Patent Document

CROSS-RELATIONSHIP TO PENDING APPLICATIONS 
     This application is a divisional of application Ser. No. 12/368,604 filed Feb. 10, 2009, which claims priority to provisional application Ser. No. 61/027,742 filed Feb. 11, 2008, which are incorporated herein by reference. 
    
    
     FIELD 
     This invention relates generally to syringe systems and methods for mixing and delivering a therapeutic agent formed by combining a diluent with a lyophilized drug or a concentrated drug. More specifically, this invention relates to syringe systems, including a passive needle guard, used for reconstitution of lyophilized or concentrated drugs and methods for using such systems. 
     BACKGROUND 
     Lyophilization is a process by which the volatile components of a drug are removed in order to extend the shelf-life of the medication. Lyophilization may involve the rapid freezing of a material at a very low temperature followed by rapid dehydration. Solvents such as water are removed from the drug yielding a substance that is more stable and can be stored. Lyophilized drugs are generally stored in a glass vial or cartridge and covered by a rubber stopper or septum. 
     In order to administer the lyophilized drugs, the drug must generally be reconstituted. Reconstitution is the process of hydrating drugs that are packaged and stored in a dry lyophilized state. A diluent, such as water, saline, 5% Aqueous Dextrose or the like, is added to the lyophilized drug and the combination is mixed until the drug is fully dissolved. A syringe is typically used to inject the diluent into the vial containing the lyophilized drug. The syringe may be pre-filled with the diluent or the user may first withdraw the diluent from a second vial or container into the syringe. After the diluent is added to the vial containing the lyophilized drugs, the contents are then mixed to form a therapeutic agent. 
     After complete mixing of the diluent and the lyophilized drug, the therapeutic agent may be aspirated back into the syringe. Once the therapeutic agent is in the syringe, the medication is administered to the patient. Usually the therapeutic agent is administered within a short time after reconstitution in order to ensure that the drug is not degraded by the solvent. 
     Most current systems for reconstitution expose the user to the risk of inadvertent needle sticks. In addition, current systems may not adequately prevent the possible reuse of the syringe. A number of needle guards for syringes have been developed that are intended to prevent accidental needle sticks and/or inadvertent reuse of a syringe. However, because syringe safety shield devices normally actuate when the plunger is fully advanced during the administration of the drug, these same devices will prematurely actuate the safety shield during the drug reconstitution phase as the diluent is added to the lyophilized drug. Therefore, a method for preventing the activation of the safety shield during drug reconstitution is highly desirable. 
     Accordingly, a syringe system that can be used for reconstitution and that would automatically activate a needle shield during or following administration of the therapeutic agent would be considered useful. 
     SUMMARY 
     The present invention is directed to a syringe system for reconstitution of lyophilized or concentrated drugs. The present invention is also directed to the combination of such a system with a passive needle guard that is automatically activated to extend a shield to cover a needle of the syringe and to methods of making and using such systems. Typically, a passive needle guard shield is activated when a radial portion or thumb pad of a plunger contacts a lateral catch or trigger finger of the passive needle guard. As the thumb pad of the plunger is moved distally, the trigger finger is forced laterally which results in a shield being forced distally to cover a needle of the syringe or in some designs, the syringe needle withdraws into the shield. 
     The present disclosure describes a needle guard device or system that can be used with drugs requiring reconstitution without activating the safety mechanism, yet provides needle safety shielding after the drug has been injected into the patient. In a preferred embodiment, the needle guard device would be assembled and sold with a syringe that is preferably pre-filled with the diluent. In a preferred embodiment, a clip is coupled to the needle guard during the reconstitution phase. The clip is configured to interact with the needle guard such that the shield is not activated to the extended position when the thumb pad of the plunger contacts the trigger fingers. Following reconstitution, the clip can be removed and the reconstituted medicine can be administered to the patient. During administration, the shield of the needle guard can be activated to extend and cover the needle. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows an unassembled version of an exemplary embodiment of the device depicting the drug vial, clip, plunger, and the needle guard with an installed syringe. 
         FIG. 2  shows an exemplary embodiment wherein the clip is attached to the proximal portion of the needle guard. 
         FIG. 3  shows an exemplary embodiment wherein the clip is attached to the proximal portion of the needle guard and the plunger is retracted fully in the proximal direction. 
         FIG. 4  shows an exploded view of the proximal portion of the device shown in  FIG. 3 . 
         FIG. 5  shows an exemplary embodiment of the device with a reconstitution needle attached. 
         FIG. 6  shows an exemplary embodiment of the device showing the plunger in the distal position and an administration needle coupled to the distal end of the syringe. 
         FIG. 7  shows a profile sectional view of the proximal portion of the needle guard with the clip removed. The dotted outline of the shield trigger fingers are shown in the unlatched position. The unlatched position is created when the plunger advances distally to an extent that the curved undersurface of the thumb pad pushes against the trigger fingers and displaces them laterally such that the latch surfaces of the shield trigger fingers and body are no longer engaged and will allow the shield to move distally with respect to the body unless prevented by the clip. 
         FIG. 8  shows an exemplary embodiment of the device with the shield in the extended position. 
     
    
    
     DETAILED DESCRIPTION 
     Turning to the figures,  FIG. 1  depicts an exemplary embodiment of the present needle safety guard device  5  and related components in an unassembled arrangement. As will be discussed in greater detail herein,  FIG. 1  shows a drug vial  200 , needle guard  40  housing a syringe  10 , clip  90 , and plunger  30 . In  FIG. 1 , the clip  90  is shown separated from the rest of the safety device to better illustrate the features of the clip  90 , however, in a preferred embodiment the clip  90  is connected to the main part of the safety device  5  as shown in  FIG. 2 . 
     In accordance with one aspect of the present disclosure, a medicine cartridge, such as a syringe  10  is provided ( FIG. 1 ). Preferably, the syringe  10  has a substantially smooth-walled cylindrical barrel  12 , a hub or distal end  14  that is the administration end, and a proximal end  16  having a flange  18 . The cylindrical barrel  12  typically is manufactured from substantially clear glass. Alternatively, the barrel  12  may be manufactured from plastic, e.g., polypropylene, k-resin, or polycarbonate, and the like. 
     The barrel  12  of the syringe  10  may be pre-filled with a diluent, or may be filled with the diluent at a later step. Preferably the syringe  10 , if pre-filled, also comprises a label or markings that indicates the quantity and type of diluent. For example, a sticker or label may be attached to the barrel  12  of the syringe  10  which provides the name of the diluent and the volume of the diluent. The diluent may be of any type known in the art including, but not limited to, sterile water, saline, 5% Aqueous Dextrose or the like. Alternatively, the user may aspirate the diluent into the syringe from a vial or container. 
     The proximal end  16  of the barrel  12  is configured to receive a stopper  20  and a plunger  30  ( FIGS. 1 and 7 ). The stopper  20  is configured to be slidably coupled into the cylindrical barrel  12  and movable from a proximal position to a distal position. The stopper  20  is preferably made of pliable rubber, thermoplastic rubber, plastic or similar material. The plunger  30  comprises a stem  32 , a distal end  34 , and a radial portion or thumb pad  36  ( FIG. 1 ). The plunger  30  is generally made of plastic, e.g. polypropylene, k-resin, or polycarbonate, or the like. 
     The distal end  14  of the cylindrical barrel  12  preferably comprises a needle port or Luer fitting ( FIG. 1 ). The Luer fitting may be configured to couple with several different sizes of needles with different diameters and lengths or with other components that include a Luer fitting or other type of holder. The needles and components may be connected by a Luer connector, Luer slip, Luer, or other holder as is known in the art. The Luer fitting can be either of the slip version (no threads) or include threads. The Luer fitting is configured to allow interchanging of the needle and/or components so a user may use the most appropriate needle or component during filling the syringe, reconstitution, and administration of the medication to a patient. 
     A first needle or reconstitution needle  8  can be attached to the Luer fitting ( FIG. 5 ). The reconstitution needle  8  is preferably used during reconstitution and then replaced by a second, administration needle  15  ( FIGS. 6 and 8 ) prior to administration of the medication. 
     The syringe  10  is housed inside the needle guard  40  wherein the needle guard  40  is preferably a passive needle guard ( FIG. 1 ). Safety shield devices generally function, by covering the needle with a rigid cylindrical shield that surrounds the needle and projects far enough beyond the distal tip of the needle so as to prevent a user&#39;s finger from coming in contact with the needle tip ( FIG. 8 ). To prevent a user from forgetting to deploy the safety shield, preferred safety devices operate passively or automatically by providing a mechanism that initiates and physically executes the shielding of the needle after the injection has been completed. The passive needle guard  40  generally comprises a body  50  for receiving and holding the syringe  10 , a shield  60  slidably attached to the body  50 , and a spring mechanism  55  ( FIG. 8 ). Both the body  50  and the shield  60  are generally molded from plastic, such as, polypropylene, k-resin, or polycarbonate, or the like. In a preferred embodiment, the body  50  and the shield  60  are substantially clear to facilitate observation of the syringe  10  therein. Alternatively, the body  50  and the shield  60  may be translucent or opaque, and may be colored, such as a latex color, a flesh tone, or a primary color. The body  50  may comprise opposing side rails defining two elongate openings or windows  51  extending at least partially between a proximal end  52  and a distal end  53  of the body  50  ( FIG. 8 ). 
     The shield  60  is a tubular member adapted to slidably fit on the body  50  and has a proximal end  62  and a distal end  64  ( FIGS. 1 and 8 ). In a preferred embodiment, one or more trigger fingers  66  extend proximally from the proximal end  62  of the shield  60  ( FIG. 7 ). The trigger fingers  66  may include a first catch  68  that is configured to engage a second catch  58  on the proximal end  52  of the body  50  of the needle guard  40 . Engagement between the first catch  68  and the second catch  58  retains the shield  60  in a first, retracted position. This latched configuration is further secured by an angled orientation of the latch surfaces, which when combined with the force of the spring  55  urging these surfaces against each other, places a component of force on the trigger fingers  66  directed toward the centerline. Preferably, the one or more trigger fingers  66  are elongate fingers having a proximal tip  67  that is engageable by the thumb pad  36  of the plunger  30  as it is depressed to axially compress and deflect the one or more trigger fingers  66  radially outwardly, as is discussed further below. In a preferred embodiment, the shield  60  further includes an anti-rotation tab  69  which extends proximally from the proximal end  62  ( FIGS. 2 and 6 ). The anti-rotation tab  69  interacts with the flange  18  of the syringe  10  and prevents rotation of the syringe  10 . Once the needle guard  40  has been activated, the anti-rotation tab  69  is no longer in proximity to the flange  18  and the syringe can be rotated as desired. 
     The passive needle guard  40  also includes a spring mechanism  55  coupled to the body  50  and the shield  60  for biasing the shield  60  towards an extended position when the trigger fingers  66  are deflected radially ( FIG. 8 ). 
     The clip  90  is removably coupled with the needle guard  40 . The clip  90  can include a tab  95  that creates a physical barrier to removal of the plunger from the needle guard safety device  5  ( FIGS. 3 and 4 ). When the plunger is moved proximally, the tab  95  on the clip  90  prevents a user from accidentally removing the plunger  30  ( FIG. 3 ). 
     To prevent the relative motion of the safety shield  60  during the steps of reconstitution, the clip  90  retains the shield in the retracted position through the interaction of one or more extensions  94 ,  96  disposed on the distal and proximal portions of the clip  90  that interact with the shield  60  and body  50  of the needle guard  40  ( FIGS. 1 and 4 ). In a preferred embodiment, the proximal extensions  94  extend axially from the clip  90  and are removably coupled with a proximal portion of the body  50 . The distal region of the clip  90  preferably includes one or more distal extensions  96  that are removably coupled with the proximal end  62  of the shield  60 . The interaction of the extensions  94 ,  96  with the shield and body prevent the movement of the shield distally with respect to the body. Therefore, even if the trigger fingers  66  are triggered during reconstitution, the shield cannot transition to the second, extended position and instead remains in the retracted position. In a most preferred embodiment, the extensions  94 ,  96  retain the body and shield in a slightly closer position than the trigger fingers  66  would on their own. This arrangement facilitates the relatching of the trigger fingers  66  following the reconstitution process as discussed below. 
     In an alternative embodiment, the clip  90  can be configured to interact with the distal end of the needle guard  40  to retain the shield  60  and body  50  in the retracted position when the clip  90  is attached. In this embodiment, the extensions  94 ,  96  of the clip  90  can be configured to engage (1) the distal end  64  of the shield  60  and (2) the body  50  slightly proximal of a catch  92  disposed near the distal end  53  of the body  50 . 
     In a preferred embodiment, the clip  90  includes a pair of opposing ribs  98  that extend laterally from the sides of the clip  90 . The ribs  98  are designed to facilitate removal of the clip  90  following the reconstitution step as discussed further below. 
     The syringe  10  can be used to administer a lyophilized or concentrated drug to a patient. The lyophilized drug or concentrated drug may be of any type known to those of skill in the art. Preferably, the lyophilized or concentrated drug is stored in a vial  200  or container such as a glass vial ( FIG. 1 ). The vial  200  may include a cover such as a rubber stopper, septum, or cap that can be penetrated by a needle. In a preferred embodiment, the vial  200  is made of a substantially clear glass so that the user can ensure that the diluent and lyophilized drug have been properly and fully mixed. 
     Assuming that the syringe is pre-filled with a diluent, the steps of reconstituting the drug and administering it into the patient would be to first insert the reconstitution or first needle  8  into the drug vial  200 . The plunger  30  is then advanced distally to expel the diluent from the syringe  10  into the drug vial  200 . 
     If the syringe is not pre-filled with the diluent, the first step in the process would be to aspirate diluent into the syringe from a vial or other source of the desired diluent. All other steps in the process would proceed as described above. 
     It is at this point that the problems with existing safety devices would arise, since advancing the plunger  30  to expel the diluent in the drug vial  200  would trigger the safety shield mechanism of existing safety devices. With the shield now covering the distal end of the device, the rest of the reconstitution steps would be impossible to perform and, additionally, the injection needle would not be accessible in order to inject the patient. 
     The clip  90  prevents the shield from transitioning to the extended position. Specifically, the extensions  94 ,  96  disposed on the distal and proximal portions of the clip  90  interact with shield  60  and body  50  such that the shield is retained in the first, retracted position. 
     The plunger  30  can then travel the full stroke to empty the syringe contents during reconstitution. Even though the safety shield mechanism will have been triggered (i.e. the thumb pad  36  will contact the trigger fingers  66 ), the shield  60  will not advance to the shielded position because the interaction of the extensions  94 ,  96  on the clip  90  maintain the shield in the first, retracted position. Because the trigger fingers  66  have an elastic force urging them back into the latched position, the latch mechanism is reversible if the shield  60  has not moved forward. When the plunger  30  is pulled proximally to draw the drug mixture from the vial  200  into the syringe  10 , the trigger fingers  66  will relatch themselves against the second catch  58  on the body  50  so that the needle guard  40  is able to trigger the next time the plunger  30  is advanced sufficiently distally ( FIG. 6 ). 
     After the drug has been dissolved in the diluent, the plunger  30  is withdrawn proximally, pulling the drug mixture into the syringe  10  ( FIG. 3 ). In a preferred embodiment, a circumferential rib  35  on the distal end  34  of the plunger  30  interferes with the tab  95  on the clip  90  preventing the full withdrawal of the plunger  30 , so that users will not inadvertently and surprisingly remove the stopper  20  from the syringe  10  and expose the drug to a non-sterile environment ( FIG. 4 ). Preferably, the needle  8  used for reconstitution is replaced with an injection needle  15  having a Luer fitting ( FIG. 6 ). The anti-rotation tab  69  on the proximal end of the shield prevents rotation of the syringe within the needle guard. Preventing rotation of the syringe facilitates removal and coupling of needles or other components to the Luer lock. The clip  90  is then removed in order to administer the medication. The medication is now ready for injection into the patient and the needle guard  40  should deploy in the normal manner after the medication has been injected into the patient. 
     As discussed above, the thumb pad  36  of the plunger  30  is sized and shaped to displace the trigger fingers  66  laterally away from the latched position that connects them to the body  50  to an unlatched position that substantially disconnects them from the body  50  when the plunger is advanced sufficiently far forward distally, preferably far enough forward that the contents of the syringe  10  are expelled, but before the plunger  30  is arrested by the stopper  20  reaching the distal end of the syringe  10  ( FIGS. 7 and 8 ). As the medication is being injected into the patient, the plunger  30  will displace the trigger fingers  66  causing the force of the spring  55  to move the shield  60  forward preventing the trigger fingers  66  from relatching and initiating the deployment of the safety shield  60 . The dotted lines in  FIG. 7  depict the movement of the trigger fingers  66  from the latched position to the unlatched position. 
     After the plunger  30  is fully advanced and the safety shield mechanism has been released, the shield  60  is either moved distally relative to the syringe  10  and needle  15  or the syringe  10  and needle  15  are moved proximally with respect to the shield  60 . Passive or automatic deployment of the safety shield  60  is accomplished by way of the compression spring  55  pushing the shield  60  distally and/or the syringe  10  and needle  15  proximally. The spring force is released to the shield  60  and body  50  when the trigger fingers  66  are displaced from the latch configuration. The spring  55  is of sufficient size to move the shield  60  far enough to shield the needle  15  from the user ( FIG. 8 ). In a preferred embodiment, a locking mechanism holds the shield in the extended position. The locking mechanism may comprise, for example, a set of cooperating detents or catches  92 ,  93  on the shield  60  and body  50  that maintain the shield in the extended position ( FIG. 6 ). Regardless of the relative motion of the safety shield  60 , what is common to all devices is that the safety shield  60  is actuated after the plunger has been advanced to empty the syringe contents. 
     Although preventing the shield from deploying or moving distally over the syringe has been described, it is understood that the present invention would also apply to devices that move the syringe and needle proximally. 
     While the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and herein described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the appended claims.

Technology Category: 1