Bearing component for a piston rod of a drug delivery device, piston rod comprising the bearing component, and drug delivery device

Bearing components for piston rods of drug delivery devices, piston rods that include bearing components, and drug delivery devices.

Drug delivery devices, especially pen-type injection devices, include a bung, which functions to drain a dose of drug from a container such as a drug cartridge and is provided as part of the drug cartridge. The stopper is driven by a piston rod, which provides a mechanism for setting a dose and advancing the piston rod to deliver the set dose. Depending on the pen-type injection device, the piston rod may lead Includes screw), which rotates as it progresses during dosing the dose. Since it is preferable that the rotation of the stopper is avoided, the piston rod rotates relative to the stopper during dosing. In this case, the direct contact between the piston rod and the stopper causes a large friction loss, and a slightly stronger driving force may be required. This inconvenience can be avoided by a suitable bearing. Further, if the contact area or contact is small, the plug is likely to be deformed during dosing, which reduces the accuracy of the dose. Therefore, it is desirable that the contact between the plug and the piston rod has as large an area as possible. Therefore, the bearing component is preferably placed between the piston rod and the stopper. The bearing part should engage with the large surface area of the plug and contact only the small surface area of the piston rod to facilitate the relative rotation of the piston rod part, such as the main screw, with respect to the bearing part. Can be formed into. The bearing parts must be able to be assembled to the main screws with a relatively small assembly force and without the risk of damaging the parts. The bearing parts must not come off the main screw after assembly or during the life of the device, as this can lead to dose errors. The bearing function must be sturdy enough to withstand the rigors of automatic assembly and bulk packaging.

Patent Document 1 discloses a drive mechanism suitable for use in a drug delivery device including a piston rod and a substantially cylindrical drive sleeve that surrounds the piston rod. The threads of the piston rod are applied to work in a spiral groove that extends along the inner surface of the drive sleeve. Further threads on the piston rod extend through the threaded openings in the insert. The longitudinal axial movement of the drive sleeve causes the piston rod to rotate along the thread of the insert, causing the piston rod to advance and thus drive the piston within the cartridge. The bearing is provided on the piston rod by a retainer, which abuts against the cartridge piston.

<p><patcit num="1"><text>US Application Publication No. 2007/0093761</text></patcit></p>

<p> An object of the present invention is to reduce friction loss between a rotating piston rod and a stopper for use in a drug delivery device.</p>

<p> This object is achieved by the bearing component of claim 1, the piston rod including the bearing component of claim 8, and the drug delivery device of claim 12. A further embodiment is derived from the dependent claim.</p><p> In one aspect, the invention relates to bearing parts for piston rods of drug delivery devices. The bearing part has a coupling feature that is arranged inside the peripheral part so that it rotatably engages with the contact surface, the peripheral part surrounding the central part, and the part of the piston rod perpendicular to the contact surface. including. The connecting function includes a flexible feature extending from the peripheral portion toward the central portion, and the flexible function is directed toward the peripheral portion by the force applied to the flexible function in the direction toward the contact surface. It is arranged to bend toward the center due to the force applied to the flexible function in the opposite direction. There may be only one flexible element, two flexible elements, or three or more flexible elements.</p><p> In one embodiment of the bearing component, the flexible function has a sloping surface that slopes with respect to the contact surface, which approaches the contact surface towards the center.</p><p> In a further embodiment, the flexible function is an integral part of the bearing component.</p><p> In a further embodiment, the flexibility function is formed by at least one flexible arm, hook, prong, tooth, or protrusion element.</p><p> In a further embodiment, the central portion comprises an opening, and the flexible function limits the opening.</p><p> In a further embodiment, the opening widens as the flexible function bends towards the periphery.</p><p> In a further embodiment, the flexible features are arranged such that the bearing components are symmetrical with respect to a 180 ° rotation around the center.</p><p> In another aspect, the invention relates to a piston rod that includes such a bearing component.</p><p> In one embodiment of the piston rod, the part of the piston rod that is rotatably engaged by the flexible function is the main screw.</p><p> In a further embodiment of the piston rod, the parts of the piston rod that engage rotatably by the flexible function include a coupler with an overhang flange, and the bearing parts are made into the coupler by the flexible function of holding the flange. Engage.</p><p> In a further embodiment of the piston rod, the parts of the piston rod that rotatably engage by the flexible function come into contact with the bearing parts, at least in the contact area near the periphery of the bearing parts.</p><p> In another aspect, the present invention relates to a drug delivery device that includes such a bearing component, the bearing component can be attached to the piston rod component. The drug delivery may be an injection device, a pen-type device, particularly a pen-type injection device.</p><p> As used herein, the term "drug" preferably means a pharmaceutical formulation comprising at least one pharmaceutically active compound, wherein in one embodiment the pharmaceutically active compound is up to 1500 Da. And / or a mixture of peptides, proteins, polysaccharides, vaccines, DNA, RNA, enzymes, antibodies or fragments thereof, hormones or oligonucleotides, or the pharmaceutically active compounds described above. Here, in a further embodiment, the pharmaceutically active compound is diabetes, or diabetes-related complications such as diabetic retinopathy, thromboembolism such as deep vein thromboembolism or pulmonary thromboembolism, acute coronary syndrome. (ACS), angina, myocardial infarction, cancer, luteal degeneration, inflammation, hay fever, atherosclerosis and / or useful for the treatment and / or prevention of rheumatoid arthritis, where further embodiments In, a pharmaceutically active compound comprises at least one peptide for the treatment and / or prevention of diabetic or diabetic-related complications such as diabetic retinopathy. Here, in a further embodiment, the pharmaceutically active compound is 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 exendin-3 or exendin. -4 or exendin -3 or an analog or derivative of exendin-4.</p><p> Insulin analogs include, 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; Prolin at position B28 is replaced by Asp, Lys, Leu, Val, or Ala, and Lys may be replaced by Pro at position B29; Ala (B26) human insulin; Des (B28-B30) human insulin; Des (B27) human insulin, and Des (B30) human insulin.</p><p> Insulin derivatives include, 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-Millitoyl LysB28ProB29 Human Insulin; B28-N-Palmitoil-LysB28ProB29 Human Insulin; B30-N-Millitoyl-ThrB29LysB30 Human Insulin; B30-N-Palmitoil-ThrB29LysB30 Human Insulin; -des (B30) Human Insulin; B29-N-(N-Lithocholyl-γ-Glutamil)-des (B30) Human Insulin; B29-N-(ω-carboxyheptadecanoyl)-des (B30) Human Insulin, and B29-N- (ω-carboxyheptadecanoyl) is human insulin.</p><p> Exendin-4, for example, 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 sequence peptide Exendin-4 (1-39) ) Means.</p><p> Exendin-4 derivatives are, for example, the compounds listed below: H- (Lys) 4-desPro36, desPro37 Exendin-4 (1-39) -NH2, H- (Lys) 5-desPro36, desPro37 Exendin-4 (1-39) -NH2, desPro36 Exendin-4 (1-39) ), DesPro36 [Asp28] Oxygen-4 (1-39), desPro36 [IsoAsp28] Oxygen-4 (1-39), desPro36 [Met (O) 14, Asp28] Oxygen-4 (1-39), desPro36 [Met (O) 14, IsoAsp28] Exendin- (1-39), desPro36 [Trp (O2) 25, Asp28] Exendin-4 (1-39), desPro36 [Trp (O2) 25, IsoAsp28] Exendin-4 (1-) 39), desPro36 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39), desPro36 [Met (O) 14Trp (O2) 25, IsoAsp28] Exendin-4 (1-39) ; Or desPro36 [Asp28] oxygen-4 (1-39), desPro36 [IsoAsp28] Exendin-4 (1-39), desPro36 [Met (O) 14, Asp28] Exendin-4 (1-39), desPro36 [Met (O) 14, IsoAsp28] Exendin-(1-39), desPro36 [Trp (O2) 25, Asp28] Exendin-4 (1-39), desPro36 [Trp (O2) 25, IsoAsp28] Exendin-4 (1-39), desPro36 [Met (O) 14, Trp (O2)) 25, Asp28] Exendin-4 (1-39), desPro36 [Met (O) 14, Trp (O2) 25, IsoAsp28] Exendin-4 (1-39), (Here, the group-Lys6-NH2 is exendin. It may be bound to the C-terminus of the -4 derivative);</p><p> Alternatively, an exendin-4 derivative having the following sequence: desPro36 Exendin-4 (1-39) -Lys6-NH2 (AVE0010), H- (Lys) 6-desPro36 [Asp28] Exendin-4 (1-39) -Lys6-NH2, desAsp28Pro36, Pro37, Pro38 Exendin-4 ( 1-39) -NH2, H- (Lys) 6-desPro36, Pro38 [Asp28] Exendin-4 (1-39) -NH2, H-Asn- (Glu) 5desPro36, Pro37, Pro38 [Asp28] Exendin-4 ( 1-39)-NH2, desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2, H- (Lys) 6-desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-9)- 1-39)-(Lys) 6-NH2, H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2, H- (Lys) 6-desPro36 [Trp (O2) 25, Asp28] Exendin-4 (1-39)-Lys6-NH2, H-desAsp28Pro36, Pro37, Pro38 [Trp (O2) 25] Exendin-4 (1-39) -NH2, H- (Lys) 6-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 ( 1-39) -NH2, H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 (1-39) -NH2, desPro36, Pro37, Pro38 [Trp (O2) ) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2, H- (Lys) 6-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 (1-39) -(Lys) 6-NH2, H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2, H-( Lys) 6-desPro36 [Met (O) 14, Asp28] Exendin-4 (1-39) -Lys6-NH2, desMet (O) 14, Asp28 Pro36, Pro37, Pro38 Exendin-4 (1-39) -NH2, H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39) )-NH2, H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39) -NH2; desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2, H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] ] Oxygen-4 (1-39)-(Lys) 6-NH2, H-Asn- (Glu) 5desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Oxygen-4 (1-39)-(Lys) 6-NH2, H-Lys6-desPro36 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39) -Lys6-NH2, H-desAsp28, Pro36, Pro37, Pro38 [Met (O) ) 14, Trp (O2) 25] Exendin-4 (1-39) -NH2, H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)- NH2, H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39) -NH2, desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2, H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (S1-39)-(Lys) 6-NH2, H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2; or selected from pharmaceutically acceptable salts or solvates of any one of the exendin-4 derivatives described above. To.</p><p> Hormones include, for example, gonadotropins (follitropin, lutropin, corion gonadotropin, menotropin), somatropin (somatropin), desmopresin, telluripresin, gonadorelin, triptolerin, leuprorelin, bucererin, nafarelin, gocerelin, etc., Rote Liste, 2008 Pituitary hormones or hypothalamic hormones or regulatory active peptides listed in and their antagonists.</p><p> Examples of the polysaccharide include glucosaminoglycan, hyaluronic acid, heparin, low molecular weight heparin, or ultra low molecular weight heparin, or derivatives thereof, or sulfated forms of the above-mentioned polysaccharides, for example, polysulfated forms, and / Or there are those salts that are pharmaceutically acceptable. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.</p><p> Antibodies are globular plasma proteins (about 150 kDa), also known as immunoglobulins that share a basic structure. These are glycoproteins because they have sugar chains added to amino acid residues. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit), and secretory antibodies are also dimers with two Ig units, such as IgA, in hard bone fish. It can be a tetramer with 4 Ig units, such as IgM, or a pentamer with 5 Ig units, such as mammalian IgM.</p><p> An Ig monomer is a "Y" -shaped molecule composed of four polypeptide chains, two identical heavy chains and two identical light chains linked by disulfide bonds between cysteine residues. Is. Each heavy chain is about 440 amino acids long and each light chain is about 220 amino acids long. The heavy and light chains each contain an intrachain disulfide bond that stabilizes these folded structures. Each strand is composed of a structural domain called the Ig domain. These domains contain approximately 70-110 amino acids and fall into different categories (eg, variable or V, and stationary or C) based on their size and function. They have a characteristic immunoglobulin folding structure that creates a "sandwich" shape in which the two β-sheets are held together by the interaction between the conserved cysteine and other charged amino acids.</p><p> There are five types of mammalian Ig heavy chains represented by α, δ, ε, γ and μ. The type of heavy chain present defines the antibody isotype, and these chains are found in IgA, IgD, IgE, IgG and IgM antibodies, respectively.</p><p> Different heavy chains differ in size and composition, α and γ contain about 450 amino acids, δ contains about 500 amino acids, and μ and ε have about 550 amino acids. Each heavy chain has two regions, the constant regions (C)._H) And variable region (V)_H). In one species, the constant region is essentially the same for all antibodies of the same isotype, but different for 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 adding flexibility, and heavy chains μ and ε have four immunoglobulins. -Has a constant region composed of domains. The variable region of the heavy chain is different for 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 consists of a single Ig domain.</p><p> In mammals, there are two types of immunoglobulin light chains, represented by λ and κ. The light chain has two contiguous domains, one constant domain (CL) and one variable domain (VL). The approximate length of the light chain is 211-217 amino acids. Each antibody always has two light chains that are identical, and for each mammalian antibody there is only one type of light chain κ or λ.</p><p> Although the general structure of all antibodies is very similar, the unique properties of a given antibody are determined by the variable (V) region, as detailed above. More specifically, three variable loops on each light chain (VL) and three on the heavy chain (HV) are involved in antigen binding, i.e. its antigen specificity. These loops are called complementarity determining regions (CDRs). Since CDRs from both the VH and VL domains contribute to the antigen binding site, it is the combination of heavy and light chains that determines the final antigen specificity, not either alone.</p><p> An "antibody fragment" comprises at least one antigen binding fragment as defined above and exhibits essentially the same function and specificity as the complete antibody from which the fragment is derived. Limited protein digestion with papain cleaves the Ig prototype into three fragments. Two identical amino-terminal fragments, each containing one complete L chain and about half the H chain, are antigen-binding fragments (Fabs). The third fragment, which is comparable in size but contains a carboxyl terminus at half of both heavy chains with interchain disulfide bonds, is a crystallizable fragment (Fc). Fc includes carbohydrates, complementary binding sites, and FcR binding sites. Limited pepsin digestion results in a single F (ab') 2 fragment containing both the Fab fragment and the hinge region containing the HH interchain disulfide bond. F (ab') 2 is divalent for antigen binding. The disulfide bond of F (ab') 2 can be cleaved to obtain Fab'. In addition, the variable regions of the heavy and light chains can be condensed to form a single chain variable fragment (scFv).</p><p> Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts include, for example, HCl or HBr salts. The basic salt is, for example, an alkali or alkaline earth, for example, a cation selected from Na +, K +, or Ca2 +, or an ammonium ion N + (R1) (R2) (R3) (R4) (in the formula, R1). ~ R4 are independent of each other: hydrogen, optionally substituted C1 to C6 alkyl groups, optionally substituted C2 to C6 alkenyl groups, optionally substituted C6 to C10 aryl groups, or optionally substituted C6 ~ A salt having a C10 heteroaryl group). Further examples of pharmaceutically acceptable salts can be found in Remington's Pharmaceutical Sciences, 17th Edition, Alfonso R. Gennaro (eds.), Mark Publishing Company, Easton, Pa., USA, 1985 and Encyclopedia of Pharmaceutical Technology. ..</p><p> A pharmaceutically acceptable solvate is, for example, a hydrate.</p><p> The following is a detailed description of the bearing components associated with the accompanying drawings and embodiments of the piston rod including the bearing components.</p>

<figref num="1">It is a top view of the embodiment of a bearing part.</figref><figref num="2">It is sectional drawing of the embodiment which concerns on FIG.</figref><figref num="3">The piston rod including the bearing parts being assembled is shown.</figref><figref num="4">The piston rod according to FIG. 3 after assembly is shown.</figref><figref num="5">The piston rod according to FIG. 4 which received the disassembling force is shown.</figref>

FIG. 1 shows an embodiment of a bearing component in a plan view. The bearing component 1 may have a substantially circular shape, especially if the bearing component is intended for a pen-type drug delivery device. At least one flexible function 8 extends from the peripheral part 3 to the central part and forms a connecting function 5 used to fasten additional parts of the piston rod. In the embodiment according to FIG. 1, the coupling function 5 is formed by two flexible functions 8, and these flexible functions 8 are arranged so as to be rotationally symmetric with respect to a rotation of 180 ° around the center 4. To. Such a bearing 1 can be easily manufactured at a lower cost. Each of the two flexible functions 8 covers an angle of about 120 ° to 160 °, preferably about 150 °. Each flexible function 8 is flexible enough to be elastically movable during assembly, while the inner edge of the flexible function 8 around the opening 10 provides stability against twisting. Stability increases with the angle of coverage. This stability helps prevent the bearing component 1 from tilting with respect to the shaft of the piston rod 7. Further, this ensures that the coupler 11 with the overhanging flange 12 has an opening 10 large enough to pass through. Alternatively, there may be only one flexible element 8 or three or more flexible elements 8. However, twist stability decreases with the number of flexible elements. The connecting function 5 may leave an opening 10 in the central portion 4 of the bearing component 1. In this case, the opening 10 is at least partially restricted by the coupling function 5.

FIG. 2 is a cross-sectional view of the embodiment according to FIG. The plane of the cross section is perpendicular to the floor plan shown in FIG. The bearing component 1 preferably includes a solid outer ring 14 that forms a peripheral portion 3 and provides mechanical stability for the bearing component 1. The contact surface 2 of the bearing component 1 is provided so as to be pressed against the corresponding surface of the stopper. The contact surface 2 may be in front of the outer ring 14. Peripheral portion 3 has a contact area 13, which may partially cover the outer ring 14, the flexible function 8, or both the outer ring 14 and the flexible function 8.

The flexible function 8 of the present embodiment has an inclined surface 9, and the inclined surface 9 is inclined with respect to the plane of the contact surface 2. Since the inclined surface 9 approaches the contact surface 2 toward the central portion 4, the connecting function 5 narrows toward the plane of the contact surface 2. The flexibility function 8 may be a flexibility arm, hook, prong, tooth, or any other protrusion element extending from the periphery 3 towards the center 4. The flexible function 8 is preferably integrated with the bearing component 1. The inclined surface 9 has the advantage of facilitating the assembly of the piston rod, as will be apparent from the description below.

FIG. 3 shows a piston rod 7 containing a bearing part 1 and an additional part 6 in the assembled state. The bearing part 1 is shown in the cross section according to FIG. 2, while the additional part 6 is shown in the perspective view. The additional component 6 may be, for example, a main screw having a thread 17. The thread 17 is used in the drive mechanism and can advance the piston rod 7. The additional part 6 is moved relative to the bearing part 1 in the direction of the vertical arrow pointing down in FIG. The end of the additional component 6 facing the bearing component 1 includes a coupler 11, which resembles, for example, a spigot or shaft rod. The coupler 11 preferably comprises an overhang flange 12. When an additional component 6 is introduced into the opening 10 of the bearing component 1, the coupler 11 exerts a force on the inclined surface 9 of the flexible function 8 as shown by the diagonal arrow in FIG. Therefore, the flexible function 8 is pushed outward in the radial direction, and the opening 10 is sufficiently widened to allow the coupler 11 to pass through the edge of the flexible function 8.

FIG. 4 shows the piston rod 7 after assembly. The flange 12 is shifted beyond the edge of the flexibility function 8, the flexibility function 8 loosens back to its original position, and the flange 12 is held back to axially lock the additional component 6. The bearing component 1 can be brought into contact with the stopper 15 of the drug cartridge 16. When the additional component 6 rotates, the coupler 11 can easily rotate within the bearing component 1, but the bearing component 1 and the plug 15 do not rotate relative to each other. The friction between the contact area 13 and therefore the parts 1 and 6 of the piston rod 7 is relatively small. Further, when the force that advances the piston rod 7 directly to the stopper 15 is applied by the flange 12, the friction can be further reduced, so that the pressure applied to the peripheral contact region 13 by the additional component 6 and therefore the torque applied to the bearing component 1 is reduced. To. Instead, the flange 12 may maintain a distance from the stopper 15. The contact surface 2 may be on the front surface of the outer ring 14 facing the plug 15.

The flexibility function 8 is preferably located within the outer ring 14 of the bearing component 1. The outer ring 14 protects the flexible function 8 from side loads due to direct loading on parts that can occur if the device is impacted or vibrated, or during autoassembly or during bulk transport conditions. .. When the piston rod 7 is pressed against the stopper 15 during dosing and the bearing part 1 is compressed, no load is applied to the flexibility function 8, so parts 1 and 6 remain firmly connected. is there.

As shown in FIG. 4, the main component 6 of the piston rod 7 is pressed against the contact region 13 of the outer ring 14 of the bearing component 1. The contact area 13 is small enough to keep the friction between parts 1 and 6 of the piston rod 7 at a low level and thus keep the torque applied to the bearing part 1 within acceptable limits. The reduced friction is especially advantageous when the piston rod rotates during operation. This can be further reduced with low friction polymers. The contact area 13 is inclined toward the axis of the piston rod and is applied to the corresponding contact surface shape of the main component 6. The contact area 13 prevents tilting of the bearing component 1 with respect to the axis of the piston rod 7 when, for example, being advanced during assembly and / or dosing operation. In addition, the tilted contact surface region 13 helps guide the bearing component 1 to align and / or maintain with the axis of the piston rod. This is especially useful when rotating the piston rod 7. The flange 12 is maintained at a distance from the plug 15 and has a contact surface 2 on the front surface of the outer ring 14 facing the plug 15. Therefore, the force for driving the piston rod 7 is transmitted to the plug 15 via the bearing component 1, particularly the contact surface 2. In this way, the piston rod 7 is rotatable, but the pushing force thereof is transmitted to the plug 15 via the contact surface 2 of the bearing portion 1. Therefore, this embodiment may be preferable when the piston rod is rotated during operation.

FIG. 5 shows how the disassembly of the piston rod 7 is prevented. Axial force, with respect to bearing part 1 shown in vertical arrow in Figure 5 to further component 6 when applied to a direction that is, parts 1,6 are slightly separated. FIG. 5 shows the contact area 13 in the bearing part 1 which is no longer covered by the additional part 6 due to the action of the separating force, and the distance between the flange 12 and the plane of the contact area 2 is increasing. In this state, the flexibility function 8 is engaged with the flange 12 of the coupler 11. When the flexible function 8 has an inclined shape as in the embodiment described, the engagement with the flange 12 forcibly causes the flexible function 8 to bend inward and bite into the coupler 11. This prevents the parts 1 and 6 of the piston rod 7 from being disassembled unless a significantly large force is applied.

1 Bearing parts 2 Contact surface 3 Peripheral part 4 Central part 5 Coupling function 6 Piston rod parts 7 Piston rod 8 Flexible function 9 Inclined surface 10 Opening 11 Coupler 12 Flange 13 Contact area 14 Outer ring 15 Plug 16 Cartridge 17 thread