WO2011130738A1 - Procédés d'utilisation d'un dispositif de mélange asymétrique pour la préparation d'un médicament inhibant la c1-estérase - Google Patents

Procédés d'utilisation d'un dispositif de mélange asymétrique pour la préparation d'un médicament inhibant la c1-estérase Download PDF

Info

Publication number
WO2011130738A1
WO2011130738A1 PCT/US2011/032890 US2011032890W WO2011130738A1 WO 2011130738 A1 WO2011130738 A1 WO 2011130738A1 US 2011032890 W US2011032890 W US 2011032890W WO 2011130738 A1 WO2011130738 A1 WO 2011130738A1
Authority
WO
WIPO (PCT)
Prior art keywords
container
adapter
diluent
esterase inhibitor
mixing device
Prior art date
Application number
PCT/US2011/032890
Other languages
English (en)
Inventor
Jack Bradley
Frank L. Nazzario
Elizabeth P. Eberhardt
Original Assignee
Viropharma Incorporated
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 Viropharma Incorporated filed Critical Viropharma Incorporated
Publication of WO2011130738A1 publication Critical patent/WO2011130738A1/fr

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
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
    • A61J1/2089—Containers or vials which are to be joined to each other in order to mix their contents
    • 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
    • A61J1/2006—Piercing means
    • A61J1/201—Piercing means having one piercing end
    • 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
    • A61J1/2006—Piercing means
    • A61J1/2013—Piercing means having two piercing ends
    • 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
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/10—Tube connectors; Tube couplings
    • A61M2039/1077—Adapters, e.g. couplings adapting a connector to one or several other connectors
    • 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
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/10—Tube connectors; Tube couplings
    • A61M2039/1094—Tube connectors; Tube couplings at least partly incompatible with standard connectors, e.g. to prevent fatal mistakes in connection
    • 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
    • A61M2209/00—Ancillary equipment
    • A61M2209/06—Packaging for specific medical equipment
    • 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
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/20—Closure caps or plugs for connectors or open ends of tubes

Definitions

  • the present invention relates to the field of preparing C1 -esterase inhibitor containing product for administration to patients for the treatment of hereditary angioedema. More specifically, the present invention relates to a method for improving the preparation of C1 -esterase inhibitor in order to reduce waste of the product and/or delaying administration of the medicine, which can be problematic in an emergency situation or prophylactic self-administration situation.
  • C1 -esterase inhibitor is a medicament used to treat patients with hereditary angioedema (HAE).
  • HAE hereditary angioedema
  • the treatment of HAE with a C1 -esterase inhibitor containing product may be done by treatment of acute attacks when they occur or by preventative treatments. The later is accomplished by prophylactic administration of suitable amounts of a C1 -esterase inhibitor product in order to reduce or prevent acute attacks and symptoms.
  • HAE is a disease
  • HAE ulcerative colitis .
  • C1 -esterase inhibitor a naturally occurring molecule that is known to modulate the inflammatory cascade. If left untreated, HAE can result in a mortality rate as high as 40% primarily due to upper airway obstruction.
  • Symptoms of an HAE attack generally present as swelling of one or more organ systems, most commonly affecting the skin, gastrointestinal tract, or respiratory tract.
  • HAE attacks account for approximately 15,000 to 30,000 emergency department (ED) visits per year. And, because symptoms of HAE can mimic a surgical emergency, about one-third of patients with undiagnosed HAE have been reported to have undergone unnecessary surgery during abdominal attacks, because the symptoms very closely resemble appendicitis and other medical conditions that frequently require surgery.
  • C1 -esterase inhibitor drug product is generally stored as a lyophilized
  • the C1 -esterase inhibitor is reconstituted using sterile water as a diluent.
  • a fluid transfer and mixing device may be used, such as the one disclosed in Zinger et al. U.S. Patent No. 6,558,365.
  • the Zinger device includes two cup-shaped elements for receiving the medicament and the diluent.
  • the diluent is first placed into the cup for the diluent container and the C1 -esterase inhibitor container is then inserted into the cup for the medicament. If the two containers are placed into the proper cups in the proper order, the diluent will flow into the powder, so that the C1 -esterase inhibitor containing product can be reconstituted and administered.
  • a method for preparing C1 -esterase inhibitor containing drug product uses an asymmetric device to transfer fluid, reconstitute and mix product components prior to administration to a patient.
  • the method comprises the steps of providing a container of lyophilized C1 -esterase inhibitor, wherein the container has a cap covering a pierceable seal, and the cap has a first diameter.
  • the method further comprises the step of providing a diluent in a second container having a second cap covering a second pierceable seal, wherein the second cap has a second diameter that is smaller than the first diameter of the C1 -esterase inhibitor container.
  • An asymmetric mixing device is provided having a diluent adapter connected with and in fluid communication with a medicament adapter.
  • the medicament adapter is selected to have an internal diameter configured to receive the cap of the C1 - esterase inhibitor container.
  • the diluent adapter is selected to have an internal diameter large enough to receive the cap of the diluent container, but small enough to significantly impede insertion of the C1 -esterase inhibitor cap into the diluent adapter.
  • the method further comprises the step of inserting the cap of the diluent container into the medicament adapter so that a cannula in the adapter pierces the second seal.
  • the C1 -esterase inhibitor container is inserted into the medicament adapter so that a cannula in the medicament adapter pierces the first seal.
  • the combined assembly of the medicament adaptor, diluent adapter, C1 -esterase inhibitor container and diluent container are oriented so that the diluent is vertically positioned over the C1 -esterase inhibitor container when the first seal is pierced thereby releasing the vacuum to allow the diluent to flow into the C1 -esterase inhibitor container.
  • the diluent adapter is disconnected from the medicament adapter, while maintaining the medicament adapter connected with the C1 -esterase inhibitor container.
  • a medical device such as a syringe is then connected to the medicament adapter and the reconstituted C1 -esterase inhibitor is withdrawn into the medical device for infusion to the patient.
  • the method includes the step of placing the connected medicament and diluent adapters into a container having a sealed opening, wherein the method includes removing the seal and inserting the diluent container into the diluent adapter while the diluent adapter is in the container.
  • Another aspect of the invention is a method of improving the safety of
  • a further aspect of the invention is a method of preventing the premature loss of vacuum within a C1 -esterase inhibitor product container by using an asymmetric mixing device during the process of reconstituting the drug product prior to administration to patient.
  • a further aspect of the invention is a method of avoiding wasting a C1 - esterase inhibitor containing product by using an asymmetric mixing device during the process of reconstituting the drug product prior to administration to patient.
  • An aspect of the invention is a method of improving doctor and/or patient compliance in connection with the use of a C1 -esterase inhibitor containing product by using an asymmetric mixing device during the process of reconstituting the drug product prior to administration to patient.
  • An aspect of the invention is a method of improving speed and/or ease of reconstituting a C1 -esterase inhibitor containing product by using an asymmetric mixing device during the process of reconstituting the drug product prior to administration to patient.
  • An aspect of the invention is a method of preventing or reducing delay in administering a C1 -esterase inhibitor containing product by using an asymmetric mixing device during the process of reconstituting the drug product prior to administration to patient.
  • An aspect of the invention is a method of improving the safety and efficacy of a C1 -esterase inhibitor containing product by including instructional information in product labeling or other product promotional materials as to how to use an asymmetric mixing device during the process of reconstituting the drug product prior to administration to patient.
  • An aspect of the invention is a method of improving the treatment of HAE disease (both acute treatment of attacks and prophylactic treatments) with a C1 -esterase inhibitor containing product by using an asymmetric mixing device to reconstitute drug product prior to administration to a patient.
  • Another aspect of the invention is a mixing apparatus for mixing
  • the mixing apparatus may include a first portion having a socket configured to receive a first container of a first size and a piercing element in the socket to pierce a seal of the first container.
  • the mixing apparatus further includes a second portion detachably connected with the first portion.
  • the second portion includes a socket sized to receive a second container having a second size that is smaller than the first size.
  • the second portion also includes a piercing element for piercing a seal of the second container.
  • the socket of the second portion is further configured to impede insertion of the first container into the socket of the second portion.
  • the second socket may be configured to impede insertion of a container of the first size into the second socket.
  • the second socket may include a stop configured to engage a container of the first size while not engaging a container of the second size.
  • the mixing apparatus may be used to mix a variety of medicaments in
  • the apparatus may be used to mix a container of medicament with a container of diluent. More specifically, the apparatus may be used to mix a container of lyophilized medicament in a container having a first diameter with a diluent in a container having a second diameter smaller than the first diameter.
  • a first portion of the apparatus is then inserted onto the diluent container while the diluent container is oriented with a pierceable seal disposed vertically above the bottom of the diluent container.
  • a first piecing element of the apparatus pierces the seal of the diluent container when the first portion is inserted onto the diluent container.
  • the medicament container is then oriented so that a pierceable seal of the medicament container is disposed vertically above the bottom of the medicament container.
  • a second portion of the apparatus is then inserted onto the medicament container so that a second piercing element pierces the seal of the medicament container.
  • the diluent flows from the diluent container into the medicament container through the two piercing elements.
  • the mixture may be administered by detaching the first portion from the second portion.
  • An injection device such as a syringe may then be releasably connected to the second portion to discharge the mixture from the medicament container into the injection device.
  • FIG. 1 is a an exploded perspective view of a mixing device for preparing C1 -esterase inhibitor medicament shown with a container of diluent and a container of lyophilized C1 -esterase inhibitor;
  • Fig. 2 is a side view of the mixing device of Fig. 1 , shown with the diluent container and C1 -esterase inhibitor container connected with the mixing device;
  • FIG. 3 is a cross-sectional view of two adapters of the mixing device shown in Fig. 1 ;
  • FIG. 4 is a perspective view of the mixing device shown in Fig. 1 ;
  • FIG. 5 is a perspective view of the mixing device shown in Fig. 1 , illustrated with the C1 -esterase inhibitor container improperly partially inserted into the device.
  • FIG. 6 is a perspective view of the mixing device of Fig. 3 illustrated in combination with a package adapted to hold the device and a container of diluent;
  • Fig. 7 is a perspective view of the mixing device of Fig. 7 after removal from the package.
  • a mixing device for preparing C1 -esterase inhibitor is generally designated 30.
  • the mixing device 30 is configured to facilitate reconstitution of lyophilized C1 - esterase inhibitor stored in a medicament container 20 by adding a diluent from a diluent container 10.
  • the mixing device 30 contains two releasably connectable adapters: a diluent adapter 40 configured to receive the diluent container 10 and a medicament adapter 60 configured to receive the medicament container 20.
  • the mixing device 30 includes cannulae for piercing seals on the containers 10, 20 to facilitate the sterile transfer of the diluent to the medicament container.
  • the medicament container 20 is a generally closed
  • the vial has a reduced diameter neck 24 and a forward open end having a circumferential bead that projects radially outwardly.
  • a pierceable seal 28 such as a septum, covers the open end of the vial, forming a fluid tight seal.
  • a cap 26 extends over the cap and is fixedly attached to the vial. For instance, the cap may be crimped onto the vial so that the cap is bent under the rim of the open end to prevent the cap from being removed from the vial.
  • the cap includes a central opening providing access to the septum 18 for piercing the septum to provide for fluid transfer into or out of the vial.
  • diluent container 10 is a generally closed container, such as a glass vial or bottle 22.
  • the diluent container 10 also has a reduced diameter neck 24 and a forward open end having a circumferential bead that projects radially outwardly similar to the medicament container.
  • the diluent container includes a pierceable seal, such as a septum 18, sealing the open end of the vial, and a cap 16 that extends over the septum to retain the septum in place on the vial.
  • the two containers are configured to differentiate the one container from the other.
  • the medicament container has an enlarged diameter opening relative to the diluent container, so that the diameter of the cap 26 is larger than the diameter of the cap 16 covering the end of the diluent container.
  • the outside diameter of the cap 26 for the medicament container is preferably at least 5% larger than the outside diameter of the cap 16 for the diluent container.
  • the dimensions of the caps for the containers may vary depending on various factors, however, in the present instance, the outside diameter of the cap 26 for the medicament container is approximately 17 mm and the outside diameter of the cap is approximately 20 mm.
  • the mixing device 30 includes two cup shaped adapters configured to releasably connect with one another.
  • the first adapter 40 is configured to cooperate with the diluent container 10.
  • the second adapter is configured to cooperate with the medicament container 20.
  • the diluent adapter 40 is a generally cup-shaped element having a socket 42 for receiving the head of the diluent container 10, specifically, the cap 16 and neck 14 of the diluent container.
  • the socket 42 has a base wall 43, forming the bottom of the socket.
  • the side walls of the socket are formed by a plurality of fingers 44, 45 that project longitudinally away from the base wall 43. The fingers are resiliently radially deformable.
  • the fingers include latching fingers 44 configured to engage and retain the diluent container in the diluent adapter.
  • the latching fingers have latching elements 48 that project radially inwardly to latch against the underside of the cap 16 of the diluent container 10.
  • the free ends of the latching fingers 44 are flat, forming a ledge as shown in Fig. 3, and as discussed further below.
  • All of the fingers of the diluent adapter 40 may be in the form of the latching fingers, as described above.
  • the socket includes a plurality of guide fingers 45 interspaced among the latching fingers.
  • the socket includes six fingers
  • the guide fingers 45 are elongated fingers, extending longitudinally away from the base further than the latching fingers.
  • the guide fingers 45 have a first portion that is generally coextensive with the latching fingers, and a second portion in the form of flared tip 46 that projects longitudinally beyond the end of the latching fingers.
  • the guide fingers may include latching elements similar to the latching fingers, in the present instance, the guide fingers do not. Instead, the first portion of the guide fingers are substantially straight, without any portion that projects radially inwardly.
  • the flared tip 46 of the guide fingers flare radially outwardly.
  • the tips 46 flare out a sufficient distance to form an internal diameter that is slightly larger than the internal diameter within the socket 42 between the latching fingers and the first portion of the guide fingers. In the present instance, the distance that the tips flare outwardly is less than approximately 2 mm.
  • a piercing cannula 50 Projecting inwardly into the socket 42 from the base wall 43 is a piercing cannula 50.
  • the piercing cannula has a tip configured to puncture the septum 18 of the diluent container 10.
  • the longitudinal length of the cannula 50 is shorter than the longitudinal length of the guide fingers, as shown in Fig. 3.
  • the cannula is illustrated as having a longitudinal length that is longer than the latching fingers.
  • the cannula 50 has a length that is shorter than the length of the latching fingers 44.
  • the cannula 50 is intergrally formed with the diluent adapter 40, and
  • the diluent adapter 40 further includes a connector 52 for releasably connecting the diluent adapter with the medicament adapter 60.
  • the connector 52 is formed on the base wall 43, on the side opposing the cannula 50.
  • the connector includes an element for releasably connecting the diluent adapter 40 with the medicament container in a manner to provide fluid communication between the diluent container 10 and the medicament container 20.
  • the connector may be a Luer type fitting.
  • the connector is a female Luer lock fitting having a stem 54 projecting from the base wall 43, and an internally threaded collar circumscribing the stem.
  • the stem 54 is in fluid communication with the cannula 50 through a hole in the base wall.
  • the second cup of the mixing device 30 is the medicament adapter 60, which is configured to engage and retain the vial of C1 -esterase inhibitor 20.
  • the medicament adapter 60 is a generally cup-shaped element having a socket 62 for receiving the head of the medicament container 20, specifically, the cap 26 and neck 24 of the medicament container.
  • the socket 62 has a base wall 63, forming the bottom of the socket.
  • the side walls of the socket are formed by a plurality of fingers 64 that project longitudinally away from the base wall 63.
  • the fingers 64 are resiliently radially deformable, and include latching elements 68 configured to engage and retain the medicament container 20 in the medicament adapter 60.
  • the latching elements 68 project radially inwardly to latch against the underside of the cap 26 of the medicament container 20. Beyond the latching elements 68, the free ends of the fingers flare radially outwardly to form an enlarged opening having a diameter larger than the diameter of the cap 26 for the medicament container.
  • a piercing cannula 70 Projecting inwardly into the socket 62 from the base wall 63 is a piercing cannula 70.
  • the piercing cannula has a tip configured to puncture the septum 28 of the medicament container 20.
  • the longitudinal length of the cannula 50 is shorter than the longitudinal length of the fingers 64, as shown in Fig. 3.
  • the cannula 70 is integrally formed with the medicament adapter 60, and includes a hollow bore for allowing fluid passage through the cannula.
  • the medicament adapter 60 further includes a connector 72 for releasably connecting the medicament adapter 60 with the diluent adapter 40, as shown in Fig. 4.
  • the connector 72 is formed on the base wall 63, on the side opposing the cannula 70.
  • the connector includes an element for releasably connecting the medicament adapter 60 with the diluent adapter 40 container in a manner to provide fluid communication between the diluent container 10 and the medicament container 20.
  • the connector may be a Luer type fitting.
  • the connector is a male Luer lock fitting having a stem 72 projecting from the base wall 63, and an externally threaded portion internally collar circumscribing the stem.
  • the internal diameter of the stem 72 is configured to mate with the external diameter of the stem 52 to form a fluid-tight seal.
  • the stem 72 is in fluid communication with the cannula 70 through a hole in the base wall.
  • the diluent adapter 40 has a socket 42 having an internal diameter that is smaller than the internal diameter of the socket 62 of the medicament adapter 60. In this way, the mixing device is asymmetric.
  • the internal diameter of the socket 42 is substantially similar to the outer diameter of the cap 16 of the diluent container 10.
  • the distance between ends of opposing fingers 44, 45 is substantially similar to or slightly larger than the external diameter of the diluent cap 16. In this way, the diluent container 10 can be readily inserted into the diluent adapter. As the cap 16 of the diluent container is inserted into the adapter 40, the guide arms 45 may flex radially outwardly to allow insertion of the container. As the cap 16 continues to enter the socket 42, the cap engages the latching elements of the latching fingers 44. The latching elements project inwardly to form a reduced diameter area that is smaller than the external diameter of the cap 16.
  • the latching elements engage the outer surface of the cap, causing the latching fingers to deform radially outwardly to provide clearance for the cap to enter the socket.
  • the longitudinal length of the latching fingers between the base wall 43 and the latching elements is longer than the longitudinal length of the cap.
  • the diluent adapter 40 is configured to impede insertion of the medicament container 20 into the diluent adapter.
  • the internal diameter of the socket 42 is smaller than the outer diameter of the cap 26 of the medicament container, and in the present instance is
  • the outer diameter of the free ends of the latching fingers 44 has a diameter of "d", which is less than the outer diameter of the cap 26 of the medicament. Therefore, as shown in Fig. 5, although the flared tips 46 of the guide fingers 45 may deform radially outwardly to accommodate the larger medicament container, as the medicament container is displaced toward the socket, the forward surface of the cap 26 will abut the flat end surfaces of the latching fingers. In this way, the ends of the latching fingers engage the cap 26 to act as stops impeding the insertion of the medicament container into diluent adapter.
  • the guide fingers operate to center the cap within the center of the socket opening, thereby reducing the possibility of inserting the container into the socket at an angle, which could allow the forward end of the cap to deflect the latching fingers radially outwardly, rather than acting as stops as described above.
  • the latching fingers extend from the base further than the cannula, the cannula will not pierce the septum of a container until the container is inserted into the socket beyond the latching elements, which act as stops against the larger medicament container.
  • the structure of the diluent adapter impedes insertion of the medicament container into the diluent adapter, and impedes and/or prevents inadvertent puncture of the medicament septum if the operator erroneously attempts to insert the medicament container into the diluent adapter.
  • a holder 80 is provided for the mixing device.
  • the holder 80 is in the form of a sterile package in which the mixing device 30 is stored prior to use.
  • the holder 80 comprises a cylindrical or frustoconical enclosed package, having an open upper end 82.
  • a removable seal (not shown) encloses the open upper end to preserve the sterility of the package. The seal may be attached so that it can be pealed off of the upper end of the package to expose the mixing device.
  • the mixing device 30 is positioned in the holder 80 so that the diluent adapter 40 faces upwardly, and the medicament adapter faces downwardly toward the bottom of the package 86.
  • the interior of the package may be configured to engage the mixing device to impede displacement of the mixing device within the package.
  • the holder tapers inwardly toward the base 86, and the interior of the base may include an annular ridge adapted to cooperate with the lip around the free ends of the latching fingers 64 of the medicament adapter.
  • a vial of lyophilized C1 -esterase inhibitor is provided in a container having a cap with a first diameter.
  • a bottle of diluent is provided in a container having a cap with a second diameter, wherein the diluent bottle is selected so that the cap of the diluent bottle is smaller than the diameter of the cap for the medicament container.
  • the vial of C1 -esterase inhibitor comprises 500 units of lyophilized product (under vacuum in the container), and the diluent container comprises 5 mL of sterile water.
  • the two containers are prepared for use by wiping the cap of the vial of C1 -esterase inhibitor with an alcohol wipe or other disinfecting item and wiping the cap of the diluent container with a similar alcohol wipe or other disinfecting item.
  • the mixing device 30 is provided in a package that also operates as a holder. The mixing device is positioned within the package so that the diluent adapter is connected to the C1 -esterase inhibitor vial and the diluent adapter faces upwardly toward the opening in the package. The cover sealing the opening of the package is removed to allow access to the mixing device, however, the mixing device is maintained within the package with the diluent adapter accessible through the package opening.
  • the diluent container is then inserted into the socket 42 of the diluent adapter while maintaining the adapter within the package 80. Specifically, the diluent container is inserted into the opening between the flared tips of the guide fingers 45. More specifically, while the diluent container is upright with the seal upward, the mixing device is attached to the diluent container by placing the package 80 and the enclosed mixing device 30 onto the diluent container 10 so that the diluent adapter 40 engages the top of the diluent container (Note: in Fig.
  • the drawing illustrates the diluent container 10 inverted and inserted into the mixing device 30 rather than the diluent container being upright with the mixing container being placed over the diluent container as described above).
  • the guide fingers tend to center the cap of the diluent container within the socket as the diluent adapter 40 is mounted onto the diluent container.
  • the cap engages the reduced diameter formed by the latching elements of the latching fingers 44, causing the latching fingers to displace radially outwardly.
  • the diluent adapter onto the diluent container pierces the cannula through the septum 18 so that the diluent can flow through the cannula.
  • the diluent adapter is inserted onto the diluent container until the latching fingers deform radially inwardly to latch onto the rearward end of the cap to retain the diluent container in the adapter. 1 ] Referring to Figs. 6-7, after the diluent adapter 40 in the holder 80 is mounted onto the diluent container 10, the mixing device is removed from the holder. More specifically, the holder 80 is displaced upwardly to uncover the mixing device 30 and expose the medicament adapter 60..
  • the medicament container (or for example a C1 -esterase inhibitor vial) is then oriented in an upright position with the cap 26 facing upwardly, such as by placing the C1 - esterase inhibitor vial on a horizontal surface, such as a counter.
  • the mixing device is inverted so that the diluent container is vertically positioned above the medicament adapter.
  • the medicament adapter 60 of the mixing device is aligned with the upward facing medicament container, and the mixing device is positioned over the medicament vial so that the cap of the medicament vial is inserted into the socket of the medicament adapter.
  • the mixing device 30 is mounted onto the medicament container 20, the cap of the container 20 engages inwardly projecting latching elements of the latching fingers.
  • the medicament container is inserted into the adapter until the piercing cannula pierces the septum of the medicament container thereby breaking the vacuum to allow diluent to flow into the piercing cannula and into the medicament container.
  • the latching fingers resiliently rebound to engage against the rearward edge of the cap to impede disconnection of the medicament container from the adapter.
  • the interior of the C1 -esterase inhibitor container (that is the medicament container) is under vacuum.
  • the diluent since the diluent is positioned vertically above the C1 -esterase inhibitor container and since the C1 -esterase inhibitor container is under vacuum, the diluent flows from the diluent container into the medicament container so that the C1 - esterase inhibitor can be reconstituted.
  • the diluent is transferred to the medicament container 20 through the cannula 50, stem 54, cannula 70 and the stem of the second connector 72.
  • the C1 -esterase inhibitor is reconstituted by agitating the assembly to dissolve the C1 -esterase inhibitor while the containers remain connected to the mixing device.
  • Fig. 2 illustrates the completed assembly once the diluent container 10 and medicament container 20 have been connected with the mixing device 40. It should be understood that the horizontal orientation of the view in Fig. 2 is for illustration of the assembly. As discussed above, during actual use, the assembly would be in a vertical orientation with the diluent container disposed vertically above the medicament container.
  • the diluent adapter 40 is disconnected from the medicament container.
  • the diluent and attached diluent container as detached by disconnecting the first connector from the second connector.
  • the first and second connectors are Luer lock fittings. Accordingly, the diluent and attached diluent adapter is disconnected from the medicament adapter by rotating the diluent adapter relative to the medicament to unscrew the female Luer fitting of the diluent container from the male Luer fitting of the medicament container.
  • the reconstituted C1 -esterase inhibitor is ready for administration.
  • the method provides for administration of the C1 -esterase inhibitor via infusion.
  • the C1 -esterase inhibitor is drawn into a syringe by attaching a mating Luer fitting on the end of the syringe with the connector 72 on the medicament adapter 60.
  • the plunger of the syringe is then withdrawn to draw the C1 -esterase inhibitor out of the medicament container so that the medicine can be administered to the patient.
  • the apparatus for mixing C1 -esterase inhibitor comprises a first adapter configured to engage the container of C1 -esterase inhibitor, wherein the first adapter comprises: (a) a first socket having a first internal diameter; (b) a first connector external of the first socket; and (c) a first piercing cannula within the first socket.
  • the apparatus further comprises a second adapter configured to engage the container of diluent and configured to substantially impede insertion of the container of C1 -esterase inhibitor into the second adapter, wherein the second adapter comprises: (a) a second socket having a second diameter smaller than the first diameter, (b) a second piercing cannula within the second socket; and (c) a second connector external of the second socket of the second adapter, and releasably connectable with the first connector to form a fluid tight seal between the first cannula and the second cannula.
  • the apparatus for mixing C1 -esterase inhibitor may be configured so that the first socket comprises a plurality of resiliently radially deformable fingers operable to latch onto the cap of the C1 -esterase inhibitor container to retain the C1 -esterase inhibitor container within the first socket.
  • the apparatus may also be configured so that the second socket comprises a stop configured to impede insertion of the C1 -esterase inhibitor container into the second adapter without substantially impeding insertion of the diluent container into the second adapter.
  • the apparatus may further be configured so that the second socket
  • the second socket may be configured so that inserting the diluent container into the socket of the second adapter causes the diluent container to engage the guide fingers prior to engaging the latching fingers.
  • the apparatus may also comprise a holder for holding the mixing device, wherein the holder is configured to enclose one of the first and second adapters while providing an opening to acess the other of the first and second adapters.
  • the mixing device may be positioned in the holder so that the first adapter is enclosed and the second adapter is accessible through the opening.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

L'invention concerne un procédé pour mélanger des médicaments issus de deux récipients. Plus spécifiquement, le procédé ci-décrit permet de mélanger un produit médicamenteux inhibiteur de la C1-estérase conservé sous forme de poudre lyophilisée dans une bouteille ou un autre récipient. L'inhibiteur de la C1-estérase est reconstitué en utilisant un dispositif de mélange asymétrique comportant une première partie configurée pour recevoir un récipient de diluant et une deuxième partie configurée pour recevoir un récipient d'inhibiteur de la C1-estérase. La première partie est agencée pour y empêcher l'insertion par erreur du récipient d'inhibiteur de la C1-estérase.
PCT/US2011/032890 2010-04-16 2011-04-18 Procédés d'utilisation d'un dispositif de mélange asymétrique pour la préparation d'un médicament inhibant la c1-estérase WO2011130738A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US32500510P 2010-04-16 2010-04-16
US61/325,005 2010-04-16

Publications (1)

Publication Number Publication Date
WO2011130738A1 true WO2011130738A1 (fr) 2011-10-20

Family

ID=44799067

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/032890 WO2011130738A1 (fr) 2010-04-16 2011-04-18 Procédés d'utilisation d'un dispositif de mélange asymétrique pour la préparation d'un médicament inhibant la c1-estérase

Country Status (1)

Country Link
WO (1) WO2011130738A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106166113A (zh) * 2016-08-03 2016-11-30 山东新华安得医疗用品有限公司 一种密闭式流体转移装置及一种密闭式流体转移方法
WO2019015769A1 (fr) * 2017-07-20 2019-01-24 Janssen Biotech, Inc. Dispositif de mélangeage de médicament
JP2020156924A (ja) * 2019-03-27 2020-10-01 テルモ株式会社 シリンジ接続具
WO2022180488A1 (fr) * 2021-02-26 2022-09-01 Koska Family Limited Ensembles pré-remplis d'administration de multiples fluides médicaux

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992022320A1 (fr) * 1991-06-14 1992-12-23 Genentech, Inc. Variantes de l'inhibiteur c1 et traitement des reactions inflammatoires avec l'inhibiteur c1
US5397303A (en) * 1993-08-06 1995-03-14 River Medical, Inc. Liquid delivery device having a vial attachment or adapter incorporated therein
US20020173752A1 (en) * 2000-02-16 2002-11-21 Polzin U1F Method for reconstituting an injection liquid and an injection appliance for carrying out such a method
US20030109846A1 (en) * 2001-01-03 2003-06-12 Freddy Zinger Fluid transfer device
US20070078428A1 (en) * 2003-01-22 2007-04-05 Reynolds David L Fluid transfer assembly for pharmaceutical delivery system and method for using same
US20090036866A1 (en) * 2007-08-01 2009-02-05 Hospira, Inc. Medicament admixing system

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992022320A1 (fr) * 1991-06-14 1992-12-23 Genentech, Inc. Variantes de l'inhibiteur c1 et traitement des reactions inflammatoires avec l'inhibiteur c1
US5397303A (en) * 1993-08-06 1995-03-14 River Medical, Inc. Liquid delivery device having a vial attachment or adapter incorporated therein
US20020173752A1 (en) * 2000-02-16 2002-11-21 Polzin U1F Method for reconstituting an injection liquid and an injection appliance for carrying out such a method
US20030109846A1 (en) * 2001-01-03 2003-06-12 Freddy Zinger Fluid transfer device
US20070078428A1 (en) * 2003-01-22 2007-04-05 Reynolds David L Fluid transfer assembly for pharmaceutical delivery system and method for using same
US20090036866A1 (en) * 2007-08-01 2009-02-05 Hospira, Inc. Medicament admixing system

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106166113A (zh) * 2016-08-03 2016-11-30 山东新华安得医疗用品有限公司 一种密闭式流体转移装置及一种密闭式流体转移方法
WO2019015769A1 (fr) * 2017-07-20 2019-01-24 Janssen Biotech, Inc. Dispositif de mélangeage de médicament
CN111107828A (zh) * 2017-07-20 2020-05-05 詹森生物科技公司 药物混合装置
JP2020533030A (ja) * 2017-07-20 2020-11-19 ヤンセン バイオテツク，インコーポレーテツド 薬剤混合装置
JP2020156924A (ja) * 2019-03-27 2020-10-01 テルモ株式会社 シリンジ接続具
WO2022180488A1 (fr) * 2021-02-26 2022-09-01 Koska Family Limited Ensembles pré-remplis d'administration de multiples fluides médicaux

Similar Documents

Publication Publication Date Title
US11219577B2 (en) Closed fluid transfer system
EP0499481B1 (fr) Adaptateur de transfert
EP2931207B1 (fr) Adaptateur pour fiole
US10278897B2 (en) Dual vial adapter assemblage including drug vial adapter with self-sealing access valve
US6997917B2 (en) Table top drug dispensing vial access adapter
EP2180867B1 (fr) Dispositifs d'administration de médicament liquide à utiliser avec des seringues dotées d'embouts distaux évasés
US8721612B2 (en) System and method for intermixing the contents of two containers
EP0974330A2 (fr) Connecteur universel pour utilisation multiple
US20120059346A1 (en) Vial handling and injection safety systems and connectors
KR20040111430A (ko) 희석제 용기용 활주식 재구성 장치
JP2011152442A (ja) 改良されたシステムを有する医療用再構成システム
US10080703B2 (en) Assembly comprising an adaptor for coupling with a medical container and a blister
WO2011115811A1 (fr) Bouchon filtrant pour seringue et son procédé d'utilisation pour l'administration de dose de médicament
WO2011130738A1 (fr) Procédés d'utilisation d'un dispositif de mélange asymétrique pour la préparation d'un médicament inhibant la c1-estérase
US10159788B2 (en) Attachment device for medical fluid container
AU2017317170B2 (en) Secured medication transfer system
AU2014277764B2 (en) Closed fluid transfer system
JP7209849B2 (ja) 点滴用ボトルと共に使用するための液体移送装置
JPH03133456A (ja) 薬剤を貯蔵し調合し使用するための装置

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11769747

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11769747

Country of ref document: EP

Kind code of ref document: A1