WO2021113405A1

WO2021113405A1 - Implantable venous valve and process for making same

Info

Publication number: WO2021113405A1
Application number: PCT/US2020/062947
Authority: WO
Inventors: Taylor KIRK; Christopher POMERLEAU; Janet Burpee
Original assignee: Venarum Medical, Llc
Priority date: 2019-12-03
Filing date: 2020-12-02
Publication date: 2021-06-10

Abstract

Implantable valve for treating venous insufficiency having a self-expanding frame encased in polymer having a distal section for blood in-flow, a bulbous center section and a proximal section for blood out-flow. Polymeric leaflets have proximal ends forming a concave S-shaped valve outlet, or a valve outlet which spirals toward the proximal section. The valve opens and closes in response to venous blood flow and has distal portions which are integral with the inner polymer surface of the distal end of said bulbous section. The leaflets define a predominantly biomimetic sinus region with the bulbous section. Opening of the valve induces flushing of blood from the sinus region for smooth non-traumatic blood flow through said valve.

Description

IMPLANTABLE VENOUS VALVE AND PROCESS FOR

MAKING SAME

CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of prior-filed U.S. Provisional

Application No. 62/942,744, filed December 3, 2019, and prior-filed U.S. Provisional Application No. 62/960,587, filed January 13, 2020; which are hereby incorporated by reference herein in their entirety. FIELD OF THE INVENTION

This invention relates to an implantable vascular or non-vascular valve and a process for making same. In particular, it relates to an implantable venous valve for treating venous insufficiency and/or related venous valve incompetence, and a method for treating a patient in need thereof. As disclosed herein, the implantable valve enables predomi nantly unidirectional optimal flow of a liquid, preferably blood. It consists of a frame composed of an expandable scaffold embedded partially or fully in a biocompatible, thrombus-resistant polymer where the frame surrounds, is connected to, and is part of a functioning inner-valve. The implantable valve can be delivered endovascularly from a catheter within a vessel; preferably, a self-expanding metal alloy (e.g., Nitinol™) going from a compressed configuration to an expanded configuration. BACKGROUND OF THE INVENTION

In the human peripheral circulatory system, veins in the leg work against gravity and pump blood towards the heart. Healthy function of venous anatomy depends strongly on a series of one-way valves that can open and close, with assistance from the venous pump, a collection of skeletal muscles that can aid in the circulation of blood by muscle con tractions; the valves act as one-way pressure regulators to negate the effects of gravity-induced hydrostatic blood pressure, especially in the standing position where pressures of over 90 mm Hg can be experienced. When the peripheral venous system does not function properly a condi tion known as venous insufficiency or over a long-term, chronic venous insufficiency or CVI develops.

CVI results from either venous valve dysfunction and blood reflux; or venous obstruction due to thrombosis; or a combination of both. Venous valve reflux causes stagnant blood to pool in the leg leading to fluid and blood cell leakage into the skin and other tissues. Venous valve dysfunction is caused either primarily by congenitally weak valves; or secondarily by direct trauma, thrombosis, hormonal changes (e.g., preg- nancy) and/or prolonged standing or sitting. The condition is diagnosed through physical examination, venous duplex ultrasonography, venous air plethysmography, or less commonly by contrast venography. CVI can manifest itself in both superficial and deep veins. Since a superficial vein is not paired with an artery, CVI in a superficial vein typi cally has minor health implications and can be more readily treated or removed without concern for circulatory health. A deep vein is well beneath the skin and is paired with an artery. These paired veins carry most of the blood in the body, and given their importance to circulation, are not typically removed. The risks related to untreated CVI are severe and include major injury and death from deep vein thrombosis (DVT); DVT is the formation of a blood clot in deep veins typically in the legs, thighs or pelvis. In mild cases, CVI may cause chronic itchy skin, slight pain and swelling; in moderate to severe cases, CVI may cause lifestyle interfering edema, ulcerations and infections (cellulitis, lymphangitis).

Current CVI treatments for dysfunctional valves range from surgical reconstruction of valves to endovascular (catheter-based) tech nologies. Surgical correction of refluxing valves is complicated and expensive. Long-term outcomes are unpredictable and procedural risks are high. Endovascular alternatives to surgery such as venoplasty ballooning, catheter-directed lysis and stent implantation have advanced rapidly. Although these new catheter-based techniques provide simplified treatment, their best outcomes are limited to recanalization of the vein, not minimizing venous reflux or reversing the long-term symptoms of

CVI and acute DVT. Early attempts at developing a prosthetic venous valve often led to tilting of the valve, thrombus formation at the valve, continued reflux from leaflet thickening or other problems after the valve was delivered.

SUMMARY OF THE INVENTION

An implantable valve for treating venous insufficiency (and/or related venous valve incompetence) according to the invention includes: an expandable scaffold, which can be a metal alloy such as a nickel- titanium alloy (e.g., Nitinol™), a stainless steel or a cobalt-chromium alloy, for example, having a distal section for blood in-flow, an enlarged bulbous center section and a proximal section for blood out-flow; a scaffold embedded in a biocompatible polymer, such as a urethane polymer, forming a frame which maintains the shape of the valve during opening and closing; the resulting frame having smooth inner and outer polymer walls throughout the distal, center and proximal sections; and an inner-valve surrounded by and smoothly joined to the frame including: (i) at least two biocompatible polymeric leaflets having proximal ends, transverse to the bulbous section, forming a concave S- shaped valve outlet which opens and closes in response to venous blood flow; (ii) the leaflets having distal portions molded of one continuous polymer with the inner polymer wall of the bulbous section such that the distal portions of the leaflets are smoothly joined to the inner polymer wall of the bulbous section and (iii) the leaflets defining a biomimetic sinus region with the bulbous section.

Closing of the valve may occur completely or in-part allowing some fluid to flow backwards; reference to closing of the valve are intended to include to partial or complete closing.

The bulbous section can be circular wherein the largest cross section is adjacent the distal section and tapers towards the proximal section. In this embodiment, the distal portions of the leaflets are trans verse to the largest cross section of the bulbous section.

In a preferred embodiment, the center section is non-circular, that is, an enlarged, non-circular and transversely symmetrical bulbous section adjacent the distal section which is wider than a vein in a front view and about the width of a vein in a side view. In this embodiment, the distal portions of the leaflets are transverse to the front view width of the bulbous section. In another embodiment, the center section of the scaffold, before formation of the bulbous section, has an open cell configuration with struts and areas of pre-compressed cells, wherein the cells upon forma tion of the bulbous section expand to provide a generally uniform open cell configuration of the bulbous section. The struts of the pre compressed areas can be wider to improve adhesion of the embedding polymer. The distal portions of the leaflets can taper in thickness towards the valve outlet. The leaflets can be thinner than other portions of the valve created, for example and as described in greater detail herein, by fewer polymer dips on the leaflet mold, removal of polymer from the leaflet mold during processing or methods which limit adherence to the leaflet mold or layers.

In an alternate embodiment, the proximal and/or distal sections can have flared end portions for anchoring an implantable valve of the invention.

The bulbous section can be less than or equal to the width of a vein in a side view and all sections of an implantable valve can be larger than the diameter of a vein such that the vein fits snugly around an implant able valve of the invention. Alternatively, the side view and front view of the bulbous section can be larger than the diameter of a vein.

Alternatively, the bulbous section can be oval shaped, racetrack shaped or formed from overlapping non-circular shapes. In alternate embodiments, the S-shaped valve outlet can spiral toward the proximal section of the valve and the valve outlet and/or the valve leaflets can include one or more reflux apertures. In a preferred embodiment, distal portions of the leaflets join the polymer embedding the bulbous section at the juncture of the distal portions of the leaflets with the distal end of the bulbous section.

The invention also provides a process for making an implantable valve for treating venous insufficiency, comprising: a. providing an expanded scaffold having a distal section, a proximal section and a center section there between having an enlarged bulbous section adjacent the distal section; b. providing a solution of a biocompatible polymer and a molding tool comprising valve leaflet areas and a contiguous skirt area; c. dip molding the molding tool in the polymer solution to form, on the molding tool, valve leaflets joined at an uncut valve outlet and a contiguous skirt section; d. removing the polymer from the valve leaflet areas of the molding tool formed in step c; e. repeating step c. to form, on the molding tool, valve leaflets joined at an uncut valve outlet and a contiguous skirt section that is thicker than the leaflets; f. positioning the distal end of the scaffold over the leaflets and the skirt section formed in step e., while still on the molding tool, such that the distal portions of the leaflets are located at the juncture of the bulbous and distal sections of the scaffold; g. roll coating the proximal and bulbous sections of the scaffold from step f. in the polymer solution to embed the scaffold and join the leaflets formed in step e. in a continuous polymer bond with the polymer embedded in the bulbous section of the scaffold; h. after allowing the polymer to dry and cure, removing the embedded scaffold and the leaflets from the molding tool; i. roll coating the distal section of the embedded scaffold from step g. in the polymer solution to embed the distal section with the polymer and overlap the skirt section formed in step e.; and j. after allowing the polymer to dry and cure, cut the valve leaflets where they are joined to form a valve outlet.

Roll coating within the context refers to a dip coating method or more descriptively a dip-roll coating process where the frame or other substrate is dip coated into a bath and the frame or substrate is rotated around a center axis. Roll coating is typically used to enable a uniform distribution of the coating material. BRIEF DESCRIPTION OF THE DRAWINGS

Figs. 1A-B are front and side plan views of an implantable valve of the invention having a bulbous center section; Fig. 2 is a front plan view of an implantable valve of the invention with flared ends;

Figs. 3A-D are perspective and plan views of a molding tool for forming parts of an implantable valve of the invention;

Figs. 4A-B are plan views of an embodiment of a scaffold used to make an implantable valve of the invention;

Figs. 5A-B are plan views of an embodiment of a scaffold used to make an implantable valve of the invention;

Figs. 6A-B are plan views of an embodiment of a scaffold used to make an implantable valve of the invention; Figs. 7A-I are schematic views of a process for making implantable valves according to the invention; Figs. 8A-C are top schematic views showing different configurations of a bulbous section of an implantable valve of the invention in relation to a native vein; and Figs. 9-13 are perspective schematic views showing alternate embodiments of a bulbous section of an implantable valve of the invention each with a concave S-shaped valve outlet.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS For purposes of consistency, certain terms related to the invention are defined or clarified here. The following terms are used interchangeably: implantable valve and device, valve leaflet and leaflet, catheter and delivery system, and crimped and compressed where both refer to the device in a smaller configuration typically ready to be inserted in a catheter. A crimped device and a catheter together form the system. Distal and proximal do not refer to the typical relationship within an artery or vein; distal refers to the inflow side or section; proximal refers to the outflow side or section. A scaffold is referred to as a frame when encapsulated or embedded in a polymer.

As used herein: a front-rear view refers to a view looking at the device with its widest width facing the viewer and a side lateral view is turned ninety degrees to the viewer (both views are perpendicular- views); a perpendicular-view of the device refers to a view of the device when looking at the device perpendicular to the longitudinal axis (there are infinite perpendicular views that can be seen as the device is rotated along its longitudinal axis; a given perpendicular view has a two-dimen sional representation); a perpendicular or transverse plane refers to any plane intersecting the device which is perpendicular to the longitudinal axis; an axial or transverse view refers to a cross sectional-view or axial cross section of the device that is taken when sectioned perpendicular to the longitudinal axis (there are infinite axial views along the longitudinal axis); a proximal axial-view refers to an axial view from the proximal section; and a distal axial-view refers to an axial view from the distal section.

As used herein, S-shaped or linear refers to a proximal axial or transverse view of the leaflets' points of contact which is also a valve outlet 25 (Fig. 8B). Parallel and helical refers to the two paths the S- shape can make relative to the perpendicular plane; however, the S- shape does not have to be perfectly parallel or helical to be referred to as parallel or helical, respectively. A chord as used herein passes through the center of a given cross-section; given this definition the chord of given circle would be its diameter.

As used herein and shown in Fig. 8, oversizing or oversized refer to the size of the device relative to the vessel where all sections of the device are larger than the diameter of the vessel such that the vessel fits snugly around the device with no significant gaps; for example, if the distal section is a tube, the diameter of the tube is larger than the ave rage diameter of a vein. Oversizing can also refer to the perimeter where the perimeter of the device is greater than the perimeter of a vein.

Referring now to the drawings wherein like elements have the same reference numerals, Figs. 1A-B and 2 illustrate implantable valve 10 comprising a scaffold encased in a polymer or layers of polymers. Valve 10 includes distal section 22 for blood-inflow (shown by arrow 24), proximal section 18 for blood outflow and center or bulbous section 20 between sections 18 and 22. Sections 18 and 22 have an average dia meter equal to or larger than the approximate inner diameter of a vein. The expandable scaffold can be, for example, a nickel-titanium alloy (e.g., Nitinol™), a stainless steel or a cobalt-chromium alloy. Center section 20 includes an enlarged, non-circular and transversely symme trical bulbous section 20 adjacent distal section 22 which tapers towards proximal section 18 and is wider than a vein in a front view (Fig. 1A) and about the width of a vein in a side view (Fig. IB).

Valve scaffold 2 has struts 12 which define open cells 45. Scaffold 2 is embedded in a biocompatible polymer, such as a urethane polymer, forming a frame which maintains the shape of an implantable valve during opening and closing thereof. The frame has smooth inner and outer polymer walls throughout the distal, center and proximal sections. Inner-valve 23 is surrounded by and smoothly joined to the frame and includes at least two biocompatible polymeric leaflets having proximal ends transverse to the wider width of bulbous section 20 forming a concave S-shaped valve outlet which opens and closes in response to venous blood flow. The concave S-shaped valve outlet is shown in Fig. IB wherein the S-shaped valve outlet is curved downwards from edges 27 of the valve outlet to center 25. Ends 27 of the outlet are higher than and dip towards central area 25 of the valve outlet. This lessens the tendency of an implantable valve to buckle when loaded into a deployment catheter, and improves nesting or folding of S-shape valve leaflets 23 when compressed in a catheter.

When deployed, a concave valve reduces the height of an implant able valve which improves self-flushing of the sinus region formed by the leaflets and the interior walls of bulbous section 20. The S-shape also facilitates expansion and contraction of the valve outlet in response to natural expansion and contraction of a native vein during blood flow. Leaflets 23 have distal portions molded of one continuous polymer with the inner polymer wall of bulbous section 20 at its distal end such that the distal portions of leaflets 23 are smoothly joined to the inner polymer wall of bulbous section 20. Leaflets 23 define a biomimetic sinus region with bulbous section 20. In a preferred embodiment, the distal portions of leaflets 23 join the polymer wall of bulbous section 20 at the juncture of the distal portions of leaflets 23 with the distal end of bulbous section 20. Figs. 3A-D show molding tool 53 for molding valve leaflets

(described in detail herein) in one continuous polymer with the inner wall of bulbous section 20. Leaflet forming areas 56 sit atop shaft 51 which forms distal section 22 of valve 10. Concave S-shaped end 52 with dip 55 corresponds to center 25 of the valve outlet.

In alternate embodiments, distal portions of leaflets 23 can taper in thickness towards the valve outlet by varying the coating process as described herein. Proximal and/or distal sections 18 and 22 can have flared end portions 14 and 15 (Fig. 2) for anchoring valve 10 in a vein.

Bulbous section 20 can be less than the width of a vein in a side view and all sections of an implantable valve can be larger than the dia meter of a vein such that the vein fits snugly around valve 10. Bulbous section 20 can be oval shaped, racetrack shaped or formed from over lapping non-circular shapes (Figs. 8A-C).

The valve outlet and/or the valve leaflets can include one or more reflux apertures.

Figs. 4A-B and 5A-B are plan views of a scaffold before formation of bulbous section 20 wherein center section 20 has an open cell confi guration and areas of pre-compressed cells (Figs. 4B and 5B) with struts 40 and 77 corresponding to the wider width of bulbous section 20. These cells upon formation of bulbous section 20 provide a generally uniform open cell configuration 45 of bulbous section 20. In Figs. 4B and 6B, cell struts 40 in the pre-compressed areas are wider or flatter to improve adhesion of the embedding polymer. In Fig. 5B, cell struts 77 in the pre- compressed areas and the same size as struts 12.

In Figs. 4A and 5A, radiopaque markers 42 and 43 extend beyond distal and proximal section 22 and 18 whereas in Fig. 6A markers 44 are recessed at the distal end to facilitate loading of an implantable valve into a delivery catheter. Markers 43 can have squared-off or blunt ends whereas markers 42 can have a round shape. Figs. 7A-I comprise a flow diagram for making valve 10 which starts with molding tool 53 (Fig. 3), an uncoated but expanded valve scaffold 2 and a solution of urethane polymer 70 in a suitable tank. An example of a protocol for preparing the tank and coating com position is as follows:

Dip coating tank preparation

Tank preparation is carried out under a fume hood with personal protection equipment in a ventilated and filtered environment maintained at 70-85°F and 10-30% Relative Flumidity.

A borosilicate (glass) tank with 3000mL capacity is filled with tetrahydrofuran (THF) to an intended volume.

Carbothane™ describes an art-recognized family of aliphatic and aro- matic, polycarbonate-based thermoplastic polyurethanes (TPUs). Carbo thane™ PC-3538A pellets (Lubrizol) are collected in a beaker and weighed on a scale to measure the correct amount for the intended per centage of polymer to solvent mix.

Endexo® pellets (Interface Biologies) are collected in a beaker and weighed on a scale to measure the correct amount for the intended per centage in the polymer mix.

The glass tank is placed on a stir plate, and a large polytetrafluoroethy- lene (PTFE or Teflon) stir bar is sunk into the tank. The stir plate is turned on to drive the mixing action of the stir bar. Carbothane™ and Endexo® pellets are slowly added to THF in the tank to avoid massing of pellets to stick together and stall the stirring action. A polytetrafluoroethylene (PTFE or Teflon) or high-density polyethylene (H DPE) lid is used to seal the tank, thereby preventing solvent loss due to evaporation.

The mixing action is continued until the pellets are fully dissolved in the tank (typically 12-24 hours).

The viscosity of the tank is measured with a viscometer to confirm target. Carbothane™ + 2% Endexo® solids or TFIF content is modified to achieve target viscosity.

General dip coating tank composition

TFIF Solvent = base volume for calculation of % solids; TFIF solvent density: 0.8784 g/mL.

Carbothane™ PC-3585A = nominal 7.5% (grams polymer) / (grams polymer + grams solvent). Prior development has worked within a range of 5-10%.

Endexo® = 2.0% weight of Carbothane™ polymer (grams Endexo®) / (grams polymer).

Target Viscosity = 135cP (+/- lOcP) at 82°F. Step 1 (Fig. 7B) is carried out by vertically dipping valve mold 53 in polymer solution 70 and spinning the valve mold horizontally to dry the coating. This is repeated for a specified number of dips after which the coating is allowed to cure. All steps in the process are automated for precision and consistency. Valve mold 53 is inserted into polymer solution 70 slowly to prevent air bubbles from being trapped on the mold.

Valve mold 53 is withdrawn from polymer solution 70 at a specific speed, which impacts the amount of polymer 23 that is collected on mold leaflet area 50 and contiguous skirt area 72 as it is pulled out. The with drawal speed is one variable used to control the final thickness of an implantable valve. The coated valve mold is slowly spun while horizontal such that the liquid solution is distributed uniformly across the valve mold as it dries.

The valve mold is dipped in the polymer solution multiple times, and the coating becomes thicker with each dip. The number of dips is another variable that is used to control the final thickness of the valve coating. Using multiple dips provides precise control over the final coating thickness. During each dip after the first, the polymer solution and the new layer of coating re-dissolve the surface of the previous coating layer such that each layer is integrated into the previous layer without any visible layer lines or risks of delamination. In Step 2 (Fig. 7C), the coating is peeled off of valve leaflet areas 56 of mold 53 while leaving polymer 72 attached to the skirt area of mold 53. The thinner the valve leaflets are, the easier it is for them to stretch and for its valve to open. An implantable valve with thinner leaflets allows for a higher forward flow rate than one with thicker leaflets.

Once the scaffold is assembled and bonded to its valve, the coating on the skirt areas of the valve mold (the coating that is not removed in this step) later becomes the coating layer on the inside of the scaffold in distal section 22. The valve leaflet coating should be thinner than the coating on the skirt areas of valve mold 53. Initially, the leaflets and the skirt areas are dipped at the same time. The purpose of peeling is to remove only the valve leaflet coating such that after the valve mold is coated again in Step 3 (Fig. 7D) the leaflet areas of the mold will have collected fewer dips (from Step 3 only) than the outer areas of the mold (from Step 1 plus Step 3).

The edges that separate the leaflet areas from the outer areas of the valve mold have a specific radius which collects less coating such that the edges are thin and able to cleanly separate when the valve leaflet coating is removed. In Step 3 (Fig. 7D), the valve mold is vertically dipped in the poly mer solution again and the valve mold is spun horizontally to dry the coating. Repeat for a specified number of dips, then allow the coating to cure. This is the same as Step 1 except the valve mold already has a coating on the skirt areas of the mold. In this step, the skirt areas of the valve mold will have collected more dips and will be thicker than the leaflet areas of the mold.

Step 4 (Fig. 7E), scaffold 2 is assembled onto the coated valve mold from Step 3. The scaffold sinus edge is aligned with the valve pocket edge as shown in the enlarged portion of Fig. 7E. The orientation of scaf fold 2 will match with the geometry of the valve mold. The bulging sinus of the scaffold aligns with the valve pockets to create sinus cavity 80 within valve 10 that allows for back flow to wash out the valve pockets and prevent stagnation that can lead to thrombus formation.

The bottom of sinus 80 aligns with the bottom edge of valve leaflets 23 to create a smooth transition between the valve leaflets and scaffold 2. If the frame is aligned too high or too low, the resultant implantable valve can have undesirable flow geometries that can lead to stagnation and/or thrombus formation. Step 5 (Fig. 7F), following the procedure for Step 1, scaffold 2 is rolled in polymer solution 70 to coat the scaffold and bond it to the rest of an implantable valve. The proximal end is open during this step to prevent popping of the cells. Spinning the part horizontally levels and distributes the polymer. Allow the coating to dry. Repeat for the specified number of dips, then allow the coating to cure. During each dip, the polymer solution and the new layer of coating re-dissolve the surface of the previous coating layer such that each layer is fully bonded to the previous layer without any visible layer lines or risks of delamination. This step fills open frame cells 76 with polymer 72, creating valve 10 with smooth polymer walls on the interior and exterior of the center and proxi mal sections of the resultant implantable valve. The polymer walls of the distal section are partly formed in this step and finished in Step 7. Step 6 (Fig. 7G), the coated scaffold and its valve are removed from mold tool 53. This is done carefully to not damage the coated scaf fold or the valve leaflets. This step is performed by rolling a thin plastic or metal rod or tube under the coated scaffold, between the coating and the valve mold.

Step 7 (Fig. 7H), like Step 5, the distal end of the scaffold is roll coated in polymer solution 70 and spun horizontally to level and distri bute the polymer and to dry the coating. Repeat for a specified number of dips, then allow the coating to cure. The immersion depth is controlled such that the polymer solution slightly overlaps with the previous coating (Step 5, Fig. 7F) to fully encapsulate the scaffold with no gaps and a thickness consistent with earlier created layers.

Step 8 (Fig. 71), the two leaflets are cut apart to open its valve using a sharp blade inserted from below the valve. Alternate cutting methods can be used, such as laser, thermal or chemical cutting. The cut should be clean without any rough edges to allow smooth blood flow through the implantable valve and to minimize any turbulence. Prior to this step, the valve leaflets are fully connected at the top of the valve mold. This step separates the two leaflets to open the implantable valve.

The scaffold is embedded in a biocompatible, thrombus-resistant polymer which form smooth inner polymer walls throughout distal, center and proximal sections (22, 20 and 18 respectively) which are substan tially even or flush with the scaffold interior without exposing same.

Center section 20 is enlarged and bulbous adjacent distal section 22 and tapers gradually towards proximal section 18 (Figs. 1 and 2).

Center section 20 is non-circular and axially non-symmetrical (Fig. 1) wherein the cross-sectional configuration at the maximum extension of center section 20 can be oval, racetrack shaped or overlapping non circular shapes such as egg shapes, overlapping ovals, racetracks and like non-circular shapes (Figs. 8A-C). The center section 20 can be wider than a natural vessel, such as a vein, in a front view and less wide or approximately the same or wider as a vessel in a side view.

Bulbous section 20 is preferably wider than vein in the front view, e.g., Figs. 1 and 2 and narrower when turned ninety degrees in the side view, or, preferably about the same size as vein or larger than the vein.

Figs. 9-13 illustrate several circular shapes for bulbous section 20 each with valve leaflets 23 and concave S-shaped valve outlets 25.

In Figs. 9 and 13, bulbous section 20 is enlarged adjacent distal section 22 and tapers gradually towards proximal section 18. The distal portions of leaflets 23 are on the same level as valve outlets 25, both being transverse to the largest cross section of bulbous section 20. In these embodiments, leaflets 23 have bowl-like shapes forming a sinus region with valve outlets 25.

In Fig. 10, bulbous section 20 is generally spherical and valve leaf lets 23 and valve outlet 25 are located generally mid-way between sections 18 and 22. As shown, leaflets 23 have a bowl-like shape forming a sinus region with valve outlet 25.

In Fig. 11, bulbous section 20 has an elongated shape largest in cross section at the center thereof which tapers towards distal section 22 from the center in one direction and towards proximal section 18 in the opposite direction. Concave S-shaped valve outlet 25 is positioned in the center of the elongated shape. As shown, leaflets 23 have a deep bowl like shape forming a sinus region with valve outlet 25.

In Fig. 12, bulbous section 20 has an inverted egg shape which is largest in cross section adjacent proximal section 18 and tapers towards distal section 22. The distal portions of leaflets 23 are on the same level as valve outlet 25, both being transverse to a narrower cross section of bulbous section 20. In this embodiment, leaflets 23 have a bowl-like shape forming a sinus region with valve outlet 25.

In Figs. 9-13, the distal portions of leaflets 23 can join bulbous section 20 at the juncture of the distal portions of valve leaflets 23 with the distal end of bulbous section 20 as generally shown in Figs. 1A-B.

A tricuspid valve with three leaflets, for example, can also have S- shaped portions along three radial lines separating each leaflet. The scaffold is embedded with a biocompatible, thrombus-resistant polymer. The scaffold can be made of a superelastic alloy such as Nitinol™. The bulbous section has an axial cross section where the mini- mum chord is smaller than the vein diameter, but the perimeter for that axial cross section is larger than the perimeter of the vein cross section such that the implantable valve, and in particular the bulbous section, is oversized. This embodiment may allow for a smaller opening at the valve's opening enabling a local maximum of pressure. The leaflets can be tapered where it is preferred that the leaflets are each thinnest at the valve outlet to maximize flexibility at the valve outlet, and thickest at the connection to the frame to maximize durability. Further, it may be desir able to have the leaflets as short as possible while still providing ade quate valve function in order to minimize possible areas of leaflet overlap, and possible areas of blood stagnation.

Usable polymers have excellent strength, elongation and durability suitable for high cycle fatigue applications in a body. The leaflets and frame polymer can be created from different polymers adjacent to one another or composed of one continuous singular polymeric material or blend. A polymer that is less thrombo-resistant may be used in con junction with another thrombo-resistant polymer or coating, which would be the primary surface for blood contact. A polymer that is less thrombo- resistant may be used if the clinical need does not require it for clinical success of given device. Alternatives for creating certain aspects of the design from dip coating, spray coating or similar methods where the polymer is liquefied in a solvent, include fabrication from sheets, pre- molds or similar solid non-liquefied materials. For example, the leaflets can be cut from a polymer sheet then welded or otherwise attached to other parts of the inner-valve or frame.

Usable polymers include polyurethane or polyurethane blends, sili- cone or silicone blends, polycarbonate or polycarbonate blends, or layers of polymers including those to enhance anti-thrombogenicity; and they can provide a smooth and hemocompatible surface, which is moldable, castable, and/or able to be applied by dip coating, spray coating or the like. Non-polymer materials can also be blended in with the polymer or polymers. The polymer or polymer blends can be optimized for thrombus formation resistance and to enhance endothelia cell formation. The poly mers may not be specifically anti-thrombogenicity if all polymers are covered with an anti-thrombogenicity coating. Examples of commercially available polymers and additives are given in the following table:

The implantable valve can be expanded by either a balloon or being self-expandable. If self-expandable, the expandable scaffold can made from certain elastically deformable materials or designs using certain metals such as spring steel, Nitinol™ or similar including a composite of different metals; or rigid polymers such as acrylate including a composite of different polymers. Further, the expandable scaffold can be made from braided or woven wire or tube, or laser cut or machined tubing. Self- expandable and self-expanding are used interchangeably. If balloon- expandable, the expandable scaffold can be made from certain plastically or permanently deformable materials or designs using certain metals such as partially annealed stainless steel, cobalt chromium, tantalum, martensitic nickel-titanium or similar including a composite of different metals; or deformable polymers including a composite of different metals. If an implantable valve is balloon-expandable, the balloon would be placed in the valve's center and the balloon would expand the frame and its valve such that the frame retains its expanded shape and the polymer inner valve returns to its shape as a functional valve. It can have radiopaque markers made from tantalum, gold or platinum alloys or other radiopaque alloys or composites.

The distal and proximal sections have some tubular length or can simply act as a small channel or opening with little or no length. The distal and proximal sections can be different such as the distal section is tubular and the proximal section is a flare out of the bulbous section, similar to the top of a pomegranate. Any combinations of straight and flared portions for the distal and/or proximal sections can be employed including no straight portion and no flared portion.

The distal section can have gradients of radial strength such that the strength is greater near the center section and weaker towards the most distal end. The proximal section can have gradients of radial strength such that the strength is greater near the center section and weaker towards the most proximal end. It can be seen that gradients of radial strength can be incorporated along the length and around the device such as around the circumference. These features allow additional oversizing without excess stress to the vessel and/or a more gradual, less traumatic taper for best fluid flow.

A venous valve is crimped or compressed into a catheter and which can radially expand when deployed in a vessel as is well known in the art. A prosthetic valve is preferably delivered from a percutaneous catheter within a body vessel. Such device is preferably adapted for transcatheter percutaneous delivery, and can be moveable from a compressed delivery state suitable for introduction to a point of treat ment with a catheter delivery system, to a radially expanded implanted state for retention within the body vessel at a point of treatment therein. Radially expandable support frames include self-expandable or balloon- expandable frames. The structural characteristics of both of these types of support frames are known in the art, and are not detailed herein. A device intended for implantation in the peripheral vasculature, such as a prosthetic venous valve, advantageously includes a self-expandable support frame.

While many of the preferred embodiments disclosed here discuss implantation of the device in a vein, other embodiments provide for implantation within other body vessels. There are many types of body canals, blood vessels, ducts, tubes and other body passages, and the term "vessel" is meant to include all such vascular or non-vascular passages.

While the invention has been disclosed here as having preferred sequences, ranges, ratios, steps, order of steps, materials, structures, symbols, indicia, graphics, color scheme(s), shapes, configurations, features, components or designs, it is understood that it is capable of further modifications, uses and/or adaptations of the invention following in general the principle of the invention, and including such departures from the present disclosure as those come within the known or custo mary practice in the art to which the invention pertains, and as may be applied to the central features hereinbefore set forth, and fall within the scope of the invention and of the limits of the claims appended hereto or presented later.

The invention, therefore, is not limited to the preferred embodi- ment(s) described herein or shown in the attached drawings, which form part of the disclosure.

Claims

WHAT IS CLAIMED IS:

1. Implantable valve for treating venous insufficiency, comprising: a. an expandable scaffold having a distal section for blood in flow, a center section, and a proximal section for blood out-flow; b. said center section comprising an enlarged bulbous section; c. said scaffold being embedded in a biocompatible polymer and forming a frame which maintains the shape of said valve during opening and closing thereof, said frame having smooth inner and outer polymer walls throughout said distal, center and proximal sections; and d. an inner-valve surrounded by and smoothly joined to said frame comprising: (i) at least two biocompatible polymeric leaflets having proximal ends, transverse to said bulbous section, forming a concave S-shaped valve outlet which opens and closes in response to venous blood flow; (ii) said leaflets having distal portions molded of one continuous polymer with said inner polymer wall of said bulbous section such that said distal portions of said leaflets are smoothly joined to said inner polymer wall of said bulbous section and (iii) said leaflets defining a biomimetic sinus region with said bulbous section.

2. Implantable valve of claim 1, wherein said bulbous section is largest in cross section adjacent said distal section and tapers towards said proximal section.

3. Implantable valve of claim 2, wherein said distal portions of said leaflets are transverse to the largest cross section of said bulbous section.

4. Implantable valve of any one of the preceding claims, wherein said center section comprises an enlarged, non-circular and transversely symmetrical bulbous section adjacent said distal section which is wider than a vein in a front view and about the width of a vein in a side view, said bulbous section tapering towards said proximal section.

5. Implantable valve of claim 4, wherein said bulbous section is less than the width of a vein in a side view.

6. Implantable valve of claim 4, wherein said distal portions of said leaflets are transverse to the front view width of said bulbous section.

7. Implantable valve of any one of the preceding claims, wherein said distal portions of said leaflets taper in thickness to said valve outlet.

8. Implantable valve of any one of the preceding claims, wherein said center section of said scaffold before formation of said bulbous section has an open cell configuration with struts and areas of pre-compressed cells, said cells upon formation of said bulbous section expanding to provide a generally uniform open cell configuration of said bulbous section.

9. Implantable valve of claim 8, wherein said struts of said areas of pre-compressed cells are wider to improve adhesion of embedding polymer.

10. Implantable valve of any one of the preceding claims, wherein said distal section joins said bulbous section at a juncture of said distal portions of said leaflets with the distal end of said bulbous section.

11. Implantable valve of any one of the preceding claims, wherein said proximal and/or distal sections have flared end portions.

12. Implantable valve of any one of the preceding claims, wherein all sections of said valve are larger than the diameter of a vein such that said vein fits snugly around said valve.

13. Implantable valve of any one of the preceding claims, wherein said one continuous polymer is a urethane polymer.

14. Implantable valve of any one of the preceding claims, wherein said frame is self-expanding from being composed of a nickel-titanium alloy (e.g., Nitinol™), a stainless steel, or a cobalt-chromium alloy.

15. Implantable valve for treating venous insufficiency, comprising: a. an expandable scaffold having a distal section for blood in flow, a center section, and a proximal section for blood out-flow; b. said center section comprising an enlarged bulbous section; c. said center section before formation of said bulbous section having an open cell configuration with struts and areas of pre compressed cells corresponding to said bulbous section; said pre compressed cells, upon formation of said bulbous section, expanding to provide a generally uniform open cell configuration of said bulbous section; d. said scaffold being embedded in a biocompatible polymer and forming a frame which maintains the shape of said valve during opening and closing thereof, said frame having smooth inner and outer polymer walls throughout said distal, center and proximal sections; and e. an inner-valve surrounded by and smoothly joined to said frame comprising: (i) at least two biocompatible polymeric leaflets having proximal ends, transverse to said bulbous section, forming a concave S-shaped valve outlet which opens and closes in response to venous blood flow; (ii) said leaflets having distal portions molded of one continuous polymer with the inner polymer wall of said bulbous section such that said distal portions of said leaflets are smoothly joined to the inner polymer wall of said bulbous section and (iii) said leaflets defining a biomimetic sinus region with said bulbous section.

16. Implantable valve of claim 15, wherein said bulbous section is largest in cross section adjacent said distal section and tapers towards said proximal section.

17. Implantable valve of claim 16, wherein said distal portions of said leaflets are transverse to the largest cross section of said bulbous section.

18. Implantable valve of any one of claims 15-17, wherein said center section comprises an enlarged, non-circular and transversely symmetrical bulbous section adjacent said distal section which is wider than a vein in a front view and about the width of a vein in a side view, said bulbous section tapering towards said proximal section.

19. Implantable valve of claim 18, wherein said distal portions of said leaflets are transverse to the front view width of said bulbous section.

20. Implantable valve of any one of claims 15-19, wherein said struts of said areas of pre-compressed cells are wider to improve adhesion of embedding polymer.

21. Process for making an implantable valve for treating venous insufficiency, comprising: a. providing an expanded scaffold having a distal section, a proximal section, and a center section there between having an enlarged bulbous section adjacent said distal section; b. providing a solution of a biocompatible polymer and a molding tool comprising valve leaflet areas and a contiguous skirt area; c. dip molding said molding tool in said polymer solution to form, on said molding tool, valve leaflets joined at an uncut valve outlet and a contiguous skirt section; d. removing the polymer from said valve leaflet areas of said molding tool formed in step c.; e. repeat step c. to form, on said molding tool, valve leaflets joined at an uncut valve outlet and a contiguous skirt section that is thicker than said leaflets; f. positioning the distal end of said scaffold over said leaflets and said skirt section formed in step e., while still on said molding tool, such that distal portions of said leaflets are located at a juncture of said bulbous and distal sections of said scaffold; g. roll coating said proximal and bulbous sections of said scaffold from step f. in said polymer solution to embed said scaffold and join said leaflets formed in step e. in a continuous polymer bond with the polymer embedded in said bulbous section of said scaffold; h. after allowing the polymer to dry and cure, removing said embedded scaffold and said leaflets from said molding tool; i. roll coating said distal section of said embedded scaffold from step g. in said polymer solution to embed said distal section with the polymer and overlap said skirt section formed in step e.; and j. after allowing the polymer to dry and cure, cutting said valve leaflets where they are joined to form a valve outlet.