Abstract
The present invention relates in part to vessels comprising a first chamber a second chamber and a seal separating the first and second chambers. In particular, the invention concerns means and methods for establishing communication between the first chamber and a second chamber of such vessels. Vessels of the invention may comprise one or more projections on an internal wall of the vessel and an actuator configured to cause the seal and the one or more projections to engage one another. The one or more projections are configured to urge a portion of the seal away from the internal wall upon engagement with the seal. This causes one or more channels to open between the first chamber and the second chamber. Vessels of the invention allow a user to establish communication between the first chamber and the second chamber at a desired time, for example in order to contact components contained within the chambers or in order to sequentially release components or doses of components from the vessel.
Claims
1. A vessel (700, 900) having a proximal end (901) and a distal end (903) and comprising a removable seal (106, 908) for defining a first chamber (704, 912) at the distal end (903) of the vessel and a second chamber (706, 910) at the proximal end (901) of the vessel (700, 900), a proximal bypass zone (902) comprising one or more proximal projections (800a, 800b, 902a) on an internal wall of the vessel (700, 900) or one or more proximal bypass channels (1502) on an internal wall of the vessel (700, 900), a distal bypass zone (904) comprising one or more distal projections (800c, 800d, 904a) on an internal wall of the vessel (700, 900), or one or more distal bypass channels (1502) on an internal wall of the vessel (700, 900), an opening at the proximal end (901) of the vessel (700, 900) for introducing a component into the vessel (700, 900), and an actuator configured to move the seal (106, 908) through the vessel (700, 900), wherein the proximal (800a, 800b, 902a) and distal projections (800c, 800d, 904a) are configured to urge a portion of the seal (106, 908) away from the internal wall of the vessel (700, 900) upon engagement with the seal (106, 908) thereby opening one or more channels (114) which bypass the seal (106, 908), and wherein the proximal and distal bypass channels are configured such that a proximal bypass zone comprising a proximal bypass channel and a distal bypass zone comprising a distal bypass channel each have a cross section that is greater than the cross section of the seal (106, 908), such that the seal (106, 908) cannot prevent communication between the first (704, 912) and second (706, 910) chambers when it is positioned in the proximal bypass zone (902) or in the distal bypass zone (904), wherein the proximal bypass zone (902) and the distal bypass zone (904) are arranged to allow fluid to bypass the seal (106, 908) are separated by a distance (802) that is greater than or equal to the thickness of the seal (106, 908), the proximal bypass zone (902) and seal (106, 908) being arranged to expel gas, that would otherwise be trapped in the first chamber (704, 912) between the seal (106, 908) and the distal end (903) of the vessel (700, 900), from the first chamber (704, 912) as the seal (106, 908) is moved through the proximal bypass zone (902) towards the distal end (903) of the vessel (700, 900), wherein the length of the proximal bypass zone (902) is selected according to the volume of a first component (906) to be contained within the first chamber (704, 912) such that the first component (906) can be stored in the first chamber (704, 912) in the absence of gas.
2. The vessel (700, 900) of claim 1, wherein the vessel (700, 900) comprises at least two circumferentially spaced proximal projections (800a, 800b, 902a) and/or at least two circumferentially spaced distal projections (800c, 800d, 904a).
3. The vessel (700, 900) of claim 1, wherein the one or more proximal projections (800a, 800b, 902a) extend to the proximal end (901) of the vessel (700, 900), and/or wherein the one or more distal projections (800c, 800d, 904a) extend to the distal end (903) of the vessel (700, 900).
4. The vessel (700, 900) of claim 1, wherein at least a portion of at least one projection tapers towards the proximal end (901) of the vessel (700, 900).
5. The vessel of claim 1, wherein at least one of the projections includes a barbed or hooked region towards a distal end of the projection, adapted to cause partial deformation of the seal (106, 908) as the seal (106, 908) passes over the barb or hook.
6. The vessel of claim 1, wherein the vessel (700, 900) has an opening at its proximal end (901) via which the seal (106, 908) is inserted into the vessel (700, 900) and/or via which gas can escape as the seal (106, 908) is moved through the vessel (700, 900).
7. The vessel (700, 900) of claim 1, wherein the actuator comprises a piston.
8. The vessel (700, 900) of claim 1, wherein the actuator is incorporated into a lid (702) configured to close an opening at the proximal end (901) of the vessel (700, 900).
9. The vessel (700, 900) of claim 8, wherein the actuator comprises a bulb or pump.
10. The vessel (700, 900) of claim 1, wherein at least one projection is generally rectangular, triangular, circular or trapezoidal in cross section.
11. The vessel (700, 900) of claim 1, wherein at least one projection comprises an opening (115) extending through an entire longitudinal axis of the projection.
12. The vessel (700, 900) of claim 1, wherein the vessel (700, 900) is a syringe or a vial.
13. The vessel (700, 900) of claim 1, wherein the seal (106, 908) includes a bypass slit (1402) that is adapted to open when the seal (106, 908) engages a projection and close when the seal (106, 908) disengages the projection.
14. The vessel (700, 900) of claim 1, wherein the distal bypass zone (904) extends to the distal end (903) of the vessel (700, 900) such that the seal (106, 908) can be used to force the entire contents of the first chamber (704, 912) into the second chamber (706, 910) by moving the seal (106, 908) to the distal end (903) of the vessel (700, 900).
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) FIGS. 1A-1C: plan, side and cross section views of an embodiment of a multi-chambered vessel according to the invention.
(2) FIGS. 2A and 2B: plan and side views of a projection according to the invention,
(3) FIG. 3: schematic diagram showing the operation of a multi-chambered vessel according to an embodiment of the invention (side view).
(4) FIG. 4: cross section of a multi-chambered vessel according to the invention showing channels formed by the engagement of projections with a seal.
(5) FIGS. 5A-5C: three embodiments of projections fixed to securing means.
(6) FIG. 6: schematic illustration of a method of dispensing multiple components from a multi-chambered vessel.
(7) FIGS. 7A and 7B: a multi-chambered vessel in the form of a bottle comprising a screw cap.
(8) FIG. 8: a multi-chambered vessel configured to exclude air/oxygen from a chamber thereof.
(9) FIGS. 9A-9E: schematic illustration showing how gas can be removed from a chamber of a vessel.
(10) FIG. 10: schematic diagram showing an alternative to step E of FIG. 9.
(11) FIG. 11: a vessel comprising a proximal projection which includes a barb/hook.
(12) FIGS. 12A and 12B: a kit comprising proximal and distal projections and a view of the kit secured to a vessel.
(13) FIG. 13: a kit having an insert sleeve comprising projections on an internal wall thereof.
(14) FIG. 14: a seal comprising a bypass slit.
(15) FIGS. 15A and 15B: a cross section of an insert sleeve for a vessel having a sealing zone and a bypass zone (A) and a vessel to which the insert sleeve has been fitted (B).
DESCRIPTION OF THE FIGURES
(16) FIG. 1A shows a side view of a multi-chambered vessel 100, specifically a syringe, comprising a first chamber 102, a second chamber 104 and a seal 106 separating the first and second chambers. Provided on an internal wall of the first chamber 102 are two projections 108. The projections have a proximal end 108a and a distal end 108b. The proximal ends 108a are aligned such that they can engage the seal 106 simultaneously. The vessel 100 further comprises an actuator in the form of a plunger 110 configured to cause engagement of the seal 106 with the projections 108. FIG. 1B shows a plan view of the syringe shown in FIG. 1B. FIG. 10 shows a cross section along the longitudinal axis of the vessel of FIGS. 1A and 1B. The two projections 108 are positioned on an internal wall 112 of the vessel.
(17) FIGS. 2A and 2B show an embodiment of projections of the invention. In this embodiment, the projection is tapered as can be seen in FIG. 2B.
(18) The engagement of the seal and the projections to cause the formation of channels will be described with reference to FIG. 3. The first chamber 102 contains first component A and the second chamber 104 contains a second component B. In this embodiment B is a liquid. The plunger 110 is actuated forcing the seal 106 to move along a longitudinal axis of vessel 100 to engage the projections 108 as shown in step 2. The projections 108 urge a portion of seal 106 away from the internal wall of the vessel 100. Step 4 shows the seal 106 and the projections 108 in a fully engaged position where the projections 108 hold a portion of the seal 106 away from the internal wall 112 along the entire thickness T of the seal 106 to form channels connecting the first chamber 102 and the second chamber 104. Component B can then move through the channels into the first chamber 102 and contact component A. In this embodiment, the thickness T of the seal 106 is substantially equal to the length L of the projections 108. At step 5, all of component B has been forced into the first chamber 102. In step 6, a portion of the seal 106 has disengaged the projections 108 and re-engaged the internal wall 112 and, as the plunger 110 pushes the seal 106 further over the projections 108, more of the seal 106 may disengage the projections and re-engage the internal wall 112. The mixture of components A and B is then expelled through an outlet 103 in the vessel (step 7).
(19) FIG. 4 shows a cross section of a vessel 100 according to an embodiment of the invention. The seal 106 and the projections 108 are in the fully engaged position. A portion 106a of the seal 106 is held away from the internal wall 112 of the vessel 100 meaning that channels 114 are formed between the internal wall 112 and the seal 106. The channels 114 facilitate communication between the first chamber and the second chamber. In this embodiment, the projection(s) 108 have a triangular cross section. One of the projection(s) 108 comprises an opening 115 extending through the entire longitudinal axis of the projection 108 to form a tunnel which represents an additional channel 114 through which one or more components may pass.
(20) FIG. 5A shows plan, side and cross section views of projections 108 fixed to securing means 500. Also shown is a vessel to the projections 108 have been fitted. In this embodiment, the securing means 500 is in the form of an annular member configured to engage a corresponding groove running around an internal circumference of a vessel 100. The projections 108 provided in a staggered formation and are tapered towards the seal 106.
(21) FIG. 5B shows plan, side and cross section views of projections 108 fixed to securing means 502. Also shown is a vessel to the projections 108 have been fitted. In this embodiment, the securing means 502 is in the form of a tunnel. The tunnel fits within the body of the vessel and abuts an end wall 116 of the vessel 100, which keeps the securing means 502 and projections 108 in the correct position inside the vessel. The projection(s) 108 protrude from the tunnel. When a seal 106 engages the projections 108, the seal 106 partially deforms and at least a portion of the seal 106 may enter the tunnel.
(22) FIG. 5C shows plan, side and cross section views projections 108 fixed to securing means 504. In this embodiment, the securing means 504 is in the form of a tunnel. Also shown is a vessel to which the projections 108 have been fitted. The tunnel extends through the entire interior of the vessel 100. A seal 106 is provided within the tunnel and forms a seal against the internal wall of the tunnel rather than against the wall of the vessel 100 itself. In this embodiment, the two projections 108 are fixed to an internal wall of the securing means 504. Upon engagement of the seal 106 with the projections 108, the seal partially deforms and channels are formed between the internal wall of the securing means 504 and the seal 106.
(23) FIG. 6 is a schematic illustration of a method of dispensing multiple components from a multi-chambered vessel. In step 1, a first component 600 is provided in a first chamber of the vessel 100 and a second component 602 is provided in a second chamber of the vessel 100. A seal 106 separates the first component 600 from the second component 602. In step 2, a plunger 110 is pushed into the vessel which causes the first component 600 to be dispensed from the vessel 100 via an outlet 604. The second component 602 is trapped within the vessel by seal 106 and can be stored for use at a later time as shown in step 3. In step 4, the plunger 110 is partially withdrawn from the vessel 100 which draws the seal 106 from left to right. This causes the seal 106 to engage projections 108 provided on an internal wall of the vessel 100. A portion of the seal 106 is urged away from the internal wall of the vessel 100 causing channels to form between the seal 106 and the internal wall. This allows the second component 106 to enter the first chamber as shown in step 5. The second component is then dispensed from the vessel 100 via the outlet 604 by once again pushing the plunger into the vessel as in step 2.
(24) FIG. 7A shows an embodiment of a vessel 700 in the form of a bottle/vial/cartridge comprising a screw cap 702. The vessel 700 also comprises a first chamber 704, a second chamber 706, a seal 106 and a projection 108. The cap 702 includes an actuator in the form of an elastic top portion 710 which can be depressed. Depression of the elastic portion 710 increases the pressure within the second chamber 706 and forces the seal 106 to engage the projections 108. Upon engagement of the seal 106 with the projections 108, the seal partially deforms and a channel is opened to provide communication between the first chamber 704 and the second chamber 706.
(25) FIG. 7B shows a related embodiment of a vessel 700 in the form of a bottle/vial/cartridge comprising a screw cap 702. The vessel 700 comprises a first chamber 704, a second chamber 706, a seal 106 and a projection 108. A mechanical linkage 708 is provided between the elastic portion 710 and the seal 106. In this embodiment, depression of the elastic portion 710 is transmitted to the seal 106 via the linkage 708 causing the seal 106 to engage the projections 108. Upon engagement of the seal 106 with the projections 108, the seal partially deforms and a channel is opened to provide communication between the first chamber 704 and the second chamber 706.
(26) FIG. 8 shows another embodiment of a vessel 700 in the form of a bottle/vial/cartridge comprising a screw cap 702. The cap 702 includes an actuator in the form of an elastic top portion which can be depressed. The vessel comprises a first chamber 704, a second chamber 706, and a seal 106. The first chamber 704 contains component B. In this embodiment, first 800a, second 800b, third 800c and fourth 800d projections are provided. The first 800a and second 800b projections are spaced circumferentially relative to one another and longitudinally relative to the third 800c and fourth 800d projections, which are in turn spaced circumferentially relative to one another. A gap 802, the length of which is at the thickness of the seal 106, separates the first 800a and second projections 800b from the third 800c and fourth projections 800c.
(27) The function of the third 800c and fourth 800d projections is to engage the seal 106 to open a channel through which component B can move from the first chamber 704 into the second chamber 706 in the manner described with reference to FIG. 7. In this embodiment, the third and fourth projections extend all the way to the base or end wall of the vessel 700. The seal 106 may therefore be moved right down to the base/end wall of the vessel, thereby forcing all of the contents of the first chamber 704 into the second chamber 706. Such a configuration may be applied to any type of vessel and is not limited to the specific embodiment of a vessel shown in this figure.
(28) The first 800a and second 800b projections are provided to allow air/oxygen to be removed from the first chamber 704 during filling of the vessel. Such vessels may be provided to a user pre-filled and hence it is advantageous to remove or exclude oxygen/air from one or more of the chambers to increase shelf life. This can be achieved using the following steps.
(29) First, component B is introduced into what will form the first chamber 704 of the vessel 700. Subsequently, the seal 106 is inserted into the vessel 700. This engages with the first 800a and second 800b projections such that one or more channels are present between the seal 106 and the internal wall of the vessel 700. The seal 106 is then forced longitudinally through the vessel 700 using the actuator (which in this embodiment is an elastic portion of the cap 702) along the first 800a and second 800b projections towards component B. Air/oxygen is forced out of the first chamber 704 through the channels by the movement of the seal 106. Eventually, the seal reaches the ends of the first 800a and second 800b projections and re-engages the internal wall of the vessel 700 at the gap 802 separating the first 800a and second 800b projections from the third 800c and fourth 800d projections. In this position (the position shown in FIG. 8), component B cannot move into the second chamber 706. The length of the projections and hence position of the gap 802 will be chosen according to the volume of component B to be stored in the first chamber 704 and the amount of air/oxygen which is to be permitted to remain in the first chamber 704. If air/oxygen is to be substantially excluded from the first chamber 704, the gap 802 may be positioned such that the seal contacts the surface of component B once it re-engages the wall of the vessel at the gap 802 as shown in FIG. 8.
(30) When a user wishes to transfer component B into the second chamber 706, the seal 106 is engaged with the third 800c and fourth 800d projections. Alternatively, in certain embodiments, the seal 106 may be re-engaged with the first 800a and second 800b projections to open a channel through which component B may pass into the second chamber 706. In such embodiments, the third 800c and fourth 800d projections may be omitted.
(31) FIGS. 9A-9E is a schematic illustration showing how gas can be removed from a chamber of a vessel. A vessel 900 has a proximal end 901 and a distal end 903. The vessel 900 comprises a proximal bypass zone 902 comprising first and second proximal projections 902a on an internal wall of the vessel. The vessel also includes a distal bypass zone 904 comprising first and second distal projections 904a on an internal wall of the vessel. The vessel 900 is partially filled with a first component 906 (FIG. 9A). A seal 908 is then inserted into the vessel 900 (FIG. 9B). The seal engages the proximal projections 902a thereby opening one or more channels between the internal wall of the vessel 900 and the seal 908 which bypass the seal 908. The seal 908 defines first 912 and second 910 chambers within the vessel (FIG. 9C). It will be appreciated that the relative sizes of the first and second chambers 912, 910, will change as the seal 908 moves though the vessel 900. As the seal 908 is moved towards the distal end 903 of the vessel 900, this action forces air trapped in the first chamber 912 passed the seal 908 via the channels and into the second chamber 910 (illustrated by the curved arrows in FIG. 9C). The seal 908 then disengages the proximal projections 902a and is positioned at a sealing position between the proximal bypass zone 902 and the distal bypass zone 904 (FIG. 9D). The proximal and distal bypass zones 902 and 904 respectively are separated by a distance d that is greater than or equal to the thickness of the seal 908. In this embodiment, the first component 906 is filled to the proximal end of the distal bypass zone 904, and d is equal to the thickness of the seal meaning that the seal 908 sits on the surface of the first component 906 and all air is excluded from the second chamber 912. A second component 914 is added into the vessel (FIG. 9D). Following this, a cap 916 may be used to close the opening in the proximal end of the vessel 901. As the seal 908 and the projections 902a are no longer engaged with each other, the channels are closed and therefore communication between the second chamber 910 and the first chamber 912 is prevented. The first component 906 and the second component 914 cannot contact each other while the seal 908 is at the sealing position. In order to contact the first component 906 with the second component 914, the seal is moved into the distal bypass zone 904 and engages the distal projections 904a thereby opening channels between the seal 908 and the vessel wall (FIG. 9E). As the seal 908 is moved further towards the distal end 903 of the vessel, the first component 906 is forced passed the seal 908 and into the second chamber 910 where it contacts the second component 914 (illustrated by the curved arrows in FIG. 9E). The mixed first and second components can be dispensed from the vessel 900 by removing the cap 916 (not shown).
(32) FIG. 10 illustrates an alternative option to the step shown in FIG. 9E. Instead of moving the seal 908 into the distal bypass zone 904, the seal 908 is moved back into the proximal bypass zone 902. The seal 908 engages the proximal projections 902a, thereby opening channels between the seal 908 and the vessel wall. As the seal 908 is moved towards the proximal end 901 of the vessel 900, the second component 914 is forced passed the seal into the first chamber 912 via the channels and can contact the first component 906. This option may be preferred if the mixed components are to be dispensed via an opening at the distal end 903 of the vessel 900 (not shown).
(33) FIG. 11 shows a vessel 900 comprising a proximal bypass zone 902 having first and second proximal projections 902a on an internal wall of the vessel. The vessel 900 also includes a distal bypass zone 904 comprising first and second distal projections 904a on an internal wall of the vessel. In this embodiment, a proximal projection 902a includes a barbed/hooked portion 916 at its distal end. The barbed/hooked portion 916 is adapted to catch a portion of the seal 908 as the seal moves towards the distal end 903 of the vessel 903, causing the seal to deform. This deformation improves fluid flow passed the seal 908.
(34) FIGS. 12A-B shows a side view of an embodiment of a kit 1200. The kit 1200 comprises proximal projections 1204 and distal projections 1206. The kit 1200 includes securing means 1208 that are configured to hook over the rim of a vessel 1202 and clip the kit to the vessel as illustrated in FIG. 12B. When the kit 1200 is fixed in the vessel 1202, the proximal projections 1204 define a proximal bypass zone 1210 and the distal projections 1206 define a distal bypass zone 1212. The proximal bypass zone 1210 is separated from the distal bypass zone 1212 by a distance d. This kit is configured for use with a seal that has a thickness that is less than or equal to the distance d.
(35) FIG. 13 shows a kit 1300 comprising an insert sleeve 1302 configured to fit tightly inside a vessel (not shown). The kit includes securing means 1304 adapted to secure the kit to the vessel. The insert sleeve includes projections 1306 on an internal wall thereof.
(36) FIG. 14 shows a seal 1400 comprising a bypass slit 1402. When the seal 1400 is located in a sealing position within a vessel 1404 as shown in FIG. 13A (front and side views), the bypass slit 1402 is closed. When the seal 1400 engages a projection 1406, the seal 1400 partially deforms, thereby opening the bypass slit 1402 (as shown in FIG. 14B).
(37) FIG. 15A shows a cross section of an insert sleeve 1500 for a vessel. The insert sleeve 1500 includes a bypass zone comprising a bypass channel 1502. FIG. 15B shows a vessel 1504 in the form of a syringe to which the insert sleeve 1500 has been fitted. A seal 1506 is provided within the vessel 1504. The insert sleeve 1500 includes a proximal sealing zone 1510, a distal sealing zone 1512 and a bypass zone 1508. When the seal 1506 is in either the proximal sealing zone 1510 or the distal sealing zone 1512, fluid cannot flow passed the seal 1506 because the cross section of the seal is substantially equal to the cross section of the proximal and distal sealing zones 1512, 1510. When the seal 1506 is in the bypass zone 1508 as shown in FIG. 15B, fluid can bypass the seal 1506 via the bypass channel 1502. The bypass zone 1508 has a larger cross section than the cross section of the seal 1506. The seal 1506 can be moved between zones using an actuator e.g. a piston 1514.
Example 1
(38) Several proof of concept tests were carried out using single use plastic syringes having a variety of capacities.
(39) In this example a low capacity syringe was chosen in order to simulate the single use prefilled syringes commonly used for the administration of intra-articular injections of hyaluronic acid in the joints for the treatment of Osteoarthritis. Moreover, such syringes (in combination with the liquid components tested) were considered to represent a high difficulty configuration (due to the narrow barrel) which could prove at the same time that the invention functions and is efficient across a wide range of applications and for use with other components and syringes.
(40) A 2.5 ml syringe (PIC Solution of Artsana SPA Italy) single use, latex free, pthalates free, pyrogen free, ethylene oxide sterilised was identified as a suitable syringe for the test. The syringe had an inner barrel diameter of 9 mm and comprised a plunger which terminated in a seal. The plunger seal comprised pronounced annular portions having a diameter of 9.2 mm, between which were two furrows, the front furrow (the one closest to the conical terminus) having a depth of 1 mm. The length (side view) of the plunger seal was 5 mm excluding the 2 mm conical terminus.
(41) A second seal (exactly the same as the plunger seal) was provided for the purpose of forming two chambers within the syringe such that two components could be stored separately (for example prior to administration). The chambers will be referred to as chamber A and chamber B, chamber B being closest to the plunger and chamber A being closest to the syringe's outlet.
(42) Two individual projections each having a generally cylindrical cross section were fixed on the internal wall of the barrel. Each projection was tapered at both ends and had a maximum height of 0.9 mm extending into the barrel of the syringe. The second projection was provided on the opposite side of the inner wall to the first projection. The length of the projections was equal to that of the second seal (excluding its conical terminus) i.e. 5 mm.
(43) The syringe was filled with 0.5 of water. The second seal was then inserted to confine the water to chamber B. The projections were situated in chamber A and it was confirmed that water could not pass into chamber A. The plunger was then depressed. This forced the second seal to engage the projections along the entire 5 mm length of the seal (with no significant resistance). This allowed water to pass into chamber A via two channels which had formed around the projections between the second seal and the internal wall of the barrel. It was surprisingly noticed that even one single projection was enough to create a channel or possibly two allowing the water to pass around the projection and enter chamber A.
Example 2
(44) A second experiment was conducted using the syringe and protocol of Example 1 except that water was replaced with a high viscosity liquid component. The selected viscous liquid component was 1.5%.sodium hyaluronate in 0.2M sodium chloride with a measured zero shear viscosity of 530 Pas.
(45) Again surprisingly, despite the high viscosity of the component, the test was successful and the sodium hyaluronate solution was able to pass into chamber A via channels formed around the projections.
(46) Surprisingly both forward and backward movement (suction) of the plunger were found to be effective in causing engagement of the second seal and the projections leading to the formation of channels through which either of the components tested could pass. It is worth noting that the resistance in engaging and riding of the projections by the second seal in both cases was insignificant, while a minimal increase in resistance in both movements (forward and backward) was only observed the moment the conical terminus of the plunger itself had to ride the projections. A small deformation of the plunger (in the shape of the projection) was noticed for that reason after the experiment was completed. Adjustments of the various parameters (as described herein) can be made to avoid this if necessary.
