Window Element and Drug Delivery Device

Abstract

The present disclosure is directed to a window element and a drug delivery device, like a pen-type injector, that provides for administration by injection of medicinal products from a multidose cartridge. The drug delivery device may comprise a housing, a dose setting member, a dial, a drive member, a clutch and/or a clicker. The window element comprises a first member with a window and being made from a rigid material, a second member and a third member, each made from an elastically deformable material and being attached to the first member.

Claims

1. A window element, for use in a housing of a drug delivery device, the window comprising: a first member comprising a window and being made from a rigid material, a second member, and a third member, each of the second and third members being made from an elastically deformable material and being attached to the first member.

2. The window element according to claim 1, wherein the window in the first member is defined by a transparent or translucent element.

3. The window element according to claim 1, wherein the window in the first member comprises a magnifying lens.

4. The window element according to claim 1, wherein the window in the first member is defined by a frame surrounding an opening.

5. The window element according to claim 1, wherein the first member comprises a guiding element configured to guide the window in an axial track or a flute.

6. The window element according to claim 1, wherein the first member comprises a coupling element configured to attach to or entrain the window.

7. The window element according claim 1, wherein the first member is displaceable relative to at least a part of the second member and/or a part of the third member by compressing one of the second member and the third member and simultaneously stretching the other of the second member and the third member.

8. The window element according to claim 1, comprising a fourth member and a fifth member, wherein each of the fourth and fifth members are made from a rigid material, and wherein the fourth member and the fifth member are attached to the second member and the third member, respectively, at a respective side of the second and third members facing away from the first member.

9. The window element according to claim 8, wherein the fourth member and the fifth member each comprise a coupling element configured to attach the fourth member and the fifth member to the second and third members, respectively, such that the first member is movable relative to the fourth member and the fifth member.

10. A drug delivery device comprising: a housing; and a window element comprising: a first member comprising a window and being made from a rigid material, a second member, and a third member, each of the second and third members being made from an elastically deformable material and being attached to the first member, wherein the first member of the window element is displaceable relative to the housing.

11. The drug delivery device according to claim 10, comprising a fourth member and a fifth member fixed to the housing, wherein the first member of the window element comprises a guiding element configured to guide the window in the housing in a slidable manner.

12. The drug delivery device according to claim 11, wherein the housing comprises an axial track or a flute in which the guiding element of the first member of the window element is guided.

13. The drug delivery device according to claim 10, comprising a drive mechanism received at least in part within the housing, wherein at least one component of the drive mechanism is coupled to a coupling element of the first member of the window element, and wherein the at least one component of the drive mechanism performs one or more of: an axial movement, a rotational movement, and a helical movement during dose setting and/or dose dispensing.

14. The drug delivery device according to claim 10, comprising a dial at least partly received within the housing and rotatable relative to the housing during dose setting and/or dose dispensing, wherein the window element and the dial are arranged such that at least a part of the dial is visible through the window in the first member of the window element.

15. The drug delivery device according to claim 10 wherein the window in the first member of the window element is disposed in the housing and configured to be displaced along a longitudinal axis of the housing, wherein a rotational motion of the dial is synchronized with a longitudinal displacement of the window, in order to display a currently set injection dose through the window.

16. The drug delivery device, according to claim 10, comprising a first component part with at least one tooth and a second component part which performs a relative rotation during operation of the device, wherein the second component part houses at least one pin, which is movable in a direction perpendicular to an axis of rotation of the first and/or second component part.

17. The drug delivery device according to claim 16, wherein the second component part comprises at least one flexible member biasing the at least one pin towards the at least one tooth.

18. The drug delivery device of claim 10, comprising a cartridge containing a medicament, and wherein the drug delivery device comprises a piston in the housing configured to expel a dose of the medicament from the cartridge.

19. The drug delivery device of claim 18, wherein the medicament comprises a pharmaceutically active compound.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In the drawings:

[0022] FIG. 1 shows a window element according to the disclosure,

[0023] FIG. 2 shows a side view on a drug delivery device according to the disclosure in a first state,

[0024] FIG. 3 shows a side view on the drug delivery device of FIG. 2 in a second state,

[0025] FIG. 4 shows a side view on the drug delivery device of FIG. 2 in a third state,

[0026] FIG. 5 shows a sectional view on the drug delivery device of FIG. 2, and

[0027] FIG. 6 shows a sectional view of a clicker according to the disclosure.

DETAILED DESCRIPTION

[0028] FIG. 1 depicts a window element which may be used in the housing of a drug delivery device. The window element has a first member 1 which comprises a window formed by a frame and a magnifying lens. The first member 1 is made from a transparent, relatively stiff plastic material. On two opposite sides of the first member 1, there are provided respectively a second member 2 and a third member 3 which are made from an elastically deformable material, especially a rubber-like material. The second member 2 and the third member 3 are permanently attached to the first member 1. Further, the second member 2 is provided with a fourth member 4 at the side facing away from the first member 1. In a similar manner, the third member 3 is provided with a fifth member 5 on its side facing away from the first member 1. The fourth member 4 and the fifth member 5 are made from a stiff or rigid material. The material of the second, third, fourth and fifth member is opaque, i.e. not transparent.

[0029] Due to the elastic material properties of the second and third member, the first member 1 may be displaced relative to the fourth member 4 and the fifth member 5 by compressing or stretching the second or third member. In other words, the fourth member 4 and the fifth member 5 may form a fixed or locating bearing with the first member being displaceably suspended between the fourth and fifth member.

[0030] FIGS. 2 to 5 depict a drug delivery device in the form of an injection pen. In the embodiment shown, the drug delivery device comprises a cartridge holder 6 for receiving an ampoule or cartridge containing a medicament and attaching same to a housing 7 of the drug delivery device. Further, a dose setting member 8 is provided which is rotatable relative to the housing 7 to set or correct a dose. A button 9 is provided to administer the dose set by the dose setting member 8. The dose setting member 8 and the button 9 may be part of a drive mechanism which is shown in more detail in FIG. 5.

[0031] The drive mechanism further comprises a dial 10 which may have the form of a number sleeve having at its outer surface a series of numbers 10a, 10b, 10c which may be arranged on a helical path. During dose setting and dose dispensing dial 10 is rotated within the housing 7. As can be seen from FIGS. 2, 3 and 4 the window element of FIG. 1 is attached to or assembled into the housing 7. The fourth member 4 and the fifth member 5 are fixed within the housing 7 and the first member 1 is guided within an axial track in the housing 7. Thus, the first member 1 may be moved along an axial path relative to the housing 7 and the fourth and fifth members by compressing and stretching the flexible second member 2 and third member 3, respectively. The first member 1 with its window is further coupled to dial 10, which preferably surrounds dose setting member 8, with the first member 1 being in threaded engagement with dial 10. Dose setting member 8 may entrain or drive dial 10 during operation of the device.

[0032] To set a dose, a user rotates the dose setting member 8 relative to the housing 7 in a clockwise direction. As the dose setting member 8 is in a threaded engagement with the housing 7, the dose setting member 8 is screwed out of the housing 7. FIG. 2 shows an initial state of the drug delivery device where the set dose is zero. In FIG. 3, a small dose has been selected by winding dose setting member 8 out of the housing 7. FIG. 4 shows the state of the drug delivery device where the maximum dose has been set.

[0033] Upon rotation of the dose setting member 8 dial 10 is rotated, too, by way of a coupling not shown in further detail. However, dial 10 is axially fixed within housing 7 such that it does not wind out of the housing 7. Due to the coupling between the first member 1 and the dose setting member 8, the window of the first element 1 follows the axial movement of the dose setting member 8 such that different numbers 10a, 10b, 10c, respectively, are visible through the window in the first element 1.

[0034] In the state of FIG. 2, the second member 2 of the window element is fully compressed whereas the third member is stretched. In contrast to that, the state shown in FIG. 4, where maximum dose has been set, shows the second member 2 fully stretched and the third member 3 fully compressed. Thus, the slot or opening in the housing 7 where the window element is received, is in any state of the drug delivery device closed to the outside to prevent dirt or the like entering the device.

[0035] In addition, only one single number which represents the presently set dose of the drug delivery device is visible through the window in the first member whereas the other numbers on dial 10 are concealed or masked by the housing 7 and the second member 2 and the third member 3.

[0036] During dose injection the user pushes button 9 which causes the dose setting member 8 to rewind into housing 7 until the state shown in FIG. 2. At the same time, dial 10 is rotated back and the first member 1 slides back to the position shown in FIG. 2. Pushing button 9 further causes the drive mechanism to entrain or push a piston rod farther into the cartridge to expel the selected dose of a medicament from the cartridge.

[0037] FIG. 6 shows in a sectional view the device of FIG. 5 with housing 7 and dial 10. Further, a clutch 11 is provided having a series of inwardly directed teeth 12 located at its inner surface. The dial 10 comprises bores or slots in which pins 13 are guided to allow movement of the pins in a radial direction, i.e. towards the teeth 12. Each bore or slot further houses a spring 14 acting on the respective pin 13 to bias the pin towards the teeth 12. In operation of the device, e.g. during dose setting and/or dose dispensing, dial 10 rotates relative to clutch 11, thus generating a feedback signal by the pins 13 riding over teeth 12. In an alternative embodiment, the pins 13 may be guided within clutch sleeve 11, while the dial 10 comprises the teeth 12.

[0038] The term “medicament”, as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a protein, a polysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or a fragment thereof, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound, wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis, wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1) or an analogue or derivative thereof, or exendin-3 or exendin-4 or an analogue or derivative of exendin-3 or exendin-4.

[0039] Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0040] Insulin derivates 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-Y-glutamyl)-des(B30) human insulin; B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0041] Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

[0042] Exendin-4 derivatives are for example selected from the following list of compounds:

[0043] H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

[0044] H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

[0045] des Pro36 Exendin-4(1-39),

[0046] des Pro36 [Asp28] Exendin-4(1-39),

[0047] des Pro36 [IsoAsp28] Exendin-4(1-39),

[0048] des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

[0049] des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

[0050] des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

[0051] des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

[0052] des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

[0053] des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

[0054] des Pro36 [Asp28] Exendin-4(1-39),

[0055] des Pro36 [IsoAsp28] Exendin-4(1-39),

[0056] des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

[0057] des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

[0058] des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

[0059] des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

[0060] des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

[0061] des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

[0062] wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative;

[0063] or an Exendin-4 derivative of the sequence

[0064] des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

[0065] H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

[0066] des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

[0067] H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

[0068] H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

[0069] des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0070] H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0071] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0072] H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

[0073] H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

[0074] H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

[0075] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

[0076] des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0077] H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0078] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0079] H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

[0080] des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

[0081] H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

[0082] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

[0083] des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0084] H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0085] H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0086] H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

[0087] H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2,

[0088] H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

[0089] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

[0090] des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0091] H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2,

[0092] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2;

[0093] or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exendin-4 derivative.

[0094] Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in Rote Liste, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.

[0095] A polysaccharide is for example 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, 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.

[0096] Antibodies are globular plasma proteins (˜150 kDa) that are also known as immunoglobulins which share a basic structure. As they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

[0097] The Ig monomer is a “Y”-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. Heavy and light chains each contain intrachain disulfide bonds which stabilize their folding. Each chain is composed of structural domains called Ig domains. These domains contain about 70-110 amino acids and are classified into different categories (for example, variable or V, and constant or C) according to their size and function. They have a characteristic immunoglobulin fold in which two β sheets create a “sandwich” shape, held together by interactions between conserved cysteines and other charged amino acids.

[0098] There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ, and μ. The type of heavy chain present defines the isotype of antibody; these chains are found in IgA, IgD, IgE,

[0099] IgG, and IgM antibodies, respectively.

[0100] Distinct heavy chains differ in size and composition; α and γ contain approximately 450 amino acids and δ approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, the constant region (CH) and the variable region (VH). In one species, the constant region is essentially identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, α and δ have a constant region composed of three tandem Ig domains, and a hinge region for added flexibility; heavy chains μ and E have a constant region composed of four immunoglobulin domains. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain.

[0101] In mammals, there are two types of immunoglobulin light chain denoted by λ and κ. A light chain has two successive domains: one constant domain (CL) and one variable domain (VL). The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals.

[0102] Although the general structure of all antibodies is very similar, the unique property of a given antibody is determined by the variable (V) regions, as detailed above. More specifically, variable loops, three each the light (VL) and three on the heavy (VH) chain, are responsible for binding to the antigen, i.e. for its antigen specificity. These loops are referred to as the Complementarity Determining Regions (CDRs). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chains, and not either alone, that determines the final antigen specificity.

[0103] An “antibody fragment” contains at least one antigen binding fragment as defined above, and exhibits essentially the same function and specificity as the complete antibody of which the fragment is derived from. Limited proteolytic digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one entire L chain and about half an H chain, are the antigen binding fragments (Fab). The third fragment, similar in size but containing the carboxyl terminal half of both heavy chains with their interchain disulfide bond, is the crystalizable fragment (Fc). The Fc contains carbohydrates, complement-binding, and FcR-binding sites. Limited pepsin digestion yields a single F(ab′)2 fragment containing both Fab pieces and the hinge region, including the H—H interchain disulfide bond. F(ab′)2 is divalent for antigen binding. The disulfide bond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, the variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv).

[0104] 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 alkali or alkaline, 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 described in “Remington's Pharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology.

[0105] Pharmaceutically acceptable solvates are for example hydrates.