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WO2018150375A1 - Dispositifs et procédés de formation et d'administration d'un agent de scellement tissulaire - Google Patents

Dispositifs et procédés de formation et d'administration d'un agent de scellement tissulaire Download PDF

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Publication number
WO2018150375A1
WO2018150375A1 PCT/IB2018/050975 IB2018050975W WO2018150375A1 WO 2018150375 A1 WO2018150375 A1 WO 2018150375A1 IB 2018050975 W IB2018050975 W IB 2018050975W WO 2018150375 A1 WO2018150375 A1 WO 2018150375A1
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WO
WIPO (PCT)
Prior art keywords
syringe
dual
solid
chamber
diluent
Prior art date
Application number
PCT/IB2018/050975
Other languages
English (en)
Inventor
Paul Jefferey Sanders
John Joseph Anthony Barry
Original Assignee
Baxter International Inc.
Baxter Healthcare Sa
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 Baxter International Inc., Baxter Healthcare Sa filed Critical Baxter International Inc.
Publication of WO2018150375A1 publication Critical patent/WO2018150375A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/1782—Devices aiding filling of syringes in situ
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/19—Syringes having more than one chamber, e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/00491—Surgical glue applicators
    • A61B2017/00495—Surgical glue applicators for two-component glue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3114—Filling or refilling

Definitions

  • the present disclosure is generally directed to tissue sealants and, more particularly, to devices and methods for quickly and easily forming and delivering a tissue sealant to a wound site.
  • Tissue sealants are often applied to wounds (e.g., open wounds of a human) to close the wound, stop bleeding, and/or prevent infectious agents and other substances from entering the wound.
  • wounds e.g., open wounds of a human
  • a number of biocompatible and biodegradable tissue sealants capable of forming closures in soft tissues are known.
  • Synthetic biocompatible and biodegradable tissue sealants are typically based on polyurethane, polyethylene glycol, and/or polyester. See Annabi et. al., Eur. J. Pharm. Biopharm, vol. 97, pp. 25-39 (2015).
  • Naturally occurring biocompatible and biodegradable tissue sealants are typically based on proteins or polysaccharides. Id.
  • Tissue sealants can be formed, for example, by mixing sealer protein and thrombin solutions.
  • TISSEEL® fibrin sealant (Baxter International Inc.) is formed by mixing sealer protein and thrombin solutions.
  • TISSEEL® fibrin sealant is currently available in "ready to use” and “kit” configurations.
  • the ready to use configuration is provided as a dual syringe device having first and second syringes incorporated therein, the first syringe containing a frozen thrombin solution and the second syringe containing a frozen sealer protein solution.
  • Care must be taken when warming the ready to use configuration to thaw the frozen thrombin and sealer protein solutions because (i) the activities of the proteins can be significantly diminished by heating the dual syringe above 37°C as this can cause the proteins to denature and (ii) contaminants can easily be introduced during the warming process.
  • the thawing temperature As a result of having to closely control the thawing temperature to preserve protein activity, it takes at least 5 minutes (with the pouch packaging removed in a sterile 33-37°C water bath) and up to 105 minutes (in a pouch packaging in an incubator held at 33-37°C) to thaw the thrombin and sealer protein solutions, which can make use in critical care situations cumbersome.
  • the resulting warmed thrombin and sealer protein solutions can be combined to form a tissue sealant via actuation of the dual syringe device at a site where such a sealant is needed (e.g., a wound site to close the wound).
  • the TISSEEL® fibrin sealant package insert teaches that long term storage requires that the dual syringe device be maintained at a temperature less than -20°C.
  • the TISSEEL® fibrin sealant package insert further teaches that the product must be used within four hours after warming to 33-37°C and within 48 hours of removal from the freezer.
  • the kit configuration is provided as a set of four vials: one vial contains lyophilized sealer protein and a magnetic stir bar, one vial contains lyophilized thrombin and a magnetic stir bar, one vial contains fibrinolysis inhibitor-containing diluent, and the last vial contains calcium chloride diluent.
  • the four vials are first pre- warmed by placing them into a heating unit such as a FIBRINOTHERM® heating and stirring device (Baxter International Inc.). After warming, the fibrinolysis inhibitor-containing diluent is transferred from its vial, using a sterile needle, into the vial containing the lyophilized sealer protein.
  • This vial is then further warmed in the heating and stirring device with the stirrer on, until the solid lyophilized sealer protein dissolves.
  • the calcium chloride diluent is transferred from its vial, using a sterile needle, into the vial containing lyophilized thrombin.
  • This vial is then further warmed in the heating and stirring device with the stirrer on, until the solid thrombin dissolves.
  • the sealer protein and the thrombin are fully reconstituted, the sealer protein and the thrombin are transferred from their respective vials to separate, first and second syringes chambers of a dual syringe device.
  • the reconstituted thrombin and sealer protein solutions can then be combined to form a tissue sealant via actuation of the dual syringe at a site where such a sealant is needed (e.g., a wound site to close a wound).
  • a site where such a sealant is needed e.g., a wound site to close a wound.
  • the TISSEEL® fibrin sealant package insert teaches that the product must be used within four hours after reconstitution.
  • a dual syringe device is provided.
  • the dual syringe device is adapted to be connected to another dual syringe device and form a tissue sealant.
  • the dual syringe device includes a first syringe and a second syringe connected to the first syringe.
  • the first syringe includes a first chamber and a first solid protein in the first chamber.
  • the first chamber containing the first solid protein is configured to mix with a first liquid diluent contained in the other dual syringe device.
  • the second syringe includes a second chamber and a solid sealer polymer, typically a second solid protein, in the second chamber.
  • the second chamber containing the solid sealer polymer is configured to mix with a second liquid diluent contained in the other dual syringe device.
  • a syringe assembly for forming a tissue sealant.
  • the syringe assembly includes a first dual syringe device and a second dual syringe device removably connectable to the first dual syringe device.
  • the first dual syringe device includes a first syringe and a second syringe connected to the first syringe, the first syringe including a first chamber and either a first solid protein or a first diluent in the first chamber, and the second syringe including a second chamber and either a solid sealer polymer, typically a second solid protein, or a second diluent in the second chamber.
  • the second dual syringe device includes a third syringe and a fourth syringe connected to the third syringe, the third syringe including a third chamber and the other of the first solid protein and the first diluent in the third chamber, and the fourth syringe including a fourth chamber and the other of the solid sealer polymer and the second diluent in the fourth chamber.
  • the third chamber is in fluid communication with the first chamber, such that the first diluent can mix with the first protein to form a first mixture
  • the fourth chamber is in fluid communication with the second chamber, such that the second diluent can mix with the solid sealer polymer to form a second mixture, the first and second mixtures being combinable to form the tissue sealant.
  • a method of forming a tissue sealant includes providing a first dual syringe device including a first syringe and a second syringe connected to the first syringe, the first syringe including either a first solid protein or a first diluent and the second syringe including either a solid sealer polymer, typically a second solid protein, or a second diluent.
  • the method includes providing a second dual syringe device including a third syringe and a fourth syringe connected to the third syringe, the third syringe including the other of the first solid protein and the first diluent and the fourth syringe including the other of the solid sealer polymer and the second diluent.
  • the method also includes connecting the second dual syringe device to the first dual syringe device such that the third syringe is in fluid communication with the first syringe and the fourth syringe is in fluid communication with the second syringe, thereby forming a syringe assembly.
  • the method includes moving the syringe assembly such that the first solid protein mixes with the first diluent to form a first mixture and the solid sealer polymer mixes with the second diluent to form a second mixture, the first and second mixtures being arranged in one of the first and second dual syringe devices.
  • the method also includes disconnecting the second dual syringe device from the first dual syringe device.
  • the method further includes combining the first mixture and the second mixture to form the tissue sealant.
  • FIG. 1 is a perspective view illustrating representative components for assembling an exemplary syringe assembly in accordance with the principles of the present disclosure
  • FIG. 2 is a perspective view showing an exemplary syringe assembly in which the first and second dual syringe devices of the syringe assembly are connected together to mix the solid components and diluents contained therein;
  • FIG. 3 illustrates one of the first and second dual syringe devices, after the syringe assembly has been moved to mix the solid components (i.e., the solid sealer polymers described herein, which are typically proteins, and the solid proteins, which are typically procoagulants), and diluents and arrange the mixtures in one of the first and second dual syringe devices, and the first and second dual syringe devices have been disconnected from one another, with a mixing and dispensing device connected to the dual syringe device containing the mixed solutions, such that a tissue sealant can be formed and delivered;
  • FIG. 4 is a flowchart of an example method of forming a tissue sealant using a syringe assembly comprising first and second dual syringe devices according to the disclosure;
  • FIG. 5 shows additional exemplary components for assembling a dual syringe device in accordance with the principles of the present disclosure.
  • FIG. 6 shows additional exemplary components for assembling a dual syringe device in accordance with the principles of the present disclosure.
  • the present invention is directed to ready to use devices and methods for quickly and easily forming and delivering a tissue sealant to a wound site (for example, to close a wound).
  • the disclosed devices and methods utilize a dual syringe device that contains a solid protein (typically, a procoagulant such as lyophilized thrombin) in one syringe and a solid sealer polymer, typically another solid protein (for example, a lyophilized sealer protein such as fibrinogen or gelatin) in another syringe.
  • a solid protein typically, a procoagulant such as lyophilized thrombin
  • a solid sealer polymer typically another solid protein (for example, a lyophilized sealer protein such as fibrinogen or gelatin) in another syringe.
  • the dual syringe device When a tissue sealant is needed (e.g., for application to a wound), the dual syringe device can be easily and quickly connected to another dual syringe device that contains respective diluents for the solid components, such that the solid components can be mixed with the respective diluents and thereby hydrated and/or reconstituted.
  • the solutions of hydrated and/or reconstituted components can then be combined to form the tissue sealant, and the tissue sealant can be applied to the wound.
  • the solid components and the diluents can be arranged differently in the dual syringe devices, e.g., the solid components need not initially be contained in the same dual syringe device and, similarly, the diluents need not initially be contained in the same dual syringe device, as long as mixing and reconstitution of the solid components and the respective diluents can be accomplished by moving the contents of the various individual syringes as described herein.
  • the disclosed devices and methods advantageously allow proteins such as thrombin and sealer protein to be shipped and stored at room temperature, such that freezers/refrigerators are not needed to transport and store the proteins.
  • the use of heating devices e.g., an incubator, a water bath, or the like
  • to thaw frozen solutions of the thrombin and sealer protein and thereby facilitate mixing of thrombin and sealer protein solutions to form the tissue sealant can also be advantageously avoided.
  • the disclosed ready to use devices can be stored at room temperature, the use of refrigeration devices for long term storage can be avoided.
  • the disclosed ready to use devices and methods also obviate the need for diluents to be manually withdrawn, e.g., using a needle, from their respective storage vials and transferred to corresponding vials containing solid proteins such as thrombin and sealer protein, as is known in the art, and thereby advantageously eliminate sources of potential contamination and deliberate and time-consuming processing steps that are often required to generate a tissue sealant.
  • the disclosed ready to use devices and methods for preparing a tissue sealant are capable of producing a tissue sealant in significantly less time and require significantly less processing steps (at least relative to the existing ready to use and kit configurations discussed above) and are particularly useful in critical care clinical settings, especially when a tissue sealant is needed unexpectedly.
  • FIG. 1 illustrates representative components for assembling an exemplary syringe assembly 100 in accordance with the teachings of the present disclosure.
  • the syringe assembly 100 generally includes a first dual syringe device 104 and a second dual syringe device 108 removably connectable to the first dual syringe device 104.
  • the first dual syringe device 104 includes a first syringe 112, a second syringe 116, and a housing 120 that at least partially houses, and generally serves to connect and align, the first and second syringes 112, 116.
  • the first and second syringes 112, 116 are, in this example, removably disposed in the housing 120, such that they can be removed and replaced and such that the first syringe 112 is oriented along a first longitudinal axis 122 and the second syringe 116 is oriented along a second longitudinal axis 123 that is parallel to but offset from the first longitudinal axis 122.
  • the first syringe 112 includes a first chamber 124 and a first plunger 128.
  • the first chamber 124 has a first outlet port 132.
  • the first syringe 112 contains a first solid protein A which is a procoagulant, e.g., thrombin.
  • procoagulants include, but are not limited to, clotting factors, such as fibrin, Factor VIII (FVIII), Factor VII (FVII), Factor IX (FIX), von Willebrand Factor (vWF), Factor II (FII), Factor V (FV), Factor X (FX), Factor XI (FXI), Factor XII (FXII), and Factor XIII (FXIII), tissue factor, collagen; styptics including anti-hemorrhagic agents and astringents; and other hemostatic agents.
  • the procoagulant is typically provided in the first chamber 124 as a lyophilized powder, for example, as lyophilized thrombin.
  • the syringe assembly 100 and more specifically the first syringe 112 of the first dual syringe device 104, is configured to mix the first solid protein A with a first diluent C contained in the second dual syringe device 108, as will be described below.
  • the first plunger 128 is movably disposed within the first chamber 124 to facilitate the mixing between the first solid protein A and the first liquid diluent C, via the first outlet port 132, as will also be described in greater detail below.
  • Pre-warming or heating for example to 33-37°C, is not required to mix the first solid protein A in the first dual syringe device 104 and the first liquid diluent C in the second dual syringe device 108, but may optionally be practiced to facilitate faster
  • the second syringe 116 includes a second chamber 136 and a second plunger 140.
  • the second chamber 136 has a second outlet port 144 that, at least in the illustrated example, has a diameter substantially equal to a diameter of the first outlet port 132. Different outlet port 132, 144 diameters are also possible.
  • the second chamber 136 contains a solid sealer polymer, typically a second solid protein B, which is a sealer protein, e.g. fibrinogen.
  • suitable solid sealer polymers include but are not limited to sealer proteins such as albumin, gelatin, collagen (e.g., soluble collagen), hemoglobin, fibrinogen, fibronectin, elastin, keratin, laminin, and derivatives and combinations thereof.
  • the solid sealer polymer may comprise a polysaccharide, such as a glycosaminoglycan, a starch derivative, a cellulose derivative, a hemicellulose derivative, xylan, agarose, alginate, chitosan, a dextrin such as icodextrin or maltodextrin, amylopectin, amylose, modified forms thereof, and combinations thereof.
  • a polysaccharide such as a glycosaminoglycan, a starch derivative, a cellulose derivative, a hemicellulose derivative, xylan, agarose, alginate, chitosan, a dextrin such as icodextrin or maltodextrin, amylopectin, amylose, modified forms thereof, and combinations thereof.
  • the solid sealer polymer may comprise a non-biologic hydrogel- forming polymer, such as polyacrylates, polymethacrylates, polyacrylamides, polyvinyl polymers, polylactide-glycolides, polycaprolactones, polyoxyethylenes, and derivatives and combinations thereof.
  • Suitable solid sealer polymers may comprise solid sealer polymers capable of being hydrated to form a hydrogel. "Derivatives thereof include any chemically modified polymer, such as e.g. a cross-linked polymer, e.g., cross-linked gelatin.
  • the solid sealer protein is typically provided in the second chamber 136 as a lyophilized powder, for example, as lyophilized fibrinogen.
  • the syringe assembly 100 and more specifically the second syringe 116 of the first dual syringe device 104, is configured to mix the second solid protein B with a second diluent D contained in the second dual syringe device 108, as will be described below.
  • the second plunger 140 is movably disposed within the second chamber 136 to facilitate mixing between the second solid protein B and the second liquid diluent D, via the second outlet port 144, as will also be described in greater detail below.
  • the second plunger 140 can be connected to the first plunger 128, e.g., via a yoke, such that the first and second plungers 128, 140 move together when the yoke is depressed, while in other cases, the second plunger 140 may be movable relative to or independently of the first plunger 128 (e.g., when no yoke is present).
  • Pre-warming or heating for example to 33-37°C, is not required to mix the second solid protein B in the first dual syringe device 104 and the second liquid diluent D in the second dual syringe device 108, but may optionally be practiced to facilitate faster dissolution/reconstitution.
  • the second dual syringe device 108 is structurally similar to the first dual syringe device 104, in that the second dual syringe device 108 includes a third syringe 150, a fourth syringe 154, and a housing 158 that at least partially houses, and generally serves to connect and align, the third and fourth syringes 150, 154.
  • the third and fourth syringes 150, 154 are, in this example, removably disposed in the housing 158, such that they can be removed and replaced and such that the third syringe 150 is oriented along a third longitudinal axis 162 and the fourth syringe 154 is oriented along a fourth longitudinal axis 166 that is parallel to but offset from the third longitudinal axis 162. It will be appreciated that the third longitudinal axis 162 is co-axial with the first longitudinal axis 122 and the fourth longitudinal axis 166 is co-axial with the second longitudinal axis 123. Non-coaxial configurations are possible, for example, if a flexible, non-linear adapter 192 is used.
  • the third syringe 150 includes a third chamber 170 and a third plunger 174.
  • the third chamber 170 has a third outlet port 178 that, at least in the illustrated example, has a diameter equal to the diameter of the first and second outlet ports 132, 144 (though in other examples, the diameter of the third outlet port 178 can be greater or less than the first and second outlet ports 132, 144).
  • the third chamber 170 contains the first diluent C, which may, for example, be a liquid diluent.
  • the first diluent may comprise an aqueous solution for reconstituting the first solid protein A contained in the first chamber 124, the first diluent optionally further comprising a salt.
  • exemplary salts include but are not limited to calcium chloride, sodium chloride, potassium chloride, magnesium chloride, and combinations of the foregoing.
  • the syringe assembly 100 and more specifically the third syringe 150 of the second dual syringe device 108, is configured to mix the first diluent C with the first solid protein A when the first and second syringe devices 104, 108 are connected to one another, as will be described below.
  • the third plunger 174 is movably disposed within the third chamber 170 to facilitate this mixing, via the third outlet port 178, when desired.
  • the fourth syringe 154 includes a fourth chamber 182 and a fourth plunger 186.
  • the fourth chamber 182 has a fourth outlet port 190 that, at least in the illustrated example, has a diameter substantially equal to the diameter of each of the first, second, and third outlet ports 132, 144, 178 (though in other examples, the diameter of the fourth outlet port 190 can vary).
  • the fourth chamber 182 contains the second diluent D, which may, for example, be a liquid diluent.
  • the second diluent may comprise an aqueous solution for reconstituting the second solid protein B contained in the second chamber 136, the second diluent optionally further comprising components selected from a buffering agent, a fibrinolysis inhibitor, a surfactant, and combinations of the foregoing.
  • a buffering agent is tri-sodium citrate.
  • a representative, exemplary fibrinolysis inhibitor is aprotinin.
  • a representative, exemplary surfactant is polysorbate 80.
  • the syringe assembly 100 and more specifically the fourth syringe 154 of the second dual syringe device 108, is configured to mix the second diluent D with the second solid protein B when the first and second syringe devices 104, 108 are connected to one another.
  • the fourth plunger 186 is movably disposed within the fourth chamber 182 to facilitate this mixing, via the fourth outlet port 190, when desired.
  • the fourth plunger 186 can be connected to the third plunger 174, e.g., via a yoke, such that the third and fourth plungers 174, 186 move together when the yoke is depressed, while in other cases, the fourth plunger 186 may be movable relative to or independently of the third plunger 174 (e.g., when no yoke is present).
  • the syringe assembly 100 can, in some cases, further include one or more adapters configured to facilitate the removable connection between the first and second dual syringe devices 104, 108, particularly when, as is the case here, the outlet ports 132, 144, 178, and 190 have identical diameters.
  • the syringe assembly 100 includes two adapters 192 to facilitate this removable connection.
  • the illustrated adapters 192 have a substantially cylindrical shape that defines an opening having a diameter that is larger than a diameter of the diameter of each of the outlet ports 132, 144, 178, and 190.
  • the first adapter 192 can be coupled to one of the first and third outlet ports 132, 178
  • the second adapter 192 can be coupled to one of the second and fourth outlet ports 144, 190.
  • the first adapter 192 can be coupled to the other of the first and third outlet ports 132, 178, and the second adapter 192 can be coupled to the other of the second and fourth outlet ports 144, 190, thereby removably securing the first and second dual syringe devices 104, 108 together such that the third syringe 150 is in fluid communication with the first syringe 112 and the fourth syringe 154 is in fluid communication with the second syringe 116, as illustrated in FIG. 2.
  • the outlet ports 132, 144, 178, 190 can be configured such that there is no need for one or both adapters 192, e.g., when the outlet ports 132, 144, 178, and 190 have external diameters that facilitate direct coupling therebetween.
  • an integral component configured to facilitate the removable connection between the first and second dual syringe devices 104, 108 can be provided.
  • the syringe assembly 100 can be moved such that the first solid protein A mixes with the first diluent C to form a first mixture Mi and the second solid protein B mixes with the second diluent D to form a second mixture M 2 .
  • Such manipulation may, for example, include rotating the syringe assembly 100 (e.g., in a back and forth direction) and/or moving one or more of the first, second, third, and fourth plungers 128, 140, 174, and 186 relative to the chambers 124, 136, 170, and 182, respectively.
  • the solutions may be left in the first dual syringe device 104 (particularly the syringes 112, 116) or the second dual syringe device 108 (particularly the syringes 150, 154), at which time the first and second dual syringe devices 104, 108 can be disconnected from one another by pulling the first and second dual syringe devices 104, 108 apart from one another.
  • the syringe assembly 100 is not shown in a "state-of-use" in FIGS. 1 and 2, i.e., the syringe assembly is not shown in a state in which a tissue sealant can be immediately generated.
  • two of plungers 128, 140, 174, and 186 are generally disposed in a forwardly advanced position within corresponding chambers 124, 136, 170, and 182 proximal to corresponding outlet ports 132, 144, 178, and 190, while the remaining two plungers of 128, 140, 174, and 186 are generally disposed in a rearwardly retracted position within corresponding chambers 124, 136, 170, and 182 distal to corresponding outlet ports 132, 144, 178, and 190.
  • the syringe assembly 100 further includes a mixing and dispensing device 196 that, when the diluents and solid proteins are mixed such that the proteins are reconstituted, the first mixture Mi and the second mixture M 2 are left in the first dual syringe device 104 or the second dual syringe device 108, and the first and second dual syringe devices 104, 108 are disconnected from one another, can be coupled to one of the first and second dual syringe devices 104, 108 (depending upon which device includes the mixed solutions) to form and dispense the tissue sealant.
  • a mixing and dispensing device 196 that, when the diluents and solid proteins are mixed such that the proteins are reconstituted, the first mixture Mi and the second mixture M 2 are left in the first dual syringe device 104 or the second dual syringe device 108, and the first and second dual syringe devices 104, 108 are disconnected from one another, can be coupled to one of the first and second
  • the mixing and dispensing device 196 in this example takes the form of an applicator tip having a Y- connector 200 and a dispensing needle 204 that is coupled to and projects outward from the Y-connector 200.
  • the Y-connector 200 is adapted to be coupled to the outlet ports 132 and 144, 178 and 190 of the dual syringe device 104, 108 containing the mixed solutions, such that the Y-connector 200 is fluidly coupled to the chambers of the respective dual syringe device 104, 108.
  • the Y-connector 200 can thus transfer the mixtures Mi and M 2 from the chambers of the respective dual syringe device to a common chamber (not shown) within the mixing and dispensing device 196, to combine the mixtures Mi and M 2 and thereby cause formation of the tissue sealant.
  • the tissue sealant can in turn be dispensed to a wound of a person, via the dispensing needle 204, so as to close the wound, to stop the wound from bleeding, and/or to prevent infectious agents and other substances from entering the wound.
  • the mixing and dispensing device 196 can take the form of a different type of in-line mixing device and/or can include a cannula, catheter, spray head, or some other means of dispensing device instead of the needle 204.
  • Other suitable mixing devices are illustrated and described in combination with a dual syringe device in U.S. Patent No. 8,753,670, which is hereby incorporated herein by reference.
  • FIG. 4 is a flow chart that depicts a method 400 of forming a tissue sealant using the syringe assembly 100, though it will be appreciated that the tissue sealant can be formed using a different syringe assembly (e.g., using differently configured dual syringe devices).
  • the method 400 includes six acts - 404, 408, 412, 416, 420, and 424, but in other examples, the method 400 can include more, less, or different acts.
  • the first dual syringe device 104 is provided.
  • the first dual syringe device 104 includes the first syringe 112, which includes the first solid protein A, and the second syringe 116, which includes the second solid protein B.
  • act 408 which can be performed before, after, or at the same time as act 404, the second dual syringe device 108 is provided.
  • the second dual syringe device 108 includes the third syringe 150, which includes the first diluent C, and the fourth syringe 154, which includes the second diluent D.
  • the solid proteins A, B and the diluents C, D can be arranged differently in the dual syringe devices 104, 108, i.e., the solid proteins A, B need not initially be contained in the dual syringe device 104 and, similarly, the diluents C, D need not initially be contained in the dual syringe device 108, because mixing and reconstitution of the solid proteins and the respective diluents can be accomplished by moving the contents of the various individual syringes as described herein as long as the solid protein A and the diluent C and the solid protein B and diluent D are contained in opposing syringes when the dual syringe devices 104, 108 are connected to one another.
  • the first and second dual syringe devices 104, 108 are removably connected to one another such that the third syringe 150 is in fluid communication with the first syringe 112 and the fourth syringe 154 is in fluid communication with the second syringe 116 (and thereby forming the syringe assembly 100), as illustrated in FIG. 2.
  • the removable connection is facilitated by the adapters 192.
  • this removable connection may be accomplished in some other way.
  • this removable connection may be accomplished by arranging the ports of one of the dual syringe devices 104, 108 inside the ports of the other dual syringe device 104, 108.
  • the syringe assembly 100 is moved such that the first protein A (contained in the first syringe 112) mixes with the first diluent C (contained in the third syringe 150) to form the first mixture Mi and the second protein B (contained in the second syringe 116) mixes with the second diluent D (contained in the fourth syringe 154) to form the second mixture M 2 .
  • Forming the first and second mixtures Mi and M 2 generally involves manipulating combinations of the first, second, third, and fourth syringes 112, 116, 150, 154 such that (i) the first solid protein A and the first diluent C are mixed and moved, or "swooshed”, back and forth to reconstitute the first solid protein A, and (ii) the second solid protein B and the second diluent D are mixed and moved, or "swooshed”, back and forth to reconstitute the second solid protein B.
  • Such manipulation may, for example, include rotating the syringe assembly 100 (e.g., in a back and forth direction) and/or moving one or more of the first, second, third, and fourth plungers 128, 140, 174, and 186 relative to the chambers 124, 136, 170, and 182, respectively. In some cases, this movement may further include quickly rotating the syringe assembly 100 (e.g., in a back and forth direction).
  • the first and second mixtures Mi , M 2 may be left in either the first syringe device 104 (with the first mixture Mi in the first syringe 112 and the second mixture M 2 in the second syringe 116) or the second syringe device 108 (with the first mixture Mi in the third syringe 150 and the second mixture M 2 in the fourth syringe 154).
  • the second dual syringe device 108 is disconnected from the first dual syringe device 104 (or vice-versa) by, for example, pulling the first and second dual syringe devices 104, 108 apart from one another.
  • the first and second mixtures Mi and M 2 can be combined to form the tissue sealant.
  • the first and second mixtures Mi and M2 can, in some cases, be combined using an applicator tip or other mixing and dispensing device coupled to the dual syringe device containing the first and second mixtures.
  • the tissue sealant once formed, can be quickly and easily delivered to a wound via the applicator tip or other mixing and dispensing device (or another similar device).
  • a first outlet port 208 may be provided on the first syringe 112.
  • An annular wall 212 terminating in a rim 216 partially surrounds the outlet port 208.
  • the annular wall 212 can include threads 220 on its interior surface.
  • the housing 120 can include an inlet 224 capable of fluid communication with the outlet port 132.
  • the inlet 224 can include a neck with a collar (or ring) outwardly protruding therefrom (not shown) capable of being received by the threads 220 on the interior surface of the annular wall 212.
  • the collar and threads 220 allow secure and releasable coupling of the first syringe 112 to the housing 120 and thereby facilitate mixing of the contents in the first syringe 112 with the third syringe 150 and ultimate delivery using a mixing and dispensing device 196 as described above.
  • the second, third, and fourth syringes 116, 150, 154 can include similar outlet ports 208, annular walls 212, rims 216, and threads 220 as described with respect to the first syringe 112, and the housing can include similar inlets 224 for coupling the syringes 116, 150, 154 to the housing 120.
  • the syringes 112, 116, 150, 154 may be snap fit into the housing 120, so as to releasably couple the syringes 112, 116, 150, 154 to the housing 120 and thereby facilitate mixing of the contents thereof and ultimate delivery using a mixing and dispensing device 196 as described above.
  • the dual syringe devices may comprise a unitary housing 320, the unitary housing 320 itself comprising (and providing) first and second chambers 324, 336 for receiving first and second plungers 328, 340, respectively.
  • the first and second syringes of the unitary housing 320 are formed by inserting the first and second plungers 328, 340 into the first and second chambers 324, 336.
  • the first and second plungers 328, 340 may be provided as separate plungers or may be coupled together via an integral yoke 360 to provide an integral, unitary structure to facilitate simultaneous movement and thereby facilitate mixing of the contents thereof and ultimate delivery using a mixing and dispensing device 196 as described above.

Landscapes

  • Health & Medical Sciences (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

L'invention concerne des dispositifs et des procédés permettant de former et d'administrer rapidement et facilement un agent de scellement tissulaire. Les dispositifs et les procédés de l'invention utilisent un dispositif à double seringue qui contient une première protéine solide (telle qu'un pro-coagulant lyophilisé) dans une seringue et un polymère de scellement (tel qu'une protéine de scellement lyophilisée) dans une autre seringue. Lorsqu'un agent de scellement tissulaire est nécessaire, par exemple, en vue d'une application sur une plaie, le dispositif à double seringue peut être relié facilement et rapidement à un autre dispositif à double seringue qui contient des diluants respectifs pour les constituants solides, de sorte que les constituants solides peuvent être mélangés et reconstitués et/ou hydratés avec les diluants respectifs. À l'aide d'un dispositif de mélange et d'administration, les mélanges peuvent être combinés pour former l'agent de scellement tissulaire, et l'agent de scellement tissulaire peut être appliqué à la plaie.
PCT/IB2018/050975 2017-02-17 2018-02-16 Dispositifs et procédés de formation et d'administration d'un agent de scellement tissulaire WO2018150375A1 (fr)

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US201762460702P 2017-02-17 2017-02-17
US62/460,702 2017-02-17

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WO2020197969A1 (fr) * 2019-03-22 2020-10-01 C. R. Bard, Inc. Appareil de distribution de produit d'étanchéité, et système et procédé de préparation de celui-ci, destinés à être utilisés dans une procédure pulmonaire
CN113181499A (zh) * 2021-06-02 2021-07-30 中国人民解放军联勤保障部队第九〇〇医院 一种枪伤辅助镇痛装置
US12114843B2 (en) 2022-03-31 2024-10-15 Ethicon, Inc. Sealant applicators having mixing and spraying assemblies with malleable sections and spray tips having reduced dimensions
US12220118B2 (en) 2022-03-31 2025-02-11 Ethicon, Inc. Systems, devices and methods for reconstituting therapeutic powders, mixing precursor solutions, and expressing sealants for controlling bleeding and sealing fluid and air leaks

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020197969A1 (fr) * 2019-03-22 2020-10-01 C. R. Bard, Inc. Appareil de distribution de produit d'étanchéité, et système et procédé de préparation de celui-ci, destinés à être utilisés dans une procédure pulmonaire
CN113181499A (zh) * 2021-06-02 2021-07-30 中国人民解放军联勤保障部队第九〇〇医院 一种枪伤辅助镇痛装置
US12114843B2 (en) 2022-03-31 2024-10-15 Ethicon, Inc. Sealant applicators having mixing and spraying assemblies with malleable sections and spray tips having reduced dimensions
US12220118B2 (en) 2022-03-31 2025-02-11 Ethicon, Inc. Systems, devices and methods for reconstituting therapeutic powders, mixing precursor solutions, and expressing sealants for controlling bleeding and sealing fluid and air leaks

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