Abstract:
Multi-component ampules for use with re-useable and disposable jet injectors are described which have primary and secondary packaging components. The primary packaging component includes an inner glass cylinder, an elastomeric diaphragm, and an elastomeric plunger. The secondary packaging components include a plastic outer shell and a plastic adapter. The primary packaging components allow medications and injectable suspensions to be stored for prolonged periods while the secondary packaging components provide structural integrity and adaptability for the ampule. Exemplary methods of use are also disclosed.

Description:
CROSS-REFERENCE TO RELATED APPLICATION  
       [0001]    The present application claims the benefit of provisional application No. 60/374,461 entitled “Multi-Component Ampule” filed Apr. 19, 2002, the content of which is expressly incorporated herein by reference. 
     
    
     
       BACKGROUND  
         [0002]    Jet injection devices are well known in the art for administering intramuscular and subcutaneous medications without needles. Examples of hypodermic jet injectors are described in U.S. Pat. Nos. 5,499,972; 5,569,189; and 5,704,911, their contents are hereby expressly incorporated herein by reference.  
           [0003]    In general, these patents disclose a hypodermic jet injector device that has an ampule for holding liquid medication and a jet injector for receiving the ampule and for injecting medication contained within the ampule subcutaneously without a needle. The ampule is generally a single integral component made from a thermoplastic material that has a nozzle on one end for discharging medication, the discharge end, and an opening on the other end for securing the ampule to a jet injector, the inlet end. The inlet end further includes a connectable end, such as an end with external or internal threads or a sleeve for mechanically coupling to the jet injector. The ampule&#39;s physical characteristics such as wall thickness and diameter are determined in part by the desire delivery dosage, the plunger type, the nozzle size, and the operating pressure for delivering the medication subcutaneously without a needle.  
           [0004]    The jet injector includes a metallic cylinder enclosed on one end, such as with a plug or cap, and open on the other end for receiving the ampule. Within the cylinder, the components of the jet injector generally include a spring, a piston, a shaft, a plunger, and a trigger. The jet injector device operates by cocking or compressing the spring, which is in mechanical communication with the piston. The trigger is used to set off the spring, which drives the piston, which then drives the shaft, and which then drives the plunger into the medication to discharge the medication out the nozzle at the distal end of the ampule. A typical operating pressure for a jet injector device to deliver medication subcutaneously without a needle is in the range of about 3,000 to 3,500 psi at the nozzle, with a much higher pressure range of about 5,000 to 6,000 psi developed during the initial thrust of the piston. Thus, a suitable ampule for use with the jet injector is one that is capable of handling the aforementioned pressure range.  
           [0005]    Subsequent to discharging the medication, the ampule, plunger, and shaft may be separated from the jet injector and be disposed of. The injector, however, can be re-used by resetting the spring, as disclosed in the &#39;911 patent. A new ampule, plunger, and shaft may then be connected to the jet injector by threading the ampule into the receiving end of the cylinder of the jet injector.  
           [0006]    Another hypodermic jet injector example is disclosed in Ser. No. 09/751,525 filed Dec. 29, 2000 and entitled “Low Cost Disposable Needleless Injector System for Variable and Fixed Dose Applications”, the content of which is incorporated herein by reference. The &#39;525 serial number discloses a jet injector assembly designed for low cost production and for disposability after a single use. The disposable jet injector assembly generally comprises an ampule threadedly or permanently attached to a jet injector. Within the jet injector, the device includes a spring that is in dynamic communication with a shaft and a piston. The shaft is coaxially disposed within the piston and is moveable or slidable within the piston even when the piston is in a cocked position. However, the disposable jet injector generally comes pre-cocked or pre-set in a package from the factory and only requires filling the ampule with medication at the point of injection. The shaft has a length such that a portion of the shaft extends out from the jet injector housing to facilitate filling the ampule, by grasping and moving the extended shaft portion.  
           [0007]    The ampule is threadedly or permanently fixed to the jet injector by adhesive, heat, or ultrasonic welding. The shaft, via the extension, allows medication to be drawn into the ampule when it is retracted from a first position to a second position, which creates a vacuum in the ampule to thereby draw in medication. The injector assembly is used by placing the discharge nozzle next to a skin and then firing the trigger, as discussed above with reference to the re-useable jet injector model.  
           [0008]    Although both the disposable and the re-useable jet injector assemblies are effective, reliable, and economical, they suffer from at least one shortcoming. Among other things, they utilize thermoplastic (“plastic”) ampules for manufacturability and for high-pressure compatibility. Plastic is relatively ductile, has a low modulus of elasticity, is highly impact resistant, and components that are made from plastic are relatively easy to fabricate. However, plastic ampules produced from plastic are generally not suitable for long term storage of medications, injectable suspensions, or the like. This is because certain ingredients that are added during the fabrication process of the plastic ampules can leach into the medication. Certain drugs or components of the drugs are also known to bind with the plastic or be absorbed by the plastic. Oxidation, degradation, and/or precipitation of the medication are also known to occur with prolonged storage of the medication in plastic ampules. It is also possible for a component of the drug to migrate through the walls of the plastic ampule, and oxygen, carbon dioxide, or other gasses may pass through the plastic into the drug. Hence, plastic ampules are generally not FDA approved for long term storage of medications and injectable suspensions.  
           [0009]    ASTM Type I Class A and United States Pharmacopeia (USP) Type I glass are FDA approved glass for prolonged storage of medications and injectable suspensions. However, glass has a high modulus of elasticity and is highly brittle. Thus, if an ampule is made from glass, the ampule has to be sufficiently thick in order to have the hoop strength necessary to accommodate an operating pressure of about 3,000 to 3,500 psi, and about 5,000 to 6,000 psi at the start of the injection cycle. A glass ampule that is capable of withstanding this pressure range, however, can be expensive, unsightly, and undesirable when used in connection with the jet injectors described.  
           [0010]    There is therefore a need for a multi-component ampule that is useable with conventional jet injectors, that is capable of long term storage of medications and injectable suspensions, and that uses FDA approved materials. Additionally, there is also a need for a method of using the multi-component ampule with the conventional jet injectors.  
         SUMMARY OF THE INVENTION  
         [0011]    The present invention specifically addresses and alleviates the above-mentioned deficiencies associated with the prior art assemblies. More particularly, the present invention comprises a multi-component ampule which has an inner FDA approved glass cylinder, an outer plastic housing, and an FDA approved elastomeric nozzle. Together, these components define a medicine space that is suitable for storing medications and the like for prolonged periods. The glass and the elastomer provide FDA approved primary packaging components while the plastic outer shell provide acceptable secondary packaging containment and reinforcement.  
           [0012]    Exemplary multi-component ampules provided in accordance with practice of the present invention include ampules that have a primary packaging component and a secondary packaging component. Broadly speaking, the multi-component ampule is characterized by an inner cylinder of a first material, an outer shell of a second material, and a diaphragm of a third material.  
           [0013]    While the primary packaging component is configured for contacting with the medication for prolonged periods, the secondary packaging component is configured for reinforcing and for covering the primary packaging component so that the primary component may be kept to a minimum thickness.  
           [0014]    The ampules discussed herein are configured for used with either reusable spring injectors or disposable spring injectors. Depending on the connection point between the multi-component ampule and the jet injector, the ampule&#39;s outer plastic housing may be modified to permanently attach or threadedly attach to the jet injector.  
           [0015]    Broadly speaking, the preferred multi-component ampule comprises an outer shell of a first material, an inner cylinder of a second material, and a nozzle section of a third material connected to a jet injector, which comprises a piston compressing a spring and being held by an engagement member located within a housing, wherein when the engagement member is released from the piston, the piston advances a shaft proximally to discharge the medication contained within the multi-component ampule out from the nozzle.  
           [0016]    Thus, according to the embodiments disclosed herein, multi-component ampules with FDA approved materials for primary packaging components are useable with various conventional injector mechanisms to facilitate the administration of injections such as vaccines, hormones, local anesthetics and insulin.  
           [0017]    It is understood that changes in the specific structure shown and described may be made within the scope of the claims without departing from the spirit of the invention. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0018]    These and other features, aspects and advantages of the present invention will be more fully understood when considered with respect to the following detailed description, appended claims and accompanying drawings, wherein:  
         [0019]    [0019]FIG. 1 is a semi-schematic cross-sectional view of an exemplary multi-component ampule provided in accordance with practice of the present invention;  
         [0020]    [0020]FIG. 2 is a semi-schematic cross-sectional view of an outer shell shown separated from the multi-component ampule of FIG. 1;  
         [0021]    [0021]FIG. 3 is a semi-schematic cross-sectional view of a diaphragm shown separated from the multi-component ampule of FIG. 1;  
         [0022]    [0022]FIG. 4 is a semi-schematic cross-sectional view of an inner cylinder shown separated from the multi-component ampule of FIG. 1  
         [0023]    [0023]FIG. 5 is a semi-schematic end view of a cap cover shown separated from the multi-component ampule of FIG. 1;  
         [0024]    [0024]FIG. 6 is a semi-schematic cross-sectional view of the cap cover of FIG. 5 taken at line  6 - 6 ;  
         [0025]    [0025]FIG. 7 is a semi-schematic end view of a cap seal shown separated from the multi-component ampule of FIG. 1;  
         [0026]    [0026]FIG. 8 is a semi-schematic cross-sectional view of the cap seal of FIG. 7 taken at line  8 - 8 ;  
         [0027]    [0027]FIG. 9 is a semi-schematic cross-sectional view of a threaded nipple shown separated from the multi-component ampule of FIG. 1;  
         [0028]    [0028]FIG. 10 is a semi-schematic side view of an exemplary plunger provided in accordance with practice of the present invention;  
         [0029]    [0029]FIG. 11 is a semi-schematic side view of an alternative plunger provided in accordance with practice of the present invention;  
         [0030]    [0030]FIG. 12 is a semi-schematic side view of an exemplary shaft coupled to yet another alternative plunger provided in accordance with practice of the present invention;  
         [0031]    [0031]FIG. 13 is a semi-schematic cross-sectional view of the ampule shown in FIG. 1 in a filled state;  
         [0032]    [0032]FIG. 14 is a semi-schematic cross-sectional view of the ampule shown in FIG. 13 with a protective housing provided in accordance with practice of the present invention covering a portion of the shaft;  
         [0033]    [0033]FIG. 15 is a semi-schematic cross-sectional view of an exemplary re-useable jet injector assembly with the ampule of FIG. 1 provided in accordance with practice of the present invention;  
         [0034]    [0034]FIG. 16 is a semi-schematic cross-sectional view of the re-useable jet injector assembly of FIG. 15 in a spent or discharged state;  
         [0035]    [0035]FIG. 17 is a semi-schematic cross-sectional view of an exemplary disposable jet injector assembly with the ampule of FIG. 1 provided in accordance with practice of the present invention;  
         [0036]    [0036]FIG. 18 is a partial semi-schematic cross-sectional view of the disposable jet injector assembly of FIG. 17 with modified attachments between the jet injector and the ampule;  
         [0037]    [0037]FIG. 19 is a semi-schematic cross-sectional side view a multi-component ampule that has a recessed section on the distal end of the outer shell with a protective housing provided in accordance with practice of the present invention;  
         [0038]    [0038]FIG. 20 is a semi-schematic cross-sectional side view of the outer shell of FIG. 19; and  
         [0039]    [0039]FIG. 21 is a semi-schematic cross-sectional side view of a disposable jet injector assembly having a multi-component ampule threaded to a jet injector.  
     
    
     DETAILED DESCRIPTION  
       [0040]    The detailed description set forth below in connection with the appended drawings is intended as a description of the presently preferred embodiments of the multi-component ampule in accordance with the present invention and is not intended to represent the only forms in which the present invention may be constructed or utilized. The description sets forth the features and the steps for constructing and using the multi-component ampule of the present invention in connection with the illustrated embodiments. It is to be understood, however, that the same or equivalent functions and structures may be accomplished by different embodiments that are also intended to be encompassed within the spirit and scope of the invention. Also, as denoted elsewhere herein, like element numbers are intended to indicate like or similar elements or features.  
         [0041]    Referring now to FIG. 1, there is shown a multi-component ampule (herein “ampule”) provided in accordance with practice of the present invention, which is generally designated  10 . The ampule  10  shown is connected to a jet injector  12  (partially shown), which may be a disposable or a reusable type jet injector, via a threaded nipple  14 . Broadly speaking, the ampule  10  shown includes an inner cylinder  16 , an outer shell  18 , a diaphragm  20 , and a cap cover  22 , herein collectively referred to as components. Together, the components provide long-term storage capability and allow the ampule  10  to be used in high-pressure applications, such as those discussed further below.  
         [0042]    In an exemplary embodiment, the inner cylinder  16  is made from an FDA approved glass for packaging human drugs and biological products, which currently includes ASTM Type I, Class A, and United States Pharmacopeia (USP) Type I glass. However, materials other than glass are contemplated to be used for the inner cylinder  16  provided they meet FDA requirements for long term storage of injectable human drugs. These alternative materials may include Type II glass, certain plastic, and certain elastomeric components which comply with USP Elastomeric Closures for Injections requirements. Such alternative materials may include polypropylene and silicone polymer.  
         [0043]    Materials for the outer shell  18  and the cap cover  22  are made from plastic such as polycarbonate, acrylonitrile-butadiene, or the like. Materials for the diaphragm  20  and the plunger  23  are preferably made from an elastomer such as silicone rubber, fluroelastomer and the like. As will be appreciated, the outer shell  18  is preferably transparent so that the contents may be observed during shipment and during use, such as before an injection. Together the diaphragm  20 , the plunger  23 , and the inner cylinder  16  make up part of the primary packaging containment while the outer shell  18  and the cap cover  22  make up part of the secondary packaging containment.  
         [0044]    Also shown in FIG. 1 is a plunger  23  and a shaft  24  disposed within the inner cylindrical bore  26  of the inner cylinder  16 . The plunger  23  is shown pushed against the diaphragm  20  as if in a fired position or a position wherein the jet injector  12  is spent, as further discussed below. The position shown also depicts a ready position for filling the ampule  10  with medication, for example, by removing the cap cover  22 , placing the tip into a medicine vial and moving the shaft proximally to draw in the medication. As shown, the plunger  23  is in a sealing engagement with the internal surface of the inner cylinder  16 , as further discussed below.  
         [0045]    A resilient cap seal  27  is shown compressed between the cap  22  and the diaphragm  20  at the distal end of the ampule (FIG. 1). The cap seal  27  is disposed between the cap cover  22  and the distal end of the ampule  10  and is configured to be compressed by the cap and the diaphragm to provide compliance for the nozzle  28 . When the ampule  10  is filled with medication (for example at the factory), the compressed cap seal  27  prevents the medication from leaking from the inner cylinder  16  via the nozzle  28  and as well as preserves the medication&#39;s sterility by preventing contaminants from passing through the nozzle and into the medication. Alternatively, instead of utilizing the cap seal  27  to seal the nozzle  28 , the present embodiment may be practiced by configuring the cap  22  with a thicker cap ridge portion  30 . This cap ridge portion  30  can then contact the diaphragm  20  at about the nozzle  28  to directly compress the nozzle. The diaphragm  20 , as previously discussed, is made from an elastomer and is therefore resilient in nature. The diaphragm&#39;s resiliency allows it to be compressed against the cap ridge portion  30  to thereby provide a seal for the nozzle  28 , without the need for a cap seal  27 .  
         [0046]    Referring now to FIG. 2, there is shown the outer shell  18  provided in accordance with practice of the present invention. In an exemplary embodiment, the outer shell  18  is an integrally molded unit that has a cylindrical body  32 , a distal end  34 , and a proximal end  36 . At the distal end  34 , the outer shell  18  includes an end wall  38  with an end opening  40  centrally located therein. The distal end  34  also includes external threads  42  for engaging with the cap cover  22 . However, instead of having external threads  42  to engage the cap, an aluminum shield can be removeably bonded to the outside surface of the end wall  38  to provide the necessary seal for the nozzle  28 , which is similar to a seal in an over-the-counter medicine container.  
         [0047]    At the proximal end  36 , there is shown a set of internal threads  44  and an enlarged portion  45 . The internal threads  44  are configured to engage with the threaded nipple  14  (FIG. 1) for coupling the ampule  10  to the jet injector  12 . However, as further discussed below in connection with FIG. 18, instead of having the internal threads  44  at the proximal end, the outer shell  18  can include a smooth tapered sleeve. The tapered sleeve would allow the outer shell to telescopically fit over or into the distal end of the jet injector and be permanently affixed to the jet injector by either adhesive or welding. The enlarged portion  45  distal of the threads  44  is a relief point for a machine tool, which may otherwise be eliminated if the threads  44  were molded instead of machined.  
         [0048]    Referring now to FIG. 3, there is shown a diaphragm  20  provided in accordance with practice of the present invention. The diaphragm includes a base portion  46 , a top portion  48 , and a protrusion  50 , which comprises the nozzle  28 . The base portion  46  includes a base  52  and a cross-sectional area that is proximate the cross-sectional area  47  of the cylindrical bore  41  (FIG. 2). The top portion  48  has a cross-sectional area that is proximate the cross-sectional area of the end opening  40 . The diaphragm  20  is configured to slidingly engage with the cylindrical bore  41  of the outer shell  18  and rests within the bore at the distal end of the outer shell. In this rested position, the top portion  48  is received within the end opening  40  and is seated flushed with the external end surface of the end wall  38  (FIG. 1). The protrusion  50 , however, projects outward from the flushed top portion  48  to provide a distinct contact point for the nozzle  28  when placed against the skin for injection. In an exemplary embodiment, the fit between the base portion  46  and the cross-sectional area  47  of the bore  41 , and between the top portion  48  and the end opening  40  of the outer shell is preferably about zero to two thousandths total clearance.  
         [0049]    As shown in FIG. 3, the diaphragm  20  further includes a beveled cutout  54  that terminates into an orifice  56 . The combination of the cutout  54  and the orifice  56  resembles a funnel and defines the nozzle  28  for discharging the medication. In an exemplary embodiment, the orifice  56  has an opening of about 0.005 to 0.010 inch, with a range of about 0.006 to 0.008 inch being more preferred.  
         [0050]    Referring now to FIG. 4, there is shown an inner cylinder  16  provided in accordance with practice of the present invention. In an exemplary embodiment, the inner cylinder  16  is a cylindrical glass tube that has a first end  56   a  and a second end  56   b . The inner cylinder  16  has an outer circumferential surface  58  configured to matingly abut against the cylindrical bore  41  of the outer shell  18 . The inner cylinder includes the inner bore  26  for containing medication, as previously discussed. When the multi-component ampule  10  is assembled (FIG. 1), the inner cylinder  16  is configured to abut against the base  52  of the diaphragm  20  by its first end  56   a  and against the threaded nipple  14  by its second end  56   b . The contact at the first end  56   a  is referred to as the first interface  62  and the contact at the second end  56   b  is referred to as the second interface  64 . When the threaded nipple  14  is engaged and tightened against the internal threads  44 , the first  62  and the second  64  interfaces are loaded and the seams defined by the interfaces are sealed from leakage (FIG. 1).  
         [0051]    Glass is highly brittle and has a high modulus of elasticity. Glass also has a narrow proportional limit and readily fails with minimum induced strain. Thus, if a glass ampule is used with a jet injector, the glass ampule will break and will explode unless it is adequately thick. This is because a pressure of about 3,000 to 3,500 psi, and about 5,000 to 6,000 psi at the start of the injection, is generally required to administer drugs subcutaneously without a needle. In the multi-component ampule  10  provided in accordance with practice of the present invention, the inner cylinder  16 , which is made from glass, is braced by the plastic outer shell  18  for reinforcement. Together, the plastic outer shell  18  and the glass inner cylinder  16  have a combined hoop strength that is sufficient to contain the pressure generated by the jet injector  12  without making the glass unnecessarily thick.  
         [0052]    For the outer shell  18  to adequately brace or reinforce the inner cylinder  16 , the slack or clearance between the cylindrical bore  26  of the outer shell and the outer circumferential surface  58  of the inner cylinder should be sufficiently tight. In an exemplary embodiment, the clearance between the outer shell  18  and the inner cylinder  16  is preferably “hand-tight”. That is, when the inner cylinder  16  is inserted into the outer shell  18 , the insertion should not require tools or machines but only a force produceable by the hand. In other words, the fit between the components can be a non-interference fit. Examples of hand-tight clearance is clearance ranging from about zero to four thousandths total clearance, with about zero to two thousandths total clearance being preferred, and with about zero to one thousandths total clearance being more preferred. Examples of the inner cylinder  16  wall thickness can range from about 0.07 to 0.095 inch with 0.083 inch being more preferred. Examples of the outer shell  18  wall thickness can range from about 0.085 to 0.15 inch with 0.09 to 0.10 inch being more preferred. A person of ordinary skill in the art can appreciate that other thickness and total clearances other than the aforementioned ranges can be implemented and that these figures are exemplary only. Indeed, by changing the operating pressure, by using a glass compound, by using different plastic, by using a thinner glass and a heavier shell, etc., the fit between the inner cylinder and the outer shell and the wall thickness of the individual components can vary. Thus, such variations are contemplated to fall within the scope of the present invention.  
         [0053]    Referring now to FIG. 5 and  6 , there is shown a cap cover  22  provided in accordance with practice of the present invention. The cap cover  22  comprises internal threads  66  for threadedly engaging the external threads  42  located on the outer shell  18 . The cap cover  22  includes a relief point  68  for machining the internal threads  66  but may be eliminated if the threads were molded rather than machined.  
         [0054]    The cap cover  22  also includes an end wall  70  and a recessed portion  72  centrally disposed thereon. The recessed portion  72  is configured to receive a cap seal  27  (FIGS. 1, 7, and  8 ). As previously discussed, the cap seal  27  provides the necessary seal to the nozzle  28  when compressed by the cap cover  22  and the protrusion  50  located on the diaphragm  20 . The cap seal  27  may be made from a number of FDA approved soft rubber or elastomer, such as silicone rubber. Still referring to FIG. 5, there is shown a series of serration members  74  circumferentially disposed along the exterior surface of the cap cover  22  for better gripping the cap cover when the same is removed. However, a smooth exterior cap surface, a dispersed array of bumps or similar gripping means may also be practiced without deviating from the scope of the invention.  
         [0055]    Referring now to FIGS. 7 and 8, there is shown a cap seal  27  provided in accordance with practice of the present invention. The cap seal  27  shown can be made from a variety of FDA approved elastomers or thermoplastics, such as silicone rubber and PTFE. The cap seal  27  resembles a coin in that it is circular, has a thickness X, and a cross-sectional area. The cross-sectional area is configured to fit within the recessed portion  72  located on the end wall  70  of the cap cover  22 . The fit between the cap seal  27  and the recessed portion  72  is slightly interference to slightly positive clearance. The cap seal  27  is configured to be compressed by the cap cover  22  and the nozzle  28  to provide a seal for the orifice  56 . Preferably, the cap seal  27  provides about 0.005 to 0.030 inch compression when compressed by the cap cover and the nozzle, with a range of about 0.008 to 0.015 inch being more preferred.  
         [0056]    Referring now to FIG. 9, there is shown a threaded nipple  14  provided in accordance with practice of the present invention. In an exemplary embodiment, the threaded nipple  14  is symmetrical about a center flange  76  and has male threads  78  disposed on either side of the flange. The threaded nipple  14  also includes a bore  80 , which acts as a channel to allow communication between the jet injector  12  and the ampule  10 .  
         [0057]    It can be appreciated that the threaded nipple  14  can be nonsymmetrical and may depend on the relative dimensions of the receiving end of the jet injector  12  and the size of the proximal end  36  of the outer shell  18 . For instance, the receiving end of the jet injector  12  may have a 0.5 inch threaded opening and the proximal end  36  of the outer shell  18  may have a 0.7 inch threaded opening. The threaded nipple  14  therefore will be non-symmetrical in order to accommodate the two different dimensions.  
         [0058]    As discussed above, a plunger is configured to move from a proximal position to a distal position in the ampule  10  when the jet injector is fired to expel the medication out of the nozzle  28  (FIG. 1). The plunger moves by the action of the spring located within the jet injector, which is configured to push the piston, which then pushes the shaft, which then pushes the plunger to discharge the medication. The distal movement of the plunger compresses the medication and builds up pressure as it compresses the medication within the ampule space to deliver the necessary medication subcutaneously. The ampule space will herein be referred to as a variable medicine space, which is defined by the space between inner bore  26 , the diaphragm  20 , and the plunger. For reference purposes, this variable medicine space is labeled as medicine space  61  (FIG. 13 &amp; 14, and further discussed below). The volume defined by the variable medicine space  61  will vary depending on the location of the plunger within the ampule  10 .  
         [0059]    For pressure to adequately build within the medicine space  61  to a working pressure of about 3,000 to 3,500 psi, and about 5,000 to 6,000 psi at the start of the injection, the plunger must maintain a seal against the glass inner cylinder  16  as it travels distally in the inner bore  60  to discharge the medication out the nozzle  28 . Leakage or blow-by of medication around the moving plunger should therefore be reduced to a minimum or even be eliminated as leakage will decrease the pressure buildup generated by the advancing plunger  
         [0060]    Referring now to FIGS. 10 and 11, there is shown exemplary plungers  82 ,  84  provided in accordance with practice of the present invention. The exemplary plungers  82 ,  84  provide satisfactory sealing against the inner bore  26  of the glass cylinder  16  for building necessary operating pressure. Referring specifically to FIG. 10, the plunger  82  shown is symmetrical and includes two pusher ends  86 , three marker rings  88 , and two wells  90 . The plunger  82  is symmetrical about the center marker ring  88  and is preferably practiced with a disposable jet injector, for reasons further discussed below. Due to its symmetrical configuration, the plunger  82  may be placed into the inner bore  26  of the glass cylinder  16  with either pusher end  86  in first. This flexibility facilitates automation by allowing a robotic machine to insert the plunger  82  into the ampule irrespective of the plunger orientation.  
         [0061]    The plunger  84  shown in FIG. 11 is an alternative plunger. The plunger  84  is symmetrical about the center and includes two pusher ends  86 , two marker rings  88 , and one well  90 . Both plungers  82 ,  84  may be made from an acceptable FDA approved elastomer such as silicone, ethylene-propylene-diene (EPDM), and the like. Alternatively, the plungers  82 ,  84  may have more than three marker rings, may have one or more marker rings with one or more a seal rings  88  (FIG. 12) or any combination thereof.  
         [0062]    Referring now to FIG. 12, there is shown a shaft  24  with an over-molded plunger  23  on one end and an integrally molded ribbed section  92  on the other end. The integrally molded ribbed section  92  is configured to be pushed against by a piston as the piston is propelled by a spring to launch the plunger  23  into the inner bore  26  of the glass cylinder  16  towards the diaphragm  20  located at the distal end of the ampule  20  (FIGS. 1 and 15). The plunger  23  shown is another alternative plunger which includes a pusher end  86 , a receiving end  92 , a marker ring  88 , a seal ring  94 , and a well  90 . The seal ring  94  is similar to the marker ring  88  except it is slightly wider and provides more surface contact with the inner bore  26  of the inner cylinder  16 . The plunger  23  is removeably connected and co-molded to the shaft as described in the &#39;525 serial number. The shaft  24  may be made from a number of plastic materials such as ABS, AB, polycarbonate, PVC plastic with fiberglass injection, and the like. The shaft  24  with the over-molded plunger  23  is preferably used with the reusable injector.  
         [0063]    [0063]FIG. 13 shows the multi-component ampule  10  in a filled position or ready position. The ampule  10  may be filled with medication in a sterile environment and packaged in the configuration shown. In the filled position, the shaft  24  is drawn proximally and extends beyond the proximal end of the nipple  14 . Medicine or injectable suspension of pre-determined quantity is filled within the medicine space  61 , which is the space defined by the glass inner bore  60 , the diaphragm  20 , and the plunger  23 . In this filled position, the plunger  23  is withdrawn proximally but still remains in contact with the glass inner cylinder  16 . That is, the plunger  23  does not move proximally beyond the proximal end of the inner cylinder  16 , such as into the bore  80  of the nipple  14 . By limiting the maximum proximal movement of the plunger  23 , the medicine that is filled within the medicine space  61  is only in contact with FDA approved package materials for long term storage. This ensures prolonged storage capability when the medication is only in contact with the primary packaging containment, which includes the inner cylinder  16 , the plunger  23 , and the diaphragm  20 . Optionally, the exterior surface of the ampule  10  (i.e., the outer shell  18 ) may have markings to identify the level or volume of medication that is filled within the ampule.  
         [0064]    The filled multi-component ampule  10  shown in FIG. 13 is configured to be received by a jet injector, such as those shown in FIGS.  15 - 17 , shown in U.S. Pat. Nos. 5,499,972; 5,569,189; and 5,704911; and shown in Ser. No. 09/751,525. The jet injector may receive the ampule  10  by threading the nipple  14  into a threaded end of the jet injector (FIG. 15) or by permanently attaching the ampule via adhesive or welding with the jet injector (FIG. 18).  
         [0065]    Turning to FIG. 14, there is shown a filled multi-component ampule  10 , as discussed in connection with FIG. 13, with a protective housing  95  mounted to the proximal end of the threaded nipple  14 . The protective housing  95  can be made from a transparent thin-walled plastic such as polyethylene or polycarbonate. The protective housing  95  includes an open base  96 , an enclosed tip  98 , and a threaded internal bore  100  for threadingly engaging with the nipple  14 . As readily understood, the protective housing prevents the shaft  24  from being accidentally moved or bumped during packaging or shipping. In addition, the protective housing  95  also preserves the sterility of the medication by acting as an enclosure and eliminating leak source or path that can contaminate the medication. Although the protective housing  95  is shown with a tapered neck  102 , the protective housing can have the shape of a uniform cylinder or any variation thereof provided it serves the aforementioned functions. The filled ampule  10  with the protective housing  95  may be packaged in the manner described in the &#39;525 serial number for shipping and storing. It is understood that the shape of the packages described in the &#39;525 serial number will have to be modified to accommodate the ampule  10  described herein.  
         [0066]    Turning to FIGS. 15 and 16, there is shown an exemplary use of the multi-component ampule  10  in accordance with practice of the present invention. In an exemplary embodiment, the filled ampule  10  (FIGS. 13 and 14) can be removed from its packaging material and assembled onto the re-useable jet injector  12  by threading the nipple  14  into the receiving end  96  of the jet injector. Once the filled ampule  10  is installed, the jet injector assembly  98  is ready for injection (FIG. 15).  
         [0067]    The re-useable jet injector  12  shown in FIGS. 15 and 16 is substantially the same as those disclosed in the U.S. Pat. Nos. 5,499,972; 5,569,189; and 5,704,911. Generally speaking, the jet injector  12  shown in FIGS. 15 and 16 includes an injector housing  100 , a main spring  102  for driving a piston  104  against the shaft  24 , which in turn drives the plunger  23  into the medicine space  61  to discharge the medicine out of the nozzle  28 . The jet injector  12  also includes a trigger  106  that is pivoted on a pivoting pin  108  and held in an inward direction by a secondary spring  110 . The trigger  106  is mechanically connected to a trigger extension arm  112 , which provides the means for depressing or activating the trigger.  
         [0068]    A safety ring  114  is provided at the distal end of the jet injector  12  that is in sliding engagement with a plastic sleeve  116 . When the safety ring  114  is engaged, by sliding the safety ring proximally with respect to the plastic sleeve  116  until it comes to rest under the trigger extension arm  112 , a downward movement by the trigger extension arm  112  about the pivoting pin  108  is delimited by the safety ring. The plastic sleeve  116  is in concentric relationship with the jet injector  12  and may be secured to the distal end of the jet injector by detents, tongue and groove means, fasteners, adhesive, or the like.  
         [0069]    The main spring  102  is held in a compressed or cocked position by the trigger&#39;s engagement tip  118 , which engages the flange  119  on the piston  104 . As readily apparent, disengagement of the engagement tip  118  from the piston  104  by depressing on the trigger extension arm  112  will cause the main spring  102  to uncoil and propel the piston  104  distally. When so propelled, the piston  104  moves distally and pushes against the shaft&#39;s receiving end  92 , which pushes the shaft  24  distally. As previously discussed, this causes the plunger  23  to propel forward and compresses the medication, which then discharges out of the nozzle  28 . It is understood that the cap  22  must be removed and the nozzle  28  placed against the skin of a patient before the trigger is fired for an effective delivery.  
         [0070]    [0070]FIG. 16 shows the jet injector assembly  98  of FIG. 15 in a fired or discharged state. As shown, the trigger extension arm  112  is depressed, the main spring  102  is fully uncoiled, the piston  104  is advanced distally against a stop member  120 , and the shaft  24  and plunger  23  are advanced distally toward the diaphragm  20 . It can be appreciated that the plunger  23  is preferably advanced until it contacts the diaphragm  20  so that all or substantially all of the medication is discharged out of the nozzle and into the patient (FIG. 16). This maximum distal travel minimizes wastes, as certain medications can be quite costly. Although the trigger extension arm  112  is shown depressed (FIG. 16), the trigger extension arm should pivot radially outward due to the secondary spring  110  (FIG. 15) immediately upon release of the trigger extension arm by the user.  
         [0071]    Referring now to FIG. 17, there is shown an and alternative use for the multi-component ampule  10  with a disposable jet injector provided in accordance with practice of the present invention, generally designated as  122 . The jet injector assembly  122  depicted in FIG. 17 is a disposable type and resembles the type disclosed in the &#39;525 serial number. The jet injector assembly  122  shown is termed disposable because once the medicine is dispensed following an injection, the entire jet injector assembly  122  is preferably discarded. The multi-component ampule  10  is used with the jet injector  124  by threading the nipple  14  to the receiving end of the jet injector in a similar manner as discussed with the re-useable model (FIGS. 15 and 16). The disposable jet injector  122  is shown in a fired or dispensed position.  
         [0072]    Broadly speaking, the disposable jet injector  124  includes a housing  125 , a main spring  126 , a piston  128 , a shaft  130 , a trigger  132 , and a safety device  134 . The shaft further includes a gripping ball  140 , a shoulder  136 , and first and second cushion members  138   a ,  138   b  for limiting the distal movement of the shaft  14 . This is implemented by configuring the cushion member  139   b  to abut the end of the nipple  14  when the shaft is propelled distally during an injection. The gripping ball  140  at the proximal end of the shaft  130  provides a gripping surface for a gripping tool (not shown) to grip and load or cock the main spring  126 , as discussed in the &#39;525 serial number.  
         [0073]    When the shaft  130  is grasped and drawn proximally (towards the left of FIG. 17), the cushion member  138   b  pushes against the piston  128 , at the drum portion  135  of the piston. As the shaft  130 , cushion member  138   b , and drum portion  135  moves proximally past the engagement tip  123  located on the trigger  132 , the engagement tip  123  pivots downward, about a pivot point  129 , to lock the piston and the spring  126 . The contact between the engagement tip  123  and the drum portion  135  of the piston  128  maintains the spring  126  in the compressed position until the jet injector is fired (not shown). As disclosed in the &#39;525 serial number, subsequent to cocking the jet injector assembly  122  by grasping and pulling on the shaft to lock the drum portion  135  against the engagement tip  123 , the shaft remains freely moveable. That is, the shaft  126  still freely moves within the piston  128 , as the shaft is coaxially disposed within the piston.  
         [0074]    In an exemplary embodiment, the shaft  130  has a substantially flat distal end  131  (FIG. 17) and is not coupled to the plunger  82 , which is preferably of a symmetrical type plunger. The advantage of using a symmetrical plunger is that the disposable jet injector assembly  124  is contemplated to be assembled automatically by robotic machines. Therefore, having components that are symmetrical or that are easily recognizable by the robotic machines will facilitate the automation process. Thus, the shaft distal end  131 , since it does not attach to the plunger  82 , can take on a number of configurations including a beveled end, a cone end, a flat end, etc.  
         [0075]    As readily apparent, the disposable jet injector assembly  122  shown is intended to be pre-filled and packaged with medication at the factory (as the shaft  130  and the plunger  82  are not attached to provide means for filling the ampule  10 ). The pre-filled multi-component ampule  10  may be packaged and shipped either as two separate components (with the multi-component  10  pre-filled and separately packaged from the disposable jet injector) or pre-filled and packaged together as shown in FIG. 17. In an injection application for a separately packaged embodiment, the user simply removes the packaging material from both the disposable jet injector and the multi-component ampule and then thread the nipple  14  onto the disposable jet injector housing. Then depending on the dosage needed, the user may move the shaft  130  distally, after removing the cap  22 , to release excess medication contained within the ampule.  
         [0076]    Although shown with the symmetrical plunger, the disposable jet injector assembly  122  may also be practiced with the plunger co-molded or attached to the shaft  130  and packaged with the spring pre-cocked at the factory. In this alternative application, when the end user uses the jet injector assembly  122 , he or she will have to fill the multi-component ampule  10  with medication by grasping and pulling the shaft proximally to draw in the medication.  
         [0077]    [0077]FIG. 17 shows the disposable jet injector assembly  124  in a fired or discharged state (as the spring is released). Thus, it is understood that the end cap  22  should be removed from the ampule  10  before the trigger  132  is depressed to deliver the medication subcutaneously. Although FIG. 17 shows the plunger  82  spaced apart from the diaphragm, it is understood that the present embodiment is preferably practiced with the plunger  82  moved completely distally until it touches the diaphragm to thereby ensure that all the mediation is discharged and not wasted by remaining in the medicine apace  61 .  
         [0078]    Referring now to FIG. 18, there is shown an alternative interface for connecting a modified multi-component ampule  141  to the disposable jet injector  124 . In the alternative embodiment, the proximal end of the outer shell  18  of the modified multi-component ampule  141  is configured to include an integrally molded coupler  142  rather than internal threads  44  as discussed with reference to FIGS. 1 and 2. The modified outer shell  18  can be filled with medication in a sterile environment with the cap  22  and the plunger  82  acting as seals to preserve the sterility of the medication.  
         [0079]    In a corresponding fashion, the disposable jet injector  124  is configured to include an integrally molded sleeve  144 . The coupler  142  on the ampule  141  is configured to fit over the sleeve  144  on the disposable jet injector  124 . Once the coupler and the sleeve are mated, the interface between the two can be welded by heat or ultrasound or permanently affixed via adhesive. Still alternatively, the coupler  142  may be molded with spaced apart ridges  146  so that after the coupler is fitted with the sleeve  144 , heat or ultrasonic energy may be applied to the interface region to cause the ridges to melt and to fuse the jet injector and the ampule together. When implemented, the fusion provides for a more permanent attachment.  
         [0080]    [0080]FIG. 19 shows an alternative multi-component ampule  150  having a generally flushed nozzle in a filled state with a protective housing  95  provided in accordance with practice of the present invention. The alternative multi-component ampule  150  includes essentially the same components as the multi-component ampule  10  disclosed with reference to FIGS. 1 and 14. For example, multi-component ampule  150  includes essentially the same protective housing  95 , nipple  14 , shaft  24 , plunger  23 , diaphragm  20 , and inner glass cylinder  16 . However, the cap cover  152  and the shell  154  have been modified to provide the multi-component ampule  150  with a flushed diaphragm  20  to outer shell configuration.  
         [0081]    Referring specifically to FIG. 20, the modified outer shell  154  includes an end wall  156  that has a recessed portion  158  and a tapered cone section  160 , which is also recessed within the end wall. The end wall  156  is configured to receive the diaphragm  20  in a flushed configuration by having a structure that corresponds to the contour of the diaphragm. For example, the tapered cone section  160  is configured to receive the diaphragm&#39;s protrusion  50 , the recessed portion  158  is configured to receive the diaphragm&#39;s top portion  48 , and the cylindrical bore  41  is configured to receive the diaphragm&#39;s base portion  46 . As a result, the nozzle  28  located on the diaphragm  20  is positioned flushed or substantially flushed with the end exterior surface of the modified outer shell  154  (FIG. 19).  
         [0082]    With a flushed or substantially flushed diaphragm  20  to outer shell  154  arrangement, the cap cover  152  is modified to include a relatively shallower recessed portion  72  than the cap cover  22  shown in FIGS. 1 and 6. Among other things, this modification is implemented to take up the space that is vacated by the diaphragm&#39;s protruding nozzle section  28 ,  50 . As readily apparent, by molding the cap ridge portion  30  with a relatively thicker dimension than the same dimension shown in FIGS. 1 and 6, the same cap seal  27  may be used to provide the necessary compliance or crushed to properly seal the nozzle  28  from leak/contamination. Alternatively, the cap cover  152  can be the same as the previously described cap cover  22  (FIG. 6) but the cap seal  27  is modified to have a wider thickness X′ to provide the necessary compliance or crushed to seal the nozzle  28 . Under either scenario, a cap seal  27  compression of about 0.005 to 0.030 inch is preferred, with a range of about 0.008 to 0.015 inch being more preferred.  
         [0083]    Use of the multi-component ampule  150  shown in FIG. 19 is the same as for the multi-component ampule  10  shown with reference to FIGS.  15 - 17 .  
         [0084]    Referring now to FIG. 21, there is shown an alternative disposable jet injector assembly  162 , which incorporates a threaded male nipple  164  into the distal end of a disposable jet injector  166  to directly couple with the multi-component ampule  150 . In directly coupling the jet injector  166  with the multi-component ampule  150 , the threaded nipple  14 , which is used with the disposable jet injector assembly shown in FIG. 17, is eliminated. Although the jet injector  166  is shown without a spring, the spring is assumed to be disposed in between the piston  128  and the housing  125 , and coaxially over the shaft  130 , similar to FIG. 17.  
         [0085]    The jet injector assembly  162  is shown in a filled state, with The multi-component ampule  150  having a symmetrical plunger  82  disposed near the proximal end of the inner glass cylinder  16  and medicine contained within the medicine variable space  61 . Preferably, medicine is separately pre-filled in the multi-component ampule  150 , under a sterile environment, before it is assembled onto the jet injector  166 . Preferably, the pre-filled multi-component ampule  150  is then assembled onto the jet injector  166  and the assembled disposable jet injector assembly  162  packaged for storage and/or shipping.  
         [0086]    Although the preferred embodiments of the invention have been described with some specificity, the description and drawings set forth herein are not intended to be delimiting, and persons of ordinary skill in the art will understand that various modifications may be made to the embodiments discussed herein without departing from the scope of the invention, and all such changes and modifications are intended to be encompassed within the appended claims. Various changes to the ampule may be made including manufacturing the dimensions differently, using different FDA approved materials, changing the tolerances, etc. Other example of changes may include modifying the way the ampule is connected to the jet injector, the way the shaft and the piston are shaped/configured, and the way the plunger is shaped/configured. Accordingly, many alterations and modifications may be made by those having ordinary skill in the art without deviating from the spirit and scope of the invention.