Abstract:
In accordance with an embodiment of the invention, a needleless injection apparatus includes a cartridge having a plunger disposed at a rearward end. The cartridge includes an inner portion with a throat at a forward portion and a displaceable outlet valve initially disposed within the cartridge throat. The cartridge further includes a generally outwardly facing surface and a system for selectively providing driving force to drive the plunger in a forward direction. The apparatus also includes a nozzle for receiving the cartridge, the nozzle defining a rearward, cartridge-receiving portion, and having a forward portion terminating in and defining a valve abutment surface with a plurality of channels and an injection orifice. The forward portion of the nozzle being configured to receive the valve when the valve is displaced to a forwardly disposed position such that the valve is disposed against the valve abutment surface, and so that the inner portion of the cartridge has fluid access to the orifice via the channels. The nozzle further includes a generally inwardly facing surface that abuts the cartridge surface, and a seal disposed between the outwardly facing surface of the cartridge and the inwardly facing surface of the nozzle for at least reducing leakage of injectate therebetween.

Description:
This application is a continuation-in-part of Ser. No. 09/207,398, filed Dec. 8, 1998, now U.S. Pat. No. 6,132,395. This invention relates to a needleless injection system which includes a prefilled cartridge. 
    
    
     BACKGROUND OF THE INVENTION 
     One of the problems inherently present in the packaging of liquid parenteral drugs is that there is not enough biocompatibility data about the interaction between those drugs and thermoplastic containers. While plastic is commonly used in many injection devices, most parenteral drugs cannot be exposed to most plastics other than for a short period immediately prior to the injection. This is because the drug or injectate may chemically react with the plastic, or cause materials in the plastic to leach into the injectate, thereby introducing impurities in the drug. In periods of extended storage, such exposure to a plastic container may result in degradation of the drug. For these reasons, the pharmaceutical industry normally avoids the storage of injectate in some thermoplastic materials such as polypropylene, which is commonly used in syringes and related injection paraphernalia. Similarly, there is no long term biocompatibility data on engineering or high strength thermoplastics, such as polycarbonate, which is the plastic most commonly used in needleless injection systems. 
     For this reason, injectates are typically stored in glass vials. Immediately prior to injection, the injectate chamber of a needleless injection system is filled from a glass vial containing the drug. This normally requires the use of a vial adapter, sometimes referred to as a blunt fill device, or an access needle which pierces the protective membrane over the top of the vial and then directs injectate down into the chamber or cartridge of the needleless injection system. 
     There are a number of drawbacks with this conventional approach. For example, the extra step of having to transfer the drug from the glass vial to the needleless injection system is time consuming and can be troublesome to a patient who is trying to administer the drug at home and who may have physical infirmities. Even for those who are not infirm, an adapter must be on-hand, and it must be sterile to prevent contamination of the injectate. The adapter typically includes a transfer needle with a sharp point at one end to pierce the vial membrane, and that can lead to injury, to unintended introduction of the injectate into the handling personnel or administrator, and/or to contamination of the injectate. This extra step of filling the needleless injection system immediately prior to injection also brings about the possibility of leakage and waste of injectate and, if improperly performed, can introduce air into the injection system. The introduction of air presents difficulties in a needleless injection system, because unlike a conventional needle and syringe system, it is not easy to bleed air out of the chamber of a needleless device. Therefore, firing the injection system with a portion of its chamber filled with air results in a lower dosage being injected into the patient. It is also possible that the injection may take place at an improper pressure. One advantage of the needleless injection systems of Bioject, Inc., assignee of this patent, is that they are able to inject a precisely predetermined amount of injectate at a predetermined, precise location in the tissue of the patient. The introduction of air may make it difficult to achieve such precision. 
     Accordingly, it is an object of the present invention to provide for the prefilling of a cartridge to be used in a needleless injection system. 
     SUMMARY OF THE INVENTION 
     The invention provides a cartridge and nozzle assembly having a nozzle with a valve-receiving portion including a plurality of channels to facilitate flow of injectate to the nozzle orifice. Specifically, the assembly includes a cartridge having a plunger disposed at a rearward end thereof, with an inner portion having a throat at a forward portion thereof, the cartridge further including a generally laterally extending interface surface. Also included is a displaceable outlet valve initially disposed within the throat, the outlet valve having a channel-less valve body. The nozzle receives the cartridge in a rearwardly-directed cartridge-receiving portion, and includes a forward portion defining a valve-receiving portion with a plurality of channels and an injection orifice. Thus, the inner portion of the cartridge has fluid access to the orifice via the channels. The nozzle also includes a generally extending interface surface which abuts the cartridge interface surface. Finally, a seal is disposed between the cartridge and the nozzle rearward of the interface surfaces for preventing or at least reducing leakage of injectate therebetween. 
     Another aspect of the invention provides a method for preparing a needleless injection system. The method includes the following steps, not necessarily in the order recited: (1) selecting a glass cartridge with a plunger positionable at a rearward end and an inner portion with a throat at a forward portion, and an outlet valve positionable within the throat, the cartridge further including a generally laterally extending interface surface; (2) positioning a seal on the cartridge rearward of the laterally extending interface surface; (3) positioning one of the plunger or the outlet valve within the cartridge; (4) filling the cartridge with injectate prior to positioning the other of the plunger or the outlet valve in the cartridge; (5) positioning the other of the plunger or the outlet valve within the cartridge; (6) selecting a nozzle which includes a rearward, cartridge-receiving portion and a forward portion defining a valve-receiving portion with a plurality of channels and an injection orifice defined therein, the forward portion being configured to receive the valve when the valve is displaced to a forwardly disposed position, the nozzle further including a generally laterally extending interface surface; (7) installing the cartridge into the nozzle to form a cartridge/seal assembly such that the interface surfaces are in abutment and the seal is disposed rearwardly of such abutment; and (8) maintaining the cartridge/seal assembly in a sterile environment prior to use. 
     An additional aspect of this method includes the step of mounting the cartridge/nozzle assembly to the front end of an injector by exerting rearward pressure on the assembly such that an injector ram exerts forward pressure on the plunger, causing the outlet valve to be displaced from the throat and into the valve-receiving portion and resulting in the injectate displacing air in the forward portion of the nozzle. 
     With this last-recited aspect, injection can be affected by activating the injector, causing the injector ram to push forwardly on the plunger, causing injectate to be driven out of the nozzle orifice. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a side elevation sectional view of the prefilled cartridge of the present invention, with its initial position prior to insertion of the cartridge shown in phantom, and the inserted position, prior to initial pressurization, shown in solid lines; 
     FIG. 2 is an end elevation sectional view taken along line  2 — 2  of FIG. 1, showing the cartridge in its inserted position; 
     FIG. 3 is a side elevation sectional view showing the position of the cartridge and nozzle within a preferred embodiment of the needleless injection system; 
     FIG. 4 is an enlarged, fragmentary, side elevation sectional view of the outlet valve and adjacent portions of the cartridge/nozzle assembly of the embodiment of FIG. 1, with the outlet valve shown in its unpressurized position; 
     FIG. 5 is a view corresponding to FIG. 4 except that the outlet valve is shown in section and is shifted to its forward position; 
     FIG. 6 is an enlarged side elevation view of the outlet valve of the embodiment of FIG. 1; 
     FIG. 7 is a side elevation sectional view taken along line  7 — 7  of FIG. 6; 
     FIG. 8 is an end elevation sectional view taken along line  8 — 8  of FIG. 6 showing the forward portion of the outlet valve; 
     FIG. 9 is an end elevation sectional view taken along line  9 — 9  of FIG. 4 showing the rearward portion of the outlet valve; 
     FIG. 10 is an isometric view of the outlet valve of FIGS. 1-9; 
     FIG. 11 is a side elevation sectional view of an alternate embodiment showing a membrane in place of the outlet valve; 
     FIG. 12A is a side elevation view of the embodiment of FIG. 11, with the membrane broken; 
     FIG. 12B is an isometric view corresponding to FIG. 12A; 
     FIG. 13A is a side elevation sectional view of a second alternate embodiment, with the outlet valve in its closed position; 
     FIG. 13B is a view corresponding to FIG. 13A except that the outlet valve is shown in its forward position; 
     FIG. 14A is an isometric view of an outlet valve corresponding to the outlet valve depicted in FIGS. 13A and B except that the valve wings are notched to facilitate tearing when pressure is exerted on the valve; 
     FIG. 14B is a view corresponding to FIG. 13A except that the notched-wing version of the outlet valve, shown in FIG. 14A, is depicted; 
     FIG. 14C corresponds to FIG. 14B except that the outlet valve is shown in its open position; 
     FIG. 15 is a fragmentary side elevation sectional view of yet another alternate embodiment of the nozzle without the cartridge or the outlet valve, showing ribs in the nozzle recess; 
     FIG. 16A is an enlarged side elevation sectional view of the embodiment of FIG. 15, showing the cartridge and the outlet valve in its closed position; 
     FIG. 16B is a view corresponding to FIG. 16A except that the outlet valve is shown in its forward position; 
     FIG. 17A is a side elevation view of an alternate embodiment of the invention; 
     FIG. 17B is a view which corresponds to that of  17 A; 
     FIG. 18 is a side elevation sectional view showing the position of the cartridge and nozzle with an alternate embodiment as depicted in FIGS. 19-22; 
     FIG. 19 is a side elevation sectional view of the embodiment of FIG. 18, with the plunger in its rearward position prior to installation of the assembly into an injector; 
     FIG. 20 is an end elevation sectional view taken along line  20 — 20  of FIG. 19; 
     FIG. 21 is a side elevation sectional view of the embodiment of FIG. 18, except that the plunger is shown in its forward position after injectate has been injected from the assembly; and 
     FIG. 22 is an end elevation sectional view taken along line  22 — 22  of FIG.  21 . 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The Embodiment of FIGS.  1 - 10   
     The objects of the invention are best achieved when the invention takes the form of the embodiment depicted in FIGS. 1-10. This description will initially make reference to those figures. Depicted generally at  10  is a cartridge/nozzle assembly in which the cartridge may be prefilled with liquid injectate. The assembly includes a cartridge  12  which, in the preferred embodiment, is formed of strengthened glass, and a nozzle  14 , which, in the preferred embodiment, is fabricated of high strength thermoplastic, typically polycarbonate. The nozzle  14  is of conventional design except the rearward (or leftward in FIG. 1) portion includes a plurality of evenly spaced tangs  16 . In the depicted embodiment, four such tangs are included, positioned at 90-degree intervals around the nozzle, two of which are shown in phantom in FIG.  1 . Alternatively, three or even two such tangs may be utilized. 
     With the cartridge  12  disposed in its partially inserted position depicted in phantom in FIG. 1, tangs  16  are displaced radially outwardly and are held there by cartridge walls  18 . It is easy to insert cartridge  12  into this partially installed position because the walls  18  of the cartridge taper at  20  at the forward end thereof. Tapered walls  20  thereby define an inner throat  21  disposed in the forward end of cartridge  12 . An O-ring  22  is typically disposed adjacent this forward, tapered end of cartridge  12  between the cartridge and nozzle  14 . A step  28  is included in the inner surface of side walls  30  of nozzle  14  to provide a stop and a sealing surface for O-ring  22  disposed between the tapered portion  20  of cartridge walls  18  and the inner surface of nozzle side walls  30 . The O-ring thus prevents the flow of injectate along the interface between the outer surface of cartridge walls  18  and the inner surface of nozzle side walls  30 . A plunger  24  is disposed within walls  18  of cartridge  12 , and controls the injection of injectate out of the cartridge, as desired by the operator. At the factory, or at the user&#39;s location, cartridge  12  is inserted into nozzle  14 , as shown in FIG. 1, and is then pressed forwardly and entirely into the nozzle, as shown in solid lines in FIG. 1, until the tapered portion  20  of walls  18  of cartridge  12  abut a cartridge abutment face  26  in the forward end of nozzle  14 . 
     One advantage of the present invention is that it permits cartridge  12  to be prefilled with injectate and then stored at a suitable location, whether that be at the factory, at a hospital or other medical facility, a pharmacy, in an ambulance, or at the residence of a patient who may need the medication. Alternatively, cartridge  12  may be prefilled and stored in position within nozzle  14 , ready to be inserted into a needleless injector, such as that shown generally at  32  in FIG.  3 . 
     The needleless injector  32  with which the cartridge/nozzle assembly  10  is typically used is depicted in Peterson et al. U.S. Pat. No. 5,399,163, although the assembly  10  may be used in a wide variety of other needleless injection systems. The Peterson &#39;163 patent is incorporated herein by reference. As shown in FIG. 3, the cartridge/nozzle assembly  10  is mounted to the front end  34  of injector  32  by a series of evenly spaced lugs  36 , three of which are typically disposed at 120-degree intervals around the periphery of nozzle  14 . The lugs  36  in nozzle  14  are aligned to pass through corresponding spaces  38  disposed in the front end  34  of injector  32 . The cartridge/nozzle assembly  10  is then rotated to lock it in position such that lugs  36  are disposed between the inner surface  40  of front end  34  of injector  32  and a lug abutment surface  42  in injector  32 . As the cartridge nozzle assembly  10  is inserted into injector  32 , the forward end of a ram  44  abuts a somewhat resilient Teflon pad  45  mounted to the rearward end of the plunger  24 . Contact between ram  44 , pad  45  and plunger  24  is made prior to lugs  36  reaching lug abutment surface  42  in injector  32 . As cartridge  12  is continued to be pushed into injector  32 , with lugs  36  disposed against lug abutment surface  42 , the ram  44 , which is stationary, will cause plunger  24  to slide forward, which in consequence, will cause liquid injectate inside cartridge  12  to move outlet valve  46  forward, allowing flow of liquid into a recessed portion  50  and toward the jet orifice  52  (see FIG.  1 ). The amount of liquid flowing through outlet valve  46  during the insertion of cartridge  12  in injector  32  is controlled by the length of ram  44  relative to the lug abutment surface  42 . 
     As shown best in FIG. 4, an outlet valve  46  is disposed adjacent the inner surface of tapered walls  21  in the forward end of cartridge  12 . This valve  46  is typically fabricated of butyl rubber or another resilient material which is capable of being sterilized prior to insertion into cartridge  12 . As shown in FIG. 4, valve  46  is designed to fit tightly within the forward end of cartridge  12 . As best shown in FIGS. 6-10, the mid-portion or body  58  of outlet valve  46  is normally round in cross-section, and is sized such that it fits snugly within the tapered walls  20  of cartridge  12 . The rearward portion of outlet valve  46  includes four rounded slots  56  which extend rearwardly from a centrally disposed body portion  58  of outlet valve  46 . The forward end  51  of outlet valve  46  includes forwardly extending members  62  which extend axially from body  58  of outlet valve  46  to define two perpendicular valve channels  64 . 
     In the preferred embodiment, the outer diameter of the outlet valve is slightly greater than the inner diameter of tapered walls  21 , with the outlet valve outer diameter being typically 0.105 inch, and the inner diameter of the taper walls being 0.098 inch. This difference in sizing, along with the somewhat elastic properties of PTFE (polytetrafluoroethylene) or other material from which outlet valve  46  is formed, permits a friction fit in the front end of cartridge  12 . However, once hydraulic pressure is exerted on outlet valve  46 , such as when the cartridge/nozzle assembly  10  is pushed into place in needleless injector  32  while ram  44  is held stationary within the injector, outlet valve  46  is forced to a forward, initially-pressurized position depicted in FIG. 5, with the forward end of outlet valve  46  disposed against valve abutment surface  48  at the forward end of recessed portion  50  of the forward end of nozzle  14 . This abutment surface  48  typically includes a surface or shoulder extending in a direction perpendicular to the longitudinal dimension of nozzle  14  and to the direction of displacement of outlet valve  46 . The forward end  51  of outlet valve  46  typically includes a surface which complements that of the abutment surface shoulder, also extending perpendicular to the longitudinal dimension of the valve and to the direction of displacement of the valve. The forward end of recessed portion  50  terminates in a jet orifice  52  having a generally conical-shaped orifice channel  54 . The relative sizing of the respective outlet valve  46 , the inner surface of tapered walls  20 , and recessed portion  50  are such that fluid is permitted to flow from the cartridge and into the recessed portion surrounding the outlet valve and perhaps even out of injection aperture  52 . 
     Operation of the Embodiment of FIGS.  1 - 10   
     In operation, at the factory or at the user&#39;s location, cartridge  12  is inserted into nozzle  14  as shown in phantom in FIG. 1, and is then pressed forwardly and entirely into the nozzle, as shown in solid lines in FIG. 1 until the tapered portion  20  of walls  18  of cartridge  12  abut cartridge abutment face  26  in the forward end of nozzle  14 . Prior to the mounting of the cartridge/nozzle assembly  10  within injector  32 , as shown in FIGS.  1  and  4 , outlet valve  46  is lodged in the throat  21  of cartridge  12  in its pre-initial pressure position. With the valve in this position, fluid disposed within the cartridge is prevented from flowing out of the throat  21  by the body portion  58  of valve  46 . 
     Because ram  44  in injector  32  is held stationary, as the cartridge/nozzle assembly  10  is inserted into an injector  32 , the pressure of plunger  24  against the fluid disposed in cartridge  12  causes outlet valve  46  to shift into its forward initially pressurized position shown in FIG.  5 . Because outlet valve  46  includes slots  56 , fluid within the cartridge is permitted to flow through cartridge throat  21  and into cartridge recessed portion  50 . Forward valve channels  64  in outlet valve  46  permit the fluid rushing into recessed portion  50  to displace any air in the recessed portion, forcing that air out orifice channel  54  and orifice  52 , so that the recessed portion, the orifice channel, and the aperture are all entirely filled with injectate. This may also result in some injectate dribbling out the jet orifice, but because it is an insignificant amount, it is of little concern. What is important is that all of the air is displaced from the front of nozzle  14 . This permits the amount of injectate which will be injected into the patient to be precisely measured, which would not be possible if an unknown amount of air was disposed in the front of the nozzle. This also permits pressure to be precisely predetermined, again, which would not be possible if an undetermined amount of air was disposed in the front of the nozzle. 
     This step of insertion of the cartridge/nozzle assembly  10  into injector  32  is typically performed immediately prior to injection. Thus, with assembly  10  in place, the needleless injector  32  can be activated, forcing ram  44  and plunger  24  forwardly, thereby driving injectate through slots  56  in outlet valve  46 , around body  58  disposed within recessed portion  50 , through valve channels  64  and into aperture channel  54  and aperture  52  and into the patient. Because of the configuration of outlet valve  46 , throat  21  and the inner walls of recessed portion  50 , there is very little pressure drop as fluid is being forced out of the cartridge and out of injection aperture  52 . 
     Embodiment of FIGS.  11 ,  12 A and  12 B 
     FIGS. 11,  12 A and  12 B depict an alternate embodiment of the prefilled cartridge/nozzle assembly, indicated generally at  110 . In place of an outlet valve, embodiment  110  includes an elastomeric membrane  166  which is designed to burst open when a predetermined pressure has been applied, as shown in FIGS. 12A and 12B. Membrane  166  normally has a weakened portion along which the break will occur. In the depicted embodiment this weakened portion takes the form of a notch  167  which extends most but not all of the 360° around the inner throat  121  of cartridge  112 . Membrane  166  is typically held in place by an aluminum seal  168  which is often used to help seal medication-containing cartridges. 
     In other respects embodiment  110  is much like embodiment  10  in that it includes O-rings  122  and nozzle  114 , and is typically prefilled with injectate. Membrane  166  is designed to burst open when it is loaded into a needleless injector system as the plunger (not shown) is slightly depressed by the injector ram (not shown) as explained earlier. Upon bursting of membrane  166 , injectate flows into the recess  155  in the forward end of the nozzle  114 , thereby displacing any air and preparing the assembly for an injection. 
     Embodiment of FIGS.  13 A and  13 B 
     FIGS. 13A and 13B depict another alternate embodiment of the cartridge/nozzle assembly, indicated generally at  210 . This embodiment utilizes an aluminum seal  268  like embodiment  110 , but also includes an outlet valve  246 . Outlet valve  246  includes a pair of radially extending wings  270  which are clamped under aluminum seal  268  until a predetermined amount of pressure forces outlet valve  246  out of the inner throat  221  of cartridge  212 . When this predetermined pressure is reached, wings  270  pull out from seal  268  and the valve shifts forwardly into the recessed portion  250  of nozzle  214  until it comes into contact with the nozzle abutment surface  248 . 
     Other than the presence of wings  270 , outlet valve  246  is the same as the previously described outlet valve  46  in the cartridge/nozzle assembly  10  of FIGS. 1-10. Thus, when outlet valve  246  is shifted to its forward position depicted in FIG. 13B, injectate is permitted to flow out of cartridge  212  and into recessed portion  250  to displace any air and thus prepare the assembly  210  for an injection, as described above. 
     Embodiment of FIGS.  14 A-C 
     The cartridge/nozzle assembly  310  of FIGS. 14A-C is identical to assembly  210  except that wings  370  of outlet valve  346  include weakened portions. In the depicted embodiment these weakened portions take the form of a pair of notches  372 . Thus, when the cartridge/nozzle assembly  310  is mounted into a needleless injection system (not shown), instead of wings  370  pulling out of engagement with seal  368 , the wings typically tear at notches  372  to permit outlet valve  346  to shift to the forward position depicted in FIG.  14 C. In other respects the operation of cartridge/nozzle assembly  310  is the same as assemblies  10  and  210  described above. 
     Embodiment of FIGS.  15 ,  16 A and  16 B 
     The cartridge/nozzle assembly  410  of FIGS. 15,  16 A and  16 B is identical to assembly  10  in FIGS. 1-10 except that recessed portion  450  of nozzle  414  includes a plurality of evenly spaced ribs  474 . In the depicted embodiment four such ribs  474  are included. They are sized such that outlet valve  446  fits snugly into recessed portion  450  as shown in FIG.  16 B. Channels  476  defined between ribs  474  permit fluid to flow around outlet valve  446  to orifice  52 . In other respects cartridge/nozzle assembly  410  is constructed and operates in the same manner as assembly  10  of FIGS. 1-10. 
     The Embodiment of FIGS.  17 A and B 
     FIGS. 17A and B depict another alternate embodiment of the cartridge/nozzle assembly shown generally at  510 . The assembly includes a cartridge  512  and a nozzle  514 . Cartridge  512  is prefilled with injectate as described above and is sealed with an aluminum seal  568  and an elastomeric membrane  566 . A spoke  578  is provided to pierce membrane  566  when the cartridge is inserted all of the way into position in the nozzle, as shown in FIG.  17 B. This is typically done shortly prior to injection. A plastic spike seal  580  is provided adjacent the spike to prevent leakage of injectate. The assembly  510  is then mounted into a needleless injector system such as described above, with the air being displaced to prepare the unit for injection. 
     In other respects, cartridge/nozzle assembly is the same in structure and operation as the previously described embodiments. 
     The Embodiment of FIGS.  18 - 22   
     FIGS. 18-22 depict another alternate embodiment of the cartridge/nozzle assembly. The assembly, shown generally at  610 , includes a cartridge  612  and a nozzle  614 . FIG. 18 shows assembly  610  being threaded into a needleless injector  632 . Injector  632  is the same as the previously-described injector  32 , except for this threaded mounting. An anti-contamination cap  633  is also shown in FIG.  18 . This cap is positioned over the forward end of nozzle  614  prior to use in order to prevent any contamination of the nozzle orifice  652  and of the injectate contained in the cartridge/nozzle assembly  610 . 
     The depicted anti-contamination cap  633  is shown to be air tight. It should, however, be understood that the cap  633  will permit air and/or injectate to leak out of the nozzle orifice  652  when fluid pressure is exerted. Thus, as will be explained below, when the cartridge/nozzle assembly is mounted onto an injector  632 , air and some injectate will leak past the cap  633 . Alternatively the anti-contamination cap may include ribs (not shown) which permit the cap to be securely mounted to the forward end of nozzle  614  but which facilitate venting of air and injectate out of the nozzle during the installation process. 
     The cartridge  612  is normally formed of strengthened glass and is prefilled with liquid injectate. The depicted nozzle  614  is fabricated of high strength thermoplastic, typically polycarbonate. The cartridge  612  includes outer walls  618  which taper slightly at  620  at the forward portion thereof. Tapered walls  620  converge to form an inner throat  621  disposed at the forward end of the cartridge  612 . An O-ring seal  622  is disposed adjacent this forward, tapered portion of cartridge  612  between the cartridge and the inner surfaces of the nozzle side walls  630 . Another way to describe the positioning of the O-ring  622  is that it is disposed between an outwardly-facing surface of the cartridge (outer walls  618 ) and an inwardly facing surface of the nozzle, adjacent the rearward end of the throat. In the depicted embodiment a step  628  is shown in the inner surface of side walls  630  to provide a stop and a sealing surface for O-ring  622 . Thus, when the cartridge is in place within the nozzle, the O-ring  622  prevents or at least reduces the flow of injectate along the interface between the outer surface of cartridge walls  618  and the inner surface of nozzle side walls  630 , and maintains the high pressures required for proper needleless injections. 
     A plunger  624  is disposed within the walls  618  of cartridge  612 , and controls the flow of injectate out of the cartridge, as desired by the operator. At the factory, where the drug is filled aseptically (in a sterilized environment), the cartridge  612  is inserted into the nozzle  614  as shown in FIG. 19, and is then pressed forwardly and entirely into the nozzle until the forward end of the cartridge  612  abuts a cartridge abutment face  626  in the forward end of nozzle  614 . This cartridge abutment face  626  will sometimes be referred to herein as a laterally extending interface surface. 
     As shown best in FIG. 19, an outlet valve  646  is initially disposed within the throat  621  adjacent the forward end of the cartridge  612 . In the depicted embodiment the outlet valve  646  is spherical in configuration, and is fabricated of PTFE (polytetrafluoroethylene) or other resilient material which is suitable for drug storage and is capable of being sterilized prior to insertion into cartridge  612 . As shown in FIG. 19, outlet valve  646  is designed to fit tightly within the forward end of cartridge  612 . Because the valve  646  is spherical in configuration and in the preferred embodiment does not include any slots or apertures therein, and is sized such that it fits snugly within the throat  621  of cartridge  612 , it might be said to include a body portion which fits against the walls of the cartridge throat  621  to prevent flow of injectate out of the cartridge until valve  646  is pushed out of the cartridge throat. 
     In the preferred embodiment, the diameter of outlet valve  646  is 0.110 inch, with the inner diameter of the throat  621  being 0.098 inch. This difference in sizing, along with the somewhat elastic properties of PTFE or other material from which outlet valve  646  is formed, permits a friction fit on the front end of the cartridge  612 . In fact, outlet valve  646  would take a more oblong configuration than that shown in FIGS. 18 and 19, given the fact that the inner diameter of throat  621  is less than the diameter of outlet valve  646 . Once hydraulic pressure is exerted on outlet valve  646 , outlet valve  646  is forced out of the cartridge throat  621  into a valve receiving cup  647  and forwardly against a valve abutment surface  648  at the forward end of the valve-receiving cup, in the forward portion of nozzle  614 . This typically happens when assembly  614  is threaded into the receiving thread of injector  632 . This threading step results in plunger  624  being pushed slightly in an outward or forward direction (to the right in FIG.  18 ), thus pushing outlet valve  646  from throat  621  in a forward direction as well. The forward end of valve-receiving cup  647  terminates in a jet orifice  652  having a generally conical-shape nozzle orifice channel  654 . The valve-receiving cup  647  will sometimes be referred to herein as a recessed portion of the nozzle. 
     To facilitate the flow of injectate from the cartridge  612  through the jet orifice  652 , a plurality of bypass channels  649   a, b  and  c  are formed in the valve-receiving cup  647  and the valve abutment surface  648 . They are of sufficient size that when the outlet valve  646  is disposed anywhere within the valve-receiving cup  647  or is disposed against the valve abutment surface  648 , sufficient clearance is provided between the valve and the channels that injectate can bypass through the channels, into the orifice channel  654  and out the jet orifice  652 . In the preferred embodiment where in the diameter of the outlet valve  646  is 0.110 inch, the valve-receiving cup is typically 0.115 inch in diameter, with the valve channels being 0.150 inch if they were measured in diameter, or 0.075 inch from the center of the valve-receiving cup to the edge of the channel. Using a configuration with three bypass channels  649   a, b, c,  each of the channels is typically 45° in width, and the channels are evenly spaced, here 120° degrees from each center line. Of course, it is possible that other channel configurations may be utilized, or other configurations may be substituted which permit flow of fluid past an outlet valve and into the orifice channel. 
     As the plunger  624  is pushed slightly in a forward direction, the pressure of the injectate fluid in cartridge  612  pushes outlet valve  624  from the throat  621  into the valve-receiving cup  647  and against valve abatement surface  648 . Injectate fluid thus fills the valve-receiving cup  647  and the channels  649   a,    649   b  and  649   c,  the nozzle orifice channel  654  and will dribble out of the nozzle orifice  652 . With anti-contamination cap  633  in place, this will cause injectate to leak out of the cap as the assembly  610  is threaded into place on the injector  632 . 
     When the device is ready to be activated, anti-contamination cap  633  is removed and the injector  632  is discharged. This drives plunger  624  forwardly, driving injectate out of the orifice  652  and into the patient (not shown). 
     In other respects, the cartridge/nozzle assembly  610  is similar to that of the embodiment of FIGS. 1-10 described above. 
     Operation of the Embodiment of FIGS.  18 - 22   
     Cartridge  612  is inserted into nozzle  614  at a factory location where aseptic conditions are assured. In such installation procedure the cartridge  612  is pressed forwardly and entirely into the nozzle until the forward end of the cartridge contacts cartridge abutment face  626  in the forward end of the nozzle. This position is depicted in FIG.  19 . Because injectate is maintained within the glass cartridge, the assembly may be stored for extended periods prior to use. It is typically stored in a sterile pouch or bag (not shown). Many such stored cartridge/nozzle assemblies  610  may be provided to the patient. In this condition, the outlet valve  646  disposed within throat  621  seals the cartridge tight, preventing leakage of injectate out of the cartridge and preventing the injectate from being contaminated. Anti-contamination cap  633  (which is only shown in FIG. 18 after the assembly has been mounted onto an injector), assists in preventing contamination. 
     When the user is ready to administer the medication, assembly  610  is removed from its pouch or sterile bag and threaded into the front end of an injector, such as that shown in FIG. 18 at  632 . As this threading is being done, plunger  624  is pushed forwardly because the injection ram  644  in the injector is stationary. This forces outlet valve  646  out of the cartridge throat  621  and into the valve-receiving cup  647  and against the valve abutment surface  648 . Injectate thus fills all of the air spaces in the front of the nozzle, causing air and some injectate to leak out of the cap  633 . 
     Once the cartridge/nozzle assembly  610  is in place, the device is ready for injection. Immediately prior to injection, anti-contamination cap  633  is removed from nozzle  614 , the nozzle is placed against the skin of the patient, and the injector is activated. 
     In other respects, the operation of the cartridge/nozzle assembly  610  is essentially the same as that of assembly  10  depicted in FIGS. 1-20. 
     Changes and modifications of the present invention can be made without departing from the spirit and scope of the present invention. Such changes and modifications are intended to be covered by the following claims.