ASSEMBLY FOR USE IN A DRUG DELIVERY DEVICE

Abstract

The present invention relates to an assembly for a drug delivery device comprising a dispensing container and a reservoir container for holding a fluid medicinal product, wherein the dispensing container and the reservoir container are connected to one another and are in fluid communication, and wherein the dispensing container is squeezable for dispensing a dose of the fluid medicinal product from the dispensing container, the dispensing container being refillable with the fluid medicinal product from the reservoir container.

Claims

1. A drug delivery device, comprising: a housing configured to receive a reservoir container holding a fluid medicinal product, wherein the reservoir container includes an outlet located at a first end of the reservoir container and the reservoir container is coupled to a dispensing spring at a second end of the reservoir container located generally opposite the first end; a needle unit coupled to the housing; a flow path comprising a flexible tube fluidly connecting the reservoir container and the needle unit; a first control member located generally at the first end of the reservoir container and configured to allow a flow of the fluid medicinal product into the flow path from the reservoir; and an actuator movably positioned within the housing and configured to dispense a dose of the fluid medicinal product.

2. The drug delivery device of claim 1, wherein the first control member fluidly connects the flexible tube to the outlet of the reservoir container.

3. The drug delivery device of claim 1, wherein the reservoir container is fixedly attached to the housing.

4. The drug delivery device of claim 1, wherein the actuator is configured to move relative to the reservoir container to dispense the fluid medicinal product.

5. The drug delivery device of claim 1, wherein the reservoir container is arranged generally parallel to a longitudinal axis of the housing.

6. The drug delivery device of claim 5, wherein the actuator is configured to move along the longitudinal axis of the housing.

7. The drug delivery device of claim 1, wherein the actuator is coupled to an actuator spring.

8. The drug delivery device of claim 1, further including a second control member configured to allow the fluid medicinal product to flow into the needle unit.

9. The drug delivery device of claim 8, wherein the second control member is coupled to the needle unit.

10. The drug delivery device of claim 8, wherein the second control member is located between the flexible tube and the needle unit.

11. The drug delivery device of claim 8, wherein the second control member fluidly connects the flow path to the needle unit.

12. A drug delivery device, comprising: a housing coupled to a reservoir container configured to hold a fluid medicinal product; a needle unit coupled to the housing; a flow path fluidly connecting the reservoir container to the needle unit, the flow path comprising at least a flexible tube; a first control member configured to open to allow the fluid medicinal product to flow from the reservoir; a second control member configured to open to allow the fluid medicinal product to flow through the needle unit; and an actuator configured to open the first and second control members and move the flexible tube to dispense a dose of the fluid medicinal product.

13. The drug delivery device of claim 12, wherein the reservoir container includes an outlet located at a first end of the reservoir container that is fluidly coupled to the first control member.

14. The drug delivery device of claim 13, wherein the reservoir container is coupled to a dispensing spring at a second end of the reservoir container located generally opposite the first end.

15. The drug delivery device of claim 14, wherein the first and second ends of the reservoir container are arranged along a longitudinal axis of the housing.

16. The drug delivery device of claim 15, wherein the actuator is configured to move along the longitudinal axis of the housing.

17. A method of operating a drug delivery device, comprising: moving an actuator relative to a housing of the drug delivery device to; a) open a first control member to allow a fluid medicinal product to flow from a reservoir to a flow path of the drug delivery device; b) move at least part of a flexible tube located within the flow path; and c) open a second control member to allow the fluid medicinal product to flow from the flow path to a needle unit of the drug delivery device.

18. The method of claim 17, further comprising applying a force to a second end of the reservoir container to force the fluid medicinal product to flow from a first end of the reservoir container.

19. The method of claim 17, wherein moving the actuator relative to the housing includes moving the actuator along a longitudinal axis of the housing.

20. The method of claim 19, further comprising applying a spring force to the actuator to return the actuator to a starting position.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0051] In the following, the invention is described in further detail with reference to the drawings, wherein

[0052] FIG. 1 shows a view of the assembly in a starting position.

DETAILED DESCRIPTION

[0053] In FIG. 1, identical reference numerals denote identical or comparable components.

[0054] FIG. 1 shows an assembly according to the present disclosure. The assembly is surrounded by a housing 10. The housing 10 comprises a right side member 12, a left side member 14, a distal bar 16, a first bar 18, a second bar 20 and a proximal bar 22. All of these bars 16, 18, 20, 22 comprise a central bore.

[0055] A base frame 30 is arranged inside the housing 10 which comprises a bearing in which the base frame 30 is movable in axial direction with respect to the housing 10. The base frame 30 comprises a right longitudinal bar 32, a left longitudinal bar 34, a front face 36 of the right longitudinal bar, a front face 38 of the left longitudinal bar, an actuator bar 40, a support bar 42 and a proximal bar 44 of the base frame.

[0056] The actuator bar 40 comprises a bore. A tube 64 is arranged inside this bore. A check valve is arranged inside the tube 64. The tube 64 is connecting the reservoir container 70 and the dispensing container 60.

[0057] A needle unit 52 is adapted to the distal end 50 of the assembly. The needle unit 52 is seated over a second control member 54.

[0058] The second control member 54 is located in the flow path between an intermediate member 56 and the needle unit 52. The first bar 18 of the housing 10 is located between the intermediate member 56 and the outlet 58 of the spherical body of the dispensing container 60. The center of the first bar 18 comprises a bore to allow for a flow path between the dispensing container 60 and the needle unit 52 passing through the first bar 18.

[0059] At the proximal end 74 of the dispensing container 70, an actuator bar 40 is located which comprises a small bore to define an aperture for a tube 64 which is connecting the dispensing container 60 with a reservoir container 70. On the right and on the left side of the actuator bar 40 the front faces 36, 38 of two longitudinal bars are shown. These front faces 36, 38 are not flush with the surface of the actuator.

[0060] A first control member 66 is arranged at a first outlet 68 located at the reservoir container 70. The reservoir container 70 is surrounded and connected to a support bar 42 of the base frame 30 which is comprising a central opening. This ensures a secure connection of the reservoir container 70 to the housing 10.

[0061] At the proximal bar 44 of the base frame 44, dose dispensing means 76 are shown which comprise a spring 72.

[0062] By pressing the dose dispensing means 76, the base frame 30 is pushed towards the distal end 50 of the housing 10. This movement causes a compression of the dispensing container 60 and liquid medicinal product is dispensed through the needle unit 52.

[0063] The distal movement is stopped by the abutment of the front faces 36, 38 of the longitudinal bars of the base frame 30 with the first bar 18 of the housing 10. The abutment indicates that the maximum dosage of the medicinal product is dispensed. This is the final position of the base frame during the dispensing process.

[0064] Due to the elastic behavior of the dispensing container 60, the dispensing container 60 is withdrawing fluid medicinal product from the reservoir container 70 by suction. This process ends after the dispensing container 60 has reached its original shape.

[0065] The check valve 54 ensures that just the fluid medicinal product from the reservoir container 70 is flowing into the dispensing container 60 by closing the dispensing flow path in proximal direction 74. This is an effective method to prevent the intaking of air, tissue or blood into the dispensing container 60.

[0066] The spring 72 at the proximal end 74 of the assembly together with the elastic behavior of the dispensing container 60 after dispensing the fluid medicinal product enables the base frame 30 to be pushed back in proximal direction 74. After the dispensing container 60 is refilled, the movement of the base frame 30 ends in its starting position.

[0067] The term drug or 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 proteine, a polysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, an antibody, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound,

[0068] 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,

[0069] 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 exedin-3 or exedin-4 or an analogue or derivative of exedin-3 or exedin-4.

[0070] 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.

[0071] 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-(-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(-carboxyheptadecanoyl) human insulin.

[0072] 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.

[0073] Exendin-4 derivatives are for example selected from the following list of compounds:

[0074] H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

[0075] H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

[0076] des Pro36 [Asp28] Exendin-4(1-39),

[0077] des Pro36 [IsoAsp28] Exendin-4(1-39),

[0078] des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

[0079] des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

[0080] des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

[0081] des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

[0082] des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

[0083] des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

[0084] des Pro36 [Asp28] Exendin-4(1-39),

[0085] des Pro36 [IsoAsp28] Exendin-4(1-39),

[0086] des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

[0087] des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

[0088] des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

[0089] des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

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

[0091] des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

[0092] wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative;

[0093] or an Exendin-4 derivative of the sequence

[0094] H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

[0095] des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

[0096] H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

[0097] H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

[0098] des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0099] H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0100] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0101] H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

[0102] H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

[0103] H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

[0104] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

[0105] des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0106] H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0107] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0108] H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

[0109] des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

[0110] H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

[0111] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

[0112] des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0113] H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0114] H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0115] H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

[0116] H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2,

[0117] H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

[0118] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

[0119] des Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

[0120] H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2,

[0121] H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2;

[0122] or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exedin-4 derivative.

[0123] 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.

[0124] 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.

[0125] 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.

[0126] Pharmaceutically acceptable solvates are for example hydrates.