Needleless syringes are known and have previously been described in the prior art.
In a broad sense, needleless syringes are used for the subcutaneous injection of therapeutic agents. An obvious advantage of the use of a needleless syringe, is the avoidance of physically perforating the epidermis. The therapeutic agents can present themselves in powder form. The active substances can be vaccines, anesthetics, medicaments, hormones, and genetic compounds, for example. These agents, while in the form of particles whose size is of the order of a few microns, are capable of penetrating the skin of a patient, due to the high velocity imparted upon them.
In their May 4, 1999 U.S. Pat. No. 5,899,880, Bellhouse et al. describe such a needleless syringe. Bellhouse et al. propose the use of a needleless syringe having a nozzle presenting a divergent downstream portion, in order to achieve a pseudo-steady-state gas expansion to accelerate the particle flow. The problem presented by this approach is double: (i) the particle flow is, in reality, not stationary, that is, it does not possess a steady state system and, (ii) the particle flow becomes detached from the inner wall of the divergent downstream nozzle, which reduces the expansion and hence the acceleration produced.
Additionally, the different needleless syringe embodiments described by Bellhouse et al., illustrate a membrane that ruptures when the pressure exerted upon it exceeds its threshold. Furthermore, a mechanism exploiting the direct rupture of the membrane as well as an approach without the use of a membrane was not explored.
Finally, Bellhouse et al. do not present concepts linking the particle dose to the gas reserve, other than the use of a quasi-static compression piston.
U.S. Pat. No. 5,865,796 issued on Feb. 2, 1999 to McCabe essentially describes a similar device, designed for the injection of genetic material in a laboratory setting.
Both of the above reported devices are capable of accelerating an inert gas, and hence the concomitant acceleration of the particles, through the expansion of the inert gas at high pressures, through a nozzle that has a convergent upstream section and a divergent downstream section (commonly referred to as convergent-divergent nozzle). Hence, one has to appreciate that the above-mentioned acceleration process functions at a constant or quasi-constant steady state, that is, once the waves resulting from the rupture of the membrane are no longer important. It becomes therefore obvious that in the Bellhouse et al. device, the particles will have been ejected from the device prior to the establishment of the so-called quasi steady state system.
The consequences of this observation are interesting, since researchers studying the Bellhouse system, carried out their optimization calculations based on the quasi steady state system hypothesis. Indeed, a recent publication (M. A. F. Kendall, N. J. Quinlan, S. J. Thorpe, R. W. Ainsworth and B. J. Bellhouse: The gas-particle dynamics of a supersonic drug delivery system. Book of Abstracts, 22nd International Symposium on Shock Waves, London, 19-23 Jul. 1999) illustrates that because of their wrongful interpretation of this phenomenon, there exists an important discrepancy between the values predicted by the theoretical model and the observed experimental values, as can be observed in FIG. 1.
The graph of FIG. 1, which is labeled “prior art”, is illustrative of a comparison between the calculated particle velocity profile and the measured particle velocity profile. It can be readily observed that the theoretical model predicts an exit velocity for the particles in the proximity of Mach 6, whereas the experimental observations illustrate a considerably lesser Mach velocity.
In their Jan. 25, 2001 PCT patent application published under no. WO 01/05455, Kendall & Brown describe a needless syringe which incorporates improvements on the Bellhouse system by correctly accounting for the starting process which thereby increases the predictability of the device. Kendall & Brown propose the use of a shock tube, comprised of two chambers of same or similar diameter, with a divergent nozzle attached to the downstream chamber. In their device, they explain that the particles are first set in motion via the production of a shock wave when the membrane initially separating the two chambers is ruptured and that further acceleration is then produced by the expansion of the gas in the divergent nozzle. In reality, this device is quite similar to that of Bellhouse et al., the only difference being the addition of a constant diameter downstream duct section before the divergent nozzle which increases the time delay between the undesirable nozzle starting phenomena and the particle acceleration phase.
Furthermore, the method for accelerating a dose of particles in a needleless device proposed by Kendall & Brown claims to comprise the production of a primary shock wave. It should be known that it is possible to carry a dose of particles with a device comprising a driver chamber and a duct section downstream of said driver chamber without producing a primary shock wave travelling in downstream direction in said duct section. Indeed, if the duct were evacuated, i.e., at zero absolute pressure, the opening of the closure means located between said driver chamber and said duct section would not, in this case, produce a primary shock wave travelling in a downstream direction in said duct section since there would be no pre-existing medium in said duct section for the shock wave to propagate into, but the dose of particles could still be accelerated by the expansion of the driver gas. The production of a primary shock wave, or any number of shock waves thereafter, is therefore not necessary to achieve particle acceleration.
The correct physical interpretation of these devices is rather obtained by examining the method of expansion of the gas contained within said driver section, which causes a gaseous piston to propagate in the downstream direction in said duct section thereby carrying particles in the same direction. By optimally producing this expansion, the performance of the device, as measured by particle velocity and uniformity of particle velocity achieved, can be predicted and maximized. This expansion can be produced through steady or quasi-steady means which usually utilize nozzles of convergent or divergent geometry. This expansion can also be produced through unsteady means, by sudden or gradual temporal changes in the flow properties, in which case unsteady trains of rarefaction waves are used.
In the device proposed by Bellhouse et al., the gaseous expansion mechanism is that of quasi-steady expansion using a converging-diverging nozzle. The shortcomings of using a divergent have been discussed above and in the patent application of Kendall & Brown (see FIG. 2 and associated discussion lines 28-32 p. 4 and lines 1-7 p. 3 of the Kendall & Brown document).
In the devices proposed by Kendall & Brown, there are either one or two driver gas expansion mechanisms. In all devices proposed by Kendall & Brown, there is an unsteady expansion produced by the opening of a closure means located between a driver chamber and a duct section located downstream of the driver chamber. The unsteady expansion waves can be seen as item 30 (comprising the leading wave 34) in FIG. 3 of the Kendall & Brown document. In most embodiments proposed by Kendall & Brown, there is also an additional quasi-steady driver gas expansion mechanism, achieved through the use of a divergent nozzle positioned downstream of said duct section. The shortcomings of using a divergent nozzle are in this case similar to those of the Bellhouse device. Kendall & Brown recognize that their proposed device could possibly work without having this divergent nozzle, but they fail to mention that to achieve the desired particle flow velocities without this nozzle, the required driver gas pressure would be very high thereby increasing the safety risks associated with the use of the device and also reducing the utility of the device since a very high pressure source of gas would be required. This is why they have to resort to a divergent nozzle in all embodiments of their invention.
In embodiment 5 of their proposed device, Kendall & Brown propose to have a driver chamber as having a larger area than the downstream duct section. However, in that proposal they have failed to recognize that a quasi-steady expansion would take place within the contraction and that for a sufficiently large area ratio a second unsteady expansion would be produced in the driver gas but downstream of the contraction.
It should be known that there exists other combinations of quasi-steady and unsteady gaseous expansion means that achieve a better performance than those in the Bellhouse and the Kendall & Brown devices.
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