WO2012013587A1

WO2012013587A1 - Multiple needle assembly for an injection device

Info

Publication number: WO2012013587A1
Application number: PCT/EP2011/062606
Authority: WO
Inventors: Christopher James Smith; Alastair Robert Clarke
Original assignee: Sanofi-Aventis Deutschland Gmbh
Priority date: 2010-07-26
Filing date: 2011-07-22
Publication date: 2012-02-02

Abstract

A needle assembly (1) for an injection device containing at least one reservoir of medicament, where the assembly has a hub (3) with at least two separate needle cannulae (2, 10, 11, 12), each having sharpened distal and proximal ends mounted thereon and where the hub has a non-threaded connector (7) for engagement with the injection device.

Description

MULTIPLE NEEDLE ASSEMBLY FOR AN INJECTION DEVICE

Field of the Present Patent Application

The present disclosure relates to needle assemblies for injection devices, more particularly to needle assemblies that have two or more needle cannulae separately mounted in a hub that attaches to an injection device. This disclosure also relates to an injection device.

Background

The art has recognized a need to inject two or more medications or medicaments simultaneously and has disclosed injection devices that hold two cartridges of medication. For example, it is medically desirable in the treatment of certain conditions of the human body to administer several types and dosage amounts of medication simultaneously. The treatment of diabetes is one such example. Different types of insulin act in different fashions. A fast acting insulin works quickly but for a short period of time after administration, whereas a longer acting insulin takes effect more slowly, but for a longer period of time. Attempts to simultaneously inject both regular, fast acting insulin and long lasting insulin when needed have met with limited success, especially when the medication is forced to flow from the two cartridges through a manifold and out a single cannula in fluid communication with the manifold. Blockage of the manifold and high injection force are two of the problems encountered by such previously proposed devices. Accordingly, there exists a need to provide users of such injection devices with an easy to use device that allows for the simultaneous injection of two or more medicaments or that provide a low injection force. It is an object of the present disclosure to facilitate provision of a novel, preferably an improved, injection device.

This object is achieved by the subject matter defined in the independent claim. Further advantageous embodiments and refinements are subject matter of dependent claims.

This disclosure may provide an improved needle assembly, and preferably an improved injection device, where two or more needle cannulae are mounted separately in a hub that is attached to or is configured to be attached to the injection device. These and other advantages will become evident from the following more detailed description of the disclosure.

SUMMARY

One aspect of this disclosure relates to a needle assembly for an injection device. The needle assembly comprises a hub. The hub may have a central axis. The hub may have a non-threaded connector, which may be configured to attach to an injection device, particularly to a distal end of the injection device. The needle assembly further comprises at least two cannulae. Each cannula has a distal end and a proximal end. Each cannula is mounted separately in the hub. The distal end and/or the proximal end of each cannula may be beveled and/or sharp.

According to an exemplary arrangement of the disclosure there is provided a needle assembly configured for attaching to an injection device, preferably without using a threaded connection. The needle assembly has a hub portion with a central axis and a non-threaded connector, such as snap lock, which may be configured such that the hub can be pushed (as opposed to rotated) onto the distal end of an injection device. The hub contains at least two needle cannulae, each having distal and proximal ends and mounted separately in the hub off center of the central axis. The distal and/or proximal ends of each cannula may be beveled and/or sharp, particularly sharpened. The needle assembly is preferably designed for a single use and easily disposable.

In a further embodiment the proximal ends of each cannula do not extend beyond the needle assembly or the hub portion.

In one embodiment the bevels on the distal ends of the cannulae are facing outwards from the central axis of the hub. In another embodiment the bevels on the distal ends of the cannulae are facing towards the central axis of the hub.

In another embodiment the bevels on the distal ends of the cannulae are facing in the same direction. Particularly, in this arrangement, the surface normals of two bevels, when viewed in projection from the distal side or in top view onto the distal ends of the cannulae, may be oriented collinearly. For example, the bevel on the distal end of a first cannula may face a second cannula with the bevel on the distal end of the second cannula facing away from the bevel of the first cannula. In another embodiment the bevels on the distal ends of two cannulae are facing each other.

In another embodiment the bevels on the distal ends of the cannulae are facing in different, preferably opposite, directions. Particularly, the bevel on the distal end of one of the at least two cannulae may face away from the bevel on the distal end of another one of the at least two cannulae.

The different orientations of the bevels on the distal ends with respect to the central axis or with respect to each other as described above provide the possibility to adjust the needle assembly to suit different requirements. Such requirements may include the way how the medicament spreads within the tissue, how much medicament may reach a predefined region within the tissue, preventing mixing of two medicaments within the tissue, particularly near the injection site, etc. For example, it may be desirable that medicament or an excess amount thereof is prevented from reaching a certain region in the tissue as seen from a given injection site of one cannula. To prevent medicament from reaching this region, the bevel of the cannula may be arranged to face away from this region. If, to the contrary, it is desired to direct medicament to this region, the bevel is expediently arranged to face this region. Accordingly the respective medicament can be directed to desired regions within the tissue or the spreading of medicament may be made more uniform by adjusting the orientation of the bevels with respect to each other or with respect to the central axis. By adjusting the orientation of bevels of two or more cannulae with respect to each other, mixing of medicaments originating from different cannulae may be promoted or prevented, depending on how the bevels are oriented with respect to each other. If two bevels face each other, mixing may be promoted. If two bevels face away from each other, mixing may be prevented. If two bevels face in the same direction the spreading of medicament in a direction opposite to the one defined by the bevels may be prevented.

In another embodiment of the disclosure each needle cannula is of a different gauge and/or length compared to the other cannula. The exact size and geometry of each cannula may be selected to suit the properties and delivery requirements of the medicament within the cartridge or reservoir associated with that particular cannula. In some circumstances it will be preferable to position the cannula in the hub such that the bevels on the distal ends of the cannula are opposed to each other with each facing outwards from the central axis of the hub. In this manner, a simultaneous injection of two different medicaments will be injected into different points in the body and kept separate to prevent mixing. The outward orientation of the bevels will tend to cause the one medicament to flow away from the other medicament exiting the other needle cannula.

In those cases where the needle assembly has two cannulae separately mounted thereon with the proximal ends separated by a distance D, the distal ends of the cannula can be separated by a distance equal to, less than or greater than D. The distance selected may depend on the corresponding injection device and may require the necessity to only permit the needle assembly to be attached to the injection device in one particular orientation, for example, so that each cartridge is pierced by the correct geometry needle. Such a special orientation also ensures that if the needle attachment is removed and reattached for any reason then any residual medicament on the septum piercing ends of the needles does not contaminate another cartridge.

Injection of a double needle may be a cause of anxiety or inconvenience to a user. For example, a user will normally inject sub-cutaneous injections into a fold of skin. This may be more difficult with a double needle, particularly if the distance between the needles or needle cannulae is large as the skin fold will need to be larger to

accommodate both needles or needle cannulae or the user will need to take more care to orient the double needle or the two cannulae in line with the fold of skin. Therefore, there may be a user advantage if the two or more needles or needle cannulae are brought closer together. In this case it is desirable that the distance of the distal ends of the cannula is much less than D, the distance between the proximal ends of the cannulae. The distance between the distal ends may be less than 0.5 D, preferably 0.3 D or less, particularly preferably 0.2 D or less, such as 0.1 D or less.

In another embodiment at least one cannula, preferably more than one cannula, is non- linear with respect to the central axis such that the proximal end is offset from the distal end.

The two or more needle cannulae mounted in the hub are not necessarily straight and parallel, however, it is preferred that the injected portion or distal portion of the cannula (the sharp or sharpened distal end) and the septum piercing portion or proximal portion (the sharp or sharpened proximal end) of the needle or needle cannula should be straight. The injected portions or distal portions of each needle should be parallel to each other and, preferably, perpendicular to the injection site. The septum piercing portions or proximal portions of each needle or needle cannula should be parallel to each other and, preferably, parallel to the proximal portions. This may permit axial attachment of the multiple needle assembly. Alternatively or additionally, the septum piercing portions or proximal portions may be perpendicular to the cartridge or reservoir septum. The portion of the needle or needle cannula in between the injected portion or distal portion and the septum piercing portion or proximal portion may be bent, curved or angled. Such a configuration will allow for varying the distances between the cannulae. One, two or more straight portions of the respective cannula are preferably collinear. One, two or more straight portions of the respective cannula may be oriented axially, e.g. along the central axis of the hub.

In another embodiment the distal ends of the cannulae are covered by a needle shield. An aspect of this disclosure relates to an injection device or an injection assembly comprising medicament. The device or assembly further comprises a needle assembly, preferably a needle assembly as described above. The at least two cannulae of the needle assembly are in fluid communication with medicament. The medicament may be arranged within a medicament housing. The medicament housing may have a non- threaded connector. The non-threaded connector of the needle assembly may cooperate with the non-threaded connector of the medicament housing to connect the needle assembly to the housing.

In another embodiment the proximal ends of each cannula do not extend beyond the needle assembly or the hub portion. Alternatively, the proximal ends of each cannula are covered by the hub portion of the needle assembly. This feature improves safe handling of the needle assembly and protects from needle stick injury when attaching the needle assembly to an injection device.

In an embodiment the needle assembly and the injection device are adapted such that the needle assembly may be attached to the injection device only in a single orientation with respect to the injection device. Bringing a wrong cannula in fluid communication with a medicament may be prevented in this way.

In an embodiment, one of the at least two cannulae is in fluid communication with medicament of a first reservoir or cartridge of medicament and another one of the at least two cannulae is in fluid communication with medicament of a second reservoir or cartridge of medicament. In another embodiment two cannulae are in fluid communication with medicament of a single reservoir or cartridge of medicament. This disclosure particularly also covers an injection device having a needle assembly, preferably the needle assembly as described above. The needle assembly may be removably or permanently attached to a medicament housing. The medicament housing may contain or comprise one or more cartridges or reservoirs of medicament, with each preferably having a pierceable membrane or septum in fluid communication with a medicament. The injection device may also have a dose setting module attached to the medicament housing. The dose setting module may contain known dose setting and injection mechanisms that may interact with the reservoirs or cartridges of medicament to cause the medicament to flow through the needle cannula during injection. The proximal ends of the needle cannulae are preferably sufficiently sharp to allow penetration of the membrane or septum so that the needle cannula is in fluid

communication with the medicament.

In a prefered embodiment the needle assembly may be removably or permanently attached to a medicament housing and the needle assembly comprises two needle cannulae. The medicament housing may contain or comprise two cartridges or reservoirs of medicament, with each preferably having a pierceable membrane or septum in fluid communication with a medicament. The injection device may also have a dose setting module attached to the medicament housing. The dose setting module may contain known dose setting and injection mechanisms that may interact with the reservoirs or cartridges of medicament to cause the medicament to flow through the needle cannulae during injection. The proximal ends of the needle cannulae may be configured to pierce a septum or seal or membrane. The proximal ends of the needle cannulae are preferably sufficiently sharp to allow penetration of the membrane or septum so that each needle cannula is in fluid communication with the medicament. The first needle cannula can pierce the septum of the first reservoir and will establish fluid communication to a first medicament and the second needle cannula can pierce a septum of the second reservoir and will establish fluid communication to a second medicament in use.

In a further embodiment of this disclosure the multiple needle assembly is specifically configured for attachment to an injection device having a single reservoir or cartridge of medicament. This configuration provides two main advantages, reduced injection pain and reduced injection force (or conversely reduced injection time for a given force). In this embodiment two or more needles are arranged within the needle assembly in such a manner as to permit all of the needles to pierce a single septum. However, the needles are not connected and are arranged, possibly using curved or angled needles as described above and illustrated in the accompanying figures.

In the following text, a set of particularly advantageous aspects is specified. Within the set, numbers are used to identify specific aspects. This facilitates making references to the features of specific aspects in other aspects.

1 . A needle assembly for an injection device comprising,

a. a hub having a central axis and a non-threaded connector configured to attach to a distal end of an injection device; and

b. at least two cannulae, each having a distal and a proximal end and

mounted separately in the hub, where the distal and proximal ends of each cannula are beveled and sharp.

2. The needle assembly of aspect 1 where one of the at least two cannula has a different gauge than the other cannula.

3. The needle assembly of aspect 1 where the bevels on the distal ends of the cannula are facing outwards from the central axis of the hub.

4. The needle assembly of aspect 1 where the bevels on the distal ends of the cannula are facing towards the central axis of the hub. 5. The needle assembly of aspect 1 where the bevels on the distal ends of the cannula are facing in the same direction.

6. The needle assembly of aspect 1 where the bevels on the distal ends of the cannula are facing in opposite directions.

7. The needle assembly of aspect 1 having two cannula where the proximal ends are separated by a distance D and the distance separating the distal ends is less than D.

8. The needle assembly of aspect 1 having two cannula where the proximal ends are separated by a distance D and the distance separating the distal ends is greater than D. 9. The needle assembly of aspect 1 where at least one cannula is non-linear with respect to the central axis such that the proximal end is offset from the distal end.

10. The needle assembly of aspect 1 where the distal ends of the cannulae are covered by a needle shield.

1 1 . An injection device comprising the following in combination,

a. a dose dialing module;

b. a medicament housing connected to the dose dialing module having a connector for attaching a needle assembly;

c. a first and a second reservoir of medicament located inside the housing, each having a septum in fluid communication with the medicament in the respective reservoir; and

d. a needle assembly non-threadedly attached to the connector having a hub with a central axis and having mounted therein at least two needle cannulae having distal and proximal ends, where the cannulae are separately mounted in the hub off center of the central axis and where the proximal end of one cannula is penetrating the septum of the first reservoir and the other cannula is penetrating the septum of the second reservoir, such that both cannula are in fluid communication with medicament.

12. An injection device comprising the following in combination,

a. a dose dialing module;

c. a reservoir of medicament located inside the housing;

d. a septum in fluid communication with the medicament; and

e. a needle assembly non-threadedly attached to the connector having a hub with a central axis containing at least two needle cannulae having distal and proximal ends, where the cannulae are separately mounted in the hub off center from the central axis and where the proximal ends of each cannulae are penetrating the septum and are in fluid communication with the medicament.

Features which are described herein above and below in connection with different aspects or embodiments may, of course, be combined with features described in connection with other aspects and embodiments.

These as well as other advantages of various aspects of the present disclosure will become apparent to those of ordinary skill in the art by reading the following detailed description, with appropriate reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments are described herein with reference to the drawings, in which:

Figure 1 illustrates an arrangement of the needle assembly in accordance with the one aspect of the present disclosure; Figure 2 illustrates another arrangement of the needle assembly of the disclosure;

Figure 3 illustrates yet another arrangement of the needle assembly of the disclosure; Figure 4 illustrates another arrangement of the needle assembly of the disclosure;

Figure 5 illustrates the combination of the needle assembly with an injection device having two cartridges of medicament; Figure 6 illustrates another combination of the needle assembly with an injection device having one cartridge of medicament; and

Figure 7 illustrates another arrangement of the needle assembly of the disclosure.

DETAILED DESCRIPTION

Referring to Figures 1 - 4 and 7, there is shown a needle assembly 1 having two cannulae 2 mounted in a hub 3. Although the Figures only show two cannulae, this disclosure includes two or more cannulas. Each hub 3 illustrated has a central axis defined by the dashed line 4. Each cannula has sharp or sharpened and beveled distal and/or proximal ends, designated by items 5 and 6, respectively. More specifically, the distal end of the needle assembly is designated by location 8 and the proximal end designated by location 9. Figs. 1 , 2, 4 and 7 illustrate the configuration where the beveled portions of the distal ends of the needle cannulae are opposed and facing outwards. This configuration will help ensure that injected medicaments will not mix at the injection site.

The hub may have one or more non-threaded connectors 7 that allow it to be axially attached to injection device 20. This connector can be any design known to the art, preferably one that is releasable by a user, for example, ramps and detents, snap locks, snap fits or other connector that has a male or female part that connects to the corresponding female or male part on the medicament housing 21 (Fig. 5). In some instances, for example a single dose pre-filled device, the hub is permanently attached to the medicament housing and once the injection is completed the entire device is disposed.

Fig. 2 illustrates a specific embodiment where the needle cannula 10 is a different gauge than cannula 1 1 . Figs. 3 and 4 illustrate situations were the proximal ends of the needle cannulae are spaced a distance D from each other and off center from the central axis 4, and the distal ends of the needle cannula are separated by >D and <D, respectively. Fig. 3 also illustrates the situation where the beveled edges of the distal ends of the needle cannulae are facing inwards.

However, the beveled edges of the distal ends of the needle cannulae may face in any direction. In particular the beveled edges of the distal ends of the needle cannulae may face in the same direction, the beveled edges of the distal ends of the needle cannulae may face each other, or the beveled edges of the distal ends of the needle cannulae may face in opposite directions. Fig. 4 illustrates one possible situation where the beveled edges of the distal ends of the needle cannulae face outwards, i.e., the beveled edges of the distal ends of the needle cannulae are facing outwards from the central axis 4 of the hub 3.

Figs. 5 and 6 show the needle assembly 1 attached to a drug delivery device having a medicament housing 21 , a dose dialing module 20, and dose adjustment knobs 22. Fig. 5 illustrates an injection device having two medicament containers, e.g., two cartridges of medicament, and Fig. 6 shows a device having a single medicament container, e.g., a single cartridge of medicament. Fig. 7 shows a needle assembly that may be used with the device illustrated in Fig. 6 where D is much smaller than the distance between the distal ends of the needle cannula. There are at least two main advantages of this embodiment, reduced injection pain and reduced injection force (or conversely reduced injection time for a given force). In this embodiment two or more needles are arranged within the needle attachment in such a manner as to permit all of the needles to pierce a single septum. However, the needles are not connected and are arranged, possibly using curved or angled needles or needle cannulae 12 as illustrated in Figs. 3 and 7.

Part of the pain associated with an injection is caused by the insertion of the needle into the skin. However, the insertion of needle gauges typically used in conjunction with injection devices, 27-31 G and smaller, actually cause only a small amount of pain and/or sensation. A further cause of injection pain is caused by the injected volume of medicament itself. For example, in a sub-cutaneous injection the injected medicament must create a space for itself in the sub-cutaneous tissue. This can be uncomfortable for users, particularly if the user is injecting larger volumes of medicament, say 0.4 ml and above. One solution to this problem that is employed by users is to split the injection into two smaller injections and deliver them into different sites. This, however, requires the user to pierce the skin twice and repeat a number of the injection steps. This disclosure where multiple needles are used in a single hub with a single reservoir of medicament may reduce the pain of the injection compared to a single needle, single injection, by splitting the injected volume into two or more smaller volume portions and delivering them to different sites simultaneously. This reduces the maximum volume of space that must be created in the tissue and also gives the medicament a larger surface area to volume ratio, which should promote dispersion of the fluid within the tissue during the injection. Thus, reducing the total volume of space that must be created in the tissue. Inserting a double needle clearly offers potential to be more painful than inserting a single needle, however, the preferred injection sites on the body do not have a high density of pain receptors. Therefore, it might be that the patient is unable to discern, at least from a pain perspective, whether the skin is being pierced by a single needle or by multiple needles. Inserting a double needle having beveled edges of the distal ends of the needle cannulae facing in opposite directions may help separating the two spaces in the tissue, where the medicament is administered.

Patient perception can also be a significant contributor to injection discomfort. The visual appearance of multi needle hubs, as illustrated in Figs. 1 , 2, 3, 4 & 7, may be more intimidating to a user compared to a single needle. In a further embodiment, the distal portion of the cannula, i.e., the portion of the cannula extending beyond the distal end of the hub, is covered by a needle shield that prevents the user from seeing the needles (not shown). Preferably, the shield would be in the shielding or covering position both before and after the injection. During the injection the needle shield would be retracted automatically by placing the needle shield against the patient's skin and pressing the injection device towards the body. After use, if the needle shield is locked in the needle covering position then the needle shield will also improve the safety of the multi needle hub by preventing accidental needle-stick injury.

The device of Fig. 5 is applicable where two or more medicaments are not suitable for co-formulation into one cartridge and where the mixing of the medicaments upon injection is undesirable for example due to chemical or physical instability, altered clinical or pharmacokinetic characteristics. Additionally, the needle assembly of this disclosure may be used for any multiple cartridge device, even where mixing is acceptable, because the double needle is less complicated to manufacture than previously known "Y-shaped" or "2 into 1 " needle designs and also offers potential for reduced injection force (by increasing the total needle cross-sectional area through which the fluid must pass) and reduced pain (by splitting the injection into two smaller portions and delivering them to different injection sites). This increased force to drive fluid through a "2 into 1 " needle is caused by a relatively tortuous fluid pathway which increases the resistance to fluid flow. It is also limited by the fact that both fluids are delivered through one single injection needle. Therefore, there is a much higher flow rate down the single injection needle than there would be when delivering the same overall fluid flow rate down the multiple injection needles of this disclosure. The distance between the distal ends of the cannulae may be 0.75 D or less or 0.5 D or less, preferably 0.3 D or less, particularly preferably 0.2 D or less, where D is the distance between the proximal ends of the cannulae. These distances facilitate piercing of a single skin fold. Alternatively, the distance between the distal ends may be 1 .2 D or more, preferably 1 .3 D or more, particularly preferably 1 .5 D or more or 1 .75 D or more. These distances facilitate keeping two medicaments separated. The needle assembly of Fig. 7 might also be used with any single cartridge injection device or applied to traditional injection syringes. The design is particularly applicable where the injected volume is high. In the needle assembly of Fig. 7, the distance between the proximal ends is much smaller than the distance between the distal ends. Preferably the distance between the proximal ends is less than one-halve, e.g. 0.3 times or less, particularly preferably 0.2 times or less, the distance between the distal ends. These distances facilitate piercing of a membrane or septum of a single cartridge by the cannulae. The drug delivery device of this disclosure may be a reusable or alternatively disposable. By disposable device it is meant an injection device that is obtained from the

manufacturer preloaded with medicament and cannot be reloaded with new

medicament after the initial medicament is exhausted. The device may be a fixed dose or a settable dose, but in either case it is a multi-dose device.

The terms "medicament", "medication" and "drug"", as used herein, preferably mean a pharmaceutical formulation containing at least one pharmaceutically active compound, wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a proteine, a polysaccharide, a vaccine, a

DNA, a RNA, an enzyme, an antibody, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound, wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever,

atherosclerosis and/or rheumatoid arthritis, wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prophylaxis of diabetes mellitus or

complications associated with diabetes mellitus such as diabetic retinopathy, wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1 ) or an analogue or derivative thereof, or exendin-3 or exendin-4 or an analogue or derivative of exendin-3 or exendin-4. Insulin analogues are for example Gly(A21 ), Arg(B31 ), Arg(B32) human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin;

Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) human insulin; B29-N- palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl- LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N- palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; Β29-Ν-(ω- carboxyheptadecanoyl)-des(B30) human insulin and B29-N-( -carboxyheptadecanoyl) human insulin. Exendin-4 for example means Exendin-4(1 -39), a peptide of the sequence H-His-Gly- Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe- lle-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

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 [lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(0)14, Asp28] Exendin-4(1 -39),

des Pro36 [Met(0)14, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Trp(02)25, Asp28] Exendin-4(1 -39),

des Pro36 [Trp(02)25, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(0)14 Trp(02)25, Asp28] Exendin-4(1 -39),

des Pro36 [Met(0)14 Trp(02)25, lsoAsp28] Exendin-4(1 -39); or des Pro36 [Asp28] Exendin-4(1 -39),

des Pro36 [lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(0)14, Asp28] Exendin-4(1 -39),

des Pro36 [Met(0)14, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Trp(02)25, Asp28] Exendin-4(1 -39),

des Pro36 [Trp(02)25, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(0)14 Trp(02)25, Asp28] Exendin-4(1 -39),

des Pro36 [Met(0)14 Trp(02)25, lsoAsp28] 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(0)14, Asp28] Exendin-4(1 -39)-Lys6-NH2,

des Met(0)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1 -39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-NH2, des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-Lys6-des Pro36 [Met(0)14, Trp(02)25, Asp28] Exendin-4(1 -39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25] Exendin-4(1 -39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25, Asp28] Exendin-4(1 -39)- NH2,

des Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25, Asp28] Exendin-4(S1 -39)- (Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(0)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.

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. A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra low molecular weight heparin or a derivative thereof, or a sulphated, e.g. a poly-sulphated form of the above-mentioned

polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCI or HBr salts. Basic salts are e.g. salts having a cation selected from alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion

N+(R1 )(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1 -C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10- heteroaryl group. Further examples of pharmaceutically acceptable salts are described in "Remington's Pharmaceutical Sciences" 17. ed. Alfonso R. Gennaro (Ed.), Mark

Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Exemplary embodiments of the present disclosure have been described. Those skilled in the art will understand, however, that changes and modifications may be made to these embodiments without departing from the true scope and spirit of the present disclosure, which is defined by the claims.

Reference numerals

1 needle assembly

2 needle cannulae

3 hub

4 central axis

5 distal ends

6 proximal ends

7 non-threaded connector

8 distal end

9 proximal end

10 needle cannula

1 1 needle cannula

12 needle cannulae

20 dose dialling module

21 medicament housing

22 dose adjustment knob

D distance

Claims

1 . A needle assembly (1 ) for an injection device comprising,

a. a hub (3) having a central axis (4) and a non-threaded connector (7)

configured to attach to an injection device, the injection device comprising one or more cartridges or reservoirs of medicament, with each having a pierceable membrane in fluid communication with a medicament; and b. at least two cannulae (2, 10, 1 1 , 12), each having a distal (5) and a proximal end (6) and mounted separately in the hub, where the distal ends of each cannula are beveled and sharp, and where the proximal ends (6) of each cannula (2, 10, 1 1 , 12) are beveled and sharp.

2. The needle assembly of claim 1 where one of the at least two cannulae (10) has a different gauge than another one of the at least two cannulae (1 1 ).

3. The needle assembly of claim 1 or 2 where the bevels on the distal ends (5) of the cannulae (2, 10, 1 1 ) are facing outwards from the central axis of the hub.

4. The needle assembly of claim 1 or 2 where the bevels on the distal ends (5) of the cannulae (12) are facing towards the central axis of the hub.

5. The needle assembly of any of claims 1 to 4 where the bevels on the distal ends (5) of the cannulae are facing in the same direction.

6. The needle assembly of any of claims 1 to 4 where the bevels on the distal ends (5) of two cannulae (12) face each other.

7. The needle assembly of any of claims 1 to 4 where the bevels on the distal ends (5) of the cannulae (2, 10, 1 1 ) are facing in opposite directions.

8. The needle assembly of any of claims 1 to 7 having two cannulae (2, 10, 1 1 , 12) where the proximal ends (6) are separated by a distance D and the distance separating the distal ends (5) is less than D.

9. The needle assembly of any of claims 1 to 7 having two cannulae (2, 10, 1 1 , 12) where the proximal ends (6) are separated by a distance D and the distance separating the distal ends (5) is greater than D.

10. The needle assembly of any of claims 1 to 9 where at least one cannula (12) is non-linear with respect to the central axis such that the proximal end (6) is offset from the distal end (5).

1 1 . The needle assembly of any of claims 1 to 10 where the distal ends (5) of the cannulae (2, 10, 1 1 , 12) are covered by a needle shield.

12. The needle assembly of any of claims 1 to 1 1 where the proximal ends (6) of each cannula (2, 10, 1 1 , 12) do not extend beyond the hub (3).

13. An injection device comprising the following in combination:

a. medicament, and

b. the needle assembly (1 ) of any of the previous claims, where

the at least two cannulae (2, 10, 1 1 , 12) are in fluid communication with medicament.

14. The injection device of claim 13 where one of the at least two cannulae (2, 10,

1 1 , 12) is in fluid communication with medicament of a first reservoir of medicament and another one of the at least two cannulae is in fluid

communication with medicament of a second reservoir of medicament.

15. The injection device of claim 13 where two cannulae (2, 10, 1 1 , 12) are in fluid communication with medicament of a single reservoir of medicament.