Abstract
An automatic mixing device, an actuating device having integrated plunger and configured to be removably mounted to the automatic mixing device, and a retractable syringe having the automatic mixing device are provided. The actuating device has an initially compressed spring and a trigger member that is rotatable to initiate spring decompression to drive depression of a mixing plunger seal of the automatic mixing device. Another seal located in an outer chamber of the mixing device is capable of axial movement upon depression of the mixing plunger, from a first position in sealing engagement with one or more apertures in an inner barrel to a second position intermediate the apertures and vents in an outer barrel. This allows depression of the mixing plunger to force a first substance from the outer chamber through the apertures to mix with a second substance in an inner chamber of the inner barrel. The mixed substance in the inner barrel is then delivered by the syringe with subsequent needle retraction.
Claims
1. A method of assembling a syringe comprising: mounting an actuating device to a mixing device, the mixing device including an inner barrel, an outer barrel, an outer chamber between the inner barrel and the outer barrel, a delivery plunger seal disposed in the inner barrel, and a mixing plunger seal disposed in the outer chamber; disposing a delivery plunger of the actuating device to bear against the delivery plunger seal; disposing a mixing plunger of the actuating device to bear against the mixing plunger seal, the mixing plunger being releasably engaged with a trigger member of the actuating device, the trigger member being operable to initiate a biasing member to facilitate depression of the mixing plunger to thereby mix a plurality of substances in the mixing device as part of a mixing process; and affixing a vent cap comprising one or more vents to a portion of the inner barrel that is located distally of one or more fluid paths in the inner barrel to allow for venting of air from the outer chamber during the mixing process.
2. The method of claim 1, wherein mounting the actuating device to the mixing device includes releasably connecting or coupling a housing of the actuating device to the outer barrel of the mixing device.
3. The method of claim 1, further comprising attaching a removable sealing membrane to the mixing device prior to mounting the actuating device to the mixing device.
4. The method of claim 3, wherein the removable sealing membrane is disposed to be manually removable, automatically removable by axial translation of the mixing plunger, or automatically removable by axial translation of the delivery plunger.
5. The method of claim 1, further comprising inserting a needle assembly into the inner barrel located distally of the one or more fluid paths.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) The foregoing will be apparent from the following more particular description of example embodiments, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments.
(2) FIG. 1 shows an isometric view of an embodiment of an automatic mixing syringe comprising an actuating device coupled to a mixing device, according to one embodiment of the present invention;
(3) FIG. 2 shows an exploded view of the actuating device shown in FIG. 1;
(4) FIG. 3A shows a cross-sectional view of the embodiment shown in FIG. 2 with the actuating device having a locked trigger member;
(5) FIG. 3B shows an isometric view of the embodiment shown in FIG. 3A;
(6) FIG. 3C shows a cross-sectional view of the embodiment shown in FIG. 3B;
(7) FIG. 3D shows an end view of coupling between a trigger member and mixing plunger of an embodiment of an actuating device;
(8) FIG. 4A shows a side view of the embodiment shown in FIG. 1 before the mixing plunger has been activated by the actuating device;
(9) FIG. 4B shows a cross-sectional view of the embodiment shown in FIG. 4A;
(10) FIG. 5A shows a side view of the embodiment shown in FIG. 1 after the mixing plunger has been activated by the actuating device;
(11) FIG. 5B shows a cross-sectional view of the embodiment shown in FIG. 5A;
(12) FIG. 6A shows an embodiment of a vent cap;
(13) FIG. 6B shows another embodiment of a vent cap;
(14) FIG. 7 shows an embodiment of a sealing membrane mounted to an automatic mixing device;
(15) FIG. 8A shows a delivery plunger engaged by a housing to initially prevent axial travel of the delivery plunger;
(16) FIG. 8B shows a delivery plunger rotated into a position relative to the housing so as to be permitted to travel axially;
(17) FIG. 8C shows an embodiment of a rotation lock formed between a trigger member and housing after rotation of the trigger member to activate mixing;
(18) FIG. 9A shows an exploded sectional view of an embodiment of a needle retraction mechanism comprising a needle assembly having a biasing member comprising a single spring;
(19) FIG. 9B shows a sectional view embodiment of a needle retraction mechanism comprising a needle assembly having a biasing member comprising a single spring;
(20) FIG. 9C shows an exploded sectional view of an embodiment of a needle retraction mechanism comprising a needle assembly having a biasing member comprising first and second springs;
(21) FIG. 9D shows a sectional view of an embodiment of a needle retraction mechanism comprising a needle assembly having a biasing member comprising first and second springs;
(22) FIG. 9E shows a sectional view of the embodiment of FIGS. 9C and 9D in a retracted position;
(23) FIG. 10A shows an alternative embodiment of a needle assembly comprising a retractable needle engageable by a delivery plunger seal;
(24) FIG. 10B shows a sectional view of the embodiment of FIG. 10A, where the biasing member of the actuating device facilitates retraction of the retractable needle when engaged by the delivery plunger seal;
(25) FIG. 10C shows a sectional view of the embodiment of FIG. 10A, where the delivery plunger engages the housing to release the biasing member of the actuating device to facilitate retraction of the retractable needle when engaged by the delivery plunger seal;
(26) FIG. 10D shows a sectional view of an embodiment of the actuating device where the trigger member and delivery plunger are in locking engagement after mixing and delivery of the mixed contents of the syringe;
(27) FIGS. 11A-11B show an embodiment of the automatic mixing syringe further comprising an optional cover mounted thereto;
(28) FIGS. 12A-12B show an embodiment of the automatic mixing syringe further comprising an alternative embodiment of a needle shield component of an optional cover; and
(29) FIG. 13 shows an embodiment of the automatic mixing syringe having proximal and distal covers.
DETAILED DESCRIPTION
(30) A description of example embodiments follows.
(31) The present invention provides an actuating device with an integrated plunger which may be mounted or otherwise connected to a dual chamber mixing device for storing, transporting, mixing, and injecting a mixed drug substance to a patient. The actuating device may be incorporated as part of an automatic mixing device and/or syringe, or removably attached to a mixing device to produce an automatic mixing syringe. In one or more of these embodiments, the actuating device and/or plunger thereof may be utilized to facilitate moving, piercing, or removal of a membrane at the proximal end of the mixing device. The membrane, as is described further herein, may be a sterile barrier utilized to maintain container integrity of the mixing device prior to operation of the device. Accordingly, the novel actuating devices of the present invention aid in maintenance of the sterility of the mixing device, and at least partial moving, piercing, or removal of the membrane prior to operation of the device and/or syringe for drug injection.
(32) While the embodiments described herein may describe certain components of the automatic mixing syringe, actuating device and mixing device as separate components, these may readily be manufactured as integrally formed or unitary components. Similarly, while the embodiments described herein may describe certain components of the automatic mixing syringe, actuating device and mixing device as integrally formed or unitary components, these may readily be manufactured as separate components that are subsequently assembled before use.
(33) Referring to FIG. 1, automatic mixing syringe 10 comprises actuating device 100, mixing device 200 and needle assembly 300. Mixing device 200 has dual concentric inner and outer barrels 210, 220. Inner chamber 230 is located within inner barrel 210 and outer chamber 240 is located between outer barrel 220 inner barrel 210. Reference is also made to FIG. 2 which shows an exploded view of an embodiment of actuating device 100 comprising housing 110 and trigger member 120 which is mountable to housing 110 and FIGS. 3A-C which show the assembled actuating device 100. Housing 110 further comprises opening 111, housing prongs 112A,B, flange 113 and housing mount 114. A delivery plunger 130 comprising shaft 131 comprising button 132 and seal-engaging member 133 is configured to pass through an opening, such as an axial opening 121 of the trigger member 120 and an axial opening 111 of the housing 110 such that it may axially translate, as will be described in more detail hereinafter. Trigger member 120 further comprises interior chamber 122 lock and trigger slots 123A, B. Mixing plunger sleeve 140 comprises sleeve members 141A, B, prongs 142A, B and sleeve plateau 143. Biasing member 150 in this embodiment is a spring which is initially compressed (i.e., energized) prior to activation of the actuating device 100. Referring again to FIG. 1, it will be appreciated that while plunger 130 is capable of axial translation within inner chamber 230 of the mixing device 200 and mixing plunger 140 is capable of axial travel within outer chamber 240 of mixing device 200, this is initially prevented or impeded until rotation of the trigger member 120, which will be described hereinafter. As shown in FIGS. 3A-3C, in at least one embodiment of the present invention the trigger member 120 is mounted at least partially upon and substantially concentric with the housing 110 of the actuating device 100, such that the trigger member 120 may be axially rotated and/or translated thereupon. FIGS. 3A and 3C show a releasable locking arrangement between the mixing plunger 140 and trigger member 120. The mixing plunger 140 is initially engaged with the trigger member 120 through releasably engageable interaction between prongs 142A, B and corresponding trigger member slots 123A, B. The biasing member 150 is initially retained in an energized state between the trigger member 120 and the mixing plunger sleeve 140. In at least one embodiment, the biasing member 150 is initially retained within an interior chamber 122 of the trigger member 120 and bearing upon a sleeve plateau 143 of the mixing plunger 140.
(34) While trigger member 120 is rotatable (i.e., capable of clockwise or anticlockwise rotation) FIG. 3D shows that ribs 117A, B, C, D in housing 110 engage complementary ridges 143A, B, C, D in mixing plunger 140 to prevent rotation of mixing plunger 140, so that rotation of trigger member 120 is not accompanied by rotation of mixing plunger 140.
(35) Referring also to FIG. 1, sleeve members 141A, B are configured to connect to, bear against or contact proximal seal 250 residing within outer chamber 240 between the outer barrel 220 and the inner barrel 210 of the mixing device 200. Distal seal 260 is also located in outer chamber 240 between the outer barrel 220 and the inner barrel 210 of the mixing device 200, the function of which will be described in more detail hereinafter. Mixing device 200 further comprises vent cap 270 mounted thereto. In this embodiment, distal seal 260 is located proximal to apertures 211A, B in inner barrel 210 which form respective fluid paths between the outer chamber 240 and the inner chamber 230. Vent chamber 280 is located distal to distal seal 260. As will be described in more detail hereinafter, manipulation and operation of the actuating device 100 facilitates the mixing of a first substance contained in the outer chamber 240 with a second substance contained in the inner chamber 230. The mixed substance may then be injected through the needle assembly 300 by axial translation of the delivery plunger 130, for drug delivery into a patient.
(36) FIGS. 4A and 4B show a side view and a cross-sectional side view of the embodiment shown in FIG. 1 and FIG. 2, in an initial locked configuration such as may be utilized for storage or transportation. Plunger 130 is incapable of axial translation within inner chamber 230 of the mixing device 200 and mixing plunger 140 is incapable of axial travel within outer chamber 240 of mixing device 200 until rotation of the trigger member 120, which will be described hereinafter. In this state, rigid needle shield 15 removably covers cannula 311. The actuating device 100 may be pre-formed with the mixing device 200 to produce an automatic mixing syringe 10, or the actuating device 100 and mixing device 200 may be separate structures that are connected or otherwise mounted together. In the latter embodiment, the mixing device 200 may comprise a mount upon which the housing 110 of the actuating device 100 may be connected. In at least one embodiment, the mount is located at the proximal end P of the outer barrel 220 of the mixing device 200. As described above, a mixing plunger 140 of the actuating device 100 is configured to at least partially reside and axially translate within outer chamber 240 of the mixing device 200. Axial translation of the mixing plunger sleeve 140 causes axial translation of the proximal seal 250 and thereby causes fluid transfer from the outer chamber 240 to the inner chamber 230 of the mixing device 200, as described further herein. The sleeve 140 is caused to axially translate by operation of a trigger member 120.
(37) FIGS. 5A and 5B show a side view and a cross-sectional side view of the embodiment shown in FIG. 1 following unlocking the trigger member 120 and activation of the actuating device 100. As shown, the trigger member 120 may be rotated clockwise or anticlockwise by a user to activate the actuating device 100. Upon activation, the mixing plunger 140 is detached from the trigger member 120, such as by disengagement between the prongs 142A, B and the trigger slots 123A,B, and caused to translate axially in the distal direction by expansion of the biasing member 150 from its initial energized state. Such axial translation of the mixing plunger 140 causes the sleeve members 141A, B to contact and axially translate the proximal seal 250 of the mixing device 100. Therefore, distal movement of the plunger member 140 of the actuating device 100 causes movement of the proximal seal 250 to which the sleeve members 141,B are engaged or bear against. A first mixing substance may be contained in outer chamber 240 between the outer barrel 220 and the inner barrel 210 and between the proximal seal 250 and the distal seal 260 in the outer chamber 240. The distal seal 260 may initially be in a first position at least partially above (i.e., proximal to) one or more apertures 211A, B that are in the inner barrel 210 between the outer chamber 230 and the inner chamber 240. Movement of the mixing plunger 140 and the proximal 250 seal is relayed to the first mixing substance in the outer chamber 240 and, similarly, to the distal seal 260. In at least one embodiment, the movement of the sleeve 140, the proximal seal 250 and, accordingly, the first mixing substance in the outer chamber 240 is relayed to the distal seal 260 by pneumatic pressure or force created in the first mixing substance by the motion of the proximal seal 250. Accordingly, axial movement of the mixing plunger 140 indirectly (i.e., without needing direct contact) facilitates axial movement of the distal seal 260 to a second position. Upon movement of the distal seal 260 to a second position (i.e., in the direction of the hatched arrow in FIG. 4A), the first mixing substance contained in the outer chamber 240 may pass-through the one or more apertures 211A, B and into the inner chamber 230 of the inner barrel 210.
(38) In some embodiments, vent cap 270 may be essentially as described in International Publication WO2013/020170. Other embodiments of vent cap 270 are shown in FIGS. 6A and 6B, wherein the vent cap 270 may optionally have “internal” vent cap features locatable within outer chamber 240 which facilitate the desired positioning of the distal seal 260 during operation of the mixing device 100. The “internal” vent cap features may be, for example, projections such as posts, prongs, flex arms, or the like which are configured to correctly position the distal seal 260 upon axial translation within the outer chamber 240, with reference to the one or more apertures 211A. B, to enable substantially all of the first substance within the outer chamber 240 to be passed-through to the inner chamber. FIG. 6A shows an embodiment of the vent cap 270 having vents 271A, B, C, D and posts 272A, B, C, D, which would be internally located inside outer chamber 240. FIG. 6B shows an embodiment of the vent cap 270 having flex arms 273A, B, C which would be internally located inside outer chamber 240. The apertures 211A, B between the outer 240 and inner 230 chambers are desired to remain open to allow movement of the first substance until substantially all of the first substance is pushed out of the outer chamber 240 by the proximal mixing plunger seal 250. This may be achieved by the compressibility of the proximal seal 250 itself. Additionally or alternatively, the dimensions and the flexing capabilities of the internal vent cap features may be configured to align the distal seal 250 with the apertures 211A, B to ensure that substantially all of the first substance within the outer chamber 240 to be passed-through to the inner chamber 230. Accordingly, the distal seal 260 is permitted to float or sell-adjust with reference to the apertures 211, B so that the apertures 211A. B remain open until the proximal mixing plunger seal 250 contacts the distal seal 260 and substantially all of the first substance is pushed out of the outer chamber 240 into the inner chamber 230 by the proximal mixing plunger seal 250.
(39) It will be appreciated that the vent chamber 280 between the distal seal 260 and vent cap 270 is never in contact with any substance(s) in mixing device 200, hence there is no need to maintain sterility in vent chamber 280. Vent chamber 280 may fill with air, which is displaced out of the annular space between outer barrel 220 and inner barrel 210 and between the vents 271 of the vent cap 270 and the distal seal 260 upon depression of proximal seal 250 and axial movement of distal seal 260 Furthermore, because distal seal 260 initially covers apertures 211A, B in inner barrel 210, sterility of this fluid path between outer chamber 240 and inner chamber 230 is maintained during use of mixing device 200. Only distal seal 260 is potentially in contact with any non-sterile portion of outer barrel 220 and inner barrel 210, as fluid is caused to flow from outer chamber 230 into inner chamber 230 without ever contacting the non-sterile portion.
(40) It will also be appreciated that automatic mixing syringe 10 is a “closed system,” meaning there is no venting of the fluid path other than by needle injection. Accordingly, delivery plunger seal 160 may axially move in inner chamber 230 in the proximal direction in response to the distal movement of sleeve 140. This is because distal movement of the sleeve 140 against proximal seal 250 forces liquid from outer chamber 240 into the inner chamber 230 and increases the pressure and/or fluid volume within inner chamber 230. With rigid needle shield 15 still closed over the needle, there is no space for volume expansion other than to force delivery plunger seal 160 in the proximal direction within inner chamber 230. This is a desirable response as it provides visual and tactile indication to the user that the mixing has completed and that injection may be initiated.
(41) As described above, a sealing membrane 290 may initially reside at the proximal end of the mixing device 200, such as at the proximal end of the inner barrel 210, to cover the proximal end of the barrel(s) 210, 220 after assembly and filling with substance(s), but before connection to the actuating device 100. The sealing membrane 290 may be any of a variety of sterile fabrics and materials, such as TYVEK, used in the medical devices and pharmaceuticals industry. The sealing membrane 290 may be removed, pierced, or otherwise bypassed by operation of the actuating device 100 or automatically by the syringe user during operation. According to an embodiment shown in FIG. 7 as the sleeve 140 is axially translated in the outer chamber 240 to contact and displace the proximal seal 250. The sealing membrane 290 is configured to seal the proximal end of the inner barrel 210 and be removed by axial translation of the sleeve members 141A, B, as shown in FIG. 7. Concurrently with this action, as previously described proximal seal 250 is axially, slidably movable in outer chamber 240 of outer barrel 220 of mixing device 200 to thereby deliver the contents of the outer chamber 240 to the inner chamber 230 via one or more apertures 211A, B in the inner barrel 210. In an alternative embodiment, the sealing membrane 290 may be discoidal and located in the inner chamber 230 without extending or otherwise having a position located in the outer chamber 240 and contactable by mixing plunger 140. In this embodiment, the sealing membrane 290 is puncturable or pierceable by the delivery plunger 130 and is not contacted by the mixing plunger 140. A delivery plunger 130 configured for such a function is shown in FIG. 9E having, for example, a pointed distal tip to pierce the sealing membrane 290 and engage delivery plunger seal 160.
(42) During rotation of trigger member 120 to disengage trigger member 120 and mixing plunger 140, delivery plunger 130 also rotates due to its connection with trigger member 120. This connection drives axial rotation of delivery plunger 130 when trigger member 120 is rotated and allows axial slidable travel of delivery plunger 130 within trigger member 120 once delivery plunger 130 is unlocked from housing 110. In the initial locked state of actuating device 100 shown in FIG. 8A abutments 115A, B of housing 110 bear against delivery plunger 130 to prevent axial travel of delivery plunger 130. Delivery plunger 130 is coupled to trigger member 120 so that rotation of trigger member 120 also rotates delivery plunger 130. This coupling may comprise any complementary mating portions that allow axial, slidable movement of the delivery plunger 130 within trigger member 120. FIG. 8B shows that when trigger member 120 is rotated (i.e., clockwise or anticlockwise) to activate mixing plunger 140, this rotation also aligns respective slots 134A, B in delivery plunger 130 with abutments 115A, 115B of housing 110 to thereby allow axial travel of delivery plunger 130 to deliver the mixed substances from inner chamber 230 to a recipient. It will be appreciated that abutments 115A, B have a longitudinal profile that allows the abutments 115A, B to fit in and slidably engage respective slots 134A, B in delivery plunger 130.
(43) In one embodiment, following rotation of trigger member 120, one or more trigger lock members engage one or more complementary housing lock members to prevent further rotation of trigger member 120. This may be facilitated by proximal movement of trigger member 120 as a result of expansion of spring 150 following disengagement of trigger member 120 and mixing plunger sleeve 140. In one particular embodiment shown in FIG. 8C, the housing lock members are locking channels 116. Suitably, one or more trigger lock members 126 engage one or more complementary locking channels 116 within the housing 110 to prevent further rotation of trigger member 120. The locking channels 116 are configured to prevent axial rotation of the trigger member 120 and/or axial translation of the trigger member 120 in the locked state,
(44) Delivery plunger 130 is mounted to delivery plunger seal 160 which is axially, slidably movable in inner chamber 230 of inner barrel 110 of mixing device 200 to thereby deliver the mixed contents of the inner chamber 230. Delivery plunger 130 may be coupled to delivery plunger seal 160 by way of screw-threaded engagement of complementary screw threads 133 and 161, as shown in FIGS. 10A-10B, or by another form of contact engagement, as shown in FIG. 9E. At this stage automatic mixing syringe 10 is ready for delivery of its mixed substances. The rigid needle shield 15 is removed, the cannula 311 of retractable needle 310 is inserted into a recipient and delivery plunger 130 is depressed to deliver the mixed, fluid contents of inner chamber 230 to the recipient. Standard medical practices, such as manual agitation of the automatic mixing syringe 10 to further facilitate mixing of the substances and/or priming the syringe to remove any residual air prior to injection, may be performed prior to needle insertion and injection of fluid contents. The actuating device 100 with integrated plunger 130 described herein may be separately assembled from the remainder of the automatic mixing syringe 10. This may be desirable where, for example, a pharmaceutical company wishes to fill the syringe 10 with the drug substance(s) in their standard fill-finish lines, and seal and ship such filled components to a separate company for final assembly. Additionally, this may be desirable for shipping, transportation, or a number of other reasons. Furthermore, it may be desirable to have the actuating device 100 as a separable component from the mixing device 200 of the automatic mixing syringe 10 for safe and efficient disposal of the components separately (i.e., only the portions contaminated by use need to be disposed in a safety sharps container, while the remaining components may be disposed of separately).
(45) In at least one embodiment of the present invention, the actuating device 100 is utilized with an automatic mixing syringe 10 having a needle retraction mechanism.
(46) A preferred needle retraction mechanism comprises a needle assembly 300 comprising one or more biasing members that facilitate needle retraction. As shown in FIGS. 9A-E, in contrast to an embodiment to be described hereinafter, the needle assembly 300 comprises one or more biasing members 340 actuatable by delivery plunger 130, wherein there is no engagement between delivery plunger seal 160 and the retractable needle 310, release of a biasing member 340 in the needle assembly 300 causing retraction of the retractable needle 310. The embodiment shown in FIGS. 9A and 9B has a single biasing member 340 (e.g., a single spring) in the needle assembly 300; the embodiment shown in FIGS. 9C-E has a biasing member 340 comprising springs 342, 344.
(47) FIGS. 9A and 9B show cross-sectional views according to one embodiment of the present invention. The needle assembly 300 includes retractable needle 310 comprising needle-over-mold (“NOM”) 322, cannula 311, and, optionally, a needle blocking mechanism adapted to block the cannula 311 following retraction. In the illustrated embodiment, the needle blocking mechanism includes a clip 324. Clip 324 may initially slidably or removably engage NOM 322 such as, for example, at an engagement between clip arms 324A and NOM engagement surface 322A. Upon retraction of the cannula 301 and axial translation in the proximal direction of NOM 322, the clip arms 324A may flex inwards (i.e., towards the axis A) to contact NOM tip 322D in a needle blocking configuration. Such a needle blocking configuration prevents axial travel in the distal direction after retraction and retains the cannula 311 substantially within the barrel tip 330 and/or the barrel of the syringe 10.
(48) Turning to FIG. 9A, the needle assembly 300 further includes an actuable locking arrangement disposed to maintain a biasing member 340 in an energized position until actuated by the actuator subassembly to retract the cannula 311. In the illustrated embodiment, the barrel tip 330 includes a spring guide 330A. In order to maintain the biasing member 340 in its initial energized position, the NOM 322 may initially be disposed in engagement with the barrel tip 330, sandwiching the energized biasing member 340 between one or more ledges 322C of the NOM 322 and an engagement surface 330C of the barrel tip 330. In one such embodiment of the actuable locking arrangement, the spring guide 330A of the barrel tip 330 may include one or more locking recesses or locking ledges 330B adapted to receive, for example, locking prongs 322B of NOM 122. As will be described further below, upon substantial completion of drug delivery through the fluid path, i.e., needle 310, the actuable locking arrangement may be actuated by the actuator subassembly to cause the locking prongs 322B to move inward and release from the locking recesses 330B of the barrel tip 330 to then permit the biasing member 340 to deenergize, exerting a force on the ledge(s) 322C of the NOM 322 to retract the needle 310.
(49) The actuator subassembly 370 is disposed to actuate the actuable locking arrangement to permit the biasing member 340 to deenergize, retracting the needle 310. In the illustrated embodiment, the actuator subassembly 370 includes a needle seal 316, a push bar 312, and an actuator 314. In some embodiments, the push bar 312 is slidably disposed relative to the needle seal 316. In at least one embodiment, push bar 312 resides at least partially within a proximal end of the needle seal 316 and in contact with actuator 314 which resides distal to needle seal 316. Depression of the push bar in such a configuration is capable of contacting and depressing (or axially translating in the distal direction) the actuator 314. In at least an initial configuration, such as for needle insertion into the body of a user, the actuator subassembly 370 may reside proximal to and either in contact with or adjacent to the needle subassembly 320.
(50) In at least one embodiment, push bar 312 includes a proximal contact surface 312A and one or more force transfer elements 312B that extend through corresponding throughways 316B in the needle seal 316. In assembly, the force transfer element 312B extending through the needle seal 316 engage the actuator 314 such that axial movement of the push bar 312 causes axial movement of the actuator 314. In this regard, the push bar 312 and the actuator 314 may be engaged and coupled together during the assembly process or the components may be disposed such assembly such that some axial movement of the push bar 312 is permitted before it engages and causes axial movement of the actuator 314. It is noted that the needle seal 316 may additionally include an opening 316A through which the proximal end of the cannula 311 extends to establish a path for drug delivery.
(51) The actuator 314 includes one or more actuating surfaces 314A disposed to engage and actuate the actuable locking arrangement to actuate the needle retraction mechanism 311. To facilitate operation, in the illustrated embodiment, the actuating surfaces 314A are sloped and disposed to engage corresponding sloped surfaces 322E of the locking prongs 322B of the NOM 322. In this way, the axial movement of the actuator 314 causes the actuating surfaces 314A to slide along the sloped surfaces 322E of the locking prongs 322B to urge the locking prongs 322B radially inward, causing disengagement of the locking prongs 322B from the locking recesses 330B of the barrel tip 330. As a result, the biasing member 340 is permitted to at least partially deenergize, retracting the cannula 311.
(52) In other words, in operation, the delivery plunger seal 160 (not shown) is caused to contact push bar 312. As a result, further depression of the plunger seal 160 during drug delivery causes axial translation of the push bar 312 in the distal direction at least partially through, or further through, needle seal 316. With the push bar 312 in contact with the actuator 314, axial translation of the push bar 312 results in axial translation of the actuator 314. Axial translation of the actuator 314 causes contact with, and flexion of, locking prongs 322B of NOM 122 to disengage the locking prongs 322B from the corresponding locking recesses 330B of the spring guide 330A.
(53) Upon disengagement of the locking arrangement between the locking prongs 322B from the corresponding locking recesses 330B, biasing member 340 is permitted to expand in the proximal direction from its initial energized state to a reduced or de-energized state. This expansion in the proximal direction of the biasing member 340 pushes upon a ledge 322C of NOM 322 causing NOM 322 and cannula 311 to translate in the proximal direction to a retracted state. As described above, upon retraction of the needle 101 and axial translation in the proximal direction of NOM 322, the clip arms 324A may flex inwards (i.e., towards the axis A) to contact NOM tip 322D in a needle blocking configuration. Such a needle blocking configuration prevents axial travel in the distal direction after retraction and retains the needle 310 substantially within the barrel tip 330 and/or the barrel of the syringe. In at least one embodiment of the present invention, push bar 312 and actuator 314 are a unified or single component.
(54) Turning to FIGS. 9C-E, there is shown another embodiment of needle assembly 300 that includes a barrel tip 330 and a needle subassembly 320, a needle retraction subassembly 360, and an actuator subassembly 370. The needle subassembly 320 includes a cannula 311 and a needle-over-mold (NOM) 322. The actuator subassembly 370 includes a needle seal 316, and a push bar 312. The needle subassembly 320 is engaged with the needle seal 316 with a proximal end of the cannula 311 extending through an opening 316A in the needle seal 316. The NOM 322 may be securely coupled to the needle seal 316 in any appropriate manner. For example, in the illustrated embodiment, the NOM 322 includes a plurality of flanges, a first of such flanges 322F engaging an internal flange 316C of the needle seal 316, and a second of said flanges 322G being disposed along a lower surface of the needle seal 316. Further features of the NOM will be described below with regard to the relationship of the needle retraction subassembly 360 and the actuator subassembly 370.
(55) The push bar 312 includes a proximal contact surface 312A and at least one depending force transfer element 312B. Here, a pair of force transfer elements 312B extends through throughways in the needle seal 316. In assembly, the proximal contact surface 312A is disposed proximal the needle seal 316. In contrast to the embodiment in FIGS. 9A and 9B, however, the force transfer element 312B of the push bar 312 includes actuating surfaces 312C, here, angled surfaces. In other words, this embodiment does not include a separate actuator. Rather, the push bar 312 and actuator are a unitary component.
(56) The needle retraction subassembly 360 includes at least one biasing member 340 and an actuable locking arrangement. In this embodiment, the biasing member 340 includes a pair of springs 342, 344. While the springs 342, 344 are disposed in parallel and the support structure is such that they move toward a deenergized position simultaneously, the springs 342, 344 could alternately be disposed and supported such that they move toward a deenergized position in series. Whether disposed in series or in parallel, the inclusion of two or more springs may provide certain advantages in reducing the size of the overall package of the barrel adapter 350. It will be appreciated, however, that supporting the springs in parallel 342, 344 may further enhance these advantages.
(57) In this embodiment, the barrel tip 330 includes multiple components. That is, the spring guide 330A is formed separately from the tip portion 330D, the spring guide 330A and the tip portion 330D being coupled together during assembly. The biasing members 340, or springs 342, 344, may be received around the spring guide 330A. Inserting the assembly of the needle subassembly 320 and the actuator subassembly 370 into the spring guide 330A, the needle subassembly 320 and the spring guide 330A may be coupled together to retain the biasing members 340 in an energized position between engagement surface 330C and ledge 322C. In contrast to the first embodiment, in this embodiment, the spring guide 330A includes at least one locking prong 330B, here, a pair of locking prongs 330B, and the NOM 322 includes a locking ledge 322B. It will thus be appreciated that when the push bar 312 is contacted by the plunger seal 160 (not shown) at the end of administration of medication, the actuating surfaces 312C of the push bar 312 push the locking prongs 330B of the spring guide 330A outward, disengaging them from the locking ledge 322B of the NOM 322. As a result, the biasing members 340 are permitted to release energy to retract the needle subassembly 320 into the barrel, as shown in FIG. 9E. In such embodiments, the trigger member 120 does not need to move substantially in the proximal direction to enable retraction of needle subassembly 320 because the push bar 312 activates retraction of the needle subassembly directly into the inner barrel 210.
(58) In an alternative embodiment, the retractable needle 310 is retracted by engagement with the delivery plunger seal 160, whereby biasing member 150 of actuation device 100 facilitates retraction of the retractable needle 310. In the particular embodiment shown in FIGS. 10A and B, delivery plunger 130 comprises shaft 131 and seal-engaging member 133, which in this embodiment is a screw threaded projection, which engages a complementary, screw-threaded recess 161 of delivery plunger seal 160. In this embodiment where the retractable needle 310 is retracted by engagement with the delivery plunger seal 160, the delivery plunger seal 160 further comprises needle-engaging portion or recess 162. In at least one embodiment, needle assembly 300 comprises retractable needle 310 comprising cannula 311 and needle body 394, retainer 391 having arms 391A, B and hook-ends 392A, B, needle seal 393 and ejector 395 having ejector ring 396. The needle retraction mechanism shown in FIGS. 10A and B is essentially similar to that described in WO2011/075760. During delivery of fluid contents, delivery plunger 130 and coupled delivery plunger seal 160 moves axially through inner chamber 230 in the direction of the hatched arrow in FIGS. 10A-C. Delivery plunger seal 160 bears against needle seal 314, which in turn bears against ejector 395. Further to this, ejector ring 396 moves hook-ends 392A, B of arms 391A, B of retainer 391 radially outwardly in the direction of the solid arrows in FIG. 10A, thereby disengaging needle body 394 from retainer 390 to release retractable needle 310 for subsequent retraction. At this point, needle-engaging portion or recess 162 of delivery plunger seal 160 has engaged retractable needle body 394 and received fluid end 3111 of cannula 311. This effectively couples retractable needle 310 to delivery plunger seal 160 and delivery plunger 130.
(59) As shown in FIG. 10B, in order for retractable needle 310 to retract at the end of delivery of fluid contents, biasing member 150 must de-energize from its partially or reduced energized state. As hereinbefore described, the biasing member 150 is initially utilized to depress the sleeve 140 (i.e., axially translate in the distal direction) to facilitate the mixing of the first and second substances. Upon suitable activation of the retraction mechanism, such as by capture of the retractable needle 310 as described herein and in WO2011/075760, the biasing member 150 can also be utilized to retract the retractable needle 310 (axially translate in the proximal direction). Initially, the trigger member 120 is held in releasable engagement by housing prongs 112A, B engaging with corresponding retention slots 125A, B of the trigger member 120. Disengagement of these components is facilitated by the proximal end of the plunger 130 and/or button 131 at the end of drug delivery. As plunger 130 and/or button 131 are substantially fully depressed (i.e., axially translated in the distal direction) to inject fluid from inner chamber 230, one or both may contact the housing prongs 112A, B. Through this contact, housing prongs 112A, B are moved radially and out of engagement with corresponding retention slots 125A, B of the trigger member 120 in the direction of the solid arrows. This disengagement allows partially compressed biasing member 150 to further decompress and push against trigger member 120 to thereby push against and retract plunger 130. Delivery plunger seal 160 coupled to retractable needle 310 is axially translated in the proximal direction by decompression of the biasing member 150, thereby retracting retractable needle 310 as shown in FIG. 10B. Trigger member 120 may be caused to translate axially in the proximal direction and retract the delivery plunger 130, delivery plunger seal 160 and retractable needle 310 connected thereto. Retainer 390, ejector 395 and needle seal 393 remain at the distal end of inner chamber 230, as shown in FIG. 10B. As shown in FIG. 10D, at the end of retraction of the trigger member 120, plunger 130, delivery plunger seal 160 and retractable needle 310, the trigger member 120 and delivery plunger 130 (and associated components connected thereto) may be locked out by one or more locking ledges 127 of the trigger member 120 and one or more respective snap arms 118 of the housing 110. In addition to retraction of the needle into the barrel(s) of the mixing device, this lockout prevents reuse or tampering of the automatic mixing syringe 10 and makes it safe to dispose. It is also shown in FIG. 10D that the interaction between the one or more locking ledges 127 of the trigger member 120 and one or more respective tabs 119 of the housing 110 limits the axial travel of the trigger member relative to the housing 110, thereby preventing any unintended uncoupling of the trigger member 120 and housing 110.
(60) The automatic mixing syringes 10 of the present invention may have optional covers which are automatically disengaged and removal only upon successful operation of the mixing stages of the syringe. FIGS. 11A and 11B show one embodiment having a distal cover 16. As shown in FIGS. 11A and 11B, the distal cover 16 comprises one or more flexible barb arms 161 that can be disengaged from housing 110, allowing removal of distal cover 16, only upon successful completion of the mixing stage as a result of axial travel of mixing plunger 140 in the direction shown by the solid arrow. Such covers may integrate or function with a safety cap and/or a rigid needle shield to prevent inadvertent operation of the mixing syringe. FIGS. 12A and 12B show another embodiment of the mixing syringe having a stand-alone collar-type safety cap 17. Upon displacement of the distal seal 260 in the direction of the solid arrow during mixing of substances, the distal seal 260 bears against and disengages collar-type safety cap 17 to thereby allow removal of needle shield 15 at the end of mixing. In the embodiments disclosed herein, it is possible to configure the safety caps 16, 17 such that they are removable only after successful completion of the mixing stages, thereby permitting removal of the rigid needle shield 15 and exposing the cannula 311 for injection.
(61) In at least one embodiment shown in FIG. 13, the automatic mixing syringe 10 may comprise distal cover 18 and proximal cover 19. Such covers may take a range of known shapes and configurations, such as conical, cylindrical, rectangular, and the like. This embodiment may be particularly useful or applicable for rapid or emergency mixing and delivery of substances that regulate blood glucose such as lyophilized insulin or glucagon. In this embodiment, proximal cover 19 is coupled to trigger member 120 so that rotation or twisting of proximal cover 19 co-ordinately rotates trigger member 120 to activate mixing of substances as hereinbefore described. Distal cover 18 is coupled to rigid needle shield 15 so that subsequent removal of distal cover 18 can “automatically” remove, in at least one embodiment, the rigid needle shield 15 to thereby expose cannula 311 for use. Proximal cover 19 can then be removed and delivery plunger 130 operated to enable delivery of the mixed substances to a recipient by injection. This embodiment provides a very rapid, safe and simply-operated mixing and delivery system for use during an emergency, such as typically encountered by diabetics. In such an embodiment, the covers 18, 19 serve as both general packaging for, and functional aspects of, the automatic mixing syringe 10.
(62) It will be appreciated from the foregoing that the actuating device, automatic mixing device and syringe disclosed herein provide an efficient and easily-operated automatic system for mixing multiple substances prior to delivery by the syringe. There is no need to rotate or otherwise orient the inner and outer barrels prior to use to open or align fluid pathways, unlike in many prior art mixing devices such as those previously described. The positioning of the distal seal relative to the vents in the outer barrel and the apertures in the inner barrel keeps the contents of the mixing device sterile while providing adequate venting, which is in contrast to many prior art mixing devices such as previously described.
(63) Assembly and/or manufacturing of actuating device, automatic mixing device, retractable syringe, or any of the individual components may utilize a number of known materials and methodologies in the art. For example, a number of known cleaning fluids such as isopropyl alcohol and hexane may be used to clean the components and/or the devices. A number of known adhesives or glues may similarly be employed in the manufacturing process. Additionally, known siliconization fluids and processes may be employed during the manufacture of the novel components and devices. To add the one or more apertures to the inner barrel, known drilling or boring methodologies such as mechanical or laser drilling may be employed. Furthermore, known sterilization processes may be employed at one or more of the manufacturing or assembly stages to ensure the sterility of the final product.
(64) In yet another aspect, the invention provides a method of assembling a syringe comprising an automatic mixing device including the step of removably mounting an actuating device to a mixing device of the syringe so that a sleeve of the actuating device is operable to depress a mixing plunger seal of the mixing device. In one embodiment, the method includes the step of releasably connecting or coupling a housing of the actuating device to an outer barrel of the mixing device. In one embodiment, the method includes the step of releasably connecting or coupling a housing of the actuating device to an outer barrel of the mixing device. In one embodiment, the method further includes, prior to step (i), affixing a vent cap comprising the one or more vents to a portion of the inner barrel that is located distally of the one or more apertures. Preferably, the distal end of the outer barrel is connected to the vent cap. In a further embodiment, the method further includes the step of attaching a sealing membrane to the proximal end of the inner barrel of the mixing device prior to attachment of the actuating device to the mixing device. In a preferred embodiment, the sealing membrane is attached such that it is at least partially pierced or penetrable by operation of the delivery plunger. In another embodiment, the sealing membrane is attached in a manner such that it is removed automatically by operation of the sleeve of the actuating device, i.e., axial translation of the sleeve in the distal direction. Preferably, the method further includes the step of inserting a needle assembly into the inner chamber located distally of the one or more apertures.
(65) In a further aspect, the invention provides a method of manufacturing a syringe including the step of removably mounting an actuating device to a mixing device mounted to a syringe.
(66) In a still further aspect, the invention provides a method of operating a syringe comprising an automatic mixing device, said method including the steps of: (i) operating an actuating device of the automatic mixing device to facilitate mixing a plurality of substances, wherein operation of the actuating device removes a removable membrane from attachment to the mixing device; (ii) connecting a plunger of the actuating device to a delivery plunger seal of the mixing device; (iii) operating the plunger to deliver the substances mixed at step (i) to a recipient.
(67) In one embodiment, the method includes the step of unlocking the plunger prior to step (iii). Unlocking the plunger may occur between steps (i) and (ii) in at least one embodiment or between steps (ii) and (iii) in other embodiments of the invention.
(68) In an alternative embodiment, a method of operating a syringe comprising an automatic mixing device includes the steps of: (iv) operating an actuating device of the automatic mixing device to facilitate mixing a plurality of substances; (v) operating a plunger of the actuating device to pierce a sealing membrane to engage a delivery plunger seal of the mixing device; (vi) operating the plunger to deliver the substances mixed at step (i) to a recipient.
(69) The method may further include the step of unlocking the plunger prior to step (iii). Unlocking the plunger may occur between steps (i) and (ii) in at least one embodiment or between steps (ii) and (iii) in other embodiments of the invention.
(70) In at least one embodiment, the method of operating a syringe comprising an automatic mixing device further includes: (iv) activating a needle retraction mechanism to retract the needle into the syringe. Preferably, the activation of the needle retraction mechanism occurs after substantially all of the substances are delivered to the recipient.
(71) As discussed above, a number of aspects of the present invention may be facilitated by separate components. Alternatively, one or more components of the present invention may be a unified component and/or the functions of such one or more components may be accomplished by a unified component. For example, the trigger member, and several other components, can be single unified components or made up of smaller sub-components (e.g., the interior aspects of the trigger member, particularly the components at the proximal interior end of the trigger member, may be sub-components that snap together or otherwise function as one component). It is readily understood by one having ordinary skill in the art that such components may be unified components or comprised of separate sub-components, such as for manufacturability, while remaining within the breadth and scope of the presently claimed invention.
(72) A number of known filling processes and equipment may be utilized to achieve the filling steps of the syringe manufacturing process. In one embodiment, the second fluid substance may be filled as a liquid substance and lyophilized in situ using certain barrel heat transfer equipment. The needle assembly, delivery plunger, and other components described in these manufacturing and assembly processes may be as described above or may be a number of similar components which achieve the same functionality as these components.
(73) The teachings of all patents, published applications and references cited herein are incorporated by reference in their entirety.
(74) While example embodiments have been particularly shown and described, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the embodiments encompassed by the appended claims.
