JP5969497B2 - Aseptic cartridge and dispenser device - Google Patents

Description

  The present disclosure relates to, but is not limited to, a disposable cartridge, preferably for use with a drug delivery device, and more particularly to a sterile mixing cartridge for a drug delivery device.

  Drugs, particularly injectable drugs, need to be stored in a sterile condition until use in a commercially available sterile package. Some medications are stored in pre-filled single dose administration devices such as pre-filled syringes, for example pre-filled syringes from Vetter (Ravensburg, Germany). However, much of the injectable drug is stored in a sterile package and transferred to the administration device (ie, drug delivery device) just prior to use. The term administration device includes, but is not limited to, a hypodermic syringe, a microneedle syringe, a micropump, an automatic injector, a jet syringe, a topical dispenser, an intradermal delivery device, a patch pump, an ear dispenser, an oral dispenser, an eye drop Device, auto-injector, infuser, or other type of drug delivery device.

  Several sterile packages are commercially available for storing injectable drugs. Perhaps the most common sterile package for injectable products is a glass vial. Some drugs are stored as separate components that are mixed just prior to use. In most cases, such storage is done to improve the stability of the drug or to extend the shelf life of the drug. In one example, the drug is a vaccine that is kept dry in one vial to increase the thermal stability of the vaccine, and the attached vial is diluted into a vaccine vial with a syringe and needle prior to injection. Store the agent. In another example, the drug is a vaccine where one vial stores the prepared antigen and the second vial stores the adjuvant.

  However, this prior art has several drawbacks. (A) These packages are many times more expensive than many injectable drugs such as vaccines and are not economically practical. (B) When mixing of drug components is required, the series of operations is complicated and errors are likely to occur. And (c) The transfer of the drug or its components from one container to another container or administration device is performed in a non-sterile area, and there is a risk of contamination.

  US Pat. No. 7,879,018 discloses one of several commercially available patented kits for mixing injectable doses. Again, the limitations of this disclosure are the reliance on vials and the cost and complexity associated with this type of glass primary container.

  Several commercial products and patents disclose flexible packages made from films or foils that allow products to be stored aseptically until use. Some of these products and patents further disclose a discharge port in communication with the product in the dosing package. In some instances, a breakable barrier is present between the port and the product until use to increase package integrity. In some examples, these flexible packages contain at least two product compartments that can be integrated prior to use to allow materials from different compartments to mix and produce an administrable product. Prepare. These packages are sometimes referred to as pouches or sachets. One drawback of the pouch package is that it is relatively difficult to efficiently squeeze the entire contents of the package. This is due to the dimensional ratio of these packages whose length and width are typically much larger than the vertical protrusions to the package plane. This dimensional ratio is an inherent limitation in the method of forming a pouch or sachet package. Pouches and pouches are formed from one or more flat films or foils (both “webs”) that are sealed along the edges to form one or more containers. The pouch is filled during or after container formation and then sealed to keep the product in a sterile package.

  When operating directly with the palm, one limitation of these relatively deep packages is that when dispensing, the two opposing walls of the package immediately contact each other with the thumb of the operator, and the dispensing stops when they touch. It is. In order to further squeeze the product out of the package, a precise peristaltic movement or folding of the package is usually required. In some forms, a compression panel is used to press the flexible package and release the contents. In these configurations, it is beneficial to operate the compression panel to press the product compartment with a smaller contact surface, thus creating a stronger pressure. Therefore, it is advantageous to create a flexible dosing package with a relatively small area of the content compartment and a small ratio between the sealing area and the package dimensions perpendicular to the package surface.

  In some applications, deliverable agents require thorough mixing of at least two substances prior to injection. As an example, a simple method for preparing highly viscous water-in-oil (W / O) at the time of use is required. Currently, emulsions are prepared manually by reciprocating and mixing the separated oil and water components via a three-way stopcock or capillary tube connecting two syringes. This method takes some time and is often inconsistent. In order to provide a more effective emulsion, but especially when the pore size is reduced to shorten the preparation time, a stronger pushing force is required, but a connector having a porous membrane in the syringe has been developed. Has been. In addition, the increased number of assembly and disassembly steps increases the risk of operational errors and deliverable dose contamination.

  At least some aspects of the present disclosure overcome the shortcomings and limitations of the prior art, for example, by providing an inexpensive, simple and easy to handle cartridge. Certain structures of cartridges allow aseptic mixing and filling of dispensers, particularly drug delivery syringes.

  In some forms of the present disclosure, the package is manufactured from at least one web material in which a first wall and a second wall of web material are joined along a compartment boundary. In some forms, the web material is preformed such that a relatively large volume compartment is obtained with a relatively small sealed area. With this pre-formed package, the overall size of the package can be reduced and storage efficiency and transport efficiency can be improved.

  According to one aspect of the present disclosure, a cartridge having a thin flexible wall package includes at least a first component compartment and a fitting for connecting the cartridge to a dispense port of a dispenser. The fitting is attached to the package in a fluid tight manner. The fitting is not limited to a luer connector, luer lock connector, press-fit connector, snap-on connector, snap, or threaded cap, and may be attached to the dispense port of the dispenser by one of the means.

  In some forms, at least one cavity is pre-formed in at least one of the web walls of the package and forms part of the at least one product compartment of the package. With this structure, the ratio between the sealed area (area) of the compartment and the dimension of the compartment perpendicular to the sealed area (bulge of the compartment) for storing the same volume of product can be further reduced. . This structure also allows the area of the compartment to be smaller than that required for a pouch or pouch package having a similar product capacity. Web forming is suitable in the art suitable for the properties of a particular web material, including, for example, thermoforming, cold forming, preheating forming, plug assist, pressure forming, vacuum forming, and combinations thereof. It may be performed by one of well-known means.

  In some forms, the package is constructed from thin walls using one of the forms well known in the art, including, for example, blisters, pouches, sachets, blow molded containers or extruded containers. In some forms, the package may have one or more compartments that store a number of substances that need to be mixed prior to delivery to a subject to produce an administrable product. A fragile seal that can be broken by compressing at least one of the compartments to exceed the at least one threshold pressure of the material, allowing the fragile seal to separate (eg, break or peel) and allow the material to mix. The compartments may be separated by The package further comprises a boundary to the dispenser.

  In some forms, the product is transferred from the cartridge to the dispensing device. In some forms, the cartridge is exchanged within the dosing device. In some embodiments, the cartridge is aseptically connected to the dispenser at the manufacturing stage, thus eliminating the step of integrating the cartridge and dispenser by the user. This configuration prevents exposure to non-sterile conditions prior to or during the dispenser loading process, thus reducing the possibility of user error or contamination of the device or deliverable product. In another form, the cartridge is stored separately from the dosing device (ie, syringe, syringe, etc.) until use. This form may be effective when the drug needs to be stored and transported in a controlled environment, such as cooling at a controlled temperature, or when packaging efficiency is important. This form may also be effective to improve logistics and user flexibility in selecting different sources and delivery device types.

  In some forms, the administration device may be a syringe. The term syringe refers to various administration products including, for example, micro-infusion pumps or reservoirs such as pen injectors, reservoir assemblies, syringes, needleless injectors, common drug delivery devices, patch devices and the like. More generally, the cartridges of the present disclosure are applicable to administration devices including, for example, eye drops, oral droppers or ear droppers, spray dispensers or foam dispensers, topical applicators, and inhalation devices.

  In another form, a static mixer is placed at the boundary between the cartridge device and the drug delivery device to facilitate mixing of the deliverable product and enhance its uniformity. An example of a static mixer is taught in US Pat. No. 4,538,920, which is incorporated herein by reference in its entirety. In some forms, the static mixer is configured as a pattern of passages formed between the walls of the flexible wall by welding and pre-forming designated areas of the walls. The static mixer may be a simple elongated nozzle or a porous member housed in the flow path between the cartridge and the delivery device. In one form, the static mixer is disposed within the cartridge port. In one form, the cartridge comprises one or more compartments holding different substances, and these compartments are integrated prior to transferring the contents to the delivery device, and a static mixer is used to deliver the substance to the delivery device. Facilitates mixing of substances when transported to.

  In some forms, the mixture may be reciprocated between the cartridge and the delivery device to further mix the substance. In some forms, at least one substance is stored in the cartridge, and at least one substance is stored in the delivery device, and the substance is mixed back and forth between the two. In one form, the cartridge comprises at least a first compartment and a second compartment, and at least one static mixer is disposed between the first compartment and the second compartment. Mixing may be facilitated by transferring the substance or mixture from one compartment to the other compartment. In order to facilitate the transfer of material across the static mixer, at least one compression panel or array of compression panels may be operated on the cartridge.

  The present disclosure also relates to forms and methods that facilitate efficient cartridge manufacture and filling. In one form, the package compartment is filled with fluid. The compartment is sealed to leave a designated passage leading to a port for introducing fluid and exhausting air. A separate passage for gas discharge may be incorporated. The passage may be configured to allow fluid entering the port to slide along the wall of the package, thus preventing jetting and minimizing foaming or bubble formation, thereby improving fill rate Enable.

  In another form, the liquid material is frozen prior to filling and introduced into the package in solid form. The ambient temperature of the package and the heat transfer to the package during the filling process are controlled so that the frozen liquid is in a substantially solid state until the compartment is sealed. The dose of frozen liquid material can be examined in its frozen form before or during filling. This filling form and method improves filling speed and material inspection capability. In one form, the dry powder material must be filled into the cartridge compartment. In order to facilitate proper filling of the powder, the powder is slightly compressed to form loosely agglomerated tablets and filled in the package compartment in the form of tablets. The tablets can be inspected before or during filling of the cartridge. In one form, after the tablet is sealed in the compartment, the compartment is manipulated from the outside to bring the tablet into a non-agglomerated state, thereby improving the solubility of the substance when mixed with the diluent. External operations include, but are not limited to, compression of the compartment, such as ultrasonic vibration, high frequency vibration, vibration including acoustic vibration, application of mechanical shock to the compartment, exposure to high or low temperature May be at least one of them.

  The present disclosure further relates to a form that enhances the barrier properties of the package by including a highly barrier and peelable opaque wall layer. The peelable high barrier layer may comprise an aluminum stack that provides light shielding benefits and an almost complete moisture and oxygen barrier. To visually inspect the contents of the cartridge prior to use, the high barrier layer is peeled from at least a portion of the package, exposing a substantially transparent wall. In one form, the release layer is an integral layer of web material from which the package is manufactured. In one form, the release layer is affixed to the see-through wall during the cartridge manufacturing process. In one form, the release layer is flat. In another form, the release layer is preformed to adjust the material to be protected or the shape of the compartment. In one form, the release layer comprises an adhesive coating that is selectively applied and precisely aligned to the sealing periphery of the release layer. In one form, the cartridge is a cylindrical body of a flexible transparent wall, and the release layer is disposed so as to wrap around the cylinder.

  Another aspect of the present disclosure relates to a cartridge for use with a benefit agent delivery device having a fillable reservoir. The cartridge includes a reconstitution unit dose package having a first compartment and a second compartment, and a mating body. The first compartment contains at least a first component of the benefit agent. The second compartment contains at least a second component of the benefit agent. A mating body is disposed on the package to connect the package to a fillable reservoir.

  Another aspect of the present disclosure relates to a sterile cartridge for use with a benefit agent delivery device having a fillable reservoir. The cartridge includes a package having at least a first compartment and a fitting body. The first compartment contains at least a first component of the benefit agent and the package is at least partially defined by a preformed flexible wall. A mating body is disposed on the package to couple the package in fluid communication with the fillable reservoir.

  A further aspect of the present disclosure relates to a cartridge for use with a benefit agent delivery device having a fillable reservoir. The cartridge includes a backing and a package assembly. The package assembly includes at least a first compartment and a fitting body. The first compartment contains at least a first component of the benefit agent and is at least partially defined by a flexible wall. A mating body is disposed on the package to couple the package in fluid communication with the fillable reservoir.

  Another aspect of the present disclosure relates to a cartridge for use with a benefit agent delivery device having a fillable reservoir. The cartridge includes a package having at least a first compartment, a fitting body, and a coupler. The first compartment contains at least a first component of the benefit agent. The fitting body is disposed in the package. The coupler is joined to the mating body to connect the package in fluid communication with the fillable reservoir.

  A further aspect relates to a cartridge for use with a benefit agent delivery device having a fillable reservoir. The cartridge includes a unit dose package containing all of the benefit agent or all components of the benefit agent. The cartridge includes at least a first compartment containing all of the benefit agent or at least a first component of the benefit agent, the first compartment being at least partially defined by a flexible wall. The cartridge also includes a mating body disposed on the package for coupling the package in fluid communication with the fillable reservoir.

  A further aspect relates to a filled cap that surrounds an administration portion in a unit dose benefit agent delivery device comprising a single reservoir. The filled cap includes at least a first compartment that contains at least a first component of the benefit agent and a fluid passage that communicates the first compartment with the administration portion.

  A unit dose dispenser of benefit agent according to the present disclosure includes a delivery device and a cartridge. The delivery device has a fillable unit dose reservoir and at least one port in communication with the fillable reservoir. The cartridge is aseptically joined to the delivery device and includes a unit dose package. The unit dose package includes at least a first compartment, a fitting, and an openable seal. The first compartment contains at least a first component of the benefit agent and the package is at least partially defined by a flexible wall. The fitting is joined to the unit dose package and couples the unit dose package to the delivery device. An openable seal is disposed between the first compartment and the reservoir.

  Another aspect of the present disclosure relates to a pre-filled syringe for administering a benefit agent. The prefilled syringe has a piston assembly, a fillable barrel with an administration portion, at least a first compartment containing at least a first component of the benefit agent and a flow passage communicating the contents in the first compartment to the barrel. And a pre-filled cartridge.

  A further aspect of the present disclosure relates to a cap for the administration portion of the delivery device. The cap includes a fluid passage, a proximal end configured to communicate with the administration portion, and a distal end.

  An exemplary method according to the present disclosure relates to a method of forming a prefilled package of benefit agent. The method comprises providing a webbing having a first surface and a second surface joined to form at least a first component compartment boundary between the first surface and the second surface; and at least the boundary Forming a fragile seal along a portion; forming the permanent seal such that the permanent seal overlaps at least a portion of the fragile seal and creates an overlapping portion having substantially the same sealing properties as the permanent seal; Filling the first component compartment.

  Another exemplary method according to the present disclosure relates to a method of forming a prefilled package of benefit agent. The method includes forming a gas filled compartment for a benefit agent, forming a filled compartment having a fill port in communication with the gas filled compartment via a sealable first flow path, and sealing. Forming an exhaust compartment having an exhaust port communicating with the gas-filled compartment via a second flowable channel. The method also includes coupling a source of at least a first component of the benefit agent to the fill port in a fluid tight manner, and exhausting gas through the exhaust port while leaving the gas fill compartment through the fill channel. Filling the chamber and sealing the sealable first flow path and the filling flow path.

  Further methods according to the present disclosure include receiving an assembled delivery device, receiving a filled sterile sealed cartridge pre-filled with at least a first component of the benefit agent, the delivery device and sterile sealing. A unit dose delivery device for a benefit agent.

  Another exemplary method relates to filling a unit dose of a liquid benefit agent into a package. The method includes freezing a metered unit dose of benefit agent in a mold to create a frozen dose, placing the frozen dose in a semi-finished compartment, and sealing the compartment.

  Another exemplary method relates to filling a package with a metered dose of at least a first component of a benefit agent that is in the form of a flowable solid. The method includes metering a dose of the first component, compressing the metered dose sufficiently to form a single body, placing the single body in a semi-finished package, and sealing the package. And directing energy through the wall of the package into a single dose and converting the single dose into granules.

  The use of the present invention is not limited to drug delivery, which is provided by way of example herein. The teachings described herein can be applied to administration devices in other fields, such as adhesive dispensing, drug delivery, and the like. The present disclosure provides various structures for accomplishing this.

FIG. 1a illustrates a syringe cartridge assembly with a blister package coupled to a cap that can be used in a variety of configurations. FIG. 1b illustrates a syringe cartridge assembly with a blister package coupled to a cap that can be used in a variety of configurations. FIG. 1c illustrates a syringe cartridge assembly with a blister package coupled to a cap that can be used in various configurations. FIG. 1d illustrates a syringe cartridge assembly with a blister package coupled to a cap that can be used in various configurations. FIG. 1e illustrates a syringe cartridge assembly with a blister package coupled to a cap that can be used in various configurations. FIG. 1f illustrates a syringe cartridge assembly with a blister package coupled to a cap that can be used in a variety of configurations. FIG. 2a illustrates a syringe assembly with a blister package coupled to a cap that can be used in various configurations. FIG. 2b illustrates a syringe assembly with a blister package coupled to a cap that can be used in various configurations. FIG. 3a illustrates a pre-filled syringe assembly that can be used in a variety of configurations, with the package connected to the stem of the piston and extending axially from the stem. FIG. 3b illustrates a pre-filled syringe assembly that can be used for various constructions, with the package connected to the stem of the piston and extending axially from the stem. FIG. 4 illustrates a syringe assembly in which a blister package is coupled to a stem and extends laterally from the stem, which can be used in various configurations. FIG. 5a illustrates a pre-filled cartridge in a spring driven needleless auto-injector. FIG. 5b illustrates a pre-filled cartridge in a spring driven needleless auto-injector. FIG. 6 illustrates a pre-filled cartridge in an ignition driven needleless auto-injector. FIG. 7 illustrates a cartridge manufactured from an extruded cylinder. FIG. 8 illustrates a cartridge manufactured from an extruded cylinder mounted on a needleless automatic injector. FIG. 9a illustrates a cartridge made from an extruded cylinder attached to a syringe. FIG. 9b illustrates a cartridge with a peelable protective foil manufactured from an extruded cylinder attached to a syringe. FIG. 10a illustrates a cartridge with a peelable portion of the molded wall and an extended wall portion that forms a sterile compartment around the discharge port, and a number of operating steps. FIG. 10b illustrates a cartridge with a peelable portion of the molding wall and an extended wall portion that forms a sterile compartment around the discharge port, and a number of operating steps. FIG. 10c illustrates a peelable portion of the molding wall and a cartridge with an extended wall portion that forms a sterile compartment around the discharge port, and a number of operating steps. FIG. 10d illustrates a peelable portion of the molded wall and a cartridge with an extended wall portion that forms a sterile compartment around the discharge port, and a number of operating steps. FIG. 10e illustrates a cartridge with a peelable portion of the molding wall and an extended wall portion that forms a sterile compartment around the discharge port, and a number of operating steps. FIG. 11 illustrates a cartridge with a flat wall peelable portion. FIG. 12 illustrates a cartridge with a flanged discharge port attached to the outer surface of the cartridge wall. FIG. 13 illustrates a cartridge coupled to a valved coupler in communication with a syringe and needle. FIG. 14 illustrates a cartridge coupled to the distal end of the syringe barrel. FIG. 15 illustrates a semi-finished cartridge that supports lyophilization of the benefit agent. FIG. 16 illustrates a cartridge with a static mixer at the discharge port that facilitates mixing of the two components stored in the cartridge. FIG. 17 illustrates a system for mixing a first component contained within a cartridge and a second component contained within a syringe. FIG. 18 illustrates a system for mixing a first component and a second component contained within a cartridge. FIG. 19 illustrates a static mixer integrally formed with a blister type cartridge. FIG. 20a illustrates a cartridge manufacturing method. FIG. 20b illustrates a cartridge manufacturing method. FIG. 20c illustrates a cartridge manufacturing method. FIG. 20d illustrates a cartridge manufacturing method. FIG. 20e illustrates a cartridge manufacturing method. FIG. 21a illustrates a syringe with a static mixer for mixing the material contained in the syringe with the material contained in the cartridge. FIG. 21b illustrates a syringe with a static mixer for mixing the material contained in the syringe with the material contained in the cartridge. FIG. 21 c illustrates a syringe with a static mixer for mixing the material contained in the syringe with the material contained in the cartridge. FIG. 21d illustrates a syringe with a static mixer for mixing the material contained in the syringe with the material contained in the cartridge. FIG. 21e illustrates a syringe with a static mixer for mixing the material contained in the syringe with the material contained in the cartridge. FIG. 22a illustrates a cartridge in communication with a fixed needle syringe via a fitting. FIG. 22b illustrates a cartridge in communication with a fixed needle syringe via a fitting. FIG. 23a illustrates a fixed needle syringe that can be attached via a cartridge and a coupler. FIG. 23b illustrates a fixed needle syringe that can be attached via a cartridge and a coupler. FIG. 23c illustrates a fixed needle syringe that can be attached via a cartridge and a coupler. FIG. 23d illustrates a fixed needle syringe that can be attached via a cartridge and a coupler. FIG. 23e illustrates a fixed needle syringe that can be attached via a cartridge and a coupler. FIG. 23f illustrates a fixed needle syringe that can be attached via a cartridge and a coupler. FIG. 24 illustrates another form of fixed needle coupler. FIG. 25a illustrates a cartridge with a coupler containing a needle. FIG. 25b illustrates a cartridge with a coupler containing a needle. FIG. 25c illustrates a cartridge with a coupler containing a needle. FIG. 26 illustrates a cartridge used in a syringe with an intradermal (ID) injection adapter. FIG. 27a illustrates a cartridge coupled to an ID syringe. FIG. 27b illustrates a cartridge coupled to an ID syringe. FIG. 28 illustrates another form of cartridge coupled to the ID syringe. FIG. 29a illustrates another form of cartridge with the form of an ID needle. FIG. 29b illustrates another form of cartridge with the form of an ID needle. FIG. 30 illustrates another form of cartridge with the form of an ID needle. FIG. 31a illustrates a cartridge with a needle safety disabling mechanism. FIG. 31b illustrates a cartridge with a needle safety disabling mechanism. FIG. 32 illustrates a cartridge with a movable needle. FIG. 33a illustrates a prefilled syringe configuration. FIG. 33b illustrates a prefilled syringe configuration. FIG. 33c illustrates a prefilled syringe configuration. FIG. 33d illustrates a prefilled syringe configuration. FIG. 33e illustrates a filled syringe configuration. FIG. 34 illustrates a cartridge with a backing and walls that protect the filled package of the cartridge. FIG. 25d shows two subassemblies of the filled cap. FIG. 25e shows an exploded view of the cap portion of the cartridge. The code | symbol 39 of FIG. 3 a has shown the fitting body. The code | symbol 39 of FIG. 3b has shown the fitting body. Reference numeral 49 in FIG. 4 indicates a fitting body. The second compartment of FIG. 15 is sealed in an empty state and can be filled via the filling device 152 as shown. FIG. 20 f shows a weak seal pattern 401. FIG. 20g shows a permanent seal pattern 402 that partially overlaps the fragile seal.

  FIG. 1 a shows the configuration of the syringe 11 and the cartridge 10. This figure provides a section line of the cross-sectional view of FIG. FIG. 1 b illustrates a cross-sectional view of the syringe assembly 11 and the cartridge 10. The syringe 11 includes a barrel-shaped main body 13 and a piston 14 that is disposed on the main body and is movable between an empty state that is advanced along the axis of the main body and a retracted filling state. Piston 14 further includes an O-ring seal 14 'that provides a fluid seal between the body and the piston and defines a compartment for receiving a fluid dose in front of the piston. The compartment is shown in an empty state in which the piston is advanced to the foremost position in the main body 13. A jet nozzle 17 at the front of the body provides a port for filling the syringe 11 with a fluid dose and delivering the fluid dose subcutaneously to the subject in a needleless jet injection manner.

  The cartridge 10 has a first thin wall 18 ′ formed to provide two cavities, and a first thin wall 18 ′ so as to define a first sealed compartment 15 and a second sealed compartment 16. The fitting 12 is attached to the package between the first wall 18 'and the second wall 18 ". The fitting body 12 is configured to engage with the front portion of the syringe body 13. The first fragile seal portion 19 ′ separates the first compartment 15 and the second compartment 16 and can be separated by a predetermined threshold force. The second fragile seal portion 19 "separates the second compartment 16 and the fitting body 12 and can be peeled off with a predetermined threshold force. The thin walls 18 'and 18" are extruded web, blow web, molded web. Multi-layer webs, laminated webs, coated webs, webs containing metallized layers such as aluminum layers, webs containing metal oxide layers such as alumina or silica, cyclic olefin polymers (COP), cyclic olefin copolymers ( From a type of film or foil (both referred to as “web” or “web material”), including webs with high barrier layers comprising COC), polychlorotrifluoroethylene (PCTFE), ethylene vinyl alcohol (EVOH) May be manufactured. The inner adhesive layer of the web material may be made from olefin ionomer, ethylene vinyl acetate (EVA) or other materials.

  An adhesive layer having a controlled peel force is incorporated into the web so that the peel force in a specified area of the outer periphery seal around the compartment is lower than the other areas, thereby providing a first wall 18 'and It may be useful to limit the area that breaks when a threshold peel force is applied to the seal area between the second wall 18 ". One such adhesive layer peels off at a seal temperature of 130 ° C. EZ Peel registered trademark (Bemis, Neenah, Wisconsin), a brand of ionomer blends that produces a permanent seal and a permanent non-peelable seal at a seal temperature of 170 ° C., so the two-step welding process is performed at different temperatures By doing so, the sealing property can be controlled well.

  Another approach to achieving the desired sealing force pattern between the first wall 18 'and the second wall 18 "is to use a web of selective adhesive patterns of at least two adhesive types with different peel strengths. The mating body 12 may be made from an olefin polymer having good adhesion to the inner layer of the web, hi some forms, the mating body may be the first wall 18 'or the second layer. A through hole in the web is attached to one outer side of the two walls 18 ″ and allows the contents of the cartridge 10 and the fitting body 12 to communicate. In this configuration, the mating material should be a material that is compatible with attachment to the web outer layer material. The cartridge compartments 15 and 16 can contain various substances. In one embodiment, the first compartment 15 contains the diluent and the second compartment contains the dry form benefit agent, and two compartments to form an administrable product dose. The contents need to be mixed. In one embodiment, the first compartment 15 contains a diluent such as saline or water for injection and the second compartment contains the vaccine in dry powder form.

  The contents of the first compartment 15 and the second compartment 16 may be liquid, gel, paste, slurry, solid, granule, pellet, flowable powder, compressed powder, cake, lyophilized cake, or well known in the art. It may be in various forms including other forms. When the first compartment contains the flowable material, the first compartment 15 is pressed to pressurize the contents, thereby applying a force to the first fragile seal 19 'to peel off the first The fragile seal 19 ′ can be separated, creating a compartment coupled between compartment 15 and compartment 16 to allow mixing of the contents of the two compartments. The second fragile seal 19 "can be broken by pressing the combined compartments to pressurize the contents of the compartments, thereby creating a peel force on the second fragile seal 19".

  FIG. 1 c shows the cartridge 10 attached to the syringe 11. The fitting body 12 is engaged with the front end of the syringe body 13, and preferably forms a sterility zone in the fitting body region. The passage of the fitting body 12 and the syringe nozzle 17 are in fluid communication. For parenteral subcutaneous drug delivery applications, all areas of the device that come into contact with the deliverable material and areas that will come into contact with the subject's body need to be kept sterile until use. In the configuration of FIG. 1c, aseptic engagement of the syringe 11 and the cartridge 10 maintains sterility for that area. Sterilization inside the barrel 13 may be maintained by a second seal at the rear end of the body 13, a local overwrap of the rear portion of the body 13 and the piston 14, or a sterilization overwrap for the entire device. In addition, a sterile cover is required for the front region of the syringe body 13 and the fitting body 12, but a similar solution can be applied to the configuration of FIG.

  Sterilization of the fitting 12 may be achieved by a lead or cap that protects the port area. The foil lead may be heat sealed to the peripheral edge of the vertical wall around the port. In one embodiment, the cartridge 10 is stored in a sterile overwrap. In some embodiments, where at least one of the materials is in a dry form, a desiccant capsule, desiccant in a sterile overwrap to prevent moisture from moving across the web 18, 18 'wall to the dry compartment. It may be advantageous to include a desiccant such as pellets or desiccant gel. In one embodiment, a dry substance may be incorporated into the web (this form is sometimes referred to as a scavenger film). Packaging the cartridge separately from the syringe improves the controlled storage and transport of the formulation. Sterilization of the front end of the body 13 in the form of FIG. 1b can be achieved in various ways, including a tight cap, a heat sealing foil around the nozzle 17 region, and by packaging the entire syringe in a sterile overwrap. Therefore, the configuration of FIG. 1c may be effective in reducing the measures that need to be taken to maintain product sterility.

  Referring now to FIG. 1d, the configuration of FIG. 1c is shown after the fragile seal (19 ′ and 19 ″ of FIG. 1c) has been broken, and the combined compartment 16 ′ is the passage of the fitting 12 In fluid communication with each other.

  FIG. 1 e shows the previous configuration of FIG. 1 d when the piston is retracted from the body 12 and fluid from the combined compartment 16 ′ flows into the syringe 11.

  FIG. 1f shows the previous configuration of FIG. 1e with the piston 14 fully retracted. The combined compartment 16 ′ is completely emptied and the contents of the compartment are completely transferred to the syringe 12. The cartridge 11 is removed and at this point the syringe 12 is loaded with a deliverable product dose and ready for use. If the form is pre-sterilized, the front of the syringe is maintained in a sterile state until this point when the fitting 12 is removed. This form may be effective even before the syringe filling step compared to a commercially available form where the application surface of the syringe is exposed to a non-sterile area and increases the risk of contamination to the subject.

  This form shows the aseptic filling form of the jet syringe cartridge. In a further form of the present disclosure, similar forms may be used, for example, intramuscular, subcutaneous, or intradermal syringes, as well as their cartridges, topical applicators, and their cartridges and reservoirs, infusion pumps, microinfusion pumps, injectors, Microinjectors, patch delivery devices, and their cartridges and reservoirs, infusion containers including infusion bags and infusion bottles, oral administration, ophthalmic or ear dispensers and their cartridges and reservoirs, adhesive dispensers, and other Provided to fill other cartridges, dispensers, or drug delivery devices well known in the art, including dispensers, various uses and intended delivery devices and applicators.

  FIG. 2 illustrates the form of a pre-filled mixing cartridge 10 and a conventional syringe 20. This figure provides the section line of the cross-sectional view of FIG. 2b. Referring to FIG. 2 b, the cartridge 10 terminates with a luer lock female connector, is coupled to the luer lock male connector of the syringe 20, and includes a fitting that forms a fluid tight connection between the cartridge 10 and the syringe 20. . Fluid may be transferred from the cartridge 10 to the syringe 20 in the same manner as the syringe of FIG. The syringe tip remains in a sterile environment until it is used until the cartridge 10 is removed. This configuration may be effective compared to commercial products where the syringe tip or needle tip is exposed to a non-sterile area prior to the filling step, thereby increasing the risk of contamination to the subject. In one form, when the cartridge and syringe are integrated via a luer connection, the cartridge is stored separately from the syringe until use. In order to maintain the sterility of the syringe 20 and cartridge 10, similar configurations and measures as those described above with respect to the configuration of FIG.

  Referring to FIG. 3, another configuration is provided in which the cartridge is connected to the rear end of the piston 31. The piston 31 includes a fluid passage 32 along the axis of the piston that communicates with the cartridge port 9 and the syringe body. The plunger 34 is displaced slightly away from the piston 31 when the piston 31 is retracted, by friction with the barrel 33, thereby allowing the contents of the cartridge to move into the barrel 33. It arrange | positions at the front end of piston 31 so that the path | route 35 (refer arrow) may be open | released. The cap 37 maintains a sterile space around the dispensing tip 36 of the syringe. FIG. 3b illustrates the configuration of FIG. 3a with the piston 31 advanced after the piston 31 has been retracted to the fully retracted position. The cartridge 10 is in a state where its contents are completely used up. Advancement of the piston 31 returns the plunger 34 to a position closer to the piston 31 head, thereby sealing the passage 32 so that the contents of the barrel 33 can only travel to the syringe port 36.

  Unlike commercially available syringes where the dispensing tip or the needle connected to the dispensing tip is exposed to a non-sterile area prior to the filling step, this construction allows the cap to be removed from the tip 36 for the first time immediately after use, after the filling step. Removed. The cartridge may be coupled to the syringe by various means well known in the art including, for example, luer connectors, barb connectors, press-fit connectors, septum devices, connecting cylinders, or adhesion to each other. In one form, the cartridge is disposed in an empty space in the piston.

  Referring now to FIG. 4, the cartridge 10 is shown connected to the rear end of the piston 43 and extending laterally from the piston 43. A valve 44 is located at the rear end of the fluid passageway 42 that allows movement of fluid from the cartridge 10 to the barrel 40, but prevents fluid from flowing in the opposite direction, so that when the piston is advanced, The entire dose flows only to the administration tip 45. In one form, the piston 44 also allows air to enter the flow passage 42 after the cartridge 10 is emptied, thereby advancing fluid from the passage to the barrel. In one embodiment, a dedicated sterile compartment allows the inflow of water or air into the fluid passageway 42 after the cartridge benefit agent is emptied and flushes away the remaining benefit agent from the passageway. In one form, the water or air compartment is part of the cartridge 10 assembly.

  FIG. 5 a illustrates a jet injector comprising a cartridge 10 disposed within a pressure chamber 51 within the syringe body 52. The cartridge 10 includes a needleless jet nozzle 17 connected to the front end of the syringe body. The piston 53 is disposed in the main body 52, is locked at a pre-use position by a locking mechanism (not shown), and is urged forward so as to reduce the volume of the pressure chamber 51. In one form, the cartridge 10 comprises more than one compartment prior to use and can be manually mixed by removing the cartridge 10 and following a procedure similar to that described in FIG. Return the cartridge 10 to.

  FIG. 5 b shows that the piston 53 is released from the detent mechanism and is pushed forward by the spring 54 to pressurize the pressure chamber 51, thereby collapsing the wall of the cartridge and passing through the nozzle 17 to the cartridge wall and the contents of the cartridge 10. The syringe 50 is shown after squeezing out the object. The nozzle 17 may be protected by a sterile cap or adhesive foil until use.

  FIG. 6 is the same as the configuration of FIG. 5 except that when the ignition module 61 is operated by the manual switch 62, the piston is urged forward by the pressurized gas generated by the ignition module 61. The form is shown.

  FIG. 7 shows a cartridge 70 manufactured from a cylindrical portion 71 that is pinched and heat sealed 72 at a number of positions 72 along the cylindrical portion 71 throughout the cylindrical portion 71 to form at least one compartment containing a beneficial agent. Indicates. In one construction of the cartridge 70, the pinched location 72 seal is a fragile seal that is made to peel in the presence of a threshold pressure or force. The cylinder portion 71 may be manufactured by extrusion, injection molding, blow molding, or other manufacturing methods known in the art. In one form, the cylinder part 71 is provided with a number of layers that provide improved barrier properties that reduce the movement of certain gases or moisture across the entire cylinder wall, with the inner layer being a heat sealing material and at least the second layer. In one form, the tube is coextruded. In one form, at least one first layer of the cylindrical wall is made from a roll sheet of plastic, metal, or metal oxide, and at least one second layer is extruded over the roll-like first layer. The

  FIG. 8 shows a needleless jet injector configuration similar to the configuration presented in FIG. 5 except that the cartridge 80 is manufactured from a cylinder portion whose front end is attached to the jet nozzle 17.

  FIG. 9a is similar to the configuration presented in FIG. 3, except that the cartridge 90 is manufactured from a cylinder 90 that is pinched and sealed at two points 99 ′ and 99 ″ ′ to form a compartment. Shows syringe and cartridge assembly, seal 99 'compresses the cartridge and breaks when the contents are pressurized, allowing fluid communication between the cartridge and the syringe with the female luer lock connector 92 attached to the end In some embodiments, the cylindrical portion and cartridge 90 may be stored separately from the syringe until use.The same system and measures as those described above with reference to FIGS. The sterilization of the product and device may be achieved with a cylindrical wall that may have a single layer or multiple layers, a high barrier PCTFE layer, an aluminum layer, a COC layer, and a peelable Chakuzaiso may have.

  FIG. 9b shows that a first seal 99 ′ and a second seal 99 ″ define a first compartment 95, and a second seal 99 ″ and a third seal 99 ″ ′ holding a first material hold a second material. Figure 2 shows a further form of cartridge manufactured from a cylinder defining a second compartment 94. The second seal 99 "is a first compartment to allow fusion of the first and second materials. 95 and the second compartment 94 or both can be broken when pressurized. The first seal can be broken to establish fluid communication between the cartridge and the syringe 97. The cartridge further provides a peelable barrier shell 96 that is sealed to each other across the first pinching seal portion 99 'and the second pinching seal portion 99 "to enhance the barrier properties between the cartridge periphery and the first compartment 95. With 'and 96 ". This form may be particularly effective when the barrier property of the cylinder 93 is insufficient to protect the first compartment 95 from the transmission of moisture, oxygen or light.

  The cylinder material may preferably be transparent to allow visual inspection of the contents, but this usually impairs some of the barrier properties. The peel shell may include a high barrier aluminum layer that interferes with visual inspection of the cartridge contents, and therefore there is a need to peel the shell for inspection. A first tab 98 'and a second tab 98 "are provided as extensions to the first peel shell 96' and the second peel shell 96", respectively, to facilitate peeling of the shell with a finger. The peeling shell may be formed in advance so as to adjust the shape of the first compartment 95. At least one of the release shells 96 ′ and 96 ″ may be extended to form a barrier shell for the second compartment 94. Pictures, texts, indicating cartridge content data, instructions, warnings, etc. At least one of the release shells can be extended to provide a printable or otherwise printable surface that includes a bar code or other opto-mechanical readable data display. Single or multilayer films or foils (both “webs”) may be manufactured and may include a pressure sensitive adhesive, an electrostatic adhesive or a temperature sensitive adhesive to form a peelable seal.

  FIG. 10 a shows another preferred form 100 in which the second compartment 16 comprises a release layer 105. In various applications, for example, visually inspecting (or by optical measurement) the contents of an integrated compartment or one or more compartments after mixing the contents of two or more compartments In desirable applications, it is desirable to make at least a portion of the package from a transparent material. However, typically transparent materials have a higher water vapor transmission rate (MVTR) than foils that are opaque and provide a lower barrier between the compartment (s) and the package perimeter. Some products are extremely sensitive to moisture, such as dry vaccines that lose their effectiveness at relative humidity levels above 2% or 3%. Furthermore, visual inspection of the vaccine powder is important to ensure that the product is free of foreign material before use and to inspect whether the vaccine powder is completely dissolved in the diluent after mixing.

  In one form of the present disclosure, the cartridge is stored in a wrapper containing a desiccant that maintains a dry environment around the cartridge. In one form, the overwrap material is of the type known in the industry as a “scavenger film” in which a desiccant material is embedded in a composition of web material. In FIG. 10a, the powder compartment of the package 100 includes a highly barrier peelable mold layer 104 that is opaque or has reduced light transmission. In some forms, the release layer may provide a barrier from light. A high barrier transparent material usually costs more than a low barrier transparent material. In some forms, to reduce manufacturing costs, the larger molded wall 18 'of the package is made from a low barrier material, while the local release layer 104 is a film that includes Aclar (Honeywell), etc. Manufactured from a transparent material having a high barrier property. The release layer 104 may be imparted with other desired properties that are lacking in the molded wall 18 '. The release layer 104 may be part of the raw material composition from which the molded wall 18 'was made. The release layer 104 may be manufactured from a separate web of the first wall 18 ', and in one manufacturing configuration, the two webs are formed together. In some forms, if the wall 108 'is a thermoformed film and the release layer 104 is a cold formed foil, the forming process may include a combination of cold forming and thermoforming. .

  In some forms, the cavity 105 of the release layer 104 is formed separately from the molding wall 18 'and later attached to the package in a sealed manner. Attachment of the release layer 104 to the package may be accomplished by one of the means well known in the art including adhesives, glues, pressure sensitive adhesives, heat stake welding, ultrasonic welding, etc. Good. In one form, the release layer 104 is sealed to the first wall 18 'via a die cut adhesive sheet. The die cut adhesive can be applied to the first wall 18 'and in the next step the release layer 104 is attached to the first wall. Alternatively, the die cut adhesive can be applied to the release layer 104, and in the next stage the first wall 18 'is attached to the release layer. The release layer 104 may have an aluminum stack or an aluminum coating.

  This form 100 further includes a discharge port compartment 103 that holds the discharge port in a sterile housing until use. The discharge port compartment 103 is formed in the extension 101 of the web material of the package 100. The tear notch 102 facilitates removal of the extension 101 for exposing the discharge port. FIG. 10b shows a configuration 100 that allows visual inspection of the contents of the second compartment through the transparent wall 18 'after the release layer 104 has been removed. In addition, the extension 101 is removed to expose the female luer lock connector shaped discharge port 12. In some procedures, it is desirable to integrate compartments 15 and 16 before removing extension 101 to minimize exposure of the discharge port and reduce the risk of contamination. The second wall 18 "of the package 100 is preferably made from a high barrier material such as laminated aluminum foil, SiOx laminate, AlOx laminate, or other materials well known in the art.

  In some forms, the second compartment 16 breaks the first barrier 19 ′ between the first compartment 15 and the second compartment 16 to unify the two compartments, and the second compartment 16. (Or an integrated compartment (15 + 16)) is pressed to break the second barrier 19 ''. The pre-formed structure of the second compartment 16 has the barrier 19 'and the desired sequence and timing in the desired order and timing. Each break of 19 ″ can be controlled. The deep shape of the compartment 16 is such that when the distal end 106 of the compartment 16 is pressed, the tension in the distal end region 106 of the first wall 18 ′ as well as the first wall proximate to the distal end region 106. The seal between 18 ′ and second wall 18 ″ is relaxed, while the proximal region 109 of the first wall 18 ′ opposite the pressing zone 106 and the first wall 18 ′ proximate to the proximal region 109; The seal between the second wall 18 "is tensioned, so that the second barrier 19" remains intact, but the first barrier 19 'breaks.

  In the next step, the proximal region of the integrated compartment (not shown) is pressurized, causing excessive strain on the second fragile seal 19 'and breaking the second fragile seal, causing the integrated compartment Establish fluid communication between the chamber and the discharge port. In addition to or as an alternative to the sterile discharge port compartment 103, a plug (such as a male luer lock cap), a welded foil portion, a plug (such as a rubber plug), or other means known in the art The port may be aseptically sealed. If another sealing mechanism protects the contents aseptically and prevents leakage of the contents, the second fragile seal may be omitted.

  FIGS. 10c-10e show one way of manipulating the cartridge 100 to achieve a controlled, sequential breakage of the fragile seals 19 ′ and 19 ″ by direct manipulation with the operator's thumb. The cartridge 100 is on the index finger and middle finger of the palm of the operator, in Fig. 10c, the distal portion 106 of the second compartment 16 is pressed with the thumb, so that the proximal of the first compartment 16 The wall 18 'in the region 107 is tensioned and exerts a peeling force on the first weakened portion 19'. At the same time, the distal region 106 of the second compartment 16 is pressed with the thumb so that the first wall 18 ' The distal region is not strained, thereby removing or minimizing the peel force on the second weakened portion 19 ". As a result, as shown in FIG. 10d, the second fragile seal 19 "remains intact, but the first compartment and the second compartment are integrated into a compartment 16 ', and the administrable product is used as a discharge port. Allowing the materials in the two compartments to mix before communicating, due to the structure of Figure 10d, the discharge port is still sealed within the discharge port compartment 104, and the integrated compartment 16 'is still discharging. Because it is not in communication with the port, it is possible to put the cartridge to one side, for example, to properly mix the materials without exposure to contamination risks.

  In FIG. 10 e, the discharge port compartment has been stripped and the port 12 is engaged with the syringe 108. The proximal end 107 of the integrated compartment 16 ′ is pressed with a thumb, tensioning the wall of the integrated compartment distal end 106, applying a peel force to the second fragile seal 19 ″ and the second fragile seal 19 To establish fluid communication between the compartment 16 ′ integrated with the syringe 108 via the discharge port 12. In another embodiment, the compartment is pressed by a compression body such as a flat plate or a roller. The present disclosure only establishes fluid communication between the cartridge and the syringe to prevent exposure of the injectable product to non-sterile areas only after the syringe and cartridge are securely fixed in a tightly sealed manner. It preferably teaches a drug cartridge for filling a syringe that reduces the risk of product spillage. Typically for vials and ampoules, a spike is typically established through the septum seal to establish fluid communication while the syringe and cartridge are integrated.

  FIG. 11 shows a configuration in which the second wall 18 ″ of the package includes a release layer 111 to provide an enhanced moisture barrier to the material in the compartment. The molded wall 18 ′ is preferably a high barrier to moisture and gas. The tab 112 makes it easier to peel off the second wall 18 ". In some forms, the release layer 111 is attached to the second wall 18 "by one of means known in the art, such as welding or gluing. In one form, the release layer 111 has a pressure sensitive adhesive. In some forms, the pressure sensitive adhesive is selectively placed on the label such that there is no pressure sensitive adhesive attachment to a particular area of the label.

  The release layer preferably comprises an aluminum layer that provides a high barrier to moisture and gas until released. In some forms, the release layer is part of the multilayer material composition of the web that makes up the second wall 18 ". In some forms, the release layer is removed from the entire second wall 18". . In some forms, a scored or die cut pattern defines the area of the release layer 111 that is removed. In some forms, the split portions of the first wall 18 ′ and the second wall 18 ″ are scored or die cut to facilitate removal of the release layer 111 (break-off tube). The cartridge 110 may be easily attached to a syringe, drug delivery device, reservoir of these or other systems, or may include a lid that is removed prior to use. Contains information printed (or otherwise printed) and receives the contents of a person, device, cartridge 110 (such as a syringe) after being peeled from the cartridge 110 as a label to display that information It may be affixed to a drug delivery device or document.

  Other labels can be affixed to the form of the cartridge according to the present disclosure, the label contains printed or otherwise printed information, is peelable or non-peelable, and can be a person, device, or It is understood that it can be affixed to other things such as a document. In some forms, the part containing cartridge information can be torn from other parts of the cartridge to include or display this information elsewhere, such as affixed to a patient or device Or it may be separable by other methods.

  FIG. 12 shows a configuration in which the discharge port is attached to the outer surface of the second wall 18 "via a flange 121. The flange is an opening (not shown) in the wall 18" that communicates the contents of the package to the discharge port. And a conduit (not shown). The port 12 is attached to the wall 18 "by one of the means well known in the art including heat welding or gluing. The cartridge 120 is easily attached to a syringe, a drug delivery device, the reservoir of these or other systems. Or may be provided with a lid that is removed prior to use.

  FIG. 13 shows a configuration in which a cartridge 133 is coupled to a manifold 134 disposed between a syringe 131 and a needle (shown here, covered by a needle shield 132). After the cartridge 133 is activated, the manifold sucks the contents of the cartridge 133 into the syringe 131 when the piston of the syringe is retracted, and delivers the contents of the syringe 131 to the needle when the piston is advanced. Is provided. In some configurations, the manifold is disengaged from the manifold 134 by manipulating the manifold when switching from a dose aspiration configuration to a dose injection configuration. U.S. Pat. No. 7,879,018 teaches a number of manifold devices to accomplish this and is hereby incorporated by reference in its entirety.

  This form of FIG. 13 discloses a unique form of pre-filled syringe with the piston in the inward position prior to use, which effectively affects product packaging efficiency. A needle safety mechanism and a syringe disabling mechanism can be incorporated into this configuration. U.S. Patent Application Publication No. 2009/0221962 teaches a retractable syringe and plunger. The syringe includes a barrel, a retractable needle base on which a needle is attached or attachable, a plunger, an initially compressed spring, a means for engaging the retractable needle base, and a plunger seal formed integrally. And a detachable control means for facilitating control of the speed at which the needle base is retracted when engaged with the plunger. In order to prevent the needle base from inadvertently retracting when the plunger is pulled to fill the syringe, the needle base is held in the barrel by the holding means. The retaining means comprises a plurality of fasteners that are formed integrally with the barrel or present on a cap that is attached to the barrel. Ejector means are also provided so that pushing the plunger can prompt the ejector means to release the needle from the holding means, thereby allowing the needle base to retract as the spring is restored. To do. In one form of the present disclosure, the cartridge is coupled to a syringe with a retractable needle base as taught in U.S. Patent Application Publication No. 2009/0221962.

  FIG. 14 shows a cartridge 133 comprising a valved port 141 connected to a syringe 131. The luer cap 142 is held in place for the step of filling the syringe barrel with an administrable product from the cartridge 133. The valved port 141 integrates the compartments of the cartridge 131 and ruptures the barrier between the integrated compartment and the discharge port 141. Then, when the syringe piston is retracted, the administrable product is removed from the cartridge 133. As the syringe flows into the syringe barrel and the piston is advanced, the administrable product is biased toward the syringe tip so that it does not return to the cartridge. In one form, the valved port includes a check valve that allows fluid out of the cartridge 133 and prevents backflow into the cartridge 133. In one form, the valved port is switched between an open state and a closed state by manual operation, for example, by rotation, axial movement, or a combination thereof.

  In some forms, the cartridge is removable during manual operation or after manual operation. U.S. Pat. No. 7,879,018 teaches a number of manifold devices to accomplish this and is hereby incorporated by reference in its entirety. In some forms, the syringe 131 is valve adjusted so that when the syringe piston is retracted, the flow cannot flow through the tip of the syringe and when the piston is advanced, the flow can flow out of the syringe barrel. Is done. In some forms, the syringe valve is a check valve. In some forms, the syringe valve is manually operated. In some configurations, the syringe valve and the cartridge valved port 142 actuate the cartridge valved port 142 to shut off, actuating the syringe valve to open, and vice versa. Mechanically linked. The configuration of FIG. 14 may be particularly effective when the dispensing tip is in a form that cannot receive a cartridge, for example, when the dispensing tip has a fixed needle, a retractable needle, or other safety mechanism.

  U.S. Patent Application Publication No. 2011/0015572 teaches a retractable syringe, a plunger and a releasable needle holding assembly. Retractable syringes typically have a glass barrel and are prefilled with fluid contents prior to use. The releasable needle retention system includes a retractable needle, a needle seal, a retention member, and an ejector member operable to release the retractable needle from the retention member. The retaining member has a mating surface for attachment to a complementary mating surface on the inner wall of the syringe barrel. The plunger comprises a plunger sheath, a plunger rod breachably connected to the control member, a spring, and a single plunger seal capable of engaging a retractable needle, the plunger rod, the plunger sheath and the control member Cooperate to releasably maintain the spring in its initial compressed state. After delivering the fluid content of the syringe, the plunger presses the ejector member to release the retractable needle from the holding member. The restoration of the spring at the end of the plunger push facilitates the retracting of the retractable needle when engaged with a single plunger seal. A double lock system prevents reuse of the syringe after storing the needle. In one form of the present disclosure, the cartridge 133 is connected to the barrel of a safety syringe as taught in US 2011/0015572 via the configuration of the valved port 141 of FIG. .

  Referring now to FIG. 15, in some forms, it is desirable to freeze and dry the material directly in the compartment 15. The first wall 18 ′ is welded to a pre-formed flat second wall 18 ″. The first compartment 15 has an open end and is larger than the sealed final dimension of this compartment. Long, compartment 15 allows sufficient filling of liquid material, and the cartridge is placed in the lyophilizer until the lyophilization process is complete and a dry cake is left on the bottom of the first compartment 15 The compartment is then sealed and aseptically accommodates the lyophilized dose, the second compartment 16 may be filled and sealed before or after the lyophilization process.

  Referring to FIG. 16, there is shown a further form of cartridge 160 comprising a first compartment 15 holding a first substance and a second compartment 16 holding a second substance, the compartments being The first material and the second material are separated by a fragile seal 19 'that can be broken so that the first material and the second material can be fused. The second compartment 16 is separated from the female luer lock fitting 12 by a second fragile seal 19 "that can be broken to allow fluid communication between the cartridge and a dispensing device such as a syringe or syringe. The combination 12 comprises a fluid passage 161 and a static mixer 162 disposed in the fluid passage 161. This configuration is used when the fused first and second materials are transferred from the cartridge 160 to the dosing device. The static mixer is configured to facilitate the mixing of these materials to produce a more uniform product, an example of a static mixer is US Pat. No. 4,538,920, the mixture may be further reciprocated between the delivery device and the cartridge in order to repeat the mixing action in the static mixer. The static mixer is configured as a pattern of passages formed between the walls of the flexible package by welding and pre-forming specified areas of the wall. It may be a nozzle or a porous member housed in the flow path between the cartridge and the delivery device.

  FIG. 17 shows a preferred embodiment where the cartridge 170 contains a first substance and comprises a compartment 171 separated from the female luer lock fitting 12 by a fragile seal 19 ″. The fitting comprises a fluid passage 161 and a fluid. A static mixer 162 disposed in the passage 161. A syringe 173 containing a second substance 174 is attached to the cartridge 170. A fragile seal 19 "allows the first and second substances to fuse. Can be broken. By pulling the syringe piston, the first substance is sucked into the syringe from the compartment 171 and fused with the second substance in the syringe. The syringe piston may be operated back and forth to transfer at least a portion of the mixture into and out of the cartridge 170 and create a more uniform mixture as the material flows through the static mixer 162. In one form, the compartment 171 is sufficiently inflatable to receive the entire amount of the first material and the second material. In some forms, the cartridge 171 may include one or more compartments that are integrated with the first compartment 171 before or after the first compartment is integrated with the syringe. It will be apparent to those skilled in the art that static mixing can be performed in any of the previous forms of the present disclosure in a form similar to that of FIG. 16 or FIG. In particular, referring back to FIGS. 3 and 4, a static mixer may be placed in the stem or plunger of the syringe.

  18 is arranged between the first compartment 15 containing the first substance, the second compartment 16 containing the second substance, the first compartment 15 and the second compartment 16, An alternative form of cartridge 180 is shown comprising a static mixer 184 separated from a first compartment 15 by a fragile seal 181 and separated from a second compartment 16 by a fragile seal 182. At the position where the first material and the second material are mixed so that the upper wall 183 is reconfigured as shown by the broken line 183 ′ and the first material and the second material can communicate with each other via the static mixer 184. The first fragile seal 181 and the second fragile seal 182 are broken. Since the first compartment 185 of the first compartment 15 and the recess 186 of the second compartment are inflatable to receive material from other compartments, the first compartment 15 and the second compartment 16 are It does not swell completely. Therefore, by alternately compressing the first compartment 15 and the second compartment 16 and transferring the mixture of the first substance and the second substance through the static mixer 184, the first substance and the second substance are mixed. Good mixing may be achieved. The static mixer 184 is shown here as a porous body and is alternatively other static mixers well known in the art.

  The third fragile seal 19 "can be broken to establish communication between the mixture and the mating body 12. This configuration further includes a backing 187 supporting the cartridge 180, a first compression panel 188 'and A rocker with a second compression panel 188 ″, for the backing 187 to alternately press the first compartment 15 by the first panel 188 ′ and the second compartment 16 by the compression panel 188 ″. The rocker and backing arrangements compress the compartments 15 and 16 more efficiently and in order and transport the contents across the static mixer 184. This facilitates the efficient implementation of the mixing process, when the first compartment 15 is emptied when ready to transfer the mixture through the fitting 12 to the dosing device. The shrunken panel 188 'may be stationary so that substantially all of the mixture is squeezed from the second compartment 16 to the mating body 12. The rocker is attached to the backing 187 via a hinge or living hinge. It may be coupled and may be operated manually or using a device.

  FIG. 19 shows the first compartment 15 containing the first substance, the second compartment 16 containing the second substance, and the substances reciprocating between the first compartment 15 and the second compartment 16. FIG. 5 shows another form of cartridge 190 with a pre-formed row of intersecting flow paths that form a static mixer that facilitates mixing of the first and second materials when they are made.

  Referring now to FIGS. 20a-20e, one possible cartridge manufacturing process is described. In one form, the manufacturing process is realized based on a molded, filled and sealed system.

  FIG. 20a is a preformed flexible wall 18 ′ of a package for storing the benefit agent component, the first cavity 15 receiving the first component, and the second cavity 16 receiving the second component; A first continuous region 19 ′ between the cavities, a fitting body cavity for receiving the fitting body, and a second continuous region 19 ″ between the second compartment 16 and the fitting body cavity 203. The first compartment is a non-flowable material such as powder, compacted or agglomerated powder, granules, pellets, solids, tablets, capsules, slurries, pastes, high viscosity fluids, emulsions, and combinations thereof. Alternatively, the first substance is filled into the first compartment by means of a suitable filling system for the type of material that needs to be filled. Fill with water or other low viscosity fluid Can also Rukoto, because it may cause outflow by other properties of the surface tension or fluid, it may be difficult to fill the cavity 16 completely.

  Another challenge is that the liquid filling is a relatively time consuming manufacturing process due to many factors, one of which is to prevent foaming or bubble formation when the liquid is filled into the cavity 16. It is to be. In one form, the task is to freeze the aliquot of fluid in a mold that preferably has the shape of the second compartment 16, and then treat the aliquot as a solid by one of the means well known in the art. It is solved by introducing to. The filling system is designed such that heat transfer to the frozen liquid aliquot is suppressed such that the frozen liquid aliquot remains substantially solid until the second cavity 16 is sealed, and after sealing, The frozen solution can be thawed. Heat transfer to the frozen aliquot during the filling process may be suppressed by controlling the temperature during this process substantially low and selecting the contact material to the package using an appropriate heat transfer coefficient. . Prior to introduction into the second cavity 16, the frozen aliquot may be inspected for weight and other characteristics and parameters.

  In one form, one or more frozen aliquots (which may have the same, similar or different composition) are filled into the second compartment 16. These aliquots may have complementary shapes that substantially form the shape of the second compartment 16 together. In one form, the aliquot is frozen directly in the cavity 16 or on the reciprocal flat wall 18 ″ (not shown) of the package. In another form, the second substance is placed in the second compartment 16. A loose powder or other form of dispersible dry substance that can be difficult to fill substantially completely, which is a limiting factor in production rate and makes it difficult to properly check the aliquot fill dose In one form, to facilitate powder filling, the powder is slightly compressed to form loosely agglomerated tablets, or a single body, one of the tablet filling methods well known in the art. In order to achieve a degree of agglomeration at a predetermined compression rate, a dedicated manufacturing method may be required.The tablet fills the second compartment 16 It may be tested before or during the filling process extent.

  In one embodiment, after the tablet is sealed in the compartment, the compartment is operated from the outside to bring the tablet into a non-agglomerated state, thereby increasing the solubility (or dispersibility) of the substance when mixed with the diluent. Improve. External operations include, but are not limited to, compression of the compartment, ultrasonic vibration, high frequency vibration, vibration including acoustic vibration, application of mechanical shock to the compartment, exposure to high or low temperature. Directing energy through the wall of the package into a single body by at least one of the following. In one form, the unitary body is formed directly in the cavity 16 or on the mutual flat walls 18 "(not shown) of the package. The first compartment 15 has a low viscosity to substantially fill the cavity 15. The first filling well 201 ′ and the second filling well 201 ″ are pre-formed on the first wall 18 ′ and the first preformed filling channel 202 is provided. 'And the second preformed fill channel 202 "connect the first and second fill wells to the first compartment 15. FIG. 20a shows a portion of the web formed to contain the details of one cartridge. It will be appreciated by those skilled in the art that in a normal manufacturing practice, an array of details for a plurality of cartridges can be formed in a large extent of the first web 18 'and processed simultaneously in subsequent molding and filling steps. Like.

  FIG. 20 b shows the next step in the manufacturing process of the cartridge 200. After the second compartment 16 (in this figure, behind the cartridge 200) is filled and sealed with the lid web 18 ", the web 18" is sealed to the entire continuous surface of the first wall 18 '. In one form, the inner layer of the first web 18 'and / or the second web 18' comprises an adhesive having a controllable peel (adhesion) force and is peelable due to a low sealing temperature (eg, 375 ° F). Adhesion (“fragile seal”) occurs, and high non-peelable adhesion occurs due to high sealing temperatures (eg, 450 ° F.). In one form, in the first sealing step shown in this figure, substantially all of the continuous surface of the web 18 ′ is adhered to the second web 18 ″ to completely surround the second compartment 16, and A fragile seal is formed that substantially surrounds the second compartment 15 except for the fill channels 202 ′ and 202 ″. Here, in a state where the second web 18 ″ is attached to the first web 18 ′, a filling compartment and an exhaust compartment are formed, and the first compartment 15 is formed via a flow path formed between the two webs. Communicate with.

  The first fill hole 204 'and the second fill hole 204 "are one of the means well known in the art, such as stamping, die cutting, and laser cutting, before introducing the second web 18" into the first wall 18'. May be pre-formed in the second web 18 ". In one form, the second filling hole 204" allows gas to be discharged from the first compartment 15 during filling while the first compartment 18 ". The chamber is filled with the first substance through the first filling hole 204 ′. To facilitate the introduction of material into the first compartment, a filling source can be connected to at least one of the fill holes 204 ′ and 204 ″ during the filling process to draw gas through the exhaust compartment. In one form, the fill coupler is a needle or tube that is curved to reach into the first fill channel 202 '.

  In one form, the fill coupler has a cylindrical tip that is larger in diameter than the fill hole 204 'so that when introduced into the fill hole 204', it tightly fits and fluid-tightly seals. In one form, the fill holes 204 ′ and 204 ″ are not pre-formed, and a sharp object (such as a hollow needle) that fills pierces the second wall 18 ″ in a fluid tight manner to fill wells 201 ′ and 201 This last form is particularly beneficial because the package is sealed prior to the introduction of components that can be performed on different parts of the filling line or on different lines. Between the sealing and filling steps. In one form, in order to facilitate sealing of the filling coupler to the cartridge, a rubber seal or semi-rigid seal is used to fill the filling wells 201 ′ and 201 ″ that form a boundary to the filling source. Arranged in at least one. In one form, the cross section of the flow path is sufficiently small to prevent leakage of the fill material from the first compartment 15 due to the surface tension of the material.

  In one form, a check valve is disposed in at least one of the first fill well 201 ′ and the second fill well 201 ″ to control the flow of material into the first compartment 15. A semi-permeate may be placed in one of the fill port 201 and the fill channel 202 to allow gas outflow therein and prevent material from exiting the first compartment 15. In one form, the outflow from the first cavity 15 during filling is monitored and filling is interrupted when the outflowing fluid switches from gas to filling material, and the first filling channel 204 ′ is in the first compartment. The ingressing material is made to slide over the second wall 18 ", thereby preventing jetting that can cause undesired bubbles or foaming of the filled dose. A dedicated flow deflector may be placed in the fill channel 202 or the fill well 201 to facilitate sliding of the fill material on the wall of the first compartment 15.

  FIG. 20 c shows the next step in the manufacture of the cartridge 200. In the second welding step, the flow paths (202 ′) and (202 ″) are pressed and welded to completely seal the first substance in the first compartment 15. The seal temperature is determined by the flow path (202 ′). ) And (202 ″) may be higher than the brittle seal welding temperature. In one form, the sealing step is further applied to the peripheral edge of the cartridge 200 to impart permanent sealability to at least a portion of the region previously sealed as a fragile seal. In order to facilitate welding and sealing of the flow path, a sealable insert may be placed in the flow path.

  Referring now to FIG. 20d, the cartridge is cut from the edge of the web by one of the means well known in the art, including stamping, ruler steel cutting, laser cutting, and the like.

  Those skilled in the art will appreciate that the order of the above manufacturing steps can be modified in whole or in part to be optimal for a particular design, application, and manufacturing facility.

  The fitting 12 is a fragile seal welding step by one of means for welding fittings known in the art including, for example, thermal stake welding, impulse welding, vibration welding, ultrasonic welding, RF welding, and beam welding. Before or during the step, before or during the permanent seal welding step, or in the next step, between the first wall 18 'and the second wall 18 ".

  FIG. 21a shows a three-dimensional exploded view of a syringe 210 with a static mixer for mixing substances. In one form, the first material is contained within the syringe 210 and the second material is transferred from a cartridge (not shown) to the syringe. In the syringe, the second substance is mixed with the first substance. In another form, at least the first substance and the second substance are separately or premixed and transferred from one or more cartridges (or another source of substance) to a syringe, within which the substance Alternatively, a mixing step is applied to the mixture. In some forms, the cartridge is coupled to the syringe 210 in a manner similar to that of FIG. Plunger 214 is movably disposed within syringe barrel 212 in a fluid tight manner. The piston 213 is coaxially arranged to be movable in the annular hole of the plunger 214 in a fluid tight manner. The piston further comprises a static mixing plate (or static mixer) 217 extending laterally from the distal end of the piston 213. A local axial groove 215 in the annular bore of the plunger 214 is made to receive a locking tooth 216 projecting laterally of the piston 213.

  FIG. 21 b shows a cross-sectional view of the mixing syringe 210 containing the first substance 218.

  FIG. 21 c shows a cross-sectional view of the mixing syringe 210 with the piston retracted to the proximal end side of the barrel 212. The static mixer pushes the plunger with the piston, allowing the second material to enter the barrel 212 to form the mixture 218 '. Although the source of the second substance is not shown, it may be a cartridge connected to the syringe 210 in one of the forms provided in the present disclosure as described above. When the second substance does not enter the syringe 210 from the tip of the luer, the tip of the luer may be sealed with a cap, a lid, a valve, or another means so that no flow is generated from the tip when the piston is retracted. I understand.

  FIG. 21d shows a mixing step in which the piston 213 is reciprocated to divert the mixture 218 ′ to flow through the gaps in the static mixer 217 and promote mixing of the mixture 218 ′ to produce a uniform product. Show. The locking teeth 216 are aligned with an axial groove 215 (not shown) so that the piston can move freely relative to the plunger 214. The plunger slides freely along the barrel, making up for the stem of the piston that moves into and out of the sealed volume between the barrel 212 and the plunger 214. In one form, the piston is rotatable to further facilitate mixing. In one form, the static mixing plate is replaced with another static mixer known in the art, such as a porous material. In one form, the piston is operated by a device such as a controlled electric actuator. The syringe tip and other ports to the syringe are preferably plugged during the mixing process to prevent the outflow of the mixture 218 'or the introduction of material into the barrel 212.

  FIG. 21 e retracts the piston so that the locking teeth 216 enter the axial groove 215 (not shown) and the locking teeth 215 engage the radial groove 219 of the plunger 214. The syringe 210 is shown when the plunger 214 and the piston 213 are firmly engaged with each other at the rotated position and can move together. In one form, the barrel and plunger have a non-axisymmetric cylindrical profile to prevent rotation of the plunger due to rotation of the piston 213. In one form, the plunger 214 includes a hard core to facilitate engagement with the piston 213. If the tip of the syringe 210 is not plugged, the mixture 218 ′ is administered by advancing the piston 213 and plunger 214 toward the distal end of the syringe 210.

  The partial cross-sectional views of FIGS. 22a and 22b illustrate a cartridge coupled to a fixed needle syringe. The cartridge 10 includes a first material compartment 15 and a second material compartment 16 separated by a breakable barrier 19 '. The cartridge 10 further includes a fitting body 222 for communicating the contents of the cartridge 10 with the fixed needle syringe 221. The proximal end 224 of the mating body 222 is sealed between the first wall 18 ′ and the second wall 18 ″ of the cartridge 10 and directly seals the first wall 18 ′ and the second wall 18 ″. Is separated from the second compartment 16 by a breakable barrier 19 "formed by the distal end 223 of the fitting 222 is made to removably receive the tip of the syringe 221 in a fluid tight manner, The proximal end 224 of the fitting 222 is made to receive and protect the tip of the needle 225. A passage 226 in the fitting 222 communicates between the needle and the contents of the cartridge 10. The cartridge 10 provides a sterile needle protector for the needle 225.

  In one form, the original needle protector (not shown) is removed from the syringe and replaced with a cartridge 10. The contents of the cartridge 10 are transferred to the syringe 221 after breaking the second barrier 19 ". In some forms, the cartridge 10 is attached to the syringe during the manufacturing process. In one form, the cartridge 10 Has only one compartment, In one form, the cartridge has at least two compartments that are integrated prior to transferring the contents of the cartridge 10 to the syringe 221. In one form, the syringe 221 is an injection. At the end, it includes a safety mechanism that retracts at least a portion of the needle 225 to a position that protects against needle sticks, In one form, the syringe 221 prevents needle sticks that at least partially protect the needle tip after the injection of the contents is complete. A safety mechanism is provided.

  Typically for a fillable syringe, the syringe is sent to the filling process and disassembled and fully assembled after the contents are filled. The configurations of FIGS. 22a and 22b are: (a) a syringe 221 is supplied, assembled and completed, (b) the cartridge 10 is filled with the desired contents, the cartridge 10 is sealed, and (c) the cartridge An effective manufacturing method for assembling 10 is provided. This process may be completed in an aseptic environment or the product may be terminally sterilized. Thus, this approach allows for the manufacture of filled syringe assemblies that do not require assembly of actual syringe components. In addition, special syringe labels or packages that provide content information may be required and the cartridge may be printed and labeled with this information. The label, i.e., a portion of the label on the cartridge 10, can be replaced with a syringe to maintain product identification after the cartridge 10 is removed.

  22a and 22b illustrate a cartridge 10 with two integrable material compartments, it will be appreciated by those skilled in the art that the cartridge 10 may comprise only one compartment or more than one compartment. Will be clear. While the connection between the syringe 221 and the mating body 222 is shown as a fluid tight sliding fit, other mating mechanisms may be incorporated to facilitate sealing, assembly, or disassembly. For example, screws, spiral ramps, luer fittings, luer lock fittings, o-rings, rubber seal members, interlock mechanisms, snap mechanisms, and other well known in the art that facilitate fluid tight and removable connections Including mechanisms, or combinations thereof. The distal end 224 of the mating body 222 fits tightly around the needle 225, prevents the contents of the cartridge 10 from reaching the space between the mating body 222 and the needle 225, and air is in that region. A fluid seal can be achieved that prevents the needle from entering the needle. The fitting may be manufactured at least partially from an elastic material. The fitting 222 may be designed to receive the cartridge 10 in different orientations relative to the syringe, and in one form, the cartridge 10 and the syringe 221 may overlap at least partially or be juxtaposed. It will be apparent to those skilled in the art that this may be done. The piston and barrel of the syringe 225 are sealed at the proximal end of the piston and barrel with a sterile membrane 229 so that the content contact surfaces remain sterile until use and without the need for a sterile overwrap. May be.

  Referring to the enlarged partial cross-sectional view of FIG. 23a in FIGS. 23a and 23b, another preferred form of cartridge and fixed needle syringe is illustrated. The fixed needle adapter 237 is axially disposed around the needle 225 and connected to the tip of the syringe 221 in a fluid tight manner. Adapter 237 protects the needle from physical damage and protects the operator and subject from needle stick accidents. The distal end of the needle 225 is further supported by a centering glider 238 disposed coaxially within the adapter 237 and around the needle 225. The mating body 232 of the cartridge 10 includes a proximal portion 234 attached to the wall of the cartridge and a distal end 233 having an elongated cylindrical shape that can be inserted axially into the syringe adapter 237. In this configuration, the needle 237 remains protected until the cartridge 10 is assembled.

  The enlarged partial cross-sectional view of FIG. 23c in FIGS. 23c and 23d illustrates the configuration of FIGS. 23a and 23b when the syringe assembly 231 and the assembly of the cartridge 10 are engaged. The distal end 233 of the mating body 232 is inserted into the adapter 237 and advances by pushing the centering member 225 to expose most of the distal end of the needle that passes through the passage 236 of the mating body, and the syringe 221 and the cartridge 10 Establish fluid communication with The fluid seal can be realized by an interference fit between the needle 225 and the fitting body 237. In order to improve the sealing performance with the needle 225, the fitting body 237 may be manufactured at least partially from an elastic material. The mating body 237 further seals the distal end 233 or other portion along the passage 236 to further enhance the seal between the mating body 237 and the needle 225 and the mating body is assembled to the cartridge 10. A member for further maintaining the cleanliness of the passage 236 may be included.

  The contents of the cartridge 10 are sucked into the syringe 221. As an alternative to the seal between the needle 225 and the fitting body 237, (a) the centering member 238 and the adapter 237, (b) the centering member 238 and the needle 225, (c) the tip of the syringe 221 and the adapter 237, and d) A seal can be established between the fitting 232 and the adapter. In some forms, two or more substance compartments in the cartridge 10 are integrated and mixed before the contents are transferred to the syringe 221. In some forms, the substance in the syringe 221 is transferred and fused with the substance in the cartridge 10, after which the fused product is aspirated. For example, the cartridge 10 may contain a dry substance and the syringe 221 may contain a diluent. The diluent is transferred to the cartridge 10 to dissolve the powder and the fused product is returned to the syringe, administered to the subject, or transferred to another device. In one form, the syringe is pre-filled with the substance and the contents of the cartridge 10 are transferred to the syringe 221 to allow the contents to merge with the substance in the syringe 221.

  The enlarged partial cross-sectional view of FIG. 23e in FIGS. 23e and 23f illustrates the configuration of FIGS. 23c and 23d when the cartridge is removed. The adapter 237 remains in the cartridge 10 where the syringe 221 is ready for injection and exposes the needle. In one form, a mechanical interlock ensures that the adapter 237 remains in the cartridge 10. Such mechanical engagement may include screws, helical ramps, snaps, interference fits or other engagement and disengagement mechanisms well known in the art. In one form, the adapter 237 remains in the syringe 221 when the cartridge 10 is removed and is removed by the operator prior to injection to continue to protect and protect the needle 225 from the needle 225.

  24 is similar to the configuration of FIG. 23 except that a rubber septum 241 is disposed at the tip of the needle and a spring 242 biases the centering member 220 and the septum 241 toward the distal end of the adapter 237. Another form of is illustrated. The needle is aseptically sealed by a septum 241. In order to transfer material between the cartridge 10 and the syringe 221, the distal end 233 of the fitting body 232 is inserted into the adapter 237, the partition wall and the centering member are displaced rearward, and the tip of the needle 225 is fitted to the fitting body. 232 is exposed to passage 226 in 232. When the cartridge 10 is removed, the spring 242 causes the septum to return and cover the tip of the needle 225, protecting the needle 225 from mechanical damage and contamination until use. The adapter 237 is removed together with the spring 242, the centering member 220, and the partition wall 241 before using the syringe 221.

  FIG. 25a illustrates a prefilled cartridge comprising a coupler 250 and a package connected via a mating body 257. FIG. The coupler assembly includes a needle assembly 253 that includes a luer lock hub 255 and a stainless steel cannula 254 attached to the hub. Needle assembly (or needle) 253 is housed in a needle cap formed in coupler 251. The coupler further includes a fluid passage 258 that communicates the needle 253 with the package 10. A rubber sheath 252 disposed within the coupler 251 forms a sterile seal between the needle hub 255 and the coupler. The tip of the rubber sheath 252 forms a fluid tight lid for the fluid passage 258 that is pierced by a cannula 254 to establish fluid communication between the needle 253 and the package. The luer end 256 of the needle hub 255 is sealed with a removable sterile lid in the form of a sealing foil, lid or other means known in the art. The package 10 includes a breakable first barrier 19 'that separates the first compartment containing the first component and the second compartment 16 containing the second component, and when the breakable barrier breaks, One component and the second component are fused. In another construction, the package 10 includes one component of a benefit agent. In yet another embodiment, the package comprises at least a third compartment containing a third component separated from the second or first compartment by a breakable barrier. The breakable second barrier 19 ″ provides a lid between the second compartment 16 and the mating body 257 leading to the passage 258 in the coupler 251.

  Fig. 25b is the configuration of Fig. 25a after the breakable first and second barriers have been opened, allowing the fusion of the first and second components and the needle of the mixture 16 'via the coupler 251 The form which established the fluid communication with H.253 is shown in figure. This configuration provides a simple filled cartridge that can be attached to a standard luer syringe 259 by engaging the female luer connector of the needle 253 with the male luer of the syringe 259. The product 16 'can then be taken into the syringe by retracting the piston of the syringe, after which the coupler is removed and the needle 253 is exposed for injection, as shown in FIG. 25c. In one construction, the syringe either aspirates the product 16 'into an already partially filled syringe or first discharges the third component from the syringe to the package 10 and then the mixture into the syringe or different delivery device By pulling back, a third component that fuses with the product 16 'may be accommodated. Coupler 251 further provides a backing for a portion of package 10.

  FIG. 26 includes a package 10 adapted to communicate with a syringe 260, includes an intradermal (ID) injection adapter (ID adapter), and facilitates easy insertion of a needle 262 shallowly into the skin ( 1 illustrates a unit dose sterile reconstituted filled cartridge with forward proofing skid) 264. FIG. US 2010/0137831 and US 2011/0224609 teach similar forms of adapters for facilitating intradermal injection, which are incorporated by reference in their entirety. Is incorporated herein by reference. The ID adapter may be an integral part of the syringe 261 or a fastener on the syringe that forms an ID syringe. A recess 267 is formed in the skid 264 so that the mating body 265 of the package 10 can be easily introduced into the needle hub 266 of the syringe 260.

  FIG. 27a illustrates the cartridge 10 mounted on an ID syringe in which the cartridge 10 and syringe 260 are positioned in a linear arrangement. From this figure, the orientation of the cross-sectional view of FIG. FIG. 27b illustrates the fitting 265 press fit into a needle hub 266 that forms a sterile connection. The rubber stopper provides a lid for the passage 272 and is pierced by the needle 262 to establish fluid communication between the syringe and the package 10.

  FIG. 28 illustrates a configuration similar to that of FIG. 10 except that the fitting 281 is made so that the package 10 is positioned parallel to the syringe barrel rather than in line with the syringe axis. .

  FIGS. 29 a and 29 b illustrate a cartridge structure comprising a coupler 293 that communicates the intradermal needle assembly 291 and the package 10. The coupler houses a needle assembly comprising a cannula 292 and a needle hub 291 with a forward projecting skid at the distal end and a luer connector at the proximal end 297. Coupler 293 is used as a sterile cap engaged to needle hub 291 in sealing area 299 that maintains the needle 292 and skid area in a sterile condition. The luer cap 298 aseptically seals the luer connector 297 of the needle hub 291 forming an integrally sealed cartridge that remains sterile without the need for sterile overwrapping. The package 10 and the coupler are connected via a fitting body 296. The fitting is preferably heat welded to the wall of the package 10 and connected to the coupler by one of the methods well known in the art including heat welding, gluing or intimate mechanical fitting. A breakable seal 19 between the first compartment 15 and the second compartment 16 provides a lid that isolates the compartment from the coupler 293.

  FIG. 29b is the configuration of FIG. 29a in which the luer cap 298 is replaced with a luer syringe 250, and the breakable seal is opened to allow the components in the first compartment 15 and the second compartment 16 to merge. FIG. 5 illustrates a configuration in which fluid communication with the needle is established through the passage 295. The rubber lid 294 limits the dead space of the component in the coupler to the minute volume of the passage 295, thereby suppressing waste of the product 15 '. This figure shows the syringe piston retracted to receive product 15 'in the syringe barrel. The coupler is removed to expose the needle and ID adapter for injection. The coupler 293 provides a backing for the package 10 that facilitates pressing of the compartment of the package 10.

  FIG. 30 illustrates a cartridge configuration 300 that is similar to the cartridge configuration 290 of FIG. 29 except that an ID adapter 291 is attached to the needle hub 301. Needle hub 301, ID adapter 291, coupler 293.

  FIG. 31a shows a cartridge having a configuration substantially similar to the configuration 300 of FIG. 30 except that the needle hub is movably disposed within the ID adapter 313 and is movable between an injection position and a safety disposal position. 310 is shown. The latch mechanism 315 holds the injection position. A spring may be placed in region 312 to bias needle hub 313 to the safe disposal position. FIG. 31b illustrates configuration 310 when the latch is operated to release the needle hub. The needle assembly is retracted to move the needle tip to the containment 316 and reduce the risk of needle stick. In one form, the needle hub is permanently locked in this position to prevent repeated use of the needle.

  FIG. 32 shows a first position in which the needle assembly is movably disposed within the coupler and the needle tip 292 does not puncture the plug 294 or only partially punctures the plug, and the needle tip punctures the plug. FIG. 30 shows a cartridge configuration 320 similar to configuration 290 of FIG. 29 except that it is movable between a second position establishing fluid communication with fluid passage 295.

  Figures 33a-33c illustrate a pre-filled syringe 259 with a conventional piston and barrel syringe configuration with a fixed needle 334 for delivering medication. The syringe cap 331 communicates with the syringe in an aseptically engaged state. A cap 331 engages the package 10 and forms a removable cartridge 330. The main body of the cap 331 functions as a coupler between the fitting body of the package and the needle. Figures 33d and 33e show enlarged cross-sectional views of the cap after activation and upon activation in filling the syringe barrel with a dose. The cap includes a rubber stopper 335 that is punctured by a needle 334.

  Similar structure includes syringe with catheter, needle with soft protective sheath, intramuscular (IM) needle, subcutaneous (SQ) needle, intradermal (ID) needle, microneedle, safety needle, retractable needle, irrigation needle, etc. It will be apparent to those skilled in the art that it works with other needle devices well known in the art.

  The syringe further comprises a barrel aseptic lid 333 so that the syringe assembly remains sterile without the need for a sterile overwrap.

  FIG. 37 illustrates a configuration similar to that of FIG. 33 with the addition of a vertically projecting protective wall 341 to protect the package 10. It will be apparent to those skilled in the art that further protection of the package may be achieved by further surrounding the package with additional walls, an inverted cover coupled to the wall 341, a slidable cover, and the like.

  A package in the form of the present disclosure may display any markings including prints, barcodes, RFID tags, embossments, inscriptions to communicate the desired information to a person or device. The package may be extended to provide sufficient printing surface as needed.

  A compression panel may be coupled to the package to facilitate pressing of the at least one compartment of the package to facilitate breakage of the breakable barrier or to facilitate squeezing of the administrable product from the package.

  The above forms and methods are applicable to other syringes or dispenser types such as the jet syringe cartridge taught in FIG. 1 or other forms discussed in this document. In one form, the retractable needle mechanism, retractable needle connector mechanism, or other needle safety mechanism, and the non-reusable mechanism are incorporated into the mixing syringe mechanism described herein.

  The cartridge form of the present disclosure may be combined with multiple forms of delivery devices or applicators to easily achieve the desired form of use. A compression panel or roller may be incorporated to facilitate efficient squeezing of the contents of the cartridge.

  The application of the present invention is not limited to the syringe and jet injector applications provided herein by way of example, and the teachings described herein are for aseptic filling of micropump reservoirs, intramuscular autoinjectors, intradermal auto It can be applied to other uses such as a syringe.
[Example of invention]
[Example 1]
A cartridge for use with a delivery device for a beneficial agent having a fillable reservoir,
A reconfigurable unit dose package comprising: a first compartment containing at least a first component of the benefit agent; and at least a second compartment containing at least a second component of the benefit agent; And a mating body disposed in the package for connecting the package to the fillable reservoir.
[Example 2]
The cartridge of example 1, wherein the cartridge is adapted to communicate with a delivery portion of the delivery device comprising one of a needle, a connector, and a nozzle.
[Example 3]
The cartridge of example 1, wherein the delivery portion comprises a needle and the fitment seals around the needle to minimize fluid dead space.
[Example 4]
The cartridge according to Example 1, further comprising a breakable barrier between the first compartment and the fitting body.
[Example 5]
The cartridge of example 1, wherein the first compartment is isolated from the second compartment by a breakable barrier.
[Example 6]
The cartridge of example 1, wherein at least a portion of the package comprises a flexible wall.
[Example 7]
The cartridge of example 6, wherein at least a portion of the flexible wall comprises a foil.
[Example 8]
7. The cartridge of example 6, wherein at least a portion of the flexible wall is preformed to define at least a portion of the first compartment and the second compartment.
[Example 9]
The cartridge of example 6, wherein at least a portion of the flexible wall comprises a peelable foil layer.
[Example 10]
The cartridge of Example 9, wherein at least a portion of the peelable foil layer is preformed.
[Example 11]
The cartridge of Example 1, further comprising a fluid passage between the first compartment and the second compartment.
[Example 12]
The cartridge of Example 11, further comprising a static mixer disposed in the fluid passage.
[Example 13]
The cartridge of Example 1, further comprising a fluid passage between the package and the delivery device and a static mixer disposed in the fluid passage.
[Example 14]
The cartridge of Example 1, wherein the package includes a flexible wall that forms at least a portion of a removable sterile lid of the mating body.
[Example 15]
Example 1 further comprising a filling compartment, a fluid passage, a first package wall and a second package wall, wherein the filling compartment is in fluid communication with the first compartment via the fluid filling passage. Cartridge.
[Example 16]
The cartridge of example 15, wherein the filling compartment is located between the first package wall and the second package wall.
[Example 17]
The cartridge of example 15, wherein the fluid passage is sealable to prevent back flow into the filling compartment during or after filling.
[Example 18]
The cartridge of example 15, further comprising a heat seal between the first package wall and the second package wall of the package to seal the fluid passage.
[Example 19]
The cartridge of example 15, further comprising a shut-off valve disposed in at least one of the filling compartment and the filling passage.
[Example 20]
The cartridge of example 15, wherein the filling compartment is at least partially defined by a well formed in at least one of the first package wall and the second package wall of the package.
[Example 21]
The cartridge of example 15, further comprising a filling system configured to communicate with the filling compartment through a fluid tight seal.
[Example 22]
The cartridge of example 15, wherein the filling passage is configured to guide a fluid dose of the package fluid along the first package wall of the first compartment to prevent ejection.
[Example 23]
An example further comprising a gas discharge chamber communicating with the first compartment through a fluid discharge passage, wherein the fluid discharge passage is sealable to prevent flow from the first compartment after filling. 15. The cartridge according to 15.
[Example 24]
The cartridge of example 1, wherein at least a portion of the package comprises a tubular structure.
[Example 25]
The cartridge of Example 1, further comprising a lid that isolates the first compartment from the fitting until it is opened.
[Example 26]
A sterile cartridge for use with a benefit agent delivery device having a fillable reservoir,
A first compartment comprising a package, the package containing at least one component of the benefit agent, wherein the package is at least partially defined by a preformed flexible wall; And a mating body disposed on the package for connecting the package in fluid communication with the filling reservoir.
[Example 27]
The package includes a first compartment containing a first component of the benefit agent and a second compartment containing a second component of the benefit agent from the first compartment by a breakable barrier. 27. The cartridge of example 26, comprising a second compartment that is isolated.
[Example 28]
The cartridge of example 26, wherein at least a portion of the flexible wall comprises a foil or film.
[Example 29]
The cartridge of example 26, wherein at least a portion of the flexible wall comprises a peelable foil layer.
[Example 30]
30. The cartridge of example 29, wherein at least a portion of the peelable foil layer is preformed.
[Example 31]
27. The cartridge of example 26, further comprising a fluid passage extending between the first compartment and the second compartment.
[Example 32]
32. The cartridge of example 31, further comprising a static mixer disposed in the fluid passage.
[Example 33]
27. The cartridge of example 26, further comprising a fluid passage located between the package and the delivery device, and a static mixer disposed in the fluid passage.
[Example 34]
27. The cartridge of example 26, wherein the package includes a flexible wall that extends to form at least a portion of a sterile lid of the mating body.
[Example 35]
An example further comprising a filling compartment, a fluid filling passage, a first package wall and a second package wall, wherein the filling compartment is in fluid communication with the first compartment via the fluid filling passage. 27. The cartridge according to 26.
[Example 36]
36. The cartridge of example 35, wherein the filling compartment is located between the first package wall and the second package wall.
[Example 37]
36. The cartridge of Example 35, wherein the fluid passage is sealable to prevent backflow into the filling compartment during or after filling.
[Example 38]
36. The cartridge of example 35, wherein the fluid filling passage is sealed by heat sealing between the first package wall and the second package wall.
[Example 39]
36. The cartridge of example 35, further comprising a shut-off valve disposed in at least one of the filling compartment and the fluid filling passage.
[Example 40]
36. The cartridge of example 35, wherein the filling compartment is at least partially defined by a well formed in at least one of the first package wall and the second package wall.
[Example 41]
36. The cartridge of example 35, further comprising a filling system configured to communicate with the filling compartment through a fluid tight seal.
[Example 42]
36. The cartridge of example 35, wherein the fluid filling passage guides fluid held by the package along a first package wall to prevent ejection.
[Example 43]
36. The cartridge of Example 35, further comprising a gas discharge chamber communicating with the first compartment through a fluid discharge passage that can be sealed to prevent flow from the first compartment after filling.
[Example 44]
27. The package of example 26, further comprising a lid that isolates the first compartment from the fitting until it is opened.
[Example 45]
A cartridge for use with a delivery device for a beneficial agent having a fillable reservoir,
Backing and
A package assembly,
The package assembly couples the package in fluid communication with the fillable reservoir with at least a first compartment containing at least one component of the benefit agent and at least partially defined by a flexible wall. And a fitting body arranged in the package.
[Example 46]
The cartridge of example 45, wherein the cartridge and the delivery device are coupled via the backing.
[Example 47]
46. The cartridge of Example 45, wherein the backing comprises a fluid passage that interconnects the cartridge and the delivery device.
[Example 48]
48. The cartridge of example 47, wherein the fluid passage is aseptically sealed.
[Example 49]
48. The cartridge of example 47, wherein the fluid passage comprises a lid that isolates the compartment of the package from the reservoir until opened.
[Example 50]
46. The cartridge of example 45, further comprising a breakable barrier between the first compartment and the fitting.
[Example 51]
46. The example 45, wherein the package assembly comprises at least a second compartment containing at least a second component of the benefit agent, the second compartment being separated from the first compartment by a breakable barrier. Cartridge.
[Example 52]
The cartridge of example 45, wherein at least a portion of the flexible wall comprises a foil.
[Example 53]
53. The cartridge of example 52, wherein the flexible wall is preformed to define at least a portion of the first compartment.
[Example 54]
The cartridge of example 45, wherein at least a portion of the flexible wall comprises a peelable foil layer.
[Example 55]
55. The cartridge of example 54, wherein at least a portion of the peelable foil layer is preformed.
[Example 56]
46. The cartridge of example 45, further comprising a fluid passage located between the first compartment and the second compartment.
[Example 57]
The cartridge of Example 56, further comprising a static mixer disposed within the fluid passage.
[Example 58]
The cartridge of Example 54, further comprising a static mixer disposed in a fluid passage positioned between the package assembly and the delivery device.
[Example 59]
The cartridge of example 45, wherein the flexible wall extends to form at least a portion of a sterile lid of the mating body.
[Example 60]
A filling compartment, a fluid filling passage, a first package wall and a second package wall are further provided, and the filling compartment is disposed in fluid communication with the first compartment via the fluid filling passage. The cartridge of Example 45.
[Example 61]
61. The cartridge of example 60, wherein the filling compartment is located between the first package wall and the second package wall.
[Example 62]
The cartridge of Example 60, wherein the fluid passage is sealable to prevent backflow into the filling compartment after filling.
[Example 63]
The cartridge of Example 60, wherein the fluid passage is sealed by heat sealing between the first package wall and the second package wall.
[Example 64]
The cartridge of example 15, further comprising a shut-off valve disposed in at least one of the filling compartment and the filling passage.
[Example 65]
The cartridge of example 15, wherein the filling compartment is at least partially defined by a well formed in at least one of the first package wall and the second package wall.
[Example 66]
The cartridge of Example 60, further comprising a filling system configured to communicate with the filling compartment through a fluid tight seal.
[Example 67]
The cartridge of example 60, wherein the fluid filling passage guides fluid retained by the package along a first package wall to prevent ejection.
[Example 68]
An example further comprising a gas discharge chamber communicating with the first compartment through a fluid discharge passage, wherein the fluid discharge passage is sealable to prevent flow from the first compartment after filling. 60. The cartridge according to 60.
[Example 69]
The delivery device is a medical syringe, a fixed needle syringe, a safety syringe, a retractable needle syringe, an auto-invalidating syringe, an automatic syringe, a jet syringe, an intradermal syringe, a hypodermic syringe, an intramuscular syringe, an infusion device, an infusion pump, a slow The cartridge of Example 45, selected from the group consisting of a releasable delivery system and a patch pump.
[Example 70]
A cartridge for use with a delivery device for a beneficial agent having a fillable reservoir,
A package, the package connecting the package in fluid communication with at least a first compartment containing at least one component of the benefit agent, a fitting disposed in the package, and the refillable reservoir; And a coupler coupled to the fitting.
[Example 71]
71. The cartridge of example 70, wherein the coupler comprises a lid that blocks the fluid communication until opened.
[Example 72]
The cartridge of Example 70, wherein the coupler is sterile sealed.
[Example 73]
The cartridge of example 70, wherein the coupler comprises an injection needle connectable to the delivery device.
[Example 74]
74. The cartridge of example 73, wherein the coupler comprises a membrane that blocks the fluid communication and is piercable at the tip of the injection needle.
[Example 75]
75. The cartridge of example 74, wherein the injection needle is movable from a first position where the membrane is not punctured to a second position where the membrane is punctured.
[Example 76]
The cartridge of Example 70, wherein the coupler is configured to communicate with a dispensing device.
[Example 77]
The cartridge of Example 70, wherein the coupler comprises a valve that controls flow into and out of the package.
[Example 78]
78. The cartridge of example 77, wherein the valve is activated by relative movement between the fitting and the coupler.
[Example 79]
The cartridge of example 70, wherein at least a portion of the package is separable from the coupler after the reservoir is at least partially filled with the benefit agent.
[Example 80]
Example 70, wherein the coupler comprises a safety device from the group consisting of a needlestick prevention device and a reuse prevention device, wherein the safety device is coupled to the delivery device when a portion of the cartridge is removed from the delivery device. Cartridge.
[Example 81]
The cartridge of example 70, further comprising a backing for the package.
[Example 82]
The cartridge of example 70, wherein the coupler is configured as a cap of the delivery device.
[Example 83]
The delivery device is a medical syringe, a fixed needle syringe, a safety syringe, a retractable needle syringe, an auto-invalidating syringe, an automatic syringe, a jet syringe, an intradermal syringe, a hypodermic syringe, an intramuscular syringe, an infusion device, an infusion pump, a slow The cartridge of Example 70, selected from the group consisting of a releasable delivery system and a patch pump.
[Example 84]
The cartridge of example 70, wherein the coupler comprises at least a portion of a syringe piston.
[Example 85]
The cartridge of example 70, wherein the coupler comprises at least a portion of a syringe barrel.
[Example 86]
The cartridge of Example 70, wherein the coupler and mating body are joined by at least one of press fit, heat welding, and joining.
[Example 87]
71. The cartridge of example 70, wherein the coupler communicates with a delivery device syringe comprising a needle and is configured to be coupled to the mating body when the package is joined to the syringe.
[Example 88]
90. The coupler of example 87, wherein the delivery device includes a needle protector that is removable when the package and the syringe are coupled.
[Example 89]
90. The coupler of Example 87, wherein the delivery device includes a sterile lid for the needle that is held until the package and syringe are combined.
[Example 90]
90. The coupler of example 87, wherein the coupler is configured to position the center within the coupler.
[Example 91]
The coupler of example 87, further comprising a plug disposed within the inner bore of the coupler, wherein the coupler is axially movable between a distal tip of the needle and a proximal end of the needle.
[Example 92]
88. The cartridge of example 87, wherein the coupler remains coupled to the mating body when the cartridge is removed from the syringe.
[Example 93]
71. The coupler of example 70, further comprising a fluid passage for fluid communication between the package and the reservoir, wherein the fluid passage is terminated by a membrane pierceable by a syringe needle.
[Example 94]
The cartridge of Example 70, wherein the package includes at least one flexible wall preformed to define at least a portion of the first compartment.
[Example 95]
The cartridge of example 70, wherein the package includes at least one flexible wall having a peelable foil layer portion.
[Example 96]
The cartridge of Example 95, wherein at least a portion of the peelable foil layer is preformed.
[Example 97]
71. The cartridge of example 70, further comprising a fluid passage located between the first compartment and the second compartment of the package.
[Example 98]
30. The cartridge of example 28, further comprising a static mixer disposed within the fluid passage.
[Example 99]
The cartridge of example 70, further comprising a fluid passage positioned between the package and the delivery device, and a static mixer disposed in the fluid passage.
[Example 100]
The cartridge of example 70, wherein the package further comprises a flexible wall extending to form at least a portion of a sterile lid of the mating body.
[Example 101]
A filling compartment, a fluid filling passage, a first package wall and a second package wall are further provided, and the filling compartment is disposed in fluid communication with the first compartment via the fluid filling passage. The cartridge of Example 70.
[Example 102]
102. The cartridge of example 101, wherein the filling compartment is positioned between the first package wall and the second package wall.
[Example 103]
102. The cartridge of Example 101, wherein the fluid passage is sealable to prevent backflow into the filling compartment after filling.
[Example 104]
102. The cartridge of example 101, wherein the fluid passage is sealed by heat sealing between the first package wall and the second package wall.
[Example 105]
102. The cartridge of example 101 further comprising a shut-off valve disposed in at least one of the filling compartment and the fluid filling passage.
[Example 106]
102. The cartridge of example 101, wherein the filling compartment is at least partially defined by a well formed in at least one of the first package wall and the second package wall.
[Example 107]
102. The cartridge of example 101, further comprising a filling system configured to communicate with the filling compartment through a fluid tight seal.
[Example 108]
102. The cartridge of example 101, wherein the fluid filling passage guides fluid retained by the package along a first package wall to prevent ejection.
[Example 109]
An example further comprising a gas discharge chamber communicating with the first compartment through a fluid discharge passage, wherein the fluid discharge passage is sealable to prevent flow from the first compartment after filling. 101. The cartridge according to 101.
[Example 110]
A cartridge for use with a delivery device for a beneficial agent having a fillable reservoir,
A unit dose package containing all of the benefit agent or all components of the benefit agent, the package containing all of the benefit agent or at least one component of the benefit agent and at least partially by a flexible wall. A cartridge comprising: at least a first compartment defined; and a mating body disposed in the package for connecting the package in fluid communication with the fillable reservoir.
[Example 111]
A pre-filled cap that surrounds an administration portion in a unit dose benefit agent delivery device comprising a single reservoir,
At least a first compartment containing at least one component of the benefit agent;
A prefilled cap comprising a fluid passage communicating the first compartment to the administration portion.
[Example 112]
113. A filling cap according to example 112, wherein the first compartment includes a wall and at least a portion of the wall comprises a flexible material.
[Example 113]
114. A filled cap according to example 113, wherein the flexible material comprises webbing.
[Example 114]
The first compartment contains a first component of the benefit agent, and the filled cap contains a second compartment containing the second component of the benefit agent, the first compartment, and the second compartment. 113. A pre-filled cap according to Example 112, comprising an openable plug that separates
[Example 115]
113. A filled cap according to example 112, wherein the dosing portion comprises one of a needle, catheter, connector, luer connector, nozzle, jet syringe nozzle, dispenser, microneedle, ID needle, IM needle, and SQ needle. .
[Example 116]
113. A filled cap according to example 112, further comprising the lid separating the compartment and the administration portion until the lid is opened.
[Example 117]
113. A filled cap according to example 112, further comprising a fluid passage.
[Example 118]
113. A filled cap according to example 112, further comprising a membrane that occludes the fluid passage.
[Example 119]
119. A pre-filled cap according to Example 118, wherein the dispensing portion comprises a needle that is movable to pierce the membrane and establish fluid communication with the fluid passage.
[Example 120]
119. A pre-filled cap according to Example 118, wherein the dispensing portion comprises a needle configured to puncture the membrane and establish fluid communication with the fluid passage.
[Example 121]
113. A filled cap according to example 112, further comprising a backing for the first compartment.
[Example 122]
113. A filled cap according to example 112, wherein the first compartment is formed in a package comprising a mating body.
[Example 123]
The filled cap of example 122, wherein at least a portion of the package comprises webbing.
[Example 124]
A unit dose dispenser of a benefit agent,
A delivery device having a fillable unit dose reservoir and at least one port in fluid communication with the fillable reservoir;
A cartridge comprising a unit dose package aseptically coupled to the delivery device, the cartridge comprising:
At least a first compartment containing at least one component of the benefit agent, wherein the package is at least partially defined by a flexible wall;
A fitting coupled to the unit dose package and connecting the unit dose package to the delivery device;
A dispenser comprising an openable seal disposed between the first compartment and the reservoir.
[Example 125]
125. A dispenser according to example 124, wherein the reservoir is substantially empty prior to use.
[Example 126]
125. A dispenser according to example 124, wherein the reservoir contains at least one component of the benefit agent.
[Example 127]
A prefilled syringe for administering a benefit agent,
A piston assembly;
A fillable barrel with an administration portion;
A pre-filled cartridge comprising: at least a first compartment containing at least a first component of the benefit agent; and a flow passage communicating the contents of the first compartment to the barrel. A pre-filled syringe.
[Example 128]
129. The example 127, wherein the administration portion comprises one of a needle, IM needle, microneedle, ID needle, SQ needle, safety needle, retractable needle, nozzle, jet injection nozzle, dispenser, and applicator. Filled syringe.
[Example 129]
128. A prefilled syringe as in example 127, further comprising a cap that seals the dosing portion, wherein the cartridge is integral with the cap.
[Example 130]
128. A pre-filled syringe according to Example 127, further comprising a flow passage that communicates with the barrel through the administration portion.
[Example 131]
The filled syringe of example 127, wherein the barrel contains at least a second component of the benefit agent.
[Example 132]
128. A filled syringe according to example 127, further comprising a lid that separates the first compartment from the barrel until it is opened.
[Example 133]
The filled syringe of example 127, wherein the filled syringe is configured for manual operation.
[Example 134]
128. A filled syringe according to example 127, wherein the filled syringe is configured to be actuated by at least one of an auto-injector, syringe pump, control actuator, mechanical ram or pressure.
[Example 135]
128. A prefilled syringe as in example 127, wherein the proximal end of the barrel is sterile sealed.
[Example 136]
A cap for a dispensing portion of a delivery device, the cap comprising a fluid passage, a proximal end configured to communicate with the dispensing portion, and a distal end.
[Example 137]
The cap of example 136, further comprising an adapter positioned at the distal end of the fluid passage in communication with a filled package.
[Example 138]
The cap of example 137, wherein the adapter is configured to communicate with a mating body of the filled package.
[Example 139]
146. The cap of Example 136, further comprising a lid disposed within the fluid passage and configured to separate the distal end and the proximal end of the fluid passage until opened.
[Example 140]
The cap of example 136, wherein the cap is configured to seal the dispensing portion.
[Example 141]
The cap of example 136, wherein the cap is configured to provide mechanical protection to the dispensing portion.
[Example 142]
The cap of example 136, further comprising a backing that supports the filled package.
[Example 143]
A method of forming a prefilled package of benefit agent comprising:
Providing a webbing having the first surface and the second surface coupled together to form at least a first component compartment boundary between the first surface and the second surface;
Forming a fragile seal along at least a portion of the boundary;
Forming the permanent seal such that a permanent seal overlaps at least a portion of the fragile seal and creates an overlapping portion having substantially the same sealing properties as the permanent seal;
Filling the first component compartment.
[Example 144]
The method of example 143, wherein the fragile seal is formed across the boundary.
[Example 145]
145. The method of Example 143, further comprising filling the first component compartment with at least a first component of the benefit agent prior to forming the fragile seal.
[Example 146]
145. The method of Example 143, wherein after forming the fragile seal and before forming the permanent seal, the first component compartment is filled with at least a first component of the benefit agent.
[Example 147]
148. The method of example 146, further comprising forming a filling access to the first component compartment, wherein the permanent seal seals the filling access.
[Example 148]
The fragile seal exhibits a first peel strength characteristic, and the permanent seal exhibits a second peel strength characteristic, and the first peel strength characteristic and the second peel strength characteristic form the fragile seal and the permanent seal. 145. The method of Example 143, obtained by the seal setting of the seal facility used for
[Example 149]
145. The method of Example 143, wherein the fragile seal exhibits a first peel strength characteristic and the permanent seal exhibits a second peel strength characteristic, wherein the first peel strength characteristic is due to a local sealability of the webbing.
[Example 150]
The method of example 143, wherein the second seal overlaps a majority of the fragile seal.
[Example 151]
145. The method of Example 143, wherein the boundary defines at least a second compartment and a fragile seal remains between the first compartment and the second compartment after the permanent seal is formed. .
[Example 152]
A method of forming a prefilled package of benefit agent comprising:
Forming a gas filled compartment for the benefit agent;
Forming a filling compartment having a filling port communicating with the gas filling compartment via a sealable first flow path;
Forming an exhaust compartment having a port communicating with the gas-filled compartment via a sealable second flow path;
Coupling a source of at least a first component of the benefit agent to the fill port in a fluid tight manner;
Exhausting gas through an exhaust port while filling the gas filling compartment from the source via a filling channel;
Sealing the first sealable flow path and the filling flow path.
[Example 153]
153. The method of example 152, further comprising cutting off an edge of the filled package and removing the plurality of ports.
[Example 154]
The method of example 152, wherein at least a portion of the filled package comprises webbing.
[Example 155]
The method of example 154, wherein the webbing is preformed to define a volume of the gas filled compartment.
[Example 156]
165. The method of example 155, wherein the filled package is received in a cavity during filling to more accurately define the volume of the gas filled compartment.
[Example 157]
The method of Example 156, wherein a vacuum is applied to the cavity.
[Example 158]
158. The method of example 157, during filling, the filled package is positioned such that an exhaust channel is higher than the fill channel.
[Example 159]
The method of example 152, wherein the fill port comprises a well.
[Example 160]
153. The method of example 152, wherein a boundary with the source of the first component is located in the fill port.
[Example 161]
The method of example 160, comprising a valve at the boundary.
[Example 162]
The method of example 152, wherein the compartment and the plurality of flow paths are sealed from the environment prior to the sealing step.
[Example 163]
166. The method of example 162, prior to the filling step, the wall of the filling port is punctured to receive a source of the first component.
[Example 164]
166. The method of example 163, wherein the source of the first component comprises a capillary tube terminating in a piercing element.
[Example 165]
166. The method of example 164, wherein the capillary punctures the web wall of the fill port, and the web wall forms a fluid tight seal with the capillary.
[Example 166]
163. The method of example 162, further comprising stacking a plurality of the filled packages and transporting the stacked filled packages to the filling machine.
[Example 167]
The method of example 152, wherein at least one of the first flow path and the filling flow path comprises a sealable insert.
[Example 168]
153. The method of example 152, wherein the filling channel is made to allow the first component to flow along the compartment wall during the filling step to prevent jetting, foaming, or bubbles.
[Example 169]
The method of example 152, further comprising providing a sensor that detects the presence of the component in the exhaust flow path and displaying with the sensor that the compartment is full.
[Example 170]
The method of Example 152, wherein the source of the first component comprises a metering pump.
[Example 171]
The method of Example 170, wherein the source of the first component comprises a non-metering pump device.
[Example 172]
155. The method of example 152 further comprising an exhaust line for receiving gas exhausted through the exhaust port.
[Example 173]
153. The method of example 152 further comprising applying a vacuum to the exhaust port.
[Example 174]
The method of Example 152, wherein the first component comprises a solid from the group consisting of powders, pellets, granules, tablets, aggregates, spheres, microspheres.
[Example 175]
175. The method of Example 174, wherein during the filling step, the first component is transferred to the compartment along with a gas stream.
[Example 176]
178. The method of example 175, wherein the size of at least one opening in the exhaust flow path prevents the first component from reaching the exhaust port.
[Example 177]
The method of Example 175, wherein the filled package is manufactured on a molded fill sealing line.
[Example 178]
153. The method of example 152, wherein a plurality of said filled packages are manufactured from a single web member.
[Example 179]
153. The method of example 152, wherein the source of the first component is attached to the fill port using a vacuum.
[Example 180]
A method of manufacturing a unit dose delivery device for a benefit agent comprising:
Receiving an assembled delivery device; receiving a filled sterile sealed cartridge filled with at least a first component of the benefit agent; and the delivery device and the sterile sealed cartridge. Integrating the method.
[Example 181]
The method of Example 180, wherein the delivery device is a syringe with a piston pre-assembled into a barrel.
[Example 182]
The method of Example 180, wherein the delivery device and cartridge are pre-sterilized and the method further comprises aseptically integrating the delivery device and the cartridge.
[Example 183]
The method of Example 180, further comprising the step of terminal sterilization of the delivery device after integration.
[Example 184]
A method of filling a unit dose of a liquid benefit agent into a package,
Freezing a metered unit dose of said benefit agent in a mold to produce a frozen dose;
Placing a frozen dose in a semi-finished compartment;
Sealing the compartment.
[Example 185]
185. The method of example 184, wherein the package comprises a blister pack and the frozen dose is placed in a preformed cavity.
[Example 186]
185. The method of example 184, further comprising the step of examining the frozen dose for at least one controlled characteristic prior to placing the frozen dose in the compartment.
[Example 187]
185. The method of example 184, further comprising manufacturing the package from at least a first web material and freezing the unit dose on the web material.
[Example 188]
The method of example 184, further comprising thawing the frozen dose after sealing the compartment.
[Example 189]
184. The method of Example 184, further comprising exposing the frozen dose to a temperature that can prevent thawing prior to sealing the compartment.
[Example 190]
A method of filling a package with a metered dose of at least a first component of a benefit agent in the form of a flowable solid, comprising:
Metering the dose of the first component;
Fully compressing the metered dose to form a single body;
Placing the single body in a semi-finished package;
Sealing the package;
Directing energy through the wall of the package to the single dose to convert the single dose into granules.
[Example 191]
195. The method of example 190, further comprising inspecting the single body for at least one controlled property prior to being placed in the package.
[Example 192]
195. The method of example 190, wherein the package is at least partially manufactured from at least a first web and the method further comprises compressing the on the web.
[Example 193]
195. The method of example 190 further comprising forming the package with a molded fill seal line.
[Example 194]
The method of example 190, wherein at least a portion of the package comprises a web material, and the method further includes directing the energy by pressing the unitary body through a flexible wall of the package.
[Example 195]
The method of example 190, wherein the energy is directed to the single dose by at least one of mechanical vibration, ultrasonic vibration, acoustic vibration and RF vibration.

Claims (13)

A cartridge for use with a delivery device for a beneficial agent having a fillable reservoir,
A reconstituted unit dose package comprising:
A first compartment containing at least a first component of the benefit agent;
A second compartment that to accommodate at least a second component of the benefit agent,
A mating body disposed in the package to connect the package to the fillable reservoir ;
A filling compartment, wherein the first compartment is in fluid communication with the filling compartment via a fluid passage, the filling compartment filling the first compartment with the first component; A filling compartment that forms the boundary of
A gas discharge chamber, wherein the first compartment is in fluid communication with the gas discharge chamber via a fluid discharge passage;
An object that is disposed in the fluid discharge passage and is permeable to gas and impermeable to liquid;
A cartridge comprising:   The cartridge of claim 1, wherein the cartridge is adapted to communicate with a delivery portion of the delivery device comprising one of a needle, a connector, and a nozzle.   The cartridge of claim 1, wherein the first compartment is isolated from the second compartment by a breakable barrier.   The cartridge of claim 1, wherein at least a portion of the package comprises a flexible wall.   The cartridge of claim 4, wherein at least a portion of the flexible wall is preformed to define at least a portion of the first compartment and the second compartment. The cartridge of claim 4, further comprising an opaque and peelable foil layer disposed on the preformed flexible wall of the second compartment .   The cartridge according to claim 1, further comprising a fluid passage between the first compartment and the second compartment, and a static mixer disposed in the fluid passage.   The cartridge of claim 1, further comprising a fluid passage between the package and the delivery device, and a static mixer disposed within the fluid passage. The cartridge of claim 1, wherein at least a portion of the first compartment or the second compartment comprises a tubular structure.   The cartridge according to claim 1, further comprising a lid that isolates the first compartment from the fitting until it is opened. The cartridge of claim 1, further comprising a check valve positioned in the filling compartment. The cartridge of claim 1, further comprising a flow deflector positioned in the fluid passage or the fill compartment. The cartridge according to claim 1, wherein the gas discharge chamber is configured to allow gas to be discharged from the first compartment.

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