Abstract:
A mechanical heart valve and packaging wherein the mechanical valve is surrounded by a liquid. In one embodiment, a glutaraldehyde solution is used. In another embodiment, organic solvents are used. The liquid will not cause a particulate to form during storage. In addition, the liquid will not produce harmful changes in the polymeric sewing ring, for example. That is, the liquid does not cause degradation of the polymeric materials comprising the heart valve, nor does it cause swelling of such materials, nor the dissolution of polymeric materials.

Description:
TECHNICAL FIELD  
         [0001]    The present invention pertains to prosthetic devices for implantation in a body of a patient and in particular to anti-bacterial packaging for mechanical prosthetic devices.  
         BACKGROUND OF THE INVENTION  
         [0002]    Prosthetic heart valves for human patients have been available since the 1950s, following the advent of blood oxygenators, which made open heart surgery possible. Today, there are two major types of heart valves: mechanical valves and bioprosthetic or tissue valves. The term “mechanical valve” as used herein, refers to a heart valve made exclusively of synthetic materials and which comprises essentially no biological components. The term “bioprosthetic valve,” on the other hand, refers to a heart valve comprising at least some biological components such as tissue or tissue components (e.g., collagen). The biological components are obtained from a donor animal (typically bovine or porcine), and the valve may comprise either biological materials alone or biological materials with man-made supports or stents. Early heart valve prostheses were exclusively mechanical valves. One such early design was the ball-and-cage valve, in which a ball or disc was housed in a cage. One side of the cage provided an orifice through which blood flowed either into or out of the heart, depending on which heart valve was being replaced. The energy of the blood flow in the forward direction forced the ball or disc to the back of the cage, allowing blood to flow through the valve. When blood attempted to flow in a reverse direction, or “regurgitate,” the energy of the blood flow forced the ball or disc into the orifice in the valve and blocked the flow of blood.  
           [0003]    Bi-leaflet and monoleaflet mechanical heart valves were developed to overcome some of the deficiencies of early cage-based mechanical valve designs. A bi-leaflet valve typically comprises an annular valve body in which two opposed leaflet occluders are pivotally mounted. Monoleaflet heart valves typically comprise a single leaflet occluder coupled to the annular valve body. Monoleaflet valves typically open by pivoting movement, although some valves open by a combination of pivoting and translational movement. For both bi-leaflet and monoleaflet mechanical valves, the occluders are typically substantially rigid, although some designs incorporate flexible leaflets. In bi-leaflet valves, the leaflets move between a closed position in which the two leaflets are mated to prevent blood flow in the reverse direction, and an open position in which the occluders are pivoted away from each other to permit blood flow in the forward direction. In monoleaflet valves, the leaflet pivots and/or translates from the closed to the open position to allow blood flow. In each case, however, the energy of blood flow causes the occluders to move between their open and closed positions.  
           [0004]    Mechanical heart valves are generally characterized by a rigid annular valve body supporting one or more occluders, with a sewing ring or sewing cuff circumscribing the annular valve body. Pyrolytic carbon is a material often used for the valve body or the occluders, although other materials such as metal, polymers or ceramics have also been proposed. The sewing ring is often comprised of silicone rubber with a polymeric fabric cover (e.g., Dacron TM fabric). A metal stiffening ring may be provided between the valve body and the sewing ring and a metal lock wire may be used to secure the stiffening ring and/or sewing ring to the valve body.  
           [0005]    Mechanical valves have also been made with flexible leaflets fabricated from man-made materials such as polyurethane, silicone rubber or other biocompatible polymer, for example, a valve described by Purdy, et al., U.S. Pat. No. 5,562,729, incorporated herein by reference. A sewing ring is provided for mounting flexible leaflet mechanical heart valves in a patient&#39;s heart.  
           [0006]    Bio-prosthetic heart valves, in contrast to mechanical valves, comprise an annulus formed by an annular stent to which three flexible leaflets, comprised of a biological material such as bovine or porcine pericardium, are coupled. When blood flows in the forward direction, the energy of the blood flow deflects the leaflets away from the center of the annulus and allows blood to flow in the forward direction. When the pressure across the valve reverses and blood begins to flow in the reverse direction, the three leaflets engage each other in a coaptive region, occluding the valve body annulus and preventing the flow of blood through the valve in the reverse direction. The valve leaflets are made from tissue, such as specially treated porcine or bovine pericardial tissue.  
           [0007]    Mechanical heart valves have usually been packaged in containers that support the mechanical valve in such a way as to protect or isolate it from mechanical shocks. Representative packaging patents include Cromie, U.S. Pat. No. 4,101,031; Lubock et al., U.S. Pat. No. 4,801,015; Dohm et al., U.S. Pat. No. 5,720,391; and Caudillo et al., U.S. Pat. No. 5,823,342, all of which are hereby incorporated herein by reference in their entirety. Mechanical valves are typically shipped and stored in a sterilized condition in airtight containers. Because mechanical valves do not comprise biological materials, air is used as the medium in the containers. Inclusion of a liquid storage medium, such as an antibacterial solution, has been deemed unnecessary at best, and possibly damaging to the structural materials during storage, and has been avoided on the basis of added cost as well as the risk of possible harm to the valve. Bioprosthetic valves, on the other hand, are almost always shipped or stored in liquid media because of the need to maintain the biological components of the valve in a hydrated condition. In addition, the medium may have anti-bacterial properties or additives to ensure sterility and protect the biological components from bacterial degradation.  
         BRIEF SUMMARY OF THE INVENTION  
         [0008]    The present invention comprises a mechanical heart valve and packaging wherein the mechanical valve is surrounded by a liquid solution. The liquid acts as an additional physical barrier for preventing bacterial contamination of the valve, and is more efficient at deterring such contamination than current air-medium containers. Because prior art valves are not immersed in liquids, they are susceptible to bacterial contamination.  
           [0009]    The liquid also has the ability to absorb mechanical vibration and shock better than containers without liquids. Accordingly, packaging in liquid further reduces the probability of mechanical damage in transporting and handling the valve. Pyrolytic carbon materials, commonly used in mechanical heart valves, are relatively brittle, and the additional dampening properties of a liquid medium can reduce the incidence of breakage during shipping.  
           [0010]    The liquid in the container may have anti-microbial properties, which may include bacteriocidal and/or antifungal or antiviral agents. In preferred embodiments, the liquid is selected to be compatible with the materials used to fabricate the mechanical valve, so that the liquid will produce no harmful changes in the polymeric sewing ring, for example, or in flexible polymeric or silicone rubber leaflets, if used. That is, the solution preferably will not cause degradation, swelling, or dissolution of the polymeric or pyrolytic carbon materials comprising the heart valve. The liquid will not cause particles to form during storage. Such particles may be a polymer or a salt, for example. In one embodiment, the liquid comprises a gluteraldehyde solution. In another embodiment, organic solvents such as alcohol provide an improved capability for wetting hydrophobic surfaces such as Teflon TM material or polyester fabric. 
       
    
    
       [0011]    These and other features and advantages of the invention will be apparent from the following description and accompanying drawings.  
       BRIEF DESCRIPTION OF THE DRAWINGS  
       [0012]    [0012]FIG. 1 is a perspective view of a container with a mechanical heart valve in a liquid.  
         [0013]    [0013]FIG. 2 is an exploded perspective view of a container with a mechanical heart valve.  
         [0014]    [0014]FIG. 3 is a cross sectional view of the container of FIG. 2 with mechanical heart valve in a sterile, anti-microbial liquid. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0015]    Containers incorporating a liquid solution for storage of a mechanical heart valve according to the present invention may be of any desired construction. While the Figures illustrate particularly preferred embodiments of the present invention, it is specifically contemplated that other embodiments of the invention, comprising either simpler or more complex container designs, are within the scope of the invention. FIG. 1 is a perspective view of an embodiment of the present invention illustrating a container  2  having a mechanical heart valve  12  therein, shown in phantom lines. The container  2  comprises a bottle  4  closed by a secure cap  6 . Mechanical heart valve  12  is disposed within an interior space  8  in the container  2 . Valve  12  is immersed in a liquid  14 , which preferably has anti-microbial properties, as more fully described below. According to the teachings of the present invention, any suitable packaging may be used to contain the heart valve  12  and liquid  14 . In the present embodiment, cap  6  is coupled to bottle  4  via a screwed connection. However, other coupling mechanisms, such as a snap-fit cap, can be used without departing from the scope of the invention. In addition, other types of containers may be used beyond bottles having caps. In particular, the invention may comprise a soft polymeric pouch package having an interior space comprising a valve (such as valve  12 ) and a liquid (such as liquid  14 ) therein.  
         [0016]    [0016]FIG. 2 is an exploded view of another embodiment of packaging  10  for a mechanical heart valve  12 , to which a liquid could be added in accordance with the present invention. In the illustrated embodiment, packaging  10  includes an outer shell comprising a first outer shell portion  16  and a second outer shell portion  18 . First outer shell portion  16  and second outer shell portion  18  are formed to removably engage one another. In the illustrated embodiment, the outer shell portions  16 ,  18  can be formed with threads such that the two portions can be screwed together. Other coupling means could be used without departing from the scope of the invention.  
         [0017]    As shown in FIGS. 2 and 3, the outer shell forms a housing for a container  48  that has a first container portion  20  and a second container portion  22 . The container portions  20 ,  22  are formed to removably engage one another. In particular, container portion  20  has a perimeter ridge  24  sized to fit inside a perimeter rim  26  of container portion  22 . Container portion  20  and container portion  22 , when engaged, have inner surfaces that define an inner compartment for housing the mechanical heart valve  12 . Container portion  20  provides support members for a heart valve comprising a shelf  28 , central ridge  30 , tab  34 , and lateral ridges  32 . These members together engage and support heart valve  12 .  
         [0018]    Shelf  28  is sized to fit inside and removably engage (e.g., press fit) rim  26  of the container portion  22 . A support member such as shelf  28  may also be formed integrally with container portion  22 . Container portion  20  further provides opposed support members that cooperate with shelf  28 , specifically a central ridge  30  and a pair of lateral ridges  32 . The central ridge  30  and lateral ridges  32  can be coupled to, or formed integrally with, the inner surface of container portion  20 . Further, central ridge  30  can include a tab  34  that extends into the inner compartment formed when container portions  20  and  22  are engaged. As shown in FIG. 3, central ridge  30 , lateral ridges  32 , and tab  34  engage heart valve  12  opposite shelf  28  to provide support to valve  12  in container  48 . In the embodiment of FIGS. 2 and 3, central ridge  30  and lateral ridges  32  are formed integral with container portion  20 . However, other implementations are also possible, for example, where the support member is a separate component from container portion  20 .  
         [0019]    Mechanical heart valve  12  is representative of the set of implantable medical devices suitable for use with the present invention. Such devices include mechanical heart valves with flexible polymeric or silicone rubber leaflets, such as the heart valve of Purdy et al., U.S. Pat. No. 5,562,729; vascular grafts, such as the grafts of Lauterjung U.S. Pat. No. 5,824,036 or Lauterjung WO97/48350 (both incorporated herein by reference in their entirety) or angioplasty rings, such as the Campbell ring, U.S. Pat. No. 6,102,945 (incorporated herein by reference in their entirety), constructed from non-biological materials.  
         [0020]    The mechanical heart valve  12 , illustrated as a bi-leaflet valve in the embodiment of FIG. 2, typically comprises an orifice  36  to which leaflets  38  are pivotally coupled. Alternatively, flexible polymeric or silicone rubber leaflets may act as occluders, as described in U.S. Pat. No. 5,562,729. Mechanical heart valve  12  preferably comprises a sewing cuff  40  that is used to affix the mechanical heart valve  12  to the patient&#39;s heart. The mechanical heart valve  12  can operate as a mitral or aortic heart valve when implanted in a human heart, depending upon its orientation when implanted. To insure that mechanical heart valve  12  can be sterilized, a hole  42  is provided in packaging  10  to allow sterilization of the inside of package  10 . Although numerous modifications and design choices may be employed by persons of skill in the art, packaging  10  is easy to manufacture and assemble by using components that are standard across the mechanical heart valve product line.  
         [0021]    When the heart valve is to be implanted, the outer shell of packaging  10  is opened, and the inner container can then be removed and positioned in the aortic or mitral orientation. In the aortic orientation, container portion  20  is positioned at the bottom with container portion  22  on top. Container portion  22  can then be removed along with shelf  28 . This leaves mechanical heart valve  12  supported by the aortic support member formed by central ridge  30  and lateral ridges  32  with leaflets  38  held open by tab  34 . A holding instrument (not shown) can then be used to extract mechanical heart valve  12  from packaging  10  and hold it for implantation in a surgical procedure. Tab  34  holds leaflets  38  open to ensure that the holding instrument can be used without having to manually manipulate leaflets  38 . Thus, in the aortic orientation, the mechanical heart valve  12  is supported such that it is prepared for receiving a holding instrument for implantation as an aortic valve.  
         [0022]    [0022]FIG. 3 is a cross-section view of the packaging  10  of FIG. 2 after assembly. As shown, an outer shell, indicated generally at  44 , is formed by the engaging of outer shell portion  18  and outer shell portion  16  using threads  46 . Container  48  is housed inside outer shell  44  and is formed by a first container portion  20  and a second container portion  22 . In this embodiment, as shown, ridge  24  of container portion  20  fits inside rim  26  of container portion  22 . In the aortic orientation of FIG. 2, the mechanical heart valve  12  rests on central ridge  30  and lateral ridges  32  with leaflets  38  held open by tab  34  on ridge  30 . As can be seen from FIG. 3, space in orifice  36  receives a holding device due to tab  30  holding leaflets  38  in an open position.  
         [0023]    After packaging  10  has been assembled around the valve  12 , the valve and packaging can optionally be steam sterilized through the hole  42 . The method of sterilization is not critical, however, and other sterilization techniques known in the art may be used. Before or after sterilization, depending upon the sterilization technique employed, liquid  14  is preferably poured through the hole  42 , to a level sufficient to cover the valve. As persons of skill in the art will readily appreciate, any desired method of introducing the liquid  14  into the valve may be employed. After the liquid is introduced into the packaging  10 , the hole  42  is then sealed with a plug  50  to provide a sealed, leakproof container for heart valve  12 .  
         [0024]    In addition to optionally having anti-microbial characteristics, the selected liquid  14  should preferably avoid forming precipitates or particles throughout a wide range of extreme conditions that may be encountered, particularly during shipping and storage. In preferred embodiments, the liquid should be able to withstand temperatures between −8° C. and 40° C. in the presence of materials comprising the mechanical heart valve and container without formation of a precipitate. Moreover, the liquid  14  should not adversely affect any of the materials comprising the mechanical heart valve, that is, the fluid should not affect the size, weight, dimensions or visual appearance of the materials. Mechanical heart valves are generally comprised of three types of materials: polymeric components, such as silicone rubber or polyurethane in the sewing ring; metal components, such as stiffening rings or lock rings; and pyrolytic carbon components, such as leaflets or an annular valve body. Various anti-bacterial liquids were tested for these criteria, as described in connection with Tables 1 and 2, below.  
         [0025]    Gluteraldehyde solution is a suitable anti-bacterial storage medium. An appropriate concentration is believed to be between 0.1% and 50%, more preferably between 0.2% and 0.6%. In certain storage media, it was determined that the pH should be controlled to inhibit the formation of particles, or deposition of a precipitate. An inorganic buffer such as phosphate buffer may be used. Because of the materials used in manufacturing mechanical heart valves, however, an organic buffer, such as HEPES buffer or triethanol amine buffer, may be used. Preferably, the pH should be kept between pH 7.0 and pH 7.4.  
         [0026]    Selected liquids were stored for twenty hours at −4° C. The solutions were then observed for precipitate or particle formation. Precipitation was present in 50% ethanol, 50% 20 mM phosphate buffered saline and in gluteraldehyde solution at pH 10.0. On the other hand, solutions of 70% isopropanol; 50% ethanol; 0.2% gluteraldehyde in HEPES or PBS (that is, at physiological pH); and acetone (10% and 100%) showed no precipitate, and were candidates for further testing. The results of this series of tests are summarized in the following Table 1.  
                         TABLE 1                           Test for Precipitation at −4° C.            Test Solution   Observation after 20 hours at −4° C.               70% Isopropanol and 30% distilled   No change       H 2 O       50% Ethanol and 50% 20 mM   Large crystalline precipitate       phosphate buffered saline       50% ethanol and 50% 10 mM   No change       triethanol amine buffer       0.2% gluteraldehyde solution with   No change       HEPES buffer at pH 7.2       0.2% gluteraldehyde solution with   No change       20 mM phosphate buffered saline       10% gluteraldehyde solution in   Thick milky precipitate       distilled H 2 O, pH adjusted       to pH 10 using 3 M NaOH       10% acetone   No change       100% acetone   No change                  
 
         [0027]    Those solutions that passed Test 1 above were tested for effects on heart valve materials. Individual components of mechanical valves from the three categories described above were stored in solutions for 11 days. Dry weight change is believed to be representative of actual change in components. The effect of storage in selected solutions is summarized in the following Table 2.  
                                                           TABLE 2                           Dry Weight Change of Mechanical Valve Components after Storage                    Pre-weight   Post-weight           Solution   Component   (g)   (g)   % Change                    70% IPA   Metal ring   2.1099   2.1099   0.000           Pyrolite   0.4509   0.4508   −0.022           Silicone   0.1343   0.1339   −0.298           Suture   0.0334   0.0336   0.599           Teflon   0.079   0.079   0.000           Fabric   0.0343   0.0339   −1.166       0.2% Glut/PBS   Metal ring   2.1043   2.1044   0.005           Pyrolite   0.4584   0.4586   0.044           Silicon   0.1481   0.1482   0.068           Suture   0.0332   0.0334   0.602           Teflon   0.0956   0.0954   −0.209           Fabric   0.0362   0.0362   0.000       0.2% Glut/HEPES   Silicon   0.1434   0.1438   0.279           Suture   0.0082   0.0081   −1.220           Teflon   0.0883   0.0878   −0.566           Fabric   0.0425   0.0426   0.235       50% EtOH/TEA   Metal ring   0.0591   0.0594   0.508           Silicon   0.1428   0.1426   −0.140           Suture   0.0075   0.0076   1.333           Teflon   0.0971   0.0972   0.103           Fabric   0.039   0.0389   −0.256       100% Acetone   Silicon   0.1334   0.1303   −2.324           Suture   0.0073   0.0076   4.110           Teflon   0.0903   0.09   −0.332           Fabric   0.0436   0.0401   −8.028                  
 
         [0028]    For the selected solutions, all the components remained within 2% of their original weight after storage with the exception of 100% acetone. In connection with this test, the size, visual appearance and dimensions of each component were measured or examined before and after storage. No significant changes were noted. The solutions identified in Table 2, with the exception of 100% acetone, are considered to be appropriate sterile liquid storage media for mechanical heart valves.  
         [0029]    The foregoing describes preferred embodiments of the invention and is given by way of example only. The invention is not limited to any of the specific features described herein, but includes all variations thereof within the scope of the appended claims.