Abstract:
The invention relates to methods and devices for delivering medicament by jet injection to an injection site in a patient. The method includes inserting a needle into an insertion point, wherein the needle has a length of less than 5 mm and is operatively associated with an orifice in a nozzle assembly in fluid communication with an ampule chamber containing the medicament. The needle extends less than about 5 mm from the nozzle assembly orifice when the medicament is expelled. Next, a force generating mechanism is activated, and a pressure wall member that is operatively associated with the force generating member moves in response to the activation of the force generating mechanism at a speed sufficient to jet inject the medicament from the ampule chamber through the orifice and needle under a pressure of less than about 4000 psi to deliver a substantial portion of the medicament through the needle and past the insertion point to the injection site. The needle tip maybe part of a retractable needle of a jet injection device, or is part of a fixed needle of a jet injection device.

Description:
PRIORITY 
     This application is a continuation of U.S. Ser. No. 09/256,310, filed Feb. 24, 1999, now U.S. Pat. No. 6,428,528, which claims the benefit of Provisional application Ser. No. 60/096,464, filed Aug. 11, 1998. 
    
    
     FIELD OF THE INVENTION 
     The present invention is directed to a device for delivery of medicament, and in particular to a jet injector with a short needle to reduce the pressure at which the jet injector must eject the medicament for proper delivery. 
     BACKGROUND OF THE INVENTION 
     A wide variety of needleless injectors are known in the art. Examples of such injectors include those described in U.S. Pat. No. 5,599,302 issued to Lilley et al., U.S. Pat. No. 5,062,830 to Dunlap, and U.S. Pat. No. 4,790,824 to Morrow et al. In general, these and similar injectors administer medication as a fine, high velocity jet delivered under sufficient pressure to enable the jet to pass through the skin. 
     As the skin is a tissue composed of several layers and the injector is applied to the external surface of the outermost layer, the delivery pressure must be high enough to penetrate all layers of the skin. The layers of skin include, the epidermis, the outermost layer of skin, the dermis, and the subcutaneous region. The required delivery pressure is typically greater than approximately 4000 p.s.i. (measured as the force of the fluid stream divided by the cross-sectional area of the fluid stream). 
     Although this pressure is readily achievable with most injectors, there are some circumstances in which delivery of medicament to the subcutaneous region under a reduced pressure is desirable. For example, drugs that require a specific molecular structural arrangement, such as a linear protein configuration, may be rendered ineffective due to shear forces caused by the delivery of the drug at high pressures that alter the structural arrangement of the drug. As it is more difficult to deliver a large volume of fluid at a high pressure compared to a small volume, using a lower pressure facilitates delivery of a larger volume of fluid. Furthermore, the lower pressure could make manufacturing an injector device less expensive. The lower pressure would also reduce adverse stresses on the device and result in a corresponding increased useable device lifetime. 
     One of the advantages associated with jet injectors is the absence of a hypodermic needle. Given the aversion to needles possessed by some, the absence of a needle provides a psychological benefit. Even devices that utilize conventional hypodermic needles have attempted to capitalize on this psychological benefit. For example, self-injectors or auto-injectors like the ones disclosed in U.S. Pat. Nos. 4,553,962, 4,378,015 have retractable needles which are hidden until activation. Upon activation, the needle extends from the bottom of the device and penetrates the user&#39;s skin to deliver medicament. As none of these devices involves delivery of the medicament using jet injection, the medicament delivery location is limited by the length of the needle. For example, if delivery in the subcutaneous region is desired, the needle must be long enough to reach the subcutaneous region. Furthermore, as auto-injectors operate like syringes, the injection time is several seconds or longer. In contrast, jet injectors typically inject in fractions of a second. 
     Thus, there exists a need for a jet injector with a short needle to reduce the pressure at which the jet injector must eject the medicament for proper delivery. 
     SUMMARY OF THE INVENTION 
     The present invention relates to a needle assisted jet injector. In one embodiment, the injection device includes a housing; a nozzle assembly defining a fluid chamber, having an opening for slidingly receiving at least a portion of the needle and removably associated with the housing; a plunger movable in the fluid chamber; a trigger assembly; an energy generating source operatively associated with the trigger assembly so that movement of the trigger assembly activates the energy source to move the plunger in a first direction to expel a fluid from the fluid chamber; and a retractable injection-assisting needle at a distal end of the injector. The retractable injection-assisting needle has a needle tip located at a distal end of the needle with at least a portion configured and dimensioned to slide through the nozzle assembly opening; a discharge channel within the needle tip and terminating in an orifice through which the fluid is expelled; a body portion to direct fluid towards the discharge channel; a plunger receptor configured and dimensioned to receive at least a portion of the plunger; and a retraction element operatively associated with the nozzle assembly. The needle is located within the nozzle assembly in a retracted position prior to activation of the energy source. Movement of the plunger in the first direction upon activation of the energy source results in at least a portion of the needle tip extending beyond the nozzle assembly opening and the retraction element returns the needle tip to the retracted position after activation of the energy source. 
     The retraction element can be a resilient O-ring, a spring, or a flexible membrane which moves to allow extension of the needle tip beyond the nozzle assembly opening and then returns to its original position to return the needle tip to its retracted position. The needle body can have an exterior surface which includes a ridge or recess for accommodating the retraction element. A shoulder can be disposed between the needle tip and the needle body for accommodating the retraction element. Preferably, the needle tip has a length of approximately 1-5 mm. 
     In another embodiment, the injector has a non-retracting fixed needle. The injection-assisting needle comprises a body fixed to a distal end of the nozzle assembly and a discharge channel extending through the needle body, in fluid communication at a first end with the fluid chamber, and terminating at a second end in an orifice through which the fluid is expelled. Preferably, the body has a length of approximately 1-5 mm. 
     The present invention also relates to a method of delivering medicament to an injection site of a patient. The method includes the steps of: inserting a needle into a needle insertion point, said needle having a length less than 5 mm and being operatively associated with an orifice in a nozzle assembly in fluid communication with an ampule chamber containing the medicament; activating an energy mechanism; and coupling a pressure wall member disposed and movable within the ampule chamber to the activated energy mechanism to move the pressure wall member at a speed sufficient to eject the medicament from the ampule chamber through the orifice and needle under a pressure which is sufficient to deliver a substantial portion of the medicament to the injection site. The needle insertion point is located more superficial than the injection site. 
     The method preferably includes the steps extending a needle from a shield prior to inserting the needle into the needle insertion point and then retracting the needle into the shield after the medicament has been delivered to the injection site. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a cross-sectional view of a needle assisted jet injector according to the present invention; 
     FIG. 2 is a cross-sectional view of the needle on the jet injector of FIG. 1; 
     FIG. 3 is a perspective view of the needle of FIG. 2; 
     FIG. 4 is an enlarged cross-sectional view of the jet injector of FIG. 1 with the needle in the retracted position; 
     FIG. 5 is an enlarged cross-sectional view of the jet injector of FIG. 1 with the needle in the extended position; 
     FIG. 6 is a perspective view of a second embodiment of the needle according to the present invention; 
     FIG. 7 is a partial cross-sectional view of a jet injector according to the present invention with the needle of FIG. 6 in the retracted position; 
     FIG. 8 is a partial cross-sectional view of a jet injector according to the present invention with the needle of FIG. 6 in the extended position; 
     FIG. 9 is a cross-sectional view of another embodiment of the present invention with a flexible member as the retraction element and the needle in the retracted position; 
     FIG. 10 is a cross-sectional view of the embodiment of FIG. 9 with the needle in the extended position; 
     FIG. 11 is a cross-sectional view of a two piece nozzle assembly having a fixed needle; 
     FIG. 12 is a cross-sectional view of another embodiment of a two piece nozzle assembly having a fixed needle; 
     FIG. 13 is a cross-sectional view of another embodiment of a two piece nozzle assembly having a fixed needle; and 
     FIG. 14 is a schematic expressing a pressure-time curve for a jet injector. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     For convenience, the same or equivalent elements of the invention of embodiments illustrated in the drawings have been identified with the same reference numerals. Further, in the description that follows, any reference to either orientation or direction is intended primarily for the convenience of description and is not intended in any way to limit the scope of the present invention thereto. 
     As shown in FIG. 1, a jet injector  10  according to the present invention comprises a nozzle assembly  12  attached to a housing  14 . As used in this application, the term distal shall designate the end or direction toward the front of jet injector  10 . The term proximal shall designate the end or direction toward the rear of the injector. The term longitudinal designates an axis connecting nozzle assembly  12  to jet injector  10 , and the term transverse designates a direction substantially perpendicular to the longitudinal direction including arcs along the surface of jet injector  10 , or nozzle assembly  12 . 
     Nozzle assembly  12  can be threadably connected to housing  14  such that it can be readily attached and detached. Alternatively, other known structures for mounting or attaching two components can be utilized as well to detachably mate nozzle assembly  12  to housing  14 . In this manner, injector  10  can be reused with various nozzle assemblies that may contain different medications of different doses either together or at different times. For instance, nozzle assembly  12  can be prefilled with medication and disposed of after each use. Further, a medication filling device such as a coupling device can be used to fill the fluid chamber with medication. U.S. Pat. No. 5,769,138 to Sadowski et al., the disclosure of which is herein incorporated by reference, is directed to such a coupling device. 
     A trigger assembly  16  is located at the proximal end of housing  14 . Trigger assembly  16  activates and triggers an energy source or energy generating means  18  which forces medicament out of nozzle assembly  12 . Energy source  18  can be a coil spring, a gas spring, or a gas propellant. 
     According to a first embodiment of the present invention, nozzle assembly  12  has an injection assisting needle  20  movable within nozzle assembly  12 . Needle  20  will be discussed in detail after first describing the other components of injector  10 . The nozzle assembly  12  includes a nozzle member  22  having an opening  24  at the distal end, preferably having a diameter of about 0.04-0.4 inches or any other suitable diameter that would allow for the introduction of injection assisting needle  20  therein. Nozzle member  22  includes a cylindrical fluid chamber  26  terminating at the distal end in a right circular cone  28 . Cone  28  can be a convex cone (as shown), a right circular cone, or any other suitable configuration. A plunger  30  having a pressure wall contoured to cone  28  is positioned to slide within fluid chamber  26 . Plunger  30  can include sealing means such as one or more O-rings or the like (not shown) that are formed around its outer periphery to provide a seal, or the plunger itself can be a seal, as described in U.S. Pat. No. 5,062,830, the disclosure of which is incorporated herein by reference. The plunger can also include additional sealing means at spaced intervals to provide a better seal. 
     Plunger  30  is connected to a ram  32  which in turn is connected to energy source  18 . Alternatively, ram  32  can be integrally formed with an energy mechanism if desired. An inertia mass  34  is connected to or integrally formed with ram  32  near the end of ram  32  closest to plunger  30 . Inertia mass  34  can be removably connected to ram  32  such that the mass can be adjusted to accommodate different types of injections, taking into consideration, for instance, the viscosity of the medication, the initial pressure build up desired, the strength of energy source  18 , and the depth of injection penetration, etc. Inertia mass  34  cooperates with ram retainer  36  to limit the distance that ram  32  can travel toward nozzle assembly  12 . One important safety aspect of this feature is that ram  32  cannot become a dangerous projectile if injector  10  is fired when nozzle assembly  12  is not present. 
     Trigger assembly  16  includes a trigger extension  38  having a trigger engaging notch  40 . Trigger extension  38  is attached to the end of ram  32 , for example, by a threaded engagement. Trigger assembly  16  also comprises a latch housing sleeve  42  fixedly attached to an actuating mechanism  44 . Actuating mechanism  44  is shown as a threaded coupling that operates by rotation movement. Alternatively, the actuating mechanism of the provisional application of DeBoer et al. filed Jul. 27, 1998 and entitled “Loading Mechanism for Medical Injector Assembly”, the disclosure of which is herein incorporated by reference, can be used. Latch housing sleeve  42  has a throughbore dimensioned to allow passage of trigger extension  38 . Latch housing sleeve  42  further has a plurality of sidewall openings  46  dimensioned to allow passage of balls or ball bearings  48 . A tubular button  50  having one open end and a closed end is telescopingly positioned with latch housing sleeve  42  as shown. Button  50  has a circumferential or annular groove  52  formed on an inner wall  54  thereof to allow portions of the balls  48  to engage groove  52  when trigger assembly  16  is in the fired position, i.e., not engaged with trigger extension  38  (not shown). Balls  48  are positioned so that they are substantially flush with an inner side wall surface  56  of latch housing sleeve  42  to allow trigger extension  38  to pass through latch housing sleeve  42 . A latch ball retaining cup  58  is telescopingly positioned within button  50 . A compression spring  60  is positioned between the cup  58  and button  50  to bias button  50  and cup  58  away from each other in the axial direction. 
     The structure of injection assisting needle  20  is best seen in FIGS. 2 and 3. Needle  20  has a plunger receptor  62  at the proximal end which is configured to accommodate plunger  30  as it slides within fluid chamber  26 . Although plunger receptor  62  can be of any shape conforming to the exterior profile of plunger  30 , it is preferably conical. A needle inner wall  64  is contoured to narrow like a funnel to a needle discharge channel  66  to accelerate the fluid as it is discharged. Needle discharge channel  66  extends to a discharge orifice  68  at the distal end of needle  20 . Needle discharge orifice  68  has a diameter of 0.004 to 0.012 inches. Preferably, the diameter is 0.005 to 0.0075 inches. 
     The outer periphery of needle  20  can be of varied geometries such that it fits within fluid chamber  26  of nozzle assembly  12 . Advantageously, needle  20  has a conical body section  70  which narrows gradually or tapers towards a cylindrical body section  72  of smaller circumference. Preferably, a shoulder  74  is positioned to separate a needle tip  76  from cylindrical body section  72 . Needle tip  76  is also cylindrical, but has a smaller circumference than cylindrical body section  72  such that needle tip  76  can fit within and extend through opening  24  of nozzle assembly  12 . However, cylindrical body section  72  of needle  20  has a circumference such that shoulder section  74 , existing at the transition between cylindrical body section  72  and needle tip  76 , prevents cylindrical body section  72  from existing within opening  24 . The length of needle tip  76  from its end to shoulder  74  is approximately 1 to 5 mm. Thus, needle tip  76  will penetrate the skin to a depth less than 5 mm. It should also be noted that although needle tip  76  is shown having a single bevelled end at a 45° angle, needle tip  76  can have any shape that penetrates the skin. 
     As shown in FIGS. 4 and 5, needle  20  is positioned coaxially and retractably within the distal end of fluid chamber  26  such that when injector  10  is fired, needle tip  76  extends out opening  24  of nozzle assembly  12  at a speed sufficient to penetrate the outer layer of skin. By inserting needle tip  76  to a depth less than 5 mm, only the epidermis of the skin is penetrated and the pressure needed to deliver the medicament to the desired region by jet injection is lower than that would otherwise be needed. While syringes and auto-injectors delivery the medicament to the depth of the needle, the needle assisted jet injector according to the present invention delivers the medicament to a depth deeper than the length of the needle. This depth can include any region of the skin and beyond including intradermal, subcutaneous, and intramuscular. 
     To provide a seal between needle  20  and fluid chamber  26 , needle  20  includes a sealing means such as an O-ring(s)  78  or the like formed around the outer periphery of needle  20  and accommodated by slot  80 . In an alternative embodiment shown in FIG. 6, needle  120  itself is the seal. Thus, slot  80  is not needed. Needle  120  also differs from needle  20  in that cylindrical body section  72  is absent so that conical body section  70  terminates at shoulder  74 . 
     FIG. 5 illustrates injection assisting needle  20  in its extended position. Needle tip  76  extends beyond the distal end of nozzle assembly  12 . Shoulder  74  abuts the bored out inner section of nozzle opening  24  to prevent needle  20  from extending beyond needle tip  76 . A retraction element  82 , in this embodiment a spring, is compressed to provide a recoil force once the medicament is expelled so that needle tip  76  will retract back into nozzle opening  24 . Needle  20  preferably has a ridge  84 , the distal surface of which provides an annular area for the compression of retraction element  82 . Alternatively, a washer can be used instead of the ridge  84  to contain O-ring  78  and compress the retracting mechanism during operation. 
     FIGS. 7 and 8 show needle  120  of FIG. 6 with nozzle assembly  12  in which retraction element  82  is a resilient O-ring or other like material known to those skilled in the art. When an O-ring is used as retraction element  82 , it can also act as a sealing mechanism, and for this reason the O-ring is preferred. The interior of needle  120  is similar to that of needle  20 . FIG. 7 illustrates needle  120  in the retracted condition, before expelling medicament, and FIG. 8 shows the extended condition during which medicament is expelled. Similar to embodiments previously described, this embodiment functions to extend the needle tip  76  beyond nozzle opening  24  and penetrate the outer layer of the patient&#39;s skin during operation. Also, similar to embodiments previously described, needle  120  also preferably has ridge  84  around the proximal end to provide a surface which compresses the resilient material when the injector is triggered. 
     Another embodiment of the present invention, shown in FIGS. 9 and 10, uses a flexible member  86  as the retraction element. FIG. 9 illustrates the neutral condition before expelling the medicament. Flexible membrane  86  spans between walls  88  of nozzle assembly  12  which define fluid chamber  26  for holding medicament. Similar to embodiments previously described, the distal end of nozzle walls  88  act to conceal needle tip  76  until the injector is fired. Needle  220  is attached to flexible membrane  86  by any conventional means known to those skilled in the art. Preferably, needle  220  is integrally attached to flexible membrane  86  with an adhesive. FIG. 10 shows needle  220  in its extended position where the needle tip  76  extends beyond the end of walls  88  such that needle tip  76  penetrates the outer layer of skin to allow injection and deliver of the medicine at reduced pressure. 
     Other embodiments of the present invention relate to injectors with a fixed needle, i.e. a non-retracting needle that permanently extends beyond the nozzle assembly. Both a one-piece and a two-piece nozzle assembly with a fixed needle can be used and are contemplated by this invention. 
     FIGS. 11 and 12 show embodiments of the present invention with a two piece nozzle assembly with a fixed needle  320 . A first section  90  of nozzle assembly  12  has needle  320  at the distal end and can either be attached internally or externally to a second section  92  to form nozzle assembly member  12 . Although any conventional attaching means can be used, such as solvent or adhesive bonding, FIG. 11 shows a preferable friction-fitting or snapping attaching means  94  for both internal and external attachment of first section  90  and second section  92 . FIG. 12 shows a preferable ultrasonic bonding means  96  of attachment. Although ultrasonic bonding features  96  can be placed at any location to attach the two pieces, preferably, the ultrasonic bonding features  96  are along the distal end at the interface between first and second sections  90 ,  92  to facilitate ease of manufacturing. 
     Another embodiment of a multi-piece nozzle assembly with fixed needle  320  is shown in FIG.  13 . The nozzle assembly consists of nozzle member  22  having an opening  24  designed to receive a tubular insert to create fixed needle  320 . Although FIG. 13 shows a multi-piece nozzle assembly, fixed needle  320  can be made to be integral with nozzle assembly  12 . 
     A significant advantage of the needle assisted jet injector according to the present invention is that it allows for a lower pressure to deliver the medicament. In this regard, administering an injection using either a fixed or retractable needle requires less energy and force than conventional jet injector devices. FIG. 14 shows a pressure-time curve for a jet injector. The peak pressure at point c is the pressure needed to penetrate the skin and point d and beyond is the pressure at which a jet stream of medicament is delivered. Needle assisted jet injectors do not need to achieve as high as peak pressure as conventional jet injectors because the outer layer of skin is penetrated by the needle. Therefore, a lower peak pressure can be used to deliver the medicament to the desired region. It is also possible that a lower steady state pressure can be used to deliver the jet stream after the needle and the jet injection have reached the desired region. 
     Experimentation has confirmed that the needle assisted injector according to the present invention can operated using a lower generating energy source and still maintain the quality of the injection. Specifically, experimentation has shown that a higher percentage of successful injections can be achieved with a needle assisted jet injector having a needle that penetrates the skin to a depth of 1 mm and 20 lb. energy generating means as with a conventional needleless jet injectors having 55 lb. energy generating means. Similar results have been achieved with needles that penetrate 1-3 mm and energy generating sources providing 20 lbs. and 40 lbs. of force. 
     Another advantage of the needle assisted jet injector according to the present invention is the decreased injection time compared to syringes or auto-injectors. As previously discussed, auto-injectors and syringes have injection times of several seconds or more. During this injection time, the quality of the injection can be comprised due to any number of factors. For example, the patient could move the syringe or auto-injector prior to completion of the injection. Such movement could occur either accidently or intentionally because of injection-related pain. In contrast, the needle assisted jet injector, like other jet injectors, has an injection time around 0.25 seconds. The short injection time minimizes the possibility of compromising the quality of the injection. 
     While it is apparent that the illustrative embodiments of the invention herein disclosed fulfil the objectives stated above, it will be appreciated that numerous modifications and other embodiments may be devised by those skilled in the art. Therefore, it will be understood that the appended claims are intended to cover all such modifications and embodiments which come within the spirit and scope of the present invention.