Note: Descriptions are shown in the official language in which they were submitted.
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Title
Medical arrangement
Field of the invention
The present invention relates to an injector device, an injector unit with a
pressure chamber and a method to perform the injection, according to the
preambles of the independent claims.
Background of the invention
The principles of the present invention can be used in connection with any
injector requiring high level pressurization of the fluid to be injected. High
pressures may be needed for expelling high viscosity product, such as products
in oil, gelled, paste, amorphous or suspension form, e.g. for dental purposes
or
to form slow release deposits in the body. Another major injector type
requiring
high pressure is jet injectors for needle-less skin penetration of a
pressurized
liquid to be further discussed below. Although for convenience the invention
will
be described in terms of such jet injection, the invention shall not be
regarded as
restricted thereto but shall be understood to embrace other high pressure
applications as well.
Jet injection apparatuses for hypodermic jet injection of medical liquids
through
the skin surface or the mucous membrane of either humans or animals under
sufficiently high pressure to force the liquids to a predetermined depth
within
the tissue beneath the skin surface or mucous membrane are known in the art
2 5 since many years.
A multi-shot injector instrument employing the jet injection principle is
known
from US-2,821,981. In this known instrument the fluid to be injected is
charged
into a distal pressure chamber, an ampoule, from a proximal fluid medicine
chamber, e.g. in the form of a conventional syringe. One mechanism is used to
transfer the fluid from the fluid chamber into the pressure chamber and
another
mechanism is then used to perform the injection. Non return valves are
provided
in the transfer bore to ensure that no back flow occurs. The mechanically
rather
complicated structure of the injector instrument makes it rather expensive to
3 5 manufacture. Another drawback with this type of complicated mechanical
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instruments is the difficulty to assemble the device in a sterile environment.
It is
sometimes today a demand to make parts non-reusable (disposable) that might
be contaminated during injection. This demand is very difficult to fulfil for
a
device of the type disclosed in US-2,821,981, or generally for mechanically
complicated devices of this kind, due to the large number of different parts
making up the device.
US-3,138,257 discloses an injector device similar to the one of US-2,821,981.
US-4,447,225 discloses a multi-dose jet injector adapted to receive a
medicament bottle or vial from which the medicament liquid is transferred into
a
transfer chamber. The medicament is then pumped through a one-way valve via
a cannula to a medicament delivery chamber. The medicament is then ready for
jet injection delivery, which is performed by imparting an ejecting force on
the
medicament liquid and thus expelling it through an orifice of the jet
injector.
One drawback with the jet injector disclosed in US-4,447,225 is that it is
structurally complicated, e.g. the two step transfer of the medicament liquid
prior injection, and thus expensive to manufacture.
US-2,591,046 discloses a hypodermic syringe assembly with two chambers
2 0 separated by a by-pass section. The liquid medicine is transferred into a
distal
chamber via the by-pass section. There are no separate chambers able to
provide different properties, e.g. resistance against high pressures.
Liquid medicaments intended for injection are ordinarily stored in glass
containers prior loaded into a syringe for injection. A rubber seal then seals
the
glass container. Thus, the liquid medicament is only in direct contact with
glass
and rubber. The major reason for not using plastic materials as material for
medical storage containers is that the plastic material does not provide an
entirely closed sealing with regard to oxygen moving into or components out
3 0 from the container. Also components from the manufacture might be deposed
in
the plastic material that can affect liquid stored in the container. Another
reason
is that plastic material may give off trace amounts of components that are
unacceptable in injectable preparations. The above mentioned drawbacks
regarding plastic material used for medical storage containers are valid only
when using plastic containers for normal medical storage times, e.g. up to 2
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years. When using plastic materials in e.g. syringes etc. where the liquid
medicine only contacts the plastic material when the injection is to be
performed
the above mention drawbacks can not be identified.
In jet injectors using glass containers, the class container must resist the
high
pressure used to expel the liquid from the container. The glass container is
then
preferably manufactured from hardened glass, which renders it expensive. ~n
the contrary, plastic materials can easily provide the necessary properties
for a
pressure chamber, such as strength and resilience with low shattering risks.
Glass materials for storage chambers and plastic materials for pressure
chambers are also suitable for disposable single-use components.
The object of the present invention is to achieve an easy to use injector
device
that is less expensive to manufacture than those known from the prior art.
Another object of the present invention is to achieve a device not having the
above-mentioned drawbacks regarding the sterile handling of parts of the
device.
A further object is to offer an injector device suitable to be pre-filled with
medical
and allowing storage over extended periods of time before injection and
wherein
all surfaces of the device and its parts being or corning into contact with
the
2 0 medical can be kept sterile during manufacture, storage and use. Yet
another
object is to offer a device suitable for ejection of multiple doses from a
storage
chamber. Still an object is to offer a device suitable for easy exchange and
disposal of parts possibly being contaminated during an injection. Still
another
object of the present invention is to achieve a device provided with sterile
parts
2 5 that inherently cannot be reused in order to prevent unauthorized
sterilization
and reselling of already used devices that might be dangerous to patients. The
invention also has for object of providing corresponding methods fox delivery
of
liquid from high pressure sources.
3 0 Summary of the invention
The above-mentioned object is achieved by an injector device, a unit with a
pressure chamber and a method of performing the injection, according to the
characterizing portions of the independent claims.
Preferred embodiments are set forth in the dependent claims.
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An easy to use injector device is thus achieved having few movable parts and
being easy to manufacture. The injector can be used for any high pressure
injector application, can be pre-filled with medical and stored without
deterioration of the medical and can be manufactured, stored and used under
sterile conditions.
The injector device according to the invention is preferably intended for
multi
dose injections.
It comprises a separate unit that includes a pressure chamber that is not
reusable. The used unit is disposed after use and a new unit is attached to
the
injector housing when a new injection is to be given.
According to one preferred embodiment of the invention the liquid is pressed
into
the pressure chamber from the storage chamber, resulting in that no suction of
the liquid into the pressure chamber has to be performed which is structurally
more complicated to achieve.
According to another preferred embodiment the mechanism is responsible for
dosing of the liquid medicine separate from the injection mechanism.
Information from the dosing unit regarding the dose volume transferred from
the
storage chamber via the liquid conduit into the pressure chamber is supplied
to
a control arrangement that in turn generates a control signal to a
pressurizing
mechanism, either as an electrical signal or as a mechanical movement. The
2 5 control signal controls the movement of a piston in the pressure chamber
so that
it moves to a position where no air is left in the pressure chamber.
According to still another embodiment of the invention is a mechanical dosing
unit used, e.g. by a rotating movement. This movement is stored in a
mechanical
3 0 (or electronic memory) in order to be used by the pressurizing mechanism.
Short description of the appended drawings
Figures lA-1C schematically illustrate different steps of the method according
to
the invention.
35 Figures 2A and 2B illustrate the injector device according to a first
embodiment
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of the invention and Figures 2C and 2 D illustrate a control, arrangement in a
similar device_
Figures SA 3E illustrate the injector device accordixxg to a second embodiment
of
the invention.
5 Figures 4A and 4B show a cross sectional view of an alternative embodiment
of
the by-pass section according to the invention.
Figure 5 illustrates the multi~dose injector device according to the
invention.
Figure 6 shows the separate unit according to the present invent~~.on.
Figure ~.~1. to 7F illustrate a mechanism for dose Metti.~.zg, de-aeration and
injection, usable with the arran~ernent embodiment of Figure s.
Figure 8 illustrates schematically a prior arl toothed plunger rod.
Figures 9A to 9D illustrates schematically a modi~Zed embodiment of that in
rigure 7, adapted for use urith a toothed plunger rod.
Figure 10 shows schematicahy a modified ram sleeve for parallel arrangements.
-~,~:a,
Detailed desert tion of referred embodiments of the invention . .
Corresponding features have the same reference numbers in all llgures.
The basic steps 3n the method according to the present.invention are
2 0 schem tically illustrated in figures 1.A-1 C.
A pressure chamber 2 comprising a pressure barrel 4 provided with a front end
opening 6 for ejection of the liquid, an opening S for receiving liquid
medicine 10
from a storage chamber (not shouir~l aiid a piston 12 sealingly inserted in
the
~~,,.
pressuxe barrel.
2 5 Figure 1A illustrates the loading step v~k~en a predetermined volume of
liquid is
inserted into the pressure barrel via the opening 8. The volume inserted is
less
than the voluu~e of the pressure barrel above the piston 12. In this si:ep the
piston is in its loading position. The up-right positions. of pressure chamber
in
combination ravith surface tension prevents the transferred.liquid to escape
3 0 through the openir~g 6. ,A.s can be seen from the figure the opening is
dose to the
piston in order to be able to ~~11 the pressure barrel from the bottozx~
forcing the
~. ~, ~, ~ectivn towards the opening.
~:~
. ~',
1~
k~gure 1S illustrates the sealing step where the piston 12 has been moved from
,,.
3 5 the loading position to a sealing position and thereby seals, off the
opening 8
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from the storage chamber. The distance that the piston has moved is related to
the volume of the liquid medicine such that substantially all air is expelled
from
the pressure chamber via the front end opening when the piston is in its
sealing
position. The figure shows a situation where a maximum dose of liquid is
transferred into the pressure chamber. If the dose is smaller the piston is of
course in a more distal position.
Figure 1C illustrates the ejecting step where a force is applied on the piston
forcing it in a distal direction and thereby ejecting the liquid medicine
through
the front end opening as a liquid jet 14.
Figures 2A and 2B illustrate the injector device according to a first
embodiment
of the invention.
An injector device for delivery of liquid from a high pressure source is shown
including a pressure chamber 2 comprising a pressure barrel 4 for
accommodation of at least one pressure piston 12 inserted in the pressure
barrel
and having a front end opening 6 for ejection of the liquid 8. The pressure
chamber being of sufficient strength to sustain the liquid pressure during the
injection, and is preferably disposable and made from plastic.
2 0 The device further comprises a storage chamber 16, separate from the
pressure
chamber, for the liquid or the liquid precursor components. The storage
chamber is preferably made from glass and has a cylindrical shape. The
chamber is provided with a membrane 18 at one end and a movable sealing
storage piston inserted from the other end. The membrane and the piston
2 5 enclose the liquid.
A conduit 22 is arranged between the pressure chamber and the storage
chamber. The conduit is preferably an integral part of the pressure chamber
and
is provided with a needle 23 having a channel in connection with the conduit.
The needle is adapted to penetrate the membrane 18 of the storage chamber in
3 0 order to establish a fluid connection between the storage barrel 8 and the
pressure barrel 4.
The device also comprises a dosing unit 24, a pressurizing mechanism 26 and a
control unit 28.
The dosing unit is adapted to apply a force on the storage piston inside the
3 5 storage chamber in order to transfer a predetermined volume of liquid from
the
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storage chamber via the conduit into the pressure barrel. The volume that is
transferred is dependent on the distance d moved by the storage piston. The
dashed line indicates the position of the storage piston when a dose has been
transferred.
The pressurizing mechanism is arranged to apply a force on the pressure piston
in the pressure barrel to create the liquid pressure.
The pressurizing mechanism arranged to apply force, directly or indirectly, on
the piston. The mechanism is only schematically indicated in the figures and
may be e.g. spring loaded as disclosed in US-4.,447,225. According to another
l0 principle is the injecting force generated by gas under pressure. These two
principles are well known in the art. The pressure inside the pressure chamber
during injection is in the order of 4000 psi (Pounds per square inch).
When a dose has been transferred into the pressure barrel information
regarding
the transferred volume is applied from the liquid transfer unit to the control
unit
28. The control unit controls the pressurizing mechanism to first move the
pressure piston in the pressure barrel from the loading position (figure 2A)
to the
sealing position (figure 2B). This; movement is related to the volume so that
when
the pressure piston 12 is in the sealing position substantially all air is
expelled
2 0 from the pressure barrel through the front end opening. After that the
pressurizing mechanism generates, on demand, the necessary force to expel the
liquid through the front end opening. This is here illustrated as a forward
movement of a plunger 17 with respect to the pressurizing mechanism 26.
2 5 Figures 2C and 2D illustrate a similar design with a slightly different
layout of
the rear control parts. The dosing unit 24 is equipped with a dose setting
button
and any known arrangement can be used to transform a rotation and/or an
axial displacement of the button 25 into a forward movement of a pusher 19 for
storage piston 20, e.g. a screw and nut arrangement, for dosing of liquid
through
3 0 conduit 22 and into the pressure chamber 2. Figure 2C shows the device
after
that such a dose transfer has taken place but before de-aeration. Figure 2D
shows the device after de-aeration. Between the Figures the pressurizing
mechanism 26 has moved forwards with respect to the pressure chamber 2 and
also with respect to the box containing the dosing unit 24 and the control
unit
3 5 28, as evident from the different location of a connection 29
therebetween, but
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plunger 17 has not moved forward with respect to the pressurizing mechanism
26. The control mechanism is arranged to give a larger forward displacement of
the pressurizing mechanism at smaller dose transfer movements for button 25
and vice versa so that the de-aeration forward movement of pressurizing
mechanism 26 is complementary to the dose volume transferred to the pressure
chamber 2. After de-aeration the pressurizing mechanism can be triggered to
perform the injection. The axial mobility of the pressurizing mechanism with
stationary plunger facilitates design of this part, e.g. with a spring and
trigger,
as it need not contain any arrangements for de-aeration.
The pressure chamber, the piston inside the pressure barrel and at least a
part
of the conduit is arranged as a separate unit that preferably is disposable.
The storage chamber, the pressurizing mechanism, the dosing unit and the
control arrangement are arranged in a housing.
The separate unit and the housing have corresponding fitting parts allowing
releasable attachment of the unit to the housing in a position permitting
fluid
connection between the storage chamber and the pressure chamber through the
conduit and permitting the pressurizing mechanism to act on the piston.
Figures 3A-3E illustrates the injector device according to a second embodiment
of the invention.
The figures 3A-3E shows a cross sectional view of the pressure chamber 2
comprising a pressure barrel 4 provided with a front end opening 6 and a
piston
2 5 12 arranged inside the barrel. The pressure chamber further comprises a
piston
rod 30 with a central channel 32 connected to a needle 34, and a rear support
36. A by pass section 38 is further provided at the inner surface of the
pressure
barrel where the piston is located in its loading position. A part of the
storage
chamber 16 with the membrane 18 is also shown in the figure. A ram 40 (partly
3 0 shown in the figure) is in mechanical connection with the pressurizing
mechanism (not shown) and adapted to submit the force generated by the
pressurizing mechanism to the piston via the support 36 and the piston rod 30.
The ram is freely moveable in relation to the storage chamber.
The support 36 preferably comprises a number of support arms, e.g. 3-5, at a
3 5 proximal part of piston rod. The support positions the needle in a central
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position of the pressure chamber and ensures that the needle is in a steady
position when the needle penetrates the membrane of the storage chamber. The
support is also a support for the ram 40 when moving the piston rod and the
piston in a distal direction.
The by-pass section 38 may be arranged in many different ways. According to
one preferred embodiment a number of traces or channels for the liquid are
provided in the inner surface of the pressure barrel. According to another
embodiment is the inner surface provided with means that causes deformation
of the piston when passing, thereby ensuring that liquid can pass the piston.
Persons skilled in the art are aware of many other alternative ways of
arranging
the by-pass section.
Figures 4A and 4B shows a cross sectional view of an alternative embodiment of
the by-pass section. According to this embodiment the piston 12 is provided
with
a number of channels 13, e.g. 1-4. In the loading step of the procedure the
channels provide a fluid connection between the central channel 32 of the
piston
rod 30. In the sealing step the piston rod 30 is in fluid tight connection
with the
piston and thereby seals off the channels (figure 4B).
2 0 Figure 3A shows the loading step of the method. A predetermined dose of
liquid
medicine is expelled from the storage chamber by the dosing unit (not shown).
The separate unit comprising the pressure chamber, the liquid conduit, the
piston and the piston rod is arranged in connection with the housing (not
shown). The upper part of the piston rod is provided with a sealing member 42
2 5 that in the loading position engages the inner surface of the pressure
barrel in
order to achieve a fluid tight connection for the liquid conduit. The needle
is
inserted through the membrane 18 into the storage chamber. The dose is
transferred from the storage chamber through the needle and the central
chanxlel of the piston rod and passes the piston in the space between the
distal
3 0 part of the piston rod and the by pass section 38 into the pressure barrel
4.
When the predetermined volume has been transferred into the pressure barrel
control arrangement (not shown) receives information from the dosing unit
related to the transferred volume and initiate the second step, the sealing
step,
3 5 where the piston is moved from the loading position to the sealing
position.
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Figure 3B illustrates the beginning of that step. The ram 40 forces the piston
rod
in a distal direction. The sealing is torn off from the piston rod and remains
in
engagement with the inner surface of the pressure chamber as a fluid-tight
sealing. The piston rod has come into contact with the piston, which closes
the
5 liquid conduit and enables piston pushing.
In figure 3C the piston 12 has been moved a predetermined distance to the
sealing position by the ram that exerts a force at the piston via the piston
rod
30. The predetermined distance that the piston has been moved is related to
the
10 volume of the dose transferred into the pressure barrel such that
substantially
all air is expelled through the front end opening 6 and that the piston has
been
moved passed the by pass section 38. During forward movement of the piston
rod 30 the needle 34 is withdrawn from the storage chamber, which is arranged
stationary with respect to the pressure chamber 2. The injector device is know
ready to perform the injection.
Figure 3D illustrates the end of the ejecting step. A force has been applied
to the
piston by the ram 40 via the piston rod 30 forcing the piston in a distal
direction
and thereby ejecting the liquid medicine through the front end opening as a
2 0 liquid jet. During this final forward movement of the piston rod the
needle 34 is
fully withdrawn from the storage chamber 2 and out from its sealing membrane
18.
In figure 3E the rarn 40 is withdrawn from the support of the piston rod and
the
2 5 separate unit (consisting of the pressure chamber, the pressure barrel,
the
piston and the piston rod with needle) may be released (e.g. unscrewed) from
the
housing and disposed. The needle is well protected by the pressure chamber
when the separate unit is to be released.
One important detail is that the piston is freely movable in relation with the
3 0 piston rod. This means that the piston rod cannot pull back the piston in
a
proximal direction to the starting position which makes reuse of the device
almost impossible. The reason why reuse must be avoided is naturally due to
the
importance of minimizing the risk of contamination or disease transfer.
Another
advantage with this arrangement is that no attachment and detachment
3 5 between piston and piston rod in connection with exchange of the
disposable
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parts described. This feature is made possible partly by the fact that with
the
invention it is not necessary to draw or aspirate liquid into the pressure
chamber by a retraction of the piston but liquid can be injected positively
into
the pressure chamber since de-aeration can later be done.
The storage chamber may be a single chamber where the liquid medicine is
stored. It may also be a two compartment (or mufti compartment) chamber
provided with a by pass section (or by pass sections) in order to prepare the
liquid prior injection.
Different storage chambers may be provided containing different concentrations
of liquid medicine. It is advantageous to use small dose volumes in that it is
less
painful to inject a smaller volume than a larger volume. If smaller injection
volumes are used the concentration of the active substance in the liquid
medicine must be higher.
Throughout the description of the present invention the high pressure jet
generated by the device is arranged to penetrate the skin of a patient.
However
the basic principles of the invention is equally applicable when performing
needle injection of liquid medicines having high viscosity, e.g. gels. If e.g.
a gel is
to be injected today by a needle syringe a needle having a comparatively large
inner diameter must be used which might be very painful. According to an
alternative embodiment of the present invention a hypodermic needle is
attached
in connection with the front end opening of the injector device. The
connection is
2 5 performed in a robust manner in order to withstand the pressure inside the
pressure chamber during injection. The needle is preferably attached to the
pressure chamber during the manufacture of the chamber, e.g. during a molding
process. The injection procedure is the same as when performing a needle less
jet injection as described above. By using a pressure chamber provided with a
3 0 needle having a similar inner diameter as the front end opening of the
pressure
chamber a liquid having a high viscosity can be injected using a thinner
needle
than before. This is very advantageous in that it is less painful for the
patient.
The necessary pressure needed to perform the needle injection according to the
alternative embodiment is inter alia dependent of the inner diameter of the
35 needle and the viscosity of the liquid gel.
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Typical maximum pressures in the pressure chamber are in general above 25
atm (2,5 MPa), often above 50 atm (5 MPa) or above 100 atm (10 MPa). Normally
the pressures are below 1000 atm ( 100 MPa), often below 800 atm (80 MPa) or
below 500 atm (50 MPa).
Figure 5 illustrates the multi-dose injector device according to the
invention. The
device comprises the housing 51 including indicator 53 indicating the size of
the
dose, adjustment control 55 for adjusting the dose size, a mechanism for
preparing the injection 57 (controls the dosing unit and the pressurizing
mechanism), a release trigger 59 that controls the pressurizing mechanism to
generate the force needed for injection, an indicating window 61 and the
separate unit 63.
Figure 6 shows the separate unit 63 in an enclosing cover 65 with a removable
film 66 to maintain sterility. The separate unit 63 is adapted to be
releasable
attached to the housing when an injection is to be performed. Threads 67 are
provided at the separate unit and corresponding threads are arranged on the
inner surface of the distal end of the housing. The unit 63 is unscrewed and
disposed after use.
Figure 7A to 7E illustrate a mechanism for dose setting, de-aeration and
injection, usable with the arrangement embodiment of Figure 3, which here
corresponds to the front parts in the Figure. The device shown, generally
designated 700, can be said to include a disposable part 701 and a reusable
part
2 5 702 containing the mechanism and the storage chamber. With the same
reference numbers as in Figure 3 the disposable part.701 includes the pressure
chamber 2 with pressure barrel 4 and piston 12 and opening 6 as well as piston
rod 30 with central channel 32, rear needle 34 and support plate 36. The
reusable part 702 can be said to include a housing 710 embracing a storage
3 0 chamber 720 and the mechanism to be further described. The housing 710 has
a front inner thread 711 for engagement with an outer thread on disposable
part
701, allowing removal of a used disposable part and attachment of a fresh,
during which operation the needle 34 penetrates the storage chamber
membrane. The storage chamber 720, here shown with a bottleneck front,
3 5 comprises a penetration membrane 722, a storage piston 724 and an open
rear
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end 726. The mechanism can be said to include an injection unit 730, better
seen in Figure 7F, comprising a ram 731 sleeve, surrounding the storage
chamber 720, having a front flange 732, arranged for push cooperation with
piston rod support 36, and a rear flange 733 to be affected by a spring 736.
The
ram sleeve is telescopically arranged in a surrounding ram support 734, having
a support flange 735 for the spring 736. The ram is axially movable with
respect
to the rarn support and the spring is biased to propel the ram forwards, and
thereby also the piston rod 30, with sufficient force to create the pressure
necessary for injection. A trigger button 737 is schematically illustrated and
being arranged to normally lock the ram 731 and the ram support 734 with
respect to each other but when pushed allows forward movement of the ram
under action of the spring. The entire injection unit 730 is arranged axially
movable in the housing 710 to allow forward movement under the de-aeration
step, before triggering of injection, and the housing has a slit 712 for
accommodation of the externally accessible trigger 737 during such an axial
movement of the injection unit 730. The mechanism can be said to further
include a de-aeration unit 740, arranged to move the injection unit 730
forwards
during the de-aeration step, thereby also moving the piston rod 30 forwards.
The
de-aeration unit 740 comprises an axially movable transition element 741,
2 0 having a front end 742, for cooperation with the ram support flange 735
when
pushing the injection unit forwards, and a rear push flange 743, for
cooperation
with a pusher to be described, and a central hole 744, allowing free axial
passage around a control drum to be described. The mechanism can also be said
to include a liquid transfer unit 750, arranged for displacement of storage
piston
2 5 724, to affect liquid transfer from the storage chamber 720 via needle 34,
central
channel 32, and by-pass 38 into the pressure chamber 2, as described in
relation to Figure 3. The liquid transfer unit 750 comprises a rotationally
arranged threaded plunger 751, which cooperates with a correspondingly
threaded nut 752, which is axially and rotationally stationary with respect to
the
3 0 housing, so that a rotation of the plunger causes the plunger to move
axially.
The rear part of the plunger is inserted in and cooperates with the control
drum,
to be described, with a non-rotational connection (not shown), e.g. a non-
circular connection, so that a rotation of the drum imparts a rotation on the
plunger and with a one-way connection (not shown), e.g. a pawl and ratchet
3 5 arrangement, so that the plunger will only rotate in the one direction
causing it
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to move axially forwards. The mechanism can also be said to include a control
unit 760, arranged to secure, in sequence, transfer of a pre-set dose volume
from the storage chamber to the pressure chamber followed by de-aeration of
the
remaining volume in the pressure chamber. The control unit secures these
actions for different set doses, i.e. a longer de-aeration stroke for small
doses
and a shorter de-aeration stroke for large dose volumes. The control unit can
be
said to include a drum 761, which is arranged axially stationary but
rotational
with respect to the housing. Aside from the drum features already described
for
cooperation with the plunger 751, the drum comprises a track 762 with a
helical
extension 763, a knee 764 and an axially straight extension 765. The knee 764
is axially located about where the rear push flange 743 of the transition
element
741 is located before the de-aeration step. The control unit further comprises
a
pusher 766, arranged both axially movable and rotational with respect to the
housing, having a track follower 767, arranged for cooperation with the track
762 of the drum 761, a surface 768 for cooperation with the transition element
741 and a rear thread 769 for cooperation with a correspondingly threaded part
of a dose setting unit to be described as well as external helical splines
(not
shown) on its outer surface. When the pusher 766 is moved forwards, and when
locked against rotation, from a position like that shown in Figure 7A, the
2 0 follower 767 cooperation with the helical track part 763 will first cause
the drum
to rotate, thereby rotating the plunger 751 to move it forwards for transfer
of
liquid from the storage chamber to the pressure chamber with the mechanism
already described. When the follower reaches the track knee 764 no further
drum rotation takes place and transfer of liquid is terminated. At the knee
the
2 5 follower surface 768 also engages the transition element 741 and further
forward
movement of the pusher will bring the transition element and the injection
unit
730 forwards in the de-aeration step. The pusher is arranged to perform the
same forward stroke length for every injection cycle, independent of the start
position for the follower in the helical part of the track. A longer movement
in the
3 0 helical part of the track will give a shorter movement in the straight
track part
and vice versa, giving the desired relationship between dose transfer and de-
aeration movements. Finally the mechanism can be said to include an actuation
unit 770 for dose setting and pusher movement. The actuation unit comprises a
manually controlled knob 771, which can be rotated for dose setting and pushed
3 5 for dose transfer and de-aeration. The knob has a screw 772 arranged for
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cooperation with the threaded part of pusher 766. A rotation of the knob will
move the pusher to a selectable initial axial position, corresponding to the
dose
volume desired. Under this dose setting step the pusher 766 is allowed to
rotate
with the follower 767 in the helical part 763 of the track, in order to
prevent that
5 any rotation is imposed on the control drum 761. This is controlled by an
inner
knob sleeve 774, which is axially fixed but but rotational with respect to the
knob 771, and axially movable but non-rotational with respect to the housing
e.g. by use of straight splines therebetween, and has external healical
splines
(not shown) for cooperation with the external helical splines on the pusher
10 surface, which helical splines have a pitch corresponding to that of
helical part
763 of the track 762 and which pitches are both not self locking whereas the
pitch of the rear thread 769 is self locking . After dose setting the pusher
is
axially fixed with respect to knob 771 and knob sleeve 774. A push on the knob
will move the pusher 766 forwards to perform the actions described. A return
15 spring 773 is arranged to bias the knob towards its rear position, which
will
bring the knob back into its rear position under reversal of the drum movement
pattern, which will not move the plunger 751 backwards due to the one-way
arrangement described and there is no force acting to move the piston 32
rearwards. The stroke length for the knob should correspond to the maximum
2 0 stroke length for the piston 12 in the pressure barrel 4, as illustrated
in Figure
7A with arrows L. Preferably also the straight extension 765 of the track 762
should be at least of the same length, corresponding to a minimum dose and
maximum de-aeration distances in the pressure chamber.
2 5 Figure 7A shows the device before any liquid has been transferred but
perhaps
after a dose setting action to bring the follower 767 to an intermediate
position
in the helical track part 763. In Figure 7B the knob 771 has been partially
pressed to a position corresponding to full transfer of the selected dose
volume.
Preferably the pushing takes place by gripping the device housing and pressing
3 0 it towards a support, as illustrated in the Figure, and preferably with
the device
in an upright position to maintain the dose transferred in the rear part of
the
pressure barrel 4. The illustrated height of the liquid is D, the air height
is L-D
as is the remaining stroke length for the knob 771. In the position shown the
pusher 766 follower 767 has reached the straight part 765 of the track and has
3 5 come into engagement with the transition element 741. The drum 761 has
been
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rotated (the lower part of helical extension 763 can be seen) to bring the
plunger
751 and the storage piston 724 forwards. In Figure 7C knob 771 has been fully
pressed the remaining distance L-D, corresponding to full de-aeration of the
pressure chamber 4. During this movement the pusher 766 has displaced the
transition element 741, the injection unit 730 with ram 731, the piston rod 30
and the piston 12 forwards a corresponding distance, to leave a remaining
travelling distance of D for the piston 12 in the pressure chamber 2. Trigger
737
has moved forwards in the slit 712. During the sarrie movement the drum 761
has been idle and non-rotating since the follower has traveled in the straight
part 765 of the track 762. The needle 34 has moved away from the storage
chamber as more fully described in relation to Figure 3. In Figure 7D the knob
771 has been released and the return spring 773 has brought it back to its
extended position. This has also reversed the movements of pusher 766 and
drum 761, which are now back in their initial positions but the plunger 751
and
storage piston 724 are unaffected due to the one-way arrangement provided. In
Figure 7E the trigger 737 has been activated to release ram 731 from the ram
support 734, allowing spring 236 to force the ram 731, the piston rod 30 and
piston 12 to their final forward positions, travelling the remaining distance
D. In
the shown embodiment the ram support 734 and the transition element 241 are
2 0 allowed to move rearwards to their initial positions under influence of
the spring
236, although it is also possible to prevent such a return movement, e.g. by a
latch arrangement or a one way mechanism such as a pawl and tratchet rail.
The injection is now completed and the disposable part 701 can be unscrewed
from the reusable part 702, the injection unit re-cocked and a new disposable
2 5 part 701 attached to repeat the cycle.
The device described illustrates the preferred embodiment of arranging the de-
aeration mechanism in series with and behind the pressurizing mechanism so
that it moves the pressure piston by moving the pressurizing mechanism
3 0 forwards. Several alternatives are possible. The de-aeration mechanism can
be
arranged still in series but between the pressure chamber and the pressurizing
mechanism and be moved forwards by elongating against the stationary
pressurizing mechanism or move together with the pressurizing mechanism. The
de-aeration mechanism can also be arranged in parallel with the pressurizing
3 5 mechanism to act fully independent of each other in which case the
pressurizing
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mechanism can remain stationary or be dragged forwards by the de-aeration
mechanism. In all alternatives the de-aeration mechanism can move the
pressure piston forwards by elongating or by moving with respect to the
housing
and the movements can take place by an actuation mechanism including release
of stored energy or by manual influence.
Figure 8 illustrates schematically a prior art toothed rod and Figures 9A to
9D
illustrates schematically a modified embodiment of that in Figure 7, adapted
for
use with a toothed, rather than screw-threaded, plunger and which is
compatible with both serial and parallel arrangement of pressurising mechanism
and de-aeration mechanisms. As illustrated in Figure 8 it is well known in
injection or ejection devices to propel a plunger 851, having a plurality of
axially
spaced dents or teeth 852, by use of a system of ratchets or latches, each
able to
override the teeth in one direction but not in the other direction. The system
shown incorporates two stationary latches 853, allowing the plunger to move
forwards (upwards in the Figure) but not rearwards (downwards in the Figure),
and two feeding latches 854, arranged for reciprocating movement as indicated
by arrows 855, which latches brings the plunger with them during their forward
movement but not during rearward movement when they instead overrides the
2 0 teeth and the plunger is prevented from rearward movement by the
stationary
latches 853. According to a known variety, e.g. DE 19900827, the teeth and/or
latches can be slightly displaced axially at different curcumferential parts
of the
plunger so as to allow smaller movement steps than corresponding to the
distance between two teeth on one side. Any of these known constructions can
2 5 be used in the embodiment to be described.
Figure 9A shows in plain view and 9B in end view a modified plunger 951 having
a generally circular cross-section and three axial sets of teeth 952
interleaved
with three axial plain parts 958 distributed around the plunger periphery.
30 Certainly any number of teeth sets and plain parts can be used, e.g. at
least one
and up to five. As best seen in Figure 9A the teeth are slightly inclined with
respect to the plunger axis. Such a plunger rod can be manufactured from a
screw of suitable pitch with the threads removed at the plain parts. As will
be
further explained below the arrangement will allow latches to either engage
the
3 5 teeth or slide along the plain parts depending on their relative angular
positions.
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In Figures 9C and 9D an arrangement similar to that of Figure 7 is shown and
the following description will focus on the differences. A plunger 951, as
described in relation to Figures 9A and 9B, is centrally arranged in the
mechanism shown and has the same purpose of transferring liquid from a
storage chamber to a pressure chamber as described in relation to Figure 7.
The
plunger 951 is axially movable but rotationally locked in relation to the
housing
910 in any manner known per se, e.g. by a part connected to the housing
permanently keying in to the plain parts of the plunger. For similar purposes
as
explained in relation to Figure 8, a set of three stationary latches 953 is
arranged to allow forward but not rearward movement of the plunger. These
latches are permanently engaged with the plunger although preferably an
arrangement can be present for release in connection with plunger retraction
at
cartridge replacement, e.g. by allowing rotation of the plunger for release
from
both the stationary latches and feeding latches when the knob is in its rear
position or allowing rotation of a support for the stationary latches when the
knob is in its pushed, forward, position. Similarly three feeding latches 954
are
arranged on a platform 955, which can both be reciprocated axially and rotated
enough to either bring the feeding latches to the shown teeth engagement or to
the plain parts. The platform 955 is connected to a plunger driver 956 in such
a
2 0 manner that it moves with the plunger driver in the axial direction but is
free to
rotate in relation to the plunger driver, e.g. by a bearing type attachment.
To be
further explained the plunger driver is driven in the axial direction by a
control
knob, in ,the shown embodiment by having a gear wheel 957 rotating between a
fixed toothed housing rail 911 on the housing and a corresponding toothed knob
2 5 rail on the control knob, the arrangement giving the plunger driver half
the
displacement of the control knob and allowing doubled pitch (axial step for
one
revolution) with reduced friction for the drum, to be explained. A spring 959
biases the plunger driver towards a retracted position. The platform 955 is
also
connected to an extension 967 of a drum 961 by which rotation can be imposed
3 0 on the platform to move feeding latches 954 between the toothed parts 952
and
the plain parts 958 of the plunger 951 but the extensions can move freely in
the
axial direction with respect to the platform. These components can be said to
be
part of a control unit 960 having the same purpose as in the embodiment of
Figure 7, i.e. to secure sequence of liquid transfer followed by de-aeration.
In the
3 5 present embodiment the drum 961 can both rotate, to engage or disengage
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19
latches 954 as described, and move axially to allow the extensions 967 to
affect
a de-aeration unit (not shown). The drum is preferably hollow to accommodate
part of the plunger. The drum has a track 962 with a helical part 963, a knee
964, a first straight part 965 connected to the helical part at a second knee
969
and a second straight part 966. The track co-operates with a track follower
968,
in this embodiment attached to the housing. When the drum is moved in the
axial direction the track follower will secure a first straight movement in
the
track first straight part 965, with the feeding latches 954 engaged to push
the
plunger forwards. When the follower 968 enters into the track helical part 963
it
will impose a rotation on the platform 955 to disengage the feeding latches
from
the plunger. Preferably the pitch of the helical part is adapted to the pitch
of the
inclined teeth 952 of the plunger so that disengagement can take place without
axial movement of the plunger. In the present embodiment the helical part
pitch
is about double that of the plunger teeth pitch because of the speed and
movement reduction in the gear wheel 957 system. However, it is also possible
to
have a slightly higher pitch on the helical part to create a liquid bleeding
during
disengagement, e.g. to give a fixed volume overdose independent of dose set
for
example to fill out dead space in the liquid transfer channel parts.
Alternatively
a lower pitch can be used to facilitate release of the latches. The helical
part
2 0 pitch should be non-locking although it is possible to fine-tune the
overall
friction in the system so that a locking occurs at high reaction forces, e.g.
to
secure that any overpressure must even out before release of the feeding
latches
is possible. The pitch of the plunger teeth can be non-locking but is
preferably
locking, to stabilise the plunger positions. When the follower reaches the
knee
2 5 964 the feeding latches are disengaged and further movement in the second
straight part 966 will take place without moving the plunger forwards. As in
the
embodiment of Figure 7 the knee 964 is axially located where de-aeration
begins,
in the present embodiment where extensions 967 comes into contact with parts
moving the piston in the pressure chamber. Further forward movement of the
3 0 drum, with the follower in the second straight part 966 of the track, will
perform
de-aeration by moving the piston in the pressure chamber. Since follower
movement in the helical part 963 does not, or only slightly, displace the
plunger
the movements in the first straight paxt 965 and the second straight part 966
become complementary for 'a given constant stroke length of the drum, such
that
35 a short movement in the first straight part (small liquid dose) corresponds
to a
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large movement in the second straight part (long de-aeration) and vice versa.
Dose setting is controlled by selection of the initial axial position for the
drum.
An actuation unit 970 comprises a manually controlled knob 971, which has a
rotatable part 972 for dose setting, connected via co-operating threads to an
5 axially displaceable part 973 used for dose transfer and de-aeration.
Rotation of
the rotateable part 972 will bring the drum 961 to a selected initial axial
position
with respect to the follower 968 in the first straight part 965 of the track,
the
position corresponding to the desired dose. The axially displaceable part 973
has
external toothed knob rails 974 engaged with the gear wheel 957. Pushing the
10 knob will rotate the gear wheel and displace the plunger driver 956 to move
the
plunger 951 for transfer of liquid. The displacement of plunger driver will be
half
of the displacement of the knob, suitable when the storage chamber has an
inner cross-section area double that of the pressure chamber inner cross-
section
area. In operation the user first sets a dose by rotating the rotateble part
972. In
15 Figure 9C the position of the follower 968 in the first straight part 965
of the
track corresponds to a minimum dose with the follower close to the helical
part
963 of the track. The feeding latches are in engagement with the teeth 952 of
the
plunger 951. The knob 971 is then pushed a standardised stroke length for all
doses to the position shown in Figure 9D. During the first part of this
movement
2 0 the plunger is advanced, to transfer the small dose set, by co-operation
of the
knob rail 974, the gear wheel 957 and housing rail 911 to advance the plunger
driver. When the follower passes the helical part 963 the feeding latches 954
are
disengaged from the plunger teeth by rotation 60 degrees (when using three
sets
of teeth), as seen in Figure 9D, and further movement of the drum, with the
2 5 follower at the knee 964 and onwards in the second straight part 966 of
the
track, serves the de-aeration purpose. In Figure 9D the follower 968 is in the
lowermost part of the second straight part of the track, corresponding to a
maximum de-aeration and maximum forward position for the extensions 967,
leaving the pressure chamber ready for injection. Upon release of the knob the
spring 959 will urge the knob 971, the plunger driver 956 and the drum 961
with extensions 967 back to their initial position. During this reverse motion
the
plunger 951 will be kept fixed by stationary latches 953 and the piston in the
pressure chamber will remain in its ready position by not being attached to
its
driving means.
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The arrangement of Figure 9 can be used together with the remaining features
of
Figure 7, not shown in Figure 9, e.g. the same disposable pressure chamber
part
and replaceable storage chamber part. It can also use the same kind of
injection
unit 730 and de-aeration unit 740, in which case the extensions 967 of Figure
9
will essentially act as the transition element 741 of Figure 7, i.e. to move
the
entire injection unit aggregate forwards during the de-aeration step in a
serial
kind of arrangement. Alternatively the Figure 9 embodiment can be combined
with a parallel kind of arrangement in which the extensions 967 act
independently on the piston rod support 36 during the de-aeration step and the
injection unit similarly acts independently on the piston rod support during
the
injection step. Such an arrangement is schematically illustrated in Figure 10.
Figure 10 shows schematically in perspective view a modification of ram sleeve
731 of Figure 7F, and corresponding features have been given the same
reference numbers. The ram sleeve is designed to surround the storage chamber
and has a front flange 732 for retention of the storage chamber and for impact
on piston rod support 36 during injection. It also has a rear flange 733 to be
affected by a spring (not shown), acting between the rear flange and a support
(not shown), which in this embodiment can be fixed to the housing since only
2 0 the ram sleeve, but not the entire injection unit shall be movable. In
partial cut-
outs in the ram sleeve are arranged independently axially movable de-aeration
rods 1001 and 1001', able to slide with respect to the ram sleeve and
independently act with their front ends on the piston rod support for de-
aeration
purposes. The two de-aeration rods are preferably joined, as illustrated at
1002,
2 5 for movement in unison. This parallel arrangement has some advantages over
the serial arrangement shown in Figure 7. During the de-aeration step the de-
aeration rams 1001 and 1001' will create a distance between the piston rod
support 36 and flange 732 of the ram sleeve, creating an initial high
penetrating
liquid pressure followed by a lower sustained injection pressure. Although
such
3 0 a pressure profile is known as such the embodiment shows its possible
implementation in the present context. A stationary support for the ram sleeve
can be made simple and stable. The parallel arrangement described can be used
together with the earlier described embodiments. For example, the stationary
support arrangement for the ram sleeve of Figure 10 can replace the movable
3 5 support 734 of Figure 7 and the transition element 741 can act on, be
integral
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with or be replaced by, the de-aeration rams 1001 and 1001' or the joint 1002.
Similarly the arrangement of Figure 10 can be used with the embodiment of
Figure 9, for example if the extensions 967 are made to act on, be integral
with
or replaced by the de-aeration rams 1001 and 1001' or the joint 1002.
Pressure chambers for use with the invention are preferably sterilized prior
to
assembly and are empty or filled with air or a gas. They are preferably
disposable but might also be reusable. The inner diameter of the front-end
opening is 0,1-0,6 mm, preferably in the order of 0,15 mm. As said, the
opening
may be adapted either for needle-free jet injection, as schematically
illustrated in
the Figures, or needle injection, in which case the front opening may have an
attachment or connector for a needle. As also known per se a short needle in
the
range of about 1 to 3 mm can be used to penetrate the outermost part of the
skin and thereby reduce the jet speed necessary to reach target depth in the
tissue.
The storage chamber is preferably separate from the pressure chamber and
preferably made from different material. According to a preferred embodiment
is
the storage chamber made from glass, e.g. Type I glass, and the pressure
chamber made from plastic, e.g. polycarbonate.
According to an alternative embodiment the storage chamber is divided, by an
intermediate piston and provided with a by-pass section, into two separate
compartments whereas the rear compartment comprises a liquid, e.g. water, and
2 5 the front compartment comprises a solid component, e.g. a lyophilized
powder.
The liquid is forced into the distal compartment via the by-pass section where
a
liquid solves the solid component. This is a well-known procedure in the art
of
two compartment syringes. The thus mixed liquid located in the distal
compartment is then transferred into the pressure chamber in exactly the same
3 0 manner as described above.
By-pass designs, for use either in the pressure chamber or a dual compartment
storage chamber, can take a variety of forms. The illustrated by-pass section
roughly comprises one or many traces, by-pass channels, on the inner surface
of
3 5 the by-pass section of the pressure chamber. The by-pass channels can be
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23
parallel to the longitudinal direction of the delivery chamber, e.g. as
described in
US 5501673. They could also being arranged in an angle to the longitudinal
direction, e.g. as described in US 5716338. The number of channels is chosen
in
dependence of the amount of liquid to be transferred, preferably in the order
of
1-15. Many further different ways to arrange the by-pass section are known
from
the prior art. It is important that not too many channels are arranged due to
the
volume of liquid that remains in the channels when the liquid is transferred.
It is
also suitable to reduce the dead volume held between any circumferential
ridges
on the pistons by keeping the difference small between the diameter through
the
ridges and through the main body of the piston respectively. According to an
alternative embodiment is the shape of the inner surface of the by pass
section
such that the piston is deformed when passing the section and thereby allows
liquid to pass from the storage chamber into the pressure chamber e.g. as
described in US 5472422 and US 5817055.
The different steps performed is basically a three step procedure comprising a
transfer step where the liquid is transferred from the storage chamber into
the
pressure chamber, a step for removing air from the pressure chamber and an
injection step. The liquid transfer and the de-aeration steps are preferably
2 0 performed fairly slowly and under low pressure compared with the
pressurizing
step, not to induce glass breakage, plunger overshooting in the by-pass,
liquid
foaming or liquid spraying through the opening. Only the injection step has to
be
performed under high pressure.
2 5 Both during the transfer step and during the air removing step the device
is
preferably held in a somewhat upright position, i.e. the front end opening of
the
pressure chamber above horizontal, aslant or substantially facing upwards, in
order to prevent the liquid to pour out.
3 0 The present invention is not limited to the above-described preferred
embodiments. Various alternatives, modifications and equivalents may be used.
Therefore, the above embodiments should not be taken as limiting the scope of
the invention, which is defined by the appended claims.
