Patent Publication Number: US-2009240208-A1

Title: Microparticle delivery syringe and needle for placing particle suspensions and removing vehicle fluid

Description:
FIELD OF THE INVENTION 
     The present invention relates to a microparticle delivery device, and, more specifically, to a dual-chambered syringe having a bifurcated needle with lumens in fluid communication with respective chambers. The device allows the injection of a suspension of microparticles and the subsequent removal of the fluid delivery media. 
     BACKGROUND OF THE INVENTION 
     Microparticles are generally defined as being particles between 0.1 to 100 microns in size and can be formed from a variety of materials, including proteins, polymers, polysaccharides and combinations thereof. It is known in the art to use microparticles for a variety of purposes, including use as carriers of active pharmaceutical substances. Because of certain requirements imposed upon the delivery of pharmaceuticals via microparticles, it is desirable that the microparticles have a substantially spherical shape and a narrow size distribution. Microparticles used for such purposes are often delivered by injection through a syringe. When delivered by this route, the microparticles may be in suspension in an aqueous solution. 
     Microparticles are typically suspended in solution for injection into a target space, which may be, for example, an anatomical space in a patient (human or otherwise), or other confined spaces, such as refillable implantable pumps, venous access ports and the like. Such target spaces may be small and therefore may limit the amount of microparticles that can be delivered. It would be desirable to be able to remove the suspension fluid after delivering the microparticle suspension into the target space so that another injection could be administered until the space is filled with the maximum or desired amount of microparticles. Hence, it would be desirable to have a device that allows the removal of the suspension fluid, without removing the therapeutic microparticles. This would allow room in the target space for an additional injection of suspended microparticles. 
     SUMMARY OF THE INVENTION 
     The objectives of the invention can be realized by administrating a microparticle suspension using a bifurcated syringe device having two chambers and a needle with two lumens, one lumen being fluidly connected to each chamber. One chamber of the device is filled with the microparticle suspension, while the other chamber remains empty or primed with a suitable fluid. Pushing the plunger of the chamber containing the microparticle suspension injects the suspension through one lumen of the needle and into the target space. Thereafter, a reverse motion of the plunger in the other chamber creates a negative pressure that pulls the suspension fluid from the target space through a filter disposed in the second lumen, the filter having pores smaller than the diameter of the microparticles which were injected. The microparticles will therefore remain in place within the target space when the fluid is removed. The removed fluid is contained in the second chamber, separate from the first chamber holding the microparticle suspension. 
     Once a volume has been withdrawn, which may be, for example, equal to or less than the fluid volume of the microparticle suspension, another injection of the suspension can be administered and the process repeated as desired until the maximum or target amount of microparticles have been delivered. The total volume of the multi-step administration delivered to the target space may be the additive volume of the accumulated microparticles in-vivo and the volume of the final injection of the microparticle suspension. This can be readily assessed by the operator as the volume expelled from the microparticle suspension chamber minus the volume in the withdrawn fluid chamber. 
     In a second embodiment, a trocar guide channel can remain in place, while separate injecting and expelling syringes and needles are interchanged for injection and withdrawal steps. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is cross sectional view of an embodiment device. 
         FIG. 2A  is a side view of the device of  FIG. 1  showing a bifurcated needle and a filter disposed in one lumen of the needle. 
         FIG. 2B  shows a lower end of the bifurcated needle of  FIG. 2  in perspective view with a filter disposed in one lumen of the needle. 
         FIG. 3A  shows a side view of the syringe of  FIG. 1 . 
         FIG. 3B  illustrates a bifurcated needle showing two lumens without a connecting mechanism used to connect the needle to a syringe. 
         FIG. 3C  illustrates the lower portion of an embodiment syringe, showing a bifurcated outlet. 
         FIG. 3D  shows the needle of  FIG. 3B  having a connecting mechanism thereon. 
         FIG. 4  is a side view of another embodiment needle. 
         FIGS. 5A-5C  are side views of a distal end of a further embodiment needle. 
         FIGS. 6A-6C  are side views of a distal end of a yet another embodiment needle. 
         FIGS. 7A-7D  are views of a distal end of still another embodiment needle. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     An embodiment bifurcated syringe  100  is shown in a cross-sectional view in  FIG. 1 . The body  29  of the syringe includes two or more chambers.  FIG. 1  shows an embodiment of the syringe  100  having two chambers, labeled  2   a  and  2   b.  One chamber may hold a microparticle suspension and the second chamber may hold the suspension fluid after removal from the target space. As previously indicated, a target space may be an anatomical space within a patient (which may be human or otherwise), or a space within a pump, depot, access port or the like. In  FIG. 1 , syringe  100  is shown with plunger  6   a  in the fully proximal position and plunger  6   b  in the fully distal position. Preferably the microparticle suspension would be loaded in chamber  2   a  to be injected into the target space by pushing plunger  6   a  distally, thereby forcing the microparticle suspension out of chamber  2   a  through channel  4   a.    
     Both chambers  2   a,    2   b  are fluidly connected to needle  12  through respective channels, labeled  4   a  and  4   b,  which are in fluid communication with the chambers  2   a  and  2   b  and needle  12 . As can be seen in  FIG. 3C , lower portion  8  of syringe  100  contains a bifurcated outlet having two or more channels  4   a,    4   b  separated by a partition  9 .  FIG. 3C  shows outlet  8  of the two chamber syringe  100  pictured in  FIG. 1 , with one half of outlet  8  communicating with chamber  2   a  through channel  4   a  and the other half of outlet  8  communicating with chamber  2   b  through channel  4   b.    
       FIG. 3A  is a side view of the syringe  100 . Note that the respective chambers  2   a  and  2   b  may share a common wall or may be completely independent of each other. In addition, they may be connected by a bracket or other suitable forms of attachment (not shown) to keep them in relative position with respect to each other. Plungers  6   a  and  6   b,  however, are ideally able to move independently of each other. 
     The body of syringe  100  may be formed from any known material of which syringes of the prior art are normally manufactured, preferably plastic or glass. Plungers  6   a  and  6   b  may be standard syringe plungers as would be found in single chamber syringes well known in the art. 
       FIG. 3B  shows the upper end of a bifurcated needle  12 , showing two lumens  14   a  and  14   b,  which are in fluid communication with chambers  2   a  and  2   b  respectively.  FIG. 3D  shows the same bifurcated needle  12  having a connecting mechanism  10  on the upper end thereof for connecting with syringe  100 .  FIG. 3C  shows the mating portion  11   b  on the syringe  100  for the connector  10 . One or more protrusions  11   b  on either side of outlet  8  of syringe  100  ride in corresponding channels  11   a,  shown in  FIG. 3D , located in connector  10  of needle  12 , and serve to ensure that lumens  14   a  and  14   b  align with channels  4   a  and  4   b  respectively in outlet  8 . The wall  15  between lumens  14   a  and  14   b  ideally lines up with partition  9  between channels  4   a  and  4   b  as well. Connector  10  may employ, for example, a gasket or the like to ensure between the needle  12  and the outlet  8 , as well as to ensure that the fluidic pathways defined by channels  4   a,    4   b  and their corresponding lumens  14   a,    14   b  remain isolated from each other. Alternatively, or in conjunction with a gasket, a male-female connection could be employed between the wall  15  of needle  12  and the partition  9  of outlet  8 . 
     Needle  12  connects to syringe  100  by a slight turning motion which engages one or more protrusions  11   b  with the corresponding threads  11   a.  Any other prior knowledge known to one of skill in the art may be used to secure needle  12  to syringe  100  as long as the individual lumens  14   a,    14   b  within needle  12  line up with their corresponding channels  4   a  and  4   b  in syringe  100  to form isolated fluidic pathways for the transfer of the suspension. 
       FIG. 2A  is a side view of syringe  100  showing one chamber  2   a  and also showing the distal end of needle  12  with the two lumens  14   a  and  14   b  being clearly visible. Preferably, the distal end of needle  12  is cut on a taper having an oblique angle, which may form an oval-shaped cross-section, thereby forming a sharp point  13  capable of piercing the skin of the patient, the surface of a device or the like. It is preferable that the tapered cut in the end of the needle  12  and the opening created thereby be bisected by the wall  15  which divides lumens  14   a  and  14   b,  preferably leaving one lumen  14   b  disposed at the lower, most distal, end of the opening and one lumen  14   a  disposed at the upper, slightly more proximal, end of the opening, as shown in  FIGS. 2A and 2B . 
     It is preferable, although not required, that the shorter lumen (i.e. the lumen disposed on the upper portion of the opening, labeled  14   a  in  FIG. 2B ), be the one through which the micro-particle suspension is injected into the target space. 
     Filter  20  is located within the second lumen  14   b  and is used for extraction of the suspension fluid from the target space. Filter element  20  includes a plurality of pores that permit fluid to pass through filter element  20 . It is desirable, however, that the pores of filter element  20  be smaller than the average diameter of the microparticles to avoid removing the microparticles from the target space when the suspension fluid is removed. In certain embodiments, the filter element  20  may actually be provided by a plurality of holes in and around the tip  13  of the needle  12 . In such embodiments the lumen  14   b  may be closed at its most distal end; fluidic communication of lumen  14   b  with the target space may be provided by a plurality of holes in lumen  14   b,  both at the tip  13  of the needle and optionally along the sidewalls of lumen  14   b.  The holes are sized to prevent the inflow of microparticles into lumen  14   b,  and may be formed by any suitable process, such as machining, etching or the like. In other embodiments the filter element  20  may be a paper insert or the like inserted into the lumen  14   b  and positioned near the tip  13  of the needle  12 . In specific embodiments the filter  20  is preferably flush with the oval-shaped cross-sectional area of the needle opening, and hence flush with the distal opening of the lumen  14   b.    
     Other configurations of the distal end  13  of needle  12  are possible. For instance, wall  15  which divides lumens  14   a  and  14   b  within needle  12  may be at any angle within the opening of the needle, thus providing different shaped openings for each of lumens  14   a  and  14   b.  It is also possible to cut the end of needle  12  at different angles, which may change the relative area of the openings of respective lumens  14   a  and  14   b.  Additionally, it is also possible that barrier  15  separating lumens  14   a  and  14   b  be off-center within the needle  12 , thus creating one lumen with a larger volume than the other lumen, which may be used, for example, to accommodate the filter element within the larger lumen. 
     In operation, plunger  6   a  is utilized in much the same manner as a typical lumen syringe and needle; whereby plunger  6   a  is proximally advanced to create a negative pressure within chamber  2   a  that draws a suspension comprising microparticles and a carrier fluid into chamber  2   a  via, for example, lumen  14   a.  Once chamber  2   a  is loaded, the needle  12  may be positioned so that the distal end  13  is in or near the target space, which may be an anatomical space within a patient or, for example, another preferred therapeutic space with a confined volume. The plunger  6   a  is then advanced distally, thereby forcing the microparticle suspension out of chamber  2   a,  through channel  4   a  and into lumen  14   a  of needle  12 , and ultimately into the target space. It may be desirable to inject only a portion of the microparticle suspension from chamber  2   a  into the target space. 
     After the initial injection of the microparticle suspension, the suspension fluid is preferably withdrawn by creating a negative pressure in chamber  2   b  by pulling proximally on plunger  6   b,  which will draw fluid in the target space through lumen  14   b,  through channel  4   b  and into chamber  2   b.  The directions of preferred fluidic flows are shown near the distal end of needle  12  in  FIG. 1 . As previously discussed, filter  20 , shown in  FIG. 2 , is disposed within lumen  14   b.  The filter  20  has pores that are ideally smaller than the average size of the microparticles which were injected from chamber  2   a,  thereby preventing the microparticles from being drawn back into chamber  2   b  with the suspension fluid. It may be advantageous to periodically reverse the fluidic flow along lumen  14   b  to flush microparticles from the filter  20  and then re-performing fluidic withdraw from the target space. 
     Once a volume of suspension fluid is withdrawn into chamber  2   b,  additional volumes of the microparticle suspension may be injected from chamber  2   a,  and the process may be repeated several times until chamber  2   a  is empty or the desired amount of microparticles have been deposited in the target space. 
     In an alternate embodiment of the invention, a trocar can remain in place while separate injecting and withdrawing syringes and needles are interchanged. In this embodiment, the syringe used for injection of the micro-particle suspension would be a standard syringe, while the syringe used for the withdrawal of the suspension fluid is a standard syringe having a filter disposed in the lumen of its needle. 
     Once the desired volume of microparticles are in place in the target space, the needle is withdrawn. A certain volume of suspension fluid may also be left in place by injecting the microparticle suspension and not withdrawing the last volume of suspension fluid which was injected. 
     Needle  12  may be of a size necessary to accommodate at least two lumens suitably sized to inject the microparticle suspension and withdraw the fluid. 
     In other embodiments, multi-chamber syringes having more than two chambers may be utilized with needles having two or more lumens, such as would be the case if it was desired to mix two microparticle suspensions in the anatomical space. In such cases there may be only one lumen of the corresponding needle which is utilized for withdrawal and which therefore is equipped with a filtering element. 
       FIG. 4  is a side view of an embodiment multiple-lumen needle  30 . The needle  30  includes a shaft  32  comprising a first lumen  32   a  and a second lumen  32   b  that are fluidly isolated from each other along the length of the shaft  30  by wall  35 . The distal end of shaft  32  preferably has an angular cut providing an oval-shaped cross-section  31  that yields a sharp point  33  at the most distal end of needle  30 . Either one of the lumens  32   a,    32   b  includes a filter  34  that is disposed at the distal end of the lumen  32   a,    32   b,  and which is preferably positioned near cross-section  31 . As discussed earlier, the filter  34  is preferably disposed within the longer lumen  32   b  of the two lumens  32   a,    32   b.  The filter is preferably positioned so that its most distal surface flush with the distal opening of the shaft  32  so that there is little or no movement of microparticles along the lumen  32   b.  However, it will be appreciated that when disposing the filter  34  at the distal end of lumen  32   b,  the filter  34  may be slightly proximally advanced along the lumen  32   b.  The amount of such proximal displacement of the filter  34  along the lumen  32   b  will be a function of how much corresponding loss of the microparticles a practitioner is willing to accept. Hence, disposing of the filter  34  at the distal end of shaft  32  should be understood to include such additional proximal displacements. 
     The proximal end of shaft  32  includes a sub-connector  36  adapted to fluidly connect the shaft  32  to two corresponding connectors  39   a,    39   b  for standard syringes (not shown) so that each syringe is fluidly connected to a corresponding lumen  32   a,    32   b.  The connector  36  has a first channel  38   a  that is exclusively fluidly connected to first lumen  32   a,  and a second channel  38   b  that is exclusively fluidly connected to second lumen  32   b.  The sub-connector may mate with wall  35  to ensure the fluidic isolation of the channels  38   a,    38   b  and their corresponding lumens  32   a,    32   b.  The proximal end of each shaft  38   a,    38   b  terminates in a corresponding connector  39   a,    39   b,  that is adapted to connect to a respective syringe. Any suitable connector  39   a,    39   b  may be employed. A non-limiting example of such a connector  39   a,    39   b  includes a luer-lock. 
     It will be appreciated that the needle  30  may have more than two lumens  32   a,    32   b,  and independently may have more than two channels  38   a,    38   b  and connectors  39   a,    39   b.  Typically there will be a one-to-one correspondence between lumens, channels and connectors. However, in the event that there are more channels  38  than lumens within shaft  32 , sub-connector  36  may route two or more channels  38  to a single lumen within shaft  32 . 
     In use, a practitioner may ready two syringes, a first loaded with a microparticle solution and the second empty or primed to receive the microparticle carrier solution. The first syringe is fluidly connected to first connector  39   a,  and the second syringe is fluidly connected to second connector  39   b.  The steps discussed above may then be performed, with first lumen  32   a  dispensing the microparticle solution into the target region, while second lumen  32   b  removes the microparticle carrier solution from the target region, with filter  34  preventing the uptake of the microparticles into the second lumen  32   b.    
     Various methods may be employed to increase the surface area that the filter  34  presents to the target space.  FIGS. 5A-5C  show different views of a distal end of an embodiment needle  40 . Needle  40  has two lumens  42   a,    42   b,  the longer of which  42   b  includes a filter  44  formed by a plurality of holes  42  in the sidewalls of lumen  42   b  that present to the target space. One of these sidewall includes the cross-sectional face of lumen  42   b  that is closed at the most distal tip  43  but is fluidly connected with the target region by way of the holes  42 . The holes  42  also extend proximally along the shaft of needle  40  to effectively increase the active surface area of filter  44 . The holes may be formed by, for example, machining, etching or any other suitable method. In some embodiments, the holes  42  are present only on the cross-sectional face of lumen  42   b  at the tip  43 , while in other embodiments the holes  42  are present only along the shaft of needle  40 . 
       FIGS. 6A-6C  show different views of a distal end of another embodiment needle  60 . The needle  60  has two lumens  62   a,    62   b,  into the longer of which  62   b  is disposed a filter  64 . The filter  64  may be, for example, an insert which is positioned so as to be near or flush with the cross-sectional opening of lumen  62   b  at most distal tip  63 , and extends proximally along the shaft of needle  60 . The filter insert  64  may be made from, for example, a suitable filter paper, cloth or the like. Lumen  62   b  may also include one or more openings  65  in its sidewall along the shaft of needle  60 . The opening or openings  65  are spaced a predetermined distance proximally from tip  63 . Filter insert  64  covers openings  65 , thus presenting a larger surface area to the target area. Alternatively, a plurality of filter inserts  64  may be used to each respectively cover an opening  65  in lumen  62   b,  including the cross-sectional opening at the tip  63 . 
     Yet another embodiment needle  70  is shown in  FIGS. 7A to 7D , in which  FIGS. 7A-7C  show various side views of the distal end of needle  70 , and  FIG. 7D  shows a top view of the distal tip  73  of needle  70 . The needle  70  uses a plurality of bevels  77   a,    77   b  to increase the effective surface area of filter  74 , which is disposed on the longer  72   b  of two lumens  72   a,    72   b.  As in the embodiment needle  40 , filter  74  of needle  70  is provided by a plurality of holes  74  present in the sidewalls of lumen  72   b.  For the embodiment needle  70 , the holes  74  are present only on the surfaces of the cross-sectional areas presented by the bevels  77   a,    77   b  on lumen  72   b.  Hence, only one of the bevels  77   a  is present across lumen  72   a,  whereas lumen  72   b  which has the filter  74  is crossed by both bevels  77   a,    77   b.  In yet other embodiments, a filter insert, as in embodiment needle  60 , may be used instead of the holes  74 . 
     Note that the specifics embodiments are described in an exemplary manner and are not intended to limit the invention. In particular, syringes and needles manufactured of any acceptable material are contemplated to be within the scope of the invention, as are syringes and needles having varying design configurations and numbers of chambers and lumens. The scope of the invention is therefore defined in the claims which follow.