NZ615854B2 - Dose setting mechanism and injection device - Google Patents
Dose setting mechanism and injection device Download PDFInfo
- Publication number
- NZ615854B2 NZ615854B2 NZ615854A NZ61585412A NZ615854B2 NZ 615854 B2 NZ615854 B2 NZ 615854B2 NZ 615854 A NZ615854 A NZ 615854A NZ 61585412 A NZ61585412 A NZ 61585412A NZ 615854 B2 NZ615854 B2 NZ 615854B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- clutch
- clicker
- dose setting
- drive member
- dose
- Prior art date
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31525—Dosing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31525—Dosing
- A61M5/31528—Dosing by means of rotational movements, e.g. screw-thread mechanisms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31533—Dosing mechanisms, i.e. setting a dose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31533—Dosing mechanisms, i.e. setting a dose
- A61M5/31535—Means improving security or handling thereof, e.g. blocking means, means preventing insufficient dosing, means allowing correction of overset dose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31533—Dosing mechanisms, i.e. setting a dose
- A61M5/31545—Setting modes for dosing
- A61M5/31548—Mechanically operated dose setting member
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31533—Dosing mechanisms, i.e. setting a dose
- A61M5/31545—Setting modes for dosing
- A61M5/31548—Mechanically operated dose setting member
- A61M5/3155—Mechanically operated dose setting member by rotational movement of dose setting member, e.g. during setting or filling of a syringe
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31533—Dosing mechanisms, i.e. setting a dose
- A61M5/31545—Setting modes for dosing
- A61M5/31548—Mechanically operated dose setting member
- A61M5/3155—Mechanically operated dose setting member by rotational movement of dose setting member, e.g. during setting or filling of a syringe
- A61M5/31551—Mechanically operated dose setting member by rotational movement of dose setting member, e.g. during setting or filling of a syringe including axial movement of dose setting member
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31533—Dosing mechanisms, i.e. setting a dose
- A61M5/31545—Setting modes for dosing
- A61M5/31548—Mechanically operated dose setting member
- A61M5/31555—Mechanically operated dose setting member by purely axial movement of dose setting member, e.g. during setting or filling of a syringe
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31565—Administration mechanisms, i.e. constructional features, modes of administering a dose
- A61M5/31576—Constructional features or modes of drive mechanisms for piston rods
- A61M5/31583—Constructional features or modes of drive mechanisms for piston rods based on rotational translation, i.e. movement of piston rod is caused by relative rotation between the user activated actuator and the piston rod
- A61M5/31585—Constructional features or modes of drive mechanisms for piston rods based on rotational translation, i.e. movement of piston rod is caused by relative rotation between the user activated actuator and the piston rod performed by axially moving actuator, e.g. an injection button
Abstract
Disclosed are dose setting mechanism for a drug delivery device and an injection device. The dose setting mechanism comprises a dose setting member (3); drive member (4) and clutch member (5). The clutch member (5) is located between the dose setting member (3) and the drive member (4). The clutch member (5) is axially movable relative to the dose setting member (3) and the drive member (4). The clutch member (5) is rotationally fixed to the drive member (4) and provides a first clutch for rotationally coupling and decoupling the dose setting member (3) and the drive member (4). A clicker (6) comprising a first component (6’) and a second clicker component (6’’) are axially movable relative to each other for producing tactile and/or audible feedback during relative rotational movement there between. The first clicker component (6’) is axially movable relative to the drive member (4) providing a second clutch member for rotationally coupling and decoupling the drive member (4) and the first clicker component (6’). The first and second clutches are designed and adapted to each other such that at any time during operation either the first clutch rotationally couples the dose setting member (3) and the drive member (4) and/or the second clutch rotationally couples the drive member (4) and the first clicker component (6’). ember (5) is axially movable relative to the dose setting member (3) and the drive member (4). The clutch member (5) is rotationally fixed to the drive member (4) and provides a first clutch for rotationally coupling and decoupling the dose setting member (3) and the drive member (4). A clicker (6) comprising a first component (6’) and a second clicker component (6’’) are axially movable relative to each other for producing tactile and/or audible feedback during relative rotational movement there between. The first clicker component (6’) is axially movable relative to the drive member (4) providing a second clutch member for rotationally coupling and decoupling the drive member (4) and the first clicker component (6’). The first and second clutches are designed and adapted to each other such that at any time during operation either the first clutch rotationally couples the dose setting member (3) and the drive member (4) and/or the second clutch rotationally couples the drive member (4) and the first clicker component (6’).
Description
Dose Setting Mechanism and Injection Device
The present invention is directed to a dose setting mechanism for a drug delivery
device, like a pen-type injector, that provides for administration by injection of me-
dicinal products from a multidose cartridge. The dose setting mechanism may com-
prise a g, a dose setting member (number sleeve), a drive member (drive
sleeve), a clutch and a clicker. Further, the invention refers to an injection device
with such a dose g mechanism.
In injection devices where the drive sleeve is coupled to the number sleeve via a
clutch during dialing (dose setting) and coupled to the housing during dispense, via
a clicker, and where coupling and decoupling is accomplished by a movement of the
clutch member between a dialing (dose g) and dispense on, it is important
to ensure that in both general and misuse scenarios at extremes of tolerance, the
user cannot decouple the drive sleeve from the number sleeve without first ensuring
that it is sufficiently d to the housing.
If at any point the drive sleeve is neither coupled to the number sleeve nor to the
housing with adequate strength, it may be possible for the user to rotate the drive
sleeve relative to the number sleeve and housing. In devices where the drive sleeve
has a threaded connection or splined connection to a piston rod that moves y
to expel the drug contents in the cartridge, rotating the drive sleeve relative to both
the number sleeve and housing allows the user to back off the piston rod from the
cartridge bung without decrementing the dialed dose, and this may lead to a severe
under dose on the subsequent dose. If the drive sleeve is rotated in the opposite
sense, it may also allow the user to expel drug without decrementing the dialed
dose, leading to loss of drug and possible confusion.
Figure 1 shows a known dose setting mechanism 1 where a spring 7 biases the
clicker 6 into ment with the clutch 5 and the clutch 5 into engagement with
the number sleeve 3. r teeth 6a, 6b of axial height 'Y1' engage between the
clicker 6 and clutch 5 components and the clutch teeth 5a, 5b of axial height 21'
engage between the clutch 5 and the number sleeve 3 components. In this 'At rest'
state a gap of 'X1' exists which is defined as the amount that the clicker 5 can move
axially towards the drive sleeve 4 before the spring 7 is compressed to a solid state
and ts further axial movement.
This gap 'X1' has a total tolerance of 'T' which is made up from the addition of the
individual tolerances of the component parts, clicker axial , clutch axial length,
number sleeve flange thickness, drive sleeve axial length and the spring height
when compressed solid.
For the device to be dialable, the gap 'X1' in its minimum nce condition, X1-T,
must still be large enough to allow the clicker teeth 6a, 6b to ride over each other
during dialing so that the clutch 5 and hence drive sleeve 4 can rotate relative to the
number sleeve 3. Hence the device must comply with the equation
X1 -T>Y1.
Similarly in order for the device to be able to dispense the gap X must be large
enough to allow the clutch teeth 5a, 5b n the clutch 5 and number sleeve 3 to
disengage. In this case, the device must comply with the equation
X1 -T>Z1.
In addition, to ensure that the drive sleeve 4 is either rotationally coupled via the
clutch 5 to the number sleeve 3 or onally coupled to the housing 2 via the
clutch 5 and clicker 6, and is not in some indeterminate state where it can rotate
relative to both parts, the device must comply with the equation
X1 +T<Z1 +Y1-K
where K is defined as the minimum overlap between either the clicker teeth 6a, 6b
or the clutch teeth 5a, 5b to ensure that the drive sleeve 4 has sufficient engage-
2012/055054
ment with one of these sets of teeth so as not to rotate relative to both sets. This
minimum overlap K will have to be larger if the device is to be able to withstand
rotation of the drive sleeve 4 relative to the housing 2 and the number sleeve 3
under a reasonable user applied . Adding the tolerance T to X1 allows to
define a worst case combination of parts for this failure mode.
Combining the above three equations,
X1-T>Z1 (1)
x1 -T > Y1 (2) and
X1+T<Z1+Y1-K (3)
one can substitute from (1) X1 = Z1 + T into (3) to give
+K
and from (2) one can substitute X1 = Y1 + T into (3) to give
Z1>2*T+K.
Due to the long tolerance chain identified above this total stack tolerance of T may
be as much as T = 0,4 mm, and to ensure adequate strength K = 0,4 mm as well. In
this case Y1 must be greater than 2 * 0.4 mm + 0.4 mm = 1,2 mm. The clicker teeth
6a, 6b however have e.g. 24 positions per turn and hence 24 teeth. A height of 1,2
mm would require the clicker teeth to have a very steep flank angle given the re—
stricted diameter of the part, and this flank angle would either make dialing not pos-
sible or give a very high dialing torque. |n prototypes tested the clicker teeth height
was only 0,7 mm and this gave a reasonable dialing torque.
A1 discloses a drive ism for a drug delivery device. The
embodiment of Figures 2 to 6 of this document includes a first clutch between a
dose setting dial and an inner cylinder and a second clutch between the inner cylin-
der and a e knob. However, A1 does not teach that at
any time during operation either the first clutch couples the dose setting member
a the drive member and/or the second clutch couples a drive member to a clicker
component. Moreover, a clicker producing a tactile and/or audible feedback is not
de- scribed in this document. In addition, in the ism of
A1 there is no clutch member located between the dose setting member to a
drive member which clutch member is movable ve to these components in
an axial direction.
It is therefore an object of this invention to e an improved and yet compact
dose setting mechanism with a clicker system that decreases the risk of
malfunction. In more detail, it is an object of the t invention to provide an
alternative design of a clicker which does not have the restriction of X1 - T > Y1. It
is an onal or alternative object of the t invention to provide the public
with a useful choice.
A first aspect of the present invention es a dose setting mechanism for a
drug delivery device, the mechanism comprising: a dose setting member, a drive
member, a clutch member located between the dose setting member and the
drive member, the clutch member being axially movable relative to the dose
setting member and to the drive member and being rotationally fixed to the drive
member, providing a first clutch for rotationally coupling and de-coupling the dose
setting member and the drive member, a clicker comprising a first clicker
component and a second clicker component axially movable relative to each
other for producing a tactile and/or audible feedback during relative rotational
movement there between, wherein the first clicker component is axially movable
relative to the drive member providing a second clutch for onally ng
and de-coupling the drive member and the first clicker component,
wherein the first clutch and the second clutch are designed and adapted to each
other such that at any time during operation either the first clutch rotationally
couples the dose setting member and the drive member and/or the second clutch
rotationally couples the drive member and the first clicker component.
Comprises/comprising and grammatical variations thereof when used in this
specification are to be taken to specify the ce of stated features, integers,
steps or components or groups thereof, but do not de the presence or
on of one or more other features, integers, steps, components or groups
thereof.
A second aspect of the present invention provides an injection device comprising
a dose setting mechanism according to the first aspect and a medicament.
A dose setting mechanism according to the t invention ses a dose
setting member, a drive member and a clutch member providing a first clutch
located between the dose setting member and the drive member. The clutch
member is preferably axially movable relative to the dose setting member and the
drive member in order that the first clutch might rotationally couple or ple
the dose setting member and the drive member. The dose setting mechanism
further comprises a clicker having a first clicker component and a second clicker
component. The first clicker is rotationally fixed to the housing in all permitted
axial positions. The second clicker is rotationally fixed to the drive member in all
permitted axial positions. The first and second clickers are axially e
relative to each other and to the drive member for producing a tactile and/or
e feedback during dialing, i.e. during relative rotational movement between
the dose g member and the housing. In addition, a second clutch is provided
for rotationally coupling and de-coupling the drive member and the first clicker
component. ing to the present invention the first clutch and the second
clutch are designed and adapted to each other such that at any time during
operation either the first clutch rotationally couples the dose setting member and
the drive member or the second clutch rotationally couples the drive member and
2012/055054
first clicker component or the first clutch onally couples the dose setting mem-
ber and the drive member and the second clutch rotationally couples the drive mem-
ber and the first clicker component. In other words, there is no point where both the
first clutch rotationally decouples the dose setting member from the drive member
and the second clutch rotationally les the drive member from the first clicker
component simultaneously.
Typically, the axial nt of the clutch member for de—coupling the first clutch
couples the second clutch and the axial movement of the clutch member de-coupling
the second clutch couples the first clutch. According to the present invention the
axial movement of the clutch member and the points of engagement / disengage-
ment of the two clutches are adapted to each other such that the first clutch couples
the dose setting member and the drive member prior to the second clutch de-
coupling the drive member from the first clicker component. In a similar manner the
second clutch couples the drive member and the first clicker ent prior to the
first clutch de-coupling the dose setting member and the drive member. This en-
sures that at all times during ion of the dose setting mechanism the drive
member is either coupled to the dose setting member and/or to the first clicker com-
ponent. Hence, the drive member is not allowed to rotate independent of either the
dose setting member or the first r component.
The present invention is not limited to the above-mentioned embodiment. ent
ways are possible to ensure that at any time during operation the drive member is
either rotationally coupled to the dose setting member or to the housing (via the first
r component). As an alternative to the above-mentioned ment, a block—
ing mechanism may be provided which blocks (prevents) de-coupling of either clutch
as long as the other clutch is not in its coupled state.
Further, the present invention is not limited to embodiments where axial movement
of the clutch member couples and de-couples the clutches. As an alternative, a
different and/or additional component of the dose setting mechanism may be used to
couple and de-couple the clutches. In this respect, it has to be assured, that at any
time during ion either the first clutch rotationally couples the dose setting
member and the drive member and/or the second clutch rotationally couples the
drive member and the first clicker component. This may be achived by a component
part wich entrains or diplaces, preferably the clutch member and/or the clicker, only
if one of the two clutches is in its d state.
According to a preferred embodiment of the invention the coupling of the second
clutch occurs as a result of the axial movement of the clutch member for rotationally
de—coupling the first clutch between drive member and the dose setting member
wherein the second clutch rotationally couples the drive member and the first clicker
component prior to the first clutch rotationally de-coupling the dose setting member
and the drive member. The coupling of the second clutch ing the axial move-
ment of the clutch member prior to de—coupling of the first clutch makes sure that the
second clutch is actuated or moved to couple the drive member to the first clicker
component before the first clutch de-couples the drive member from the dose setting
member.
In a similar manner the coupling of the first clutch occurs as a result of the axial
movement of the clutch member for onally de—coupling the second clutch be-
tween drive member and the first clicker component, wherein the first clutch rota-
tionally couples the dose setting member and the drive member prior to the second
clutch rotationally de-coupling the drive member and the first clicker component.
Again, the coupling of the first clutch following the axial movement of the clutch
member prior to de-coupling of the second clutch makes sure that the drive member
is coupled to the dose setting member prior to being de-coupled from the first clicker
component.
According to a preferred ment of the present invention the second clutch
comprises first clutch teeth or splines provided on the drive member and corre-
sponding second clutch teeth or splines provided on the first r component. In
other words, the second clutch may either comprise separate components for cou-
pling and de-coupling the drive member and the first clicker component or means for
coupling or de-coupling the drive member and the first clicker component may be
ed directly on the drive member and/or the first clicker component.
In addition, the first clutch preferably comprises first clutch teeth or splines provided
on the dose setting member and corresponding second clutch teeth or splines pro-
vided on the clutch member. The clutch member could be a tubular element dis-
posed on the drive member. Preferably, the tubular clutch member is interposed
between the drive member and the dose setting member. Preferably, the clutch
member is arranged such that it is rotationally coupled, but axially free, relative to
the drive member, for example by means of s along the length of the clutch
member and drive member.
In a preferred arrangement of the dose setting mechanism according to the present
invention the first clicker component is interposed between the clutch member of the
first clutch and the second clicker component. The clutch member may have an end
face ng to a corresponding end face of the first clicker component.
According to a further development of this idea, the first clicker component prefera-
bly comprises first ng teeth or splines and the clutch member of the first clutch
comprises corresponding second coupling teeth or s for rotationally coupling
the first clicker component and the clutch member. The coupling teeth or splines
may be provided as a series of shallow tooth profiles that engage n the clutch
member and the first r ent directly. Such shallow teeth serve to bias
the clutch member towards one of a number of preferred rotational ons, for
example aligning the clutch member, and hence the dose setting member, relative to
the housing such that one of a given number of defined dose values can be se-
lected. The shallow height of these teeth ensures minimal axial movement of the first
clicker during dose g, when the second clutch, coupling first clicker and drive
member, must not be engaged. ore, only a small movement of the clutch
member is required in order to engage the second clutch. Thus, the design accord-
ing to the present invention combines good dose number alignment and minimal
close button travel, which in turn minimizes the length of the pen.
2012/055054
It is preferred to have the first clicker component ently rotationally coupled to
a housing member and the second clicker component permanently rotationally cou—
pled to the drive member. Thus, the two clicker components conduct a relative rota-
tional movement if the drive member is rotated, e.g. during setting of a dose, to
provide a angularly detented position for the dose setting member during dose dial-
ing and to produce a tactile and audible feedback to the user as the dose g
member is turned. Further, the first clicker ent being permanently rotationally
coupled to a housing member allows coupling the drive member to the housing
member via the first clicker component.
To produce a tactile and audible feedback to a user it is preferred to provide a
clicker spring acting upon the first and second clicker components. Further, the
clicker spring may bias the first clutch into its position coupling the dose setting
member and the drive member.
According to red embodiment of the present invention, the dose setting mem—
ber comprises a dose dial sleeve which is rotatable relative to the housing to set a
dose. Further, the drive member may comprise a drive sleeve which is e in a
first axial direction relative to the housing member during dose setting and which is
movable in a second axial direction ve to the housing member during dose
dispensing, which second axial direction is opposite to said first axial direction.
Preferably, the movement of the drive sleeve during dose setting includes a transla-
tional component and a rotational component, e.g. a movement along a l path.
During dose dispensing it is preferred that the drive sleeve moves only axially, i.e.
without any rotational components of the movement.
If the first clutch rotationally couples the dose g member and the drive member
during dose setting and rotationally de-couples the dose setting member and the
drive member during dose sing, the drive member follows a nt of the
dose setting member along a helical path during dose setting while the dose setting
member is allowed to rotate relative to the drive member during dose dispensing.
It is red if the first clicker component and the second clicker component are
allowed to rotate relative to each other during dose setting and are rotationally
locked together during dose dispensing.
Thus, the dose setting mechanism of the present invention provides an r
detent of the dose setting member for each dose division , (giving both tactile
and audible feedback), whilst ensuring that the drive sleeve is either d to the
number sleeve or coupled to the g at all times. The design of a two piece
clicker ensures that the drive sleeve in a reusable injection device is coupled to
either the number sleeve (during dialing) or to the housing (during dispense). This is
to ensure that there is no mid position where the drive sleeve is free to rotate rela-
tive to the housing without incrementing or decrementing the displayed dose, for
example during the transition between g and se or in case the user
should, either deliberately or inadvertently, push on the close button whilst a-
neously rotating the dose setting member.
The present invention is suitable for different types of injection devices. One exam-
ple is a device similar to that shown in Figure 2. This device may be either a dispos—
able device, i.e. a device which has to be discarded after the cartridge ning a
medicament is empty, or it may be a resettable device, i.e. a device having means
allowing to replace an empty cartridge by a new one. In the latter case it is required
to push back a spindle (piston rod) by either decoupling the spindle from the drive
member or by allowing the drive member to spin relative to the dose setting member
(e.g. a number sleeve). According to a preferred embodiment of the present inven—
tion, the drive member is a two-part component comprising a first driver part and a
second driver part which may be rotationally coupled during dose setting and dose
dispensing and which may be rotationally pled during resetting. Preferably, a
spring urges the two driver parts into engagement during dose setting and dose
dispensing. This spring may be the clicker spring.
In addition or as an ative to the above mentioned features, it is a basic idea of
the present invention to provide a dose setting mechanism for a drug delivery de-
vice, the mechanism comprising: a dose setting member, a drive member, a clutch
member located between the dose setting member and the drive member providing
a first clutch for rotationally ng and pling the dose setting member and
the drive member, a clicker comprising a first clicker component and a second
clicker component axially movable relative to each other for producing a tactile
and/or audible feedback during relative onal movement there between and for
onally coupling and de-coupling the drive member and the first clicker compo-
nent, and further comprising a sping wherein the spring performs at least three of
the following functions:
- The spring biases in a able mechanism comprising a distal drive member part
and a proximal drive member part the distal and proximal drive member parts into an
d position (including re-engagement after reset).
- The spring biases the first clicker component and the second clicker ent
together in order that they positively engage and deliver detented dialing positions
and also the audible/tactile dialing click.
- The spring biases the first clicker component and the clutch member (shallow
biasing teeth) together in order that the clutch member and the first r compo—
nent tend to rotate in such a way as to take up the slack between the various splines
and grooves and therefore ensures good number alignment in the close window.
- In a resettable mechanism comprising a distal drive member part and a proximal
drive member part, the spring provides a force during dose dispense that drives the
distal (front) part of the drive member forwards, thus delivering the dose. At the end
of the dose the compressed spring provides the force ed to complete the de-
livery of the dose.
WO 30703
- The spring resists in a resettable mechanism decoupling of the distal and proximal
drive member parts with a small force. Therefore, when resetting the spindle (piston
rod) cannot ‘fall back’ into the device under gravity. This is a disadvantage of certain
other resettable devices because if their cartridge holder becomes partially detached
then reset of the spindle can occur without the user noticing, resulting in underdose
on the next dose.
— The spring biases the dose setting member (e.g. a dial sleeve) and teeth of the
clutch member into engagement at the tion of the dose, thus ensuring that
they are coupled during g of the subsequent dose.
According to a preferred embodiment, the spring is designed as a wave spring. In
particular, the ‘wave’ spring design of spring has advantages over other, more con-
ventional, coil springs. For example, the wave spring takes up less space when in its
coil bound condition. This reduces the overall length of the device. Further, the force
profile of the spring is non-linear. Thus the spring can apply a relatively low force for
its initial compression (including when resetting the device) but the force will rise
rapidly as the spring approaches its coil-bound state (e.g. under high dispense
loads).
In the following, the invention will be described by a way of an example and with
reference to the tic drawings in which:
Figure 1 shows a known dose g mechanism,
Figure 2 shows a dose setting mechanism ing to the ion,
Figure 3 shows an enlarged detail of a dose setting mechanism similar to that of
Figure 2,
Figure 4 shows a perspective view of the spring of the dose setting mechanism of
Figure 2, and
Figure 5 a detail of the inner surface of the clutch member of the dose setting
mechanism of Figure 2.
Figure 1 shows a typical dose setting mechanism 1 of an injection device with a
clicker mechanism. The dose setting mechanism comprises an (internal) housing
member 2, a dose setting member 3 comprising a number sleeve (dose dial sleeve)
for ying the set dose to the user, a drive member 4 in the form of a drive
sleeve, a clutch member 5 and a clicker 6. The clutch member 5 is located n
the dose setting member 3 and the drive member 4. The clutch member 5 is axially
movable ve to the dose setting member 3 and the drive member 4 for on-
ally coupling and de-coupling the dose setting member 3 and the drive member 4.
As shown in Figure 1, the first clutch 5 uses two sets of matching face teeth 5a, 5b
which are ed on an inner end face of the dose g member 3 and a corre—
sponding end face of the tubular clutch member 5.
In a similar manner, the clicker mechanism uses two sets of matching face teeth 6a,
6b in conjunction with a coil spring 7 to provide the detents for the dialed dose and
the clicks for tactile and audible feedback. In other words, teeth 6a, 6b, which are
provided on tubular clutch member 5 and a clicker member 6 tively, will tend
to rest in an engaged position and are allowed to ride one over the other during dose
setting.
In the dose setting mechanism shown in Figure 1, clicker member 6 is keyed to the
housing member 2 by means of longitudinally directed splines to prevent relative
rotation between the clicker member 6 and the housing member 2, while allowing
ve axial movement there between. In a similar manner, clutch member 5 is
keyed to the drive member 4 by means of longitudinally directed splines to prevent
relative rotation between the clutch member 5 and the drive member 4, while allow-
ing relative axial movement there between.
2012/055054
The spring 7 serves to e the necessary axial force to engage clutch teeth 5a
on clutch component 5 (which is splined to the drive sleeve 4) with clutch features
5b on the number sleeve 3 at the end of a delivered dose and during subsequent
dialing of the next dose. Further, the spring provides the axial force n the
clutch component 5 and clicker component 6 that causes the matching face teeth
6a, 6b to click during dialing. In this way the one spring 7 serves two functions.
Figure 1 shows the device with a dose button (not shown) depressed. This causes
axial movement of the clutch member in the direction which decouples the clutch
teeth 5a, 5b between the clutch member 5 and the number sleeve 3 and com-
presses the clicker spring 7. Whether or not the clicker spring 7 is compressed to a
solid state, the axial force provided by this spring is sufficient to prevent the clicker
face teeth 6a, 6b from disengaging under any se loads applied by the user to
the button during dispense. These clicker face teeth 6a, 6b therefore rotationally lock
the clicker 6 to the clutch member 5 and as the clicker 6 is d to the housing
member 2 and the clutch member 5 is splined to the drive sleeve 4, this effectively
locks the drive sleeve 4 to the housing member 2 in on.
However in order to allow for dialing, the clicker 6 must be free to rotate relative to
the drive sleeve 4 when the dose button is not depressed. This causes a problem in
the device which is highlighted in Figure ‘I. Here the user has pushed the close
button in, ling the clutch teeth 5a, 5b between the clutch member 5 and
number sleeve 3, and has then d the close button. The close button is splined
to both the clutch member 5 and drive sleeve 4 and in some tolerance conditions a
user may be able to rotate the close button and hence drive sleeve 4 and clutch
member 5 bumping over the clicker teeth 6a, 6b without the clutch teeth 5a, 5b
between the clutch member 5 and number sleeve 3 re—engaging, this enabling the
drive sleeve 4 to be rotated relative to the number sleeve 3. A similar problem can
occur even at nominal tolerances if the user applies rotational torque to the close
button whilst the dose button is held in a partially depressed condition. In this condi—
tion both the clutch teeth 5a, 5b and clicker teeth 6a, 6b would be only minimally
engaged, e.g. at the tips of both sets of teeth. Should the user continue to apply
further rotational torque then these teeth can deform either elastically or plastically
and permit rotational movement of the drive sleeve 4 relative to the number sleeve
3. Once plastic deformation of the teeth has occurred then the rotational th of
the couplings is icantly reduced, making uent failures more likely to
OCCUF.
Such failures are most likely to occur when the number sleeve 3 is dialed either to
the minimum or maximum dose (e.g. 80 units stop). At the m dose the de-
vice of Figure 1 has maximum dose rotational stop features between the number
sleeve 3 and the outer housing (not shown). By pressing the close button, the user is
able to decouple the number sleeve 3 from the drive sleeve 4, effectively bypassing
this stop and then continue to rotate the button and hence drive sleeve 4, thus dis-
pensing some drug.
Alternatively if the close button is rotated at the minimum dose rotational stop (0
units stop) so as to dial down, the number sleeve 3 is prevented from rotation and
rotation of the drive sleeve 4 in this case will cause the piston rod (not shown) to be
wound back into the drive sleeve 4, and 'back off' the piston rod from the cartridge
bung, opening a gap between the piston rod and the cartridge bung. This gap may
not be obvious to the user and, if not corrected by the user ming a priming
step to check for correct operation, would result in an underdose on any subsequent
dialed dose, as the piston rod would first have to e to close the gap before
any drug is dispensed, reducing the volume of drug dispensed.
The axial cement of clicker 6 during dose dialing is equal to the height of the
clicker teeth 6a, 6b (approximately 0,7 mm plus and minus a tolerance). During the
axial displacement, i.e. during dose g, the clicker 6 must be free to rotate rela-
tive to the drive sleeve 4. The rotational lock of the clicker 6 to the drive sleeve 4
during dispense, can therefore only occur after the clicker has moved axially by at
least the 0,7 mm plus tolerance. As the clutch teeth 5a, 5b in the design of Figure 1
decouple after only 0,8 mm plus tolerance, rotationally locking the clicker 6 to the
drive sleeve 4 before the clutch teeth 5a, 5b disengage in all tolerance conditions is
not le. Even at nominal ions the clicker teeth 6a, 6b are only minimally
engaged (by a maximum of 0,1 mm) at the point where the clutch teeth 5a, 5b dis—
engage. Increasing the ‘overlap’, e.g. by lengthening the engagement of clutch teeth
5a, 5b increases the overall length of the pen by at least double the amount of the
increase (the mechanism inside the housing must accommodate the increased
movement of the clutch member and the dose button to housing gap must also
increase by the same amount to permit this movement). In addition this changes the
dispensing characteristics of the pen — the user must now press the close button
further before dispensing will begin.
A solution according to the present invention is shown in Figures 2 and 3 keeping
the clutch axial engagement at 0,8 mm, the clicker teeth height at 0,7 mm but ensur-
ing that the drive sleeve 4 is prevented from rotating relative to the clicker 6 before
the clutch 5 has fully disengaged.
In Figure 2, a dose setting mechanism is shown where the r is split into two
parts, first clicker ent 6' and second clicker component 6". The first clicker
component 6' is similar to the clicker 6 in Figure 1 in that it is splined to the housing
member 2 and therefore must rotate relative to the drive sleeve 4 and clutch compo—
nents 5 during dialing. However, the r teeth 6a, 6b have been moved from the
end face that engages with the clutch member 5 to the opposite end face where they
engage with the additional part, second clicker component 6". Hence, first clicker
component 6' has very limited axial movement during dialing (only moving by the
height of the shallow teeth 8a, 8b) and therefore it can be onally locked to the
drive sleeve 4 after only a very small relative axial displacement, as shown in Figure
3, and well within the axial engagement of the clutch teeth 5a, 5b.
The second clicker component 6" component is always rotationally coupled to the
drive sleeve 4 and moves axially compressing the clicker spring 7 to me the
clicker face teeth 6a, 6b during dialing.
This design solution requires an extra component, however it enables a lower button
travel and steeper clicker teeth 6a, 6b (giving a stronger audible and tactile click),
compared to the single clicker design shown in Figure 1 for the reasons described
above, and it also ensures that during g and dispense, the clicker spring 7 does
not have to rotate relative to any other component. This second age ensures
that the dialing tactile and audible ck is improved, and will reduce wear on the
faces that contact the metal clicker spring 7.
ing to a preferred embodiment, spring 7 is a wave spring as depicted in Fig-
ure 4. The wave spring 7 may se a series of curved or dished elastically
deformable washers (perforated disks) which are arranged conversely, i.e. the cur-
vature of adjacent washers is contrariwise such that adjacent washers contact each
other (or may be fixed to each other) in two points and are spaced from each other
for the rest. Thus, the wave spring takes up less space when in its coil bound condi-
tion. A further advantage is that the force profile of wave spring 7 is non—linear.
It is preferred to avoid that the rotational coupling between the clutch member 5 and
hence number sleeve 3 relative to the first r component 6' and hence housing
member 2 has to pass via two additional interfaces compared to Figure 1 because
this would increase the chain of tolerances between the housing member 2 and the
number sleeve 3 and therefore lead to poor alignment of the displayed dose number
relative to the housing member 2. Assuming the absence of shallow teeth features
8a, 8b, then the first additional interface would be from the second clicker compo—
nent 6" to the drive sleeve 4 and the second additional interface would be the
d connection between the clutch member 5 and the drive sleeve 4. These two
additional interfaces would result in more play and misalignment between the num-
bers yed on the number sleeve 3 and the dose number window aperture on
the housing member 2 which can make the reading of the dialed dose ing for
the user. To avoid the above drawback, a series of shallow tooth profiles 8a, 8b is
added that engage between the clutch member 5 and the first clicker component 6'
directly, similar to the clicker teeth shown in Figure 1, but much smaller in .
These shallow teeth 8a, 8b are shown in Figure 3 and serve to rotationally bias the
clutch ent 5, within the angular limits provided by the play in the rotational
interfaces between second clicker 6” to drive sleeve 4 and drive sleeve 4 to clutch
member 5, towards one of a number of preferred rotational positions, thus combining
a good dose number alignment, with the ness and minimal button travel of the
present invention.
Figure 3 shows in more detail how the second clicker component 6" component is
keyed to the drive member 4 to prevent relative rotation between the the second
clicker component 6" and the drive member 4, while allowing relative axial move-
ment there between during dose setting. The drive sleeve 4 is provided with at least
one longitudinally directed spline 1O (protrusion) located on the outer face of the
drive member 4. The second r component 6" has at least one corresponding
groove 9 for ing spline 10. The length of spline 10 is designed to be long
enough to guide the second clicker component 6" and to prevent relative rotation
between the second clicker component 6" and the drive member 4 even if the sec-
ond r component 6" moves relative to the drive member 4 in its axial direction
whilst riding over the clicker teeth of the first clicker ent 6' during dialing.
In a similar manner, the first clicker component 6' is provided with a groove 11 for
receiving spline 10 if the clutch member 5 and the first clicker component 6' are
pushed to the right in Figure 3 against the force of the clicker spring 7. Thus, spline
and groove 11 constitute a second clutch for coupling the drive sleeve 4 (via first
clicker component 6') to the housing member 2.
As depicted in Figure 3, the length L1, the distance by which the clutch teeth 5a, 5b
have to be axially displaced for de-coupling the drive sleeve 4 from the number
sleeve 3, is larger than the length L2, the distance by which the first clicker 6’ must
be axially displaced before coupling the drive sleeve 4 to the first r 6’. Thus,
spline 10 of the drive sleeve 4 will rotationally lock the first clicker ent 6' by
engaging groove 11 prior to de-coupling of the drive sleeve 4 from the number
sleeve 3.
Regarding the equations ned above with respect to Figure 1, the design
shown in Figures 2 and 3 has the clicker split into two parts, with one part splined to
the g, clicker part 6', and the second part splined to the drive sleeve, clicker
part 6". As mentioned above, in this ement a second clutch is introduced
between clicker part 6' and the drive sleeve which does not engage during dialing,
but does engage when the button is depressed and crucially engages before the
clutch teeth between the clutch and number sleeve have disengaged for all toler-
ance conditions. Because this second clutch is ndent to the clicker teeth it
can be designed to engage soon after the button has been depressed. This second
clutch cannot be seen in Figure 2 but a schematic cross section of Figure 2 is shown
in Figure 3, where it can be seen that this second clutch engages after the button
has been depressed a distance L2.
In addition the design in Figures 2 and 3 also has a second set of clicker teeth 8a,
8b between the clutch and clicker part 6'. This second set of clicker teeth have an
axial height 'V2' and are t purely to ensure that at rest, these teeth engage to
control the relative rotational position of the clutch relative to the clicker part 6' to
ensure that the number sleeve (which is coupled to the clutch) has good number
alignment with the close window which is splined to the clicker part 6' via the hous—
ing.
Looking at the equations again this time using X2, Y2 and Z2 as before with in addi—
tion a further ion 'V2' which is the axial tooth height of the second set of
clicker teeth 8a, 8b between the clutch member 5 and the clicker part 6' the device
must comply with the following equations
X2 - T > Y2 + V2 (1) to enable the device to be dialed,
L2 - T2 > V2 (2) again to enable the device to be dialed
(where T2 is the tolerance on the stack
that defines gap L2),
X2 - T > Z2 (3) to enable the device to be dispensed and
2012/055054
L2 + T2 < Z2 + Y2 - K (4) to ensure one of the clutches are always
engaged by an amount greater than K.
If T2 is 0,2 mm (due to the shorter nce chain of parts) and V2 is 0,15 mm (just
enough to give a detent position n the clutch member 5 and the clicker part
6‘) one gets from on (2) L2 > V2 + T2, i.e. L2 > 0,35 mm.
A good value for Z2 is 1,2 mm and as already mentioned above a value of
Y2 = 0,7 mm gives a good dialing . Inserting these values into equation (4), K
< Z2 + Y2 — L2 - T2, i.e. K < 1,2 + 0,7 — 0,35 - 0,2 or K < 1,35 mm. Note that equa—
tions (1) and (3) are also satisfied with these values above.
This means that the device can be designed to always have an overlap between the
clutches of K = 1,35 mm which will be enough to ensure that the user is unable to
disengage the drive sleeve from both the housing and the number sleeve at the
same time even if a high torque is applied to the plastic parts.
Clicker spring 7 may have a wave sping design. The r spring 7 is particularly
advantageous in that it performs several functions. Preferably, spring 7 biases the
first clicker component 6' and the second clicker component 6" together in order that
they positively engage and deliver detented dialing positions and also the audi-
ble/tactile dialing click. In addition, the clicker spring 7 biases the first clicker compo-
nent 6' and the clutch member 5 (shallow biasing teeth) together in order that the
clutch member 5 and the first clicker component 6' tend to rotate in such a way as to
take up the slack between the various splines and grooves and therefore ensures
good number alignment in the close window. Further, the clicker spring 7 biases the
dose setting member 1 (e.g. a dial sleeve) and teeth of the clutch member 5 into
engagement at the completion of the dose, thus ensuring that they are d
during dialing of the subsequent dose.
In Figures 2 and 3, the drive member 4 (drive sleeve) is not depicted in . The
drive member may be a single part or may alternatively se two drive member
parts. The latter is especially preferred if the dose setting mechanism is a resettable
mechanism allowing to replace a cartridge containing a medicament. In this case,
the clicker spring 7 may perform additional function. The r spring 7 preferably
biases the distal and proximal drive member parts into an engaged position (includ—
ing re-engagement after reset). In addition, the clicker spring 7 may provide a force
during dose dispense that drives the distal (front) part of the drive member fonNards,
thus delivering the dose. At the end of the dose the compressed spring provides the
force required to complete the delivery of the dose. The spring may further resists
decoupling of the distal and proximal drive member parts with a small force. There-
fore, when resetting the spindle (piston rod) cannot ‘fall back’ into the device under
gravity. This is a disadvantage of n other resettable devices because if their
cartridge holder s partially detached then reset of the spindle can occur
without the user noticing, resulting in underdose on the next dose.
There are ent embodiments ensuring that at any time during operation either
the first clutch 5a, 5b rotationally couples the dose setting member 3 and the drive
member 4 and/or the second clutch 9, 11 rotationally couples the drive member 4
and the first clicker component 6' as depicted in Figures 2 and 3:
According to a first embodiment both clutch member 5 and first r component 6'
move together y as one component when the button (not shown) is de—
pressed/released to engage and disengage the two clutches with the clutch between
the first r component 6' and drive sleeve 4 engaging before the clutch between
the clutch member 5 and dose g member 3.
According to a second embodiment, when the clutch member 5 starts to move axi—
ally the first clicker component 6' also starts to move axially and when the clutch
member 5 stops moving the first clicker component 6' stops moving. |.e. they are
coupled but the axial distance that each part travels is not necessarily the same. If
for instance the two parts engage each other with helical ramps, and for instance the
clutch member 5 rotates relative to the first clicker component 6' during this axial
travel then some relative axial movement will occur between the two ents
and they will not move axially by exactly the same distance. This is what happens in
the device depicted in Figure 2 as the first coupling teeth or splines 8a are helical
ramps between the clutch member 5 and first clicker component 6' if there is a step
in the groove in the clutch member 5 which engages a spline of the drive member 4
which causes the clutch member 5 to rotate relative to the first clicker component 6'
when the clutch member 5 is moved axially.
Such a feature is shown in Figure 5 depicting a detail of the inner surface of clutch
member 5 which is keyed to drive member 4 by means of longitudinally directed splines
formed on the drive member 4 outer surface which engage corresponding grooves of
the clutch member 5 to prevent relative rotation between the clutch member 5 and the
drive member 4, while allowing ve longitudinal movement there between. In each
groove there is a step 50 which prevents proximal nt of the drive member 4
during normal reset. In other words, said grooves have a distal portion of larger width
and a proximal portion of smaller width with the step 50 located at the transition be-
tween these two portions. Thus, depending on the axial arrangement of the spline within
the groove proximal movement of the spline is either stopped by step 5c or allowed
g the spline in the portion of the groove with the smaller width. As an alternative
the spline(s) may be provided on the clutch member and the groove(s) may be provided
on the drive .
A third embodiment could be where there is a delay between the axial travel of the
first clicker component 6' and axial travel of the clutch member 5 so that it is d
that the first clicker component 6' has moved y to lock the first clicker compo-
nent 6' in rotation to the drive member 4 before the clutch between the clutch mem-
ber 5 and dose setting member 3 starts to disengage. This could be achieved by
either acting on the first clicker component 6' to move it axially and then after a pre-
defined movement this part ns the clutch member 5 so that they then move
together. Or as an alternative, the clutch member 5 could be split into two parts, a
part that acts on the first clicker component 6' and second part that is rotationally
coupled to the first part that also forms the clutch to the dose setting member 3.
These two parts are sprung apart with a spring force that is weaker than the main
clutch spring 7 so that when the first clutch part is moved axially it acts on the first
clicker component 6' but the second part of the clutch remains fully d with the
dose setting member 3. Only after a predefined displacement of the first part of the
clutch member 5 does it entrain the second part of the clutch so as to disengage this
from the dose setting member 3.
The dose setting mechanism may be part of an injection device further comprising a
cartridge containing a medicament. The cartridge may be held in a cartridge holder
which can be permanently or releasably ed to the dose setting ism.
The term ,,medicament“, as used herein, means a pharmaceutical formulation con-
taining 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 ccharide, a vaccine, a
DNA, a RNA, an enzyme, an antibody or a nt thereof, a hormone or an
oligonucleotide, or a mixture of the above-mentioned pharmaceutically active com-
pound,
wherein in a further embodiment the pharmaceutically active compound is useful for
the ent and/or prophylaxis of diabetes mellitus or complications associated
with diabetes us such as diabetic retinopathy, oembolism disorders such
as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS),
angina, dial tion, cancer, macular degeneration, inflammation, hay
fever, atherosclerosis and/or rheumatoid arthritis,
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,
2012/055054
wherein in a further embodiment the pharmaceutically active compound comprises
at least one human insulin or a human insulin analogue or derivative, on-like
peptide (GLP—1) or an analogue or derivative thereof, or exendin—3 or exendin-4 or
an analogue or derivative of exendin-3 or exendin-4.
Insulin analogues are for example G|y(A21), Arg(BB1), Arg(832) human insulin;
Lys(BS), G|u(829) human insulin; Lys(BZ8), 9) human insulin; 8)
human insulin; human insulin, wherein proline in position 828 is replaced by Asp,
Lys, Leu, Val or Ala and wherein in position 829 Lys may be replaced by Pro;
A|a(826) human insulin; Des(BZ8-BSO) human insulin; Des(BZ7) human insulin and
Des(BSO) human insulin.
Insulin tes are for example BZQ-N-myristoyI-des(BBO) human n; BZQ-N-
palmitoyl—des(B30) human insulin; BZQ—N-myristoyl human insulin; B29—N—palmitoyl
human insulin; B28—N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-
LysBZ8Pr0829 human insulin; BSO-N-myristoyl—ThrBZQLysBBO human insulin; BBON-palmitoyl
— ThrB29Ly5830 human n; B29—N—(N—palmitoyl-Y-glutamyl)—
des(BBO) human insulin; BZQ-N-(N-Iithocholyl-Y-glutamy|)-des(BBO) human insulin;
B29—N-(w-carboxyheptadecanoyl)-des(BBO) human insulin and BZQ-N-(w-
carboxyheptadecanoyl) human insulin.
Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence H-His-
GIy-G|u-GIy-Thr-Phe-Thr-Ser-Asp-Leu-Ser—Lys-GIn-Met-GIu-GIu—GIu-AIa-VaI-Arg-
Leu-Phe-lle-Glu-Trp-Leu-Lys-Asn-GIy—GIy-Pro-Ser—Ser-GIy-Ala-Pro-Pro-Pro-Ser-
NH2.
Exendin-4 derivatives are for example selected from the following list of compounds:
H-(Lys)4-des Pr036, des Pr037 Exendin-4(1-39)-NH2,
)5—des Pr036, des Pr037 Exendin-4(1-39)-NH2,
des Pr036 n-4(1-39),
des Pr036 [Asp28] Exendin-4(1-39),
des Pr036 [|soAsp28] Exendin-4(1-39),
des Pr036 [Met(O)14, Asp28] Exendin-4(1-39),
des Pr036 [Met(O)14, |soAsp28] n-4(1-39),
des Pr036 [Trp(02)25, Asp28] Exendin-4(1-39),
des Pr036 [Trp(02)25, |soAsp28] Exendin-4(1-39),
des Pr036 [Met(O)14 Trp(02)25, Asp28] Exendin-4(1—39),
des Pr036 [Met(O)14 Trp(02)25, |soAsp28] Exendin—4(1-39); or
des Pr036 ] Exendin-4(1-39),
des Pro36 [|soAsp28] Exendin—4(1-39),
des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),
des Pr036 [Met(O)14, |soAsp28] Exendin-4(1-39),
des Pr036 2)25, Asp28] Exendin-4(1—39),
des Pro36 [Trp(02)25, |soAsp28] Exendin—4(1—39),
des Pr036 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),
des Pr036 [Met(O)14 Trp(02)25, |soAsp28] Exendin—4(1-39),
wherein the group —Ly56—NH2 may be bound to the C—terminus of the Exendin-4
derivative;
or an Exendin-4 derivative of the sequence
des Pr036 Exendin-4(1-39)-Lys6-NH2 (AVEOO10),
H—(Lys)6—des Pr036 [Asp28] Exendin-4(1-39)—Lys6—NH2,
des Asp28 Pr036, Pr037, Pr038Exendin-4(1—39)-NH2,
)6-des Pr036, Pr038 ] Exendin-4(1-39)-NH2,
H—Asn-(Glu)5des Pr036, Pr037, Pr038 [Asp28] Exendin-4(1-39)—NH2,
des Pr036, Pr037, Pr038 [Asp28] Exendin-4(1-39)-(Lys)6—NH2,
)6—des Pr036, Pr037, Pr038 [Asp28] Exendin-4(1-39)-(Lys)6—NH2,
H-Asn-(GIu)5-des Pr036, Pr037, Pr038 [Asp28] Exendin—4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pr036 [Trp(02)25, Asp28] Exendin-4(1-39)-Lys6—NH2,
H-des Asp28 Pr036, Pr037, Pr038 2)25] Exendin-4(1—39)-NH2,
H-(Lys)6-des Pr036, Pr037, Pr038 [Trp(02)25, Asp28] Exendin-4(1-39)—NH2,
H-Asn-(GIu)5-des Pr036, Pr037, Pr038 [Trp(02)25, Asp28] Exendin-4(1-39)-NH2,
des Pr036, Pr037, Pr038 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6—NH2,
H-(Lys)6—des Pr036, Pr037, Pr038 [Trp(02)25, Asp28] Exendin—4(1-39)-(Lys)6-NH2,
(GIu)5—des Pr036, Pr037, Pr038 [Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-
NH2,
H—(Lys)6—des Pr036 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,
des 14 Asp28 Pr036, Pr037, Pr038 Exendin-4(1—39)—NH2,
H-(Lys)6-desPr036, Pr037, Pr038 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
H—Asn-(GIu)5-des Pr036, Pr037, Pr038 [Met(O)14, Asp28] Exendin—4(1—39)-NH2,
des Pr036, Pr037, Pr038 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6—NH2,
H-(Lys)6-des Pr036, Pr037, Pr038 )14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H—Asn-(Glu)5 des Pr036, Pr037, Pr038 [Met(O)14, Asp28] Exendin—4(1—39)-(Lys)6-
NH2,
H-Lys6-des Pr036 [Met(O)14, Trp(02)25, Asp28] Exendin—4(1-39)-Lys6-NH2,
H—des Asp28 Pr036, Pr037, Pr038 [Met(O)14, Trp(02)25] Exendin—4(1-39)-NH2,
H-(Lys)6-des Pr036, Pr037, Pr038 [Met(O)14, Asp28] Exendin-4(1—39)-NH2,
H-Asn-(GIu)5-des Pr036, Pr037, Pr038 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-
39)—NH2,
des Pr036, Pr037, Pr038 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)—(Lys)6-
NH2,
H-(Lys)6—des Pr036, Pr037, Pr038 [Met(O)14, Trp(02)25, Asp28] n-4(Sl-39)-
(Lys)6-NH2,
H—Asn-(GIu)5-des Pr036, Pr037, Pr038 [Met(O)14, )25, Asp28] Exendin-4(1—
39)—(Lys)6—NH2;
or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned
Exendin-4 derivative.
es 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 tropin, Lutropin, Choriongonadotropin,
Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,
relin, Leuprorelin, Buserelin, Nafarelin, Goserelin.
A polysaccharide is for example a glucosaminoglycane, a onic acid, a heparin,
a low molecular weight n or an ultra low molecular weight n or a deriva-
tive f, or a sulphated, e.g. a ulphated 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
arin sodium.
Antibodies are globular plasma proteins (~150 kDa) that are also known as immu-
noglobulins which share a basic structure. As they have sugar chains added to
amino acid residues, they are glycoproteins. The basic functional unit of each anti—
body is an immunoglobulin (lg) monomer (containing only one lg unit); secreted
antibodies can also be dimeric with two lg units as with lgA, tetrameric with four lg
units like teleost fish lgM, or pentameric with five lg units, like ian lgM.
The lg monomer is a "Y"-shaped molecule that consists of four polypeptide chains;
two identical heavy chains and two identical light chains connected by disulfide
bonds between cysteine residues. Each heavy chain is about 440 amino acids long;
each light chain is about 220 amino acids long. Heavy and light chains each contain
intrachain disulfide bonds which stabilize their folding. Each chain is composed of
structural domains called lg domains. These domains contain about 70-110 amino
acids and are classified into different categories (for example, variable or V, and
constant or C) according to their size and function. They have a characteristic im-
munoglobulin fold in which two B sheets create a “sandwich” shape, held together by
interactions between conserved cysteines and other d amino acids.
There are five types of mammalian Ig heavy chain denoted by d, 6, a, y, and p. The
type of heavy chain present defines the isotype of antibody; these chains are found
in lgA, lgD, lgE, lgG, and lgM antibodies, respectively.
Distinct heavy chains differ in size and composition; or and y contain approximately
450 amino acids and 6 imately 500 amino acids, while u and a have approxi—
WO 30703
mately 550 amino acids. Each heavy chain has two s, the constant region
(CH) and the variable region (VH). In one species, the constant region is essentially
identical in all antibodies of the same isotype, but differs in dies of different
isotypes. Heavy chains y, d and 6 have a constant region composed of three tandem
lg domains, and a hinge region for added flexibility; heavy chains u and a have a
constant region composed of four immunoglobulin domains. The variable region of
the heavy chain s in antibodies produced by different B cells, but is the same
for all antibodies produced by a single B cell or B cell clone. The variable region of
each heavy chain is approximately 110 amino acids long and is composed of a
single lg domain.
In mammals, there are two types of immunoglobulin light chain denoted by A and K.
A light chain has two successive domains: one constant domain (CL) and one vari-
able domain (VL). The approximate length of a light chain is 211 to 217 amino acids.
Each antibody contains two light chains that are always identical; only one type of
light chain, K or A, is present per antibody in mammals.
Although the general structure of all antibodies is very similar, the unique property of
a given antibody is determined by the variable (V) regions, as detailed above. More
specifically, variable loops, three each the light (VL) and three on the heavy (VH)
chain, are responsible for g to the antigen, i.e. for its antigen specificity. These
loops are referred to as the Complementarity Determining Regions (CDRs). Be-
cause CDRs from both VH and VL domains contribute to the antigen-binding site, it
is the combination of the heavy and the light chains, and not either alone, that de-
termines the final antigen specificity.
An “antibody fragment” ns at least one n binding fragment as defined
above, and exhibits essentially the same function and specificity as the complete
antibody of which the fragment is derived from. Limited proteolytic digestion with
papain s the Ig prototype into three fragments. Two identical amino terminal
fragments, each containing one entire L chain and about half an H chain, are the
antigen binding fragments (Fab). The third fragment, r in size but containing
the carboxyl terminal half of both heavy chains with their interchain ide bond, is
the crystalizable fragment (Fc). The Fc contains ydrates, complement-
binding, and FcR—binding sites. Limited pepsin ion yields a single F(ab')2
fragment containing both Fab pieces and the hinge region, including the H-H inter-
chain disulfide bond. F(ab')2 is divalent for antigen binding. The disulfide bond of
F(ab')2 may be cleaved in order to obtain Fab'. Moreover, the variable regions of the
heavy and light chains can be fused together to form a single chain variable frag-
ment (scFv).
Pharmaceutically acceptable salts are for example acid addition salts and basic
salts. Acid addition salts are e.g. HCl 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: hy—
drogen, an optionally substituted C1—CB—alkyl group, an optionally tuted C2—
C6—alkenyl group, an optionally substituted C6—ClO-aryl group, or an optionally
substituted C6-C10-heteroaryl group. Further examples of pharmaceutically accept-
able salts are described in "Remington's Pharmaceutical Sciences" 17. ed. Alfonso
R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., USA, 1985 and in
Encyclopedia of Pharmaceutical logy.
ceutically acceptable solvates are for example hydrates.
W0 2012/130703
Reference numerals:
1 dose setting mechanism
2 g member
3 number sleeve (dose setting member)
4 drive sleeve (drive member)
(first) clutch member
5a, 5b clutch teeth
6 clicker
6a, 6b clicker teeth
6' first clicker component
6" second clicker component
7 clicker spring
83, 8b shallow teeth (detent teeth)
9 groove
spline (second clutch)
11 groove (second clutch)
L1 distance by which the clutch teeth 5a, 5b have to be axially displaced
for de-coupling the drive sleeve 4 from the number sleeve 3
L2 the distance by which the first r 6’ must be axially displaced
before coupling the drive sleeve 4 to the first clicker 6’
Z1, Z2 axial height of clutch teeth 5a, 5b
Y1, Y2 axial height of clicker teeth 63, 6b
X1, X2 gap ble due to compression of spring 7
SH solid height of spring 7
V2 axial height of detent teeth 8a, 8b
Claims (18)
1. Dose g mechanism for a drug delivery , the mechanism comprising: a dose setting , a drive member, a clutch member located between the dose setting member and the drive member, the clutch member being axially e relative to the dose setting member and to the drive member and being rotationally fixed to the drive member, providing a first clutch for rotationally coupling and de-coupling the dose setting member and the drive member, a clicker comprising a first clicker component and a second clicker ent axially movable relative to each other for producing a tactile and/or e feedback during relative rotational movement there n, wherein the first clicker component is axially movable relative to the drive member providing a second clutch for rotationally coupling and de-coupling the drive member and the first clicker component, wherein the first clutch and the second clutch are designed and adapted to each other such that at any time during operation either the first clutch rotationally couples the dose setting member and the drive member and/or the second clutch rotationally s the drive member and the first clicker component.
2. Dose setting ism according to claim 1, characterized in that the first clicker follows the axial movement of the clutch member during the axial movement of the clutch member for rotationally de-coupling the first clutch between drive member and the dose setting member, wherein the second clutch rotationally couples the drive member and the first clicker component prior to the first clutch rotationally de-coupling the dose setting member and the drive member.
3. Dose setting mechanism according to claim 1 or 2, characterized in that the clutch member follows the axial movement of the first clicker during the axial movement of the first clicker for rotationally de-coupling the drive member and the first clicker component, wherein the first clutch onally couples the dose setting member and the drive member prior to the second clutch rotationally decoupling the drive member and the first clicker component.
4. Dose setting mechanism according to any one of the preceding claims, terized in that the second clutch comprises first clutch teeth or splines provided on the drive member and ponding second clutch teeth or splines provided on the first clicker component.
5. Dose setting mechanism according to any one of the preceding claims, characterized in that the first clutch comprises first clutch teeth or splines provided on the dose setting member and corresponding second clutch teeth or splines provided on the clutch member.
6. Dose setting mechanism according to claim 5, characterized in that the first clicker ent is osed between the clutch member of the first clutch and the second clicker component.
7. Dose setting mechanism according to claim 5 or 6, characterized in that the first r component comprises first coupling teeth or splines and the clutch member comprises corresponding second coupling teeth or splines for rotationally aligning the first clicker component and the clutch member.
8. Dose setting mechanism according to any one of the preceding claims further comprising a housing member, characterized in that the first r component is permanently onally coupled to the housing member and the second clicker component is permanently rotationally coupled to the drive member.
9. Dose setting mechanism according to any one of the preceding claims, characterized in that a clicker spring is provided acting upon the second clicker ent.
10. Dose setting mechanism according to claim 8 or claim 9 when dependent on claim 8, characterized in that the dose setting member comprises a dose dial sleeve or number sleeve which is rotatable relative to the housing member to set a dose, and that the drive member comprises a drive sleeve which is movable in a first axial direction relative to the housing member during dose setting, and which is movable in a second axial ion relative to the housing member during dose dispensing, which second axial direction is opposite to said first axial direction.
11. Dose g mechanism according to any one of the preceding claims, characterized in that the clutch member rotationally couples the dose g member and the drive member during dose setting and rotationally de-couples the dose setting member and the drive member during dose dispensing.
12. Dose setting ism ing to any one of the preceding claims, characterized in that the first clicker component and the second clicker ent are allowed to rotate relative to each other during dose setting and are rotationally locked together during dose dispensing.
13. Dose setting mechanism according to any one of the preceding claims, characterized in that the second clicker component free to move axially relative to the drive member but is rotationally locked to the drive member.
14. Dose setting mechanism according to claim 9 or any one of claims 10 to 13 when dependent on claim 9, wherein the clicker spring biases the first clicker component and the second clicker component together, biases the first clicker component and the clutch member together, biases the dose g member and the clutch member into engagement, biases two parts of the drive member, which comprises a distal and proximal drive member part, into an d position, provide a force during dose dispense that drives the distal part of the drive member forwards, and/or s decoupling of the distal and proximal drive member parts with a force in the magnitude order of y.
15. Injection device comprising a dose setting mechanism according to any one of the preceding claims and a medicament.
16. Injection device according to claim 15 wherein the medicament is contained in a dge.
17. Dose setting mechanism substantially as herein described with reference to any embodiments shown in s 2 to 5 of the accompanying drawings.
18. Injection device substantially as herein described with reference to any embodiment shown in
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11159756.3 | 2011-03-25 | ||
| EP11159756 | 2011-03-25 | ||
| PCT/EP2012/055054 WO2012130703A1 (en) | 2011-03-25 | 2012-03-22 | Dose setting mechanism and injection device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ615854A NZ615854A (en) | 2014-07-25 |
| NZ615854B2 true NZ615854B2 (en) | 2014-10-29 |
Family
ID=
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