System and method for controlling flow of therapeutic agent delivered to infusion catheter

Abstract

Described herein are devices and systems and methods for treating a patient for use with or including at least one infusion catheter having a proximal end with a seat, a distal end with a distal tip, and a lumen extending from the proximal end to the distal tip. The device includes a connector body having a first connector for fluidly coupling and removably connecting to a seat of at least one infusion catheter, a second connector for fluidly coupling and removably connecting to at least one manual injector pump, and a passive pressure controlled mechanical flow regulator, the passive pressure controlled mechanical flow regulator regulates the flow of fluid supplied to and delivered by the infusion catheter into the vascular system of the patient by the manual pumping action of the at least one manual syringe pump. The mechanical flow regulator may be configured to deliver a therapeutic agent or auxiliary fluid supplied under pressure by a pumping action of the at least one manual injector pump into and through a lumen of the infusion catheter at a desired infusion rate.

Description

[0001] Cross Reference to Related Applications

[0002] This application claims priority to U.S. Patent Application Serial No. 18 / 087,767, filed December 22, 2022, the entire contents of which are incorporated herein by reference. BACKGROUND

[0003] 1. Field

[0004] The present disclosure generally relates to systems and methods for delivering a therapeutic agent into a patient’s vasculature to treat a disease of a target organ.

[0005] 2. State of the Art

[0006] Infusion catheters are used to deliver a therapeutic agent into a patient’s vasculature to treat a disease of a target organ. Infusion catheters have a hub for connecting a source of the therapeutic agent.

[0007] For cases where infusion under pressure and / or at a controlled flow rate is required, current systems typically use electrically controlled pumps to provide consistent flow for effective infusion. Operation of the electrically controlled pumps is managed by a control system configured to automatically control and regulate the flow of the therapeutic agent through the infusion catheter. The use of electrically controlled pumps complicates the process, requiring tubing extensions and personnel to handle the therapeutic agent outside the sterile field. SUMMARY

[0008] Described herein are devices and systems for treating a patient that are used with or include at least one infusion catheter having a proximal end with a hub, a distal end with a distal tip, and a lumen extending from the proximal end to the distal tip. The device includes a connector body having a first connector for fluidly coupling and detachably connecting to the hub of the at least one infusion catheter, a second connector for fluidly coupling and detachably connecting to at least one manual syringe pump, and a passive pressure-controlled mechanical flow regulator that regulates a flow of fluid supplied by manual pumping action of the at least one manual syringe pump into the infusion catheter and delivered by the infusion catheter into a patient’s vasculature.

[0009] In embodiments, the passive pressure-controlled mechanical flow regulator can be configured to deliver a therapeutic agent or auxiliary fluid supplied under pressure by the pumping action of the at least one manual syringe pump into and through the lumen of the infusion catheter at a desired infusion rate.

[0010] In embodiments, the connector body can further include a first flow path extending through the first connector and fluidically coupled to a lumen of the infusion catheter during use, and a second flow path extending through the second connector and fluidically coupled to the at least one manual syringe pump during use. The passive pressure-controlled mechanical flow regulator can be fluidically coupled to both the first flow path and the second flow path.

[0011] In embodiments, the connector body can further include a third connector for fluidically and detachably connecting to at least one additional manual syringe pump, and a third flow path extending through the third connector and fluidically coupled to the at least one additional manual syringe pump during use. The passive pressure-controlled mechanical flow regulator can be fluidically coupled to the third flow path.

[0012] In embodiments, the passive pressure-controlled mechanical flow regulator can include:

[0013] i) a first pressure-reducing valve having an inlet fluidically coupled to the second flow path and an outlet fluidically coupled to the first flow path;

[0014] ii) a second pressure-reducing valve having an inlet fluidically coupled to the first flow path and an outlet fluidically coupled to the third flow path;

[0015] iii) a third pressure-reducing valve having an inlet fluidically coupled to the third flow path and an outlet fluidically coupled to the first flow path; and

[0016] iv) a fourth pressure-reducing valve having an inlet fluidically coupled to the first flow path and an outlet fluidically coupled to the second flow path.

[0017] The first pressure-reducing valve and the third pressure-reducing valve can be configured to open at a respective first predetermined supply pressure corresponding to a desired infusion rate, and the second pressure-reducing valve and the fourth pressure-reducing valve can be configured to open at a respective second predetermined supply pressure greater than the first predetermined supply pressure.

[0018] In embodiments, the first pressure-reducing valve and the second pressure-reducing valve can be configured to deliver a therapeutic agent supplied under pressure by pumping action of the at least one manual syringe pump into and through the lumen of the infusion catheter at the desired infusion rate, and to direct any excess flow into the at least one additional manual syringe pump, and the third pressure-reducing valve and the fourth pressure-reducing valve can be configured to deliver a therapeutic agent supplied under pressure by pumping action of the at least one additional manual syringe pump into and through the lumen of the infusion catheter at the desired infusion rate, and to direct any excess flow into the at least one manual syringe pump.

[0019] In embodiments, the connector body can further include a passive flow restrictor coupled to the flow path downstream of the passive pressure control mechanical flow regulator. The passive flow restrictor can take the form of a fixed size orifice or plug or other suitable passive flow regulating mechanism. The passive flow restrictor can be configured such that a low flow of fluid through the connector body generates sufficient pressure to activate the first pressure reducing valve and the second pressure reducing valve.

[0020] In embodiments, the connector body can further include a second connector for fluidically coupling and removably connecting to at least one additional manual syringe pump in a configuration that bypasses the passive pressure control mechanical flow regulator.

[0021] In embodiments, the connector body can further include a first flow path extending through the first connector and fluidically coupled to a lumen of the infusion catheter during use, a second flow path extending through the second connector and fluidically coupled to the at least one manual syringe pump during use, and an additional flow path extending through the second connector and fluidically coupled to the at least one additional manual syringe pump during use. The passive pressure control mechanical flow regulator can be fluidically coupled to both the first flow path and the second flow path, and the additional flow path can be fluidically coupled to the second flow path downstream of the passive pressure control mechanical flow regulator.

[0022] In embodiments, the connector body can further include a check valve disposed between the passive pressure control mechanical flow regulator and the additional flow path.

[0023] In embodiments, the connector body can be configured to deliver a therapeutic agent supplied under pressure by pumping action of the at least one manual syringe pump into and through the lumen of the infusion catheter at a desired infusion rate. The connector body can be further configured to deliver an auxiliary fluid supplied under pressure by pumping action of the at least one additional manual syringe pump into and through the lumen of the infusion catheter.

[0024] In embodiments, the passive pressure control mechanical flow regulator can include a chamber having an inlet to an interior space of the chamber, and a restrictor tube extending into the interior space of the chamber, wherein the restrictor tube includes a restrictor inlet disposed within the interior space of the chamber and an annular resilient membrane spaced apart from the restrictor inlet.

[0025] In embodiments, the resilient membrane can be configured to deform or deflect radially inward to regulate fluid flow through the restrictor tube.

[0026] In embodiments, the restrictor tube can further include a bypass valve having an inlet in fluid communication with the interior space of the chamber and an outlet in fluid communication with the lumen of the restrictor tube. The bypass valve can be configured to open at a predetermined pressure within the interior space of the chamber that is greater than a pressure corresponding to a desired infusion rate of fluid flow through the restrictor tube.

[0027] In embodiments, the passive pressure-controlled mechanical flow regulator can include a fixed size restrictor orifice corresponding to a desired infusion rate.

[0028] In embodiments, the fixed size of the restrictor orifice can be based on an infusion of a fluid of a known viscosity pumped by a manual syringe pump of a predetermined size over a predetermined operating pressure range.

[0029] Related systems and kits and methods are also described and claimed. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1A is a schematic illustration of a medical system according to a first embodiment of the present disclosure.

[0031] Figure 1B is a schematic illustration of a connector body of the system of Figure 1A

[0032] Figure 1C illustrates an example helical spring valve.

[0033] Figures 1D-1F illustrates an example slit valve.

[0034] Figure 1G illustrates an example resilient duckbill valve.

[0035] Figure 2 is a flowchart illustrating a medical procedure for treating a patient using the system of Figure 1A

[0036] Figure 3 is a schematic illustration of an example infusion catheter.

[0037] Figure 4 is a schematic illustration of a medical system according to a second embodiment of the present disclosure.

[0038] Figure 5 is a schematic illustration of a medical system according to a third embodiment of the present disclosure.

[0039] Figure 6A is a schematic illustration of an example pressure-controlled mechanical flow regulator that can be part of a connector body of the system of Figure 5

[0040] Figure 6B and​​​6C is Figure 6A schematic views of different configurations of an annular elastic (flexible) membrane of an exemplary pressure-controlled mechanical flow regulator.

[0041] Figure 7 is a schematic view of a medical system according to a fourth third embodiment of the present disclosure. DETAILED DESCRIPTION

[0042] With reference to the following description, the terms“proximal” and“distal” are defined with reference to the hand of a user of the devices and systems described herein, with the term“proximal” being closer to the hand of the user and the term“distal” being further from the hand of the user, so as to generally be located further into the patient during use. The term“passive” is defined with reference to the flow regulation mechanism described herein, with the term“passive” meaning that the flow regulation mechanism does not employ a source of electromotive force.

[0043] Turning to Figure 1A and 1B , a medical system 11 is provided that includes a connector body 13 having a first syringe connector 15A, a second syringe connector 15B, and a catheter hub connector 15C integral with the connector body 13. The first syringe connector 15A can be configured to fluidically and detachably connect to a first manual syringe pump 17A, for example, using a luer fitting 19A at a distal tip of the first manual syringe pump 17A as shown. The second syringe connector 15B can be configured to fluidically and detachably connect to a second manual syringe pump 17B, for example, using a luer fitting 19B at a distal tip of the second manual syringe pump 17B as shown. The first and second manual syringe pumps 17A, 17B can be conventional manual syringe pumps, each including a piston having a proximal handle that axially sealably slides within an annular pump body. The pump body defines a variable-volume reservoir that holds fluid therein for egress from an open distal tip when the piston is moved distally toward the open distal tip, or ingress into the reservoir from the open distal tip when the piston is moved proximally away from the open distal tip. The catheter hub connector 15C is configured to fluidically and detachably connect to a hub 21 of an infusion catheter as shown. The infusion catheter can be configured to deliver a therapeutic agent and / or an ancillary fluid (such as a bolus of contrast media for vascular imaging and visualization, saline or other non-therapeutic agent, or a different therapeutic agent) into the vascular system of a patient for treatment of a disease of a target organ. For example, the hub 21 can correspond to the hub 308 of the exemplary infusion catheter of Figure 3 , or other suitable infusion catheter can be used.

[0044] The first syringe connector 15A and the connector body 13 provide an internal flow path (channel) 23A that branches and fluidly couples to two valves Vl and V4 that are integral with the connector body 13. Specifically, one branch of the flow path (channel) 23A fluidly couples to an inlet of the valve Vl, while another branch of the flow path (channel) 23A fluidly couples to an outlet of the valve V4. The valves Vl and V4 also fluidly couple to an internal flow path (channel) 23C that extends through the connector body 31 and through the catheter hub connector 15C to the hub 21. Specifically, an outlet of the valve Vl fluidly couples to the internal flow path (channel) 23C, and an inlet of the valve V4 fluidly couples to the internal flow path (channel) 23C.

[0045] Similarly, the second syringe connector 15B and the connector body 13 provide an internal flow path (channel) 23B that branches and fluidly couples to two valves V2 and V3 that are integral with the connector body 13. Specifically, one branch of the flow path (channel) 23B fluidly couples to an inlet of the valve V3, while another branch of the flow path (channel) 23B fluidly couples to an outlet of the valve V2. The valves V2 and V3 also fluidly couple to the internal flow path (channel) 23C that extends through the connector body 31 and through the catheter hub connector 15C to the hub 21. Specifically, an outlet of the valve V3 fluidly couples to the internal flow path (channel) 23C, and an inlet of the valve V2 fluidly couples to the internal flow path (channel) 23C.

[0046] Figure 1B The components shown separately integral with the connector body 13 (not connected to both manual syringe pumps and a catheter hub). In embodiments, the connector body 13 can be hand-holdable and / or include one or more housing portions that enclose and / or mechanically support the first syringe connector 15A, the second syringe connector 15B, and the catheter hub connector 15C along with the flow paths (channels) 23A, 23B, 23C and the valves Vl, V2, V3, and V4 shown. The flow paths / channels 23A, 23B, 23C can be implemented by tubing and associated fluid couplings or other suitable fluid transport structures and devices. The valves Vl, V2, V3, and V4 can be embodied as medical grade pressure reducing valves suitable for controlling fluid flow therethrough without reacting with and contaminating the fluid.

[0047] For example, the valves Vl, V2, V3, and V4 can be as Figure 1CThe illustrated coil spring valve employs a coil spring to provide a spring bias that holds the valve in a closed state to block fluid flow through the valve. When sufficient pressure at the inlet of the valve overcomes the spring bias provided by the coil spring, the valve opens to allow flow through the valve. Alternatively, the valve can employ a leaf spring or other spring to provide a spring bias that holds the valve in a closed state.

[0048] In another example, the valves VI, V2, V3, and V4 can be slit valves as illustrated in Figures 1D-1F The slit valve employs a resilient diaphragm or sealing gasket having a slit that is configured to be in a closed state to block flow through the valve, as illustrated in Figure 1E When sufficient pressure at the inlet of the valve opens the slit of the diaphragm or gasket, the valve opens to allow flow through the valve, as illustrated in Figure 1F .

[0049] In another example, the valves VI, V2, V3, and V4 can be resilient duckbill valves as illustrated in Figure 1G The resilient duckbill valve employs a resilient cone leading to an outlet that is configured to be in a closed state to block fluid flow through the valve. When sufficient pressure at the inlet of the valve deforms the resilient cone and opens the outlet of the valve, the valve opens to allow flow through the valve.

[0050] The system 11 can be configured to maintain consistency of delivery of the therapeutic agent and / or auxiliary fluid into the vasculature of the patient in conjunction with manual pumping actions provided by a user (physician) of one or both of the first and second manual syringe pumps 17A and 17B. In this manner, the system 11 can significantly reduce the complexity of the procedure while maintaining the favorable distribution and uptake patterns observed for the desired infusion rate (or desired infusion rate window).

[0051] In an embodiment, the valve VI can be designed and configured to open at a predetermined supply pressure SP V1 at which a desired infusion rate is produced. In this manner, when the pressure within the flow path (channel) 23A coupled to the inlet of the valve VI is less than such predetermined supply pressure SP V1 , the valve VI will remain closed and block flow through the valve VI and into the internal flow path (channel) 23C that extends through the connector body 31 and through the catheter hub connector 15C to the hub 21. When the pressure within the flow path (channel) 23A coupled to the inlet of the valve VI reaches or exceeds such predetermined supply pressure SP V1 , the valve VI will open and allow flow to be able to pass through the valve VI and into and through the internal flow path (channel) 23C that extends through the connector body 31 and through the catheter hub connector 15C to the hub 21.

[0052] In an embodiment, the valve V2 may be designed and configured to operate at a predetermined supply pressure SP higher than that of the valve V1. V1 Set supply pressure SP V2 In this way, when the pressure in the flow path (channel) 23C connected to the inlet of the valve V2 is less than the set supply pressure SP V2 , valve V2 will remain closed and prevent flow through valve V2 and into the internal flow path (channel) 23B, which extends through the connector body 31 and through the second syringe connector 15B to the second manual syringe pump 17B. When the pressure within the flow path (channel) 23C coupled to the inlet of valve V2 reaches or exceeds this predetermined supply pressure SP V2 When , valve V2 will open and enable flow through valve V2 and into the internal flow path (channel) 23B, which extends through the connector body 31 and through the second syringe connector 15B to the second manual syringe pump 17B.

[0053] In an embodiment, valve V3 may be designed and configured to produce a desired infusion rate at a predetermined supply pressure SP V3 Thus, when the pressure in the flow path (channel) 23B connected to the inlet of the valve V3 is less than the predetermined supply pressure SP V3 , valve V3 will remain closed and prevent flow through valve V3 and into internal flow path (passageway) 23C, which extends through connector body 31 and through catheter hub connector 15C to hub 21. When the pressure within flow path (passageway) 23B coupled to the inlet of valve V3 reaches or exceeds the predetermined supply pressure SP V3 When , valve V3 will open and enable flow through valve V3 and into internal flow path (passageway) 23C, which extends through connector body 31 and through catheter hub connector 15C to hub 21.

[0054] In an embodiment, valve V4 may be designed and configured to operate at a predetermined supply pressure SP higher than valve V3. V3 Set supply pressure SP V4 , opens to relieve excess pressure / excess flow and allow flow into the reservoir of the first manual syringe pump 17A. In this way, when the pressure in the flow path (channel) 23C connected to the inlet of the valve V4 is less than the set supply pressure SP V4, valve V4 will remain closed and prevent flow through valve V4 and into the internal flow path (channel) 23A, which extends through the connector body 31 and through the first syringe connector 15A to the first manual syringe pump 17A. When the pressure within the flow path (channel) 23C coupled to the inlet of valve V4 reaches or exceeds this predetermined supply pressure SP V4 When , valve V4 will open and enable flow through valve V4 and into the internal flow path (channel) 23A, which extends through the connector body 31 and through the first syringe connector 15A to the first manual syringe pump 17A.

[0055] exist Figure 1A and Figure 1B In the configuration, valves V1, V2, V3 and V4 of the connector body 14 provide a passive pressure control mechanical mechanism for regulating the flow of therapeutic agent and / or auxiliary fluid, which is supplied to the infusion catheter and delivered into the patient's vascular system through the infusion catheter at a desired infusion rate or close to the desired infusion rate.

[0056] In an embodiment, Figure 1A and Figure 1B The connector body 13 may optionally include a passive flow restrictor FR coupled to the flow path downstream of valves V1, V2, V3, and V4. The passive flow restrictor FR is a device that regulates the flow rate of the fluid flowing through the flow path. The passive flow restrictor FR may be a fixed-size orifice or plug, or other suitable passive flow regulating mechanism. The passive flow restrictor may be configured such that a low flow rate of fluid through the connector body generates sufficient pressure to activate the first and second pressure-reducing valves V1 and V2.

[0057] Figure 2 The operation of the system 11 of Figure 1 during a medical procedure in which a therapeutic agent is delivered to the patient's vascular system is shown. As part of such a medical procedure, an infusion catheter is introduced into a target vessel of the vascular system by a user (physician). In an embodiment, the target vessel may extend into or near a tumor or other diseased tissue. The target vessel may supply blood or drain blood from any of a variety of organs, including but not limited to the pancreas, spleen, gastrointestinal tract, liver, lungs, uterus, prostate, or brain, as well as target vessels in communication with head and neck tumors. The target vessel may also be in communication with other organs or tissues of interest for treatment in other parts of the body. In an embodiment, the therapeutic system may be introduced into or adjacent to a target vessel non-vascularly.

[0058] In block 201 , a therapeutic agent is loaded into the reservoir of a first manual syringe pump 17A.

[0059] In block 203, the reservoir of the second manual syringe pump 17B is initially empty.

[0060] In block 205 , the user (physician) manually initiates the pumping action of the first syringe pump 17A.

[0061] In block 207, during the manual pumping action of block 205, valve V1 is configured to open at a predetermined supply pressure that produces the desired infusion rate, and valve V2 is configured to open at a set supply pressure that is higher than the predetermined supply pressure of V1 to relieve any overpressure / overflow and allow excess flow of therapeutic agent to enter the reservoir of second syringe pump 17B. In this configuration, manual pumping action of first syringe pump 17A causes the flow of therapeutic agent to be delivered through valve V1 into and through flow path (channel) 23C, and into and through catheter adapter connector 15C for delivery through the infusion catheter at or near the desired infusion rate. Any overpressure and excess flow of therapeutic agent into flow path (channel) 23C caused by the manual pumping action of first syringe pump 17A will be diverted via valve V2 to the reservoir of second syringe pump 17B.

[0062] In box 209, the user's pumping action of boxes 205 and 207 and the delivery of therapeutic agent from the reservoir of the first syringe pump continue until the reservoir of the first syringe pump is empty (or nearly empty), and if the reservoir of the second syringe pump is not empty (or nearly empty), the operation continues to box 211.

[0063] In block 211 , the user (physician) manually initiates the pumping action of the second syringe pump 17B.

[0064] In block 213, during the manual pumping action of block 211, valve V3 is configured to open at a predetermined supply pressure that produces the desired infusion rate, and valve V4 is configured to open at a set supply pressure that is higher than the predetermined supply pressure of V3 to relieve any overpressure / overflow and allow excess flow of therapeutic agent to enter the reservoir of first syringe pump 17A. In this configuration, manual pumping action of second syringe pump 17B causes the flow of therapeutic agent to be delivered through valve V3 into and through flow path (channel) 23C, and into and through catheter adapter connector 15C for delivery through the infusion catheter at or near the desired infusion rate. Any overpressure and excess flow of therapeutic agent into flow path (channel) 23C caused by the manual pumping action of second syringe pump 17B will be diverted via valve V4 to the reservoir of first syringe pump 17A.

[0065] In block 215, the user's pumping action and delivery of therapeutic agent from the reservoir of the second syringe pump continues until the reservoir of the second syringe pump is empty (or nearly empty), and if the reservoir of the first syringe pump is not empty (or nearly empty) at block 217, the operation may return to block 205. Once both syringes have been emptied of the prescribed delivery dose (which may be set to leave a predetermined volume of therapeutic agent in the first or second syringe) at block 219, the process ends.

[0066] In this way, the process can be combined with the manual pumping action provided by the user (physician) operation of one or both of the first manual syringe pump 17A and the second manual syringe pump 17B (including alternating use of the first manual syringe pump 17A and the second manual syringe pump 17B) to maintain consistent delivery of the therapeutic agent into the patient's vascular system at a desired infusion rate or close to the desired infusion rate until the infusion is complete. In addition, the therapeutic agent can include suspended particles (e.g., large particles of protein, resin spheres, glass spheres, gel beads, other embolic particles) and / or emulsions of liquids that do not normally mix (typically in iodized oil), in which case the regulated flow provided by the connector body 13 can keep the suspended particles and / or emulsified liquid uniformly dispersed in the flow through the connector body during administration.

[0067] In an embodiment, the desired infusion rate can be in the range of from 0.1 ml / second to 4 ml / second or in the range of larger, and for such infusion rate, the supply pressure at the catheter seat is in the range of from 9psi to 2000psi. These supply pressure values ​​can be used for designing the flow path of the valve and connector body for the desired infusion rate, and a suitable manual syringe pump can also be selected. Specifically, the maximum pressure of the manual syringe pump can vary according to the size of the syringe pump, and thus the size of the manual syringe pump should be selected to have a maximum pressure that matches or exceeds the supply pressure that provides the desired infusion rate. For example, if the desired infusion rate is 0.5 ml / second at a supply pressure of 90 to 99psi, a manual syringe pump (e.g., a conventional syringe pump of 10cc or less) with a maximum pressure exceeding 100psi can be used in this process.

[0068] exist Figure 2During the course of treatment, a high pressure flow of an auxiliary fluid (e.g., a bolus of contrast media for angiographic imaging and visualization, saline or other non-therapeutic agent, or a different therapeutic agent) can also be delivered into the patient's vasculature through the infusion catheter of system 11. For example, the auxiliary fluid can be loaded into the reservoir of an additional hand-held syringe pump (not shown). The additional hand-held syringe pump can be a conventional hand-held syringe pump as described herein. The additional hand-held syringe pump can be fluidly coupled to and detachably connected to one of the first and second syringe connectors (e.g., 15A), while the other of the first and second syringe connectors (e.g., 15B) is capped to prevent flow through the other syringe connector. The user (physician) can manually initiate pumping action of the additional hand-held syringe pump to deliver the auxiliary fluid from the additional hand-held syringe pump into and through the flow path (channel) 23C, and into and through the catheter hub connector 15C for delivery into and through the infusion catheter and into the patient's vasculature. In this configuration, the pressure relief valve (V2 or V4) whose outlet is open to the capped syringe connector does not operate to relieve overpressure / overflow. Thus, the manual pumping action of the additional hand-held syringe pump can be used to deliver a flow of the auxiliary fluid into and through the infusion catheter and into the patient's vasculature at the desired infusion rate of the therapeutic agent or at a pressure above the desired infusion rate. In embodiments, after infusion of the therapeutic agent, the manual pumping action of the additional hand-held syringe pump can be used to deliver a flow of the auxiliary fluid into and through the infusion catheter and into the patient's vasculature, and such auxiliary fluid delivery can be performed at an overpressure / overflow above the desired infusion rate of the therapeutic agent, such that the flow of the auxiliary fluid pushes the therapeutic agent in the vasculature toward the diseased tissue.

[0069] Figure 3 An embodiment of an exemplary infusion catheter 101 is shown in FIG. 3, which includes a flexible tubular body 302 having a proximal end 304 and a distal end 306. The tubular body 302 preferably has a length of two to eight feet and preferably has an outer diameter of 0.67 mm to 3 mm (corresponding to catheter sizes 2 French to 12 French). The tubular body 302 preferably includes an inner liner, an inner braid, and an outer coating. As an example, the liner can be made of a fluorinated polymer, such as polytetrafluoroethylene (PTFE) or fluorinated ethylene propylene (FEP). As an example, the braid is made of a metal, such as stainless steel or nickel-titanium alloy, or a polymer, such as polyethylene terephthalate (PET) or a liquid crystal polymer. As an example, the outer coating is made of a polyether block amide thermoplastic elastomer resin polyurethane, polyamide copolymer, polyester, polyester copolymer, fluorinated polymer (e.g., PTFE, FEP), polyimide, polycarbonate, or any other suitable material, or any other standard or specialty material used to manufacture catheters for use in blood flow.

[0070] The proximal end 304 of the tubular body 302 is preferably provided with a hub 308. The infusion lumen 320 extends internally through the hub 308 and through the interior of the tubular body 302 to the distal end 306 and exits at an open distal tip or orifice 307. The hub 308 and infusion lumen 320 are adapted to deliver a therapeutic agent from outside the patient's body into the patient's vasculature (arterial or venous) to treat a disease in a target organ. The hub 308 can also be adapted to facilitate the advancement of a guidewire through the infusion lumen 320. Any hub 308 suitable to at least facilitate the delivery of a therapeutic agent into the infusion lumen can be used.

[0071] A occlusion device 308 is preferably coupled with the distal end 306 of the tubular body 302. The occlusion device prevents backflow of the therapeutic agent between the vessel wall and the catheter to non-treatment tissue during the agent delivery. The occlusion device can be static or dynamic during use. Static occlusion devices include inflatable balloons. Dynamic occlusion devices include microvalves that inflate and deflate in response to changes in the surrounding fluid pressure within the vessel. When the therapeutic agent is being infused, the microvalves open and contact the vessel wall to prevent backflow of the therapeutic agent, which would otherwise be caused by the vessel resistance. In a preferred embodiment, the occlusion device 308 includes elastic wires 322, each of which includes a proximal portion 324, a central portion 326, and a distal portion 328. The proximal portion 324 is attached circumferentially to the outer surface 330 of the tubular body 302 at a location proximal of the open distal tip or aperture 307. The central portion 326 extends radially outward and toward the open distal tip or aperture 307. The distal portion 328 turns back into the occlusion device 308 and is coupled circumferentially around the outer surface 330. The proximal portion 324 and the central portion 326 are coated with a polymeric filter coating 334 that extends between and across the wires 322. The distal portions 328 of the wires 322 are uncoated. The infusion catheter 301 is commercially produced and sold as the TRINAV Infusion System by Trisalus Life Sciences, Inc., Westminster, CO. In use, the infusion catheter 301 can be deployed from a guide sheath (shown schematically as 336) at the target vessel location; but need not be used with a guide sheath. Rather, the infusion system can be advanced over a guide wire without any guide sheath, providing good results with trackability. Upon introduction into the vessel, the valve occlusion device 308 has been shown to operate dynamically in synchronization with the patient's cardiac cycle and to maintain over seventy percent antegrade blood flow in the vessel behind the microvalve occlusion device, while providing the expected retrograde treatment blockage. In addition, the design allows for non-invasively increasing the pressure of the therapeutic agent into the locally resistive tumor vessels to achieve deeper perfusion delivery of the therapeutic agent. In alternative embodiments, one or more other infusion catheters can be used as part of the systems and methods described herein.

[0072] Figure 4 Another embodiment of a medical system 11' is shown, which is similar to the above-described medical system 11, but with a different configuration of the medical device 12'. The medical device 12' comprises a catheter 13' and a medical device 14' coupled with the catheter 13'. The catheter 13' comprises a tubular body 15' and a distal end 16' of the tubular body 15'. The medical device 14' comprises a distal portion 17' and a proximal portion 18'. The distal portion 17' is coupled with the distal end 16' of the tubular body 15'. The proximal portion 18' is coupled with the proximal end of the tubular body 15'. The medical device 14' is configured to be advanced distally along the tubular body 15' from the proximal portion 18' to the distal portion 17'. The medical device 14' is configured to be advanced proximally along the tubular body 15' from the distal portion 17' to the proximal portion 18'. The medical device 14' is configured to be advanced distally and proximally along the tubular body 15' from the proximal portion 18' to the distal portion 17' and vice versa. Figure 1A and 1BThe described embodiment adds a second syringe connector 25 and a check valve CV integral with the connector body 13. The second syringe connector 25 can be capped to block flow through the second connector 25 during pumping operations of the first manual syringe pump 17A and / or the second manual syringe pump 17B. Alternatively, the second syringe connector 25 can be fluidically coupled and detachably connected to an additional manual syringe pump (not shown) whose reservoir is loaded with an ancillary fluid (e.g., a bolus of contrast for vascular imaging and visualization, saline or other non-therapeutic agent, or a different therapeutic agent). The second syringe connector 25 and the connector body 13 provide an internal flow path that is fluidically coupled to the internal flow path (channel) 23C that extends through the connector body 13 and through the catheter hub connector 15C to the hub 21, as shown. The check valve CV is fluidically coupled to the flow path (channel) 23C upstream of the flow path to the second connector 25 and downstream of the flow paths to the valves VI, V2, V3, and V4, as shown. In this configuration, the check valve CV allows flow in one direction (i.e., flow toward the catheter hub connector 15C) and blocks flow in the opposite direction, thus blocking the ancillary fluid from flowing back toward the valves VI, V2, V3, V4, and the first and second manual syringe pumps 17A, 17B. An optional passive flow restrictor (FR) is coupled to the flow path downstream of the valves VI, V2, V3, and V4. The passive flow restrictor FR is a device that regulates the flow of fluid through the flow path. The passive flow restrictor FR can take the form of a fixed size orifice or plug or other suitable passive flow regulating mechanism. The passive flow restrictor FR can be configured such that low flow of fluid through the connector body 13 creates sufficient pressure to activate the first and second pressure relief valves VI, V2. In other embodiments, the check valve CV and the passive flow restrictor FR can be provided by a single device configured as both a check valve and a passive flow restrictor as described herein.

[0073] The system 11' can be used to perform the methods as described herein Figure 2process. Additionally or alternatively, manual pumping actuation of an additional manual syringe pump fluidically coupled to second syringe connector 25 can supply a flow of auxiliary fluid into and through flow path (channel) 23C, and into and through catheter adapter connector 15C for delivery through an infusion catheter to the patient's vascular system. In this configuration, check valve CV prevents the auxiliary fluid from flowing upstream toward valves V1, V2, V3, and V4, so that pressure relief valves V2, V4 (whose outlets lead to syringe connectors 15A, 15B) do not operate to relieve excess pressure / excess flow. The manual pumping action of the additional syringe pump can be used to deliver a flow of auxiliary fluid into and through the infusion catheter into the patient's vascular system at a pressure equal to or greater than the desired infusion rate of the therapeutic agent. In an embodiment, following the infusion of the therapeutic agent, the manual pumping action of an additional syringe pump can be used to deliver a flow of auxiliary fluid into the infusion catheter and through the infusion catheter into the patient's vascular system, and such auxiliary fluid delivery can be performed at an overpressure / overflow rate that is higher than the desired infusion rate of the therapeutic agent, such that the flow of auxiliary fluid (e.g., a bolus of saline) pushes the therapeutic agent in the vascular system toward the diseased tissue. In other embodiments, the manual pumping action of the additional syringe pump can be used to deliver the auxiliary fluid at a different infusion rate, which can be lower or higher than the desired infusion rate of the therapeutic agent.

[0074] Go to Figure 5 , a medical system 511 is provided, which includes a connector body 513 having a syringe connector 515A and a catheter seat connector 515C integral with the connector body 513. The syringe connector 515A can be configured to be fluidically coupled and detachably connected to a manual syringe pump 517, for example, using a Luer connector 519 at the distal end of the manual syringe pump 517 as shown. The manual syringe pump 517 can be a conventional manual syringe pump as described herein. The catheter seat connector 515C can be configured to be fluidically coupled and detachably connected to a seat 521 of an infusion catheter, as shown. The infusion catheter can be configured to deliver therapeutic agents and / or auxiliary fluids (such as contrast agents for vascular imaging and visualization, boluses of saline or other non-therapeutic agents, or different therapeutic agents) into the patient's vascular system for treating diseases of the target organ. For example, the seat 521 can correspond to Figure 3 The seat 308 of the exemplary infusion catheter is shown, or other infusion catheters may be used.

[0075] The syringe connector 515A and the connector body 513 provide an internal flow path (passage) 523 that extends through the connector body 513 and through the catheter hub connector 515C to the hub 521. The internal flow path (passage) 523 includes a passive pressure-controlled mechanical flow regulator 525 configured to regulate the flow of a therapeutic agent that is supplied to the infusion catheter and delivered by the infusion catheter into the vasculature of a patient at or near a desired infusion rate.

[0076] In embodiments, the connector body 513 can be hand-holdable and / or include one or more housing portions that enclose and / or mechanically support the syringe connector 515A and the catheter hub connector 515C along with the flow path (passage) 523 and the regulator 525. The flow path / passage 523 can be embodied by tubing and associated fluid couplings or other suitable fluid transfer structures and devices.

[0077] The system 511 can be configured to maintain consistency of delivery of a therapeutic agent and / or an auxiliary fluid (such as a bolus of a contrast agent for vascular imaging and visualization, saline or other non-therapeutic agent, or a different therapeutic agent) into the vasculature of a patient in conjunction with manual pumping actions provided by a user (physician) operating one or more manual syringe pumps. In this manner, the system 511 can significantly reduce the complexity of the procedure while maintaining the favorable distribution and uptake patterns observed for a desired infusion rate (or a desired infusion rate window). The therapeutic agent can include suspensions of particles (e.g., large-particle proteins, resin spheres, glass spheres, gel beads, other embolic particles) and / or emulsions of liquids that are normally immiscible (typically in iodine oil). Further, the regulated flow provided by the system 511 can be calibrated to a range of flow rates based on the size of the syringe and the resistance of the selected catheter.

[0078] Figure 6A An exemplary embodiment of a passive pressure-controlled mechanical flow regulator 525' is shown that is suitable for use as Figure 5regulator 525 in system 511. Regulator 525' includes a hollow body (or chamber) 601 having an inlet port 603 that opens to an interior space 605 of the hollow body 601. The body 601 also supports or defines a restrictor tube 607 that extends into the interior space 605 of the chamber. One end of the restrictor tube 607 defines a restrictor inlet 609 that is located within the interior space 605. The opposite end of the restrictor tube 607 defines an outlet 611 that extends from the body 601. The restrictor tube 607 defines a lumen 613 that extends from the restrictor inlet 609 to the outlet port 611, with a portion of the lumen 613 being defined by an annular elastic (flexible) membrane 615 that is configured as a variable size restrictor orifice that is pressure controlled. The inlet port 603 and the outlet port 611 can be fluidly coupled to the interior flow path (channel) 523 that extends through the connector body 531. In this configuration, the therapeutic agent supplied to the flow path (channel) 523 fills the interior space 605 of the body 601. The restrictor inlet 609 is configured to provide a pressure drop between the interior space 605 and the lumen 613. This pressure drop causes the annular elastic membrane 615 to elastically deform or deflect inwardly toward the central axis of the lumen 613 and act as a restrictor orifice for the flow of the therapeutic agent through the lumen 613 and out of the outlet port 613, as indicated by arrows 617A and 617B. In embodiments, the elastic deformation or deflection of the elastic membrane 615 can occur in a radially inward direction, but such deformation or deflection is not limited to this configuration. For example, the elastic membrane 615 can have a linear design that pinches down between two surfaces or pinches down on a hard surface. The deformation or deflection of the annular elastic membrane 615 and thus the size of the restrictor orifice can vary based on the pumping pressure. The size of the restrictor inlet can be smaller than the lumen of the infusion catheter and is configured to provide an initial flow restriction at relatively low pressures. The annular elastic membrane 615 provides an auxiliary flow restriction at higher pressures. Figure 5

[0079] Figure 6B A configuration of the annular elastic membrane 615 in an initial high pressure state is shown, in which the pressure PI in the interior space 605 is greater than or equal to the pressure P2 in the lumen 613 upstream of the annular elastic membrane 615, which is greater than the pressure P3 in the lumen 613 downstream of the annular elastic membrane 615. In this configuration, PI > P2 > P3, the deformation experienced by the annular elastic membrane 615 is proportional to the size of the pressure differential between PI, P2 relative to P3. In this way, the annular elastic membrane 615 of the restrictor tube 607 regulates the flow of the therapeutic agent that is supplied to and delivered by the infusion catheter into the vasculature of the patient at or near the desired infusion rate.

[0080] Figure 6C ​A configuration of the annular elastic membrane 615 in a low pressure steady state is shown in which the pressure PI in the interior space 605 is nearly equal to the pressure P2 in the lumen 613 upstream of the annular elastic membrane 615, which is nearly equal to the pressure P3 in the lumen 613 downstream of the annular elastic membrane 615. In this configuration, PI is nearly equal to P2, P2 is nearly equal to P3, and the annular elastic membrane 615 experiences minimal deformation or deflection. Flow of the therapeutic agent is then controlled by the restrictor inlet 609 and the resistance of the infusion system.

[0081] The restrictor tube 607 can also include an optional bypass valve 619 disposed downstream of the annular elastic membrane 615. The bypass valve 619 can be designed and configured to open at a predetermined supply pressure within the interior space 605 that exceeds an operating pressure of the desired flow through the restrictor orifice provided by the membrane 615 to the outlet port 611. In this manner, when the pressure within the interior space 605 is less than such predetermined supply pressure, the bypass valve 619 will remain closed and prevent flow through the bypass valve 619 and into the lumen 613 that extends through the restrictor tube 607 to the outlet port 611. When the pressure within the interior space 605 reaches or exceeds such predetermined supply pressure, the bypass valve 619 will open and enable flow through the bypass valve 619 and into the lumen 613 that extends through the restrictor tube 607 to the outlet port 611 as shown by arrows 621 and 617B. The bypass valve 619 can be implemented by a pressure reducing valve that is adapted to control the flow of fluid therethrough without reacting with and contaminating such fluid as described herein.

[0082] In embodiments, Figure 5 The connector 515A of the system of FIGS. 1-6 can be coupled to a first manual syringe pump 517 whose reservoir is loaded with a therapeutic agent. The first manual syringe pump 517 can be a conventional manual syringe pump as described herein. The catheter hub connector 515C can be configured to fluidically couple and detachably connect to a hub 521 of an infusion catheter as shown. For example, the hub 521 can correspond to the hub 308 of the exemplary infusion catheter of FIGS. 1-5. Figure 3 The syringe connector 515A and the connector body 513 provide an internal flow path that fluidically couples to an internal flow path (channel) 523 that extends through the connector body 513 and through the catheter hub connector 515C to the proximal hub 521 of the infusion catheter as shown. The first manual syringe pump 517 is manually actuated to pump the therapeutic agent into and through the internal flow path (channel) 523. The regulator 525' of FIG. 6 regulates the flow of the therapeutic agent supplied to and delivered by the infusion catheter to the vasculature of a patient at or near the desired infusion rate.

[0083] Additionally, or alternatively, Figure 5 The connector 515A of the system of 6 can be coupled to an additional manual syringe pump (for example, similar to the second manual syringe pump of 517), and the reservoir of this manual syringe pump is loaded with auxiliary fluid (for example, for the contrast agent of vascular imaging and visualization, saline or other non-therapeutic medicament bolus or different therapeutic agents). Additional manual syringe pump can be a conventional manual syringe pump as described herein. Catheter adapter connector 515C can be configured to fluidly couple and be detachably connected to the seat 521 of infusion catheter, as shown in the figure. In this configuration, syringe connector 515A and connector body 513 provide internal flow path, and this internal flow path fluid is coupled to internal flow path (channel) 523, and this internal flow path 523 extends through connector body 513 and passes through catheter adapter connector 515C and arrives the proximal seat 521 of infusion catheter, as shown in the figure. Manually actuate additional syringe pump to pump auxiliary fluid into internal flow path (channel) 523 and pass through this internal flow path. The bypass valve 619 of the restrictor tube 607 can be configured to open and allow flow through the bypass valve 619 and into the lumen 613 extending through the restrictor tube 607 to the outlet port 611 at a predetermined pressure and infusion rate desired for infusion of the auxiliary fluid. In this configuration, the manual pumping action of an additional syringe pump can be used to deliver the auxiliary fluid flow into the infusion catheter and through the infusion catheter into the patient's vascular system at a pressure at or above the desired infusion rate of the therapeutic agent. In embodiments, following infusion of the therapeutic agent, the manual pumping action of an additional syringe pump can be used to deliver the flow of auxiliary fluid into the infusion catheter and through the infusion catheter into the patient's vascular system, and such auxiliary fluid delivery can be performed at an overpressure / overflow rate that is higher than the desired infusion rate of the therapeutic agent, such that the flow of the auxiliary fluid (e.g., a bolus of saline) pushes the therapeutic agent in the vascular system toward the diseased tissue. In other embodiments, the manual pumping action of an additional syringe pump may be used to deliver the auxiliary fluid at a different infusion rate, which may be lower or higher than the desired infusion rate of the therapeutic agent.

[0084] As described above, the maximum pressure of a manual syringe pump varies with the size of the syringe pump, and thus the size of the manual syringe pump can be selected to have a maximum pressure that matches the supply pressure that provides the desired infusion rate for the therapeutic agent and the auxiliary fluid, respectively. For example, if the desired infusion rate of the therapeutic agent is 0.5 milliliters per second at a supply pressure of between 90 to 99 psi, and the desired infusion rate of the auxiliary fluid is 1 milliliter per second at a supply pressure of 155 to 180 psi, a manual syringe pump with a maximum pressure at or above 100 psi but below the range of 155 to 185 psi (e.g., a conventional 10 cc syringe pump) can be used to infuse the therapeutic agent, and a manual syringe pump with a maximum pressure above the range of 155 to 185 psi (e.g., a conventional 6 cc syringe pump) can be used to infuse the auxiliary fluid. In this example, the bypass valve 619 can be configured to open and provide flow through the bypass valve 619 at pressures in the range of 155-180 psi for infusion of the auxiliary fluid.

[0085] Turning to Figure 7 , a medical system 711 is provided that includes a connector body 713 having a syringe connector 715A and a catheter hub connector 715C integral with the connector body 713. The syringe connector 715A can be configured to fluidically couple and detachably connect to a manual syringe pump 717, for example, using a luer fitting 719 at a distal tip of the manual syringe pump 717 as shown. The catheter hub connector 715C can be configured to fluidically couple and detachably connect to a hub 721 of an infusion catheter as shown. The infusion catheter can be configured to deliver a therapeutic agent and / or an auxiliary fluid, such as a bolus of contrast agent for vascular imaging and visualization, saline or other non-therapeutic agent, or a different therapeutic agent, into a vascular system of a patient for treatment of a disease of a target organ. For example, the hub 721 can correspond to the hub 308 of the exemplary infusion catheter of Figure 3 .

[0086] The syringe connector 715A and the connector body 713 provide an internal flow path (passage) 723 that extends through the connector body 713 and through the catheter hub connector 715C to the hub 721. The internal flow path (passage) 523 includes a fixed size restrictor orifice 724 that is configured as a passive pressure controlled mechanical flow regulator that regulates the flow of therapeutic agent or auxiliary fluid to the infusion catheter and through the infusion catheter into the vasculature of the patient at or near the desired infusion rate. An optional pressure gauge can be provided to measure and display the pressure of the fluid supplied to the flow path (passage) 723. The display of such pressure measurement can be used to provide feedback to the user (physician) as to the manual pumping action can be performed within a desired operating pressure range when the manual syringe pump 717 is actuated.

[0087] In embodiments, the connector body 713 can be hand-holdable and / or include one or more housing portions that enclose and / or mechanically support the syringe connector 715A and the catheter hub connector 715C along with the flow path (passage) 723 and the fixed size restrictor orifice 724. The flow path / passage 723 and the fixed size restrictor orifice 724 can be implemented by tubing and associated fluid couplers and nozzle structures or other suitable fluid transfer structures and devices.

[0088] The system 711 can be configured to maintain consistency of delivery of therapeutic agent and / or auxiliary fluid (such as a bolus of contrast agent for vascular imaging and visualization, saline or other non-therapeutic agent, or a different therapeutic agent) into the vasculature of the patient in conjunction with the manual pumping action provided by the user (physician) operation of the one or more manual syringe pumps. In this manner, the system 711 can significantly reduce the complexity of the procedure while maintaining the favorable distribution and uptake patterns observed for the desired infusion rate (or desired infusion rate window). Moreover, the therapeutic agent can include a suspension of particles (e.g., large particle proteins, resin spheres, glass spheres, gel beads, other embolic particles) and / or an emulsion of liquids that are normally immiscible (typically in iodine oil).

[0089] In embodiments, the fixed size d of the opening of the restrictor orifice 724 can be designed to regulate the flow of therapeutic agent or auxiliary fluid through the flow path (passage) 723 at or near the desired infusion rate, provided that the fluid viscosity and the catheter lumen diameter are known and the manual pumping action of the syringe pump is performed within a predetermined operating pressure range. This flow is shown by arrows 728 and continues through the catheter hub connector 715C to the infusion catheter and through the infusion catheter into the vasculature of the patient at or near the desired infusion rate.

[0090] In embodiments, a kit of connector bodies 713 can be provided, where each connector body in the kit is configured to have an opening of a fixed size D of the restrictor bore 724 that supports a desired infusion rate of fluid of different manual syringe pumps having different fluid viscosities and / or having different catheter lumen diameters and / or having different operating pressure ranges. For example, a first connector body in the kit can be configured to have an opening of a fixed size D1 of the restrictor bore 724 that supports a desired infusion rate of a first therapeutic agent of a known viscosity (e.g., a medium viscosity) at a first predetermined catheter lumen diameter (e.g., 0.021 inches) with a 3 cc syringe pump operating at a pressure range of approximately 200-250 psi. In another example, a second connector body in the kit can be configured to have an opening of a fixed size D2 of the restrictor bore 724 that supports a desired infusion rate of a second therapeutic agent of a known viscosity (e.g., a high viscosity) at a second predetermined catheter lumen diameter (e.g., 0.025 inches) with a 10 cc syringe pump operating at a pressure range of approximately 100-125 psi. In yet another example, a third connector body in the kit can be configured to have an opening of a fixed size D3 of the restrictor bore 724 that supports a desired infusion rate of a saline fluid of a known viscosity (e.g., a low viscosity) at a third predetermined catheter lumen diameter (e.g., 0.019 inches) with a 1 cc syringe pump operating at a pressure range of approximately 500-750 psi. The different connector bodies in the kit can be labeled with visual indicia or a predetermined color scheme, which can assist a user in selecting a connector body of the kit that matches the infusion system and procedure that will be used to treat a patient. The display of pressure measurements provided by the optional pressure gauge 726 can be used to provide feedback to the user (physician) as to whether the manual pumping action can be performed within the desired operating pressure range when the manual syringe pump 717 is actuated.

[0091] The selection of a connector body in the kit that matches the infusion system and procedure that will be used to treat a patient can also be aided by a lookup table. Table 1 provides an example connector body lookup table.

[0092]

[0093]

[0094] The lookup table can be provided by a printed card packaged or distributed with the kit. Alternatively, the lookup table can be provided from a software application executed on a computing device, via a graphical user interface. For example, the lookup table can be displayed as part of a graphical user interface provided by a web browser application or a smart phone application.

[0095] Embodiments of systems and methods for therapeutic agent delivery have been described and shown herein, and in embodiments, are pressure-activated therapeutic agent delivery. Although specific embodiments of the application have been described, the application is not so limited and the scope of the application is as broad as the scope of the art allows and the specification as filed should be construed in the light most favorable to the claimant. Thus, while the systems and methods are primarily applicable to therapeutic treatment of humans, have been demonstrated on porcine tissue and organs, and can generally be used for treatment of mammals. For the purposes of this disclosure, both humans and animals are to be considered "patients." Furthermore, the therapy delivered herein can be a single therapeutic agent or a combination of therapeutic agents. Accordingly, those skilled in the art will recognize that other modifications can be made to the provided application without departing from the scope of the application as claimed.

Claims

1. A device for use with at least one infusion catheter for treating a patient, wherein the at least one infusion catheter has a proximal end with a seat, a distal end with a distal tip, and a lumen extending from the proximal end to the distal tip, the device comprising: a connector body having a first connector for fluidly coupling and removably connecting to the seat of the at least one infusion tube, a second connector for fluidly coupling and removably connecting to at least one manual syringe pump, and a passive pressure-controlled mechanical flow regulator that regulates the flow of fluid supplied to the infusion tube by the manual pumping action of the at least one manual syringe pump and delivered by the infusion tube into the patient's vascular system.

2. The device according to claim 1, wherein: The passive pressure controlled mechanical flow regulator is configured to deliver a therapeutic agent or auxiliary fluid supplied under pressure by the pumping action of the at least one manual syringe pump into and through the lumen of the infusion catheter at a desired infusion rate.

3. The device according to claim 1, wherein: The connector body also includes a first flow path and a second flow path, wherein the first flow path extends through the first connector and is fluidically coupled to the lumen of the infusion catheter during use, and the second flow path extends through the second connector and is fluidically coupled to the at least one manual syringe pump during use, wherein the passive pressure-controlled mechanical flow regulator is fluidically coupled to the first flow path and the second flow path.

4. The device according to claim 3, wherein: The connector body also includes a third connector and a third flow path, wherein the third connector is used for fluid connection and can be detachably connected to at least one additional manual syringe pump, and the third flow path extends through the third connector and is fluidly connected to the at least one additional manual syringe pump during use, wherein the passive pressure-controlled mechanical flow regulator is fluidly connected to the third flow path.

5. The device according to claim 4, wherein: The passive pressure controlled mechanical flow regulator comprises: i) a first pressure reducing valve having an inlet fluidly coupled to the second flow path and an outlet fluidly coupled to the first flow path; ii) a second pressure reducing valve having an inlet fluidly coupled to the first flow path and an outlet fluidly coupled to the third flow path; iii) a third pressure reducing valve having an inlet fluidly coupled to the third flow path and an outlet fluidly coupled to the first flow path; and iv) a fourth pressure reducing valve having an inlet fluidly coupled to the first flow path and an outlet fluidly coupled to the second flow path.

6. The device according to claim 5, wherein: the first and third pressure reducing valves being configured to open at respective first predetermined supply pressures corresponding to a desired infusion rate; and The second pressure reducing valve and the fourth pressure reducing valve are configured to open at respective second predetermined supply pressures greater than the first predetermined supply pressure.

7. The device according to claim 6, wherein: the first pressure relief valve and the second pressure relief valve being configured to deliver the therapeutic agent supplied under pressure by the pumping action of the at least one manual syringe pump into and through the lumen of the infusion catheter at the desired infusion rate and to direct any excess flow into the at least one additional manual syringe pump; as well as The third and fourth pressure reducing valves are configured to deliver the therapeutic agent under pressure supplied by the pumping action of the at least one additional manual syringe pump into and through the lumen of the infusion catheter at the desired infusion rate and to direct any excess flow into the at least one manual syringe pump.

8. The apparatus according to claim 5, wherein: The connector body also includes a passive flow restrictor located downstream of the first pressure reducing valve, the second pressure reducing valve, the third pressure reducing valve, and the fourth pressure reducing valve.

9. The apparatus according to claim 1, wherein: The connector body further includes a second connector for fluidly coupling and detachably connecting to at least one additional manual syringe pump in the configuration of the passive pressure-controlled mechanical flow regulator.

10. The apparatus according to claim 9, wherein: The connector body also includes a first flow path, a second flow path, and an additional flow path, wherein the first flow path extends through the first connector and is fluidically coupled to the lumen of the infusion catheter during use, the second flow path extends through the second connector and is fluidically coupled to the at least one manual syringe pump during use, and the additional flow path extends through the second connector and is fluidically coupled to the at least one additional manual syringe pump during use, wherein the passive pressure-controlled mechanical flow regulator is fluidically coupled to both the first flow path and the second flow path, and the additional flow path is fluidically coupled to the second flow path downstream of the passive pressure-controlled mechanical flow regulator.

11. The apparatus according to claim 10, wherein: The connector body further includes a check valve disposed between the passive pressure-controlled mechanical flow regulator and the additional flow path.

12. The apparatus according to claim 9, wherein: the connector body being configured to deliver the therapeutic agent, supplied under pressure by the pumping action of the at least one manual syringe pump, into and through the lumen of the infusion catheter at the desired infusion rate; and The connector body is further configured to deliver an auxiliary fluid under pressure supplied by the pumping action of the at least one additional manual syringe pump into and through the lumen of the infusion catheter.

13. The apparatus according to claim 1, wherein: The passive pressure-controlled mechanical flow regulator includes a chamber and a restrictor tube, wherein the chamber has an inlet port leading to the interior space of the chamber, and the restrictor tube extends into the interior space of the chamber, wherein the restrictor tube includes a restrictor inlet arranged in the interior space of the chamber and an annular elastic membrane spaced apart from the restrictor inlet.

14. The apparatus according to claim 13, wherein: The elastic membrane is configured to deform or deflect radially inward to regulate fluid flow through the restrictor tube.

15. The apparatus according to claim 13, wherein: The restrictor tube also includes a bypass valve having an inlet in fluid communication with the interior space of the chamber and an outlet in fluid communication with the lumen of the restrictor tube.

16. The apparatus according to claim 15, wherein: The bypass valve is configured to open at a predetermined pressure within the interior space of the chamber, the predetermined pressure being greater than a pressure corresponding to a desired infusion rate of fluid flow through the restrictor tube.

17. The apparatus of claim 1, wherein: The passive pressure controlled mechanical flow regulator includes a fixed sized restrictor orifice corresponding to a desired infusion rate.

18. The apparatus according to claim 17, wherein: The fixed size is based on the infusion of a fluid of known viscosity pumped by a manual syringe pump of predetermined size within a predetermined operating pressure range.

19. A system for treating a patient, comprising: at least one infusion catheter for treating a patient, wherein the at least one infusion catheter has a proximal end with a seat, a distal end with a distal tip, and a lumen extending from the seat to the distal tip through which a first fluid is infused into the patient; and at least one connector body having a first connector for fluid coupling and detachably connecting to the seat of the at least one infusion catheter, a second connector for fluid coupling and detachably connecting to at least one manual syringe pump containing the first fluid, and a passive pressure-controlled mechanical flow regulator, which regulates the flow of the first fluid supplied to the infusion catheter by the manual pumping action of the at least one manual syringe pump and delivered by the infusion catheter into the patient's vascular system.

20. The system of claim 19, wherein: The passive pressure controlled mechanical flow regulator is configured to deliver the first fluid, supplied under pressure by the pumping action of the at least one manual syringe pump, into and through the lumen of the infusion catheter at a desired infusion rate.

21. The system of claim 19, wherein: The connector body also includes a first flow path and a second flow path, wherein the first flow path extends through the first connector and is fluidically coupled to the lumen of the infusion catheter during use, and the second flow path extends through the second connector and is fluidically coupled to the at least one manual syringe pump during use, wherein the passive pressure-controlled mechanical flow regulator is fluidically coupled to the first flow path and the second flow path.

22. The system of claim 21, wherein: The connector body also includes a third connector and a third flow path, wherein the third connector is used for fluid connection and can be detachably connected to at least one additional manual syringe pump, and the third flow path extends through the third connector and is fluidly connected to the at least one additional manual syringe pump during use, wherein the passive pressure-controlled mechanical flow regulator is fluidly connected to the third flow path.

23. The system of claim 22, wherein: The passive pressure controlled mechanical flow regulator includes i) a first pressure reducing valve having an inlet fluidly coupled to the second flow path and an outlet fluidly coupled to the first flow path; ii) a second pressure reducing valve having an inlet fluidly coupled to the first flow path and an outlet fluidly coupled to the third flow path; iii) a third pressure reducing valve having an inlet fluidly coupled to the third flow path and an outlet fluidly coupled to the first flow path; as well as iv) a fourth pressure reducing valve having an inlet fluidly coupled to the first flow path and an outlet fluidly coupled to the second flow path.

24. The system of claim 23, wherein: The connector body also includes a passive flow restrictor located downstream of the first pressure reducing valve, the second pressure reducing valve, the third pressure reducing valve, and the fourth pressure reducing valve.

25. The system of claim 23, wherein: the first and third pressure reducing valves being configured to open at respective first predetermined supply pressures corresponding to a desired infusion rate; and The second pressure reducing valve and the fourth pressure reducing valve are configured to open at respective second predetermined supply pressures greater than the first predetermined supply pressure.

26. The system of claim 25, wherein: the first pressure relief valve and the second pressure relief valve being configured to deliver the first fluid, supplied under pressure by the pumping action of the at least one manual syringe pump, into and through the lumen of the infusion catheter at the desired infusion rate and to direct any excess flow into the at least one additional manual syringe pump; as well as The third and fourth pressure reducing valves are configured to deliver the first fluid under pressure supplied by the pumping action of the at least one additional manual syringe pump into and through the lumen of the infusion catheter at the desired infusion rate, and to direct any excess flow into the at least one manual syringe pump.

27. The system of claim 19, wherein: The connector body also includes a second connector for fluidly coupling and removably connecting to at least one additional manual syringe pump in a configuration that bypasses the passive pressure control mechanical flow regulator.

28. The system of claim 27, wherein: The connector body also includes a first flow path, a second flow path, and an additional flow path, wherein the first flow path extends through the first connector and is fluidically coupled to the lumen of the infusion catheter during use, the second flow path extends through the second connector and is fluidically coupled to the at least one manual syringe pump during use, and the additional flow path extends through the second connector and is fluidically coupled to the at least one additional manual syringe pump during use, wherein the passive pressure-controlled mechanical flow regulator is fluidically coupled to both the first flow path and the second flow path, and the additional flow path is fluidically coupled to the second flow path downstream of the passive pressure-controlled mechanical flow regulator.

29. The system of claim 28, wherein: The connector body further includes a check valve disposed between the passive pressure-controlled mechanical flow regulator and the additional flow path.

30. The system of claim 27, wherein: the connector body being configured to deliver the first fluid, supplied under pressure by the pumping action of the at least one manual syringe pump, into and through the lumen of the infusion catheter at the desired infusion rate; and The connector body is further configured to deliver an auxiliary fluid under pressure supplied by the pumping action of at least one additional manual syringe pump into and through the lumen of the infusion catheter.

31. The system of claim 19, wherein: The passive pressure-controlled mechanical flow regulator includes a chamber and a restrictor tube, wherein the chamber has an inlet port leading to the interior space of the chamber, and the restrictor tube extends into the interior space of the chamber, wherein the restrictor tube includes a restrictor inlet arranged in the interior space of the chamber and an annular elastic membrane spaced apart from the restrictor inlet.

32. The system of claim 31 , wherein: The elastic membrane is configured to deform or deflect radially inward to regulate fluid flow through the restrictor tube.

33. The system of claim 31 , wherein: The restrictor tube also includes a bypass valve having an inlet in fluid communication with the interior space of the chamber and an outlet in fluid communication with the lumen of the restrictor tube.

34. The system of claim 33, wherein: The bypass valve is configured to open at a predetermined pressure within the interior space of the chamber, the predetermined pressure being greater than a pressure corresponding to a desired infusion rate of fluid flow through the restrictor tube.

35. The system of claim 19, wherein: The passive pressure controlled mechanical flow regulator includes a fixed sized restrictor orifice corresponding to a desired infusion rate.

36. The system of claim 33, wherein: The fixed size is based on the infusion of a fluid of known viscosity pumped by a manual syringe pump of predetermined size within a predetermined operating pressure range.

37. The system of claim 19, wherein: The infusion catheter includes an occluder at a distal end thereof, the occluder being adapted to prevent backflow of the first fluid.

38. The system of claim 37, wherein: The occluder is a dynamic occluder.

39. The system of claim 38, wherein: The dynamic occluder is a microvalve.

40. The system of claim 19, wherein: The first fluid is a therapeutic agent or an auxiliary fluid.

41. A kit for use with at least one infusion catheter for treating a patient, wherein the at least one infusion catheter has a proximal end with a seat, a distal end with a distal tip, and a lumen extending from the proximal end to the distal tip, the kit comprising: a plurality of connector bodies having a first connector for fluidly coupling and removably connecting to the seat of the at least one infusion catheter, a second connector for fluidly coupling and removably connecting to at least one manual syringe pump, and a passive pressure-controlled mechanical flow regulator that regulates the flow of fluid supplied to the infusion catheter by the manual pumping action of the at least one manual syringe pump and delivered by the infusion catheter to the patient's vascular system, wherein the passive pressure-controlled mechanical flow regulators of the plurality of connector bodies include restrictor holes of different fixed sizes corresponding to desired infusion rates for a plurality of different fluids.

42. The kit of claim 37, wherein: The different fixed sizes are based on the infusion of different fluids of known viscosities pumped by manual syringe pumps of predetermined sizes within different predetermined operating pressure ranges.

43. A method of treating a patient, comprising: A system is provided that includes an infusion catheter having a proximal end with a hub, a distal end with a distal tip, and a lumen extending from the proximal end to the distal tip, and a connector body having a first connector for fluid coupling and detachably connecting to the hub of the infusion catheter, a second connector for fluid coupling and detachably connecting to at least one manual syringe pump, and a passive pressure-controlled mechanical flow regulator; and fluidly coupling and removably connecting the first connector of the connector body to the hub of the infusion catheter; fluidly coupling and removably connecting the second connector of the connector body to a first manual syringe pump; as well as The first manual syringe pump is manually pumped to pump fluid into the infusion catheter, wherein the passive pressure-controlled mechanical flow regulator of the connector body regulates the flow of fluid into and through the infusion catheter for delivery through the infusion catheter to the patient's vascular system.

44. The method of claim 43, wherein: The connector body is configured to deliver a therapeutic agent into and through the lumen of the infusion catheter at a desired infusion rate, wherein the therapeutic agent is supplied to the connector body under pressure by manual pumping of the first manual syringe pump.

45. The method of claim 44, wherein: The connector body also includes a first flow path and a second flow path, wherein the first flow path extends through the first connector and is fluidically coupled to the lumen of the infusion catheter during use, and the second flow path extends through the second connector and is fluidically coupled to the first manual syringe pump during use, wherein the passive pressure-controlled mechanical flow regulator is fluidically coupled to the first flow path and the second flow path.

46. ​​The method of claim 45, wherein: The connector body further includes a third connector and a third flow path, the third connector being adapted to fluidically couple and detachably connect to at least one additional manual syringe pump, the third flow path extending through the third connector and being fluidly coupled to the at least one additional manual syringe pump during use, wherein the passive pressure-controlled mechanical flow regulator is fluidly coupled to the third flow path; The passive pressure controlled mechanical flow regulator comprises: i) a first pressure reducing valve having an inlet fluidly coupled to the second flow path and an outlet fluidly coupled to the first flow path; ii) a second pressure reducing valve having an inlet fluidly coupled to the first flow path and an outlet fluidly coupled to the third flow path; iii) a third pressure reducing valve having an inlet fluidly coupled to the third flow path and an outlet fluidly coupled to the first flow path; and iv) a fourth pressure reducing valve having an inlet fluidly coupled to the first flow path and an outlet fluidly coupled to the second flow path; and The method also includes fluidly coupling and detachably connecting the third connector of the connector body to a second manual syringe pump that is separate and different from the first manual syringe pump.

47. The method of claim 46, wherein: the first and third pressure reducing valves being configured to open at respective first predetermined supply pressures corresponding to a desired infusion rate; and The second pressure reducing valve and the fourth pressure reducing valve are configured to open at respective second predetermined supply pressures greater than the first predetermined supply pressure.

48. The method of claim 47, wherein: the first and second pressure relief valves being configured to deliver therapeutic agent supplied under pressure by manual pumping of the first syringe pump into and through the lumen of the infusion catheter at the desired infusion rate and to direct any excess flow into the second manual syringe pump; as well as The third and fourth pressure reducing valves are configured to deliver the therapeutic agent supplied under pressure by manual pumping of the second manual syringe pump into and through the lumen of the infusion catheter at the desired infusion rate and to direct any excess flow into the first manual syringe pump.

49. The method of claim 43, wherein: The connector body further includes a second connector for fluidly coupling and removably connecting to at least one additional manual syringe pump in a configuration that bypasses the passive pressure control mechanical flow regulator; as well as The method also includes fluidly coupling and removably connecting the second connector of the connector body to the second manual syringe pump.

50. The method of claim 49, wherein: the connector body being configured to deliver the therapeutic agent supplied under pressure by manual pumping of the first manual syringe pump into and through the lumen of the infusion catheter at a desired infusion rate; and The connector body is further configured to deliver auxiliary fluid under pressure supplied by manual pumping of the second manual syringe pump into and through the lumen of the infusion catheter.

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