Syringe devices & method for mixing and administering medication

IS 2 575 163 T3

DESCRIPTION

Syringe Devices and Method for Mixing and Administering Medications

Technical field

The method relates to syringe devices, piercing structures, drug preparation systems, mixing and delivery systems, component mixing methods, and methods of preparing a drug for administration to an individual.

Background of the invention

The preparation of drugs or medicaments and the administration of such agents to an individual often involves mixing two or more components to form the agent and the subsequent administration of the mixed drug to the individual. Mixing of components can typically involve removing a component in fluid form from a vial or other container and transferring said components to a different container containing another component. In particular cases, only a part of the content of a vial or container will be used to prepare a mixture before administration. Consequently, extraction and transfer may involve the precise measurement of one or more components to be mixed.

Various problems can arise when conventional methods and devices are used to mix and / or administer drugs to an individual. For example, where multiple components must be mixed, the removal and transfer of one component and the introduction of that component into another component can potentially expose one or both of the components to a non-sterile or contaminated environment, causing contamination of the resulting drug. Additionally, incomplete extraction or inappropriate measurement of one or more components can result in the preparation and / or administration of an inappropriate dose. In particular cases, once a drug is mixed, the mixture must be drawn back from a vial or container into a syringe before it is administered to an individual. Such additional transfer can cause additional contamination opportunities, incomplete content extraction, and / or inaccurate measurement of a component or the resulting drug. In practice, there is limited availability of sterile environments to maintain sterility during transfer and / or mixing of components, or preparation and transfer of drugs. Additional errors can result from using the wrong diluent to reconstitute the drug. Finally, drug preparation using multiple components can be tedious and time consuming due to factors such as the need to access individually packaged items such as vials and / or separate transfer devices, or to measure one or more components to combine to form the drug.

WO2004 / 064706 describes pharmaceutical delivery systems and methods for using them. An assembly for transferring fluid between a container that includes a slide plunger and a vial includes a vial cap assembly for receiving and engaging a vial, the vial cap having a retaining member comprising a plurality of shaped retaining closures. of an annular ridge around the inner circumference of the vial cap.

It would be desirable to develop alternative methodology and systems for drug preparation and administration.

Summary of the invention

To the extent that the term "invention" is used hereinafter and / or features are presented as optional, it should be interpreted so that the only protection sought is that of the invention as claimed.

In one aspect the invention encompasses a syringe device. The device includes a syringe body having a cylindrical housing and a chamber within the housing. The device further includes a plunger having a stem, a first end, and a second end opposite the first end. The first end is external to the chamber included in the syringe body. A passageway for fluid extends through the first end through the stem and through the second end of the plunger. The syringe device further includes a valve that is associated with the passage for fluid through the plunger so that the valve controls the selective passage of fluid through the plunger. A cap can be reversibly attached to the syringe body to provide a seal for fluids.

In one aspect, the invention encompasses a piercing structure having a head segment comprising a tip disposed at a first end of the structure. The head has a front surface and an opposite back surface. The piercing structure further includes a body portion comprising a base surface disposed at a second end opposite the first end of the structure. A passageway for fluid passes through the second end of the frame through the body portion and through at least one of the front surface and the rear surface of the head without passing through the tip.

In one aspect, the invention encompasses a drug preparation system. The system comprises a syringe

ES 2 575 163 T3 having a cylindrical body with an internal chamber, and a plunger having a first end, a second end and a passage for fluid that passes longitudinally through the plunger. At least a part of the plunger comprising the first end is inserted into the chamber. A piercing structure having a fluid channel is associated with the second end of the plunger. A vial is disposed proximal and movable with respect to the tip of the piercing structure. A first drug component is disposed within the inner chamber of the syringe barrel and a second drug component is disposed within the vial. A valve is associated with the passage for fluid that passes through the plunger.

In another aspect, the invention encompasses a method of preparing a medicament for administration to an individual. The method includes providing a syringe having a syringe barrel and a plunger disposed at an initial position relative to the syringe barrel. A first component is provided within the barrel of the syringe and a second component is provided within a vial. A valve is associated with a passageway for fluid between the vial and the syringe barrel with the valve being initially disposed in a closed position, blocking the passage of fluid through the passageway. The method includes repositioning the valve to allow passage of fluid between the vial and the barrel of the syringe. After repositioning the valve, the plunger slides in a first direction to join the first component with the second component. The first and second components are mixed to produce the drug. Mixing can be facilitated by agitation, reversal of the device, and / or repeated sliding of the plunger in opposite directions. The method further includes drawing the drug into the barrel of the syringe.

In a further aspect, the invention includes a method of preparing a composition. A packaging material containing a mixing device is provided in which the mixing device includes a housing having a chamber therein containing a first material. The device also includes a plunger slidable within the chamber with the plunger having a length that is greater than the length of the chamber. The mixing device further includes a container containing a second material. A fluid passage is arranged longitudinally through the plunger with a valve being associated with the fluid passage. Without exposing the device to an environment exposed to the packaging material, the valve is repositioned from a closed position to an open position. With the valve in the open position, the plunger slides in a first direction from a first position within the chamber to a second position within the chamber. The sliding of the plunger moves one of the first and second components through the plunger. The first and second materials are then mixed to form a mixture where the mixing comprises sliding the plunger in a second direction and subsequently causing the plunger to return in the first direction. The mixture is then drawn into the chamber through the plunger.

In one aspect, the invention encompasses a drug preparation device. The device includes a cylindrical syringe body having a first end, a second end, and a longitudinal axis between them. A plunger is insertable with the barrel of the syringe through the second end, with the plunger being slidable within the barrel. The device further includes a vial containing a material and an adapter component. The adapter component includes a vial housing portion configured to reversibly receive a vial. The adapter also has a connecting element configured to attach to the syringe at the first end. A first fluid passageway extends through the connecting member to a valve, and a second fluid passageway extends from the valve to the vial housing. The drug preparation device further includes a container that is configured to allow manipulation of the valve and sliding of the plunger without opening the container.

In a general aspect, the invention includes a device comprising a housing around a chamber, a plunger having a first end, a second end, and a passage for fluid between the first and second ends with the plunger being insertable into the chamber. . The device also includes a valve associated with the fluid passage so that flow through the fluid passage is selectively regulated by the valve.

Brief description of the drawings

Preferred embodiments of the invention are described below with reference to the following accompanying drawings.

Figure 1 is a side view and partial cross-sectional view of a mixing assembly in accordance with embodiments of the invention.

Figure 2 is an exploded side view of the assembly shown in Figure 1.

Figure 3 is a side view of a part of a syringe device according to one aspect of the invention.

Figure 4 is a side view of a syringe plunger in accordance with one aspect of the invention.

Figure 5 is a perspective view of an exemplary valve in accordance with one aspect of the invention.

Figure 6 is a fragmentary perspective view of a syringe plunger in accordance with one aspect of the invention.

Figure 7 is a perspective view of a piercing device according to one aspect of the invention.

Figure 8 is a side view of a container that can be used in one aspect of the invention.

Figure 9 is a fragmentary side view and a partial cross-sectional view of a portion of a

ES 2 575 163 T3 mixing assembly as illustrated in figure 1.

Figure 10 is a fragmentary perspective view of a portion of the mixing assembly illustrated in Figure 1. Figure 11 is an exploded perspective view of a mixing assembly in accordance with an alternative aspect of the present invention.

Figure 12 is a side view and a partially cross-sectional view of a portion of a mixing assembly in accordance with another alternative aspect of the invention.

Figure 13 is an exploded perspective view of an alternative mixing assembly in accordance with another aspect of the invention.

Figure 14 illustrates an extension housing from a perspective view (Panel A) and an end view (Panel B) according to the aspect shown in Figure 13.

Figure 15A is a side view of an alternative embodiment of a plunger in accordance with one aspect of the invention.

Figure 15B is an exploded view of the plunger structure shown in Figure 15A.

Figure 15C is an exploded cross-sectional fragmentary view of the plunger structure shown in Figure 15A.

Figure 15D is a fragmentary cross-sectional side view of the plunger structure shown in Figure 15A.

Figure 16A is a side view and partial cross-sectional view of a mixing assembly in accordance with an alternative aspect of the invention.

Figure 16B is a side and partially cross-sectional view of an adapter portion of the assembly shown in Figure 16A shown in association with an exemplary vial.

Figure 17 is a side view of an alternative mixing assembly in accordance with one aspect of the invention. Figure 18A is an exploded view of another alternative embodiment of a device in accordance with the invention.

Figure 18B is an exploded fragmentary cross-sectional view of the device shown in Figure 18A.

Figure 18C is a partially fragmentary cross-sectional view of the device shown in Figure 18A.

Figure 19 is a perspective view of an exemplary mixing and container assembly in accordance with one aspect of the invention.

Figure 20 shows additional packaging and labeling aspects in accordance with the invention.

Figure 21 shows a device and package according to an alternative aspect of the invention.

Figure 22 shows a container configuration for a particular aspect of the invention.

Detailed description of the preferred embodiments

In general, the invention provides methodology for blending and blending to produce a blend and encompasses device configurations to allow blending and blending of components. In particular, the methodology of the invention involves combining and mixing components to produce an agent ready for administration, such as a drug and, in particular aspects, includes administering said agent to an individual. Accordingly, the device configurations of embodiments of the invention allow for the combination of independent components so that the combined and mixed components are ready for administration. In particular aspects the devices covered are further configured for use during administration of the ready-to-administer agent. General concepts and exemplary devices in accordance with the invention and related aspects not forming part of the invention are illustrated in the accompanying Figures 1-22.

Where devices according to the invention are used for the preparation of a drug, the devices are preferably closed system mixing assemblies. An exemplary mixing assembly 10 in accordance with the invention is illustrated in Figure 1. The various components of mixing assembly 10 are described generally with reference to Figure 1 and will be described in more detail with reference to subsequent figures. It should be understood that the general features described with reference to Figure 1 are exemplary and the invention encompasses modifications, alternative embodiments, and adaptations including, but not limited to, those specifically illustrated in subsequent drawings.

Mixing assembly 10 may comprise a container such as a syringe body (or barrel) 100 and a plunger 200 having a passageway for fluid that passes completely through the length of the plunger (further described below). In some cases, a reversibly attached cap (not shown) may be present providing a fluid seal at a forward end of the syringe body. A valve 300 may be associated with plunger 200 and may preferably be configured to allow selective passage of fluid through the plunger passageway. The mixing assembly may have an extension 600 which may comprise a cylindrical housing or alternatively configured to receive a vial 500 or alternative second container within a chamber or opening within the extension. The assembly 10 may further comprise a piercing device 400 associated with the plunger 200. Although Figure 1 and the subsequent figures represent assemblies comprising syringes and the description presents a methodology primarily in terms of preparing a drug, it should be understood that the invention encompasses alternative container shapes and adaptation of

ES 2 575 163 T3 devices for use in mixing components to form different drug mixtures or agents.

As illustrated in FIG. 1, a vial 500 which may be, for example, a standard medical type line, may be used and the extension housing 600 may preferably be configured so that the vial 500 is insertable so that it can slide into an internal area of ​​the housing 600.

A mixing and delivery system comprising a mixing assembly 10, as illustrated in Figure 1 can be described as being a closed system in which independent components of an agent can be combined and mixed without exposing the components to an external environment. to the mix set. For example, a first component may be provided within vial 500 and a second component may be provided within syringe 100. Syringe 100 may be capped to retain the second component, with the cap being reversibly attached to allow removal as appropriate (described below).

As described in more detail below, the passageway for fluid through plunger 200 preferably extends longitudinally and, more preferably, along the longitudinal axis from a first end of the plunger rod through the plunger and out of a second end so that fluid communication between vial 500 and chamber of syringe 100 can be established. Accordingly, when valve 300 is positioned in an "open configuration", bi-directional fluid flow is established through the plunger passage allowing fluid communication between the barrel of the syringe (preferably capped) and the vial 500.

Referring to Figure 2, this shows an exploded view of the various general components of the mixing assembly 10. Said view illustrates the general relationship of the various components, each of which is independently described in subsequent figures. Primarily, referring to FIG. 2, it is noted that the plunger 200 may comprise an independently fabricated seal or plug portion 208 and that each of the valve 300 and piercing structure 400 may be fabricated independently of the rod or stem portion of the plunger. However, it should be noted that the invention contemplates alternative aspects where one or more of the plug 208, the valve 300, and the piercing structure 400 are integral with the stem portion of the plunger. It should be further noted that the extension 600, as depicted in Figure 2, having an open end to receive the vial 500 may be manufactured to be independent of the plunger 200, as illustrated, or it may be manufactured to form one piece with the piston rod portion (not shown).

Referring to Figure 3, the syringe body 100 may comprise a cylindrical housing 102 having an inner region or chamber 104 within the housing. The chamber can be described as having a longitudinal axis extending from a first end 105 of the syringe body. A second end 106 of the syringe body is disposed opposite the first end 105. In particular cases, the syringe may comprise a LUER-LOK® type connecting element 108 (Becton, Dickinson and Company, Corp., Franklin Lakes, NJ) arranged near the second end, as illustrated in Figure 3. Although A Luer-Lok connector is illustrated, it should be understood that the invention contemplates alternative connector / connection element configurations. Preferably, connector 108 is capable of and preferably reversibly receiving a needle, alternate cannula, tube, and / or adapters that can be used, for example, during administration of a drug from within chamber 104 to an individual or, in particular cases, for transfer into a different container (not shown). In particular applications, it may be preferred that the syringe body 100 comprises a male Luer-Lok connection element to allow connection and preferably reversible connection with a female LuerLok connection element included in an administration needle.

Syringe housing 102 may have volume markings such as those illustrated, or it may have alternate volume indicators to aid in measuring or verifying volume. Although not specifically illustrated in Figure 3, a cap may be provided to seal the second end 106 (see Figure 19). The cap can prevent the passage of fluid from within the syringe barrel during storage, shipping, mixing, etc., and can prevent exposure of drug components to an environment external to the syringe device. The cap may be configured to be reversibly attached by Luer-Lok or other connecting element mechanism, to allow removal and replacement with a suitable delivery or transfer accessory.

Syringe body 100 can be a conventional syringe barrel or can be manufactured for a particular application in accordance with the invention. The housing can be manufactured to comprise, for example, one or more medical grade / approved glass or plastic materials. Exemplary materials that can be used for syringe shell formation include, but are not limited to, polyethylenes, polypropylenes, polycycloolefins, polyvinyl chloride (PVC), polyamides (including aliphatic and aromatic variants), polyesters, polycarbonates, copolymeric materials that include but are not limited to those containing ethylene-diene-propylene monomer (EPDM), polyacrylates, polyurethanes, composites, mixtures or combinations of said materials, or alternative composite materials.

The volume of the syringe (or alternative container) is not limited to a particular value and the syringe body can be configured to hold a maximum volume, for example, from 1 ml to more than 10 ml. Preferably, the volume of the syringe will be less than or equal to 10 ml. For purposes of the present description, the volume of the syringe

ES 2 575 163 T3 refers to the volume of liquid that the syringe housing is configured to retain, and not to the overall volume within the internal region 104.

Referring now to Figure 4, an exemplary plunger 200 is illustrated having a stem portion 201, a first end 204, and a second end 202. The plunger can be described as having a length represented by di extending from the first end 204 to second end 202. The length di is not limited to a particular value and may preferably be a value greater than the length of the longitudinal axis of the internal syringe chamber 104.

A fluid path 206 traverses the length of the plunger, as illustrated by dashed lines. The fluid path diameter 206 is represented in Figure 4 by "d₂”. In some cases, path 206 may have a non-uniform diameter, however d₂, as used herein, indicates the minimum diameter of the passageway. Although di and d2 are not limited to particular values, it may be preferable in some cases that the ratio of di to d2 is at least about 10: 1. Capillary action can be promoted by maximizing the aspect ratio of length to diameter of the passageway. Such capillary action can help create a watertight compartment within the passage when an associated valve is in a closed position, thereby preventing contact of a liquid component / diluent, to the valve prior to opening of the valve at the start of a test. merge event (described below). However, smaller ratios can advantageously allow the entire plunger rod to be manufactured as a single piece by, for example, injection molding techniques. Accordingly, the invention contemplates alternative di to d2 ratios (ie, less than about 10: 1).

As illustrated in Figure 4, a cap portion 208 may be provided to be received at the second end 202 of plunger 201. In contrast to conventional syringe drivers, the cap portion 208 may be configured to have an opening or channel 210 that passes completely through plug allowing fluid to pass from within passage 206 through plug 208. Although a single channel 210 is depicted, the invention contemplates plug configurations having a plurality of channels that provide passage of fluid through the plug to / from the passage through the plunger rod. As depicted in FIG. 1, plunger 200 is configured so that second end 202 can be received within the syringe chamber, so that fluid communication can be established between the syringe chamber and plunger passage 206 a through plug 208 via one or more openings 210 as illustrated in FIG. 4.

Where the plug 208 is formed as a separate structure relative to the plunger rod, the plug may preferably comprise a relatively soft material (relative to the plunger, described below). Exemplary materials that may be appropriate for cap fabrication, based on manufacturability, biocompatibility and / or chemical compatibility, and ability to produce a fluid seal include elastomeric materials such as rubber, butyl, silicones, silanes, polypropylene, polypropylene-EPDM, polyurethanes, and other suitable plastics, as well as various copolymers, blends, and combinations thereof.

Referring again to Figure 4, plunger 210 may further comprise various support rings 212, 216, and 217. It should be understood that such rings are an optional feature and that stem portion 201 may be manufactured to comprise fewer rings than shown. , not to include any of the represented rings, or to comprise additional rings with respect to those shown. The ring structures may additionally be alternately positioned along the piston rod with respect to the positioning shown. In embodiments where the plug 208 is an independently formed structure, at least two of the rings 212 are provided to mount, position, and retain the plug on the plunger. Ring structures 212, 216, and 217 may be advantageous, for example, to stabilize and / or drive plunger 200 and to help reduce or avoid contamination of internal surfaces of the syringe body during syringe handling, especially for embodiments. where the container is removed prior to handling the mixing assembly (described below).

As further illustrated in FIG. 4, plunger 200 may comprise an opening 214 extending through plunger rod 201. Said opening may preferably orthogonally intersect fluid passage 206. Said opening may be configured to allow the insertion of a valve, such as the exemplary valve depicted in Figure 5. The depicted positioning of aperture 214 along the piston rod length 201 of FIG. 4 is exemplary. The positioning of the valve opening 214 is not limited to any particular location and can be anywhere along the length of the fluid path 206. It may be preferable, in some cases, that the valve insertion opening 214 is positioned at the point midway along the distance di or, alternatively, is closer to the end 204 than to the end 202. This Positioning may advantageously allow ease of manipulation of the associated valve.

As depicted in Figure 1, assembly 10 may be configured so that valve 300 is, when disposed in association with aperture 214, at least partially insertable within syringe housing 100. However, the invention contemplates positioning of valve 300 closer to end 204 than depicted, especially for small volume syringes where an exemplary valve 300 shown is

ES 2 575 163 T3 too large to fit so that it can be inserted into the syringe housing. It should be understood that alternative valve types can be used which may allow insertion or partial insertion of the valve into the syringe housing even for very small volume syringes.

Exemplary valve 300 is shown in more detail in Figure 5. As illustrated, valve 300 has a body portion 302 and a head portion 304. The head portion 304 may be configured to have extension tabs or protrusions. 307 and 308. Although Figure 5 depicts two extension tabs it should be understood that fewer or more than two extension tabs can be used. The extension tabs 307 and 308 can advantageously assist in the proper positioning and alignment of a fluid passage 306 that passes through the stem portion 302 of the valve 300. The invention further contemplates alternative shapes for the head portion 304 with respect to to the round configuration shown. For example, the head portion may be arrow-shaped to allow visual and / or tactile indication of the valve position. Head portion 304 may also be configured to have alternative or additional visual and / or tactile indicators.

The valve body 302 is preferably configured to allow the insertion of said part into, and in particular cases completely through, the opening 214 of the plunger 200, as illustrated in Figure 4. Consequently, and as illustrated In Figure 5, one or more gaskets or O-rings 310 may be provided to provide a fluid seal within the opening 214. Alternatively, a gasket can be formed as an integral part of valve body 302 (not shown). Although aperture 214 and associated valve 300 are illustrated being configured such that the valve passes completely through plunger rod 201, it should be understood that the invention contemplates alternative configurations where aperture 214 and an associated valve encompass less than a totality. of the cross section of the plunger rod 201 (not shown). Additionally, although Figure 5 shows a two-way stopcock (open / close) type valve, the invention contemplates alternative valve types and appropriate opening configurations. For example, instead of the uniform diameter cylindrical valve opening shown, the opening 214 may be configured to be conical, rectangular, or other shape. In such cases, the valve body 302 may be appropriately shaped to be received within the opening. Alternative valve types such as bi-directional stop valves, slide type valve, ball valves, push valves, or gate valves can be used and can be appropriately configured based on the dimensions of the opening 214.

In addition to the one-piece plunger rod 201 illustrated in Figure 4, the invention contemplates the use of multi-part plunger rods. Referring to Figure 6, an exemplary two-part plunger rod 201 is illustrated having a first part 230 and a second part 232. In the illustrated exemplary two-part plunger rod, parts 230 and 232 interface at the longitudinal position of the opening 214 along the axis of the plunger. Portions 230 and 232 can be joined by, for example, heat welding, ultrasonic welding, radio frequency welding, adhesive bonding, or other appropriate bonding techniques. Alternatively, the two parts may be configured to fit together or may be secured by various attachment structures such as pins, clamps, threads, or alternative mechanical fastening techniques known in the art or yet to be developed.

Although the illustrated two-part plunger rod represents an interface between the two parts that match the position of the valve receiving opening 214, it should be understood that the positioning of the interface is not limited to any particular location it may, for For example, anywhere along the longitudinal length of the plunger rod. The proper positioning of the interface and the length of the resulting segments can be adapted, as appropriate, based on the ease of manufacture of an appropriate valve and plunger segments. The invention further contemplates multi-part plunger rods having more than two independently fabricated segments (not shown).

The plunger and syringe housing parts of the devices of the invention can typically comprise standard materials used for conventional syringe and plunger / driver formation. Typically the plunger, with the exception of the plug, will be a relatively hard plastic. In embodiments where the plug is one piece with the plunger, the integrated piece can be formed of a common plastic material. Exemplary plastics that can be used for plunger formation include, but are not limited to, polyethylenes, polypropylenes, polycycloolefins, polyvinyl chloride (PVC), polyamides (including aliphatic and aromatic variants), polyesters, polycarbonates, polyacrylates, polyurethanes, copolymers, blends , composite materials and combinations thereof.

Valve 300 is also not limited to a particular material and may preferably comprise plastic and / or elastomeric materials. In particular applications, it may be preferable that the valve body portion 302 (as illustrated in Figure 5) comprises an elastomeric material to allow a better fit and / or seal within the opening 214 of the plunger rod 201, especially where the plunger 200 comprises a hard plastic material. Exemplary elastomeric materials that can be used for body portion 302 include, but are not limited to, polyurethanes, polypropylene-EPDM, other polypropylenes, polysiloxane and / or silicone materials, butyl materials, isoprene, neoprene, polyethylenes, and various copolymers, composites, blends, or other combinations of such materials. Additional suitable materials may include natural rubbers, nitrile rubbers, and combinations thereof. Valve 300, with the exception of O-ring 310, may be

ES 2 575 163 T3 constructed as a single piece and therefore may be formed of a particular material or type of material. Alternatively, head portion 304 may be independently formed and comprise a material that differs from body portion 302. For example, in particular cases, the head portion 304 may be formed of a hard plastic such as any of those listed above and the body portion 302 may comprise a different hard plastic material or any of the elastomeric materials listed above.

Referring to Figure 7, this shows an exemplary piercing structure 400 in accordance with the invention. Piercing structure 400 can be described as having a head segment 401 comprising a tip

402 arranged at a first end. The piercing structure 400 additionally has a stem / body part

403 extending from the head portion 401 to a base surface 404 disposed at a second end of the frame opposite the first end. A channel 406 or other passageway for fluid extends through the base surface and preferably through an entirety of the body portion 403.

Piercing structure 400 shown at 406 illustrates exemplary geometry and shape of head segment 401. As illustrated, head portion 401 may have an outer surface that comprises a front surface 414 (or top surface, as illustrated). and an opposite rear surface 415. In a preferred aspect of the invention, channel 406 extends less than a totality of an internal length of head segment 401 so that the channel does not pass through tip 402. Instead, one or more holes are provided. access port 408, for example, through one or both of surfaces 414 and 415. That configuration in which the channel does not pass through the tip can advantageously minimize or prevent central cupping ("coring") of the septum material or obstruction of the channel during a drilling operation.

Access holes 108 may be arranged orthogonal to the longitudinal axis of channel 406, as shown in Figure 7, or they may intersect channel 406 at an angle other than 90 ° (not shown). Additionally, the placement of the holes 408 along the head segment 401 is not limited to the position shown. It may be advantageous for holes 408 to be disposed close to the body portion of the piercing device to allow such holes to be positioned just inside a vial after piercing. This can maximize fluid access by allowing efficient and complete removal of vial contents without repositioning of the piercing structure after perforation of a septum or other barrier material.

To aid the piercing and passing of the head segment 401 through a perforated material such as, for example, a septum, the head portion 401 may be configured to have one or more edges 410 and 412 that are cutting edges, where the term "cutting edge" refers to an edge that is sharp enough to cut the material being drilled during a drilling operation. As illustrated in Figure 7, cutting edges 410 and 412 may preferably be disposed at the edges of head portion 401 where surfaces 414 and 415 meet. Although the figure illustrates two cutting edges, it should be understood that the invention contemplates configurations of head portions 401 that have no cutting edges, that have one cutting edge or more than two cutting edges. As further illustrated, one or both of surfaces 414 and 415 may be beveled. Such chamfering of the surface can further assist the passage of the head segment 401 through a perforated material.

The body portion 403 of the piercing structure 400 may be, for example, cylindrical as illustrated in Figure 7. The body portion 403 may have a uniform circumference along its entire length (not shown) or it may have segments that vary in circumference with respect to each other. For example, as illustrated in Figure 7, the body portion 403 may have a tube segment 416 and a base segment 418 where the base segment 418 extends from the base surface 404 to the tube segment 416. The lengths of segments 418 and 416 are not limited to any particular value. Nor is the segment length ratio limited to a particular value. Preferably, where base portion 418 will be seated within another component of a mixing assembly in accordance with the invention (such as plunger 200), the length of segment 418 may be such as to allow stabilization and / or retention of the piercing structure 400 in the seated position.

Base portion 418 is preferably of sufficient length and appropriate shape to seat firmly within a seat opening comprised of the plunger (see below). An O-ring or boss portion of the base 418 (not shown) may be provided to allow a tight fit. Accordingly, a suitable notch or groove (not shown) may be provided within the seat opening of the plunger. In particular cases, a press fit or friction fit will be used to provide sufficient retention of the piercing structure. Optionally, firm bonding can be used using for example an adhesive, welding or other appropriate bonding technique.

With respect to segment 416, it may preferably be of sufficient length to pass completely through a perforated material to allow fluid to pass through the perforated material through access hole 408 and through passage 406. Accordingly, an appropriate length of segment 416 can be determined by the thickness of a septum or other barrier to be perforated, while positioning the access hole 408 as close to the perforated material as possible to allow maximum fluid access (described above). . Furthermore, although the piercing device is not limited to a particular shape, the configuration in

ES 2 575 163 T3 "arrowhead" shape depicted in Figure 7, where head segment 401 has crest surfaces 409 extending laterally outward from tube segment 416, can help stabilize and retain the piercing device through a septum after perforation has occurred. Retention of the piercing device through the septum can prevent inadvertent contact of the device by an individual that could cause injury and / or drug contamination.

Numerous suitable materials are available for the manufacture of piercing device 400. Such materials include, but are not limited to, metals, such as stainless steel, and various plastics such as polyamides, polyacrylates, polycarbonates, epoxies, polyurethanes, polysulfones, polyetherimides, polypropylenes. , copolymers, etc., in thermoplastic or thermoset varieties.

In addition to the piercing structure depicted in Figure 7, and variations of that configuration, the invention contemplates the use of alternative structures to pierce a container barrier. Plunger 200 can be adapted accordingly. Alternative structures may include, for example, a needle or a non-coring piercing structure alternatively to the arrowhead design shown. Such alternative configurations can be especially useful where multiple vials must be accessed sequentially (ie during the preparation of a drug comprising three or more components).

An exemplary vial 500 that can be used as part of a mixing assembly in accordance with the invention is illustrated in Figure 8. For purposes of the invention, the term "vial" is not limited to a particular container structure and can be used to refer to various containers including containers used for parenteral as well as non-parenteral materials. Vial 500 can be, for example, a bottle as illustrated in Figure 8 having a cap portion 504 and a top surface 502. Vial 500 can be a glass bottle or alternatively it can be a container. made of plastic or other material conventionally used or yet to be developed to retain and / or access a drug or component thereof.

Referring to Figure 9, this shows an exemplary mating configuration of piercing structure 400 and vial 500. In the coupling illustration, device 400 is illustrated passing through a septum 506 into cap portion 504 of the vial 500. Accordingly, fluid access is provided from within vial 500 through access hole 408 to the interior and through fluid passage 406.

An exemplary association of a piercing device 400 and a plunger 200, in accordance with the invention, is shown in Figure 10. As illustrated, the base portion 418 (shown in Figure 9) of the piercing device is seated within a terminal portion of the passage 206 of the plunger rod 201. Said terminal portion may preferably be diametrically enlarged with respect to other portions of the passage 206 to allow seating of the piercing structure. Figure 10 further illustrates an exemplary connecting element 203 and a ridge 205 present at the first end 204 of the plunger structure. As illustrated, the connecting member 203 may have an interior area 207 having a base surface 213 with the piercing device 400 passing through said interior area and base surface. Although base surface 213 is illustrated as being flat, the invention contemplates seating configurations in which a central portion of base surface 213 protrudes into area 207 to form a pedestal or flange (not shown), in which a The central opening within the protrusion is an extension of the passage for fluid through the plunger and is configured to seat the piercing device. It may be advantageous to provide a projecting portion to provide a space between the base surface 213 and the top of the vial 500. The projecting rim configuration can be adjusted to allow proper fit and / or positioning of a particular vial within the vial housing. reception and association with the stabbing device.

The interior area 207 may be of sufficient size to allow a portion of a vial or container, such as the cap portion 504 illustrated in Figures 8 through 9, to be at least partially insertable within the connecting member 203. Additionally, the connecting element 203 may have an external diameter of an appropriate size to allow insertion of the connecting element 203 into an extension structure (such as the cylindrical housing extension structure shown in Figures 1 and 2). Where the connecting element 203 is configured for insertion into an extension structure, the ridge 205 may preferably be configured to interface with the extension structure to allow proper positioning of the extension structure relative to the plunger 200, such as as illustrated in figure 1, for example.

Referring again to Figure 1, a general methodology in accordance with the invention for the illustrated embodiment may comprise mixing a first component provided within vial 500 with a second component provided within syringe barrel 100. In an initial state before By combining the two components, each component is isolated from the other. Plunger 200 is preferably provided in an initial position relative to the syringe barrel with valve 300 initially being disposed in a "closed" position, blocking the passage for fluid through the plunger.

In the initial state, the syringe 100 is preferably capped or otherwise sealed (not shown) to prevent

ES 2 575 163 T3 passage of material into or out of syringe barrel 100 through the second end of the syringe. Plunger 200 is initially disposed in a position inserted through the first end of syringe barrel 100 and positioned to allow containment of the second component within the syringe barrel. Cap 208 (illustrated in FIG. 2) preferably prevents passage of the component from within the syringe barrel between the internal surfaces of the housing and the cap.

Although the valve 300 is in the closed position, the vial 500 is positioned by partial insertion into the extension housing 600. It should be noted that such insertion may, in alternative aspects, be performed by an end user of the mixing assembly or it may be performed before packaging the whole (described below). Regardless, the vial cap / septum is initially provided to be intact and preferably to be separate from the stabbing device 400 so that the tip of the stabbing device is not in physical contact with any part of the vial 500, as initially provided.

Once the combination and mixing of the independent components is desired, the vial 500 can be repositioned by sliding, for example, the vial 500 further into the extension 600 to allow the device 400 to pierce and partially insert through the septum. or the alternative barrier portion of the vial.

Once perforation has occurred, valve 300 can be rotated or otherwise repositioned to an open position that allows fluid to pass through the plunger. Said repositioning establishes fluid communication between the interior of the vial 500 and the interior of the syringe barrel 100 without exposing either component to an environment external to the mixing assembly. One or both of the first component and the second component may preferably be in liquid form. Typically, at least the component within the syringe barrel will be in liquid form. Often times, the component within vial 500 will be in a dry, powdery, or lyophilized form, but may alternatively be in the form of a liquid, solution, suspension, or other mixture.

Where the vial 500 contains a non-fluid component, a liquid component contained within the syringe 100 can be introduced into the vial 500 and can be combined with the component within the vial 500 by sliding, for example, the plunger 200 from an initial position to a second position. position, so that the cap 208 is repositioned to be closer to the second end of the syringe body 100. Said sliding motion allows fluid to flow from within the syringe chamber through plunger 200 and into vial 500 through valve 300. During passage, the fluid further passes through piercing device 400.

Mixing of the combined components can be accomplished by, for example, a forward and reverse sliding motion of the plunger 200 relative to the syringe barrel in a "pump" type motion. The pumping movement is carried out with valve 300 in the open position which allows fluid communication between the syringe barrel and vial 500, typically with the vial being in an inverted position. Alternatively, mixing can be accomplished by shaking or shaking the vial 500 and / or the entire mixing assembly, or by a combination of pumping and shaking action, shaking, etc. Once the components have been mixed, the assembly can be prepared for transfer of the mixed agent or, where the mixture is an agent ready for administration, the device can be prepared to administer the agent to an individual. Alternatively, if additional components are to be combined with the mixture, these can be introduced, for example, by flowing into the syringe through the second end, and mixing as described above.

To prepare for transfer and / or administration of the agent, the mixture can be drawn into the syringe body 100 by sliding, for example, the plunger 200 in a backward motion, usually with the vial in an inverted position. In other words, plunger 200 is partially removed by moving plug 208 toward the first end of the syringe housing. Upon attraction of all or an appropriate metered portion of the mixture into the cylindrical syringe body, the valve 300 can be rotated or otherwise repositioned in the closed position that blocks the passage for fluid from the body. cylindrical syringe through the plunger. The syringe barrel can then be uncapped by, for example, removal of a cap such as a Luer-lok cap connecting element. It should be understood that the invention also contemplates performing drug mixing / preparation with a needle connected to the Luer-lok connector during the preparation phase. However, the needle is preferably capped and sealed during said operation or otherwise prevented from allowing passage or exposure of the syringe barrel material to an environment external to the assembly.

Where a cap is removed in preparation for transfer or administration of the agent, an appropriate transfer device such as a needle, cannula, transfer tube, and / or other appropriate connecting element can be attached to the Luer-lok connection and the transfer / Administration can occur by sliding the plunger forward within the barrel, thereby expelling the contents of the barrel through the needle or alternate transfer structure at the Luer-lok end of the syringe. Said transfer is made with valve 3 remaining in the closed position throughout. Alternatively, handoff can be accomplished by providing assembly 10 in an appropriate syringe pump, as will be understood by those skilled in the art

ES 2 575 163 T3 matter.

Referring now to Figure 11, this shows alternative aspects of the invention that have a variation from the mixing assembly shown in Figures 1-10. Components that vary from those illustrated in previous figures are given numeric identifiers that have an "a" added or a unique identifier from those previously used. In the embodiment shown in FIG. 11, plunger portion 200a is shown having lateral rib structures 220a that extend longitudinally along stem portion 201a. Such rib features can be similar or identical to those present in conventional syringe pusher devices. The presence of ribs 220a can provide additional support and thus strengthen the plunger. As illustrated, ring structures 212a, 216a are present at various positions along the length of the stem portion. It should be understood that the invention contemplates alternate placement and / or alternate numbers of both ring and rib structures relative to the exemplary configuration depicted in Figure 11.

As shown in FIG. 11, one or more of the rib structures 220a may be provided to be spaced in the region of the valve receiving opening 214a. The width of the space may be configured to allow sufficient space for insertion of the valve and to allow positioning of the head portion of the valve within the space. It is noted that the extension tabs present on the valve head may be specifically configured to contact a rib at the time of rotation of the valve head. This may advantageously allow proper open / closed positioning of the valve and alignment of the passage for fluid through the valve and plunger rod 201a.

Mixing assembly 10a as shown in FIG. 11 uses an extension portion 600 having a groove 602 that extends partially along the length of the extension housing. The extension portion 600 may comprise two grooves as illustrated or it may comprise a smaller or greater number of grooves. Such grooves can allow a slight expansion on the inner circumference of the extension shell. This feature may allow a tight but reversible fit to be established between the extension housing 600 and the vial 500. For example, where the internal area 604 of the extension has a circumference that is slightly less than or equal to the maximum circumference of the vial 500, the grooves 602 may allow a slight expansion of the housing to allow insertion of the vial 500. Such a configuration may further allow retention of vial 500 within internal region 604 until a force is applied to remove the vial.

The length of the one or more grooves 602 may be configured to allow positioning and stabilization of the vial 500 within the housing in a position that disposes a septum or vial cap 500 in a spaced relationship with respect to the piercing device 400 (described below continuation). The separate relationship may allow packaging and / or shipping of an assembly as a linearly assembled device where the cap of the vial 500 remains intact prior to the removal of some or all of the packaging materials and / or the intentional coupling. Accordingly, the length of the grooves 602 and the relative length of the grooves and the overall length of the housing 600 may vary with appropriate lengths and length ratios depending on the relative length and the positioning of the device 400 within said housing and the relative size of vial 500.

A further alternative aspect of the invention is described with reference to Figures 12-13. Referring initially to Figure 12, this shows the variation of the components of the mixing assembly 10b with respect to the mixing assemblies described in previous figures. Components that vary from those illustrated in previous figures are given a numerical identifier that has a "b" attached to it, or a unique identifier from those previously used. In the embodiment depicted in FIG. 12, the plunger portion 200b is shown having an alternate connecting element configuration 203b. Such a configuration may allow a part of the extension housing 600b to be received within an internal area of ​​the connecting element 203b. As illustrated by the exploded view, the piercing device 400 can be seated within the plunger 200b in a manner similar to that described above with respect to prior embodiments. Additionally, the various rings and fins depicted in Figure 12 in association with plunger 200b may be as illustrated or may have any of the alternative configurations described above.

Valve 300b as depicted in Figure 12 may comprise one or more alignment markers 312 preferably on an upper surface of valve head 304 to allow for visible and / or tactile alignment of the valve upon insertion into the valve. opening 214b of plunger 200b. Although represented as cast arrows, it should be understood that the invention contemplates alternative alignment markers.

Extension 600b shown in Figure 12 illustrates aspects of the invention where the extension housing has a non-uniform outer circumference. As shown, the extension housing 600b may comprise a first part 605b having a smaller circumference than a second part 606b. Such a configuration may allow insertion and seating of portion 605b into the connecting configuration of plunger 203b as illustrated.

IS 2 575 163 T3

Features of extension 600b are more fully described and illustrated with reference to Figures 13A and B. As shown in Figure 13A, extension housing 600b has an internal area 604b configured to receive a vial such as a vial. standard or alternative container as described above. One or more slots 602b may extend longitudinally from the receiving end of the extension housing to allow slight expansion of the housing. In some cases, the receiving / opening end of the housing 600b may have an internal diameter equal to or slightly smaller than the diameter of a vial prior to insertion of the vial. Insertion of the vial can expand the housing due to the presence of grooves 602b. Such a configuration may allow a snug fit and stabilization of the inserted vial. In combination with particular aspects of packaging (described below) the grooves 602b may further allow stabilization of vial positioning during storage and / or shipping.

Referring to Figure 13B, at least a portion of a length of the interior area may comprise interior ribs 607b. Preferably, at least one inner length associated with segment 605b contains ribs 607b that can help position and retain vial 500 (shown in Figure 12) within the extension housing. Such ribs may further provide support for the vial within the housing at the time of piercing an alternative septum or barrier material.

Although Figure 13 depicts the extension 600b having ribs 607 along only a portion of the inner side walls of the opening 604b, it should be understood that the invention contemplates alternative aspects where ribs are provided along a portion or all of the inner surface of segment 606b. The inner side wall and / or rib portions within the housing 600b may be profiled to correspond to an outer shape of the vial 500 either the vial of the conventional shape illustrated or has an alternative vial or container shape.

Although housing configurations having non-equivalent circumferential segments are illustrated in Figure 12 being used as a one-piece plunger rod, it should be understood that the invention contemplates the use of such a housing configuration with any of the alternative plunger configurations. described in this document.

In addition to the embodiments described above, in which the vial 500 is provided independently of the plunger portion of the assembly, the invention further encompasses configurations in which a container is integral with the plunger portion as exemplified in FIG. 14. Exemplary plunger 200c has elements that have numerical identifiers with an appended "c" to distinguish them from prior embodiments. It should be noted, however, that the general concepts and variations of the above embodiments can also be applied to the embodiment depicted in Figure 14. It should be further noted that, in the plunger 200c, the plug portion may be provided as a separate component or it may be an integral part of plunger 200c. Accordingly, the plug 208c may comprise a material that differs from the plunger rod or it may be formed from a material identical to the material used to form the plunger rod 201c.

Alternative aspects of the invention depicted in Figure 14 include a variation of the extension portion to form a container 650c having a base surface 652c that opposes the first end 204c of the plunger forming a closed compartment.

The container 650c may be formed to be integral with the plunger during a common manufacturing event (such as molding), or by attaching an independently formed container structure to the connecting element portion 203c of the plunger. Alternatively, the container portion 605c may be reversibly attached to the plunger. Attachment (either permanent or reversible) of a independently formed container to second end 204c may comprise insertion of connecting element portion 203c similar to attachment of extension portion 600 described above. The attachment and attachment of the container part to the plunger may comprise for example a snap-type seal or weld.

Alternative one-piece vial-plunger configurations contemplated by the invention include, for example, providing an opening through the vial portion, for example through base surface 652c (not shown), which can be used during provision of the drug component into the vial and / or during drying or lyophilization of the component. Said opening can subsequently be plugged or otherwise sealed.

The material used for the construction of the container 650c is not limited to a particular material or class of materials. The container 650c can be , in particular cases, formed of a plastic material that can be a rigid material or a collapsible material.

A component of a drug or other mixture to be formed can be provided within container 650c and can be isolated from an associated syringe barrel (not shown) by providing a valve in the receiving opening of valve 214c. A suitable valve can be, for example, any of the valves described above. The component provided in the container 650c may be provided within the container prior to attachment of the container or, alternatively, it may be provided in the container in one piece or secured by

ES 2 575 163 T3 the fluid path 206 through the plunger and the plug opening 210c. The associated valve can then be closed to prevent the contained component from flowing out through the plunger.

Where container 650c is independently formed and is reversibly or permanently attached to the plunger, an O-ring 230c may be provided in association with connecting element 203c to provide a fluid seal between the plunger and the internal surfaces of the container. 650c. Alternatively, other appropriate sealing techniques can be used. Plunger 200c is seen to lack an associated piercing structure. Accordingly, the first end 204c of the plunger can be modified from configurations described above to lack housing elements for the piercing device. Furthermore, the illustrated attachment of the container 650c to the plunger 200c is an exemplary configuration and alternative attachment shapes and methods are contemplated.

While the illustrated one-piece container / plunger structure is shown to have rings and ribs220c it should be understood that ribs and rings are optional as is the number of such ribs and / or rings, as discussed above with respect to to aspects described above. Additionally, the plunger rod 201c, shown as a single piece, may alternatively comprise multiple segments, as described above (and / or the rotational valve-type configuration described below).

Another alternative plunger configuration involving a rotational valve type plunger is indicated as an example and described with reference to Figures 15A-D. Referring initially to FIG. 15A, a plunger 200d is depicted that can be used in conjunction with additional components of the mixing assembly described above. Plunger 200d may comprise a two-part plunger rod 201d which may optionally include ribs 220d and / or rings 212d. The stem 201d comprises a first part 230d and a second part 232d. The lengths of the first segment 230d and the second segment 232d may be identical or they may differ. The length of each segment and their relative lengths thereof can be determined by manufacturability and overall length of the plunger. Plunger 200d is shown as having an independently formed plug 208d. However, it should be understood that said plug may be integral with the first part 230d of the plunger 200d. An exemplary extension portion 600d is illustrated that can be configured to receive a vial as described above. As illustrated in FIG. 15, the extension portion 600d may be integral with the second portion 232d. Such a one-piece plunger / extension configuration may be adapted for use with any of the alternative one-piece plunger rod aspects described.

Referring now to Figure 15B, said figure shows an exemplary piercing device 400d that can be disposed within an internal region of extension 600d and that can be positioned to allow communication between a vial and an associated fluid path 206d traversing the tube. length of plunger rod 201d. The first segment 230d and the second segment 232d can be configured to interact to provide valve action. As illustrated, the first segment 230d may comprise a frusto-conical protrusion 226 having a pair of openings 228 that pass completely through the frusto-conical protrusion. Second portion 232d may be configured to have a corresponding frusto-conical inner chamber region 227 configured to receive boss 226. Although a frusto-conical shape is illustrated, the invention contemplates corresponding protrusion shapes and receiving chamber shapes other than the exemplary frusto-conical shape.

Fluid passage 206d is shown partially extending through frusto-conical protrusion 226 discontinuously so as to impede longitudinal fluid passage. Fluid passage 206d resumes its longitudinal advance on an opposite side of a solid block of material 223. One or more grooves 229 may be disposed within an interior side wall of second segment 232d which, when aligned with openings 228, may allow passage of fluid from fluid passage 206d of first portion 230d into the interior of the portion of said passageway for fluid passing through the second part 232d. Alignment of openings 228 with grooves 229 can be achieved by opposite rotation of portion 230d relative to portion 232d. Such a valve / plunger configuration is further described with reference to FIG. 15C. As illustrated, protrusion 226 may comprise one or more O-rings 222 to allow a fluid seal to be formed upon insertion of the protrusion into receiving chamber 227.

With reference to second segment 232d of plunger 200d, a pair of grooves 229 are illustrated being arc-shaped grooves formed in the plunger side wall material. It should be understood that alternatively shaped grooves are contemplated and the arcuate grooves are but one exemplary configuration. Referring now to Figure 15D, upon insertion of the protrusion into the receiving chamber of the second segment 232d, the rotation of the portion 230d and 232d with respect to each other can be performed to align the access openings. of fluid 228 with grooves 229 to allow connection of passage 206 through access openings 228 allowing passage of fluid between segments 230d and 232d. Additional rotation or reverse rotation may be used to misalign the access openings 228 and groove 229 to reseal the fluid access between the two parts of the plunger.

Although the fluid access openings 228 are shown extending completely through the

ES 2 575 163 T3 protrusion 226 (see FIG. 15C), it should be understood that said openings may extend less than a full width of said protrusion. Alternatively, access openings 228 may be provided on only one side of said protrusion. In another alternative, additional access openings may be provided partially or completely through the protrusion 226. Similarly, fewer or more than the two illustrated connecting grooves can be provided within the second segment 232d.

In addition to the characteristics shown and described above, in particular cases one or more filters can be used to remove particulate materials before administration. One or more appropriate filters can be incorporated into any of the above devices, for example, into the passageway for fluid through the plunger. Additionally or alternatively, one or more filters may be provided in association with the syringe outlet, internally or externally to the syringe barrel.

The methodology for mixing components to prepare a mixture using the rotational plunger type valve configuration illustrated in Figures 13A-D can be carried out in a similar manner to the methodology described with reference to Figure 1. Using the rotational plunger-type device, instead of rotating or repositioning independent valve component 300 illustrated in FIG. 1, the first and second plunger segments would be rotated oppositely to open or close the passage for fluid through. of the plunger at the appropriate stage of the mixing procedure.

Another alternative embodiment of a mixing device according to the invention is described with reference to Figures 16A-B. Referring to Figure 16A, a mixing system 10e may comprise a syringe 100 and an adapter 700 that may be reversibly attachable to syringe 100 by providing, for example, a female or alternate Luer-lok connection element 708 in a first end of adapter 700. Syringe 100 may preferably be a conventional syringe using a conventional type plunger / pusher 200e. The adapter 700 may be provided to have a first fluid passage 706 (indicated by dashed lines) that passes through the female Luer-lok connection element 708 and through a segment of the adapter housing 704 to a valve 800, and a second segment of the fluid passageway 707 (indicated by dashed lines) that passes from valve 800 to an interior area 703 of a vial housing 702. Although represented as in-line passages, the invention contemplates passages 706 and 707 that are angled or orthogonal to one another.

As illustrated in Figure 16B, the inner chamber 703 may be configured to receive a vial 500 such as, for example, a standard vial. Alternative vials or containers can be used, as described above. The vial housing 702 may be further configured to contain an associated stabbing device 400e which may be similar to or identical to the stabbing devices described above. Insertion of vial 500 into housing 702 may be as previously described with respect to extension housing 600 with reference to Figures 1-10.

Adapter 700 can be formed of any suitable material and, in particular cases, will comprise a plastic material such as any of the plastic materials described above with respect to syringe housings and plungers. Valve 800 may be any of the types of valve described above with respect to exemplary valve 300 and may therefore comprise any of the materials described with reference to such exemplary valve. Alternatively, adapter 700 may be configured to have a rotary type valve system, as described with reference to Figures 15A-D.

The methodology for mixing separate components to prepare a mixture or ready-for-administration agent using the set illustrated in Figures 16A-B may comprise providing a first component in a separate vial 500 and providing a second component to be combined and mixed with the first component. into syringe 100. Syringe 100 and vial 500 are then attached each to adapter 700. Attachment and piercing of vial 500 can be performed as described above with respect to prior embodiments having piercing device 400. The order of attachment of vial 500 and syringe 100 is not limited to a particular sequence. Preferably, valve 800 is in a closed position during vial and syringe attachments.

At the time of assembly, valve 800 may be rotated or otherwise repositioned to an open position to establish fluid communication between the first segment of path 702 and the second segment of path 707 that allows fluid to pass through. through the adapter. Consequently, fluid communication is established between vial 500 and syringe 100.

The combination of the first and second components may comprise drawing the first component from the vial 500 into the syringe (usually with the vial in an inverted position), or it may comprise ejecting the second component from the syringe into the vial 500. Mixing of the components may comprise a pumping action as described above with previous embodiments independently or in combination with shaking or otherwise agitating the combined components. The resulting mixture can be drawn internally into syringe housing 102e normally while the vial is inverted, and valve 800 can be closed. Where the mixture is to be subsequently transferred or administered to an individual, the 700 adapter

ES 2 575 163 T3 can be removed from attachment to the Luer-lok connecting element 108e and a transfer device such as a needle, cannula, transfer tube, or other transfer structure can be attached to the Luerlok device 108e. Transfer or administration of the mixture can then be achieved by expelling the mixture from the internal chamber within the syringe housing 102e.

An alternative configuration of an adapter included in a set is illustrated in Figure 17. Assembly 10e 'comprises an alternative adapter configuration 700e' with respect to that shown in Figures 16A and 16B. The illustrated adapter is a "three-way" adapter having a first segment 710e 'extending from a three-way valve 800e' to a first port 711e 'having a connecting element (for example, a connecting element of the type Luer-lok) for connection to syringe 100e '. Adapter 700e 'further includes a second segment 712e' that extends from valve position 800e 'to a second port 713e'. The adapter further has a third segment 714e 'extending from valve position 800e' to a third port 715e 'which may comprise a connecting element configured for insertion or other association with housing extension 600e' as illustrated. . Port 715e 'may be further configured to include a piercing structure (not shown) such as the various piercing devices described above. Extension portion 600e 'may have any of the configurations described above to receive, stabilize, and / or retain vial 500 shown in a partially inserted position within extension 600e'. Syringe 100e 'may be a standard conventional syringe with an associated standard-type plunger 200e' as illustrated, or it may be an alternative syringe configuration, including but not limited to those described above.

The triple port adapter configuration illustrated in Figure 17 may advantageously allow the introduction and / or withdrawal of material into or from the system without dissociation of the syringe and / or vial 500. For example, after mixing or preparing a drug Using methodology analogous to that described above, the prepared drug can be transferred or otherwise withdrawn from the assembly device 10e 'through port 713e'. Such transfer or removal can be accomplished by attaching, for example, a vial, transfer conduit, or other appropriate transfer apparatus to port 713e '. As illustrated, the port 713e 'has a general type connecting element. However, a Luer-lok or alternative connection element may be used as appropriate for attachment to a desired transfer device or container.

Transfer of material from the pool via port 713 may be useful for applications such as IV administration. An alternative administration such as intramuscular injection, you can use a 100e 'syringe independently after removal of the assembly. In either case, the plunger sinking during injection can be done manually or using a syringe pump.

Where a material such as a liquid material for example, must be introduced into the assembly 10e 'said introduction can be achieved by passing through the port 713 and the adapter segment 712e'. The introduced fluid can be directed into a vial 500 or into a syringe 100e 'as appropriate, by manipulating and positioning the valve 800e'. The introduction of a fluid into the assembly may be appropriate, for example, where each of the first and second components (within the vial and the syringe respectively) is provided in a dry or concentrated form.

The configuration of adapter 700e 'illustrated in Figure 17 may allow linear alignment of syringe housing 102e' and vial 500. It should be understood that the invention further contemplates configurations that have the positions of segments 714e 'and 712e' interchanged, such that vial 500 and syringe body 102e 'are positioned in an orthogonal arrangement. Additionally, adapter 700e 'may be alternatively configured to provide segments 710e', 712e ', and 714e' at alternate angles to each other compared to the orthogonal arrangement shown. The adapter 700e 'may optionally have additional segments and ports and may comprise a valve of a higher order than the three-way valve shown.

A further alternative device configuration according to the invention is described with reference to Figures 18A-18C. Referring to FIG. 18A, the assembly 10f includes a plunger 200f having a rotational-type valve portion disposed at the second end 204f. Valve portion 226f is functionally and structurally analogous to valve portion 226 as shown in FIG. 15B and as previously described. However, instead of being disposed at a junction between two parts of a plunger rod, as illustrated in FIG. 15B, the valve part 226f is disposed at the end of the plunger and is insertable into an opening 557 of the plunger. a vial cap 550 according to the invention. The vial cap 550 may be configured for use in conjunction with a vial such as the exemplary vial 500f depicted in FIG. 18A. The vial 500f can be, for example, a standard drug vial or an alternative container. The vial cap 550 may comprise a base portion 552 and a cylindrical or alternatively protruding portion 554 having an opening 557 configured to receive the valve portion 226f of the plunger structure.

Upon insertion of the valve portion 226f of the plunger into the receiving opening 557 of the cap 550, the cap / plunger combination may function as a rotational valve as described above with respect to the rotational valve shown. in figure 15.

IS 2 575 163 T3

Referring now to FIG. 18B, grooves 559 provided within the interior side walls of opening 557 may be aligned with fluid passages 228f of valve portion 226f. The alignment may provide fluid passage between passage 206f through plunger 200f and a corresponding fluid passage 560 that passes from aperture 557 through base portion 552 of cap 550, thereby allowing passage of fluid. between a cylindrical syringe body associated with plunger 200f and a vial or container associated with cap 552. The fluid alignment and the resulting contiguous passages are depicted in FIG. 18C. Selective fluid communication can be interrupted by opposing rotation of plunger 200f with respect to vial cap 550. In the configuration depicted in Figure 18 AC, fluid access is provided directly between plunger 200f and a vial, so that the cap 550 may be used in the absence of any piercing structure, such as the exemplary piercing structure described above.

The invention also contemplates the use of features of the device shown in Figure 18 also contemplated in combination with one or more features described in alternative embodiments above. In particular applications, it may be preferable to provide multiple fluid barriers between a syringe barrel and a vial. Accordingly, the rotational valve configuration depicted in Figure 18 can be used in combination with a second rotational valve, as depicted in Figure 15, or an alternative valve, as described above with reference to previous figures. Such multi-valve configurations can advantageously provide an additional safety feature against inadvertent contact or mixing of separate components housed within a barrel syringe and drug vial. Filters, such as those described above, can additionally be used with the device of Figure 18 and variants thereof.

The methodology for using the configuration of the assembly represented in Figures 18A-C is analogous to the methodology described above (in the absence of performing steps to pierce the cap of a vial). Where multiple valves are provided, fluid communication can be established between the syringe barrel and the drug vial by placing each of the valves in the open position. Mixing can be achieved by, for example, stirring and / or using a pumping action of the plunger. One or both valves can be used to interrupt the flow of fluid, allowing transfer and / or delivery of the prepared drug.

Although various devices of the invention using a syringe vial 500 are described, it should be understood that the invention encompasses aspects where multiple vials are used. In such cases, a first vial can be removed from the set after removing all or a desired part of the contents of the original vial, and can be replaced by a second vial comprising additional or different material. Accordingly, the mixing systems of the invention can be used to prepare drugs that are composed of three or more components. Mixing of the additional component can be achieved in a manner analogous to the mixing methodology described above for a corresponding assembly configuration.

Mixing / administration sets according to the invention can be shipped as a single unit including a linear arrangement of the syringe device and the vial. Where a set uses a separate vial, the vial may be provided in or out of alignment with the mixing / delivery device. Alternatively, where a vial is self-contained, it can be packaged separately from the mixing device. An exemplary container in accordance with the invention that can be used for a linearly aligned mixing device and vial combination is described with reference to Figures 19 and 20.

As illustrated in Figure 19, a drug preparation system 20 in accordance with the invention may comprise a container component 900 configured to receive assembly 10 in linear alignment with a vial 500. The container component 900 may be a tray-like component, as illustrated, having a multi-part cavity 901, 902, 903. Cavity part 901 may be configured to approximate the shape of syringe 100 and associated cap 50. The cavity portion 902 may be shaped to approximate the shape of the plunger portion 200. The cavity portion 903 may be shaped to correspond to the shape of the combined extension portion (including the fit to the plunger 200 in the illustrated embodiment ) and an associated vial 500 that can be partially inserted into housing 600.

In most circumstances, it may be preferable that the vial 500 is only partially inserted with the housing 600. In particular cases, it may be highly preferred to avoid contact between the piercing structure comprised by the assembly and the cap or septum comprised by the assembly. vial 500. Accordingly, a projection 904 may be provided within the cavity portion 903 which may be insertable within the groove 602 of the extension housing 600. The projection 904 may be positioned within the groove to stabilize a spaced relationship between the vial 500 and the piercing device to avoid contact with the piercing structure prior to removal of the assembly from the container cavity.

The cavity 901, 902, 903 may be configured to be closely conformed to the shape of the assembly to provide stability to the assembly, preferably to stabilize the position of the plunger relative to the barrel of the syringe. Although the recesses depicted in Figure 19 reproduce the overall shape of the assembly, it should be understood that the recess may be alternatively shaped to provide placement and position stability.

IS 2 575 163 T3

Container component 900 can be formed, for example, by molding. Appropriate materials for container component 900 include plastic materials, preferably plastics that have adequate strength to provide positioning and stability of the packaged assembly.

A cover 905 may optionally be provided which may be associated with the container component 900. The cover 905 may be provided to cover at least the upper part / opening of the tray to protect the assembly within the container. In particular cases, the cover 900 can be used to seal the package and can allow a sterile environment to be created and maintained within the package. The cover can comprise a translucent or opaque material. It may be preferable that at least a part of the cover is transparent to allow visual inspection of the contents (device and / or labels).

As shown, cover 905 is a sheet of material that can be attached to component 900. Alternatively, the cover can be a lid-type cover that can be configured to fit so that it can be inserted into the tray opening. or to make at least one upper part of the tray fit so that it can be inserted into a cavity in the lid (not shown).

As illustrated in Figure 19, one or more labels 910, 912 may be provided in association with assembly 10. A first label 910 may be used in association with the syringe portion of the device and may provide information regarding the contents of the device. syringe. A second label 912 can be provided associated with the vial 500 and can be used to identify or provide information regarding the component within the vial. Where the drug is being provided to a particular individual, one or more of the labels 910 and 912 may contain discriminating markings of the patient. Although Figure 19 depicts two labels, an alternative number of labels may be provided. The content of the information provided on the label is also not limited to any particular content and may provide additional information such as, for example, instructions, warnings, etc. Additionally or alternatively, the labeling may be provided in association with container component 900 and / or 905 (not shown).

The type of the one or more labels used in association with the mixing device 10 and / or the associated vial 500 is not limited to a particular type of label. Exemplary labels may include barcodes, as illustrated. Alternatively or additionally, one or both of the tags 910 and 912 may be a radio frequency identification (RFID) tag (not shown). Appropriate barcode and / or RFID labeling can be particularly useful for identifying and tracking batches, for purposes of maintaining drug-related records and / or patient-specific information. Such labeling can provide an additional measure of security. For example, in the event of an adverse reaction after administering the prepared drug, the information provided on the label can be used to identify the source, lot number, etc., which, in turn, can be used to trace other assembly devices. or device components containing material from the identified lot. Such labeling can further be used to identify others who may be at risk and / or provide information regarding the particular reaction, etc.

In the event of an adverse reaction or identification of a defect, the analysis of any material retained within the device after administration can be analyzed by, for example, analytical techniques including but not limited to mass spectrometry and / or gas chromatography- liquids. The appropriate notification to the FDA can then be made.

With reference to Figure 20, this shows one aspect of the further package of the invention. The assembly device 10 may be provided within a second container component 920 which may be a sealed bag type component as illustrated. The container component 920 may preferably provide a closed environment around the device 10 that protects the device and components from exposure to an environment external to the container component 920. In particular cases, it may be preferable that the internal environment is sterile, especially where the drug components and / or the components of the system 10 are sterile and must be kept in a sterile state prior to administration.

Container component 920 may preferably be translucent and may be formed of a suitable translucent plastic material. The particular material used may preferably be selected to provide flexibility to allow handling of assembly 10 without opening of container component 920. In particular, it may be preferable that component 920 is provided to have sufficient internal volume and material flexibility to allow the vial to be manipulated for cap / septum engagement and piercing. Component 920 may also preferably be retained in the sealed state while the valve and plunger are manipulated during combining and mixing of the drug components (described above). The ability to prepare the drug for administration without opening the container component 920 can minimize or prevent contamination by avoiding exposure to an environment external to the container component. At the time of preparation of a drug ready for administration, container component 920 can be opened, the protective cap on the front end of the syringe can be removed, and transfer and / or administration can be accomplished using methods described above.

Although each can be used independently, the packaging components 920 and 900 depicted in the

Figures 20 and 19 respectively, are configured to allow the use of both components for a given device. For example, a mixing device can be enclosed within container component 920 and component 920 and its enclosed device can be inserted into the cavity of component 900. Accordingly, component 900 can be used to provide positioning and stabilization during shipping and the storage. The mixing system can be removed from container component 900 while it is being retained within component 920. Bag component 920 can be retained in a sealed state during combining and mixing of the separate components to prepare a drug ready for administration. Where each of the components 920 and 900 are used, the cover 905 may be optionally provided.

Although Figures 19 and 20 depict a particular configuration of the mixing system, it should be understood that similar packaging concepts can be used and adapted for any of the alternative mixing systems described herein.

Each of Figures 19 and 20 represent labels associated only with the components of the device. Additional labels (not shown) can be associated with the package by enclosing them within the package or by attaching them externally to the one or more package components. The additional labeling can be, for example, any of the label types described above or alternative labels known to those of skill in the art.

A further packaging aspect in accordance with the invention is illustrated in Figure 21. Assembly 10, as illustrated, corresponds to the configuration illustrated in Figure 17 and described with reference thereto. Container component 920 corresponds to container component 920 described above with reference to FIG. 20. As illustrated in Figure 21, component 920 may be configured to alternatively provide access to assembly 10 via tear tape 921 or seal opening. The illustrated container configuration may allow mixing and preparation of a drug in a sealed environment followed by opening the container along tear tape 921. Where appropriate, the prepared drug can be transferred from assembly 10 by attaching, for example, an appropriate transfer apparatus to the available port (port 713 as described and illustrated in Figure 17). Said attachment and transfer can be carried out while all or part of the assembly 10 remains within the container enclosure.

Where the preparation of a drug involves the addition of material to the interior of assembly 10 (described above), such material can be added, for example, by opening tear tape 921 and connecting an appropriate transfer device to the available (unoccupied) access. ) and positioning of the valve to allow introduction of the material into the syringe or vial, as appropriate. Additional mixing and preparation steps may be performed, as described above, with or without removal of the assembly 10 from the container 920. The transfer or administration of a drug prepared from the assembly may comprise placing the entire assembly into a pump of syringe, may comprise removal of the vial and / or adapter from the assembly prior to placement of the syringe in a syringe pump, or may comprise manual manipulation of the syringe plunger.

An alternative tray type container component 900a is illustrated in Figure 22. As illustrated, a single cavity 913 may be provided, having projecting portions 914, 915, 916, and 917. The projecting portions 914-917 may be structures. platform type that are shaped and positioned appropriately to stabilize an inserted mixing assembly. Alternative numbers and positioning of the protruding portions are contemplated with respect to the particular configuration shown in Figure 22. The container 900a may further include a protruding protrusion (not shown) similar in shape and function to the protrusion 904 shown in Figure 19 and described above. Said protrusion may be configured to insert into a slot present in the extension housing as described above to retain vial 500 in an unattached position with respect to the piercing structure. Although container component 900a is depicted as being configured for the device illustrated in Figure 17, it may be adapted for any of the alternative embodiments described above. Additionally, container component 920 as illustrated in FIG. 21 may be used simultaneously with component 900a by providing, for example, an assembly within container component 920 prior to insertion of the assembly into the tray-like component of the container. .

Container component 900a may comprise a lid portion 905a analogous to that shown and described with reference to Figure 19. Appropriate labeling of components of the set (i.e. vial and / or syringe) may be used independently of or in addition to labeling of one. or more of the packaging components, as described above.

Where additional material must be added to the exemplary assembly depicted in Figure 22, the lid 905a, or a portion thereof, may be removed from the container component 900a followed by opening a tear tape 921, such as that depicted in Figure 21. An appropriate transfer device may be attached to the unoccupied port prior to removing the assembly from the container tray. Introduction of material can be accomplished by manipulation of the valve and plunger without further removal of the assembly from the container component 920. Such accessibility to the valve and access may allow the introduction of additional materials into the assembly while limiting the exposure of the assembly. and the components inside to an external environment.

IS 2 575 163 T3

Aspects of the invention may comprise features taken from any of the following numbered clauses

1. A syringe device comprising: a syringe body comprising a cylindrical housing and a chamber within the housing, the chamber having a longitudinal axis;

a plunger comprising a stem a first end and a second end opposite the first end, the first end being external to the chamber, a passageway for fluid which extends through the first end, through the stem and through the second end of the plunger; and a valve, associated with the fluid passage, the valve controlling the selective passage of fluid through the plunger.

two. The device of clause 1 further comprising a hollow extension extending from the first end of the impeller.

3. The device of clause 2, in which the hollow extension is cylindrical.

Four. The device of clause 2, in which the hollow extension is configured to house a vial.

5. The device of clause 2, wherein the hollow extension is configured to reversibly receive a vial.

6. The device of clause 2, wherein the hollow extension comprises a base surface distally distal to the first end of the plunger, and wherein the hollow extension is configured to selectively retain a liquid.

7. The device of clause 2, further comprising a piercing structure arranged at least partially within the hollow extension.

8. The device of clause 7, in which the piercing structure comprises a channel through it.

9. The device of clause 8, wherein the piercing structure has a tip, an outer surface, and a base surface opposite the tip, and in which the channel passes through the base surface and through the surface external in a different position from the tip.

10. The device of clause 8, wherein the channel is in fluid communication with the fluid passage included in the plunger.

eleven. The device of clause 8, wherein the piercing device is configured to pierce a septum associated with a vial and to traverse the septum, such that selective fluid communication is provided between the chamber and the vial through the passage for fluid and through the channel by means of the valve.

12. The device of clause 1, further comprising a seal associated with the second end of the plunger, passing the passage for fluid through the seal.

13. The device of clause 12, in which the passage for fluid passes centrally through the gasket.

14. The device of clause 1, in which the stem comprises a first part and a second part, and in which the valve is arranged at a junction between the first part and the second part.

fifteen. The device of clause 1, in which the valve is selected from the group consisting of a stopcock, a ball valve, a push valve, a slide valve and a gate valve.

16. The device of clause 1, wherein the plunger is longitudinally slidable with respect to the chamber, wherein the valve is configured to be at least partially disposed within the chamber when the plunger is slid in the most forward position.

17. The device of clause 1, wherein the valve comprises an elastomeric material.

18. The device of clause 17, wherein the stem comprises a hard plastic material.

19. A piercing structure comprising: a head segment comprising a tip disposed at a first end of the structure, the head segment having a front surface and an opposite rear surface; a body part comprising a base surface arranged at a second end opposite the first end; and a passageway for fluid that passes through the second end, through the body portion, and through at least one of the front surface and the rear surface without passing through the tip.

twenty. The piercing structure of clause 19, wherein the frame is configured to pierce a partition material having a thickness, and wherein the body portion has a length that is greater than the thickness.

twenty-one. The piercing structure of clause 20, wherein the body part has a first segment that has a first cross-sectional area, and a second segment that has a second cross-sectional area greater than the first cross-sectional area, in where the second segment extends from the base surface of the structure to the first segment.

22. The piercing structure of clause 21, wherein the second segment has a uniform circumference along its entire length.

2. 3. The piercing structure of clause 19, wherein the structure is shaped like an arrowhead.

24. The piercing structure of clause 19, further comprising cutting edges consisting of a first cutting edge arranged at a first intersection of the front and rear surfaces, and a second opposite cutting edge, arranged at a second intersection of the front and rear surfaces .

25. The piercing structure of clause 19, wherein at least one of the front and rear surfaces is beveled.

26. A drug preparation system comprising: a syringe comprising: a syringe barrel having an internal chamber; and a plunger having a first end, a second end, and a passageway for fluid that passes longitudinally through the plunger, at least a portion of the plunger being inserted into the chamber, the portion comprising the first end; a perforating structure associated with

ES 2 575 163 T3 second end of the plunger, the piercing structure having a fluid channel and a tip; a vial arranged proximal and movable with respect to the tip of the piercing structure; a first component of a drug disposed within the inner chamber; a second component of the drug disposed within the vial; and a valve associated with the passage for fluid.

27. The clause 26 system, in which the valve selectively isolates the first component from the second component.

28. The system of clause 26, further comprising a packaging material, wherein the vial is disposed at a position within the packaging material in non-contact relationship with the piercing structure at the time of initial packaging, and wherein the packaging material provides stabilization for the non-contact relationship.

29. The system of clause 28, in which the vial comprises a septum, and in which the packaging material comprises a closed compartment which encloses the vial and the syringe and which allows manipulation of the position of the vial by an individual so that the septum can be pierced by the perforating structure without opening the closed compartment.

30. The system of clause 28, in which the packaging material comprises a closed compartment that encloses the syringe, valve, and vial, and in which the packaging material allows manipulation of the valve through the packaging material for repositioning the valve from a closed position to an open position.

31. The clause 28 system, wherein the packaging material provides an internal environment that encompasses the syringe, vial, and valve; wherein the plunger is disposed in a first position with respect to the chamber at the time of being initially packaged; wherein the packaging material allows manipulation of the position of the vial relative to the piercing device, manipulation of the valve, and manipulation of the position of the plunger within the chamber without exposing any of the vial, syringe, or valve to an environment outside the snow.

32. The clause 31 system in which the internal environment is sterile.

33. The system of clause 31 in which manipulation of the vial, valve and plunger provides mixing of the first and second components to form the drug.

3. 4. A method of preparing a medicament for administration to an individual, comprising:

providing a syringe comprising a syringe barrel and a plunger arranged in an initial position with respect to the syringe barrel; providing a first component within the barrel of the syringe; providing a second component within a vial; providing a valve associated with a passageway for fluid between the vial and the syringe barrel, the valve being initially provided in a closed position that blocks the passage of fluid through the passageway; repositioning the valve to allow the passage of fluid between the vial and the barrel of the syringe; after repositioning the valve, sliding the plunger in a first direction to join the first component with the second component; mixing the first and second components to produce the drug by repeatedly sliding the plunger in opposite directions; and attracting the drug into the barrel of the syringe.

35. The method of clause 34, further comprising: providing a piercing structure; and prior to repositioning, using the piercing structure to pierce a septum comprised by the vial, wherein the fluid passage between the vial and the syringe barrel comprises passing through the piercing structure.

36. The method of clause 34, further comprising closing the valve after drawing the drug into the barrel of the syringe.

37. The method of clause 34, in which the passage for fluid passes through the plunger.

38. The method of clause 37, wherein the valve is associated with the plunger, wherein the valve is arranged external to the syringe barrel while the plunger is in the initial position, and wherein the valve at least partially enters the cylindrical body during mixing.

39. The method of clause 37, wherein the plunger comprises: a gasket arranged at a first end; a second end opposite the first end; and a stem portion between the first end and the second end, wherein the passage for fluid extends through the joint, through the stem, and through the second end.

40. The method of clause 39, wherein the stem portion comprises a first segment, a second segment, and a junction between the first and second segments, wherein the valve is arranged at the junction.

41. The method of clause 37, further comprising providing a piercing structure, wherein the passage for fluid passes through the piercing structure.

42. The method of clause 34, wherein at least one of the first and second components is in liquid form.

43. The method of clause 34, in which the first component is a liquid and in which joining the first and second components comprises flowing the first component into the vial.

44. The method of clause 34, in which the second component is a liquid and in which joining the first and second components comprises flowing the second component into the barrel of the syringe.

Four. Five. The method of clause 34, wherein the drug is ready for administration upon being drawn into the syringe barrel, and wherein administering the agent to an individual comprises expelling the agent from the syringe barrel while the valve it is in the closed position.

46. The method of clause 45, further comprising attaching a needle to the syringe, and wherein the administration

ES 2 575 163 T3 comprises expelling the agent through the needle.

47. The method of clause 46, wherein the needle is attached after attracting the agent into the barrel of the syringe.

48. A method of preparing a composition, comprising: providing a packaging material containing a mixing device, the mixing device comprising: a housing having a chamber inside, the chamber having a first length and containing a first material ; a plunger slidable within the chamber, the plunger having a second length that is greater than the first length; a container that has a second material inside; a fluid passage arranged longitudinally through the plunger; and a valve associated with the passage for fluid; without exposing the device to an environment external to the packaging material, repositioning the valve from a closed position to an open position; with the valve in the open position, sliding the plunger in a first direction from a first position within the chamber to a second position within the chamber, the slide attracting one of the first and second components through the plunger; mixing the first and second materials to form a mixture, comprising the mixture, after sliding the plunger in the first direction and with the valve in the open position, sliding the plunger in a second direction opposite to the first direction, and subsequently sliding the plunger again in the first direction; and drawing the mixture into the chamber through the plunger.

49. The method of clause 48, in which mixing is performed without exposing the mixing device to the external environment.

fifty. The method of clause 48, wherein the mixing device further comprises a piercing structure disposed between the plunger and the container, and further comprising piercing the container with the piercing structure prior to repositioning the valve from the closed position to a open position.

51. The method of clause 50, in which the composition is a medicine and in which the container is a medical vial.

52. The method of clause 48, wherein the housing is a syringe housing.

53. The method of clause 48, in which the housing is a syringe housing, in which the container is a medical vial, and further comprising: after drawing the mixture into the chamber, returning the valve to the position closed; and filter the mixture.

54. A drug preparation device comprising: a syringe barrel having a first end, a second end, and a longitudinal axis between them; a plunger insertable within the barrel of the syringe through the second end, the plunger being slidable within the barrel; a vial containing a material; an adapter component comprising: a vial housing portion configured to reversibly receive the vial; a connecting element configured to be attached to the syringe at the first end; a valve; a first passage for fluid extending through the connecting element to the valve; and a second fluid passageway extending from the valve to the vial housing; and a container configured to allow manipulation of the valve and sliding of the plunger without opening the container.

55. The device of clause 54, in which the first and second passages are orthogonal with respect to each other.

56. The device of clause 54, wherein the adapter component further comprises a third fluid passage extending from the valve, and wherein the valve is a three-way valve.

57. The device of clause 54, wherein at least a part of the container comprises a translucent material.

58. The device of clause 54, in which the container comprises a removable part, in which before the removal of the removable part at least one of the plunger and the valve are tamper resistant, and in which the removable part is removed it decreases the tamper resistance of at least one of the plunger and the valve without exposing the syringe barrel, plunger or adapter component to an environment external to the container.

59. The device of clause 54, wherein a vial containing a first component of a drug is contained within the package.

60. The device of clause 59, wherein a second component is provided within the barrel of the syringe.

61. The device of clause 54, further comprising a piercing structure associated with the adapter component.

62. The device of clause 54, wherein a vial having a septum is contained within the package, wherein the device further comprises a piercing structure, wherein the package allows manipulation of the vial's position relative to the perforating structure, and wherein the perforating structure does not come into contact with the septum prior to manipulation.

63. A device comprising: a housing around a chamber, a plunger having a first end, a second end, and a passageway for fluid from the first end to the second end, the plunger being insertable in the chamber; and a valve associated with the fluid passage so that flow through the fluid passage is selectively regulated by the valve.

64. The device of clause 63, wherein the plunger is insertable into the chamber through a first end of the housing and wherein the housing is configured to receive a needle at an opposite second end.

65. The device of clause 63, in which the plunger comprises a seal arranged at the first end and in which the passage passes through the seal.

66. The device of clause 63, wherein the plunger comprises a stem having a first part and a second part, and wherein the valve is arranged at a junction between the first and second parts.

IS 2 575 163 T3

67. The clause 63 device, wherein the plunger has a plunger length between the first and second ends, wherein the passage has a minimum diameter along the length of the plunger, and wherein a ratio of the Plunger length relative to minimum diameter is greater than or equal to about 10: 1.

68. The device of clause 63, further comprising a one-piece container with the plunger, wherein the container is in selective fluid communication with the chamber through the fluid passage.

69. The device of clause 63, further comprising: a hollow one-piece extension with the second end of the plunger; and a piercing structure within the hollow extension, wherein the hollow extension is configured to receive a vial comprising a septum, and wherein the septum can be pierced by the piercing structure upon at least partial insertion of the vial within the casing.

70. The device of clause 69, wherein the fluid passageway is a first fluid passageway, and wherein the piercing structure has a second fluid passageway that allows fluid communication between the first fluid passageway and an internal region of the vial after piercing the septum.

71. The device of clause 70, in which the piercing structure has a base end close to the plunger and a point opposite the base end, and in which the second passage does not pass through the point.

72. A device comprising: a housing around a chamber; a plunger structure having a first end that is insertable into the chamber, and a second end opposite the first end, the second end having a container enclosing a compartment; a passage for fluid from the enclosed compartment to the first end; and a valve associated with the fluid passage so that flow through the fluid passage is selectively regulated by the valve.

73. The device of clause 72, wherein the plunger structure is molded as a single piece.

74. The device of clause 72, wherein the plunger comprises a two-part stem having a first part extending from the first end and a second part extending from the container, the first and second parts meeting in a joint .

75. The device of clause 74, in which the valve is arranged at the junction.

76. The device of clause 74, in which the container and the second part are molded in common.

77. The device of clause 74, in which the container and the second part are independently molded and subsequently fixed to each other.

78. The device of clause 77, in which the container and the second part are fixed by welding.

79. A system for preparing a drug comprising: a syringe having an opening at a first end and a plunger insertable into a second end; a container having a first component disposed therein; an adapter fixable to the first end of the syringe and comprising a connecting element configured to receive the container; and - a valve associated with the adapter, the valve being configured to control the passage of fluid through the opening in the first end of the syringe.

80. The system of clause 79, wherein the valve is a three-way valve configured to controllably establish fluid communication between the container and the syringe.

81. The clause 79 system, wherein the adapter comprises: a first segment extending from the valve position to a first connecting element attachable to the first end of the syringe; a second segment extending from the valve position; and a third segment extending from the valve position, the third segment comprising a housing configured to receive the container, wherein the third segment is orthogonal to the first segment.

82. A method of preparing a drug comprising: providing a mixing device comprising: a syringe having a first end and a plunger inserted into a second end; and an adapter connected to a first end of the syringe, the adapter comprising a first port, a second port, a third port, and a valve comprising the passage of fluid through the ports; and flowing a fluid into the adapter through the first port and into the syringe through the second port.

83. The method of clause 82, wherein a vial containing a first component of a drug is associated with the second port, and further comprising mixing the fluid with the first component.

84. The method of clause 83, in which the syringe contains a second component, and in which the fluid is mixed with the second component before mixing with the first component.