EP4598665A2 - Procédés et adaptateurs pour mélanger des complexes pharmaceutiques - Google Patents

Procédés et adaptateurs pour mélanger des complexes pharmaceutiques

Info

Publication number
EP4598665A2
EP4598665A2 EP23800637.3A EP23800637A EP4598665A2 EP 4598665 A2 EP4598665 A2 EP 4598665A2 EP 23800637 A EP23800637 A EP 23800637A EP 4598665 A2 EP4598665 A2 EP 4598665A2
Authority
EP
European Patent Office
Prior art keywords
adapter
channel
mixing
port
substance
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.)
Pending
Application number
EP23800637.3A
Other languages
German (de)
English (en)
Inventor
Dan Lennon
Emer Moloney
Aidan Byrne
Martin Mcgarry
Patrick Dowling
Michael J. Sullivan
Rajiv Kumar
Md Abu HASAN
Jorge SANTOS
Richard J. BROUGH
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.)
West Pharmaceutical Services Inc
Original Assignee
West Pharmaceutical Services Inc
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 West Pharmaceutical Services Inc filed Critical West Pharmaceutical Services Inc
Publication of EP4598665A2 publication Critical patent/EP4598665A2/fr
Pending 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
    • A61J1/14—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
    • A61J1/2048—Connecting means
    • A61J1/2058—Connecting means having multiple connecting ports
    • 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
    • A61J1/2096—Combination of a vial and a syringe for transferring or mixing their contents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/44—Mixers in which the components are pressed through slits
    • B01F25/441—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits
    • B01F25/4416—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits the opposed surfaces being provided with grooves
    • B01F25/44162—Circumferential grooves formed on opposed surfaces, e.g. on planar surfaces or on cylinders or cones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/44—Mixers in which the components are pressed through slits
    • B01F25/441—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits
    • B01F25/4416—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits the opposed surfaces being provided with grooves
    • B01F25/44163—Helical grooves formed on opposed surfaces, e.g. on cylinders or cones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/44—Mixers in which the components are pressed through slits
    • B01F25/441—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits
    • B01F25/4416—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits the opposed surfaces being provided with grooves
    • B01F25/44164—Crossing sets of grooves forming a labyrinth formed on opposed surfaces, e.g. on planar surfaces or on cylinders or cones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/44—Mixers in which the components are pressed through slits
    • B01F25/441—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits
    • B01F25/4416—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits the opposed surfaces being provided with grooves
    • B01F25/44167—Mixers in which the components are pressed through slits characterised by the configuration of the surfaces forming the slits the opposed surfaces being provided with grooves the grooves being formed on the outer surface of the cylindrical or conical core of the slits
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/165—Making mixers or parts thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/56—General build-up of the mixers
    • 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
    • A61J1/2048—Connecting means
    • A61J1/2055—Connecting means having gripping means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F2025/91—Direction of flow or arrangement of feed and discharge openings
    • B01F2025/913—Vortex flow, i.e. flow spiraling in a tangential direction and moving in an axial direction
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/22—Mixing of ingredients for pharmaceutical or medical compositions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/2305—Mixers of the two-component package type, i.e. where at least two components are separately stored, and are mixed in the moment of application
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing

Definitions

  • the disclosure relates to adapter, systems, and methods of use for mixing at least two substances to produce a pharmaceutical complex.
  • mRNA-LNP messenger RNA encapsulated lipid nanoparticle
  • CMC Chemical & Manufacturing Control
  • mRNA messenger RNA provided alone is not readily absorbed or delivered effectively to human immune cells and has unstable chemical and physical properties, therefore is not effective for use as a vaccine.
  • absorption and stability of mRNA can be increased to effective levels if it is encapsulated within lipid nanoparticle (LNP) vectors.
  • Preparation of mRNA-LNP vaccines is achieved by mixing lipids dissolved ethanol with RNA in buffers, under closely controlled conditions. Such mixing is usually carried out in a laboratory using devices which are often inappropriate for high-scale distribution, due to their low durability, high cost, high complexity, low lot-to-lot consistency and/or high interbatch variation.
  • RNA-LNP lipid nanoparticle compositions
  • RNA-LNP drugs can be chemically modified to improve their stability and shelf life at room temperature (such chemical modification is not possible for mRNA-LNP technology which requires interaction with cellular proteins to function appropriately). Chemical modification of RNA-LNP can be difficult and expensive to achieve but is nonetheless often preferred to avoid the significant distribution costs associated with non-modified RNA-LNP drugs which must similarly be kept at very’ low temperatures, as well as the difficulty’ associated with managing drug efficacy over time due to the limited molecular half-life.
  • a first aspect of the present disclosure is directed to an adapter having: a body having a first port configured to connect with a first container to receive a first substance, a second port configured to connect with a second container to receive a second substance, a third port configured to connect with a recipient container to output a mixture of the first substance and the second substance, and a mixing chamber having a first portion in communication with the first port and the second port and a second portion in communication with the third port; and a mixing pin inserted into the mixing chamber w herein the mixing pin at least partially defines at least one microfluidic path for mixing the first substance and the second substance.
  • the adapter may have one or more of the following features.
  • the body further may have an opening in the first portion of the mixing chamber configured to receive the mixing pin.
  • the mixing pin may be removable from the mixing chamber.
  • the mixing pin may have a flange, and the body may have a recess configured to receive the flange.
  • the mixing pin may have a sealing portion configured to seal the first portion of the mixing chamber.
  • the first port and/or the second port may be substantially parallel to the mixing chamber.
  • the body may further include a first branch channel in communication w ith the first port and extending at a first angle relative to the mixing chamber, and a second branch channel in communication with the second port and extending at a second angle relative to the mixing chamber. The first angle and/or the second angle may be greater than 90 degrees.
  • the first angle and/or the second angle may be about 120 to about 160 degrees.
  • the adapter may further include a first plug inserted into an end of the first branch channel, and a second plug inserted into an end of the second branch channel.
  • the first branch channel may be configured to guide the first substance toward the mixing pin
  • the second branch channel is configured to guide the second substance toward the mixing pin.
  • the mixing pin defines a first edge surface may be formed by a first surface and a second surface and a second edge formed by a third surface and a fourth surface, the first edge is configured to divide the first substance, and the second edge is configured to divide the second substance.
  • the first port may be a female Luer connector
  • the second port may be a female Luer connector
  • the third port is a male Luer connector.
  • the at least one microfluidic path may be tortuous.
  • the at least microfluidic path may be formed by at least one channel.
  • the at least one channel may have a dimension of about 200 pm to about 1000 pm.
  • the at least one channel may have a dimension of about 400 pm to about 600 pm.
  • the at least one channel may include at least one helical channel.
  • the at least one helical channel may include a first helical channel and a second helical channel, wherein the first helical channel and the second helical channel intersect along a longitudinal length of the mixing pin at a plurality of intersection points.
  • the at least one channel may extend through the mixing pin.
  • the mixing pin may include a plurality of protrusions that extend at least partially around a circumference of the mixing pin and define at least a portion of the at least one channel.
  • the plurality of protrusions may extend uniformly around the circumference of the mixing pin and form at least one radial gap with respect to an inner surface of the body, the at least one radial gap forming at least a portion of the at least one channel.
  • Each of the plurality of protrusions may have at least one first surface configured to create a seal against an inner surface of the body and at least one second surface forming at least one radial gap with respect to the inner surface of the body, the at least one radial gap forming at least a portion of the at least one channel.
  • a second aspect of the present disclosure is directed to a system having: an aqueous solution; a lipid solution; a first container configured to receive the aqueous solution; a second container configured to receive the lipid solution; a recipient container; an adapter including: a body having: a first port configured to connect with the first container and to receive the aqueous solution, a second port configured to connect with the second container and to receive the lipid solution, a third port configured to connect with the recipient container to output a mixture of the aqueous solution and the lipid solution, a mixing chamber extending between a first portion in communication with the first port and the second port and a second portion in communication with the third port; and a mixing pin configured to be inserted into the mixing chamber wherein the mixing pin at least partially defines at least one microfluidic path for mixing the aqueous solution and the lipid solution.
  • the system may have one or more of the following features.
  • the system may include a second pin configured to be inserted into the mixing chamber, wherein the second mixing pin has a different geometry than the mixing pin.
  • the system may include a first storage container containing the aqueous solution, and a second storage container containing the lipid solution.
  • a third aspect of the present disclosure is directed to a method including: introducing a first substance into a first port of an adapter; introducing a second substance into a second port of the adapter; mixing the first substance and the second substance in at least microfluidic path through, along, and/or around a mixing pin in the adapter; and producing a pharmaceutical complex with the first substance and the second substance.
  • the method may have one or more of the following features.
  • the first substance may be an aqueous solution
  • the second substance may be a lipid solution
  • the pharmaceutical complex may include lipid nanoparticles.
  • a fourth aspect of the present disclosure is directed to an adapter including: a body having: a first port configured to connect with a first container to receive a first substance, a first channel in communication with the first port, a second port configured to connect with a second container to receive a second substance, a second channel in communication with the second port, a third port configured to connect with a recipient container to output a mixture of the first substance and the second substance, a mixing chamber having a first portion in communication with the first port and the second port and a second portion in communication with the third port; and a mixing pin inserted into the mixing chamber, wherein at least one of the first channel and the second channel is oriented offset of a central plane of the body.
  • the adapter may have one or more of the following features.
  • the body may include an opening in the first portion of the mixing chamber configured to receive the mixing pin.
  • the mixing pin may be removable from the mixing chamber.
  • the mixing pin may have an end cap, and the body may have a rim configured to engage the end cap.
  • the adapter may include a sealing member configured to seal the first portion of the mixing chamber.
  • the first port and/or the second port may be substantially parallel to the mixing chamber.
  • the first channel may extend at a first angle relative to the mixing chamber, and the second channel may extend at a second angle relative to the mixing chamber.
  • the first angle and/or the second angle may be greater than 90 degrees.
  • the first angle and/or the second angle may be about 120 to about 160 degrees.
  • the adapter may include a first plug in an end of the first channel, and a second plug in an end of the second channel.
  • the first channel and the second channel may be offset of the central plane of the mixing pin.
  • the first channel and the second channel may be on the same side of a lateral axis of the adapter body.
  • the first channel and the second channel may be on opposite sides of a lateral axis of the adapter body.
  • the first channel and the second channel may be connected to the body at different longitudinal positions.
  • the first port may be a female Luer connector
  • the second port may be a female Luer connector
  • the third port may be a male Luer connector.
  • the mixing pin may form by at least one channel.
  • the at least one channel may have a dimension of about 200 pm to about 1000 pm.
  • the system may have one or more of the following features.
  • the system may include a second pin configured to be inserted into the mixing chamber, wherein the second mixing pin has a different geometry than the mixing pin.
  • the system may include a first storage container containing the aqueous solution, and a second storage container containing the lipid solution.
  • the method may have one more of the following features.
  • the first substance may be an aqueous solution
  • the second substance may be a lipid solution
  • the pharmaceutical complex may include lipid nanoparticles.
  • FIG. 2 illustrates an exploded view of a first embodiment of an adapter of the system of Fig. 1.
  • FIG. 3 illustrates a first cross-sectional view of the adapter of FIGS. 1 and 2.
  • FIG. 4 illustrates a second cross-sectional view of the adapter of FIGS. 1-3.
  • FIG. 5 illustrates a first side view of a mixing pin of the adapter of FIGS. 1-4.
  • FIG. 6 illustrates a second side view of the mixing pin of the adapter of FIGS. 1-5.
  • FIG. 7 illustrates a third side view of the mixing pin of the adapter of FIGS. 1-6.
  • FIG. 8 illustrates a cross-sectional view of a second embodiment of a mixing pin in the adapter of the system of FIGS. 1-4.
  • FIG. 10 illustrates an isometric view of a third embodiments of a mixing pin of the system of FIGS. 1-4.
  • FIG. 11 illustrates a cross-sectional view of the third embodiments of the mixing pin of FIG. 10 in the adapter of FIGS. 1-4.
  • FIG. 12 illustrates a liquid volume cross-section of the adapter of FIGS. 11.
  • FIG. 13 illustrates an isometric view of a fourth embodiment of a mixing pin of the system of FIGS. 1-4.
  • FIG. 14 illustrates a partially transparent view of a second embodiment of an adapter of the system of FIGS. 1-4.
  • FIG. 15 illustrates a partially transparent view of a third embodiment of an adapter of the system of FIGS. 1-4.
  • FIG. 18 illustrates an isometric view of the adapter of FIGS. 15-17.
  • FIG. 19 illustrates an exploded view of the adapter of FIGS. 15-18.
  • FIG. 22 illustrates a second isometric view of the mixing pin of FIGS. 15-17 and 19.
  • FIG. 23 illustrates an isometric view of a first plug of the adapter of FIGS. 15-19.
  • FIG. 24 illustrates an isometric view of a second plug of the adapter of FIGS. 15-19.
  • FIG. 25 illustrates an isometric view of a fourth embodiment of an adapter of the system of FIGS. 1-4.
  • FIG. 26 illustrates a longitudinal view of the adapter of FIG. 25.
  • FIG. 27 illustrates a first cross-sectional view of the adapter of FIGS. 25-26.
  • FIG. 28 illustrates a second cross-sectional view of the adapter of FIGS. 25-26.
  • FIG. 29 illustrates a method of mixing a first substance and a second substance using one or more of the embodiments of FIGS. 1-28.
  • the RNA may be in the form of oligonucleotide RNA, tRNA (transfer RNA), snRNA (small nuclear RNA), rRNA (ribosomal RNA), mRNA (messenger RNA), antisense RNA, siRNA (small interfering RNA), shRNA (short-hairpin RNA), ncRNA (noncoding RNA), aptamers, ribozymes, chimeric sequences, or derivatives of these groups.
  • Gene editing complexes may include gRNA (guide RNA), cas 9 protein, mRNA or DNA encoding for cas 9 protein or the CRISPR-cas9 gRNA complex.
  • the aqueous solution may then be introduced from the first container 20 into the first storage container 80 to reconstitute the therapeutic agent.
  • the first solution including the therapeutic agent may then be introduced into the first container 20 to be introduced into the adapter.
  • the first substance (with the therapeutic agent in the lyophilized state or as a solution) and the second substance may be adapted for transportation and medium-term or long-term storage at room temperature.
  • the system 10 and adapter 100 disclosed herein may enable the obstacles associated with storing and transporting RNA-LNP complexes at prohibitively low temperatures to be mitigated.
  • the adapter 100 may be easy to use at the point of care.
  • the adapter 100 may include a body 101 having a first port 102 configured to connect to the syringe connector 26 of the first container 20 and a second port or connector member 104 configured to attach to the syringe connector 46 of the second container 40.
  • the first port 102 may be configured to be received by the first syringe connector 26 and have an external thread 106 configured to threadably engage the internal threads of the first connector 26.
  • the second port 104 may be configured to be received by the second connector 46 and have an external thread 108 around the second tubular member 104 configured to threadably engage the internal threads of the second syringe connector 46.
  • the ports 102, 104 may be a female Luer connector
  • the connectors 26, 46 of the containers 20, 40 may be a male Luer connector.
  • the ports 102, 104 may, additionally or alternatively, connect to the containers 20, 40 with other types of connections such as a snap-fit, friction-fit and/or a press-fit.
  • the adapter 100 may be configured to connect to any number of the first and second containers 20, 40, the adapter 100 may have an equal number of ports 102, 104 for connecting to each of the containers 20, 40 accordingly. Furthermore, one or more of the ports 102, 104 may include a one-way valve (not shown) to allow fluid flow from the container 20, 40 into the adapter 100, and to restrict or substantially prevent fluid flow out of the adapter 100 back to the respective container 20, 40.
  • the first port 102 may define a first connector channel or port 110
  • the second connector member 104 may define a second connector channel 112.
  • the first connector channel 110 may be configured to receive the tip of the first syringe 20 to place the chamber of the first syringe body 22 in fluid communication with the first connector channel 110
  • the second connector channel 112 may be configured to receive the tip of the second syringe 40 to place the chamber of the second syringe body 42 in fluid communication with the second connector channel 112.
  • the first tubular member 102 and the second tubular member 104 may extend substantially parallel to each other to facilitate joint actuation of the syringes 20, 40, as discussed herein.
  • the first tubular member 102 and the second tubular member 104 may extend substantially parallel to a longitudinal axis of the adapter body 101.
  • the adapter body 101 may further include a first branch member 114, a second branch member 116, and a mixing member 118.
  • the first port 102 may extend from the first branch member 114, and the first branch member 114 may connect the first port 102 to the mixing member 118.
  • the second port 104 may extend from the second branch member 116, and the second branch member 116 may connect the second port 104 to the mixing member 118.
  • the first branch member 114 may have a first branch channel 120 configured to receive the fluid flow from the first container 20 through the first connector channel 110.
  • the second branch member 116 may have a second branch channel 122 configured to receive the fluid flow from the second container 40 through the second connector channel 112.
  • the first second branch channel 120 and the second branch channel 122 may be in communication with a first or upper portion of the mixing chamber 124.
  • the first branch channel 120 and the second branch channel 122 may be angled relative to the longitudinal axis of the mixing member 118, adapter body 101 and/or mixing pin 160 to converge the fluid flow from the first syringe 20 and the second syringe 40 into the mixing member 118.
  • the angle of at least one of the first branch channel 120 and the second branch channel 122 may be at least 90 degrees relative to the mixing member 118, adapter body 101 and/or mixing pin 160.
  • the angle of at least one of the first branch channel 120 and the second branch channel 122 may be about 120-160 degrees relative to the mixing member 118, adapter body 101 and/or mixing pin 160.
  • the first branch channel 120 and the second branch channel 122 may form a Y-shape with the mixing member 118.
  • This configuration of the branch channels 120, 122 and the ports 102, 104 may be favorable for manual mixing such that the syringes may be syringes 22, 42 are sufficiently spaced apart to be able to fit on the adapter body 101 while allowing joint actuation of the syringes 22, 42.
  • the ports 102, 104 may be closer together when configured to attach to microtubes of a pump.
  • the first branch channel 120 and the second branch channel 122 may be aligned with a central plane of the adapter body 101, and that the first branch channel 120 and the second branch channel 122 may direct the first and second substances to opposite faces of the mixing pin 160 and/or to create a collusion between the two fluid fluids for initial mixing.
  • the first branch channel 120 and the second branch channel 122 may have the same or substantially the same width or diameter (as illustrated in FIGS. 3 and 8) for applications where the same flow rate is desired for the first substance and the second substance. In some embodiments (as illustrated in FIGS.
  • the first branch channel 120 and the second branch channel 122 may have a different width or diameter for applications where differing flow rates are desired for the first substance and the second substance.
  • the first branch channel 120 may have a larger width or diameter than the second branch channel 122.
  • at least one or both of the first branch channel 120 and the second branch channel 122 may be formed with an open outer end, and the adapter 100 may include a plug 140 inserted into one or both of the branch members 1 14, 1 1 to seal the outer end of the respective branch channel 120, 122.
  • FIG. 2 illustrates illustrated in FIG.
  • the plugs 140 may be removable, replaceable, interchangeable, and/or adjustable.
  • the plugs 140 may facilitate manufacturing of the adapter body 101 by allowing the branch channels 120, 122 to be formed in the adapter body 101 through injection molding by insertion of a straight pin (not shown).
  • the pin may be removed from the injector body 101 after formation through an opening, and the plugs 140 may be inserted to seal the opening in the branch channels 120, 122.
  • the plugs 140 may further extend through the branch channels 120, 122 to reduce the negative space in the branch channels 120, 122. For example, as illustrated in FIGS.
  • the plugs 140 may include a pin 642 that occupies space in the branch channels 120. 122 to reduce the negative space. In this manner, the inventors have found that the volume of the branch channels 120, 122 may be reduced or optimized without creating manufacturing complications in injection molding and/or 3d printing small components in the adapter 101. Furthermore, replacing and/or adjusting the plugs 140 may alter the inlet volume of one or both of the first connector channel 110 and/or the second connector channel 112. For example, the plugs 140 may be replaced with similar plugs 140 having different lengths and/or geometries to at least partially occlude one or both of the first connector channel 110 and/or the second connector channel 112. In some embodiments, the plugs 140 may be adjusted by being pushed or translated into the branch channels 120.
  • the plugs 140 may have an adjustable length such as being telescopic to at least partially occlude the first connector channel 110 and/or the second connector channel 112. Altering the inlet volume with the plugs 140 may adjust the fluid mixing ration and/or reduce dead volume of fluid left inside of the adapter body 101.
  • the mixing member 118 may have a mixing chamber 124 configured to receive the mixing pin 160.
  • the mixing pin 160 may be removably insertable into the mixing chamber 124, for example, to allow interchangeability' of the mixing pins 160, 260, 360, 460, 660, 760 depending on the intended application and/or substance.
  • the geometry of the mixing pins 160, 260, 360, 460, 660, 760 may affect characteristics of the pharmaceutical complex, such that the adapter 100 is configured to produce different ty pes of LNPs based on the intended application.
  • the adapter body 101 may have an opening 126 longitudinally aligned and in communication with the mixing chamber 124.
  • the mixing pin 160 may be inserted through the opening 126 into the mixing chamber 124.
  • the opening 126 may be on an upper portion of the body 7 101, between the first port 102 and the second port 104, and in communication with the upper portion of the mixing chamber 124.
  • the mixing pin 160 may include a flange 162 and the body 101 may include a countersunk recess
  • the opening 126 and/or the recess 128 may have a non-circular and/or axially asymmetric cross-section
  • the flange 162 may have a non-circular and/or axially asymmetric cross-section corresponding to the opening 126 and/or the recess 128, in order to ensure that the mixing pin 160 is inserted into the mixing chamber 124 in a specific orientation.
  • the recess 128 and the flange 162 may each be non-circular, but bilaterally symmetric such as a substantially D-shaped cross-section to ensure that the mixing pin 160 is aligned properly with respect to the branch channels 120, 122.
  • the cross-section of the recess 128 and the flange 162 may similarly be rectangular and/or oval shaped. In some embodiments (as illustrated in FIGS. 2-4). the recess 128 may be in a tubular member
  • the tubular member 129 extending upwardly from the mixing member 118 between the branch members 114, 116.
  • the tubular member 129 may have a width or diameter larger than a width of the mixing member 118 to receive the flange 162.
  • the tubular member 129 may be omitted.
  • the mixing pin 160 may be releasably secured in the mixing chamber 124 through a press-fit of the flange 162 inside of the recess 128.
  • the mixing pin 160 may, additionally or alternatively, be releasably secured in the mixing chamber 124 by a snap-fit, a clip, a threaded connection, and/or a bayonet connection.
  • the mixing chamber 124 may have a substantially uniform crosssection below the branch channels 120, 122 at least partially defining at least one microfluidic flow path and/or microfluidic channel for flow of the first substance and the second substance.
  • FIG. 13 illustrates a fourth embodiment of a mixing pin 460 of the system 10 of Figs. 1-4.
  • the disclosure of the mixing pins 160, 260. and/or 360 is expressly incorporated herein, unless otherwise indicated.
  • the mixing pin 460 may be inserted into the mixing chamber 124 of the adapter 100 with the flange 462 received in the recess 128 and the sealing portion 464 sealing the upper portion of the mixing chamber 124.
  • the first substance may be introduced into the first port 102, and the second substance may be introduced into the second port 104.
  • the first substance may pass through the first connector channel 110 and the first branch channel 120, and into the mixing chamber 124.
  • the second substance may pass through the second connector channel 114 and the second branch channel 122, and into the mixing chamber 124.
  • At least one path may be defined at least partially around the mixing pin 460 for mixing the first flow of the first substance and the second flow of the second substance through turbulent flow.
  • the mixing pin 460 may include side portions facing one of the branch channels 120, 122 configured to divide the flow from at least one of the branch channels 120, 122 into two separate flow streams.
  • the side portion of the mixing pin 460 facing the first branch channel 120 may have first and second surfaces 466 joined at a first edge 468.
  • the side portion of the mixing pin 460 facing the second branch channel 122 may have first and second surfaces 470 joined at a second edge (not shown).
  • the plurality of second protrusions 484 may form impediments and flow constrictions to the fluid path generating turbulence to producing mixing in the second fluid path.
  • the protrusions 482, 484 may divide each of the fluid paths and/or form narrow gaps therebetween to constrict the fluid flow causing local accelerations, intersection points, and/or eddies in the fluid flow.
  • Each of the protrusions 482, 484 may have an angled or V-shaped proximal portion that divides the fluid flow.
  • the first branch member 514 may have a first branch channel 520 configured to receive the fluid flow from the first syringe 20 through the first port 502, and the second branch member 516 may have a second branch channel 522 configured to receive the fluid flow from the second syringe 40 through the second port 504.
  • the first branch channel 520 and the second branch channel 522 may be angled relative to the longitudinal axis of the adapter body 501 and/or mixing pin 160 to converge the fluid flow from the first syringe 20 and the second syringe 40 into the mixing member 518.
  • the angle of at least one of the first branch channel 520 and the second branch channel 522 may be greater than 90 degrees relative to the mixing chamber 524, adapter body 501 and/or mixing pin 160.
  • FIGS. 15-24 illustrates a third embodiment of an adapter 600 of the system 10 of FIGS. 1-4.
  • the adapter 600 may include a body 601 having a first port or connector member 602 configured to attach to the syringe connector 26 of the first container 20 and a second port or connector member 604 configured to attach to the syringe connector 46 of the second container 40.
  • the adapter 600 may include a mixing member 618 that receives a mixing pin 660.
  • the disclosure of the adapter 100, 500 and/or the mixing pin 160, 260, 360. 460 is expressly incorporated herein its entirety, unless otherwise indicated.
  • the first port 602 may be configured to be received by the first syringe connector 26 and have an external thread 606 configured to threadably engage the internal threads of the first syringe connector 26.
  • the second connector 604 may be configured to be received by the second connector 46 and have an external thread 608 around the second tubular member 608 configured to threadably engage the internal threads of the second syringe connector 46.
  • the first port 602 may be a female Luer connector
  • the connector 26 of the first syringe 20 may be a male Luer connector.
  • the ports 602, 604 may, additionally or alternatively, connect to the containers 20, 40 with other ty pes of connections such as a snap-fit, friction-fit and/or a press-fit.
  • the first connector channel 610 may be configured to receive the tip of the first syringe 20 to place the chamber of the first syringe body 22 in fluid communication with the first connector channel 610
  • the second connector channel 612 may be configured to receive the tip of the second syringe 40 to place the chamber of the second syringe body 42 in fluid communication with the second connector channel 612.
  • the first port 602 and the second port 604 may extend substantially parallel to each other to facilitate joint actuation of the syringes 20, 40. In some embodiments, as illustrated in FIG. 15, the first port 602 and the second port 604 may extend substantially parallel to a longitudinal axis of the adapter body 601.
  • the adapter body 601 may further include a first branch member 614 and a second branch member 616.
  • the first port 602 may extend from the first branch member 614, and the first branch member 614 may connect the first port 602 to the mixing member 618.
  • the second port 604 may extend from the second branch member 616, and the second branch member 616 may connect the second port 604 to the mixing member 618.
  • the first branch member 614 may have a first branch channel 620 configured to receive the fluid flow from the first syringe 20 through the first connector channel 610
  • the second branch member 616 may have a second branch channel 622 configured to receive the fluid flow from the second syringe 40 through the second connector channel 612.
  • the first second branch channel 620 and the second branch channel 622 may be in communication with the upper portion of the mixing member 618.
  • the first branch channel 620 and the second branch channel 622 may be angled relative to the longitudinal axis of the adapter body 601 and/or mixing pin 660 to converge the fluid flow from the first syringe 20 and the second syringe 40 into the mixing member 618.
  • the angle of at least one of the first branch channel 620 and the second branch channel 622 may be greater than 90 degrees relative to the mixing member 618, adapter body 601 and/or mixing pin 160.
  • the angle of at least one of the first branch channel 620 and the second branch channel 622 may be about 120-160 degrees relative to the mixing member 618, adapter body 601 and/or mixing pin 160.
  • the first branch channel 620 and the second branch channel 622 may be oriented offset of or not aligned with a central plane of the adapter body 601 (as indicated by central axis A as illustrated in FIG. 16).
  • the first branch channel 620 and the second branch channel 622 may have the same or substantially the same width or diameter (as illustrated in FIG. 15) for applications where the same flow rate is desired for the first substance and the second substance.
  • the first branch channel 620 and the second branch channel 622 may have a different width or diameter for applications where the differing flow rates are desired for the first substance and the second substance.
  • the plugs 640a,b may be removable, replaceable, interchangeable, and/or adjustable.
  • the plugs 640a, b may facilitate manufacturing of the adapter body 601 by allowing the branch channels 620, 622 to be formed in the adapter body 601 through injection molding by insertion of a straight pin (not shown).
  • the pin may be removed from the injector body 601 after formation through an opening, and the plugs 640 may be inserted to seal the opening in the branch channels 620, 622, as discussed above with reference to plug 140 as expressly incorporated herein.
  • Replacing and/or adjusting plugs 640a may alter the inlet volume of one or both of the first connector channel 610 and/or the second connector channel 612.
  • the plugs 640a.b may be replaced with similar plugs 640a, b having different lengths and/or geometries to at least partially occlude one or both of the first connector channel 610 and/or the second connector channel 612.
  • the plugs 640 may be adjusted by being pushed or translated into the branch channels 620, 622 to at least partially occlude the first connector channel 610 and/or the second connector channel 612.
  • the plugs 640 may have an adjustable length such as being telescopic to at least partially occlude the first connector channel 610 and/or the second connector channel 612.
  • the plugs 640a, b may adjust the fluid mixing ration and/or reduce dead volume of fluid left inside of the adapter body 601.
  • the plugs 640a, b may include an end cap 641 and a pin 642.
  • the end cap 641 may be configured to attach to the branch channels 620. 622 to secure the plug 640a.b.
  • the pin 642 may be configured to extend into at least one of the branch channels 620, 622.
  • the pin 642 may be configured to occupy space in the branch channels 620, 622 to reduce the negative space.
  • the plugs 640a.b may further include a groove 643 configured to receive a sealing member (not shown).
  • the plugs 640a, b may be the same for each branch channels 620, 622 or different.
  • the plug 640a, b for one of the branch channels 620, 622 may include the pin 642
  • the plug 640a,b for another of the branch channels 620, 622 may not include the pin 642.
  • the mixing member 618 may have a mixing chamber 624 configured to receive the mixing pin 660.
  • the mixing pin 660 may be removably inserted into the mixing chamber 624, for example, to allow interchangeability of the mixing pins depending on the intended application and/or substance.
  • the body 601 may have an opening 626 longitudinally aligned and in communication with the mixing chamber 624.
  • the mixing pin 660 may be inserted through the opening 626 into the mixing chamber 624.
  • the opening 626 may be on an upper portion of the body 601, between the first port 602 and the second port 604, and in communication with the upper portion of the mixing chamber 624.
  • the sleeve portion 663 may include one or more flexible protrusions 665 configured to flex radially outwardly when receiving the rim 628 in the sleeve portion 663 and releasably engage the rim 628 to secure the mixing pin 660 in the mixing chamber 624 in a press-fit and/or snap-fit.
  • the one or more flexible protrusions 665 may be cantilevered to the upper portion of the end cap 662.
  • the mixing pin 660 may. additionally or alternatively, be releasably secured in the mixing chamber 624 by other types of snap-fit, press-fit, a threaded connection, and/or a bayonet connection.
  • the mixing pin 660 may have a relatively large diameter, such as greater than 8 mm.
  • the diameter of the mixing pin 660 may provide design flexibility on the configuration of the first branch channel 620 and/or the second branch channel 620.
  • the first branch channel 620 and/or the second branch channel 622 may be positioned or oriented offset of or not aligned with the lateral axis A (representing the central plane) of the adapter body 601 and/or the mixing pin 660 when inserted into the mixing chamber 624.
  • the offset nature of the first branch channel 620 and/or the second branch channel 622 may generate angular momentum of the fluid flow around the mixing pin 660 and potential vortexes. In some embodiments (as illustrated in FIGS.
  • the pitch of the at least one helical channel 676 may be chosen to provide a desired degree of mixing, while avoiding impractically high resistance for use with a manually driven syringe.
  • the at least one helical channel 676 may include a double helix, as discussed and illustrated with regard to the embodiment of FIGS. 5-7 as expressly- incorporated herein by reference.
  • the at least one helical channel 676 have a width of about 200 pm to about 1000 pm. In a preferred embodiment, the at least one helical channel 676 may have a width of about 400 pm to about 600 pm to facilitate manufacturing and optimize mixing and hydraulic pressure.
  • the bottom of the at least one helical channel 676 may be spaced apart from the inner surface of the adapter body 601 by of about 200 pm to about 1000 pm. In a preferred embodiment, the bottom of the at least one helical channel 676 may be spaced apart from the inner surface of the adapter body 601 by about 400 pm to about 600 pm.
  • the body 601 may have a third port or connector member 630 at a bottom portion of the mixing member 618.
  • the third port 630 may be a male Luer connector including a tip 632 and a sleeve 634 configured to attach to the recipient container 60 via the vial adapter 70.
  • the tip 632 may have the tip channel 625 in communication with a second or bottom portion of the mixing chamber 624.
  • the tip 632 may be received in the connector 74 of the vial adapter 70 and the sleeve 634 may be threadedly connected to an outer surface of the connector 74 in a Luer connection.
  • the third port 630 may be a male Luer connector configured to connect to a female Luer connector of the vial adapter 70.
  • FIGS. 25-28 illustrate a fourth embodiment of an adapter 700 of the system 10 of FIGS. 1-4.
  • the adapter 700 may include a body 701 having a first port or connector member 702 configured to attach to the syringe connector 26 of the first container 20 and a second port or connector member 704 configured to attach to the syringe connector 46 of the second container 40.
  • the disclosure of the adapter 100, 500, 600 and/or the mixing pin 160, 260, 360, 460, 660 is expressly incorporated herein its entirety, unless otherw ise indicated.
  • the adapter body 701 may further include a first branch member 714, a second branch member 716, and a mixing member 718.
  • the first port 702 may extend from the first branch member 714, and the first branch member 714 may connect the first port 702 to the mixing member 718.
  • the second port 704 may extend from the second branch member 716, and the second branch member 716 may connect the second port 704 to the mixing member 718.
  • the first branch member 714 may have a first branch channel 720 configured to receive the fluid flow from the first syringe 20 through the first connector channel 710
  • the second branch member 716 may have a second branch channel 722 configured to receive the fluid flow from the second syringe 40 through the second connector channel 712.
  • the first second branch channel 720 and the second branch channel 722 may be in communication with the upper portion of the mixing member 718.
  • the first branch channel 720 and the second branch channel 722 may be angled relative to the longitudinal axis of the adapter body 701 and/or mixing pin 760 to converge the fluid flow from the first syringe 20 and the second syringe 40 into the mixing member 718.
  • the first branch channel 720 and the second branch channel 722 may be oriented offset of or not aligned with a central plane of the adapter body 701 (as indicated by axis A in FIG. 26).
  • At least one or both of the first branch channel 720 and the second branch channel 722 may be formed with an open outer end, and the adapter 700 may include a plug 740 inserted into one or both of the branch members 714, 716 to seal the outer end of the respective branch channel 720, 722.
  • at least one or both of the first branch channel 720 and the second branch channel 722 may have a closed outer end formed by the adapter body 601.
  • this disclosure also includes a method 1000 of mixing at least two substances to generate a pharmaceutical complex via any one of the adapters 100, 500, 600, 700 and/or mixing pins 160, 260, 360, 460, 660, 760, as disclosed herein.
  • the method may include transferring the first substance from the first storage container 80 to the first container 20 and transferring a second substance from the second storage container 82 to the second container 40.
  • the first container 20 and/or the second container 40 may be packaged as prefilled containers, such as prefilled syringes, omitting the storage containers 80, 82 from the system or kit.
  • the method may include attaching the first container 20 to the first port 102, 502, 602, 702 of the adapter 100, 500, 600, 700 and attaching the second container 40 to the second port 104, 504, 604, 704 of the adapter 100, 500, 600, 700.
  • the method may further include introducing the first substance and the second substance into the adapter 100, 500. 600, 700 by depressing the plunger rod 24, 44 of each of the first container 20 and the second container 40.
  • the first substance may pass through the first branch channel 120, 520, 620, 720 into the mixing chamber 124, 524, 624
  • the second substance may pass through the second branch chamber 122, 522, 622, 722 into the mixing chamber 124, 524, 624.
  • the first branch channel 120, 520, 620, 720 and/or the second branch channel 122, 522, 622, 722 may be aligned with a lateral axis of the adapter body 101, 501, 601, 701.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Fluid Mechanics (AREA)
  • Physics & Mathematics (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Mixers With Rotating Receptacles And Mixers With Vibration Mechanisms (AREA)
  • Accessories For Mixers (AREA)

Abstract

Des modes de réalisation d'un adaptateur, un système comprenant l'adaptateur et des procédés d'utilisation de l'adaptateur peuvent être destinés à mélanger une première substance et une seconde substance. L'adaptateur peut comprendre un corps comprenant un premier orifice configuré pour être relié à un premier contenant pour recevoir une première substance, un deuxième orifice configuré pour être relié à un second contenant pour recevoir une seconde substance, un troisième orifice configuré pour être relié à un contenant receveur pour fournir un mélange de la première substance et de la seconde substance, et une chambre de mélange comprenant une première partie en communication avec le premier orifice et le deuxième orifice et une seconde partie en communication avec le troisième orifice. L'adaptateur peut en outre comprendre une broche de mélange insérée dans la chambre de mélange. Dans certains modes de réalisation, la broche de mélange définit au moins partiellement au moins un trajet microfluidique pour mélanger la première substance et la seconde substance. Dans certains modes de réalisation, le premier canal et/ou le second canal sont orientés de manière décalée par rapport à un plan central du corps.
EP23800637.3A 2022-10-03 2023-10-03 Procédés et adaptateurs pour mélanger des complexes pharmaceutiques Pending EP4598665A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263378230P 2022-10-03 2022-10-03
PCT/US2023/034399 WO2024076590A2 (fr) 2022-10-03 2023-10-03 Procédés et adaptateurs pour mélanger des complexes pharmaceutiques

Publications (1)

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EP4598665A2 true EP4598665A2 (fr) 2025-08-13

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EP (1) EP4598665A2 (fr)
JP (1) JP2025532319A (fr)
KR (1) KR20250097839A (fr)
CN (1) CN120322290A (fr)
WO (1) WO2024076590A2 (fr)

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2301281A1 (fr) * 1975-02-18 1976-09-17 Exxon France Dispositif statique pour mettre des fluides en contact ou pour pulveriser un liquide
US5104375A (en) 1989-10-16 1992-04-14 Johnson & Johnson Medical, Inc. Locking holder for a pair of syringes and method of use
JPH10216491A (ja) * 1997-02-12 1998-08-18 Daiwa Kasei Kogyo Kk 液体混合装置
GB2339545B (en) * 1998-07-15 2002-12-11 Johnson & Johnson Medical Ltd Mixing device
US6840921B1 (en) 2002-01-11 2005-01-11 Timothy D. Haider Apparatus and methods for simultaneously administering two or more medications to a patient
CH699191A1 (de) 2008-07-21 2010-01-29 Medmix Systems Ag Austraganordnung mit Einzelspritzen und Spritzenhalter.
US8753325B2 (en) 2010-02-24 2014-06-17 Medimop Medical Projects, Ltd. Liquid drug transfer device with vented vial adapter
WO2014029035A1 (fr) * 2012-08-21 2014-02-27 Medmix Systems Ag Dispositif de mélange pour une unité de distribution
EP2983745B1 (fr) 2013-05-10 2018-07-11 Medimop Medical Projects Ltd Dispositifs medicaux avec adaptateur pour flacon avec inline sec module de drogue
EP2915581B1 (fr) * 2014-03-06 2017-07-12 Fluitec Invest AG Mélangeur statique
JP7223496B2 (ja) * 2017-12-14 2023-02-16 株式会社堀場エステック 混合器及び気化装置
CA3233847A1 (fr) 2021-10-04 2023-04-13 Claudia LEE Adaptateur et procede de melange de constituants d'un complexe pharmaceutique par l'intermediaire d'un adaptateur

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JP2025532319A (ja) 2025-09-29
KR20250097839A (ko) 2025-06-30
CN120322290A (zh) 2025-07-15
WO2024076590A3 (fr) 2024-05-16
WO2024076590A2 (fr) 2024-04-11

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