Abstract:
A multi-stage drug administration device which, after connection to a standard IV port in the arm of a patient, administers the entire batch of drugs required by a patient automatically. The inventive device operates without any required stages of flushing, requiring no further supervision by a medical operative, thereby saving manpower and enabling full mobility of the patient while the drugs are being administered.

Description:
FIELD OF THE INVENTION  
       [0001]     The present invention relates to an apparatus and method for dispensing therapeutic drugs via infusion.  
       BACKGROUND OF THE INVENTION  
       [0002]     In the field of drug administration, there are many cases in which it is required to administer to a patient several types of drugs in series, via a standard IV port located in a patient&#39;s arm or other accessible vein. This normally requires a number of steps, including the following: first, flushing the IV port with a saline solution by means of a syringe; second, connecting to the IV port an infusion bag containing a first drug; third, after the entire amount of drug has been administered, removing the infusion bag and repeating the step of flushing; fourth, connecting to the IV port an infusion bag containing a second drug. This process is repeated for as many drugs as are required to be administered.  
         [0003]     A disadvantage with the above-described process, is that it is labor intensive, requiring a medical operative to perform all the stages of connecting and disconnecting the syringes and infusion bags, and that it also substantially immobilizes the patient, until the entire batch of drugs has been fully administered.  
         [0004]     Therefore, it would be desirable to provide an apparatus which simplifies the administration to a patient of a batch of drugs.  
       SUMMARY OF THE INVENTION  
       [0005]     Accordingly, it is a principal object of the present invention to overcome the disadvantages of prior art drug administration procedures and provide a multi-stage drug administration device which, after connection to a standard IV port in the arm of a patient, administers the entire batch of drugs required by a patient automatically. The inventive device operates without any required stages of flushing, requiring no further supervision by a medical operative, thereby saving manpower and enabling full mobility of the patient while the drugs are being administered.  
         [0006]     There is thus provided, in accordance with a preferred embodiment of the invention, a multi-stage drug administration device for administering a sequence of pharmacological agents to a patient, which includes:  
         [0007]     a generally cylindrical housing having distal and proximal ends, having formed at the distal end an outlet port for connection to an IV port; and  
         [0008]     at least first and second compressible, mutually sealed chambers located within the housing between the distal and proximal ends, for containing therebetween in mutual isolation a corresponding plurality of pharmacological agents for sequential administration to a patient, wherein a rupture susceptible portion of a common dividing wall between adjacent chambers is adapted to rupture in the presence of at least a critical pressure differential thereacross,  
         [0009]     wherein upon exposure to a predetermined source of pressure associated with the proximal end of the housing, the plurality of sealed chambers becomes compressed towards the distal end so as to cause an outflow of the pharmacological agent in the first chamber through the outlet port,  
         [0010]     and wherein, at the time of emptying of the first chamber, the pressure differential across the rupture susceptible portion of the common dividing wall reaches the critical pressure differential causing rupture thereof, and a consequent outflow of the pharmacological agent contained in the second chamber through the outlet port.  
         [0011]     Additionally in accordance with a preferred embodiment of the present invention, the common dividing wall is a disk-shaped piston spaced apart along the length of the cylinder, each piston being circumferentially sealed with an interior wall surface of the cylinder, thereby to form the plurality of chambers, each piston being adapted to rupture in the presence of the critical pressure differential.  
         [0012]     Additionally in accordance with a preferred embodiment of the present invention, the device also includes puncturing apparatus located at the distal end, for puncturing a piston proximal thereto, in the presence of the critical pressure differential.  
         [0013]     Additionally in accordance with a preferred embodiment of the present invention, each piston has formed thereon additional puncturing apparatus for puncturing an adjacent piston when brought into proximity therewith.  
         [0014]     Additionally in accordance with a preferred embodiment of the present invention, each chamber includes a volume of a preselected pharmacological agent, contained within an impervious membrane.  
         [0015]     Additionally in accordance with a preferred embodiment of the present invention, the impervious membrane is a flexible membrane.  
         [0016]     In accordance with an alternative embodiment of the present invention, there is provided a multi-stage drug administration system for administering a sequence of pharmacological agents to a patient, which includes:  
         [0017]     a generally cylindrical housing having distal and proximal ends, having formed at the distal end an outlet port for connection to an IV port;  
         [0018]     at least first and second compressible, mutually sealed chambers located within the housing between the distal and proximal ends, for containing therebetween in mutual isolation a corresponding plurality of pharmacological agents for sequential administration to a patient, wherein a rupture susceptible portion of a common dividing wall between adjacent chambers is adapted to rupture in the presence of at least a critical pressure differential thereacross; and  
         [0019]     a source of pressure associated with the proximal end of the housing,  
         [0020]     wherein upon exposure to the pressure source, the plurality of sealed chambers becomes compressed towards the distal end so as to cause an outflow of the pharmacological agent in the first chamber through the outlet port,  
         [0021]     and wherein, at the time of emptying of the first chamber, the pressure differential across the rupture susceptible portion of the common dividing wall reaches the critical pressure differential causing rupture thereof, and a consequent outflow of the pharmacological agent contained in the second chamber through the outlet port.  
         [0022]     In accordance with yet a further embodiment of the present invention, there is provided a multi-stage drug administration system for administering a sequence of pharmacological agents to a patient, which includes: 
        a plurality of mutually connectable sealed modules, each containing a preselected pharmacological agent, arranged in a connected stack which includes a proximal end module and a distal end module;     a dispensing module connected to the distal end module;     and a pressure module, for connecting a source of pressure to the proximal end module.        
 
         [0026]     The multi-stage drug administration system may further comprise a housing and a drive element, wherein said housing is adapted for disposing the modules and the drive element therewithin such that the drive element is in contact with the proximal module, and for attaching the dispensing module to a distal end thereof and the pressure module to a proximal end thereof.  
         [0027]     The housing of the multi-stage drug administration system may comprise one or more narrow openings through which portions of stopper pins may be externally introduced into the interior of the housing such that drug administration is halted whenever the drive element reaches the location of a stopper pin which blocks further advancement thereof.  
         [0028]     Additional features and advantages of the invention will become apparent from the following drawings and description. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0029]     For a better understanding of the invention with regard to the embodiments thereof, reference is made to the accompanying drawings, in which like numerals designate corresponding sections or elements throughout, and in which:  
         [0030]      FIGS. 1A-1C  are schematic representations of a multi-stage drug administration device, constructed and operative in accordance with a first embodiment of the invention;  
         [0031]      FIG. 2  is a variation of the embodiment of  FIGS. 1A-1C ;  
         [0032]      FIG. 3  is yet a further variation of the embodiment of  FIGS. 1A-1C ;  
         [0033]      FIGS. 4A-4C  illustrate a device which is generally similar to that depicted in  FIGS. 1A-1C , but having a modular construction, in accordance with an alternative embodiment of the present invention;  
         [0034]      FIGS. 5A-5E  illustrate a quasi-modular drug administration device, constructed in accordance with yet a further embodiment of the present invention;  
         [0035]      FIGS. 6A-6D  illustrate a quasi-modular drug administration device constructed in accordance with an additional embodiment of the present invention;  
         [0036]      FIG. 6E  illustrates a collapsible module employed in the embodiment of  FIGS. 6A-6D , in a compressed configuration, prior to use;  
         [0037]      FIG. 6F  illustrates the collapsible module of  FIG. 6E , in an expanded configuration;  
         [0038]      FIGS. 7A-7B  illustrate a variation of the device of  FIGS. 6A-6E ; and  
         [0039]      FIGS. 8A-8D  illustrate a quasi-modular drug administration device wherein the drug administration may be halted at predetermined stages of administration. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0040]     Referring now to the drawings generally, there is provided a multi-stage drug administration device for administering a sequence of pharmacological agents to a patient. While each different embodiment shown and described hereinbelow has specific features special to that embodiment, various features of the present invention may be found in all embodiments, either in an identical form, or in a form whose function or purpose is equivalent to those in other embodiments; these features are thus are not described separately with regard to each embodiment, except as may be required for an understanding of that embodiment, and are denoted in the drawings by reference numerals which are the same throughout, except for the addition of a prefix indicating the Figure numbers. Thus, for example, the multi-stage drug administration device of the invention is referenced  100  in  FIGS. 1A-1C ,  200  in  FIG. 2 , and  300  in  FIG. 3 , and so on. Furthermore, features common to more than one embodiment of the invention will normally be described with respect to the first embodiment in which they occur only, unless otherwise required for an understanding of the later embodiment.  
         [0041]     Referring now to  FIGS. 1A-1C , device  100  is formed of a generally cylindrical housing, referenced  110 , having distal and proximal ends, respectively referenced  112  and  114 . An outlet port  116 , adapted for connection to an IV port (not shown), is provided at distal end  112 , and a driver  118  is arranged in association with proximal end  114 .  
         [0042]     In the present embodiment, it is seen in  FIG. 1A  that in an initial position, prior to use, a plurality of compressible, mutually sealed chambers a, b, c, and d is contained within the housing  110  between the distal and proximal ends  112  and  114 , each containing in mutual isolation a plurality of pharmacological agents for sequential administration to a patient.  
         [0043]     In the present embodiment, the chambers a, b, c and d are formed between a plurality of partitions  120 A,  120 B,  120 C,  120 D, each formed as a movable piston which is sealed against the inner face  122  of housing  110  by a suitable seal, referenced  124 . Typically all but the rearmost partition  120 D are further formed to include a rupture susceptible portion, shown schematically at  126 A,  126 B and  126 C, which are adapted to rupture in the presence of at least a critical pressure differential thereacross or shearing force applied thereto. In the present embodiment, there is provided a rupture element  128  which is seen, by way of example, to be formed as a hollow spike formed contiguously with outlet port  116 . As each partition has a predetermined thickness, and it is desired to completely empty the chamber immediately distal thereto, the rupture susceptible portions are formed to accommodate the hollow spike at positions which require a previous emptying of the immediately preceding chamber.  
         [0044]     Driver  118  may be any suitable means for forcing the partitions  120  towards the distal end  112  of the housing. In the present embodiment driver  118  is exemplified as a liquid or gas pressure source, such as an aerosol or other suitable pressurized fluid source, although it could equally be a mechanical driving means, spring-driven or the like, so as to provide a driving force which is sufficient to dispense the pharmacological agents contained in device  100  of the invention, at a predetermined, desired rate.  
         [0045]     It is an aim of the present invention to provide a multi-stage drug administration device which is not merely easy to use, but which may also be pre-filled in the factory, with attendant advantages to drugs manufacturers. Accordingly, while different embodiments of the present invention provide different ways to achieve this, as described hereinbelow, in the present embodiment, there is provided a plurality of filler ports  130 , spaced along the length of the housing  110 , in registration with the chambers A-D, to be filled. Preferably, a plurality of bleeding ports  132  is also provided, so as to enable bleeding of each chamber as it is filled. Clearly, once each chamber is filled, each of the ports  130  and  132  associated therewith is sealed by means of a suitable cap  134 .  
         [0046]     It will thus be appreciated that the use of device  100  is as follows:  
         [0047]     Initially, the partitions  120  are arranged in the positions illustrated in  FIG. 1A . Clearly, while the chambers are seen to have similar volumes, the partitions  120  may be arranged, prior to filling, so as to have different volumes, corresponding to different quantities of different pharmacological agents, as may be required.  
         [0048]     Once the chambers have been filled and the ports  130  and  132  sealed, an outlet cap  136  ( FIG. 1A ) is removed, in order to enable outlet port  116  to be connected to an IV port, or the like.  
         [0049]     The agent in chamber A is then dispensed by operation of driver  118  which, as mentioned above, is typically a suitable fluid pressure source. Pressurization of the interior of housing  110  between the rearmost partition  120 D, closest to proximal end  114 , causes the application of a driving force to rearmost partition  120 D, and consequently, on the entire array of partitions and the pharmacological agents contained therebetween in chambers A-D, so as to cause the agent contained in chamber a to be dispensed through outlet port  116 .  
         [0050]     As seen with reference to  FIGS. 1A and 1B , as partition  120 A approaches distal end  112  of the housing  110 , the rupture susceptible portion  126 A of partition  120 A accommodates almost the entire length of hollow spike  128 , until it becomes punctured by the spike  128 , as shown in  FIG. 1B . At this point, chamber A has been completely emptied, and the agent contained in chamber B begins flowing out through outlet port  116 , via spike  128 .  
         [0051]     It will be appreciated that as the driving pressure is sustained, the contents of the entire device  100  are dispensed as each partition is ruptured by spike  128 , and each successive chamber is exhausted, thereby completing the administration of the desired pharmacological agents in a manner which, after initialization, is entirely automatic, and does not require the presence or intervention of medical personnel.  
         [0052]     As mentioned above, the basic characteristics of the invention are present in each of the embodiments; each embodiment now being described specifically in respect of its specific features, in conjunction with  FIGS. 2-7B , as follows:  
         [0053]     Referring now to  FIG. 2 , there is provided a multi-stage infusion device  200  which is generally similar to device  100  shown and described above in conjunction with  FIGS. 1A-1C , except for the provision of a single spike  228  for rupturing partitions  220 A- 220 C during dispensing of the agents contained in the various chambers of the device, as these are driven by driver  218 . As seen in the drawings, in the present embodiment, driver  218  is exemplified as a resilient compression member, located within a proximal end portion  214  of housing  210 , so as to abut partition  220 D.  
         [0054]     In the case of the embodiment of  FIG. 3 , it is seen that the single rupture element of the previous embodiments is replaced by a first rupture element  328  formed within housing  310  adjacent to the outlet port  316 , and which is operative to rupture partition  320 A upon engagement therewith; and smaller, proximally facing rupture elements  328 A and  328 B, operative to rupture partitions  320 B and  320 C when engaged therewith.  
         [0055]     Referring now to  FIGS. 4A-4C , it is seen that the housing of device  400  of the present invention may be formed in segments or stages, respectively referenced  410 A- 410 D, which connect together as via screw threads  421  and  423 . Each segment includes a single chamber which may be pre-filled with any agent required, and which includes a pair of piston like partitions, generally similar to partitions  120  in the embodiment of  FIGS. 1A-1C . The exception to this is distal segment  410 A which typically has a single partition  420 A only, and which is formed so as to include outlet port  416 . In the present embodiment there is also typically provided an additional, proximal end portion  419 , associated with driver  418 . As seen in the drawings, driver  418  is a pressurized liquid/gas source, operative to drive the partitions and chambers, substantially as shown and described above in conjunction with the embodiment of  FIGS. 1A-1C , but with an intervening inflatable drive element  417 .  
         [0056]     Referring now to  FIGS. 5A-5E , in accordance with a further embodiment of the invention, there is provided a multi-stage drug administration device  500 , which is also formed with a plurality of segments or stages, as in the embodiment of  FIGS. 4A-4C . In the present embodiment however, the different stages are formed so as to be nestable within each other, and so as to have cylindrical housing portions  510 A- 510 D, which nest within each other and which are housed when fully assembled, in housing  510 .  
         [0057]     As seen, each segment encloses a chamber containing a pharmacological agent as desired, and has a distal end  550  which incorporates an outlet portion  552 , and a proximal end  554  in which is disposed a partition  520 . Each chamber is filled via outlet portion  552 , and is then positioned in abutting engagement with a central, rupture susceptible portion  526  of partition  520 . Once assembled, as seen in  FIG. 5B , and the assembly is placed within housing  510 , an inflatable drive element  517  is then inserted behind and in touching engagement with the proximal partition  520 D, as seen in  FIG. 5D . Subsequently, housing  510  is closed by an end cap  556 , through which a driver  518 , exemplified herein as a pressurized liquid/gas source, is placed in operative contact with drive element  517 , as seen in  FIG. 5D .  FIG. 5E  illustrates the device  500  after use.  
         [0058]     Referring now to  FIGS. 6A-6D , there is also provided a multi-stage drug administration device  600  which employs a plurality of pre-filled, pre-sealed, collapsible modules  660 . As seen in  FIG. 6E , each module  660  is concertina-shaped and has a first rupture susceptible portion  626 ′ on a proximal side thereof and a second rupture susceptible portion  626 ″ on a distal side. These rupture susceptible portions are adapted to rupture when subjected to a predetermined driving force, as described hereinabove.  
         [0059]     Preferably, the first and second portions  626 ′ and  626 ″ are formed as female and male portions, and so as to matingly engage a corresponding portion of an adjacent module, so that an assembly of the modules  660  can be packed together in a desired sequence ( FIG. 6A ), and then loaded into housing  610 . As seen in  FIGS. 6B and 6C , a drive element  617 , illustrated herein as a piston, is then inserted behind and in touching engagement with the proximal module  660 D, and the housing  610  is closed by an end cap  656 , through which a driver  618 , exemplified herein as a pressurized liquid/gas source, is placed in operative contact with drive element  617 .  FIG. 6D  illustrates the device  600  after use.  
         [0060]     Referring once more to  FIGS. 6E and 6F , in accordance with one embodiment of the invention, collapsible module  660  may be manufactured in a flat pack configuration, illustrated in  FIG. 6D , and so as to be expandable to the configuration seen in  FIG. 6F . This is facilitated by the provision of inward facing teeth  670 , which are adapted to grip the inward-facing side  672  of first rupture susceptible portion  626 ′, thereby to substantially prevent any undesired expansion of module  660 , prior to use thereof. When it is desired to fill module  660 , it may be manually expanded, either before or during filling with a desired pharmacological agent.  
         [0061]     Referring now to  FIGS. 7A-7B , device  700  is generally similar to device  600 , except that modules  760  are typically smooth walled, preferably being formed of a thin polymer membrane. Furthermore, rupture element  728  is, in the present embodiment, exemplified as a hollow spike, as shown and described above in conjunction with  FIGS. 1A-1C . Operation of device  700  by exposure to the pressurized liquid/gas contents of driver  718  is operative to force drive element  717  from its initial, proximal position, shown in  FIG. 7A , towards the distal end  712 . As this happens, it forces each module in succession into puncturing contact with spike  728 , thereby causing the contents of each module to be dispensed successively, in order to provide a user with a predetermined, desired sequence of medication therapy.  
         [0062]     Referring now to  FIGS. 8A-8D , there is also provided a multi-stage drug administration device  800  which employs a plurality of pre-filled, pre-sealed, collapsible modules  860 . In this preferred embodiment of the invention each module  860  is concertina-shaped and has a first and second rupture susceptible portions on proximal and distal sides thereof, respectively, as in the embodiment shown in  FIGS. 6A  to  6 F, which was described in details hereinabove. Similarly, the first and second rupture susceptible portions may be formed as matingly engageble female and male portions, so that an assembly of the modules  860  can be packed together in a desired sequence, and then loaded into housing  810 . A drive element  817 , illustrated herein as a piston, is then inserted behind and in touching engagement with the proximal module  860 D, and the housing  810  is closed by an end cap  856 , through which a driver  818 , exemplified herein as a pressurized liquid/gas source, is placed in operative contact with drive element  817 .  
         [0063]     The drug administration in this preferred embodiment may be halted at predetermined stages of drug administration by stopper pins  891 . For this purpose narrow openings  890  are provided on the outer surface of housing  810  such that a portion of said stopper pins  891  may be externally introduced into the interior of housing  810  via said openings  890 , such that said opening  890  are sealed by said stopper pins  891 . As demonstrated in  FIGS. 8A-8D , the drug administration is carried out by the application of pressurized gas/liquid through the end cap  856  via driver  818  attached thereto. If stopper pins  891  are present the advancement of drive element  817  is stopped whenever it reaches the location of a stopper pin  891 .  
         [0064]     In the example shown in  FIG. 8B  the drug administration is stopped when drive element  817  reaches the location in which stopper pin  891 B is placed such that only the agent in the first module  860 A is dispensed. As demonstrated in  FIG. 8C , drug administration may continue by removal of stopper pin  891 B, and in this example the drug administration will proceed until drive element  817  reaches the location in which stopper pin  891 A is placed, such that the agent in the second module  860 B is dispensed. Accordingly, the agents in the third and fourth modules,  860 C and  860 D respectively, may be dispensed by removing stopper pin  891 A.  FIG. 8D  illustrates the device  800  after dispensing all the modules  860 .  
         [0065]     Collapsible module  860  may be manufactured in a flat pack configuration, similar to that shown in  FIG. 6D , which is expandable to the configuration shown in  FIG. 6F . Similarly, an inward facing teeth ( 670  in  FIG. 6F ) may be utilized to grip an inward-facing side ( 672  in  FIG. 6F ) of the first rupture susceptible portion, thereby to substantially prevent any undesired expansion of modules  860 , prior to use thereof.  
         [0066]     It will be appreciated by persons skilled in the art that the scope of the present invention is not limited by what has been specifically shown and described above in conjunction with the drawings. Rather, the scope of the invention is limited solely by the claims, which follow.