Patent Description:
Needle-based medicament delivery devices are one of the most commonly used means for the administration of medicament to a patient. Despite significant advances, this type of devices still have disadvantages. One such disadvantage is that the use of a needle to inject medicament into the patient's skin unavoidably involves making a hole into the injection site, thereby causing tissue injury. In addition, it is known that the penetration of the injection needle into the skin can be painful for the patient, in particular for a child.

Patch pumps, such as insulin pumps used by Type <NUM> or Type <NUM> diabete sufferers, are a particular type of needle-based medicament delivery devices. This type of devices are configured to automatically and periodically inject a fixed amount of insulin to the patient, by means of an hypodermic injection needle. One disadvantage is that the needle has to be permanently inserted into the patient's body. This may be unpleasant and uncomfortable for the patient and may lead to irritations and complications.

At least in certain embodiments, the present invention sets out to overcome or alleviate at least some of the problems mentioned above. In particular, the present invention sets out to provide a device for delivery of medicament which reduces the discomfort induced by the introduction and/or presence of a needle into the skin of the patient.

<CIT> discloses delivery devices and systems for the delivery of particles into a biological tissue. The device includes a gas source comprising a gas or capable of selectively producing a gas, a first particle source comprising a first plurality of particles, and a first collimator fluidly connected with the gas source and adapted to form a collimated stream of the first plurality of particles entrained in the gas. The device also includes a tissue-interfacing surface adapted to interface with a surface of the tissue and orient the first collimator with the tissue such that the collimated stream of the first plurality of particles will penetrate the tissue in a direction substantially perpendicular to the surface of the tissue. The gas source may be, for example, a system that relies upon phase transformation, such as boiling of water to generate steam.

<CIT> discloses a transdermal delivery system including a support structure and a fluid reservoir within the support structure configured to contain a fluid to be delivered transdermally. There is also at least one exit orifice defined in the support structure that is in communication with the fluid reservoir. The orifice has a diameter of between about <NUM> micrometre and <NUM> micrometre. Furthermore, a repeatable activation means is disposed within the support structure and is in cooperation with the exit orifice for ejection of fluid in response to an activation signal.

<CIT> discloses a jet dispenser using inkjet technology, such as that used in printing, that cutaneously delivers bioactive agents. The dispenser propels volumes of bioactive agent toward the skin, where they exert a local or topical effect, or move through the skin for transdermal systemic delivery. Drugs are either delivered directly to the skin, or are introduced into a transdermal patch, which may receive repeated dosages. A controller in the dispenser may control delivery of multiple different drugs, timing of drug administration, or change drug regimens in response to a changing medical condition of a patient, such as those monitored by a sensor in communication with the controller, for example to prevent an overdose. The dispenser may act as an electromechanical patch, capable of long term administration of drugs to the skin, to achieve local or systemic pharmaceutical effects. Also disclosed is a transdermal application system for applying a bioactive substance to a skin surface using a patch. The system comprises a vaporisation chamber which receives the bioactive substance from a reservoir and vaporises the bioactive substance. The system further comprises a film firing resistor which when energised ejects the bioactive substance in the form of a fluid sroplet towards the patch.

Aspects of the present invention relate to a medicament delivery device.

According to the present invention, there is provided a medicament delivery device comprising a medicament receiving element configured to directly receive a medicament from a medicament reservoir, at least one fluid chamber having a fluid outlet configured to direct fluid vapour towards the medicament receiving element, a heating element for heating the fluid in the at least one fluid chamber, the device being configured such that, in use, the heating element heats the fluid in the at least one fluid chamber to at least partially evaporate the fluid so that the vapor pressure in the at least one fluid chamber increases until reaching a threshold value at which the fluid is expelled out of the at least one fluid chamber through the fluid outlet towards the medicament receiving element and entrains the medicament towards the patient's skin.

The fluid outlet may comprise a micro-nozzle.

The fluid outlet may comprise a non-return valve.

The heating element may be resistive and may be configured to receive pulses of electrical current to heat the fluid.

The at least one fluid chamber may comprise an insulating element to prevent heat dissipation.

The medicament delivery device may comprise a fluid reservoir and a fluid pump mechanism for pumping the fluid from the fluid reservoir to the at least one fluid chamber.

The medicament receiving element may comprise a porous member configured to retain the medicament and arranged such that, in use, medicament passes from the porous member towards the patient's skin when entrained in fluid expelled out of the fluid outlet of the at least one fluid chamber.

The medicament receiving element may comprise a distribution sieve arranged such that, in use, medicament passes through the distribution sieve towards the patient's skin when entrained in fluid expelled out of the fluid outlet of the at least one fluid chamber.

The medicament receiving element may comprise a chamber configured to receive the medicament, the chamber including a delivery portion for delivering the medicament from the chamber to the patient.

The medicament delivery device may comprise a plurality of fluid chambers.

The medicament delivery device may comprise a cartridge of medicament.

The medicament delivery device may comprise a processor for controlling the medicament delivery to the patient.

The medicament delivery device may be an insulin delivery device.

The medicament delivery device may comprise a blood glucose sensor configured to send data relating to the blood glucose of the patient to the processor so that the processor controls the insulin delivery to the patient.

In one embodiment, the medicament receiving element is gas permeable.

In one embodiment, the medicament delivery device is configured such that the fluid is expelled out of the at least one fluid chamber through the fluid outlet and passes through the medicament receiving element.

In one embodiment, the medicament delivery device is configured such that medicament is transported to the medicament receiving element and, subsequently, the heating element heats the fluid in the at least one fluid chamber to at least partially evaporate the fluid.

In one embodiment, the heating element is configured to increase in temperature to heat the fluid in the at least one fluid chamber.

The present disclosure further presents a method of expelling a medicament from a medicament delivery device comprising a medicament receiving element configured to directly receive a medicament from a medicament reservoir, at least one fluid chamber having a fluid outlet configured to direct fluid vapour towards the medicament receiving element, and a heating element for heating the fluid in the at least one fluid chamber, the method comprising using the heating element to heat the fluid in the at least one fluid chamber to at least partially evaporate the fluid so that the vapor pressure in the at least one fluid chamber increases until reaching a threshold value at which the fluid is expelled out of the at least one fluid chamber through the fluid outlet towards the medicament receiving element and entrains the medicament towards the patient's skin.

The terms "drug" or "medicament" which are used interchangeably herein, mean a pharmaceutical formulation that includes at least one pharmaceutically active compound.

The term "medicament 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. patch devices, autoinjectors, injection pen devices and spinal injection systems.

Exemplary embodiments of the present invention are described with reference to the accompanying drawings, in which:.

Embodiments of the present disclosure provide a medicament delivery device comprising a medicament receiving element, at least one fluid chamber having a fluid outlet configured to direct fluid vapour towards the medicament receiving element, a heating element for heating the fluid in the at least one fluid chamber, the device being configured such that, in use, the heating element heats the fluid in the at least one fluid chamber to at least partially evaporate the fluid so that the vapor pressure in the at least one fluid chamber increases until the fluid is expelled out of the at least one fluid chamber through the fluid outlet towards the medicament receiving element and entrains the medicament towards the patient's skin. Providing such a medicament delivery mechanism allows to avoid the use of an injection needle for delivering the medicament to the patient. Since no injection needle is needed, the medicament delivery does not require making a hole into the injection site and therefore avoids causing tissue injury, as well as pain and discomfort. In addition, irritations and complications that may occur due to the introduction and/or presence of a needle into the skin of the patient are avoided.

According to some embodiments of the present disclosure, an exemplary drug delivery device <NUM>, herein simply referred to as "device <NUM>", is shown in <FIG>.

In the context of this application, the terms "proximal" and "distal" herein respectively refer to as relatively closer to the patient and relatively further away from the patient. Moreover, the terms "upstream" and "downstream" are used herein in relation to the direction of medicament flow and fluid flow through the device in normal use. Furthermore, the terms "vertically", "horizontally" and so forth are used herein in relation to the orientation of the device shown in the accompanying drawings.

The drug delivery device, as described herein, may be configured to inject a medicament into a patient. Such a device could be operated by a patient or care-giver, such as a nurse or physician. The device in accordance with the present invention includes a large volume device ("LVD") or patch pump, configured to adhere to a patient's skin for a period of time (e.g., about <NUM>, <NUM>, <NUM>, <NUM>, <NUM> minutes or longer) to deliver a "large" volume of medicament (typically about <NUM> to about <NUM> or more). As will be explained in more detail below, in the embodiment described herein, the medicament delivery device is configured to deliver medicament by repeated medicament discharges or "shots".

In combination with a specific medicament, the presently described device may also be customized in order to operate within required specifications. For example, the device may be customized to inject a medicament within a certain time period (e.g. about <NUM> minutes to about <NUM> minutes or longer).

The delivery devices described herein can also include one or more automated functions. For example, the medicament injection can be automated. Energy for one or more automation steps can be provided by one or more energy sources. Energy sources can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, elastomers, or other mechanical mechanisms to store or release energy. One or more energy sources can be combined into a single device. Devices can further include gears, valves, or other mechanisms to convert energy into movement of one or more components of a device.

The one or more automated functions of the present drug delivery device may each be activated via an activation mechanism. Such an activation mechanism can include one or more of a button, a lever, or other activation component. Activation of an automated function may be a one-step or multi-step process. That is, a user may need to activate one or more activation components in order to cause the automated function. For example, in a one-step process, a user may depress a button or interact with a user interface in order to cause injection of a medicament. Other devices may require a multi-step activation of an automated function.

Device <NUM> includes a body or housing <NUM> which typically contains a reservoir <NUM> pre-filled with liquid medicament to be injected, and the components required to facilitate one or more steps of the delivery process. Device <NUM> can also include a protective cover <NUM> that can be detachably mounted to the housing <NUM>. Typically, when using the device <NUM> for the first time, a user must remove the protective cover <NUM> from the housing <NUM> before the device <NUM> can be operated.

As shown in <FIG>, the device <NUM> includes a medicament retaining element or medicament receiving element <NUM> configured to receive medicament from the medicament reservoir <NUM>. The device <NUM> also comprises a fluid reservoir <NUM> and a plurality of fluid chambers <NUM> configured to receive fluid from the fluid reservoir <NUM>. The device <NUM> further comprises a processor <NUM> for monitoring and/or controlling the operation of the device <NUM> and a power supply <NUM>, such as a disposable or rechargeable battery, or a power supply <NUM> configured to generate a pulsed current. The device <NUM> further comprises a user interface <NUM> and a wireless communication unit <NUM>.

The device <NUM> is preferably a wearable device. Such devices are commonly referred to as "patch pumps" due to their nature of being worn or affixed to the user's skin. The device <NUM> comprises a device holding element <NUM> operating e.g. with vacuum to adhere the device <NUM> to the patient's skin. Alternatively, the holding element <NUM> may be in the form of an adhesive pad configured to adhere to the patient's skin. The adhesive pad is attached to the skin attachement side of the device <NUM> and covered by the protective cover <NUM> prior to the first use of the device <NUM>.

In the device <NUM> described herein, the medicament receiving element <NUM> is in the form of distribution sieve, or mesh, or fleece <NUM>. The distribution sieve <NUM> is arranged downstream of the fluid chambers <NUM>. In use, the distribution sieve <NUM> is fed with medicament flowing from the medicament reservoir <NUM>, and delivers droplets of medicament to the patient's skin. The protective cover <NUM> may be attached to the distribution sieve <NUM> prior to the first use of the device <NUM>.

The device <NUM> comprises a medicament outflow line <NUM> through which medicament can flow, from the medicament reservoir <NUM> towards the distribution sieve <NUM>. A medicament pump mechanism <NUM> is provided in the medicament outflow line <NUM> for pumping the medicament from the medicament reservoir <NUM> towards the distribution sieve <NUM>. The medicament pump mechanism <NUM> comprises a non-return valve or check valve <NUM> for allowing the medicament to flow through the medicament outflow line <NUM> in only one direction, from the medicament reservoir <NUM> towards the distribution sieve <NUM>.

The fluid reservoir <NUM> is adapted to receive and/or store a fluid intended to evaporate and entrain or propel the medicament through the distribution sieve <NUM> towards the patient's skin. The fluid used in the device <NUM> described herein is a liquid, e.g. sterile water. Water, used as the fluid to expel the medicament out of the device <NUM>, has the advantage of being a neutral solution and not causing any side effect to the patient.

The fluid reservoir or water reservoir <NUM> is connected to the fluid chambers <NUM> by means of a fluid outflow line <NUM>. A fluid pump mechanism <NUM> is provided in the fluid outflow line <NUM> for pumping the fluid from the fluid reservoir <NUM> to the fluid chambers <NUM>. The fluid pump mechanism <NUM> comprises a non-return valve or check valve <NUM> for allowing the fluid to flow through the fluid outflow line <NUM> in only one direction, from the fluid reservoir <NUM> towards the fluid chambers <NUM>.

The fluid chambers <NUM> are disposed downstream of the fluid reservoir <NUM> and upstream of the distribution sieve <NUM>. The fluid chambers <NUM> are aligned horizontally with each other. A fluid chamber <NUM> includes a fluid inlet 29a and a fluid or steam outlet 29b. The fluid inlet 29a is arranged in an upper wall of the fluid chamber <NUM>. The fluid outlet 29b is arranged in a bottom wall of the fluid chamber <NUM>. The fluid outlet 29b extends substantially vertically from the fluid chamber <NUM>. The fluid outlet 29b is configured to direct fluid vapour towards the distribution sieve <NUM>. The fluid chambers <NUM> are similar to each other. The number of fluid chambers <NUM> in the device <NUM> depends on the quantity of fluid or medicament to be injected over time. In the embodiment where the device <NUM> is intended to be used for long-term administration of medicament such as insulin, the device may comprise a single fluid chamber <NUM> (as shown in <FIG>). In the embodiment where the device <NUM> is a large volume device ("LVD"), e.g. configured to deliver <NUM> or more of medicament in e.g. one hour, the device <NUM> may comprise two or more fluid chambers <NUM>. In a preferred embodiment, the device <NUM> comprises two fluid chambers <NUM>. In use, the device <NUM> may be positioned at several different locations on the patient's skin, to avoid any irritation of the patient's skin due repeated medicament injections at a same injection site. Moreover, the device <NUM> may be positioned at several different locations on the patient's skin in order to reduce the pain feeling due to the memory of the nerves, that may appear after repeated injections at a same injection site.

The fluid outlet 29b has a cross-sectional area substantially smaller than the cross-sectional area of the fluid chamber <NUM>. In the device <NUM> described herein, the fluid outlet 29b is in the form of a micro-nozzle. Such a configuration for the fluid outlet 29b ensures that when the fluid evaporates in the fluid chamber <NUM>, a surge of vapour pressure is produced within the fluid chamber <NUM>. When the fluid evaporates in the fluid chamber <NUM>, the vapour pressure in the fluid chamber <NUM> increases until reaching a threshold value at which the fluid vapour is ejected out of the fluid chamber <NUM> through the micro-nozzle and discharges abruptly in the distribution sieve <NUM>. In other words, a water vapour explosion or steam blast occurs in the fluid chamber <NUM> when the vapour pressure reaches the threshold value in the fluid chamber <NUM>, such that water steam is propelled out of the fluid chamber <NUM>, through the fluid outlet 29b, into the distribution sieve <NUM>.

A heating element <NUM> is provided for heating the fluid within the fluid chamber <NUM>. The heating element <NUM> is arranged in the fluid chamber <NUM>. The heating element <NUM> is arranged such that, in use, the heating element <NUM> is in contact with the water received in the fluid chamber <NUM>. The heating element <NUM> is for example in the form of a resistive layer or mold arranged on a inner wall of the fluid chamber <NUM>. In the embodiment described herein, the heating element <NUM> is configured to receive pulses of electrical current from the power supply <NUM> to heat the water in the fluid chamber <NUM>. More generally, the heating element <NUM> is configured to heat the fluid discontinuously in the fluid chamber <NUM>, to cause corresponding discontinuous surges of vapour pressure within the fluid chamber <NUM>, and thereby corresponding medicament discharges towards the patient's skin.

To estimate the heating power needed to evaporate water in the fluid chamber <NUM>, the following formula is used : <MAT> where ΔQ is the amount of energy transferred from the heating element <NUM> to the water, ΔT is the temperature difference, C is the heat capacity of water vapour, m is the mass of water heated and c is the mass heat capacity of water vapour. For example, heating a water droplet of <NUM>µL, during <NUM> second, using a temperature increase of <NUM>, requires a heating power of <NUM>,<NUM> W. Heating the same volume of water using the same temperature increase, during only <NUM>, requires <NUM>,<NUM> W. To have a heating power of <NUM> W, the device <NUM> can for example include a heating element <NUM> in the form of a resistor having a resistance of <NUM>,<NUM> Ohms at a voltage of <NUM> Volts.

The heating element <NUM> may be protected by an over temperature protection (not shown), such as a bimetal thermal protector or a temperature sensor combined with the appropriate electronic components.

The heating element <NUM> is arranged to optimally heat the water, with minimum thermal loss. To further minimize thermal losses, the fluid chambers <NUM> comprise an insulating element <NUM>. The insulating element <NUM> is provided to prevent heat dissipation from the fluid chambers <NUM> and thereby enhances the efficiency of the heating of water in the fluid chamber <NUM>. The insulating element <NUM> is for example in the form of an insulating layer provided on an outer wall of the fluid chamber <NUM>, e.g. surrounding an outer wall of the fluid chamber <NUM>.

The parameters of the medicament delivery can be adapted depending on the medicament to be delivered and depending on the patient which the medicament is to be delivered to. Specifically, and not exhaustively, the speed of the medicament flow through the distribution sieve <NUM>, the size of the micro-nozzles, the water vapour temperature, and the quantity of water used, can be adapted depending on characteristics of the active ingredient of the medicament, e.g. the viscosity of the active ingredient, and depending on the patient, e.g. the type of the patient's skin etc..

The processor <NUM> controls the wireless communication unit <NUM>, which is configured to transmit and/or receive information to/from another device in a wireless fashion. Such transmission may for instance be based on radio transmission or optical transmission. In some embodiments, the wireless communication unit <NUM> is a Bluetooth transceiver. Alternatively, wireless communication unit <NUM> may be substituted or complemented by a wired unit configured to transmit and/or receive information to/from another device in a wire-bound fashion, for instance via a cable or fibre connection. When data is transmitted, the units of the data (values) transferred may be explicitly or implicitly defined. For instance, in case of an insulin dose, always International Units (IU) may be used, or otherwise, the used unit may be transferred explicitly, for instance in coded form.

The device <NUM> may include a blood glucose sensor (not shown) configured to send data relating to the blood glucose of the patient to the processor <NUM>. The processor <NUM> can therefore control the insulin delivery to the patient depending on e.g. the blood glucose level of the patient. For example, a blood glucose sensor as described in <CIT> may be used.

The operation of the medicament injection device <NUM> in accordance with the present invention will now be described.

The device <NUM> can be pre-programmed, e.g. either by the manufacturing facility or a healthcare provider so that no additional user programming is required. The device <NUM> can be programmed to deliver drug to the patient at different rates for different times of day or under different conditions. For example, for a patient that needs a quantity of insulin of <NUM> maximum per day, the device <NUM> can be programmed to deliver <NUM> of insulin per hour during <NUM> hours, e.g. by performing four injections of <NUM>µL per hour.

An injection is performed as follows. In use, the user activates the device <NUM> via the user interface <NUM>. The medicament is pumped by means of the medicament pump mechanism <NUM> from the medicament reservoir <NUM> through the medicament outflow line <NUM> towards the distribution sieve <NUM>. Meanwhile, the sterile water is pumped by means of the fluid pump mechanism <NUM>, from the fluid reservoir <NUM> through the fluid outflow line <NUM> towards the fluid chambers <NUM>. The water enters the fluid chambers <NUM> via the fluid inlets 29a. Then, pulses of current are generated by the power supply <NUM> and circulate through the resistive heating elements <NUM>. Consequently, the temperature of the heating elements <NUM> increases, and heat is transferred from the heating elements <NUM> to the water within the fluid chambers <NUM>. As water is heated, water evaporates and the vapour pressure in the fluid chambers <NUM> increases. It should be noted that as water is heated and evaporates in the fluid chambers <NUM>, water is sterilised again in the fluid chambers <NUM>. The vapour pressure increases until reaching a threshold value at which the water vapour is ejected out of the fluid chambers <NUM> through the micro-nozzles 29b, discharges abruptly towards the distribution sieve <NUM>, and entrains the medicament through the distribution sieve <NUM>, towards the patient's skin.

The water streams propelled out of the fluid chambers <NUM> ensure that the medicament flow has a sufficient speed to overcome the skin barrier and penetrate deep enough into the patient's skin. The injection depth of the medicament into the patient's skin also depends on the diameter of the micro-nozzles forming the fluid outlets 29b. As an example, a micro-nozzle diameter of approximately <NUM> and a medicament flow travelling at around <NUM>/s can achieve an injection depth of around <NUM>.

Moreover, as the vapour pressure of the water vapour decreases in the distribution sieve <NUM>, the temperature of the stream decreases consequently. The liquid medicament being at room temperature, the temperature of the stream of medicament flowing out of the device <NUM> through the distribution sieve <NUM> is sufficiently low such that, during the injection, the patient does not feel discomfort due to the temperature of the medicament stream.

Although the device <NUM> of the first embodiment has been described as having a medicament receiving element <NUM> in the form of a distribution sieve, the invention is not intended to be limited to this particular type of device and other types of device are intended to fall within the scope of the invention. For example, in an alternative embodiment, the medicament receiving element comprises a porous member, e.g. a carrier web or an absorbent pad. The absorbent pad is arranged downstream of the fluid chambers and is adapted to retain the medicament by absoption. In use, the absorbent pad is fed with medicament flowing from the medicament reservoir. The water vapour expelled out of the fluid chambers through the fluid outlet flows through the absorbent pad where it contacts the medicament and entrains the medicament towards the patient's skin. In a further alternative embodiment, the medicament receiving element comprises both the absorbent pad and the distribution sieve. The absorbent pad is disposed above the distribution sieve. The absorbent pad and the distribution sieve are disposed downstream of the fluid chambers. In use, the water vapour which is expelled out of the fluid chambers through the fluid outlet flows into the absorbent pad where it contacts the medicament and entrains the medicament through the distribution sieve, towards the patient's skin.

A medicament delivery device <NUM> of a second embodiment is shown in <FIG> and is similar to the device <NUM> of the first embodiment. Like features retain the same reference numerals and a detailed description of such like features will not be repeated.

A difference with the device <NUM> of the second embodiment over the device <NUM> of the first embodiment is that, in the device <NUM> of the second embodiment, the device <NUM> comprises a single fluid chamber <NUM>. However, in a variant, the device <NUM> could comprise two or more fluid chambers <NUM>.

An additionnal difference with the device <NUM> of the second embodiment over the device <NUM> of the first embodiment is that, in the device <NUM> of the second embodiment, the fluid inlet 29a is arranged in a side wall of the fluid chamber <NUM>. In addition, the medicament receiving element <NUM> is in the form of a chamber <NUM> connected to the steam outlet 29b, downstream of the steam outlet 29b. The chamber <NUM> comprises a delivery portion in the form of a dispensing nozzle <NUM> extending downwards from the chamber <NUM>. The dispensing nozzle <NUM> may be a micro-nozzle. The dispensing nozzle <NUM> not only provides an orifice through which the medicament flows out of the device <NUM>, but also provides a surface which contacts the patient's skin. The fluid outlet 29b is in the form of a passage of reduced diameter, thereby forming a venturi passage or venturi nozzle <NUM>. A non-return valve or check valve <NUM>, for example a spring-tensioned ball check valve (represented in <FIG>) is disposed in the venturi nozzle <NUM>. The check valve <NUM> ensures that the water vapour does not leak from the fluid chamber <NUM> before the vapour pressure reaches the threshold value. The check valve <NUM> can be adjusted such that the medicament stream flowing through the dispensing nozzle <NUM> has a sufficient speed when flowing towards the patient's skin. In an alternative embodiment, the fluid outlet 29b comprises a solenoid valve in combination with a pressure sensor. Such alternative arrangement provides the advantage that the steam flow through the fluid outlet 29b is easy to control.

In the device <NUM>, the water vapour cools down while flowing in the chamber <NUM>. This decrease of temperature allows for an efficient mixing of the water and the medicament, thereby allowing an efficient transport of the medicament out of the device <NUM> towards the patient's skin.

Although the devices <NUM>, <NUM> of the first and second embodiments have been described as having a fluid pump mechanism <NUM> disposed in the fluid outflow line <NUM>, the invention is not intended to be limited to this particular type of device and other types of device are intended to fall within the scope of the invention, for example devices in which the fluid pump mechanism <NUM> is disposed in the fluid inlet 29a of the fluid chambers <NUM>, as represented in <FIG>.

Although the fluid chambers of the first and second embodiments <NUM>, <NUM> each comprise a single fluid outlet, the invention is not intended to be limited to this particular type of fluid chambers and other types of fluid chambers are intended to fall within the scope of the invention, for example fluid chambers having two or more fluid outlets.

The devices <NUM>, <NUM> include a medicament reservoir <NUM> pre-filled with medicament. However, the invention is not intended to be limited to this particular type of device and other types of device are intended to fall within the scope of the invention, for example devices comprising a cartridge holder for receiving a cartridge of medicament that may be changed between two consecutive uses of the device, or when the cartridge is empty.

The medicament reservoir <NUM> and the fluid reservoir <NUM> are refillable such that the devices <NUM>, <NUM> are reusable. However, the invention is not intended to be limited to this particular type of device and other types of device are intended to fall within the scope of the invention, for example devices which are fully disposable, or devices which include a disposable part, e.g. a disposable medicament cartridge and/or a disposable fluid reservoir, and a reusable part, e.g. the remainder of the device.

In the above described embodiments, the heating element <NUM> comprises a resistive heating element. However, it should be recognised that in alternative embodiments (not shown) the heating element may have a different arrangement. For example, the heating element may comprise a thermoelectric controller, such as a Peltier controller, that is configured to heat the fluid in the fluid chamber. In another embodiment, the heating element is configured to heat the fluid in the fluid chamber via combustion. For instance, the heating element may comprise a fuel source, for example, a gas such as propane, which is ignited to heat the fluid in the fluid chamber. In another embodiment, the heating element emits radiation to heat the fluid in the fluid chamber. In one embodiment, the heating element comprises a laser that irradiates a surface of the fluid chamber to heat the fluid.

The term "drug delivery device" shall encompass any type of device or system configured to dispense a drug or medicament into a human or animal body. Without limitation, a drug delivery device may be an injection device (e.g., pen injector, auto injector, large-volume device, pump, perfusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), skin patch (e.g., osmotic, chemical), inhaler (e.g., nasal or pulmonary), an implantable device (e.g., drug- or API-coated stent, capsule), or a feeding system for the gastro-intestinal tract.

The drug container may be, e.g., a cartridge, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body.

The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste <NUM>, for example, without limitation, main groups <NUM> (antidiabetic drugs) or <NUM> (oncology drugs), and Merck Index, 15th edition.

Examples of APIs for the treatment and/or prophylaxis of type <NUM> or type <NUM> diabetes mellitus or complications associated with type <NUM> or type <NUM> diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-<NUM>), GLP-<NUM> analogues or GLP-<NUM> receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-<NUM> (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analogue" and "derivative" refer to any substance which is sufficiently structurally similar to the original substance so as to have substantially similar functionality or activity (e.g., therapeutic effectiveness). In particular, the term "analogue" refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term "derivative" refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); 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-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); 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.

Examples of GLP-<NUM> , GLP-<NUM> analogues and GLP-<NUM> receptor agonists are, for example, Lixisenatide ( Lyxumia®, Exenatide (Exendin-<NUM>, Byetta®, Bydureon®, a <NUM> amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), 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.

An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia.

Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')<NUM> fragments, which retain the ability to bind antigens. In some embodiments, the antibody has effector function and can fix a complement. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

Claim 1:
A medicament delivery device (<NUM>, <NUM>) comprising:
a medicament receiving element (<NUM>) configured to directly receive a medicament from a medicament reservoir (<NUM>);
at least one fluid chamber (<NUM>) having a fluid outlet (29b) configured to direct fluid vapour towards the medicament receiving element (<NUM>);
a heating element (<NUM>) for heating the fluid in the at least one fluid chamber (<NUM>);
the device (<NUM>) being configured such that, in use, the heating element (<NUM>) heats the fluid in the at least one fluid chamber (<NUM>) to at least partially evaporate the fluid so that the vapor pressure in the at least one fluid chamber (<NUM>) increases until reaching a threshold value at which the fluid is expelled out of the at least one fluid chamber (<NUM>) through the fluid outlet (29b) towards the medicament receiving element (<NUM>) and entrains the medicament towards the patient's skin.