EP2155303A1 - Ampoule à deux chambres - Google Patents

Ampoule à deux chambres

Info

Publication number
EP2155303A1
EP2155303A1 EP08758925A EP08758925A EP2155303A1 EP 2155303 A1 EP2155303 A1 EP 2155303A1 EP 08758925 A EP08758925 A EP 08758925A EP 08758925 A EP08758925 A EP 08758925A EP 2155303 A1 EP2155303 A1 EP 2155303A1
Authority
EP
European Patent Office
Prior art keywords
pro
exendin
asp
lys
cylinder
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08758925A
Other languages
German (de)
English (en)
Inventor
Werner Seiferlein
Jörn Möckel
Martin Zink
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Aventis Deutschland GmbH
Original Assignee
Sanofi Aventis Deutschland GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi Aventis Deutschland GmbH filed Critical Sanofi Aventis Deutschland GmbH
Priority to EP08758925A priority Critical patent/EP2155303A1/fr
Publication of EP2155303A1 publication Critical patent/EP2155303A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/06—Ampoules or carpules
    • A61J1/062—Carpules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
    • A61J1/202—Separating means
    • A61J1/2041—Separating means having removable plugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2093—Containers having several compartments for products to be mixed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3103—Leak prevention means for distal end of syringes, i.e. syringe end for mounting a needle
    • A61M2005/3104—Caps for syringes without needle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3103—Leak prevention means for distal end of syringes, i.e. syringe end for mounting a needle
    • A61M2005/3106—Plugs for syringes without needle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/3129—Syringe barrels
    • A61M2005/3142—Modular constructions, e.g. supplied in separate pieces to be assembled by end-user
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31501—Means for blocking or restricting the movement of the rod or piston
    • A61M5/31505—Integral with the syringe barrel, i.e. connected to the barrel so as to make up a single complete piece or unit
    • A61M2005/31506—Integral with the syringe barrel, i.e. connected to the barrel so as to make up a single complete piece or unit formed as a single piece, e.g. moulded
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
    • A61M5/2448—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic comprising means for injection of two or more media, e.g. by mixing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/3129—Syringe barrels
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T29/00—Metal working
    • Y10T29/49—Method of mechanical manufacture
    • Y10T29/49229—Prime mover or fluid pump making

Definitions

  • Two-chamber carpules are used in medicine for the administration of preparations consisting of two components. There are two ways to combine the components, namely the combination liquid / liquid and the
  • Partial cylinder containing a liquid component.
  • the needle-side part cylinder contains the bypass and is closed with a plug at the proximal end.
  • the piston-side partial cylinder is closed with a stopper at the proximal, piston-side end (FIG. 2) and optionally with a further stopper at the distal end (FIG. 3).
  • Both sub-cylinders are connected by means of cohesive (by welding) or non-positively (by gluing).
  • the syringe barrels described have a bypass, which is preferably shaped so that it does not increase the diameter of the syringe barrel.
  • the material of the front part of the cylinder is preferably plastic.
  • the syringe head of the first part cylinder is closed by a so-called tip cap, ie by a loose closure through which the surrounding vacuum can be passed to the interior of the syringe barrel after filling with a lyophilizate during the subsequent freeze-drying. and that is tightly closed after the lyophilization step.
  • the separate bottling in a first and a second part cylinder avoids a "cross contamination" and allows optimal utilization of the process space of the lyophilizer.
  • European Patent Application EP 520618 describes a prefilled syringe consisting of two sub-cylinders, the first sub-cylinder, preferably the head-side sub-cylinder containing the needle or the outlet, containing a lyophilized, powdered medicament, and the second sub-cylinder, preferably the piston-side sub-cylinder, contains a second, liquid component.
  • the powdered medicament mixes with the liquid component via a bypass.
  • the needle-side part cylinder contains the bypass and is closed with a plug at the proximal end.
  • the piston side sub-cylinder is closed with one stopper at the distal and at the proximal end.
  • Both sub-cylinders are sealed separately by means of the plugs and connected to each other via flanges, wherein the proximal plug of the head-side sub-cylinder and the distal plug of the piston-side sub-cylinder are positively connected after assembly and the total length of both plugs is shorter than the length of the bypass.
  • GB 2010681 describes a two-chamber syringe for administering a liquid consisting of two sub-cylinders, wherein the first part-cylinder is formed as a needle holder and includes a channel to the outlet and the second, piston-side part-cylinder liquid.
  • the first part cylinder contains no substance to be administered.
  • a plug with which the piston-side partial cylinder is closed at the distal end is moved in the direction of the syringe head, whereby the liquid can be applied via the channel of the first part-cylinder.
  • FR 1099362 describes a two-chamber syringe consisting of two sub-cylinders, wherein the first, head-side sub-cylinder contains a sterile powder or a sterile liquid, and the second, piston-side sub-cylinder, contains a liquid.
  • the sterile powder or liquid of the first mixes Partial cylinder with the liquid of the second part of the cylinder via a bypass in the first, needle-side part cylinder.
  • the piston side sub-cylinder is closed with a plug on the distal and a piston on the proximal end.
  • Both sub-cylinders are connected by flanges or by means of another (over) cylinder whose inner diameter corresponds to the outer diameter of the two sub-cylinders by gluing or welding together.
  • the syringe systems in the prior art have the disadvantage that they are not suitable for insertion into an application system (for example in a pens system) due to the distal end designed with a needle holder and / or the solid component must first be lyophilized in the needle-side partial cylinder. to obtain a solid, powdery component.
  • no solution is mentioned in the prior art, according to which the pressure resulting from the joining of the two partial cylinders is compensated.
  • the object of the present invention is therefore to provide an improved two-chamber carpule and an improved and more economical method for producing two-chamber carpules and for filling two-chamber carpules.
  • the present invention relates to a two-chamber carpule comprising a) a first head-side sub-cylinder (1) forming a chamber containing a bypass (3), an opening for receiving an intermediate stopper (6) at the proximal end (4), and an intermediate stopper (6) in the opening of the proximal end, b) a liquid- and gas-tight closure cap (5) at the head end of the first, head-side sub-cylinder (1), c) a second, piston-side sub-cylinder (2), the second, the second Chamber associated portion of the two-chamber carpule, comprising an opening at the distal end (8), an opening (9) for receiving an end plug (10) at the piston end, and an end plug (10) in the opening of the piston end of the second
  • Partial cylinder optionally a second intermediate plug (17) at the distal end, d) optionally a sealing element (7) between the first and the second part of the cylinder.
  • the proximal end of the first sub-cylinder and the distal end of the second sub-cylinder are sealed together.
  • the invention further relates to the head of a two-chamber carpule as described above comprising a bypass (3), an opening for receiving an intermediate plug (6) at the proximal end (4), a liquid-tight closure cap (5) at the distal end for piercing with an application needle, and an intermediate plug (6) in the opening of the proximal end.
  • the front chamber which is formed in the assembled state in the first part of the cylinder, contains a solid or a liquid component.
  • the chamber contains a solid component, more preferably a lyophilisate or a powder.
  • the rear chamber which is formed in the assembled state in the second part cylinder, contains a liquid component.
  • the solid or liquid component of the anterior chamber and the liquid component of the posterior chamber form the drug to be administered.
  • the medicament contains one or more pharmaceutically active ingredients selected from the group consisting of (i) a low molecular weight compound (having a molecular weight of up to 1,500 Da), (ii) a peptide, (iii) a protein, (iv) DNA, (v) RNA , (vi) antibodies, (vii) enzyme and (viii) oligonucleotide, preferably containing at least one peptide, preferably a peptide for the treatment of diabetes mellitus or complications of diabetes mellitus such as diabetes retinopathy,
  • a pharmaceutically active ingredients selected from the group consisting of (i) a low molecular weight compound (having a molecular weight of up to 1,500 Da), (ii) a peptide, (iii) a protein, (iv) DNA, (v) RNA , (vi) antibodies, (vii) enzyme and (viii) oligonucleotide, preferably containing at least one peptide, preferably a
  • Insulin analogues are, for example, Gly (A21), Arg (B31), Arg (B32) - human insulin; Lys (B3), Glu (B29) - human insulin; Lys (B28), Pro (B29) - human insulin; Asp (B28) - human insulin; Human insulin in which proline at position B28 has been substituted by Asp, Lys, Leu, VaI or Ala and where in position B29 Lys may be substituted by Pro; Ala (B26) - human insulin; Des (B28-B30) - human insulin; Des (B27) - human insulin and Des (B30) - human insulin.
  • Insulin derivatives are, for example, B29-N-myristoyl des (B30) human insulin; B29-N-palmitoyl-des (B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl
  • LysB28ProB29 human insulin B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N- (N-palmitoyl-Y-glutamyl) des (B30) human insulin; B29-N- (N-lithocholyl-Y-glutamyl) des (B30) human insulin; B29-N- ( ⁇ -carboxyheptadecanoyl) -des (B30) human insulin and B29-N- ( ⁇ ; -carboxyheptadecanoyl) human insulin.
  • Exendin-4 is preferably exendin-4 (1-39), a peptide having the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu Glu-Alu-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH 2 .
  • exendin-4 derivatives are selected from the following group of compounds:
  • the pharmaceutically active ingredient is the solid component in the chamber of the front part cylinder, more preferably a lyophilisate or a powder.
  • Pharmaceutically acceptable salts include, for example, acid addition salts and basic salts.
  • Acid addition salts are, for example, HCl or HBr addition salts.
  • Examples of basic salts are salts in which the cation is selected from the group of alkali salts, for example Na + or K + , or the alkaline earth salts, for example Ca 2+ , or ammonium ions N + (Ri) (R 2) (R 3) (R 4) wherein Ri to R 4 independently represent hydrogen, C r C 6 alkyl, C 2 -C 6 alkenyl, C 6 -C 0 aryl, or C 6 -C o-heteroaryl. Further examples of pharmaceutically acceptable salts are described in Remington's
  • either the proximal end (4) of the first head-side sub-cylinder or the distal end of the second, piston-side sub-cylinder (8) includes an axial groove (11) on the inside of the female sub-cylinder.
  • the groove is shaped to have a length axially less than the length of engagement of the proximal end of one sub-cylinder with the corresponding end of the other sub-cylinder.
  • the groove is formed so that it further reduces the wall thickness of the female sub-cylinder. For example, as shown in FIG.
  • the pressure which is built up during assembly can initially escape through the groove (11) , Only in the last step of the assembly can the pressure no longer escape via the groove, but it is so small that it can no longer push out the end plug (10).
  • the Partial cylinder (1) and (2) one of which contains an axial groove, connected to each other by means of clamping.
  • the proximal end (9) of the second piston-side partial cylinder has a stop (13).
  • the stop prevents slipping of the end plug (10) by the resulting pressure during assembly in the direction of the proximal end.
  • the stopper is shaped such that a piston can transmit force to the end stopper through the proximal opening of the second sub-cylinder.
  • the distal end (8) of the second piston-side partial cylinder has a plug (17).
  • the two-chamber carpule includes both an axial groove (11) in the female sub-cylinder and a stop (13) at the proximal end (9) of the second piston-side sub-cylinder.
  • the two-chamber carpule includes an axial groove (11) in the female sub-cylinder and a stop (13) at the proximal end (9) of the second piston-side sub-cylinder and a plug at the distal end (8) of the second piston-side sub-cylinder.
  • Proximal means the end of a component which, when assembled, will be known to the end stopper (10), ie to the operator's butt and thumb when the dual chamber carpule is installed in a pen system and an application system piston engaging the end stopper (10)
  • the proximal end of the first sub-cylinder is the end of the sub-cylinder, which in the assembled state is connected to the second sub-cylinder.
  • distal means the end of a component which, in the assembled state, is in the direction of the shutter (5) or the outlet opening, for example, the distal end of the second sub-cylinder is the end of the sub-cylinder, which in the assembled state is connected to the first sub-cylinder.
  • the "head end of the two-chamber carpule" is the end of the two-chamber carpule which forms the head of the two-chamber carpule, that is, which includes the shutter (5) and the outlet port, respectively.
  • the "piston-side end of the two-chamber carpule" is the end of the two-chamber carpule that includes the end plug (10) and at which the force of a piston is transmitted in a pen system.
  • the closure cap (5) is a device which seals the distal end of the part cylinder (1) in a liquid-tight and gas-tight manner.
  • the cap consists of a sealing element (15), z. B. a rubber-like disc, and a closure element (16), z.
  • the compound can be prepared by methods known to those skilled in the art, for example by crimping, crimping, bouncing or screwing.
  • the plugs (6), (10) and (17) and the sealing element (7) are independently of each other of elastic material, for example rubber, preferably bromobutyl, chlorobutyl or fluorobutyl rubber.
  • the plugs are coated with PTFE.
  • the plugs are preferably cylindrical basic shape, but also other basic shapes corresponding to the inner shape of the sub-cylinders are possible.
  • the plugs have both a sealing and a closure function, for example, closes and seals intermediate plug (6) the proximal end of the first part of the cylinder (4).
  • the sealing function is preferably ensured by one or more lamellar formations of the cylindrical basic shape.
  • "Dense" means the impermeability to solids, liquids, gases, as well as to germs.
  • the bypass (3) is an opening which, when using the two-chamber carpule, allows a liquid component (14) to be displaced from the sub-cylinder (6) and sub-cylinder (5) during administration of the medicament, bypassing the intermediate stopper (6). 2) in the sub-cylinder (1) can flow.
  • the bypass (3) can be created by one or more channels located in the wall material of the sub-cylinder (1), i. embedded in the wall material or incorporated.
  • the bypass can also be formed by corresponding shaping of the wall material inwards (recess running on the inner wall, not shown) or outward (extension of the outer diameter, as shown for example in FIG. 1).
  • the arrangement may be designed to be axially or radially deviating from the axial direction.
  • the partial cylinders (1) and (2) are formed independently from glass, plastic, metal or other materials, preferably transparent materials such as glass or plastic.
  • Preferred plastics are polycarbonates, polyesters, cyclo-olefin copolymers (COC) or cyclic olefin polymers (COP).
  • the first, head-side sub-cylinder (1) and the second, piston-side sub-cylinder (2) are connected in a manner known to those skilled form and / or non-positively connected, for example by screw, buckle, bayonet, snap closure or clamp closure (shown in the figures).
  • the compound is preferably self-sealing or is accomplished for example by gluing or welding.
  • a sealing element (7) can be used.
  • the first, head-side sub-cylinder (1) is the female component.
  • first head-side partial cylinder (1) and the second piston-side partial cylinder (2) are connected to one another, for example by screw closure, the first, head-side partial cylinder (1) has an internal thread at the distal end, and the second, piston-side partial cylinder (2) at proximal end a corresponding external thread.
  • the second piston-side partial cylinder (2) is the female component. If the second piston-side partial cylinder (2) and the first, head-side partial cylinder (1) connected to each other, for example by screw, the second, piston-side part cylinder (2) at the proximal end an internal thread, and the first, head-side part of cylinder (1) on distal end of a corresponding external thread.
  • both partial cylinders (1) and (2) are made of plastic.
  • both plastic sub-cylinders are connected to one another via a screw closure, wherein a sealing element is optionally inserted for sealing between the sub-cylinders.
  • the distal end (8) of the second, piston-side partial cylinder contains an axial groove (11) through which the pressure built up in the partial cylinder (2) can escape during the assembly of the two partial cylinders;
  • the end plug (10) can be positioned in the sub-cylinder (2) so that it is displaced during assembly by the pressure built up in the desired end position.
  • the second partial cylinder (2) preferably contains a plug (17) at the distal end.
  • partial cylinder (2) contains a stop (13) at the proximal end.
  • the first part cylinder (1) consists of glass and the second part cylinder (2) consists of plastic, which are particularly preferably connected to one another via a clamp closure or a plug-in closure.
  • the sealing of the sub-cylinder can be done by gluing using conventional pharmatau Mother adhesive, optionally between the sub-cylinder a
  • the distal end (8) of the second, piston-side partial cylinder contains an axial groove (11) through which the pressure built up in the partial cylinder (2) can escape during the assembly of the two partial cylinders;
  • the end plug (10) can be positioned in the sub-cylinder (2) so that it is displaced during assembly by the pressure built up in the desired end position.
  • the second partial cylinder (2) preferably contains a plug (17) at the distal end.
  • partial cylinder (2) contains a stop (13) at the proximal end.
  • both partial cylinders (1) and (2) are made of plastic, and the partial cylinders are connected to one another via a plug-in closure, wherein a sealing element is optionally inserted for sealing between the partial cylinders.
  • the distal end (8) of the second, piston-side partial cylinder contains an axial groove (11) through which the pressure built up in the partial cylinder (2) can escape during the assembly of the two partial cylinders;
  • the end plug (10) can be positioned in the sub-cylinder (2) so that it is displaced during assembly by the pressure built up in the desired end position.
  • the second partial cylinder (2) preferably contains a plug (17) at the distal end.
  • partial cylinder (2) contains a stop (13) at the proximal end.
  • the two-chamber carpule according to the invention has the advantage that both sub-cylinders can be filled separately from one another by the entire diameter of the sub-cylinders, and that the first, head-side sub-cylinder (1) and in the presence of the plug (17) and the second, piston-side sub-cylinder (2) separated from each other producible and thus storable.
  • the second intermediate plug (17) also ensures that there is no risk of contamination by solid or liquid component at the contact points between the first and second part of the cylinder.
  • the filling over large openings ensures a reduced likelihood of contamination of the other sub-cylinder or the carpule outside. Since powders can be filled directly, no lyophilization is necessary.
  • a lyophilisate or other solid component preferably in powder form
  • the gentle powder filling also ensures that no influence on the crystalline structure of the powder can occur via shear forces, such as may occur during filling through small openings, so that no influence on the bioavailability of the drugs to be administered is to be expected.
  • the two-chamber carpule according to the invention can be used in any application system, for example a pen system, wherein the application system preferably contains a needle for piercing the sealing disc (15) and a drive mechanism for moving the end plug (10) in the distal direction.
  • the application system preferably contains a needle for piercing the sealing disc (15) and a drive mechanism for moving the end plug (10) in the distal direction.
  • the carpule is further distinguished by excellent cost-effectiveness, since the speed and speed of filling the head-side sub-cylinder to the filling of the piston-side sub-cylinder, the process for producing and filling the two-chamber carpule is advantageous.
  • both partial cylinders are injection-molded in the clean room, then sterilized in hermetic packaging.
  • the use of plastic as a material for the sub-cylinder also ensures the cost-effective production of the parts, the integration of functional parts to one of the sub-cylinders, which are required for operating a pen system (synergies), a simple process for the production of particle freedom, sterilization , Depyrogenation, high dimensional stability and recyclability.
  • the invention further relates to an application device comprising a two-chamber carpule as described above.
  • the invention further relates to a method for producing and filling two-chamber carpules, characterized in that a) a first, head-side part-cylinder (1) with a liquid-tight and gas-tight closure cap (5) is closed at the head end; b) the chamber of the first head-side sub-cylinder (1) is preferably filled with a solid component (12), particularly preferably a powder, and closed by means of an intermediate stopper (6); c) a second piston-side partial cylinder (2) is closed at the proximal end with an end plug (10); d) the chamber of a second, piston-side part-cylinder (2) is filled with a liquid component (14) and optionally closed with an additional intermediate stopper (17); and e) the two sub-cylinders (1) and (2) are joined together optionally with a sealing element (7) inserted between the first and second sub-cylinders.
  • the components of the two-chamber carpule are as defined above in their general and preferred embodiments.
  • the first four steps may also be performed in the order c), d), a), b).
  • the end plug (10) is positioned before joining the two sub-cylinders (1) and (2) so that the built-up pressure shifts the plug (10) to the desired end position.
  • the end plug (10) can in principle be introduced from both ends of the sub-cylinder (2); Preferably, the end plug (10) is introduced via the proximal end.
  • the partial cylinders are assembled under vacuum conditions.
  • both partial cylinders are made of plastic, in particular a welded connection is possible; but also a bond is possible, a connection technique that can be applied even if both partial cylinders are made of glass.
  • the two cylinder parts regardless of whether they are made of glass or plastic, be connected to each other by means of a sealing snap connection or contain a sealing element (7).
  • FIG. 1a shows the basic structure of the two-chamber carpule according to the invention as an exploded view.
  • Figure 1 b shows the structure of the carpule in the mounted state.
  • Figure 1c shows the structure of the closure cap (5).
  • FIG. 2a shows the carpule according to the invention in comparison with a conventional two-chamber carpule in FIG. 2b.
  • Figures 3a and 3b show the machining of the sub-cylinder (2) with the addition of the end plug (10) and the liquid component (14).
  • FIG. 3c shows the partial cylinder (2) which is closed in a sterile manner by setting an additional plug (17).
  • Figures 4a to 4d show the preparation and filling of the first part of the cylinder (1), wherein first the cap (5) is placed at the proximal end, then a dry preparation of active compound (12) is filled, and the intermediate stopper (6) is set.
  • FIG. 5a shows the joining together of the two partial cylinders (1) and (2) filled with liquid carrier medium or dry active ingredient preparation.
  • FIG. 5b shows the usable, assembled two-chamber carpule.
  • Insertion of the plug (10) in part cylinder (2) The end plug (10) can be inserted from both ends of the sub-cylinder (2) with the preferred end being the proximal end ( Figure 3a).
  • the sub-cylinder (2) is filled with liquid carrier medium (14) ( Figure 3b).
  • the length of the sub-cylinder (2) is determined by the volume of the carrier medium (14) to be filled.
  • the partial cylinder (2) can then be sealed sterile with a stopper (17).
  • Part cylinder (1) is first closed by placing the cap (5) at the head end ( Figure 4a). If a sealing washer (15) is used, this can then be placed or the sealing washer can be attached, before the cap (5) is placed.
  • the partial cylinder (1) is filled with a dry preparation of active compound (12) ( Figure 4b).
  • the sub-cylinder (1) is slid into the opening at the distal end (8) of the sub-cylinder (2) ( Figure 5a), i. the part cylinder (2) is closed by the first part cylinder (1) ( Figure 5b).

Landscapes

  • Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
  • Package Specialized In Special Use (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne une ampoule à deux chambres constituée (1) d'une première partie de cylindre comprenant un capuchon de fermeture, une dérivation et un bouchon intermédiaire, d'un élément d'étanchéité optionnel et (3) d'une deuxième partie de cylindre comprenant un bouchon d'extrémité et éventuellement une butée, une rainure axiale et un bouchon intermédiaire supplémentaire, ainsi qu'un procédé de fabrication et de remplissage de l'ampoule à deux chambres.
EP08758925A 2007-06-14 2008-05-31 Ampoule à deux chambres Withdrawn EP2155303A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP08758925A EP2155303A1 (fr) 2007-06-14 2008-05-31 Ampoule à deux chambres

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP07011686 2007-06-14
EP08758925A EP2155303A1 (fr) 2007-06-14 2008-05-31 Ampoule à deux chambres
PCT/EP2008/004356 WO2008151737A1 (fr) 2007-06-14 2008-05-31 Ampoule à deux chambres

Publications (1)

Publication Number Publication Date
EP2155303A1 true EP2155303A1 (fr) 2010-02-24

Family

ID=38596116

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08758925A Withdrawn EP2155303A1 (fr) 2007-06-14 2008-05-31 Ampoule à deux chambres

Country Status (7)

Country Link
US (2) US8092421B2 (fr)
EP (1) EP2155303A1 (fr)
JP (1) JP2010528792A (fr)
CN (1) CN101678174A (fr)
AR (1) AR066985A1 (fr)
TW (1) TW200916138A (fr)
WO (1) WO2008151737A1 (fr)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101678174A (zh) * 2007-06-14 2010-03-24 塞诺菲-安万特德国有限公司 双室卡普耳
DE102008030267B3 (de) * 2008-06-19 2010-01-28 Arzneimittel Gmbh Apotheker Vetter & Co. Ravensburg Verfahren zum Befüllen von Doppelkammersystemen in vorsterilisierbaren Trägersystemen und vorsterilisierbares Trägersystem
KR101939557B1 (ko) 2008-10-17 2019-01-17 사노피-아벤티스 도이칠란트 게엠베하 인슐린과 ｇｌｐ－1 효능제의 병용물
DE102008060960A1 (de) * 2008-12-06 2010-06-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Optische Füllstandsmessung
CN107308442B (zh) 2009-11-13 2022-10-18 赛诺菲-安万特德国有限公司 包含glp-1激动剂、胰岛素和甲硫氨酸的药物组合物
PT3345593T (pt) 2009-11-13 2023-11-27 Sanofi Aventis Deutschland Composição farmacêutica compreendendo despro36exendina- 4(1-39)-lys6-nh2 e metionina
EP2581102A4 (fr) * 2010-06-11 2013-11-20 Nipro Corp Seringue pré-remplie
WO2012025550A2 (fr) * 2010-08-27 2012-03-01 Sanofi-Aventis Deutschland Gmbh Ensemble d'administration de microdoses de médicament
EP2609019B1 (fr) * 2010-08-27 2015-02-18 Sanofi-Aventis Deutschland GmbH Systeme de conditionnement pour des produits medicaux a composants multiples
LT2611458T (lt) 2010-08-30 2016-12-27 Sanofi-Aventis Deutschland Gmbh Ave0010 panaudojimas gaminant vaistą, skirtą 2 tipo cukrinio diabeto gydymui
US9821032B2 (en) 2011-05-13 2017-11-21 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
US20120298856A1 (en) * 2011-05-27 2012-11-29 Dsa Detection Llc Multi-dopant permeation tube
MX370264B (es) 2011-08-29 2019-12-09 Sanofi Aventis Deutschland Combinacion farmaceutica para uso en el control glucemico en pacientes con diabetes de tipo 2.
AR087744A1 (es) 2011-09-01 2014-04-16 Sanofi Aventis Deutschland Composicion farmaceutica para uso en el tratamiento de una enfermedad neurodegenerativa
US8911395B2 (en) 2011-11-01 2014-12-16 George Just Syringe carpule for storing, transporting and in situ mixing of lidocaine and sodium bicarbonate and delivery of buffered anesthetic solution
US9616176B2 (en) 2011-11-01 2017-04-11 George Just Syringe carpule for storing, transporting and in situ mixing of local anesthetic and buffer, and for delivery of buffered anesthetic solution and a piercing-mixing unit therefore
US9751056B2 (en) 2012-01-23 2017-09-05 Merit Medical Systems, Inc. Mixing syringe
US8834449B2 (en) 2012-01-23 2014-09-16 Ikomed Technologies, Inc. Mixing syringe
CN103285454A (zh) * 2012-02-29 2013-09-11 山东威高集团医用高分子制品股份有限公司 双室多功能预灌封注射器
US8870028B2 (en) 2012-05-25 2014-10-28 Restek Corporation Dispensing device
CA2894462A1 (fr) 2012-12-14 2014-06-19 Bryan LARSON Carpule de medicament double pour seringues dentaires
TWI641381B (zh) 2013-02-04 2018-11-21 法商賽諾菲公司 胰島素類似物及／或胰島素衍生物之穩定化醫藥調配物
USD755957S1 (en) 2013-12-13 2016-05-10 Bryan Larson Dental carpule
EP3091995B1 (fr) 2014-01-09 2024-03-20 Sanofi Formulations pharmaceutiques stabilisées d'insuline aspart
BR112016013832A2 (pt) 2014-01-09 2017-08-08 Sanofi Sa Uso de análogo e/ou derivado de insulina, formulação farmacêutica e processo para a preparação da mesma, kit e dispositivo médico
JP6810031B2 (ja) 2014-10-29 2021-01-06 ウォックハート リミテッドＷｏｃｋｈａｒｄｔ Ｌｉｍｉｔｅｄ ユーザ操作可能な可変用量ロッキング機構を有する独立してユーザ選択可能な２つ以上の複数用量の薬剤を送達するための薬品送達装置
AU2015360746B2 (en) 2014-12-08 2020-10-01 Genentech, Inc. Versatile syringe platform
SI3229828T1 (sl) 2014-12-12 2023-06-30 Sanofi-Aventis Deutschland Gmbh Formulacija s fiksnim razmerjem inzulin glargin/liksisenatid
TWI748945B (zh) 2015-03-13 2021-12-11 德商賽諾菲阿凡提斯德意志有限公司 第２型糖尿病病患治療
TW201705975A (zh) 2015-03-18 2017-02-16 賽諾菲阿凡提斯德意志有限公司 第２型糖尿病病患之治療
TW201735960A (zh) * 2016-02-09 2017-10-16 賽諾菲阿凡提斯德意志有限公司 兩腔室卡普耳
TWI746569B (zh) 2016-06-08 2021-11-21 瑞士商瑞健醫療股份有限公司 計量器具、注射裝置、及其應用
JP7053614B2 (ja) 2016-11-28 2022-04-12 エスエイチエル・メディカル・アーゲー 物質を投与する装置
DE102017202607A1 (de) * 2017-02-17 2018-08-23 Vetter Pharma-Fertigung GmbH & Co. KG Medikamentenbehälter zur Bevorratung und Bereitstellung von mindestens zwei miteinander vermischbaren Medikamentensubstanzen und Verfahren zum Betreiben eines solchen Medikamentenbehälters
DE102017208255A1 (de) * 2017-05-16 2018-11-22 Vetter Pharma-Fertigung GmbH & Co. KG Medikamentenbehälter mit einem Endstopfen, Verwendung eines Stopfensicherungsteils zum Sichern eines Endstopfens in einem Medikamentenbehälter und Stopfensicherungsteil
FR3081299B1 (fr) * 2018-05-23 2020-09-11 Oreal Dispositif de preparation d'une compostion cosmetique, et procede associe

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL180634C (nl) 1977-12-23 1987-04-01 Duphar Int Res Injectiespuit alsmede naaldhouder hiervoor.
US4226236A (en) * 1979-05-07 1980-10-07 Abbott Laboratories Prefilled, vented two-compartment syringe
US4254768A (en) * 1979-09-14 1981-03-10 Ty Perla J Hypodermic syringe
DE3916101A1 (de) * 1989-05-17 1990-11-22 Vetter & Co Apotheker Spritze fuer medizinische zwecke
JPH0614756Y2 (ja) 1991-06-26 1994-04-20 株式会社アルテ 組み立て式の２室式容器兼用注射器
DE4445969C1 (de) * 1994-12-22 1996-03-14 Schott Glaswerke Spritzenzylinder für eine Zweikammer-Fertigspritze, Zweikammer-Fertigspritze und Verfahren zum Herstellen und Füllen derselben
US5607400A (en) * 1995-05-19 1997-03-04 Becton, Dickinson And Company Pre-fillable syringe and stopper assembly therefor
FR2749169B1 (fr) * 1996-06-04 1998-08-21 Delab Procede pour constituer une preparation injectable et dispositif pour la mise en oeuvre de ce procede
JP4399752B2 (ja) * 1999-07-06 2010-01-20 日本ケミカルリサーチ株式会社 薬剤溶解機構内蔵注射器
JP2001112867A (ja) * 1999-10-18 2001-04-24 Terumo Corp 薬剤入りシリンジ
DE10140704A1 (de) * 2001-08-18 2003-03-06 Vetter & Co Apotheker Verfahren zur Durchmischung einer schwer löslichen pharmazeutischen Substanz mit einem Lösungsmittel und Spritze zur Anwendung des Verfahrens
US20060173409A1 (en) * 2004-12-28 2006-08-03 Chang-Ming Yang Safety syring
CN101678174A (zh) * 2007-06-14 2010-03-24 塞诺菲-安万特德国有限公司 双室卡普耳

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2008151737A1 *

Also Published As

Publication number Publication date
JP2010528792A (ja) 2010-08-26
CN101678174A (zh) 2010-03-24
US20100262074A1 (en) 2010-10-14
TW200916138A (en) 2009-04-16
AR066985A1 (es) 2009-09-23
WO2008151737A1 (fr) 2008-12-18
US8092421B2 (en) 2012-01-10
US20120118139A1 (en) 2012-05-17

Similar Documents

Publication Publication Date Title
EP2167169B1 (fr) Ampoule à deux chambres avec garniture
WO2008151737A1 (fr) Ampoule à deux chambres
EP2224982B1 (fr) Système de seringue à deux chambres comportant une membrane perméable aux gaz
DE4445969C1 (de) Spritzenzylinder für eine Zweikammer-Fertigspritze, Zweikammer-Fertigspritze und Verfahren zum Herstellen und Füllen derselben
AT500930B1 (de) Verfahren und vorrichtung zum lyophilisieren, rekonstituieren und verabreichen eines rekonstituierten wirkstoffes
DE69628772T2 (de) Glassampulle für Injektionsspritze vorgefüllt mit flüssigem Arzneimittel
DE69823481T2 (de) Wegwerfbare, vorgefüllte medikamentenkartusche
DE19652708C2 (de) Verfahren zum Herstellen eines befüllten Kunststoff-Spritzenkorpus für medizinische Zwecke
DE102008025011B4 (de) Ampulle mit Ampullenhalterung
EP1263387B1 (fr) Procede servant a la reconstitution d'un liquide pour injection et appareil pour injection servant a l'execution d'un tel procede
EP2445552B1 (fr) Appareil d administration à fonction d amorçage
DE4438360C2 (de) Vorfüllbare partikelarme, sterile Einmalspritze für die Injektion von Präparaten und Verfahren zu ihrer Herstellung
DE2854527A1 (de) Injektionsspritze
EP1915184A1 (fr) Contenant a deux chambres sans derivation dans le corps cylindrique
DE10203598A1 (de) Injektionsgerät mit steril montierter Injektionsnadel sowie Nadelträger und Ampulle für solch ein Injektionsgerät
WO2007020239A1 (fr) Contenant a deux chambres et procede pour le remplir
DE2455509A1 (de) Zweikammermischspritze
DE102005038497A1 (de) Doppelkammer-Behälter ohne Bypass
DE202010018605U1 (de) Kartuschenhalter und Medikamentenabgabevorrichtung
EP3976139A1 (fr) Corps médical creux, corps médical creux doté d'un capuchon de fermeture, procédé de fabrication d'un corps médical creux, et kit
DE2329390A1 (de) Injektionsspritze
EP4374896A1 (fr) Unité d'entraînement pour une seringue médicale, seringue comprenant une telle unité d'entraînement et auto-injecteur
EP4279054A1 (fr) Ampoule de principe actif pour seringue médicale et procédé de remplissage d'une telle ampoule de principe actif
DE1491850C (de) Spritzampulle

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100114

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20110823

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20120303