Note: Descriptions are shown in the official language in which they were submitted.
WO 2010/115818 PCT/EP2010/054343
Description
Drug delivery device
The present invention relates to a drug delivery device, particularly to a
portable pen-
type drug injector.
Portable drug delivery devices are used for the administration of a medicinal
fluid or
drug. A drug injection device is especially useful in the shape of a pen. A
dose of a
drug is delivered by means of a drive mechanism using a piston driven by a
piston rod.
The device may be refillable, especially by means of exchangeable cartridges,
which
contain the drug to be injected and are inserted in the body of the injection
pen. In this
case the piston can be arranged within the cartridge, while the piston rod is
a
component of the drive mechanism. When an emptied cartridge is substituted
with a
new one, the drive mechanism has to be reset.
EP 1 923 083 Al describes a drug delivery device in the shape of an injection
pen
having a drive mechanism, which allows to deliver a plurality of different
prescribed
doses.
WO 2008/074897 Al describes a syringe device in the shape of a pen. It
comprises a
container for a drug and a piston for the delivery of the drug, further a
housing having a
helical thread, a dose dial sleeve having a helical thread engaged with the
helical
thread of the housing, a drive sleeve detachably connected to the dose dial
sleeve and
a clutch means located between the dose dial sleeve and the drive sleeve. When
the
dose dial sleeve and the drive sleeve are coupled via the clutch means, both
are
allowed to rotate with respect to the housing. When the dose dial sleeve and
the drive
sleeve are decoupled, rotation of the dose dial sleeve with respect to the
housing is
allowed whilst rotation of the drive sleeve with respect to the housing is not
allowed,
whereby axial movement of the drive sleeve is allowed so that a force is
transferred in
the longitudinal direction to a piston rod for drug delivery.
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It is an object of the present invention to disclose a drug delivery device
comprising a
mechanism with a means that facilitates a reset of the mechanism.
This object is achieved with the drug delivery device according to claim 1.
Further
aspects and variations of the invention derive from the depending claims.
The drug delivery device comprises a housing or body with a receptacle for a
drug.
The body contains a piston rod, which is provided for delivering the drug out
of the
receptacle. A mechanism in the body is used to drive the piston rod and
comprises
means for guiding the movement of the piston rod relatively to the body while
delivering the drug. Further means are provided for releasing the piston rod
from the
means for guiding the movement, thus enabling a reset of the piston rod to a
start
position, especially after the receptacle has been emptied and is to be
refilled, for
example. The device is constructed in such a manner that a reset of the piston
rod is
facilitated.
The term "drug delivery device" according to the invention shall mean a device
designed to dispense a dose of a medicinal product, preferably multiple
selected
doses, e.g. of insulin, growth hormones, low molecular weight heparins, and
their
analogues and/or derivatives etc. Said device may be of any shape, e.g.
compact or
pen-type. Dose delivery may be provided through a mechanical, electrical or
electro-
mechanical dosing mechanism or by a stored energy dosing mechanism, such as a
spring, etc. Furthermore, said device may comprise a needle or may be needle-
free.
Preferably, the term "drug delivery device" shall mean a reuseable multi-dose
pen-type
device having mechanical and manual dose selection and dose delivery
mechanisms,
which is designed for regular use by persons without formal medical training
such as
patients. Preferably, the drug delivery device is of the injector-type. Most
preferably the
drug delivery device is designed to deliver a fluid drug.
The term "piston rod" according to the invention shall mean a device driving a
piston,
which is used to expel a substance or fluid from the receptacle. The
dimensions of the
piston rod may comprise a longitudinal major extension or axis, which is
sufficiently
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large to enable an axial translational movement corresponding to the travel of
the
piston.
An embodiment of the drug delivery device comprises a body having a proximal
and a
distal end, a receptacle provided for a drug or pharmaceutical fluid near the
distal end
of the body, a piston rod which is movable in an axial direction from the
proximal end
towards the distal end for drug delivery, and a drive mechanism for the
advancement
of the piston rod.
A reset mechanism is provided for resetting the piston rod to a start position
at the
proximal end when the receptacle is empty.
The receptacle can be provided to be filled by inserting a cartridge
containing the drug
and a piston, which is to be moved by the piston rod. A receptacle provided
for a
cartridge is refilled by removing an emptied cartridge, resetting the piston
rod, and
inserting a new cartridge.
The term õdrug", as used herein, means a pharmaceutical formulation containing
at
least one pharmaceutically active compound,
wherein in one embodiment the pharmaceutically active compound has a molecular
weight up to 1500 Da and/or is a peptide, a proteine, a polysaccharide, a
vaccine, a
DNA, a RNA, a antibody, an enzyme, an antibody, a hormone or an
oligonucleotide, or
a mixture of the above-mentioned pharmaceutically active compound,
wherein in a further embodiment the pharmaceutically active compound is useful
for
the treatment and/or prophylaxis of diabetes mellitus or complications
associated with
diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such
as
deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina,
myocardial infarction, cancer, macular degeneration, inflammation, hay fever,
atherosclerosis and/or rheumatoid arthritis,
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wherein in a further embodiment the pharmaceutically active compound comprises
at
least one peptide for the treatment and/or prophylaxis of diabetes mellitus or
complications associated with diabetes mellitus such as diabetic retinopathy,
wherein in a further embodiment the pharmaceutically active compound comprises
at
least one human insulin or a human insulin analogue or derivative, glucagon-
like
peptide (GLP-1) or an analogue or derivative thereof, or exedin-3 or exedin-4
or an
analogue or derivative of exedin-3 or exedin-4.
Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) human insulin;
Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28)
human
insulin; human insulin, wherein proline in position B28 is replaced by Asp,
Lys, Leu,
Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26)
human
insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human
insulin.
Insulin derivates are for example B29-N-myristoyl-des(B30) human insulin; B29-
N-
palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-
palmitoyl
human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-
LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-
palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30)
human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-
(w-
carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-
carboxyheptadecanoyl)
human insulin.
Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence H-His-
Gly-
Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-
Phe-
Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-N H2.
Exendin-4 derivatives are for example selected from the following list of
compounds:
H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,
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H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,
des Pro36 [Asp28] Exendin-4(1-39),
des Pro36 [IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),
5 des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),
des Pro36 [Trp(02)25, Asp28] Exendin-4(1-39),
des Pro36 [Trp(02)25, IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(02)25, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(02)25, IsoAsp28] Exendin-4(1-39); or
des Pro36 [Asp28] Exendin-4(1-39),
des Pro36 [IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),
des Pro36 [Trp(02)25, Asp28] Exendin-4(1-39),
des Pro36 [Trp(02)25, IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(02)25, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(02)25, IsoAsp28] Exendin-4(1-39),
wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4
derivative;
or an Exendin-4 derivative of the sequence
H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,
des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,
H-Asn-(GIu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(GIu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36 [Trp(02)25, Asp28] Exendin-4(1-39)-Lys6-NH2,
H-des Asp28 Pro36, Pro37, Pro38 [Trp(02)25] Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-NH2,
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H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-
NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-
NH2,
H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,
des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,
H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-
NH2,
H-Lys6-des Pro36 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)-Lys6-NH2,
H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25] Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-
39)-NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-
NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(S1-39)-
(Lys)6-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-
39)-(Lys)6-NH2;
or a pharmaceutically acceptable salt or solvate of any one of the afore-
mentioned
Exedin-4 derivative.
Hormones are for example hypophysis hormones or hypothalamus hormones or
regulatory active peptides and their antagonists as listed in Rote Liste, ed.
2008,
Chapter 50, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin,
Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin,
Gonadorelin,
Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.
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A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid, a
heparin, a
low molecular weight heparin or an ultra low molecular weight heparin or a
derivative
thereof, or a sulphated, e.g. a poly-sulphated form of the above-mentioned
polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example
of a
pharmaceutically acceptable salt of a poly-sulphated low molecular weight
heparin is
enoxaparin sodium.
Pharmaceutically acceptable salts are for example acid addition salts and
basic salts.
Acid addition salts are e.g. HCI or HBr salts. Basic salts are e.g. salts
having a cation
selected from alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion
N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean:
hydrogen,
an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-
alkenyl
group, an optionally substituted C6-C10-aryl group, or an optionally
substituted C6-
C10-heteroaryl group. Further examples of pharmaceutically acceptable salts
are
described in "Remington's Pharmaceutical Sciences" 17. ed. Alfonso R. Gennaro
(Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia
of
Pharmaceutical Technology.
Pharmaceutically acceptable solvates are for example hydrates.
In a further embodiment of the drug delivery device, the reset operation is
merely
generated by the weight of the piston rod. The reset operation is started by a
release
of the piston rod, so that the piston rod is free to move. If the device is
then held with
its proximal end pointing downwards, the gravitation makes the piston rod
return to a
start position at the proximal end. This movement may be accompanied with a
rotation
of the piston rod relatively to the body of the device and may especially be a
helical
movement generated by a screw thread of the piston rod.
The materials of the piston rod and further elements of the mechanism on which
the
piston rod slides during the reset operation are selected in view of making
these
components sufficiently smooth-running on one another, and the surfaces are
given a
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finish that is most suitable to this purpose. If the device is held with its
proximal end
pointing down, the downward force exerted by the piston rod due to its weight
suffices
to generate a sliding movement of the piston rod back into the drive
mechanism. A
dedicated reset element is therefore not necessary.
In a further embodiment of the drug delivery device, a mechanism is provided,
by
which the doses to be administered can be preset. A mechanism of this kind may
be
constructed according to the following description, for example. The piston
rod
comprises a screw thread at the distal end and a further screw thread at the
proximal
end, the screw threads having different pitches and opposite senses of
rotation. The
first screw thread is provided for the generation of a helical movement of the
advancing
piston rod, during the delivery of a preset dose, by means of a piston rod
nut, which is
kept fixed relatively to the body. The further screw thread is provided for a
threaded
engagement with a drive sleeve of the drive mechanism. During the setting of a
dose
the piston rod is prevented from rotation and axial translation relatively to
the body by
the combined effect of the thread of the fixed piston rod nut and the thread
of the drive
sleeve, which moves helically around the piston rod without changing the
position of
the shape of the surface that faces the further screw thread of the piston
rod. The
thread of the drive sleeve therefore appears during the set operation as if it
were
fastened to the body, apart from the sliding movement on the surface of the
piston rod.
When a reset operation is started, the piston rod nut is detached from the
body. This
may be effected by removing the empty cartridge, for example. The piston rod
is now
able to rotate relatively to the body like a screw into the drive sleeve,
until a start
position is attained. Furthermore, the piston rod nut is also allowed to
rotate freely in
order to compensate for a discrepancy between the actual helical movement of
the
piston rod and a helical movement that would be generated by the thread of the
piston
rod nut if it were still fixed relatively to the body. After the detachment of
the piston rod
nut a translational movement of the piston rod in the axial direction towards
the
proximal end is therefore possible independently of the pitch of the thread of
the piston
rod nut.
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In a further embodiment of the drug delivery device, the mechanism is
constructed in
such a manner that to reset the piston rod it has to be rotated relatively to
the body in a
sense of rotation that is opposite to the sense of rotation of the piston rod
during drug
delivery. The means for guiding the movement of the piston rod are provided to
generate a rotation of the piston rod relatively to the body while delivering
the drug. A
spring element is loaded by the rotation of the piston rod, while delivering
the drug, in
such a manner as to make the spring element tend to rotate in a sense of
rotation that
is opposite to the sense of rotation of the piston rod while delivering the
drug. The
spring element is engaged with the piston rod in such a manner that a rotation
of the
spring element generates a rotation of the piston rod of the same sense of
rotation.
In a further embodiment comprising a spring element, a reset nut is provided
for the
reset operation. The reset nut is located coaxially around the piston rod,
which passes
through a central hole of the reset nut. The diameter of the hole is
sufficient to permit a
free movement of the piston rod through the reset nut. On the inner sidewall
of the
hole, there is at least one spline, which engages a groove of the piston rod.
The
groove is formed on the surface of the piston rod, irrespective of a screw
thread of the
piston rod, and extends at least mainly in axial direction. It may especially
run straight
along the piston rod, parallel to the axis of the piston rod. Instead, the
groove may be
wound helically around the piston rod. It may be favourable to have at least
two
splines, arranged at opposite locations of the circumference of the hole, and
two
corresponding grooves on the piston rod.
The reset nut carries a spring, which can be a spiral spring arranged in a
plane
perpendicular to the axis of the piston rod. The ends of the spring are
fastened to the
body and to the reset nut, respectively, in such a manner that the spring is
loaded
when the reset nut is turned in the rotational sense of the piston rod during
the drug
delivery operation. Because of the spline or splines and the corresponding
groove or
grooves and the fastening of the spring to the body, the reset nut is rotated
by a helical
movement of the piston rod without being moved in axial direction. The spring
of the
reset nut is held fixed to the same location of the inner surface of the body,
while the
reset nut is rotated by the rotation of the piston rod, irrespective of the
translational
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movement of the piston rod. The groove or grooves of the piston rod may be
wound
helically around the piston rod in such a manner as to generate a suitable
number of
rotations of the reset nut in total, until the piston rod reaches its final
position at the
distal end. The number of rotations of the reset nut can thus be adapted to
the
5 properties of the spring, which does not reach its state of maximal tension
or stress
before the axial translation of the piston rod is completed. The loaded spring
reverses
the total rotation of the piston rod once the piston rod nut is detached, and
the piston
rod is driven to perform a helical movement into the drive mechanism.
10 Further aspects and examples of the invention are described in conjunction
with the
appended figures.
FIG. 1 shows a cross-section of an injection pen having a mechanism comprising
a
reset operation.
FIG. 2 shows an enlarged cross-section of a part of the mechanism that is
involved in
the reset operation.
FIG. 3 shows a partial cross-section of a further embodiment of an injection
pen
comprising a reset nut.
FIG. 4 shows an enlarged plane view of the arrangement of the reset nut, at
the
position indicated in FIG. 3.
FIG. 5 shows an enlarged cross-section of a part of the mechanism that is
involved in
the reset operation.
FIG. 1 shows a cross-section of an injection device 1 in the shape of a pen
having a
proximal end 2, a distal end 3 and a housing or body 4 carrying a needle 5 at
the distal
end 3. A receptacle 6 serving as a reservoir for a drug that is to be injected
through the
needle 5 is provided at the distal end 3 and can be refilled. The delivery of
the drug is
effected by means of a piston 7, which is moved by a piston rod 8 in the axial
direction,
along the longitudinal extension of the device, thus reducing the volume of
the
reservoir according to the doses to be administered. The receptacle 6 can be
provided
for the insertion of a cartridge 16 containing the drug. In this case, the
piston 7 is
moved in the cartridge 16 and the piston rod 8 moves through a hole in the
bottom of
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the cartridge 16. At the distal end 3 the body 4 comprises a distal part 20,
which can
be taken off from a proximal part 21 of the body 4, so that the cartridge 16
can be
removed and substituted with another one.
The piston rod 8 carries a screw thread 9 at its distal end and passes through
a central
hole of a piston rod nut 14, which has a thread of the same pitch on the inner
wall of its
central hole. The piston rod 8 and the piston rod nut 14 are interlocked by
the screw
thread 9 and can be rotated relatively to one another. Simultaneously with the
rotation,
the screw thread 9 generates an axial relative movement resulting in an
overall helical
relative movement. The piston rod 8 and the piston rod nut 14 thus form a pair
of
sliding elements. The friction between these elements is reduced if they are
formed
from low-friction synthetic materials.
A lock nut 13 is engaged with the piston rod nut 14 by means of a coupling
device. A
spring 15 is arranged between the lock nut 13 and a barrier rim 27 or
transverse inner
wall of the body 4. The coupling device can be realized, for instance, by a
gear formed
by surface structures of the nuts 13, 14. When the injection pen 1 is ready
for use, the
spring 15 is compressed by the cartridge 16 inserted in the receptacle 6, and
the
coupling device engages the nuts 13, 14. The compressed spring tends to shift
the
lock nut 13 towards the distal end 3 and thereby disengage the lock nut 13 and
the
piston rod nut 14.
FIG. 2 shows an enlarged view of the arrangement of the lock nut 13 and the
piston
rod nut 14. In the center of FIG. 2, a section of the piston rod 8 is shown.
An imaginary
central axis 18 is indicated by the broken line of alternating dots and
dashes. The
piston rod 8 goes through a hole 23 of the lock nut 13, a hole 24 of the
piston rod nut
14 and a hole 26 in the bottom of the cartridge 16, which is inserted in the
receptacle
6. The spring 15, which may be a helical spring, surrounds the piston rod 8
and is
arranged between the lock nut 13 and the barrier rim 27, which can be an
integral part
of the body 4. The outermost surfaces of the spring 15 are in contact with the
surfaces
of the lock nut 13 and the barrier rim 27 facing the spring 15.
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The coupling device 17 engaging the lock nut 13 and the piston rod nut 14 can
be
formed by a sequence of interlocking teeth or some other kind of gear, for
example.
This is indicated in FIG. 2 by the lock nut 13 partially intruding the outer
margin of the
piston rod nut 14 in the area of the coupling device 17. The lock nut 13 is
engaged with
the body 4, by means of protruding parts or recesses, for example, so that the
lock nut
13 cannot rotate relatively to the body 4 around the axis 18 of the piston rod
8, but can
axially move at least a small distance towards the distal end 3. In the
embodiment
shown in FIG. 2 this is effected by grooves 25 forming internal splines in the
inner
sidewall of the body 4, which guide external splines on the circumference of
the lock
nut 13. An axial movement of the lock nut 13 towards the distal end 3 is
inhibited by
the presence of the cartridge 16. An axial movement of the nuts 13, 14 in the
direction
towards the proximal end 2 can be inhibited by barrier rims 27, spikes or a
partial
transverse wall of the body 4, for example, fixed at the inner surface of the
body 4 or
forming an integral part of the body 4 on the side of the nuts 13, 14 facing
away from
the piston 7.
The hole 24 of the piston rod nut 14 is supplied with a thread 19 having the
same pitch
as the screw thread 9 of the piston rod 8. Thus, the thread 19 of the piston
rod nut 14
is the female thread counterpart of the male screw thread of the piston rod 8.
If the
nuts are engaged by the coupling device 17 as shown in FIG. 2, a relative
rotation of
the lock nut 13 and the piston rod nut 14 is inhibited, and the piston rod nut
14 cannot
rotate relatively to the body 4 around the piston rod 8 because the lock nut
13 is
rotationally fixed by the protruding parts, recesses or grooves 25.
If the cartridge 16 is removed and the spring 15 is released, the coupling
device 17 is
no longer interlocked, and the lock nut 13 and the piston rod nut 14 are
disengaged.
This means that the piston rod nut 14 can freely rotate around the piston rod
8, and the
piston rod 8 is able to perform a translational movement along its axis 18
irrespective
of a rotation around its axis 18. This is, because the piston rod nut 14 will
freely rotate
and compensate for a discrepancy between the actual translational movement of
the
piston rod 8 and a translational component of a helical movement of the piston
rod 8
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that would be generated by the threads 9, 19 when the piston rod nut 14 is
rotationally
fixed.
The operations of setting and delivering a dose will now be described in
conjunction
with FIG. 1, which shows, by way of example, an embodiment that comprises
means
for setting a dose, including the piston rod 8 and further components arranged
in the
proximal part 21 of the body 4. The piston rod 8 is provided with a further
screw thread
at its proximal end. A drive sleeve 11 having an inner thread 12 of the same
pitch is
interlocked with the further screw thread 10 of the piston rod 8. A dial
sleeve 28 having
10 a helical thread engaged with a helical thread 29 of the body 4 and having
the same
pitch as the further screw thread 10 of the piston rod 8 is arranged around
the drive
sleeve 11 and can be rotated by the user by means of a dial grip 36, which
surpasses
the proximal end 2 of the body 4, for example. A clutch 30 of essentially
cylindrical
shape is arranged between the drive sleeve 11 and the dial sleeve 28.
The drive sleeve 11 is provided with a kind of rim or collar 31 at its distal
end. A spring
32 is arranged between the collar 31 and the clutch 30 and tends to press the
clutch
30 against the inner surface of a proximal end face of the dial sleeve 28,
where a gear
37 or similar surface structure is provided to inhibit, when engaged, a
relative rotation
of the clutch 30 with respect to the dial sleeve 28. A translational movement
of the
drive sleeve 11 relatively to the clutch 30 can preferably be limited by hooks
35 of the
drive sleeve 11, which are stopped by the proximal end of the clutch 30. A
relative
rotation of the clutch around the drive sleeve 11 is permanently inhibited,
for instance,
by clutch leads 33 engaging a gear 34 at the proximal end of the drive sleeve
11 in
such a manner that the clutch 30 can be shifted a short distance relatively to
the drive
sleeve 11 towards the distal end of the drive sleeve 11 against the force of
the clutch
spring 32. This shift can be effected by means of an operation button 39
arranged at
the proximal end 2 of the body 4 in contact with an end face 38 of the clutch.
If the
operation button 39 is pressed, the clutch 30 is shifted towards the distal
end 3 and
disengaged from the gear 37 of the dial sleeve 28, so that a relative rotation
between
the clutch 30 and the dial sleeve 28 is made possible.
WO 2010/115818 PCT/EP2010/054343
14
During the set operation to select a dose of the drug to be delivered, the
operation
button 39 is not pressed and the dial sleeve 28 and the clutch 30 are
rotationally
coupled by the gear 37. By rotating the dial grip 36, the dial sleeve 28 is
moved out of
the body 4 in a helical movement generated by the thread 29. Because of the
rotational coupling, the dial sleeve 28, the clutch 30 and the drive sleeve
11, forming a
dial assembly, always rotate by the same angle. Because the threads of the
drive
sleeve 11 and the dial sleeve 28 have the same pitch, the position of the
shape of the
surface that faces the further screw thread 10 of the piston rod 8 does not
change
during the helical movement of the dial assembly. The piston rod 8 thus always
sees
the same spatial position of the inner thread of the drive sleeve 11, as if
this thread
were an integral part of the body 4. The piston rod nut 14 is fixed during the
set
operation, so that its thread 19 also appears as if it were an integral part
of the body 4.
Since the two threads 9, 10 of the piston rod 8 have different pitches, and
also different
senses of rotation, the different helical movements corresponding to the
different
pitches cannot be performed simultaneously by the stiff piston rod 8, which is
therefore
fixed relative to the body 4 and neither moves in axial direction nor rotates.
The
rotation of the dial assembly takes therefore place without changing the
relative axial
position of the dial sleeve 28 and the drive sleeve 11, so that the clutch 30
remains
engaged with the dial sleeve 28 by means of the gear 37.
After the desired dose has been set, it may be delivered by pressing the
operation
button 39 and moving the piston rod 8 towards the distal end 3. The operation
button
39 extends through the dial grip 36 and is in contact with a proximal end face
38 or
other extreme end part of the clutch 30. When the operation button 39 is
pressed,
clutch 30 is axially shifted towards the distal end 3 of the device with
respect to the dial
sleeve 28, thereby decoupling the clutch 30 from the dial sleeve 28. However,
the
clutch 30 remains keyed in rotation to the drive sleeve 11. Therefore the
decoupling of
the clutch 30 results in a decoupling of the dial sleeve 28 and the drive
sleeve 11. The
dial sleeve 28 is free to rotate in a helical movement according to the thread
29, thus
moving back into the body 4 to its original position. The clutch 30 is being
kept from
rotation either by the operation button 39 directly, for instance, or by some
other
means not shown in FIG. 1, which may be arranged between an outer structure of
the
WO 2010/115818 PCT/EP2010/054343
clutch 30 and axial grooves in the body 4, for instance, in order to guide the
movement
of the clutch, allowing an axial translation but inhibiting a rotation. The
drive sleeve 11,
which cannot be rotated relatively to the clutch 30, is therefore not wound
around the
piston rod 8 as during the set operation, but shifts the piston rod 8 towards
the distal
5 end 3. The piston rod 8 performs a helical movement with respect to the body
4
through the piston rod nut 14. Because of the different senses of rotation of
the screw
threads 9, 10 of the piston rod 8, the drive sleeve 11 is moved towards the
piston rod
nut 14, and the axial displacement of the drive sleeve 11 exceeds the
displacement of
the piston 7, which is defined by the axial translation of the piston rod 8
relatively to the
10 body 4. The different pitches of the screw threads 9, 10 of the piston rod
8 define the
relation between the distance that the dial assembly is axially moved per unit
dose
during the set operation and the distance that the piston 7 is moved during
the delivery
of one unit dose, and the pitches can be adjusted to provide a desired
transmission for
easy use. The pitch of the thread of the drive sleeve 11, corresponding to the
further
15 screw thread 10 of the piston rod 8, is preferably larger than the pitch of
the thread of
the piston rod nut 14.
When the final dose has been dispensed, the cartridge 16 is empty and may be
removed. To this end, the distal part 20 of the body is taken off together
with the
cartridge 16, and the lock nut 13 is released. The spring 15 moves the lock
nut 13
away from the piston rod nut 14, so that the nuts 13, 14 are no longer engaged
by the
coupling device 17. Then the piston rod nut 14 can rotate relatively to the
body 4 and is
ready for the reset operation.
During reset, the piston rod 8 is screwed into the drive sleeve 11 towards the
proximal
end 2. To this purpose it may suffice to hold the injection device with its
proximal end 2
downwards and have the piston rod 8 rotate into the drive sleeve 11, following
the
gravitation of its own weight. In order to achieve this, the materials of the
sliding
elements are selected to be sufficiently smooth-running.
The friction between rough planar surfaces of two bodies that are in contact
and move
relatively to one another, so that the surfaces slide on one another,
generates a force
WO 2010/115818 PCT/EP2010/054343
16
FR of a retarding effect directed within the plane of the surfaces, thus
decreasing the
velocity of the relative movement. At a certain specified relative speed of
the bodies,
the absolute value of the frictional force FR can generally be regarded as
being
proportional to the absolute value of a force FN perpendicular to the plane of
the
surfaces, by which the bodies are pressed on one another. The quotient of the
absolute value of the frictional force FR and the absolute value of the
perpendicular
force FN is called coefficient p of sliding friction, so that the equality FR
= p(vr)x FN is
supposed for any specified relative velocity yr of the bodies.
If the mechanical elements are made of synthetic or plastic material, a value
of the
coefficient p of sliding friction of typically 0.25 or less at a relative
velocity of the sliding
surfaces of 2 mm per second can be obtained. The piston rod 8 may be a liquid
crystalline polymer and the piston rod nut 14 and the drive sleeve 11
polyoxymethylene, for example. A comparable value of p can be obtained for the
sliding movement of the piston rod nut 14 on a surface or barrier rim 27 of a
body 4
made of synthetic or plastic material.
The properties of the materials can also be specified by the roughness of
their
surfaces. The roughness can be measured by the deviation of the actual rough
surface
from a smooth reference surface. A characteristic parameter of the roughness
is the
average of the absolute value of the distance between a point of the actual
surface and
the corresponding point of the reference surface, called centre line average.
The mate-
rials of the piston rod 8, the piston rod nut 14 and the drive sleeve 11 are
preferably
selected to have a centre line average of less than 1.6 pm.
A further parameter that is relevant with respect to the ease of the sliding
motion of the
piston rod 8 through the threads is the pitch of the threads. A pitch of a
screw thread
can be specified, depending on the diameter of the screw, by the angle between
the
axis of the screw and the tangents of the helix formed by the thread. The
reset
operation is promoted if the angle between the axis 18 of the piston rod 8 and
the
tangents of the helices of the threads 9, 10 is as large as feasible. This
angle can be
made at least 25 for the thread of the piston rod nut 14 and at least 40 for
the thread
WO 2010/115818 PCT/EP2010/054343
17
of the drive sleeve 11. Larger values may be favourable to the reset
operation, but
upper limits of the angles are imposed by the shape and dimensions of the
device.
In a further embodiment of the injection device according to FIG. 3, the reset
operation
is effected by a reset element. In this embodiment the mechanism is
constructed in
such a manner that to reset the piston rod 8 it has to be rotated relatively
to the body 4
in a sense of rotation that is opposite to the sense of rotation of the piston
rod 8 during
drug delivery. Although a mechanism of this kind may be constructed without
the nuts
13, 14 and spring 15 described above, the distal part of the mechanism of the
embodiment of FIG. 3 is represented in a fashion to be comparable to the
mechanism
of the embodiment according to FIGs. 1 and 2 for easy reference.
The mechanism of the embodiment according to FIG. 3 comprises a reset nut 43
having a central hole with a sidewall carrying a protruding structure, which
can be at
least one spline 41 or spike, for example, as shown in FIG. 4. The piston rod
8 goes
through the central hole of the reset nut 43, which is arranged transversely
to the axis
18 of the piston rod 8. The protruding structure of the reset nut 43 is
engaged in at
least one groove 42 of the piston rod 8, which runs along the surface of the
piston rod
8 and intersects the thread without affecting the helical movement generated
by the
thread. The groove 42 can run along a straight line parallel to the axis 18 or
be wound
helically around the piston rod 8. The engagement between the piston rod 8 and
the
reset nut 43 generates a rotation of the reset nut 43 according to the
rotation of the
piston rod 8. The piston rod 8 can move axially through the reset nut 43,
owing to the
longitudinally extending groove 42, while the reset nut 43 is only rotated and
can be
held in its axial position.
A spring 40, which is preferably a spiral spring, is attached to the reset nut
43 and
fastened to an inner surface 44 of the body 4 or another element that is
relatively fixed
to the body 4. The positions of the fastening 45 of the spring 40 to the body
4 and of
the fastening 46 of the spring 40 to the reset nut 43 as well as the
arrangement of the
spiral spring 40 on a surface of the reset nut 43 can be seen in cross-section
in FIG. 3,
in a plan view in FIG. 4, and in an enlarged cross-section in FIG. 5.
WO 2010/115818 PCT/EP2010/054343
18
The spiral spring 40 is arranged in such a manner that it is loaded when the
reset nut
43 is turned in the rotational sense of the piston rod 8 during the drug
delivery
operation. Because of the spline 41 or splines 41 and the corresponding groove
42 or
grooves 42 and the fastening of the spring 40 to the body 4, the reset nut 43
is rotated
by the helical movement of the piston rod 8 without being moved in axial
direction. The
spring 40 and with it the reset nut 43 are thus always held at their axial
position with
respect to the body 4. The total number of rotations performed by the reset
nut 43 until
the reservoir is empty can be adjusted by the straight or helical shape of the
groove 42
or grooves 42. The spring 40 is repeatedly loaded to increase its tension or
stress, but
does not reach its state of maximal tension or stress before the axial
translation of the
piston rod 8 is completed.
When the reset operation is initiated by releasing the piston rod 8, the
spring 40
reverses the overall rotation of the piston rod 8, and the piston rod 8 is
driven like a
screw back into the drive mechanism. While the rotation is generated by the
spring 40,
the helical movement can be generated by a screw thread of the piston rod 8
sliding in
the thread of a fixed piston rod nut 14, for example, or, if the piston rod
nut is released
or if no piston rod nut is used, sliding in a thread of another element of the
mechanism.
FIG. 5 shows a variant of the embodiment according to FIG. 3, which comprises
at
least two spiral springs 40 arranged at the reset nut 43. Each spiral spring
40 is
fastened to the body 4 and to the reset nut 43 by fastenings 45, 46. The
spiral springs
40 can be arranged so as to form a double or multiple line or band winding
along a
spiral.
Features of the described embodiments can be combined. In particular, the
reset nut
can be provided in a mechanism comprising sliding elements formed from smooth-
running materials. The pitch of the screw thread that is responsible for the
helical
motion of the piston rod 8 during the reset can be made large enough to
facilitate the
back-winding of the reset nut 43 and spring 40. The angle between the axis 18
of the
WO 2010/115818 PCT/EP2010/054343
19
piston rod 8 and the tangents of the helix formed by said screw thread can be
more
than 400 to this purpose.
WO 2010/115818 PCT/EP2010/054343
Reference numerals
1 injection pen
2 proximal end
5 3 distal end
4 body
5 needle
6 receptacle
7 piston
10 8 piston rod
9 screw thread
10 screw thread
11 drive sleeve
12 thread of drive sleeve
15 13 lock nut
14 piston rod nut
15 reset spring
16 cartridge
17 coupling device
20 18 axis
19 thread of the piston rod nut
20 distal part of the body
21 proximal part of the body
22 ------- (free)
23 hole of the lock nut
24 hole of the piston rod nut
25 groove
26 bottom hole of the cartridge
27 barrier rim
28 dial sleeve
29 thread
30 clutch
WO 2010/115818 PCT/EP2010/054343
21
31 collar of the drive sleeve
32 clutch spring
33 clutch lead
34 gear of the drive sleeve
35 hook of the drive sleeve
36 dial grip
37 gear of the dial sleeve
38 end face of the clutch
39 operation button
40 spiral spring
41 spline
42 groove of the piston rod
43 reset nut
44 inner surface of the body
45 fastening of the spiral spring to the body
46 fastening of the spiral spring to the reset nut
