U.S. patent application number 10/071784 was filed with the patent office on 2002-09-05 for drug delivery systems and methods.
This patent application is currently assigned to ELAN PHARMA INTERNATIONAL LIMITED. Invention is credited to Gross, Joseph, Lavi, Gilad, Tsals, Izrail, Ygal, Gil.
Application Number | 20020123719 10/071784 |
Document ID | / |
Family ID | 26805839 |
Filed Date | 2002-09-05 |
United States Patent
Application |
20020123719 |
Kind Code |
A1 |
Lavi, Gilad ; et
al. |
September 5, 2002 |
Drug delivery systems and methods
Abstract
The present invention related to a drug delivery device for
mixing and delivering a drug by injection. The devices includes a
housing having a first port or opening therein that receives a
first container that contains a fluid or powdered drug, for
example, a lyophilized drug. The housing can also include a second
port or opening that receives a second container that contains a
fluid to be mixed with the drug to form an injectable fluid. The
device includes a manifold having a channel that fluidly connects
the first and second containers. A penetrating membrane such as a
needle is used to inject the drug into a patient which is in fluid
communication with the first container. The needle is movable from
a storage position in the housing to an injection position
extending through the housing.
Inventors: |
Lavi, Gilad; (Holon, IL)
; Ygal, Gil; (Gan-Yavne, IL) ; Tsals, Izrail;
(Sudbury, MA) ; Gross, Joseph; (Dublin,
IE) |
Correspondence
Address: |
CAESAR, RIVISE, BERNSTEIN,
COHEN & POKOTILOW, LTD.
12TH FLOOR, SEVEN PENN CENTER
1635 MARKET STREET
PHILADELPHIA
PA
19103-2212
US
|
Assignee: |
ELAN PHARMA INTERNATIONAL
LIMITED
|
Family ID: |
26805839 |
Appl. No.: |
10/071784 |
Filed: |
February 7, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10071784 |
Feb 7, 2002 |
|
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|
09439614 |
Nov 12, 1999 |
|
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6364865 |
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60108382 |
Nov 13, 1998 |
|
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60131644 |
Apr 29, 1999 |
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Current U.S.
Class: |
604/82 ; 210/188;
210/198.1 |
Current CPC
Class: |
A61M 5/1782 20130101;
A61M 5/3234 20130101; A61M 5/2425 20130101; A61M 2005/3128
20130101; A61J 1/2058 20150501; A61M 2205/583 20130101; A61M
2005/3223 20130101; A61J 1/2082 20150501; A61J 1/2089 20130101;
A61M 2005/14252 20130101; A61M 2205/215 20130101; A61J 1/201
20150501; A61J 1/2051 20150501; A61M 5/148 20130101; A61M 5/2448
20130101; A61M 5/162 20130101; A61M 5/19 20130101; A61M 5/2046
20130101; A61J 1/2017 20150501; A61M 2005/1581 20130101; A61M
5/2053 20130101; A61J 1/2013 20150501 |
Class at
Publication: |
604/82 ; 210/188;
210/198.1 |
International
Class: |
A61M 037/00 |
Claims
We claim:
1. A material mixing device, said device comprising: a housing; a
first port in said housing that receives a first container having
first contents therein; a second port in said housing that receives
a second container that contains second contents to be mixed with
said first contents to form a material; a first passageway in said
housing for placing said first port and said second port into fluid
communication with each other, said passageway comprising a first
end having a first needle and a second end having a second needle,
said first needle penetrating said first container and said second
container penetrating said second container; and a movable seal in
said second container that is displaced during insertion into said
second port to expel said second contents under pressure through
said passageway and into said second container.
2. The device of claim 1 wherein said first contents is a
lyophilized drug and said second contents is a diluent.
3. The device of claim 2 wherein said housing comprises interlock
means to prevent said second container from being engaged into said
second port before said first container is inserted into said first
port.
4. The device of claim 3 wherein first and second ports are
adjacent each other in said housing and wherein said interlock
means comprises a pivoting bar that blocks said first port whenever
said second port is vacant and which pivots out of said second port
whenever said first container is engaged with said first port.
5. The device of claim 1 wherein said first port and said second
port are on opposite sides of said housing.
6. The device of claim 1 wherein said second container also
comprises a controlled volume of gas.
7. The device of claim 6 wherein said gas is air.
8. The device of claim 6 wherein said device does not need to be
shaken to thoroughly mix said first contents and said second
contents to form said material.
9. The device of claim 6 further comprising: a second passageway in
said housing in fluid communication with said first passageway for
conveying said material from said second container; and a
hydrophillic membrane in said second passageway, said hydrophillic
membrane preventing the passage of said controlled volume of air
into said second passageway while permitting said material to pass
through.
10. The device of claim 6 further comprising: a second passageway
in said housing, parallel with said first passageway, for conveying
said material from said second container; and a hydrophillic
membrane in said second passageway, said hydrophillic membrane
preventing the passage of said controlled volume of air through
said second passageway while permitting said material to pass
through.
11. A material mixing device, said device comprising: a housing; a
first port in said housing that receives a first container having
first contents therein; a second port in said housing for receiving
a second compressible container having second contents therein; a
first passageway in said housing for placing said first port and
said second port into fluid communication with each other; and
means for compressing said second compressible container to drive
out said second contents into said first container to form said
material.
12. The device of claim 11 wherein said passageway comprises a
first end having a first needle and a second end having a second
needle, said first needle penetrating said first container and said
second needle penetrating said second compressible container.
13. The device of claim 11 wherein said second compressible
container comprises a flexible bag and wherein said means for
compressing comprises a pair of rotating drums between which said
flexible bag passes.
14. The device of claim 11 wherein said first contents comprises a
lyophilized drug and wherein said second contents comprises a
diluent.
15. The device of claim 13 wherein said rotating drums are operated
by a rack and pinion mechanism.
16. A container pressurization device, said device comprising: a
housing; a port in said housing for receiving a container of a
liquid; gas storage means; a passageway for coupling said gas
storage means in fluid communication with said container when said
container is engaged with said port; and activating said gas
storage means to introduce a gas into said container through said
passageway to pressurize the liquid contained therein.
17. The device of claim 16 wherein said gas storage means comprises
a bellows that forces air into said container.
18. The device of claim 17 wherein movement of said container
within said port compresses said bellows to force air into said
container.
19. The device of claim 17 wherein said passageway comprises a
needle.
20. The device of claim 18 wherein said passageway comprises a
needle.
21. The device of claim 19 wherein said liquid comprises a
reconstituted drug for injection.
22. The device of claim 20 wherein said liquid comprises a
reconstituted drug for injection.
23. A material mixing device, said device comprising: a housing; a
first port in said housing that receives a first container having
first contents therein; a second port in said housing that receives
a second container that contains second contents to be mixed with
said first contents to form a material; a first passageway in said
housing for placing said first port and said second port into fluid
communication with each other, said passageway comprising a first
end having a first needle and a second end having a second needle,
said first needle penetrating said first container and said second
needle penetrating said second container; a second passageway for
coupling a pressure source in fluid communication with said first
contents; and a third passageway for conveying said material out of
said housing.
24. The device of claim 23 wherein said pressure source is a
bellows.
25. The device of claim 23 wherein said pressure source is a
syringe.
26. The device of claim 23 wherein said pressure source is a
cylinder.
27. The device of claim 23 wherein said pressure source is a
compressed air canister.
28. The device of claim 23 wherein said pressure source is a
chemical gas generator.
29. The device of claim 23 further comprising a hydrophillic
membrane in said third passageway, said hydrophillic membrane
preventing the passage of said gas through said third passageway
while permitting said material to pass through.
30. The device of claim 23 wherein said first contents is a
diluent.
31. The device of claim 23 wherein said second content is a
lyophilized drug.
32. The device of claim 23 wherein said second needle is
vertically-positioned and is adjustable in height.
33. The device of claim 23 wherein said third passageway comprises
a cavity and piston, said cavity including indicia thereon so that
a user can operate said piston to withdraw a desired amount of said
material.
34. The device of claim 26 wherein said housing comprises interlock
means to prevent said cylinder from being activated until both said
first container and said second container are engaged with said
first and second ports, respectively.
35. The device of claim 34 wherein said interlock means comprises a
lip at a piston end of said cylinder that is prevented from moving
by an edge in a flexible wall that receives said cylinder, said
flexible wall being deflected by the entry of said first and second
containers into said respective first and second ports to disengage
said lip from said edge.
36. The device of claim 26 wherein said housing comprises interlock
means to prevent said cylinder from re-pressurizing once said gas
is injected.
37. The device of claim 36 wherein said interlock means comprises a
lip at a piston end of said cylinder that is trapped under a
locking element at a completion end of the cylinder stroke which
injects said gas.
38. A material mixing device, said device comprising: a housing; a
first port in said housing that receives a first container having
first contents therein; a second port in said housing that receives
a second container that contains second contents to be mixed with
said first contents to form a material; a third port in said
housing that receives an air pressurization system; a first
passageway in said housing for placing said first port and said
second port into fluid communication with each other, said first
passageway comprising a first end having a first needle and a
second end having a second needle, said first needle penetrating
said first container and said second needle penetrating said second
container; and a second passageway for coupling said air
pressurization in fluid communication with said first contents for
forming said material under pressure.
39. The device of claim 38 wherein said material comprises a low
viscosity drug.
40. A material mixing device, said device comprising: a housing; a
first port in said housing that receives a first container having
first contents therein; a second port in said housing that receives
a second container that contains second contents to be mixed with
said first contents to form a material; a passageway in said
housing that can be manually switched for placing said first port
and said second port into fluid communication with each other, said
passageway comprising a first end having a first needle and a
second end having a second needle, said first needle penetrating
said first container and said second container penetrating said
second container; and a movable seal in said second container that
is displaced during insertion into said second port to expel said
second contents under pressure through said passageway and into
said second container.
Description
RELATED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser.
No. 09/439,614, filed on Nov. 12, 1999, which claims priority to
U.S. Provisional Application No. 60/108,382 filed Nov. 13, 1998 and
U.S. Provisional Application No. 60/113,644 filed Apr. 29, 1999,
the entire teachings of all of these applications being
incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to the preparation and
administration of a product and, more particularly, to the
injection of the same into a living organism, for example, a human
body.
[0003] Previously, various devices have been developed for the
percutaneous delivery of medications into living organisms
including syringes in which a liquid is delivered from a chamber
using pressure asserted by a manual plunger through a needle
inserted under the skin.
[0004] Additionally, it is well known in the art that the storage
life of certain injectable substances such as glucagon, used to
dissolve blood clots, is increased when the substance is stored in
a powdered or lyophilized state, for example. These lyophilized
substances (i.e., drugs or compounds) are presently used for
injection of materials that would otherwise be unstable.
Lyophilization, for example, is the rapid freezing of a material at
a very low temperature followed by rapid dehydration by sublimation
in a high vacuum. The resulting lyophilized compound is typically
stored in a glass vial or cartridge which is closed by a cap, such
as a rubber stopper or septum.
[0005] It is necessary to reconstitute the powdered or solid
material, such as a lyophilized compound, prior to administration.
This is accomplished by mixing the solid compound with a suitable
diluent or liquid. Reconstitution typically involves the use of a
syringe with a needle to withdraw the diluent from a separate vial
and inject it into the vial containing the compound. The compound
is then thoroughly mixed, typically by shaking the vial by hand,
and a separate syringe with a needle withdraws the desired amount
to be injected into the patient. Because two separate containers
are used, the person reconstituting the compound must be certain to
mix the correct amounts such that a proper concentration of the
mixture results. When a syringe is used to mix the diluent and
drug, the exact volume of diluent to drug ratio is difficult to
obtain. Thus, precise concentration levels of administered drug may
be compromised.
[0006] Moreover, because the diluent and compound are in separate,
sterilized containers, the manual withdrawal of diluent via a
syringe and reinjection of the same into the container containing
the solid material such as a powdered or lyophilized drug may
compromise sterility, and safety due to the use of a syringe.
[0007] Because of increased use of powdered compounds or
lyophilized drugs, for example, it is desirable to provide both
professional and non-professional personnel with a reconstituted
drug delivery system. It is desirable to have a simple, reliable
system that facilitates preparation and safe delivery of an
accurate dosage of a reconstituted compound. In addition, it is
desirable to provide a system that reconstitutes a lyophilized drug
while maintaining sterility throughout the process. Also, it is
desirable to provide improvements in the percutaneous delivery of
medication generally, which provide for safe, effective
administration by the user.
SUMMARY OF THE INVENTION
[0008] The present invention relates to systems and methods for
delivering liquid drugs to a user. The drug delivery system can
include delivery of reconstituted powdered drugs such as, for
example, lyophilized drugs, or more generally for the transfer and
delivery of liquid drugs. Powdered or lyophilized drug delivery
further includes a system to reconstitute the powdered drug. The
drug delivery systems may further include a pressurization system
which pressurizes the drug for transfer to a delivery system or for
direct subcutaneous delivery. Further, the drug delivery system in
accordance with the present invention includes an injector system
which contacts the tissue and delivers the drug to the patient or
user. In the alternative, the drug delivery system in accordance
with the present invention includes filling of detachable delivery
devices, for example, a standard syringe, a needleless injector, an
infusion device or different types of pumps. Another example uses a
pen injector which aspirates the liquid drug from the system and in
turn delivers the drug subcutaneously.
[0009] The methods for delivering a powdered drug such as a
lyophilized drug include the steps of pressurizing a diluent
solution in a diluent vial. The pressurizing systems may include,
but are not limited to, a compressed air supply, a chemical gas
generator, a collapsible volume supply, a bellow canister, a
standard syringe or a cylinder, for example. The methods further
include the step of delivering the pressurized diluent solution to
the powdered drug vial. The next step in the method includes the
reconstitution of the drug to form a liquid drug by mixing the
powdered drug with the diluent solution. The methods further
include the steps of providing the liquid drug to an injector
system or transferring the liquid drug to detachable delivery
devices. The following step includes the injection of the liquid
drug into the tissue of the patient or user. The methods further
include the steps of moving the injection needle from a delivery or
injection position to a retracted or storage position once delivery
is complete. It should be noted that, depending on the application
or delivery of different medicaments, the features of the drug
delivery systems may vary. For example, the pressurization level
can vary depending upon the viscosity level of the medicament, and
the needle type or length can vary depending upon subcutaneous
injection or intermuscular injection. For example, for subcutaneous
injections, the needle length ranges from 5 to 12 mm while the
needle length may vary up to about 3 cm for intermuscular
injections.
[0010] The methods for delivering a liquid medicament to a patient
include the steps of pressurizing the liquid drug solution in the
vial with a pressurizing system. The subsequent steps are similar
to the steps described with respect to the methods for delivering a
powdered medicament.
[0011] A preferred embodiment of the present invention features an
injector system having an angled or unshaped needle. Another
preferred embodiment of the present invention features an injector
system having a straight needle. Yet another preferred embodiment
of the present invention employs a transfer system for transferring
the drug to delivery devices such as, for example, a standard
syringe with a needle or a needleless pen injector. The devices
receive the liquid drug from a container, such as a vial containing
the liquid drug. The delivery devices subsequently deliver the
medication to the user's tissue as described herein.
[0012] Another preferred embodiment of the present invention
features a combination system having the ability to reconstitute
drug into solution and subsequently inject it into a user. In
accordance with this embodiment the reconstituted drug delivery
system has a housing having a first opening or port that receives a
first container that contains a solid substance, such as a powdered
lyophilized drug, for injection. It should be noted that the
container is a rigid container, such as, for example, a vial or a
cartridge containing the powdered drug. The housing can also
include a second opening or port that receives a second container
that contains a fluid to be mixed with material in the first
container, to form an injectable fluid. The drug delivery system
may include a manifold having a first channel that provides fluid
communication between the first and second containers. The manifold
further includes a second channel between the first container and a
delivery or transfer device. The manifold can also include a
communication channel to a pressurization system which provides the
driving pressure to deliver the liquid drug. In a preferred
embodiment, the penetrating member is a needle, in fluid
communication with the first container after the needle moves
between a storage position in the housing to an injection position
extending outside the housing and into the user.
[0013] A preferred embodiment of the invention provides for
concealment of the injection needle within the main housing of the
drug delivery device except during the injection of the drug to the
user. This embodiment can include a needle retraction device for
withdrawing the needle into the housing after injection to minimize
the risk of exposure to a contaminated needle.
[0014] In accordance with other aspects of the present invention,
the length of the delivery path from the container with the
injectable fluid to the injection needle is reduced to minimize
loss of residual amount of liquid drug. According to another aspect
of the invention, the injection needle first pierces the skin of
the person being injected and is concurrently placed in fluid
communication with the first container that contains the injectable
fluid. According to yet another aspect of the invention, the
container that contains the injectable fluid is substantially
visible during reconstitution and injection such that the user can
visually observe the process. A compressed fluid, such as a gas in
the container with the injectable fluid, is used to force the
injectable liquid through the injection needle and into the tissue
being injected. In an alternative embodiment, the device has a
single port with a compression element such that a container with a
liquid medication, such as a previously reconstituted material, can
be inserted into the housing and simultaneously pressurized to the
needed pressure to deliver the correct dose over a predetermined
time period.
[0015] In a preferred embodiment of the system, the device is used
with the injectable fluid container being vertically oriented
during injection. To reduce the risk of injecting any gas into the
injection site, a gas impermeable membrane such as a hydrophilic
membrane is disposed in the fluid path, which in a wetted state
minimizes or preferably prevents gas flow while allowing liquid to
flow through the membrane. The rigid containers need to be in a
vertical orientation during reconstitution for appropriate
pressurization. In an embodiment including a cartridge having
diluent and air, a vertical orientation is not required for
reconstitution. According to a further aspect of the present
invention, the axis of the injection needle is perpendicular to the
longitudinal axis of the container with the injectable fluid. In a
preferred embodiment, the containers containing a powdered or
lyophilized drug and diluent are inserted in the housing in the
same direction along parallel axes. In another embodiment, the
containers are inserted along a common axis or parallel axes in the
opposite direction. The system can have housing apertures, ports,
or openings that have a size compatible with standard vial and
cartridge sizes such that existing vials and/or cartridges can be
used. The container contents do not have to be mixed until
immediately prior to injection. Because the contents of the
containers are only in contact with other sterile parts, sterility
prior to and during the reconstitution process is maintained.
[0016] According to another aspect of the present invention a
further improvement to reduce and preferably prevent the risk of
injecting gas into the injection site, includes the use of a drug
which is gas impermeable once wetted. Further, since the gas
impermeable membrane can sustain pressure, the delivery time for
the liquid drugs is shortened as a higher driving force is
generated using pressurization systems. By disposing such a
membrane such as a hydrophilic membrane in the drug delivery path
that is gas impermeable in a wetted state, gas needed to control
injection pressure and duration can be added in the system as the
membrane checks the delivery of gas to the user. The container
containing the fluid can be a changeable volume container which
contains a controllable volume of a gas, for example, air. This
controllable volume of air and/or fluid are forced into the drug
container, resulting in a drug under pressure to deliver the
correct dose over a selected time period. According to a further
aspect of the -invention, the device includes a manifold system to
minimize the drug delivery path and simplify assembly costs, and
increase system reliability. The simplicity and flexibility of the
manifold system facilitates the use of standard prefilled
cartridges and syringes. In a preferred embodiment, the manifold is
a two-piece polycarbonate molding in which the two molded elements
are ultrasonically welded together. The gas impermeable membrane is
attached or welded to one piece of the polycarbonate molding.
[0017] According to another aspect of the present invention, a
further improvement to deliver an accurate predicted volume of a
drug includes adjustable height penetrating members, such as, for
example, outlet spikes. In the alternative, delivery of an accurate
predicted volume, for example 50% or 80% etc., can be gauged from
the residual drug volume or the use of detachable delivery devices,
for example, a standard syringe or a pen-type pump injector.
[0018] According to another aspect of the present invention, a
further improvement to the drug delivery systems includes
interlocks and indicators which ensure the safe and accurate
delivery of the drugs. The interlocks include, but are not limited
to latches which provide for a desired sequence of operation such
as pressurization of containers to follow the step of insertion of
the containers, or prevention of displacement of the needle to an
injection position after a first injection use. The indicators
include a vertical orientation indicator and end of delivery
indicators.
[0019] According to another aspect of the present invention, the
housing of the drug delivery device is shaped and designed to
function appropriately to enable single handed operation. For
example, the bottom surface of the housing is flat in shape to
allow table top placement to accommodate single handed operation by
the user. Further, the device is sized to enable the insertion of
vials and subsequent activation of the device using one hand.
[0020] In a preferred embodiment, the system housing is lightweight
and compact, having a weight of less than 30 grams and a volume of
less than 100 cm.sup.3. This provides a portable disposable device
that can be discarded or recycled after a single use and that is
readily transported by the user. In addition, the present invention
is self-contained and maintains sterility throughout the
reconstitution and injection of a fluid such as a lyophilized drug.
It should be noted, the weight and volume of the system housing can
vary depending upon the different embodiments and the volume of
drug being delivered to a user.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIGS. 1A-1F illustrate the operation of a preferred
embodiment of a drug delivery device in accordance with the present
invention.
[0022] FIGS. 2A and 2B illustrate cutaway views of the drug
delivery device shown in FIGS. 1A-1F, along line 2A, 2B-2A, 2B in
FIG. 1F.
[0023] FIGS. 3A-3D illustrate the sectional views of the internal
components of the drug delivery device of FIGS. 1A-1E and FIG. 2
during administration of the reconstituted drug.
[0024] FIGS. 4A-4O illustrate the operation of a preferred
embodiment of a drug delivery device in accordance with the present
invention.
[0025] FIG. 5A-5C are perspective views of a preferred embodiment
of a drug delivery device in accordance with the present
invention.
[0026] FIGS. 6A-6C illustrate the operation of a drug delivery
device substantially similar to the device shown in FIGS.
5A-5C.
[0027] FIGS. 7A-7C are partial perspective views of the drug
delivery device of FIGS. 5A-5C and 6A-6C illustrating the injection
of the drug.
[0028] FIGS. 8A-8F illustrate the operation of a drug delivery
device substantially similar to the device shown in FIGS.
5A-5C.
[0029] FIGS. 9A-9F illustrate the operation of a preferred
embodiment of a drug delivery device in accordance with the present
invention.
[0030] FIGS. 10A and 10B are graphical illustrations of the
pressure, weight, and delivery characteristics of a preferred
embodiment of the invention.
[0031] FIGS. 11A-11D illustrate cutaway views of an alternative
embodiment including a drug container subassembly of the drug
delivery device in accordance with the present invention.
[0032] FIGS. 12A-12B illustrate perspective views of a preferred
embodiment of the diluent container subassembly shown in FIGS.
11A-11D.
[0033] FIGS. 13A and 13B illustrate cutaway views of an alternate
embodiment of the drug delivery device in accordance with the
present invention.
[0034] FIG. 14 illustrates a cutaway view of another preferred
embodiment of the drug delivery device in accordance with the
present invention.
[0035] FIGS. 15A and 15B illustrate cutaway views of an alternate
embodiment of the drug delivery device in accordance with the
present invention.
[0036] FIG. 16 illustrates a cutaway view of an injection device in
accordance with the present invention.
[0037] FIGS. 17A-17C illustrate cutaway views of an alternate
embodiment of the drug delivery device in accordance with the
present invention.
[0038] FIGS. 18A-18C illustrate cutaway views of an alternate
embodiment of the injector system of the drug delivery system in
accordance with the present invention.
[0039] FIGS. 19A-19F illustrate alternate embodiments of
pressurization systems included in the drug transfer system in
accordance with the present transfer invention.
[0040] FIGS. 20A-20C illustrate views of an alternate embodiment of
the drug delivery system in accordance with the present invention
which uses standard vials containing a liquid medicament.
[0041] FIG. 21 illustrates a view of another preferred embodiment
of the drug delivery system in accordance with the present
invention which uses standard vials containing a liquid
medicament.
[0042] FIGS. 22A-22E illustrate cutaway and perspective views of an
alternate embodiment of the drug delivery system in accordance with
the present invention.
[0043] FIGS. 23A and 23B illustrate alternate preferred embodiments
to control the dose of drugs in accordance with the present
invention.
[0044] FIGS. 24A-24C illustrate cutaway views of an alternate
embodiment of the drug delivery system in accordance with the
present invention incorporating filling devices, for example a
syringe, to inject the drug system.
[0045] FIG. 25 illustrates a cutaway view of an alternate
embodiment of the drug transfer system in accordance with the
present invention incorporating filling devices, for example a pen
type pump to inject the liquid medicament.
[0046] FIGS. 26A-26D illustrate perspective views of a preferred
embodiment of a drug transfer system in accordance with the present
invention.
[0047] FIGS. 27A-27C illustrate cutaway views of a preferred
embodiment of a drug delivery system in accordance with the present
invention.
[0048] FIGS. 28A-28C illustrate cutaway views of the operation of a
preferred embodiment of a drug delivery system in accordance with
the present invention.
[0049] FIG. 28D illustrates an enlarged cutaway view of a preferred
embodiment of the spike which brings the liquid drug in
communication with the delivery system in FIGS. 28A-28C.
[0050] FIGS. 29A and 29B illustrate partial cutaway views of a
preferred embodiment of the drug transfer delivery system in
accordance with the present invention.
[0051] FIGS. 30A and 30B are views showing the two piece
construction of the manifold in accordance with the drug delivery
system of the present invention.
[0052] FIGS. 31A-31G are perspective views of a preferred
embodiment of a drug delivery system in accordance with the present
invention.
[0053] FIGS. 32A-32E are perspective views of another preferred
embodiment of a drug delivery system in accordance with the present
invention.
[0054] FIGS. 33A-33I are cutaway views illustrating the interlocks
built into the drug delivery system in accordance with the present
invention.
[0055] FIGS. 34A-34D are views of a preferred embodiment
illustrating an end of delivery indicator of the drug delivery
system in accordance with the present invention.
[0056] FIG. 35 is a graphical illustration of a delivery profile of
a preferred embodiment of the drug delivery system with no
additional volume of air in the liquid vial in accordance with the
present invention.
[0057] FIG. 36 is a graphical illustration of the delivery duration
and delivery pressure of a preferred embodiment of the drug
delivery system in accordance with the present invention.
[0058] FIG. 37 is a graphical illustration of delivery parameters
of injecting a drug with no additional volume of air in accordance
with the present invention.
[0059] FIG. 38 is a graphical illustration of the air pressure
gradient on a hydrophilic membrane in the drug delivery system in
accordance with the present invention.
[0060] FIG. 39 is a graphical illustration of the delivery profile
with respect to time for a vial system containing about 7.5 ml of
air in accordance with the present invention.
[0061] FIG. 40 is a flowchart describing the method of delivery of
a reconstituted drug in accordance with the present invention.
[0062] FIG. 41 is a flowchart describing the method of delivery of
a liquid drug in accordance with the present invention.
[0063] The foregoing and other objects, features, and advantages of
the drug delivery systems and methods 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.
DETAILED DESCRIPTION OF THE INVENTION
[0064] The present invention is directed to drug delivery systems
and methods. The drug delivery system provides generally-for the
delivery of a drug in solution under pressure, and more
particularly to the injection of powdered or lyophilized drugs that
require reconstitution. The drug delivery system includes a
reconstitution system, a pressurization system to facilitate drug
delivery, a transfer system and an injector system. Different
embodiments of the present invention may use only one of the
systems described and other embodiments can employ combination of
these systems, depending on the requirements of different
applications. For example, a preferred embodiment can deliver a
liquid drug and not require reconstitution. Therefore the drug
delivery systems and methods are a combination of some or all of
the systems or processes described below.
[0065] With reference to FIG. 1A-1E, the general operation of a
preferred embodiment of a drug delivery device 100 is illustrated.
FIGS. 2A-2B, and 3A-3D provide sectional views of the same
embodiment for clarity. As specifically illustrated in FIG. 1A,
drug delivery device 100 comprises a first member or housing 304
and a pivotally connected second member or handle 106. The device
100 is used to mix, within a sterilized environment, a first liquid
such as a diluent 166 (for example, a fluid such as sterilized
water) with a second powdered drug such as a lyophilized drug or
compound concentrate 164, e.g., interferon, and to inject the
resulting reconstituted lyophilized drug into a living organism,
which in the preferred embodiment is a human being. Advantageously,
the device 100 utilizes a standard vial or first storage container
102, which contains the lyophilized drug or compound 164, and a
standard cartridge or second storage container 116, which contains
the diluent 166. The device 100 may be formed from inexpensive
materials, such as plastic or the like, such that it is
economically feasible to dispose of the device after a single
injection.
[0066] In preparation for the administration of the drug, the user
removes protective packaging which envelops the device 100. This
packaging maintains sterility of the device 100 prior to use. In
the preferred embodiment of the invention, cartridge 116 containing
diluent 166 comes preassembled, being locked into the bottom of
housing 304 by the arms 133 as shown in FIGS. 2A and 2B.
[0067] The sterility protector of the vial 102 is removed and then
locked into the top of housing 304 as shown in FIG. 2A with a
needle 124 from the housing penetrating a stopper 112 of the vial.
At this stage, vial 102 is filled with air at ambient pressure. The
cartridge 116 is pushed upward, i.e., toward vial 102. The
cartridge 116 is punctured and the diluent 166 is delivered to the
vial 102 as shown in part in FIG. 1C. At this stage, as will be
explained below, there is a fluid such as gas in vial 102 which is
compressed by transfer of diluent 166 into vial 102. The user
swills the device 100 to ensure the lyophilized drug is
appropriately reconstituted. The reconstituted lyophilized drug, or
injectable fluid, is identified as reference number 160.
[0068] Now, drug in solution with the diluent is ready for
injection. The device 100 is pressed against the skin of the person
to be injected with the vial 102 in a vertical orientation to
ensure that the compressed gas, for example, air is used to inject
the reconstituted drug and that the gas or air is not injected into
the injection site. The user presses the handle 106 which causes
the injection needle 130 to move between a first position, or
storage position, within the housing 304 as shown in FIG. 3A, and a
second position, or injection position, outside the housing as
shown in FIG. 3C. It is preferred that the needle extend out of the
housing 304 in the range of 5 to 12 millimeters. The second
extended position of the injection needle 130 is also illustrated
in FIG. 1D. At this point, the injection needle 130 is fluidly
connected to vial 102 such that the reconstituted lyophilized drug
160, under pressure from the compressed gas in vial 102, is
delivered to the injection site. The delivery of the reconstituted
lyophilized drug 160 can be completed in a time period in the range
of 10 -30 seconds.
[0069] Upon release of handle 106, a biasing mechanism 108 (to be
detailed below) returns the handle to the original position.
Simultaneously, a needle retraction mechanism (also to be described
below) locks the injection needle 130 within the housing 304,
thereby reducing and preferably preventing exposure of the
contaminated needle. The final stage of operation is illustrated in
FIG. 1E, wherein the device 100 may be safely discarded.
[0070] FIG. 1F is a view taken along line 1F-1F of FIG. 1E and
illustrates the relative positions of vial 102 and cartridge 116 in
housing 304. As shown, the longitudinal axes of vial 102 and
cartridge 116 are parallel but offset relative to the positioning
within the housing 304. This allows for both vial 102 and cartridge
116 to be inserted into the housing 304 without interfering with
the internal components of the device 100, for example, the needle
retraction mechanism described below.
[0071] FIGS. 2A and 2B illustrate cutaway views along lines 2A,
2B-2A, 2B of Figure IF of the device 100 including vial 102 and
cartridge 116. More particularly, vial 102 is preferably a standard
vial, for example, a 2 milliliter vial, which typically comprises
glass and includes a puncturable rubber stopper 112 held in place
by an aluminum band or other sealing mechanism 114. The upper end
of housing 304 includes a grooved portion 132 which locks the vial
102 to the housing by passing the lip of the aluminum band 114
under a pair of spaced apart arms that hook up into the housing. A
first needle 124, or other suitable means, is mounted to the
housing 304 and is configured to pierce the rubber stopper 112 of
vial 102 upon insertion of the vial into the locking position
provided by arms 133. First needle 124 is fluidly connected to a
first channel or tube 122 for receiving the diluent from cartridge
116 as illustrated in FIG. 2B. Cartridge 116, similar to vial 102,
preferably comprises a standard cartridge (for example, a 2
milliliter cartridge with about 1 milliliter diluent) and includes
a rubber stopper 118 which is pierced by a second needle 126, or
other suitable means. Second needle 126 is fixedly mounted on an
extending member or compression element 238 of housing 304 such
that the cartridge is pierced upon insertion of the cartridge.
First tube 122 is fluidly connected to the second needle 126. Upon
insertion of the cartridge 116, extending member 238 or compression
element of housing 304 contacts and pushes rubber stopper 118
toward the bottom of cartridge 116. In this manner, the diluent 166
is forced up tube 122 into vial 102 to mix with the drug 164
contained therein. In the preferred embodiment of the present
invention, cartridge 116 contains approximately 1 milliliter of
diluent which is forced into vial 102, resulting in a pressure
inside vial 102 of approximately 2.25 bars. This pressure can be
adjusted, for example, by decreasing the amount of diluent or air
in cartridge 116. A higher pressure inside vial 102 injects the
reconstituted drug 160 more quickly.
[0072] Thus, a sterilized solution is provided wherein the diluent
166 is mixed with the lyophilized drug 164 with minimal exposure to
outside contaminants. It is preferable that vial 102 containing the
reconstituted lyophilized drug 160 be visible during reconstitution
and injection such that the user can properly visually verify that
the lyophilized drug 160 is thoroughly mixed with diluent 166 and
that the vial 102 is vertical during injection to ensure the
compressed gas is not being injected into the injection site.
[0073] Handle member 106 is pivotally connected to the housing 304
at a first end by a pivoting mechanism 110 which can include a
rivet or other suitable means such that the handle member rotates
in the direction of arrow 240. Handle member 106 includes biasing
mechanism 108 which resiliently biases handle member such that the
end opposite the pivotally connected end is forced away from
housing 304. Biasing mechanism 108 includes an extending member
from handle member 106 which contacts housing 304, thereby
providing a resilient biasing force away from the housing when the
handle member is forced toward the housing. Alternatively, or
additionally the biasing mechanism 108 can comprise a conventional
spring, or other suitable means, interposed between housing 304 and
handle, member 106 which provides the biasing force.
[0074] Also shown in FIG. 2A is a needle injection and retraction
mechanism for injecting the reconstituted drug 160 into the person
and retracting the injection needle 130 within the housing 304. The
mechanism includes a first bar member 140, which is pivotally
connected at a first end by member 136, and guidably mounted at a
second end to the handle member 106 by a first coupling device 142,
such as a pin, rivet, bolt, or other suitable means. Member 136
fixedly supports injection needle 130 and is guided by an opening
138, or needle aperture, in the housing 304. In the preferred
embodiment of the invention, injection needle 130 is in the range
of a 24-28 gauge needle. The movement of first coupling device 142
is controlled by a J-shaped slot 134 which can comprise a slot or
groove in handle member 106. A second bar member 148 is pivotally
connected at a first end to first coupling device 142 and pivotally
connected at a second end to a third bar member 152 by a third
coupling device 150. Third bar member 152 fixedly supports a third
needle 128 and may be guided by internal bore in housing 304. A
second channel or tube 120 fluidly connects the third needle 128
and injection needle 130. It is preferable to minimize the length
of tube 120 such that the residual volume of drug remaining in the
tube after injection is reduced to increase the accuracy of the
dosage.
[0075] The operation of drug delivery device 100 shown in FIGS. 2A
and 2B is illustrated in FIGS. 3A-3D. FIG. 3A illustrates the stage
at which the cartridge 116 is inserted forcing diluent 166 up tube
122 into vial 102. It will be recalled that the rubber stopper of
118 of cartridge 116 is forced to the bottom of the cartridge by
member 238 as shown in FIGS. 2A and 2B. This causes the diluent 166
to be forced up tube 122 which results in the reconstituted drug
160 being under pressure, which in the preferred embodiment is
approximately 2.25 bars. The device 100 is preferably vigorously
shaken to ensure the lyophilized drug is properly mixed with
diluent 166.
[0076] In FIG. 3B, the device 100 is placed against the skin of the
person being injected. The user presses handle member 106 toward
the housing 304 in a direction shown by arrow 240A, thereby
displacing injection needle 130 from the first position within the
housing to a second position outside the housing such that the
needle penetrates the skin of the body being injected.
[0077] As shown in FIG. 3C, continued pressure of the handle 106
towards the housing 304 causes the first bar member 140 to ride up
the J-shaped slot 134. Simultaneously, second bar member 148, which
includes a linear slot 244, is rotated such that first coupling
device 142 rides up to the top of slot 244.
[0078] FIG. 3D illustrates the continued pressing motion of the
handle member 106 toward the housing 304. As the handle member 106
continues to pivot, the second bar member 148 forces third bar
member 152 and hence third needle 128 upward such that third needle
penetrates the rubber stopper 112 of vial 102. Because the
reconstituted lyophilized drug 160 is under pressure, it is forced
through tube 120 and thus into the person being injected. At this
point, biasing mechanism 108 is compressed. As the handle member
106 is released, biasing mechanism 108 forces the handle member
away from the housing 304 as indicated by arrow 240B and thus
withdraws injection needle within the housing. This is illustrated
in FIG. 3D. J-shaped slot 134 is beneficially provided with an end
locking portion 146 which catches coupling device 142 such that the
injection needle 130 is "locked" within the housing 304 after a
single injection. Now, the device 100 can be safely discarded.
[0079] FIGS. 4A-4K illustrate a drug delivery device 100-1 in
accordance with a preferred embodiment of the present invention
wherein the same reference numbers refer to the same or similar
elements. More particularly, FIG. 4A illustrates the device 100-1
which includes a housing 304-1 having a first port or opening 176
for receiving a diluent cartridge 116 and a second port or opening
262 for receiving vial 102. In this embodiment, it is preferred
that cartridge 116 containing diluent 166 be preassembled such that
the cartridge is partially penetrated by needle 126-1 and such that
the device 100-1 (without vial 102) is wrapped by a packaging
material to maintain sterility prior to use. Again, it is
preferable to use a standard 2 milliliter vial and cartridge that
contains 1 milliliter of diluent. Thus, the user unwraps the
packaging material and places vial 102 containing the lyophilized
drug 164 into the opening 262. Alternatively, vial 102 and
cartridge 116 are packaged separately from the device 100-1 as
shown in FIG. 4A. The user removes the sterility protector and
presses the vial 102 firmly into the opening until needle 124-1
penetrates the rubber stopper 112. The user then forces cartridge
116 into the housing 304-1. As cartridge 116 is forced into the
housing 304-1, the rubber stopper 118 is first penetrated by needle
126-1 such that the needle extends into the diluent 166. This stage
is illustrated in FIG. 4B.
[0080] Continuing to insert the cartridge 116 into the housing
304-1 forces the rubber stopper 118 to the bottom of the cartridge,
as shown in FIG. 4C. That is to say, the first opening 176 of
housing 304-1 is preferably circular, thereby allowing the walls of
cartridge 116 to enter the housing and not the rubber stopper 118.
This forces the diluent 166 through needle 126-1 to a manifold or
communication passageway 168 and into the vial 102. Again, the
resulting reconstituted lyophilized drug 160 in vial 102 is
preferably under pressure of about 2.25 bars. A greater or lower
pressure may be necessary depending on the volume to be injected.
The device 100-1 is preferably vigorously shaken to ensure the
reconstituted lyophilized drug 160 is properly mixed in preparation
for injection.
[0081] It is preferable to insert vial 102 containing the
lyophilized drug 102 before insertion of cartridge 116 containing
diluent 166 such that the diluent is not spilled into opening 262.
In order to ensure the proper insertion sequence of vial 102 and
cartridge 116, an interlocking mechanism is provided in accordance
with another aspect of the present invention. Interlocking
mechanism comprises a bar member 266 pivotally connected to the
housing 304-1 between the openings 176 and 262. The bar member is
configured to be moved in the direction of arrow 264 (FIG. 4A) upon
insertion of vial 102. Thus, as shown in FIG. 4A, bar member 266
prevents cartridge 116 from being inserted. As vial 102 is
inserted, it rotates bar member 266 in the direction of arrow 264
as shown in FIG. 4A such that cartridge 116 can subsequently be
inserted.
[0082] As shown in FIG. 4B, the device 100-1 is further provided
with an actuator or pushing member 174 for displacing the injection
needle 130-1 between a first position within the housing 304-1 and
a second position outside the housing. It is preferred that the
injection needle 130-1 extend out of the housing 304-1 in the range
of 5-12 millimeters. The injection needle 430-1 is in the range of
a 24-28 gauge needle and is preferably a "U" type needle having a
second end 172 configured to puncture sealing member 170. Sealing
member 170, which can be any puncturable material such as butyl
rubber, sealingly maintains the liquid in the upper part of housing
304-1 prior to use.
[0083] It is preferable to prevent displacement of the injection
needle 130 when the device 100-1 is not properly oriented, for,
example, upside down, in order to prevent the compressed gas in
vial 102 from being injected. Also, it is preferable to lock the
injection needle 130-1 within the housing 304-1 after a single
injection to reduce exposure to the contaminated needle.
Additionally, it is preferable to only allow displacement of needle
130-1 after insertion of cartridge 116. Accordingly, a locking
assembly 268A is provided to accomplish the foregoing.
[0084] The locking assembly 268A comprises member 268 as shown in
FIG. 4C having a first end configured to be moved by pushing member
174 and a second end configured to displace a ball 270 or other
appropriate movable locking device. With the pushing member 174 in
the first position such that injection needle 130 is within the
housing, groove 272 of the pushing member 174 aligns with groove
274 such that ball 270 can freely travel around the groove 274 of
the pushing member. When vial 102 is vertically oriented with the
compressed gas above the liquid, thus being properly positioned for
injection as shown in FIGS. 4B and 4C, ball 270 rests in the bottom
of groove 274 allowing the pushing member 174 to displace the
injection needle 130. If the vial 102 is not properly positioned
(for example, the assembly being upside down such that compressed
gas would be injected, as shown in FIGS. 4E and 4F), the ball 270
is positioned within grooves 272 and 274 to prevent displacement of
the pushing member 174.
[0085] The locking assembly 268A can be further configured to allow
displacement of the pushing member 174 only after cartridge 116 is
inserted. FIGS. 4G-4L illustrate this aspect of the invention. More
particularly, FIG. 4G is similar to FIG. 4C except cartridge 116 is
shown outside of the housing 304-1. FIG. 4H is a sectional view
taken along line 4H-4H of FIG. 4G and shows member 276 of the
locking mechanism having a slotted portion 278 therein. Member 276
is slidable within the housing 304-1 and configured to be moved by
insertion of cartridge 116. The lower end of member 276 is
positioned within grooves 272 and 274 as shown in FIG. 41. Thus,
with member 276 in the position shown in FIG. 4H, or before
cartridge 116 is inserted into the housing 304-1, the pushing
member 174, and hence injection needle 130-1, is prevented from
moving to the injection position.
[0086] When the cartridge 116 is fully inserted into housing 304-1
as shown in FIG. 4J, member 276 is moved downward as shown in FIG.
4K. As shown in FIG. 4L, this allows slotted portion 278 to align
such that pushing member 174 and hence injection needle 130-1 can
be moved to the injection position.
[0087] With the device 100-1 properly held by the user such that
vial 102 is vertically oriented as shown in FIG. 4M, the user
presses pushing member 174 such that the injection needle 130-1
first extends out of the housing 304-1, thus penetrating the skin
of the person being injected. Continued pressing of pushing member
174 causes the second end 172 of injection needle 130-1 to puncture
sealing member 170, thereby allowing the pressurized reconstituted
lyophilized drug 166 to travel from vial 102 into the person being
injected. It may take in the range of 10-30 seconds to deliver the
injection fluid. This pressing motion compresses spring 190 such
that upon release of pushing member 174, the member returns to the
original position, i.e., the needle 130-1 is withdrawn within the
housing 304-1 and locked therein. Insertion of the pushing member
174 into the housing 304-1 also moves in member 268 such that ball
270 is biased against the pushing member. This is shown in FIG. 4N.
When the pushing member 174 is returned to the first position, the
ball 270 is positioned and held within groove 272 by member 268,
thereby preventing displacement of the pushing member and hence the
injection needle 130-1 after a single injection. This configuration
is illustrated in FIG. 40. With the injection needle 130-1 locked
within the housing 304-1, the device 100-1 may be safely
discarded.
[0088] FIGS. 5A-5C illustrate a drug delivery device 100-2 in
accordance with a preferred embodiment of the present invention.
More particularly, FIG. 5A illustrates the device 100-2 with the
cartridge 116 installed but not inserted or penetrated by any
needle, and the vial 102 in place ready to be inserted. FIG. 5B
illustrates the inserted vial 102, while FIG. 5C shows the
subsequently inserted cartridge 116. At this stage, the diluent
from cartridge 116 has been transferred to vial 102, resulting in a
pressurized liquid in the vial. The device 100-2 is vigorously
shaken to ensure proper mixing of the reconstituted lyophilized
drug. The device 100-2 is now ready for injection. It should be
noted that the housing 304-2 advantageously includes a cutaway
portion 254 which allows the user to visually inspect vial 102 to
verify that the lyophilized drug 160 is thoroughly mixed with
diluent 166 and to verify that vial 102 is vertically oriented
during injection to ensure air is not being injected into the
injection site.
[0089] FIGS. 6A-6C are plan views of a similar device 100-3
corresponding to FIGS. 5A-5C, respectively. Accordingly, FIG. 6A
illustrates the cartridge 116 installed but not punctured by needle
126-3. Vial 102, containing the lyophilized drug 164, is also shown
ready to be inserted into housing 304-3.
[0090] FIG. 6B shows the inserted vial 102 which is punctured by
needle 124-3. Vial 102 pushes first against surface 178-3 of
puncturing device 182-3 and pushes device downward before being
pierced by needle 124. Pushing puncturing device 182 downward sets
a spring which (as will be explained in FIGS. 7A-7C) moves
puncturing device upward such that needle 128-3 penetrates vial
102. Alternatively, the spring can be preloaded. As shown, needles
124-3 and 126-3 are fluidly connected by a manifold 127 comprising
a channel 129 or tube. Upon insertion of cartridge 116, the rubber
stopper is first pierced by needle 126, and as cartridge 116 is
further inserted into the circular opening 176-3 of housing 304-3,
the rubber stopper 118 is forced to the bottom of cartridge 118,
thereby forcing the diluent 166 through the manifold 127 into vial
102. This also compresses the gas that was heretofore contained in
the vial 102 to a pressure sufficient for injection. The resulting
stage is shown in FIG. 6C. The device 100-3 is preferably
vigorously shaken to ensure proper mixing of the lyophilized drug
164. Now, the device 100-3 is ready to inject the reconstituted
drug solution 160 contained in the vial 102.
[0091] FIGS. 7A-7C illustrate partial perspective views of the
device 100-2, 100-3 shown in FIGS. 5A-5C and 6A-6C. More
particularly, FIG. 7A shows the pushing member 174-3 including an
internal bore with member 252 slidably contained therein. Member
252 fixedly supports injection needle 130 which is in fluid
communication with needle 128 via tube or channel 120. Needle 128
shown in FIG. 7A has yet to pierce the rubber stopper 112 of vial
102. Needle 128 is fixedly supported by puncturing device 182. As
the pushing member 174-3 is pressed toward the housing 304-3 (i.e.,
in the direction of arrow 180), a first spring 190 is compressed
allowing the member 252 to move downward until contacting the
housing. This allows injection needle 130-3 to extend out of needle
aperture 256 in housing 304-3 to penetrate the skin of the person
being injected. The spring 190 is set such that it creates both
axial and rotational movement. Only upon complete insertion of the
vial 102 is the rotational movement of the spring enabled which in
turn enables the puncturing of the vial 102. In the preferred
embodiment, injection needle 130-3 extends in the range of 5-12
millimeters out of the housing through needle aperture 256. The
injection needle 130 partially extending out of the housing 304-3
is illustrated in FIG. 7B.
[0092] As the pushing member 174 is further pressed toward housing
304-3, spring 200, which is stiffer than spring 190, is compressed
allowing ridge 258 of pushing member 174-3 to contact puncture
device 182. This causes rotation of puncturing device 182 in the
direction of arrow 186 as shown in FIG. 7C, such that surface 178
no longer contacts the vial 102. The spring 190 which, as described
above, was loaded upon insertion of vial 102, now causes the
puncturing device 182 to rotate in the direction of arrow 184,
thereby causing needle 128 to penetrate the rubber stopper 112 of
vial 102. This arrangement is illustrated in FIG. 7C. The
reconstituted drug 160 is forced by the compressed gas within vial
102 through injection needle 130 into the person being injected in
a time range of approximately 10-30 seconds.
[0093] FIGS. 8A-8E illustrate a drug delivery system 100-4 in
accordance with a preferred embodiment of the present invention
wherein the same reference numbers refer to the same or similar
elements. More particularly, FIG. 8A illustrates the device 100-4
which includes housing 304-4 having a first port or opening 176-4
for receiving cartridge 116 and a second port or opening 262-4 for
receiving vial 102.
[0094] Vial 102 containing the reconstituted drug 164 is inserted
into the housing 304, followed by the insertion of cartridge 116
containing the diluent 166. Again, a rubber stopper of the
cartridge 116 is forced to the bottom of the cartridge which forces
the diluent under pressure into vial 102. This stage is shown in
FIG. 8B. Advantageously, the housing 304-4 includes a cutaway
portion 400 such that vial 102 is substantially visible during
reconstitution and injection. This allows the user to visually
verify that the drug is properly reconstituted and that the vial
102 is vertically oriented during injection with the compressed gas
above the reconstituted drug.
[0095] FIG. 8C is a rear view taken of FIG. 8B and illustrates the
injection of the reconstituted drug. More particularly, the pushing
member or actuator 174-4 is pressed into housing 304-4 which forces
injection needle 130-4 out of the housing and into the person being
injected. In the preferred embodiment, the injection needle extends
out of the housing in the range of 5-12 millimeters. The
reconstituted drug, in fluid communication with the vial 102, is
transferred from the vial and into the person being injected. FIGS.
8D-8F are isometric views of the device 100-4 in the stages shown
in FIGS. 8A-8C, respectively.
[0096] FIGS. 10A and 10B graphically illustrate system
characteristics of a preferred embodiment of the drug delivery
device. To provide effective delivery of a specified amount of
fluid and minimize patient discomfort, the system requires a
sufficient fluid pressure in the delivery vial that is manually
actuated by the user within a short time period. FIG. 10A shows the
pressure (millibars) and weight (grams) characteristics of the
system during a delivery period of about 30 seconds for a delivery
volume of about 1.6 milliliters. FIG. 10B illustrates test results
of the delivery of 1.6 milliliters into different animals using a
single drug deliver device for the same time period.
[0097] Referring to FIGS. 11A-11D, cutaway views of a preferred
embodiment of a diluent container subassembly and a manifold, which
may be used with the drug delivery devices or with an ordinary
syringe or other drug delivery devices, are illustrated. The
diluent container subassembly 300 includes a preassembled
compression portion 310 which allows the user to hold the diluent
container 312, which can be in the form of a compressible sealed
bag, and insert it into a needle 314. The diluent container 312
contains about 1 milliliter diluent and a controlled volume of gas,
such as air, for example, and upon insertion into housing 304-6, is
pierced by the needle 314. During storage or shelf life, the
diluent container 312 is sized to allow for expansion of the
container as a result of changes to the environment. In addition,
the compression portion 310 is used to compress the exterior of the
diluent container and apply pressure to the contents of container
during delivery of the diluent for mixing. The diluent containers
are formed from flexible, collapsible materials, for example,
polyethylene, polypropylene and nylon. The compression portion 310
includes a slider element 316 and two longitudinally extending arms
318, 320 extending therefrom. Two cylindrical drums 322, 324 are
spaced between the longitudinally extending arms 318, 320.
[0098] FIG. 11A illustrates the diluent container subassembly 300
positioned in the housing 304-6 of the drug delivery system in
accordance with the present invention. FIG. 11D further illustrates
the fully compressed state of a preferred embodiment of the diluent
container subassembly 300. The slider element 316 of the
compression portion 310 translates in at least one axis, for
example, in the illustrated embodiment, it can move up or down. The
downward movement of the slider element 316 causes the diluent
container 312 to wrap around the cylindrical drum 324 which
compresses the contents of the diluent container 312, thus forcing
the diluent from the container 312 and through the needle 314 and
into the vial 102. The movement of the slider element 316 is
limited by an end of travel position. At this end of travel
position, the slider element 316 may be locked by a locking
mechanism which ensures that the diluent container is kept
compressed.
[0099] A manifold 330 includes two needles 314, 332 fixedly mounted
at the ends of an extending member 334. The needles can also
comprise a penetrating member that is formed from an injection
molded material such as medical grade polycarbonate or acrylic with
the required level of rigidity to penetrate the vial or container.
A channel 331 provides for fluid communication between the needles
314 and 332. Needle 314 pierces the diluent container 312 upon
insertion of the container, while needle 332 pierces the vial 102
upon insertion of the vial containing the lyophilized drug 164. In
a preferred embodiment of the present invention, container 312
contains approximately 1 milliliter of diluent and a controlled
volume of air which is forced into vial 102, resulting in a
pressure inside vial 102 of approximately 2.25 bars. The pressure
inside vial 102 results from forcing the controlled volume of air
in the diluent container 312 into the rigid volume in the vial 102.
Thus, the diluent 166 is forced into vial 102 to mix with the
lyophilized drug 164 contained therein. The entire assembly is
preferably shaken to ensure the reconstituted drug 160 is properly
mixed in preparation for injection. The vial 102 is vertically
oriented during injection to ensure air is not being injected into
the injection site.
[0100] Referring to FIG. 11C, the injector needle 130-6 is shown in
a first position within the housing 304-6. As described
hereinbefore, the injection needle 130-6 is in the range of a 24-28
gauge needle and is preferably a "U" shaped needle having a second
end 172-6 configured to puncture sealing member 170-6. An area 171
is located adjacent to the sealing member 170-6 and is in
communication with the channel 331 as shown in 11B.
[0101] When the user compresses the button 305, it causes the
needle 130-6 to penetrate the skin and the second end 172 to
penetrate the sealing member 170. The drug and diluent solution
will flow from the needle 332, through the channel 331, and area
171 and to the user via the injector needle 130-6. As the user
compresses the button 305, which is spring loaded by spring 306, a
pair of mating pawls 307, 308 fit together and prevent the button
from being pulled out and the reuse of the device as shown in FIG.
11C.
[0102] FIGS. 12A-12B illustrate perspective views of a preferred
embodiment of the diluent container subassembly 300 and provide
further details of the components of the compression portion 310.
The cylindrical drum 324 is slotted such that the diluent container
can be inserted therein. The cylindrical drum 322 serves as a
backing drum. Thus, the diluent container 312 is typically inserted
between the cylindrical drum 324 and the backing drum 322. The drum
apparatus 322, 324 moves in a rack and pinion gear apparatus 340.
An end of travel position 342 in the rack and pinion gear apparatus
340 constrains the movement of the cylindrical drum 324 at its end
of movement position. This end of travel position correlates with
the end of the wrapping of the diluent container 312 around the
cylindrical drum and maximum compression of the contents of the
container. A flange 344 can be used to hold the diluent container
312 at the bottom of the subassembly 300. The diluent container 312
can be sealed by means of heat welding techniques or ultra sonic
techniques to the flange 344 after it has been filled with the
diluent. The longitudinally extending arms 318, 320 in the
compression portion 310 each comprise two members 350, 352, as
shown in FIG. 12B. A cylindrical drum is attached to each member.
The two members 350, 352 are spaced apart from each other to
accommodate the wrapping of the diluent container on the
cylindrical drum 324.
[0103] Referring to FIGS. 13A-13B, cutaway views illustrate an
alternate embodiment of the invention similar to that shown in
FIGS. 11A-11D including a manifold 350. The manifold 350 has two
needles 352, 354 for the purpose of piercing the vial 102 and
diluent container 312 respectively. Once the diluent 166 and the
controlled volume of air are forced to move into vial 102, the
diluent mixes with the lyophilized drug 164 and results in the
reconstituted drug 160 which is under pressure. Because the
reconstituted drug is under pressure due to the controlled volume
of air, it is forced through the needle 352 and into the person
being injected through a needle 351 that is actuated by movement of
pushing member 353. This embodiment of the device provides a user
comfort as it does not have to be vigorously shaken to ensure the
reconstituted lyophilized drug 160 is properly mixed in preparation
for injection. The controlled volume of air facilitates the mixing
of the diluent and the lyophilized drug. The pushing member 353
displaces the injection needle 351 between a first position within
the housing 304 and a second position outside the housing, or in an
injection state.
[0104] It is preferable to prevent displacement of the injection
needle 351 when the device 100-7 is not properly oriented, for
example, upside down, in order to prevent the compressed gas in
vial 102 from being injected. Also, it is preferable to lock the
injection needle 351 within the housing 304-7 after a single
injection to reduce and preferably to prevent the exposure to the
contaminated needle. Additionally, it is preferable to only allow
displacement of needle 351 after insertion of diluent container
312. Accordingly, a locking mechanism comprising member 268 as
shown in FIG. 4B is provided to accomplish the foregoing. The
member 268 has a first end configured to be moved by pushing member
353 and a second end configured to displace a movable locking
device, substantially similar to the device shown in FIG. 4B.
[0105] With the device 100-7 properly held by the user such that
vial 102 is vertically oriented, the user presses pushing member
353 such that the injection needle 351 first extends out of the
housing 304-7, thus penetrating the skin of the person being
injected. Continued pressing of the pushing member 353 causes the
second end 355 of injection needle 351 to puncture sealing member
357, thereby allowing the pressurized reconstituted drug 166 to
travel from vial 102 into the person being injected. It may take in
the range of 10-30 seconds to deliver the injection fluid. The
pressing motion compresses spring 359 such that upon release of
pushing member 353, the member returns to the original position,
i.e., the needle is withdrawn within the housing 304 and locked
therein.
[0106] Referring to FIG. 14, a cutaway view illustrates a manifold
of another preferred embodiment of the drug delivery device 100-8
in accordance with the present invention. The manifold 350 has two
needles 352, 354 for the purpose of piercing vial 102 and diluent
container 312, respectively. A flange, substantially similar to the
flange 127 shown in FIG. 6B, holds the septum or stopper 313 in
place in the container 312. An extending member or communication
chamber 356 which is in fluid communication with the needles 352,
354, has a membrane such as a hydrophilic membrane or barrier 360
disposed therein. It should be noted that the hydrophilic membrane
needs to be wetted before it functions to minimize or preferably
prevent the flow of gas into a user's tissue. The hydrophilic
membrane allows gas, for example, air to pass freely till it comes
in contact with liquid and gets wet. Thus, when wet, no air such as
the controlled volume of air in the diluent container 312 can pass
through the hydrophilic membrane, preventing air from entering the
user's tissue. The presence of the hydrophilic membrane prevents
risks caused by any wrong use of the device 100-8 by the user such
as incorrect positioning of vials or containers.
[0107] Referring to FIGS. 15A-15B, cutaway views illustrate another
preferred embodiment of a manifold of the drug delivery device in
accordance with the present invention, The needle 352 pierces the
vial 102 while needle 354 pierces the diluent container 312. The
needle 354 and channel 352 on spike 352A are in fluid
communication. Diluent 166 moves from the diluent container 312
into vial 102, thus mixing with the lyophilized drug to result in a
reconstituted drug. A channel 358 is in communication with an area
361 sealed by a stopper 313. Channel 358 also includes a
hydrophilic membrane. Thus, upon the introduction of air to the
channel, the membrane expands in the presence of air and disallows
the passage of air therethrough.
[0108] In use, the user presses the button 363 which first moves
injector needle 130 into the users skin. Further movement of the
button 363 causes piercing member 172 to penetrate the stopper 313.
This enables liquid drug/diluent solution to move, via the air
pressure in the vial 102 through the injector needle 130 and the
user's skin.
[0109] It should be noted that the embodiment illustrated with
respect to FIGS. 15A and 15B being more position independent, is
not subject to air blocking the flow of liquids through the gas
impermeable membrane until all the drug solution has been
transferred out of the vial 102. FIG. 15A shows the position of
channel 358 relative to channel 352. Thus, only if the vial 102 is
completely filled with air would it pass into channel 358. In
contrast, the embodiment illustrated with respect to FIG. 14 and
the absence of the lower channel 358 is more position dependent and
thus subject to air blocking the flow of liquids through the gas
impermeable membrane even while the drug solution is being
transferred out of the vial 102.
[0110] Further, it should be noted that the delivery times of the
drugs is dependent on the volume of vial which maybe adjusted. The
pressure is adjusted in part by adjusting the vial volume size. A
large vial volume of air relative to the drug would result in
greater air pressure and faster drug delivery.
[0111] In the preferred embodiments of the present invention the
drug vials and the diluent containers are shown as being inserted
in the housing 304 and aligned in the same direction along parallel
axes. In the alternative, it is contemplated that the vials and
containers may not be aligned in the same direction along parallel
axes. The vials and containers may be inserted along two different
axes that are oriented at oblique or orthogonal angles relative to
each other.
[0112] Referring to FIG. 16 a cutaway view illustrates an alternate
preferred embodiment of an injection device 236 in accordance with
the present invention. The device 236 facilitates the sterilized
injection of a prefilled cartridge or vial containing an injectable
liquid, for example, a vial containing a liquid drug 160. The
device 236 includes first opening 161 for receiving vial 102 and a
manifold 370 including member 372 sealingly engaged with the first
opening 161. Member 372 fixedly supports needle 374 and is
supported by a collapsible volume, such as bellows 378, or any
other device capable of injecting a fluid such as a gas upon being
compressed. A check valve 380 ensures that the flow from the
bellows is unidirectional, that is, the drug under pressure can not
enter the bellows 378. The check valve 380 comprises a tubular
member 381 adapted to deliver gas, for example air, to the vial
102. Air is moved out of the bellows and into the tubular member
332 by compressing, the bellows 378. The check valve 380 allows the
flow of air out of the bellows 378 and into the vial but disallows
the reverse flow of air from the vial into the bellows. Air from
the bellows 378 is forced up through needle 374 and into vial 102
applying pressure to the contents of the vial 102. The liquid drug
160 is under pressure and is injected into the user directly from
the vial 102. The injection process is the same as discussed
earlier with respect to embodiments in FIGS. 13-15, in that the use
of a U-shaped needle assembly is compressed into the skin to
activate injection. As discussed earlier, due to the nature of the
hydrophilic material, a hydrophilic membrane 360 in the drug
delivery path minimizes and preferably prevents gas from being
injected into the user.
[0113] Referring to FIGS. 17A-17C, cutaway views illustrate an
alternate embodiment of the drug delivery device 100 in accordance
with the present invention. The diluent container comprises a
syringe 390. When pressure is applied to a plunger shaft 392, the
diluent 166 is forced out of the syringe 390 through the channel
398 and into the contents of vial 102 via the needles 394, 396
which are in fluid communication with each other through the member
398. Thus, the diluent 166 is provided to vial 102 under pressure
and is mixed with the reconstituted drug to result in a
reconstituted drug solution ready for injection or delivery under
pressure to a patient. The drug solution is delivered to a user
using a u-shaped needle assembly as disclosed with respect to FIGS.
13A-13B, 14, and 15A and 15B. This syringe embodiment facilitates
the use of a standard prefilled container or cartridge containing
only a diluent. The device is flexible and does not require special
means or training.
[0114] The present invention includes alternate preferred
embodiments of injection devices. FIGS. 9A-9F illustrate an
injection device 236 which facilitates the sterilized injection of
a prefilled cartridge or vial containing an injectable liquid, for
example, a vial containing a reconstituted drug 160. It is
preferable to use a standard vial, for example, a 2 milliliter
vial, with this device 236. As shown in FIG. 9A, device 236
includes a first opening for receiving the vial 102 and a manifold
including member 232 which is slidably and sealingly engaged with
the first opening. Member 232 fixedly supports needle 224 and is
supported by a collapsible volume, such as bellows 228, or any
other device capable of injecting air upon being compressed. Needle
224 is in sealed communication with the bellows 228 as shown in
FIG. 9A. The vial 102 is pressed into the housing 304-5 such that
needle 224 pierces the rubber stopper 112. This arrangement is
shown in FIG. 9B.
[0115] The vial 102 is further pressed into the housing 304-5 which
forces member 232 to compress bellows 228, thus forcing the air
contained in bellows 228 up through needle 224 and into cartridge
116. Now, as illustrated in FIG. 9C, the cartridge 116 is under
pressure for forcing the drug 166 into the person being injected.
The bellows or other compression device can also be actuated by
member 174-5.
[0116] As shown in FIGS. 9A-9F, device 236 is further provided with
a pushing member 226 for displacing the injection needle 130-5
between a first position within the housing 304-5 and a second
position outside the housing, or in an injection state. In the
preferred embodiment a distal end of the injection needle 130-5 can
extend out of the housing 304-5 in the range of 5-12 millimeters.
In this particular embodiment, the injection needle 130 is
preferably a "U" type needle having a second end 250 configured to
puncture sealing member 230. Sealing member 230, which may comprise
any puncturable material such as butyl rubber, maintains the liquid
in the upper part of housing 304. As the user presses pushing
member 226 into housing 304, the first end of the injection needle
130 first penetrates the skin of the person being injected as shown
in FIG. 9D. Continued pressing of pushing member 226 into the
housing 304 causes the second end 250 of injection needle 130-5 to
puncture sealing member 230, thereby allowing the reconstituted
drug 160 to travel from cartridge 116 into the person being
injected. This is illustrated in FIG. 9E. The pressing of the
pushing member 226 into the housing 304-5 compresses a spring such
that upon release of pushing member 226, the member returns to the
original position, i.e., the injection needle 130-5 is in the first
position within the housing 304-5 as shown in FIG. 9F. This
embodiment may be further provided with a locking mechanism similar
to that disclosed in FIGS. 4A-4K. With the injection needle locked
within the housing 304-5, the device 236 may be safely
discarded.
[0117] Further, FIGS. 18A-18C illustrate an injection device in
accordance with an alternate preferred embodiment of the present
invention. More particularly, the drug delivery device 400 includes
a straight needle 402 having a lancet 404 disposed on a first end.
A cavity 405 in the septum 406 contains a liquid drug under
pressure. The straight needle 402 includes a side hole 407 disposed
on the shaft. The second end 408 of the straight needle is blocked.
In operation, as shown in FIGS. 18A, 18A-1, 18B and 18B-1, when the
member 410 is moved forward toward the housing 412, the injection
needle 402 is displaced from a first position in the housing 412 to
a second position outside the housing such that the needle 402
penetrates the skin of the user. After the lancet 404 penetrates
the user's tissue, continued pressing motion of the member 410
toward the housing causes the side hole 407 to be in fluid
communication with the cavity 405 of the septum 406 creating a path
for the drug under pressure to flow into the user's tissue. The
straight needle punctures the septum 406 at two locations. As shown
in FIG. 18C, as the member 410 is released, the injection needle is
withdrawn within the housing 412.
[0118] More particularly, referring to FIG. 18A-1, a 3 part ring
structure including member 414, latch 416, gap 418 and spring 419,
as shown in FIG. 18A provide an interlocking system. This safety
mechanism which includes the members 410, 414, latch 416, gap 418
and spring 419 provides an interlock to ensure against reuse of the
drug delivery device 300 and exposure of needle 402 after the first
use. Once the member 410 is compressed the mating ridges 413A and
413B come together. The ridges are angled on one side to allow
ridge 413B to pass under 413A when member 410 is depressed against
the housing 412. The ridges are pressed together when the force of
the spring 419 moves member 410 away from the housing 412. Because
the ridges interface at a right angle to the direction of movement
of the member 410 they serve to prevent further movement by the
member and the needle 402. This mechanism ensures that the device
400 is not reused.
[0119] FIGS. 19A-19F illustrate cutaway views of alternate
preferred embodiments of systems which allow reconstitution of drug
and subsequent transfer into a drug delivery device in accordance
with the present invention. Once the drug is made into a solution
it may be transferred into a user by means of direct injection as
shown in FIG. 11, for example, or into a drug delivery device such
as an infusion pump, needleless injector or the like. The systems
include a vial 420 containing a predetermined volume of a drug and
a vial 422 containing a volume of a diluent. The use of standard
vials facilitate the use of the drug delivery device by different
drug suppliers.
[0120] An air source 424 maybe included for the delivery of drugs.
With drugs of higher viscosity, the use of pressure becomes more
important. As illustrated in FIG. 19A, the sources of pressurized
air can vary and may include, but are not limited to, a compressed
air delivery supply 426, a chemical gas generator 428, a standard
syringe 430 and a collapsible volume container, such as a bellow
container 432. The air source supplies the driving force to the
diluent volume which moves the diluent solution 434 into the
standard lyophilized drug vial 420. Once reconstituted, the liquid
drug is transferred via the air separator, such as a hydrophilic
membrane 436, to a drug delivery system. It should be noted that
spike 438 in the diluent vial 422 and spike 440 in the drug vial
420 each have two paths. The spike 438 has a first path for
compressed air to enter the diluent vial 422 and a second path for
the pressurized diluent 434 to be in fluid communication with the
drug vial 420. The spike 440 has a first path for the pressurized
diluent to enter the drug vial 420 and a second path for the
delivery of the drug solution into a drug delivery device. As
discussed earlier, it is contemplated that other drug delivery
devices may be received into this system to receive the drug
solution.
[0121] Referring to FIG. 19B, the air source is a compressed air
canister 426. The compressed air canister typically is a standard
addition for domestic drug delivery devices. The user attaches the
compressed air canister 426 to the drug delivery system 450 and
punctures a seal 452 located in the compressed air canister. The
air canister is then in fluid communication with the diluent vial
422 by means of channel 453. Air is released from the compressed
air canister 426 and is introduced into the diluent vial 422, which
in turn forces the diluent solution 434 to move into the drug vial
420 via channel 455. After reconstitution is completed, the liquid
drug is ready to be transferred. The concentration of the
reconstituted drug can be controlled in this and other embodiments
by changing the quantity of diluent transferred to reconstitute the
drug. A hydrophilic membrane 436 in the drug delivery path
minimizes and preferably prevents gas from being transferred to the
drug delivery device.
[0122] FIG. 19C shows a chemical gas generator 428 as the air
source used in this particular embodiment to deliver the diluent
434 under pressure to the lyophilized drug vial. The chemical gas
generator 428 includes a chemical compartment 456 which typically
contains two materials 458, 460. The two materials 458, 460 can be
two liquids or a liquid and a solid palette 460 that are separated
during shelf life. It should be noted that the materials used in
the chemical compartment 456 and the reaction that ensues during
the mixing of the materials are safe and biocompatible. Pushing a
member 462, in the chemical compartment 456 results in tearing of a
seal 464, for example, aluminum foil, which separates the two
materials 458, 460 during shelf life. The two materials are then in
fluid communication and react to produce a gas such as, for
example, carbon dioxide. The chemical gas generator 428 also
includes a gas compartment 466 which is typically an air reservoir
having a flexible enclosure 468. The carbon dioxide produced in the
chemical compartment 456 due to the reactions enters the gas
compartment 466 and is accommodated in the flexible layers 468 that
form the gas compartment. The movement of the flexible layers 470,
472 force the air or carbon dioxide into the diluent vial 422
through the air pathway 423. It should be noted that the gas
compartment 466 has a double layer 470, 472 comprising the flexible
containment area. The two layers 470, 472 provide for safety as if
the air or gas generated as a result of the reaction in the
chemical compartment does leak, it can be accommodated between the
flexible enclosure 468 of the gas compartment 466. Further, the gas
compartment 466 is vented using a gas leakage pathway or vent port
474. The air that is released from the chemical gas generator 428
enters the diluent vial 422 via the channel 423 which in turn
forces the diluent solution 434 to move into the drug vial 420 via
the channel 425. After reconstitution is completed, the drug is
ready to be used, and is transferred to a drug delivery system such
as one described with respect to FIG. 19B.
[0123] Referring to FIG. 19D, the air source used in this
particular embodiment to deliver the diluent under pressure is a
standard syringe 430 or an air reservoir. The syringe 430 is locked
at an end of travel position. When pressure is applied to a plunger
shaft 480 the air is forced out of the syringe 430 and into the
contents of the diluent vial 422 through the needle 482 and needle
434 which are in fluid communication through the member 484. The
diluent 434 is then forced into the drug compartment or drug vial
420 via member 484 under pressure which provides for the mixing
with the lyophilized drug to result in a reconstituted drug which
is then ready for injection or delivery under pressure to a user.
In an alternate embodiment, a lever can be included to reduce the
force required for pushing the plunger member 480. The lever will
increase the displacement and thus delivery of pressurized air to
the diluent container in this case, the drug solution may be
injected as shown in FIG. 19D, the sectional of which is the same
as shown and described in other needle assemblies, for example,
shown in FIGS. 11, 13, 14, 15, 16, and 32 or transferred into a
drug delivery device.
[0124] Referring to FIG. 19E, the air source used in this
particular embodiment to deliver the diluent under pressure to the
lyophilized drug is a collapsible volume container such as a bellow
container 432. A check valve 488 or a one-way valve insures that
the flow from the bellow container 432 is unidirectional, that is,
the drug or diluent can not enter the bellows. The check valve 488
comprises a tubular member 490 adapted to deliver gas, for example
air, to the diluent vial 422. The resilient nature of the bellows
is checked by the check valve 480 which does not allow air to enter
the bellows and thus reinflate the bellows once the bellows have
been compressed and air has exited. Once compressed, air contained
in the bellows 432 is forced through needle 438 and into the
diluent vial 422 via channel 491 applying pressure to the contents
of the diluent vial. The diluent solution 434 in turn, is delivered
under pressure to the drug vial 420 where the drug is reconstituted
and can be transferred either by injection as described above or
into a drug delivery device, as also described and shown relating
to the embodiment of FIG. 19A.
[0125] Referring to FIG. 19F, the air source used in this
particular embodiment to deliver the diluent under pressure Is
cylinder 490. This embodiment is similar to the embodiment
containing a standard syringe as described with respect to FIG.
19D. The plunger 492 is depressed to compress the air in the
cylinder 490. The air is driven into the diluent vial 422 through
channel 494 which brings the cylinder and the diluent vial in fluid
communication. The pressurized diluent in diluent vial 422 then
moves into the vial 420 and mixed with the drug. The pressurized
drug solution is then ready to be delivered. This can either
comprise delivery to a drug delivery device as described with
respect to the embodiment of FIG. 19A or injected as shown in the
present embodiment having a straight needle assembly as shown and
described in FIG. 18.
[0126] Referring to FIGS. 20A-20C, an alternate embodiment of the
drug delivery system 498 in accordance with the present invention
includes standard vial 500 containing a liquid drug 502. A volume
of gas, for example air, contained in an air chamber 504 is
introduced in the standard liquid drug vial 500, creating air
pressure above the liquid drug which allows for delivery of a
liquid drug under pressure. The usage is position dependent, that
is the delivery of the liquid drug, is performed with the standard
vial 500 in a vertical position. In addition, a hydrophilic
membrane minimizes or preferably prevents the introduction of the
extra volume of air into the user's tissue.
[0127] In use, as shown in FIG. 20A, the standard vial 500
containing the liquid medicament 502 is inserted into the drug
delivery device 498 in accordance with the present invention. An
air chamber 504 is provided which upon insertion of the drug vial
500 and the puncturing of the seal 506 of the vial, is in fluid
communication with the drug vial. Once inserted, the lip 505A of a
standard vial 500 is locked into position by means of a pair of
arms 505 having ridges 507 projecting inwardly therefrom. The
injector system is the straight needle 402 embodiment as disclosed
in FIGS. 18A-18C. Once the air from the air chamber is introduced
into the standard drug vial 500 the liquid drug is pressurized and
is ready to be injected using the injector system described with
respect to FIGS. 118A-118C. After injection into the user's tissue,
the needle is retracted automatically. The drug delivery device 498
is then disposed.
[0128] Referring to FIG. 21, an alternate preferred embodiment of a
drug delivery system 510 which uses standard vial 500 containing a
medicament is disclosed. A plunger 512 is included in the drug
delivery device 510. In order to reduce forces which are required
to insert the standard vial 500 in the drug delivery device 510. In
an alternate embodiment, the drug delivery system 510 can have a
compact configuration without a plunger. Snaps 514 lock the
standard vial 500 into position. Snaps 516 hold the end portion of
the vial having the seal 506 in place to ensure that the spike 518
pierces the seal 506 of the vial 500 before the vial is moved in
the downward direction. Air in the air chamber 520 is delivered to
the vial 500 when the air is compressed and displaced by the
downward movement of the vial 500. The liquid drug under pressure
is delivered to an injector using tubing 522. A hydrophilic
membrane 524 minimizes or preferably prevents gas from entering the
user's tissue. The injector system used can be similar to one
described with respect to FIGS. 18A-18C. The member 410 is moved to
displace the injection needle 402.
[0129] Referring to FIGS. 22A-22E, the views illustrate an
alternate preferred embodiment of the drug delivery system 530 in
accordance with the present invention. This particular embodiment
may be used as a reconstituted system and a drug delivery system
and includes two vials 532, 534 a first containing a diluent 533
and a second containing the lyophilized drug 535. In addition,
there is an air delivery system for pressurizing system, such as a
built-in air cylinder 533 in fluid communication with the diluent
vial 532 which is disposed between the lyophilized drug vial 534
and the diluent vial 532. Air is pushed into the diluent vial 532
forcing the diluent 533 from its vial into the lyophilized drug
compartment or vial 534. After reconstitution is completed, the
liquid drug is ready for injection. A hydrophilic membrane is used
as an air separator to minimize or preferably prevent the entry of
air into the user's tissue. This particular embodiment uses a
straight needle 402 injector system as described with respect to
FIGS. 18A-18C. Additionally, a positioning interlock, such as the
mechanism, described with respect to FIGS. 2A-2B is used. Further,
in an alternate embodiment, the air cylinder can be replaced with a
standard syringe to be the air source as shown in FIGS. 22D and
22E. A check valve (as shown in FIG. 16) disposed in the air inlet
between the syringe and manifold is included in the embodiment
containing the syringe. The drug delivery system of the present
invention is used to deliver an accurate volume of a drug solution.
The predetermined volume can be delivered using different
methodologies. A first embodiment controls the dose by changing the
height of the outlet spike 535 in the liquid drug vial 537 as shown
in FIGS. 23A, i.e. the higher the spike, the lesser is the amount
of drug transferred out of the vial 537. The spike is adjusted by
means of threads 539 upon which the spike rotates or upon which it
sealably slides. This can be used for to transfer or to inject the
drug solution. Another preferred embodiment which increases the
accuracy of the volume of drug delivered uses the residual drug
volume as a parameter to indicate the volume delivered. One way of
controlling delivered drug solution volume is to use the assembly
shown in FIG. 23B. After the drug is pushed in solution in vial 102
the solution may be pulled into cavity 541 by piston 555. The
cavity 541 has indications thereon to aid the user in determining
the proper volume. At the desired level, the piston is stopped. The
drug solution is then transferred from the cavity 541 either via a
needle into a user or into a drug delivery device. Yet another
embodiment to provide an accurate volume of drug is disclosed with
respect to FIGS. 24A-24C and FIG. 25. The reconstitution system
drug delivery device. The dialing process retracts a floating
piston which moves upward and creates an internal pressure which
provides for aspiration of the reconstituted drug. A trigger 564
releases a preloaded spring to push the floating piston.
[0130] Thus aspiration occurs by dialing the dose into the pen-type
injector. Once the pump 560 is filled as indicated by an indicator
566, it is disconnected from the filling device.
[0131] Injection and disposal of the pump is performed after
disconnection with a process similar to the process described with
respect to FIGS. 2A-24C.
[0132] FIGS. 26A-26D are perspective views of a drug transfer
system having a drug delivery device 510 in accordance with the
present invention. A diluent vial is inserted in a cavity 572 and a
lyophilized drug vial is inserted in cavity 574. A cavity 576
accommodates an air pressurization system to deliver drugs having a
low level of viscosity. Further, the drug transfer system includes
an access 578 to receive a drug delivery device. The drug is
transferred thereto via a needle 580.
[0133] FIGS. 27A-27C are cutaway views of a preferred embodiment of
a transfer system 600 in accordance with the present invention.
Once pressurized by the air in cavity 603, the liquid drug from
vial 602 is transferred to a drug delivery device 604 via an
extension 606. The liquid drug flows out of the vial 602 through
spike 608 and through the tubing 610 into the needle 616 which is
received into the drug delivery device 604. Referring to FIG. 27B,
the drug delivery device 604 is attached to the transfer system
600. The filling process continues until the entire drug level
reaches the outlet 604A (shown in phantom in FIG. 26B) of the
device 604. At this point the filling process is completed. It
should be noted that during the filling process, if the user stops
pushing the vial 602 into the transfer system 600 the drug may
drain into the cylinder 614. This is prevented by getting the
friction forces higher than the impedance of the tubing 610 to the
drug flow. In the alternative, it is also possible to dispose a
one-way valve at the end of the tubing 610. Once the drug delivery
device 604 is filled with a liquid drug, it is disconnected from
the transfer system 600. Any residual drug in the system 600 can
stay protected, and the needle 616 is retracted and as described
earlier with respect to the needle locking mechanisms is secured in
the cover 606, and cannot be reexposed to cause harm or injury.
[0134] FIGS. 28A-28C are cutaway views of the operation of another
preferred embodiment of a drug delivery system 630, in particular
of a position independent injection system in accordance with the
present invention. In this embodiment, the injection system 630 is
position independent, that is the injector is not required to be in
a vertical position during the injection process. Referring to 28A,
the drug delivery system 630 includes a vial 632 containing the
liquid drug 634. The liquid drug 634 flows through the spike 636
along a tube 644A into a cavity 652. The spike includes two paths,
one path 642 for delivering pressurized air into vial 632 from
chamber 641 and another path 644 to deliver the liquid drug to the
user via a needle 664. The liquid drug exits from the path 644 and
travels along tube 644A disposed at the bottom of the spike. A
one-way valve 638 insures the unidirectional flow of the liquid
drug 634 into the cavity 652A. Spring 640 holds piston 656 within
the cavity 652. A floating piston 650 moves in the cavity 652. A
seal 654 is included in the floating piston. Member 660 rests atop
a needle assembly 664A. Member 660 is hingedly connected to member
662. Member 662 has a finger 662A. Prior to use, the finger 662A
rests within an aperture 662B of the housing 660A. The notch 656 is
the end of travel position for the piston 656.
[0135] The path 642 from the air chamber 641 to the vial 102
pressurizes the vial by delivering air thereto. The air chamber 641
is depleted of air when the vial is moved downward. As the vial
moves downward, a member 641A sealably slides within the walls of
the chamber and forces the air into the vial. The member 641A is
prevented from leaking air out of the chamber by the seal 641B.
[0136] In use, when vial 632 is pushed into the device 630, air
from the cavity 641 enters into the vial 632 and pressurizes the
liquid drug. This drug 634 under pressure flows via path 644
through the one-way valve 638 into the left side of the cavity 652.
Pressurized air pushes the floating piston 650 to the right side of
the cavity 652. The floating piston 650 moves until the position of
the notch 658, which is the end of travel position for the piston
656 and thus for filling of the cavity 652. Thus, as illustrated in
FIG. 28B, an accurate volume of liquid drug is filled in cavity 652
and the device 630 is ready to be used.
[0137] As illustrated with respect to FIG. 28C, once the member 660
is depressed, it causes the needle 664 to move downwardly outside
the housing 660A and into the user's tissue. Member 662 is hingedly
connected to member 660. When 660 is depressed, it causes member
662 to move upwardly disengaging the finger 662A from the aperture
662B and enables the spring 640 to return to a less compressed
state. As it does, the spring 640 forces the piston towards the
opposing end of the cavity 652. This causes the liquid drug therein
to move via channel 652A and needle 664 into the user's tissue, the
piston 656 is released due to the movement of member 662 in the
upward direction. The piston 656 moves to the left. The floating
piston 650 is under pressure and moves the liquid drug in cavity
652 through the injector needle 664 and into the user. It should be
noted that after delivery of the liquid drug, the position of the
floating piston 650 depends on the load on the spring 640. To
prevent the flow of residual drug under pressure, the spring 640
continues to be in a preloaded state. The seal 654 is pushed to the
left side of the cavity 652 under pressure of spring 640 to seal
against the exit of the pressurized residual drug via the channel
652A. Although disclosed as having a pushing spring 640, other
mechanisms may be included in the injector system to result in a
position independent injector.
[0138] Referring to FIG. 28D, a cutaway view of a spike 636 which
brings the liquid drug 634 in fluid communication with the injector
system is illustrated. The spike 636 penetrates the septum 639 of
the vial 632 when the vial is inserted into the cavity 640. The
spike functions as a piston 641A and is sealably and slidably
movable by means of the seal 641B within the interior walls of the
chamber 641. As described hereinabove, the spike also consists of
two paths, an air inlet 642 and a drug outlet 644. Once the vial
632 is inserted, pressurized air enters the vial 632 from an air
chamber 641 and forces the liquid drug 634 via a flexible tube 644A
to the injector system. The filling process for the injector system
in a preferred embodiment is preferably done under a maximum
pressure gradient of 0.3 bar. This includes a margin for example,
priming at an altitude of 5,500 feet and is the maximum expected
back pressure.
[0139] FIGS. 29A and 29B illustrate partial cutaway views of
another preferred embodiment of the drug transfer system 670 in
accordance with the present invention. The drug vial 672 containing
the liquid drug 674 is inserted into a cavity 676. A spike 678
provides air into the liquid drug vial 672 for pressurization of
the drug 674 and additionally the spike provides for an outlet for
the liquid drug to be delivered to a drug delivery system 680. The
drug transfer system 670 is in fluid communication with the liquid
drug vial 672 through a flexible tubing 682 and a needle 684. A
hydrophobic membrane 686 is disposed in the flexible tubing 682 to
prevent the transfer of air into the drug delivery system. This
hydrophobic membrane 686 prevents back flow. The air to pressurize
the liquid drug 674 is provided by air in the reservoir 675.
Further, a latch mechanism 688 secures the vial 672 to the
detachable delivery system 680 during a filling process.
[0140] Referring to FIG. 29A-1, an enlarged view of the interface
between the drug transfer system 670 and the detachable drug
delivery device 680 is illustrated. A hydrophobic membrane 692 is
disposed at the interface for blocking the flow of the drug once
the drug delivery device 680 is filled. An elastomeric cover 694 is
disposed around the needle 684 for protection against the needle
684. Tab 693 is pulled off to remove the hydrophobic membrane 692
prior to use of the device 680.
[0141] In operation the liquid drug vial 672 is pressed into the
cavity 676 which causes the air in the reservoir 675 to be
compressed and enter the liquid drug vial 672. Air is prevented
from leaking out of the cavity 675 by means of seal 685. The liquid
drug 674 is pressurized and delivered through the spike outlet 690.
Residual air from the air reservoir 675 is vented from an opening
in the latch mechanism 688 once the latch is disengaged from the
drug delivery device at the end of travel of the vial and
subsequent end of the transfer process.
[0142] Referring to FIGS. 30A and 30B, the two piece 696, 697
construction of the manifold in accordance with the present
invention is illustrated. The manifold is a biocompatible material
such as, for example, polycarbonate or acrylic or pvc molding
having a gas impermeable membrane 698 welded in the part 696. The
two pieces 696, 697 are ultrasonically welded together.
[0143] Referring to FIGS. 31A-31E, perspective views illustrate an
alternate preferred embodiment of a drug delivery system 700 in
accordance with the present invention. This particular embodiment
maybe used with the reconstituted drug delivery system and includes
two vials 702 and 704, a first containing a diluent and a second
containing a drug that needs to be reconstituted. In addition there
is a pressurizing system, such as a built-in cylinder 706 in fluid
communication with the diluent vial 702. The built-in
pressurization system such as the cylinder 706, is disposed between
the lyophilized drug vial and the diluent vial. A plunger 708 is
slidably received into the cylinder 706 to provide the necessary
air pressure to effect drug transfer. Air is pushed into the
diluent vial forcing the diluent from its vial into the lyophilized
drug compartment or vial 704. As discussed previously, a
hydrophilic membrane is used as an air separator to minimize or
preferably prevent the entry of air into the user's tissue. In use,
a diluent vial is inserted into the drug delivery system 700
followed by the insertion of a drug vial. The plunger 708 is pushed
downwards to pressurize the air in the cylinder 706 and deliver it
to the diluent vial 702. Once the diluent solution is pressurized
it is delivered to the drug vial 704 to reconstitute the drug.
Pressing the knob mechanism 710 displaces an injection needle which
is used to inject the reconstituted drug into a user tissue. The
depression of the knob mechanism and subsequent injection is
similar to that described earlier with regard to either the
straight needle assembly shown in FIG. 18 or the U-shaped needle
shown in FIGS. 11, 13 through 17.
[0144] Referring to FIGS. 31F and 31G, two preferred embodiments
711, 713 which provide a visual indication of device orientation
are illustrated. The vertical indicators 711, 713 are shown as
being disposed on the top of the plunger 708, however their
location can vary to provide appropriate visual indication. In the
first embodiment of the vertical indicator 711, a metal ball 714
rests upon a curved surface having visual having the vial
containing the reconstituted drug is essentially used as a filling
station by a detachable delivery device, for example, a standard
syringe or a pen type pump.
[0145] Referring to FIGS. 24A-24C a position independent injector
system 540 is illustrated. The drug 545 is reconstituted similar to
the description provided with respect to earlier systems such as
illustrated in FIG. 19F. After the drug has been reconstituted it
can be aspirated by a conventional standard syringe 542 for the
exact dose required. The accuracy using this method is about +/-
5%. The fluid level in the cavity 550 is controlled by adjusting
the pressure and geometry of the device 540. The needle is held in
place by the elastomeric septum or stopper 552. In use, once the
reconstituted drug is aspirated into the syringe 542 by moving
plunger 548 which moves the stopper 554 upwards allowing the
syringe 542 to be filled with the liquid drug, the syringe 542 is
removed from the drug delivery device 540. The accuracy of the
volume of the liquid drug delivered is determined by the scale on
the syringe. The user then injects the drug and disposes of the
syringe by one of several potential ways. One of the ways of
disposing the syringe is by attaching the syringe to the open
cavity 550 left in the drug delivery device 540. A second way is by
securing the needle 547 prior to disposing the syringe by locking
it with a piece of plastic tubing. The system 540 and procedure
used is free of air inclusions and does not require an air
separator. The syringe needle 547 is placed in a closed cavity
penetrating a septum 544 and thus allows for fluid communication
between the needle 547 and the reconstituted drug. The volume of
the closed cavity is designed to ensure the availability of the
liquid drug to the needle 547 under controlled pressurized
conditions. The position of the syringe piston 548 is fixed under
pressurized conditions and the dose is manually aspirated from the
syringe.
[0146] Referring to FIG. 25 an alternate preferred embodiment of
the drug delivery system 540 as described in FIGS. 24A-24C is
illustrated. The reconstitution stage is similar to the one
described with respect to FIGS. 24A-24C. However, the injector
system including an attachable delivery device is different. The
user dials or tunes the required dose using a pen type pump 560
that includes a dial 562 that is inserted into the indicators or
scale 712 thereon. The ball 714 is enclosed within a clear casing
712A. The positioning of the ball 714 in the middle of the scale is
an indication of vertical orientation. In the second embodiment 713
of the vertical indicator, an air bubble 716 disposed in a liquid
718 enclosed within a clear housing 718A is used as the visual,
indicator of orientation with respect to the scale 719. The
positioning of the air bubble 716 in the middle of the scale is an
indication of vertical orientation.
[0147] Referring to FIGS. 32A-32E, perspective views illustrate a
further alternate embodiment of the drug delivery system 720 in
particular a reconstitution and injection system, in accordance
with the present invention. In this embodiment the reconstitution
of the drug occurs by the mixing of the diluent solution with the
drug. A separate pressurization system for the diluent is not
required for this particular embodiment and can only be used with
low viscosity drugs. In use, the knob 730 is moved in a counter
clockwise direction to begin the reconstitution process of the drug
which opens a pathway connecting the diluent with the drug. The
knob 730 is turned from a non-use position (as indicated when
notches A and B align) to a ready to use position as indicated with
the alignment of notches B and C. At this point, the knob 730 may
be depressed and the solution injected. The internal pressure of
the diluent vial and gravity cause the diluent to transfer to the
vial containing the drug. Further movement of the knob or dial 730
activates an injection needle which interfaces with the user's
tissue to deliver the reconstituted drug. Again, the injection
assembly is similar to the embodiments shown in FIGS. 11,
13-17.
[0148] Referring to FIGS. 33A-33I, cutaway views of preferred
embodiments of the drug delivery system emphasizing the interlocks
disposed to provide for a safe system are illustrated. Referring in
particular to FIG. 33A and 33B, the interlocks as required during
shelf life of the drug delivery device 750 are illustrated. The end
of the cylinder 752 has a biasing lip 766 extending outward to
matingly fit with wall 758 and the lip must be flexible enough to
bend with the pressure of wall 758 when vials are inserted in the
assembly. During shelf life the cylinder 752 is secured by latch
754 and mating lip 756. This mating fit prevents the movement of
the movable cylinder 752 in the vertical direction prior to use. As
previously described, the cylinder 752 provides pressurized air to
the drug delivery system 750. The movement in the downward
direction of the cylinder 752 is minimized or preferably prevented
by holding the latches 754 and 756 on the wall 758. An upward
movement of the cylinder 752 is prevented by latch 754.
[0149] Referring to FIG. 33C, the next step includes the insertion
of the vials 760 and 762 into the device 750. Only after the
insertion of both vials 760, 762 is the cylinder 752 free to be
pushed in the vertical direction. The insertion of the vials forces
the lip 766 inward enabling it to clear the wall 758 and thus
enable the cylinder 752 to move downward. In addition, the latches
754 secure the vials in the device 750.
[0150] Referring to FIGS. 33D and 33E, the interlocks that play a
role once the cylinder 752 is pushed as illustrated. The cylinder
752 is pushed downward until the end of travel position and is
locked by the mating of lip 766 and interlock element 768. Again,
as described above with regard to pre-use, the lip 766 moves
downward and catches on element 768 and moves to a radially
expanded position which prevents the cylinder from travelling
upward again. A locking element 768 keeps the cylinder in the
bottomed out position. The element 768 is formed as a part of the
wall 758.
[0151] In the area where the drug solution is injected there is a
pushing member that moves in a relative perpendicular fashion to
the direction of travel by the cylinder. A ball 772 is positioned
prior to use within the housing to prevent depression of the member
776. When the cylinder is fully depressed, the lip 766, pushes a
member 770 which allows the ball 772 to drop into a groove 774
making the movement of the pushing member 776 possible only if the
device is in a vertical orientation.
[0152] Referring to FIGS. 33F and 33G, during the injection process
different interlock elements insure the safe use of the drug
delivery system. As the pushing member 776 is depressed, which is
only allowed if the drug delivery system 750 is in a vertical
orientation, the horns 778 spread the latch 780 which allows the
member 770 to press the ball 772 in the upward direction. Note the
pushing member 776 is already pushed to expose the needle 782.
[0153] Referring to FIGS. 33H and 33I, the interlocks during the
phase of disposing of the drug delivery device which follows the
injection phase are illustrated. The pushing member 776 is released
by the action of the spring 777 pushing the member 776. Since the
movement of the ball 772 was limited by the body of the member 776,
with the release of the member 776, the ball 772 can now move back
into the groove 774 as it is assisted by the pressure applied by
the rear shell latch 780. This locks the pushing member 776 into
position thereby preventing further use of the drug delivery device
750.
[0154] Referring to FIGS. 34A through 34D, a preferred embodiment
of the drug delivery device having an end of delivery indicator is
illustrated. As discussed previously with respect to preferred
embodiments of the drug delivery system of the present invention,
the drug delivery system is activated by pressurized gas, for
example, air. The air forces the drug to the injection site by
pressurizing the drug. A hydrophillic membrane minimizes and
preferably prevents the passage of air into the user's body. The
hydrophillic membrane is disposed in the drug path to the user's
tissue. Once wetted, the hydrophillic membrane allows liquid drug
to proceed into the user's tissue and stops the passage of air into
the user's tissue. In order to insure the effectiveness of the
membrane, the hydrophillic membrane has to become wetted. To
enhance the effectivity of the drug delivery device, a Hydrophobic
membrane is also positioned in the drug path. Referring to the
FIGS. 34A and 34B, an inlet 800 which provides the liquid drug 802
into a cavity 803 has both a hydrophobic membrane 806 and a
hydrophillic membrane 810 disposed therein. The hydrophobic
membrane 806 allows air to pass, but stops liquids. On the other
side of the cavity 803 the hydrophillic membrane 810 allows liquid
drug to pass while stopping the flow of gas. At one end of the
hydrophobic membrane 806 a flexible elastomeric diaphragm is
disposed that acts as an indicator once filled with gas, for
example, air. The membrane being flexible, once filled with air
gives an external indication for end of delivery. The presence of
air occurs only once the liquid drug has been delivered. It should
be noted that the hydrophillic membrane 810 is disposed close to
the injection site as it allows liquid to go through to the
injection site minimizing or preventing the flow of gas into the
user's tissue. FIG. 34D illustrates a manifold structure utilizing
the end of delivery indicator 804 built into the manifold. The
septum 814 surrounds a cavity containing the liquid drug. The
spikes 816 and 818 interface with the elastomeric stoppers of vials
containing a diluent and a medicament.
[0155] FIG. 35 graphically illustrates the delivery profile from a
high volume vial having no additional air pressure in the vial. The
profile illustrates pressure (in millibars) versus time (in
seconds). The initial pressure in the vial is in the order of about
300 millibars which decreases during the delivery process to
approximately 0 millibars at the end of delivery process. This is
in contrast to the pressure in a vial that initially contained
approximately 3 milliliters of air as illustrated with respect to
FIG. 33. As a result, there is no residual air pressure in the vial
once delivery is complete. The delivery process spanned a time
period of approximately 86.4 seconds.
[0156] FIG. 36 graphically illustrates delivery duration and
delivery pressure with respect to an air volume in a vial. Three
different profiles are illustrated with a first one 830 which is
indicative of the pressure (in millibars) before delivery, a second
profile 832 indicative of the residual pressure of the delivery and
a third profile 834 which is indicative of delivering 0.95 ml of a
liquid drug over a time span of about 8 seconds.
[0157] FIG. 37 is a graphical illustration of the delivery
parameters for an injection of a liquid drug having no additional
air in the vial. As delivery of the drug occurs, the pressurization
within the liquid vial decreases over the approximately 17 seconds
of delivery. These curves illustrate test results of the delivery
process of approximately 1 gram of liquid drug using a single drug
delivery device for the same time period.
[0158] FIG. 38 illustrates test results showing the air pressure
gradient on hydrophilic membranes used to minimize or preferably
prevent the entry of gas for example, air into the user's tissue.
The test results prove membrane safety to insure that the membrane
can withstand the pressures in the order of 2,700 millibars for a
time duration of about six minutes.
[0159] FIG. 39 graphically illustrates the performance of a drug
delivery device in accordance with the present invention. Three
delivery profiles 840, 842, 844 (in ml) vs. time (in seconds) are
illustrated for a reconstituted lyophilized drug delivery system.
The system includes a 0.45 micron pore size hydrophilic membrane to
minimize or preferably prevent the flow of gas into the user's
tissue. This particular pore size of the membrane provides an
adequate particle filter and also allows the shortest time to
deliver the drug to the user's tissue.
[0160] FIG. 40 is a flow chart that describes the methods for
delivery of a lyophilized drug in accordance with the present
invention. The methods include the step 899 of inserting the drug
and diluent containers into the drug delivery device. Further per
step 900, the method includes activating a pressurized air source
which in turn is followed by the step 902 of pressurizing a diluent
solution in a diluent vial. As discussed with respect to FIGS.
19A-19F, the pressurizing can be provided by subsystems which
include but are not limited to a compressed air supply, a chemical
gas generator, a collapsible volume air supply, a standard syringe
or cylinder.
[0161] The methods further include the step 904 of delivering the
pressurized diluent solution to the lyophilized drug vial. The
lyophilized drug is reconstituted per step 906 as a result of the
mixing of the diluent with the lyophilized drug. The methods
further include the step 908 of providing the liquid drug to an
injector system or transferring the liquid drug to a detachable
delivery device. The liquid drug is then injected into a user's
tissue per step 910. The injection needle is then moved to a safe
storage position per step 912.
[0162] FIG. 41 is a flow chart that describes the methods for
delivering a liquid medicament in accordance with the present
invention. The methods include the step 913 of inserting a drug
container such as a vial into the drug delivery system. Further,
per step 914 the method includes activating a pressurized air
source for low viscosity drugs. It should be noted that for drugs
with a high level of viscosity no pressurization may be required.
The method then includes the step 916 of pressurizing the standard
drug vial. The pressurized liquid drug is transferred to a drug
delivery system such as an injector system, or detachable delivery
devices per step 918. The liquid drug is then injected into the
tissue of a user per step 920. The method further includes the step
922 of retracting the injector into a safe storage position.
[0163] 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 (and mimetic
thereof), antigens, vaccines, hormones, analgesics, anti-migraine
agents, anti-coagulant agents, medications directed to the
treatment of diseases and conditions of the central nervous system,
narcotic antagonists, immunosuppressants, agents used in the
treatment of AIDS, chelating agents, anti-anginal agents,
chemotherapy agents, sedatives, anti-neoplastics, prostaglandins,
antidiuretic agents and DNA or DNA/RNA molecules to support gene
therapy.
[0164] Typical drugs include peptides, proteins or hormones (or any
mimetic or analogues or any thereof) such as insulin, calcitonin,
calcitonin gene regulating protein, atrial natriuretic protein,
colony stimulating factor, betaseron, erythropoietin (EPO),
interferons such as .alpha., .beta. or .gamma. 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 VIII, interleukins such as interleukin-2, and
analogues or antagonists thereof, such as IL-1ra; analgesics such
as fentanyl, sufentanil, butorphanol, buprenorphine, 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, metoclopramide, and
analogues thereof; cardiovacular agents, anti-hypertensive agents
and vasodilators such as diltiazem, clonidine, nifedipine,
verapamil, isosorbide-5-monotritate, organic nitrates, agents used
in treatment of heart disorders, and analogues thereof; sedatives
such as benzodiazepines, phenothiazines, and analogues thereof;
chelating agents such as defroxanune, and analogues thereof;
anti-diuretic agents such as desmopressin, vasopressin, and
analogues thereof; anti-anginal agents such as fluorouracil,
bleomycin, 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, treatments for attention deficit disorder,
methylphenidate, fluvoxamine, bisoprolol, tacrolimus, sacrolimus
and cyclosporin.
[0165] 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
spirit and scope of the invention as defined by the appended
claims. For example, some of the features of the position
independence can be used in connection with reconstitution
combination systems, transfer systems or injection systems.
Likewise interlock features may be used with any of the
aforementioned systems.
* * * * *