Gas-powered auto-injector

Abstract

The present invention relates to an automatic injector (100) comprising: a housing (170) that is airtight to the outside; a fluid reservoir (110) containing a fluid, the fluid reservoir (110) comprising a flexible material; and a container (140) including at least one first section configured to contain a first substance that contains a gas or can be converted into a gas, wherein the container (140) is configured to be in two different states: a first state in which the first section is sealed so that at least the first substance is contained in the first section; and a second state in which the at least first substance is released from the first section into the housing (170), causing an increase in gas pressure within the housing (170), which acts on the fluid reservoir (110), causing fluid within the fluid reservoir (110) to move through the fluid reservoir (110) toward and through an outlet (230) of the automatic injector (100).

Description

[Technical Field]

[0001] The present disclosure relates to auto-injectors. [Background technology]

[0002] In a typical drug delivery device, a single drive mechanism may be contained in the housing of the drug delivery device and used in conjunction with multiple cartridges, syringes, or ampoules to dispense the drugs contained in the cartridges, syringes, or ampoules from the device.

[0003] However, these types of devices are designed to house a cartridge or syringe, which are rigid components, and because of the shape of those components, the overall shape of the device is adapted to the syringe, cartridge, or ampoule, which is usually the determining or at least limiting factor for the form factor of the device. Summary of the Invention [Problem to be solved by the invention]

[0004] It is an object of the present disclosure to provide an alternative auto-injector. That object is achieved by the present disclosure, in particular by the subject matter of the independent claims. Advantageous embodiments and refinements are subject to the dependent claims. [Means for solving the problem]

[0005] The present disclosure relates to an automatic injector including an airtight housing and a fluid reservoir containing a fluid, the fluid reservoir comprising a flexible material. The housing further includes a container including at least one first section configured to contain a first substance that contains a gas or can be converted into a gas. The container is configured to have two distinct states: a first state in which the first section is sealed so that the at least first substance is contained in the first section; and a second state in which the at least first substance is released from the first section into the housing, causing an increase in gas pressure within the housing, which acts on the fluid reservoir and moves fluid within the fluid reservoir through the fluid reservoir toward and through an outlet of the automatic injector. In this manner, movement of the fluid toward the outlet is triggered by an increase in gas pressure within the housing of the automatic injector. The increase in gas pressure within the housing is then triggered by a change of the container from the first state to the second state.

[0006] The first substance may be a pressurized gas or a liquefied gas that has a high vapor pressure, and which changes into a gas at a certain temperature, for example, room temperature.

[0007] The use of a flexible fluid reservoir has the advantage that there is some freedom in choosing the shape of the reservoir, which can for example have a different shape than a syringe.

[0008] In one embodiment, the fluid reservoirs are circumferentially arranged about the longitudinal axis, with the reservoirs oriented along an arc. In one embodiment, the reservoirs include a pouch or another hollow shaped body configured to move fluid therethrough. The pouch can be collapsible.

[0009] The use of a flexible reservoir has the advantage of improved robustness, particularly compared to glass syringes, which are fragile and prone to breakage. Furthermore, since the reservoir contains only one opening, on the injection side, that needs to be sealed, the integrity of the drug is improved and the risk of contamination is reduced. In auto-injectors with syringes, for example, the stopper side must also be sealed.

[0010] Another advantage is that the reservoir can be adjusted to fit the device configuration, allowing for different configurations with maneuverability benefits. Its compactness and consistency avoids the large tolerances of pre-filled syringes (PFS), reducing injection variability. Specifically, the reservoir can be made of plastic instead of glass, which can be manufactured with greater precision than glass. Furthermore, because no stopper is required, there is a lower risk of stalling and no stopper friction. The reservoir can be filled, for example, by vacuum filling, which eliminates any air, or by steam purging before closing the container. In the case of vacuum filling, the pouch can be pulled apart (e.g., by vacuum), which creates a vacuum within the pouch. This draws liquid from the connected container into the pouch.

[0011] In one embodiment, the reservoir includes a tapered portion that connects the reservoir to the delivery tube, ensuring that fluid is forced into the delivery tube and the amount of fluid that is not released from the reservoir is reduced to a minimum.

[0012] In one embodiment, the container comprises a gas vessel having the shape of a hollow cylindrical segment whose longitudinal axis is its major axis and which has a notch along its periphery, such a shape having the advantage that available and accessible space located radially inside the inner wall of the cylindrical segment can be used to place further components, thus keeping the overall size of the device small.

[0013] In one embodiment, the container includes a second section configured to contain a second substance that can be converted into a gas, and the first and second sections are separated by a separator such that, when the separator is opened, the first substance containing the substance that can be converted into a gas mixes with the second substance, generating a gas. The first substance may be a liquid or a solid. Similarly, the second substance may be a liquid or a solid. It is necessary to ensure that the first and second substances are mixable and that, when mixed, a gas is generated. For example, the first substance may be citric acid and the second substance may be sodium bicarbonate.

[0014] Liquefied gases can contain a vapor pressure such that at a certain temperature, eg, room temperature, the fluid boils and changes at least partially to a gas.

[0015] In one embodiment, the container includes a gas seal that seals the first and / or second sections and is opened when switching from the first state to the second state. The gas seal may include a plastic material or a welded metal lid. A seal according to the present disclosure has the advantage that it can be opened more easily than a vessel, thereby allowing gas to escape and increase pressure within the housing.

[0016] In one embodiment, the separating member is configured to be opened during assembly of the auto-injector or by a tool. Preferably, the separating member is opened before the gas seal is opened so that gas has already been generated when the gas seal is opened and is released into the housing.

[0017] In one embodiment, the auto-injector includes a trigger movable along a longitudinal axis from a first trigger position to a second trigger position; - in a first trigger position, the trigger is separated from the gas seal; In the second trigger position, the trigger mechanically contacts the gas seal, thereby opening the gas seal and allowing gas to be released from the container into the housing, thereby increasing gas pressure within the housing, which in turn compresses the fluid reservoir and moves fluid within the fluid reservoir to the outlet. The trigger can be pressed from the first position to the second position by a user, specifically a patient. In this way, the user can determine when gas pressure within the housing increases and when fluid is subsequently moved to the outlet.

[0018] In one embodiment, the auto-injector includes a trigger seal disposed between the housing and the trigger such that the housing is gas-tight, the seal ensuring that the housing remains gas-tight during movement of the trigger from the first position to the second position.

[0019] In one embodiment, the auto-injector includes a trigger spring that is mechanically coupled to the trigger such that when the trigger moves from the first position to the second position, the trigger moves the trigger spring from the first position to the second position.

[0020] The trigger spring may be extensible and compressible along the longitudinal axis such that when the trigger moves from the first position to the second position, the trigger moves the trigger spring from an extended state to a compressed state, thereby acting against the force of the trigger spring.

[0021] The trigger spring ensures that the trigger is held in its starting position, aligning it with the exterior surface of the housing and resulting in a continuous exterior housing surface, unless the trigger is depressed, at which point some force is required against the trigger spring to move the trigger from the first position to the second position.

[0022] The trigger spring may comprise a pressure spring, a compression spring, a torsion spring, or an extension spring. The trigger spring may comprise a metal.

[0023] In one embodiment, the automatic injector includes a delivery tube configured to be in fluid communication with the fluid reservoir and configured to be in fluid communication with the outlet, such that fluid from the fluid reservoir is movable from the fluid reservoir through the delivery tube to the outlet. This ensures that the delivery tube is highly flexible so that it can guide the flow of fluid in a predetermined direction. The delivery tube can include a flexible material such as an elastomer or a rigid material such as a plastomer or thin metal.

[0024] In one embodiment, the auto-injector includes an outlet interface movable relative to the longitudinal axis from a first interface position to a second interface position and in fluid communication with the outlet. In the first interface position, the outlet interface is not in fluid communication with the delivery tube, and in the second interface position, the outlet interface is in fluid communication with the delivery tube. By moving the outlet interface, it is possible to control whether fluid communication is established between the fluid reservoir and the outlet. Such fluid communication is established only when a trigger is pressed to open a seal and allow gas to increase pressure within the housing.

[0025] In one embodiment, the auto-injector includes an interface spring that is mechanically coupled to the outlet interface.

[0026] The interface spring can be extensible and compressible along the longitudinal axis such that it is more compressed when in the second tube position than when in the first tube position, ensuring that the outlet interface is not in fluid communication with the fluid reservoir unless pressure causes the outlet interface to move against the force of the interface spring toward the base of the housing to a position in fluid communication with the fluid reservoir.

[0027] In one embodiment, the outlet includes a needle movable along the longitudinal axis from a first needle position to a second needle position, wherein in the first needle position the needle is fully contained within the housing and in the second needle position at least a portion of the needle is moved through a housing seal disposed on the housing about the longitudinal axis.

[0028] In one embodiment, the trigger is integrated into the housing such that a portion of the exterior surface of the housing includes the trigger. In this manner, the functionality for initiating the injection process is integrated into the housing.

[0029] In one embodiment, the housing can have a shape with a base that is larger in diameter than it is tall along the longitudinal axis, hi one embodiment, the shape comprises a cylinder, particularly a cylinder with rounded edges.

[0030] In one embodiment, the fluid reservoir contains a drug or medication.

[0031] In one embodiment, the auto-injector is a disposable or single-use device for delivering a single dose.

[0032] In one embodiment, the fluid reservoir is disposed at the base of the housing along a circular arc. The fluid reservoir can have essentially the shape of a torus segment. For example, the fluid reservoir extends along the circular arc at least 180°, at least 200°, or at least 270°. For example, the fluid reservoir is at least partially disposed circumferentially around a longitudinal axis. The longitudinal axis can extend through the center of the circular arc.

[0033] In one embodiment, the container is disposed within the housing. The container can be disposed such that it is at least partially circumferentially surrounded by the fluid reservoir. For example, a longitudinal axis extends through the container, or the container is disposed radially between the longitudinal axis and the fluid reservoir.

[0034] The container may have a cylindrical shape with a hollow lateral surface, and the interior of the container is therefore delimited in the radial direction by two opposing walls of the container, the walls having the lateral shape of a cylinder with different radii.

[0035] The container can circumferentially surround the trigger spring and / or the outlet interface and / or the needle. The container can be radially disposed between the fluid reservoir and the trigger spring or the outlet interface or the needle, respectively.

[0036] Embodiments will now be described, by way of example only, with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0037] [Figure 1] FIG. 1 shows a top cross-sectional perspective view of an auto-injector. [Figure 2] 1 shows a side cross-sectional view of an auto-injector. [Figure 3] The housing seal is shown. [Figure 4A] 1 shows a top perspective view of a button. [Figure 4B] The button is shown in 3D side view. [Figure 5] 1 shows a diagram of vapor pressure versus temperature for common refrigerants. DETAILED DESCRIPTION OF THE INVENTION

[0038] Like reference numbers refer to like features throughout the figures and the following description.

[0039] 1 shows a top cross-sectional perspective view of an auto-injector. A housing 170 and base 175 are shown having a circular cross-sectional shape. Of course, other shapes are possible.

[0040] Within the housing 170, the pouch 110 is disposed on a base 175 about a longitudinal axis y, which is disposed in a cross section of a circular element. The pouch 110 contains a fluid material, such as a liquid drug or drug formulation. One end of the pouch 110 is in fluid communication with a needle 230. The end includes a tapered portion 120, which is in fluid communication with a delivery tube 150. The delivery tube 150 is configured to be in fluid communication with the needle 230. An additional spout 160 can be provided to connect the delivery tube 150 and the tapered portion 120. The spout 160 enables connection between the pouch 110 and the delivery tube 150. The spout 160 has different material properties than the pouch 110. For example, the spout 160 can be stiffer so that the alignment of the pouch 110 within the housing 170 is based on the position and orientation of the spout 160.

[0041] A gas vessel 140 is disposed about the longitudinal axis y. The gas vessel 140 is disposed within the housing radially between the pouch 110 and the longitudinal axis y and has the shape of a hollow cylindrical segment whose cross section comprises a circular arc. The hollow cylindrical segment includes an inner wall and an outer wall, which form a cavity in which pressurized gas is contained. An opening also extends axially along the longitudinal axis y. The gas vessel 140 includes a gas seal 130 disposed at one end of the hollow cylindrical segment to cover its cross-sectional area. The end may be opposite the end at the base 175 with respect to the longitudinal axis y. The gas seal 130 may include a plastic material or a welded metal lid. The gas seal 130 may cover the entire cross section of the circular arc. A button spring 260 is disposed along the inner wall of the hollow tube segment about longitudinal axis y, the button spring 260 being extensible and compressible along longitudinal axis y and mechanically coupled to button 300 (not shown here, see e.g., FIG. 2).

[0042] The gas vessel 140 may comprise a polymer vessel, for example a fluoropolymer, capable of containing gas at a pressure of 40-60 bar, particularly 50 bar. The vessel may comprise a very small size of 0.5-1.5 ml, particularly around 1 ml.

[0043] Additionally, a needle carrier 190 is disposed about the longitudinal axis y. The needle carrier 190 is disposed radially inward relative to the gas vessel 140. A needle 230 is attached to the needle carrier 190. The delivery tube 150 is disposed at an angle in the tapered portion 120 and oriented along the longitudinal axis y, thereby extending through the open portion of the arc of the gas vessel 140 from an outer surface of the gas vessel 140 opposite the inner surface of the housing 170 to a region bounded by the inner surface of the gas vessel 140. The inner and outer surfaces can face in opposite directions. Gas can be held in a space defined between the inner and outer surfaces.

[0044] FIG. 2 shows a side cross-sectional view of the auto-injector 100. The retaining portion 210 is disposed about the longitudinal axis y and includes a cylindrical portion. The retaining portion 210 is fixed to the base 175 of the housing 170. The needle carrier 190 is disposed inside the cylindrical portion of the retaining portion 210. A button 300 is disposed on the housing 170 and is movable along the longitudinal axis y toward the gas seal 130 of the gas vessel 140, the retaining portion 210, and the needle carrier 190. The retaining portion 210 and the gas vessel 140 are mechanically coupled by a bridge 290 extending about the longitudinal axis y. A button spring 260 is radially disposed between the retaining portion 210 and the inner wall of the hollow cylindrical segment of the gas vessel 140. The button spring 260 is extensible and compressible along the longitudinal axis y between the bridge 290 and the button 230. The trigger spring may comprise a pressure spring, a compression spring, a torsion spring, or an extension spring. The trigger spring may comprise a metal.

[0045] The retaining portion 210 further includes a tube interface 280 that is in fluid communication with the delivery tube 150. The tube interface 280 is axially disposed between the bridge 290 and the base 175. A needle carrier seal 220 is disposed radially outward of the needle carrier 190 and is in contact with the radially inner side of the retaining portion 210.

[0046] The needle carrier 190 includes a needle tube 270 that is fluidly connectable to the delivery tube 150. The needle 230 is mechanically secured to the needle carrier 190 and is in fluid communication with the needle tube 270.

[0047] The needle tube 270 is also in fluid communication with the needle 230, which is disposed along the longitudinal axis y.

[0048] A tube spring 240 is axially disposed within the cylindrical portion of the retaining portion 210 relative to the longitudinal axis y between the needle carrier 190 and the base of the housing 170. The tube spring 240 is extensible and compressible along the longitudinal axis y.

[0049] The button 300 includes at least one piercing spike 310, which is directed toward the inside of the housing 170 toward the gas seal 130. Instead of or in addition to one or more piercing spikes 310, the button 300 can include other sharp elements configured to open the gas seal 130. The housing 170 can include two components joined together. In this case, the housing can include an additional sealing member 200 at the location where the two components are joined together, for example, by gluing or soldering. The sealing member 200 can include a thicker region where the two components are joined together, which improves overall stability. The button 300 is movable within the housing 170 along the longitudinal axis y against the force of the button spring 260. A button seal 180 is axially disposed between the housing 170 and the button 300, ensuring that the housing 170 remains airtight against the outside when the button 300 moves along the longitudinal axis y. Housing 170 should be designed to remain gas tight even if there is a failure of gas seal 130. At base 175 of housing 170, housing seal 250 is disposed about longitudinal axis y.

[0050] The function of the auto-injector 100 is described below.

[0051] A user can axially push button 300 along longitudinal axis y toward housing 170. At some point during the movement, piercing spike 310 breaks gas seal 130, allowing pressurized gas to escape from gas vessel 140. The gas disperses within housing 170, which is airtight to the outside. The overall gas pressure within housing 170 increases. This causes pouch 110 to squeeze, which forces fluid within pouch 110 through tapered portion 120, down delivery tube 150, and to tube interface 280.

[0052] The increase in gas pressure within the housing 170 pushes the needle carrier 190 along the longitudinal axis y toward the base 175 of the housing 170. Along with the needle carrier 190, the needle tube 270 and the needle 230 move toward the base 175. When the needle carrier 190 can no longer move toward the base 175, the needle tube 270 and the tube interface 280 are aligned so that they are in fluid communication. The tube interface 280 includes the same cross-section as the needle tube 270. Fluid moving through the delivery tube 150 is then forced through the tube interface 280, through the needle tube 270, and into the needle 230. The needle 230, also moved downward along with the needle carrier 190, is advanced partially out of the housing 170 through the housing seal 250 for injection.

[0053] Because the interior volume of the housing 170 is greater than the volume of the pouch 110, the driving pressure towards the fluid remains relatively constant throughout the course of the injection.

[0054] Gases can include low to medium pressure CO2 (at pressures above 57 bar, it condenses to a liquid and acts as a saturated mixture), N2, air, or nitrous oxide. The gas should be non-toxic, non-flammable, and available at low cost.

[0055] Pouch 110 can be constructed from two or more materials, which may be specifically adapted for its interior and exterior according to chemical and / or mechanical requirements. For example, for the exterior of pouch 110, a material is required that does not participate in chemical reactions with the gas in gas vessel 140 and is mechanically stable against pressure exerted on pouch 110 by the gas escaping from gas vessel 140. For the interior of pouch 110, a material is required that does not participate in chemical reactions with the fluid contained in pouch 110.

[0056] In another embodiment (not shown here), a container 140 is used instead of a gas vessel. The container 140 includes two sections, each containing a liquid or solid substance that generates a gas when mixed. The sections are separated by a separator. When the separator is opened, the substances mix, thereby generating a gas. When the gas is released from the container 140 into the housing 170, the gas acts on the pouch 110. The pressurized gas causes the pouch 110 to compress as described above. Exemplary substances that can be mixed to generate a gas are sodium bicarbonate and citric acid; preferably, non-toxic reactants that produce a safe product are used, and the gas generated is CO2. Criteria for fluid selection may be the chemical compatibility of the pouch with the reactants and products, the temperature dependence of the reactants and products to achieve a certain reaction rate (affected by particle size), non-toxicity, and not being significantly exothermic or endothermic.

[0057] 3 shows the housing seal 250 having a circular shape. A central needle hole 330 is shown through which the needle 230 can be advanced during an injection operation. Additionally, a window 320 is shown through which the container can be visually viewed for its integrity prior to injection, for example, to visually check the medication for unclear or light-colored areas, to track the injection process, and to visually confirm that the full dose has been delivered.

[0058] 4A shows a top perspective view of button 300 and its integral part of housing 170. Button 300 has a circular shape, but may have another shape, such as rectangular or square.

[0059] 4B shows a 3D side view of button 300. Button 300 includes a cylindrically shaped frame with piercing spikes located inside.

[0060] In another embodiment (not shown here), a container 140 is used instead of a gas vessel. The container 140 is configured to contain a liquid with a high vapor pressure so that gas is generated within the container 140 when a certain temperature is reached. FIG. 5 shows a diagram of vapor pressure versus temperature for common refrigerants, such as R134a, R32, R402A, or R404A, that can be used in this embodiment. These refrigerants that become gases at a certain temperature can be contained in the container 140. They should have a vapor pressure close to the required driving pressure. The container 140 includes a gas seal 130. The gas can then be released from the container 140 into the housing 170 by opening the gas seal 130, as shown in FIG. 2. In this embodiment, examples of gases include a refrigerant such as R134a, high-pressure CO2, or an alkane such as propane or butane. Criteria for selecting a gas may include vapor pressure at the temperature at which the device will be used, such as room temperature, the sensitivity of vapor pressure to temperature, and diffusivity (related to molecular size).

[0061] The device can have a height of 10 to 40 mm, particularly 15 to 30 mm. The base of the device can have a diameter of 45 to 90 mm, particularly 50 to 70 mm. Specifically, the height of the device can be less than one-third the size of a typical auto-injector including a syringe. This is advantageous for users, such as patients, because the distance from the skin to where the device is triggered is much smaller.

[0062] The scope of protection is not limited to the examples given herein above. Every invention disclosed herein is embodied in each and every novel feature and each combination of features, and they include in particular any combination of any features set out in the claims, even if that feature or combination of features is not explicitly set out in the claims or examples.

[0063] The terms "drug" or "medicament" are used interchangeably herein to describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient ("API"), in its broadest sense, is a chemical structure that has a biological effect on humans or animals. In pharmacology, drugs or medications are used to treat, cure, prevent, or diagnose disease or otherwise improve physical or mental well-being. Drugs or medications can be used for a limited duration or periodically for chronic disorders.

[0064] As described below, drugs or pharmaceutical agents may contain at least one API or a combination thereof in various types of formulations for the treatment of one or more diseases. Examples of APIs include small molecules with a molecular weight of 500 Da or less, polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes), carbohydrates and polysaccharides, as well as nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids, such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids can be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0065] The drug or agent can be contained in a primary package or "drug container" adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other rigid or flexible vessel configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some cases, the chamber can be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber can be designed to store the drug for about one month to about two years. Storage can occur at room temperature (e.g., about 20°C) or refrigerated temperatures (e.g., from about -4°C to about 4°C). In some cases, the drug container can be or include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation to be administered (e.g., an API and a diluent, or two different drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge can be configured to allow mixing between two or more components prior to and / or during administration to the human or animal body. For example, the two chambers can be configured to be in fluid communication with each other (e.g., via a conduit between the two chambers) and to allow mixing of the two components by a user, if desired, prior to administration. Alternatively or additionally, the two chambers can be configured to allow mixing upon administration of the components to the human or animal body.

[0066] The drugs or agents contained in the drug delivery devices described herein can be used to treat and / or prevent many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, and thromboembolic disorders, such as deep vein thromboembolism or pulmonary embolism. Further examples of disorders include 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 listed in handbooks such as Rote Liste 2014 (e.g., but not limited to, Main Group 12 (antidiabetic agents) or 86 (oncology agents)) and the Merck Index, 15th edition.

[0067] Examples of APIs for the treatment and / or prevention of type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin, e.g., human insulin, or a human insulin analog or derivative; glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof; a dipeptidyl peptidase-4 (DPP4) inhibitor; or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analog" and "derivative" refer to a polypeptide having a molecular structure that is formally derivable from the structure of a naturally occurring peptide, e.g., the structure of human insulin, by deletion and / or replacement of at least one amino acid residue present in the naturally occurring peptide and / or by addition of at least one amino acid residue. The added and / or replaced amino acid residue can be either a codable amino acid residue, another naturally occurring residue, or a purely synthetic amino acid residue. Insulin analogs are also referred to as "insulin receptor ligands." In particular, the term "derivative" refers to a polypeptide having a molecular structure formally derivable from the structure of a naturally occurring peptide, for example, the molecular structure of human insulin in which one or more organic substituents (e.g., fatty acids) are attached to one or more of the amino acids. Optionally, one or more amino acids present in the naturally occurring peptide are deleted and / or replaced by other amino acids, including non-codable amino acids, or amino acids, including non-codable ones, are added to the naturally occurring peptide.

[0068] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin in which the proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and the Lys at position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0069] 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-myristoylLysB28ProB29 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-carboxyheptadecanoyl) human insulin.

[0070] Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists are, for example, lixisenatide (Lyxumia®), exenatide (exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide produced by the salivary glands of the flathead monster), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), rexendin -4, CJC-1134-PC, PB-1023, TTP-054, langrenatide / HM-11260C, CM-3, GLP-1 Erigen, ORMD-0901, NN-9924, NN-9926, NN-9927, nodexene, Viadol-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, exenatide-XTEN, and glucagon-Xten.

[0071] An example of an oligonucleotide is, for example, mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia.

[0072] Examples of DPP4 inhibitors are vidagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0073] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0074] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low-molecular-weight heparin or ultra-low-molecular-weight heparin or derivatives thereof, or sulfated polysaccharides, such as the polysulfated forms of the aforementioned polysaccharides, and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low-molecular-weight heparin is enoxaparin sodium. Examples of hyaluronic acid derivatives include Hylan G-F20 (Synvisc®) and sodium hyaluronate.

[0075] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments that retain antigen-binding ability. An antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single-chain antibody. In some embodiments, an antibody has effector function and is capable of fixing complement. In some embodiments, an antibody has reduced or no binding ability to Fc receptors. For example, an antibody can be an isotype or subtype, antibody fragment, or mutant that does not support Fc receptor binding, e.g., has a mutation or deletion of the Fc receptor binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTIs) and / or dual variable region antibody-like binding proteins (CODVs) with a crossover binding region orientation.

[0076] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., an antibody heavy and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include the full-length antibody polypeptide but comprises at least a portion of the full-length antibody polypeptide that is still capable of binding to antigen. Antibody fragments can include truncated portions of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments, e.g., bispecific, trispecific, tetraspecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments, e.g., bivalent, trivalent, tetravalent, and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0077] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences within the variable regions of both heavy and light chain polypeptides that are not CDR sequences and that are primarily responsible for maintaining the proper orientation of the CDR sequences to enable antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids within the CDRs to interact with the antigen.

[0078] Examples of antibodies are anti-PCSK-9 mAb (e.g., alirocumab), anti-IL-6 mAb (e.g., sarilumab), and anti-IL-4 mAb (e.g., dupilumab).

[0079] Pharmaceutically acceptable salts of any of the APIs described herein are contemplated for use as drugs or medicaments in drug delivery devices. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0080] Those skilled in the art will understand that modifications (additions and / or omissions) can be made to the various components, formulations, devices, methods, systems and embodiments of the API described herein without departing from the overall scope and spirit of the invention, and that the invention encompasses such modifications and all equivalents thereof.

[0081] This patent application claims priority from European Patent Application No. 20315496.8, the disclosure of which is incorporated herein by reference. [Explanation of symbols]

[0082] 100 auto-injector 110 pouches 120 Tapered part 130 Gas sealing part 140 Gas Vessel 150 delivery tubes 160 spout 170 Housing 175 base 180 Button sealing part 190 Needle Carrier 200 Sealing member 210 Holding part 220 Needle carrier seal 230 needles 240 Tube spring 250 Housing sealing part 260 Button spring 270 Needle Tube 280 Tube Interface 290 Bridge 300 buttons 310 Piercing Spike 320 Window 330 Needle hole y longitudinal axis

Claims

1. An automatic injector (100), comprising: a housing (170) that is airtight to the outside; A fluid reservoir (110) having a fluid, the fluid reservoir (110) comprising a flexible material; a vessel (140) including at least one first section configured to contain a first substance that includes a gas or that can be converted to a gas; Including, The container (140) has two different states: a first state, the first section being sealed such that at least a first substance is contained within the first section; a second state, in which at least a first substance is released from the first section into the housing (170) causing an increase in gas pressure within the housing (170) that acts on the fluid reservoir (110) to move fluid within the fluid reservoir (110) through the fluid reservoir (110) toward and through the outlet (230) of the automatic injector (100); and The automatic injector is configured to take

2. the container (140) includes a second section configured to contain a second substance that can be converted into a gas, the first section and the second section being separated by a separating member such that when the separating member is opened, the first substance, including the substance that can be converted into a gas, mixes with the second substance to generate gas; and / or 2. The automatic injector of claim 1, wherein the container (140) includes a gas seal (130) that seals the first and / or second sections and that is opened when switching from the first state to the second state.

3. a trigger (300) movable along a longitudinal axis (y) from a first trigger position to a second trigger position; In a first trigger position, the trigger (300) is separated from the gas seal (130); 3. The automatic injector of claim 2, wherein in the second trigger position, the trigger (300) mechanically contacts the gas seal (130), thereby opening the gas seal (130) such that gas can be released from the container (140) into the housing (170), thereby increasing the pressure of the gas within the housing (170) such that the fluid reservoir (110) is squeezed and fluid within the fluid reservoir (110) is forced to the outlet (230).

4. a trigger spring (260) that is mechanically coupled to the trigger (300) such that when the trigger (300) moves from the first position to the second position, the trigger moves the trigger spring (260) from the first position to the second position; and / or 4. The automatic injector of claim 3, wherein the trigger (300) is integrated into the housing (170).

5. 5. The automatic injector of claim 3 or 4, wherein the trigger (300) includes an element (310) configured to open the gas seal (130).

6. 6. The automatic injector of claim 3, further comprising a trigger seal (180) that acts to seal the interface between the housing (170) and the trigger (300) such that the housing (170) is airtight.

7. 3. The automatic injector of claim 2, wherein the separation member is configured to be opened during assembly of the automatic injector or by a tool.

8. 8. The automatic injector of claim 1, further comprising a delivery tube (150) configured to be in fluid communication with the fluid reservoir (110) and configured to be in fluid communication with the outlet (230), such that fluid in the fluid reservoir (110) is movable from the fluid reservoir through the delivery tube (150) to the outlet (230).

9. an outlet interface (270) movable relative to the longitudinal axis (y) from a first interface position to a second interface position and in fluid communication with the outlet (230); In the first interface position, the outlet interface (270) is not in fluid communication with the delivery tube (150); 9. The automatic injector of claim 3 or 8, wherein in the second interface position, the outlet interface (270) is in fluid communication with the delivery tube (150).

10. the outlet includes a needle (230) movable along a longitudinal axis (y) from a first needle position to a second needle position; In the first needle position, the needle (230) is fully contained within the housing (170); The automatic injector of any one of claims 1 to 9, wherein in the second needle position, at least a portion of the needle (230) is moved through the housing seal (250).

11. The automatic injector (100) according to any one of the preceding claims, wherein the housing (170) has a shape with a base having a diameter greater than its height extending along the longitudinal axis (y).

12. The fluid reservoir (110) contains a drug or agent; and / or The automatic injector (100) of any one of claims 1 to 11, wherein the automatic injector (100) is a disposable or single-use device for delivering a single dose.

13. The fluid reservoir (110) is disposed in a base (175) of the housing (170) along an arc; The automatic injector (100) of any one of claims 1 to 12, wherein the container (140) is disposed within the housing (170) and is at least partially circumferentially surrounded by the fluid reservoir (110).

14. 5. The automatic injector (100) of claim 4, further comprising an outlet interface (270) movable from a first interface position to a second interface position relative to the longitudinal axis (y) and in fluid communication with the outlet (230).

15. The automatic injector (100) according to any one of the preceding claims, wherein the reservoir (140) is arranged about the longitudinal axis (y).

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