U.S. patent application number 16/422370 was filed with the patent office on 2019-09-19 for drug delivery device.
The applicant listed for this patent is Sanofi-Aventis Deutschland GMBH. Invention is credited to Joseph Butler, Paul Richard Draper, Stephen Francis Gilmore, David Moore, Anthony Paul Morris.
Application Number | 20190282766 16/422370 |
Document ID | / |
Family ID | 45816171 |
Filed Date | 2019-09-19 |
United States Patent
Application |
20190282766 |
Kind Code |
A1 |
Butler; Joseph ; et
al. |
September 19, 2019 |
Drug Delivery Device
Abstract
A drug delivery device comprising; a housing; a cylindrical
member configured to be rotatably supported inside the housing,
wherein the outer surface of the cylindrical member is provided
with at least first and second tracks together forming an encoder,
each track comprising conductive segments and non-conductive
segments; and at least first and second groups of contacts
configured to engage the first and second tracks respectively at
predetermined intervals along the length of the track.
Inventors: |
Butler; Joseph; (Rugby
Warwickshire, GB) ; Moore; David; (Leicestershire,
DE) ; Draper; Paul Richard; (Worcestershire, GB)
; Gilmore; Stephen Francis; (Bristol, GB) ;
Morris; Anthony Paul; (Coventry, GB) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Sanofi-Aventis Deutschland GMBH |
Frankfurt am Main |
|
DE |
|
|
Family ID: |
45816171 |
Appl. No.: |
16/422370 |
Filed: |
May 24, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15414679 |
Jan 25, 2017 |
10300210 |
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16422370 |
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14131646 |
Jan 8, 2014 |
9586009 |
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PCT/EP2012/063627 |
Jul 12, 2012 |
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15414679 |
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61570307 |
Dec 14, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 5/31541 20130101;
A61M 2205/50 20130101; A61M 5/31585 20130101; A61M 5/31525
20130101; A61M 2005/3126 20130101; A61M 5/31593 20130101; A61M
2205/3306 20130101; G01D 5/25 20130101; A61M 2205/52 20130101; A61M
2205/3375 20130101; A61M 5/31551 20130101; A61M 2205/502 20130101;
A61M 2205/8206 20130101; A61M 2005/2488 20130101; G01D 5/2497
20130101; A61M 2005/3125 20130101; G01D 5/252 20130101 |
International
Class: |
A61M 5/315 20060101
A61M005/315; G01D 5/249 20060101 G01D005/249; G01D 5/25 20060101
G01D005/25 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 15, 2011 |
EP |
11174124.5 |
Claims
1. A drug delivery device comprising; a housing; a cylindrical
member configured to be rotatably supported inside the housing,
wherein an outer surface of the cylindrical member is provided with
at least a first track and a second track, the first and the second
tracks together forming an encoder, each of the first and the
second tracks comprising conductive segments and non-conductive
segments, wherein the first and the second tracks are separated by
a non-conductive strip; and at least first and second groups of
contacts configured to engage the first and second tracks,
respectively, at predetermined intervals along the length of the
track, wherein the first group of contacts comprises more contacts
than the second group of contacts does.
2. The drug delivery device of claim 1, wherein the first group of
contacts comprises five contacts and the second group of contacts
comprises two contacts.
3. The drug delivery device of claim 1, wherein the contacts of the
first group of contacts are spaced to engage every sixth segment of
the first track, and wherein the contacts of the second group of
contacts are spaced to engage every twenty-seventh segment of the
second track.
4. The drug delivery device of claim 1, wherein the tracks are
helical tracks and wherein the housing and the cylindrical member
are configured such that the cylindrical member moves in a first
axial direction relative to the housing when rotated in a first
rotational direction relative to the housing.
5. The drug delivery device of claim 1, wherein the cylindrical
member is configured to be rotatable from an initial position into
a number of discrete rotational positions and wherein the contacts
of the first group of contacts are arranged such that a sequence of
conductive and non-conductive segments engaged by the contacts of
the first group of contacts in successive discrete rotational
positions forms a Gray code.
6. The drug delivery device of claim 1, wherein the encoder has a
higher bit depth than each individual track.
7. The drug delivery device of claim 1, wherein a coding depth of
the first track and a coding depth of the second track are combined
such that a combined coding depth of the encoder equals a sum of
the coding depths of the first track and the second track.
8. The drug delivery device of claim 1, wherein each of the first
track and the second track comprises a single track bit code.
9. The drug delivery device of claim 1, further comprising a switch
configured: in a first position, connect electrically the first
track and the second track; and in a second position, isolate
electrically the first track and the second track.
10. The drug delivery device of claim 9, further comprising a user
actuatable plunger configured to cause expulsion of a drug from the
drug delivery device, wherein depression of the plunger causes the
switch to switch from the first position to the second
position.
11. The drug delivery device of claim 1, wherein the conductive
segments within each of the first and the second tracks are
electrically connected to all other conductive segments in that
track.
12. The drug delivery device of claim 11, wherein the conductive
segments within each of the first track and the second track are
electrically connected together by first and second common ground
tracks immediately adjacent to respective ones of the first track
and the second track.
13. The drug delivery device of claim 1, wherein the conductive and
the non-conductive segments of the first and the second tracks are
arranged such that when the cylindrical member is in an initial
position, each contact is configured to engage a conductive
segment.
14. The drug delivery device of claim 1, further comprising: a
display; and a processor configured to receive and interpret
electrical signals from the contacts, to control application of
electrical signals to the contacts and to control an operation of
the display.
15. The drug delivery device of claim 14, wherein the processor is
configured to cause an electrical signal to be applied to at least
a first contact of the second group of contacts and simultaneously
to monitor signals at at least one other contact in order to
determine a position of the cylindrical member.
16. The drug delivery device of claim 14, wherein the processor is
configured: to cause an electrical signal to be applied to a first
contact of the second group of contacts and simultaneously to
monitor electrical signals at the first group of contacts; and when
no signals are detected at any of the first group of contacts, to
cause an electrical signal to be applied to a second contact of the
second group of contacts and simultaneously to monitor electrical
signals at the first group of contacts.
17. The drug delivery device of claim 16, wherein the processor is
configured to: in response to detecting no signals at any of the
first group of contacts when an electrical signal is applied to the
second contact of the second group of contacts, cause an electrical
signal to be applied to a first contact of the first group of
contacts and simultaneously to monitor electrical signals at other
contacts of the first group of contacts.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent
application Ser. No. 15/414,679, filed Jan. 25, 2017, which is a
continuation of U.S. patent application Ser. No. 14/131,646, filed
Jan. 8, 2014, now U.S. Pat. No. 9,586,009, which is a U.S. National
Phase Application pursuant to 35 U.S.C. .sctn. 371 of International
Application No. PCT/EP2012/063627, filed Jul. 12, 2012, which
claims the benefit of U.S. Provisional Patent Application No.
61/570,307, filed Dec. 14, 2011 which claims priority to European
Patent Application No. 11174124.5, filed Jul. 15, 2011. The entire
disclosure contents of these applications are herewith incorporated
by reference into the present application.
FIELD
[0002] The present invention relates to a drug delivery device.
BACKGROUND
[0003] Pen type drug delivery devices have application where
regular injection by persons without formal medical training
occurs. This is increasingly common among patients having diabetes
where self-treatment enables such patients to conduct effective
management of their diabetes.
[0004] For good or perfect glycemic control, the dose of insulin or
insulin glargine has to be adjusted for each individual in
accordance with a blood glucose level to be achieved. The present
invention relates to injectors, for example hand-held injectors,
especially pen-type injectors, that is to injectors of the kind
that provide for administration by injection of medicinal products
from a multidose cartridge. In particular, the present invention
relates to such injectors where a user may set the dose.
[0005] A user undertaking self-administration of insulin will
commonly need to administer between 1 and 80 International
Units.
SUMMARY
[0006] A first aspect of the invention provides a drug delivery
device comprising; [0007] a housing; [0008] a cylindrical member
configured to be rotatably supported inside the housing, wherein
the outer surface of the cylindrical member is provided with at
least first and second tracks together forming an encoder, each
track comprising conductive segments and non-conductive segments;
and [0009] at least first and second groups of contacts configured
to engage the first and second tracks respectively at predetermined
intervals along the length of the track.
[0010] The encoder is formed at least of first and second tracks
wherein the coding depth of the at least two tracks is combined.
Describing the coding depth in numbers of bits, the combined bit
depth of the encoder comprising the at least first and second track
equals the sum of the individual bit depth of each track. For
example, the encoder could have a 7-bit depth comprising a 5-bit
depth first track and a 2-bit depth second track. Alternatively,
the individual tracks comprise 4-bit and 3-bit depths,
respectively, together forming an encoder of 7-bit depth. A 7-bit
code that is capable of encoding 2.sup.7 different states is
sufficient to encode the positions of an 80 unit medicament
pen-type drug delivery device.
[0011] The encoder may be adapted to capture a dose that has been
set.
[0012] The tracks may comprise conductive ink printed onto a
non-conductive substrate
[0013] The first and second tracks may be separated. The first and
second tracks may be separated by a non-conductive strip. The
non-conductive strip may be the cylindrical member itself or a
secondary substrate which is subsequently attached to the
cylindrical member.
[0014] The cylindrical member may be operationally coupled to the
dose setting and delivery mechanism, for example by securing the
cylindrical member to a dose dial grip and by having a rotatable
engagement between the cylindrical member and an inner housing that
is connected to a spindle that is driven during dose
administration.
[0015] The tracks may be helical tracks and the housing and the
cylindrical member may be configured such that the cylindrical
member moves in a first axial direction relative to the housing
when rotated in a first rotational direction relative to the
housing.
[0016] The cylindrical member may be configured to be rotatable
from an initial position into a number of discrete rotational
positions and the contacts of the first group of contacts may be
arranged such that the sequence of conductive and non-conductive
segments engaged by the contacts of the first group of contacts in
successive discrete rotational positions forms a Gray code.
[0017] The first group of contacts may comprise more contacts than
the second group of contacts. The first group of contacts may
comprise five contacts and the second group of contacts may
comprise two contacts.
[0018] The contacts of the first group of contacts may be spaced
such as to engage every sixth segment of the first track and the
contacts of the second group of contacts may be spaced such as to
engage every twenty-seventh segment of the second track.
[0019] The device may further comprise a switch configured: [0020]
in a first position, to connect electrically the first and second
tracks; and [0021] in a second position, to isolate electrically
the first and second tracks.
[0022] The device may further comprise a user actuatable plunger
configured to cause expulsion of a drug from the drug delivery
device wherein depression of the plunger may cause the switch to
switch from the first position to the second position.
[0023] The conductive segments within each of the first and second
tracks may be electrically connected to all of the other conductive
segments in that track. The conductive segments within each of the
first and second tracks may be electrically connected together by
first and second common ground tracks immediately adjacent to
respective ones of the first and second tracks. The conductive and
non-conductive segments of the first and second tracks may be
arranged such that, when the cylindrical member is in an initial
position, each contact is configured to engage a conductive
segment.
[0024] The device may further comprise; [0025] a display; and
[0026] a processor configured to receive and interpret electrical
signals from the contacts, to control application of electrical
signals to the contacts and to control the operation of the
display.
[0027] The processor may be configured to cause an electrical
signal to be applied to at least a first contact of the second
group of contacts and simultaneously to monitor signals at at least
one other contact in order to determine a position of the
cylindrical member. Based at least in part on the monitored
signals, the processor may be configured to determine the position
of the encoded member. The processor may further be configured to
determine the mode of operation.
[0028] The processor may be configured: [0029] to cause an
electrical signal to be applied to a first contact of the second
group of contacts and simultaneously to monitor electrical signals
at the first group of contacts; and [0030] if no signals are
detected at any of the first group of contacts, to cause an
electrical signal to be applied to a second contact of the second
group of contacts and simultaneously to monitor electrical signals
at the first group of contacts.
[0031] The processor may be responsive to detecting no signals at
any of the first group of contacts when an electrical signal is
applied to the second contact of the second group of contacts to
cause an electrical signal to be applied to a first contact of the
first group of contacts and simultaneously to monitor electrical
signals at the other contacts of the first group of contacts.
[0032] Another aspect of the invention relates to combining of at
least two smaller bit depth single track encoders to create a
higher bit depth encoder.
[0033] A standard 7-bit track encoder, e.g., comprises 7 tracks
arranged in parallel that require a relatively wide area on an
encoded member. Having, for example, the encoder track on a
rotating sleeve, a helical version of the encoder would need to fit
in the axial pitch, i.e. the space between two windings. According
to our example, the 7 parallel tracks would have to fit the space
between two windings for a given pitch, wherein the width of each
track is very limited. This puts constraints with regards to the
individual track width, and construction complexity increases.
Fitting 7 parallel tracks in the restricted space results in a high
requirement for the read-out accuracy of the encoder with regards
to both, the coded tracks as well as the sensors. The length of the
tracks depends on the number of positions that are requested to be
encoded, e.g. 81 positions for an 80 unit pen, including a zero
position.
[0034] An alternative 7-bit single track encoder, e.g., could be
adapted to require a width smaller than the standard 7-bit track
encoder described before. Instead of having the tracks in parallel,
a single track is used where the sensors representing the bits are
equally spaced along this track. For an encoder track on a rotating
sleeve, a single track could more easily to fit in the axial pitch,
i.e. the space between two windings. The encoder may be constructed
using a single track gray code, where each column is a cyclic shift
of the first column (according to the number of sensors) and from
any row to the next row only one bit changes. The spacing of the
sensors may be 12, e.g., i.e. a sensor is positioned every
12.sup.th position. When the first sensor is at position "1" the
seventh sensor is at position "72". Having, for example, the
encoder track on a rotating sleeve, a helical version of the
encoder would require adding the pattern of the single track to the
end, because otherwise, the sensors would have no track to read.
This means that an extra 72 positions are required to make sure
that the seventh sensor or bit 7 maintains engagement with the
track. Therefore the solution for a 7-bit single track encoded is
81+72=153 units long compared with 81 units long for the standard 7
track version discussed before. The effect of having a track of
relatively small width results in extended total length of the
track, compared to the standard 7-bit encoder. A rotating sleeve
carrying a single track encoder would consequently have an
increased axial size. This could add complexity to the design of
the device and eventually could lead to an extended overall
delivery device length.
[0035] The above mentioned principles apply to encoders regardless
of the number of bits for the encoder track.
[0036] An encoder according to the invention, wherein the at least
first and second tracks together forming an encoder, could help
mitigating the deficiencies of the two types of encoders mentioned
above. An encoder according to the invention requires a width
smaller compared to a standard "parallel-track" encoder. The
encoder according to the invention requires a length shorter
compared to a "single track" encoder. Thus the encoder according to
the present invention provides an improved encoder that may
increase manufacturing quality, reduce cost, and/or increase code
efficiency.
[0037] The encoder according to the present invention comprises at
least two single track bit-codes, e.g. single track gray codes,
together forming an encoder, wherein the encoder has a higher bit
depth than each individual track.
[0038] In one example, a combination of a 5-bit track and a 2-bit
track together form an encoder of 7-bit depth. The 5-bit track may
have a spacing of 6, therefore the 5th sensor or contact is at
position 24. The overall track length required for a helical
version is 81+24=105. The 2-bit track may have a spacing of 27,
therefore the helical track length is 81+27=108.
[0039] The combined encoder having a 7-bit depth comprises two
tracks and has a length of 108. Compared to a single track 7-bit
code, the length is reduced by approximately 1/3 (compared 153)
which reduces the overall size of the encoded member. Compared to a
standard 7-bit track, the width is reduced from "7" to "2" which
leaves more space for each individual track.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] Embodiments will now be described, by way of example only,
with reference to the accompanying drawings, in which:
[0041] FIG. 1 shows an external view of a drug delivery device
suitable for implementing the present invention;
[0042] FIG. 2 shows a schematic diagram of some of the electronic
components present in the drug delivery device of FIG. 1;
[0043] FIG. 3 shows a dose setting mechanism of a drug delivery
device suitable for use with the invention;
[0044] FIG. 4 shows detail of the dose setting mechanism of FIG.
3;
[0045] FIG. 5 shows a close up of the region marked `A` in FIG. 3;
and
[0046] FIG. 6 is an exploded view showing details of a driver
forming part of the dose setting mechanism of FIGS. 3 to 5;
[0047] FIG. 7 shows an encoded member according to an embodiment of
the invention;
[0048] FIG. 8 is a table illustrating a track layout, contact
positions, results as registered at the contacts and a dispensing
mode decoding type;
[0049] FIG. 9 shows a contact support member;
[0050] FIG. 10 shows the contact support member of FIG. 9 in
position within the drug delivery device; and
[0051] FIG. 11 is a flow chart illustrating the steps involved in
determining the rotational position of the encoded member.
DETAILED DESCRIPTION OF THE DRAWINGS
[0052] Referring firstly to FIG. 1, an external view of a drug
delivery device 100 according to embodiments of the invention is
shown. The device 100 shown in FIG. 1 is a pen type injection
device, having an elongate cylindrical shape, for setting and
delivering a medicament, such as insulin. The device 100 comprises
a housing 102 having a first housing part 104 and a second housing
part 106. A rotatable dial 108 is located at a first (or proximal)
end of the first housing part 104. The rotatable dial 108 has
substantially the same outer diameter as the first housing part
104. The second housing part 106 may be detachably connected to the
second end of the first housing part 104. The second housing part
106 is configured to have a needle (not shown) or similar drug
delivery apparatus attached to it. To achieve this, the second (or
distal) end of the second housing part 106 may have a threaded
portion 110. The threaded portion 110 may have a smaller diameter
than the remainder of the second housing part 106.
[0053] A display mount 112 is located on the first housing part
104. A display may be supported on the display mount 112. The
display may be an LCD display, a segmented display or any other
suitable type of display. The display mount 112 may cover a recess
(not shown) in the first housing portion 104. A number of
electronic components, described in greater detail with reference
to FIG. 2, may be disposed underneath the display mount 112.
[0054] The first housing part 104 contains a drug dose setting and
delivery mechanism. The second housing part 106 contains a drug
cartridge (not shown). The drug contained in the drug cartridge may
be a medicament of any kind and may preferably be in a liquid form.
The drug delivery mechanism of the first housing part 104 may be
configured to engage with the drug cartridge of the second housing
part 106 to facilitate expulsion of the drug. The second housing
part 106 may be detached from the first housing part 104 in order
to insert a drug cartridge or to remove a used cartridge. The first
and second housing parts 104, 106 may be connected together in any
suitable way, for example with a screw or bayonet type connection.
The first and second housing parts 104, 106 may be non-reversibly
connected together is such a way as the drug cartridge is
permanently contained with the drug delivery device 100. Further
the first and second housing parts 104, 106 may form part of a
single housing part.
[0055] The rotatable dial 108 is configured to be rotated by hand
by a user of the drug delivery device 100 in order to set a drug
dose to be delivered. The dial 108 may be connected to an internal
threading system which causes the dial 108 to be displaced axially
from the housing 102 as it is rotated in a first direction. The
dial 108 may be rotatable in both directions or only in a first
direction. The device 100 is configured, once a drug dose has been
set by rotation of the rotatable dial 108, to deliver the set drug
dose when a user exerts an axial force at the proximal end of the
device. The rotatable dial 108 may support a button (not shown)
which must be depressed in order to deliver the set drug dose. The
display 112 may be configured to display information on the drug
dose which has been set and/or delivered. The display 112 may
further show additional information, such as the actual time, the
time of the last usage/injection, a remaining battery capacity, one
or more warning signs, and/or the like.
[0056] Referring now to FIG. 2, a schematic diagram of electrical
circuitry 200 forming part of the drug delivery device 100 is
shown. The circuitry 200 comprises a microprocessor 202, a
non-volatile memory such as a ROM 204, a volatile memory such as a
RAM 206, a display 210, contacts 212 and a bus 208 connecting each
of these components. The circuitry 200 also comprises batteries 214
or some other suitable source of power for providing power to each
of the components and a switch 216, described in greater detail
below.
[0057] The circuitry 200 may be integral with the device 100.
Alternatively, the circuitry 200 may be contained within an
electronic module that can be attached to the device 100. In
addition, the circuitry 200 may comprise additional sensors, such
as optical or acoustical sensors.
[0058] The ROM 204 may be configured to store software and/or
firmware. This software/firmware may control operations of the
microprocessor 202. The microprocessor 202 utilises RAM 206 to
execute the software/firmware stored in the ROM to control
operation of the display 210. As such the microprocessor may also
comprise a display driver.
[0059] The batteries 214 may provide power for each of the
components including the contacts 212. The supply of electricity to
the contacts 212 may be controlled by the microprocessor 202. The
microprocessor 202 receives signals from the contacts 212 and so
can determine when the contacts are energised, and is configured to
interpret these signals. Information is provided on the display 210
at suitable times by operation of the software/firmware and the
microprocessor 202. This information may include measurements
determined from the signals received by the microprocessor 202 from
the contacts 212.
[0060] A number of contacts 212 may be present in the device 100.
In a preferred embodiment, seven contacts 212 are present and may
be addressed individually by the microprocessor. These seven
contacts 212 are arranged into two groups of contacts. In some
embodiments, five contacts 212 comprise a first group of contacts
and two contacts 212 comprise a second group of contacts. The
contacts 212 may be mounted on an inner surface of the housing
102.
[0061] A fuller explanation of the operation of the dose setting
and delivery mechanism supported within the second housing part 106
will now be given with reference to FIGS. 3 to 6. FIG. 3 is a
cross-sectional view of a dose setting mechanism 400 of a drug
delivery device. FIG. 4 is a detailed view of a portion of the dose
setting mechanism 400. FIG. 5 illustrates a close up view of the
region marked `A` in FIG. 3.
[0062] The dose setting mechanism 400 comprises an outer housing
404, an inner housing 408 and an encoded member 406. These
components are preferably hollow cylinders arranged concentrically.
The encoded member 406 is disposed between the outer and inner
housings 404, 408. The inner housing 408 comprises a groove 432
provided along an external surface 434 of the inner housing 408. A
groove guide 436 provided on an inner surface 438 of the encoded
member 406 is rotatably engaged with this groove 432. The encoded
member 406 has information encoded on its outer surface 440 as will
be described in more detail below with reference to FIGS. 7 and
8.
[0063] A dose dial grip 402 is located at a proximal end of the
outer housing 404. The dose dial grip 402 is disposed about an
outer surface of a proximal end of the encoded member 406. An outer
diameter of the dose dial grip 402 preferably corresponds to the
outer diameter of the outer housing 404. The dose dial grip 402 is
secured to the encoded member 406 to prevent relative movement
between these two components. The dose dial grip 402 is represented
in the external view of FIG. 1 by the rotatable dial 108. The dose
dial grip 402 supports a dose button 416 which has a sprung bias in
a proximal direction and is configured to be depressed into the
dose dial grip 402 by a user of the device 100.
[0064] A spindle 414 is disposed centrally within the mechanism
400. The spindle 414 is provisioned with at least one helical
groove. In the embodiment depicted, the spindle 414 has two
opposite handed overlapping groove forms that preferably extend
over at least a majority of a length of the spindle. Each groove
form is effectively continuous over a number of turns. In one
preferred arrangement, each groove of the spindle 414 engages
either a non-continuous helical groove form on a body portion or on
a driver. Preferably, either or both a non-continuous thread form
on a body and a driver consists of less than one complete turn of
thread. A first thread of the spindle 414 is configured to connect
with a portion of the inner housing 408.
[0065] The dose setting mechanism 400 also comprises a spring 401,
a clutch 405 and a driver 409 having a first driver portion 407 and
a second driver portion 412. These driver portions 407, 412 extend
about the spindle 414. Both the first and the second driver
portions 407, 412 are generally cylindrical. The clutch 405 is
disposed about the driver 409. In one arrangement, the first driver
portion 407 comprises a first component part 410 and a second
component part 411. Alternatively, the first driver portion 407 is
an integral component part.
[0066] With the dose setting mechanism 400, as a user dials a dose
with the dose dial grip 402, the metal spring 401 is selected to be
strong enough to maintain engagement of both clutched couplings:
the clutched coupling between the clutch 405 and the encoded member
406 and clutched coupling between the first driver portion 407 and
second driver portion 412. The encoded member 406 is coupled to the
dose dial grip 402 such that when a user rotates the dose dial grip
402, the encoded member 406 also rotates. As the encoded member 406
is rotated in a first rotational direction, it moves axially in a
proximal direction due to its threaded connection to the inner
housing 408.
[0067] When the drug delivery device is being dispensed, the user
applies an axial load to the dose button 416 located at the
proximal end of the mechanism 400. The dose button 416 is axially
coupled to the clutch 405 and this prevents relative axial
movement. Therefore, the clutch 405 moves axially towards the
cartridge end or the distal end of the dose setting mechanism 400.
This movement disengages the clutch 405 from the encoded member
406, allowing for relative rotation while closing up the Gap `a`.
The clutch 405 is prevented from rotating relative to a clicker 420
and hence relative to the inner housing 408. However, in this
scenario, the coupling between the first driver portion 407 and the
second driver portion 412 is also prevented from becoming
disengaged. Therefore, any axial load on the spindle 414 only
disengages the first and second driver portions 407, 412 when the
dose button 416 is not axially loaded. This therefore does not
happen during dispense.
[0068] A dose limiter 418 (visible in FIG. 4) is provided on first
driver portion 407 and in the illustrated arrangement comprises a
nut. The dose limiter 418 has an internal helical groove matching
the helical groove of the first driver portion 407. In one
preferred arrangement, the outer surface of the dose limiter 418
and an internal surface of the inner housing 408 are keyed together
by way of splines. This prevents relative rotation between the dose
limiter 418 and the housing 408 while allowing relative
longitudinal movement between these two components.
[0069] FIG. 6 shows in detail a first arrangement of the first
driver portion 407 and the second driver portion 412 illustrated in
FIGS. 3 to 5. As illustrated in FIG. 10, the second driver portion
412 is generally tubular in shape and comprises at least one drive
dog 450 located at a distal end of the second driver portion 412.
The first driver portion 407 also has a generally tubular shape and
comprises a plurality of recesses 452 sized to engage with the
drive dog 450 on the second driver portion 412. The construction of
the drive dog and recesses allow disengagement with the drive dog
450 when the first and second driver portions are axially pushed
together. This construction also creates a rotational coupling when
these components are sprung apart.
[0070] In some embodiments, the first driver portion 407 comprises
a first portion (first component part) 410 that is permanently
clipped to a second portion (second component part) 411. In this
arrangement, the second component part 411 comprises the plurality
of recesses 452 and the first component part 410 includes the outer
groove for the dose limiter 418 nut as well as an internal groove
454. This internal groove 454 is used to connect to the spindle 414
and drives the spindle 414 during dose administration. In the
illustrated embodiment, the internal groove 454 comprises a part
helical groove rather than a complete helical groove. One advantage
of this arrangement is that it is generally easier to
manufacture.
[0071] One advantage of this dose setting mechanism 400 utilizing
the inner housing 408 is that the inner housing 408 can be made
from an engineering plastic that minimizes friction relative to the
encoded member 406 groove guide 436 and the groove 432. For
example, one such an engineering plastic could comprise Acetal.
However, those skilled in the art will recognize that other
comparable engineering plastics having a low coefficient of
friction could also be used. Using such an engineering plastic
enables the material for the outer housing 404 to be chosen for
aesthetic or tactile reasons with no friction related requirements
since the outer housing 404 does not engage any moving components
during normal operation.
[0072] The effective driving diameter (represented by `D`) of the
grooved interface between the encoded member 406 and the inner
housing 408 is reduced compared to certain known drug delivery
devices for the same outer body diameter. This improves efficiency
and enables the drug delivery device to function with a lower pitch
(represented by `P`) for this groove and groove guide connection.
In other words, as the helix angle of the thread determines whether
when pushed axially, the encoded member will rotate or lock to the
inner body wherein this helix angle is proportional to the ratio of
P/D.
[0073] A recess 442 in the outer housing 404 of the drug delivery
device 100 can be seen in FIG. 3. This recess 442 may be configured
to receive an insert or electronic module (not shown), comprising
the Microprocessor 202, ROM 204, RAM 206, display electronics and
batteries 214 previously described. A number of the contacts 212
may be supported on a lowermost surface of the insert, while others
of the contacts 212 may be supported at other positions on the
inner surface of the outer housing 404 and linked to the
microprocessor 202 and batteries 214 by conductive paths or wires.
The display mount 112 shown in FIG. 1 may be disposed on top of the
insert or may be integral with the insert. The display mount 112 is
configured to support the display 210. The display 210 may be
larger than the recess 442 and may therefore protrude from the
outer housing 404. Alternatively, both the display mount 112 and
display 210 may be configured to be received by the recess 442 such
that the display 210 is flush with the outer surface of the outer
housing 404. The contacts 212 are configured to contact the encoded
member 406 in order to facilitate a determination of the rotational
position of the encoded member 406, as will be described in more
detail with reference to FIGS. 7 to 10.
[0074] The dose setting mechanism 400 illustrated in FIG. 3-6 is
configured to be re-set to an initial position after the medicament
in the attached drug cartridge has been expelled. This allows a new
cartridge to be inserted and the drug delivery device 100 to be
re-used. This re-setting may be achieved by pushing axially on the
distal end of the spindle 414 i.e. the end which usually engages
with the drug cartridge and does not require any mechanism
associated with removal of a cartridge holder. As illustrated in
FIGS. 3 and 4, when the first driver portion 407 is pushed axially
towards the second driver portion 412 (i.e., pushed in a proximal
direction) the driver 409 is de-coupled from the rest of the dose
setting mechanism 400.
[0075] An axial force on the spindle 414 causes the spindle 414 to
rotate due to its threaded connection to the inner housing 408.
This rotation and axial movement of the spindle 414 in turn causes
the first driver portion 407 to move axially towards the second
driver portion 412. This will eventually de-couple the first driver
portion 407 and second driver portion 412.
[0076] This axial movement of the first driver portion 407 towards
the second driver portion 412 results in certain advantages. For
example, one advantage is that the metal spring 401 will compress
and will therefore close the Gap `a` illustrated in FIGS. 3-5. This
in turn prevents the clutch 405 from disengaging from the clicker
420 or from the encoded member 406. The second driver portion 412
is prevented from rotation since it is splined to the clutch 405.
The clicker 420 is splined to the inner housing 408. Therefore,
when the Gap `a` is reduced or closed up, the second driver portion
412 cannot rotate relative to either the inner housing 408 or the
encoded member 406. As a consequence, the encoded member 406 cannot
rotate relative to the inner housing 404. If the encoded member 406
is prevented from rotating then, as the spindle 414 is retracted
back into the dose setting mechanism 400 and thereby re-set, there
will be no risk of the encoded member 406 being pushed out of the
proximal side of the dose setting mechanism 400 as a result of a
force being applied on the spindle 414.
[0077] Another advantage of a dose setting mechanism 400 comprising
an inner housing 408 is that the dose setting mechanism 400 can be
designed, with a slight modification, as a drug delivery device
platform that is now capable of supporting both re-settable and
non-resettable drug delivery devices. As just one example, to
modify the re-settable dose setting mechanism 400 variant
illustrated in FIGS. 3-6 into a non-resettable drug delivery
device, the first component part 410 and the second component part
411 of the first driver potion 407 and the second driver portion
412 can be moulded as one unitary part. This reduces the total
number of drug delivery device components by two. Otherwise, the
drug delivery device illustrated in FIGS. 3-6 could remain
unchanged. In such a disposable device, the second housing part 106
would be fixed to the first housing part 104 or alternatively made
as a single one piece body and cartridge holder.
[0078] The dose setting mechanism described above is merely one
example of a mechanism suitable for supporting the encoded member
406 and for implementing the present invention. It will be apparent
to the skilled person that other mechanisms may also be suitable.
For example, a mechanism which does not include an inner housing
408, but in which the encoded member 406 is still visible to the
sensor 112 would be equally suitable.
[0079] FIG. 7 illustrates the encoded member 406. The encoded
member 406 is a hollow cylinder. An outer surface 440 of the
encoded member 406 comprises a first helical track 300 and a second
helical track 302 arranged adjacent to one another. Each of the
first and second tracks 300, 302 comprises conductive and
non-conductive segments. In FIG. 7, the conductive segments are
shown in black and the non-conductive segments are shown in white.
In some embodiments, each of the first and second tracks 300, 302
comprises a measurement track and a ground or power track
immediately adjacent to the measurement track. The effect of the
ground track is to maintain an electrical connection between all of
the conductive segments of each track 300, 302.
[0080] An inner surface 438 of the member 406 may have a helical
thread (shown as inner groove 436 in FIGS. 3 to 5). This thread 436
may extend over a single turn or over a partial turn.
[0081] Alternatively, this thread 436 may comprise several turns.
The member 406 may be made of a plastic material. The encoded
member 406 is configured to be incorporated into the drug delivery
device 100 as shown in FIGS. 3 to 5. The inclusion of an inner
housing 408 enables the encoded member 406 to have a helical thread
436 on the inner surface 438 rather then the outer surface 440.
This results in a number of advantages. For example, this results
in the advantage of providing more surface area along the outer
surface 440 of the encoded member 406 for the helical tracks 300,
302. Another advantage is that this inner groove 436 is now
protected from dirt ingress. In other words, it is more difficult
for dirt to become logged in this inner groove interface than if
the groove were provided along the outer surface 440 of the encoded
member 406. This feature is particularly important for a
re-settable drug delivery device which is required to function over
a much longer period of time compared to a non-resettable
device.
[0082] The helical tracks 300, 302 formed on the outer surface 440
of the member 406 may be formed by wrapping one or more metallic
strips around the member 406. The metallic strip 300, 302 may have
a non-conductive backing to support the metallic layer. The
non-conductive backing may have an adhesive on the reverse side for
securing the strip to the outer surface 440 of the member 406. The
first and second helical tracks 300, 302 may be separated by a
non-conductive strip. In some other embodiments, the tracks 300,
302 may comprise conductive ink printed onto a non-conductive
substrate. This non-conductive substrate may be the member 406
itself or a secondary substrate which is subsequently attached to
the member 406.
[0083] An electrical conduction path (not shown) joins the two
tracks 300, 302. The switch 216 is disposed in this electrical
conduction path. The switch 216 is configured to connect
electrically the two tracks 300, 302 to one another when the device
100 is idle or when a drug dose is being set by rotation of the
rotatable dial 108. The switch 216 is configured to isolate
electrically, or disconnect, the two tracks 300, 302 when the
selected drug dose is being delivered. The switch 216 is coupled to
the dose button 416 supported by the rotatable dial 108, such that
when the button is depressed, the switch 216 disconnects the two
tracks 300, 302 from one another.
[0084] Each of the first and second tracks 300, 302 is configured
to be engaged by a number of contacts 212. The contacts 212 may be
biased against the outer surface 440 of the encoded member 406 in
order to provide a stable electrical connection. The contacts 212
are spaced along the length of their respective track 300, 302. The
contacts 212 are arranged to engage, if present, the measurement
track of their respective helical track 300, 302. In a preferred
embodiment, the first track 300 is engaged by five contacts 212
(contacts 1-5) and the second track 302 is engaged by two contacts
212 (contacts 6 and 7). The pitch of the helical tracks 300, 302 is
the same as the pitch of the groove guide 436 of the encoded member
406 which engages with the inner housing groove 432. Therefore,
when the encoded member 406 rotates and moves axially within the
housing 102, the helical tracks 300, 302 are always positioned
directly underneath the contacts 212. The contacts 212 are spaced
such as to engage non-adjacent segments of their respective track
300, 302. In some embodiments, contacts 1 to 5 are spaced so as to
engage every 6th segment of the first track 300 and contacts 6 and
7 are spaced so as to engage every 27th segment of the second track
302.
[0085] The microprocessor 202 may be configured to address each of
the contacts 212 individually. The microprocessor 202 is also
configured to control the flow of electricity from the batteries
214 to each contact. However, when the batteries 214 provide a
signal having a voltage to one of the contacts, certain others of
the contacts may also be energized by virtue of being in electrical
connection with the first contact via the conductive segments of
the helical tracks 300, 302 or via the electrical conduction path
joining the two tracks 300, 302. Thus, the batteries may provide a
voltage to a first of the contacts (for example) and the
microprocessor 202 may detect signals from each of the contacts 212
which are energized by their electrical connection to the first
contact. Since the microprocessor 202 can address the contacts 212
individually, it is able to apply a signal to different contacts in
a sequence, each time monitoring signals from the other contacts
212.
[0086] The conductive and non-conductive segments of the helical
tracks 300, 302 are arranged in a repeating sequence. As the
contacts 212 are spaced along the tracks 300, 302, each contact
sees a shifted version of the same sequence of code. Having seven
contacts 212 results in a seven bit encoding system. Seven bits
allows for a maximum of 27=128 unique positions to be encoded. Thus
the full 0-80 unit dial-able dose for an injection device can be
absolutely encoded with redundant positions available.
[0087] It should be noted that the first and second tracks 300, 302
do not begin at the same relative angular position on the encoded
member 406 in the embodiment shown in FIG. 7. The tracks 300, 302
are offset such that the second track 302 begins and ends first.
The start of the first track 300 and the end of the second track
302 are visible in FIG. 7.
[0088] FIG. 8 shows a table 500 illustrating a track layout for the
first and second tracks 300, 302 and the track segments as
registered at each of the seven contacts 212 in each rotational
position. The arrangement of the segments of the first track 300 is
shown in column "#1". The arrangement of the segments of the second
track 302 is shown in column "#2". The columns headed "G" represent
the ground or power tracks which are immediately adjacent to each
of the measurement tracks (#1, #2). In FIG. 8, the darker regions
represent a conductive segment and the lighter regions represent a
non-conductive segment. A code digit with a value of "1" may be
represented by a conductive segment and a value of "0" may be
represented by a non-conductive segment.
[0089] The two columns headed "contact" illustrate the segment
intervals between the contacts engaging the first and second tracks
300, 302 respectively in dose position "0". The columns headed 1 to
7 show the type of segment (conductive or non-conductive)
positioned under each of the seven contacts 212 in each rotational
position, represented by the column "Dose Position". The repeating
sequence which is laid out on the first track 300 (column #1) is
arranged such that when contacts 1 to 5 are positioned over every
6th segment (see first "contact" column), the result at these
contacts forms a type of Gray code, or reflected binary code, as
shown in columns 1-5 of the table 500. A Gray code is a binary
coding system in which only one binary bit changes value between
each successive encoded value. The illustrated Gray code repeats
every 30 rotational positions. Coupled with the output from
contacts 6 and 7, which changes every 27 rotational positions (see
second "contact" column), the rotational position of the encoded
member 406, and hence the dose position, can be determined
absolutely.
[0090] Contacts 6 and 7 engage with the second track 302 at an
interval of 27 segments. Thus the second track 302 is 27 segments
longer than the 81 needed to encode the dose positions 0-80, i.e.
when the sixth contact is positioned over the 81st segment, the
seventh contact is positioned over the 108th segment. Similarly,
the first five contacts are spaced at intervals of 6 segments
meaning that the first track 300 is 24 segments longer than the 81
needed to encode the dose positions 0-80, i.e. when the first
contact is positioned over the 81st segment, the fifth contact is
positioned over the 105th segment.
[0091] The Gray code shown in columns 1 to 5 of the table 500
deviates from a pure Gray code such that at position zero contacts
1 to 5 all have a value of "1". This arrangement aids with error
checking of the device 100 as any inoperable contacts will not
initially register a value.
[0092] Each conductive segment within each track 300, 302 is
electrically connected to every other conductive segment within
that track due to the presence of the ground or power tracks. Thus,
in all rotational positions of the encoded member 406, when a
voltage is provided from the batteries 114, via a contact 212, to a
conductive segment, every conductive segment on the respective
track 300, 302 is also energized. Any contact 212 (other than the
contact which has the voltage provided to it) which is positioned
over a conductive segment therefore registers a binary value of
"1".
[0093] FIG. 9 shows a contact support member 600 supporting seven
contacts 212. FIG. 10 shows the contact support member 600 in
position within the drug delivery device 100. The contact support
member 600 may have a generally cylindrical hollow body. The
support member 600 may be a partial cylinder (as shown in FIG. 9),
or it may be a full cylinder. The contacts 212 are supported on an
inner surface 602 of the support member 600. The support member 600
is configured to extend about the encoded member 406 such that the
contacts 212 engage with the tracks 300, 302 on the encoded member
406. An outer surface 604 of the support member 600 may abut
directly an inner surface of the outer housing 404 and may be
secured to the outer housing 404 in order to prevent relative
movement between these components. Alternatively a recess (not
shown) may be provided in the outer housing 404 to accommodate the
contact support member 600.
[0094] Each contact 212 has a respective contact terminal 606. The
contact terminals 606 may extend through the thickness of the
contact support member 600 so that the contacts 212 may be
addressed from the outer surface 604 of the support member 600. The
contacts 212 may have a sprung bias towards the encoded member 406
such that a stable connection is made between each contact 212 and
the tracks 300, 302. The contacts 212 are positioned such that
contacts 1 to 5 engage the first track 300 at every 6th segment and
contacts 6 and 7 engage the second track 302 at every 27th segment.
The microprocessor 202 and other electronic components may be
located adjacent to the contact terminals 606 on the outer surface
604 of the contact support member 600.
[0095] When a user of the device 100 rotates the rotatable dial 108
to set a drug dose, the microprocessor 202 may be activated and may
be controlled by software stored in the ROM 204 to execute a
predefined check on the contacts 212 to determine the absolute
rotational position of the encoded member 406, and hence the drug
dose which has been dialled. This checking process may also allow
the microprocessor 202 to determine the status of the switch 216
and hence whether the device 100 is in dialling mode or dispensing
mode. If the microprocessor 202 determines that the device 100 is
in a dispensing mode, further steps may be preformed in order to
determine the rotational position of the encoded member 406. The
microprocessor 202 may also be configured to determine the number
of drug units which have been delivered.
[0096] Referring to FIG. 11, the process of determining the
rotational position of the encoded member 406 is now described.
Each contact 212 represents a bit of the encoding system and may
alternatively be referred to as "bits". When a contact 212 is
positioned over a conductive segment, it may be referred to as a
"high bit". When a contact 212 is positioned over a non-conductive
segment, it may be referred to as a "low bit". A contact 212 or bit
may be "set high" by applying a voltage to it in some way. Each of
the contacts 212 may individually have a voltage applied and the
status (high or low) of each bit may be individually determined by
the microprocessor 202.
[0097] In step S1, bit 7 is set high by the microprocessor 202 and
the status of bits 1 to 6 are determined. As previously mentioned,
the microprocessor 202 may receive electrical signals from each of
the contacts 212 and may be configured to interpret these signals
to determine the binary code digit for the contacts 212.
[0098] At step S2 it is determined whether any of bits 1 to 5 were
detected as "high" in step S1. If any high bits were detected in
bits 1 to 5 then, at step S3, the microprocessor 202 can use the
result of the bit determination in step Si to conclude that the
device 100 is in a dialling mode and to determine absolutely the
rotational position of the encoded member 406 and hence the drug
dose which has been dialled. The microprocessor 202 may achieve
this by searching a lookup table stored in the ROM 204, the lookup
table providing a conversion from a seven bit binary code result to
a dose unit dialled. The process ends at step S3 while requiring
only steps 1 and 2 to be performed in the situation where a user of
the device 100 dials between 0 and 53 units.
[0099] If at step S2 none of bits 1 to 5 are determined to be
"high", then the microprocessor 202 proceeds to step S4, in which
it is determined if bit 6 was detected as high in step S1. If bit 6
was not detected as high then, at step S5, bit 6 is set high and
the status of bits 1 to 5 are determined. At step S6 it is
determined whether any of bits 1 to 5 were detected as "high" in
step S5. If any high bits were detected in bits 1 to 5 then, at
step S3, the microprocessor 202 can use the result of the bit
determination in step S5 to conclude that the device 100 is in a
dialling mode and to determine absolutely the rotational position
of the encoded member 406 and hence the drug dose which has been
dialled. Steps 1 to 6 of the process are performed before the
process ends at step S3 in the situation where a user of the device
100 dials between 54 and 80 units.
[0100] If bit 6 is detected as high in step S4, or if bit 6 is not
detected as high in step S4 but no high bits are subsequently
detected in bits 1 to 5 in steps 5/6, then the process proceeds at
step S7. The microprocessor 202 may also determine at this point in
the process that the device 100 is in a dispensing mode. Because
there is at least one conductive segment on each track 300, 302 at
each rotational position, the fact that no high bits were detected
in bits 1 to 5 at either step S2 or, if performed, step S6 means
that the two tracks 300, 302 are not electrically connected. As
previously described, this occurs when the dose button 416 is
depressed causing the switch 216 to isolate electrically, or
disconnect, the two tracks 300, 302. When the dose button 416 is
depressed, the device is in a dispensing, or drug delivery,
mode.
[0101] At step S7, bit 1 is set high by the microprocessor 202 and
the status of bits 2 to 5 are determined. At step S8 it is
determined whether any of bits 2 to 5 were detected as "high" in
step S7. If any high bits were detected in bits 2 to 5 then, at
step S9, it is determined whether both bit 6 and bit 7 were
detected as "high" in step S1. If both bit 6 and bit 7 were
detected as high in step S1 then, at step S10, the microprocessor
202 can use the results obtained in steps 1 and 8 to determine
absolutely the rotational position of the encoded member 406. As
previously mentioned, the microprocessor 202 may determine that the
device is in a dispensing mode upon reaching step S7 of the process
but may only record this determination upon reaching a process end
step.
[0102] If both bits 6 and 7 are not detected as "high" in step S9,
i.e. neither bit 6 or 7 is detected as high then, at step S11, the
microprocessor 202 records that the device is in a dispensing mode
and that a quasi-absolute solution may be determined. In the
quasi-absolute solution scenario, the microprocessor 202 may search
a five bit lookup table (or the first five bits of the seven bit
lookup table) stored in the ROM 204. This search yields more than
one possible position, and since neither bit 6 not bit 7 were
detected as high, these positions yield the same bit code result.
Due to the isolation of the second track 302 from the first, there
is no situation in which only one of bit 6 or bit 7 is detected as
high.
[0103] Referring back to FIG. 8, the last columns of the table 500
list the type of solution which can be determined for each
rotational position when the device 100 is in a dispensing mode.
Quasi-absolute solutions are present in both the first and last 27
dose positions. For example, dose positions 6 and 66 are
indistinguishable from one another when the first and second tracks
300, 302 are not electrically connected together. However, the
microprocessor 202 may still determine or predict the position of
the encoded member 406 using the last known absolute position. For
example, if a user dials a dose of 10 units and then delivers only
4 of those units, the microprocessor 202 can determine that the
current rotational position is dose position 6, rather than
position 66, since the last absolutely known position was much
lower than position 66, and it is mechanically prevented for the
dial position to increase whilst the device is in dispensing
mode.
[0104] At step S8 it is determined whether any of bits 2 to 5 were
detected as "high" in step S7. If no high bits were detected in
bits 2 to 5 then, at step S12, the next lowest untested bit is set
high and the status of the other first track bits are determined.
For example, if the result of step S8 is negative, then bit 2 is
set high in step S12 and the status of bits 1, 3, 4 and 5 are
determined. At step S13 it is determined whether any high bits were
detected in step S12. If it is determined that high bits were
detected then the process continues to step S9, described above. If
high bits are not detected in any of the first track bits at step
S13 then, at step at 14, it is determined whether all of bits 2 to
4 have been tested. If all of bits 2 to 4 have not been tested then
the process returns to step S12, where the next lowest untested bit
is tested. For example, if bit 2 is set high in step S12 and it is
determined in step S13 that no high bits are detected in any of the
first track bits, then the result of step S14 will be negative and
the process will return to step S12, in which bit 3 is set high and
the status of bits 1, 2, 4 and 5 are determined.
[0105] If at step S14 it is determined that all of bits 2 to 4 have
been tested then the process ends at step S15 where the
microprocessor 202 records that the device is in a dispensing mode
and that an incremental solution may be determined. In this
situation the microprocessor 202 has not been able to establish the
status of any of the seven bits. The microprocessor 202 therefore
predicts the dose position based on the last know absolute
position.
[0106] As can be seen from the table 500 of FIG. 8, during
dispensing of the device 100 there are 23 dose positions which can
be absolutely determined. There are 45 positions in which the 5 bit
track 300 can be decoded to give a quasi-absolute solution.
Repeated quasi-absolute solutions are separated by 60 dose
positions. There are 13 positions, equally spaced every 6th dose,
where an incremental solution must be determined.
[0107] In the depicted embodiment dose positions 58 to 60 have a
quasi-absolute solution, however in some other embodiments, the
software executed by the microprocessor 202 may allow these dose
positions to be determined absolutely. For example dose positions
58 to 60 have the same five bit code, from bits 1 to 5 on track
300, as dose positions 28 to 30 respectively. No other dose
positions return the same five bit codes. As dose positions 28 to
30 can be absolutely determined during dispensing as both bit 6 and
bit 7 would be detected as "high" in step S1, dose positions 58 to
60 can be deduced absolutely as uniquely coded positions.
[0108] When dispensing a selected dose, if for any reason the user
does not dispense the full dose, the display 210 may be configured
to show the dose which is remaining to be dispensed. In this
situation, the microprocessor 202 may determine the drug dose which
has been dispensed by subtracting a remaining drug dose from the
initially dialled drug dose.
[0109] Although a seven bit system has been described, the method
is equally applicable for any number of contacts greater than
three. The seven bit system is preferred as it allows the full 0-80
unit dose range to be absolutely encoded.
[0110] In some alternative embodiments of the invention, the
encoded member 406 may comprise a metallic ring having protrusions
round the circumference representing the conductive "1" value of
the binary code. The recesses representing binary "0" can then be
filled with a non-conductive material.
[0111] In an alternative embodiment of the invention the operation
of the switch 216 is reversed. In this alternative embodiment, the
switch 216 is configured to disconnect electrically the two banks
of tracks 300 when the device 100 is idle or when a drug dose is
being set by rotation of the rotatable dial 108. The switch 216 is
configured to connect the two banks of tracks 300 when the selected
drug dose is being delivered. The switch 216 is coupled to the dose
button 416 supported by the rotatable dial 108, such that when the
button is depressed, the switch 216 connects the two banks of
tracks 300.
[0112] The microprocessor 202 may perform the cyclic check
described above while the encoded member is rotating, i.e. while
the device is being dispensed. Therefore the same method as
described above may be used to determine a dispensed dose, rather
than a dialled dose.
[0113] Having determined the drug dose which has been dispensed,
the microprocessor 202 may store the result in the ROM 204. The
display 210 may be controlled to display the result of the
dispensed dose determination. The display 210 may display the
result of the dispensed dose determination for a predetermined
time, for example 60 seconds. Alternatively or in addition, the
dispensed dose history may be retrieved electronically from the ROM
204 by a user of the device 100 or by a health care professional.
During dialling of the device, the dialled dose may be indicated to
the user in any conventional way, for example by use of numerals
printed on the number sleeve. Alternatively or in addition, a more
complex cyclic check may be performed on the contacts 212 in order
to determine the absolute rotational position of the encoded member
406 during dialling. This may involve checking each of the seven
contacts in turn. In some other embodiments, the dialled dose is
not determined or indicated to the user.
[0114] It will be appreciated that the above described embodiments
are purely illustrative and are not limiting on the scope of the
invention. Other variations and modifications will be apparent to
persons skilled in the art upon reading the present application.
Moreover, the disclosure of the present application should be
understood to include any novel features or any novel combination
of features either explicitly or implicitly disclosed herein or any
generalization thereof and during the prosecution of the present
application or of any application derived therefrom, new claims may
be formulated to cover any such features and/or combination of such
features.
[0115] The term "drug" or "medicament", as used herein, means a
pharmaceutical formulation containing at least one pharmaceutically
active compound,
[0116] 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, an enzyme,
an antibody or a fragment thereof, a hormone or an oligonucleotide,
or a mixture of the above-mentioned pharmaceutically active
compound,
[0117] 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,
[0118] 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,
[0119] 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 exendin-3 or exendin-4 or an
analogue or derivative of exendin-3 or exendin-4.
[0120] 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.
[0121] 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-(.omega.-carboxyheptadecanoyl)-des(B30) human
insulin and B29-N-(.omega.-carboxyheptadecanoyl) human insulin.
[0122] 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-Gl-
u-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly--
Ala-Pro-Pro-Pro-Ser-NH2.
[0123] 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,
H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,
des Pro36 Exendin-4(1-39),
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(O2)25, Asp28] Exendin-4(1-39),
des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(O2)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(O2)25, Asp28] Exendin-4(1-39),
des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),
[0124] 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
des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),
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-(Glu)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-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,
H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25]
Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)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(O2)25, Asp28]
Exendin-4(1-39)-Lys6-NH2,
H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)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(O2)25, Asp28]
Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)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;
[0125] or a pharmaceutically acceptable salt or solvate of any one
of the afore-mentioned Exendin-4 derivative.
[0126] 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.
[0127] 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.
[0128] Antibodies are globular plasma proteins (.about.150 kDa)
that are also known as immunoglobulins which share a basic
structure. As they have sugar chains added to amino acid residues,
they are glycoproteins. The basic functional unit of each antibody
is an immunoglobulin (Ig) monomer (containing only one Ig unit);
secreted antibodies can also be dimeric with two Ig units as with
IgA, tetrameric with four Ig units like teleost fish IgM, or
pentameric with five Ig units, like mammalian IgM.
[0129] The Ig 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
Ig 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 immunoglobulin fold in which two .beta. sheets
create a "sandwich" shape, held together by interactions between
conserved cysteines and other charged amino acids.
[0130] There are five types of mammalian Ig heavy chain denoted by
.alpha., .delta., .epsilon., .gamma., and .mu.. The type of heavy
chain present defines the isotype of antibody; these chains are
found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.
[0131] Distinct heavy chains differ in size and composition;
.alpha. and .gamma. contain approximately 450 amino acids and
.delta. approximately 500 amino acids, while .mu. and .epsilon.
have approximately 550 amino acids. Each heavy chain has two
regions, the constant region (C.sub.H) and the variable region
(V.sub.H). In one species, the constant region is essentially
identical in all antibodies of the same isotype, but differs in
antibodies of different isotypes. Heavy chains .gamma., .alpha. and
.delta. have a constant region composed of three tandem Ig domains,
and a hinge region for added flexibility; heavy chains .mu. and
.epsilon. have a constant region composed of four immunoglobulin
domains. The variable region of the heavy chain differs 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 Ig domain.
[0132] In mammals, there are two types of immunoglobulin light
chain denoted by .lamda. and .kappa.. A light chain has two
successive domains: one constant domain (CL) and one variable
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, .kappa. or .lamda.
is present per antibody in mammals.
[0133] 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 binding to the antigen, i.e. for
its antigen specificity. These loops are referred to as the
Complementarity Determining Regions (CDRs). Because 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 determines the final antigen specificity.
[0134] An "antibody fragment" contains at least one antigen 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
cleaves 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, similar in size but containing the carboxyl terminal half
of both heavy chains with their interchain disulfide bond, is the
crystalizable fragment (Fc). The Fc contains carbohydrates,
complement-binding, and FcR-binding sites. Limited pepsin digestion
yields a single F(ab')2 fragment containing both Fab pieces and the
hinge region, including the H--H interchain 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 fragment (scFv).
[0135] 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: 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.
[0136] Pharmaceutically acceptable solvates are for example
hydrates.
* * * * *