Patent Description:
A variety of diseases exist that require regular treatment by injection of a medicament. Injection devices known in the art include infusion and patch pumps for delivering injections of medicament. Another type of injection device is a bolus injector device. Some biological medicaments comprise higher viscosity injectable liquids and are to be administered in larger volumes than traditional liquid medicaments, typically at least <NUM> and maybe a few ml. Such high capacity bolus injectors can be called large volume devices (LVDs). Such injection devices may be first supported on a suitable injection site of a patient and, once installed, injection is initiated by the patient or another person (a user).

The drug delivery process of such devices can last for several minutes or even hours, particularly in the case of large volume devices. However, for effective treatment of the medical condition, it is important that the device reliably and completely delivers the entire medicament dose to the patient.

<CIT> discloses a fluid reservoir system, an outlet structure having an outlet port, and a constant force system coupled to the fluid reservoir. The fluid reservoir system includes a fluid chamber for holding a volume of a fluid. The fluid reservoir system is fluidically coupled to the outlet port. The constant force system is adapted to apply a force to the fluid chamber, where the force causes the volume of the fluid to flow out of the fluid chamber and through the outlet port at a substantially constant pressure.

<CIT> discloses a medical infusing device which is used for infusion bags and separated packing bags of soft package. The device comprises a box-type outer shell, and an upper bottom part in the outer shell is connected with a pressurizing mechanism. The pressurizing mechanism applies positive pressure to the infusion bag by a pressurizing rod, a wheel axle, a rolling wheel and a pressurizing board under the torsion of left and right torsion spring sets to generate pressure such that medical liquid in the bag is infused into the human body by an infusion tube.

<CIT> discloses a drug delivery device. The drug delivery device includes a drug reservoir in fluid communication with a microneedle array. The drug delivery device has a sliding actuation mechanism that may be activated by a button or lever. Actuation of the drug delivery device inserts the microneedle array into the skin of a subject and causes a piston to compress the drug reservoir, thereby delivering the drug through the microneedle array to the subject.

The present invention provides a medicament delivery system for use with a medicament delivery device, the medicament delivery system comprising a support member, a compression member spaced from the support member to define a gap therebetween, a collapsible and/or flexible medicament reservoir disposed in the gap between the support member and the compression member, a mechanical coupling between the support member and the compression member comprising a plurality of connecting members extending between the support member and the compression member, and a biasing element connected to the compression member and configured to exert a rotational force on the compression member relative to the support member, wherein the mechanical coupling is configured such that rotation of the compression member relative to the support member causes the compression member to be drawn towards the support member to reduce the gap therebetween such that when medicament is contained in the medicament reservoir the medicament is dispensed therefrom.

Each connecting member may be pivotally connected to the support member and to the compression member.

Each connecting member may be pivotally connected to the support member and the compression member by a ball and socket coupling. This may advantageously facilitate rotational movement of the compression member relative to the support member.

The connecting members may comprise inextensible rigid rods. This may advantageously facilitate constant translation of the compression member relative to the support member upon rotation of the compression member.

The biasing element may also be configured to bias the compression member towards the support member. This may advantageously facilitate compression of a body between the support and compression members.

The biasing member may comprise a spiral torsion spring. This may advantageously facilitate rotational biasing of the compression member.

The spiral torsion spring may be conically shaped. This may advantageously facilitate compact and/or space-efficient packaging of the biasing member, such as within a medicament delivery device.

The support member and the compression member may comprise substantially parallel spaced plates. This may advantageously facilitate retention of a body between the plates.

The collapsible medicament reservoir may advantageously facilitate containment and delivery of a medicament.

The present invention also provides a medicament delivery device comprising a housing, a medicament delivery system as described above disposed within the housing, and an injection needle fluidly connected to the medicament reservoir.

The medicament delivery device may include a releasable locking mechanism configured to retain the compression member against the biasing force of biasing element. This may advantageously facilitate holding the compression member apart from the support member until a medicament delivery process is to be initiated.

The locking mechanism may include an actuator operable to release compression member to move from an expanded state to a compressed state under the biasing force of the biasing element. This may advantageously facilitate initiation of a medicament delivery process.

The medicament delivery device may further comprise a needle control mechanism configured to move the needle between a retracted position in which it is disposed within the housing, and an extended position in which it projects from the housing. This may advantageously facilitate prevention of needle exposure until a medicament delivery process is to be initiated.

The medicament reservoir may contain liquid medicament.

There is also disclosed a method of operating a medicament delivery system for use with a medicament delivery device, the medicament delivery system comprising a support member, a compression member spaced from the support member to define a gap therebetween, a collapsible medicament reservoir disposed within said gap, a mechanical coupling between the support member and the compression member comprising a plurality of connecting members extending between the support member and the compression member, and a biasing element connected to the compression member, the method comprising the biasing member exerting a rotational force on the compression member relative to the support member, the mechanical coupling converting rotation of the compression member relative to the support member to move the compression member towards the support member to reduce the gap therebetween and collapsing the medicament reservoir to expel liquid medicament from the medicament reservoir.

A fluid medicament delivery device <NUM> for delivering fluid medicament to a patient is described below. The device <NUM> as shown comprises a medicament injection device, although other types of medicament delivery devices are intended within the scope of the invention. The device <NUM> comprises a medicament delivery system <NUM> for delivering liquid medicament to the patient. The delivery system <NUM> may comprise a medicament reservoir <NUM> for storing a quantity of medicament. The device <NUM> is configured to be worn against a patient's skin and to deliver the medicament by injection. The device <NUM> is described below in the context of a bolus injector, but it will be appreciated that it could alternatively be another type of Large Volume Device (LVD) or other medicament injection device.

Referring to <FIG>, the device <NUM> comprises a housing <NUM> in which the delivery system <NUM>, including the medicament reservoir <NUM> is located, together with other components of the device <NUM> (not all shown). The housing <NUM> is formed from moulded plastics or another suitable material. The medicament reservoir <NUM> is provided as a flexible and/or collapsible container <NUM>, which may contain a single dose of the medicament. The medicament reservoir <NUM> may be replaceable to allow re-use of the device <NUM>. Alternatively, the medicament reservoir <NUM> may be non-replaceable in the device <NUM> so that, once the medicament within the medicament reservoir <NUM> has been expelled, the device <NUM> can no longer be used to deliver medicament and must be disposed of. This single-use nature of the device <NUM> facilitates ease of operation and improves safety by ensuring that a patient cannot mistakenly install an incorrect replacement medicament reservoir <NUM>.

The device <NUM> includes an injection element for injection of the medicament from the device <NUM> into the patient. The injection element is explained below in the context of a hollow injection needle <NUM>, as illustrated in <FIG>. However, other injection elements are envisaged within the scope of the invention, as discussed below, although it will be appreciated that other types of injection element could alternatively be used. The medicament is delivered through the needle <NUM>. A proximal end (not shown) of the needle <NUM> is fluidly connected to the medicament reservoir <NUM>. The needle <NUM> is therefore arranged to receive medicament from the medicament reservoir <NUM>. The needle <NUM> comprises a distal end <NUM> which, during use, protrudes through the housing <NUM> of the device <NUM> into the body tissue of the patient.

The injection needle <NUM> may be controllably extendable and/or retractable through the exterior of the housing <NUM> in order to allow it to be safely stowed in the housing <NUM> when not in use. Such a control mechanism is not shown in <FIG>, although is described with reference to <FIG> showing an alternative embodiment of the invention, hereafter. Such control mechanism may also include means to control delivery of the medicament from the medicament reservoir <NUM> through the needle <NUM> and/or may automatically extend and retract the needle <NUM> during a medicament delivery program.

The housing <NUM> includes a contact region <NUM> arranged to be worn against the skin of the patient during use of the device <NUM>. The contact region <NUM> comprises a contact face of the housing <NUM> in the exemplary embodiment shown in <FIG>. The contact region <NUM> may have geometric and tactile properties that are selected to be comfortable when worn against the skin of the patient. The contact region <NUM> includes an aperture <NUM> through which the injection needle <NUM> protrudes into the body tissue of the patient during delivery of the medicament.

During use of the device <NUM>, the contact region <NUM> is held against the skin of the patient by a fastener. The fastener is suitable for holding the contact region <NUM> in a stable position against the skin for a significant period of time, such as several hours, in order to ensure that the injection needle <NUM> is maintained in a fixed position relative to the body of the patient during use of the device <NUM>. The exemplary fastener shown in <FIG> is an adhesive layer <NUM> for temporarily adhering the contact region <NUM> to the skin of the patient. The adhesive layer <NUM> may comprise a standard biocompatible glue, as used in common adhesive bandages. In order to protect the adhesive layer <NUM> from damage and to prevent it from sticking to unwanted objects prior to it being attached to the skin of the patient, the contact region <NUM> of the device <NUM> may include a protective covering (not shown) which overlies the adhesive layer <NUM>. The protective covering is selectively removable from the contact region <NUM> in order to expose the adhesive layer <NUM> before use of the device <NUM>, for example by peeling the covering away from the adhesive layer <NUM>.

The medicament delivery system <NUM> of the medicament injection device <NUM> comprises a support member in the form of a support plate <NUM> and a compression member in the form of a compression plate <NUM>. The support plate <NUM> and compression plate <NUM> are substantially parallel to, and spaced from each other. The support and compression members <NUM>, <NUM> are preferably substantially rigid planar components. In the embodiment shown, the support and compression plates <NUM>, <NUM> are circular and coaxial about a common axis X-X. A gap <NUM> is defined between the support plate <NUM> and the compression plate <NUM>. The medicament reservoir <NUM> is disposed in the gap <NUM> and is contacted on opposite sides by the support plate <NUM> and the compression plate <NUM>. The support member <NUM> is fixed relative to the housing <NUM>. The compression member <NUM> is moveable relative to the support member <NUM> and to the housing <NUM>.

A mechanical coupling connects the support plate <NUM> and compression plate <NUM> in a manner that permits the compression plate <NUM> to rotate relative to the support plate <NUM> about the axis X-X, and also permits the compression plate <NUM> to move towards and away from the support plate <NUM> in the axial direction. Furthermore, the mechanical coupling is configured such that rotation of the compression plate <NUM> relative to the support plate <NUM> causes the compression plate <NUM> to move towards and away from the support plate <NUM>. The mechanical coupling comprises a plurality of connecting members in the form of rigid connecting rods <NUM>. Each connecting rod <NUM> is connected at one end to the support plate <NUM> and at its other end to the compression plate <NUM>. In the embodiment shown, the connections between the connecting rods <NUM> and the support plate <NUM>/compression plate <NUM> comprise ball-and-socket type joints. Each connecting rod <NUM> has a ball element <NUM> at each end. The support plate <NUM> and compression plate <NUM> are each formed with part-spherical sockets <NUM> configured to receive and rotatably retain the ball elements <NUM> of the connecting rods <NUM>.

A biasing member is provided on the opposite side of the compression member <NUM> to the medicament reservoir <NUM>. The biasing member is configured to at least exert a rotational force on the compression member <NUM> to urge the compression member <NUM> to rotate relative to the support member <NUM>. In the exemplary embodiment of the invention shown, the biasing member is in the form of a conical torsion spring <NUM>. A first end <NUM> of the torsion spring <NUM> is secured to the compression plate <NUM>. A second, opposite end <NUM> of the torsion spring <NUM> is fixedly secured relative to the housing <NUM>. The second end <NUM> may be fixedly secured to the housing <NUM> itself, or to a component or mechanism that is fixed relative to the housing <NUM>. The conical torsion spring <NUM> may also be configured to exert a force on the compression plate <NUM> to bias the compression plate <NUM> towards the support plate <NUM>, substantially in a direction of axis X-X.

The device <NUM> includes a locking mechanism <NUM> configured to engage with the compression plate <NUM> and/or the torsion spring <NUM> to hold the support plate <NUM> in place against the force of the torsion spring <NUM>. The locking mechanism <NUM> may be provided in the housing <NUM> and the second end <NUM> of the torsion spring <NUM> may be secured to the locking mechanism <NUM>. The locking mechanism <NUM> includes a release button <NUM> accessible from the outside of the housing <NUM>. The release button <NUM> may be operable by a user to disengage the locking mechanism <NUM> to release the compression plate <NUM>/torsion spring <NUM> to allow the compression plate <NUM> to move under the biasing force of the torsion spring <NUM>.

The medicament delivery system <NUM> is shown in more detail in various stages during use in <FIG>. As with <FIG>, <FIG> show the medicament delivery system <NUM> without the medicament reservoir <NUM>, for ease of illustration. <FIG> show the medicament delivery system in a fully expanded state. That is, the support plate <NUM> and the compression plate <NUM> are spaced as far apart by the maximum distance permitted by the connecting rods <NUM>. In such configuration, the connecting rods <NUM> extend substantially perpendicular to the support and compression plates <NUM>, <NUM>. Therefore, the respective spherical sockets <NUM> in the support and compression plates <NUM>, <NUM> are aligned in the axial direction. In the fully expanded state, the gap <NUM> is therefore at its maximum size and accommodates the medicament reservoir <NUM> when full with medicament. This configuration is shown in <FIG>, with the omission of the torsion spring <NUM>.

<FIG> show the medicament delivery system <NUM> is a partially compressed state. Here the torsion spring <NUM> has been released by the locking mechanism <NUM> and urges the compression plate <NUM> in a rotational direction about axis X-X relative to the support plate <NUM>. The compression plate <NUM> is thereby caused to rotate in the direction shown by arrow 'A' relative to the support plate <NUM>. This causes the respective spherical sockets <NUM> in the support and compression plates <NUM>, <NUM> to be rotationally off-set about the axis X-X. Since the connecting rods <NUM> are rigid and inextensible, this causes the compression plate <NUM> to be drawn towards the support plate <NUM>, reducing the size of the gap <NUM>. This causes the medicament reservoir <NUM> to be compressed and the medicament therein to be expelled from the medicament reservoir through the needle <NUM> into the patient.

<FIG> show the medicament delivery system <NUM> in a fully compressed state. Here, the torsion spring <NUM> has continued to urge the compression plate <NUM> in the direction of arrow 'A' in a rotational direction about axis X-X relative to the support plate <NUM>. The compression plate <NUM> has been further drawn towards the support plate <NUM>, further reducing the size of the gap <NUM>. A medicament reservoir <NUM> disposed in the gap <NUM> would therefore have been further compressed and the full dose of the medicament therein would have been expelled from the medicament reservoir <NUM> through the needle <NUM> into the patient. As mentioned above, the torsion spring <NUM> may also be configured to exert a force on the compression plate <NUM> in an axial direction towards the support plate <NUM>, as well as exerting a rotational force. This may beneficially further urge the medicament delivery system into the compressed state and so help compress the medicament reservoir <NUM> to expel the medicament therein.

Operation of the medicament injection device <NUM> will now be described. A user initially removes the protective covering from the adhesive layer <NUM> and applies the device <NUM> at the intended injection site, with the contact region <NUM> facing the patient's body. The distal end <NUM> of the needle <NUM> pierces the patient's skin. This may be by the control mechanism (not shown) moving the needle to an extended position, or by the placement of the device <NUM> at the injection site.

The release button <NUM> is pressed to disengage the locking mechanism <NUM>. This releases the torsion spring <NUM> and/or compression plate <NUM>. The torsion spring <NUM> urges the compression plate <NUM> in a rotational direction about axis X-X, as shown by arrow 'A' in <FIG> and <FIG>. The compression plate <NUM> rotates relative to the support plate <NUM> about the axis X-X. However, since the connecting rods <NUM> are rigid and inextensible, the compression plate <NUM> is caused to also move towards the support plate <NUM> from the expanded state shown in <FIG> to the partially compressed state shown in <FIG>. The size of the gap <NUM> thereby reduces and so the flexible medicament reservoir <NUM> is squeezed between the support plate <NUM> and the compression plate <NUM>. This causes the medicament within the medicament reservoir <NUM> to be expelled through the needle <NUM> into the patient's body.

The torsion spring <NUM> continues to rotationally urge the compression plate <NUM> and cause it to rotate relative to, and move towards, the support plate <NUM>. This continues through the partially compressed state shown in <FIG> until the device reaches the fully compressed state shown in <FIG>. Once in the fully compressed state, the medicament reservoir <NUM> is collapsed to a point by which the full dose of medicament has been expelled though the needle <NUM> into the patient's body. The device <NUM> can then be removed from the patient's body and discarded or saved for reuse, if it is a reusable device that can be refilled/a replacement medicament reservoir installed.

<FIG> shows an alternative embodiment of a medicament injection device <NUM>' of the invention, including a medicament delivery system <NUM> of the invention. Like features in common with the embodiment shown in <FIG> retain the same reference numerals and description thereof will not be repeated. The embodiment shown in <FIG> illustrates a control mechanism <NUM> configured to extend and retract the injection needle <NUM> and control a medicament injection process. The control mechanism <NUM> may comprise a control unit <NUM> to which the needle <NUM> is connected. The needle <NUM> may be connected to the control unit <NUM> via a valve <NUM> to enable control of the flow of medicament. A conduit <NUM> fluidly connects an outlet of the medicament reservoir <NUM> to the needle <NUM> via the control unit <NUM> and the valve <NUM>.

The control unit <NUM> is mounted on a piston <NUM> to enable the needle <NUM> to move between a retracted position and an extended position, as shown by arrow 'B' in <FIG>. In the retracted position, the needle is contained within the housing <NUM>. In the extended position, the needle <NUM> extends through the hole <NUM> in the contact region <NUM>. An injector spring <NUM> is provided to provide additional biasing force to assist the needle <NUM> moving to the extended position and piercing the patient's skin. An actuator <NUM> is provided on the housing <NUM> and is connected to the control unit <NUM>. The actuator may comprise a button, switch or other suitable component. Pressing the actuator <NUM> causes the control unit <NUM> to move the injection needle <NUM> into the extended position ready for a medicament delivery process to be initiated by pressing the release button <NUM>, as described previously. In an alternative embodiment however, the locking mechanism <NUM> may be connected to the control unit <NUM> (as shown by the dashed line in <FIG>). In such an embodiment, the actuator <NUM> may be omitted. In such an embodiment, pressing the release button <NUM> would cause the control unit <NUM> to move the needle <NUM> into the extended position, and would also initiate medicament delivery by the medicament delivery system <NUM> as described previously. Flow of the medicament through the needle <NUM> may be controlled by the control unit <NUM> by opening the valve <NUM> once the needle <NUM> is fully inserted into the patient's body tissue. It will be appreciated that in such an embodiment, the needle injection step and the medicament delivery step would not be two independent steps to be performed by a user.

The control mechanism <NUM> may be electrically powered. For example, the piston <NUM> may be electrically powered. Electrical power may also be used to retract the injector spring <NUM>, control unit <NUM> and injection needle <NUM> back to the retracted position, thereby withdrawing the injection needle <NUM>. For this purpose, the control mechanism <NUM> may comprise an electrical motor (not shown) and a suitable drive mechanism (not shown) coupled to the piston <NUM>. The electrical power may be provided by a battery (not shown) or other power source in the device <NUM>, which may be rechargeable.

The control unit <NUM> may comprise an electronic controller (not shown) which is configured to control operation of various elements of the device <NUM>. An alternative is for the control unit to operate under the control of a timing element, such as a mechanical timer. The timing element may be a count-down timer. The elapse of a count-down period of the timing element may indicate that an event has occurred, such as the completion of an injection of a dose of medicament. The elapse of the count-down period may cause the piston <NUM> to move the injection needle <NUM>, for example by withdrawing the injection needle back into the housing <NUM> of the device <NUM>.

Examples of alternative injection elements intended within the scope of the invention include a cannula which may be sharpened to facilitate its insertion into the body tissue of the patient. A separate needle (not shown) or trocar (not shown) may be provided for aiding the insertion of a distal end of such a cannula into the body tissue. The needle may be controllably extendable and/or retractable from the housing <NUM> of the device <NUM> in a similar manner to the hollow injection needle <NUM> discussed above. The needle may be configured to pierce the skin of the patient in order to allow the cannula to move into the body tissue. The needle may, for example, be arranged to extend through the centre of the cannula. Once the skin has been pierced, the device <NUM> may be configured to retract the needle back into the housing before delivery of the medicament. In the case that the device <NUM> comprises a separate needle of the type described above, the device may comprise an actuator to facilitate the extension and retraction of the needle.

It will be appreciated that the inventive concept of the medicament delivery system the present invention may be applicable to LVDs. However, the invention is not intended to be limited to this particular type of medicament delivery device and the present invention is intended to cover alternative types of medicament delivery devices which include a medicament container to be received in a medicament delivery device which may include, but are not limited to, patch pumps and infusion pumps.

The terms "drug" or "medicament" which are used interchangeably herein, mean a pharmaceutical formulation that includes at least one pharmaceutically active compound. The term "drug delivery device" shall be understood to encompass any type of device, system or apparatus designed to immediately dispense a drug to a human or non-human body (veterinary applications are clearly contemplated by the present disclosure). By "immediately dispense" is meant an absence of any necessary intermediate manipulation of the drug by a user between discharge of the drug from the drug delivery device and administration to the human or non-human body. Without limitation, typical examples of drug delivery devices may be found in injection devices, inhalers, and stomach tube feeding systems. Again without limitation, exemplary injection devices may include, e.g., syringes, autoinjectors, injection pen devices and spinal injection systems.

Those of skill in the art will understand that modifications (additions and/or removals) of various components of the substances, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

Exemplary insulin derivatives 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-gamma-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta¬decanoyl) human insulin. Exemplary GLP-<NUM>, GLP-<NUM> analogues and GLP-<NUM> receptor agonists are, for example: Lixisenatide / AVE0010 / ZP10 / Lyxumia, Exenatide / Exendin-<NUM> / Byetta / Bydureon / ITCA <NUM> / AC-<NUM> (a <NUM> amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide / Victoza, Semaglutide, Taspoglutide, Syncria / Albiglutide, Dulaglutide, rExendin-<NUM>, CJC-<NUM>-PC, PB-<NUM>, TTP-<NUM>, Langlenatide / HM-11260C, CM-<NUM>, GLP-<NUM> Eligen, ORMD-<NUM>, NN-<NUM>, NN-<NUM>, NN-<NUM>, Nodexen, Viador-GLP-<NUM>, CVX-<NUM>, ZYOG-<NUM>, ZYD-<NUM>, GSK-<NUM>, DA-<NUM>, MAR-<NUM>, MAR709, ZP-<NUM>, ZP-<NUM>, TT-<NUM>, BHM-<NUM>. MOD-<NUM>, CAM-<NUM>, DA-<NUM>, ARI-<NUM>, ARI-<NUM>, Exenatide-XTEN and Glucagon-Xten.

Claim 1:
A medicament delivery system (<NUM>) for use with a medicament delivery device (<NUM>, <NUM>'), the medicament delivery system (<NUM>) comprising:
a support member (<NUM>);
a compression member (<NUM>) spaced from the support member (<NUM>) to define a gap (<NUM>) therebetween;
a collapsible and/or flexible medicament reservoir (<NUM>) disposed in the gap (<NUM>) between the support member (<NUM>) and the compression member (<NUM>);
a mechanical coupling between the support member (<NUM>) and the compression member (<NUM>) comprising a plurality of connecting members (<NUM>) extending between the support member (<NUM>) and the compression member (<NUM>); and
a biasing element (<NUM>) connected to the compression member (<NUM>) and configured to exert a rotational force on the compression member (<NUM>) relative to the support member (<NUM>);
wherein the mechanical coupling is configured such that rotation of the compression member (<NUM>) relative to the support member (<NUM>) causes the compression member (<NUM>) to be drawn towards the support member (<NUM>) to reduce the gap (<NUM>) therebetween such that when medicament is contained in the medicament reservoir (<NUM>) the medicament is dispensed therefrom.