Patent Application
20180250475
The disclosure relates to a piston rod, to a drug delivery device comprising such a piston rod and to a method for assembling such a drug delivery device.
In certain types of drug delivery devices, such as pen-type devices, pre-filled cartridges are used. These cartridges are housed in a cartridge holder or housing. To dispense a certain set dose of a medicament contained in such cartridge, the drug delivery device has a dose setting element. During drug delivery, a piston rod coupled to the dose setting element presses against a piston (also commonly referred to as a “bung”, a “stopper”, or a “plunger”) contained within the cartridge in order to dispense the medicament through an attached needle assembly.
The piston rod may be engaged to the housing which accommodates the cartridge. For example, the piston rod is threaded to the housing, wherein the piston rod is rotated with respect to the housing in order to deliver the set dose of medicament. An assembly of a drug delivery device comprising such threaded piston rod may be implemented by an axial insertion of the piston rod into the housing until the corresponding threads abut against each other. After that, the piston rod is initially rotated relative to the housing in order to establish the threaded engagement between the piston rod and the housing.
There remains a need for an improved piston rod that enables an improved thread engagement between the piston rod and the housing with respect to the related art. There remains furthermore a need for a drug delivery device comprising such an improved piston rod and to a method for assembling such a drug delivery device.
Certain aspects of the present disclosure can be implemented to provide an improved piston rod with a higher efficiency, a drug delivery device comprising such an improved piston rod and to a method for assembling such a drug delivery device.
Certain aspects of the present disclosure can be implemented as a piston rod according to claim 1, by a drug delivery device according to claim 6 and by a method according to claim 10.
Exemplary embodiments of the disclosure are given in the dependent claims.
A piston rod is provided configured to engage a housing of a drug delivery device, wherein the piston rod comprises an outer thread that corresponds with an inner thread of the housing. According to the disclosure, the piston rod comprises a support element that is configured as a supplement thread section of the outer thread, wherein the support element comprises a lead-in for assembly of the drug delivery device and wherein the lead-in is distally spaced from another lead-in arranged on a distal outer thread end.
The support element thus provides an additional contact surface during assembly, thereby increasing the thread engagement between the piston rod and the housing. As a result, an axial length of the drug delivery device may be reduced with respect to the related art due to a possible reduction of windings on a proximal end of the outer thread of the piston rod that engages a distal end of the inner thread of the housing at the end of medicament delivery (last dose of medicament).
The support element may be configured as a projection that extends over an outer piston rod circumference with an angle less than 180 degrees, for example with an angle of 60 degrees.
In an exemplary embodiment, the lead-in is arranged on a proximal end of the support element and the other lead-in is arranged on the distal outer thread end. For example, the lead-ins respectively comprise an edge shape, in particular an edge shape in form of a triangular chamfer. Additionally, there may be also lead-ins on other thread portions of the piston rod and housing that first engage when the piston rod is rotated. Due to the angled contact faces on the threads, when an axial load is applied to the piston rod, a radial load is generated. If there is sufficient engagement in the thread, i. e. something approaching 360°, the radial forces are cancelled out. But if the initial engagement is less than 360° (it is desirable to minimized this to improve the efficiency of the assembly process), the radial load generated on the thread must be balanced by an additional radial contact between the piston rod and the housing, typically between the cylindrical face on the piston rod at the root of the thread and the cylindrical face on the housing at the tip of the thread. This additional radial contact creates friction and reduces the efficiency of the piston rod.
Furthermore, the lead-ins may be angularly offset from one another at an angle of approximately 150 degrees to 180 degrees. Preferably, the angle is about 180 degrees, thus radial forces getting balanced during an initial small rotation of the piston rod with respect to the housing during assembly in order to engage the piston rod and the housing.
In a further exemplary embodiment, a drug delivery device for dispensing a dose of a medicament comprises the provided piston rod and a housing including an inner thread corresponding with the outer thread of the piston rod. Thereby, the inner thread comprises at least one recess whose dimensions at least partially correspond with those of the support element.
The at least one recess enables an easy assembly, wherein the piston rod is moved axially with respect to the housing until the threads abut against each other.
In an exemplary embodiment, the at least one recess engages the support element during assembly. Thus, the support element may pass the recess, thereby allowing the proximal inner thread end to abut the distal outer thread end.
In a further exemplary embodiment, the at least one recess angularly extends with a central angle of approximately 60 degrees. This angle corresponds with those of the support element.
Furthermore, the at least one recess may be arranged within a thread flank of the inner thread part between a proximal inner thread end and a distal inner thread part, wherein the recess is angularly spaced approximately 170 degrees to 200 degrees from the proximal inner thread end. This allows the inner thread to pass the support element during assembly.
According to a further exemplary embodiment, a method for assembly of the drug delivery device comprises the following steps:
The assembly of the drug delivery device may be performed as some kind of bayonet mount, wherein the piston rod is initially moved axially with respect to the housing and afterwards rotated with respect to the housing, thereby mechanically engaging the housing. Due to the support element, the piston rod provides an additional contact surface for the inner thread of the housing during assembly. This increases the strength of the thread engagement after the initial rotation of the piston rod and stabilizes the initial rotation.
Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating exemplary embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
The present invention will become more fully understood from the detailed description given herein below and the accompanying drawings which are given by way of illustration only, and thus, are not limitative of the present invention, and wherein:
Corresponding parts are marked with the same reference symbols in all figures.
The drug delivery device 2 comprises a piston rod 1 inserted into a housing 3, a dial grip 4 and a button 5.
The drug delivery device 2 extends axially between a proximal direction P and a distal direction D. In the present application, the proximal direction P refers to a direction that under use of the drug delivery device 2 is located the furthest away from a drug delivery site of a patient. Correspondingly, the distal direction D refers to a direction that under use of the drug delivery device 2 is located closest to the drug delivery site of the patient.
The piston rod 1 and the housing 3 will be described in more detail in the following
The piston rod 1 is configured as an elongated member of the drug device 2 which is illustrated in
The piston rod 1 further comprises a support element 1.2 that may be configured as a projection or a thread flank that extends over the outer circumference of the piston rod 1 with a central angle less than 180 degrees, for example with a central angle of 60 degrees. The support element 1.2 is arranged spaced from the outer thread 1.1 in a distal direction D and is adapted to form a blocking member after assembly of the drug delivery device 2 as it is described in more detail in the following
The outer thread 1.1 may be configured as a well-known external thread with a left-handedness or alternatively with a right-handedness. The outer thread 1.1 comprises a distal outer thread end 1.1.1 and a not shown proximal end, wherein the distal outer thread end 1.1.1 faces the support element 1.2 and the proximal end faces the proximal end of the piston rod 1 in a proximal direction P.
The support element 1.2 and the outer thread 1.1 respectively comprise a lead-in L1, L2 for assembly, for example an edge shape in form of a triangular chamfer, wherein the lead-in L1 of the support element 1.2 is arranged on a proximal end of the support element 1.2 and the second lead-in L2 (illustrated in
The housing 3 comprises the inner thread 3.1 as described already above. As it is illustrated by the cross section, the inner thread 3.1 comprises a recess 3.1.2 that extends angularly with a central angle of approximately 60 degrees over an inner circumference of the housing 3, thereby corresponding with the central angle of the support element 1.2 at which it extends over the outer circumference of the piston rod 1. The recess 3.1.2 is arranged within a thread flank of inner thread part 3.1 and that is angularly spaced approximately 170 degrees to 200 degrees from the proximal inner thread end 3.1.1. The recess 3.1.2 allows the support element 1.2 to pass through during assembly, thereby enabling an axial movement of the piston rod 1 with respect to the housing 3 in order to engage the outer thread 1.1 and the inner thread 3.1.
As it can be seen by the illustrated sequence from
Furthermore, the drug delivery device 2 described before enables an improved strength of the thread engagement between the piston rod 1 and the housing 3 after the initial rotation of less than approximately 60 degrees. Moreover, a time for assembly will be reduced with respect to the related art.
The terms “drug” or “medicament” are used herein to describe one or more pharmaceutically active compounds. As described below, a drug or medicament can include at least one small or large molecule, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Exemplary pharmaceutically active compounds may include small molecules; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double 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 may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more of these drugs are also contemplated.
The term “drug delivery device” shall encompass any type of device or system configured to dispense a drug into a human or animal body. Without limitation, a drug delivery device may be an injection device (e.g., syringe, 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, micro-needle), inhaler (e.g., nasal or pulmonary), implantable (e.g., coated stent, capsule), or feeding systems for the gastro-intestinal tract. The presently described drugs may be particularly useful with injection devices that include a needle, e.g., a small gauge needle.
The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more pharmaceutically active compounds. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20° C.), or refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of 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 of the drug or medicament prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.
The drug delivery devices and drugs described herein can be used for the treatment and/or prophylaxis of many different types of disorders. Exemplary 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 exemplary disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.
Exemplary drugs for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue 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 term “derivative” refers 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).
Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.
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-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example: Lixisenatide/AVE0010/ZP10/Lyxumia, Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993(a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide, Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Viador-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.
An exemplary oligonucleotide is, for example: mipomersen/Kynamro, a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia.
Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
Exemplary hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.
Exemplary polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodium hyaluronate.
The term “antibody”, as used herein, 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, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region.
The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present disclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.
The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region 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 region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit 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 certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.
Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).
The compounds described herein may be used in pharmaceutical formulations comprising (a) the compound(s) or pharmaceutically acceptable salts thereof, and (b) a pharmaceutically acceptable carrier. The compounds may also be used in pharmaceutical formulations that include one or more other active pharmaceutical ingredients or in pharmaceutical formulations in which the present compound or a pharmaceutically acceptable salt thereof is the only active ingredient. Accordingly, the pharmaceutical formulations of the present disclosure encompass any formulation made by admixing a compound described herein and a pharmaceutically acceptable carrier.
Pharmaceutically acceptable salts of any drug described herein are also contemplated for use in drug delivery devices. Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g. salts having a cation selected from an alkali or alkaline earth metal, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are known to those of skill in the arts.
Pharmaceutically acceptable solvates are for example hydrates or alkanolates such as methanolates or ethanolates.
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.
| Number | Date | Country | Kind |
|---|---|---|---|
| 15306372.2 | Sep 2015 | EP | regional |
The present application is the national stage entry of International Patent Application No. PCT/EP2016/068857, filed on Aug. 8, 2016, and claims priority to Application No. EP 15306372.2, filed in on Sep. 9, 2015, the disclosures of which are expressly incorporated herein in entirety by reference thereto.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2016/068857 | 8/8/2016 | WO | 00 |
