Abstract:
The present disclosure refers to hand operated disposable devices for the administration of drugs, vaccines and other medicaments in the form of solid injectable needles. The devices incorporate mechanisms for the automatic retraction of the injection rod even when the user continues to exert pressure on the device. The devices can incorporate an injectable needle in a sheath or cartridge that facilitates its manufacture and manipulation. These injection devices can only be used once and their use results in a change of configuration that renders them non operational and prevents contact with parts that have been exposed to the patient&#39;s tissues.

Description:
FIELD OF INVENTION 
       [0001]    The invention refers to hand operated disposable devices for the administration of drugs and vaccines in the form of solid injectable needles. The devices are an alternative to conventional needle and syringe devices, and avoid the need for reconstitution, refrigeration and trained personnel in the administration of drugs and vaccines. 
       BACKGROUND 
       [0002]    Many drugs and vaccines are administered parenterally by means of injection by medically trained personnel. This involves a first step of reconstitution of the medicament with sterile water for injection, a second step for loading a syringe with an appropriate volume of the dissolved drug, a third step for assembling a sterile needle for injection, a fourth step of administration to the patient by injection, and a final step for safe disposal of the used device. This injection process can be problematic, especially in geographic locations with limited resources. In particular many medicaments require refrigeration in their transport and storage, and failure in maintaining the cold chain can result in significant wastage. More so, the need for reconstitution with sterile water can also be a problem in cases of microbial contamination or use of incorrect reconstitution volumes. Furthermore, the reuse of syringes and needles represents a serious global health problem due to the potential transmission of infectious agents such as Hepatitis or HIV. These problems are specially acute in the administration of vaccines in the developing world, where the World Health Organisation has for long recognised the need for alternative methods (Jodar L. et al. 1998. Revolutionising Immunisations. Gen. Eng. News 18-4). 
         [0003]    An alternative method proposed in the administration of medicaments incorporates the administration of solid injectable needles with enough strength and hardness that permits their injection. Once these needles are injected they dissolve or degrade to liberate the medicament. Examples of these injectable needles are illustrated in WO/03023773, and U.S. Pat. No. 6,102,896. If formulated appropriately, injectable needles should avoid the need for refrigeration, reconstitution and use of conventional stainless steel hypodermic needles in the administration of medicaments. 
         [0004]    The administration of medicaments in the form of solid injectable needles requires the appropriate devices. Examples of these include those proposed in U.S. Pat. No. 5,542,920 that describes simple devices for the administration of injectable needles which have a sharp tip and are hard enough to penetrate the skin. More so, U.S. Pat. No. 6,102,896 describes an injector for the administration of injectable needles that incorporates breakable tabs that facilitate injection. Injection of injectable needles by means of the devices described in the preceding documents is carried out by direct manual compression action by the user over an actuator. These devices have the inconvenient that the retraction of the injection rod requires the user to liberate the device from the pressure used for the injection, or the removal of the device from immediate contact with the skin. This can result in the injection rod remaining in the body for longer than required and undesirable pain. More so, these devices can be reused or result in accidental third party contamination through accidental contact with the injection rod which has penetrated the patients skin. Furthermore, none of these documents describes methods or designs that facilitate loading the injectable needles into the injectors. 
         [0005]    More recently, WO/03023773 proposes injectable needles composed of a solid soluble tip followed by the medicament in the form of a liquid, a paste or a solid. The devices described incorporate a disposable head section and a reusable body. In these devices the user loads the device by means of extending the device and compression of an internal spring. Triggering the device results in the extension of the spring and impact of a piston with another piston attached to the injection rod which pushes forward the injectable needle containing the medicament. The device incorporates a simple mechanism that allows for a small retraction of the injection rod and in its realisation it describes that the injection rod penetrates the skin just enough for the injectable needle to cross the superficial skin. One limitation of the design is that the injectable needles cannot be injected at any significant depth. This can be a serious problem in the administration of medicaments that require a greater injection depth as is the case for most vaccines with optimum depths between 10 mm and 25 mm. Furthermore, the invention focuses on complex devices that can be reused by means of exchangeable head pieces but that presumably have a high economic cost. 
         [0006]    In general, previous designs do not allow for simple disposable devices that permit a deep injection and the automatic retraction of the injection rod, to provide efficacious rapid and painless injection while avoiding possible reutilisation of the device and possible third party infection through accidental contact with the injection rod. 
         [0007]    It is therefore desirable to have simple disposable devices for the injection of injectable needles containing a medicament at the required depth and that, a) facilitate the manufacture and loading of the injectable needle into the injection device, b) have a mechanism that results in a rapid entry and retraction of the injection rod that pushes forward the injectable needle, and c) that incorporate mechanisms that avoid their reuse and risk of third party contamination. 
       SUMMARY 
       [0008]    The administration of medicaments in the form of injectable needles by means of simple devices avoids the need for trained personnel, cold chain, reconstitution with water for injection, and possible reuse of needles and syringes. This is of particular interest in human health, especially in the developing world or in situations that require self administration of a medicament. The present invention describes simple single use disposable devices for the administration of medicaments in the form of solid injectable needles. The devices incorporate in their design mechanisms that permit the administration of injectable needles at depths up to 25 mm, the automatic retraction of the injection rod once the injection is completed, and the inactivation of the device. The devices can also be made to incorporate a sheath to contain the injectable needle and facilitate its manipulation and manufacture. 
     
    
     
       DESCRIPTION OF FIGURES 
         [0009]      FIGS. 1A-G . Show a realisation of a device for the injection of injectable needles with a retractile injection rod that automatically retracts after rotation of an internal plunger induced by a tab. 
           [0010]      FIGS. 1A-C  depict longitudinal section views, between opposite corners of its square section, of an injection device at different times during its utilisation.  FIG. 1A  shows the device prior its operation by the user by exerting force on the actuator  101 .  FIG. 1B  shows the device at the moment of maximum penetration in the skin  100  of the injection rod  104  and the injectable needle  108 , rotation of the internal plunger  103 , and liberation of the spring  105  to allow for the retraction of the internal plunger  103  and the injection rod  104  in the direction of the arrow.  FIG. 1C  depicts the final position of the different parts of the device after extension of the spring  105 , retraction of the internal plunger  103  and the injection rod  104 . In this position the device is disabled and ready for its disposal.  FIGS. 1D-E  show different views of transversal sections of the device at the level of the tabs  109 .  FIG. 1D  shows the position of the tabs  109  and the internal plunger  103  before the utilisation of the device as is depicted in  FIG. 1A .  FIG. 1E  shows the point of maximum penetration of the injection rod  104  represented by  FIG. 1B , at which point the internal plunger  103  rotates in the direction shown by the arrow and is liberated from the tabs  109 . 
           [0011]      FIGS. 1F-G  shows the arrangement of the internal plunger  103 , the body of the injector  106 , and the arrangement of the tabs  110  and  111 .  FIG. 1F  shows the moment immediately before the interaction of the tabs  110  and  111  which have an oblique vertical section. The arrow indicates the direction of the vertical movement of the internal plunger  103 .  FIG. 1G  depicts the rotation mechanism of the internal plunger  103  in the direction of the arrow induced by the descending movement of the internal plunger  103  and interaction of tabs  110  and  111  at the moment of maximum penetration of the injection rod  104  represented in  FIG. 1B . 
           [0012]      FIGS. 2A-F . Show a realisation of a device for the injection of injectable needles with a retractile injection rod that automatically retracts after rotation of an internal plunger induced by guides. 
           [0013]      FIGS. 2A-C  depict longitudinal section views, coinciding with the tabs  209 , of an injection device at different times during its utilisation. 
           [0014]      FIG. 2A  shows the device prior its operation by the user by exerting force on the actuator  201 .  FIG. 2B  shows the device at the moment of maximum penetration in the skin  200  of the injection rod  204  and the injectable needle  208 , rotation of the internal plunger  203 , and liberation of the spring  205  to allow for the retraction of the internal plunger  203  and the injection rod  204  in the direction of the arrow.  FIG. 2C  depicts the final position of the different parts of the device after extension of the spring  205 , retraction of the internal plunger  203  and the injection rod  204 . In this position the device is disabled and ready for its disposal.  FIGS. 2D-E  depict transversal sections of the device at the level of the tabs  209 , showing the internal plunger  203 , the guides  211  and the longitudinal apertures  210  in the body  206  of the injector.  FIG. 2D  shows a transversal section of the device prior its utilisation as is shown in FIG.  2 A, and the arrangement of the tabs  209  against the internal plunger  203 .  FIG. 2E  shows the point of maximum penetration of the injection rod  204  represented by  FIG. 2B , at which point the internal plunger  203  is forced to rotate by the guides  211  in the direction shown by the arrow and is liberated from the tabs  209 .  FIG. 2F  shows a longitudinal section of the injector body  206  that incorporates a tubular sheath  207  and septa  212  covering the injectable needle  208 . 
           [0015]      FIGS. 3A-F . Show a realisation of a device for the injection of injectable needles with a retractile injection rod that automatically retracts after the deformation of tabs. 
           [0016]      FIGS. 3A-C  depict longitudinal section views of an injection device at different times during its utilisation.  FIG. 3A  shows the device prior its operation by the user by exerting force on the actuator  301 .  FIG. 3B  shows the device at the moment of maximum penetration in the skin  300  of the injection rod  304  and the injectable needle  308 , deformation or rupture of tabs  310 , and liberation of the spring  305  to allow for the retraction of the internal plunger  303  and the injection rod  304  in the direction of the arrow. 
           [0017]      FIG. 3C  shows the final position of the different parts of the device after extension of the spring  305 , retraction of the internal plunger  303  and the injection rod  304 . In this position the device is disabled and ready for its disposal. 
           [0018]      FIGS. 3D-E  depict transversal sections of the device at the level of the tabs  310 , showing the internal plunger  303 , the rods  309 , the tabs  310  and spring  305 .  FIG. 3D  shows the device prior its utilisation as is shown in  FIG. 3A , and the arrangement of the tabs  310  preventing the retraction of the internal plunger  303 .  FIG. 3E  shows the point of maximum penetration of the injection rod  304  represented by  FIG. 3B , at which point the tabs  310  are broken or deformed, liberating the rods  309  and permitting the automatic retraction of the internal plunger  303  by the action of the spring  305 . 
           [0019]      FIGS. 3F-G  show longitudinal sections of the device at the level of tabs  310 .  FIG. 3F  shows the arrangement of the tabs  310  and the wedges  311  prior utilisation of the device as is shown in  FIGS. 3A and 3D .  FIG. 3G  shows the arrangement of tabs  310  and wedges  311  at the point of maximum penetration of the injection rod  304 , as depicted in  FIGS. 3B and 3E . At this moment the tabs  310  come into contact with the wedges  311  and are broken or deformed in the direction of the arrows, liberating the rods  309  and permitting the retraction of the internal plunger  303 . 
           [0020]      FIGS. 4A-E . Show a realisation of a device for the injection of injectable needles with a retractile injection rod that automatically retracts by means of apertures in the actuator. 
           [0021]      FIGS. 4A-C  depict longitudinal section views of an injection device at different times during its utilisation.  FIG. 4A  shows the device prior its operation by the user by exerting force on the actuator  401 .  FIG. 4B  shows the device at the moment of maximum penetration in the skin  400  of the injection rod  404  and the injectable needle  408 , deformation of the apertures  410  induced by the conical shape elevation  411 , and liberation of the internal plunger  403  from the tabs  409 . The direction of the arrow indicates the retraction movement induced by the spring  405  over the internal plunger  403  and the injection rod  404  once these are liberated from the tabs  409 .  FIG. 4C  shows the final position of the different parts of the device after extension of the spring  405 , retraction of the internal plunger  403  and the injection rod  404 . In this position the device is disabled and ready for its disposal. 
           [0022]      FIGS. 4D-E  depict transversal sections of the device at the level of the tabs  409  showing the internal plunger  403 , the actuator  401 , the tabs  409  and the apertures  410 .  FIG. 4D  shows the device prior its utilisation as is shown in  FIG. 4A , and the arrangement of the tabs  409  preventing the retraction of the internal plunger  203 .  FIG. 4E  shows the point of maximum penetration of the injection rod  404  represented by  FIG. 4B , at which point the elevation  411  causes the apertures  410  of the actuator  401  to deform and open, liberating the internal piston  403  from the tabs  409 . 
       
    
    
     DETAILED DESCRIPTION 
       [0023]    The present invention incorporates simple single-use disposable devices for the administration of medicaments in the form of injectable needles at a depth up to 25 mm. The injectable needles administered with these devices are made to incorporate a medicament, are solid and hard enough to cross the skin. These needles can be formulated from amorphous or crystalline solids and can be made to be more or less soluble. The injectable needles have a diameter to length ratio between 1:15 and 1:5, a diameter between 0.2 mm and 1 mm, and a length between 1 mm and 10 mm. 
         [0024]    The devices are operated manually by compression in direct contact with the skin, and incorporate simple mechanisms for the automatic retraction of the injection rod that pushes the injectable needle. The automatic retraction of the injection rod originates a rapid and controlled exit of the injection rod even when the user continues to put pressure on the device actuator. This avoids the injector rod from being inside the patient&#39;s body for longer than is strictly necessary. More so, these mechanisms provide with devices that are rendered useless after their use and avoid possible third party contact with parts of the device that have been in direct contact with the patient&#39;s tissues. The ease in their operation facilitates the administration by untrained personnel and self administration of medicaments formulated as solid injectable needles 
         [0025]    The devices of the present invention, as illustrated with out limitation in  FIGS. 1A-G ,  2 A-F,  3 A-G y  4 A-E, incorporate an actuator  101 ,  201 ,  301  or  401  which receives the direct pressure exerted by the user to permit the advance of the internal plunger  103 ,  203 ,  303  or  403  on which the injector rod  104 ,  204 ,  304  or  404  is mounted. The injectable needle  108 ,  208 ,  308  or  408  is forced forward by the injector rod  104 ,  204 ,  304  or  404  into the patients tissues  100 ,  200 ,  300  or  400  to a depth up to 25 mm. The devices contain a spring  105 ,  205 ,  305  or  405  that is compressed as the internal plunger  103 ,  203 ,  303 , or  403  is forced to advance. Once the injection is completed, the compressed spring forces the retraction of the injection rod  104 ,  204 ,  304  or  404 . In a realisation of the present invention shown in  FIGS. 1A-G  the plunger  101  transmits the force exerted by the user to the internal plunger  103  by means of tabs  109 . Once the internal plunger  103  has traveled to the end of its path, it is liberated from the tabs  109  by a rotation movement of the internal plunger  103  forced by tabs with an oblique vertical section  110  y  111 . The liberation of the internal plunger  103  results in the extension of the spring  105 , the rapid retraction of the internal plunger  103  and the injection rod  104 . In its final position after use, the injector is deactivated and the injector rod is located hidden within the body of the injector. In this realisation, the square section of the injector permits the advance of the actuator  101  at the corners at the same time as the device provides lateral support to the spring  105  during its compression. 
         [0026]    In another embodiment of the present invention illustrated in  FIGS. 2A-F  an actuator  201  located concentrically outside the body  206  of the injector transmits the force exerted by the user to the internal plunger  203  by means of tabs  209  that come through the body  206  of the injector through longitudinal apertures  210 . Once the internal plunger  203  has traveled to the end of its path, it is freed from the tabs  209  by a rotating movement of the internal plunger forced by the guides  211  on the body  206  of the injector. This release of the internal plunger  203  from the tabs  209  permits the extension of the spring  205 , and originates in the rapid retraction of the internal plunger  203  and the injection rod  204 . In the final position after use, the injector is deactivated and the injector rod  204  located within the body  206  of the injector. 
         [0027]    In another embodiment of the present invention shown in  FIGS. 3A-G , the actuator  301  transmits the force exerted by the user to the internal plunger by means of rods  309  that come through the internal plunger  303  and are hooked to it by deformable tabs  310 . Once the internal plunger  303  has traveled to the end of is path, the tabs are deformed laterally or broken by the action of a wedge  311  located on the body of the injector. This results in the release of the internal plunger  303 , the extension of the spring  305  and retraction of the internal plunger and injector rod  304 . In the final position after use, the injector is deactivated and the injector rod  304  located within the body  306  of the injector. 
         [0028]    Yet in another embodiment of the present invention illustrated in  FIGS. 4A-E , the internal piston  403  is freed from the tabs  409  and the actuator  401  by deformation of the apertures  410 . The deformation of these apertures  410  is caused by the interaction of the actuator  401  and the conical protrusion  411  at the end of the path taken by the internal plunger  403 . Liberation of the internal plunger  403  from the tabs  409  permits the extension of the spring  405  originating the rapid retraction of the internal plunger  403  and the injector rod  404 . At its final position after use, the injector is deactivated and the injector rod  404  hidden within the body of the injector  406 . 
         [0029]    In another preferred embodiment of the present invention the devices can incorporate tabs  102 ,  202   302  or  402  that block the device prior to use and prevent the movement of the actuator  101 ,  201 ,  301  or  401  until the user exerts sufficient manual pressure. 
         [0030]    Furthermore, in another embodiment of the present invention, the devices can incorporate a sheath  107 ,  207 ,  307  or  407  that contains the injectable needle  108 ,  208 ,  308  or  408 . In one embodiment of the present invention the sheath  107 ,  207 ,  307  or  407  serves as a mould in the manufacture of the injectable needle  108 ,  208 ,  308  or  408 . This can facilitate the incorporation of the injectable needle  108 ,  208 ,  308  or  408  to the device in its final assembly during manufacture. More so, the sheath can incorporate septa  212  that keep the injectable needle  108 ,  208 ,  308  or  408  within the sheath  107 ,  207 ,  307  or  407  prior to the device being used, and that are pierced by the injector at the time of injection. 
         [0031]    Devices as those described in the present invention permit the injection of injectable needles containing medicaments as is illustrated, with out limitation, in the following examples. The devices are preloaded and simple to use by an unskilled operator exerting hand pressure on the device. The use of these devices preloaded with drugs, vaccines and other medicaments is of special interest in the developing world. 
       Example 1 
     Injection of Injectable Needles Made from Calcium Salts by Means of an Injector that Incorporates Mechanisms for the Automatic Retraction of the Injection Rod and Inactivation of the Device 
       [0032]    A prototype as represented in  FIGS. 1A-G  was loaded with an injectable needle based on a cement mixture resulting from the reaction of 0.7 g of tetracalcium phosphate [Ca 4 PO 4 O 2 ] and 1.8 g of calcium hydrogenphosphate [CaHPO 4 ], in 1 ml of a 0.5 M of de disodium hydrogen phosphate [Na 2 HPO 4 ]. The mixture was made to contain crystal violet as a model medicament. Prior to hardening, the mixture is introduced in Teflon tube with 0.4 mm internal diameter and 1.57 mm external diameter, which is used as a mould and the mix is pressed lightly with a concave piston to conform a sharp point. 
         [0033]    Following this, the hardened needle container within the mould was introduced in a 1.57 mm orifice on the head of the injector device. Operation of the injector permitted the injection of the injectable needle in a model human tissue up to a depth of 25 mm.