Instrumentation for injection of therapeutic fluid into joints

Described are novel medical delivery devices that can be used to effectively distribute a medical agent to multiple sites within a tissue volume without requiring the device to be repositioned, including for example to distribute the medical agent within the nucleus pulposus tissue of a spinal disc. Also described are medical delivery devices configured to simultaneously remove fluid from the tissue volume into which a medical agent is being delivered, thus avoiding or otherwise decreasing any pressure build-up and facilitating an effective, uniform delivery of the therapeutic agent.

FIELD OF THE INVENTION

The present invention relates generally to devices useful for delivering medical agents to patient tissues, and in one particular aspect to medical delivery devices, such as needles, that provide improvements in the diffuse or regional delivery of medical agents through a volume of patient tissue.

BACKGROUND

Many needle devices in current use deliver a single stream of medical agent, and either provide a focused delivery of the agent, or require frequent repositioning to distribute the agent through a volume of tissue. Repeated positioning of a device can cause discomfort to the patient and can lead to extended tissue damage. Additionally, current devices and methods for delivering medical agents can cause localized pressure as the agent is delivered, making delivery of additional amounts of agent more difficult and potentially causing other patient-related complications.

In view of this background, needs remain for improved or alternative medical agent delivery devices and methods, including for example those that facilitate regional delivery of the agent and/or reduce complications which may arise due to pressure increases in the immediate and/or surrounding tissues. The present invention provides embodiments addressed to these and other needs.

SUMMARY OF INVENTION

The present invention fills the foregoing need by providing methods and systems for injection of large volumes of biological therapeutic fluids into anatomical spaces.

The present invention provides medical delivery devices, such as needles, that can be used to effectively distribute a medical agent to multiple sites within a tissue volume without requiring the device to be repositioned, including for example to distribute the medical agent within the nucleus pulposus tissue of a spinal disc. In certain embodiments, medical delivery devices of the invention are also configured to simultaneously remove fluid from the tissue volume into which a medical agent is being delivered, thus avoiding or otherwise decreasing any pressure build-up and facilitating an effective, uniform delivery of the therapeutic agent.

In specific embodiments, methods and devices are adapted for medical agent delivery into nucleus pulposus tissue of a spinal disc. Such deliveries in accordance with the invention provide particular advantage in many respects, since the nuclear tissue of the disc is substantially non-vascularized and thus the native capacity for distribution of the medical agent is limited. As well, in instances where the disc annulus remains substantially intact or has a relatively small opening, a relatively closed volume exists into which the agent is to be delivered thus increasing the potential for pressure build within the disc space and/or undesired expulsion of delivered and/or tissue material back out of the opening.

In one aspect, needles for delivering a therapeutic fluid to a target space are provided. Such needles comprise one or more elongated tissue-penetrating members for penetrating into a target space, at least one extraction orifice located on said one or more tissue-penetrating members, an extraction fluid path in fluid communication with said at least one extraction orifice, at least one injection orifice located on said one or more tissue-penetrating members and positioned remotely from said at least one extraction orifice, and an injection fluid path in fluid communication with said at least one injection orifice.

The number of extraction and injection orifices, their size, and their position relative to each other are selected to create a pressure gradient within the target space when a therapeutic fluid is injected through the at least one injection orifice. The location of the extraction and injection orifices relative to each other depends on the type of target space being treated, and more specifically, on the content and type of target space content, such as target space fluids or target space tissue.

The lumens of the needle may be in a concentric relation or may be adjacent to each other. When the lumens are adjacent to each other, preferably the orifices are formed in the sidewalls of the lumen. Such orifices may be referred herein as sidewall orifices. In one specific embodiment, a sidewall extraction orifice may comprise a series of holes with progressively increasing diameter towards the proximal end of the needle, while a sidewall injection orifice may comprise a series of holes with progressively increasing diameter towards the distal end of the needle. When the lumens are in a concentric relationship, the outside lumen may have a sidewall orifice and the inside lumen may have a orifice at the distal end, with outside lumen, preferably, serving as an extraction lumen.

The instant needle may be connected to an infusion device such as a infusion device, a catheter, or a pump. Such device may comprise extraction and injection chambers that are fluidly isolated from each other. The extraction chamber and the injection chamber are in fluid communication with the extraction lumen and the injection lumen of the needle respectively. Alternatively, independent infusion devices may be connected to each lumen of the instant needle.

In a preferred embodiment, the infusion device comprises a multi-chamber infusion device. Such infusion device may include an extraction plunger slidably disposed in the extraction chamber and an injection plunger slidably disposed in the injection chamber. The plungers can be activated independently of each other to create a positive or negative pressure within their respective chambers.

In another aspect, a method of delivering therapeutic fluid to a target space is provided. The method comprises inserting the instant needle into the target space, creating one or more pressure gradients in the target space, and injecting the therapeutic fluid into the target space. The target space content may be extracted from the target space through the one or more extraction orifices by activating the extraction plunger to create a negative pressure within the extraction chamber. Concurrently or sequentially, the therapeutic fluid may be injected into the target space through the one or more injection orifices by activating the injection plunger to create a positive pressure within the infusion chamber. Preferably, the fluids are exchanged in equal amounts.

DETAILED DESCRIPTION

As disclosed above, the present invention provides methods, medical devices, and components of medical devices useful for delivering one or more medical agents into patient tissues, including in certain specific embodiments into the nucleus of a spinal disc. Certain methods and devices of the invention desirably achieve a regional, rather than single pinpoint, delivery of the medical agent. In alternative forms, methods and devices of the invention capitalize upon the removal of fluid and/or other volume-occupying tissue material to minimize or eliminate pressure buildup upon the delivery of medical substances into the tissue region.

With reference now toFIGS. 1A,1B and1C, shown is one embodiment of a medical delivery device of the invention that generally includes a needle1, in certain embodiments a spinal needle configured for penetration through a disc annulus and into nucleus pulposus tissue, and a syringe50. Needle1comprises an elongated member10formed of a biocompatible material and has a proximal end11, a distal region12, and a plurality of orifices or apertures13at its distal region. The elongated member10additionally has an inner surface14(FIG. 1C) defining a lumen15or fluid channel within and along its length. The distal end of elongated member10has a penetrating (desirably non-coring) tip16to assist penetration into a spinal disc or other patient tissue and ensure the delivery of a medical agent through apertures13. The proximal end of elongated member10has a connector17for engaging a distal end of syringe50. Syringe50has a housing54having a proximal end52, a distal end53and forming a cavity or internal chamber55to provide a supply reservoir for the medical agent. Syringe50additionally has a syringe plunger56equipped with a plunger head57and a connector51for attaching to connector17of spinal needle1. With reference particularly toFIG. 1B, the syringe50and spinal needle1ofFIG. 1Aare engaged through luerlock connectors17and51causing cavity55, lumen15and apertures13to be in fluid communication. It will be understood, however, that other mechanisms or means for connecting the needle1and syringe50can be used and are contemplated as being within broader aspects of the present invention.

With reference toFIGS. 2A,2B and2C, another medical delivery device of the invention is illustrated that includes a needle2and syringe50. Like needle1(FIGS. 1A-1C), spinal needle2comprises an elongated tissue-penetrating member formed of a biocompatible material and has a proximal end11, a distal region12, and a plurality of orifices or apertures13and36in the distal region. Orifice21and connector19are located at the proximal end11of elongated member10. Connector19has a lumen35and is positioned over orifice21causing orifice21and lumen35to be in communication. The proximal end of elongated member10additionally has a connector17for engaging a distal end of syringe50. The elongated member's distal region12has a closed penetrating tip22. Inner member46, a wall-like structure in contact with the interior surface14, partitions the interior of elongated member10and in combination with inner surface14, forms first channel15and second channel20(see e.g.FIG. 2C). Inner member46is positioned within elongated member10to cause lumen35, orifice21, channel20, and apertures36to be in fluid communication and provide a pathway independent of channel15for withdrawal of fluid from a spinal disc or other patient tissue. Inner member46is similarly positioned to provide for fluid communication between channel15and apertures13. Syringe50has a housing54having a proximal end52, a distal end53and a cavity or chamber55. Syringe50additionally has a syringe plunger56equipped with a plunger head57and a connector51for attaching to connector17of needle2. With reference particularly toFIG. 2B, the syringe50and needle2ofFIG. 2Aare engaged through luer-lock connectors17and51causing cavity55, lumen15and apertures13to be in fluid communication and providing a route for the delivery of a therapeutic agent from syringe50through apertures13. As before, other arrangements for associating the needle and syringe50can be used.

With reference toFIGS. 3A,3B and3C and3D, another embodiment of a medical device is illustrated that generally includes a needle assembly3and a syringe50. Needle assembly3includes a plurality of elongate tissue penetrating members (four needles in the illustrated embodiment) formed of a biocompatible material. In particular, at the proximal end11, needle assembly3has a manifold component24and at its distal region12, a plurality of elongated penetrating members23in a generally planar arrangement. Each elongated member23has a proximal end25, a distal region26and a plurality of sidewall apertures13in its distal region. Elongated members23and the manifold piece24additionally have inner surfaces14and28(see e.g.FIG. 3C) defining elongated member lumens27and manifold cavity32. Manifold component24also defines a plurality of lumens27A which receive the proximal ends of elongated members23and communicate with their lumens27. The distal end of elongated member23has a closed penetrating tip22to assist penetration into a spinal disc upon the application of pressure and allow the delivery of a therapeutic agent through sidewall apertures13which in the illustrated embodiment are distributed radially around elongated members23. The proximal end of manifold piece24has a connector17for engaging a distal end of syringe50. Manifold cavity32is in fluid communication with lumens27and apertures13. Syringe50is as described with regard toFIG. 1. With reference particularly toFIG. 3B, the syringe50and spinal needle3ofFIG. 3Aare engaged through luer-lock connectors17and51causing syringe cavity55, manifold cavity32, lumen27and apertures13to be in fluid communication.

With reference toFIGS. 4A,4B and4C, another embodiment of an inventive medical delivery device is illustrated that includes a needle assembly4and syringe50. This device is similar to that depicted inFIGS. 3A and 3B, except having separate internal pathways for delivery of medical agent and removal of tissue (e.g. fluid) material. In particular, needle assembly4includes a manifold piece24and a plurality of elongated tissue penetrating members44and45. Needle assembly4has inner walls providing an independent internal pathway18for withdrawing or otherwise allowing passage of fluid and/or other material from a spinal disc or other tissue region in conjunction with delivering a therapeutic or other medical agent. Manifold element24has a connector19positioned on the manifold's outer surface about aperture21. Connector19provides lumen35in communication with orifice21, with channels37A and37B of internal pathway18and with lumens42within elongated members44(FIG. 4B).

Elongated members44and45have a proximal end25, a distal end26, a penetrating tip34at the distal end26, and a plurality of apertures13and38. Syringe50is as described with regard toFIG. 1. With reference toFIG. 4C, the syringe50and needle assembly4ofFIG. 4Aare engaged through luer-lock connectors17and51causing syringe cavity55, manifold cavity32, lumens43within delivery members45and apertures13to be in fluid communication. Thus, plunger56can be actuated to deliver medical agent from syringe cavity55into manifold cavity32, through lumens43and out of apertures13. At the same time, tissue fluid or other material can be withdrawn from the tissue volume to receive the medical agent through internal pathway18including apertures38in elongated members44, through internal lumens42, and out through lumen35. In this regard, the withdrawal of fluid can be active, in the sense that a negative pressure can be applied to pathway18through lumen35(e.g. using a syringe) to withdraw tissue material, or can be passive in the sense that pressure created in the receiving tissue volume due to the delivery of medical agent can force tissue fluid or other material out through pathway18.

With reference toFIGS. 5A through 5F, another embodiment of an inventive medical delivery device is illustrated that includes a needle assembly5and syringe50. Needle assembly5includes a manifold element24and a plurality of elongated tissue penetrating members23A and23B constructed from a biocompatible material. Needle assembly5is configured to allow for the simultaneous deliver and withdrawal of materials from a spinal disc or other tissue. Withdrawal is achieved through apertures38of withdrawing elongated members23A coupled to withdrawal pathway including channel33, orifice21, and lumen35of connector19. The delivery of a medical agent is achieved through apertures13of delivery elongated members23B by way of manifold cavity32.FIG. 5Bis a sectional view of the spinal needle ofFIG. 5Aillustrating the needle's internal structure. An internal pathway is provided within the elongated members23A and manifold24causing apertures38, channel33, orifice21and lumen35within connector19to be in fluid communication. A separate internal pathway is provided causing apertures13, lumen27, and manifold cavity32to be in fluid communication. With reference toFIG. 5C, a cross-section of the elongated members23A and23B taken along line5C-5C ofFIG. 5Band viewed in the direction of the arrows is provided illustrating the position of the elongated members. With reference toFIG. 5D, a cross-section of the proximal end of manifold element24taken along line5D-5D ofFIG. 5Bis provided illustrating manifold cavity32for receiving and transferring medical agent(s) delivered to the patient, and channel33for directing material withdrawn from the patient through orifice and lumen35. With reference toFIG. 5E, a cross section of manifold element24at internal wall40is provided illustrating the cavity32in fluid communication with the connector opening of manifold element24for medical agent delivery and internal wall40interrupting fluid communication with the connector opening of manifold element24and thereby establishing a separate chamber or channel (33,FIG. 5B) for fluid withdrawal. With reference toFIG. 5F, the syringe50and needle assembly5ofFIGS. 5A-5E, are engaged through luer-lock connectors17and51causing syringe cavity55, manifold cavity32, lumens27and apertures13to be in fluid communication.

With reference toFIG. 5G, shown is an inventive medical delivery device including the assembly ofFIG. 5Gengaged with a cannulated retraction sleeve member75having a plurality of cannulas76having curved end portions to deflect elongated members23A and23B to provide a desired injection pattern. In this regard, elongated members23A and23B for this embodiment can be constructed of a biocompatible material that is resiliently flexible or deflectable from a relaxed (e.g. straight) configuration, whereby the curved cannulas76direct the elongated members to the desired injection pattern when the tips of elongated members23A and23B are advanced through and out of the curved cannulas76, and the elongated members return substantially to their relaxed (e.g. straight) condition when withdrawn back into the cannulas76beyond their curved end portions. In other embodiments, the cannulas76are straight, and the elongated members have a curved configuration when relaxed but are deflectable to a straight configuration for travel through the cannulas76. Upon exiting cannulas76the elongated members assume their curved configuration to provide the desired delivery pattern. As well, combinations of curved lumens and curved elongated members can be used to achieve a desired delivery pattern. Still further, in alternative embodiments, either some or all of the plurality of elongated members can be of a deflectable nature, and each deflectable elongated member can have a corresponding, dedicated cannula in the cannulated member configured to provide deflection to the desired delivery pattern.

As shown inFIG. 5G, cannulated member75can be configured to slide overtop syringe50and can include handle or grip elements for facilitating manipulation in proximal and distal directions relative to syringe50. As well, cannulated member75can include windows or cutouts for any syringe components that need or are desired to exit the side of cannulated member75(e.g. as in the connector19of syringe50).

With reference toFIG. 6, an embodiment of an inventive medical device is illustrated that includes a needle assembly6and syringe50. Needle assembly6is similar in construction to that shown inFIGS. 3A,3B and3C, and has elongated penetrating members23constructed of flexible biocompatible material having shape memory properties capable of being constrained within sleeve or cannulated member75having a single lumen76and assuming an original configuration when expelled from lumen76. In the embodiment shown, the outermost members23have curved portions in their unconstrained (relaxed) condition thereby providing a generally wider, planer delivery configuration.

FIG. 7illustrates the medical delivery device ofFIG. 1Bin use. In particular, medical agent85is being delivered through the plurality of apertures13into the nucleus81of identified spinal disc80to which access has been provided, for example minimally invasive access using the syringe needle assembly potentially in combination with a tubular introducer sleeve.) Although syringe50attached to spinal needle1is fitted with a plunger56and plunger head57, a syringe having a screw drive mechanism, a ratcheting mechanism, a trigger, or another delivery mechanism for forcing or otherwise moving the medical agent through the system can be utilized with needle assembly1and other needle assembly embodiments of the invention.

FIG. 8shows the medical delivery device ofFIG. 2Bin use. After providing access to disc80(e.g. minimally invasive access as discussed above) a medical agent85is shown being delivered with needle assembly2through apertures13into the nucleus81of spinal disc80simultaneously with the withdrawal of material (e.g. tissue fluid)86through apertures38, for example using a separate syringe device100coupled to connector19. It will be understood that syringe device100could be replaced with a simple container that can collect fluid at ambient pressure in situations wherein the pressure generated in the disc or other tissue bed is sufficient to drive fluid and/or other tissue material through the withdrawal fluid path (i.e. assisted withdrawal with reduced pressure or other active mechanisms will not necessarily be required in all situations). Connector19can be adapted to be fitted with a flexible tubing or fitted with a special connector such as a luer-lock fitting to assist in creating a suitable pathway into syringe device100or another collection device.

FIG. 9illustrates the syringe needle assembly ofFIG. 5Gin use. After providing minimally invasive or other access to disc80, a medical agent85is shown being delivered with needle assembly5through apertures13into the nucleus81of spinal disc80simultaneously with the withdrawal of fluid86through apertures38and delivered into syringe100through connector19. The elongated members23are engaged in cannulated member75having a plurality of lumens76which direct the elongated members23according to a desired delivery pattern. To achieve delivery, the end of cannulated member75can be docked or positioned against the disc annulus while the elongated penetrating members23are fully received in sleeve75. The syringe-needle assembly (50and5) can then be advanced into sleeve75to drive the penetrating members23through their respective curved lumens, out the end of sleeve75, through the disc annulus, and into the nucleus81. The sleeve75with its curved lumens allows penetration of the disc annulus in a defined, relatively small region, but directs the members23to a desired, differing pattern, such as a more spaced pattern, a directional pattern deflected from the longitudinal axis of the sleeve75(e.g. to the right, the left, up or down), a radial pattern, etc. After delivery of the medical agent is complete, the syringe needle assembly can be pulled back through cannulated member75to withdraw members back into their respective, dedicated lumens, and the overall device removed from the operational field.

FIG. 10shows the medical delivery device ofFIG. 6in use. After providing access to disc80, a medical agent85is shown being delivered with needle assembly6through apertures13into the nucleus81of spinal disc80. The elongated members23, constructed from a biocompatible material having shape memory properties are engaged in sleeve75having a single lumen76. When fully engaged within sleeve75, the elongated members23are constrained together and as they are expelled during insertion into spinal disc80they separate, regaining their original, wider conformation to deliver the therapeutic agent according to a predetermined delivery pattern. Again, to achieve delivery, the sleeve75can be positioned against the disc annulus with the elongated members23fully received therein, whereafter the members can be ejected from the sleeve75to penetrate the annulus and enter into the nucleus pulposus tissue within. The medical agent can then be delivered from the elongated members23by actuation of the syringe plunger, whereafter the members23can be retracted back into sleeve75, and the delivery device removed from the operational field.

With reference toFIG. 11, shown is another medical delivery device110of the invention. Device110includes a syringe50as previously described, and a needle assembly112. Needle assembly112includes a connector17for fluid connection to syringe50, and a branching elongated needle113. Branching needle113includes a straight portion114having an internal lumen that is common to and feeds a plurality of branching needle portions115which extend arcuately and radially away from the longitudinal axis of the straight portion114. Each branching portion115includes a tissue penetrating tip116, and a plurality of sidewall117for delivery of a medical agent. Tissue penetrating tips116can be open, but are preferably closed to facilitate advantageous flow of medical agent out of sidewall orifices117. In advantageous embodiments, branching elongated needle114is constructed of a resilient material such that branching portions115can be constrained to a smaller overall profile for delivery into a spinal disc or other tissue region, potentially within single lumen sleeve members (e.g.75) as described hereinabove, which sleeve members themselves may incorporate tissue penetrating tips for facilitating penetration to a desired tissue level for launch of the needles (e.g.114) received therein.

With reference toFIGS. 12A and 12B, an further medical agent delivery device of the present invention will be described. The illustrated device120is configured to simultaneously deliver and withdraw material from patient tissue upon actuation of a single syringe plunger. Generally, in the illustrated device120, medical agent forward of an advancing plunger head will be expelled through one or more first fluid paths, and material such as fluid from within tissue of the patient will be withdrawn though one or more second fluid paths coupled to and activated by a negative pressure zone generated rearward of the advancing plunger head (see, generally, arrows inFIG. 12Aillustrating material flow directions). In this manner, a simple operation can be performed to both deliver and withdraw material to and from patient tissue, and the delivered and withdrawn material will be of substantially the same volume since the volumetric displacement forward and rearward of the advancing plunger head will be similar.

Turning now specifically to the features of the drawings, delivery device120includes a plurality of needles121and122which, as shown, can include a curved configuration in a relaxed condition. Straight, deflectable or non-deflectable needles can also be used within the invention, as discussed above. Needles121and122have their distal ends received within a distal cap piece123. Distal cap piece123defines a plurality of internal lumens124and125corresponding to and communicating with internal lumens of needles121and122. Device120has a barrel portion defined by an outer cylindrical member126and an inner cylindrical member127, which define a generally annular chamber128between them. The distal end of the outer cylindrical member126is sealingly received around shoulder portion123A of distal cap member123, while the distal end of inner cylindrical member127is sealingly received within an annular notch123B defined within distal cap member123.

At the proximal end of device120, proximal cap member129having a central opening130is sealed against the proximal ends of outer and inner cylindrical members126and127. The plunger apparatus includes plunger head131received within and cooperating with the internal walls of inner cylindrical member127. Plunger arm132is connected to plunger head131and extends through central opening130in proximal cap129. In the illustrated device120, plunger arm132is either a hollow or solid cylinder, although other shapes can also be used within the invention. A proximal grip plate133is secured to the outer surface of proximal cap129. Grip plate133includes a central opening134generally corresponding in size to the central opening130of proximal cap129, and is grooved partially through its thickness about the opening to create an annular shoulder135, which in turn creates an internal volume when the grip plate133is secured to the proximal cap129. A sealing element such as an “O”-ring136is received within such internal volume, and cooperates to substantially maintain a pressure seal against plunger arm132as it is advanced into and withdrawn from the barrel of device120. A push-pull handle element137is provided at the end of plunger arm132to facilitate manually advancing and withdrawing the plunger apparatus in and out of the device120.

That portion of inner chamber140A (defined by the internal volume of inner cylindrical member127) forward of the plunger head131fluidly communicates with lumens124for delivery of a medical agent from forward chamber140B through and out of delivery needles121. Annular chamber128fluidly communicates with that portion of inner chamber140B rearward of plunger head131through one or more openings141defined in inner cylindrical member127. Annular chamber128, in turn, fluidly communicates with peripheral lumens125defined in distal cap123, which communicate with internal lumens of withdrawal needles122. It will be understood that needles121and122can include a single opening at their distal end, and/or can include one or a plurality of sidewall openings142as in other needles disclosed hereinabove.

In operation, chamber portion140A forward of plunger head131can be filled with a medical agent at manufacture, or just prior to delivery. The latter may be achieved, for example, by advancing the plunger head131to its forward-most position within inner cylindrical member127, positioning the distal ends of delivery needles121into a volume of the medical agent, and drawing the plunger back up the inner cylindrical member127(but desirably stopping short of openings141). Thereafter, the distal ends of needles121and122can be advanced into disc nucleus or other tissue for delivery, and plunger head131advanced distally within inner cylindrical member127. In this manner, the medical agent will be delivered from forward chamber portion140A through lumens124and out of sidewall openings142of delivery needles121. At the same time, a negative pressure zone will be created rearward of the plunger131within rearward chamber portion140B, and this negative pressure will be communicated through openings141into annular chamber128, through lumens125and ultimately to sidewall openings142in withdrawal needles122. Fluid or other tissue will thereby be withdrawn under pressure from the nucleus pulposus or other tissue, will fill into annular chamber128, and if sufficient in volume will spill through holes141and into rearward chamber portion140B occurring behind the now-advanced position of plunger head131. After this, in one mode of use, needles121and122can be withdrawn from the patient tissue while leaving the plunger head in its advanced position after delivery of the medical agent.

It will be understood that a variety of other configurations can be used while achieving a simultaneous delivery and withdrawal of material as effectuated by device120ofFIGS. 12A and 12B. For example, an inverse operation can be provided, wherein a medical agent to be delivered is originally loaded rearward of plunger head131in an advanced position and within annular chamber128, and the plunger head131withdrawn proximally to force the agent out of needles122while simultaneously withdrawing material from needles121. As well, separate plungers could be provided for separate, discrete chambers for withdrawal of material and delivery of material. In one mode, a first plunger could be advanced in a first chamber to deliver an agent through a first needle or needles of the assembly, while a second plunger is withdrawn through a second chamber to withdraw material from a second needle of the assembly. These and still other adaptations can be used within the ambit of the present invention.

In addition or as an alternative to relieving pressure created by delivered medical agent to tissue volumes, the withdrawal (including simultaneous and/or intermittent withdrawal) of patient fluid from adjacent tissue regions can potentially facilitate the creation of flow or diffusion gradients that assist in spreading or regionalizing the delivered agent. Thus, in certain instances, it will be desired to have withdrawal openings somewhat spaced from delivery openings on medical delivery devices of the invention. This spacing will also help to prevent or minimize withdrawal of amounts of the delivered agent when that is undesired. Such spacing may be achieved by having multiple needles with openings spaced from one another as in certain embodiments disclosed herein, and/or by having openings spaced from one another on a single needle having a bifurcated lumen, wherein one side of the bifurcation communicates with one or more delivery openings and the other communicates with one or more withdrawal openings. Spacing of delivery and withdrawal openings may be achieved for example by radial spacing and/or by longitudinal spacing along a single needle body.

Referring now toFIG. 13, shown is another medical delivery device150of the present invention. Device150is similar to the device depicted inFIGS. 6 and 10, except elongated members23have a relaxed condition in which they each curve to one direction away from the longitudinal axis of device150and provide a generally planar, laterally-facing ejection pattern. In this fashion, device150can be advanced to position sleeve75against the annulus fibrosus of a spinal disc, and elongated members23advanced out of sleeve, through the annulus fibrosus (or an opening already therein), whereafter upon further advancement they assume their original laterally-facing configuration for delivery of agent to one side of the interior disc space. The members23can thereafter be withdrawn back into sleeve75, and either the sleeve/needle/syringe assembly rotated 180 degrees, or the needle/syringe assembly rotated within the sleeve 180 degrees. Advancement of the members23out of sleeve member75again thereafter enables delivery of amounts of the medical agent to the other side of the interior space of the disc.

FIG. 14depicts still another medical delivery device160of the present invention. Device160can have syringe-needle assemblies similar to those depicted inFIGS. 6 and 13. Device160, however, includes a retraction sleeve having a modified, more flattened distal region and an elongated opening76A such as an elongated ovate opening. Elongated opening76A beneficially contributes to assuring that needles23remain in a substantially planar array. In this regard, needles23can be generally straight and provide a planar array, can include needles that flare but return to extend generally parallel to their original longitudinal axis (as shown inFIG. 15), can curve laterally to one side (shown in phantom inFIG. 15) or both sides, or any combination of these or other desired configurations.

The medical agent delivered to the patient using methods and devices of the present invention can be, for example, therapeutic or diagnostic. Diagnostic agents include, for example, imaging agents such as x-ray contrast agents, magnetic resonance imaging (MRI) agents, and the like. Therapeutic agents may include, for example, cells, including disc nucleus cells and/or adult or embryonic stem cells, drugs, anti-inflammatory agents, tissue growth factors, anesthetics, antibiotics, MMP inhibitors, extracellular matrix components, keratin-family proteins, platelet-rich plasma, bone marrow, morphogenic proteins including bone morphogenic proteins such as BMP-2 or BMP-7, nucleic acid constructs such as expression vectors including nucleic acid molecules encoding morphogenic proteins such as those mentioned above or LIM mineralization protein (LMP), and a wide variety of other known medical agents. Such medical agents can be delivered in certain embodiments in controlled release fashion, for example by the injection of suspensions of controlled release particles such as controlled release microspheres which are deposited within the recipient tissue (e.g. disc nucleus pulposus tissue) for sustained release of the medical agent.

With reference toFIGS. 15aand15b, an embodiment of a needle for injecting therapeutic fluid into a target space is illustrated. The term “target space” as referred to herein means anatomical space within a patient (human or otherwise), such as, a joint, a blood vessel, a body cavity, and so on. The term therapeutic fluid means any flowable substance that may prevent, treat, or alleviate signs or symptoms of the disease or condition. The term therapeutic fluids includes, but is not limited to, solutions, syrups, dispersions, suspensions, emulsions, lotions, gels, creams, slurries, flowable polymers, hydrogels, and so forth.

The needle210includes one or more elongated non-coring tissue-penetrating members formed of a biocompatible material for penetrating into a target space and has a proximal end211and a distal end212. The proximal end211may include at least one connector, described below, for connecting the needle210to an infusion device, such as, an infusion device, a pump, a catheter, and so forth. Preferably, the needle210is a hypodermic needle with the distal end adapted to be capable of penetrating a target space. Accordingly, the needle is preferably made of rigid material, such as surgical steel or rigid plastic, with the distal end comprising a cutting edge, such as a bevel, adapted to pierce through a patient's skin or other tissue, such as a joint capsule, to enter the target space. Although the needle210may be inserted into the target space using a guide channel, such as a guide wire or a cannula, in the preferred embodiments the needle210may be used to pierce the target space without any additional instruments.

The needle210further comprises at least one extraction orifice and at least one injection orifice located on said one or more tissue-penetrating members and are in fluid communication with an extraction fluid path and injection fluid path, respectively. The at least one injection orifice is positioned remotely from the at least one extraction orifice. The lumens213and214are adjacent to each other in the embodiment shown inFIG. 15a, although other variations are possible. Each lumen may comprise a single lumen or multiple lumens which may or may not be in fluid communication with each other.

At least one extraction orifice and at least one injection orifice may be formed in the sidewalls at or proximally to the distal ends of their respective lumens. In addition to or instead of these sidewall orifices, the extraction lumen, injection lumen, or both may include orifices at their distal ends. In some embodiments, the needle210may include one or more obtuators plugging the orifices during the insertion of the needle into a target space to prevent the orifices from plugging up with tissue.

The one or more extraction orifices may be used to extract target space content, such as target space fluids, catabolic tissue fluids, target space tissue, native degenerative factors and so forth, from the target space, whereas the one or more injection orifices may be used to inject a therapeutic fluid into the target space. Extracting target space contents from the target space may allow for injection of a larger volume of the therapeutic fluid and may flush out natural degenerative factors making the treatment more effective. Preferably, the one or more extraction orifices and the one or more injection orifices are remote from each other to avoid or, at least, to minimize extracting the therapeutic fluid from the target space.

In addition, since the needle is used to exchange fluids in a stagnant environment, the orifices may be designed to create pressure gradients within the target space. The number of orifices, their size and their positions relative to each other may be varied to create one or more pressure gradients to force the target space contents to flow from one area of the target space to another making room for injection of therapeutic fluid into the target space. Pressure gradients may also facilitate an uniform diffusion of the therapeutic fluid throughout the target space. In embodiments when exchanging viscous materials, it may be advantageous to have multiple extraction and multiple injection orifices to create localized pressure gradients which may further improve distribution of the therapeutic fluid in the target space.

Location of the one or more extraction orifices and one or more injection orifices depends on the type of target space being treated, and more specifically, the target space content's characteristics. For example, if the instant needle is used for replacing or augmenting nucleus pulposus, because the injected fluid is relatively viscous and, thus, cannot diffuse quickly, the orifices can be closer to each other than if the needle is used for exchanging fluids in a knee joint because the knee joint fluids are generally less viscous. More specifically, the orifices may be located only about 1 to about 5 mm apart when exchanging fluids in a disc, whereas the orifices may be located about 5 to about 20 mm apart when exchanging fluids in a knee joint. Furthermore, when replacing viscous fluids or dense tissue, multiple extraction and injection orifices may be desirable to provide for a more uniform distribution of the therapeutic fluid.

The needle design is such that the one or more extraction orifices can remove fluid through the surrounding tissues via diffusion through the tissues at a rate which allows injection of the therapeutic fluid into the same tissues. In other words, there is an approximately equivalent volumetric exchange of catabolic tissue fluids with the therapeutic fluids. Target spaces, and joints in particular, are normally fully hydrated making injection of additional therapeutic fluids into them difficult, if not impossible. Therefore, some target space content may need to be removed at the same or faster rate than the therapeutic agent being injected into the target space. If the rate of injection is faster, the excess therapeutic agent may leak out of the target space during injection and flow into unwanted locations. For example, if, when injecting therapeutic fluid into a disc joint, the disc fluid is extracted at about 1 cc/min, the therapeutic fluid may be injected into the disc space at about 1 cc/min or slower. Injecting the therapeutic fluid at a faster rate may result in an overflow of the therapeutic fluid from the disc space into the spinal canal. The fluid in the spinal canal is likely to exert pressure on the spinal cord causing pain to the patient.

The size and number of the orifices may depend on the type of the target space being treated. Since, a larger amount of fluid may need to be delivered to a larger target space, larger holes and/or more holes may be necessary to minimize the duration of the procedure. In addition, larger holes may be desirable when viscous fluids are being extracted or injected. Lastly, larger number of holes may ensure that the therapeutic fluid is more thoroughly distributed throughput the target space or may ensure a more even extraction of the native fluid from the target space. By way of a non-limiting example, the orifices may be about 0.05 mm to about 1 mm in diameter and about 1 mm to about 5 mm apart when exchanging fluids in an intervertebral disc and may be about 0.5 mm to about 3 mm in diameter and about 5 mm to about 20 mm apart when exchanging fluids in a knee joint.

Referring toFIG. 15a, in one non-limiting embodiment, a sidewall orifice215of the instant needle210may comprise a series of orifices215a,215b,215c. As explained above, it is desirable to create pressure gradients within the target space which may facilitate a more uniform diffusion of the therapeutic fluid throughout the target space. Accordingly, the diameter of these orifices may be progressively varied to create the desired pressure gradient. For example, if the pressure gradient that aids diffusion of the therapeutic fluid from the center to the periphery of the target space is preferred, the diameter of the orifices of the one or more extraction orifices may progressively increase toward the proximal end243of the needle240, that is, the diameter of the orifice242ais larger that the diameter of the orifice242bwhich is, in turn, larger than the diameter of the orifice242c. In such embodiment, the therapeutic fluid may be injected through a distal end of the injection lumen into the center of the target space or through a sidewall injection orifice with a orifice size changes in a reverse order so that more fluid is injected in the center of the target space further increasing the gradient between the center and periphery. If a pressure gradient that aids diffusion of the therapeutic fluid from the periphery to the center of the target space is preferred, the diameter of the orifices of the sidewall extraction orifice may progressively decrease toward the proximal end of the needle, while the diameter of the orifices of the sidewall injection orifice may progressively increase toward the proximal end of the needle. Additionally or alternatively, the target space fluid may be extracted from the distal end of the extraction lumen.

Another embodiment of the instant needle220for delivering a therapeutic fluid to a target space is shown inFIGS. 16aand16b. Compared to the needle210, the fluidly isolated lumens223and224are in a concentric relation with each other. Similarly to the needle210, the needle220includes a proximal end221having at least one connector and a blunt or sharp distal end222. The outside lumen223may have one or more orifices225in its sidewall or at its distal end (not shown), whereas the inside lumen224has one or more orifices226at the distal end222. As in the embodiments described above, the extraction orifice and the injection orifice are remote from each other to prevent or, at least, to minimize extraction of the therapeutic fluid from the target space. The outside lumen may have multiple orifices located along both the longitudinal and radial directions.

Relative position of the extraction lumen or the injection lumen to each other depends on the desired direction of the pressure gradients. For example, if the pressure gradient forcing fluids in the center of the target space to flow towards the periphery is desired, the outside lumen may be used as an extraction lumen. On the other hand, if the pressure gradient forcing fluids to flow from the periphery of the target space to the center is desired, the outside lumen may be used as an injection lumen. In preferred embodiments, the outside lumen is used as an extraction lumen so that the therapeutic fluid is injected into the center of the target space.

In operation, the instant needle may be connected to an infusion device, such as a infusion device, a catheter, or a pump. The needle may be an integral part of the infusion device or may be connected to the device using a connector. In one embodiment, a multi-chamber infusion device, catheter or pump may be utilized. Such infusion device, catheter, or pump may include an extraction chamber and an injection chamber that are fluidly isolated from each other. Each chamber may, in turn, comprise a single chamber or multiple chambers that may or may not be fluidly connected among each other. When a multi-chamber infusion device, catheter, or pump is connected to the instant needle, its chambers are in fluid communication with the corresponding lumen of the needle. Alternatively, multiple independent catheters, infusion devices or pumps may be connected to the instant needle, some of which will be in fluid communication with the extraction lumen of the needle to be used for extraction of the target space content while others will be in fluid communication with the injection lumen of the needle to be used for injecting fluid into the target space.

In some embodiments, the needle may be removably connected to an infusion device through one or more connectors. Such connectors are known in the art and may employ, for example, a gasket or the like to form a fluidic pathway between the lumens of the needle and the corresponding chambers of the infusion device connected to the needle and to ensure that such fluidic pathways remain isolated from each other. Additionally or alternatively, a male-female connection could be employed between the needle and the infusion device or the catheter. Finally, any other type of connector known to one skilled in the art may be used to secure the needle to the infusion device or to the catheter as long as the extraction and injection lumen line up with the corresponding chambers or lumens to form isolated fluidic pathways. Some suitable examples are disclosed in, for example, U.S. Pat. No. 7,347,458.

FIG. 17presents a non-limiting example of a multi-chamber infusion device230connected to the instant needle231using a connector234. Alternatively, the needle231may be an integral part of the infusion device230. The body of the infusion device may be formed from any known material of which infusion devices of the prior art are normally manufactured, preferably plastic or glass. The infusion device230may comprise an extraction chamber232and an injection chamber233that are fluidly isolated from each other. The extraction chamber232is fluidly connected to an extraction lumen232aof the needle231via an extraction channel232b. Similarly, the injection chamber233is in fluid communication with an injection lumen233aof the needle231via the injection channel233b. Although an embodiment of the needle with adjacent lumens is shown inFIG. 17, it will be understood that any other embodiment, such as, an embodiment where the lumens are in concentric relationship, may also be used.

The extraction chamber232may hold the fluid extracted from the target space, whereas the injection chamber may hold the therapeutic fluid to be injected into the target space. The chambers may share a common wall, as shown inFIG. 17, or may be completely independent of each other. In addition, they may be connected by a bracket or other suitable forms of attachment to keep them in relative position of each other.

Furthermore, each chamber includes a plunger, referred to herein as an extraction plunger235or an injection plunger236respectively. The plungers may be standard infusion device plungers as would be found in single chamber infusion devices well known in the art. The plungers move independently of each other. InFIG. 17, the injection chamber233is shown loaded with the therapeutic fluid and with the injection plunger236in a fully proximal position. The therapeutic fluid may be injected into the target space by moving the injection plunger distally. On the contrary, the extraction plunger is shown in the most distal position and, by pulling the extraction plunger proximally, the target space content may be extracted from the target space into the extraction chamber of the infusion device.

In another aspect, a method of delivering therapeutic fluid to a target space is provided. Initially, the extraction chamber of an infusion device may be emptied while the injection chamber of the infusion device may be loaded with therapeutic fluid in preparation for the procedure. The needle may be inserted into the joint space using any known technique by itself or with the aid of a guidewire. The insertion and positioning of the needle may be performed under radiographic or image guided control to verify proper positioning inside the joint space. Once the needle is inserted into the target space, at least a portion of the target space content is extracted from the target space, thus creating a pressure gradient as described above. To extract at least a portion of the target space content, a negative pressure is created in the extraction chamber to draw the target space content through the one or more extraction orifices and extraction lumen into the extraction chamber. Concurrently or sequentially, a positive pressure is created in the injection chamber forcing the therapeutic fluid from the infusion chamber through the injection lumen and injection orifice into the target space.

As explained above, the needle is designed to extract the target space fluid or hydrated target space tissue while replacing it with therapeutic fluid. This method may allow for the introduction of a larger volume of therapeutic agent, a larger distribution of therapeutic agent, and flushing out of natural degenerative factors making the treatment more effective.

The variety of compounds encompassed by the anti-inflammatory group of agents are well-known to those skilled in the art. For detailed disclosure of the chemical structure, synthesis, side effects, etc. of non-steroidal anti-inflammatory compounds, reference may be made to standard texts, including Anti-inflammatory and Anti-Rheumatic Drugs, K. D. Rainsford, Vol. I-III, CRC Press, Boca Raton, (1985), and Anti-inflammatory Agents, Chemistry and Pharmacology 1, R. A. Scherrer, et al., Academic Press, New York (1974). Mixtures of these non-steroidal anti-inflammatory compounds may also be employed, as well as the pharmacologically acceptable salts and esters of these compounds.

In some embodiments, analgesics may also be included. Analgesics may comprise, without limitation, non-steroid anti-inflammatory drugs, non-limiting examples of which have been recited above. Further, analgesics also include other types of compounds, such as, for example, opioids (such as, for example, morphine and naloxone), local anaesthetics (such as, for example, lidocaine), glutamate receptor antagonists, adenosine, canabinoids, cholinergic and GABA receptors agonists, and different neuropeptides. A detailed discussion of different analgesics is provided in Sawynok et al., (2003) Pharmacological Reviews, 55:1-20.

The instruments and methods described above are particularly suitable for delivering therapeutic fluids to joint spaces such as knee joints and intervertebral discs. In one non-limiting embodiment, a nucleus pulposus of a degenerated intervertebral disc may be replaced or supplemented with a tissue bulking material that preserves the movement in the intervertebral joint. A wide variety of biocompatible polymeric materials may be used as a tissue bulking material.

They may include, but are not limited to, elastic materials, such as elastomeric materials, hydrogels or other hydrophilic polymers, or composites thereof. Suitable elastomers include silicone, polyurethane, copolymers of silicone and polyurethane, polyolefins, such as polyisobutylene and polyisoprene, neoprene, nitrile, vulcanized rubber and combinations thereof. Suitable hydrogels include natural hydrogels, and those formed from polyvinyl alcohol, acrylamides such as polyacrylic acid and poly(acrylonitrile-acrylic acid), non-resorbable polyurethanes, polyethylene glycol, poly(N-vinyl-2-pyrrolidone), acrylates such as polyacrylates, poly(2-hydroxy ethyl methacrylate), methyl methacrylate, 2-hydroxyethyl methacrylate, and copolymers of acrylates with N-vinyl pyrrolidone, N-vinyl lactams, acrylamide, polyurethanes and polyacrylonitrile, or may be other similar materials that form a hydrogel. The hydrogel materials may further be cross-linked to provide further strength to the implant. Examples of polyurethanes include thermoplastic polyurethanes, aliphatic polyurethanes, segmented polyurethanes, hydrophilic polyurethanes, polyether-urethane, polycarbonate-urethane and silicone polyether-urethane. Other suitable hydrophilic polymers include naturally-occurring materials such as glucomannan gel, polyphosphazenes, hyaluronic acid, polysaccharides, such as cross-linked carboxyl-containing polysaccharides, alkyl celluloses, hydroxyalkyl methyl celluloses, sodium chondroitin sulfate, cyclodextrin, polydextrose, dextran, gelatin, and combinations thereof.

Other suitable examples of the bulking materials include lightly cross-linked biocompatible homopolymers and copolymers of hydrophilic monomers such as 2-hydroxyalkyl acrylates and methacrylates, N-vinyl monomers, and ethylenically unsaturated acids and bases; polycyanoacrylate, polyethylene oxide-polypropylene glycol block copolymers, polygalacturonic acid, polyvinyl pyrrolidone, polyvinyl acetate, polyalkylene glycols, polyethylene oxide, collagen, sulfonated polymers, vinyl ether monomers or polymers, alginate, polyvinyl amines, polyvinyl pyridine, and polyvinyl imidazole. One can also use superabsorbent polymers (SAP) with or without additives. Superabsorbent polymers may include polymer chains that are synthetic, natural, and hybrid synthetic/natural polymers. Exemplary superabsorbent polymers may include, but are not limited to, polyacrylic acid, polymethacrylic acid, polymaleic acid, copolymers thereof, and alkali metal and ammonium salts thereof; graft copolymers of starch and acrylic acid, starch and saponified acrylonitrile, starch and saponified ethyl acrylate, and acrylate-vinyl acetate copolymers saponified; polyvinylpyrrolidone, polyvinyl alkylether, polyethylene oxide, polyacrylamide, and copolymers thereof; copolymers of maleic anhydride and alkyl vinylethers; saponified starch graft copolymers of acrylonitrile, acrylate esters, vinyl acetate, and starch graft copolymers of acrylic acid, methyacrylic acid, and maleic acid; the product of crosslinking acrylamide with backbones of kappa-carrageenan and sodium alginate using methylenebisacrylamide and potassium persulfate; and the product of crosslinking, using a bifunctional crosslinking reagent, an acyl-modified protein matrix such as soy protein isolate which has been acyl-modified by treatment with ethylenediaminetetraacetic acid dianhydride; mixtures and combinations thereof. Further, one can use silicone-based materials, polyethylene terephthalate, polycarbonate, thermoplastic elastomers and copolymers such as ether-ketone polymers such as poly(etheretherketone.

Alternatively, the disc may be removed and adjacent vertebrae may be fused together by a procedure known as interbody fusion. The materials, referred to as fusion disc materials, provide scaffolding through and around which the patient's new bone can grow, gradually replacing these materials as the adjacent vertebrae fuse. Some examples of materials suitable for interbody fusion include, but are not limited to, flowable growth factor carriers, such as polysaccharides, proteins and polypeptides, glycosaminoglycans, proteoglycans, collagen, elastin, hyaluronic acid, dermatan sulfate, chitin, chitosan, pectin, (modified) dextran, (modified) starch, or mixtures or composites thereof. In addition, injectable matrices include Norian® SRS® Bone Void Filler, Synthes, West Chester, Pa.; CORTOSS® Injectable Synthetic Bone Filler, Orthovita, Malvern, Pa.; and Cerament Bone Void Filler, Bone Suporifice AB, Sweden. Other materials that are suitable as matrices include

Any suitable bone cement including, but not limited to, acrylic based bone cement, pastes comprising bone particles, or ceramic based cements may be used. Preferably, a low-viscosity liquid bone cement is employed. Synthetic polymers may also be employed, including for example biodegradable synthetic polymers such as polylactic acid, polyglycolide, polylactic polyglycolic acid copolymers (“PLGA”), polycaprolactone (“PCL”), poly(dioxanone), poly(trimethylene carbonate) copolymers, polyglyconate, poly(propylene fumarate), poly(ethylene terephthalate), poly(butylene terephthalate), polyethyleneglycol, polycaprolactone copolymers, polyhydroxybutyrate, polyhydroxyvalerate, tyrosine-derived polycarbonates and any random or (multi-)block copolymers, such as bipolymer, terpolymer, quaterpolymer, etc., that can be polymerized from the monomers related to the previously-listed homo- and copolymers.

When treating a knee joint, the instant needle may be used to deliver visco-supplements to the joint. Because Hyaluronic Acid (“HA”) is a natural component of synovial fluid and plays an essential part in its viscoelastic properties, HA is a natural candidate for a visco-supplement. Currently, there are at least five FDA approved HA based products on the market, including Euflexxa™, Hyalgan®, Synvisc®, Supartz® and Orthovisc®. Any of these products or any combinations thereof may be used as the lubricating agent for the combinations described herein. Another suitable example of the visco-supplement comprises Lubricin which is available from, for example, Affinity BioReagents, Inc. of Golden, Co.

While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes and modifications that come within the spirit of the invention are desired to be protected. It should be understood that while the use of the word preferable, preferably or preferred in the description above indicates that the feature so described may be more desirable, it nonetheless may not be necessary and embodiments lacking the same may be contemplated as within the scope of the invention, that scope being defined by the claims that follow. In reading the claims it is intended that when words such as “a,” “an,” “at least one,” “at least a portion” are used there is no intention to limit the claim to only one item unless specifically stated to the contrary in the claim. Further, when the language “at least a portion” and/or “a portion” is used the item may include a portion and/or the entire item unless specifically stated to the contrary.