Abstract:
The invention provides a delivery mechanism for an autoinjector comprising: a first drive member configured to drive a first component in an axial direction; a second drive member configured to drive a second component in an axial direction; and a release mechanism configured to control a sequence of release of the first drive member and the second drive member, wherein the release mechanism is positioned at least partially within the first or second drive member.

Description:
FIELD OF THE INVENTION 
       [0001]    This invention relates to devices for drug storage and drug administration to a patient. In particular the invention relates to mechanisms for automated administration of a dose of drug to a patient. 
       BACKGROUND TO THE INVENTION 
       [0002]    One type of drug delivery device known in the art is an autoinjector which contains a medical, therapeutic, diagnostic, pharmaceutical or cosmetic compound (drug) before it is administered, and which is used to administer the compound through the skin of the patient via a hollow needle. Autoinjectors may be used by the patient themselves or by a different user, and are also used to administer drugs to animals. 
         [0003]    Autoinjectors are typically used because they reduce the amount of training and effort needed by a user compared with that needed for a syringe, by automating either or both processes of inserting the needle into the patient and expelling the drug through the needle. They can also reduce the fear of injection by hiding the needle from the patient. 
         [0004]    Some autoinjectors use a single spring to provide the motive power to both insert the needle into the patient and deliver the drug. Examples of this approach include the EpiPen autoinjector from Meridian and the Humira autoinjector from Abbot. 
         [0005]    Where an autoinjector includes only one spring to provide the force to drive both functions, the force that the spring provides for one of the functions may be higher than needed, to enable the spring to provide sufficient force for the other function. Advantageously the two functions happen one after another rather than simultaneously in order that the drug is delivered only after the needle is correctly positioned. Because the force provided by a spring typically reduces as the spring delivers energy, the spring inevitably provides a higher force for driving the first function, i.e. needle insertion, than for the following function i.e. drug delivery, whether or not this is desirable. The strength of the spring is determined by the requirement for the spring to be able to provide sufficient force and energy at every point during the drug delivery process. This often means that much higher force than is needed or desirable is provided during the needle insertion phase. 
         [0006]    However some autoinjectors use two separate springs within their operating mechanisms to provide the motive power to insert the needle and deliver the drug. Examples of this approach are described in U.S. Pat. No. 4,642,099 and U.S. Pat. No. 7,749,195. 
         [0007]    Where an autoinjector includes two springs, the force provided by each spring can be tailored to better suit the requirements of each function. The overall maximum stored spring force required in the autoinjector mechanism can be significantly reduced, because each spring on its own no longer needs to provide sufficient energy to drive both functions. 
         [0008]    The use of two springs in this way typically requires an interlock mechanism to coordinate the sequence of the two functions so that significant drug is not expelled through the needle before the needle is inserted correctly into the patient. The interlock mechanism typically adds size and complexity to the autoinjector. 
         [0009]    It is an object of the present invention to provide an improved mechanism to control the sequence of release of two drive members, such as springs, within an autoinjector, which allows the size and complexity of the autoinjector to be kept to a minimum. 
       SUMMARY OF THE INVENTION 
       [0010]    Aspects of the present invention are defined in the appended independent claims, to which reference should be made. The various aspects of the invention may be provided alone or in combination with one or more of the other aspects. Preferred features of the invention are defined in the dependent claims. 
         [0011]    The use of two drive members, such as springs, in an autoinjector, instead of just one, can provide various benefits including those listed below:
       The level of pain and distress perceived by the user can be reduced due to lower needle insertion speeds and reduced noise and shock during drug delivery.   The risk of breakage of the drug container within the autoinjector can be reduced because of the lower maximum spring force required. This is of particular benefit where the drug container within the autoinjector consists of a relatively fragile glass syringe or cartridge.   The cost and size of the device can be reduced because one spring can be positioned within the other, and because a reduction in the maximum spring force can allow smaller autoinjector mechanisms. Reduced size makes the autoinjector more portable, which in turn increases the likelihood that a patient will carry it with them and therefore have it available if it is needed to treat an emergency condition.       
 
         [0015]    In one aspect the present invention provides a release mechanism to control the sequence of release of two drive members, such as springs, within an autoinjector, but which allows the size of the autoinjector to be kept to a minimum. It also provides accurate control of a sequence of needle insertion and drug delivery, and allows the number of components and cost of the autoinjector to be minimised. This is achieved by providing the release mechanism at least partially within the drive members. 
         [0016]    Many existing autoinjectors typically have a mechanism mounted on the opposite end of the autoinjector from the needle which engages with one or more of the springs to prevent accidental activation of the autoinjector. This can take the form of a button or removable safety cap. For this reason the interlock mechanism to control the sequence of needle insertion and drug delivery is typically mounted on the outside of one or more of the springs. These interlock mechanisms therefore generally have the disadvantage that they add to the size and complexity of the autoinjector. In contrast, the present invention allows for a release mechanism to be positioned at least partially inside a drive member. This minimises the size of the autoinjector. 
         [0017]    In a first aspect, a delivery mechanism for an autoinjector comprises: a first drive member configured to drive a first component; a second drive member configured to drive a second component; and a release mechanism configured to control a sequence of release of the first drive member and the second drive member, wherein the release mechanism is positioned at least partially within the first or second drive member. 
         [0018]    Preferably, the release mechanism is positioned at least partially within both the first and the second drive member. 
         [0019]    Typically, the first and second drive members are configured to drive the first and second components in the same direction, but it is possible for them to be different directions. For example the second direction may be parallel but opposite to the first direction. 
         [0020]    The first drive member may be a helical spring. The second drive member may be a helical spring. Helical springs can be placed one within the other to provide a stable and compact delivery mechanism. 
         [0021]    Preferably, one of the first and second drive members is mainly responsible for providing a force to insert a needle into a subject, and the other of the first and second drive members is mainly responsible for providing a force to expel a drug through the needle. However, the separate actions of the drive members may or may not correlate exactly with the separate functions of inserting the needle to the patient and delivering the drug; in other words, one drive member may provide the force needed for all of one function and part of the other, whereas the other drive member may provide only part of the force needed for the other function. 
         [0022]    In one embodiment, the release mechanism comprises a locking surface, the locking surface being fixed to, or part of, the main body; and an inner retaining component configured to retain the second drive member until the locking surface is moved a predetermined distance relative to the inner retaining component, after which the second drive member is released; wherein release of the first drive member moves the inner retaining component relative to the locking surface in order to release the second drive member. This provides a robust, stable and compact release mechanism. 
         [0023]    The inner retaining component may comprise a latch which engages on a bearing surface on the first component. The locking surface may maintain the latch in an engaged position with the bearing surface before the first drive member is released. The latch may be fixed to or part of the second component. 
         [0024]    In use, the first drive member moves from an initial position before it is released to a final position after it has been released, and the second drive member moves from an initial position before it is released to a final position after it has been released. The mechanism may comprise a noisegenerating mechanism configured to generate a sound when the first and second drive members have moved to their final positions. The noise generating mechanism informs a user when drug delivery has been successfully completed. 
         [0025]    The noisegenerating mechanism may be positioned at least partially, and preferably fully, within the first or second drive member. This allows the device to be made compact. The noisegenerating mechanism is preferably positioned at least partially within both the first and second drive members. 
         [0026]    The release mechanism is preferably part of an autoinjector. The autoinjector may comprise a drug container and a plunger within the drug container, and the second component may be a pusher configured to push the plunger within the drug container to deliver a drug. 
         [0027]    The autoinjector may comprise a drug container containing a drug to be dispensed, and the first component may be fixed to the drug container so that it is not displaced relative to the drug container when the second drive member is released. 
         [0028]    In another aspect, the invention provides a system for releasing a locking device that prevents the activation of the delivery mechanism, the releasing system being provided at a front end of the drug container, where the front end is the end to which the needle is attached and which is closest to the patient in use. This provides further opportunities to reduce the size, and in particular the width, of the overall device. It also allows for a simplified user interface which can be easier to use than that found on most autoinjectors available on the market. 
         [0029]    In this aspect an autoinjector may comprise: a housing; a drug container having a front end coupled to a needle; a releasable drive mechanism coupled to a rear end of the drug container, in use the drive mechanism moving from a initial configuration to a final configuration to move the drug container and needle relative to the housing in order to insert the needle into a subject; and a releasable locking mechanism retaining the drive mechanism in the initial configuration, the locking mechanism being fixed to the housing and engaging the front end of the drug container. 
         [0030]    The locking mechanism may comprise a resilient arm fixed relative to the housing. 
         [0031]    The releasable locking mechanism may be coupled to a skin sensor configured to sense a skin surface of a subject. The skin sensor may comprise a movable element that moves relative to the housing when it is pressed against a skin surface, movement of the movable element releasing the locking mechanism from engagement with the front end of the drug container. The movable element may be configured to be in contact with the locking mechanism when the locking mechanism is engaged with front end of the drug container. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0032]    Examples of the present invention will now be described in detail with reference to the accompanying drawings, in which: 
           [0033]      FIG. 1   a  shows a longitudinal crosssection of a first embodiment of an autoinjector before administration of the drug to the patient; 
           [0034]      FIG. 1   b  shows the section view of the autoinjector of Figure la from a different perspective; 
           [0035]      FIG. 2   a  shows the same autoinjector after the needle cover has been removed; 
           [0036]      FIG. 2   b  shows the section view of  FIG. 2   a  from a different perspective; 
           [0037]      FIG. 3   a  shows the same autoinjector in the process of inserting the needle into the patient; 
           [0038]      FIG. 3   b  shows the section view of  FIG. 3   a  from a different perspective; 
           [0039]      FIG. 4   a  shows the same autoinjector with the needle fully extended and the second spring released so that it can expel the drug into the patient; 
           [0040]      FIG. 4   b  shows the section view of  FIG. 4   a  from a different perspective; 
           [0041]      FIG. 5   a  shows the same autoinjector as the drug is being expelled; 
           [0042]      FIG. 5   b  shows the autoinjector of  FIG. 5   a  from a different perspective; 
           [0043]      FIG. 6   a  shows the same autoinjector after the drug has been expelled; 
           [0044]      FIG. 6   b  shows the section view of  FIG. 6   a  from a different perspective; 
           [0045]      FIG. 7  shows the autoinjector after the drug has been expelled and the autoinjector has been removed from the patient, allowing a needle safety mechanism to extend; 
           [0046]      FIG. 8  shows an alternative design of autoinjector to  FIG. 1   b , incorporating a piercable foil and lowfriction plunger 
           [0047]      FIG. 9   a  shows the drug container coupled to the drive mechanism from the autoinjector of  FIG. 1 ; 
           [0048]      FIG. 9   b  is a section view of  FIG. 9   a;    
           [0049]      FIG. 10   a  shows the outer spring component; 
           [0050]      FIG. 10   b  shows a section view of  FIG. 10   a;    
           [0051]      FIG. 11   a  shows the inner spring component; 
           [0052]      FIG. 11  b shows a section view of  FIG. 11   b;    
           [0053]      FIG. 12  shows a section view of a second embodiment of an autoinjector having only a single drive spring prior to drug delivery; 
           [0054]      FIG. 13  shows the autoinjector of  FIG. 12  after drug delivery; 
           [0055]      FIG. 14  shows the autoinjector of  FIG. 1   a  from a different perspective, with the housing not shown; 
           [0056]      FIG. 15  shows the autoinjector of  FIG. 2   a  from a different perspective with the housing not shown; 
           [0057]      FIG. 16  shows the autoinjector of  FIG. 15  with the skin sensor pushed back; 
           [0058]      FIG. 17  shows the autoinjector of  FIG. 16  a moment later; and 
           [0059]      FIG. 18  shows the autoinjector of  FIG. 3   a  from a different perspective with the housing not shown. 
       
    
    
     DETAILED DESCRIPTION 
       [0060]      FIG. 1   a  shows a longitudinal crosssection of an autoinjector in accordance with a first embodiment of the invention, before administration of the drug to the patient. 
         [0061]      FIG. 1   b  shows the section view of the autoinjector of  FIG. 1   a  from a different perspective. The autoinjector comprises a drug container  10  in which a dose of drug  12  is contained. A hollow hypodermic needle  14  is fixed to a front end of the drug container  10  and a plunger  16  provided within the drug container  10 . Movement of the plunger  16  towards the needle  14  causes the drug to be expelled from the drug container through the needle. As used herein “front” refers to the end of the drug container or autoinjector closest to the patient in use, i.e. the end through which the drug is delivered to the patient. 
         [0062]    This basic syringe assembly is housed within a housing  18  that contains drive mechanisms for inserting the needle  14  into a subject and for moving the plunger  16  within the drug container  10  to expel the drug  12 . The housing also contains a skin sensing mechanism for activating the drive mechanisms on contact with the skin of a subject and a noise generating mechanism to indicate to a user when delivery of the drug has been completed. 
         [0063]    The drive mechanism comprises two springs, one for inserting the needle and one for moving the plunger. In this example, helical springs formed from metal are used. However, it should be clear that other forms of spring may be used, such as gas springs or indeed any suitable mechanical drive incorporating a resilient member that can store potential energy to be subsequently released for driving the needle or plunger, and in any combination. 
         [0064]    The helical springs are arranged one within the other, in a coaxial relationship. However, it is not essential that they are coaxial, nor that they nest within each other, but there are advantages to both these features. The outer spring  20  is used for driving the drug container  10  and needle  14  forward through the housing  18  to insert the needle into a subject. The inner spring  22  is used to drive the plunger within the drug container to expel the drug  12  through the needle. However, in other embodiments the roles may be reversed with an inner spring driving the needle and an outer spring driving a plunger. 
         [0065]    The sequence of operation of the two springs  20  and  22  will now be described.  FIGS. 1   a  and  1   b  show the autoinjector in an initial state as it is delivered to an end user. The autoinjector includes a needle cover  24  for safety, which must be removed prior to use of the autoinjector. 
         [0066]    The needle cover  24  can be simply pulled off by a user or caregiver to expose the skin sensor  26 .  FIGS. 2   a  and  2   b  show the autoinjector with the needle cover  24  removed. The skin sensor  26 , which extends beyond the front end of the housing, is placed against the skin of a subject in a position where the drug is to be injected. Application of pressure to the body of the autoinjector towards the skin surface pushes the skin sensor  26  back relative to the autoinjector housing  18 . The needle  14  is still covered by a front end housing  28 , so the user applied pressure does not directly cause the needle  14  to be inserted through the skin. Instead the skin sensor acts as a trigger. The needle  14  and drug container  10  are retained relative to the front end housing  28  by needle insertion latches  30  that engage a front end of the drug container  10 . Once the skin sensor is pushed back a predetermined distance the needle insertion latches  30  are released, as is explained in detail with reference to  FIGS. 14 to 18 . Once the needle insertion latches  30  are disengaged from the drug container  10 , the outer spring  20  pushes the drug container  10  and needle  14  forward through the housing  18  to insert the needle into the patient. This is illustrated in  FIGS. 3   a  and  3   b.    
         [0067]    The outer spring  20  is positioned between the main housing  18  and a first component  32 , in this embodiment referred to as outer spring component  32 . The outer spring component is coupled to the drug container, as can be seen more clearly in  FIGS. 9   a  and  9   b . The outer spring component  32  comprises engaging arms  34  that engage with lugs  36  formed on an outer surface of the drug container  10 . However, any suitable means of engagement between the outer spring component and the drug container  10  may be used, or simply abutment of the outer spring component  32  against the drug container  10 . 
         [0068]    The outer spring component  32  moves with the drug container  10  as the needle  14  is inserted. The inner spring  22  is held between the outer spring component  32  and a second component  38 , in this embodiment also referred to as an inner spring component  38 . The inner spring component acts on the plunger during expulsion of the drug. But the outer spring component  32  retains the inner spring  22  in a compressed condition until the needle is partially or fully inserted. The outer spring component  32  extends around the inner spring  22 , over a back side of the inner spring, and has leg portions  40  positioned within the inner spring. The leg potions  40  are clearly illustrated in  FIG. 10   b . The inner spring component  38  comprises a front end pusher portion  44  that engages with the plunger, as will be described with reference to  FIGS. 5   a  and  5   b . The inner spring component  38  also comprises an inner retaining component in the form of inner resilient leg portions  42  that include inner spring retaining lobes  46  at their back ends. The inner resilient leg portions are pressed outwardly by a locking surface  48  that is part of (or rigidly fixed to) the main housing so that retaining lobes  46  engage with an inner spring retaining surface  47  on the outer spring component  32  and are prevented from disengagement by the locking surface  48 . In this way the inner spring is locked in a compressed state, and moves with the outer spring component  32 , until the retaining lobes  46  can be released from the inner spring retaining surface  47 . 
         [0069]    Once the outer spring is released by the needle insertion latches  30 , it drives the outer spring component  32  down through the housing. The locking surface  48  is dimensioned so that the inner resilient leg portions  42  disengage with the locking surface  48  as or just before the drug container  10  reaches the end of its travel within the main housing  18 , i.e. as the outer spring reaches its fullest extension. As soon as the inner resilient leg portions  42  are disengaged from the locking surface  48 , the lobes  46  disengage from the retaining surface  47 . This disengagement is due to the action of the inner spring  22 . 
         [0070]      FIGS. 4   a  and  4   b  show the autoinjector in a position when the inner spring  22  has been released and lobes  46  of the inner resilient leg portions  42  are pressed within the outer spring component  32 . The front end pusher portion  44  of the inner spring component is driven towards the plunger  16 . As illustrated in  FIG. 8 , a seal  56  may be provided across the back end of the drug container  10  to maintain the drug in pristine condition during storage, and this seal is ruptured by the front end pusher portion  44 . The front end pusher portion  44  then engages the plunger  16  and drives it within the drug container to expel the drug, as shown in  FIGS. 5   a  and  5   b.    
         [0071]    When the plunger  16  reaches the bottom of the drug container  10 , the drug is fully expelled. The leg portions  40  of the outer spring component are dimensioned so that at or just before the point when the plunger reaches the end of its travel, the lobes  46  on the inner spring component  42  are released from the leg portions  40 . This release causes the inner resilient arms  42  to expand outwardly from their compressed state, and percussive surfaces  50  on the inner resilient arms above the lobes  46  strike the end of the leg portions  40  to generate an audible sound. This position is illustrated in  FIGS. 6   a  and  6   b . The sound indicates to the user that delivery of the drug is complete and that the needle can be withdrawn from the subject. 
         [0072]      FIG. 7  illustrates the autoinjector after the drug has been expelled and the autoinjector has been removed from the patient, allowing a needle safety mechanism to extend to cover the needle. 
         [0073]    The materials used for the housing  18 , cap  24 , skin sensor  26 , front end housing  28 , needle insertion latches  30 , outer spring component  32  and inner spring component  38  may be plastic, such as EVOH or polyamide, or metal. The inner surface of the drug container must be compatible with the drug and the drug container may be formed from glass or plastic. The various elements described as resilient must have suitable elasticity. 
         [0074]    The plunger may be a standard rubber plunger  16  or may be a cup seal plunger  52 , as illustrated in  FIG. 8 . A cup seal plunger, used in conjunction with a back end sealing element  56  which is ruptured by the inner spring component, provides for a more reliable and low friction engagement with the inner wall of the drug container  10 . The cup seal plunger may be formed from a substantially nonelastomeric material such as polypropylene, polyethylene or FEP (Fluorinated Ethylene Propylene). 
         [0075]    The drive mechanism described with reference to  FIGS. 1 to 11  allows for different drive members to be used for needle insertion and for drug expulsion. The release mechanism for the drug expulsion is provided internally of the both the drive means, i.e. the outer and inner springs  20 ,  22 . This allows for compact springs to be used that supply an appropriate force for each stage of drug delivery, and for a compact overall device. 
         [0076]    The noise generating mechanism provided by the percussive surface  50  on the inner spring component striking the outer spring component  32  can be reversed or enhanced by forcing a surface on the outer spring component  32  to strike a portion of the inner spring component  38  as, or just before, drug delivery is completed. This can be achieved by forming legs  40  with an inwardly extending lower end  54 , as shown in the Figures. When the lobes  46  pass the legs  40 , the inwardly extending lower ends  54  are flexed outwardly by the lobes. The ends  54  then snap back to strike the percussive surface  50  once the lobes  46  have passed. However, it should be clear that the noise generating mechanism does not require the lower ends of the legs  40  to be inwardly extending; they may simply be straight, and struck by percussive surface  50  to generate a noise. 
         [0077]    It should be clear that a noise generating mechanism of this type may also be used in autoinjectors employing only a single drive spring to provide for either or both needle insertion and drug expulsion. This is illustrated in  FIGS. 12 and 13 .  FIG. 12  shows second embodiment of an autoinjector with a single drive spring  60  that drives both a needle  62  and a drug container  64  through a housing  66  for needle insertion and a drives a plunger  68  through the drug container  64  for expulsion of the drug. The drive mechanism is activated by a push button  70  that squeezes spring component  72  to release it from bearing surface  74 . The same lobe and percussive surface structure described with reference to the first embodiment is used in this embodiment. As the spring reaches its fullest extension, as shown in  FIG. 13 , the percussive surfaces  76  strike the end of legs  78  to generate an audible indication to a user that drug delivery is complete. 
         [0078]      FIGS. 14 to 18  illustrate more clearly the mechanism used to release the outer spring  20  of the first embodiment using the skin sensor  26 .  FIG. 14  is a view of the autoinjector shown in  FIG. 1   a  from a different perspective, with the main housing  18  removed.  FIG. 14  illustrates more clearly that the skin sensor  26  extends to about midway up the drug container  10 . The needle insertion latches  30  are resilient arms  300  on which heads  310  are provided. The heads engage the front end of the drug container  10  to retain the outer spring. The latches  30  may be formed as a single moulding with the front end body  24 . In the position shown in  FIG. 14  heads  310  are held in engagement with the drug container by the skin sensor  26 , including skin sensor lugs  260 . 
         [0079]      FIG. 15  is a view of the autoinjector shown in  FIG. 2   a  from a different perspective, with the main housing  18  removed. The cap  26  has been removed. 
         [0080]      FIG. 16  illustrates the autoinjector of  FIG. 15  with the skin sensor moved back as a result of contact with the skin of a patient. The skin sensor has cut out portions  262  that correspond to heads  310  which are moved into alignment with heads  310  in the position shown in  FIG. 16 . 
         [0081]      FIG. 17  shows the autoinjector of  FIG. 16  a moment later. The space provided by cut out portions  262  allow the arms  300  to flex outwardly under the force provided by the outer spring  20  through the drug container  10 . The heads  310  are thus moved out of engagement with the front end of the drug container and the drug container  10  can then move forward within the housing to insert the needle  14 . 
         [0082]      FIG. 18  is a view of the autoinjector shown in  FIG. 3   a  from a different perspective, with the main housing  18  removed. In  FIG. 18  the outer spring  20  is fully extended and the needle in an inserted position. The arms  300  remain flexed away from the drug container  10 , and the heads remain within cut out portions  262 . 
         [0083]    Again it should be clear that a skin sensor activation mechanism of this type which releases a front end of a drug container to activate a needle insertion mechanism may be used with an autoinjector having only a single drive means for either or both needle insertion and drug expulsion.