GB2488735A

GB2488735A - Two medicament syringe with split spindle

Info

Publication number: GB2488735A
Application number: GB1211538.2A
Authority: GB
Inventors: Daniel Thomas De Sausmarez Lintell; Malcolm Stanley Boyd; David Martin Leak; Elizabeth Anne Marshall
Original assignee: Sanofi Aventis Deutschland GmbH
Current assignee: Sanofi Aventis Deutschland GmbH
Priority date: 2012-06-29
Filing date: 2012-06-29
Publication date: 2012-09-05
Also published as: GB201211538D0

Abstract

A drug delivery device and corresponding method for simultaneous delivery of at least two medicaments via a single dispense interface. In one example, the device 104 comprises a dose setting mechanism 110, a drive mechanism 112 and a divided spindle 114 with a first 122 and second section 124, where the first section 122 is operably coupled to a first cartridge 126 containing a first medicament 106 and where the second section 124 is operably coupled to a second cartridge 128 containing a second medicament 108, the second cartridge 128 being arranged alongside the first cartridge. Activation of the device by trigger 114 forces the divided spindle 114 in the distal direction 116, thereby causing the device to deliver a respective dose of the first and second medicaments. The dose ratio may be changed by altering the diameter of the cartridges (see figure 3). In another example, the device comprises a rotational coupling mechanically linking a first drive mechanism to a second drive mechanism such that activation of the device causes a torsional spring to unwind, thereby causing the device to deliver a respective dose of the first and second medicaments.

Description

DRUG DELIVERY DEVICE FOR SIMULTANEOUSLY

DELIVERING AT LEAST TWO MEDICAMENTS

Field of the Present Patent Application

This present patent application relates to medical devices and methods of delivering at least two medicaments from separate reservoirs using devices having only a single dose setting mechanism and a single dispense interface. A delivery procedure initiated by the user causes a user settable dose of a first medicament and a non-user settable dose of a second medicament to be delivered to the patient.

The medicaments are contained in two or more cartridges (also commonly referred to 1 5 as "reservoirs"), containers or packages, each containing independent (single compound) or pre-mixed (co-formulated multiple compounds) drug agents. The disclosed device and method is of particular benefit where the therapeutic response can be optimized for a specific target patient group, through control and definition of the therapeutic dose profile (i.e., the quantitative relationship between two or more medicaments (and their respective drug agents) that can be delivered to a patient).

Background

Certain disease states require treatment using one or more different drug agents (i.e., combination therapy). Some drug agents need to be delivered in a specific relationship with each other in order to deliver the optimum therapeutic dose. The disclosed device and corresponding method is of particuiar benefit where combination therapy is desirable, but not possible in a single medicament formulation for reasons such as, but not limited to, stability, compromised therapeutic performance, and toxicology.

For example, in some cases it might be beneficial to treat a diabetic with a long-acting insulin and with a glucagon-like peptide-1 (GLP-1), which is derived from the transcription product of the proglucagon gene. GLP-1 is found in the body and is secreted by the intestinal L cell as a gut hormone. GLP-1 possesses several physiological properties that make it (and its analogs) a subject of intensive investigation as a potential treatment of diabetes mellitus.

There are a number of potential problems associated with the storage and delivery of two active drug agents. For instance, the two active drug agents may interact with each other during long-term storage. Therefore, it is advantageous to store the active drug agents separately and only combine them at the point of delivery via injection, needle-less injection, pumps, or inhalation. However, the process for combining the two active drug agents needs to be simple and convenient for the user to perform reliably, repeatedly, and safely.

A further problem is that the quantities and/or proportions of each active drug agent making up the combination therapy may need to be varied for each user or at different stages of their therapy. For example, certain active drug agents may require a titration period to gradually introduce a patient to a "maintenance" dose. A further example would be if one active drug agent requires a non-adjustable fixed dose while the other is varied in response to a patient's symptoms or physical condition. This problem means that pre-mixed medicament formulations of multiple active drug agents may not be suitable as these pre-mixed formulations would have a fixed ratio of the active drug agents, which could not be varied by the healthcare professional or user.

Additionally, many users cannot cope with having to use more than one drug delivery system or make the necessary accurate calculation of the required dose combination.

This is especially true for users with dexterity or computational difficulties. Accordingly, there exists a strong need to provide devices and methods for the delivery of two or more drug agents in a single injection or delivery step that is simple for the user to perform.

The disclosed device and corresponding method helps overcome the above-mentioned problems by providing separate cartridges for two or more active drug agents making up a desired combination therapy. The two or more active drug agents are only combined and/or delivered to the patient during a single delivery procedure. Thus, the two or more active drug agents will not interact with each other during long-term storage.

Further, the disclosed device and corresponding method is capable of achieving a wide variety of therapeutic dose profiles, therefore, making combination therapy that may need to be varied for each user or at different stages of their therapy possible.

These and other advantages will become evident from the following more detailed

description of the invention.

SUMMARY

Disclosed herein are various examples of a drug delivery device and corresponding method for delivering (herein, sometimes referred to as "dispensing") at least two medicaments, where each medicament contains independent (single compound) or pre-mixed (co-formulated multiple compounds) drug agents. In particular, the disclosed device and corresponding method allows a user to set and dispense at least two medicaments via a device with a single dose setting mechanism and a single dispense interface. A single dose setter (e.g., a dial) controls the dose setting mechanism such that a predefined combination of drug agents is set when a single dose of one of the medicaments is set. After the predefined combination of drug agents is set, the combination can be dispensed through the single dispense interface (e.g., a needle cannula) by activating the device. Although principally described in this application as a drug delivery device such as an injection device, the basic principle could be applicable to other forms of drug delivery, such as, but not limited to, inhalation, nasal, ophthalmic, oral, topical, and like devices.

By defining the therapeutic relationship (i.e., therapeutic dose profile) between various drug agents of various respective medicaments, Applicants' drug delivery device helps ensure that a patient receives the optimum therapeutic combination dose without the inherent risks associated with multiple inputs, where the user has to calculate and set the correct dose combination every time they use the device. One or more of the medicaments may be a fluid, defined herein as a liquid, gas or powder that are capable of flowing and that change shape at a steady rate when acted upon by a force tending to change its shape. Alternatively or additionally, one or more of the medicaments may be a solid, powder, suspension of slurry that may be carried, solubilized or otherwise dispensed with another fluid medicament. In one example, the therapeutic combination dose comprises a first and a second medicament. The first medicament may be a fluid and the second medicament may be a powder that is either dissolved or entrained in another fluid before it is injected with the first fluid medicament through a single dispense interface.

The disclosed device and corresponding method is of particular benefit to users with dexterity or computational difficulties as it requires only a single setting step to set a combination dose according to a predefined therapeutic dose profile, which removes the need for the user to calculate their prescribed dose every time they use the device.

Further, the device enables the combination dose to be delivered via one dispense interface and in one injection step. This offers a convenient benefit to the user in terms of reduced user steps compared to administering two separate dose settings and respective injections. This convenience benefit may also result in improved compliance with the prescribed therapy, particularly for users who find injections unpleasant, or who have dexterity or computational difficulties. Moreover, the use of one injection instead of two reduces the possibility for user errors and so may increase patient safety.

In one example of the proposed device, a first medicament, such as insulin, is contained in a first cartridge and a second medicament is contained in a second cartridge. With a single setting step, a user sets a desired dose of the first medicament, and with a single delivery step, the user activates the drug delivery device (e.g., actuates a dose button) and the set dose of the first medicament along with a fixed ratio dose of a second medicament is delivered via a single dispense interface.

Although Applicants' present patent application specifically mentions insulin, insulin analogs or insulin derivatives, and GLF-1 or GLP-1 analogs as two possible drug combinations, other drugs or drug combinations, such as an analgesics, hormones, beta agonists or corticosteroids, or a combination of any of the above-mentioned drugs could be used with Applicants' proposed device and method.

As used herein, the term "insulin" shall mean insulin, insulin analogs, insulin derivatives or mixtures thereof, including human insulin or a human insulin analogs or derivatives.

Examples of insulin analogs are, without limitation, 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 or Des(B30) human insulin. Examples of insulin derivatives are, without limitation, 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 LysB28FroB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB3O human insulin; B30-N-palmitoyl-ThrB29LysB3O human insulin; B29-N-(N-palrnitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(330) human insulin; B29-N-(w-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyhepta-'decanoyl) human insulin.

As used herein the term "GLP-1" shall mean GLP-1, GLP-1 analogs, or mixtures thereof, including without limitation, exenatide (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-Va l-Arg-Leu-Phe-l le-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-N H2), Exendin-3, Liraglutide, or AVEOO1 0 (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-Gl y-Pro-Ser-Ser-G ly-Ala-Pro-P ro-Ser-Lys-Lys-Lys-Lys-Lys-Lys-N H2).

Examples of beta agonists are, without limitation, salbutamol, levosalbutamol, terbutaline, pirbuterol, procaterol, metaproterenol, fenoterol, bitolterol mesylate, salmeterol, formoterol, bambuterol, clenbuterol, indacaterol.

Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.

In another example of the drug delivery device, the drug delivery device comprises a single dose setting mechanism having a dose setter and a dose button, a single dispense interface, a first cartridge containing multiple doses of a first medicament, a second cartridge containing multiple doses of a second medicament, and a housing.

The single dose setting mechanism is operably coupled to the first cartridge and the dose setter corresponds with doses of the first medicament. Herein, "operably coupled" may mean directly coupled or indirectly coupled via another component.

A single activation of the dose setter by a user sets a dose of the first medicament and automatically sets a non-user settable dose of the second medicament. After a desired dose of the first medicament has been set by a user, a single activation of the dose button causes the set dose of the first medicament and the non-user settable dose of the second medicament to be expelled through the single dispense interface. This dose button can be any type of mechanism that triggers the delivery procedure, whether driven mechanically or through a combination of electronics and mechanics. The button can move or be a touch sensitive virtual button, for example, a touch sensitive screen.

As noted above, the drug delivery device has a single dispense interface. The single dispense interface is configured for fluid communication with the first cartridge and with the second cartridge. The dispense interface can be any type of outlet that allows the two or more medicaments to simultaneously exit the device and be delivered to the patient. Types of interfaces include needle cannulas, catheters, atomizers, pneumatic injectors, needle-less injectors, mouthpieces, nasal-applicators, and the like.

As noted above, the device is designed such that a single activation of the drug delivery device causes a user settable dose of the first medicament and a non-user settable dose of the second medicament to be expelled through the single dispense interface.

Activating the drug delivery device may comprise actuating a dose button of the device.

As used herein, a "user settable dose" means a dose that the user (patient or health care provider) can physically manipulate the device to set. Additionally, a user settable dose can be set remotely through the use of wireless communication (Bluetooth, WiFi, satellite, etc.) or the dose could be set by another integrated device, such as a blood glucose monitor after performing a therapeutic treatment algorithm. By "non-user settable dose, it is meant that a user (or any other input) cannot independently set or select a dose. In other words, when the user (or another input as described above) sets the dose of the first medicament, the dose of the second medicament is automatically set.

In another example, the drug delivery device comprises a single dose setting mechanism, a drive mechanism comprising a drive spindle, and a divided spindle comprising a first section and a second section that is laterally offset from the first section. The first section of the divided spindle is operably coupled to a first cartridge containing a first medicament and the second section of the divided spindle is operably coupled to a second cartridge containing a second medicament. Activation of the drug delivery device causes the drive spindle to force the divided spindle in a distal direction, thereby causing the drug delivery device to deliver a dose of the first medicament and a dose of the second medicament. In an example, the divided spindle may be slidably coupled to the drive mechanism.

In another example, the drug delivery device comprises a dose setting mechanism, a first drive mechanism comprising a torsional spring, a second drive mechanism, and a rotational coupling. The first drive mechanism is operably coupled to a first cartridge containing a first medicament and a proximal end of the torsional spring is coupled to the dose setting mechanism such that setting the dose setting mechanism causes the torsional spring to wind up. The second drive mechanism is operably coupled to a second cartridge containing a second medicament. The rotational coupling is operably coupled to the torsional spring and mechanically links the first drive mechanism to the second drive mechanism such that, after setting the dose setting mechanism, activation of the drug delivery device causes the torsional spring to unwind, thereby causing the drug delivery device to deliver a dose of the first medicament and a dose of the second medicament.

To help achieve the above-mentioned functionality, the rotational coupling may comprise a drive gear and a driven gear, where the drive gear and the driven gear are engaged. The drive gear is operably coupled to a spindle of the first drive mechanism and the driven gear is operably coupled to a spindle of the second drive mechanism.

The drug delivery device may further comprise a trigger engaged with the rotational coupling and configured to prevent the drug delivery device from delivering the first and second medicaments until activation of the drug delivery device. In such an example, activation of the drug delivery device comprises disengaging the trigger from the rotational coupling.

Applicants' present disclosure also covers a method of dispensing a variable dose of a first medicament and a fixed dose of a second medicament from separate cartridges. In one example, the method involves the steps of first setting a dose of a first medicament contained in a first cartridge of a drug delivery device having a single dose setter.

Setting the dose of the first medicament automatically sets a dose of the second medicament without a separate input by the user. Next, a dose button is actuated thereby delivering both the set dose of the first medicament from the first cartridge and the automatically set dose of the second medicament from the second cartridge through a single dispense interface.

In another example, the method involves the following steps: 1. Attach a single dispense interface to the distal end of a drug delivery device such that the proximal end of the single dispense interface is in fluidic communication with both a first medicament and a second medicament.

2. Dial up (i.e., set) the single dose setter of the drug delivery device such that it is ready to dispense the desired dose of the first medicament. As the single dose setter sets the dose of the first medicament, a predefined non-user settable dose of the second medicament is automatically set at the same time.

3. Insert or apply the distal end of the single dispense interface to the patient at or into the desired administration site. Dispense the first medicament by activating a single dose button, which also causes the second medicament to automatically dispense.

The drug delivery device disclosed herein is capable of delivering a combination of medicaments via a single dispense interface as discrete units or as a mixed unit, thus providing a combination therapy that, from a user's perspective, is achieved in a manner that closely matches the currently available injection devices that use standard needles.

The drug delivery device disclosed herein may be designed in such a way as to limit its use to exclusive first and second cartridges through employment of dedicated or coded features.

A particular benefit of Applicants' proposed device and corresponding method is that two multi-dose cartridges (a first and a second cartridge) may be used, which makes it possible to tailor dose regimes when required, especially where a titration period is necessary for a particular medicament. For instance, the second cartridge may be supplied in a number of different titration levels or strengths with obvious differentiation features such as, but not limited to, aesthetic design of features or graphics, numbering etc, so that a user may use multiple second cartridges in a specific order to facilitate titration. Alternatively, the prescribing physician may provide the patient with a number of "level one" titration second cartridges and then when these are finished, the physician may then prescribe the next level. An advantage of these titration programs is that the drug delivery device may remain constant throughout.

These as well as other advantages of various aspects of the present invention 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

Various examples of Applicants' drug delivery device and corresponding method are described herein with reference to the following drawings, wherein like numerals denote like entities: Figure 1 a illustrates an example therapeutic dose profile that can be achieved with the

drug delivery device of Applicants' disclosure;

Figure 1 b illustrates another example therapeutic dose profile that can be achieved with the drug delivery device of Applicants' disclosure; Figure 2 illustrates an example of the drug delivery device; Figure 3a illustrates an example of the relative diameters of the first and second cartridges of the drug delivery device shown in Figure 2; Figure 3b illustrates another example of the relative diameters of the first and second cartridges of the drug delivery device shown in Figure 2; Figure 3c illustrates yet another example of the relative diameters of the first and second cartridges of the drug delivery device shown in Figure 2; Figure 4 illustrates another example of the drug delivery device; Figure 5 illustrates yet another example of the drug delivery device; Figure 6 illustrates still yet another example of the drug delivery device; Figure 7 is an enlarged view of various components of the drug delivery device shown in Figure 6; Figure 8 is an isometric view of the rotational coupling of the drug delivery device shown in Figure 6; Figure 9 is an enlarged view of the trigger mechanism and the rotational coupling of the drug delivery device shown in Figure 6; Figure 1 Oa illustrates the drug delivery device shown in Figure 6 during an example dose setting step (i.e., first step) of an example medicament delivery procedure; and Figure 1 Ob illustrates the drug delivery device shown in Figure 6 during an example delivery step (i.e., third step) of an example medicament delivery procedure.

DETAILED DESCRIPTION

The drug delivery device disclosed herein is capable of delivering at least two medicaments through a single dispense interface. More specifically, the drug delivery device disclosed herein is capable of simultaneously delivering at least two medicaments through a single dispense interface with a single setting step and a single delivery step. Herein, "simultaneous delivery" means that the at least two medicaments are delivered at the same time or close to the same time, in either an intermixed state, side-by-side or sequentially. In some instances, the at least two medicaments may be delivered in a combination of these states (e.g., partially intermixed and partially sequential).

In one example, the drug delivery device comprises a single variable dose setting mechanism for setting a dose of a first medicament. With a single setting step, a user sets a desired dose of the first medicament, and with a single delivery step, the user activates the drug delivery device and the set dose of the first medicament along with a fixed ratio of a second medicament is delivered via a single dispense interface. Such a therapeutic dose profile 100 is shown in Figure 1 a, where Compound A represents the first medicament and Compound B represents the second medicament. As shown, increasing the variable dose of the first medicament increases the dose of the second medicament by a predetermined fixed percentage.

Alternatively, in another example, the drug delivery device comprises a single fixed dose setting mechanism. With a single setting step, a user sets the drug delivery device. Because the dose setting mechanism is not variable, the setting step sets a predetermined ratio between the first and second medicaments that is fixed for the life of the drug delivery device. After setting the drug delivery device, the user activates the drug delivery device thereby delivering a fixed dose of the first medicament and a fixed dose of the second medicament via a single dispense interface. Such a therapeutic dose profile 102 is shown in Figure 1 b, where Compound A represents the first medicament and Compound B represents the second medicament.

Figures 2 and 4-6 illustrate various examples of Applicants' proposed drug delivery device. While these examples are described as comprising a single variable dose setting mechanism, a single fixed dose setting mechanism may be used depending on the desired therapeutic dose profile.

Figure 2 illustrates one example of the drug delivery device 104. As shown, drug delivery device 104 is a multi-use injection device for simultaneously delivering a user settable dose of a first medicament 106 and a fixed ratio dose of a second medicament 108. Drug delivery device 104 generally comprises a variable dose setting mechanism 110, a drive mechanism 112, and a divided spindle 114.

Variable dose setting mechanism 110 may be any variable dose setting mechanism known in the art. For instance, dose setting mechanism 110 may be a rotationally driven variable dose setting mechanism. As shown, dose setting mechanism 110 comprises (i) a dose setter 11 3, such as a dose dial, for setting a dose of the first medicament 106 and (ii) a dose button 114 for activating the drug delivery device 104 thereby causing the first and second medicaments 106, 108 to be delivered. Although this example is described as having a dose setter 113 that is configured to correspond with doses of the first medicament 106, other examples may have a dose setter 113 configured to correspond with doses of the second medicament 108. Dose setting mechanism 110 is operably coupled to drive mechanism 112.

For simplicity, drive mechanism 112 is described with reference to a drive spindle 118 only. However, those skilled in the art will appreciate that drive mechanism 112 may comprise one or more additional components. Moreover, drive mechanism 112 may be any drive mechanism known in the art that is capable of driving a spindle (also commonly referred to as a "piston rod" or "lead screw"), such as drive spindle 118, in the distal direction 116. As shown, drive spindle 118 is operably coupled to divided spindle 114 such that when the drive spindle is driven in the distal direction 116, the divided spindle is also driven in the distal direction.

In addition to being coupled to drive spindle 118, divided spindle 114 is slidably coupled to an outer surface 120 of drive mechanism 112 which helps guide the divided spindle in the distal direction 116 when the divided spindle is driven by the drive spindle.

Moreover, coupling the divided spindle 114 to the outer surface 120 as shown in Figure 2 minimizes the total device length by offsetting the divided spindle from the drive spindle 118. The geometry of the divided spindle 114 is such it can be supported both internally (by surrounding the outer surface 1 20 of drive mechanism 112) and/or externally (by external housing (not shown) of the device 104). Support of the divided spindle 114 is helpful in minimizing flexion, which could cause deviations between the advancement of the drive spindle 118 and the associated advancement of the divided spindle.

As shown, divided spindle 114 comprises a first section 122 and a second section 124 laterally offset from the first section. The first section 122 is operably coupled to a first cartridge 1 26 containing the first medicament 1 06 and the second section 124 is operably coupled to a second cartridge 128 containing the second medicament 108.

Each cartridge 126, 128 may contain one or more doses of its respective medicament 106, 108. Additionally, each cartridge 126, 128 may be self-contained and provided as a sealed and sterile cartridge. For instance, as shown, each cartridge 126, 128 comprises (i) a pierceable seal or septa 130, 132 at its distal end to accept a dispense interface (examples of the dispense interface are described below with reference to Figures 2, 4-6, 1 Oa, and 1 Ob) and (ii) a bung 134, 136 (also commonly referred to as a "piston" or a "stopper") for forcing medicament in the distal direction 11 6 when a predefined distally directed force is applied to the bung. Although the divided spindle 114 shown in Figure 2 has two sections 122, 124, in other examples, the divided spindle may comprise one or more additional sections operably coupled to one or more respective cartridges containing respective medicam ents.

When the divided spindle 114 is driven in the distal direction 116 by the drive spindle 118, the first and second sections 122,124 are equally displaced and respectively force the first and second cartridge bungs 134, 136 in the distal direction. Because the divided spindle 114 provides equal displacement of both sections 122, 124, a fixed ratio of medicament is delivered from the cartridges 126, 128. However, the ratio between respective amounts of a dose of the first medicament 106 and a dose of the second medicament 108 that are delivered upon activation of the drug delivery device 104 is dependent on relative respective diameters Dl, D2 of the first and second cartridges 126, 128. The relative respective diameters Dl, D2 of the first and second cartridges 126, 128 may be varied according to the desired therapeutic dose profile. For instance, with reference to Figures 3a-c, if the first and second cartridges 126, 128 have the same diameter (i.e., Dl equals D2) as shown in Figure 3a, then a 1:1 ratio between the respective amounts of medicament doses will be delivered. However, if the diameter Dl of the first cartridge 126 is 9.8 millimeters (mm) for example and the diameter D2 of the second cartridge 128 is 6.8mm for example, as shown in Figure 3b, then approximately a 2:1 ratio between the respective amounts of medicament doses will be delivered. Although the ratios in the above two examples only include whole numbers, the ratio X:1 between the respective amounts of med icament doses to be delivered may include any real number X (e.g., 2.5:1) as shown in Figure 3c.

Due to the equal displacement of both sections 122, 124, the example shown in Figure 2 may be advantageously suited to be a disposable device (although could also be embodied as a reusable device) as the sections 122, 124 will always reach the distal end of their respective cartridges 126, 128 at the same time. Consequently, there will be minimal or no medicament wastage, which is particularly advantageous, compared to other disposable multi-medicament devices where wastage is unavoidable without cartridge replacement.

Figures 4 and 5 show two alternative examples of the drug delivery device 104. These two alternative examples are similar to the example shown in Figure 2 with the exception of the geometry of the divided spindle 114 and the relative diameters Dl, D2 of the first and second cartridges 126, 128.

As shown in Figures 4 and 5, the first and second cartridges 126, 128 have different diameters. As noted above, the effect of providing the drug delivery device 104 with cartridges 1 26, 128 having different diameters is that the ratio between respective amounts of a first medicament dose and a second medicament dose that are delivered upon activation of the drug delivery device 104 is not 1:1.

The divided spindle 114 shown in Figure 4 partially surrounds the drive mechanism 112, however, the divided spindle shown in Figure 4 it is not coupled to the outer surface 120 of the drive mechanism 112 as in Figure 2. The divided spindle 114 shown in Figure 5 does not surround the drive mechanism 112. Instead, the entire divided spindle 114 is positioned distal to the drive mechanism 112.

Turning now to Figure 6, another example of the drug delivery device 104 is shown.

Similar to the examples shown in Figures 2, 4, and 5, the drug delivery device 104 shown in Figure 6 comprises a variable dose setting mechanism 110 for setting a dose of a first medicament 106. However, unlike the examples shown in Figures 2, 4, and 5, the drug delivery device 104 shown in Figure 6 does not comprise a divided spindle 114.

Further distinguishing from the examples shown in Figures 2, 4, and 5, the drug delivery device 104 shown in Figure 6 comprises a first drive mechanism 138, a second drive mechanism 140, and a rotational coupling 142 that mechanically links the first drive mechanism to the second drive mechanism thereby facilitating simultaneous delivery of the first medicament 106 and a second medicament 108.

Devices simultaneously delivering multiple medicaments from separate cartridges via a single dispense interface inherently have to push' more fluid through the single dispense interface and, as a consequence, require a higher force. This force (i.e., the dispense or dose force) may be proportional to the amount of fluid being dispensed over a given time period. To help remedy this issue, the first drive mechanism 138 may be primarily spring driven, which decreases the required dose force. Accordingly, the drug delivery device 104 may be similar to an auto injector known in the art in that the user is required to apply a relatively small force to activate the drug delivery device. In this example, such a force is applied to a trigger 144. Moreover, in this example, the trigger 144 may be held down by the continual application of force in order to dispense an entire user set dose of the first medicament 106 and a fixed ratio dose of the second medicament 108.

Variable dose setting mechanism 110 may be any variable dose setting mechanism known in the art. For instance, dose setting mechanism may be a rotationally driven variable dose setting mechanism. As shown, variable dose setting mechanism 110 comprises a dose setter 113 such as a dial. A user can set a dose of the first medicament 106 by rotating the dose setter 113. Although this example is described as having a dose setter 113 that is configured to correspond with doses of the first medicament 106, other examples may have a dose setter configured to correspond with doses of the second medicament 108. In this other example, the doses of the second medicament would be the user-variable doses of medicament.

The first drive mechanism 138 may be similar to an auto injector type drive mechanism know in the art. The first drive mechanism 138 comprises a torsional spring 146 and a spindle 148. The second drive mechanism 140 comprises a spindle 150 and is similar to a spindle type mechanism (or similar device) known in the art. As noted above, the first and second drive mechanisms 138, 140 are linked together via the rotational coupling 142.

As shown, the first drive mechanism 1 38 is operably coupled to a first cartridge 1 26 containing the first medicament 106 and the second drive mechanism 140 is operably coupled to a second cartridge 128 containing the second medicament 108. When the spindle 148 of the first drive mechanism 138 is driven a predetermined distance in the distal direction 11 6, it forces the bung 134 of the first cartridge 126 in the distal direction.

Likewise, when the spindle 150 of the second drive mechanism 140 is driven a predetermined distance in the distal direction 11 6, it forces the bung 136 of the second cartridge 1 28 in the distal direction.

The rotational coupling 142 comprises a drive gear 152 engaged with a driven gear 154.

The drive gear 152 is operably coupled to the spindle 148 of the first drive mechanism 138 and is capable of driving the spindle 148 in the distal direction 116 such that the first medicament 106 can be delivered. The driven gear 154 is operably coupled to the spindle 150 of the second drive mechanism 140 and is capable of driving the spindle in the distal direction 116 such that the second medicament 108 can be delivered.

As shown, each spindle is axially guided by a respective body nut 156, 158.

Figure 7 is an enlarged view of various components of the drug delivery device 104 shown in Figure 6 including the first and second drive mechanisms 1 38, 140, the rotational coupling 142, the trigger 144, and the body nuts 156, 158. The torsional spring 146 is held at its proximal end by retention features inside the dose setting mechanism 110 and at its distal end by a connection to the device body. Rotating the dose setter 113 during dose setting winds up the torsional spring 146, storing energy for use during delivery. In this example, the distal end of the torsional spring 146 remains fixed while the proximal end is rotated.

The dose setter 11 3 is fixed to a drive shaft which is concentrically arranged between the spindle 148 and the torsional spring 146. Rotating the dose setter 11 3 and the drive shaft overhauls a one-way ratchet inside the drive gear 152. However, because the drive gear 152 is prevented from rotation by the trigger 144, the internal ratchet of the drive gear prevents the torsional spring 146 from rotating the drive shaft and dose setter 113 back to their original positions (i.e., pre-wind-up positions) until the trigger is released Figure 8 is an isometric view of the rotational coupling 142 of the drug delivery device 104 shown in Figure 6. Counter-clockwise rotation of the drive gear 152 causes clockwise rotation of the driven gear 154 and vice versa. As shown, both spindles 148, have a respective longitudinal groove 160, 162 along their length that are keyed to rib features inside their respective body nuts 156, 158, thereby preventing relative rotation but allowing axial translation between each spindle and its respective body nut.

In normal operation of the drug delivery device 104, the body nuts 156, 158 are prevented from rotating via engagement with the device body. Both the drive gear 152 and the driven gear 154 are internally threaded to their respective spindles 148, 150 such that gear rotation causes the spindles to advance and deliver their respective medicaments 106, 108.

Figure 9 is an enlarged view of the trigger mechanism. As shown, the drive gear 152 has features 164 that engage corresponding features 1 66 of the trigger 144 thus preventing the drive gear from rotating while the trigger is in its upward biased position.

A trigger spring 168 ensures that the drive gear engagement features 164 engage the trigger engagement features 1 66 during dose setting. When a user is ready to delivery the medicaments 1 06, 108, the user presses the trigger 144 in the distal direction 116, which compresses the trigger spring 168 thus releasing the drive gear 152 and allowing the torsional spring 146 to unwind. As the torsional spring 146 unwinds, the drive gear 152 rotates under the action of the drive shaft acting on the ratchet features, which in turn rotates the driven gear 154. Rotation of each gear 152, 154 drives its respective spindle 148, 150 in the distal direction 116. As noted above, the trigger 144 must be held down by the continual application of force in order to dispense an entire user settable dose of the first medicament 106 and a fixed ratio dose of the second medicament 1 08. Once the trigger 144 return to its biased position the drive gear 1 52 is no longer free to rotate.

Operation of the drug delivery device 104 will now be described with reference to Figures 1 Oa and 1 Ob. The first step: setting the dose. Rotation of the dose setter 113 by the user simultaneously sets a dose of the first medicament 106 and winds up the torsional spring 146. The desired dose of the first medicament 146 is set by the user rotating the dose setter 113. A dose of the second medicament 108 is automatically set when the dose of the first medicament is set. The amount of the second medicament 108 dose is determined at least in part by the gear ratio between drive gear 152 and the driven gear 154. The therapeutic dose profile that can be achieved is shown in Figure 1 a. The dose setter 113 simultaneously counts doses and winds up the torsional spring 146 by rotating the proximal end of the spring while the distal end of the spring is held stationary. The dose setter 113 causes the drive shaft, which is connected to the drive gear 152 via a one-way ratchet, to rotate. The drive gear 152 does not rotate as it is held in place by the trigger 144. Both spindles 148, 150 remain stationary as neither of the gears 152, 154 undergo any rotation during dose setting.

The second step: initiation of dosing. Initiation of the dosing phase begins with actuation of the trigger 144, which allows the drive gear 152 to rotate as its engagement features 164 are no longer engaged with the corresponding engagement features 166 of the trigger. This action initiates the release of energy stored in the torsional spring 146, which rotates the dose setter 113 back toward its initial position. The drive shaft is fixed to the dose setter 113 and operably coupled to the drive gear 152. Thus, when the dose setter 113 rotates so does the drive shaft, which in turn rotates the drive gear 152 and hence causes rotation of the driven gear 154.

The third step: delivering the medicaments. During delivery, both the drive gear 152 and the driven gear 154 are forced to rotate as a result of the energy release from the torsional spring 146. Both spindles 148, 150 are prevented from rotation relative to the device body by their engagement to their respective body nuts 156, 158. Because the drive gear 152 and driven gear 154 are internally threaded to their respective spindles 148, 150, as the drive gear and the driven gear rotate, they force their respective spindles to advance in the distal direction 116, which is best shown in Figure 1 Ob. This action simultaneously delivers the first and second medicaments 106, 108.

The ratio between respective amounts of a first medicament dose and a second medicament dose that are delivered upon activation of the drug delivery device 104 is dependent at least in part on (i) the relative respective diameters Dl, D2 of the first and second cartridges 126, 128 (described above), (ii) the relationship between the drive gear 152 and the driven gear 154 (e.g., the gear ratio), and (iii) the relationships between the gears 152, 154 and their respective spindles 148, 150 (e.g., the thread pitch). Varying these parameters has the added benefit of being able to tailor the therapeutic dose profile to meet the needs of a specific therapy or particular patient requirements. Further, the ability to vary these parameters means that multiple drug delivery devices each having a different therapeutic dose profile can be manufactured.

Specifically, this allows variation of the therapeutic dose profile to suit a specific titration regime and ultimately individual patient requirements.

Variation of the spindle thread pitch changes the advance of the spindle for a given amount of gear rotation. Differing amounts of advance between the spindles 148, 150 has the effect of creating different dose delivery ratios between the first and second medicaments 106, 108. Additionally, differing amounts of spindle advance can be achieved by changing the relative diameters of the drive and driven gears 152, 154.

These two design variables can be used independently, or in combination, to achieve the desired ratio. In combination, they may have the effect of extending the operational window of the device 104 in terms of the range of ratios that can be achieved.

As the spindle thread pitch is adjusted it should be kept in mind that certain pitches better allow for resetting of the device 104. It is understood that the spindle thread pitch must be within a certain range for it to allow the spindle to be manually wound backwards into the device 104. As the pitch of the spindle thread gets finer it becomes more difficult to back wind and, at a given pitch, it tends to lock-up. This if of particular importance if the device 104 is designed as a reusable unit.

If the pitch of a spindle is reduced, then the amount of the medicament dispensed by that spindle is reduced by a proportional amount regardless of the dose dialed (assuming various other parameters stay constant). If the pitch of spindle 148 is less than the pitch of spindle 150 (i.e., it takes more rotations to advance spindle 148 the same distance as spindle 150), and other various parameters are equal (e.g., the diameters Dl, D2 of the cartridges 126, 128 and the diameters of the gears 152, 154), then the amount of the first medicament 106 that will be delivered upon activation of the drug delivery device 104 is less than the amount of the second medicament 108 that will be delivered. Although the pitch of spindle can be altered compared to the pitch of the other spindle, in an example the pitch on any one spindle does not vary along its length.

If the pitch of one spindle did vary along its length, then there could potentially be quantitative variation between the "same" dialed doses.

The example drug delivery device 104 described above with respect to Figures 6-1 Ob may be particularly suitable to be a modular disposable or re-usable device in terms of managing medicament wastage. This is because, with a therapeutic dose profile that follows a fixed linear ratio (see Figure 1), there is a reasonable probability that one medicament will be exhausted before the other unless there is a strict 1:1 ratio between the two medicaments 106, 108. Where each drive mechanism 138, 140 is resettable, new cartridges can be inserted and the device 104 can continue to be used. Possible embodiments for a modular disposable device could be, but are not limited to, replacement of the entire device 104 fitted with new cartridges and replacement of the drive mechanisms fitted with new cartridges. Regardless of whether the device 104 is modular disposable or re-usable, suitable re-engagement features may be integrated into the device to facilitate the alignment and fastening of the individual device 1 5 components together in a robust, intuitive and user-friendly fashion.

A re-usable device may feature spindles 148, 150 that can be back wound into their respective drive mechanisms 138, 140 once they had reach their respective limits of travel. This may be achieved by placing the device 104 into a reset state, for example by removing one or both of the cartridges 126, 128, after which the respective body nut(s) 156, 158 becomes free to rotate relative to the device body. Manual rotation of a body nut would then cause the respective spindle to be rotated and this in turn will cause the spindle to wind its way back up the thread inside its respective gear and return to its initial position. In addition to this functionality, the re-usable device may have a mechanism for easy replacement of the cartridges 126, 128 after the resetting of their respective spindles 148, 150.

In all of the examples described above, the first and second medicaments 106, 108 are capable of being delivered via a single dispense interface. As best shown in Figure 2, the first and second cartridges 126, 128 have respective attachment means 170, 172 at their distal end. However, in other examples, the cartridges 126, 128 may be housed in respective cartridge holders and the cartridge holder may comprise the attachment means.

The attachment means 170, 172 may be compatible with a needle assembly 174 that comprises a hub 176 and a single dispense interface 178. The needle assembly may be removable and may be either disposable or reusable. Such a needle assembly 174 is shown in Figures 4-6, 1 Oa, and 1 Ob. The needle assembly 174 can take any form, provided that it allows for fluid communication between the first and second medicaments 106, 108 and the single dispense interface 178. An exemplary needle assembly would include what is referred to in the art as a "2-to-i needle" configuration.

Although not shown, needle assembly 174 may be supplied by a manufacturer in a protective and sterile capsule or container that completely or partially contains the needle assembly. A user may peel and/or rip open a seal or the container itself to gain access to the sterile single dispense interface 1 78. In some instances it might be desirable to provide two or more seals for each end of the needle assembly 174. The seal may allow for the display of information required by regulatory labeling requirements.

Attachment of the needle assembly 174 to the drug delivery device 104 via the hub 176 creates a fluid connection between dispense interface 178 and the first and second medicaments 106, 108.

Although the various examples of the drug delivery device 104 described herein comprise a single dispense interface, other examples may comprise multiple dispense interfaces, for example, a different dispense interface for each respective cartridge/medicament.

Examples of the present drug delivery device have been described. Those skilled in the art will understand, however, that changes and modifications may be made to these examples without departing from the true scope and spirit of the present invention, which is defined by the claims.

Claims

Claims 1. A drug delivery device (104) for delivering at least two medicaments, the drug delivery device (104) comprising: a dose setting mechanism (110); a drive mechanism (112) comprising a drive spindle (118); and a divided spindle (114) comprising a first section (122) and a second section (124) laterally offset from the first section (122), wherein the first section (122) is operably coupled to a first cartridge (126) containing a first medicament (106), wherein the second section (124) is operably coupled to a second cartridge (128) containing a second medicament (108), such that activation of the drug delivery device (104) causes the drive spindle (118) to force the divided spindle (114) in a distal direction (116), thereby causing the drug delivery device (104) to deliver a dose of the first medicament (106) and a dose of the second medicament (106).
2. The drug delivery device (104) of claim 1, wherein the dose setting mechanism (110) is a rotationally driven variable dose setting mechanism for selectively setting a dose of the first medicament (106), and wherein activation of the drug delivery device (104) causes the drug delivery device (104) to deliver a selected dose of the first medicament (106) and a fixed ratio dose of the second medicament (108).
3. The drug delivery device (104) of claim 1 or claim 2, wherein a ratio between respective amounts of the dose of the first medicament (106) and the dose of the second medicament (108) that are delivered upon activation of the drug delivery device (104) is dependent on relative respective diameters (Dl;D2) of the first and second cartridges (126;128).
4. The drug delivery device of claim 3, wherein the respective diameters (Dl;D2) of the first and second cartridges (1 26;1 28) are equal.
5. The drug delivery device (104) of any of the preceding claims, wherein activation of the drug delivery device (104) advances the first and second sections (1 22;1 24) an equal distance in the distal direction (116).
6. The drug delivery device (104) of any of the preceding claims, wherein the divided spindle (114) is slidably coupled to the drive mechanism (112).