Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
WO 95/11051 ~ PCT/SE94/00949
1
Injection cartridge
The preser:~ invention refers to an injection cartrid-
ge of the duel-chamber type. In more detail, the in-
vention refers to an injection cartridge of the dual-
chamber type which has an improved arrangement of by-
pass means fcr the liquid component.
Injection cartridges of the dual-chamber type are
well-known and have found a wide use. Such cartridges
are primarily intended to be used when the liquid phar-
maceutical composition to be injected is not stable for
any extended period of time. In such cases, the compo-
sition to be injected is provided as two separate com-
ponents, one solid component comprising the active
pharmaceuticGl component in a dry state, and one liquid
component comprising a solvent or dispersing agent for
the solid component. These two components are enclosed
in an injection cartridge of the dual-chamber type,
such that the solid component is usually enclosed in a
front chamber, while the liquid component is enclosed
in a rear chamber. (In the following specification and
claims, the expressions "front" and "rear" are to be
.
regarded in relation to the direction in which the
injectable composition is transported when an injection
is administered.)
The two components are separated by a movable wall
which seals against the interior wall of the cartridge.
The rear chamber, which contains the liquid component,
is also closed at its rear end by a piston which seals
against the interior wall of the cartridge.
At its front end, the cartridge is usually closed by
a rubber septum which is held into place by a metal
capsule. This metal capsule has a central opening which
exposes the rubber septum. Through this opening, a
hollow needle may be inserted through this the septum
to give a connection with the interior of the cartrid-
ge.
For conducting the liquid component over to the solid
WO 95/11051 PCT/SE94/00949
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2
component for dissolution or dispersion, conventional
dual-chamber injection cartridges are provided with at
least one bypass channel in the wall of the cartridge.
When the movable wall which separates the two chambers
is at a suitable position, the bypass channel is ,
exposed, so that the liquid component may flow around
said movable wall and be mixed with the solid compo-
nent.
When the cartridge is to be readied for the admini-
stering of one or more injections, pressure is applied
to the rear piston to urge it forward. This pressure
will be transmitted through the liquid phase, which is
largely incompressible, so that also the movable wall,
which separates the two chambers, is urged forward.
When front movable wall has been moved forward a deter-
mined length, it will be situated at the bypass chan-
nel, such that a flow of liquid from the rear chamber
to the front chamber becomes possible. Further forward
movement of the rear piston will now push the liquid
from the rear chamber into the front chamber, while the
movable wall remains essentially stationary.
When all the liquid has been expelled from the rear
chamber, the rear piston will abut the movable wall,
and further pressure forward will move the two walls
together, to act like a single piston. The rubber sep-
tum closing the front end of the cartridge should now
have been pierced by a hollow needle, which makes it
possible to expel the ready-mixed preparation from the
front chamber to be administered to a patient.
The dual-chamber injection cartridges described above
have a number of important advantages and have found a
wide use. One important use is in injection devices
which are intended to be used by the patient to admini-
ster injections to himself. It is easy for the patient
to prepare the injectable preparation from the two
components immediately before the administering, and
the risk of contamination is greatly reduced.
WO 95/11051 ~~ PCT/SE94/00949
3
However, the conventional injection cartridges of the
dual-chamber type also have certain shortcomings. The
cartridges are often used in injection devices which
more or less have the appearance of a fountain pen, and
it is desirable that such a device should not be unduly
thick or long. Thus, any measure which may make such a
device slimmer and/or shorter is highly desirable.
The bypass channel in the wall of conventional car-
tridges creates a longitudinal ridge in the outer wall
of the cartridge, and makes it necessary to use an
injection device having an undesirably thick barrel to
make room for the cartridge. Furthermore, it is desi-
rable to make the forward movement of the movable wall
as short as possible, as this makes it possible to use
an injection device having a shorter barrel.
The desirable improvements mentioned above are obtai-
ned by the present invention. According to the inven-
tion, an injection cartridge of the dual-chamber type
is provided, which comprises a tubular barrel which at
its front end is sealed by a closure which may be pe-
netrated by an outlet conduit for a liquid preparation
from the cartridge, at its rear end is closed by a
piston which may be moved forward, and which comprises
a movable transversal wall inside the barrel, said
movable wall dividing the cartridge into two separate
chambers, and a bypass connection between the two
. chambers, said connection being openable by the dis-
placement of said movable wall to permit a bypass flow
of a liquid between the chambers. The connection be-
tween the two chambers is arranged as a modification of
the interior wall of said barrel along a determined
area, such that said movable wall does not seal com-
pletely against the interior wall of the barrel within
said area. Said modified area extends completely around
the circumference of the interior wall of the car-
tridge, such that a flow of liquid is permitted around
the complete circumference of the movable wall.
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3a
According to a broad aspect of the invention,
there is provided an injection cartridge of the dual-chamber
type, comprising a tubular barrel wherein said barrel has a
front end, a rear end, interior wall and interior suzface,
and wherein said front end is sealed by a closure which may
be penetrated by an outlet conduit for a liquid preparation
fxom the cartridge, said rear end is closed by a piston
which may be moved forward, and a movable transversal wall
inside said barrel, said movable transversal wall dividing
l0 the cartridge into two separate chambers, and a bypass
connection between the two separate chambers, said
connection being openable by the displacement of said
movable transversal wall to permit a bypas9 flow of liquid
between the two separate chambers, whezein said bypass
connection between the two separate chambers is arranged as
a modification of the interior surface of the barrel along a
predetermined area wherein said predetermined area extends
completely around the circumference of said interior wall of
the barrel, such that said movable transversal wall does not
seal completely against said interior wall of the barrel
within said axes, wherein said modification is arranged as a
plurality of lands and grooves having an inclined direction
in relation to the longitudinal axis of said barrel, said
lands and grooves extending along all of said predetermined
area, and wherein said tubular barrel has a nominal interior
circumference and said lands extend inward from the nominal
interior circumference of the tubular barrel.
WO 95/11051 r ~ PCT/SE94/00949
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4
What characterizes the invention is that the modifi-
cation of the interior wall of the cartridge is ar-
ranged as a plurality of lands and grooves in said ,
interior wall, said lands and grooves having an in-
s clined direction in relation to the axial direction of
the barrel and extending along all of said modified
area. In a more preferred version of this embodiment,
the lands extend inward from the interior wall of the
cartridge such that the interior diameter between the
lands is smaller than the nominal interior diameter of
the cartridge.
In a further preferred embodiment of the invention,
said axial lands and grooves are interrupted by essen-
tially peripheral grooves having essentially the same
depth as said axial grooves.
In a still further preferred embodiment, the modified
area of the interior wall of the cartridge is divided
into at least two circumferential areas, which have the
same spacing as the distance between the same number of
circumferential sealing ridges on the movable wall.
The depth of said grooves and the height of said
lands is preferably between 0.06 and 0.6 mm from the
interior wall of the cartridge.
Thus, the dual-chamber cartridge no longer contains a
bypass channel, but a bypass area of modifications of
the interior wall. Such an area affords a great number
of shallow channels, which have at least the same flow
capacity as one large channel. However, because of the
shallow depth of the modifications, no exterior ridge
or increased thickness of the cartridge wall will be
necessary, and this makes it possible to use an injec-
tion device having a slimmer barrel. The inclined ar-
rangement of the lands and grooves in relation to the
longitudinal axis of the cartridge also brings new and
unexpected advantages in the manufacture of the car-
tridge with its bypass area.
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The grooves and lands cnay be embossed in the interior.
wall. of the cartridge barrel by means of a rotating
embossing toot which works on the heat softened materi-
al of the barrel. It has been found that when'the
5 grooves and lands are parallel to the axis of the bar-
rel, the embossing action of the tool v.ill cause vibra~
tions which may lead to a distortion of the barrel. r~
the grooves and lands are instead embossed at an angle
to the lcngitudirlal axis, no such vibratxor~s will oc-
cur. This is an important and unexpected advantage of
the invention,
The angle between the grooves and the longitudiaal-
axis of the cartridge can be from S to 45 degrees. A ,
pre f erred value is f ro~u 1 o . to 3 o degrees , and about
2 0
degrees is especially preferred.
International patenC publication no. WO 1993/20868,
which has not yet been published, discloses an iaj~ec-
tion cartridge of the dua~.~chamber type, wherein a
bypass area is arranged as a modification of .the inte..
2o rior cartridge wa~.l. ~iowever, nothing is mentioned
about any inclxaed arrangement of grooves and lards.
.
The invention will now be
described in closer dttail,
with reference to the enclosed drawinga_
In the drawings, Figure 1 shows a dual-chamber injec-
tion cartridge according to the invention. Figure 2
shows a sectional view of such a eartridge_ Figure 3
shows another embodiment of a du,ai-chaa~be~c injection
cartridge of the invention, and Figure 4 shows the same
cartridge xn the stage when the two components arm mix- ~~
~ ed_ Figure S shows a preferred embodibent of an injec-
rio:~ cartridge of the invention, and Figure 6 shows a
transverse sectional view of the same cartridge at the
position of the piston_ Fa.gure 7 shows the same eaibodi-
ment of the cartridge with the piston displaced from
tn~ bypass zone, and Figure 8 shows a sectional view of
the same cartridge at this position of the piston.In~
the fxguxes of the drawing, like parts have the same
WO 95/11051 ~ ~ PCT/SE94100949
6
reference numbers. Furthermore, some of the details in
the drawing are shown in an exaggerated scale for
clarity.
Figure 1 shows a dual-chamber injection cartridge
having 'a cylindrical barrel 1 and a neck portion 2 at .
its forward opening 3. This opening is closed by a sep-
tum 4 of rubber or some similar material which has
sealing properties, and the septum is held in place by
a metal capsule 5, which is fastened around a flange 6
at the forward end of the neck portion 2. The capsule 5
has a central opening 7, where the septum is exposed
and may be penetrated by a hollow needle when desired.
At its rear end, the barrel 1 of the cartridge is
closed by a piston 8, which may be moved forward when
the cartridge is to be readied for an injection.
The cartridge is divided into a front chamber 9,
which usually contains the solid component of the in-
jectable preparation, and a rear chamber 10, which
usually contains the liquid component of said prepara-
tion, by means of the movable wall 11. In the position
shown in the figure, the movable wall seals against the
interior wall of the cartridge, and nothing can pass
between the two chambers.
In front of the movable wall 11, the interior wall of
the barrel 1 of the cartridge is provided with modifi-
cations 12, which cause that the movable wall 11 in
this area does not seal completely against the interior
wall. In the figures of the drawing, these modifica-
tions are shown as shallow grooves extending at an
angle to the longitudinal direction of the barrel 1.
This is also shown in Figure 2, which is a sectional
view of the barrel 1 along the line A-A in Figure 1.
In Figure 2, it is shown how the barrel 1, which here
encloses the front chamber 9, is provided with a plura-
lity of shallow grooves 13. For clarity, the depth of
these grooves is exaggerated in the drawing. The shal-
low grooves are evenly distributed along the internal
WO 95111051 ty ~~~ PCT/SE94/00949
3
circumference of the barrel. However, it is also possi-
ble to have the grooves present in certain discrete
areas only. What is important is that the grooves
should together afford a passage that is sufficient for
the flow of the liquid component from the rear chamber
to the front chamber.
It is understood that the area of surface modifica-
tions should have such an extension in the axial direc-
tion that it is somewhat longer than the movable wall
11, to make it possible for a flow of liquid to bypass
said movable wall.
It will also be seen that the grooves 13 can take up
so much of the interior wall that the movable wall 11
is properly guided only by small ridges. This is usu-
ally not a problem.
The inclined grooves 13 may also be broken by a
number of peripheral grooves around the interior cir-
cumference of the barrel 1. This may improve the flow
of the liquid and will aid in removing air from the
system.
Furthermore, it should be noted that it is not
strictly necessary that the bypass area 12 is formed by
grooves. Other modifications of the interior surface
are also possible, such as small projections, and the
like. In a preferred embodiment, such projections are
shaped as lands extending at an angle to the axial
direction. The height of such projections should also
preferably be between 0.06 and 0.6 mm. The important
feature is that in said area 12, the movable wall 11
should not seal completely against the barrel, but
permit a bypass flow of the liquid component between
' the chambers.
When the cartridge is to be readied for injection, a
forward-directed pressure is applied to the piston 8 at
the rear of the cartridge. This pressure is transmitted
through the essentially incompressible liquid in the
rear chamber 10 and acts on the movable wall 11 to urge
WO 95/11051 PCTISE94/00949
....
8
it forward. Wher~~the movable wall has
been moved for-
,
ward so far that it is in the area of the modified
internal surface of the barrel 1, it will no longer
seal completely against the interior wall of the bar-
s rel, and it will be possible for the liquid component
to flow from the rear chamber 10 into the front chamber
9, to be mixed with the solid component in this cham-
ber. Further pressure on the rear piston 8 will expel
all of the liquid from the rear chamber 10, until fi-
=0 nally the rear piston will rest against the rear surfa-
ce of the movable wall 11. At this stage, the movable
wall 11 and the rear piston 8 will act together as one
single piston.
Before the liquid component is made to flow over into
.5 the front chamber 9, the septum 4 closing the front
chamber 9 will usually have been pierced with a hollow
needle which is connected to a needle for administering
the injection, or which itself serves as such an injec-
tion needle by means of its forward pointed end. This
20 prevents the build-up of an excessive overpressure in
the front chamber 9. After all of the liquid component
has been made to flow over into the front chamber 9 and
has been thoroughly mixed with the solid component,
further pressure on the combined rear piston 8 and
25 movable wall 11 will serve to expel the mixed injec-
table preparation through the hollow needle for admini-
stering to a patient.
Before the cartridge is readied for injection, it is
placed in a suitable holder device. Such devices are
30 known for carrying out the mixing of the two components
and for subsequent administering of the injectable
preparation. In many cases, they also comprise means
for metering out predetermined amounts of the prepara-
tion to be injected. There are a number of such devices
35 commercially available, which are arranged such that a
patient may himself make the cartridge ready for injec-
tion, and administer the injections to himself by means
WO 95/11051 PCT/SE94100949
°~~3
9
of such a device .
Figures 3 and 4 show a preferred embodiment of the
invention. The arrangements at the front and rear ends
of the cartridge are the same here as shown in Figure
1.
However, the area of modification of the internal
wall of the barrel 1 ~ here divided into at least two
areas 15 and 16. Thes-- areas are arranged as spaced
bands 15 and 16, which each contain the same types of
inclined surface modificationshas those mentioned in
connection with Figures 1 and 2. A sectional view along
the lines A-A in Figure 3 will show exactly the same as
Figure 2 in connection with Figure 1.
The movable wall 11_is composed of a central part
having a smaller diameter than the interior diameter of
the barrel 1, and at least two circumferential sealing
ridges 17 and 18 at the front and rear end of the mo-
vable wall, respectj,vely. This gives a space 19 defined
by the two sealing ridges 17 and 18, the part of the
movable wall having a smaller diameter, and the inte-
rior wall of the barrel 1.
The spacing between the two sealing ridges 17 and 18
is the same as the spacing between the two bands 15 and
16 of surface modifications of the interior wall. These
bands also have a somewhat greater axial length than
the axial length of each of the sealing ridges 17 and
18, such that a flow of liquid around said sealing
ridges becomes possible.
In the initial stage, before the cartridge has been
readied for injection, the movable wall is in such a
position inside the barrel 1 of the cartridge that the
front sealing ridge 17 lies between the two bands of
modification 15 and 16. The reax sealing ridge 18
should lie behind the rear band ~.6. In this way. a
complete seal between the front and rear chambers is
assured.
When the cartridge is to be readied for injection,
WO 95/11051 PCT/SE94100949
pressure is applied on the rear piston 8, as described
previously. This will bring about that the movable wall
11 is urged forward, until it is in the position shown
in Figure 4. It will be seen that the two sealing rid-
5 ges are now positioned opposite the bands of modifica-
tion 15 and 16, and a liquid flow is now possible from
the rear chamber 10 around the rear sealing ridge 18,
into the space 19, and around the front sealing ridge
17 into the front chamber 9.
10 The advantage of this embodiment is that the movable
wall 11 will only have to be moved the short distance
corresponding approximately to half the spacing between
the two bands 15 and 16. This makes it possible to use
a shorter cartridge and a shorter injection device for
housing the cartridge. For injection devices which are
to be carried around by the patient himself, this can
be of considerable importance.
It is also possible to use more than two areas of
surface modification and corresponding sealing ridges
of the movable wall. This gives a more secure seal, but
the construction becomes more complicated and therefore
also more expensive.
In Figures 5 to 8 is shown an especially preferred
embodiment of an injection cartridge according to the
invention. In these figures, only the part of the car-
tridge around the bypass area and the front piston is
shown, while the arrangements at the front and rear
ends of the cartridge are the same as shown in the
previous figures.
Figure 5 shows the barrel of the cartridge 20 with
the piston 21 positioned in the bypass area 22. Figure
6 is a sectional view along A-A in figure 5 (in a
larger scale for the sake of clearness) which shows the
shape of the cartridge wall in the bypass area and of
the piston therein. It will be seen that the interior
wall of the cartridge 20 is provided with inclined
lands 23 and grooves 24, and that the piston 21 has
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0368-715
m -
been deformec to adapt to the lands 23 and grooves 24
- ~ in this bypass area. This adapti,on is not complete,
however, and axial channels 25 are foamed between the
bottoms of ti:e grooves 24 and the deformed piston 2a.
S These ehanne~s 25 afford the bypass for the liquid from
the rear char,~ber to the flout chamber of the cartridge.
Figure 7 shows the cartridge 20 after the piston~21
has been moved further forward of the bypass area 22,
and figure.8 shows a sectional view (in a larger scale)
1o along A-A in figure 7. Yt will be seen that the piston
21 has now adapted to the staooth interior wah of the
. cartridge 20 and completely seals against said interior
wall. .
It is important feature of the embodi~aent shown in
1.5 f figures 5 to a , especially then is f~.gure 6 , that the
inclined lands 23 extend inward from the nominal inte-
rior c~.rcumference of the cartridge 20, while the
grooves 24 extend outvrard fro~a said nom~.nal circumfer-
ence. The nominal interior circumference aad:interior
2o diameter of the cartridge are defiaed as the interior
circu~uference and interior diameter, respectively, of
the smooth-wa3.led portion of the cartridge and said -
~
circum$erence xs symbolized by
the-dashed line 26 in
figure G_ The height of the lands 23 and the depth of
25 the grooves 29;, as well as their muaber, should be
.
correlated to each ether such that the piston 21 has
the sa~ae cross-sectional area when it is in the bypass
part as when it is in the smooth-walled parts of the
ca=tridge.
30 . When the pisCon 21 is in the smooth-walled part of
the cartridge, it has to be compressed to a certain
ex~ent to seal securely against the interior wall of
the cartridge_ This compression of the piston will make
its length increase to some extent_ The compression of
35 the piston will also ~.ncrease its resistance against
. movement in the axial direction. A suitable degree of
xesi.stance can be obtained by the selection of an
WO 95/11051 : ' . PCT/SE94/00949
,. ~.', ,; :~ :. ...
.:~ 210
12
appropriate degree of compression, as well as by a
suitable treatment of the interior wall of the car-
tridge, such as siliconizing. A siliconizing treatment, .
however, may also cause contamination of the product in
the cartridge.
When the piston 21 has been moved to the bypass area
22, parts of it will be further compressed by the lands
23 extending inwards from the nominal circumference 26,
while other parts of it are allowed to expand into the
grooves 24, without filling up said grooves completely.
. It is an important feature of this embodiment of the
invention that this further compression and expansion
should balance each other out, such that the cross-
section area of the piston in the bypass part will be
essentially the same as the cross-section area of the
piston=ihy.the smooth-walled part of the cartridge. This
will mean that the length of the piston 21 will be
essentially unchanged, as a consequence of which the
resistance against axial displacement of the piston
will also be essentially unchanged. This is an
important advantage, as the constant resistance contri-
butes to an increased accuracy in the mixing and
metering out of the product in the cartridge.
In the bypass areas of the prior art, the diameter is
usually somewhat greater than in the smooth-walled
parts of the cartridge. Thus, the resistance against
axial displacement of the piston is less in the bypass
area, and the change in resistance may be rather
abrupt. This may cause a user pushing the piston for-
ward to move the piston too fast in the bypass area, so
that the piston will pass over the bypass area before
all the liquid in the rear chamber has been transferred
to the front chamber. The risk of this occurring is
greater when the piston is moved forward by manual
pressure instead of by the use of a screw mechanism.
Thus, the interaction between the piston and the
interior wall of the cartridge in the bypass area is a
WO 95/11051 ,2~' PCT/SE94100949
3
13
critical feature for obtaining a correct and accurate
mixing of the liquid and the solid components in the
cartridge. Through this embodiment of the present in-
vention, the risk of errors in the mixing process is
greatly diminished.
The lands and grooves in the interior wall of the
cartridge can be manufactured by a mechanical treatment
of the interior wall while the cartridge barrel is in a
softened state. Thus, the cartridge barrel, which is
usually made of glass or a thermoplastic material, is
heated to a suitable degree of softness, and a wheel
having a circumferential shape corresponding to the
profile desired for the interior wall is inserted into
the barrel and is rolled around the circumference of
the interior wall at the place of the bypass area. The
wheel will then emboss the interior wall with the
desired pattern. The wave form shown in figure 6 has
turned out to be advantageous, but other shapes of the
lands and grooves are also possible. An essential fea-
ture is that the dimensions of the lands and grooves
should be such that the piston in its deformed state in
the bypass part should have essentially the same cross-
section area as in the smooth-walled portion of the
cartridge barrel, while affording bypass channels in
the bottoms of the grooves.
When the lands and grooves are arranged at an angle
to the longitudinal axis of the cartridge, this will
mean that the projections on the embossing wheel will
strike the interior wall of the cartridge barrel gradu-
ally, and not abruptly, as is the case when grooves are
embossed which are parallel to the longitudinal axis.
This gradual process will give rise to less vibrations
and a lessened risk that the heat softened cartridge
barrel will be deformed.
It goes without saying that the preferred embodiment
shown in figures 5 to 8 may be combined with the
embodiment shown in figures 3 and 4, where the modifi-
WO 95/11051 . .~ ; v
PCT/SE94/00949
14
cation of the interior wall in the bypass area is
divided into at least two separate areas.
The injection cartridge of the invention is especial-
ly.advantageous to use together with sensitive prepara-
tions, such as growth hormones and other proteins. Such
preparations have to be reconstituted under very mild
conditions, as there is otherwise a risk that they will
be denatured. Through the present invention, where the
risk of deformation has been lessened, an even liquid
flow around the whole circumference of the movable wall
is arranged, and this makes possible a mixing of the
two components under very mild conditions. This type of
liquid flow also aids in removing trapped air from the
composition.
The manufacture of the injection cartridges according
to the present invention does not present any difficul-
ties to a person skilled in the art. The modifications
of certain areas of the interior wall may be carried
out by the use of a suitable grinding tool, or as
described in the foregoing for the preferred embodi-
ment. In all other respects, the preparation and
filling of the cartridges are carried out in the same
way as for conventional injection cartridges of the
dual-chamber type.
The injection cartridge of the invention may be
manufactured from conventional materials, such as glass
or suitable plastic materials. Such materials are well-
known to those skilled in the art.
