Patent Grant
7909793
The present invention relates generally to the field of particle delivery and more particularly to needleless syringes which accelerate particles in a gas stream so as to deliver them into a target (such as the tissue of a subject).
WO 94/24263 discloses a needleless syringe for the injection of particles. Upon activation of the device, pressurised gas is supplied to a small rupture chamber in which there is located a particle cassette comprised of particles sandwiched between two rupturable membranes. Once pressure in the small rupture chamber has reached a certain value, the membranes rupture and gas continues to be supplied such that the particles are accelerated down a nozzle and into the target. After the particles have impacted the target, the gas used for accelerating the particles is routed past a series of baffles, to break down the reflected shockwave and provide a silencing effect, before being vented to the atmosphere.
In a device of this type, the chamber in which gas builds up initially is of a small volume and gas flowing into the chamber after rupture of the membranes is important in accelerating the particles. This fact is confirmed by WO 99/01168 in which a device having a large area valve is provided so that gas can continue to flow from the gas reservoir and down the nozzle after rupture of the membranes. This document suggests the same silencing mechanism as WO 94/24263.
WO 01/05455 discloses a needleless syringe device in which substantially all of the particles are delivered in a quasi-steady gas flow which is established after the passage of a starting process. This allows the particles to be reliably and repeatedly delivered.
In contrast to WO 94/24263 and WO 99/01168, WO 01/05455 proposes the use of a bleed-hole which limits the flow of gas from the reservoir to the chamber behind a closure means once the closure means has burst. In fact, substantially all of the particles are accelerated by the gas which builds up behind the closure means prior to bursting and the gas which flows from the reservoir after bursting has a negligible effect on accelerating the particles.
It has been found that the shockwave emitted by the device of WO 01/05455 can cause a loud noise to emanate from the device in use. It is desirable for this noise to be kept as small as possible so as to avoid alarming users of the device. At present, no silencer has been proposed that is suitable for use with a syringe of the form disclosed in WO 01/05455.
An attempt to apply the silencing teaching of WO 94/24263 or WO 99/01168 to the syringe at WO 01/05455 has not proved to be fruitful since the earlier silencer confines pressurised gas to an area near the target plane which creates a substantial lift-off force tending to move the device away from contact with the target. This is undesirable because the device should stay in contact with the target during injection if proper injection is to be ensured and because lift-off of the device releases gas allowing sound to escape, increasing noise. Any lift-off also allows particles to escape to the atmosphere instead of impacting the target. The high pressure near the target plane also impedes particle flow resulting in lower particle impact velocities, reducing the performance of the device.
Thus, there is a need for a needleless syringe having the improved operation of WO 01/05455 but which is quieter in operation, the silencing not affecting the performance of the device in delivering particles. The teaching of the present invention may be advantageously applied to other types of needleless syringes as well.
Accordingly, the present invention provides a needleless syringe device comprising:
an energy source;
at least one bleed-hole, said bleed-hole(s) having an effective bleed-hole area for the passage therethrough of pressurised gas from the energy source to a driver chamber to entrain particles and accelerate them into a target; and
a silencer for receiving said gas from said driver chamber and for venting that gas to the surroundings of the silencer through at least one silencer vent opening, said vent opening(s) having an effective venting area;
wherein said effective bleed-hole area and said effective venting area are such that, during use of the device for particle delivery, the mass flow rate of gas through aid effective venting area is substantially equal to or greater than the mass flow rate of gas through said effective bleed-hole area.
The fact that the mass flow rate of gas through the venting area is equal to or greater than the mass flow rate of gas through the bleed-hole area ensures that as much or more gas leaves the device during operation as is provided by the energy source. This ensures that the pressure inside the silencing shroud of the device does not increase as the device is operated and thus serves to limit a deleterious build up in back pressure which can result in the device lifting off from the target plane. Preferably, the venting area and bleed-hole areas are sized to ensure that the mass flow rate through the venting area is greater than the mass flow rate through the bleed-hole area during use such that, after the initial expansion of gas from the driver chamber to the shroud, the pressure actually reduces inside the shroud during use. Preferably, the venting area is small enough to provide adequate silencing and large enough to ensure that pressure does not build up in the device during use.
Preferably, the energy source is a reservoir of pressurised gas, such as helium or nitrogen.
To ensure that the mass flow rate of gas through the venting area is greater than the mass flow rate of gas through the bleed-hole area, the ratio of venting area to bleed-hole area should be equal to or greater than a constant, k, given by the following expression:
wherein γ1 is the ratio of specific heats for the gas in the reservoir, R1 is the gas constant for the gas in the energy source (reservoir), γ2 is the ratio of specific heats for the gas in the surroundings, R2 is the gas constant for the gas in the surroundings, P0 is the pressure in the energy source after gas has been received by said silencer and PS is the pressure in the silencer after gas has been received by said silencer.
More preferably, the ratio of venting area to bleed-hole area should be greater than or equal to 1.2 k to ensure a sufficient decay of pressure within the silencer. To ensure adequate silencing, the ratio of venting area to bleed-hole area should preferably be less than 20 k, more preferably less than 10 k, still more preferably less than 5 k.
In a preferred embodiment, the silencer comprises a shroud having a predetermined volume for containing the gas received from the driver chamber prior to venting it.
The volume of the shroud, the volume of the driver chamber and the size of the exit opening should preferably be chosen such that when the closure is opened and gas flows from the driver chamber to the shroud, the resulting equalisation in pressure results in a lift-off force on the device of less than 20N, more preferably less than 15N.
In this specification the term ‘closure’ includes both ‘closure means’ and ‘closure member’.
Preferably, the particles are delivered through a particle exit opening in the shroud which is pressed against the target during use.
Preferably, said at least one silencer vent opening is formed by at least one hole provided in the shroud and this at least one hole is preferably located in the upstream end of the device so that the gas must travel substantially the length of the device before it can be vented through said at least on hole.
To provide further passages for the gas, a cover may be attached to the device to create an annular channel for the passage of gas from the shroud to the surroundings. This annular channel may comprise a plurality of baffles which interact with the gas flow vented out of the shroud and attenuate any shockwaves in the gas flow. Alternatively or additionally, baffles or the like may be included inside the shroud volume itself.
Preferably, the particle-containing gas which flows from the driver chamber is expanded by a nozzle connected to the driver chamber and this nozzle is preferably substantially correctly expanded, although it need not be to obtain adequate performance.
To further limit the lift-off force experienced during use of the device, the particle exit opening in the shroud should be preferably no more than 100% larger than the exit area of the nozzle. The particle exit opening should also be axially spaced from the nozzle exit so that a path for the venting of gas is provided.
The present invention also provides a method of silencing a particle-accelerating gas flow, the method comprising:
wherein said second mass flow rate is substantially equal to or greater than said first mass flow rate.
The present invention furthermore provides a needleless syringe device comprising:
an energy source;
at least one bleed-hole, said bleed-hole(s) having an effective bleed-hole area for the passage therethrough of pressurised gas from the energy source to a driver chamber;
a first closure located at a downstream end of said driver chamber;
a second closure located downstream of said first closure to create a particle retention chamber therebetween; and
at least one transfer duct providing a gas flow path between said driver chamber and said particle retention chamber,
wherein said effective bleed-hole area and the minimum area of said transfer duct(s) are selected such that, in use, said first closure opens before said second closure and said second closure opens at least 2 ms after gas starts to flow through said transfer duct(s).
Correct selection of the bleed-hole size and transfer duct size allows the correct sequence of closure opening to be effected in use, avoiding problems associated with the downstream closure opening first or with both closures opening before the particles have properly mixed with the gas provided by the transfer duct(s). More preferably, particle mixing times of at least 3.5 ms or 5 ms are provided. In a preferred embodiment, the first and second closure are rupturable membranes which open by rupturing.
There is also provided a method of uniformly accelerating particles in a gas flow, the method comprising:
wherein said downstream closure opens at least 2 ms after said supplying step (b) starts.
There is furthermore provided a particle retention assembly comprising:
a particle retention chamber bounded by an upstream closure and a downstream closure;
at least one duct providing a gas flow path into said chamber;
wherein said duct is constructed to supply gas to said particle retention chamber from a substantially annular space around said particle retention chamber.
The annular space around the particle retention chamber allows, in a simple and convenient manner, one or more transfer ducts to be supplied with gas. The annular space means that the transfer ducts can be located virtually anywhere on the inside surface of the particle retention chamber. The annular space used to supply the gas is also a particularly convenient shape from the point of view of manufacturing and it will be seen that a particle retention assembly according to this aspect of the invention can be manufactured from only three separate cassette parts and three membranes.
There is furthermore provided a particle retention assembly comprising:
a particle retention chamber bounded by an upstream closure and a downstream closure;
a first duct providing a first gas flow path into said chamber,
wherein said first duct is arranged, in use, to create a first swirl of gas in said particle retention chamber.
The swirl of gas in the particle retention chamber is particularly efficient in fluidizing the particles so that they form a “cloud” which substantially spans the particle retention chamber, resulting in a more uniform particle distribution and velocity and, hence, penetration profile.
Preferably, there are at least two ducts which, in use, create at least two swirls of gas in the particle retention chamber, these swirls of gas being preferably directed in substantially different directions. The swirls of gas may advantageously be created by jets emanating from the transfer ducts, these jets being at least momentarily sonic or supersonic during use. To aid particle fluidization, the ducts can be off-set from one another in the direction of gas flow, and circumferentially.
The annular space around the particle retention chamber is preferably connected to a region upstream of the upstream closure by means of a series of circumferential ports.
A further closure provided to ensure the sterility of particle retention assembly may be provided.
There is also provided a method of fluidizing particles in a particle retention chamber, the method comprising:
supplying pressurised gas to an annular space around said particle retention chamber;
supplying said gas to said chamber using at least one transfer duct so as to fluidize any particles located in said particle retention chamber.
There is furthermore provided a method of fluidizing particles in a particle retention chamber, the method comprising:
supplying pressurised gas to a first duct fluidly connected to said particle retention chamber;
creating a first swirl of gas in said particle retention chamber so as to fluidize any particles located in said particle retention chamber.
Embodiments of the invention will now be further described, by way of example only, with reference to the accompanying schematic drawings, in which:—
a to 10d are drawings showing stages in the flow of gas around the particle retention assembly during which particles are fluidized and entrained in a gas flow;
In
Upon actuation of the valve, gas flows from the reservoir (1) into the driver chamber (3) where it is contained by the closure (4). Gas continues to flow from the reservoir (1) to the driver chamber (3) until a certain predetermined pressure is established in the driver chamber (3), this pressure being the pressure required to open the closure (4). In the illustrated embodiment, this pressure corresponds to the pressure at which the diaphragms (6, 7) rupture. Upon rupturing of the diaphragms (or, more generally, upon opening of the closure) a pressure discontinuity is created in the device such that a shockwave travels downstream towards a nozzle (8). The shockwave is a front delimiting gas at a high pressure from the gas at atmospheric pressure initially in the nozzle. The shockwave travels down the nozzle and impacts the target plane adjacent the exit opening (10), at which point it is reflected so that a portion of it travels in the annular space internally of the silencing shroud (9) and externally of the nozzle (8). At the same time, the gas which flows from the driver chamber behind the shockwave entrains the particles (5) such that they pass along the nozzle and through the exit opening (10) to impact the target plane at a velocity sufficient to penetrate it.
The silencer shroud (9) is configured to encapsulate a predetermined volume of gas VS. This volume is defined as all of the volume inside the silencer shroud, including that of the driver chamber and the nozzle. Once the shockwave has passed out of the silencer shroud through the plurality of holes (11) included in the shroud, the gas in initially in the driver chamber has expanded into the silencer shroud and the resulting pressure inside the silencer shroud becomes generally constant and is given by the following equation:
where PS is the pressure in the silencer shroud after pressure equalisation, PD is the pressure in the driver chamber just prior to opening of the closure (4), PS0 is the pressure in the silencer initially, VD is the volume of the driver chamber (ie that volume between the bleed-hole (2) and the closure (4)) and VS is the volume of the shroud (which incorporates the volume of the driver chamber and the nozzle). If the mass flow rate through the venting area is larger than that through the bleed hole, this pressure then decays with time as gas is vented from the silencer.
The above equation assumes an isothermal expansion in which the temperature of the gas before expanding is the same as after expanding. Thus, in the usual case where the silencer shroud is initially at atmospheric pressure (PS0=100 kPa) and for a typical driver chamber volume VD of 4.5 ml, silencer shroud volume VS of 50 ml and driver pressure PD of 1570 kPa, the pressure PS in the silencer shroud would settle down to around 232 kPa once the shockwave has passed. It is this pressure which determines the initial lift-off force that a user experiences upon activating the device. In particular, the lift-off force is equal to the pressure (PS−P0) multiplied by the area of the exit opening (10) (i.e. the area over which the differential pressure acts, P0 being the pressure in the surroundings, typically 100 kPa). A typical exit opening area is 100 mm2 which results in a lift-off force of approximately 13.2 N.
In all cases, there is a large initial sudden increase in pressure as the shock wave passes through the device. The pressure decays very quickly to a value of about 260 kPa and then follows a decay curve that is determined by the relationship between bleed hole size and effective venting area. The references hereinafter to peak shroud pressure refer to the maximum shroud pressure attained in the decay curve, i.e. after the large initial pressure increase shown in
The line numbered “1” is the case where the effective venting area/bleed hole ratio is too low. This results in an absolute peak shroud pressure of about 340 kPa after 7.5 ms which is large enough to cause an unacceptable lift-off force. A peak sound level of 102-108 dB at 300 mm from the device was measured.
The line numbered “2” is the case where the effective venting area/bleed hole ratio has been increased. This results in a peak shroud pressure of about 270 kPa after 4.25 ms. The measured peak sound level was increased to 106-110 dB at 300 mm from the device.
The line numbered “3” is the case where the effective venting area/bleed hole ratio is increased further. This results in a shroud pressure which has its peak as soon as the shock wave has passed and decays. A peak sound level of 115-118 dB at 300 mm from the device was measured.
Thus, the ratio of curve “1” is unacceptable but that of curves “2” and “3” are acceptable since the pressure does not increase substantially as a result of higher mass flow rate through the bleed hole than through the effective venting area. Curve “2” is more desirable than curve “3” since the peak lift-off force is about the same as for curve “3” but the silencing effect is greater, there being a 8-9 dB difference in sound levels obtained.
It will be appreciated that one preferable way of reducing the lift-off force is to ensure that the volume of the silencer shroud (VS) is as large as possible so as to reduce the value of PS (see equation above). Another preferable way to reduce the lift-off force is to make the area of the exit opening (10) as small as possible so that the pressure PS acts over a smaller area, creating a lower force.
The noise that is experienced upon actuation of the device is mainly due to the shockwave initiated from the sudden opening of closure (4) which is reflected from the target and exits the device through the venting area. It has been found that passing such a shockwave through a restriction, thereby breaking it down into compression waves, creates a lower level of audible sound. Thus, the effective silencer restriction presented to the shockwave (and subsequent flow) is an important device parameter. The effective silencer restriction is defined as the smallest area through which the shockwave travels on its way from the target plane to the surroundings. In
The second restriction is presented by the plurality of holes (11) formed in the outer wall of the shroud (9), the sum of the areas of each of the holes is equal to the area that the shockwave must pass through.
The third restriction is created by the cover member (15) placed around the shroud (9) and the series of baffles (12, 13) on the outer surface of the shroud (they may equally be provided on the inner surface of the cover member (15)). The annular passage created between the cover member and the shroud has an area through which the shockwave must pass. The third restriction is the part of this annular passage presenting the smallest area to the shockwave.
The smallest of the first second and third areas described above will be equal to the effective venting area of the silencer and will determine the maximum mass flow rate that can pass through the silencer and into the surroundings. The smaller this area, the smaller the mass flow rate of gas that can pass into the surroundings but also the more noise attenuation occurs through the breakdown of the primary shock. In the limit of a restriction have an area of zero mm2 (i.e. the shroud is completely closed), no gas can pass into the surroundings and the device should in theory be silent at a result.
Since the effective venting area affects the mass flow rate that can pass into the surroundings, there is a relationship between this area and the pressure that builds up in the shroud (9) during use. In particular, if the maximum mass flow rate that can pass out of the silencer (comprising the shroud (9), the holes (11), the baffles (12, 13) and the member (14)) is less than the mass flow rate being supplied by the reservoir (1) through the bleed-hole (2) then it will be seen that pressure builds up in the device once the shockwave has passed, serving to increase the lift-off force, which is undesirable. Thus, in accordance with the present invention, the effective venting area of the silencer should be such that the mass flow rate out of the silencer is equal to or greater than the mass flow rate of gas through the bleed-hole (2) once the closure has opened and the shockwave has passed out of the device. To achieve this condition with the schematically shown device (i.e. one in which the energy source is a reservoir of pressurised gas), the following equation gives the relative size of the bleed-hole area and venting area:
wherein γ1 is the ratio of specific heats for the gas in the reservoir (1), R1 is the gas constant for the gas in the reservoir (1), γ2 is the ratio of specific heats for the gas in the surroundings (18), R2 is the gas constant for the gas in the surroundings (18), P0 is the pressure in the energy source (1) after gas has been received by said silencer (9) and PS is the pressure in the silencer (9) after gas has been received by said silencer (9).
Since it is beneficial to have as small an effective venting area as is possible (to maximise the silencing effect), it is necessary to have a small bleed-hole (2) to ensure that the mass flow rate through the bleed-hole does not exceed the mass flow rate through the silencer. There is a limit, however, to the smallest size that the bleed-hole can be since the bleed-hole must be large enough to allow the efficient transfer of gas from the reservoir (1) to the driver chamber (3) upon actuation. The flow of gas through a restriction such as a bleed-hole creates a loss in energy due to friction meaning that higher initial pressures are required in the reservoir (1) in order to achieve a pressure sufficient to open the closure (4) in the driver chamber (3) if very small bleed-holes are used. Furthermore, a sufficient driver chamber filling rate is required to ensure a repeatable rupture of the membrane, or more generally, a repeatable opening of the closure. If the filling rate is very low, it has been found that the variation in rupture pressure for the same specification membranes is wider than if a higher filling rate is used.
It can be seen therefore that the provision of a bleed-hole along with a silencer having a predetermined effective venting area ensures a useful silencing effect without unduly increasing the pressure inside the device during the operation, thereby avoiding an increased lift-off force which is deleterious to device performance and ease of use. In addition, the subsidiary features of the invention (such as the large silencer volume and small particle exit opening) further reduce the problem of lift-off force without affecting the silencing that can be achieved or the device performance.
The silencing achieved can be such that the use of porous media as was envisaged in WO 94/24263 is not required, thereby reducing the device cost. Nevertheless it may be employed as an alternative or additional restriction method to reduce the noise further.
The gas reservoir (1) has a frangible tip (21) which can be cracked off by application of the button (19). Upon pressing the button gas flows out of the reservoir (1) and into the annular space (20) surrounding the reservoir (1) (see
The plurality of holes (11) in
Further, the invention is applicable to the case where “transfer ducts” as disclosed in
To achieve good particle mixing, a gas jet should enter the cassette before either membrane ruptures to thereby mix the particles so they span the entire volume of the cassette. Then, the membranes should burst in sequence with the upstream membrane (6) bursting before the downstream membrane (7). If the downstream membrane (7) bursts first then there is a chance the upstream membrane (6) may never burst, with the gas flow being driven by flow from the reservoir to the driver chamber and through the transfer duct (80).
This example is shown in
The actual values for the bleed hole and transfer duct sizes depend on the reservoir, driver and cassette volumes, but, once these parameters are selected, the skilled person is able to determine by appropriate simple experiment the correct bleed hole and transfer duct sizes to achieve the results described herein.
The embodiments described have used particle cassettes in which the particles are initially located between two rupturable membranes. However, other mechanisms for locating the particles may be used, not necessarily requiring membranes, for example fast-opening valves. In this regard, reference is made to WO 99/01169 for examples of non-membrane cassettes.
An embodiment of particle cassette (“particle retention assembly”) designed to provide pre-mixing and fluidization of the particles, prior to acceleration of the particles will now be described, with reference to
a to 10b illustrate the working of the particle retention assembly. In use, the particle retention assembly (60) is used as a particle cassette (4) for the needleless syringe shown in
On actuation, gas is allowed to flow through the bleed-hole (2) from the reservoir (1) so that the pressure in the driver chamber (5) increases. When the pressure in the driver chamber (3) increases to a magnitude larger than the pressure in the chamber (73) by a predetermined amount, the membrane (61) ruptures. For most applications it is envisaged that the initial pressure in the chamber (73) (and thus in the chamber (71)) will be atmospheric pressure (approximately 100 kPa). When the membrane (61) ruptures (e.g. at a differential pressure of 600 kPa), that is to say a pressure downstream of the membrane (61) of 100 kPa and a pressure upstream of the membrane (61) of 700 kPa), gas flows into the chamber (73) and impinges on the membrane (62) (see
Since the volume of particle retention chamber (71) is generally fairly small, it does not take long before the pressure upstream of membrane (63) is such as to cause bursting of that membrane, as shown in
One preferred physical construction of the particle retention assembly (60) will now be described. It should be appreciated that this is a preferred construction only and that it may be modified in various ways to achieve the desired result. For example, it is not necessary that there are two transfer ducts (46) leading to two openings (43) and satisfactory operation has been obtained when there is only one opening (43). Furthermore, the openings (43) are not limited to being adjacent the membrane (62) or (63) and can in general be located anywhere along the inside wall (72) of the particle retention chamber (71). Moreover, the cylindrical inside walls and circumferential ports are merely preferred and any shape that achieves the function may be used.
Referring back to
As is clear from
The third cassette part (50), in common with the first and second cassette parts, has generally cylindrical inner and outer walls forming an annular-shaped member. One or more protrusions (51) may be formed on the outer walls and these are intended to provide an interference fit against the inner wall (34) of the second cassette part (30), when the particle cassette is assembled. The lower end of the third cassette part (50) has a number of formations (52) around the circumference. The formations (52) are stepped and are designed such that the top part (53) of the formations (52) abuts the top surface of the first cassette part (40) when assembled, as shown in
The particle cassette takes the form shown in
To assemble the particle cassette, a first membrane (62) is heat sealed or bonded to the upper edge of the first cassette part (40). Similarly, the second membrane (63) is heat sealed or bonded to the seating face (32) of the second cassette part (30). The third membrane (61) is heat sealed or bonded to the upper face of the third cassette part (50). The first membrane and first cassette part thus define a receptacle in which the particles may be contained. The openings (43) are very small such that it is very difficult for the particles to pass out of the chamber once inside. Once the particles have been supplied to the chamber of the first cassette part (40), the first cassette part (40) is brought together with the second cassette part (30) with the leading edge of the first cassette part engaging the shoulders (31) of the second cassette part. The first cassette part (40) is pushed in until the seating face (41) of the first cassette part abuts the seating face (32) of the second cassette part (with the second membrane (63) between the two seating faces). In this configuration, the particles are trapped between the first and second membranes. The third cassette part (50) having the third membrane (61) thereon is then pushed in so that the formations (52) slide into the annular gap created between the first and second cassette parts. Interference and/or friction ensure that this movement firmly secures the first and second parts together and effectively “locks” the cassette. It will be appreciated that it is quite difficult to remove the third cassette part once it is installed, especially if the top face (55) of the third cassette part is dimensioned so as to be flush with the top face of the second cassette part when assembled (this is not shown in
The membrane (61) ensures that the particles inside the cassette may not come into contact with any external particles or gases and thus the membrane (61) ensures the sterility of the cassette.
In use, the cassette is inserted into a needleless syringe such as that shown in
Following such fluidizing, the upstream membrane (62) bursts and the particles are entrained in the bulk of the gas flow followed by the bursting of the downstream membrane (63) shortly thereafter.
Heat sealing or adhesive is not necessary to seal the membranes and the first and second membranes may be sealed against the first and second cassette parts respectively due to the tight fit between the various cassette parts. For example, the first membrane (62) may be sealed by virtue of being trapped between the first and third cassette parts. Similarly, the second membrane (63) may be trapped between the first and second cassette parts, with no special heat sealing or adhesive step being required.
For each of the embodiments, the materials used to manufacture the cassette parts and the membranes may be conventional, for example, the membranes may be mylar as disclosed in WO 94/24263 and the first and second cassette parts are preferably manufactured from a plastics material, using injection moulding for example. Both the membranes and cassette parts may be made from polycarbonate such as Evaxone 260 (EVA) polymer. If heat sealing is used, a temperature of 110° C. and pressure of 760 kPa (110 psi) for 1.5 seconds has been found to be acceptable.
The cassette is suitable for any type of particle, including powdered drugs and carrier particles coated in genetic material.
| Number | Date | Country | Kind |
|---|---|---|---|
| 0118266.6 | Jul 2001 | GB | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/GB02/03412 | 7/25/2002 | WO | 00 | 3/12/2004 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO03/011380 | 2/13/2003 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 3308818 | Rutkowski | Mar 1967 | A |
| 5238003 | Baidwan et al. | Aug 1993 | A |
| 5503627 | McKinnon et al. | Apr 1996 | A |
| 5865803 | Major | Feb 1999 | A |
| 6004286 | Bellhouse et al. | Dec 1999 | A |
| 6004287 | Loomis et al. | Dec 1999 | A |
| 6010478 | Bellhouse et al. | Jan 2000 | A |
| 6475181 | Potter et al. | Nov 2002 | B1 |
| 6592545 | Bellhouse et al. | Jul 2003 | B1 |
| 7060048 | Nat et al. | Jun 2006 | B1 |
| 7207967 | Bellhouse et al. | Apr 2007 | B1 |
| 7320677 | Brouillette | Jan 2008 | B2 |
| 20020004641 | Bellhouse et al. | Jan 2002 | A1 |
| Number | Date | Country |
|---|---|---|
| 1 090 651 | Apr 2001 | EP |
| 873453 | Jul 1942 | FR |
| WO 9424263 | Oct 1994 | WO |
| WO 9604947 | Feb 1996 | WO |
| WO 9612513 | May 1996 | WO |
| WO 9901168 | Jan 1999 | WO |
| WO 9901169 | Jan 1999 | WO |
| WO 0062846 | Oct 2000 | WO |
| WO 0105455 | Jan 2001 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 20050010168 A1 | Jan 2005 | US |
