CN110891527A

CN110891527A - Vascular valve prosthesis

Info

Publication number: CN110891527A
Application number: CN201880046434.1A
Authority: CN
Inventors: 安德鲁·夸克; 奥斯丁·沃克; 阿尔伯特·K·钦; 托马斯·A·克拉默; 埃里克·陈; 安德鲁·莫尔
Original assignee: Innovein Inc
Current assignee: Innovein Inc
Priority date: 2017-06-13
Filing date: 2018-06-13
Publication date: 2020-03-17
Also published as: MA49391A; WO2018232026A1; EP3638154A1

Abstract

A valve prosthetic implant for treating veins or other blood vessels includes a tubular expandable anchoring frame extending from a proximal end to a distal end of the implant, a valve seat formed at or near a middle portion of the anchoring frame, an expandable ball disposed within a lumen of the anchoring frame, and a ball retaining tether connected to the expandable ball and connected to the valve seat and/or the anchoring frame. The anchor frame may include a cylindrical proximal portion at a proximal end, a cylindrical distal portion at a distal end, an inwardly angled inlet portion between the cylindrical proximal portion and a middle portion of the anchor frame, and an inwardly angled outlet portion between the cylindrical distal portion and the middle portion of the anchor frame.

Description

Vascular valve prosthesis

This application was filed as a PCT international patent application on

day

13, 6, 2018 and claims priority benefits of U.S. provisional patent application serial No. 62/518,859 filed on

day

13, 6, 2017 and U.S. provisional patent application serial No. 62/610,338 filed on day 26, 12, 2017, the entire disclosures of both of which are incorporated herein by reference in their entirety.

Cross reference to related applications

This application is a continuation-in-part application of U.S. application serial No. 15/247,523, entitled "venous valve prosthesis", filed 2016, 8/25/2016, which claims priority to U.S. provisional application No. 62/209,351, filed 2015, 8/25/2016, and U.S. provisional application No. 62/356,337, filed 2016, 6/29/2016 (both entitled "venous valve prosthesis").

Technical Field

The present application relates generally to the field of medical devices. More particularly, the present application relates to prosthetic valve implant devices, systems, and methods for implantation within the vasculature.

Background

Veins in the human body are thin-walled blood vessels that carry blood from the limb back to the heart under low pressure. To help move blood toward the heart (most commonly against gravity), the vein has a one-way valve that opens in the direction of forward moving blood flow and closes to prevent backflow of blood. When these valves are damaged, the veins do not function properly. Venous disease due to venous valve insufficiency is a widespread clinical problem. In the united states, 2000 million patients exhibit chronic venous insufficiency with swelling, pain and/or ulceration of the affected limb. Another 7400 million patients exhibit enlargement and malformation of varicose veins.

To address the clinical problem of poor function of venous valves, various approaches have been proposed. Mauch et al (U.S. patent No. 7,955,346) teach a percutaneous method for creating a venous valve from natural venous tissue. Laufer et al (U.S. patent No. 5,810,847) describe placing a catheter holding a device over the tip of a valve to restore the function of an incompetent lower extremity venous valve. Various designs for implantable venous valves have also been described. These designs involve an implantable prosthetic valve that mimics the patient's native (native) valve; that is, the implant uses flexible leaflets or flap valves to restore unidirectional venous flow. Examples of such implantable venous valves are described, for example, by Acosta et al (U.S. patent No. 8,246,676), shaolan et al (U.S. patent No. 6,299,637), and Thompson (U.S. patent No. 8,377,115).

To simulate a natural human peripheral venous valve, the leaflets or flap-like valve are formed of a very thin membrane material to allow the valve to open properly for regurgitation in the low pressure venous system while still providing a proper seal and avoiding valve insufficiency. Prosthetic diaphragms or flap valves are prone to failure due to tears from repeated opening and closing of the leaflets, permanent closure caused by thrombosis and cell adhesion to the prosthetic leaflets, or leaflet inversion and dysfunction over time. Currently available replacement venous valves, whether artificial or implanted tissue valves, also often cause problems with thrombosis (clotting) during long-term valve implantation.

Accordingly, it would be advantageous to have an improved implantable venous valve device. For example, it would be desirable to have a prosthetic venous valve that would prevent and/or accommodate thrombosis or cell adhesion to the valve component during long-term valve implantation. Ideally, an improved prosthetic valve would be relatively easy to implant and would address at least some of the challenges in currently available valve implants discussed above.

Summary of The Invention

Embodiments described herein relate to implantable prosthetic vascular valve devices, systems, and methods of use thereof. Typically, the vascular valve implants described herein are used in veins to replace or complete the work of defective or non-existent venous valves. However, the implant may be used in arteries or other structures in the human body, such as heart valves or other body lumens that may benefit from a prosthetic valve. Thus, the description herein of venous valve implants may also be applicable to arteries and other structures.

In many embodiments, the valve prosthetic device includes a ball-shaped valve mechanism to help promote blood flow through a vein, artery, or other body lumen. A balloon-shaped valve embodiment generally includes an anchoring mechanism, a balloon disposed within the anchoring mechanism, and a valve seat on which the balloon is disposed to prevent retrograde flow of blood through the valve. The ball valve also includes some type of ball retention mechanism that prevents the ball from leaving the prosthesis and drifting away in the direction of blood flow. In some embodiments, the mechanism is a blocking member (or members) of some kind. In other embodiments, the mechanism is a tether of some sort. In either case, the ball moves back and forth within the lumen of the anchoring mechanism between an open position in which blood flows through the valve and around the ball and a closed position in which the ball seats against the valve seat and prevents backflow of blood through the valve. Many different embodiments of such implantable valve prosthesis devices and methods for delivering the devices are described herein.

The vascular valve prosthesis systems described herein generally include a delivery catheter. During placement of an implantable vascular valve prosthesis, it is desirable to minimize the diameter of the delivery catheter used to deploy the valve to facilitate access into the vein and insertion of the prosthesis. A smaller diameter delivery catheter is desirable because it can be inserted into a vein using a smaller puncture, and because it reduces trauma to the vein endothelium during advancement and manipulation of the catheter. In another aspect, it is desirable to maximize the diameter of the ball used in venous valves, as a larger diameter ball may be paired with a valve seat containing a larger diameter valve orifice to reduce flow resistance through the valve. It is important to enhance the flow characteristics through the valve, thereby avoiding thrombus (clot) formation in the valve, which can cause valve occlusion. According to various embodiments, the balloon within the prosthetic valve may be collapsible/expandable (or "non-rigid") such that it will change from a smaller diameter configuration during delivery to a larger diameter configuration after implantation. Other embodiments include different or additional mechanisms for preventing clot formation, as will be described further below.

In one aspect of the present application, a valve prosthetic implant for treating a vein includes a tubular expandable anchoring frame, a valve seat formed at or near a middle portion of the anchoring frame, an expandable ball disposed within a lumen of the anchoring frame, and a ball retention tether connected to the expandable ball and connected to the valve seat and/or the anchoring frame. The anchor member may be a stent extending from the proximal end to the distal end of the implant and forming a lumen from the proximal end to the distal end. The anchor frame may include a cylindrical proximal portion at a proximal end, a cylindrical distal portion at a distal end, an inwardly angled inlet portion between the cylindrical proximal portion and a middle portion of the anchor frame, and an inwardly angled outlet portion between the cylindrical distal portion and the middle portion of the anchor frame. The expandable balloon expands from a compressed configuration for delivery into a vein through a delivery catheter to an expanded configuration outside the delivery catheter. The inflatable balloon in the inflated configuration moves between an open position in which the inflatable balloon is positioned away from the valve seat to allow blood to flow forward through the implant, and a closed position in which the inflatable balloon contacts the valve seat to prevent backflow of blood through the implant.

Some embodiments may also include a material disposed on at least a portion of the anchoring frame. For example, the material may be made of at least one substance such as, but not limited to, polymers, hyaluronic acid, heparin, and anticoagulants. The anchor frame may optionally include a plurality of outward projections on a proximal portion other than the proximal end and/or on a distal portion other than the distal end. The plurality of outward projections may be barbs (barb), hooks (hook), U-shaped projections, V-shaped projections, or the like. In some embodiments, each of the plurality of outward projections forms an angle of 25 degrees to 45 degrees with an adjacent portion of the anchor frame. In some embodiments, the valve seat is an annulus connected to at least one of an inner surface or an outer surface of the anchor member. Alternatively, the valve seat may be formed from the material used to make the anchoring frame or from a material used to coat or cover the anchoring frame.

In some embodiments, the inflatable bulb is a solid, compressible foam bulb. Such embodiments may also optionally include at least one weight embedded within the ball. Alternatively, the inflatable balloon may include an elastomeric shell and a filler substance inside the elastomeric shell. For example, the filler substance may be air, a gel or a fluid. Some embodiments include at least one weight inside the elastic shell. Optionally, the filler material may be a curable material that hardens upon curing. In some embodiments, the filler material is a helically-cut elastomeric hollow sphere. In some embodiments, the inflatable ball includes an aperture through which the ball retention tether passes. In some embodiments, the inflatable balloon has a density of less than 2.5 grams per square centimeter. The ball retains the tether connected to the valve seat, wherein the tether and the valve seat form a filling lumen, and wherein the valve seat is accessible through the filling port such that filler material passes through the valve seat and the tether to fill the inflatable ball. In some embodiments, the inflatable balloon has a density of no greater than 1.06 grams per square centimeter and the tether is elastic to pull the balloon toward the valve seat to prevent backflow of blood through the implant.

In some embodiments, the inlet portion and the outlet portion each form an angle of 15 degrees to 35 degrees with respect to a longitudinal axis of the implant. In some embodiments, the ball retention tether has a length of 0.5 millimeters to 10 millimeters. In some embodiments, the ball retention tether is long enough to allow the inflatable ball to be positioned outside of the distal end of the anchoring frame. In various embodiments, the inflatable balloon may be made of materials such as, but not limited to: thermoplastic polyurethane, elastomeric thermoplastic polyurethane, PVC, polyethylene, polycarbonate, PEEK, polyetherimide (ultem), PEI, polypropylene, polysulfone, FEP, PTFE, coated hollow heavy metals, or combinations thereof.

In another aspect of the present application, a venous valve prosthetic implant system for treating a vein includes an implant according to any of the above aspects and embodiments, and a delivery device. The delivery device includes an elongate flexible catheter body and a deployment plunger disposed within the catheter body for pushing the implant out of the catheter body.

In some embodiments, the deployment plunger comprises a curing member for curing a curable material, the inflatable balloon being at least partially made of the curable material. For example, the curing member may be configured to emit a curing agent, such as, but not limited to, heat, light, electricity, sound waves, or a chemical mixture. In some embodiments, the delivery device further comprises an inflation tube disposed within the catheter body, wherein the inflation tube comprises a distal end configured to enter the aperture in the inflatable balloon to inflate the inflatable balloon. In some embodiments, the inflation tube further comprises a curing member configured to emit a curing agent. In alternative embodiments, the delivery device may further include an inflation accessory configured to pass fluid through a lumen in at least one of the valve seat or the ball retention tether to inflate the inflatable ball.

Optionally, the system may further comprise a ball retrieval device configured to retrieve the expandable ball from the implant. In one embodiment, the bulb extraction device includes a grasper for grasping the inflatable bulb and a cutter for cutting a tether connecting the inflatable bulb to at least one of the anchor frame or the valve seat. In some embodiments, the ball retrieval device is configured to pass through a catheter body of a delivery device. The delivery device may also optionally include at least one orientation indicator for indicating the orientation of the implant within the catheter body.

In another aspect of the disclosure, a method for implanting a venous valve prosthetic implant into a vein or other vessel first includes advancing a delivery catheter containing the implant into the vein. Next, the method includes retracting the catheter body of the delivery catheter and/or advancing a deployment plunger of the delivery catheter to cause the implant to exit the distal end of the delivery catheter. The tubular stent anchoring member and the balloon disposed inside the anchoring member are then expanded within the vein and outside of the delivery catheter. When expanded, the anchor member contacts an inner wall of the vein to retain the implant within the vein. When inflated, the ball moves between an open position in which the ball is positioned to allow blood to flow forward through the implant and a closed position in which the ball contacts the valve seat to prevent backflow of blood through the implant. Finally, the method includes removing the delivery catheter from the vein.

In some embodiments, expanding the anchor member and the ball includes releasing the anchor member and the ball from binding within the catheter body, and both the anchor member and the ball are made of at least one shape memory material. Some embodiments may further include curing a curable material using the delivery catheter, the ball being made at least in part of the curable material. Such curing may include emitting a curing agent, such as heat, light, electricity, sound waves, or a chemical mixture.

In some embodiments, the method further comprises advancing an inflation tube outside of the catheter body of the delivery catheter, wherein a distal end of the inflation tube is positioned through the aperture of the balloon, and inflating the balloon using the inflation tube. In various embodiments, the ball may be inflated with air, fluid, gel, or a resilient hollow sphere. In some embodiments, inflating the ball includes using an inflation attachment of the delivery catheter to pass fluid through a lumen in the valve seat and/or ball retention tether of the implant. In some embodiments, the method further comprises orienting the implant with the catheter body using at least one orientation feature on at least one of the implant, the catheter body, or a handle connected to the catheter body.

Optionally, the method may also include removing the ball from the implant using a ball removal device. For example, retrieving the ball may include using a grasper of the retrieval device to grasp the ball and using a cutter of the retrieval device to cut a tether connected to the ball.

These and other aspects and embodiments are described in more detail below with reference to the figures.

Brief Description of Drawings

FIGS. 1A and 1B are side views of a vascular prosthetic valve implant according to one embodiment;

2A-2C are front and side views of three different shaped ball members for a vascular prosthetic valve implant according to three alternative embodiments;

fig. 3A and 3B are side views of an expandable anchoring frame of a vascular prosthetic valve implant in a pre-formation (fig. 3A) and post-formation (fig. 3B) configuration according to one embodiment;

FIGS. 4A and 4B are side and front views, respectively, of a vascular prosthetic valve implant according to one embodiment;

FIG. 5 is a side view of a vascular prosthetic valve implant with a V-shaped ball retention member according to one embodiment;

FIG. 6 is a side view of a vascular prosthetic valve implant with a tether according to one embodiment;

fig. 7A and 7B are side views of a vascular prosthetic valve implant system showing delivery of the implant out of a delivery device, according to one embodiment;

FIG. 8 is a view of a compressible foam bulb of a vascular prosthetic valve implant according to one embodiment;

FIG. 9 is a view of an elastomeric filled ball of a vascular prosthetic implant according to one embodiment;

FIG. 10 is a view of an inflatable balloon with internal weights of a vascular prosthetic valve implant according to one embodiment;

11A and 11B are side views illustrating a method for delivering a vascular prosthetic valve implant and inflating the elastic bulb of the implant according to one embodiment;

FIG. 11C is a front view of the dual lumen inflation catheter of FIGS. 11A and 11B;

12A-12E are side views illustrating a method for inflating an elastic bulb of a vascular prosthetic valve implant according to one embodiment;

figures 13A-13D are side views illustrating a method for delivering a vascular prosthetic valve implant into a blood vessel, according to one embodiment;

fig. 14A is a cross-sectional view of a vascular prosthetic valve implant bulb including a hollow sphere filler, according to one embodiment;

FIG. 14B is a view of the hollow sphere packing of FIG. 14A;

FIG. 14C is a view of the hollow sphere of FIGS. 14A and 14B in tension;

FIG. 14D is a side view of a conduit delivering a stretched hollow sphere into the shell of the bulb of FIG. 14A;

FIG. 15 is a plurality of views of a ball of a vascular prosthetic valve implant configured as an expandable housing with a spring ball retainer, according to one embodiment;

figures 16A and 16B are side views illustrating a system and method for delivering a vascular prosthetic valve implant according to one embodiment;

17A and 17B are side views illustrating a system and method for delivering a vascular prosthetic valve implant according to an alternative embodiment;

FIG. 18 is a side view illustrating a system and method for delivering a vascular prosthetic valve implant according to another alternative embodiment;

FIGS. 19A and 19B are side views of two embodiments of a vascular valve prosthetic implant having an inner annular valve seat (FIG. 19A) and an outer annular valve seat (FIG. 19B) according to two alternative embodiments;

FIG. 20 is several views of a vascular prosthetic valve implant with an asymmetric expandable anchoring frame, according to one embodiment;

FIG. 21 is several views of a vascular prosthetic valve implant with an asymmetric expandable anchoring frame according to an alternative embodiment;

FIG. 22 is a side view of a vascular prosthetic valve implant with a V-shaped tether according to one embodiment;

FIG. 23 is a side view of a vascular prosthetic valve implant with a two-piece tether according to an alternative embodiment;

FIG. 24 is a side view of a vascular prosthetic valve implant with a two-piece tether according to another alternative embodiment;

FIG. 25 is a side view of a vascular prosthetic valve implant showing regions of shear stress within the implant;

FIG. 26 is a side view of a vascular prosthetic valve implant with a short tether according to one embodiment;

FIG. 27 is a side view of a vascular prosthetic valve implant with a long tether according to one embodiment;

FIG. 28 is a side view of a vascular prosthetic valve implant with an elongate end expandable anchor frame according to one embodiment;

FIG. 29 is a side view of a vascular prosthetic implant showing the exit angle within the implant;

FIG. 30 is a side view of a vascular prosthetic valve implant implanted intravenously at a native venous valve location according to one embodiment;

31A-31C are side, front and side views, respectively, of a vascular prosthetic valve implant having a sheet-like valve bulb retaining member, according to one embodiment;

FIG. 32 is a side view of an expandable anchor frame of a vascular prosthetic valve implant with barbs projecting outwardly in a position spaced from the ends of the frame, according to one embodiment;

FIG. 33 is a side view of an expandable anchor frame of a vascular prosthetic valve implant according to one embodiment, with V-shaped protrusions protruding outward in a position spaced from the ends of the frame;

34A-34C are side views of a system and method for removing a ball from an implanted vascular prosthetic valve implant according to one embodiment;

FIGS. 35A and 35B are side views of a vascular prosthetic valve implant with a single leaflet-like valve, according to one embodiment;

FIGS. 36A and 36B are side views of a vascular prosthetic valve implant with a single leaflet-like valve, according to one embodiment;

FIGS. 37A and 37B are side views of a vascular prosthetic valve implant with a tether showing the effect of gravity on the ball of the implant;

FIG. 38 is a side view of a vascular prosthetic valve implant having an anchor member with a central rounded portion according to one embodiment;

FIGS. 39A and 39B are side views of a ball without and with a tether, respectively, of a vascular prosthetic valve implant according to one embodiment;

FIG. 40 is a side view of a ball and tether of a vascular prosthetic valve implant according to an alternative embodiment;

FIG. 41 is a side view of a ball and tether of a vascular prosthetic valve implant according to another alternative embodiment; and is

Fig. 42A and 42B are side views of a vascular prosthetic valve implant having a ball with a central post according to one embodiment.

Detailed Description

Various embodiments and features are described herein relating to devices, systems, and methods for implanting in a vessel to improve vessel function. In many cases, vascular valve prostheses are used in human veins to help treat venous insufficiency. However, in alternative embodiments, the valve prosthesis may be used in arteries, other locations in the body, such as heart valves or other body lumens, and/or it may be used in animals. Thus, although the following description focuses on the use of a valve prosthesis in a vein, this should not be construed as limiting the scope of the claims.

In contrast to prior art leaflet or sheet valve approaches, many of the embodiments described herein are vascular balloon valve prostheses. A number of embodiments of a balloon valve prosthesis are described in U.S. patent application publication No. 2017/0056175 entitled "venous valve prosthesis" (hereinafter "venous valve prosthesis application"), filed by the assignee of the present application on 25/8/2016 (the entire disclosure of which is incorporated herein by reference). As mentioned above, some potential challenges with the use of vascular balloon valves include: (1) the ability to compress the valve prosthesis into a small diameter catheter for delivery while also allowing good fluid dynamics through the valve once implanted; (2) prevent clot formation on the ball or other components of the prosthetic valve; and (3) prevent the valve prosthesis from migrating intravenously due to the vein diameter increasing as the vein approaches the heart. The embodiments described below address these challenges.

Referring now to fig. 1A and 1B, in one embodiment, a prosthetic venous valve implant 10 may include an anchoring member 12 (or "anchoring frame") such as a self-expanding stent-like frame for anchoring the implant 10 within a vein. The anchor member 12 may have a first end 14 (sometimes referred to herein as an "upstream end"), a second end 16 (sometimes referred to herein as a "downstream end"), and an intermediate valve portion 13. Although not labeled in fig. 1A and 1B, the portions of the anchor member 12 between the first end 14 and the middle valve portion 13 and the portions between the second end 16 and the middle valve portion 13 may be referred to as "upstream portions" and "downstream portions" of the anchor member 12, respectively. In many embodiments, there is no clear boundary or line between the various portions of the anchor member 12, and these descriptive terms are for illustrative purposes only and should not be construed as limiting the scope of the invention.

Optionally, as shown in fig. 1B, all or a portion of the anchor member 12 may be coated or otherwise covered with a material or membrane 26 to help direct blood flow through the implant 10 and prevent blood flow through the wall of the anchor member 12 in the coated portion. In some embodiments, the septum 26 may be made of or coated with an anticoagulant substance. However, in alternative embodiments, the anchor member 12 may not include a septum or coating material. For example, this is possible in such embodiments: the embodiment is sufficiently inflated so that the natural vein wall itself acts as the wall, whereby blood is conducted by the vein wall itself. Generally, the anchoring member 12 is configured to anchor the valve implant 10 to a vein lumen surface.

The venous valve implant 10 may also include a tubular frame 20 received within the anchor member 12, and a ball 28 received within the tubular frame 20. Attached to or integrally formed with the tubular frame 20 are the valve seat 18, the retaining member 22, and a plurality of through holes 24 through which blood freely exits the tubular frame 20. In some embodiments, the tubular frame 20, valve seat 18, retaining member 22, and ball 28 may be referred to as the "valve portion" of the implant device 10, which is housed within the anchoring member 12.

In alternative embodiments, which will be described further below, the prosthetic venous valve implant may include fewer components than the valve implant 10 of fig. 1A and 1B. For example, alternative embodiments do not include a tubular frame. These embodiments may include only the valve seat (which is directly connected), the self-expanding stent anchoring member, the ball and the ball retaining feature such as a tether or tethered portion of the anchoring member. Other embodiments may include additional components or features, such as retention barbs on the anchor member. A number of these alternative embodiments and features are described in more detail below.

The embodiments of the ball 28 described further below can be collapsible (or "compressible" or "flexible") to help allow the valve implant 10 to be compressed and loaded into a small diameter delivery catheter. In some embodiments, the density of the bulb 28 may be equal to, approximately equal to, or slightly greater than the average density of venous blood (or arterial blood in other embodiments), so the valve functions with both low opening and low closing pressures. For example, in some embodiments, ball member 28 may have a density of about 1.06 grams per cubic centimeter (approximate blood density) to about 2.5 grams per cubic centimeter, or, more specifically, about 0.9 to about 2.5 grams per cubic centimeter, or, even more specifically, about 0.9 to about 2.0 grams per cubic centimeter. In alternative embodiments, the density of ball 28 may fall outside of these ranges, such as from about 0.1 grams per cubic centimeter to about 5 grams per cubic centimeter. Various additional density ranges for ball 28 include, but are not limited to, 0.96 to 1.16 grams per cubic centimeter, 0.7 to 1.42 grams per cubic centimeter, 0.1 to 1.06 grams per cubic centimeter, 0.5 to 1.06 grams per cubic centimeter, 1.06 to 2.5 grams per cubic centimeter, and 1.06 to 2.0 grams per cubic centimeter.

In various embodiments, ball 28 may be constructed of any of a number of suitable materials, including but not limited to: PTFE (polytetrafluoroethylene), silicone rubber (silicone rubber), siliconized rubber (silastic rubber), silicone, stainless steel, Teflon (Teflon), thermoplastic polyurethane, elastomeric thermoplastic polyurethane, PVC, polyethylene, polycarbonate, PEEK, polyetherimide, PEI, polypropylene, polysulfone, FEP, coated hollow heavy metals, or any combination thereof. Optionally, an anticoagulant (such as heparin) or another coating (such as hyaluronic acid) may be bonded to the surface of ball 28. The valve seat 18 may be formed from an annular elastomer, silicone rubber, or other material.

In various alternative embodiments, ball 28 may have any suitable shape, size, one or more surface features, and the like. For example, in its simplest form, ball member 28 may be spherical as well as solid. Alternatively, and referring now to fig. 2A-2C, the ball incorporated into the prosthetic valve implant of the present disclosure can have any of a variety of alternative shapes, such as an oval, an oblong, an asymmetrical shape, and the like. In fig. 2A-2C, the left side view is a front view and the right side view is a side view. As shown in fig. 2A, the ball 240 according to one embodiment may have a cylindrical shape 242 with a pointed end when viewed from the side. As shown in fig. 2B, a ball 244 according to another embodiment may have a diamond shape 246 when viewed from the side. As shown in fig. 2C, a ball member 248 according to yet another embodiment may have a cylindrical shape 250 with rounded ends when viewed from the side. According to alternative embodiments, any other shape may be used. In some embodiments, ball 28 may have an outer shell and an inner core, and these two components may be made of different substances. In some embodiments, the inner core may be made of a liquid material, and in some embodiments, a liquid may be injected through the outer shell to fill the core. The substance may be an anticoagulant or other pharmaceutical or therapeutic substance, and may in some embodiments leak out of one or more holes in the housing. The ball 28 may also have surface features such as dimples (dimples), grooves (grooves), grooves (indentations), dimples (pockets), or the like. In various embodiments, for example, the surface features may promote the flow of blood around the ball-shaped member 28. Again, these and other embodiments of ball member 28 will be described more fully below.

Referring now to fig. 3A and 3B, the anchor member 12 (or "anchor frame") is shown in greater detail. In various embodiments, the anchor member 12 may be formed as a stent-like lattice structure 30, (or sometimes simply referred to herein as a "stent") with open portions 32 within the lattice. The anchor member 12 is typically self-expanding, but in alternative embodiments it may be expandable, such as using a balloon catheter. In some embodiments, all or a portion of the self-expanding anchor frame 12 may be coated to render it impermeable to blood flow. (in other words, such that blood flows through the lumen of the anchor member 12 and does not flow through the open portion 32.) the anchor member 12 may be a frame constructed of an engineering polymer (i.e., PEEK, polypropylene, PTFE, etc.), stainless steel, or a superelastic metal, such as Nitinol (Nitinol). For example, a nitinol tube may be laser cut into the grid pattern 30 to form the anchor member 12.

As shown in fig. 3B, in some embodiments, the middle valve portion 13 of the anchor member 12 may not expand, or may expand to be smaller (to a smaller diameter than) the upstream and

downstream portions

15, 17 of the anchor member 12. The upstream and

downstream portions

15, 17 may expand to, for example, 1mm to 30mm, and the middle valve portion 13 may be 1mm to 30 mm. More specifically, some embodiments may have an upstream portion 15 and a downstream portion 17 that expand to 10mm to 20mm, and a middle valve portion 13 that may be 2mm to 10 mm. The length of the anchor member 12 may be 1mm to 200mm, with some embodiments being 20mm to 40 mm. The first and second ends 14, 16 of the anchor member 12 may have a plurality of apices that, when expanded, anchor the anchor member 12 to the inner wall of the vein. The anchor member 12 may be heated above its transformation temperature and quenched to place it in its austenitic self-expanded state.

Referring again to fig. 1B, in some embodiments, some or all of the open areas 32 of the mesh 30 may be closed via a membrane 26, which may be a thin layer of silicone rubber or a covering film such as PET (polyethylene terephthalate), PTFE, nylon, hyaluronic acid, or other material. In some embodiments, the septum 26 may have anticoagulant properties, and thus may be referred to herein as an "anticoagulant septum," although anticoagulant properties are not required. The septum 26 may also be referred to as a "hemostatic septum" in this application because it prevents or helps prevent blood from flowing through the opening 32 in the wall of the anchor member 12. The septum 26 may cover the inlet and/or outlet sections of the anchor member 12 and may thus form a seal against the inner vein wall when the anchor member 12 is expanded to prevent leakage around the exterior of the anchor member 12. Sealing may also be facilitated by adding a short barb 34 to the apex first end 14 (or "inlet" or "upstream" end). In various alternative embodiments, barbs 34 may be included on second end 16, on both first and second ends 14, 16, on middle valve portion 13, or any combination thereof. The first end 14 of the implant 10 with the septum 26 may form a circumferential linear seal against the inner surface of the vein, facilitated by barbs 34 projecting into the vein wall. The edges of the diaphragm 26 may also be thickened relative to the rest of the diaphragm 26 to enhance its sealing ability.

One advantage of the self-expanding venous valve prosthesis 10 is its sealing mechanism, which includes a significantly more robust valve structure — a movable ball 28 that sits on a ring of the valve seat 18. Other advantages include a self-expanding frame/anchor member 12 that expands the vein wall upon deployment to prevent valve migration, maximize flow area, and minimize the sheath size for the introduction device 10 and impermeable cover 26. The use of a spherical valve instead of an ultra-thin membrane or leaflet provides long life for the implant 10. Due to the larger size and mass of the bulb 28 compared to the thin leaflets, and due to the greater deflection of the rolling bulb 28 when opening and closing the valve, the bulb valve will avoid at least some of the sealing and fatigue problems encountered with thin diaphragm and leaflet valves. Another advantage of the venous valve implant device 10 is that it is capable of at least partially self-cleaning as the ball 28 rolls back and forth, and thus cleaning the inner surface of the anchoring member 12, the valve seat 18, and/or the retaining member 22. To provide sufficient offset of the rolling ball 28 for the purpose of the self-cleaning device 10, the distance between the valve seat 18 and the retaining member 22 may be about two to four times the diameter of the ball 28. For example, in alternative embodiments, the distance may be longer or shorter, such as about 1.5 to about five times the diameter of ball 28. As the ball 28 moves back and forth, it rubs against the interior of the ball-shaped valve frame 20, removing potentially adherent cells and thrombus. In embodiments described further below that do not include a tubular frame 20, the ball 28 may alternatively clean the inner surface of the anchor member 12.

Referring now to fig. 4A and 4B, in another embodiment, a venous valve prosthesis 160 may include an anchor member 162 (or "anchor frame") having a first end 164, a second end 166, and a middle valve portion 163. Internal to the anchor member 162 are a ball 170, a valve seat 168, and a ball retaining member 172. In this embodiment, there is no internal tubular frame. Instead, the first and second ends 164, 166 of the anchor member 162 expand to anchor the implant 160 within the vein, and the middle valve portion 163 maintains a smaller diameter and serves as a substantially tubular support for the ball 170. As discussed above, the anchor frame 162 may be made of a continuous superelastic material (such as nitinol), which may be fully or partially coated with a material such as PTFE, silicone, or hyaluronic acid. The coating funnels blood through the central valve assembly. Ball retention member 172 may include a plurality of transverse sutures extending across the lumen of the implant in any suitable pattern or configuration. The entire implant 160 may be compressible (ball 170, valve seat 168, anchor frame 162, ball retaining member 172) so that it may fit into a small delivery catheter for implantation. Any of the valve seat, ball, anchoring feature (such as barbs), or retainer embodiments described in this application may be used in this embodiment. This embodiment may also be applied with an external compression and/or ferromagnetic ball and an externally placed magnet to clear clots. The entire device 160 or just the ball 170 may also be removed. The same deployed funnel can be mated to the proximal end of the prosthesis 160 using a grasper or small scissors to cut the retaining member 172 and using the grasper or aspirator to remove the bulb 170 from the valve 160.

In some embodiments, the ball 170 may have a ball diameter such that the distance between the valve seat 168 and the ball retaining member 172 is two to four times the ball diameter. The diameter of the ball may also be sized so that the ball 170 contacts the inner surface of the middle valve portion 163 as the ball 170 moves back and forth between the valve seat 168 and the ball retaining member 172 so that contact between the ball 170 and the middle valve portion 163 can remove matter formed on or attached to the middle valve portion 163. Thus, this size of ball 170 and the diameter of middle valve portion 163 may provide "self-cleaning" capability for implant device 160. For example, in some embodiments, ball 170 may have a diameter of 0.5mm to 30 mm. More specifically, in some embodiments, ball 170 may have a diameter of 1mm to 8 mm.

The valve seat 168 may be formed from an annular elastomer, silicone rubber, nitinol, or any other material. In some embodiments, the valve seat 168 and the anchor frame 162 can be made of the same material, such as nitinol in one embodiment. The valve seat 168 may be rigid (e.g., stainless steel, nitinol, or polycarbonate) or flexible/collapsible (e.g., silicone) to facilitate encasing in a smaller delivery sheath. In some embodiments, the inner surface of the valve seat 168 may be lined with the same continuous material as the anchor members 162 to limit or prevent lumen or blood exposure. The valve seat 168 may be expanded to a diameter greater than the diameter of the delivery sheath and/or the vein wall to maximize the flow area. The valve seat 168 may be permanent or replaceable.

As described above, the anchor member 162 may be a self-expanding or balloon expandable anchor frame having a stent-like lattice structure. In this embodiment, the first or upstream end 164 and the second or downstream end 166 are expanded to a larger diameter than the middle valve portion 163 of the anchor member 162. The two ends 164, 166 generally dilate the vein or other vessel in which they are implanted. In some embodiments, the middle valve portion 163 is also expanded to a diameter sufficient to dilate the vein when delivered. In some embodiments, implant 160 further includes a material, membrane, or coating (not shown) disposed on a portion of anchor member 162. The coating may serve as a hemostatic barrier for funneling blood through the central lumen of device 160. The coating may be composed of a hemostatic material such as a polymer (e.g., PTFE, silicone, PET, nylon, or hyaluronic acid), and may also be infused or conjugated with heparin, hyaluronic acid, or other agents. A hemostatic membrane covering the inlet and/or outlet sections of the anchor frame 162 may seal against the inner vein wall to prevent or reduce leakage around the exterior of the implant 160. Additionally, the most downstream end 166 may expand to a slightly larger diameter than the immediately downstream portion, thereby forming a wider expandable portion, which may also be uncovered/uncoated and may serve as multiple anti-migration tips when the anchor member 162 is expanded. These tips may help prevent downstream migration of the implant 160 within the vein. Optionally, some embodiments may include additional anti-migration barbs on the anchoring frame 162.

The anchor member 162 may be a frame constructed of an engineering polymer (i.e., PEEK, polypropylene, PTFE, etc.), stainless steel, or a superelastic metal, such as Nitinol (Nitinol). The nitinol tube may be laser cut into a mesh pattern and its proximal and distal sections (or "downstream and upstream sections", respectively) may be expanded while the middle valve portion 163 may be kept at a smaller diameter. In some embodiments, the proximal and distal sections of the anchor member 162 may expand to 0.1mm to 100 mm. More specifically, some embodiments may have proximal and distal sections that expand to 10mm to 20 mm. In some embodiments, the anchor member 162 may be 1mm to 200mm in length, and 20mm to 40mm in some embodiments. In some embodiments, the central narrowed middle valve portion 163 can have a diameter of 1mm to 100mm and a length of 0.1mm to 100 mm. More specifically, in some embodiments, the middle valve portion 163 can have an outer diameter of 3mm to 20mm and a length of 5mm to 15 mm. The anchor member 162 may be self-expandable from a collapsed configuration for delivery through a delivery catheter, and have an expanded configuration when released from the delivery catheter. Alternatively, the anchor frame 162 may be balloon expandable. The upstream and downstream ends 164, 166 of the anchor frame 162 are sized to dilate the vein when the implant 160 is implanted in the vein. The size of the middle valve portion 163 of the anchoring frame may also expand the vein when the implant 160 is implanted in the vein. As in fig. 4A, the middle valve portion 163 may have a mostly flat configuration, or may have an hourglass shape.

Fig. 5 and 6 show two further alternative embodiments of a prosthetic venous valve implant. In the embodiment of fig. 5, the venous valve implant 260 includes an anchor member 262, a ball 264, a valve seat 266, and a retaining member 268. In this embodiment, the retaining member 268 is an expandable wire anchor connected to the ball 264. The expandable wire anchor retaining member 268 may be made of a shape memory material for loading into the delivery catheter and includes a first end connected to the ball 264 and a V-shaped end facing away from the ball 264. The V-shaped end is large enough when expanded to not fit through the valve seat 266, thereby preventing the ball 264 from passing out of the valve implant 260 in the downstream direction. The end of retaining member 268 connected to ball 264 may be connected via an adhesive, by threading into or through a hole in ball 264 and then tying, by welding to ball 264, or by any other suitable means. In alternative embodiments, the V-shaped end may have other shapes. The valve implant 260 can include any of the features described above, such as a material disposed on all or a portion of the anchoring member 262, a collapsible valve seat 266, barbs projecting from the anchoring member 262, and/or the like.

In the embodiment of fig. 6, implant 270 includes an anchoring member 272, a ball 274, a valve seat 276, and a retaining member 278. In this embodiment, the retaining member 278 is a tether that connects the ball 274 to the valve seat 276. The retaining member 278 may be made of suture, wire (such as nitinol), elastic material, or similar material. Again, the tether retaining member 278 prevents the ball 274 from passing out of the valve implant 270 in the downstream direction. The end of retaining member 278 that is connected to ball 274 may be connected via an adhesive, by being threaded into or through a hole in ball 274 and then tied, by being welded to ball 274, or by any other suitable means. As shown, the opposite end of the tether retention member 278 may be connected to the valve seat 276, to the anchor member 272, or to both. The valve implant 270 can include any of the features described above, such as a material disposed on all or a portion of the anchoring member 272, a collapsible valve seat 276, barbs projecting from the anchoring member 272, and/or the like. Either of these two retaining

members

268, 278 may be applied to the other embodiments described herein.

Fig. 7A and 7B are diagrammatic illustrations of one embodiment of a vascular balloon valve prosthesis system 100 that includes the prosthetic vascular valve 102 (or "implant") itself and a delivery catheter 120 for delivering the prosthetic valve 102 to its target location in a vein (or alternatively in an artery). Fig. 7A and 7B, as well as many of the remaining figures in this application, include diagrammatic illustrations of different embodiments of a vascular prosthetic valve and a delivery catheter for delivering the valve into a vein (or other vessel in other embodiments). In any of these illustrated embodiments, the prosthetic valve can be the same as or similar to any of the embodiments described above with reference to fig. 1A-6 or any of the embodiments described in any of the references previously incorporated by reference. Any of the features, elements or components described with respect to the valve prosthesis embodiments described above or in any of the references previously incorporated by reference may be applied to the latter embodiments. Thus, the size, shape, and features of the embodiments described via the illustrative figures should not be limited by the nature of the figures themselves.

Returning to fig. 7A and 7B, fig. 7A shows the prosthetic valve 102 in a collapsed or compressed configuration within the delivery catheter 120, and fig. 7B shows the prosthetic valve 102 in an expanded configuration (as it can be seen inside a vein) outside the delivery catheter 120. In this embodiment, the prosthetic valve 102 includes an expandable anchor frame 104 (or "anchor member") that includes a wide proximal portion 112, a wide distal portion 116, and a narrower intermediate portion 114. The narrower intermediate portion 114 includes an inwardly angled proximal portion between the wide proximal portion 112 and a middle of the anchor frame 104, and an inwardly angled distal portion between the wide distal portion 116 and the middle of the anchor frame 104. The valve 102 also includes a valve seat 106 connected to a middle portion of the anchor member 104, a ball 108, and a tether 110 connected at one end to the valve seat 106 (and/or the anchor frame 104 in an alternative embodiment) and at an opposite end to the ball 108. The delivery catheter 120 includes a tubular catheter body 122 and a deployment plunger 124 slidably disposed within the catheter body 122. In some embodiments, a light source (not visible) may be provided inside the plunger 124 or at the distal end of the plunger 124 to emit light 126, which will be described further below.

Many features and aspects of the implant 102 are more fully described in the venous valve prosthesis application, which was previously incorporated by reference. In various embodiments, the anchoring frame 104 is formed as an expandable stent. The anchor frame 104 is a one-piece structure that extends from one end of the implant 102 to an opposite end of the implant 102. The anchoring frame 104 may have any suitable size and shape, some variations of which will be further shown and described below. The anchoring frame 104 may be made of any expandable or self-expanding material and is configured to anchor the implant 102 within a vein being treated when expanded. The anchoring frame 104 may be made of any shape memory metal or polymer, such as nitinol, for example. In some embodiments, at least a portion of the anchoring frame 104 is coated or covered with a material that may be completely or partially impermeable to blood. Examples of such materials include polymers, hyaluronic acid, heparin, and/or anticoagulants.

In use, the delivery catheter 120 is advanced into a target vein, with the prosthetic valve 102 (fig. 7A) loaded within the catheter body 122. Once in the proper vascular location, the catheter body 122 can be retracted relative to the deployment plunger 124 to move the valve 102 away from the catheter body 122 (fig. 7B). Alternatively, the plunger 124 may be advanced while the catheter body 122 remains stationary, or a combination of advancing the plunger 124 and retracting the catheter body 122 may be employed. Once released, the anchor member 104 expands to anchor the inner wall of the vessel. During and after deployment, as the anchor member 104 expands, the compressive force it exerts on the inflatable balloon 108 in its compressed configuration inside the catheter body 122 is removed. Thus, the ball 108 expands to assume its default spherical shape. In some embodiments, as shown in fig. 7B, the deployment plunger 124 may emit light 126 to cure the curable substance that at least partially forms the ball 108. The curing process may make the ball 108 harder or more resistant to compression, thereby preventing it from being accidentally squeezed through one end of the anchor member 104 after deployment. In alternative embodiments, the ball 108 may be cured via other methods, such as, but not limited to, applying sound, heat, or electricity to the ball 108. In other embodiments, no curing is used.

The embodiment shown in fig. 7A and 7B may be referred to as a self-expanding embodiment because the anchor member 104, the ball 108, and the valve seat 110 all self-expand from a compressed delivery configuration to an expanded deployed configuration. In alternative embodiments, one or more of the three components (the anchor member 104, the ball 108, and the valve seat 110) may be expandable, but not self-expanding. For example, in one embodiment, a balloon catheter or other inflation device can be used to inflate the anchor member and the valve seat 110. While this increases the complexity of the delivery and deployment procedure, it may be part of some alternative embodiments. However, unless otherwise specified, the embodiments described herein assume to be self-expanding, and thus the anchor member 104, the ball 108, and/or the valve seat 110 self-expand when released from binding within the delivery catheter 120.

There are a variety of alternative embodiments for the inflatable bulb 108, some of which are described below. In general, various embodiments of the inflatable balloon 108 may be classified as self-inflating or inflatable. The self-expanding embodiment of the ball 108 is made at least in part of a resilient or shape memory material, such as a compressible foam, a resilient shell filled with a gel or fluid, or other embodiments, some of which are described below. As described further below, an expandable (non-self-expanding) embodiment of the ball 108 generally involves some sort of inflation or other expansion mechanism.

As is apparent by comparing the two figures, the valve seat 106 in the embodiment of fig. 7A and 7B is compressible and may have any of the materials and properties described above for the valve seat. For example, the valve seat 106 may be formed from silicone rubber, a flexible polymer such as Viton, a shape memory metal such as nitinol, or any other suitable material. Which may be insert-molded or otherwise attached to the inner and/or outer surfaces of the anchor member 104.

Referring to fig. 8-10, three different embodiments of compressible bulb members of a vascular prosthetic valve are shown. In each embodiment, the compressibility of the ball allows it to be positioned within the compressible anchoring frame of the vascular valve prosthesis in an extended configuration and then expanded to a spherical geometry after valve deployment in the vein.

In one embodiment, as depicted in fig. 8, the vascular valve prosthesis bulb 300 may be constructed of a closed cell polymer foam (such as a polyurethane foam). The foam bulb 300 may be stored in a compressed state inside the valve anchoring frame and delivery catheter, and expanded to a spherical configuration after valve deployment. Optionally, the foam material may be covered in a shell of another material (such as PTFE, silicone, or the like) that acts as a barrier between the blood and the foam material. As previously mentioned, in various embodiments, ball 300 may have any of a number of suitable densities, which may be greater than, equal to, or less than the density of blood. The various density ranges and spherical element materials are listed above and therefore will not be repeated here.

As shown in fig. 9, an alternative embodiment of a compressible bulb 310 may include a hollow spherical shell 312 constructed of an elastomeric material, such as silicone rubber or polyurethane, filled with a filler substance 314, which may be a fluid, gel, or air. The filler substance 314 may be selected such that the overall density of the ball 310 is slightly higher than the density of blood, so that gravity causes the ball 310 to abut the valve seat to close the valve, but a low forward pressure is sufficient to open the valve, resulting in a low valve opening pressure.

In another alternative embodiment, as shown in fig. 10, the ball 322 may also include a resilient shell 322, in this case filled with air, but also a small diameter inner weight 324 constructed of a material such as stainless steel. The size of the inner weight 324 may be selected to give the desired overall density to the ball 320. As ball 320 moves toward and away from the valve seat, weight 324 drops within ball 320, causing ball 320 to rotate within the valve frame in an asymmetric manner. The asymmetric contact of the ball 320 to the valve frame may help prevent cells and thrombus from adhering to the ball 320, and thus may prevent valve occlusion.

In other alternative embodiments, the bulb of the vascular valve prosthesis may be comprised of, or filled with, any other suitable combination of foam, fluid, gel, gas, or solid. The combination of filler materials may be selected such that the overall density of the ball is slightly higher than the blood density. It may also be formed such that it has an asymmetrically distributed weight or altered shape that encourages ongoing ball movement and limits stagnation. Furthermore, the material may be selected such that it coagulates or solidifies at about blood temperature. This would allow the ball to deform while compacted for delivery, but then expand once deployed in the presence of blood, then coagulate. Any of the various compressible bulb embodiments described with respect to fig. 8-10 or in any other figure may be used with any of the vascular valve prosthesis embodiments described herein.

Referring now to fig. 11A and 11B, another embodiment of a vascular valve prosthesis system 350 includes an implantable prosthetic valve 352 and a delivery device 370. The valve 352 includes an anchoring frame 354, a valve seat 356, a collapsible ball 358, and a tether 360 connecting the ball 358 to the valve seat 356. The delivery device 370 includes a catheter body 372, a deployment plunger 374, and an inflation catheter 376 connected to the ball 358. Ball 358 may be an inflatable balloon (or "inflatable sheath") that is inflated with an inflation fluid. In some embodiments, the fluid may be curable, and thus harden after curing. The inflatable balloon may be present in an uninflated state during valve delivery (fig. 11A), to be inflated by a fluid, gel, or gas (fig. 11B), and then, in some embodiments, cured after valve deployment. Alternatively, the balloon may be pre-filled with a curable fluid, gel or gas, which is then cured and solidified after deployment. The fluid, gel or gas may be cured by injecting a curing agent. It may be cured via heat, light (e.g., blue or UV light), electricity, sound waves, chemical mixtures, or other curing methods. The curable fluid may be liquid silicone rubber, liquid polyurethane foam, adhesives (such as epoxy or uv curable adhesives), or other curable materials.

Fig. 11C is a cross-sectional front view of the inflation catheter 376 shown in fig. 11A and 11B. In this embodiment, inflation catheter 376 is a dual lumen catheter having a light lumen 378 that houses a fiber optic cable that transmits light and an inflation lumen 380 for fluid injection into ball 358. In alternative embodiments, the light lumen 378 may be used with any other curing device and method.

Fig. 12A-12E illustrate one embodiment of a method for inflating and curing the ball 358 using an inflation catheter 376. In further detail, the inflation catheter includes an outer sheath coaxially over the dual-lumen catheter body. The housing of the ball 358 includes a self-sealing valve that protrudes into the interior of the ball 358, leaving a smooth surface on the exterior of the ball 358 for proper sealing of the valve seat 356. The self-sealing valve may be a cylindrical plug of elastomeric material with a collapsed center tube that seals against gas or fluid pressure within the balloon.

Fig. 12A shows the self-sealing valve with the conduit 376 inserted into the ball 358, according to this method embodiment. Then, in fig. 12B, ball 38 is inflated to the desired diameter using an inflation fluid without disengagement of ball 358 from the catheter. In this embodiment, fluid via inflation catheter 376 is injected into lumen 380, and light curable adhesive fluid is used to inflate ball 358. As in fig. 12C, after the bulb 358 is inflated to the desired volume, light is transmitted through the fiber optic cable lumen 378 to solidify the fluid inside the bulb 358. In fig. 12D, disengagement of ball 358 is performed by: the catheter body of the inflation catheter 376 is pulled out of the ball 358 while the outer sheath of the inflation catheter 376 remains stationary to support the ball 358 during catheter withdrawal. Instead of a fiber optic cable, the second channel may be used to transport heat, sound waves, electricity and/or chemicals that react with chemicals from another channel to cure it. Finally, as in fig. 12E, the ball 358 is inflated, cured, and detached from the inflation catheter 376.

Referring back to fig. 11A, in an alternative embodiment, the inflation catheter 376 (and/or a separate curing catheter) may be pre-connected to the ball member 358 and loaded into the delivery device 370 with the ball member 358 in the collapsed configuration. Inflation catheter 376 may then be used to inflate and cure ball 358 after deployment outside of delivery device 370. Alternatively, the ball 358 may be pre-filled with a curable fluid and still be collapsible for delivery, such that the catheter 376 may instead be a single lumen catheter designed to be cured only (rather than inflated) by delivering light, chemicals, sound, and the like. In either case, the fluid may be cured by heat, light, electricity, sound waves, chemical mixtures, or other methods, as described above.

Alternatively, ball 358 may be made of a material or thickness that is less deformable once filled with any fluid, gel, or gas. Ball 358 may be empty during loading and deployment to allow for small catheter sizes, but filled with material after deployment using a catheter tube. The fluid need not be a curable fluid, but rather the pressure causes it to retain its desired shape once sufficient fluid has been injected into ball 358.

Fig. 13A-13D illustrate an alternative embodiment of a vascular prosthetic valve system 400, which includes a prosthetic valve 402 and a delivery device 420. As in the previous embodiment, the prosthetic valve 402 includes an anchoring frame 404, a valve seat 406, a collapsible ball 408, and a tether 410. The delivery device 420 includes a catheter body 422, a deployment plunger 424, and an inflation fitting 426 connected to the deployment plunger 424. An inflation accessory 426, which in various embodiments may include an arm or arms, extends over a portion of the anchor frame 404 during delivery. The inflation attachment 426 has a lumen that is in fluid communication with the lumens in the valve seat 406 and tether 410, which in turn lead into the interior of the ball 408. Thus, inflation fluid may pass through the inflation attachment 426, the valve seat 406, and the tether 410 to inflate the ball 408.

Fig. 13A shows a prosthetic valve 402 positioned entirely inside a delivery device 420 for delivery into a vein or other vessel. As shown in fig. 13B, the catheter body 422 may be retracted such that the first portion of the anchor frame 404 is expanded inside the vein. As shown in fig. 13C, inflation fluid may then be passed through the inflation attachment 426, the valve seat 406, and the tether 410 to inflate the ball 408. Optionally, the ball 408 may be cured using any of the curing methods listed above or any other suitable curing method. The inflation accessory 426 is then retracted, as in fig. 13D. As described above, the inflation accessory 426 may have one arm or prong, or it may have multiple arms or prongs. One or more of the tines may have a single lumen or a double lumen as described above. In the single lumen approach, a fluid may be injected to expand the ball 408 to a desired shape, with outward pressure sufficient to prevent deformation and potential movement through the valve seat 406. Alternatively, ball 408 may be pre-filled with a curable agent. The single lumen may then be used to transmit curing agents (such as light).

Referring now to fig. 14A-14D, in another embodiment, the collapsible/inflatable bulb 430 may include a shell 436 and a helically slotted elastomeric hollow sphere filler 432 that fills the interior cavity of the shell 436. As shown in fig. 14C, the hollow sphere is made of a telescoping tube that can be extended for delivery through a delivery catheter (fig. 14D) and then resume its default spherical shape inside the housing 436 of the ball 430. The hollow spheres 432 may be formed from a superelastic material, such as nitinol, cut to form continuous strands. Alternatively, the nitinol wire may be formed into a spherical shape, heat treated, and quenched in a fluid to place it in the austenitic superelastic phase. The elongated wire may be advanced into the housing via a catheter, causing the housing 436 to expand and reform into a sphere inside the housing 436. The connection of the catheter to the self-sealing valve inside the housing 436 may be a rigid mechanical engagement, rather than a friction fit, due to the higher forces applied inside the housing 436 as the superelastic strand or wire is advanced forward. The distal end of the conduit 434 may be externally threaded and mate with internal threads on the interior of the self-sealing valve.

Referring now to fig. 15, in one embodiment, a fluid-filled, gel-filled, or air-filled balloon 440 may be in an elongated configuration for delivery, thereby reducing its diameter to fit within a delivery catheter. The elongated balloon 440 may be released after intravenous insertion. A system for providing a releasable, elongate balloon 440 may include a resilient balloon containing an internal self-sealing valve. The spring ball retainer 442 is attached to the inner face of the self-sealing valve. The spring ball retainer 442 may be a ball constructed of a spring material, such as stainless spring steel, or a high durometer polymeric material, such as polycarbonate or polyetherimide. The ball 442 is centrally slotted along most of its length and it contains a through hole in the center of its rear side. The spring ball 442 retainer is in a normally closed position. When the wire core 444 is inserted through a rearward hole in the spring bulb retainer 442, the bulb twists open to assume an enlarged vertical cross-section. The catheter, which is designed to deliver and release the elongate balloon 440, contains a distal clamp and a lumen that houses a wire core 444. The opening in the distal jaw of the balloon release catheter is sized so that the balloon 440 containing the closed spring bulb retainer 442 slides inside the jaw. However, as the guidewire core 444 is advanced through the self-sealing valve and the spring bulb retainer 442, the bulb retainer 442 opens in a clamshell fashion, locking the balloon 440 inside the distal clamp. The wire core 444 is further advanced to axially elongate the balloon 440, thereby reducing its cross-sectional diameter.

To release the elongated balloon 440, the wire core 444 is pulled out of the spring bulb retainer 442 and self-sealing valve, causing the spring bulb retainer 442 to close and the balloon 440 to exit the jaws in the balloon release catheter. The releasable, elongated balloon concept may be combined with the curable fluid-filled balloon concept, but the wire core 444 is replaced with a single or dual lumen tubular core containing one or both of a fluid injection lumen and a curing agent lumen (e.g., an optical fiber cable). The balloon 440 may be inflated with a curable fluid, the tubular core may be withdrawn from the spring bulb retainer without withdrawing from the self-sealing valve to release the balloon 440 from the distal clamp, and light may be transmitted into the balloon to cure the fluid adhesive inside the balloon 440. Removing the tubular core from the self-sealing valve releases the inflated balloon 440.

Referring now to fig. 16A and 16B, in some embodiments of a vascular prosthetic valve, the ball 454 may be connected to the self-expanding valve anchoring frame 452 via an elastic tether (not visible because inside the frame 452). One end of the elastic tether is connected to the valve frame near or at the valve seat location and the other end of the tether is connected to the ball 454. As in fig. 16A, for delivery, the elastic tether is elongated such that the ball 454 is positioned outside of the distal end of the valve frame 452. The valve frame 452 is loaded into the delivery catheter 450 in a compressed configuration, with the tethered ball 454 positioned in the tip of the delivery catheter 450 proximate the distal end of the valve frame 452. As the implant is ejected from the delivery catheter 450, the valve frame 452 expands and the elastic tether contracts to pull the ball 454 into the valve frame 452, as in fig. 16B. This design allows the ball 454 to have a maximum diameter that is contained within the interior of the delivery catheter 450.

Referring to fig. 17A and 17B, in some embodiments, the ball member 464 may be tethered via a non-elastic tether 466 that is long enough to allow the ball member 464 to be positioned distal to the self-expanding frame 462 when the frame 462 is compressed inside the delivery catheter 460. In this design, the ball 464 has a long offset between its closed position in contact with the valve seat and its open position (in which it extends past the distal end of the expanded valve frame 462). This and the previous embodiments allow for a smaller delivery catheter by moving the ball outside of the anchoring frame during loading and delivery.

Referring to fig. 18, in one embodiment, a vascular prosthetic valve delivery device 470 may include two portions-a small diameter conduit portion 472 and a larger diameter conduit portion 474. The larger diameter portion 474 is sized to receive the prosthetic valve implant 476, while the smaller diameter portion 472 is designed for easier advancement and maneuverability through the vessel. This embodiment may be combined with other methods described in this application.

Referring now to fig. 19A, in one embodiment of a vascular valve prosthesis 480, the valve seat may include a semi-rigid ring 484 connected to an anchor frame 482, which is made of a material such as FEP, PTFE, or similar material. The ring 484 is configured to resist deformation of the device 480 after implantation. In this embodiment, the ring 484 is connected to the inner surface of the anchor frame 482.

In alternative embodiments, the valve seat may be formed as part of the anchoring frame or part of the material used to cover or coat the anchoring frame. Thus, in these embodiments, the valve seat is not a separate piece connected to the anchor frame. For example, the valve seat in some embodiments can be a thickened portion of the anchoring frame. Alternatively, a coating substance (such as PTFE) may be used to form the valve seat. Thus, the ring embodiments of fig. 19A and 19B are merely examples.

In the embodiment of fig. 19B, the valve prosthesis 490 includes a ring 494 connected to an outer surface of the anchoring frame 492. In this embodiment, the ring 494 serves as part of the anchor member 492. In either of these two embodiments, the

rings

484, 494 may be covered or coated in the same continuous layer of material (such as PTFE) as the rest of the anchoring frames 482, 492 to give a smooth continuous surface exposed to blood.

In either of the two embodiments just described, as well as in any other alternative embodiment, the dimensions of the valve seats 484, 494 and anchoring

frames

482, 492, along with the ball members, may optimize blood flow through the valve. For example, to assess or interpret blood flow through the prosthetic valve, two different regions may be compared — the open area of the valve seat and the area around the ball, which is between the ball and the inner wall of the anchoring member when the valve is in the open position (flat circular ring shape around the ball). In some embodiments, the two regions may be designed to be exactly or approximately the same, and this may provide advantageous flow through the valve. In other embodiments, the two regions may be within 50% of each other, or more desirably within 25% of each other, or even more desirably within 10% of each other.

Referring now to fig. 20, in another alternative embodiment, a vascular valve prosthetic implant 500 may include an asymmetric anchor frame 502 having a valve seat 512 and a ball 508 disposed in the anchor frame 502. The anchor frame 502 has an asymmetric shape with a downstream end 506 having a small diameter and an upstream end 504 having a large diameter. The small downstream end 506 is small enough to trap the ball 508 so that the ball 508 cannot escape the anchoring frame 502 from the end 506. Thus, the small diameter end 506 acts as a ball retaining member or feature such that no additional ball retaining member is required. The large diameter end 504 is large enough to anchor the anchoring frame 502 in the vein. As seen in the two right-hand illustrated front views, this configuration includes an oval valve outlet with two side passages 510 for blood flow through the implant 500 around the ball 508. In an alternative embodiment, the downstream end 506 may include a wide larger diameter portion following a narrowed small diameter portion to prevent flow between the device and the vessel wall. This will allow the same flow area at the necked down portion while obtaining device symmetry and stability at the inflow and outflow regions. Similarly, and also optionally, small diameter end 506 may also include a large diameter anchoring portion (not shown) around a smaller interior, such that both ends 504, 506 are anchored in the vessel even though a portion of small diameter end 506 is still configured to trap ball 508.

Referring now to fig. 21, another embodiment of a vascular valve prosthesis 520 is shown. The anchor frame 522 is again asymmetric, having a wider end 524 and a narrower end 526. Also included are ball 528 and valve seat 532. As seen in the front views of the right two panels, this embodiment includes an X-shaped opening 530, which can provide a more defined constriction of ball 528. The contracted upstream end 526 of the superelastic frame 502 always contains the ball 508 even when the frame 502 is compressed from different directions. After implantation, compression of the patient's thigh may occur due to applied external forces. Thus, in this embodiment, opening 530 includes a plurality of grooves to prevent opening 530 from deforming in a manner that would allow ball 528 to escape. Compression of the outlet 530 from any direction will collapse the cruciform outlet 530 inwardly thereby preventing release of the bulb 528. The blood flow area between the outer surface of the spherical element and the contour of the cross-shaped outlet 530 may be greater than that of a symmetrical design. Again, the small diameter end 526 may optionally include a large diameter anchoring portion (not shown) around the smaller interior so that both ends 524, 526 are anchored in the vessel.

Referring now to fig. 22, in one embodiment, a vascular valve prosthetic implant 540 may include an anchoring frame, a tether 544, a valve seat 546, and a collapsible bulb 548. In the foregoing embodiments, the ball tether is shown coupled at one end to the ball and at an opposite end to the valve seat or anchor member. In contrast, in this embodiment, tether 544 is connected at one end to ball member 548 and has an opposite end that is V-shaped and connected to two locations on anchoring frame 542. Alternatively, the V-shaped end may be divided into three, four, or any other number of ends that are connected to the anchor frame 542. The V-shaped two-point connection of tether 544 allows ball member 548 to be located at the point of maximum shear-i.e., at the center of valve implant 540, and may also increase the strength of the tether connection.

Fig. 23 shows another embodiment of a vascular valve prosthetic implant 550 comprising an anchoring frame 552, two tethers 554, a valve seat 556, and collapsible bulbs 558. In this embodiment, two tethers 554 are connected between ball member 548 and anchoring frame 552. Alternatively, three, four, or any other number of tethers 554 may be used.

Fig. 24 shows another embodiment of a vascular valve prosthetic implant 560 comprising an anchoring frame 562, two tethers 564, a valve seat 566, and a collapsible ball 568. In this embodiment, two tethers 564 are coupled between the ball member 568 and the anchoring frame 562. Alternatively, three, four, or any other number of tethers 564 may be used. In alternate embodiments, any suitable number, length and configuration of tethers may be used.

Referring now to fig. 25, in some embodiments, such as those just described, the attachment location of the tether to the anchoring frame 578 and the ball 576 may be selected, at least in part, to attempt to limit clot formation at the attachment point by positioning the attachment point at a maximum shear location (with blood flow). For example, a tether (not shown in this illustration, as these principles may be applied to many different embodiments) may be coupled to the ball 576 along a maximum shear region 570 of blood flow around the ball 576. The tether may also be connected to the anchor frame 578 at any location around the circumference of the inlet 572 to the valve seat, or to the valve seat itself. These areas for locating the connection points may help to reduce the risk of thrombosis (clot formation) as they represent the areas with the lowest risk of blood stagnation.

When the tether is connected to the stent-valve anchor, it may be threaded through the wall of the device and tied around the exterior of the device. It may also be fused directly to the wall of the device or to the valve seat of the device. Additional material may be used or fused to cover any exit point of the device. When the tether is connected to the ball, it may extend through the ball and be knotted at the other end to hold it in place. It may also be channeled and molded directly to the ball itself. It may also be one continuous piece of material. The process of attaching the device and the balloon is important because any breaks or irregularities in the material can act as foci of clot formation.

Referring now to fig. 26, another embodiment of a vascular prosthetic valve implant 580 includes an anchoring frame 582, a tether 584, a valve seat 586, and a compressible ball 588. In this embodiment, tether 584 is coupled to an entry portion of anchor frame 582. The length of tether 584 may be important because it controls the position of ball member 588, which may affect clot formation. In this embodiment, the tether 584 is relatively short such that the ball member 588 is located just forward of the valve seat when the valve is open. This may optimize flow around ball member 588, increase shear to reduce clot formation, and help keep ball member 588 centered within the lumen of implant 580. In various alternative embodiments, the tether 584 may have a length in the range of about 0.1 millimeters to about 25 millimeters, or more desirably about 0.5 millimeters to about 10 millimeters.

Referring to fig. 27, an alternative embodiment of a vascular prosthetic valve implant 590 includes an anchoring frame 592, a tether 594, a valve seat 596, and a compressible ball 598. In this embodiment, tether 594 is long and extends beyond the end of implant 590 such that ball 598 is located outside of anchoring frame 592 and in the natural vein, thereby preventing foreign material from resting on the foreign material. The vein wall is known to have antithrombotic properties, and these can prevent thrombosis at the bulb-wall contact area.

Referring to fig. 28, in the venous system, there is a balance between minimizing the amount of material in the blood and separating the valve portion of the device from the rim where there may be a rim stenosis. The embodiment of the vascular valve prosthesis 600 in fig. 28 comprises an asymmetric design, wherein the anchoring frame 602 comprises long ends 603. This allows the edge, which is at risk of stenosis, which may lead to valve complications, to be further separated from the valve itself. The long end 603 may be proximal or distal depending on the vessel being treated. Also depicted in fig. 28 is a tether 604, a valve seat 606, and a ball 608.

Referring to fig. 29, an anchoring frame 610 for any of the valve prosthesis embodiments described herein can have an entrance taper angle 612 and/or an exit taper angle 614 designed to optimize flow through the implant and prevent clot formation. In various embodiments, the

angles

612, 614 may be the same or different. Generally, a more gradual taper is preferred. For example, the anchor frame 610 may have an entrance taper angle 612 and an exit taper angle 614 in a range of about 5 degrees to about 60 degrees, or more desirably about 15 degrees to about 35 degrees.

Referring to fig. 30, in some embodiments, a prosthetic venous valve implant 620 may have an anchoring frame 622 with a coated portion 624 and a non-coated portion 626. Additionally or alternatively, the implant 620 may be positioned within the vein V such that it is located within the native valve NV. Either or both of these features (the non-coated portion 626 and placement within the native valve NV) can help stimulate secretion of the antithrombotic agent by the vein V. For example, if the entire portion 626 of the implant 620 behind the valve seat is not coated with a hemostatic layer, blood will accumulate in the space between the implant 620 and the wall of the vein V. Similar to the native venous valve NV, the antithrombotic agent of the vein may reduce the likelihood of clotting in this region. Similarly, if the implant 620 is placed so that the native valve NV is on the implant 620, it may further reduce the risk of clotting via the native anticoagulant. This also creates more physiological space similar to the natural leaflet valve NV.

Fig. 31A-31C depict yet another alternative embodiment of a venous valve prosthesis 630, in this case including an anchor frame 632, a ball retainer member 636, a sheet-like valve 634 (having an opening 635 that serves as a valve seat), and a ball 638. Fig. 31A is a partial cross-sectional view depicting the ball 638 seated in the opening 635 of the sheet-like valve 634 (front view in fig. 31B), with the implant 630 in its closed position. In fig. 31C, the valve implant 630 is in an open position with the sheet-like valve 634 oriented in the opposite direction and the ball 638 positioned between the sheet-like valve 634 and the ball retention member 636. As shown in fig. 31A and 31C, the sheet-like valve 634 may be made of a thin material that can be inverted and inverted. Blood flows through the opening 635 in one direction, but when blood flows in the other direction, the ball 638 seals the hole 635 and prevents reverse flow. In an alternative embodiment, a tether may be used in place of the ball retention member 636.

Referring now to fig. 32, in some embodiments, an anchoring frame 640 for a vascular valve prosthesis may include a plurality of anti-migration barbs 642 positioned away from either of the two extremes of the frame 640. Anti-migration features, such as barbs 642, are explained above and are generally configured to prevent the anchor frame 640 from moving within a vein or other vessel after it has been delivered. In contrast to some embodiments described above, the barbs 642 of this embodiment of the anchor frame 640 are positioned away from the two extremes of the anchor frame 640. Barbs 642 in this position help anchor the valve implant and prevent device migration, and may also be less susceptible to fibrosis reactions promoted by barbs positioned at the proximal and distal edges of the anchoring frame. The barbs 642 are not in the areas where the risk of stenosis is high and are not exposed to blood flow due to the continuous PTFE layer on the anchoring frame. This is important in reducing the risk of edge narrowing and potential device failure. In an alternative embodiment, the barbs 642 may be positioned toward only one end of the anchoring frame 640, rather than near both ends as depicted in fig. 32.

Referring now to fig. 33, in another embodiment, a venous valve implant 650 may include an anchor frame 652 having a plurality of anti-migration V-shaped protrusions 654 instead of single point barbs. The V-shaped projections 654 may also be positioned away from any of the extremes of the anchor frame 652, and they may help retain the valve implant 650 in the vessel and prevent migration thereof. Alternative embodiments may include U-shaped projections, hooks, or any other anti-migration member configuration. And again, in some embodiments, the V-shaped projections 654 may be located near either end of the anchor frame 652 and need not be near both ends.

In various embodiments, the anti-migration barbs 642, V-shaped protrusions 654, or other anti-migration features may form any range of angles with respect to the adjacent portions of the anchor frames 640, 650 from which they protrude. For example, in some embodiments, the anti-migration features may form an angle with the anchoring frames 640, 650 of about 15 degrees to about 60 degrees, or more desirably about 25 degrees to about 45 degrees.

Referring to fig. 34A-34C, in some embodiments, it may be desirable to remove the ball from the vascular valve implant, for example, to replace it with a new ball. As shown in fig. 34A, a vascular valve implant 660 includes an expandable anchoring frame 662, a ball 664, and a tether 666, as described above with respect to many embodiments. The ball removal device 670 may be advanced into a vein to remove the ball 664. Ball removal device 670 includes a catheter 672, a grasper 674, and a tether cutter 676. In fig. 34A, the grasper 674 is advanced outside the catheter 672 toward the ball 664. In fig. 34B, grasper 674 has been used to grasp ball 664 and advance tether cutter 676 to cut tether 666. In fig. 34C, cutter 676 has cut tether 666 and has retracted into catheter 672. Grasper 674 can then be used to pull ball 664 out of valve implant 660. The grasper 674 may be connected to the ball 664 via suction, magnetic attraction, adhesion, or any other suitable mechanical connection or modality. Ball 664 can then be pulled toward guide tube 672 prior to use of cutter 676 to pull on taught tether 666. Cutter 676 may have a scissor end or any other suitable cutting device end. After removal of the ball 664, the anchoring frame 662 may remain in place in the vessel. In some embodiments, ball 664 may be replaced with a new ball.

In alternative embodiments, the valve implant may not include a tether and tether cutter 676 may not be required. Thus, in an alternative embodiment, the ball removal device may comprise only the catheter 672 and the grasper 674.

Referring to fig. 35A and 35B, in an alternative embodiment, a venous valve implant 700 may include an expandable anchor frame 702 and a single-leaflet-shaped valve 704. Fig. 35A shows valve 704 in an open position allowing blood 706 to flow through implant 700. Fig. 35B shows the valve 704 in a closed position preventing retrograde flow of blood flow 708 through the implant 700.

In another alternative embodiment, as shown in fig. 36A and 36B, a venous valve implant 710 may include an expanding anchor frame 712 and two leaflet-like valves 714. Fig. 36A shows valve 714 in an open position, which allows blood 716 to flow through implant 710. Fig. 36B shows the valve 714 in a closed position, which prevents retrograde flow of blood 718 through the implant 710. In either of the two

leaflet valve embodiments

700, 710, one or more pieces of the

valve

704, 714 can be made of delrin (delrin), titanium, silicone rubber, teflon, silicone coated teflon, pyrolyte, or any other suitable leaflet material. The

valves

704, 714 are mechanical valves, and thus differ from existing leaflet valves of bioprostheses, which are thin and more prone to failure. In addition, placement in the expandable/collapsible anchor frames 702, 712 allows for easier delivery in a percutaneous system.

Fig. 37A and 37B illustrate the effect of gravity on one embodiment of a venous valve prosthetic implant 720, including an expandable anchoring frame 722, a tether 724, and a ball 726. In certain asymmetric embodiments, such as one utilizing a single tether 724, the orientation of implant 720 may change how ball 726 moves and rests in the vascular system. For example, if the patient is in a sitting or supine position, gravity will push the ball 726 downward and blood flow will push the ball laterally, as depicted in fig. 37A and 37B. The location of the tether connection relative to the direction of gravity may affect the likelihood that the ball will "kick" up with blood flow and move within implant 720. FIG. 37A depicts the force and tether orientation that will enhance the movement of the ball. The tether orientation depicted in fig. 37B is unlikely to enhance ball movement. Increased ball movement results in less stagnant areas or minimized blood flow, thereby reducing the likelihood of clotting. Thus, the orientation of the venous valve implant 720 may play an important role in the success of the implant 720. In this or other embodiments, one or more radiopaque markers may be placed on the implant 720 and/or on the delivery catheter to visualize the orientation of the implant 720 on fluoroscopy during implantation. The delivery catheter may be rotated to properly orient the valve implant 720 prior to deployment from the catheter. This allows orientation to be controlled at deployment. Alternatively, the delivery catheter handle may have a limit or indicator corresponding to the orientation of the valve implant 720 in the sheath. The catheter can then be rotated appropriately to orient the valve prior to deployment.

Fig. 38 depicts an alternative embodiment of a venous valve implant 730 that includes an expandable anchoring frame 732 having two ends and a central rounded portion 734, a valve seat 736, a ball retainer member 738, and a ball 740. The central circular portion 734 of the anchoring frame 732 may provide a more uniform forward blood flow around the ball 740 with reduced stagnation areas due to abrupt changes in geometry or angle. This helps prevent stagnation areas that would otherwise be seen behind the ball 740, since the geometry of the anchoring frame 732 promotes backflow of blood behind the ball 740. More uniform blood flow and reduced stagnation areas help prevent thrombosis and device failure. In alternative embodiments, the central circular portion 734 may be more elongated, more oval, etc. In other alternative embodiments, a tether may be used to retain the ball 740.

The previously disclosed ball-valve type venous valve prosthesis includes a self-expanding anchoring frame and a polymer ball having a density greater than that of blood to ensure that the ball will contact the valve seat and close properly when the patient is in an upright or supine position. In one embodiment, for example, the polymer bulb may have a density of about 2.2g/cm3 and a blood density of about 1.06g/cm 3. In an alternative embodiment, it may be advantageous to use a spherical element having a density of less than 2.2g/cm 3. For example, some embodiments of venous valve implants may use polymer bulbs having a density close or approximately equal to the density of blood (1.06g/cm 3). In the present disclosure, such a ball is referred to as a "neutral density ball". Active movement of the neutral density ball can help prevent thrombus formation on the ball. In various embodiments, the neutral density balloon of the venous balloon valve prosthesis may have a density of less than about 2.2g/cm 3. More preferably, the ball may have a density of about 0.9g/cm3 to about 1.2g/cm 3. In one embodiment, the ball may have a density of about 1.06g/cm 3. The neutral density of the ball may be achieved in any of several suitable ways. First, a material having a natural density within this range (e.g., polyurethane) may be used. Alternatively, materials having a natural density below this range may be weighted to have an effective density within this range.

As discussed above, it is also desirable that the ball of the venous valve implant be compressible, as this allows introduction of the implant via a smaller diameter catheter. The compressible bulb may be made of a biocompatible flexible foam such as polyurethane or silicone rubber. Foam bulbs that exhibit a significant degree of compressibility are also characterized by low density. For example, a 7mm diameter polyurethane foam bulb that can be compressed to fit into a 4mm inner diameter catheter may have a density of 0.064g/cc compared to a blood density of 1.06 g/ml. Thus, the foam is approximately 1/16 of blood density, and weight must be added to the foam bulb to make it valve-functional.

Referring now to fig. 39A and 39B, in one embodiment, a ball 740 of a venous valve implant may include a compressible foam outer portion 742 and a weighted core 744, which may be, for example, a spherical stainless steel ball. As depicted in fig. 39B, both the compressible foam outer 742 and the core 744 can have holes through which the tether 746 can pass. (the hole is not visible in the drawings.) the hole may extend all the way through the core 744 such that the tether 746 may be knotted 748 outside of one end of the hole. As described above, the tether 746 may be any suitable tether material, such as a monofilament formed of Polytetrafluoroethylene (PTFE).

Referring now to fig. 40, in an alternative embodiment of a venous valve implant, a foam bulb 752 (or other lightweight bulb material) may be used without a weight, but rather with a resilient tether 754. A compressible foam bulb 752 is located on one side of the valve seat and a resilient tether 754 is connected to the valve frame (not shown) on the opposite side of the valve seat. The resilient tether 754 is connected to the frame under tension so that the compressible foam bulb is biased toward the valve seat with a calibrated force. The calibration force may correspond to a spherical element having the same outer diameter with a density close to that of blood. The flexible tether 754 may extend through the diameter of the compressible foam bulb 752. The distal end of the flexible tether 754 may be knotted and the knot 756 may be retracted into the profile in the foam bulb 752. The knot 756 may be covered with an implantable grade adhesive filler 758 to create a smooth contour to the surface of the foam bulb 752 at the location of the knot 756. The elastic tether 754 may be constructed of silicone rubber, polyurethane, or other elastic material. It may be a solid strand having a circular cross-section with an outer diameter of about 0.1-0.2 mm.

Referring to fig. 41, in another embodiment, a compressible ball 760 for a vascular valve implant may include a compressible ball portion 762 having a plurality of higher density weights 764, such as stainless steel microspheres, dispersed throughout the ball portion 762. This allows the ball 760 to have the same overall desired density while allowing for more complete compressibility. As mentioned above, the ball member 760 may also include a bore extending through its diameter to receive the tether 766.

As previously mentioned, a venous valve prosthesis having a ball with a tether, wherein the ball has a density close to neutral for blood and is also compressible and self-expanding is advantageous as this allows the prosthesis to be delivered via a delivery catheter having an outer diameter that is significantly smaller than would be possible with a rigid, non-compressible ball. The compressible bulb may be constructed of flexible polyurethane foam because polyurethane foam is biocompatible and relatively non-thrombogenic. Flexible polyurethane foams are available which can be molded from a two-part liquid mixture which can be combined and subsequently self-expand to form a compressible solid. Some of these foams form a skin that makes them fluid-tight.

To form a flexible foam characterized by high compressibility (e.g., 10:1 compressibility); the resulting solid foam is typically required to have a much lower density than blood (e.g., 0.064g/cm3 as compared to a blood density of 1.06g/cm 3). Weight may be added to such a compressible foam bulb to make it density neutral to blood. Biocompatible weights 764, such as stainless steel microspheres, may be added to the mold during formation of the foam bulb 760. For example, 0.5mm to 1.0mm microspheres may be distributed within the flexible foam balloon portion 762, providing a balloon density that is neutral to blood, while still allowing it to be substantially compressed within the valve frame for insertion via a small diameter delivery catheter. Stainless steel microspheres 764 incorporated in polyurethane foam bulb portion 762 make bulb 760 radiopaque for visualization during fluoroscopy. Alternatively, barium sulfate powder may be mixed into the polyurethane foam to provide sufficient weight to form a blood neutral density foam bulb 760, which is also radiopaque.

For example, the non-elastic tether connecting the foam bulb to the valve frame may be comprised of PTFE monofilament suture. Attachment of the tether to the foam bulb may be performed in several ways. In one embodiment, a knot is tied near the end of the PTFE suture, the tied suture is pulled into a central channel formed in the foam bulb, and the suture is bonded inside the channel using an ultraviolet curable adhesive. In another embodiment, a short length of thick-walled stainless steel tubing is crimped near the distal end of the suture, and the crimped suture is bonded into a central channel in the foam bulb. Alternatively, the foam may be molded around the suture or the knotted ends of the suture. In other alternative embodiments, the suture may be attached to one of the microspheres, and the foam subsequently molded thereon.

Alternatively, mechanical means may be used to retain the ball in the central lumen of the device to avoid contact of the ball with the wall means. For example, a semi-rigid tether (e.g., nitinol) may be used to allow the ball to translate proximally and distally in the body and device, but not medially or laterally to the wall on the device. This allows the ball to still act as a functional valve, while avoiding the ball to contact the wall.

Referring to fig. 42A and 42B, in some embodiments, compressibility of the vascular valve implant 770 may be limited or concentrated in certain dimensions. For example, in the depicted embodiment, the implant 770 includes, among other features, an expandable anchoring frame 772, a collapsible ball 774, a tether 778, and a valve seat 779. Ball 774 includes a central post 776, which may be made of metal, plastic, or other rigid material. As shown in fig. 42A, when the posts 776 are longitudinally oriented, the ball 774 and anchoring frame 772 can be collapsed, such as for delivery through a delivery catheter. As shown in fig. 42B, when the posts 776 are oriented horizontally (or perpendicular to the longitudinal axis of the anchoring frame 772), the posts 776 prevent the ball members from collapsing inward toward the center of the frame 772. In other words, posts 776 allow ball 774 to compress in two dimensions, rather than three dimensions. In some embodiments, the tether 778 may be coupled to the post 776. By orienting the tether 778 perpendicular to the central post/limiter 776, when the device 770 is deployed (fig. 42B), the ball 774 will be prevented from being squeezed through or wedged into the valve seat 779. This design allows ball 774 to have a lower density and be compressible while also preventing ball 774 from being compressed and squashed through valve seat 779 due to back pressure.

Claims

1. A venous valve prosthetic implant for treating a vein, the implant comprising:

a tubular expandable anchoring frame consisting of a stent extending from a proximal end to a distal end of the implant, wherein the anchoring frame forms a lumen from the proximal end to the distal end, and wherein the anchoring frame comprises;

a cylindrical proximal portion at the proximal end;

a cylindrical distal portion at the distal end;

an inwardly angled entry portion between the cylindrical proximal portion and a middle portion of the anchoring frame; and

an inwardly angled outlet portion between the cylindrical distal portion and the mid-portion of the anchor frame;

a valve seat formed at or near the middle of the anchoring frame;

an inflatable balloon disposed within the lumen of the anchor frame, wherein the inflatable balloon is inflated from a compressed configuration for delivery into the vein through a delivery catheter to an inflated configuration outside the delivery catheter, and wherein the inflatable balloon in the inflated configuration moves between an open position in which the inflatable balloon is positioned away from the valve seat to allow blood to flow forward through the implant and a closed position in which the inflatable balloon contacts the valve seat to prevent backflow of blood through the implant; and

a ball retaining tether connected to the inflatable ball and to at least one of the valve seat or the anchor frame.

2. The implant of claim 1, further comprising a material disposed on at least a portion of the anchoring frame.

3. The implant of claim 2, wherein the material is made of at least one substance selected from the group consisting of: polymers, hyaluronic acid, heparin, and anticoagulants.

4. The implant of claim 1, wherein the anchoring frame includes a plurality of outward projections on at least one of: a proximal portion other than the proximal end and/or a distal portion other than the distal end.

5. The implant of claim 4, wherein the plurality of outward projections are selected from the group consisting of: barbs, hooks, U-shaped projections, and V-shaped projections.

6. The implant of claim 4, wherein each of the plurality of outward projections forms an angle of 25 to 45 degrees with an adjacent portion of the anchor frame.

7. The implant of claim 1, wherein the valve seat comprises a ring connected to at least one of an inner surface or an outer surface of the anchoring member.

8. The implant of claim 1, wherein the expandable bulb comprises a solid, compressible foam bulb.

9. The implant of claim 8, wherein the expandable ball further comprises at least one weight embedded within the ball.

10. The implant of claim 1, wherein the inflatable balloon comprises:

an elastic housing; and

a filler substance inside the elastomeric shell.

11. The implant of claim 10, wherein the filler material is selected from the group consisting of: air, gel, and fluid.

12. The implant of claim 10, further comprising at least one weight inside the elastic shell.

13. The implant of claim 10, wherein the filler material comprises a curable material that hardens upon curing.

14. The implant of claim 10, wherein the filler material comprises a helically-slotted, resilient hollow sphere.

15. The implant of claim 1, wherein the expandable ball comprises a hole through which the ball retention tether passes.

16. The implant of claim 1, wherein the inflatable balloon has a density of less than 2.5 grams per square centimeter.

17. The implant of claim 1, wherein the ball-retaining tether is coupled to the valve seat, wherein the tether and the valve seat form a filling lumen, and wherein the valve seat is accessible through a filling port such that filler material passes through the valve seat and the tether to fill the inflatable ball.

18. The implant of claim 1, wherein the inflatable balloon has a density of no greater than 1.06 grams per square centimeter, and wherein the tether is elastic to pull the balloon toward the valve seat to prevent backflow of blood through the implant.

19. The implant of claim 1, wherein the inlet portion and the outlet portion of the anchoring frame each form an angle of 15 to 35 degrees relative to a longitudinal axis of the implant.

20. The implant of claim 1, wherein the ball retention tether has a length of 0.5 millimeters to 10 millimeters.

21. The implant of claim 20, wherein the ball retention tether is long enough to allow the inflatable ball to be positioned outside of the distal end of the anchoring frame.

22. The implant of claim 1, wherein the inflatable balloon is made of a material selected from the group consisting of: thermoplastic polyurethane, elastomeric thermoplastic polyurethane, PVC, polyethylene, polycarbonate, PEEK, polyetherimide, PEI, polypropylene, polysulfone, FEP, PTFE, coated hollow heavy metals, and combinations thereof.

23. A venous valve prosthetic implant system for treating a vein, the system comprising:

an implant, the implant comprising:

a cylindrical proximal portion at the proximal end;

a cylindrical distal portion at the distal end;

a valve seat formed at or near the middle of the anchoring frame;

a ball retaining tether connected to the inflatable ball and to at least one of the valve seat or the anchor frame; and

a delivery device, the delivery device comprising:

an elongate flexible catheter body; and

a deployment plunger disposed within the catheter body for pushing the implant out of the catheter body.

24. The system of claim 23, wherein the deployment plunger includes a curing member for curing a curable material, the inflatable bulb being made at least in part of the curable material.

25. The system of claim 24, wherein the curing member is configured to emit a curing agent selected from the group consisting of: thermal, optical, electrical, acoustic, and chemical mixtures.

26. The system of claim 23, wherein the delivery device further comprises an inflation tube disposed within the catheter body, wherein the inflation tube comprises a hole configured to enter into the inflatable balloon to inflate the distal end of the inflatable balloon.

27. The system of claim 26, wherein the inflation tube further comprises a curing member configured to emit a curing agent selected from the group consisting of: thermal, optical, electrical, acoustic, and chemical mixtures.

28. The system of claim 23, wherein the delivery device further comprises an inflation accessory configured to pass fluid through a lumen in at least one of the valve seat or the ball retention tether to inflate the inflatable ball.

29. The system of claim 23, further comprising a ball retrieval device configured to retrieve the inflatable ball from the implant.

30. The system of claim 29, wherein the ball removal device comprises:

a grasper for grasping the inflatable bulb; and

a cutter for cutting a tether connecting the inflatable bulb to at least one of the anchoring frame or the valve seat.

31. The system of claim 29, wherein the ball retrieval device is configured to pass through the catheter body of the delivery device.

32. The system of claim 23, wherein the delivery device further comprises at least one orientation indicator for indicating an orientation of the implant within the catheter body.

33. A method for implanting a venous valve prosthetic implant in a vein, the method comprising:

advancing a delivery catheter containing the implant into the vein;

retracting at least one of a catheter body of the delivery catheter or advancing a deployment plunger of the delivery catheter to cause the implant to exit a distal end of the delivery catheter.

Expanding a tubular stent anchoring member and a ball disposed inside the anchoring member within the vein and outside of the delivery catheter, wherein when expanded, the anchoring member contacts an inner wall of the vein to retain the implant within the vein, and wherein when expanded, the ball moves between an open position in which the ball is positioned to allow blood to flow forward through the implant and a closed position in which the ball contacts a valve seat to prevent backflow of blood through the implant; and is

Removing the delivery catheter from the vein.

34. The method of claim 33, wherein expanding the anchoring member and the ball comprises releasing the anchoring member and the ball from binding within the catheter body, and wherein both the anchoring member and the ball comprise at least one shape memory material.

35. The method of claim 33, further comprising curing a curable material using the delivery catheter, the ball being made at least in part of the curable material.

36. The method of claim 35, wherein curing the curable material comprises emitting a curing agent selected from the group consisting of: thermal, optical, electrical, acoustic, and chemical mixtures.

37. The method of claim 33, further comprising:

advancing an inflation tube out of the catheter body of the delivery catheter, wherein a distal end of the inflation tube is positioned through the aperture of the bulb; and is

Inflating the bulb using the inflation tube.

38. The method of claim 37, wherein inflating the bulb comprises inflating using a substance selected from the group consisting of: air, fluid, gel, and elastic hollow spheres.

39. The method of claim 33, further comprising inflating the ball using an inflation accessory of the delivery catheter to pass fluid through a lumen in at least one of a valve seat or a ball retention tether of the implant.

40. The method of claim 33, further comprising orienting the implant with the catheter body using at least one orientation feature on at least one of the implant, the catheter body, or a handle connected with the catheter body.

41. The method of claim 33, further comprising removing the ball from the implant using a ball removal device.

42. The method of claim 41, wherein removing the ball comprises:

grasping the ball using a grasper of the retrieval device; and

cutting the tether coupled to the ball using a cutter of the retrieval device.