[0001] The present invention relates to the field of packaging assemblies and in particular
to packaging assemblies adapted to accommodate at least two drug delivery devices,
such like injection devices.
Background and Prior Art
[0002] Drug delivery devices for setting and dispensing a single or multiple doses of a
liquid medicament are as such well-known in the art. Generally, such devices have
substantially a similar purpose as that of an ordinary syringe.
[0003] Drug delivery devices, in particular pen-type injectors have to meet a number of
user-specific requirements. For instance, with patient's suffering chronic diseases,
such like diabetes, the patient may be physically infirm and may also have impaired
vision. Suitable drug delivery devices especially intended for home medication therefore
need to be robust in construction and should be easy to use. Furthermore, manipulation
and general handling of the device and its components should be intelligible and easy
understandable. Moreover, a dose setting as well as a dose dispensing procedure must
be easy to operate and has to be unambiguous.
[0004] Typically, such devices comprise a housing or a particular cartridge holder, which
is adapted to receive a cartridge at least partially filled with the medicament to
be dispensed. The device further comprises a drive mechanism, usually having a displaceable
piston rod which is adapted to operably engage with a piston of the cartridge. By
means of the drive mechanism and its piston rod, the piston of the cartridge is displaceable
in a distal or dispensing direction and may therefore expel a predefined amount of
the medicament via a piercing assembly, which is to be releasably coupled with a distal
end section of the housing of the drug delivery device.
[0005] The medicament to be dispensed by the drug delivery device is provided and contained
in a multi-dose cartridge. Such cartridges typically comprise a vitreous barrel sealed
in distal direction by means of a pierceable seal and being further sealed in proximal
direction by the piston. With reusable drug delivery devices an empty cartridge is
replaceable by a new one. In contrast to that, drug delivery devices of disposable
type are to be entirely discarded when the medicament in the cartridge has been completely
dispensed or used-up.
[0006] Drug delivery devices may also comprise conventional syringes, in particular pre-filled
syringes that are intended for single use. Moreover, injection-based treatment of
patients may require to make use of different pharmaceutical substances or medicaments
to be injected or dispensed by different injection devices or drug delivery devices,
respectively.
[0007] Typically, at the beginning of a therapy a first medicament may have to be administered
before a second medicament should be used later on. In many cases, the two medicaments
to be administered sequentially are commercially distributed as a treatment kit, in
which first and second medicaments to be delivered by respective first and second
drug delivery devices mutually complement. Since the two medicaments together with
respective drug delivery devices are mutually correlated it is only natural, that
said kit consisting of at least two medicaments and drug delivery devices is commercially
distributed in form of a common packaging assembly.
[0008] Providing at least two different drug delivery devices in a common packaging assembly
may be confusing to the end user or patient. In particular with self-medication or
home treatment the patient himself has to correctly identify the particular drug delivery
device which is to be used initially. Even though the packaging assembly may be provided
with respective instructions about general usage of first and second drug delivery
devices, the patient himself, for whichever reason, may disregard or misunderstand
respective instructions. Hence, there is a certain risk, that the two drug delivery
devices are mixed up and that they are used in an inappropriate way.
Objects of the invention
[0009] It is therefore an object of the present invention to improve patient safety and
to reduce a risk of health for medical treatment making use of multiple medicaments
and respective drug delivery devices. It is a particular aim of the present invention
to provide an intuitive and unequivocal approach to instruct a user in regard of the
order of usage of at least two drug delivery devices provided in a common packaging
assembly. Respective instructive means should be easy to implement in a cost efficient
way.
Summary of the Invention
[0010] In a first aspect the invention relates to a packaging to accommodate an item, in
particular, to accommodate a medical device, such like an injection device, e.g. a
pen-type injector or a pre-filled syringe. The packaging comprises a bottom portion
as well as a first sidewall portion and a second sidewall portion. First and second
sidewall portions extend along opposite sides of the bottom portion.
[0011] Furthermore, the packaging comprises at least one front face extending between an
end of the first sidewall portion, the second sidewall portion and the bottom portion.
Typically, the outer shape and contour of the packaging is confined by the first and
second sidewall portions, the bottom portion and the at least one front face extending
there between. Moreover, first and second sidewall portions may be integrally formed
with the bottom portion.
[0012] The first and second sidewall portions may be folded or bended along folding axes
extending between and separating the bottom portion from the first and second sidewall
portions. Typically, these folding lines or folding axes extend substantially parallel
to each other to form a cubic-shaped packaging. The at least one front face comprises
a surface normal extending substantially parallel to these folding lines or folding
axes.
[0013] The packaging further comprises at least one fixing flap portion extending as an
extension of the bottom portion and extending beyond the front face of the packaging.
The at least one fixing flap portion extends outwardly, hence in a direction opposite
to the interior of the packaging. The at least one foldable fixing flap portion is
adapted to engage with an outer packaging that is in turn adapted to receive the packaging.
Mutual engagement of the packaging's fixing flap portion with the outer packaging
is typically obtainable when the packaging is disposed inside the outer packaging.
[0014] The at least one foldable fixing flap portion is adapted to positively engage with
an interior structure of the outer packaging so as to assemble and to fix the packaging
to and into the outer packaging without the necessity of adhesively attaching said
packaging to the outer packaging. By making use of the foldable fixing flap portion,
a well-defined, irreversible and non-releasable interconnection of the packaging inside
the outer packaging can be attained, in particular when the packaging is completely
inserted into the surrounding outer packaging.
[0015] In this way, the packaging is adapted and particularly suitable to provide a nested
arrangement of an inner packaging and an outer packaging. By means of the at least
one foldable flap portion, the packaging, serving as an inner packaging, can be non-reversibly
attached and fixed to the interior of the outer packaging. With an alternative solution
it is however also conceivable, that the foldable flap portion allows for a non-destructive
removal of the packaging from the outer packaging.
[0016] Typically, the at least one fixing flap portion is adapted to positively engage with
inside facing sidewall portions, in particular with an inside facing portion of a
front face of the outer packaging featuring a stepped or recessed section, by way
of which the bottom portion's foldable flap portion can be fixed or clipped to the
outer packaging in a hooking manner.
[0017] According to another embodiment, the packaging comprises a first and a second fixing
flap portion extending from opposite ends of the bottom portion and/or extending from
oppositely located front faces. Typically but not necessarily, the bottom portion,
as well as first and second sidewall portions are of rectangular geometry. By providing
first and second fixing flap portions at opposite sides of the bottom portion, the
present packaging may engage with both opposite ends or with both oppositely located
front faces with corresponding end faces of the exterior packaging.
[0018] It is generally to be mentioned here, that the front faces of the packaging denotes
an arbitrary side face of the packaging that is adapted and designed to engage with
a corresponding side face of the outer packaging.
[0019] In a typical embodiment, the foldable fixing flap portions are provided at a longitudinal
end of respective bottom and/or sidewall portions. Hence, the front face, which may
be formed or constituted by mutually overlapping flap portions of the sidewall portions
is located at a longitudinal end of the elongated and substantially rectangular packaging.
[0020] According to another embodiment the at least one fixing flap portion is integrally
formed or connected with the bottom portion. Hence, the at least one fixing flap portion
may be designed as a longitudinal extension of the bottom portion. Typically, first
and second but longitudinally oppositely located fixing flap portions are provided
and integrally formed with opposite longitudinal ends of the bottom portion.
[0021] Even though the at least one fixing flap portion extends as an extension of the bottom
portion it does not necessarily have to be integrally formed or connected with the
bottom portion. Instead and according to another embodiment, the at least one fixing
flap portion may also be integrally formed with at least one of first and second sidewall
portions or with first and/or second flap portions of first and/or second sidewall
portions.
[0022] Depending on the shape, size and geometry of the item or items to be deposited in
the packaging and/or the outer packaging various flap portions may be additionally
or alternatively provided also at a short end section of the bottom portion and/or
of the first and/or second sidewall portions.
[0023] By providing both opposite ends of the bottom portion with first and second fixing
flap portions, respectively, opposite ends of the bottom portion of the packaging
may non-releasably or non-reversibly engage with the outer packaging as soon as the
packaging is put or inserted into the outer packaging.
[0024] Typically, the longitudinal dimensions of the outer packaging are substantially identical
or match with the longitudinal extension of the present packaging so that the foldable
flap portions of the packaging's bottom portion are folded upwardly by oppositely
located front faces of the outer packaging. In particular, the longitudinal extension
of the interior of the outer packaging typically matches with the exterior longitudinal
dimensions of the packaging's bottom portion plus the thickness of the packaging's
front faces and the thickness of the bottom portion's foldable flap portions folded
upwardly to overlap with and to abut against the packaging's front face.
[0025] In an assembly configuration, the foldable fixing flap portions of the packaging
are typically sandwiched between the inside facing portion of the outer packaging's
front face and the exterior portion of the packaging's front face. In this way and
when longitudinally squeezed between oppositely located inside facing portions of
the outer packaging's front faces, the folded fixing flap portions of the packaging
are effectively hindered to fold downwardly to disengage from the outer packaging.
[0026] Typically, and according to an embodiment the first sidewall portion comprises at
least one foldable flap portion overlapping with a foldable flap portion of the second
sidewall portion or directly overlapping with the second sidewall portion. In this
way, the foldable flap portions that are typically unitary or integrally formed with
said first and/or second sidewall portions respectively, are adapted to form or to
contribute to the front face of the packaging when arranged in an at least partially
overlapping configuration.
[0027] According to another embodiment, at least one of first and second sidewall portions
comprises first and second flap portions extending from opposite ends of the respective
sidewall portion. Depending on the overall extension and geometry of respective flap
portions it may be sufficient, when only the first sidewall portion is provided with
first and second flap portions so that first and second flap portions can be arranged
in an overlapping and e.g. two times folded manner with the second sidewall portion.
In this configuration, the first and second flap portions of the first sidewall portions
may provide or constitute the front face of the packaging extending between longitudinal
end sections of first and second sidewall portions.
[0028] In an alternative embodiment, first and second sidewall portions at least comprise
one, either a first or a second flap portion, so that e.g. a first flap portion of
the first sidewall portion forms a first front face and wherein a second flap portion
of the second sidewall portion forms a diametrically oppositely located second front
face.
[0029] In a further embodiment, both, first and second sidewall portions each comprise first
and second oppositely located flap portions that mutually overlap to form or to contribute
to respective first and second, oppositely located front faces of the packaging.
[0030] In general and if not otherwise specified, overlapping portions of the packaging,
and in particular mutually overlapping flap portions are typically interconnected
and fixed to each other, e.g. by means of a glue or an adhesive. Moreover, the entire
packaging may be formed and provided by a single blank of a sheet material, such like
cardboard or a sheet of a plastic material.
[0031] In particular, inner and outer packaging may be made of cardboard or may comprise
a plastic material featuring numerous folded portions to form a packaging assembly
of box-like shape. When integrating the inner packaging into the outer packaging,
e.g. by respectively folding a cardboard or plastic blank, a rather cost- and resource
sensitive way of manufacturing can be provided.
[0032] Additionally and according to another embodiment the packaging also comprises a lid
portion extending along the second sidewall portion. Typically, the lid portion is
pivotable along a lid axis or pivot axis extending along the upper end of the second
sidewall portion. In this way, the lid portion can be pivoted in order to selectively
provide access to the interior of the packaging. Additionally and according to another
embodiment, the lid portion also comprises a lateral flap portion overlapping with
the first sidewall.
[0033] When overlapping with the first sidewall, the flap portion may either positively
and releasably engage with the first sidewall portion. Alternatively, it is also conceivable,
that the lid portion's lateral flap portion is adhesively attached to a portion of
the first sidewall. The flap portion or the first sidewall portion may further comprise
a structurally weakened portion, by way of which an interconnection of the lateral
flap portion and the first sidewall portion may be abrogated or destroyed if required,
e.g. for gaining access to the packaging's interior.
[0034] Said flap portion of the lid portion may form a lateral end section of the blank
of sheet material, of which the present packaging is made from. An opposite lateral
end of the blank may be provided by the first sidewall portion to at least partially
overlap with the lid portion's lateral flap portion.
[0035] According to another embodiment, the lid portion also comprises at least a first
longitudinal flap portion extending from a longitudinal end thereof and overlapping
with at least one of the sidewall's flap portions. In this way, also the longitudinal
flap portion of the lid portion may contribute to the formation of the longitudinal
front face of the packaging. Hence, the front face as already mentioned above may
be formed and provided by the lid portion's first longitudinal flap portion overlapping
at least partially with first and/or second flap portions of first and/or second sidewall
portions of the packaging. By providing such a threefold overlapping configuration
at the front face, a rather stable and robust front face of the packaging can be provided.
[0036] According to another embodiment, the lid portion also comprises at least a first
longitudinal extension extending from a longitudinal end of its first longitudinal
flap portion. Typically, the lid portion extends substantially perpendicular to the
adjacently located first flap portion. In a similar way also the first longitudinal
extension extends substantially perpendicular to the first longitudinal flap portion
of the packaging's lid portion. Since folding lines or pivot axes extending between
and separating flap portion, lid portion and longitudinal extension align substantially
parallel, the first longitudinal extension of the lid portion extends substantially
parallel to the lid portion and hence substantially parallel to the bottom portion.
Typically, the at least first longitudinal extension of the lid portion at least partially
abuts and overlaps with the bottom portion. Therefore, the lid portion itself may
e.g. adhesively attach to the bottom portion. In this way, overall stability of the
packaging and in particular of its front face can be further enhanced. By means of
a rather rigid and stiffened front face, the at least one packaging's foldable fixing
flap portion may experience a respective mechanical support in a direction parallel
to the surface normal of the front face. In this way, the positive engagement of e.g.
the upwardly bended foldable fixing flap portions with the interior or inside facing
front face structure of the outer packaging can be stabilized and structurally reinforced.
[0037] Moreover, and according to another embodiment the lid portion comprises first and
second longitudinal flap portions at opposite longitudinal ends thereof. In this way,
a rather symmetric configuration of the packaging can be attained. Additionally, first
and second longitudinal flap portions may both comprise first and second longitudinal
extensions allowing to fix and to attach both longitudinal end sections of the lid
portion directly to the respective longitudinal ends of the packaging's bottom portion.
[0038] Alternatively it is also conceivable that the at least first extension of the lid
portions does not extend inwardly to engage with the bottom portion but does extend
outwardly from the front face to form or to contribute to the at least one fixing
flap portion.
[0039] According to another embodiment the lid portion also comprises a foldable or removable
strip portion to provide access to the interior of the packaging. Since the lid portion
may be directly interconnected with the bottom portion, lifting of the lid portion,
e.g. by raising the lateral flap portion of the lid portion into an elevated position
with regard to the bottom portion may not be attainable. Instead, by providing a foldable
or removable strip portion in or on the lid portion, the lid portion itself may provide
a frame structure that remains attached to the sidewall portions and/or to the bottom
portion of the packaging while the foldable or removable strip portion may be folded
or torn away for establishing a through opening in the lid portion that allows to
remove the item provided in the packaging.
[0040] In a further embodiment, said strip portion may also comprise a gripping flap which
at least partially protrudes from one of the first and second sidewall portions. Having
a gripping flap integrally formed with the foldable or at least partially removable
strip portion and having the gripping flap at least partially extending from e.g.
an upper edge or upper end of first and/or second sidewall portions, the gripping
flap and hence the strip portion integrally formed therewith can be easily gripped
in order to raise or to fold the strip portion for gaining access to the packaging's
interior.
[0041] According to another aspect, the invention also relates to a packaging assembly to
accommodate at least two items. The packaging assembly comprises an inner packaging
as described above, wherein said inner packaging is adapted to accommodate a first
item, such like a drug delivery device. Additionally, the packaging assembly comprises
an outer packaging to accommodate a second item and to accommodate the inner packaging.
Typically, the second item also comprises a drug delivery device, e.g. a second drug
delivery device.
[0042] In this way, the packaging assembly features a nested arrangement of an inner and
an outer packaging. When opening the outer packaging, only the second drug delivery
device is directly accessible to be used while the first drug delivery device remains
packed and sealed by the inner packaging contained in the outer packaging. Such an
interleaved configuration of inner and outer packaging provides an intuitive approach
to indicate to a user, that the second drug delivery device should be used prior to
the first drug delivery device, which is separately packed by the inner packaging.
[0043] When opening the outer packaging there is only one, namely the second drug delivery
device of a plurality of drug delivery devices, which is ready to use. The user may
then intuitively take the second drug delivery device. Hence, a risk of interchanging
first and second drug delivery devices can be reduced, simply by wrapping the first
drug delivery device in a separate inner packaging.
[0044] In a preferred embodiment, the inner packaging is adapted to completely enclose the
first drug delivery device. Additionally, the outer packaging is adapted to accommodate
and to receive the second drug delivery device in a configuration, in which the second
drug delivery device is ready to use. Preferably, when assembled in the outer packaging,
the second drug delivery device can be free of any further packaging means.
[0045] According to a further embodiment, the inner packaging is positively engageable with
the interior of the outer packaging by means of the inner packaging's fixing flap
portions. Typically, the inner volume of the outer packaging is adapted and configured
in accordance with the outer dimensions of the inner packaging in such a way, that
the inner packaging can be completely fitted into the outer packaging in such a way,
that the fixing flap portions of the inner packaging, in particular of its bottom
portion, are folded by e.g. oppositely located front faces of the outer packaging.
[0046] Moreover, the inside facing portion of the outer packaging's front faces typically
comprise a somewhat uneven or recessed structure so as to positively engage with the
free end of the inner packaging's fixing flap portions. Typically, the fixing flap
portions are folded upwardly, towards the lid portion upon insertion of the inner
packaging into the outer packaging. Upon reaching a mutual abutment configuration
of the inner packaging's bottom portion with the outer packaging's bottom portion,
the upwardly bended fixing flap portions of, e.g. the inner packaging's bottom portion
may relax and bend outwardly and may thus engage with e.g. a lower edge of at least
one flap portion extending along the inside portion of the outer packaging's front
face. This engagement may further be accompanied and may coincide with an audible
click-like noise indicating to a user, that inner and outer packaging mutually engaged.
[0047] According to a further embodiment, the outer packaging comprises a somewhat similar
overall geometry compared to the inner packaging except that the outer packaging's
lateral dimensions are substantially larger than respective lateral dimensions of
the inner packaging since the outer packaging is adapted to receive both, the inner
packaging as well as a second item, such like a second drug delivery device.
[0048] Consequently, the outer packaging also comprises a bottom portion, a first sidewall
portion and a second sidewall portion, wherein said sidewall portions extend along
opposite sides of the bottom portion. Moreover, the outer packaging's first sidewall
portion comprises at least one foldable flap portion overlapping with a foldable flap
portion of the outer packaging's second sidewall portion. Alternatively, said foldable
flap portion of the outer packaging's first sidewall portion may also directly overlap
and engage with the second sidewall portion to form a front face of the outer packaging.
[0049] Additionally, the at least one inner packaging's foldable fixing flap portion abuts
and engages with the interior of said front face of the outer packaging and/or with
the at least one foldable flap portion of at least one outer packaging's sidewall
portion.
[0050] Typically, the at least one foldable flap portion provided at a longitudinal end
of at least one of first and second outer packaging's sidewall portions is located
at a predefined distance from a longitudinal end of the outer packaging's bottom portion.
In this way, the folded flap portions of at least one of the outer packaging's first
and second sidewall portions form an inwardly extending protrusion or protruding structure
on the inside facing portion of the outer packaging's front face. The size or the
thickness of this inward facing protrusion typically corresponds to the thickness
of the sheet material the packaging, and hence first and second sidewall portions
are made of.
[0051] Especially when first and second sidewall portions both comprise foldable flap portions
overlapping and forming the front face, the size or thickness of these inwardly facing
protrusions may be about twice the thickness of the sheet material, the outer packaging
is made of. The at least one foldable fixing flap portion of the inner packaging's
comprises such a geometry, that it snugly fits into the recessed structure formed
between the outer packaging's bottom portion and the inside facing protrusion provided
and formed by overlapping flap portions of first and/or second sidewall portions of
the outer packaging.
[0052] Typically, the inner packaging comprises two fixing flap portions located on opposite
ends of the inner packaging's bottom portion. In this way, the inner packaging can
be inserted into the outer packaging by folding both fixing flap portions upwardly
to engage with respective recessed portions of the inside wall structure of the outer
packaging.
[0053] Here, it is of particular benefit when the fixing flap portions feature a pre-defined
flexibility or flexural strength. Hence, an upwardly directed folding or bending of
the fixing flaps may occur against a restoring force. As soon as the fixing flap coincide
with a recessed wall structure of the outer packaging the fixing flap may relax into
said recesses and may non-releasably engage with the outer packaging's recessed structure.
[0054] According to a further embodiment, a first drug delivery device is arranged in the
inner packaging while a second drug delivery device is arranged in the outer packaging.
In order to prevent a damage of first and/or second drug delivery devices, at least
one or even both drug delivery devices may be detachably fixed in the inner packaging
and in the outer packaging, respectively. Here, the inner packaging as well as the
outer packaging may comprise and feature respective fixing members, such like clamps,
clips or fixing straps.
[0055] According to a further embodiment, at least one of the first and second drug delivery
devices comprises an injection device containing an injectable medicament. The drug
delivery devices may comprise a pre-filled syringe or may further comprise a pen-type
injector, e.g. a disposable pen-type injector intended to be discarded after a single
use or after repeated usage.
[0056] Typically, at least one of the first and second drug delivery devices is at least
partially filled with a medicament to be dispensed by the respective drug delivery
device. In particular, the drug delivery device may comprise a prefilled syringe having
a medicament or a respective pharmaceutical active substance provided therein. In
an alternative embodiment the drug delivery device may also comprise an inhaler, e.g.
pre-filled with a medicament.
[0057] Alternatively, it is even conceivable, that one of first and second drug delivery
devices is designed and comprises a reusable pen-type injector, wherein a cartridge
filled with a medicament is removably and interchangeably arranged in a respective
device.
[0058] According to another embodiment, an inside-facing wall portion of the outer packaging
is provided with a label. The label may comprise and provide operation instructions
of the first and/or the second drug delivery device as well as instructions regarding
the sequential use of first and second drug delivery devices. Additionally, the label
may be indicative about the order, in which the first and second drug delivery devices
are to be used. Moreover, the label may be indicative of an opening procedure for
opening the inner packaging.
[0059] In still another embodiment, also an outside-facing wall portion of the inner packaging
may be provided with a label. This label attached to the inner packaging may be indicative
to the user, that it is the second drug delivery device which is to be used prior
to opening the inner packaging and hence prior to make use of the first drug delivery
device located therein.
[0060] Additionally, inner and outer packagings may also be provided with visually perceptible
indicators by way of which the order of use of first and second drug delivery devices
can be intuitively communicated to a user. Hence, the second drug delivery device
and the inner packaging may distinguish by their colour and/or by surface finish.
Moreover, the outer circumference of the second drug delivery device may comprise
a roughness distinguishing from the roughness of the inner packaging.
[0061] In this way, the inner packaging and the second drug delivery device may also be
distinguishable in a tactile way. Consequently, even persons suffering impaired vision
may unequivocally distinguish the inner packaging and the second drug delivery device.
[0062] According to another embodiment, the first drug delivery device is actually arranged
in the inner packaging and the second drug delivery device is actually arranged in
the outer packaging. Even though the packaging assembly is just designed to receive
first and second drug delivery devices in inner and outer packagings, respectively,
the packaging assembly may be readily equipped with respective drug delivery devices
when commercially distributed to medical staff or patients.
[0063] The term "drug" or "medicament", as used herein, means a pharmaceutical formulation
containing at least one pharmaceutically active compound,
[0064] 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,
[0065] 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,
[0066] 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,
[0067] 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.
[0068] 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.
[0069] 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-(ω-carboxyheptadecanoyl)-des(B30)
human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.
[0070] Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.
[0071] 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(02)25, Asp28] Exendin-4(1-39),
des Pro36 [Trp(02)25, IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(02)25, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(02)25, IsoAsp28] Exendin-4(1-39); or
des Pro36 [Asp28] Exendin-4(1-39),
des Pro36 [IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),
des Pro36 [Trp(02)25, Asp28] Exendin-4(1-39),
des Pro36 [Trp(02)25, IsoAsp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(02)25, Asp28] Exendin-4(1-39),
des Pro36 [Met(O)14 Trp(02)25, IsoAsp28] Exendin-4(1-39),
wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative;
or an Exendin-4 derivative of the sequence
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(02)25, Asp28] Exendin-4(1-39)-Lys6-NH2,
H-des Asp28 Pro36, Pro37, Pro38 [Trp(02)25] Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,
des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,
H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-Lys6-des Pro36 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)-Lys6-NH2,
H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25] Exendin-4(1-39)-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)-NH2,
des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2,
H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2;
or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned
Exendin-4 derivative.
[0072] 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.
[0073] 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.
[0074] Antibodies are globular plasma proteins (∼150kDa) 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.
[0075] 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 β sheets create a "sandwich" shape, held together by interactions
between conserved cysteines and other charged amino acids.
[0076] There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ, and µ. The
type of heavy chain present defines the isotype of antibody; these chains are found
in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.
[0077] Distinct heavy chains differ in size and composition; α and γ contain approximately
450 amino acids and δ approximately 500 amino acids, while µ and ε have approximately
550 amino acids. Each heavy chain has two regions, the constant region (C
H) and the variable region (V
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
γ, α and δ have a constant region composed of three tandem Ig domains, and a hinge
region for added flexibility; heavy chains µ and ε 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.
[0078] In mammals, there are two types of immunoglobulin light chain denoted by λ and κ.
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, κ or λ, is present per antibody in mammals.
[0079] 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.
[0080] 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).
[0081] 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.
[0082] Pharmaceutically acceptable solvates are for example hydrates.
[0083] It will be further apparent to those skilled in the pertinent art that various modifications
and variations can be made to the present invention without departing from the spirit
and scope of the invention. Further, it is to be noted, that any reference signs used
in the appended claims are not to be construed as limiting the scope of the present
invention.
Brief description of the drawings
[0084] In the following, an embodiment of the present invention is described by making reference
to the drawings, in which:
- Fig. 1
- shows a top view of a preconfigured blank of sheet material to be folded to form an
inner packaging featuring a bottom portion with two oppositely located foldable fixing
flap portions,
- Fig. 2
- is a schematic and perspective illustration during insertion of the inner packaging
into an outer packaging, and
- Fig. 3
- shows an enlarged view of the inner packaging positively engaged and non-removably
arranged inside the inner packaging.
Detailed description
[0085] In Fig. 1, a top view of a blank 11 of a sheet material to form an inner packaging
10 is illustrated. The blank 11 and hence the packaging 10 comprises a bottom portion
12 of rather rectangular shape which is laterally sandwiched between a first sidewall
portion 14 and a second sidewall portion 16. First and second sidewall portions 14,
16 are foldable along the indicated fold lines separating respective sidewall portions
14, 16 from the bottom portion 12.
[0086] Adjacent to the second sidewall portion 16, there is provided a lid portion 18 featuring
an overall size and geometry that substantially matches the size and geometry of the
bottom portion 12. As further indicated in Fig. 1, also first and second sidewall
portions 14, 16 comprise substantially identical shape and size, so that a rather
rectangular shaped or cubic shaped inner packaging 10 can be provided. The lid portion
18 is further integrally formed with a lateral flap portion 15 forming a lateral end
of the blank 11.
[0087] When folding first sidewall portion 14, the bottom portion 12, the second sidewall
portion 16, the lid portion 18 and the lateral flap portion 15 along the indicated
folding lines separating the adjacently located portions 14, 12, 16, 18, 15, the lateral
flap portion 15 may at least partially overlap with the first sidewall portion 14.
In the present embodiment, said lateral flap portion 15 may be adhesively or releasably
attached to the first sidewall portion 14.
[0088] As further indicated in Fig. 1, the two sidewall portions 14, 16 each comprise first
and second foldable flap portions 14a, 14b, 16a, 16b at their longitudinal ends. Said
flap portions 14a, 14b, 16a, 16b extend beyond the lateral end sections of respective
sidewall portions 14, 16. As indicated in Fig. 1, the foldable flap portions 14a,
14b, 16a, 16b are integrally formed with respective first and second sidewall portions
14, 16.
[0089] Additionally, also the lid portion 18 comprises first and second foldable flap portions
18a, 18b. Moreover, said longitudinal flap portions 18a, 18b may further extend into
longitudinal extensions 18c, 18b. While the longitudinal flap portions 18a, 18b of
the flap portion may substantially form a front face 17 of the packaging, the respective
first and second longitudinal extensions 18c, 18b may substantially overlap with an
end section of the bottom portion 12. In this way, the lid portion may be directly
engaged and fixed to the bottom portion 12.
[0090] Additionally, the oppositely located foldable flap portions 16a, 16b of the second
sidewall portion 16 as well as oppositely located and longitudinally separated foldable
flap portions 14a, 14b of the first sidewall portion may either at least partially
and mutually overlap or may additionally overlap with the longitudinal flap portions
18a, 18b of the lid portion 18.
[0091] By means of the various longitudinal and foldable flap portions 14a, 14b, 16a, 16b,
18a, 18b of first and second sidewall portions, 14, 16 and of the lid portion 18,
a rectangular-shaped three-dimensional packaging 10 can be formed, especially by mutually
interconnecting overlapping flap portions 14a, 16a, 18a, 14b, 16b, 18b, e.g. by making
use of an adhesive.
[0092] Since the lid portion 18 provides and substantially constitutes the longitudinally
located front faces 17 by means of its downwardly foldable flap portions 18a, 18b,
the lid portion 18 is substantially hindered from folding into a lifted or elevated
configuration to provide access to the interior of the packaging 10. However, in order
to gain access to the packaging's interior, the lid portion 18 is further equipped
with a strip or strap portion 19 featuring a gripping flap 19a extending at least
partially from the second sidewall portion 16.
[0093] Additionally and as indicated by the dashed lines 19b, 19c, the strip portion 19
may be at least partially torn away or torn off from the lid portion 18. Here, dashed
lines 19b, 19c may represent predetermined breaking structures or respective lines
of weakening providing a well-defined and pre-determined breaking and separating of
the strip portion 19 from the lid portion 18.
[0094] Furthermore and as becomes apparent from Fig. 2, the inner packaging 10 comprises
longitudinally extending foldable fixing flap portions 12a, 12b extending from opposite
longitudinal ends of the bottom portion 12 and extending beyond and outwardly from
a lower edge of the front face 17. Hence, the fixing flap portions 12, 12b protrude
from the front face 17 of the inner packaging 10.
[0095] In the illustrated embodiment the fixing flap portions 12a, 12b are integrally formed
as longitudinal extensions of the inner packaging's bottom portion 12. In other embodiments
the fixing flap portions may be connected and may be integrally formed with the flap
portions 14a, 14b, 16a, 16b, 18a, 18b of the first sidewall portion 14, the second
sidewall portion 16 and/or of the lid portion 18.
[0096] A secondary or outer packaging 20 as illustrated in Fig. 2 comprises a rather conventional
structure. The packaging 20 features a bottom portion 22 having foldable flap portions
22a, 22b that are adapted to form and to provide oppositely located longitudinal front
faces 27 of the outer packaging 20. Attached to the inside of said flap portions 22a,
22b there are attached inwardly folded first and second flap portions of sidewall
portions 24, 26. In Fig. 2, only the first foldable flap portion 24a of the first
sidewall and the first foldable flap portion 26a of the second sidewall portion 26
are illustrated.
[0097] As further illustrated in Fig. 2, said first flap portions 24a, 26a are adhesively
attached to the interior of the upwardly folded flap portion 22a of the bottom portion
22. Additionally, the bottom portion is further provided with oppositely located longitudinal
extensions 22c, 22d that extend upwardly or inwardly from an upper end section of
the bottom portion's 22 foldable flap portions 22a, 22b. Similar as already described
in view of Fig. 1, the outer packaging's 20 second sidewall portion 26 is further
connected with a foldable lid portion 28 featuring a lateral flap portion 25 that
is adapted to releasably or non-reversibly engage with the first sidewall portion
24.
[0098] As in particular indicated in the enlarged view according to Fig. 3, the first flap
portions 24a, 26a of respective first and second sidewall portions 24, 26 of the outer
package 20 form a recessed structure at a lower edge thereof towards the longitudinal
end of the outer packaging's 20 bottom portion 22. The depth of the recessed structure,
which may feature a wedged shape, is governed by the thickness of the sheet material,
of which the sidewalls 24, 26 and their foldable flap portions 24a, 26a are made.
[0099] The recessed structure 30 provided between a lower edge of the first flap portions
24a, 26a of first and second sidewall portions 24, 26 corresponds to the size and
shape of the bottom portion's 12 foldable and longitudinally extending fixing flap
portions 12a, 12b of the inner packaging 10. As indicated in Fig. 3, the upwardly
folded fixing flap portions 12a, 12b of the inner packaging 10 engage with a lower
edge of the first foldable flap portion 26a of the second sidewall 26 of the outer
packaging 20.
[0100] On the opposite longitudinal end, a corresponding snap-in mechanism is typically
provided, so that the inner packaging 10 can be inserted into the outer packaging
20 to attain a positively engaged mutual attachment of the interleaved and nested
packagings 10, 20. The upwardly bended foldable fixing flap portions 12a, 12b of the
inner packaging's 10 bottom portion 12 engage with the recessed structure 30 in a
hooking manner and effectively prevent an uncontrolled release of the inner packaging
10 from the outer packaging 20.
[0101] Since longitudinal dimensions of inner packaging 10 and outer packaging 20 mutually
match and correspond to each other in such a way, that the inner packaging is snugly
fitted inside the outer packaging 20, an uncontrolled or self-acting release of the
inner packaging 10 from the outer packaging 20 can be effectively prevented. In effect,
the first packaging 10 can be fixedly attached inside the outer packaging without
the use of any adhesives. Moreover, once the inner packaging 10 is connected with
the outer packaging 20, a destructionless release and removal of the inner packaging
10 from the outer packaging 20 can be effectively prevented and may therefore be excluded.
List of Reference Numerals
10 |
packaging |
11 |
blank |
12 |
bottom portion |
12a, 12b |
fixing flap portion |
14 |
sidewall portion |
14a, 14b |
flap portion |
15 |
flap portion |
16 |
sidewall portion |
16a, 16b |
flap portion |
17 |
front face |
18 |
lid portion |
18a, 18b |
flap portion |
18c, 18d |
extension |
19 |
strip portion |
19a |
gripping flap |
19b, 19c |
breaking structure |
20 |
packaging |
22 |
bottom portion |
22a, 22b |
flap portion |
22c, 22d |
extension |
24 |
sidewall portion |
24a |
flap portion |
25 |
flap portion |
26 |
sidewall portion |
26a |
flap portion |
27 |
front face |
28 |
lid portion |
30 |
recessed structure |