Abstract:
In general, the invention features an injection device including a housing, the housing having proximal and distal ends and designed to contain a liquid or semi-solid drug composition; a hollow needle, the needle affixed to the distal end of the housing and extending longitudinally within the housing; a plunger, the plunger arranged to slide within the proximal end of the housing; and a hollow sleeve, the hollow sleeve arranged to cover the needle prior to injection and to retract into the housing during injection; wherein the device is designed such that when the sleeve is pressed against the subject, the sleeve retracts into the housing and the drug composition is delivered through the needle and into the subject.

Description:
BACKGROUND OF THE INVENTION  
         [0001]    The invention relates to a device for the parenteral administration through a needle of liquid or semi-solid drug compositions wherein the needle is protected before and after the injection.  
           [0002]    The parenteral introduction of pharmaceutically active compounds is preferred over oral dosage for many indications, e.g. where the drug to be administered would partially or totally degrade in the gastrointestinal tract or where there is need for rapid biological response. The need for extratemporaneous preparation of such parenteral compositions is eliminated, or simplified, by the use of pre-filled administration devices in which the liquid to be injected is pre-loaded into the device (e.g. a pre-loaded syringe). Such pre-loaded devices, however, have a number of drawbacks, including the inability to preserve the asepsis or sterility of the needle, as well as the general danger of using an exposed needle. To eliminate these drawbacks, it is necessary to avoid the direct exposure of the needle with the environment both prior to and following injection.  
         SUMMARY OF THE INVENTION  
         [0003]    The invention features a comparatively inexpensive injection device with a needle for parenteral injection of liquid or semi-solid drug compositions into a subject, e.g. a mammal such as a human, wherein the needle is protected before and after the injection.  
           [0004]    In general, the invention features an injection device including a housing, the housing having proximal and distal ends and designed to contain a liquid or semi-solid drug composition; a hollow needle, the needle affixed to the distal end of the housing and extending longitudinally within the housing; a plunger, the plunger arranged to slide within the proximal end of the housing; and a hollow sleeve, the hollow sleeve arranged to cover the needle prior to injection and to retract into the housing during injection; wherein the device is designed such that when the sleeve is pressed against the subject, the sleeve retracts into the housing and the drug composition is delivered through the needle and into the subject.  
           [0005]    In one embodiment, the device is further designed such that when the drug composition is forced from the housing, the plunger forces the sleeve out of the housing to cover the needle. In a further embodiment, the housing contains the liquid or semi-solid drug composition.  
           [0006]    In another embodiment, the device further comprises a septum plunger, the septum plunger slidably arranged within the housing between the plunger and the distal end of the housing. In a further embodiment, the device is configured such that when the drug composition is forced from the housing, the plunger forces the septum plunger into the sleeve, and the septum plunger forces the sleeve out of the housing to cover the needle. In still a further embodiment, the housing contains the liquid or semi-solid drug composition between the plunger and the septum plunger.  
           [0007]    In still another embodiment, the housing contains a liquid and a dry drug composition, where the device is designed to combine the liquid and the dry drug composition prior to injection.  
           [0008]    In a further embodiment the device comprises a releasable lock which inhibits the movement of the plunger into the housing. In a still further embodiment the device comprises a removable cap which covers the sleeve. In yet a still further embodiment the proximal end of the housing comprises a flange and/or the plunger comprises a flange.  
           [0009]    An optional feature of the device comprises a cartridge or tube, said cartridge or tube comprising a distal end, said distal end closed by a cap, seal or septum; a proximal end, said proximal end closed by a plunger tip slidably arranged within the cartridge or tube; and a reservoir between said cap, seal or septum and said plunger tip.  
           [0010]    Optionally said cap, seal or septum may be attached to said distal end with a classical clip means, e.g., using a metal ring. The cap, seal or septum and the plunger tip each is made of a suitable material, i.e., a material compatible with the intended use of the injection device. In a preferred embodiment the cap, seal or septum and the plunger tip each independently is made of a non-rigid solid material such as rubber, polybromobutyl, or the like. In a more preferred embodiment the cap, seal or septum and the plunger tip each is made of the same material.  
           [0011]    The cartridge or tube is configured to contain a liquid or semi-solid drug composition within the reservoir and is introduced into the housing of the device, e.g., through the proximal end of the housing. The cartridge or tube is further configured such that it can be moved within the housing, e.g., toward or away from the proximal end of the needle. Said cartridge or tube is optionally of a standard variety.  
           [0012]    The injection device is configured such that, after the cartridge or tube is connected to the proximal end of the needle, i.e., after the proximal end of the needle pierces the cap, seal or septum located at the distal end of the cartridge or tube, then when the sleeve is pressed against the subject the sleeve retracts into the housing thereby exposing the distal end of the needle and allowing the distal end of the needle to penetrate the subject. Thereafter, when the plunger tip at the proximal end of the cartridge or tube is urged into the cartridge or tube, i.e., toward the distal end of the cartridge or tube, the drug composition is urged from the cartridge or tube through the needle and into the subject.  
           [0013]    According to a particular variant of this invention, the cartridge or tube further comprises a proximal compartment located toward the proximal end of the cartridge or tube and a distal compartment located toward the distal end of the cartridge or tube, wherein the proximal compartment and the distal compartment are separated by a plunger. In this variant said proximal compartment contains a liquid component of a composition and the distal compartment contains a solid component of said composition. In this variant the device is configured such that, in operation, the liquid and solid components are mixed prior to injection.  
           [0014]    In one embodiment, the device is further configured such that when the drug composition is forced from the cartridge or tube, the cartridge or tube urges the sleeve out of the housing thereby covering the needle after the injection and, optionally, urging the withdrawal of the needle from the subject. In a further embodiment, the cartridge or tube contains the liquid or semi-solid drug composition.  
           [0015]    In another embodiment, the cartridge or tube further comprises a septum cap or seal to close the distal end and a septum plunger to close the proximal end of the tube. Said septum cap or seal is fixed by a clip and said septum plunger is slidably arranged within the cartridge or tube. In a further embodiment, the device is configured such that, when the cartridge or tube is urged sufficiently into the housing the proximal end of the needle passes through the septum cap or seal, and, when the drug composition is urged from the cartridge or tube by the septum plunger, said septum plunger urges the cartridge or tube and the cartridge or tube urges the sleeve out of the housing to cover the needle. In still a further embodiment, the cartridge or tube contains the liquid or semi-solid drug composition between the septum cap or seal and the septum plunger.  
           [0016]    In still another embodiment, the cartridge or tube contains a liquid and a dry drug composition, where the device is designed to combine the liquid and the dry drug composition prior to injection.  
           [0017]    The device can further include a cartridge or tube locking means to inhibit the movement of the cartridge or tube in the housing, e.g., after the cartridge or tube has been connected to the needle. The proximal end of the housing may have a flange and the plunger may also have a flange.  
           [0018]    In still another embodiment of the injection device the housing comprises the reservoir and the hollow needle is affixed to the distal end of the reservoir and extends only longitudinally outside said reservoir. A housing or protection sleeve is configured on the plunger and is arranged to slide around the reservoir. The device is configured such that when the drug composition is urged from the reservoir, the plunger housing covers said reservoir. At the end of the injection the plunger is released from the plunger housing, e.g., by the proximal end of the reservoir, and the plunger slides into said plunger housing thereby allowing the plunger housing to cover the needle.  
           [0019]    A further object of the invention is therefore an injection device for injecting liquid or semisolid composition into a subject, the device comprising: a reservoir having a proximal and distal end, said distal end being configured to contain a liquid or semi-solid composition; a hollow needle, said needle affixed to the distal end of the reservoir and extending longitudinally outside said reservoir; a plunger arranged to slide within the proximal end of the reservoir; said plunger arranged to retract after injection into a plunger housing slidably connected to the proximal end of the reservoir and arranged to cover the plunger, the reservoir and the needle after injection; wherein the device is designed such that when the plunger housing is pushed around the reservoir, the plunger is pushed into the reservoir, the composition is pushed from the reservoir through the needle and into the subject.  
           [0020]    According to a preferred execution mode of this injection device, said plunger housing is disconnected from said plunger due to a release mechanism into said proximal end of the reservoir. According to another preferred execution mode, the protection sleeve is designed to be locked in an irreversible manner by, e.g., mechanical means once the needle has been protected.  
           [0021]    Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described below. All publications, patents, patent applications, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.  
           [0022]    Other features and advantages of the invention will be apparent from the following detailed description, and from the claims. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0023]    [0023]FIG. 1 is a partial cross-sectional view of an injection device prior to use.  
         [0024]    [0024]FIG. 2 is a partial cross-sectional view of the injection device of FIG. 1 during use.  
         [0025]    [0025]FIG. 3 is a partial cross-sectional view of the device with the needle injected into a subject.  
         [0026]    [0026]FIG. 4 is a partial cross-sectional view of the injection device being withdrawn from the subject with the drug composition remaining in the subject.  
         [0027]    [0027]FIG. 5 is a partial cross-sectional view of the injection device following complete withdrawal of the needle from the subject.  
         [0028]    [0028]FIG. 6 is a partial cross-sectional view of the injection device through line  6 - 6  in FIG. 1.  
         [0029]    [0029]FIG. 7 is a view of the sleeve of the injection device.  
         [0030]    [0030]FIG. 8 is a partial cross-sectional view of a cartridge injection device prior to pre-introduction of the cartridge.  
         [0031]    [0031]FIG. 9 is a partial cross-sectional view of a cartridge injection device prior to use.  
         [0032]    [0032]FIG. 10 is a cross-sectional view of the cartridge injection device of FIG. 9 during use after connection of the cartridge to the needle.  
         [0033]    [0033]FIG. 11 is a partial cross-sectional view of the cartridge injection device of FIG. 10 during use after plunger setting.  
         [0034]    [0034]FIG. 12 is a cross-sectional view of the cartridge injection device with the needle injected into a subject.  
         [0035]    [0035]FIG. 13 is a partial cross-sectional view of the cartridge injection device being withdrawn from the subject with a drug composition remaining in the subject.  
         [0036]    [0036]FIG. 14 is a partial cross-sectional view of the cartridge injection device following complete withdrawal of the needle from the subject.  
         [0037]    [0037]FIG. 15 is a cross-section of the injection device through line  6 - 6  in FIG. 8.  
         [0038]    [0038]FIG. 16 is a cross-section of a cartridge containing a liquid or semi-solid composition.  
         [0039]    [0039]FIG. 17 is a cross-section of a cartridge containing a liquid and a dry drug:  
         [0040]    [0040] 17 A: prior to rehydration;  
         [0041]    [0041] 17 B: after rehydration.  
         [0042]    [0042]FIG. 18 is a cross-section of the housing with the two options or the cartridge (right) and the tube (left).  
         [0043]    [0043]FIG. 19 is a cross-section of the tube containing a liquid and a dry drug before and after rehydration.  
         [0044]    [0044]FIG. 20 is a cross-section view at the stage of FIG. 10 in a case where tube containing a liquid and a dry drug before and after rehydration.  
         [0045]    [0045]FIG. 21 is a cross-section view of a reservoir injection device prior to use.  
         [0046]    [0046]FIG. 22 is a cross-sectional view of the reservoir injection device after drug composition injection.  
         [0047]    [0047]FIG. 23 is a cross-sectional view of the reservoir injection device following complete withdrawal of the needle from the subject.  
     
    
     DETAILED DESCRIPTION  
       [0048]    It is believed that one skilled in the art can, based on the description used herein, utilize the present invention to its fullest extent. The following specific embodiments are, therefore, to be construed as merely illustrative, and not limiting.  
         [0049]    [0049]FIG. 1 shows injection device  1  including housing  10 , having a proximal end and a distal end  14   a ,  14   b . The distal end of the housing  10  has two holes  40   a  and  40   b  partially separating the two parts  14   a  and  14   b  of said distal end (as best seen in FIG. 6). Needle  12  is attached to part  14   a  of the distal end. The housing  10  can be made from a suitably rigid material such as glass, plastic, metal, and the like. The needle  12  is hollow and double-ended, wherein its distal end, remaining outside housing  10 , has a point capable of piercing the skin of a subject, and its proximal end, remaining within housing  10 , is capable of piercing septum plunger  16 . On the proximal end of housing  10  is a flange  28  to assist in removal of device  1  from the subject following injection.  
         [0050]    A sleeve  22  surrounds needle  12  so that needle  12  is not fully exposed to the environment until used. Sleeve  22  has longitudinal slots  45   a  and  45   b  along its length (see FIG. 7; slot  45   b  is on the back of the sleeve and is thus not shown). The two parts  14   a  and  14   b  of the distal end are joined by radially extending connecting members  42   a  and  42   b  (see FIG. 6). Connecting members  42   a  and  42   b , respectively, slide through slots  45   a  and  45   b  in sleeve  22 , while sleeve  22  slides through holes  40   a  and  40   b  in housing  10 . Sleeve  22  can be made of suitably rigid material, such as metal, glass, plastic, and the like. Seal  24  covers the opening  23  of sleeve  22  to maintain the sterility of needle  12  and prevent sleeve  22  from unintentionally retracting into housing  10  through holes  40   a  and  40   b  prior to injection.  
         [0051]    Seal  24  can be made of a thin material, such as plastic or wax, which is easily penetrated by needle  12  during injection. A similar seal can also cover slots  45   a  and  45   b  in sleeve  22 , to further protect the sterility of needle  12 .  
         [0052]    Septum plunger  16 , contained within housing  10 , includes a bore  26 , in which needle  12  rests prior to subsequently piercing septum plunger  16 . A liquid or semi-solid composition  20  is isolated in housing  10  between the septum plunger  16  and the plunger tip  30 , attached to plunger  29 . Septum plunger  16  and plunger tip  30  may be made of non-rigid, solid material such as rubber, polybromobutyl, and the like, which allows septum plunger  16  and plunger tip  30  to slide within housing  10  but still maintain sufficient friction with the inner sides of housing  10  to seal composition  20  within housing  10 .  
         [0053]    The proximal end of plunger  29  has a thumb flange  18  to assist in the depression of plunger  29  into housing  10 , and the distal end of plunger  29  has a longitudinal bore  27  to receive needle  12  following injection of composition  20  out and through needle  12 . Plunger  29  can be made from a suitably rigid material, such as glass, metal, plastic, and the like. A removable lock  25  may be placed between flange  18  and flange  28  to inhibit further depression of plunger  29  into housing  10  after activation of the device  1 , i.e. after the housing  10  is filled with a drug composition and the proximal end of the needle is pierced through septum plunger  16 . A removable cap  21  can also be used to protect both needle  12  and sleeve  22  prior to use. Both cap  21  and lock  25  can be made from suitably rigid material such as plastic, metal, rubber, and the like.  
         [0054]    [0054]FIG. 2 shows device  1  wherein plunger  29  has been pressed into housing  10  to activate device  1  as follows. When plunger  29  is depressed, plunger tip  30 , composition  20 , and septum plunger  16  are displaced towards the distal end of housing  10 . Septum plunger  16  is pierced at bore  26  by needle  12 . As a result, the proximal end of needle  12  is exposed to composition  20 . Device  1  is now in an activated state. Lock  25 , by contacting both flange  18  and flange  28 , inhibits the further displacement of composition  20  from housing  10  to needle  12  following activation of device  1 , i.e. composition  20  is allowed to fill needle  12 , but lock  25  inhibits significant release of composition  20  through needle  12 .  
         [0055]    [0055]FIG. 3 shows device  1  wherein needle  12  has penetrated skin  32  of the subject being treated. As device  1  is pressed against skin  32 , sleeve  22  is retracted into housing  10 , through holes  40   a  and  40   b , by the force of pressure against skin  32 . Needle  12  passes through sleeve  22  at opening  23 . As shown, needle  12  has penetrated through skin  32  into the subcutaneous layer  34 .  
         [0056]    [0056]FIG. 4 shows device  1  wherein lock  25  has been removed and plunger  29  has been depressed, which moves plunger tip  30  toward septum plunger  16 , thereby injecting composition  20  into subcutaneous layer  34  through needle  12 . Once composition  20  has been injected and plunger tip  30  rests against septum plunger  16 , housing  10  is moved away from skin  32  by exerting pressure against the lower part of the flange  28  while simultaneously exerting oppositing pressure on flange  18  of plunger  29 . This relative movement of the plunger  29  and housing  10  causes plunger tip  30  to force septum plunger  16  against sleeve  22  as both plunger tip  30  and septum plunger  16  slide towards parts  14   a  and  14   b  of the distal end of housing  10 , which in turn forces sleeve  22  out of housing  10  through holes  40   a  and  40   b . As plunger tip  30  and septum plunger  16  are moved toward distal end of housing  10 , needle  12  penetrates septum plunger  16 , plunger tip  30 , and enters bore  27  in plunger  29 .  
         [0057]    [0057]FIG. 5 shows needle  12  fully withdrawn from skin  32  and sleeve  22  fully covering needle  12 . Composition  20  remains in the subcutaneous layer of the patient. As can also be seen in FIG. 5, the proximal end of needle  12  has been pushed through septum plunger  16  and plunger tip  30  and remains in bore  27  of plunger  29 .  
         [0058]    [0058]FIG. 6 is a cross-sectional view of FIG. 1 at  6 - 6 . FIG. 6 shows holes  40   a  and  40   b  in housing  10 . Radially extending connecting members  42   a  and  42   b  extend through slots  45   a  and  45   b , respectively, to connect parts  14   a  and  14   b  of the distal end. Needle  12  is fixed to central part  14   a  of the distal end, and sleeve  22  can slide through holes  40   a  and  40   b.    
         [0059]    [0059]FIG. 7 shows an isolated sleeve  22  having slots  45   a  and  45   b  ( 45   b  is not shown but positioned directly opposite to slot  45   a  on the other side of sleeve  22 ) and opening  23 . Radially extending connecting members  42   a  and  42   b , respectively, slide through slots  45   a  and  45   b.    
         [0060]    [0060]FIG. 8 shows a cartridge injection device  1  including a housing  10  having a proximal and a distal end.  
         [0061]    The distal end of housing  10  has at least one hole and for example two holes,  40   a  and  40   b , partially separating the two parts of the distal end (as best seen in FIG. 15). Needle  12  is attached to the distal end. The housing  10  can be made from a suitably rigid material such as glass, plastic, metal, and the like. The needle  12  is hollow and double-ended, wherein its distal end, remaining outside housing  10 , has a point capable of piercing the skin of a subject, and its proximal end remaining within housing  10  is capable of piercing septum cap  17  and septum plunger  30  of the cartridge or tube  11 . On the proximal end of housing  10  is a flange  28  to assist in injection. The removal of device  1  from the subject following injection is assisted by extension of sleeve  22 .  
         [0062]    A sleeve  22  surrounds needle  12  so that needle  12  is not fully exposed to the environment until used. Sleeve  22  has at least one longitudinal slot along its length, and for example two,  45   a  and  45   b  (see FIG. 15). The two parts of the distal end are joined by radially extending connecting members  42   a  and  42   b  (see FIG. 15). Connecting members  42   a  and  42   b  respectively slide through slots  45   a  and  45   b  in sleeve  22 , while sleeve  22  slides through holes  40   a  and  40   b  in housing  10 . Sleeve  22  can be made of suitably rigid material such as glass, plastic, metal and the like.  
         [0063]    A seal  24  (not shown) on needle  12  can be made of a thin material, such as a plastic sheet, a plastic packaging material or a bag which is easily penetrated by needle  12  during injection. A similar seal can also cover the sleeve  22  to further protect the sterility of the needle  12 .  
         [0064]    Septum plunger  16 , contained within housing  10 , can include a bore  26  in which needle  12  rests prior to subsequently piercing septum plunger  16 . A liquid or semi-solid composition  20  is isolated in the cartridge  11  between septum plunger  16  and plunger tip  30 . Septum plunger  16  and plunger tip  30  may be made of non-rigid solid material such as rubber, polybromobutyl, or the like, which allows plunger tip  30  to slide within cartridge  11  but maintaining sufficient friction with the inner sides of the cartridge  11  to seal composition  20  within cartridge  11 .  
         [0065]    The proximal end of plunger  29  has a thumb flange  18  to assist in the depression of plunger  29  into cartridge  11  and the distal end of plunger  29  has a longitudinal bore  27  to receive needle  12  following injection of composition  20  out and through needle  12  (see FIG. 11). Plunger  29  can be made from a suitably rigid material such as glass, plastic, metal and the like. A removable lock  25  may be placed between flange  18  and flange  28  to inhibit the further depression of plunger  29  into housing  10  after activation of device  1 , i.e. after the housing  10  is filled with a tube or a cartridge and the proximal end of the needle is pierced through septum cap  17 .  
         [0066]    A removable cap  21  can also be used to protect both needle  12  and sleeve  22  prior to use. Both cap  21  and lock  25  can be made from suitably rigid material such as plastic, metal, rubber, and the like  
         [0067]    Septum cap  17  on distal end of cartridge  11  is sealed, e.g., with a metal ring (not shown). A liquid or semi-solid composition  20  is isolated in cartridge or tube  11  between the septum cap  17  and the plunger tip  30 , which will be attached to plunger  29  (see FIG. 11). The cartridge or tube  11  can be connected to the proximal end of needle  12  by applying pressure to the proximal end of the cartridge or tube, e.g., by pushing with the thumb (see FIG. 10).  
         [0068]    Septum cap  17  and plunger tip  30  may be made of non-rigid material such as rubber, polybromobutyl, and the like, which allows needle  12  to pierce septum cap  17  and plunger tip  30 , and allows plunger tip  30  to slide sealably within cartridge or tube  11 .  
         [0069]    [0069]FIG. 9 shows, during use of device  1 , the introduction of cartridge or tube  11  into the housing  10 .  
         [0070]    [0070]FIG. 10 shows the connection of cartridge or tube  11  on needle  12  through septum cap  17 .  
         [0071]    [0071]FIG. 11 shows settlement of plunger  29  on plunger tip  30 .  
         [0072]    [0072]FIG. 12 shows injection of needle  12  with retraction of sleeve  22  into housing  10 .  
         [0073]    [0073]FIG. 13 shows injection of composition  20  into the tissue, e.g., using thumb on plunger flange  18  and the other fingers on housing flange  28 .  
         [0074]    [0074]FIG. 14 shows removal of the device from the subject following injection, where cartridge or tube  11  urges sleeve  22  from housing  10  around needle  12  and, consequently, removes needle  12  from body tissue.  
         [0075]    [0075]FIG. 15 shows a cross-section, through line  6 - 6  shown in FIG. 8, of distal end  14   b  of housing  10  with two apertures or holes  40   a  and  40   b  through which slots  45   a  and  45   b  of sleeve  22  slide. Two connecting members  42   a  and  42   b  separate the holes and connect external part of the housing  10  with the internal part where needle  12  is fixed.  
         [0076]    [0076]FIG. 16 shows a cartridge or tube  11  used in the housing  10  of device  1  with composition  20  between septum cap  17  and plunger tip  30 .  
         [0077]    [0077]FIG. 17A shows a cartridge or tube  11  used in the housing  10  of device  1  with a releasable lock  50 . The liquid part of the composition  20 B is loaded in cartridge or tube  11  between two septum plunger  30 A and septum plunger  30 B. Septum plunger  30 A is placed into cartridge or tube  11  just before by-pass  51 . Septum plunger  30 B is locked with the lock  50  in contact with cartridge or tube  11 . The solid part of the composition  20 A is loaded, e.g., under vacuum, in cartridge or tube  11  between septum plunger  30 A and septum cap  17 .  
         [0078]    [0078]FIG. 17B shows cartridge or tube  11  of FIG. 17A after removal of the releasable lock  50 . The composition  20  is prepared by passage of the liquid part of the composition  20 B through the by-pass  51  into the solid part under vacuum.  
         [0079]    [0079]FIG. 18 shows device  1  with the tube option  11 A or the cartridge option  11 B presented with the dual chamber arrangement of FIG. 17. The housing  10  can be the same for both options ( 11 A or  11 B). Before removal of releasable lock  50 , tube  11 A or cartridge  11 B cannot be connected on needle  12  through septum cap  17 . After removal of releasable lock  50 , the rehydration is realized as described in FIG. 17 or FIG. 19 and tube  11 A or cartridge  11 B can be operably connected to needle  12 . The plunger  29  is attached to septum plunger  30 B and the injection is performed.  
         [0080]    [0080]FIG. 19 shows, for tube  11 A, the rehydration process described in FIG. 17, performed by removing lock  50 . Before removing lock  50  on FIG. 12A, tube  11 A cannot be introduced into the housing deep enough to introduce needle  12  through septum cap  17  into the tube  11 A. Releasable lock  50  also maintains plunger  30 A at the top of by-pass  51  despite the vacuum in the solid part of the composition  20 A. After removing lock  50  on FIG. 12B, tube  11 A can be introduced into the housing to introduce needle  12  through septum cap  17  into the tube  11 A. Before this introduction by removing lock  50 , the composition  20  is prepared by mixing the solid part  20 A and the liquid part  20 B due to the rehydration obtained by the vacuum of the chamber containing solid part  20 A.  
         [0081]    [0081]FIG. 20 shows  2  possible variations in the arrangement of FIG. 8 during use after connection of the cartridge or tube  11  on the needle  12  when the needle  12  is not directly attached to the distal end of housing  10  but to a support  50  which corresponds to distal end of housing  10  in the way sleeve  22  is affixed to it.  
         [0082]    This independent support  50  can be connected to housing  10 , e.g., like a pen or cartridge disposable needle is connected, e.g., by screwing onto housing  10  after needle  12  is introduced through septum cap  17 .  
         [0083]    In FIG. 20A, the removal of the device from the subject following injection is obtained by sleeve  22  as in FIG. 8 due to the displacement of cartridge or tube  11 .  
         [0084]    [0084]FIG. 20B shows another alternative where the extension of sleeve  22  after injection is facilitated by spring  51  without displacement of cartridge or tube  11 . This allows the thread to be a standard one and the device to be adapted on any other existing cartridge pen or syringe injector.  
         [0085]    [0085]FIG. 21 shows injection device  1 , including reservoir  10 , having a distal end  14   a  and a proximal end  14   b . The proximal end of the reservoir  10  has two holes  40   a  and  40   b  adapted to operatively accept arms  22   a  and  22   b . Needle  12  is operatively attached to distal end  14   a . Reservoir  10  can be made from a suitably rigid material such as glass, plastic, metal, or the like. The needle  12  is hollow and single-ended outside the reservoir  10  with a tip capable of piercing the skin of a subject. On the proximal end of housing is a flange  28  having, e.g., an elliptic shape, which assists both plunger movement in the reservoir and removal of device  1  from the subject via extension of sleeve  22  following injection.  
         [0086]    In this embodiment the sleeve  22  comprises a plunger housing made of a suitably rigid material such as metal, glass, plastic, or the like. The plunger housing  22  surrounds plunger  29  so that when plunger  29  slides into reservoir  10 , plunger housing  22  slides around reservoir  10 . Plunger housing  22  has longitudinal slots (not shown) and arms  22   a  and  22   b  along its length. Arms  22   a  and  22   b  pass through holes  40   a  and  40   b  respectively in the proximal end  14   b.    
         [0087]    The proximal end of plunger  29  is covered by plunger housing  22  up to a flange  18 . Flange  18  assists depression of plunger  29  into reservoir  10  along with simultaneous depression of plunger housing  22  around reservoir  10  due to the removable lock  17  or connection means with plunger  29  into plunger housing  22 .  
         [0088]    [0088]FIG. 22 shows device  1  as depicted in FIG. 21 wherein plunger  29  has been depressed by plunger housing  22  thereby injecting composition from reservoir  10  through needle  12 .  
         [0089]    Once composition has been injected plunger  29  rests against the bottom or distal end of reservoir  10 , which is also completely covered by plunger housing  22 .  
         [0090]    Reservoir  10  is then moved away from the injection needle site by exerting pressure against the lower part of the flange on proximal end  14   b  of the reservoir  10  while simultaneously exerting opposing pressure on flange  18  of plunger housing  22 . This relative movement of the plunger housing  22  and reservoir  10  causes plunger  29  to be released from removable lock  16  due to sliding guide and release mechanism on reservoir proximal end  14   b , and plunger housing slides around reservoir  10  and needle  12 , which in turn urges needle  12  out of injection site.  
         [0091]    [0091]FIG. 23 shows needle  12  fully withdrawn from the injection site and plunger housing  22  covering reservoir  10  and needle  12 .  
         [0092]    Flange  18  is equipped with means  46  to secure, optionally irreversibly, the plunger housing  22  once the needle  12  has been protected.  
         [0093]    Composition  20  is a liquid or a semi-solid composition containing a drug. The drug of composition  20  can be any drug capable of being parenterally administered as a liquid or a semi-solid. For example, the drug can be a vaccine, a peptide, a protein, or a small chemical entity. Examples of suitable drugs include, e.g., insulin and heparin. For drugs which are not stable in liquids over an extended period of time, the liquid and the dry drug can be stored in separate chambers within housing  10 . The device can be configured such that the liquid and the dry drug are combined together just prior to injection.  
         [0094]    For example, the chamber created between septum plunger  16  and plunger tip  30  (e.g. in FIG. 1) in housing  10  can be separated into two separate parts by a fixed wall or film that can be punctured, e.g. by pressure of the plunger  29  on the plunger tip  30 , or a puncturing means. Alternatively, the two parts of the chamber can be separated by a moving wall or septum. In this case, the top or proximal part of the chamber above the moving wall or septum contains the liquid portion of the composition, and the distal part of the chamber contains the solid, e.g., powder, portion of the composition. When plunger  29  is urged into housing  10 , it applies pressure to plunger tip  30  and plunger tip  30  applies pressure to the liquid portion of the composition. This, in turn, applies pressure on the moving septum, causing it to move in a distal direction. The housing is configured with a liquid bypass (e.g., a bulge or passage in the housing wall) in a location that initially prevents passage of liquid from one part of the chamber to the other, but when the moving septum reaches a specific location, the bypass allows the liquid to pass from the top or proximal part of the chamber into the lower or distal part of the chamber on the other side of the moving septum.  
         [0095]    To maintain sterility, the device of the invention can be stored in a conventional blister pack or pouch prior to use.  
       OTHER EMBODIMENTS  
       [0096]    It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the appended claims. Other aspects, advantages, and modifications are within the claims.