Therapeutic treatment device with woven microvalve occluder with collapsible covering

Abstract

A treatment device for use in a blood vessel is provided, the treatment device comprising a catheter and a microvalve. A flexible low friction reconfigurable cover is attached at or adjacent to a distal end of the microvalve. The cover is deployed between an occluder and a vessel wall to intervene between the occluder and the vessel wall during movement of the occluder relative to the vessel wall in order to reduce the occurrence of vasospasm.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. patent application serial number 17 / 970,329, filed on October 20, 2022, the entirety of which is incorporated herein by reference.

[0003] This application is related to commonly owned US Patent Nos. 8,696,698 and 10,588,636, which are hereby incorporated by reference in their entireties. Background of the Invention 1. Technical Field

[0004] The present disclosure relates generally to catheters for delivering therapeutic treatments into blood vessels. More particularly, the present disclosure relates to catheters having a microvalve at its distal end to increase penetration of the therapeutic treatment into the targeted blood vessel and reduce backflow of the therapeutic treatment into non-target blood vessels. 2. Existing Technology

[0005] Endovascular therapeutic therapies are commonly delivered clinically to treat a wide variety of conditions. For example, endovascular embolization, chemoembolization, and radioembolization are used to treat a range of conditions, such as hypervascular liver tumors, uterine fibroids, secondary intrahepatic cancer metastases, preoperative treatment of hypervascular meningiomas, and bronchial artery embolization for hemoptysis.

[0006] Untargeted delivery of various therapies can lead to adverse events and morbidity. Additionally, untargeted delivery indicates that the intended target of the delivery does not receive the full dose of the therapy.

[0007] Infusion using a standard infusion microcatheter achieves bidirectional flow. That is, infusing a therapeutic agent using a microcatheter allows the blood and infused therapeutic agent to move forward in addition to allowing it to be pushed backward (backflow). The backflow of the therapeutic agent causes non-target damage to surrounding healthy organs. In interventional oncology treatment procedures, the goal is to bombard the cancer tumor with radiation or chemotherapy. In order to deliver therapy to the distal vasculature, where the therapy can be most effective, it is important to maintain forward flow throughout the vascular tree in the target organ. This problem is particularly prominent in patients with poorly vascularized tumors or those who have undergone chemotherapy, where slow blood flow limits the dose of therapeutic agent delivered, and backflow of the agent to non-target tissues may occur long before the physician has delivered the desired dose.

[0008] During a therapeutic infusion procedure, vascular pressure changes at multiple locations in the vascular tree. Initially, the pressure is higher proximally and decreases over the length of the vessel. When there is a pressure drop, forward flow of therapy occurs. If there is no pressure drop over the length of the vessel, the therapy will not flow downstream. If there is a higher pressure at one location (such as at the orifice of the catheter), the therapeutic therapy will flow in the direction of the lower pressure. If the pressure generated at the orifice of the infusion catheter is greater than the pressure in the vessel proximal to the catheter orifice, a portion of the infused therapeutic therapy will travel upstream (backflow) into non-target vessels and non-target organs. If the infusion pressure (the pressure at the orifice of the catheter) is high enough, this phenomenon can occur even in vessels with strong forward flow.

[0009] In clinical practice using standard infusion catheters, physicians attempt to infuse therapeutic agents at a pressure that does not cause reflux. When doing so, physicians slow the infusion rate (and infusion pressure) or stop the infusion altogether. The clinical impact of current infusion catheters and techniques is twofold: lower doses of therapeutic agents are delivered, and distal penetration into the target vessel is poor.

[0010] Additionally, reflux can be a time-sensitive phenomenon. Sometimes, reflux occurs in response to the injection of a therapeutic agent, in which case the reflux occurs rapidly (e.g., on a millisecond timescale) at a rate too fast for a human operator to react to. Furthermore, reflux can occur briefly, after which forward flow in the vessel is temporarily restored, but is followed by additional reflux.

[0011] Various devices have been proposed to increase distal permeability while preventing backflow. For example, co-owned U.S. Patent No. 8,696,698 (which has been incorporated herein by reference) describes a microvalve infusion system for infusing therapeutic agents, which has a dynamically adjusted filter valve connected to the distal end of a delivery catheter. The delivery catheter and filter valve self-expand when deployed from the delivery catheter. The filter valve is naturally spring-biased due to its filamentous element structure so that it automatically partially expands within the blood vessel when it is deployed from the outer catheter, and is coated with a porous polymer coating having a pore size small enough to filter the therapeutic agent. Given this structure, during infusion, an increase in fluid pressure is generated within the filter valve and causes the filter valve to open, extend across the blood vessel, and thereby prevent backflow of the infused therapeutic agent. In addition, when the fluid is pressurized through the delivery catheter and enters the filter valve, the downstream pressure in the blood vessel increases, which promotes maximum uptake of the therapeutic agent delivered into the target tissue. Further, the filter valve responds to local pressure around the valve, which thereby enables substantially unrestricted forward flow of blood in the blood vessel and reduces or prevents reflux (backflow or backward flow) of therapeutic agents introduced into the blood.

[0012] However, the device of U.S. Patent No. 8,696,698 has certain characteristics that may not always be advantageous for a given situation. The disclosed filter valve device generally adapts well in situations where tracking the occluder into small vessels is not a critical requirement; tracking capabilities in tortuous branching vascular systems may be limited. The distal end of the device in the retracted, undeployed state is defined by the size of the deployment catheter, which may be significantly larger than the catheter supporting the filter valve and significantly larger than the outer diameter of the guidewire used to guide the microvalve to the target location within the vessel. Therefore, tracking the filter valve into smaller vessel branches may not be optimal. In addition, once the device is tracked to the treatment location, deployment of the filter valve requires overcoming friction between the filter valve and the external deployment catheter.

[0013] Commonly owned U.S. Patent No. 10,588,636 (previously incorporated herein) describes a microvalve infusion system for infusing therapeutic agents that addresses device tracking. Figure 1 The system 10 includes a flexible infusion catheter 12 having a hub 14 at a proximal end 16 and a filter valve occluder 18 coupled to a distal end 20. The filter valve occluder 18 includes braided elastic strands 22, each of which includes a proximal portion 24, a central portion 26, and a distal portion 28. The proximal portion 24 is circumferentially attached around an outer surface 30 of the catheter 12 at a location proximal to a distal orifice 32 of the catheter, the central portion 26 extends radially outward toward the orifice 32, and the distal portion 28 of the strands inverts back into the filter valve occluder 18 and is coupled circumferentially around the outer surface 30 of the catheter 12. The proximal and central portions 26 of the strands 22 are coated in a polymer filter coating 34 that extends between and across the strands 18. The distal portion 28 of the strands 22 is not coated in a polymer filter. A variation of this microvalve infusion system 10 is marketed by Trisalus Life Sciences, Inc., Westminster, CO. The infusion system is commercially manufactured and sold. When in use, the microvalve infusion system can be deployed from the introducer cannula 36 at the target vessel location; but it is not required to be used with an introducer cannula. Instead, the infusion system can be advanced over a guidewire without any introducer cannula, thereby providing good tracking results. When introduced into the blood vessel, the filter valve occluder 18 has been demonstrated to operate dynamically in sync with the cardiac cycle and maintain more than 70% of the antegrade blood flow in the vessel through the microvalve occluder while providing the intended retrograde blockade of the therapy. Further, the design allows for non-invasively increasing the pressure of therapeutic infusions into local resistance tumor vessels to achieve deeper therapy perfusion delivery.

[0014] It has been demonstrated that some microvalve occluders, particularly those with larger dimensions, experience significant resistance when they are longitudinally displaced within a blood vessel. As the microvalve occluder is advanced, it deforms, increasing the surface area in contact with the vessel wall. This creates resistance at the interface between the occluder surface and the vessel wall. Therefore, the greater the surface area in contact with the vessel wall, the greater the resistance generated.

[0015] This resistance may cause trauma or irritation to the artery, which may lead to vasospasm. Vasospasm is a condition in which the smooth muscle of the artery contracts. This may occur locally or initiate a cascade effect along the length of the vessel. This narrowing may significantly reduce blood flow within the vessel and subsequently reduce distal pressure in the vessel. If this occurs proximal to the microvalve occluder, the antegrade flow will be insufficient, which may hinder downstream flow after infusion, creating an effect similar to that of a occluding balloon. If the spasm is distal to the microvalve occluder, the distal flow may be significantly reduced, thereby inhibiting the delivery of the therapeutic agent. Additionally, the tracking of the microvalve occluder forward or backward throughout the spasm may cause device damage or greater vascular damage. Summary of the Invention

[0016] An infusion device is provided, comprising a catheter and an occluder. The catheter has a proximal end, a distal end with a distal tip, and a lumen extending from the proximal end to the distal end and opening at a distal orifice through the distal end. The occluder may be a microvalve.

[0017] According to one aspect of the infusion device, a flexible covering is attached at or adjacent to the distal end of the microvalve. The flexible covering can be made of a smooth, lubricating sheet material. The flexible covering is adapted to be interposed between the occluder and the patient's blood vessel wall to provide a low-friction surface against the vessel wall when the occluder is advanced within the vessel. The covering reduces or prevents vasospasm during device tracking and navigation.

[0018] As the occluder is advanced through the vessel, the covering preferably deploys in response to the resistance to forward motion. Then, when the motion ceases, the force of the antegrade flow within the vessel moves the covering away from the occluder, and the occluder functions as intended. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Existing technology Figure 1 is a side view of a prior art infusion system.

[0020] Figure 2 is a side view of an infusion system according to an embodiment described herein.

[0021] Figure 3 yes Figure 2 An enlarged view of the distal end of the infusion system is shown in FIG.

[0022] Figures 4 to 6 is a schematic diagram of the operation of the infusion device in the blood vessel: Figure 4 ) when stationary and subjected to forward fluid flow ( Figure 5 ); and when administering a therapeutic agent via an infusion device ( Figure 6 )period.

[0023] Figures 7 to 9 is a schematic diagram of the operation of a variant of an infusion device in a blood vessel: Figure 7 ) when stationary and subjected to forward fluid flow ( Figure 8 ); and when administering a therapeutic agent via an infusion device ( Figure 9 )period.

[0024] Figures 10 to 12 is a schematic diagram of the operation of a variant of an infusion device in a blood vessel: Figure 10 ) when stationary and subjected to forward fluid flow ( Figure 11 ); and when administering a therapeutic agent via an infusion device ( Figure 12 )period. DETAILED DESCRIPTION

[0025] With reference to the human body and to components of the devices and systems described herein that are intended to be manually operated by a user, the terms "proximal" and "distal" are defined with respect to the user's hand, with the term "proximal" being closer to the user's hand and the term "distal" being farther away from the user's hand, unless an alternative definition is specifically provided.

[0026] Figure 2 and Figure 3 A first exemplary embodiment of an infusion device 110 according to the present invention is shown in FIG. It should be noted that the corresponding parts of the system shown in these figures are not shown to scale with their intended size, but rather the distal parts are shown in a significantly enlarged manner for the purpose of explanation. Figure 2 As shown, an infusion set 110 includes a flexible catheter 112 having a proximal end 116 and a distal end 120, a hub 114 coupled to the proximal end 116 of the catheter, and a vascular occluder 118 (described in greater detail below) coupled to the distal end 120 of the catheter 112. According to one aspect of the infusion system, a deployable covering 124 (also described in greater detail below) is provided to isolate the patient's vessel wall from the outer surface of the vascular occluder 118 when the infusion set 110 is tracked over a guidewire and / or otherwise navigated to a target location within the patient's vessel.

[0027] The catheter 112 is between two and eight feet long and has an outer diameter between 0.67 mm and 3 mm (corresponding to catheter sizes of 2 French to 12 French) and is made of: an inner liner made of a fluorinated polymer such as polytetrafluoroethylene (PTFE) or fluorinated ethylene propylene (FEP); a braid 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; and an outer coating made of a polyether block amide thermoplastic elastomer resin such as ), polyurethane, polyamide, polyamide copolymer, polyester, polyester copolymer, fluorinated polymer (such as PTFE, FEP, polyimide, polycarbonate or any other suitable material) or any other standard or specialty material used to make catheters for use in the blood stream.

[0028] The hub 116 may include a Luer connector or other standardized connector. The infusion lumen extends from the hub 116 to the distal end 122 of the catheter and opens at the distal orifice 132 of the catheter, such that the hub 116 is adapted to deliver a therapeutic agent from outside the patient's body to a target vessel (artery or vein) inside the patient's body. The hub 116 is preferably also adapted to facilitate advancement of a guidewire through the infusion lumen and / or coupling of a syringe for infusion of the therapeutic agent through the infusion lumen. Any hub suitable for at least facilitating delivery of a therapeutic agent into the infusion lumen may be utilized.

[0029] The occluder 118 is preferably a dynamic microvalve, which is manufactured as follows. Figure 3 , forming or providing a braid of multiple strands 142 in a tubular form. The tubular braid is composed of a variety of metal (e.g., stainless steel or nickel-titanium alloy) or polymer filaments or strands 142 in a tubular braided structure that forms a substantially closed shape when deployed and is not subject to external forces. When utilizing polymer filaments, the filaments 142 may be composed of PET, polyethylene naphthalate (PEN), liquid crystal polymer, fluorinated polymer, nylon, polyamide, or any other suitable polymer. If desired, when utilizing polymer filaments, one or more metal filaments may be used in conjunction with the polymer filaments. According to one aspect of the present invention, when utilizing metal filaments, the metal filaments may be made of a radiopaque material to facilitate tracking of the filter valve occluder 118 and its configuration within the body. The filaments 142 are not bonded to each other between their ends to enable them to move relative to each other between their ends. The filaments are spring-biased (i.e., they have "shape memory") to assume a desired crossing angle relative to each other. A diamond-shaped gap 144 is formed between each two adjacent groups of crossing filaments, wherein the intersection of the filaments defines the apex of the diamond-shaped gap. The specific shape and size of the diamond-shaped gap is determined by the braiding angle between the crossing filaments in the tubular braid.

[0030] The diameter of the filaments 142 is selected within the range of 0.025 mm to 0.127 mm, but other diameters may be utilized. Preferably, the pitch angle (i.e., the crossing angle exhibited by the braided filaments in the fully opened, deployed position) is selected within the range of 100° to 150°, but other pitch angles may be used.

[0031] According to one aspect of the infusion device, a primer is provided to the strands 142 of the tubular braid. The primer is used to promote adhesion of the polymer coating discussed below, as well as to maintain stability and polymer on the filaments to avoid degradation over time. Exemplary primers include Polyether polyurethane, polyamic acid and parylene.

[0032] A polymer coating 160 is then applied over the elastic strands 142 and across the diamond-shaped gaps 144 formed between the strands. The polymer 160 can be applied to the woven fabric by any of several methods, including spraying, spinning, electrospinning, adhesive bonding, heat fusion, mechanical capture of the woven fabric, melt bonding, dip coating, or any other desired method to form a coating suitable for use as a filter. The filter can be a material with pores (such as ePTFE), a solid material with added pores (such as polyurethane with laser-drilled holes), or the filter can be a web of very fine filaments laid onto the woven fabric.

[0033] In the case where the polymer filter 160 is a filament web, the characteristic pore size of the filter can be determined by trying to make beads of different diameters pass through the filter and finding out which diameter beads can pass through the filter in large quantities. According to U.S. Patent 4,738,740, very fine filaments can be spun onto a rotating mandrel with the help of an electrostatic field or in the absence of an electrostatic field or in the case of both. The filter thus formed can be adhered to a braided structure using an adhesive, or the braid can be placed on a mandrel, and the filter can be spun onto the braid or below the braid or both above and below the braid, to capture the braid substantially. The filter can be formed into some pores by spraying or electrostatic spinning, and then a secondary step is carried out, wherein a hole is formed by laser drilling or by a secondary operation. In one embodiment, a filter is formed on the braid using a material capable of electrostatic deposition or spinning, wherein a preferred material is capable of self-bonding. The filter can be made of polyurethane, Pellethane, polyolefin, polyester, fluoropolymer, acrylic polymer, acrylate, polycarbonate, silicone and / or other suitable materials. The polymer is spun onto the fabric in a wet state, and therefore it is desirable that the polymer be soluble in the solvent. In one embodiment, the filter is formed from a polyurethane solution in dimethylacetamide (DMA) and tetrahydrofuran (THF). The polymer is spun from the solution, with a preferred concentration of 5% to 10% solids for electrospinning processes and 15% to 25% solids for wet spinning processes.

[0034] As another alternative method of polymer coating of braid, braid can be dip-coated to form polymer filter onto the braid. Braid is mounted on a mandrel, which has an outer diameter identical to the inner diameter of the fully expanded braid. The mandrel can be a steel coated with polytetrafluoroethylene (PTFE), wherein PTFE serves as a release surface. Alternatively, an uncoated mandrel can be used. Importantly, when the braid is mounted on the mandrel, the inner diameter of the braid and the outer diameter of the mandrel should not be spaced apart from each other. Therefore, they preferably have a common diameter within the tolerance of ± 0.065mm. Keeping the entire inner braid in contact with the mandrel allows the filament to be uniformly coated with polymer, as described subsequently, so that the filter valve expands uniformly after the polymer is dried. Alternatively, a tubular braid can be mounted on a mandrel that is oversized (greater than the inner diameter of the braid), but this will result in an increase in the braiding angle of the filament, and thus the filter valve will be sized and affect its expansion force. In an alternative arrangement, the braid can be mounted inside a tubular mandrel having the same dimensions as the outer diameter of the braid, with similar tolerances as described above. As yet another alternative, the braid can be mounted inside a tubular mandrel that is undersized (having an inner diameter that is smaller than the outer diameter of the braid), but this will result in a reduction in the braiding angle of the filaments and thereby also size the filter valve and affect its expansion force. The type of mandrel (solid or tubular) and the position of the braid on it (external or internal) will affect the positioning of the polymer on the braid (providing a smooth internally coated filter valve for external mounting on a solid mandrel; and providing a smooth externally coated filter valve for internal mounting within a tubular mandrel) and thereby change the lubrication area of ​​the resulting filter valve.

[0035] Once the braid 140 is securely mounted on (or within) the mandrel, the braid is dipped into a polymer solution at a controlled, steady rate. The solution is an elastomeric thermoplastic polymer dissolved in a solvent system having a boiling point range of 30°C-200°C to produce a solution having a dynamic viscosity range of 50 cP-10,000 cP. The rates of descent and rise are inversely proportional to the viscosity of the solution and range from 1 mm / sec-100 mm / sec. This rate is critical to providing a uniform coating of polymer on the braid to allow wetting of all surfaces of the braid even at locations where the braid filaments are in contact with the mandrel, and to subsequently wick the polymer coating into the braid, particularly to the surface in contact with the mandrel, and to allow the release of bubbles that may have been trapped during the dipping process. For example, in a process for dipping into a thermoplastic polyurethane solution (dissolved in the solvents dimethylacetamide (DMA) and tetrahydrofuran (THF) ), the rate should be such that the residence time for 135 mm (6 inches) of braid is 16 seconds. The rate should also preferably be such that the polymer wicks along the entire length of the braid during its removal from the solution. The braid is dipped into the solution only once to limit the thickness of the coating and thereby prevent constraint of the braided filaments and / or to control the smoothness of the polymer coating film. The controlled rate can be controlled by coupling the mandrel to a mechanized device that dips the braid on the mandrel into the polymer solution and lifts it at a steady and controlled rate.

[0036] After braid 140 is taken out from the polymer solution, the solvent evaporates in a time range relative to the solvent boiling point and a temperature range corresponding to the solvent boiling point, wherein for high boiling point solvents, higher temperatures and longer durations are utilized. All preferred polymer solutions use some DMA to control the uniformity of the coating thickness, and THF can be used to control the rate of solvent evaporation. The ratio of a high boiling point solvent such as DMA to a low boiling point solvent such as THF allows control of the transition rate from a low viscosity, high solvent content polymer solution to a high viscosity, low solvent content polymer solvent to a solid solvent-free material, thereby affecting the quality of the polymer film. In one method, the solvent is released into an oven heated to a temperature higher than the DMA boiling point (165°C) in order to quickly release DMA. The preferred time for heating at this temperature is 5 minutes, which is enough to release DMA. It should be understood that THF has a significantly lower (66°C) boiling point and will evaporate quickly when not heated in large quantities. Alternatively, the polymer-coated braid can be oven-heated at a temperature below the boiling point of DMA (e.g., 80°C-100°C), which will release DMA from the coated braid, but at a slower rate than would occur at a temperature above the boiling point of DMA. This temperature rapidly removes DMA while maintaining the integrity of the coated braid. The preferred time for heating at this temperature is 10 minutes, which is sufficient to release DMA. As yet another alternative, the polymer-coated braid can be allowed to dry at room temperature, which results in DMA release occurring at a slower rate than either of the above.

[0037] After the solvent has been released from the polymer coated braid, the coated braid is cooled to below the glass transition temperature of the polymer on the braid. Once cooled, the coated braid is released from the mandrel. If the mandrel is coated with PTFE, the braid may release from the mandrel on its own, or it may be easily released. If the mandrel is not coated, a release agent such as isopropyl alcohol (IPA) may be used to facilitate the removal of the coated braid from the mandrel. The resulting elastic membrane filter formed on the braid can be elastically deformed within an elongation range of 100%-1000%. In addition In addition, the film can also be formed from the following, but not limited to: other polyether-based aromatic thermoplastic polyurethanes, polyether-based aliphatic thermoplastic polyurethanes (e.g., ), polyether block amides (e.g., ), styrene-isoprene-butadiene-styrene copolymer (SIBS), silicone and other polymers. These polymers can be dissolved in a suitable solvent or heated to their melting point to form a fluid.

[0038] Depending on the polymer and coating technique, the coating may be fluid-impermeable or porous. If porous, the coating may have a characteristic pore size between 10 μm and 500 μm, or more preferably between 15 μm and 100 μm, or even more preferably less than 40 μm, and still more preferably between 20 μm and 40 μm.

[0039] According to various embodiments, the polymer coating 160 is located on strands 142 having a higher primer thickness (region 152a), a lower primer thickness (region 152b), and / or no primer (region 152c). According to an embodiment, the polymer coating is not uniformly applied between the proximal and distal ends of the braided tubular form.

[0040] In yet other embodiments, the coating on the braid of filaments can be non-polymeric and can be applied by a suitable method. For example, the coating can include a metal mesh. In another example, the coating can include a biological tissue material. Such coating materials, when applied to the braid of filaments, are configured to form a barrier to the passage of therapeutic agents through the constructed occluder.

[0041] The polymer-coated braid is also preferably provided with a hydrophilic coating, a hydrophobic coating, or other coating that affects how proteins in the blood adhere to the filter. More specifically, the coating is resistant to the adhesion of blood proteins. Suitable coatings include ANTI-FOGCOATING 7-TS-13 from Hydromer, Inc. of Branchburg, NJ, and SERENE COATING from Surmodics, Inc. of Eden Prairie, MN. These and other coatings can be applied to the filter by, for example, dip coating, spray coating, or roll coating or flow coating.

[0042] After the tubular braid is polymer coated, it is assembled to the catheter 112. The plurality of braided strands 142, the primer, and the polymer filter 160 in the tubular form have an inner surface and an outer surface. In one embodiment, a first end 170 of the tubular form is secured to the catheter 112 at a first position 172 proximally adjacent to the distal end 122 of the catheter. The tubular form is then reshaped by flipping the tubular form over and bending it backward so that the previous inner surface of the second end 174 of the catheter now faces outward on the tubular form. The second end is then coupled to the catheter at a second position 176 proximally offset from the first position to define a shape that flares outward in a proximal-to-distal direction and maximizes to a maximum diameter at a center portion 178.

[0043] In one embodiment, the polymer coating is removed or perforated from a portion of the occluder distal to the occluder's maximum expanded diameter. This provides access to the occluder, which is important for operation of the occluder embodiment. This coating removal or perforation exposes the braid's strands.

[0044] The resulting microvalve occluder dynamically responds to the local pressure around the occluder. That is, when the fluid pressure on the proximal side of the occluder is at a determined level higher than the fluid pressure on the distal side of the occluder, the occluder automatically moves to a contracted (or partially contracted) configuration (closed position) with a smaller diameter, which allows blood to flow around the occluder and through the blood vessel in the forward direction; and when the fluid pressure on the distal side of the occluder is at a determined level higher than the fluid pressure on the proximal side of the occluder blood (such as occurs during a therapeutic infusion through an infusion lumen and out of the distal orifice), the occluder automatically moves to an expanded configuration (open position) with a larger diameter, in which the occluder contacts the vessel wall, thereby preventing reflux (backflow or backward flow) of the therapeutic agent. The difference between the proximal and distal pressures used for the dynamic operation of the microvalve occluder is at least partially based on the radial expansion force of the braid, as discussed above.

[0045] As noted above, the deployable covering 124 is provided to isolate portions of the occluder 118 from the patient's vessel wall during movement of the occluder relative to the vessel wall (such as during tracking and navigation to the occluder's target location) to reduce or prevent vasospasm prior to therapeutic delivery. The covering is preferably constructed of a thin, strong, lubricious, and flexible polymer. Exemplary polymers include silicone rubber, natural and synthetic rubbers, and other elastomers such as Pellethane, aliphatic polyether polyurethanes (such as and ) and thermoplastic vulcanizates (such as and styrene-isobutane-styrene (SIBS). Other materials may also be used, including polyethylene terephthalate (PET), nylon, and polyimide. In addition, the covering may be constructed from a spun polymer fabric. Exemplary materials for spun polymer fabrics include Pellethane and polytetrafluoroethylene (PTFE). The covering may be impermeable, semipermeable, or permeable. It is preferred to isolate at least the braided strands exposed at the distal end of the occluder because these strands are structured to cause maximum friction against the vessel wall.

[0046] In one embodiment, a portion 180 of the covering 124 is attached to the catheter by sandwiching a portion of the covering between an outer surface 182 of the catheter 112 and the braid of the occluder 118. More specifically, the covering portion 180 is attached between the first end 170 of the occluder and the first location 172 on the catheter. The covering 124 is structured to have a slight bias or memory such that when in blood or a fluid having substantially the same properties as blood, the covering 124 is biased to expand open and generally toward the distal portion of the occluder 118. Additionally, with reference to Figure 4 As the occluder 118 moves forward in the direction of arrow 192 within the patient's vessel 190, the fluid pressure on the distal surface 184 of the cover 124 overcomes any force on the cover generated by the directional fluid flow 194 and pushes the cover into conformity with the distal portion of the occluder, and particularly with respect to the portion that would otherwise come into contact with the vessel wall. Because the cover 124 has significantly greater lubricity than the occluder itself, the friction between the occluder and the vessel wall is greatly reduced during the forward advancement of the occluder. Figure 5 Then, when the forward movement stops, the fluid pressure generated by the antegrade flow 194 in the blood vessel 190 causes the occluder to partially contract to provide space between the exterior of the occluder and the blood vessel wall, and overcomes the expansion force of the cover 124 to cause the cover to extend distally away from the occluder. Therefore, when the occluder is at rest in the blood vessel, the cover does not interfere with the occluder. Next, refer to Figure 6 As the therapeutic agent 196 is injected through the infusion lumen of the catheter and exits the distal orifice 132, eddies and turbulence 198 are generated near the distal tip 122 of the catheter. However, the increased fluid pressure generated by the infusion causes the occluder 118 to fully expand into contact with the vessel wall 190 and prevent fluid from flowing past the occluder. Thus, while the covering 124 may vibrate in the turbulent flow, the covering 124 does not interfere with the operation of the occluder. Once the infusion is stopped, the occluder 118 with the covering 124 will again expand as described above. Figure 5 Operates as shown and described.

[0047] Steering Figures 7 to 9, another embodiment of an infusion set 210 that is substantially similar to the infusion set 110 is shown (wherein like components have reference numbers incremented by 100). The infusion set 210 includes a covering 224 that is attached to the catheter 212 at a location displaced from the occluder 218. For example, the covering 224 can be attached to the catheter between the occluder 218 and the distal orifice 232. The covering 224 can be attached by a crimping tape 202 and / or an adhesive or bonding agent. The covering 224 is structured to extend rearwardly and toward the distal portion of the occluder. Figure 7 As the occluder 218 moves forward in the direction of arrow 292 within the patient's vessel, the fluid pressure on the distal surface 284 of the covering overcomes any forces on the covering generated by the directional fluid flow 294 and maintains the covering 224 in conformity with the distal portion of the occluder 218, and particularly the portion that will contact the vessel wall 290. Figure 8 Then, when the forward advancement stops, the fluid pressure generated by the directional flow 294 moves the occluder 218 and moves the cover 224 away from the occluder 218. As shown, the cover 224 can also be partially retracted, or even flipped. Therefore, when the occluder 218 is at rest in the blood vessel, the cover 224 does not interfere with the occluder and the fluid flow in the blood vessel. Figure 9 When the therapeutic agent 296 is injected through the infusion lumen of the catheter and exits the distal orifice 232, the higher pressure at the distal orifice compared to the proximal side 206 of the occluder 218 causes the occluder to expand to block the flow of fluid in the blood vessel 290 past the occluder 218 and allow the cover 224 to extend back over the distal side of the occluder. Once the infusion stops, the occluder with the cover will re-open as described above. Figure 8 After the therapeutic agent has been infused and the intravascular procedure has been completed, the infusion set 210 is removed from the patient.

[0048] Now turn Figures 10 to 12 , showing the Figures 4 to 6Another embodiment of an infusion device 310 is shown that is substantially similar to the infusion device 110 shown in FIG (wherein like components have reference numerals incremented by 200). The infusion device 310 includes an occluder 318 mounted on a catheter 320 and provided with a cover 324 to promote friction reduction during advancement of the occluder through a blood vessel. The catheter 320 is provided with a plurality of side holes 400 extending through the catheter wall; the occluder 318 is disposed over the portion of the catheter 320 with the side holes 400. The side holes are preferably radially oriented. The side holes are preferably uniformly displaced circumferentially. For example, but not limited to, four to twelve catheter side holes 400 may be spaced apart along the portion of the catheter within the occluder. The catheter 320 additionally includes a distal orifice 332. The catheter 320 preferably includes a fluid pressure sensor 402 located at the distal end 382 of the catheter, adjacent to the distal orifice 332.

[0049] The occluder 318 is advanced within the patient's blood vessel 390 in the direction of arrow 392, and the cover 324 operates as described above. When movement within the blood vessel ceases, the cover 324 on the device further operates as described above, specifically, the cover moves away from the occluder when the pressure differential on opposite sides of the occluder 318 allows antegrade flow around the occluder, as shown in FIG. Figure 11 Then, refer to Figure 12 During the infusion of medication through the infusion lumen of the catheter, a portion 404 of the medication leaves the catheter holes 400 inside the occluder 318 and generates pressure within the occluder, which displaces the cover 324 from the occluder. The size and number of holes 400 are determined to have a larger surface area than the distal orifice 332; therefore, the flow rate from the infusion through the side holes 400 is always higher than the flow rate 406 at the distal orifice 332, which prevents the cover 324 from blocking the occluder 318.

[0050] Furthermore, for end-hole infusion sets, there is typically significant turbulence and a Venturi effect near the distal orifice. This turbulence can cause a localized pressure drop and produce errors in the pressure readings in the blood vessel. However, the placement of the side hole 400 and its location (i.e., away from the pressure sensor and on the side of the cover 324 opposite the sensor 402, as shown in FIG. 4 ) may be a problem. Figure 12 ) allows the pressure sensor 402 to obtain a pressure reading that is more stable and less susceptible to local turbulence artifacts. This advantage is provided even if the cover is eliminated from the embodiment, and the present disclosure contemplates that an embodiment can be implemented with or without a cover to obtain the advantages of the side hole, including but not limited to reducing turbulence at the distal orifice and reducing turbulence artifacts on the readings from the pressure sensor at the distal end of the catheter.

[0051] While the above description has been primarily directed to using the device to infuse a therapeutic agent, it will be understood that the device has functionality even if delivery of a therapeutic agent is not the primary function.

[0052] Embodiments of devices and methods for reducing vasospasm when administering a therapeutic agent or performing other procedures in a blood vessel using an infusion device with an occluder have been described and illustrated herein. Although specific embodiments of the present invention have been described, the present invention is not intended to be limited thereto, as the present invention is intended to be as broad as possible within the scope permitted by the art, and the specification should be read accordingly. Thus, although various materials for coverings, microvalve filaments, valve coatings, and catheters have been described, it should be understood that other materials may be utilized in combination and without restriction for each of them in each of the various embodiments. Although the occluder is described as a preferred microvalve, the covering may also be used with other occluders (including static occluders, including balloons and malecot occluders). In addition, although the infusion of therapeutic agents has been mentioned throughout this article, therapeutic agents should be broadly understood to include any therapeutic agent, including but not limited to drugs and immunotherapeutics targeting cancer cells (including immunomodulators, vaccines, modified cells, and checkpoint inhibitors), as well as agents that assist in the delivery of therapeutic agents (including but not limited to contrast agents). Furthermore, while the present invention may have been described with reference to specific human blood vessels, it should be understood that the present invention is applicable to any blood vessels and other vessels of humans and animals, including catheters. Specifically, the device may also be used to treat tumors, such as liver cancer, kidney cancer, or pancreatic cancer. Furthermore, the embodiments have been described with reference to their distal end portions, as the distal end portions of the embodiments may take any of a variety of forms, including forms well known in the art. Therefore, those skilled in the art will appreciate that further modifications may be made to the provided invention without departing from the scope of the invention as claimed.

Claims

1. A therapeutic device for delivering a therapeutic agent within a blood vessel of a patient, the blood vessel having a vessel wall, the device comprising: a) a catheter having a proximal end and a distal end; b) a vascular occluder mounted adjacent to the distal end of the catheter; as well as c) a flexible covering attached to the catheter and adapted to extend between a portion of the occluder and the vessel wall as the occluder is advanced through the vessel and to automatically move away from the occluder when predetermined pressure conditions inside the vessel are met.

2. The treatment device according to claim 1, wherein a portion of the covering is sandwiched between the outer surface of the catheter and the distal end of the occluder.

3. The treatment device of claim 1, wherein the cover is secured to the catheter at a location distal to the distal end of the occluder.

4. The therapeutic device of claim 1 , wherein the covering is self-expanding.

5. The therapeutic device of claim 1, wherein the covering is made of a lubricating material.

6. The therapeutic device of claim 1 , wherein the covering is impermeable.

7. The therapeutic device of claim 1, wherein the covering is semipermeable.

8. The therapeutic device of claim 1, wherein the covering is made of an elastomeric material.

9. The therapeutic device of claim 1, wherein the covering is made of a polymer material.

10. The therapeutic device of claim 9, wherein the polymer is at least one of Pellethane and polytetrafluoroethylene.

11. The treatment device of claim 1 , wherein the catheter comprises a distal opening and a side hole proximal to the distal opening, and the occluder extends over the side hole.

12. The treatment device of claim 11, further comprising a pressure sensor at the distal end of the catheter.

13. The therapeutic device of claim 12, wherein the covering is located between the side hole and the pressure sensor.

14. A therapeutic device for delivering a therapeutic agent within a blood vessel of a patient during vascular surgery, the blood vessel having a vessel wall, the therapeutic device comprising: a) a flexible catheter sized for introduction into the blood vessel, the catheter having proximal and distal ends, an outer surface, a lumen extending between the proximal and distal ends and opening at a distal orifice; as well as b) an occluder mounted adjacent the distal end of the catheter, the occluder having a proximal side and a distal side, the occluder being adapted to dynamically change shape in response to relative fluid pressures at the proximal and distal sides of the occluder, wherein Under a first fluid pressure condition in the blood vessel wherein the fluid pressure on the proximal side of the occluder is higher than the fluid pressure on the distal side, the occluder moves to a first configuration having a first diameter that permits proximal-to-distal flow of blood around the occluder and through the blood vessel, and Under a second fluid pressure condition in the blood vessel wherein the fluid pressure on the distal side of the occluder is higher than the fluid pressure on the proximal side, the occluder moves to a second configuration having a relatively larger second diameter sized to contact the blood vessel wall and prevent passage of fluid in the blood vessel and past the occluder; and c) a flexible covering attached to the catheter and adapted to extend between a portion of the occluder and the vessel wall as the occluder is advanced through the vessel and to move away from the occluder when the second fluid pressure condition exists.

15. The treatment device according to claim 14, wherein the occluder comprises: i) a plurality of elastic filamentary strands in a tubular braid, the strands having a proximal portion, a central portion, and a distal portion, the distal portion being longitudinally secured to the outer surface of the catheter at a first location, The proximal portion is longitudinally secured to the outer surface of the catheter at a second location, and the central portion being offset to extend radially outwardly from the outer surface between the proximal portion and the distal portion; and ii) a polymeric material coated onto the filamentous strands to form a barrier to the passage of the therapeutic agent.

16. The therapeutic device of claim 15, wherein: The polymeric material coats at least the proximal portions of the strands and at least a portion of the central portion of the strands, and the distal portions of the strands are substantially free of the polymeric material to enable the therapeutic agent to flow through the occluder between the distal portions.

17. The treatment device of claim 15, wherein the distal portion of the strand is inverted to be at least partially radially within the central portion of the strand.

18. The treatment device of claim 15, wherein the strands are made of nickel titanium alloy.

19. A therapeutic device for delivering a therapeutic agent within a blood vessel of a patient during vascular surgery, the blood vessel having a vessel wall, the therapeutic device comprising: a) a flexible catheter sized for introduction into the blood vessel, the catheter having proximal and distal ends, an outer surface, a lumen extending between the proximal and distal ends and opening at a distal orifice and a plurality of side holes located proximal to the distal orifice; as well as b) an occluder mounted adjacent to the distal end of the catheter, the occluder having a proximal side and a distal side, the occluder extending over the side hole, the occluder being adapted to dynamically change shape in response to relative fluid pressures at the proximal and distal sides of the occluder, wherein Under a first fluid pressure condition in the blood vessel wherein the fluid pressure on the proximal side of the occluder is higher than the fluid pressure on the distal side, the occluder moves to a first configuration having a first diameter that permits proximal-to-distal flow of blood around the occluder and through the blood vessel, and Under a second fluid pressure condition in the blood vessel wherein the fluid pressure on the distal side of the occluder is higher than the fluid pressure on the proximal side, the occluder moves to a second configuration having a relatively larger second diameter sized to contact the blood vessel wall and prevent passage of fluid in the blood vessel and past the occluder.

20. The treatment device of claim 19, further comprising a pressure sensor at the distal end of the catheter.

21. A therapeutic device for delivering a therapeutic agent within a blood vessel of a patient during vascular surgery, the blood vessel having a vessel wall, the therapeutic device comprising: a) a flexible catheter sized for introduction into the blood vessel, the catheter having proximal and distal ends, an outer surface, a lumen extending between the proximal and distal ends and opening at a distal orifice and a plurality of side holes located proximal to the distal orifice; as well as b) an occluder mounted adjacent the distal end of the catheter, the occluder having a maximum diameter and a proximal fluid-impermeable side and a distal fluid-permeable side located on opposite sides of the maximum diameter, the occluder extending over the side hole, the occluder being adapted to dynamically change shape in response to relative fluid pressures at the proximal and distal sides of the occluder.

22. The treatment device of claim 21, further comprising a pressure sensor at the distal end of the catheter.

23. The treatment device of claim 22, wherein the pressure sensor is located distal to the occluder.

Images