WO2000067679A1

WO2000067679A1 - Implant for restoring venous valvular function

Info

Publication number: WO2000067679A1
Application number: PCT/US2000/011414
Authority: WO
Inventors: Rodolfo C. Quijano; Raul Garcia-Rinaldi; Robert J. Demel
Original assignee: Venpro Corporation
Priority date: 1999-05-06
Filing date: 2000-04-28
Publication date: 2000-11-16
Also published as: AU4673700A; EP1187581A1

Abstract

An implant for restoring venous valvular function is formed from a vein segment of a biological source. The implant includes a wall section of the vein segment and a single valvular leaflet formed on the wall section. The wall section and leaflet are excised from the vein segment to form a patch. The patch is implanted within a valve-deficient vein of a patient. The size of the leaflet is selected such that when the valve is closed, the single leaflet substantially prevents backflow of blood through the patient's vein. A holding device can be used with the patch to ease storage, transportation and/or implantation of the patch within the patient. The holding device includes a base portion and a detachable holder. The base portion can be attached to an outer surface of the wall section of the patch.

Description

IMPLANT FOR RESTORING VENOUS VALVULAR FUNCTION

Background of the Invention Field of the Invention

The present invention is directed to an implant for restoring venous valvular function to a vein, and to methods of making and using the-same. In particular, the present invention is directed to an implant formed from venous valve tissue extracted from a quadruped or other animal source. Description of the Related Art

In the vascular system, blood is circulated from the arterial to the venous system, with the blood pressure being the greatest in the arterial system. Blood pressure in the arteries as provided by heart activity is normally sufficient to maintain the flow of -blood in one direction throughout the venous system. The pressure of the blood in the veins, however, is much lower than in the arteries, principally due to the distance from the heart. Therefore, numerous venous valves are located throughout the veins to ensure that the blood travels unidirectional through the veins and towards the heart.

The primary benefit of venous valves is the ability to limit backflow of blood travelling through the venous system. The normally low blood pressure in the venous system is supplemented by the contraction of skeletal muscles. The contractions of the muscles compress and drive the blood through the veins. The venous valves check blood flow through the veins, thereby ensuring that the blood is driven toward the heart. Therefore, damage to the venous valves disrupts this normal blood flow.

Venous valves also evenly distribute blood in the veins by segregating portions of blood flowing through the venous system, thereby minimizing or reducing the effect of any sudden increase in blood pressure, e.g., upon heavy exertion.

Venous valves are particularly important in the arms and legs. The venous system in the lower extremities generally consists of deep veins and superficial veins which lie just below the skin surface. The deep and superficial veins are interconnected by perforating veins. In the legs, blood generally flows upwards towards the heart and against the pull of gravity. Venous valves aid the forward flow of blood by closing when fiow tends to reverse, thereby preventing reflux of blood.

Venous valves can become incompetent or damaged by disease, injury, or as a result of inherited malformation. Incompetent or damaged valves usually leak blood, even at very low blood pressures. These valves fail to prevent the backflow of blood, which is particularly troublesome in the veins of the lower extremities leading to increase in the blood pressure within the veins. The backflow of blood passing through leaking venous valves can cause numerous problems. Leaking venous valves allow for blood regurgitation (reflux), which causes blood to improperly flow back down through the veins and away from the heart. Blood can then stagnate in sections of certain veins, particularly in the veins in the lower extremities. This stagnation of blood raises blood pressure and further dilates the veins and renders the venous valves more incompetent. The dilation of one vein can disrupt the proper functioning of other venous valves. The dilation of these veins can lead to chronic venous insufficiency. Chronic venous valve insufficiency can lead to skin pigmentation, edema and formation of indolent ulcers. If left neglected, chronic valve insufficiency will require bed rest and eventually limb amputation. Numerous therapies have been suggested to treat ulcers resultant from incompetent venous valves.

Conservative treatment include the use of elastic stockings and the application of antibiotics, proteolytic enzymes and UNNA Boots. These measures, however, are usually inadequate for most conditions. Other procedures involve surgical operations to repair, reconstruct, or replace the incompetent or damaged valve. Attempts have been made to repair incompetent valves by surgically restricting the valve circumference, such as by suturing the vein to form a tighter closing or restrict dilation of the valve. Other attempts have been made to restrict dilation of the valve by application of a prosthetic graft around the vein.

Other surgical procedures include valvuloplasty, transplantation and transposition of valves and veins Valvuloplasty involves the surgical reconstruction of the valve Transplantation involves surgically transpoπding one or more of the patient's healthy venous valves for the incompetent or damaged valve. Transposition of veins can include surgically bypassing sections of veins possessing the incompetent or damaged valves with veins possessing competent valves. For a more detailed discussion of these techniques, see "Reconstruction of Venous Valves", R. Gottlob and R. May, Venous Valves, Part V, Section 3 (Spπnger-Verlang/Wien, 1986).

The above surgical procedures provide limited results for a number of reasons. Because the leaflets of venous valves are generally thin, once the valve becomes incompetent or destroyed, any repair provides only marginal relief. Further, venous valves are usually damaged during handling when the venous valve is being reconstructed, transpositioπed or transplanted. The endothelium tissue layer of the vein may also be damaged during handling, which reduces the viability of the vein graft after implantation.

Another disadvantage with transplantation procedures is the need to use the patient's own vein segment in an attempt to avoid the possibility of rejection. The use of the patient's own vein segment, however, presupposes that the incompetence or damage did not arise from inherited factors or diseases which will also eventually affect the transplanted valve. For a complete discussion concerning the disadvantages of the discussed surgical procedures, see the above referenced portion of Venous Valves.

A not very useful alternative to the preceding surgical procedures is to remove the valve completely. The removal of an incompetent valve will prevent an impediment to normal blood flow, however, the problem associated with backflow is usually worsened by simply removing the valve. Therefore, in many applications, it is desirable to replace the damaged valve with a suitable valvular prosthesis that functions similarly to a natural venous valve.

A design of an artificial venous valve prosthesis was reported in "Development of a Prosthetic Venous Valve," Schmidt et al., Journal of Biomedical Materials Research, Vol. 19, pages 827 832 (1985). An attempt was made to prepare an artificial venous valve. One type of artificial valve was constructed by molding glutaraidehyde fixed, umbilical cord segments. Specially treated segments were placed over the end of an aluminum rod which had been sculpted into a bicuspid shaped valve. Another type of artificial valve was prepared by dip casting a mandrel in liquid Pellethane polymer. The prepared casting was cut with a scalpel to define the separate valve leaflets.

In another investigation, researchers implanted cardiac prosthetic valves in canines. See, "Venous Prosthetic Valves, The First Step Toward An Investigation In The Canine Model," Amil Gerlock M.D., Travis Phifer, M.D., and John

McDonald, M.D., Investigative Radiology, Vol. 20, pages 42-44 (1985). This study demonstrated the unsuitabiiity of cardiac valvular prostheses for transplantation in the venous system. The purpose of this investigation was to observe the operation of the larger, more rigid cardiac valve in the venous system. The geometry of porcine aortic or pulmonary heart valves prepared (or fixed) with glutaraldehyde formulations does not conform to the venous system. The geometry also appears to be unsuitable for the bovine pericardial bioprosthesis, which has been used as a valve replacement bioprosthesis for diseased aortic valves. These valves have diameters and heights larger than that of the usual venous valves, and leaflets with thicknesses many times that of the human or animal venous valve leaflet. Thus, such valves become inflexible to venous flow passage and the low pressures of that system.

A titanium venous valvular prosthesis has been used in animal experiments. See, "Experimental Prosthetic Vein Valve," Syde A. Taheri et al., The American Journal of Surgery, Vol. 156, pages 1 11-114 (1988). A titanium venous valve was fashioned after the shape of a prosthetic heart valve. The major disadvantage with this type of prosthesis is that such valves require treatment of the patient with anti-coagulants.

Xenograft monocusp patches were examined for possible use in repairing incompetent venous valves. See,

"Femoral Vein Valve Incompetence: Treatment with a Xenograft Monocusp Patch," Raul Garcia-Rinaldi, M.D., Ph.D. et al., Journal of Vascular Surgery, Vol. 3, pages 932-935 (1986). This prosthesis consisted of an anatomically exact sinus of

Valsalva made of bovine pericardium mounted on a bovine pericardial patch. Other xenograft patches have been suggested to replace a single damaged leaflet of a multi-leaflet valve. See, U.S. Patent No. 5,500,014, issued to Quijano et al.

More recently, the need for a substitute valve has been acknowledged to be one of the most acute of unmet clinical needs. See, "Vascular Surgery: Proceedings of the Second Pacific Vascular Symposium: Advances in Venous Disease, Scientific Session V: The Future: The Substitute Valve", Robert L. Kistner, M.D., The Need for Substitute Valves,

Vol. 31, No. 3, pages 395-407 (1997).

Summary of the Invention The present invention provides a biological venous implant formed from a leaflet of a venous valve. The terms "open" and "closed" refer to the state of the valve. That is, when the leaflet is in an open position, the leaflet is generally in close proximity to the wall of the vein such that the venous valve is open. When the leaflet and thus the valve are in a closed position, the leaflet is a distance away from the vein wall such that the leaflet substantially prevents backflow of blood through the vein. Thus, the leaflet is prepositioned to open under normal forward blood flow conditions, and to close under minimal backflow pressure. In accordance with the present invention, a method is provided for restoring venous valvular function within a valve-deficient vein of a patient. The method includes extracting a vein segment from a biological source other than the patient. The vein segment has a venous valve with a single leaflet formed therein. A patch having a single leaflet formed thereon is formed from an excised wall section of the vein segment. The patch is attached to the valve deficient vein of the patient such that the leaflet opens and closes in response to changes in blood flow within the vein. The vein segment is preferably extracted from the jugular vein of a bovine, equine, ovine, caprine, or cervine animal source.

In accordance with another aspect of the invention, a valvular implant includes an excised wall section of a vein segment from a biological source and a single valvular leaflet formed thereon The leaflet is movable between an open position in which a substantial portion of the leaflet is in close proximity to the wall section, and a closed position in which a substantial portion of the leaflet is a distance away from the wall section The leaflet is of a sufficient size to substantially prevent backflow of blood through the patient's vein when in the closed position. In some instances, the vein segment is extracted from the jugular vein of an animal source, such as bovine, equine, ovine, caprine or cervine.

In accordance with yet another aspect of the present invention, a method is provided for constructing a valvular patch for implantation into a valve-deficient vein of a patient. A vein segment is extracted from a biological source other than the patient. The vein segment includes a venous valve having at least one leaflet. A wall section having a single leaflet formed thereon is excised from the vein segment. The wall section can be surgically shaped to a desired size and shape. In addition, the leaflet is selected such that the size of the leaflet is sufficient to substantially occlude the vein of the patient when the leaflet is in a closed position.

Brief Description of the Drawings The present invention may be better understood and the advantages will become apparent to those skilled in the art by reference to the accompanying drawings; wherein like reference numerals refer to like elements in the figures. Figure 1A is a perspective view of a partial section of a valvular implant in accordance with an embodiment of the invention within a vein of a patient, the valvular implant having a single leaflet in a substantially closed position;

Figure 1B is a perspective view of a partial section of the valvular implant of Figure 1 A with the valvular leaflet in a substantially open position;

Figure 2 is a plan view of the inside surface of an extracted vein segment that has been cut longitudinally to expose the leaflets of a venous valve;

Figure 2A is a plan view of a patch shaped in a semi-sinus configuration; Figure 2B is a side view of the patch of Figure 2A; Figure 2C is a plan view of a patch shaped in a no-sinus configuration; Figure 2D is a side view of the patch of Figure 2C; Figure 3 is a perspective view of a valve deficient vein of a patient in which the valvular implant is to be implanted, illustrating an incision within the patient's vein;

Figure 4 is a perspective view of a monocusp valvular patch partially sewn to a portion of the patient's vein at the site where the incision is made;

Figure 5 is a plan view of the outer surface of the patient's vein after the monocusp valvular patch has been completely sewn within the patient's vein;

Figure 6 is a perspective view of a partial section of a patient's vein in which two valvular patches, each having a single leaflet, are implanted in the patient's vein in accordance with another embodiment of the present invention;

Figure 7 is a perspective view of a partial section of a patient's vein in which a valvular patch having two leaflets is implanted in the patient's vein in accordance with another embodiment of the present invention, the leaflets being in a substantially closed position;

Figure 8 is a perspective view of a valvular implant attached to a holding device; and Figure 9 is a top plan view of a base portion of the holding device shown in Figure 8.

Detailed Description of the Preferred Embodiment The present invention relates generally to a biological valvular implant and to methods of making and using the implant. In particular, the present invention is directed to an implant formed from venous valve tissue extracted from a quadruped or other animal source.

Venous valves normally remain open during forward flow, i.e. flow of blood towards the heart, through the vein. In this context, the leaflets of the valve are in an "open" position when a venous valve is open, and the leaflets are in a "closed" position when the venous valve is closed. Normal flow rate of blood through the veins is generally at least 100 milliliters per minute (ml/m), and approximately 250 ml/m to about 550 ml/m. The valves close upon the exertion of backflow pressure. The term "backflow" is used to describe flow in a direction away from the normal forward blood flow, such as in a direction away from the heart or away from the deep veins. Generally, the necessary backflow to close a venous valve will be at a pressure of at least 0.1 mm Hg. Figure 1A illustrates a valvular implant 100 according to a preferred embodiment of the present invention implanted within a patient's vein 102. The valvular implant 100 is made from a vein segment from a biological source. The valvular implant 100 includes a valvular leaflet 104 and a wall section 106 of the harvested vein segment. The wall section 106 of the valvular implant is attached to the vein 102 of the patient as a patch to form a continuous vein wall.

The leaflet 104 of the valvular implant is movable between an open and a closed position. The arrows indicate the direction of the backflow of blood within the patient's vein 102, and in this illustration, the backflow pressure is sufficient to cause the single leaflet 104 of the valvular implant to substantially close, thereby closing the valve. The size of the leaflet 104 is selected such that a single leaflet 104 is sufficient to substantially occlude the vein, as shown in Figure 1A, when the leaflet 104 is in a closed position.

A valvular leaflet 104 is very thin, often being about 0.003 of an inch or less. The thin, flexible nature of valvular leaflets enables the leaflet 104 of the implant 100 to close under low pressure. Thicker types of tissue, such as pericardial tissue, require greater backflow pressure in order for the leaflet to close. In addition, pericardial tissue is fibrous and is subject to fraying.

Figure 1B illustrates the leaflet 104 of the valvular implant in a substantially open position. During the normal forward flow of blood toward the heart, as shown by the direction of the arrows, the leaflet 104 of the valvular implant is pushed generally against the inner surface of the patient's vein 102 to allow blood to flow normally through the vein 102.

In this manner, once the valvular implant 100 is implanted within the patient's vein 102, it functions as a venous valve.

The valvular implant 100 is prepared from a harvested vein segment having a valve with one or more leaflets formed therein. It is not necessary that the valve within the harvested vein segment be a competent or intact valve because only a portion of the valve, i.e. only a single leaflet in some instances, is used to form the valvular implant 100. Generally, venous valves include one, two or three leaflets which form the valve. The venous valve of the harvested vein segment can have one or more leaflets. In a preferred embodiment, only a single valvular leaflet 104 is needed to form the valvular implant 100. In other embodiments, however, it may be desirable to use two or more leaflets to form the valvular implant 100.

Venous valves can be found in veins upon which gravity acts, such as in veins located in the limbs or the jugular veins of quadrupeds. Venous valves can also be located in other parts of the body. For example, the stomach may contain venous valves. The vein segment 112 is preferably extracted from a biological source other than the patient in which the valvular implant 100 will be implanted. For instance, the vein segment 112 can be extracted from a bovine, equine, ovine, caprine or cervine animal source. Figure 2 illustrates a harvested vein segment 112 which has been cut longitudinally to transform the vein segment 112 from a generally cylindrical shape to a generally flat shape. The vein segment 112 includes a wall section 106 and two leaflets 104, one of which has been bisected by the cutting operation. Other vein segments can have other numbers of leaflets which form the valve. The number of leaflets 104 within a vein segment will vary depending on the type of animal and type of venous valve from which the vein segment 112 is extracted. The size of the leaflet and the number of the leaflets which form the venous valve will also vary depending on the source of the vein segment 112. The wall section 106 has an inner surface 108 and an outer 110 surf ace (shown in Figure 5). The leaflets 104 are attached to the inner surface 108 of the wall section 106.

Upon extraction of a vein segment 112 from a biological source, the harvested vein segment 112 is fixed. Fixation can be accomplished in a variety of ways known to those skilled in the art, including but not limited to, exposure to a chemical fixation solution, UV light or freeze drying. Various ways of fixing the vein segment 112, including subjecting the vein segment to a chemical tanning process, are described in detail in U.S. Patent No. 5,500,014, issued to Quijano et al., which is incorporated herein by reference.

Tanning is a well-known process involving the treatment of the vein segment with a suitable fixing agent, such as an aldehyde solution. Typically, a solution of glutaraldehyde in a pH balanced electrolyte buffer is used as the fixing agent.

A concentration of glutaraldehyde should include approximately 0.025 percent to about 0.626 percent of the tanning solution to prepare supple valve leaflets. For a more detailed discussion of tanning processes, see the discussion of tissue tanning procedures in Tissue Valves, Aubry Woodruff, Chapter 15, Ed. Marion lonescur, which reference is incorporated herein by reference. To ensure permeation of the fixation solution throughout the tissue of the vein segment 112, the vein segment

112 is maintained in a fixation solution at room temperature for at least 72 hours without any flow through the valve. The fixation process can be expedited by maintaining the fixation solution at higher temperatures.

The harvested vein segment 112 can be fixed with the valve in an open or a closed position, or by cycling between the open and closed positions. The chemical fixing of the valve leaflets in a substantially open position is provided by subjecting the harvested vein segment to a tanning process while maintaining a substantially constant flow of tanning fluid through the vein segment 112. The extent to which the valve leaflets 104 are open is controlled by varying the flow rate of the tanning solution through the vein segment 112 during the fixation process. The resulting implant will have the leaflets fixed anywhere from a completely open valve to about 10 to 70 percent of the normal open position of the valve.

In certain embodiments, the valve leaflets 104 are fixed such that the valve is in a substantially open position, in other embodiments, however, it is suitable to fix the valve leaflets with the valve in a closed position or by cycling between an open and a closed position. Fixing the leaflets with the valve in a closed position is performed by reversing the flow of the fixation solution through the vein segment and maintaining a minimal backflow pressure against the valve leaflets Typically, the pressure applied against the leaflets in this position is approximately 0.1 mm Hg. In certain embodiments, the leaflets are subjected to a low concentration fixation solution to maintain the flexibility of the valve leaflets. The concentration of aldehyde in the tanning solution and the amount of time to which the tissue is subjected to the tanning solution affect the stiffness of the tissue. The flexibility and suppleness of the leaflets allows the leaflets to close the valve under a minimal backflow. The concentration of the aldehyde, e.g. glutaraldehyde, in the tanning solution is preferably from about 0.025 percent to about 0.626 percent of the tanning solution to prepare flexible, supple valve leaflets. In one embodiment, the glutaraldehyde is about 0.15 percent of the tanning solution. Other suitable tanning solutions include acrolein or polyepoxy compounds.

In one embodiment of the present invention, the outer surface 110 of the wall section 106 of the vein segment 112 is subjected to a fixation solution having a higher concentration of glutaraldehyde than the solution to which the leaflets are subjected. For instance, in a preferred embodiment, the tanning solution for fixing the wall section 106 of the vein segment contains about 2.5 percent of glutaraldehyde, while the tanning solution to which the leaflets 104 are exposed contains 2.5 percent of glutaraldehyde. The higher concentration of glutaraldehyde makes the wall section 106 stiff er and less flexible than the leaflets 104.

In a preferred embodiment, after the vein segment 1 12 has been fixed and cut longitudinally, an incision or cut 109 is made in the wall of the vein segment 112 around the intact leaflet 104. In certain other embodiments, the leaflet and wall portion can be excised from the vein segment prior to fixation. The single leaflet 104 and wall portion 106 form a valvular patch. A valvular patch 100 having only a single leaflet 104 is referred to as a monocusp patch. A valvular patch can also be formed from a wall section having two or more leaflets.

The valvular patch 100 is surgically shaped to an appropriate size and shape, in some instances, a patch 100 of the desired size and shape is cut directly from the vein segment 112 so that additional shaping is not necessary. Typically, the wall section 106 of the resulting patch 100 has a generally elliptical shape, i.e., full-sinus configuration, as shown in Figure 2. Figures 2A and 2B illustrate a patch having a wail section shaped in a semi-sinus configuration and Figures 2. and 2D illustrate a patch having a wall section with a no-sinus configuration. The reduced sinus area of the patches shown in Figures 2A-2D requires less removal of the patient's vein in order to implant the patch. Further, the amount of suturing necessary for implementation is also reduced in those embodiments.

The patch 100 is attached to a valve-deficient vein 102 of a patient by suturing a perimeter of the patch to a wall of the patient's vein 102. With reference to Figure 3, an incision is made in the vein 102 of a patient in which the valvular patch 100 is to be implanted. Tissue may be removed from the vein 102 as is necessary in order to accommodate attachment of the valvular patch within the patient's vein 102. For instance, a portion of the wall of the patient's vein may need to be removed to allow the vein to receive the valvular implant 100.

In addition, the valvular patch may be implanted at the same location within the patient's vein where an incompetent or damaged valve exists. In these cases, it is not necessary to remove the dysfunctional valve in order to implant the patch. Thus, when a patch is used the patient's native vein tissue is conserved. With reference to Figure 4, the wall section 106 of the valvular patch 100 is attached at the incision site on the patient's vein 102. The valvular patch 100 can be attached to the vein 102 by suturing or otherwise attaching the wall portion 106 of the patch to the patient's vein wall, such as with biocompatible adhesives. Figure 5 is a side view of the patient's vein 102 after the patch 100 is sutured to the vein. The outer surface 100 of the wall section of the patch is flush with the outer surface of the vein wall.

After the valvular patch 100 is attached to the patient's vein, the leaflet 104 of the valvular patch 100 acts as a substitute valve. The desired size of the leaflet 104 will vary depending on the size of the vein in which the valvular implant 100 is to be implanted. The single leaflet 104 is preferably selected to be of a sufficient size to substantially prevent backflow of blood through the patient's vein when the leaflet 104 is in a closed position. Thus, the leaflet 104 acts as a competent venous valve and restores valvular function to the patient's vein.

Depending on the size of the leaflet 104 and the size of the diameter of the patient's vein, it may be sufficient to implant a single monocusp patch within the vein to form a venous valve. For instance, a valvular leaflet from the jugular vein of a large animal may be of a sufficient size to form a valve within a human vein. In some cases, however, it may be necessary or desirable to implant two or more leaflets within a patient's vein to form the venous valve, as illustrated in Figure 6. Figure 6 illustrates a patch having two leaflets 104, 107 implanted within the vein of a patient. In a closed position, each leaflet covers about half the cross-sectional area of the vein. The two leaflets 104, 107 work together to form a bi-leaflet valve. Alternatively, monocusp patches can be implanted within the patient's vein to form a valve or at different locations within the venous system. For example, a patch may be implanted within the femoral vein in the upper leg and also within the popliteal vein in the lower leg. Figures 7 and 8 illustrate a holding device 118 for holding the valvular patch 100 in position while attaching the patch 100 to the patient's vein 102. The holding device 118 includes a base portion 120 and detachable holder 122. The base portion 120 has a perimeter portion 124 and a plurality of suture holes 126 along the perimeter portion 124 of the base 120. The base perimeter portion 124 is sized and shaped generally similar to the desired size and shape of the valvular patch 100. The size of the base portion 120 can be slightly smaller than the desired size of the patch so that a small amount of tissue is exposed along the base perimeter 124.

In one embodiment, the perimeter portion 124 has a generally elliptical shape. Other configurations, including construction and shape, of the base 120 and perimeter portion 124 are also possible. For instance, the base portion 120 can have a continuous flat surface, rather than the wheel and spoke configuration shown in Figures 7 and 8.

The perimeter portion 124 of the base portion 120 is placed against the outer surface 110 of the wall section 106 of the harvested vein segment 112. The wali section 106 of the vein segment 112 is sutured to the base perimeter

124 at the locations of the suture holes 126. Superficial sutures which do not extend all the way through the tissue are sufficient to attach the vein segment 112 to the base portion 120. Alternatively, the vein segment 112 can be attached to the base 120 in ways other than suturing, such as using adhesives. Using the base perimeter 124 as a guide, a wall section 106 is cut from the vein segment 112 to form the valvular patch 100 The valvular implant 100 can be stored, shipped, and/or sold with the base portion 120 attached to it. The base 120 can be used to identify the size of the patch 100. For example, the base portion 120 can be marked with the size of the leaflet 104.

The holder 122 is attached to the base portion 120 at a threaded location 128 to facilitate handling of the valvular patch 100. In the illustrated embodiment, the holder comprises an elongate rod 130 threaded at its distal end and having a handle 132 at its proximal end. In other embodiments, the holder 122 and handle 132 can have other shapes which facilitate handling of the implant.

The holder 122 can be detached from the base 120 during storage or transport of the patch 100, and can be attached to the base 120 for use during surgery to facilitate positioning and manipulation of the patch 100 at the desired location within the patient's vein. Once the patch 100 is attached to the patient's vein, the base 120 can be removed from the patch 100 by removing the sutures.

Although this invention has been described in terms of certain preferred embodiments, other embodiments that are apparent to those of ordinary skill in the art, including embodiments which do not provide all of the benefits and features set forth herein, are also within the scope of this invention. Accordingly, the scope of the present invention is defined only by reference to the following claims.

Claims

WHAT IS CLAIMED IS:

I . A method of restoring venous valvular function within a valve-deficient vein of a patient, the method comprising: extracting a vein segment from a biological source other than the patient, the vein segment having a venous valve formed therein, the venous valve having at least one leaflet; forming a patch which comprises an excised wall section of the vein segment, the patch having a single leaflet formed thereon; and attaching the patch to the valve deficient vein of the patient such that the leaflet opens and closes in response to changes in blood flow within the vein.

2. The method of Claim 1, wherein the single leaflet patch is attached at a location within the patient's vein to replace an incompetent or damaged venous valve.

3. The method of Claim 1, wherein extracting a vein segment comprises extracting a vein segment from a bovine, equine, ovine, caprine, or cervine animal source.

4. The method of Claim 3, wherein the vein segment is extracted from a jugular vein of the animal source.

5. The method of Claim 1, wherein forming the patch comprises dissecting the vein segment to remove the wall section, and surgically shaping the wall section to form the patch.

6. The method of Claim 5, wherein surgically shaping comprises forming a patch which has a generally elliptical configuration.

7. The method of Claim 1 additionally comprising fixing the patch.

8. The method of Claim 7, wherein fixing the patch involves exposing the patch to a chemical fixing agent.

9. The method of Claim 7, wherein fixing the patch involves exposing the patch to UV light or freeze drying.

10. The method of Claim 8, wherein exposing the patch to a chemical fixing agent involves passing the fixing agent through the vein segment.

I I. The method of Claim 1, wherein attaching the patch to the valve-deficient vein involves suturing a perimeter of the patch to a wall of the valve-deficient vein.

12. The method of Claim 1, wherein attaching the patch involves using a biocompatible adhesive to attach the patch to the valve-deficient vein.

13. The method of Claim 1 additionally comprising releasably attaching the patch to a holding device, and using the holding device to maintain the patch in position during implantation.

14. The method of Claim 13, wherein releasably attaching the patch to the holding device comprises suturing a surface of the patch to a surface of the holding device.

15. The method of Claim 1, wherein forming the patch involves selecting a single leaflet having a size sufficient to substantially occlude the vein of the patient.

16. An implant for restoring valvular function within a vein, the implant comprising: an excised wall section of a vein segment from a biological source; and a single valvular leaflet formed on the excised wall section, the leaflet being movable between an open position in which a substantial portion of the leaflet is in close proximity to the wall section, and a closed position in which a substantial portion of the leaflet is a distance away from the wall section, the leaflet being of a sufficient size to substantially prevent backflow of blood through the patient's vein when in the open position.

17. The venous implant of Claim 16, wherein the vein segment is harvested from a jugular vein of an animal source.

18. The venous implant of Claim 16, wherein the vein segment is harvested from a bovine, equine, ovine, caprine, or cervine animal source.

19. The venous implant of Claim 16 additionally comprising a base portion of a holding device attached to the wall section of the implant.

20. The venous implant of Claim 19, wherein the wall section of the implant includes an inner surface and an outer surface, the leaflet being positioned on the inner surface of the wall section, at least a portion of the base portion of the holding device attached to the outer surface of the wall section.

21. The venous implant of Claim 19, wherein the base portion of the holding device identifies the size of the implant.

22. The venous implant of Claim 19, wherein the base portion of the holding device has a generally elliptical configuration.

23. The venous implant of Claim 19, wherein the holding device additionally comprises a detachable holder.

24. The venous implant of Claim 23, wherein the detachable holder is an elongate rod.

25. A method of constructing a valvular patch for implantation into a valve-deficient vein of a patient, the method comprising: extracting a vein segment from a biological source other than the patient, the vein segment having a venous valve formed therein, the venous valve having at least one leaflet; and excising a wall section of the vein segment, the wall section having a single leaflet formed thereon.

26. The method of Claim 25, wherein extracting a vein segment comprises extracting a vein segment from a bovine, equine, ovine, caprine, or cervine animal source.

27. The method of Claim 25, wherein the vein segment is extracted from a jugular vein of the animal source.

28. The method of Claim 25 additionally comprising surgically shaping the wall section to a desired size and shape.

29. The method of Claim 25 additionally comprising selecting a leaflet having a size sufficient to substantially occlude the vein of the patient when the leaflet is in a closed position.

30 The method of Claim 25 additionally comprising fixing the leaflet

31. The method of Claim 30, wherein fixing the leaflet involves exposing the leaflet to a chemical fixing agent.

32. The method of Claim 31, wherein exposing the leaflet to a chemical fixing agent involves passing the fixing agent through the vein segment.

33. The method of Claim 30, wherein a chemical fixing solution having a low concentration of glutaraldehyde is passed through the vein segment.

34. The method of Claim 33 additionally comprising exposing an outer surface of the vein segment to a chemical fixing solution having a higher concentration of glutaraldehyde than the chemical fixing solution being passed through the vein segment.

35. The method of Claim 25 additionally comprising releasably attaching a wall section of the vein segment to a holding device.

36. The method of Claim 35, wherein releasably attaching the wall section to the holding device comprises suturing a surface of the holding device to an outer surface of the wall section.

37 A method of restoring venous valvular function within a valve-deficient vein of a patient, the method comprising attaching an implant to a vein of the patient, the implant comprising an excised wall section of a vein segment from a biological source other than the patient and a valvular leaflet formed on the wall section.

38. The method of Claim 37, wherein the implant is attached at a location within the patient's vein to replace an incompetent or damaged venous valve.

39. The method of Claim 37 additionally comprising removing an incompetent or damaged venous valve from the vein of the patient.

40. The method of Claim 37, wherein attaching the implant involves suturing a perimeter of the implant to a wall of the patient's vein.

41. The method of Claim 37, wherein attaching the implant involves using a biocompatible adhesive to attach the patch to the patient's vein.

42. The method of Claim 37 additionally comprising selecting an implant having a valvular leaflet of a size sufficient to substantially occlude the vein of the patient.

43. A method of restoring venous valvular function within a valve deficient vein of a patient, the method comprising: surgically attaching a first patch to a valve deficient vein of the patient, the patch comprising an excised wall section of a vein segment from a biological source other than the patient and a valvular leaflet formed on the wall section; and surgically attaching a second patch to the patient's vein, the first and second patches positioned within the patient's vein such that the leaflets form a venous valve.

44. The method of Claim 43 additionally comprising selecting a patch having a leaflet of a sufficient size to substantially occlude the patient's vein when the leaflet is in a closed position.

45. The method of Claim 43, wherein the second patch is attached within the patient's vein at a location downstream from the first patch.