TW201325646A - Drug delivery device and method for a drug delivery device - Google Patents

Abstract

A drug delivery device (1) is provided comprising a housing (4) comprising a distal end and a proximal end and a cartridge (3) adapted and arranged to contain at least one dose of a drug (16), a bung (5) being movably arranged within the cartridge (3). In an initial state of the device (1), the bung (5) is arranged in a proximal end position with respect to the cartridge (3). The device (1) further comprises a piston rod (9) adapted and arranged to move the bung (5) in the distal direction with respect to the cartridge (3) for delivering a dose of the drug (16). The device (1) further comprises a mechanism operable such that, after a dose delivery operation was completed, the piston rod (9) is moved into the proximal direction with respect to the bung (5) by a back off distance (D), wherein in the initial state, a distance between a distal end of the piston rod (9) and a proximal end of the bung (5) is greater than zero, with the distance between the piston rod (9) and the bung (5) in the initial state being defined by the back off distance (D). Furthermore, a method for assembling a drug delivery device (1) is provided.

Description

Drug delivery device and method for a drug delivery device

The present disclosure relates to a drug delivery device and a method for assembling a drug delivery device.

In a drug delivery device, a plug of a drug containing a plurality of doses is often displaced by a piston rod. Therefore, a dose of the drug is expelled from the sputum.

A drug delivery device is described, for example, in document WO 2008/058666 A1.

One of the objects of the present disclosure is to provide an improved drug delivery device. Still, it is an object of the present disclosure to provide a method for assembling an improved drug delivery device.

This object can be achieved by applying the subject matter of the independent patent scope. Advantageous embodiments and refinements are the subject matter of the patent application scope.

A morphology relates to an assembly for a drug delivery device. The assembly can include a housing. The housing can include a distal end and a proximal end. The assembly may further comprise a stack. The mash can be adapted and configured to contain at least one dose of a drug, preferably a plurality of doses of the drug. A plug can be removably disposed within the bore. In an initial state of the device, the plug member can be disposed in a proximal position relative to the jaw.匣 can be completely filled in the initial state, such as not dispensing medication from sputum. The initial state of the device may be set And the state before dispensing a first dose of the drug from the sputum. The initial state may be the state of the device that supplies the status quo from the manufacturer. The assembly further includes a piston rod. The piston rod can be adapted and configured to move the plug in a distal direction relative to the ankle for delivery of a dose of medication. The assembly can include an institution. The mechanism is operable to cause the piston rod to be moved a retracted distance relative to the plug member or away from the plug member, preferably automatically moving into the proximal direction, after a dose delivery operation is completed. Therefore, the pressure of the piston rod on the plug can be reduced. In the initial state, a distance between a distal end of the piston rod and a proximal end of the plug member may be greater than zero. The distance between the piston rod and the plug in the initial state can be defined by the receding distance.

The mechanism ensures that the piston rod is positioned at a receding distance from the plug after a dose delivery operation is completed. It is thus possible to reduce or even avoid pressure on the plug which may cause the droplets. In particular, after the dose delivery operation is completed, the deformed plug can be allowed to relax in the proximal direction. This way, it is possible to avoid uncontrolled relaxation of the plug which may accidentally waste the drug from the sputum.

The mechanism can be further configured such that in the initial state, the piston rod and the plug are separated by a predetermined initial distance. The predetermined initial distance may be equal to the back distance or may be less than the back distance. In particular, the mechanism can define a predetermined initial distance between the piston rod and the plug member in the initial state to achieve a predetermined initial value in total, depending on the value of the receding distance. The predetermined initial value can be in the range of 0.1 mm to 1.0 mm. The predetermined initial value can be, for example, 0.2 mm. For arranging the piston rod at a predetermined distance from the plug prior to setting and dispensing a first dose from the device The adjustment or priming steps of the user may be redundant. This method prevents underdosing. In particular, if the user skips a necessary priming step but injects the priming volume, this will result in a significant dose deficiency. By making the priming step redundant, this dose deficiency can be prevented, and thus the accuracy of the dose can be improved. Moreover, this can help reduce the risk of erroneous operation by inexperienced users and thus also reduce drug waste. Moreover, some users who are overly cautious in performing an priming step before each dose not only waste the first dose of the drug, but also unnecessarily empty the sputum, so the device cannot deliver the required number of doses. Making the priming step redundant can help avoid all of these problems.

In the initial state, there is a distance between the piston rod and the plug, and the 匣 is not pressurized. For this reason, if a needle is attached to the crucible, there will be no drug droplets emerging from the needle due to the pressure in the crucible. Some drugs that are in contact with the user's skin will be harmful to the user. The risk of exposure of the skin to the drug due to droplets can be reduced or even avoided by the distance between the piston rod and the plug in the initial state.

Another aspect relates to a method for assembling a drug delivery device. The device can be a device as described above. In the first step, a unit can be provided. The unit can include a holding member. The unit can contain one.匣 can be held in the 匣 holder. The sputum may hold at least one dose of a drug, preferably a plurality of doses of the drug. A plug can be movably disposed within the bore. Preferably, the plug is disposed in a proximal position relative to the bore. In particular, the crucible can be in a fully filled state. In the next step, a drive unit can be provided. The drive unit may be releasable or It is non-releasably connected to the unit. The drive unit can include a piston rod. The drive unit can further include a mechanism. The mechanism can be configured to move the piston rod a retracted distance when the mechanism is switched from an activated state to a deactivated state. In the next step, the organization can be activated. In the next step, particularly when the mechanism is activated, the position of the proximal end of the plug relative to a predetermined reference point on the cymbal unit, such as a mark on the tamper holder holding the cymbal, can be measured. In the next step, the position of the distal end of the piston rod relative to a predetermined reference point on the drive unit, such as a mark on a housing, can be measured. In the next step, information relating to the relative position of the distal end of the piston rod and the proximal end of the plug can be derived from the results of the previous measurements. In the next step, the mechanism can be deactivated such that the piston rod is displaced for a retracted distance. In the next step, the unit and the drive unit can be connected to each other, so that the piston rod and the plug are disposed at an initial distance relative to each other when the mechanism is released.

In an embodiment, the deriving information includes determining a connection position of a connection for the unit and the driving unit from the result of the measurement, so if the units are connected at the connection position, when the mechanism is deactivated, The piston rod and the plug are disposed at an initial distance from each other. In this case, the unit and the drive unit may be connected to each other by means of a weld. Therefore, the unit and the drive unit can be brought into variable relative positions for connecting the unit and the drive unit to each other. In particular, neither the unit nor the drive unit may include a connecting member having a fixed position relative to the respective unit for connecting the unit and the driving unit to each other.

According to another embodiment, the derivation information includes: if the unit and The driving unit is connected by a connecting member disposed on the unit and the driving unit, and a relative position of the proximal end of the plug and the distal end of the piston rod is determined from the result of the measurement. In this embodiment, the weir unit and the drive unit may be connected to each other by a riveted connection or a thread. In this example, the unit and the drive unit each may include a connecting member having a fixed position relative to the respective unit for connecting the unit to the driving unit. The connecting part of the unit can contain, for example, a pin. The connecting part of the drive unit can, for example, comprise an indentation. Alternatively, the unit may comprise a recess and the drive unit may comprise a pin for establishing a riveted connection between the unit and the drive unit. Alternatively, the unit may comprise a thread and the drive unit may comprise a pair of threads.

The previously described mechanism can be configured such that when the mechanism is in the activated state and the device is fully assembled, the distal end of the piston rod is placed against the proximal end of the piston or at a distance relative to the proximal end. The mechanism can be configured such that when the mechanism is in the activated state, the plug may not be deformed or compressed or it may only be slightly compressed by the piston rod. The mechanism can be configured such that when the mechanism is in the activated state, the plugs and the piston rods abut each other to prevent the piston rod from exerting substantial pressure or thrust on the plug to prevent the generation of droplets. If the drug in the sputum is pressurized, droplets may occur and a needle unit is connected to the 匣 unit, thus establishing fluid communication between the 匣 unit and the environment.

When the mechanism is in the activated state, such as because all of the components are pushed distally relative to the housing, the clearance between the components of the drive unit can be reduced to a minimum. To this end, the measurement system is reliable since all components contain a well defined or biased position during measurement. To this end, the components are The relative position after assembly is also well defined. In addition, since the initial distance between the piston rod and the plug can be adjusted very precisely during the assembly process, the user-operated piloting step can be redundant.

When the device is fully assembled and in an initial state and the mechanism is deactivated, there may be no abutment between the piston rod and the plug. In particular, the plug member and the piston rod may be disposed at a predetermined initial distance from each other. The predetermined initial distance may be less than or equal to the back distance. By arranging the piston rod at a predetermined initial distance, a means for ensuring that the plug member and the piston rod are positioned relative to each other, thereby ensuring that a predetermined amount is dispensed by a first dose setting and a subsequent dose dispensing step The user-driven priming step of the drug may be redundant. The dose accuracy of the device can be increased.

According to a preferred embodiment, a drug delivery device is provided comprising: a housing comprising a distal end and a proximal end, the cartridge being adapted and configured to contain at least one dose of a drug, a stopper Removably disposed within the bore, wherein in an initial state of the device, the plug is disposed in a proximal position relative to the bore, a piston rod that is adapted and configured to move the plug in a distal direction relative to the bore For delivery of a dose of the drug.

The device further includes a mechanism operable to cause the piston rod to be moved a retracted distance into the proximal direction relative to the plug after a dose transfer operation is completed, and wherein in the initial state, a distal end of the piston rod and the plug A distance between a proximal end of the piece is greater than zero, wherein the distance between the piston rod and the plug in the initial state is determined by the receding distance Defined.

According to a preferred embodiment, a method for assembling a drug delivery device is provided, the method comprising the steps of: A) providing a unit comprising a cartridge, the cartridge securing at least one dose of a medicament, The plug is movably disposed in the cymbal, B) providing a drive unit connectable to the cymbal unit, the drive unit including a piston rod and a mechanism, wherein the mechanism is configured to switch from a start state to a release In the starting state, the piston rod is moved to a retracted distance, C) the mechanism is activated, D) the position of the proximal end of the plug is measured relative to a predetermined reference point on the unit, and E) is relative to a predetermined reference point on the drive unit. Measuring the position of the distal end of the piston rod, F) deriving information about the relative position of the distal end of the piston rod and the proximal end of the plug from the results of the measurements made in steps D) and E). G) deactivating the mechanism to cause the piston The rod is displaced by the retracted distance, H) the unit and the drive unit are connected to each other, so that the piston rod and the plug are disposed at an initial distance from each other when the mechanism is released.

The clearance between the movable components of the device can be removed by the activated mechanism. To this end, a very reliable measurement can be made which results in a device with high dose accuracy without an priming step that must be performed by the user.

Of course, the features described above in terms of different modalities and embodiments The systems can be combined with each other and with the features described below.

Further feature configurations and refinements are found in the following description of exemplary embodiments in conjunction with the drawings.

In Figures 1 and 2, a drug delivery device 1 is shown. The drug delivery device 1 comprises a housing 4. The drug delivery device 1 and the housing 4 have a distal end and a proximal end. The distal end is represented by arrow 17. The proximal end is represented by arrow 18. The term "distal" refers to the endpoint of the drug delivery device 1 or a component thereof that is or is configured to be closest to a dispensing end of the drug delivery device 1. "Proximal" refers to the end of the device 1 or a component thereof that is or is configured to be furthest from the dispensing end of the device 1. The distal end and the proximal end are separated from each other in an axial direction. The axis can be the longitudinal axis of the device 1.

The drug delivery device 1 comprises a tamper holder 2 . The drug delivery device 1 comprises a cassette 3. The crucible 3 is held in the crucible holder 2.匣 2 is a mechanically stable position of 匣3. The crucible holder 2 can be attached to the housing 4, for example, by a threaded engagement, by a weld or by a riveting. The crucible holder 2 and the housing 4 are non-releasably connected to each other. A cover 6 can be secured to the drug delivery device 1 to protect the device 1 and, in particular, the tether holder 2 or the crucible 3 from the environment, when the device 1 is not in use.

匣3 contains a drug 16, preferably a plurality of doses of drug 16. By "pharmaceutical" herein is meant a pharmaceutical formulation comprising at least one pharmaceutically active compound, wherein in one embodiment, the pharmaceutically active compound has a molecular weight of up to 1500 Da and/or is a peptide, a protein, a multi- sugar, a vaccine, a DNA, an RNA, an enzyme, an antihousing or a fragment thereof, a hormone or an oligonucleotide, or a mixture of the above pharmaceutically active compounds, wherein in another embodiment, Pharmaceutical active compounds can be used to treat and/or prevent diabetes or complications associated with diabetes such as diabetic retinopathy, thrombotic disorders such as deep veins or pulmonary thrombosis, acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macula Degeneration, inflammation, hay fever, arteriosclerosis and/or rheumatoid arthritis, wherein in another embodiment, the pharmaceutically active compound comprises at least one peptide for the treatment and/or prevention of diabetes or complications associated with diabetes Such as diabetic retinopathy, wherein in another embodiment, the pharmaceutically active compound comprises at least one human insulin or a human insulin analog or derivative, a glucagon-like peptide (GLP-1) or an analog or derivative thereof Or a substance similar to insulin secretagogue-3 or insulinotropic hormone-4 or insulinotropic hormone-3 or insulin secretagogue-4 Or derivative thereof.

Insulin analogues such as 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 the proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein Lys can be replaced by Pro in position B29; Ala (B26) human insulin; Des (B28-B30) Human insulin; Des (B27) human insulin and Des (B30) human insulin.

Insulin derivatives such as B29-N-mercapto-des (B30) human insulin; B29-N-palmitino-des (B30) human insulin; B29-N-mercapto human insulin; B29-N- Palmitoyl human insulin; B28-N-mercapto LysB28ProB29 human insulin; B28-N-palmitino-LysB28ProB29 human insulin; B30-N-mercapto-ThrB29LysB30 human insulin; B30-N-palmitino-ThrB29LysB30 Human insulin; B29-N-(N-palmitoyl-Y-glutamine)-des(B30) human insulin; B29-N-(N-stone-Y-glutamine)-des ( B30) Human insulin; B29-N-(ω-carboxyheptyl)-des (B30) human insulin and B29-N-(ω-carboxyheptadecanyl) human insulin.

Insulin-secretin-4 such as insulin-secretin-4-(1-39), 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 a peptide of -Ser-NH2).

The insulinotropic-4 derivative is, for example, a list selected from the group consisting of H-(Lys)4-des Pro36, des Pro37 insulin secretagin-4(1-39)-NH2, H-(Lys)5-des Pro36, des Pro37 insulin secretin-4(1-39)-NH2, des Pro36 insulin secretin-4 (1-39), Des Pro36[Asp28] Insulin Secretin-4 (1-39), des Pro36 [IsoAsp28] Insulin Secretin-4 (1-39), des Pro36[Met(O)14, Asp28] Insulin Secretin 4(1-39), des Pro36[Met(O)14, IsoAsp28] Insulin Secretin-4 (1-39), des Pro36[Trp(O2)25, Asp28] Insulin Secretin-4 (1- 39), des Pro36[Trp(O2)25, IsoAsp28] Insulin Secretin-4 (1-39), des Pro36[Met(O)14 Trp(O2)25, Asp28] Insulin Secretin-4 (1) -39), des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Insulin Secretin-4 (1-39); or des Pro36[Asp28] Insulin Secretin-4 (1-39), Des Pro36[IsoAsp28] Insulin Secretin-4 (1-39), des Pro36[Met(O), Asp28] Insulin Secretin-4 (1-39), des Pro36[Met(O), IsoAsp28] Insulin Secretin-4 (1-39), des Pro36 [Trp(O2)25, Asp28] Insulin Secretin-4 (1-39), des Pro36 [Trp(O2)25, IsoAsp28] Insulin Secretin- 4(1-39), des Pro36[Met(O)14 Trp(O2)25, Asp28] insulinotropic Prostaglandin-4 (1-39), des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Insulin Secretin-4 (1-39), in which the group -Lys6-NH2 can be bound to C-end point of the insulin secretin-4 derivative; or an insulin secretagogue-4 derivative of the following sequence: des Pro36 insulin secretagin-4(1-39)-Lys6-NH2 (AVE0010), H-( Lys)6-des Pro36[Asp28] Insulin Secretin-4(1-39)-Lys6-NH2, des Asp28 Pro36, Pro37, Pro38 Insulin Secretin-4(1-39)-NH2,H-(Lys 6-des Pro36, Pro38[Asp28] Insulin Secretin-4(1-39)-NH2, H-Asn-(Glu)5des Pro36, Pro37, Pro38[Asp28] Insulin Secretin-4 (1-39) )-NH2,des Pro36,Pro37,Pro38[Asp28]insulin-secretin-4(1-39)-(Lys)6-NH2,H-(Lys)6-des Pro36,Pro37,Pro38[Asp28]insulin Secretin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Asp28] Insulin Secretin-4(1-39)-(Lys) 6-NH2,H-(Lys)6-des Pro36[Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36, Pro37, Pro38[Trp(O2)25] Insulin Secretin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin Secretin-4 (1-39) -NH2, des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin secretin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Trp(O2)25 , Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36[Met(O)14, Asp28] Insulin Secretin-4 (1-39 )-Lys6-NH2, des Met(O)14, Asp28 Pro36, Pro37, Pro38 Insulin Secretin-4(1-39)-NH2, H-(Lys)6-desPro36, Pro37, Pro38[Met(O) 14, Asp28] Insulin secretin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin secretin-4 (1 -39)-NH2, des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin secretin-4(1-39)-(Lys)6-NH2,H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2, H-Lys6-des Pro36[ Met(O)14, Tro(O2)25, Asp28] Insulin Secretin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36, Pro37, Pro38[Met(O)14, Trp(O2) 25] Insulin-secretin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin-secretin-4(1-39)- NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-NH2, des Pro36, Pro37 , Pro38[Met(O)14, Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38[ Met(O)14, Trp(O2)25, Asp28] Insulin secretin-4(S1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met (O)14, Trp(O2)25, Asp28] Insulin-secretin-4(1-39)-(Lys)6-NH2; or one of the above-mentioned insulinotropic secretin-4 derivatives Accepted salt or solvate.

Hormones such as pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, such as Rote Liste, 2008 edition, listed in Chapter 50, such as Gonadotropine (Follitropin) Lutropin, chorionic gonadotropin (Choriongonadotropin), Menotropin, Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin (Triptorelin), Leuprorelin, Buserelin, Nafarelin, Goserelin.

The polysaccharide is, for example, a glycosaminoglycan, hyaluronic acid, heparin, low molecular weight heparin or ultra low molecular weight heparin or a derivative thereof, or a sulfated hydrazine such as a polysulfated form of the above polysaccharide, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.

The anti-system is a ball plasma protein (~150 kDa), also known as immunoglobulin, which shares a basic structure. Since it has a sugar chain added to the amino acid residue, it is a glycoprotein. The basic functional unit of each antihousing is an immunoglobulin (Ig) monomer (containing only one Ig unit); the secreted antibody may also be a dimeric having two Ig units, like IgA, A tetrameric having four Ig units, like the teleost fish IgM, or a penameric having five Ig units, like a mammalian IgM.

The Ig single system is a "Y" shaped molecule consisting of four polypeptide chains; two identical heavy chains and two identical light chains, linked by a disulfide bond between the cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. The heavy and light chains each contain an intrachain disulfide bond that stabilizes their folding. Each chain is divided into structures called Ig subdomains. (structural domains) constitute. These subdomains contain from about 70 to 110 amino acids and are classified into different classes depending on their size and function (for example, variable or V, and fixed or C). It has a characteristic immunoglobulin fold in which the two beta sheets form a "sandwich" shape that is held together by the interaction between the retained cysteine and other charged amino acids.

There are five types of mammalian Ig heavy chains, designated as alpha, delta, epsilon, gamma and mu. The type of heavy chain that appears is defined as the isotype of antihousing; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

Different heavy chains have different sizes and compositions; alpha and gamma contain approximately 450 amino acids and δ contains approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, a fixed region (C _H ) and a variable region (V _H ). In one species, the imprinted regions are substantially identical in all antibodies of the same isotype, but are different in different isotypes of antibodies. The heavy chain γ, α, and δ have a fixed region composed of three columnar Ig domains, and a hinge region for adding flexibility; the heavy chain μ and ε have four immunoglobulin domains. One of the fixed areas. The variable regions of the heavy chain differ in the antibodies produced by different B cells, but are identical for all antibodies produced by a single B cell or a B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and consists of a single Ig domain.

In mammals, there are two types of immunoglobulin light chains, designated as λ and κ. A light chain has two successive sub-domains: a fixed sub-domain (CH) and a variable sub-domain (VL). The approximate length of a light chain is 211 to 217 amines Base acid. Each of the anti-shells contains two light chains that are always identical; only one type of light chain, kappa or lambda, appears in each anti-shell.

Although the general structure of all antibodies is very similar, the unique properties of a given anti-shell are dependent on the variable (V) region, as described above. More specifically, three variable loop systems, each on the light (VL) and heavy (VH) chains, are responsible for binding to the antigen, ie for antigen specificity. These loops are called complementarity determining regions (CDRs). Since the CDR lines from the VH and VL domains contribute to the antigen binding site, it is the combination of heavy and light chains that is not the sole one to determine the final antigen specificity.

An "antihousing fragment" contains at least one antigen-binding fragment as defined above and exhibits substantially the same function and specificity as the intact anti-capsid from which the fragments are derived. The Ig prototype was chopped into three fragments using limited proteolytic digestion of papaya peptone. Two identical amino terminal fragments each containing a complete L chain and about half of the H chain are antigen-binding fragments (Fab). A third fragment of a carboxyl terminal half having a similar size but comprising a double chain having an interchain disulfide bond is a crystallizable fragment (Fc). Fc contains carbohydrates, complementary binding, and FcR binding sites. The restricted peptone digestive system produces a single F(ab')2 fragment containing a Fab block and a hinge region, including an H-H interchain disulfide bond. F(ab')2 is bivalent for antigen binding. The disulfide bond of F(ab')2 can be chopped to obtain Fab'. Also, the variable regions of the heavy and light chains can be fused together to form a single-chain variable fragment (scFv).

Pharmaceutically acceptable salts are, for example, acid addition salts and base salts. Acid addition The salt is such as HCl or HBr salt. The alkali salt is, for example, a salt having an anion selected from the group consisting of a strong base or a basic such as Na+, or K+, or Ca2+, or a monoammonium ion N+(R1)(R2)(R3)(R4), Wherein R1 to R4 independently of each other represent: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, a selectively substituted C6-C10-aryl group, or an optional one. Sex substituted C6-C10-heteroaryl. Other examples of pharmaceutically acceptable salts are described in "Remington's Pharmaceutical Sciences", 17th edition, Alfonso R. Gennaro (eds.), Mark Publishing Company, Easton, Pennsylvania, 1985 , and the pharmacy science encyclopedia.

Pharmaceutically acceptable solvates are, for example, hydrates.

A plug 5 is slidably held in the crucible 3. The plug 5 is used to seal the crucible 3 in a proximal direction. The movement of the plug 5 relative to the 匣3 in the distal direction results in the dispensing of the drug 16 from the 匣3. The plug 5 is placed in a proximal position relative to the crucible 3 in an initial state of the device 1, i.e., in a state of being supplied from the manufacturer prior to setting and dispensing a first dose.匣3 can be completely filled in the initial state, for example, drug 16 has not been dispensed from 匣3.

The drug delivery device 1 can be a one-piece device, in particular a one-piece syringe. The device 1 is preferably configured to dispense a fixed dose of the drug 16, i.e., a dose that is not modifiable by the user. The device 1 is a reusable device, which means that the cassette 3 can be replaced by a replacement cassette during a reset operation for dispensing a plurality of doses from the replacement cassette. Alternatively, the device 1 can be a disposable device 1 that is non-releasably coupled to the crucible holder 2 on behalf of the crucible 3.

The device 1 comprises a drive mechanism 7A, 7B, 13, 14. The drive mechanism is used to set and dispense a dose of medication 16. For details of the drive mechanism, please refer to the aforementioned document WO 2008/058666 A1. The device 1 comprises a piston rod 9. The piston rod 9 is configured to operate via the housing 4 of the device 1.

In an embodiment of the device 1 (see Figures 1, 2 and 7A to 7D), the length of the piston rod 9 can be varied. This effect can be achieved by an adjustment member 10. The adjustment member 10 may be part of the piston rod 9. The adjustment member 10 can be displaceably disposed on the piston rod 9. The adjustment member 10 can be disposed at the distal end of the piston rod 9. The adjustment member 10 can be coupled to the piston rod 9 and can preferably be displaced relative to the piston rod 9 along the longitudinal axis of the piston rod, such as in the axial direction, for increasing or decreasing the length of the piston rod 9 prior to final assembly of the device 1. , which is described in more detail later. In an alternative embodiment, the length of the piston rod 9 is fixed (see the embodiment of Figure 5).

In an embodiment where the length of the piston rod 9 is variable, the adjustment member 10 is interconnected with a distal end section of the piston rod 9 facing the plug member 5. Therefore, at least one adjustment member 10 is disposed between the piston rod 9 and the plug 5. The adjustment member 10 thus serves as an interface member that is intended to compensate for variations in the mutual distance and/or relative position of the piston rod 9 and the plug member 5 that may occur, for example, due to manufacturing and/or assembly tolerances. The piston rod 9 can further comprise at least one interlocking component. The interlocking members are adapted to interact with the adjustment member 10 and/or with the piston rod 9 for locking the adjustment member 10 and the piston rod 9 in position relative to each other in any relative position. In particular, the axial position of the adjustment member 10 relative to the piston rod 9 can be continuously modified, preferably to eliminate such manufacturing and assembly. difference. Once the adjustment member 10 has been positioned with the piston rod 9 in a tolerance relief configuration, its relative position to the piston rod 9 can be permanently or releasably locked by at least one interlocking member. The adjustment member 10 and the piston rod 9 are mutually displaceable relative to each other during a tolerance elimination procedure, such as the assembly process described below. In other words, it may be telescopically displaced in the axial direction. Once a tolerance elimination configuration is reached, the adjustment member 10 and the piston rod 9 can be interlocked with each other in this manner, and the piston rod 9 can transfer a respective thrust or force required to displace the plug member 5 in the distal direction to the plug. Item 5. By displaceably attaching or coupling the piston rod 9 and the adjustment member 10 thereto, the overall axial dimension and extent of the piston rod 9 becomes variable, particularly for tolerance relief applications.

In another preferred embodiment (see Figures 7A through 7C), the adjustment member 10 and the piston rod 9 are threadedly engaged to axially displace the piston rod 9 and the adjustment member 10 relative to each other. The adjustment member 10 and the piston rod 9 are threadedly engaged by mechanical cooperation of an internal thread 23 of the adjustment member (see Fig. 7C) and an external thread 12 of the piston rod (see Figs. 7A and 7C). The tread is preferably self-locking. By adjusting the threaded engagement of the member 10 and the piston rod 9, the overall axial dimension of the piston rod 9 can be modified in a continuous manner. Here, the interlocking member is further adapted to inhibit the self-acting relative rotation of the piston rod 9 and the adjusting member 10. Thus, the interlocking member prevents the adjustment member 10 from autonomously rotating relative to the piston rod 9 and vice versa. By means of a threaded engagement, the axially guided forces and thrusts can be transferred from the drive mechanism to the adjustment member 10, for example via the piston rod 9, and eventually to the plug 5.

Since the interlocking member is designed to inhibit the self-acting relative rotation of the piston rod 9 and the adjusting member 10, the interlocking member itself may not have to withstand the large axial force or individual thrust required to displace the plug member 5 in the far end direction.

In another preferred form (see Figure 7C), the adjustment member 10 includes a threaded receptacle adapted to receive a corresponding threaded distal socket portion of one of the piston rods 9.

In an alternative embodiment (not explicitly shown), the piston rod 9 includes a threaded receptacle at its distal end section that is adapted to receive a corresponding threaded proximal socket portion of one of the adjustment members 10. Thus, the threaded engagement of the piston rod 9 and the adjustment member 10 can be generally implemented in any manner.

In another preferred form (see Figure 7D), the interlocking member includes at least one resiliently biased tongue member 24, and at least one resiliently biased tongue member 24 is adapted to engage the adjustment member 10 or the piston rod 9. A wave of pleated surface portion 25. Preferably, the interlocking member is positively engageable with a side wall of the receptacle of either of the adjustment member 10 or the piston rod 9. Further, the interlocking member is preferably disposed on the portion including the socket portion.

In another preferred embodiment, the tongue member 24 is configured to be laterally offset relative to the socket portion. The axially projecting socket portion is typically disposed on the center of the adjustment member 10 relative to the transverse plane of the piston rod 9 that extends orthogonally to the longitudinal axis of the piston rod. Here, the toughly biased tongue member 24 is configured and displaced to be offset laterally or radially relative to the socket portion. Accordingly, the mutual arrangement of the socket portion and the tongue member 24 is such that a gap is formed between a side wall portion of the receptacle that is adapted to receive the receptacle.

In another preferred embodiment, the radially inward side wall of the pocket is Threaded to provide a threaded engagement with a corresponding threaded socket portion. The side wall section of the receptacle facing outwardly is preferably pleated or comprises a rib-like structure for establishing a positive or frictional engagement of the receptacle with the tongue member, thereby suppressing the receptacle from being opposite the socket portion Self-acting relative rotation.

In an alternative embodiment, it is also contemplated that an outwardly facing sidewall section of the pocket is threaded, and wherein the inwardly facing sidewall section of a pocket is pleated or comprises a ribbed surface structure. In these embodiments, the toughly biased tongue member is preferably configured to be radially inward relative to the threaded engagement of the adjustment member 10 with the piston rod 9.

The mutual engagement and interaction of the toughly biased tongue member and the pleated surface provides a snap-in feature. Depending on the overall number of longitudinally extending ribs or pleats and the pitch of the threads, one of the fine adjustments of the piston rod and the adjustment member 10 in the sub-millimeter range, preferably in the range of 1/10 mm or even 1/100 mm, can be achieved. .

In another preferred embodiment (not explicitly shown), the threaded and corrugated sidewall sections of the pocket are configured to be at least partially offset relative to each other in the axial direction. Moreover, the pleats or ribs of the wall segment comprise an axial extension that substantially extends axially substantially corresponding to one of the corresponding threads of the receptacle and the socket portion.

According to another embodiment (not explicitly shown), the piston rod 9 comprises at least two tongue members which are arranged on the piston rod 9 and are axially displaced in the immediate direction with respect to the distal end section of the piston rod. Here, preferably, the tongue members that are opposite to each other in the transverse plane comprise lug portions that are radially inwardly pointed, A pleated or ribbed outer sidewall section that is adapted to engage a proximal end of the adjustment member 10 that includes a cup-like receptacle.

In another form (see Figures 1 and 2), it is intended that the adjustment member 10 includes a contact surface at its distal end portion, and if the drug delivery device 1 is in an initial state, its tether is facing a proximal end portion of the stopper member 5. . The contact or abutment surface has a substantially planar shape and preferably extends in the transverse plane and thus extends orthogonally to the axial or longitudinal direction of the piston rod. Preferably, the outwardly facing outer surface of the cup-shaped receptacle of the adjustment member 10 acts as a contact surface.

Hereinafter, the abutment of the piston rod 9 and the plug 5 may refer to the adjustment member 10 abutting against the plug 5.

The foregoing embodiment of the piston rod 9, adjustment member 10 and/or interlocking member results in a piston rod having an adjustable length that can be used to compensate for manufacturing tolerances as described below. As further described above, in an alternative embodiment of the device 1, the length of the piston rod 9 can be fixed. In this case, the foregoing embodiment may be redundant and the tolerance may be compensated by adjusting a connection position between the yoke holder 2 and the housing 4. Eliminating the tolerance results in a defined initial position of the piston rod 9 relative to the plug 5 after the connection of the tamper holder 2 and the housing 4 is completed and before the first dose of medication is dispensed from the 匣3.

The device 1 comprises a mechanism, in particular a receding mechanism. The mechanism includes a spring member 15, such as a helical coil spring. The spring member 15 is axially fixed within the housing 4. The spring member 15 is flexibly mounted within the housing. The spring member 15 is flexible in the axial direction. Spring member 15 and housing 4 or a portion of drive mechanism 7A or an insert of the housing Formed in one piece. With the retracting mechanism, after a dose delivery operation, the piston rod 9 is moved proximally by a retracted distance D, which will be described in more detail later. The receding distance D can be less than 1.0 mm. Preferably, the receding distance D is less than 0.5 mm. The receding distance D can be greater than 0.1 mm. The receding distance D is preferably, for example, a total of 0.3 mm.

In the initial state of the device, the proximal end of the piston rod 9 is disposed at a predetermined initial distance from the proximal end of the plug member 5. The predetermined initial distance is equal to or smaller than the back distance D. In particular, the predetermined initial distance may be defined by the receding distance D, which is described in terms of the assembly process of the device 1. The predetermined initial distance, for example, reaches a total of 0.2 mm. To this end, in the initial state of the device 1, the piston rod 9 and the plug member 5 are disposed at a predetermined initial position with respect to each other. The user's operation, such as the priming step, to dispose the piston rod 9 and the plug 5 in a predetermined relative position is redundant.

The device 1 comprises an actuating member 14. The actuation member 14 is at least partially disposed within the housing 4 of the device 1. Actuating member 14 can include a dose button. Actuating member 14 can include a drive member. The actuation member 14 is displaceable relative to the housing 4. The actuation member 14 can be positioned relative to the housing 4 in a first position (see Figure 6A). The first position may be the furthest position of the actuation member 14 relative to the housing 4. Alternatively, the actuation member 14 can be positioned in a second position relative to the housing 4 (see Figure 6B). The second position of the actuation member 14 can be a retracted or initial position. Alternatively, the actuation member 14 can be positioned in a third position relative to the housing 4 (see Figure 6C). The third position may be the closest position of the actuation member 14 relative to the housing 4. The second position is configured relative to the housing 4 as compared to the first position More neighbors. The third position is disposed closer to the housing 4 than the second position.

After a dose delivery operation is fully completed, the actuation member 14 is positioned in the first position (see Figure 1). When the actuation member 14 is in the first position, the mechanism is activated. Prior to initiating a dose setting operation, such as in an initial state, the actuation member 14 is positioned in the second position (see Figure 2). When the actuating member 14 is in the second position, the mechanism is deactivated. After a dose setting operation is completed, the actuation member 14 is positioned in the third position. When the actuation member 14 is in the third position, the mechanism is deactivated.

The actuation member 14 is moveable from the second or third position into the first position for activation of the mechanism of the device 1. The actuation member 14 is movable from the third position into the first position for delivery of a set dose of medicament 16. The movement of the actuating member 14 from the third position into the first position is transferred to the piston rod 9 by mechanical cooperation of the actuating member 14 and the piston rod 9.

The actuating member 14 is movable from the first position, i.e., the most distal position, into the second position, i.e., the retracted or initial position, for deactivating the mechanism of the device 1. The motion of the actuating member 14 to be displaced from the first position into the second position is transferred to the piston rod 9 for displacing the piston rod 9 by a receding distance D, which will be described in more detail later.

The actuation member 14 can be further moved from the second position into the third position for setting a dose of the medicament 16. The movement of the actuating member 14 for being displaced from the second position into the third position is prevented from being transferred to the piston rod 9 by the mechanical cooperation of the housing 4 with the piston rod 9.

The operation of the receding mechanism, together with the assembly and operation of the device 1, is described below.

In order to assemble the device 1, the following steps are performed. The steps can be, but are not limited to, performed in the following order. Please note that the steps described below apply to the case where the length of the piston rod can be adjusted. This is hereinafter referred to as embodiment "A". A connection between the housing 4 and the crucible holder 2 can be varied to compensate for tolerances without the need for a piston rod 9 having an adjustable length, hereinafter referred to as embodiment "B" and described later.

A.1) In the first step, a crucible holder 2 containing crucible 3 is provided. The 匣3 series is in a fully filled state. In particular, the plug 5 is disposed in a proximal position relative to the crucible 3.

A.2) In a second step, a housing 4 is provided in which the actuation member 14, the spring member 15 and the piston rod 9 are held. The actuation member 14 is in the second position and the mechanism is thus deactivated. In particular, the spring 15 is in a relaxed state. The housing 4 is not yet connected to the crucible holder 2.

A.3) In the next step, the aforementioned back-off mechanism is activated. This effect is achieved by moving the actuating member 14 distally from the second position into the first position. The distance by which the actuating member 14 is moved distally is, for example, a total of 0.6 mm. This distance can be greater than 0.1 mm. The distance can be less than 2.0 mm. The actuating member 14 is moved against a proximally directed force provided by the spring member 15. To this end, the spring member 15 is biased when the actuating member 14 is moved distally. When the actuating member 14 is moved into the first position, the piston rod 9 also moves distally. For example, the piston rod 9 is moved distally by one-half of the distance traveled by the actuating member 14. For example, the piston rod 9 is far Move up to 0.3 mm. To this end, the mechanical benefits of the device 1 total up to 2:1 (see the example of "racks and pinions" in document WO 2008/058666 A1). When the actuation member 14 is positioned in the first position, the receding mechanism is fully activated.

A.4) In the next step, the position of the proximal end of the plug 5 relative to a predetermined reference point on the unit is measured. For example, the reference point can be placed on the 匣3 or the 匣 holder 2 (see Figure 3).

A.5) In the next step, the position of the distal end of the piston rod 9 relative to a predetermined reference point 19 on the housing 4 is measured.

A.6) In the next step, when the crucible holder 2 and the housing 4 are connected, the relative position of the proximal end of the plug 5 in which the mechanism is activated and the distal end of the piston rod 9 are taken from the two previous steps (step A). The measurement results performed in .4) and A.5)) are calculated, for example, the known and reliable dimensions of the retaining member 2 and the housing 4, the marking position and the measured value of the crucible holding member 2 and the casing 4 Based on. This relative position is preferably such that when the mechanism is activated and the device 1 is fully assembled, the plug 5 is not compressed by the piston rod 9 or is only minimally compressed. The relative position is preferably such that when the mechanism is activated and the device 1 is fully assembled, the plug 5 and the piston rod 9 abut each other or have a small distance therebetween.

A.7) In the next step, the organization is deactivated. This effect is achieved by releasing the actuating member 14. Once released, the actuating member 14 automatically moves from the first position into the second position due to the proximally directed force exerted by the spring member 15 on the actuating member 14. The movement of the actuating member 14 from the first position into the second position is transferred to the piston rod 9 such that the piston rod 9 is displaced to a retreat distance D. The piston rod 9 is displaced by a receding distance D, which for example amounts to 0.3 mm in total. When the actuating member 14 is in the second position, the mechanism is fully deactivated.

A.8) In the next step, it is checked whether the relative position calculated in step A.6) corresponds to a predetermined relative position. The predetermined relative position can be selected such that when the mechanism is activated and the device 1 is fully assembled, the plug 5 is not compressed by the piston rod 9 or only slightly compressed. Therefore, the predetermined relative position should be selected such that the plug 5 and the piston rod 9 abut each other such that the piston rod 9 does not exert substantial pressure or thrust to the plug 5 to prevent the generation of droplets.

A.9) If the relative position calculated in step A.6) does not correspond to the predetermined relative position (see step 8)), the length of the piston rod 9 may be changed as described above.

If the relative position calculated in step A.6) is such that when the mechanism is activated and the device 1 is finally assembled, there will be a gap between the distal end of the piston rod 9 and the proximal end of the plug 5, in the far direction The adjustment member 10 is screwed with respect to the piston rod 9 to increase the length of the piston rod 9. Otherwise, underdosing can occur, which can have life-threatening or even fatal consequences for the user.

On the other hand, if the relative position calculated in step A.6) is such that the distance between the distal end of the piston rod 9 and the proximal end of the plug 5 is too small when the device 1 is assembled, the piston rod 9 will strongly compress the plug 5 . This can result in microdroplets or even too much dose of drug 16. To this end, in this example, the piston rod 9 is reduced by screwing the adjustment member 10 relative to the piston rod 9 in the proximal direction. length.

After adjusting the length of the piston rod 9, steps A.3) to A.8) are repeated. If the relative position calculated in step A.6) does not correspond to the predetermined relative position at this time, step A.8) is repeated again.

A.10) If after step A.8) and the selectivity is after A.9), the relative position calculated in step A.6) corresponds to the predetermined relative position, then the crucible holder 2 and the housing 4 are moved to Each other (arrow 21 of Figure 4) is connected to each other (see Figure 4). Therefore, the crucible holder 2 and the casing 4 are non-releasably connected by screwing or riveting the crucible holder 2 and the casing 4 to each other. Thus, the connecting members, such as the two butt threads or the two butt fitting components, are arranged in a fixed position relative to the housing 4 and the cymbal holder 2.

The steps for assembling the device 1 according to Embodiment B are described below. In embodiment B, the length of the piston rod 9 can be fixed and the piston rod 9 may not be used to compensate for tolerances.

With regard to steps B.1) to B.5), reference is made to steps A.1) to A.5), which also applies to the case where the length of the piston rod 9 is not adjustable.

B.6) In the next step, the measurement results of steps B.4) and B.5) are used to determine the connection position of one of the connection of the holding member 2 and the housing 4, such as the holding member 2 and the housing. The known and reliable dimensions of the body 4, the position and measurement values of the markings on the crucible holder 2 and the housing 4 are based. Therefore, the connection position is selected such that if the housing 4 and the crucible holder 2 are connected at the connection position, when the mechanism is deactivated, the piston rod 9 and the plug member 5 are disposed at a predetermined initial distance from each other. In particular, from the steps The measurements made in B.4) and B.5) determine which joint locations the yoke holder 2 and the housing 4 should have to achieve an initial distance between the plug 5 and the piston rod 9 when the device 1 is fully assembled. This distance is preferably such that when the mechanism is activated and the device 1 is fully assembled, the plug 5 is not compressed by the piston rod 9 or is only minimally compressed. When the mechanism is activated, the distance between the piston rod 9 and the plug 5 can be zero or greater than zero. This distance is preferably such that when the mechanism is activated and the device 1 is fully assembled, the plug 5 and the piston rod 9 abut each other or have a small distance therebetween.

B.7) In the next step, the organization is deactivated. With regard to step B.7), reference is made to step A.7), which also applies to embodiments in which the length of the piston rod 9 is not necessarily adjustable.

B.8) In the next step, the crucible holder 2 and the housing 4 are moved toward each other and connected to each other. Therefore, the crucible holder 2 and the casing 4 are non-releasably connected by, for example, a weld, which is shown in FIG. The crucible holder 2 and the housing 4 are welded to each other, for example, by a laser. The crucible holder 2 and the housing 4 are welded to each other, for example by a weld surface 22 (Fig. 5). This has the advantage that the crucible holder 2 and the housing 4 can be brought into a variable relative position when the crucible holder 2 and the housing 4 are connected to each other. To this end, the piston rod 9 and the plug 5 can be led in a variable relative initial position. In particular, by fusing the crucible holder 2 and the housing 4 to each other, a variable predetermined initial distance between the piston rod 9 and the plug member 4 can be established. This is possible because the weld surface 22 can be applied to different locations on the outer surface of the housing 4 and the crucible holder 2. For this reason, in this example, the adjustment of the length of the piston rod 9 is redundant.

When the crucible holder 2 and the casing 4 are joined, the apparatus 1 is completely assembled, particularly after the step A.10) of the embodiment "A" or the step B.8 of the embodiment "B" has been carried out. At this time, the device 1 is in the aforementioned initial state. The initial distance between the distal end of the piston rod 9 and the proximal end of the plug 5 is greater than zero. The initial distance is defined by the retraction distance D of the piston rod 9 as it moves from the first position into the second position during the assembly process. The distance in the initial state may correspond to the receding distance D.

The device 1 is supplied to the user in an initial state. To operate the device 1, the following steps are performed: To set a dose of the medicament 16, the user moves the actuation member 14 from the second position into the third position (see Figure 2). The piston rod 9 is held in its position by mechanical cooperation with the housing 4. The piston rod 9 is disposed at a predetermined initial distance from the plug 5, which corresponds to the receding distance in FIG.

To deliver the dose, the user moves the actuation member 14 from the third position into the first position. The movement of the actuating member 14 is thus transferred to the piston rod 9 for dispensing the dose. When the actuating member 14 is moved distally, the spring member 15 is biased and the mechanism is thereby activated. When the actuation member 14 is in the first position, the mechanism is activated. The dose delivery operation is completed when the actuation member 14 is in the first position. This state is depicted in Figure 1.

The user now releases the actuation member 14. The actuation member 14 is automatically moved by the spring member 15 from the first position into the second position. because Therefore, the machine is released. When the actuating member 14 is moved into the second position, the piston rod 9 is moved proximally by a receding distance D. The receding distance D is less than the distance the piston rod 9 is moved distally during a dose transfer operation, that is, when the actuating member 14 is moved from the third position into the first position. The amount of receding distance D is preferably less than 30% of the distance that the piston rod 9 is moved distally during a dose transfer operation. At this point, device 1 is ready to set and dispense another dose of drug 16.

1‧‧‧Drug delivery device

2‧‧‧匣 holding parts

3‧‧‧匣

4‧‧‧Shell

5‧‧‧plugs

6‧‧‧ Cover

7A‧‧‧ inserts

7B‧‧‧ drive mechanism

9‧‧‧ piston rod

10‧‧‧Adjustment components

11‧‧‧ bearing surface

12‧‧‧ thread

13‧‧‧Drive mechanism

14‧‧‧Actuating components

15‧‧‧Spring components

16‧‧‧ drugs

17‧‧‧ distal

18‧‧‧ Near end

19‧‧‧ Reference point

20‧‧‧ distance

22‧‧‧welding plane

D‧‧‧Retraction distance

23‧‧‧ internal thread

24‧‧ ‧ tongue members

25‧‧‧Surface

1 is a cross-sectional side view schematically showing a drug delivery device, and FIG. 2 is a schematic cross-sectional side view showing the drug delivery device of FIG. 1 after performing a dose setting operation, and FIG. 3 is a view schematically showing the drug delivery device of FIG. FIG. 4 schematically shows the drug delivery device of FIG. 3 after assembly is completed; FIG. 5 schematically shows a perspective side view of the assembled drug delivery device of FIG. 5; FIGS. 6A to 6C schematically show the operation. 1 is a side elevational view of a portion of the drug delivery device of FIG. 1 in different states; FIGS. 7A and 7B are schematic perspective views showing portions of the drug delivery device of FIG. 1; FIG. 7C is a schematic view of the portion shown in FIGS. 7A and 7B a cross-sectional side view of a portion of the drug delivery device; Figure 7D schematically shows the drug delivery device shown in Figures 7A through 7C The bottom view of the part.

Similar elements, elements of the same kind, and elements of the same function may have the same number in several figures.

1‧‧‧Drug delivery device

2‧‧‧匣 holding parts

3‧‧‧匣

4‧‧‧Shell

5‧‧‧plugs

7A‧‧‧ inserts

7B‧‧‧ drive mechanism

9‧‧‧ piston rod

10‧‧‧Adjustment components

11‧‧‧ bearing surface

13‧‧‧Drive mechanism

14‧‧‧Actuating components

15‧‧‧Spring components

16‧‧‧ drugs

17‧‧‧ distal

18‧‧‧ Near end

Claims (15)

A drug delivery device (1) comprising: a housing (4) comprising a distal end and a proximal end, a raft (3) adapted and configured to contain at least one dose of a drug (16) a plug (5) is movably disposed in the weir (3), wherein in an initial state of the device (1), the plug (5) is disposed adjacent to the weir (3) An end position, a piston rod (9) adapted and configured to move the plug (5) in the distal direction relative to the jaw (3) for delivering a dose of the medicament (16), wherein the device (1) comprising a mechanism operable to move the piston rod (9) relative to the plug member (5) by a back off distance (D) into the neighbor after a dose transfer operation is completed Direction, and wherein in the initial state, a distance between a distal end of the piston rod (9) and a proximal end of the plug member (5) is greater than zero, wherein the piston in the initial state The distance between the rod (9) and the plug (5) is defined by the receding distance (D). The device of claim 1, further comprising an actuating member (14) movable relative to the housing (4), wherein the actuating member (14) is movable in a first position and Between a second position, and wherein the motion member of the actuating member (14) for being displaced from the first position into the second position is transferred to the piston rod (9) for the piston rod ( 9) The displacement reaches the retreat distance (D). Such as the device described in claim 1 or 2, wherein the latter The retraction distance (D) is greater than or equal to the distance between the distal end of the piston rod (9) and the proximal end of the plug (5) in the initial state. The device of claim 2, wherein the actuating member (14) is further movable between the second position and a third position, wherein the actuating member (14) is positioned at a After the dose setting operation is completed, wherein the third position is disposed closer to the housing (4) than the second position. The device of any one of claims 2 to 4, comprising a spring member (15) mounted in the housing (4), wherein the spring member (15) is configured and configured Applying a force to the actuating member (14) to move the actuating member (14) from the first position into the second position, thereby moving the piston rod (9) proximally to the retracted distance ( D). The device of claim 5, wherein the receding distance (D) is in the range of 0.1 to 1.0 mm. The device of claim 5, wherein the receding distance (D) is less than the distance that the piston rod (9) is moved distally during a dose transfer operation. The device of any one of claims 1 to 7, wherein the piston rod (9) is configured such that the axial dimension of the piston rod (9) can be varied. A method for assembling a drug delivery device (1), the method comprising the steps of: A) providing a unit comprising a crucible (3), the crucible (3) being held to a dose (16) of less than one dose, a plug (5) is movably disposed within the crucible (3), B) providing a drive unit connectable to the crucible unit, the drive unit including a piston a rod (9) and a mechanism, wherein the mechanism is configured to move the piston rod (9) to a retracted distance when the mechanism is switched from a starting state to a deactivated state, C) actuating the mechanism, D) relative Measuring a position of the proximal end of the plug (5) at a predetermined reference point on the unit, and E) measuring a position of the distal end of the piston rod (9) with respect to a predetermined reference point on the drive unit, F Deriving information indicating the relative position of the distal end of the piston rod (9) and the proximal end of the plug (5) from the results of the measurements made in steps D) and E), G) deactivating the mechanism Causing the piston rod (9) to be displaced by the retracted distance (D), H) connecting the unit and the driving unit to each other, so that the piston rod (9) and the plug (when the mechanism is deactivated) 5) The distances are arranged at an initial distance from each other. The method of claim 9, wherein deriving the information comprises determining, from the results of the measurements, a connection location for the connection unit and the drive unit, so if the units are The connection in the connection position is connected, and when the mechanism is released, the piston rod (9) and the plug (5) are spaced apart from each other. Placed at this initial distance. The method of claim 9 or 10, wherein the connection is a fusion. The method of claim 9, wherein the deriving the information comprises: if the unit and the driving unit are connected by a connecting component disposed on the unit and the driving unit, the measured from the The result determines a relative position of the proximal end of the plug (5) to the distal end of the piston rod (9). The method of claim 12, further comprising the step of: checking whether the relative position of the proximal end of the plug (5) and the distal end of the piston rod (9) corresponds to the proximal end of the plug (5) and a predetermined relative position of the distal end of the piston rod (9). The method of claim 13, wherein if the relative position does not correspond to the predetermined relative position, modifying an axial dimension of the piston rod (9) such that the relative position corresponds to the predetermined relative position. The method of claim 13 or 14, wherein the predetermined relative distance is selected such that when the device (1) has been assembled and the mechanism is activated, the plug (5) proximal end and the This initial distance between the distal ends of the piston rods (9) is equal to or slightly greater than zero.