U.S. patent application number 14/751778 was filed with the patent office on 2015-10-15 for apparatuses, systems, and methods for filling a container with a liquid drug.
The applicant listed for this patent is Roche Diagnostics International AG. Invention is credited to Tilo Callenbach, Christian Classen, Maurice Ducret, Roger Haenggi, Christoph Huwiler, Florian Kuhni, Andreas Lischewski, Franco Moia, Marcel Mueller, Urs Rindlisbacher, Joerg Wermelinger, Louis Widmer.
Application Number | 20150290082 14/751778 |
Document ID | / |
Family ID | 42109836 |
Filed Date | 2015-10-15 |
United States Patent
Application |
20150290082 |
Kind Code |
A1 |
Haenggi; Roger ; et
al. |
October 15, 2015 |
APPARATUSES, SYSTEMS, AND METHODS FOR FILLING A CONTAINER WITH A
LIQUID DRUG
Abstract
In one embodiment, a method of filling a container with a liquid
drug from a drug reservoir may include: a) connecting a container
and a drug reservoir with a cannula such that the drug reservoir
and the container fluidically communicate with each other via the
cannula, while being hermetically sealed; b) reducing a first
volume contained within the container to displace a gaseous medium
from the first volume of the container via the cannula into a
second volume contained within the drug reservoir; c) increasing
the first volume of the container to displace the liquid drug from
the second volume of the drug reservoir into the first volume of
the container to fill the container; and d) disconnecting the
container and the drug reservoir. Before performing action d),
action b) and action c) can be successively performed more than
once to stepwise increase an amount of liquid drug displaced.
Inventors: |
Haenggi; Roger; (Nunningen,
CH) ; Rindlisbacher; Urs; (Thoerishaus, CH) ;
Moia; Franco; (Frenkendorf, CH) ; Mueller;
Marcel; (Therwil, CH) ; Huwiler; Christoph;
(Baar, CH) ; Kuhni; Florian; (Rohrbach, CH)
; Wermelinger; Joerg; (Schaffhausen, CH) ;
Lischewski; Andreas; (Loehningen, CH) ; Classen;
Christian; (Tengen, DE) ; Callenbach; Tilo;
(Donaueschingen, DE) ; Widmer; Louis; (Ulisbach,
CH) ; Ducret; Maurice; (Burgdorf, CH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Roche Diagnostics International AG |
Rotkreuz |
|
CH |
|
|
Family ID: |
42109836 |
Appl. No.: |
14/751778 |
Filed: |
June 26, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13492008 |
Jun 8, 2012 |
9089647 |
|
|
14751778 |
|
|
|
|
Current U.S.
Class: |
141/27 |
Current CPC
Class: |
A61J 1/2048 20150501;
A61J 1/201 20150501; A61J 1/20 20130101; A61M 5/24 20130101; B65B
3/003 20130101; A61J 1/2096 20130101 |
International
Class: |
A61J 1/20 20060101
A61J001/20; B65B 3/00 20060101 B65B003/00 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 9, 2009 |
EP |
09 405 222.2 |
Dec 7, 2010 |
EP |
PCT/EP2010/007423 |
Claims
1. An apparatus for filling an ampoule with a drug from a
reservoir, wherein the ampoule is formed by a container and
comprises a piston arranged therein in a displaceable manner, the
apparatus comprising: a housing; a piston rod that is moveable
relative to the housing along a longitudinal axis of the piston
rod, the piston rod comprising a coupling member, wherein, when the
coupling member couples the piston rod to the piston of the
ampoule, such that a positive locking or a non-positive locking
occurs between the piston rod and the piston along both directions
of the longitudinal axis; and a drive that actuates the piston rod
along the longitudinal axis, wherein, upon activation of the drive,
the piston rod is actuated back and forth along the longitudinal
axis a plurality of times.
2. The apparatus according to claim 1, further comprising a holding
member that, when the coupling member couples the piston rod to the
piston of the ampoule, holds the container of the ampoule such
that, while the drive is activated, a positive connection and/or a
frictional connection is maintained between the container of the
ampoule and the housing along both directions of the longitudinal
axis.
3. The apparatus of claim 1, wherein the container is a syringe
type container, or a bag type container.
4. The apparatus of claim 1 wherein the drive is configured to be
controlled by an electric control, an electronic control, or a
mechanical control.
5. The apparatus of claim 1 wherein the drive is configured to be
controlled by electric motors in combination with gears and/or
linkage arrangements.
6. The apparatus of claim 1 wherein the drive is configured to be
controlled by hydraulic or pneumatic drive arrangements,
7. The apparatus of claim 1 wherein the drive is configured to be
controlled by spring force driven mechanical actuators.
8. An apparatus for filling an ampoule with a liquid drug from a
drug reservoir, wherein the ampoule is formed by a container and
comprises a piston arranged therein in displaceable manner, the
apparatus comprising: a housing; a piston rod that is fixed with
respect to the housing, the piston rod comprising a coupling member
wherein, when the coupling member of the piston rod is coupled to
the piston of the ampoule a positive locking or a non positive
locking occurs between the piston rod and the piston in both
directions of a longitudinal axis; a holding member that, when the
coupling member couples the piston rod to the piston of the
ampoule, holds the container of the ampoule such that the holding
member is moveable relative to the piston rod along the
longitudinal axis of the piston rod; and a drive for moving the
holding member along the longitudinal axis of the piston rod,
wherein, at least while the drive is activated, a positive locking
and/or frictional locking is made between the container of the
ampoule and the holding member in both directions of the
longitudinal axis of the piston rod, and wherein the drive , upon
being activated, actuates the holding member back and forth along
the longitudinal axis of the piston rod a plurality of times.
9. The apparatus of claim 8, wherein the drive actuates the holding
member back and forth at least three times each.
10. The apparatus of claim 8 wherein the drive is configured to
oscillate the piston rod.
11. The apparatus of claim 8 wherein the drive is configured to
oscillate the holding member.
12. The apparatus of claim 8 wherein the drive is configured to be
controlled by spring force driven mechanical actuators.
13. The apparatus of claim 12 further comprising a viscous damping
element utilized to control the spring
14. The apparatus of claim 13 further comprising a knee lever
arrangement, wherein the energy of the spring is transmitted to the
knee lever arrangement via the viscous damping element.
15. A system for extracting a liquid drug from a drug reservoir,
the system comprising: an ampoule formed by a container, wherein
the ampoule comprises a piston arranged therein in displaceable
manner and the container and the piston bound a changeable volume
of the ampoule; a drug reservoir hermetically sealed to the
ampoule, wherein the drug reservoir contains an interior volume
having a liquid drug contained therein; a cannula in fluidic
communication with the changeable volume of the ampoule and the
interior volume of the drug reservoir; and a drive for causing
relative motion along a longitudinal axis between the container and
the piston of the ampoule, wherein the drive is actuated to: a)
reduce the changeable volume of the ampoule such that a gaseous
medium is displaced from the changeable volume into the interior
volume of the drug reservoir; and b) increase the changeable volume
of the ampoule such that the liquid drug is displaced from the
interior volume of the drug reservoir drug reservoir into the
changeable volume of the ampoule, wherein action a) and action b)
are successively performed more than once to stepwise increase an
amount of liquid drug displaced to the changeable volume of the
ampoule.
16. The system of claim 15, wherein the cannula is mounted to an
opening of a cavity in a housing of the system by a bayonet joint.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 13/492,008 filed Jun. 8, 2012, which is a continuation of
International Application No. PCT/EP2010/007423 filed Dec. 7, 2010,
which claims priority to EP 09 405 222.2 filed on Dec. 9, 2009. The
contents of each of these applications are hereby incorporated by
reference in their entirety into this disclosure.
TECHNICAL FIELD
[0002] The embodiments of the present disclosure relate generally
to filling apparatuses, systems, and methods thereof, to methods of
filling containers with a liquid drug from a drug reservoir, to
apparatuses for use in a method of filling a container with a
liquid drug from a drug reservoir , and to systems for extracting a
liquid drug from a drug reservoir.
BACKGROUND
[0003] In the medical field, liquid drugs, such as insulin, can be
supplied from a reservoir container that contains an amount of the
liquid drug. The liquid drug can be transferred from the reservoir
container to a container that receives a single dose of the drug,
or an amount of the drug, which is suitable for a limited time of
therapy of a patient. For example, doctors and nurses can draw
medications from vials into syringes in order to inject the
medications into patients. Patients can also inject themselves in a
similar manner. For example, diabetes can be treated with the use
of an insulin pump that supplies insulin from insulin ampoules. The
insulin ampoules can be purchased without being filled with
medication, i.e., as empty ampoules. Accordingly, patients may fill
the empty ampoules from a vial containing an amount of insulin
prior to use.
[0004] Some of the patients that fill the empty ampoules may suffer
from movement disorders due to their disease and/or age. Thus, some
patients may have difficulties in safely handling standard syringe
assemblies or the like. Filling systems have been developed to
assist with the process of filling ampoules from vials.
[0005] One example system is shown and described in EP 1 820 485
A1. The system provides a number of empty, single use ampoules made
of plastic. Each of the ampoules can be formed by a container and a
piston arranged therein in displaceable manner. A multi use piston
rod can have a thread arranged at one end of the piston rod that is
coupled to the piston of the ampoules. At the end of the ampoule
facing away from the end of the ampoule where the piston rod can be
coupled to the piston, each ampoule can include a connector with a
cannula. The ampoule can be connected to a commercially available
vial in via the connector such that the ampoule and the vial
fluidically communicate with each other via the cannula, while the
ampoule and the vial are structurally connected with each
other.
[0006] One of the ampoules can be filled with insulin from a vial.
Specifically, the piston rod is connected with the piston of the
ampoule by screwing it with its threaded end into a corresponding
thread formed in the piston. After that, the piston is pulled back
with the piston rod, which can cause the inside of the ampoule is
filled with air. The ampoule can then be coupled with the connector
facing downwards to a vial. Next, the piston can be pushed into the
container of the ampoule with the piston rod in order to displace
the air contained inside the ampoule into the vial, and create an
overpressure in the vial. In this state, the assembly can be turned
upside down such that the vial is now on top. Then, the piston rod
can be released. The overpressure in the vial can cause insulin to
flow through the connector into the ampoule, and the piston to be
displaced. Once the overpressure has dissipated, the displacement
of the piston is stopped. The piston can be displaced until it
reaches its original position via the piston rod to draw additional
insulin into the ampoule. In this state the vial, the connector and
the piston rod can be removed from the ampoule, which leaves the
ampoule full of insulin and ready for use.
[0007] Accordingly, the example system can be utilized for filling
ampoules from vials without needles. Thus, the risk of accidental
needle sticks can be reduced compared filling a syringe
arrangement. However, proper use of the system is required to avoid
formation of foam and air bubbles within the ampoule. Furthermore,
when the ampoule is filled with insulin from a smaller pen
cartridge instead of from a vial, there is the risk that insulin
may be spilled. Specifically, when the piston is fully pushed into
the container of the ampoule with the piston rod, a piston of the
pen cartridge can be pushed out of the cartridge causing the
insulin contained therein to be spilled.
[0008] Another example of an ampoule filling system having similar
functionality and shortcomings is disclosed in US 2002/0189712
A1.
[0009] Accordingly, additional methods, apparatuses and systems for
filling containers with liquid drugs are needed.
SUMMARY
[0010] It is against the above background that the present
disclosure is provided.
[0011] In one embodiment, a method of filling a container with a
liquid drug from a drug reservoir may include: a) connecting the
container and the drug reservoir with a cannula such that the drug
reservoir and the container fluidically communicate with each other
via the cannula, while being hermetically sealed; b) reducing a
first volume contained within the container to displace a gaseous
medium from the first volume of the container via the cannula into
a second volume contained within the drug reservoir; c) increasing
the first volume of the container to displace the liquid drug from
the second volume of the drug reservoir into the first volume of
the container to fill the container; and d) disconnecting the
container and the drug reservoir. Before performing action d),
action b) and action c) can be successively performed more than
once to stepwise increase an amount of liquid drug displaced to the
first volume of the container.
[0012] In another embodiment, an apparatus for filling an ampoule
with a drug from a reservoir may include a housing, a piston rod,
and a drive. The ampoule can be formed by a container and may
include a piston arranged therein in a displaceable manner. The
piston rod that can be moveable relative to the housing along a
longitudinal axis of the piston rod. The piston rod may include a
coupling member. When the coupling member couples the piston rod to
the piston of the ampoule, a positive locking or a non-positive
locking can occur between the piston rod and the piston along both
directions of the longitudinal axis. The drive can actuate the
piston rod along the longitudinal axis. Upon activation of the
drive, the piston rod can be actuated back and forth along the
longitudinal axis several times.
[0013] In yet another embodiment, an apparatus for filling an
ampoule with a liquid drug from a drug reservoir may include a
housing, a piston rod, a holding member, and a drive. The ampoule
can be formed by a container and may include a piston arranged
therein in displaceable manner. The piston rod that can be fixed
with respect to the housing. The piston rod may include a coupling
member. When the coupling member of the piston rod is coupled to
the piston of the ampoule, a positive locking or a non-positive
locking can occur between the piston rod and the piston in both
directions of a longitudinal axis. When the coupling member couples
the piston rod to the piston of the ampoule, the coupling member
can hold the container of the ampoule such that the holding member
is moveable relative to the piston rod along the longitudinal axis
of the piston rod. The drive can move the holding member along the
longitudinal axis of the piston rod. At least while the drive is
activated, a positive locking and/or frictional locking can be made
between the container of the ampoule and the holding member in both
directions of the longitudinal axis of the piston rod. Upon being
activated, the drive can actuate the holding member back and forth
along the longitudinal axis of the piston rod several times.
[0014] In a further embodiment, a system for extracting a liquid
drug from a drug reservoir may include an ampoule, a drug
reservoir, a cannula, and a drive. The ampoule can be formed by a
container. The ampoule may include a piston arranged therein in a
displaceable manner. The container and the piston can bound a
changeable volume of the ampoule. The drug reservoir can be
hermetically sealed to the ampoule. The drug reservoir can contain
an interior volume having a liquid drug contained therein. The
cannula can be in fluidic communication with the changeable volume
of the ampoule and the interior volume of the drug reservoir. The
drive can cause relative motion along a longitudinal axis between
the container and the piston of the ampoule. The drive can be
actuated to: a) reduce the changeable volume of the ampoule such
that a gaseous medium is displaced from the changeable volume into
the interior volume of the drug reservoir; and b) increase the
changeable volume of the ampoule such that the liquid drug is
displaced from the interior volume of the drug reservoir into the
changeable volume of the ampoule. Action a) and action b) can be
successively performed more than once to stepwise increase an
amount of liquid drug displaced to the changeable volume of the
ampoule.
[0015] These and other features and advantages of the present
disclosure will be more fully understood from the following
detailed description taken together with the accompanying
claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The following detailed description of the embodiments of the
present disclosure can be best understood when read in conjunction
with the following drawings, where like structure is indicated with
like reference numerals and in which:
[0017] FIG. 1 schematically depicts a side view of an ampoule
filling system according to one or more embodiments shown and
described herein;
[0018] FIGS. 2a and 2b each schematically depict an arrangement for
performing methods according to one or more embodiments shown and
described herein;
[0019] FIG. 3 schematically depicts a method according to one or
more embodiments shown and described herein;
[0020] FIGS. 4a to 4c schematically depict an apparatus according
to one or more embodiments shown and described herein;
[0021] FIGS. 5a and 5b schematically depict an apparatus according
to one or more embodiments shown and described herein;
[0022] FIGS. 6a graphically depicts system pressures and the
Reynolds number in the cannula during performance of methods
according to one or more embodiments shown and described herein
using an embodiment of the apparatus schematically depicted in
FIGS. 4a to 4c;
[0023] FIG. 6b graphically depicts system pressures and the
Reynolds number in the cannula during performance of methods
according to one or more embodiments shown and described herein
using an embodiment of the apparatus schematically depicted in
FIGS. 5a to 5b; and
[0024] FIG. 7 schematically depicts a method according to one or
more embodiments shown and described herein.
DETAILED DESCRIPTION
[0025] For the purposes of promoting an understanding of the
principles of the present disclosure, reference will now be made to
the embodiments illustrated in the drawings, and specific language
will be used to describe the same. It will nevertheless be
understood that no limitation of the scope of this disclosure is
thereby intended.
[0026] According to the embodiments described herein, methods for
filling a container with a liquid drug, like e.g. a liquid
painkiller or insulin, from a drug reservoir are provided.
Referring now to FIG. 7, in at least one exemplary embodiment, a
method 100 may include one or more of the following actions:
[0027] At process 102, the following action can be performed--a)
connecting the container and the drug reservoir with a cannula such
that the inside of the drug reservoir and the inside of the
container fluidically communicate with each other via a cannula,
while being hermetically sealed against the outside;
[0028] At process 104, the following action can be performed--b)
reducing the volume of the inside of the container, thereby
displacing a gaseous medium from the inside of the container via
the cannula into the inside of the drug reservoir;
[0029] At process 106, the following action can be performed--c)
increasing the volume of the inside of the container, thereby
displacing liquid drug from the inside of the drug reservoir into
the inside of the container for filling the container; and
[0030] At process 108, the following action can be performed--d)
disconnecting the filled container and the liquid drug
reservoir.
[0031] According to at least one embodiment of the method for
filling a container of the present disclosure, actions b) and c)
can be successively performed more than once before action
(generally indicated in FIG. 7 by dashed arrow line) d) is
performed. Accordingly, in at least one embodiment the amount of
liquid drug contained inside the container can be increased
stepwise before the container and the liquid drug reservoir are
disconnected.
[0032] It is noted that, the maximum pressure inside the liquid
drug reservoir can be reduced significantly during the filling
process of the container. Thus, the risk of formation of foam
and/or air bubbles within the liquid drug that is filled into the
container can be reduced. Furthermore, when the liquid drug
reservoir is a pen cartridge, the risk that the piston of the pen
cartridge will be pushed out of the cartridge, which can lead to
the liquid drug contained therein being spilled, can be
reduced.
[0033] The container that is filled, according to at least one
embodiment of the present disclosure, can be at least one of a
syringe type container, an ampoule, or a bag type container.
Syringe type containers may be formed from a substantially rigid
container body having a piston arranged therein in displaceable
manner, which defines a changeable volume. The volume contained
within the container can be altered through displacing the piston.
An ampoule can be a syringe type container that, for example, has a
septum or a Luer-type connector, at a front face. A bag type
container can have a collapsible container body and connectors for
establishing fluidic communication to the interior of the
container. While the container types described herein are suitable
for use the methods of the present disclosure, it is noted that
additional container types can find favorable utility with the
embodiments described herein.
[0034] According to the embodiments of the methods described
herein, actions b) and c) can be successively performed at least
three times before performing action d) such as, for example, at
least five times in one embodiment, at least eight times in another
embodiment or at least ten times in yet another embodiment.
Accordingly, the container can be filled in several small steps,
which may further reduce the risk of foam and/or air bubble
formation within the liquid drug transferred to the container.
Moreover, the maximum pressure in the liquid drug reservoir can be
kept below critical values, especially for pen cartridges, which
can reduce the risk of both foam and/or air bubble formation and
the piston being pushed out from the pen cartridge.
[0035] In at least one embodiment of the present disclosure, the
full capacity of the container can be filled. For example, in one
exemplary method actions b) and c) can be successively performed
until the container is substantially filled with the liquid drug,
i.e., until the container contains a design capacity of liquid
drug.
[0036] In one embodiment of the method, action d) can be performed
with a container having an inside volume that is about equal to the
inside volume it had when action b) was commenced for the first
time. Accordingly, when filling an ampoule, an empty ampoule can
initially be connected to the liquid drug reservoir with a piston
of the ampoule in a desired position. The filled ampoule can be
disconnected from the liquid drug reservoir with the piston
positioned in substantially the same position within the container
body.
[0037] In at least one embodiment of the method, before action c)
is performed for the first time, action b) can be performed or
before action b) is performed for the first time, action c) can be
performed. Further, in some embodiments, the respective order of
actions b) and c) can depend upon the total pressure level in the
filling system.
[0038] The volume of the inside of the container can in at least
one embodiment be reduced in action b) incrementally from the
maximum volume in several small steps. For example, the reduction
may be less than one half of the maximum volume of the inside of
the container, less than one fourth of the maximum volume of the
inside of the container or less than one tenth of the maximum
volume of the inside of the container. Accordingly, several small
filling steps can result when filling the container until it
contains its design volume of liquid drug.
[0039] The inside of the container can in at least one embodiment
be increased in action c) proceeding action b) in an amount that is
substantially identical to the reduction in volume of action b).
Accordingly, the pressure increase generated inside the filling
system when performing action b) can be subsequently revoked in
action c). Thus, a stepwise increase of the pressure in the system
can be avoided. As is noted above, when the liquid drug reservoir
is provided as a pen cartridge, a stepwise increase in filling
system pressure can cause the piston of a pen cartridge to be
pushed out of the cartridge and the liquid drug contained therein
to be spilled.
[0040] In further embodiments of the method of the present
disclosure, action b) can be performed more rapidly than action c)
that immediately proceeds and/or precedes the action b).
Alternatively, action c) can be performed more rapidly than action
b) that immediately precedes the action c). The type of liquid
drug, type of container to be filled and the dimensions of the
filing system can have an impact on the relative speed of actions
b) and c). Specifically, a relatively fast action b) may be
preferable with regard to a short filling time, while a relatively
fast action c) may be preferable with regard to prevention of foam
or bubble formation.
[0041] In at least one embodiment of the present disclosure, the
speed of the increase in volume of the inside of the container in
action c) is substantially constant. Accordingly, peaks in the flow
velocity of the flow of liquid drug through the cannula can be
avoided.
[0042] The volume of the inside of the container can be increased
in action c) such that the flow velocity of the liquid drug in the
cannula does not exceed a predetermined rate. The predetermined
rate can be selected in at least one embodiment of the method of
the present disclosure, such that the flow velocity in the cannula
does not exceed about 2 m/s, does not exceed about 1.4 m/s, does
not exceed about 1.0 m/s or does not exceed about 0.5 m/s.
Alternatively or additionally, the increase in the volume of the
inside of the container during exemplary action c) can be
controlled based upon the Reynolds number of the flow of liquid
drug in the cannula. For example, the change in volume can be
limited such that the Reynolds number does not exceed a value where
the flow transitions from laminar flow to turbulent flow. Moreover,
the reduction of the volume of the inside of the container during
action b) can be controlled based upon the pressure in the drug
reservoir. For example, reduction in volume can be controlled such
that the pressure in the drug reservoir does not exceed 2000 mbar,
does not exceed 1000 mbar, or does not exceed 500 mbar.
[0043] Without being bound to theory, it is believed that the
limits on volume change, described above, can reduce the risk of
foam formation and/or bubble formation in the liquid drug filled
into the container.
[0044] When, after performing action d), the volume contained
within the container may include liquid drug with trapped gases. In
an exemplary action e) the volume contained within the container
may be alternately increased and reduced several times to release
gases that might be present in the liquid drug.
[0045] In one embodiment, at least during actions b) and c), the
drug reservoir can be arranged above the container. Accordingly,
gravity forces can assist the filling process.
[0046] According to the embodiments described herein, actions b)
and c) and, where applicable, action e) may be performed by a drive
actuator. The drive actuator can be controlled by an electric
control, an electronic control or mechanical control. Examples for
such drive actuators include electric motors in combination with
gears and/or linkage arrangements, hydraulic or pneumatic drive
arrangements, spring force driven mechanical actuators, or the
like. Alternatively, the actions may be performed manually.
[0047] A connector element can provide, in at least one embodiment,
a cannula for providing a fluidic connection between the drug
reservoir and the container. When performing action a), the drug
reservoir and the container can be structurally connected with each
other via the connector element. Accordingly, the connector element
can contemporaneously provide a mechanical connection and a fluidic
connection between the reservoir and the connector. Furthermore,
the end of the cannula can be located within a cavity formed in the
connector. Thus, the risk of unintentional contact between a
cannula end and another object (e.g., a user) can be significantly
reduced.
[0048] In at least one embodiment of the method of the present
disclosure, after performing action d), the connector element can
be separated from the drug reservoir and from the container.
Accordingly, the embodiments described herein can be provided with
disposable connector elements. Without being bound to theory, it is
believed that the use of a new connector for each filling process
can reduce the risk of contamination of the liquid drug in the
liquid drug reservoir and in the container.
[0049] According to the embodiments described herein, an apparatus
can be used for filling an ampoule with a liquid drug such as,
e.g., insulin, from a liquid drug reservoir. In at least one
embodiment, the apparatus can be suitable for use with one or more
of the methods described herein. An ampoule to be filled can
include a container and a displaceable piston arranged therein. The
apparatus may include a housing, a piston rod for driving the
piston of the ampoule and a drive for driving the piston rod.
[0050] The piston rod can in at least one embodiment be moveable
relative to the housing along a longitudinal axis of the housing.
Further, the piston rod can include a coupling member for coupling
the piston rod to the piston of the ampoule such that, in both
directions of the longitudinal axis of the piston rod, a positive
or a non-positive locking between can be maintained between the
piston rod and the piston. Suitable coupling members include, for
example, threaded connections, bayonet connections, snap in
connections, magnet couplings, frictional connections (e.g., cone
shaped frictional connections), or the like.
[0051] The drive in at least one embodiment can actuate the piston
rod along the longitudinal axis. The drive may be operable to
oscillate the piston rod back and forth along the longitudinal axis
several times.
[0052] In an exemplary embodiment, the apparatus can be configured
for fully automated filling. In one embodiment, the apparatus may
include a holding member that holds the container of the ampoule
such that, at least while the drive is activated, a positive
connection and/or a frictional connection is maintained between the
container of the ampoule and the housing in both directions of the
longitudinal axis.
[0053] As is noted above, the ampoule to be filled may include a
container and a displaceable piston arranged therein to define a
changeable volume. In at least one embodiment, the apparatus may
include a housing, a piston rod that couples to the piston of the
ampoule, a holding member for holding the container of the ampoule
and a drive for actuating the holding member.
[0054] The piston rod can in at least one embodiment be fixed
within the housing of the apparatus. The piston rod can include a
coupling member for coupling the piston rod to the piston of the
ampoule such that a positive or a non-positive locking between the
piston rod and the piston is maintained in both directions of
movement of the piston rod along the longitudinal axis. Suitable
coupling members include, for example, threaded connections,
bayonet connections, snap in connections, magnet couplings,
frictional connections (e.g., a cone), or the like.
[0055] The holding member can be moveable relative to the piston
rod along the longitudinal axis of the piston rod. Further, the
holding member can be adapted for holding the container of the
ampoule such that, at least while the drive is activated, a
positive and/or a frictional locking between the container of the
ampoule and holding member is maintained in both directions of the
longitudinal axis of the piston rod there exists.
[0056] According to the embodiments described herein, the maximum
pressure inside the liquid drug reservoir can be reduced during the
filling process of the ampoule. Thus, the risk of a formation of
foam and/or air bubbles within the filled container can be reduced.
Furthermore, when the liquid drug reservoir is a pen cartridge, the
risk of pushing the piston of the pen cartridge out of the
cartridge and of spilling the liquid drug contained therein can be
reduced.
[0057] In some embodiments of the apparatus, the drive can be
oscillated such that drive moves back and forth. For example, the
drive can oscillate a movable piston rod or a movable holding
member that holds the container along said longitudinal axis of the
piston rod. In some embodiments, the drive can oscillate at least
three times such as, for example, at least five times in one
embodiment, at least eight times in another embodiment or at least
ten times in yet another embodiment. Accordingly, filling can take
place in several small steps and the pressure within the filling
system can be kept at a moderate level.
[0058] The apparatuses described herein may further include a
sensor for detecting a filling level of an ampoule to be filled.
Specifically, the sensor can detect a filled ampoule and emit a
signal indicative of a filled ampoule such as, for example,
acoustical signal, optical signal, electrical signal or a
combination thereof.
[0059] Accordingly, the sensor can provide a signal that controls
the drive (i.e., activates or deactivates). Thus, the sensor and
the drive can cooperate to automatically fill an ampoule to a
specific filling level.
[0060] Moreover, the at least one embodiment of the apparatus can
be configured such that drive starts at an initial position upon
activation and returns to the initial position upon deactivation.
For example, upon deactivation of the drive, the movable piston rod
can be positioned in the same position relative to the housing in
which it had been positioned before the activation of the drive.
Similarly, the holding member can be positioned in the same
position relative to the housing in which it had been before the
activation of the drive means.
[0061] In further embodiments, the apparatus can be designed such
that the drive starts at the initial position prior to activation.
The movable piston rod or the holding member can be positioned at
the initial position by the drive. The initial position can be set
such that an ampoule has a maximum interior volume with respect to
a stroke when the drive is at the initial position and the ampoule
is coupled to the piston rod and held by the holding member.
Alternatively, the initial position can be set such that an ampoule
has, with respect to the stroke, a minimum inside volume when the
drive is at the initial position and the ampoule is coupled to the
piston rod and held by the holding member. Depending on the total
pressure level that is acceptable in the filling system, the one or
the other alternative might be more preferable.
[0062] Furthermore, the drive can be configured such that the back
and forth movement of a stroke of the drive are substantially
identical, i.e., during a single stroke, the amount of reduction of
the changeable volume of the container can be about equal to the
amount of increase. Accordingly, the drive can cause relative
motion between the piston rod and the container. Specifically, the
drive can actuate the movable piston rod or the moveable holding
member along a stroke having substantially identical back and forth
movement. Accordingly, the pressure inside the filling system can
be increased step wise, which could mitigate spilling of liquid
drug contained within reservoirs such as pen cartridges.
[0063] In some embodiments, the drive can be designed such that
different portions of a stroke are performed at different speeds.
For example, the forth movement of the movable piston rod or the
movable holding member can be actuated more rapidly than the back
movement of the same stroke. Although the type of liquid drug, the
type of container and the dimensions of the filling system may
impact filling speed, a more rapid forth movement may shorten
filling time. Alternatively, the back movement of the movable
piston rod or the movable holding member can be actuated more
rapidly than the forth movement of the same stroke. Although the
type of liquid drug, the type of container to be filled and the
dimensions of the filling system may impact foam or bubble
formation, a more rapid back movement may reduce the risk of foam
or bubble formation.
[0064] Moreover, the drive can be designed such that the speed of
the back movement of the drive is substantially constant.
Accordingly, the movable piston rod the movable holding member can
be moved in the back direction at a substantially constant speed.
The substantially constant speed in the back direction can mitigate
undesired peaks in the flow velocity of the flow of liquid drug
from the liquid drug reservoir to the ampoule, which may be
desirable if the fluidic connection is established by a
cannula.
[0065] According to the embodiments described herein, the drive may
comprise a drive actuator that is controlled by electric controls,
electronic controls or mechanical controls. The drive actuator can
be any suitable actuator such as, for example, electric motors in
combination with gears and/or linkage arrangements, hydraulic or
pneumatic drive arrangements, spring force driven mechanical
actuators, or the like.
[0066] Embodiments of the present disclosure further relate to
systems for extracting a liquid drug, such as e.g. insulin, from a
drug reservoir. In some embodiments, the systems are suitable for
use in the methods described herein. The systems may include one or
more of the apparatuses described herein and an ampoule comprising
a container with a displaceable piston arranged therein. The
ampoule can be coupled by the displaceable piston to the coupling
member of the piston rod. The ampoule can be held or be held and
moved by the holding member that holds the container. With such a
system, ampoules can be filled with a liquid drug from a liquid
drug reservoir in a convenient manner.
[0067] In at least one embodiment of the present disclosure, the
ampoule and the drive can be operably coupled such that the drive
reduces the interior volume of the ampoule by displacing the
movable piston rod or the movable holding member in a forth motion.
In some embodiments, the drive can be configured to reduce the
volume of the inside of the ampoule with the stroke of the forth
movement drive by less than about one half of the maximum volume of
the inside of the ampoule, by less than about one fourth of the
maximum volume of the inside of the ampoule, or by less than one
tenth of the maximum volume of the inside of the ampoule in various
embodiments. Accordingly, the container can be filled with several
small filling steps and the maximum pressure in the filling system
is kept low compared to systems that decrease greater amounts of
the maximum volume inside the ampoule. The pressure in the liquid
drug reservoir can be kept below critical values for pen cartridges
and, when the ampoule and the liquid drug reservoir are fluidically
interconnected via a cannula, foam and air bubble formation can be
mitigated within the liquid drug that is filled into the
container.
[0068] Exemplary embodiments of the system may further comprise a
drug reservoir containing a liquid drug and a connector with a
cannula for fluidically connecting the inside of the ampoule with
the inside of the liquid drug reservoir for transferring liquid
drug from the drug reservoir to the ampoule.
[0069] The systems described herein can be designed such that the
maximum flow velocity of the liquid drug is controlled. For
example, the drug reservoir, the connector and the drive of the
apparatus may be designed such that, when the drive is activated,
the maximum flow velocity of the flow of liquid drug in the cannula
does not exceed a predetermined rate. In an exemplary embodiment
the predetermined rate can be about 2.0 m/s, about 1.4 m/s, about
1.0 m/s, or about 0.5 m/s.
[0070] Alternatively, or additionally, the systems can be designed
such that the Reynolds number of the flow of the liquid drug is
controlled. For example, the ampoule, the drug reservoir, the
connector and the drive of the apparatus may be designed such that,
when the drive is activated, the Reynolds number of the flow of
liquid drug in the cannula does not exceed a value that indicates
the flow has transitioned from laminar flow to turbulent flow.
[0071] Moreover, the systems can be designed such that the maximum
pressure in the drug reservoir is controlled. For example, in at
least one embodiment of the system, the ampoule, the drug
reservoir, the connector and the drive of the apparatus may be
designed such that, when the drive is activated, the maximum
pressure in the drug reservoir does not exceed a predetermined
pressure. The predetermined pressure can be about 2000 mbar, about
1000 mbar, or about 500 mbar.
[0072] Accordingly, the risk of formation of foam and bubbles in
the liquid drug that is filled into the ampoule can be reduced.
[0073] In some embodiments, the apparatus of the system may further
comprise a sensor for detecting the state of the connection between
the drug reservoir and the ampoule. Accordingly, the sensor can
detect when the drug reservoir and the ampoule are disconnected
from each other after a transfer of liquid drug from the drug
reservoir to the ampoule. Thus, while the ampoule is still coupled
to the piston rod and, where applicable, is still held by the
holding member the drive can be activated to remove any gas present
in the liquid drug contained in the ampoule. Specifically, the
drive can actuate the piston rod or the holding member back and
forth several times.
[0074] Referring now to FIG. 1, a side view of an exemplary
embodiment of an ampoule system is schematically depicted. The
system of FIG. 1 comprises a single use ampoule 1 that can be made
of plastic. The ampoule 1 can be formed by a container 8 and a
piston (not depicted in FIG. 1) arranged therein in displaceable
manner. At the backside of the ampoule 1, a multi-use piston rod 10
is coupled to the piston by a threaded connection. At its front
face, the ampoule 1 is coupled by a connector 7 with a drug
reservoir 2 containing a liquid drug, such as insulin, such that
the interior of the ampoule 1 and of the drug reservoir 2
fluidically communicate with each other via a cannula 3 (see FIG.
2) provided by the connector 7. The connector 7 can
contemporaneously structurally connect the ampoule 1 and the drug
reservoir 2 with each other. As depicted FIG. 1, the liquid drug
reservoir 2 can be provided as a vial. It is noted that other
embodiments the liquid drug reservoir 2 may be provided, such as a
pen cartridge (FIGS. 5a and 5b). In still other embodiments, the
drug reservoir 2 may be any device suitable for holding a liquid
drug and communicating fluidically with the ampoule 1 via the
connector 7. As the use of the ampoule system is described
hereinabove, for purposes of brevity, similar details are not
repeated hereafter.
[0075] Referring now to FIGS. 2a and 2b, an arrangement for
performing the embodiments described herein is schematically
depicted. The arrangements comprise an ampoule 1, which is formed
by a container 8. A piston 6 can be arranged within the container 8
and be displaceable therein. The piston 6 can be coupled via a
piston rod 10 with a drive actuator 4. The drive actuator 4 can be
electrically powered and operably coupled to the piston rod 10 and
the piston 6. The drive actuator 4 can alternately move the piston
rod 10 and the piston 6 forward and backward along the longitudinal
axis X of the piston rod 10. Accordingly, the inside volume of the
ampoule 1 can be alternately reduced and increased. At its front
face, the ampoule 1 can be both mechanically coupled and
fluidically coupled with a liquid drug reservoir 2, such as e.g.
containing insulin, via a connector 7. The connector 7 can comprise
a cannula 3 for establishing the fluidic connection between the
inside of the ampoule 1 and the inside of the reservoir 2. For
example, the cannula 3 can pierce the septums (not depicted) at the
front faces of the ampoule 1 and of the reservoir 2.
[0076] In some embodiments of the methods described herein, the
drive actuator 4 can oscillate several times back and forth and
move the piston 6 and the piston rod 10 between the fully retracted
position (FIG. 2a) and the partially pushed in position shown in
(FIG. 2b).
[0077] Referring now to FIG. 3, an exemplary filling process is
schematically depicted from the left to the right. Various
situations (a) to (f) can be encountered during the course of
filling the ampoule 1. Beginning with situation (a), which
corresponds to the fully retracted position of FIG. 2a, the ampoule
1 can be empty. The piston 6 can be moved forth and back
(situations (b) to (e)) several times. Accordingly, the ampoule 1
can be stepwise filled with insulin from the reservoir 2, until it
is substantially filled as depicted in situation (f).
[0078] Referring collectively to FIGS. 4a to 4c, an embodiment of
an apparatus of the present disclosure is schematically depicted.
FIG. 4a schematically depicts an embodiment of the apparatus, FIG.
4b schematically depicts an embodiment of the apparatus in use and
FIG. 4c schematically depicts the drive arrangement of an
embodiment of the apparatus.
[0079] In one embodiment the apparatus comprises a housing 9 having
a cavity 12 for receiving the ampoule 1 to be filled. A piston rod
10 can be located at the bottom of the cavity 12. The piston rod 10
can be moved up and down by a crank mechanism. The crank mechanism
is formed by a crankshaft 13 and a connecting rod 14, which can be
moved by an electric drive unit. The electric drive unit comprises
the drive actuator 4 provided e.g., as an electric motor. The drive
actuator 4 can be operably coupled with a gearbox 15. The gearbox
15 can be rotatably connected to the crankshaft 13 via an
Oldham-coupling 16. The drive unit furthermore comprises two
batteries 17 for providing the electric energy for the drive
actuator 4 and an electric or electronic control system for
controlling the drive actuator 4. The control system can comprise
an activating switch 18 which can be actuated by pressing a button
19 at the outside of the housing 9 and a mechanical counting switch
21. The mechanical counting switch 21 can be actuated at a
predetermined number of revolutions (e.g., about every thirteen) of
the crankshaft 13 by a counting gear arrangement. The counting
arrangement can formed by a pusher dog 22 on the Oldham-coupling
which drives a counting pinion 23 which in turn rotates a cam disk
24 that actuates the mechanical counting switch 21. Instead of, or
in addition to, the mechanical counting switch 21, the counting
arrangement can comprise a sensor 27 with a printed circuit board
20. Specifically, the sensor 27 can be triggered once a magnetic
element 5 is positioned in front of it.
[0080] Referring now to FIG. 4b, the ampoule 1 to be filled can
comprise a container 8 (body) and a piston 6 arranged therein in a
displaceable manner. The ampoule 1 can be inserted into the cavity
12 (FIG. 4a) in the housing and be radially guided by the boundary
walls 11 of the cavity 12. When the ampoule 1 is introduced into
the cavity 12, the piston 6 of the ampoule can be coupled to the
piston rod 10 of the apparatus by rotating the ampoule 1 when the
ampoule 1 has reached the bottom of the cavity 12. Accordingly, a
bayonet joint can be established between corresponding bayonet
joint mating halves formed by the piston 6 and the piston rod 10.
After the bayonet joint is established, a connector 7 with a
cannula 3 can be mounted to the opening of the cavity 12 by a
bayonet joint and axially securing the ampoule 1 in the cavity 12
by positively locking it between the bottom of the cavity 12 and
the connector 7. The cannula 3 can penetrate a septum 25 arranged
at the front face of the ampoule 1. The reservoir 2 containing
insulin can then be pushed top down into a receiving cavity of the
connector 7. The cannula 3 can pierce a septum 26 of the reservoir
2 with the other end of the cannula 3. Thus, a fluidic connection
can be established between the inner spaces of the ampoule 1 and
the reservoir 2.
[0081] Referring collectively to FIGS. 4a to 4c, in order to
achieve a maximum filling of the ampoule 1, at the start of the
filling operation, the piston 6 of the ampoule 1 is positioned in
the fully retracted position. The filling operation can be started
by pressing the button 19, which in turn actuates the activating
switch 18. Now the batteries 17 supply electrical energy to the
drive actuator 4, which via the gearbox 15, the Oldham-coupling 16
and the crankshaft 13, drives the connecting rod 14. The connecting
rod 14 is pivotably connected with the piston rod 10 such that a
stroke movement of the piston rod 10 results, i.e. the rotation of
the axis of the drive actuator 4 is transformed into translational
(linear) movement of the piston rod 10 and the connected piston 6
along the longitudinal axis X. Each upward movement of the piston 6
displaces some air from the ampoule 1 into the reservoir 2, and
each downward movement of the piston 6 displaces some insulin from
the reservoir 2 into the ampoule 1. The number of strokes needed to
fill the ampoule 1 is determined mainly by the ratio of the stroke
to the length of the ampoule 1. Accordingly, the operating
principle can be followed to avoid an overfilling of the ampoule 1.
For example, in at least one embodiment about 10 to about 15
strokes can be sufficient for completely filling the ampoule 1. The
piston 6 can be returned to the fully retracted position at the end
of the filling process to achieve a maximum filling volume. This
can be ensured by the counting switches in combination with the
counting gear arrangement described above in greater detail. For
every complete stroke of the piston 6, the Oldham coupling 16 is
rotated a full revolution (360.degree.) so that the pusher dog 22
arranged thereon rotates the counting pinion 23 further by one
tooth. After a full revolution of the counting pinion 23, the cam
disk 24 actuates the mechanical counting switch 21. Alternatively
the magnetic element 5 can triggers the sensor 27 with the printed
circuit board 20, which in turn stops the filling process. The
number of teeth in this construction determines the number of
strokes that are performed during one filling process. After the
filling process has been stopped, the reservoir 2 and the ampoule 1
can be removed with the connector 7 out of the cavity 12.
[0082] Referring collectively to FIGS. 5a and 5b, another
embodiment of an apparatus is schematically depicted. This
embodiment of the apparatus differs from the embodiment of the
apparatus described above with reference to FIGS. 4a to 4c mainly
in that it comprises a mechanical drive unit instead of an
electrical drive unit. The interconnection between the piston rod
10 and the piston (not depicted in FIGS. 5a and 5b) of the ampoule
1 as well as between the ampoule 1 and the reservoir 2 via the
connector 7 is established in a substantially similar manner as the
embodiment described above with reference to FIGS. 4a to 4c.
However, in the present embodiment, the reservoir 2 is not formed
by a vial, but as a pen cartridge, which, e.g., contains
insulin.
[0083] In at least one embodiment of the apparatus, actuating
button 28 can be pushed down to put a spring 29 under compressive
stress. A mechanism can be utilized allow the actuating button 28
to be pushed down without starting the filling process. For
example, the filling process can be started once the spring 29 has
been compressed to a certain level (e.g., a maximum compressive
stress). The energy stored in the spring 29 can then be transmitted
to the piston of the ampoule 1 in a controlled manner. One
difference between using such a mechanical drive unit instead of an
electric drive unit involves controlling the spring 29 during its
energy delivery. A viscous damping element 30 (rotary damper) can
be utilized to control the spring. The viscous damping element 30
can ensure that the energy of the spring 29 is transmitted, with
the correct pace, to a knee lever arrangement 31. The knee lever
arrangement 31 transforms a rotational force provided from a gear
mechanism 32 that is driven by the spring 29 into translational
movement. The translation movement drives the piston rod 10 and the
piston in the ampoule 1 upward and downward. The apparatus can be
designed such that the filling process can be started with only one
actuation of the actuating button 28. The filling process is
complete once the spring 29 is relaxed and thus no longer supplies
energy to the filling mechanism. The upward and downward movement
of the piston can fill the ampoule 1 as is described in greater
detail hereinabove.
[0084] FIG. 6a graphically depicts an exemplary indication of the
pressure P in units of bar inside the reservoir 2 and inside the
ampoule 1 over the time t in units of seconds during performance of
a method according to the embodiments described herein with an
embodiment of the apparatus depicted in FIGS. 5a and 5b. FIG. 6a
graphically depicts the Reynolds number Re of the flow of insulin
in the cannula over the time t in units of seconds during
performance of a method according to the embodiments described
herein with an embodiment of the apparatus depicted in FIGS. 5a and
5b.
[0085] Referring now to FIG. 6a, the pressure c1 inside the drug
reservoir 2, which can be a reservoir for insulin, and the pressure
c2 inside the ampoule 1 are graphically depicted. During each
forward movement of the piston in the ampoule 1, which displaces
air from the ampoule 1 into the drug reservoir 2, the pressure c1
and the pressure c2 are increased from about 0.00 bar to about 0.25
bar. During the subsequent downward movement of the piston, which
displaces insulin from the drug reservoir 2 via the cannula into
the ampoule 1, the pressure c1 and pressure c2 fall back to about
0.00 bar. However, with an increase of the number of strokes
performed (generally indicated by the number of periods) the
pressure c2 inside the ampoule 1 increasingly falls slightly below
0.00 bar, as a result of the decreasing volume of air inside the
ampoule 1.
[0086] Referring now to FIG. 6b, the maximum Reynolds number Re of
the flow of insulin in the cannula during a single stroke (i.e.,
one forward and backward movement) increases as the total number of
strokes increases. Specifically, the maximum Reynolds number Re
increases from about 200 during the first stroke to about 700
during the last stroke, which is a result of the pressure c2 (FIG.
6a) in the ampoule 1 increasingly falling slightly below 0.00
bar.
[0087] For the purposes of describing and defining the present
disclosure it is noted that the term "substantially" is utilized
herein to represent the inherent degree of uncertainty that may be
attributed to any quantitative comparison, value, measurement, or
other representation. The term "substantially" is also utilized
herein to represent the degree by which a quantitative
representation may vary from a stated reference without resulting
in a change in the basic function of the subject matter at
issue.
[0088] While various embodiments of the systems, methods, and
apparatus of the present disclosure have been described in
considerable detail herein, the embodiments are merely offered by
way of non-limiting examples of the disclosure described herein. It
will therefore be understood that various changes and modifications
may be made, and equivalents may be substituted for elements
thereof, without departing from the scope of the disclosure.
Indeed, this disclosure is not intended to be exhaustive or to
limit the scope of the disclosure.
[0089] Further, in describing representative embodiments, the
disclosure may have presented a method and/or process as a
particular sequence of steps. However, to the extent that the
method or process does not rely on the particular order of steps
set forth herein, the method or process should not be limited to
the particular sequence of steps described. Other sequences of
steps may be possible. Therefore, the particular order of the steps
disclosed herein should not be construed as limitations of the
present disclosure. In addition, disclosure directed to a method
and/or process should not be limited to the performance of their
steps in the order written. Such sequences may be varied and still
remain within the scope of the present disclosure.
* * * * *