downward
travel of the actuator 80 is stopped when the plunger stopper 86
contacts the base 64 of the reservoir chamber 62.
[0041] After use, the needle is preferably retracted back into the
housing 52 as illustrated in FIGS. 2I and 2J. The position of the
reservoir chamber 62 carrying the needle 72 is preferably biased to
the pre-activation position by biasing means such as a spring, a
vacuum bulb or a moldable bulb. Once pressure is released on the
actuator 80, the base 64 of the reservoir chamber moves up in the
housing thus automatically retracting the used needle into the
housing. This provides for safe disposal of the device. In a
preferred embodiment, the needle is preferably locked in the
retracted position. FIG. 2J shows a retracted reservoir chamber
that is locked in position when tab 102 slides into indent 104.
[0042] In the embodiment illustrated in FIGS. 3A and 3B, an
actuator 106 is continuous with an upper casing 108 that fits over
a housing 110. The housing 110 receives a reservoir chamber 112
that has a needle 114 transversely mounted through its base 116. A
drug reservoir 118 is contained within the chamber 112. As shown in
FIG. 3B, pressure on the actuator 106 causes the reservoir chamber
112 to descend until it abuts the base 120 of the housing 110. As
the chamber 112 descends, it drives the tip 122 of the needle 114
through an aperture 124 in the housing 110. Further pressure causes
the rear 126 of the needle to puncture the reservoir 118. Upon
continued pressure, the contents of the reservoir are expelled
through the needle.
[0043] In another embodiment, a flexible dome fits over the plunger
rod and activation flange. It is also clearly apparent the manual
activation flange can be exposed. The device also optionally
includes a spring that is located around or below the reservoir
chamber base such that when pressure on the activation flange is
released the compressive energy of the spring causes the needle to
be retracted back into the housing.
[0044] FIGS. 4A to 4C illustrate another embodiment of the device.
The device 130 includes a housing 132 and an upper casing 134. An
actuator 136 is operably linked to a reservoir chamber 138 disposed
within the housing 132. For use, a drug filled reservoir 140 is
placed in the reservoir chamber 138. A needle 142 is mounted so as
to transverse the base 144 of the chamber 138. The device also
includes a spring 146 that biases the reservoir chamber 138 upwards
in the housing 132. Upon pressure on the actuator 136, the spring
compresses and the reservoir chamber travels downward carrying the
needle and the needle tip 148 exits the housing 132. Upon further
pressure, the actuator 136 compresses the drug filled reservoir 140
until the back 150 of the needle punctures the reservoir and the
contents flow through the needle as shown in FIG. 4C.
[0045] In another aspect of the invention, a method for delivering
an effective amount of a liquid active agent to an animal,
preferably a human, is provided. The method comprises providing a
drug delivery device according to the present invention, said
device containing a reservoir filled with the desired drug;
applying the bottom surface of the drug delivery device of the
invention to the skin of an animal, applying pressure on the
actuator to cause the needle to enter the skin, applying continued
pressure to puncture the reservoir and deliver the contents of the
reservoir through the cannula of the needle.
[0046] The device of the present invention can be used to deliver a
variety of active agents. The term "drug" is used loosely herein to
refer to prophylactic as well as therapeutic agents. For example,
vaccines may be delivered using the device. In addition, the term
refers broadly to active agents, such as nucleic acids, small
molecules, therapeutic proteins, hormones, analgesics, etc. in
additional to traditional pharmacologic agents. Typical drugs
include peptides, proteins or hormones such as insulin, calcitonin,
calcitonin gene regulating protein, atrial natriuretic protein,
colony stimulating factor, betaseton, erythropoietin (EPO),
interferons such as .alpha., .beta., or .gamma. interferon,
somatropin, somatotropin, somatostatin, insulin-like growth factor
(somatomedins), luteinizing hormone releasing hormone (LHRH),
tissue plasminogen activator (TPA), growth hormone release hormone
(GHRH), oxytocin, estradiol, growth hormones, leuprolide acetate,
factor VIII, interleukins such as interleukin-2, and analogues
thereof; analgesics such as fentanyl, sufentanil, butorphanol,
buprenorphine, levorphanol, morphine, hydromorphone, hydrocodone,
oxymorephone, methadone, lidocaine, bupivacaine, diclofenac,
naproxen, pavefin, and analogues thereof; anti-migraine agents such
as sumatriptan, ergot alkaloids, and analogues thereof,
anti-coagulant agents such as hepafin, hirudin, and analogues
thereof; anti-emetic agents such as scopolamine, ondansetron,
domperidone, metoclopramide, and analogues thereof; cardiovascular
agents, anti-hypertensive agents and vasodilator such as diltiazem,
clonidine, nifedipine, verapamil, isosorbide-5-mononitrate, organic
nitrates, agents used in treatment of heart disorders, and
analogues thereof; sedatives such as benzodiazepines,
phenothiozines, and analogues thereof; narcotic antagonists such as
naltrexone, naloxone, and analogues thereof; chelating agents such
as deferoxamine, and analogues thereof; anti-diuretic agents such
as desmopressin, vasopressin, and analogues thereof;
antineoplastics such as 5-fluorouracil, bleomycin, and analogues
thereof; prostaglandins and analogues thereof; and chemotherapy
agents such as vincristine, and analogues thereof. Stabilized
preparations of drugs that can be stored at room temperature are
particularly preferred for use in the device and method.
[0047] The term "fluid" refers to any fluid containing an active
agent or communication of agents that can pass through the cannula
of the microneedle. This includes a liquid, a solution, a gel, a
dispersion or a fine suspension.
[0048] All citations are hereby incorporated by reference.
[0049] The present invention has been described with regard to one
or more embodiments. However, it will be apparent to persons
skilled in the art that a number of variations and modifications
can be made without departing from the scope of the invention as
defined in the claims.
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