HK1193057B - Dual chamber mixing device for a syringe - Google Patents

Description

Dual chamber mixing device for syringe

Technical Field

The present invention relates to a mixing device for a syringe. More particularly, the present invention relates to a mixing device for a retractable syringe capable of storing, mixing, injecting one or more medicinal substances.

Background

It is known to provide syringes comprising mixing means for mixing the deliverable substance prior to injection. This allows, for example, the addition of a diluent to a dehydrated, lyophilized, dried or powdered active substance immediately prior to injection, which is particularly useful for substances that undergo deterioration or loss of activity when stored in hydrate form.

Most mixing devices for syringes that have a barrel with a first proximal lumen and a second distal lumen separated by, for example, a membrane or elastomeric seal utilize a continuous lumen. Many such continuous chamber mixing syringes utilize bypass projections at the cross-section of the barrel to enable fluid in the proximal chamber to bypass the separating membrane and mix with fluid or powder in the distal chamber.

However, some mixing syringes utilize a concentric barrel configuration. However, the concentric barrel mixing syringes heretofore required complex assemblies, multiple operating steps by the user or other particularly subtle differences that made them difficult to manufacture, assemble or operate. For example, some existing concentric barrel mixing syringes require concentric inner and outer barrels that are selectively rotatable relative to each other and require one or more sealing rings containing a channel means therein. The cartridge must be rotated to align with the bore in the inner cartridge through the passage means in the sealing ring. The channel means in the sealing ring comprises a radially extending opening through the sealing ring and a groove extending from the radially extending opening and in the longitudinal direction of the sealing ring. The arrangement is such that the grooves connect the outer barrel with the radially extending openings, and the radially extending openings selectively couple the grooves with the apertures in the inner barrel. This enables fluid to flow from the outer cartridge into the inner cartridge, thereby mixing the fluid with the substance in the inner cartridge. Such a construction requires complex components, requiring the user to laboriously manipulate the device.

Other concentric barrel designs utilize outer and inner cannula telescoping tubular elements disposed within the barrel and coaxial with the longitudinal axis. The outer tubular member and the barrel form a cavity of a reservoir containing a liquid. The outer tubular member has a fluid passage therein that allows liquid to flow from the lumen into the inner tubular member. The inner tubular member has an end near the injection port with a seal thereon with a small hole therein. The inner tubular member receives the end of a plunger with an elastomeric seal thereon. Thus, this mixing syringe configuration requires three tubular elements and has an outer concentric cavity and an inner concentric cavity inside the third barrel.

There are a number of complexities associated with the use of concentric barrels for mixing syringe configurations. Mixing syringes utilizing concentric barrels must address other factors in addition to those described above, such as maintenance of container sterility, interaction of elements for sealing, venting requirements, and internal force distribution, among others. Some dual chamber syringes have concentric inner and outer barrels that form an annular space to hold a fluid and utilize one or more small holes between the inner and outer barrels to enable the liquid to flow from the annular space into the inner barrel, thereby mixing the liquid with the contents of the inner barrel. The liquid is forced from the annulus into the inner barrel by depressing a plunger slidably movable in the annulus. First and second sealing bands are slidably received about and spaced along the inner barrel in the annular space. The location of the sealing band may determine how sterile the fluid path is maintained, how internal forces are distributed, and how venting occurs. For example, both the first and second sealing bands may be initially placed over the aperture to form a sealed annular volume for the first liquid component. Due to this arrangement, the aperture must also act as a vent so that any air in the annular space remote from the second sealing band (which space must be sterile) can be vented through the aperture when the plunger is depressed. This venting requirement can cause difficulties and requires additional equipment and processing steps, such as requiring filling of the lumen under vacuum to remove all air from the lumen and the distal portion of the outer barrel located below the second reconstitution seal.

Typically, prior art mixing devices comprising concentric barrels are relatively complex in construction and often require rotation of the barrel to align one or more orifices that enable liquid substances to flow from one chamber into another. In addition to this, the various aseptic, sealing and venting arrangements that have been used have severe limitations in terms of ease of manufacture and operation of the mixing device.

Disclosure of Invention

It is therefore an object of the present invention to provide a mixing device and/or a syringe comprising a mixing device, thereby alleviating one or more of the problems associated with prior art mixing devices and/or syringes, such as those described above.

In one aspect, the present invention provides a mixing device for a syringe, the device comprising: an outer barrel and an inner barrel in substantially coaxial relationship, the mixing device capable of comprising a plurality of mixing substances, wherein at least a first mixing substance is locatable in an outer chamber between the outer barrel and the inner barrel and at least a second mixing substance is locatable in an inner chamber in the inner barrel, the inner barrel comprising one or more fluid pathways through which the first mixing substance can enter the inner chamber in the inner barrel to form a mixture with the second mixing substance; one or more vents in fluid communication with the outer chamber; and at least one seal located in the outer chamber axially movable from a first position in sealing engagement with the one or more fluid paths in the inner barrel to a second position at least partially between the one or more fluid paths and the one or more vents. Suitably, the inner and outer barrels are non-rotatable relative to each other.

The one or more fluid paths may include one or more apertures, holes, perforations, ports, passageways, or conduits. These may be of any suitable shape, configuration, arrangement and/or number. Preferably, the fluid path comprises a plurality of small holes. The apertures may be radial perforations (i.e., perpendicular to the axis of the barrel), angled perforations (i.e., at an angle to the axis of the barrel), spiral (e.g., passages that are angled and radial with respect to the thickness through the barrel wall), or any number of other configurations. The location spacing and number and placement of orifices in the array can also be adjusted for desired mixing characteristics. Accordingly, the parameters of these orifices may be configured to enhance the desired mixing, dilution, and other fluid flow characteristics of the mixing syringe.

Suitably, the mixing device further comprises an axially moveable mixing plunger within an outer chamber between the outer and inner barrels to facilitate entry of at least a first mixing substance into the inner chamber in the inner barrel and to facilitate axial movement of the seal from a first position in sealing engagement with the one or more fluid paths in the inner barrel to a second position intermediate or at least partially between the one or more fluid paths and the vent. For ease of operation or aesthetics, the mixing plunger may have one or more extensions, such as finger and/or thumb extensions.

Preferably, the fluid mixing device comprises a plurality of seals. Preferably, the plurality of seals includes a proximal seal and a distal seal. In a preferred embodiment, the plurality of seals comprises: a proximal seal engageably or connectably coupled, connectable or attached to the mixing plunger and slidably movable in the outer chamber; the distal seal initially in a first position in sealing engagement with the one or more fluid paths in the inner barrel and slidably movable in the outer chamber from sealing engagement with the one or more fluid paths to a second position intermediate or at least partially between the one or more fluid paths and the vent. Movement of the mixing plunger causes movement of a proximal seal to which the plunger engages or is connectably coupled or attached. This movement is transferred (relay) to the first mixing substance in the outer chamber and similarly to the distal seal. Thus, axial movement of the mixing plunger indirectly (i.e., without direct contact) facilitates axial movement of the distal seal to the second position.

Preferably, the one or more vents are operable to facilitate venting of air from the outer chamber to ambient air as the mixing plunger and distal seal slidably move within the outer chamber. The one or more vent holes may be integrally formed in the outer barrel, or may be a vent cap mounted or attached to the inner and/or outer barrels. In either embodiment, conduits, pores, porous membranes, collapsible elements, and the like may be utilized. For example, in at least one embodiment, the vent cap is a plastic vent cap containing one or more vent conduits that closes the outer chamber at the distal end of the outer barrel, while allowing air to pass through the one or more vent conduits to ambient air when the mixing plunger is depressed and the distal seal is moved.

In an embodiment, the mixing device further comprises a removable safety cap. Preferably, the removable safety cap prevents unwanted movement of the distal seal prior to use (e.g., during shipping). The removable safety cap may include a plurality of protrusions that are insertable through respective vent conduits so as to be proximate to or in contact with the distal seal.

The mixing device may further comprise a barrel extension mounted to or integrally formed with the outer barrel. The barrel extension may optionally include a finger flange or handle, or may alternatively have an optional finger flange or handle connected to the barrel extension.

The mixing device may further comprise one or more mixing plunger locks. In one embodiment, elements of the mixing plunger and the barrel extension are engageable to form the mixing plunger lock. In a particular embodiment, the mixing plunger lock prevents removal of the mixing plunger from the outer chamber during use. In another particular embodiment, the mixing plunger lock prevents proximal, axial movement of the mixing plunger after mixing is complete.

The first and second mixing substances may comprise one or more fluids or one or more solids. The first mixing substance, which may be located in the outer chamber, may be a fluid. The fluid may be a pharmaceutically active fluid or a pharmaceutically inactive fluid, such as a diluent. The second mixing substance that may be located in the lumen may be a pharmaceutically active solid or a pharmaceutically active fluid or a pharmaceutically inactive fluid.

In one embodiment, the inner chamber contains a pharmaceutically active solid and the outer chamber contains a pharmaceutically inactive diluent, such as water, whereby the diluent passes from the outer chamber into the inner chamber through one or more small holes to facilitate mixing with the pharmaceutically active solid. The interaction between the diluent and the pharmaceutically active solid enables reconstitution of the pharmaceutically active solid for subsequent delivery to a patient.

In another embodiment, the inner chamber contains a pharmaceutically active solid and the outer chamber contains a pharmaceutically active fluid, whereby fluid from the outer chamber enters the inner chamber through one or more orifices to facilitate mixing with the pharmaceutically active solid in the inner chamber. The interaction between the pharmaceutically active fluid and the pharmaceutically active solid enables reconstitution of the pharmaceutically active solid for subsequent delivery to a patient.

In another embodiment, the inner lumen contains a first pharmaceutically active fluid and the outer lumen contains a second pharmaceutically active fluid, whereby said second pharmaceutically active fluid enters the inner lumen from the outer lumen through one or more small holes facilitating mixing with said second pharmaceutically active fluid in the inner lumen. The interaction between the first pharmaceutically active fluid and the second pharmaceutically active fluid is capable of mixing the pharmaceutically active fluids for subsequent delivery to a patient.

Thus, the mixing device may facilitate storage of the multi-component pharmaceutical substance in the outer and inner chambers, thereby maintaining the stability and efficacy of the pharmaceutical substance during shipping and over-extended periods of storage.

In another aspect, the invention provides a syringe comprising a delivery plunger, a needle assembly and a mixing device according to the above aspects. Syringes may be used to store, transport, mix, and inject one or more mixed substances to treat a patient. As will be described further below, the syringe may further contain a safety feature that retracts the needle after use, providing the desired needle stick prevention, and preventing syringe reuse.

Suitably, the delivery plunger is slidably moved within the inner barrel of the mixing device to thereby facilitate delivery of the mixed substance or mixture to a user, patient or other recipient.

In a preferred form, the syringe is a retractable syringe comprising a retractable needle. Preferably, the delivery plunger is capable of engaging the needle to retract the needle. Suitably, retraction of the needle is facilitated by a biasing member, such as a spring, resilient member or other member capable of storing energy and releasing energy to facilitate needle retraction. It will be appreciated that the retractable syringe may include a needle retraction mechanism operable by the mixing device disclosed in this specification. For example, the needle retraction mechanism may be as described in, but not limited to, international publication WO2006/119570, international publication WO2006/108243, international publication WO2009/003234, and international publication WO 2011/075760.

According to one embodiment, the retractable syringe comprises: a plunger comprising a biasing member, a plunger housing, and one or more detent members, wherein the plunger member and the plunger housing cooperate to releasably maintain the biasing member in an initial energized state; and a needle assembly comprising a retractable needle, wherein the retractable needle comprises a cannula and a needle engageable by a plunger member.

Preferably, a plunger seal is mounted to the plunger member, the plunger seal being capable of engaging the needle body.

Preferably, the needle assembly may further comprise a needle seal retaining the retractable needle, wherein the cannula of the retractable needle passes through the needle seal to allow the mixed substance or mixture to be delivered to a user, patient, or other subject.

In at least one embodiment, the mixing plug further comprises a release ring. Suitably, the release ring is at the proximal end of the mixing plunger (i.e. opposite the distal end, it is engageably or connectably coupled, connectable or attached to the first or proximal seal of the mixing plunger). The release ring may be a separate element or integrated with the mixing plunger. In a preferred embodiment, the release ring is a smaller diameter proximal portion of the mixing plunger. The release ring may initiate needle retraction after the plunger member of the retractable syringe engages the needle body. Upon actuation of needle retraction, the plunger member and plunger housing disengage such that the biasing member expands from its initial energized state. The plunger housing remains substantially in contact or connected with the release ring, while the plunger member is axially translated in the proximal direction by release of the biasing member, thereby enabling retraction of the cannula and needle.

Suitably, the retractable syringe comprises one or more delivery plunger detent systems. In one embodiment of the detent system, the plunger housing of the delivery plunger comprises a detent member that is capable of engaging the release ring of the mixing plunger upon needle retraction to thereby prevent or hinder further movement of the delivery plunger relative to the release ring. In another embodiment of the detent system, the plunger housing includes a clip that engages the plunger member after retraction of the plunger member and the needle engaged therewith.

In at least one embodiment of the present invention, the retractable syringe comprises a retraction mechanism substantially as described in WO2011/075760, functionally modified to the release ring of the mixing plunger described above.

In another aspect, the present invention provides a method of assembling a mixing device, comprising the steps of:

(i) placing a coaxially aligned outer barrel over an inner barrel, the inner barrel having one or more apertures in communication with an inner cavity of the inner barrel, the coaxial alignment of the outer barrel and the inner barrel forming an outer cavity, wherein the outer cavity has one or more vents in fluid communication with the outer cavity, the one or more vents being located distal to the one or more apertures; and

(ii) inserting a seal into the outer chamber in releasable sealing engagement with the one or more apertures.

In one embodiment, the method further comprises, prior to step (i), attaching a vent cap comprising one or more vent holes to a portion of the inner barrel distal to the one or more apertures. Preferably, the distal end portion of the outer cylinder is connected to the exhaust cap.

Preferably, the method further comprises the step of inserting a needle assembly into the lumen distal to the one or more apertures.

In a further aspect, the present invention provides a method of manufacturing a syringe including a mixing device, the method comprising the steps of:

(i) placing a first mixing substance in the outer chamber of the mixing device and inserting a first or proximal seal into the outer chamber of the mixing device in contact with the first mixing substance;

(ii) placing a second mixing substance in the inner chamber of the mixing device;

(iii) inserting a delivery plunger into the inner barrel, wherein the delivery plunger is proximal to one or more apertures in the inner barrel; and

(iv) installing a mixing plunger in the outer chamber, wherein the mixing plunger contacts the first or proximal seal.

In a further aspect, the present invention provides a method of operating a syringe comprising a mixing device, the method comprising the steps of:

(i) operating a mixing plunger of a mixing device to mix a plurality of substances;

(ii) (ii) operating the delivery plunger to deliver the substance mixed in step (i) to the recipient.

In at least one embodiment, the method of operating a syringe comprising a mixing device further comprises: (iii) the needle retraction mechanism is activated to retract the needle to the syringe. Preferably, activation of the needle retraction mechanism occurs after substantially all of the substance has been delivered to the subject.

In this specification, unless the context requires otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be used inclusively rather than exclusively, and accordingly a stated integer or group of integers may include one or more other integers or groups of integers not stated.

Drawings

Non-limiting embodiments of the present invention are described herein with reference to the following drawings, in which:

FIG. 1A shows a side view of an embodiment of a mixing device;

FIG. 1B shows a side view of an embodiment of a mixing device with the distal seal removed to reveal a fluid path aperture;

FIG. 2 shows an embodiment of the mixing device further comprising an optional safety cap mounted thereon;

FIG. 3A shows an embodiment of a retractable syringe comprising a mixing device;

FIG. 3B shows an exploded view of an embodiment of a retractable syringe including a mixing device;

FIG. 4 shows a cross-sectional view of the delivery plunger of the retractable syringe;

FIG. 5 shows an embodiment of a retractable syringe including a mixing device after removal of the safety cap and prior to depression of a mixing plunger of the mixing device;

FIG. 6 shows an embodiment of a retractable syringe including a mixing device after depression of a mixing plunger of the mixing device;

FIG. 7 shows an embodiment of a retractable syringe including a mixing device after depression of a delivery plunger;

FIG. 8 shows an embodiment of a needle assembly engaged by a delivery plunger prior to retraction;

FIG. 9 shows an embodiment of a release ring that disengages the plunger housing from inside the plunger to facilitate spring decompression and needle retraction; and

fig. 10 shows an embodiment of a locking system for a retractable syringe.

Detailed Description

Referring to fig. 1A and 1B, an embodiment of a mixing device 100 includes an inner barrel 110, an outer barrel 120 including a wall 121, and a mixing plunger 130, the inner barrel 110 including a wall 111 and an inner chamber 112. The outer chamber 140 is formed between the wall 111 of the inner cylinder 110 and the wall 121 of the outer cylinder 120. The inner barrel 110 and outer barrel 120 can be made from any number of materials, including plastic and glass, but are preferably made from glass. The inner barrel 110 and the outer barrel 120 are in a substantially concentric relationship such that the inner barrel 110 and the outer barrel 120 have a substantially common central longitudinal axis. The inner and outer barrels 110, 120 are non-rotatable relative to each other.

The outer barrel extension 150 includes a finger grip 151A, B to assist in user grip. The outer barrel extension 150 may be integrally formed on the outer barrel 120 or may be a separate element attached to the outer barrel 120. The outer barrel extension 150 further includes an inner lip 152 and a locking ring 153, the function of which will be described in detail below.

Typically, the outer chamber 140 contains a liquid substance and the inner chamber 112 contains a solid substance, whereby the liquid substance and the solid substance mix in the inner chamber 112 to form a mixed substance suitable for injection. However, in at least one embodiment, both the outer chamber 140 and the inner chamber 112 contact a liquid substance.

In the embodiment shown in fig. 1A and 1B, the outer barrel 120 is shorter than the inner barrel 110. This configuration provides certain advantages, such as allowing a heat transfer jacket (not shown) to be placed around and in direct contact with a portion of the inner barrel 110. This is useful to be able to freeze dry the liquid substance located in the internal cavity 112 in situ by allowing for filling with the liquid substance during or after manufacture of the mixing device 100, and then freeze drying the liquid substance to a powder.

In other embodiments, the lengths of the inner barrel 110 and the outer barrel 120 are substantially similar. This embodiment may be more aesthetically pleasing or provide additional volume through the outer chamber 140. Also disposed within the outer lumen 140 is a first or proximal seal 160 and a second or distal seal slidably disposed within the outer lumen 140.

The outer chamber 120 further includes a vent cap 123, the vent cap 123 including a plurality of vents 122, whereby the vent space 142 is located between the vents 122 and a second or distal seal 170. Since the substance does not contact this exhaust space 142, the exhaust space 142 may not be sterile and open to ambient air. This feature enables the second or distal seal 170 to be displaced toward the plurality of vent holes 122 during the mixing step of operation, thereby opening one or more apertures 114 for passage of fluid from the outer chamber to the inner chamber. The fluid path from the outer lumen 140 to the inner lumen 112 remains sterile due to the displaced position of the second or distal seal 170.

The mixing plunger 130 includes a button 131 and a cylindrical shaft 132 slidably axially movable in an outer chamber 140. Mixing plunger 130 may further include spring teeth 133A, B located on shaft 132 that are biased outwardly from shaft 132. When the mixing plunger 130 is inserted into the outer chamber 140 of the mixing device 100, the spring teeth 133A, B move inward (i.e., opposite the bias). In the assembled mixing device 100, the spring teeth 133A, B prevent the mixing plunger 130 from being removed from the outer chamber 140, as will be described in more detail below. Mixing plunger 130 further includes locking teeth 134A, B (134B not visible) located on shaft 132 and biased outwardly from shaft 132. The locking teeth 134A, B are biased outwardly to engage the inner lip 152 of the barrel extension 150 to facilitate locking the mixing plunger 130 from moving proximally after mixing is complete.

Mixing plunger 130 further includes a release ring 136 at the proximal end of cylindrical shaft 132 (i.e., proximal to the user). The release ring 136 may be a separate element or an integral element of the mixing plunger 130. In a preferred embodiment, the release ring 136 is a smaller diameter proximal portion of the mixing plunger 130. The function of the release ring 136 will be described in detail below.

The first or proximal seal 160 contacts the distal end 135 of the cylindrical shaft 132 of the mixing plunger 130. A second or distal seal 170 is positioned within the outer lumen 140 distal to the proximal seal 160. The first or proximal seal 160 is slidably movable axially within the outer chamber 140 by movement of the shaft 132 of the mixing plunger 130. As best seen in fig. 1B, the small holes 114 in the inner cylindrical wall 111 provide fluid paths that allow fluid to flow from the outer chamber 140 into the inner chamber 112. Initially, the second or distal seal 170 is in sealing engagement with the aperture 114 (e.g., covering the aperture 114; compare FIGS. 1A and 1B).

In the embodiment shown in fig. 2, an optional safety cover 180 is removably mounted to the bracket 125 of the tub 120. Safety cap 180 includes a ring 182 and projections 181, which projections 181 are inserted through respective vent holes 122 (not visible in fig. 2) to access or contact distal seal 170. This prevents unwanted movement of the distal seal 170, such as due to air pressure changes during shipping or inadvertent movement of the mixing plunger 130 prior to intentional activation by a user.

Referring now to fig. 3-4 and 8-10, the mixing device is an element of a retractable syringe 1000 that includes a delivery plunger 200 and a retractable needle assembly 400. The delivery plunger 200 is axially slidably movable within the lumen 112 of the inner barrel 110 of the mixing device 100 to deliver fluid contents of the lumen 110 and subsequently retract the retractable needle 400.

The plunger 200 comprises a plunger member 210, said plunger member 210 comprising a shaft 211, an annular ledge 212 and a seal engaging member 216, said seal engaging member 216 in this embodiment being a threaded protrusion 217, said threaded protrusion 217 engaging a complementary threaded recess 820 of a plunger seal 800. Plunger seal 800 further includes a needle-engaging portion 810.

Plunger 200 further includes plunger housing 220, plunger housing 220 having elongate body 221, said elongate body 221 having a bottom 225 and a top 222 and a locking member 227.

The lever 230, which is releasably connected to the plunger member 210, includes a button 231, an arm 232, and a shaft 233. Plunger 200 further includes a compression spring 270 mounted between plunger member 210 and plunger housing 220, which is held in an initial compressed state between ledge 212 of plunger member 210 and bottom 225 of plunger housing 220. In at least one embodiment, the lever 230 is releasably coupled to the plunger member 210 by a shaft 233, the shaft 233 being releasably connected to the plunger member 210 by an optional frangible junction 234 (shown in fig. 10). The control rod 230 also releasably engages the plunger housing 220 to thereby maintain the spring 270 in an initial compressed state, which is retained between the annular ledge 212 of the plunger member 210 and the bottom 225 of the plunger housing 220 in the elongate portion 221. Initially, the lugs 235 of the arms 232 abut the rim 229 of the plunger housing 220 to retain the control rod 230 and prevent axial movement of the control rod 230 relative to the plunger housing 220. However, the arms 232 of the lever 230 are resiliently flexible and movable in the direction of the solid arrows shown in FIG. 4, which disengages the lever 230 from the plunger housing 220 to facilitate decompression of the spring 270, as will be described later.

Needle assembly 400 includes retractable needle 400, holder 300, needle seal 430 and ejector 600, retractable needle 400 including cannula 410 and needle body 420.

The operation of the mixing device 100 will be described with particular reference to fig. 1A, 1B, 5 and 6. In these embodiments, the outer chamber 140 contains a fluid substance and the inner chamber 112 contains a solid substance, whereby the fluid can mix with the solid substance in the inner chamber 112 to form a mixed fluid substance suitable for injection. As shown in fig. 5, the safety cap 180 (shown in fig. 2) has been removed from the outer barrel 120 to allow movement of the second or distal seal in the outer lumen 140.

Initially, the second or distal seal 170 covers the small hole 114 in the inner cartridge wall 111 to prevent liquid from moving from the outer chamber 140 into the inner chamber 112. Pressing the mixing plunger 130 in the direction of the solid arrow (i.e., axial movement toward the needle 400 in the direction of the shaded arrow) forces the first or proximal seal 160 to move distally of the outer chamber 140, which forces the liquid contained in the outer chamber 140 to move the second or distal seal 170 (i.e., toward the retractable needle 400), thereby opening the aperture 114 to allow fluid to pass from the outer chamber 140 to the inner chamber 112.

As shown in FIG. 6, continued depression of the mixing plunger 130 in the direction of the shaded arrow further forces the first or proximal seal 160 to move distally within the outer chamber 140, forcing fluid from the outer chamber 140 to the inner chamber 112 until the first or proximal seal 160 contacts the second or distal seal 170. The seals 160 and 170 may be made to reach the end of travel within the outer chamber 140 where the second or distal seal 170 will contact the vent cap 123. In this position, either the seal 160 is in sealing engagement with (i.e., covers) the aperture 114 or the seals 160 and 170 may be in partial sealing engagement with the aperture 114. It is possible that the seals 160 and 170 may be in partial sealing engagement with the apertures 114, for example, without requiring the second or distal seal 170 to fully open the apertures 114 as fluid flows from the outer chamber 140 to the inner chamber 112.

At this point, delivery of fluid from the outer lumen 140 to the inner lumen 112 is complete. The mixing plunger 130 cannot be withdrawn from the outer chamber 140 because the locking teeth 134A, B on the shaft of the mixing plunger shaft 132 (which are biased outwardly) will engage the inner lip 150 of the barrel extension 150 to form a lock that prevents the mixing plunger 130 from moving distally beyond this point (i.e., toward the user). Locking the mixing plunger 130 after mixing may help direct the force of the delivery plunger 200 through the needle 400 to inject the liquid substance, rather than forcing the liquid substance back into the outer chamber 140. This may also be accomplished by the final positioning of the first or proximal seal 160 in sealing contact with the aperture 114. Similarly, full axial movement of the mixing plunger 130 and/or engagement between one or more detent aspects of the mixing plunger 130 and the outer barrel 120 can unlock a locking aspect of the delivery plunger 200 or the inner barrel 110 to enable axial depression of the delivery plunger. This provides useful user feedback to ensure that the device follows the correct injection procedure and that the medication can be reconstituted or mixed prior to injection into the patient.

It should be understood that the vent space 142 between the second or distal seal 170 and the vent 122 is never in contact with any substance in the mixing device 100, and therefore does not need to maintain sterility in the area of the vent space 142. The vent space 142 can be filled with air that moves out of the annular space between the outer barrel 120 and the inner barrel 110 and between the vent 122 and the second or distal seal when the mixing plunger 130 is depressed and the second or distal seal 170 is moved axially. In addition, because the second or distal seal 170 initially covers the apertures 114 in the wall 111 of the inner barrel 110, the sterility of this fluid path between the outer chamber 140 and the inner chamber 112 is maintained during use of the mixing apparatus 100. Only the second or distal seal 170 may come into contact with any unsterile portions of the outer barrel 120 and the inner barrel 110 because fluid is encouraged to flow from the outer chamber 140 into the inner chamber 112 without contacting the unsterile portions.

It should also be understood that retractable syringe 100 is a "closed system," meaning that there is no venting of the fluid path other than through the needle injection. Thus, in response to distal movement of the mixing plunger 130, the delivery plunger 200 may move axially in the proximal direction (i.e., toward the user) within the inner lumen 110. This is because the distal movement of the mixing plunger 150 forces liquid from the outer chamber 140 into the inner chamber 112 and increases the pressure and/or fluid volume in the inner chamber 112. Since the rigid needle sheath 119 on the retractable needle 400 remains closed, there is no space for volume expansion other than to force the delivery plunger 200 in the proximal direction within the inner barrel 120. This is exactly the response desired, as it provides a visual and tactile indication to the user that mixing has been completed and that an injection can be initiated.

Upon completion of mixing of the substances in the lumen 112, the syringe 1000 is ready for use. The rigid needle shield 119 is removed, the cannula 410 of the needle 400 is inserted into the subject, and the delivery plunger 200 is depressed to deliver the mixed fluid contents of the lumen 112 to the subject. Standard medical practice (e.g., manual agitation of the syringe to further mix the substance and/or priming the syringe to remove any residual air prior to injection) may be performed prior to syringe insertion and injection of the fluid substance.

In at least one embodiment of the invention, needle retraction is substantially similar to that described in WO2011/075760 and will be described briefly below with reference to fig. 7 to 9. During fluid delivery, the delivery plunger 200 moves axially through the barrel 110 in the direction of the solid arrows in fig. 7. As shown in fig. 8, plunger seal 800 abuts needle seal 430, which needle seal 430 in turn abuts ejector 600. In addition, ejector ring 610 moves hooked ends 321A, 321B of arms 320A, 320B of cage 300 radially outward in the direction of the solid arrows in fig. 8, thereby disengaging needle body 420 from cage 300 to release retractable needle 400 for subsequent retraction. At this point, recessed seat 810 of plunger seal 800 has engaged section 425 of retractable needle 420 and recess 860 has received fluid end 412 of cannula 410. This effectively couples retractable needle 400 to plunger member 210.

As shown in fig. 9, to retract retractable needle 400 at the end of delivery of fluid, compression spring 270 must be decompressed, which facilitates disengagement from plunger housing 220 by plunger member 210. This disengagement is facilitated by releasing the ring 136. As the plunger member 210 and plunger housing 220 are substantially fully depressed (i.e., axially translated in the distal direction in accordance with the shaded arrows) to inject fluid from the lumen 110, one or both of the plunger member 210 and plunger housing 220 may contact the release ring 136. With this contact, the release ring 136 moves the arms 232 radially inward (in the direction of the solid arrows) and disengages from the rim 229 of the plunger housing 220. This disengagement causes compression spring 270 to decompress and push against ledge 212 of plunger member 210 to retract plunger member 210 via control rod 230 coupled to plunger member 210. The plunger housing 220 substantially maintains contact or connection with the release ring 136, while the plunger member 210 coupled to the needle 420 and cannula 410 is axially translated in the proximal direction by the decompression of the spring 270, thereby retracting the cannula 410 and needle 420.

Suitably, the retractable syringe 1000 includes one or more detent systems for the delivery plunger 200. In one embodiment of the locking system, as shown in fig. 10, the plunger housing 220 of the delivery plunger 200 includes a locking member 227, the locking member 227 including an edge 228 that engages the underside 137 of the release ring 136 after needle retraction to prevent or hinder further movement of the delivery plunger 200 relative to the release ring, as shown in fig. 10. Thus, in addition to initially assisting in initiating needle retraction, the secondary release ring 136 may serve to lock the delivery plunger 200 after initial use to thereby prevent reuse.

Another version of the one or more detent systems for plunger 200 is also shown in fig. 10. After retraction, clip 224 of plunger housing 220 and detent groove 219 of plunger member 210 cooperate to form a detent system that detents plunger member 210 and plunger housing 220 together and prevents plunger member 210 from moving relative to plunger housing 220.

At the end of retraction of plunger member 210 and retractable needle 410, control rod 230 may be selectively disconnected from plunger member 210 at frangible junction 234 and manually removed from retractable syringe 100 and discarded as "clean" waste, so that there is little likelihood of attempting to force delivery plunger 200 back into barrel 110 and attempt to re-engage the needle (not shown) if any plunger member 210 protrudes externally from the syringe. This optional frangible joint 234 (shown in fig. 10) may be located at a point that extends beyond the tip 222 in the proximal direction of the plunger member 210 when the plunger is locked in the retracted position and optionally prevents reuse.

Some other variations of the mixing device 100 are contemplated. As an alternative to the rigid needle sheath 119, the vented rigid needle shield may comprise first and second protective elements which are slidably joined such that venting may occur when the elements are slid apart into the expanded state. When the first and second members are engaged and in a collapsed state, venting through the needle end is not permitted. However, when the first and second elements are joined but in an expanded state (e.g. sliding apart along an axis), air is allowed to vent through the needle without risk of exposure of the needle to the patient. Such venting through the needle may be used, if desired, to vent a change in air volume and/or pressure within the inner chamber 112 as fluid is displaced from the outer chamber 140 into the inner chamber 112.

In another variation, at the end of depression, mixing plunger 130 may be locked to outer barrel 120 by a complementary locking key aspect (not shown) that is engaged by mixing plunger 130 at a point on axial travel in the distal direction to prevent subsequent axial travel in the proximal direction. These complementary locking key aspects may be used in conjunction with the previously described locking teeth 134A, 134B, or as an alternative to the locking teeth 134A, 134B.

In another variation, the barrel extension 150 may include the above-described complementary detent aspect (not shown) of the outer barrel 120 that engages the mixing plunger 130 upon full axial translation of the mixing plunger in the distal direction.

In another variation, the internal cavity 140 may be compartmentalized (i.e., include a plurality of compartments), e.g., by one or more frangible or porous membranes, walls, sealing members, etc., each compartment containing a different fluid or solid substance, whereby depression of the mixing plunger 130 causes mixing of each different fluid or solid substance. Additionally or alternatively, the inner cavity 112 may be similarly compartmentalized, with each compartment including a different fluid or solid substance. Thus, the mixing device 100 may include two or more substances for mixing and injection.

From the foregoing, it will be appreciated that the mixing device syringes disclosed herein provide an efficient and easy to operate system for mixing multiple substances through the syringe prior to delivery. There is no need to rotate or otherwise orient the inner and outer barrels to open or align the fluid paths prior to use, unlike many prior art mixing devices, such as those described previously. The positioning of the distal seal relative to the vent hole in the outer barrel and the aperture in the inner barrel maintains the contents of the mixing device sterile while providing adequate venting, as opposed to many prior art mixing devices such as those described previously.

The assembly and/or manufacture of the mixing device 100, retractable syringe 1000, or any of the individual elements may utilize many materials and methods known in the art. For example, many known cleaning fluids (e.g., isopropyl alcohol and hexane) may be used to clean the elements and/or devices, and many known adhesives or glues may similarly be employed in the manufacturing process. Additionally, it is known that siliconizing fluids and processes may be employed in the manufacture of novel components and devices. To add one or more small holes to the inner barrel, known drilling or perforating methods, such as mechanical or laser drilling, can be employed. In addition, it is known that sterilization processes may be employed in one or more manufacturing or assembly stages to ensure sterility of the final product.

In one embodiment, a method of assembling a mixing device comprises the steps of:

(i) attaching a vent cap having one or more vents to a distal end portion of the inner barrel, wherein the inner barrel has one or more apertures therethrough, the vent cap attaching a distal end of the one or more apertures;

(ii) placing an outer barrel coaxially aligned along the inner barrel and connecting a distal end portion of the outer barrel to the vent cap, wherein the outer barrel has a diameter greater than a diameter of the inner barrel and the two barrels are aligned such that an annular space between the two barrels forms an outer cavity;

(iii) inserting a distal seal into the outer lumen and positioning the distal seal in sealing engagement with the one or more apertures; and

(iv) the needle assembly is inserted into the lumen such that the needle assembly remains distal to the aperture.

As discussed above, glue or adhesive may be utilized to attach one or more elements of the mixing device to one another. Alternatively, one or more elements of the mixing device may be unitary elements. For example, the vent cap may be a separate element attached to the inner and outer barrels by glue, or the vent cap may be a preformed aspect at the distal end of the outer barrel that is glued to the inner barrel. These elements may be sterilized separately or together, and may be assembled in a sterile environment or sterilized after assembly. The one or more cartridges may be siliconized either before or after assembly.

A mixing device may be utilized as an element of the mixing syringe. In one embodiment of the process of the present invention,

the method of manufacturing a syringe comprising a mixing device comprises the steps of:

(i) at least partially filling the outer lumen with a first fluid substance and inserting the proximal seal into the outer lumen in contact with the first fluid substance;

(ii) at least partially filling the lumen with a second fluid substance and inserting a delivery plunger into the inner barrel, wherein the delivery plunger is proximal to the aperture of the inner barrel; and

(iii) a mixing plunger is mounted in the outer barrel, wherein the mixing plunger may be held in contact with the proximal seal.

The filling step of the syringe manufacturing process may be accomplished using any number of known filling processes and equipment. In one embodiment, the second fluid material may be filled as a fluid material and lyophilized in situ by using some sort of cartridge heat transfer device. The needle assembly, delivery plunger, and other elements described in these manufacturing and assembly processes may be as described above, or may be many similar elements that accomplish the same function as these elements.

Throughout the specification, the aim has been to describe the preferred embodiments of the invention without limiting the invention to any one embodiment or specific combination of features. Various changes or modifications may be made to the embodiments described and illustrated without departing from the present invention.

The disclosure of priority application US provisional application No.61/515,554, filed on 5/8/2011, and the various patent and scientific documents, computer programs and algorithms referred to in this specification are incorporated herein by reference in their entirety.

Claims (32)

1. A mixing device for a syringe, the mixing device comprising: an outer barrel and an inner barrel in generally coaxial relationship, the mixing device capable of comprising a plurality of mixing substances, wherein at least a first mixing substance is located in an outer chamber between the outer barrel and the inner barrel and at least a second mixing substance is located in an inner chamber in the inner barrel, the inner barrel comprising one or more fluid pathways through which the first mixing substance is capable of passing from the outer chamber into the inner chamber in the inner barrel to form a mixture with the second mixing substance; one or more vents in fluid communication with the outer chamber; and at least one seal located in the outer chamber, the at least one seal being axially movable from a first position in sealing engagement with the one or more fluid paths in the inner barrel to a second position at least partially between the one or more fluid paths and the one or more vents.

2. The mixing device of claim 1, wherein the inner barrel and outer barrel are concentric.

3. The mixing device of claim 1, wherein the inner barrel and outer barrel are non-rotatable relative to each other.

4. The mixing device of any one of claims 1 to 3, wherein the one or more fluid paths comprise a plurality of apertures in a wall of the inner barrel.

5. The mixing device of claim 1, further comprising an axially movable mixing plunger within the outer chamber between the outer barrel and the inner barrel.

6. The mixing device of claim 5, further comprising a proximal seal bonded, coupled, connected or attached to the mixing plunger and slidably movable in the outer chamber.

7. The mixing device of claim 5, wherein the at least one seal in sealing engagement with the one or more fluid paths in the inner barrel is a distal seal, axial movement of the mixing plunger indirectly facilitating axial movement of the distal seal to the second position intermediate the one or more fluid paths and the one or more vents.

8. The mixing device of claim 5, wherein axial movement of the mixing plunger urges at least a first mixing substance into the inner chamber in the inner barrel.

9. The mixing device of claim 5, wherein the at least one or more vents facilitate air exiting from the outer chamber to ambient air as the mixing plunger slidingly moves within the outer chamber.

10. The mixing device of claim 1, wherein the one or more vents are on a wall of the outer barrel or in a vent cap.

11. The mixing device of claim 1, further comprising a removable safety cap having a plurality of protrusions insertable through respective vent holes to approach or contact the at least one seal in sealing engagement with the one or more fluid paths in the inner barrel.

12. The mixing device of claim 5, further comprising one or more mixing plunger locks.

13. The mixing device of claim 1, wherein the first mixing substance locatable in the outer chamber comprises one or more fluids.

14. The mixing device of claim 13, wherein the fluid is a pharmaceutically active fluid or a pharmaceutically inactive fluid.

15. The mixing device of any one of claims 1 to 3, wherein the second mixing substance locatable in the lumen comprises one or more pharmaceutically active solids or one or more pharmaceutically active fluids.

16. The mixing device of claim 13, wherein the inner chamber contains a pharmaceutically active solid and the outer chamber contains a pharmaceutically active fluid or a pharmaceutically inactive fluid, whereby fluid enters the inner chamber from the outer chamber through the one or more fluid paths facilitating mixing of the fluid with the pharmaceutically active solid.

17. The mixing device of claim 13, wherein the inner chamber contains a first pharmaceutically active fluid and the outer chamber contains a second pharmaceutically active fluid, whereby the second pharmaceutically active fluid enters the inner chamber from the outer chamber through the one or more fluid paths facilitating mixing of the first pharmaceutically active fluid and the second pharmaceutically active fluid.

18. A syringe comprising a delivery plunger, a needle and the mixing device of any one of claims 1 to 17.

19. The syringe of claim 18, which is a retractable syringe comprising a retractable needle.

20. The syringe of claim 19, wherein the delivery plunger is capable of engaging the needle to retract the needle.

21. The syringe of claim 19, wherein the retractable needle is a component of a needle assembly.

22. The syringe of claim 21, wherein the needle assembly comprises an ejector, a needle seal, and/or a needle holder.

23. The syringe of claim 19, wherein retraction is facilitated by a biasing member.

24. The syringe of claim 23, wherein the delivery plunger comprises the biasing member.

25. The syringe of claim 24, wherein the delivery plunger comprises a plunger member and a plunger housing cooperating to releasably maintain the biasing member in an initial energized state, wherein disengagement of the plunger member and plunger housing releases the biasing member to facilitate retraction of the plunger member and the needle engaged therewith.

26. The syringe of claim 25, wherein the delivery plunger further comprises a lever.

27. The syringe of claim 23, wherein the biasing member is a spring.

28. A method of assembling a mixing device for a syringe, the method comprising the steps of:

(i) placing a coaxially aligned outer barrel over an inner barrel, the inner barrel having one or more apertures in communication with an inner cavity of the inner barrel, the coaxial alignment of the outer barrel and the inner barrel forming an outer cavity, wherein the outer cavity has one or more vents in fluid communication with the outer cavity, the one or more vents being located distal to the one or more apertures; and

(ii) inserting a seal into the outer chamber in releasable sealing engagement with the one or more apertures.

29. The method of claim 28, further comprising the step of:

(a) (ii) prior to step (i), attaching a vent cap comprising one or more vent holes to a portion of the inner barrel distal to the one or more apertures;

(b) (iii) prior to step (ii), attaching a distal end of the outer barrel to a vent cap of the vent; and

(c) inserting a needle assembly into the lumen distal to the one or more apertures.

30. The method of claim 28 or claim 29, wherein the mixing device is the mixing device of any one of claims 1 to 17.

31. A method of manufacturing a syringe including a mixing device, the method comprising the steps of:

(i) placing a first mixing substance in the outer chamber of the mixing device and inserting a first or proximal seal into the outer chamber of the mixing device in contact with the first mixing substance;

(ii) placing a second mixing substance in the inner chamber of the mixing device;

(iii) inserting a delivery plunger into the lumen, wherein the delivery plunger is proximal to one or more apertures in an inner barrel of the mixing device; and

(iv) installing a mixing plunger in the outer chamber, wherein the mixing plunger contacts the first or proximal seal.

32. The method of claim 31, wherein the syringe is the syringe of claim 18.