durable multi-layer high-strength polymer composite suitable for implant and articles derived from i

专利摘要:
DURABLE MULTI-LAYER HIGH-RESISTANCE POLYMER COMPOSITE SUITABLE FOR IMPLANT AND ARTICLES DERIVED FROM IT A thin, biocompatible, high-strength composite material is disclosed and suitable for use in various implanted configurations. The composite material maintains flexibility in high flexion cycle applications, which makes it particularly applicable to highly flexible implants, such as cardiac or cusp stimulation of the heart valve. The composite material includes at least one layer of expanded porous fluorinated polymer and a substantially filling elastomer all pores of the expanded porous fluorinated polymer.
公开号:BR112013030992B1
申请号:R112013030992-0
申请日:2012-06-01
公开日:2021-01-26
发明作者:William C. Bruchman；Cody L. Hartman
申请人:W. L. Gore & Associates, Inc.；
IPC主号:

专利说明:

[0001] [001] This application is a continuation application in part of the patent application pending in the United States Serial No. 13 / 078,774 filed on April 1, 2011, and also claims the priority of provisional application serial No. 61 / 492,324 filed in June 1, 2011. TECHNICAL STATUS FIELD OF THE INVENTION
[0002] [002] This disclosure refers to materials used in medical implants. More particularly, the disclosure relates to a biocompatible material suitable for use in high flexion cycle applications, including artificial heart valves. State of the art
[0003] [003] Artificial heart valves should preferably last at least ten years in vivo. To last a long time, artificial heart valves must have sufficient durability for at least four hundred million cycles or more. Valves and, more specifically, heart valve cusps, must withstand structural degradation, including the formation of holes, tears, and the like, as well as adverse biological consequences, including calcification and thrombosis.
[0004] [004] Fluorinated polymers, such as the expanded and unexpanded forms of polytetrafluoroethylene (PTFE), modified PTFE, and PTFE copolymers, offer a number of desirable properties, including excellent inertia and biocompatibility, and therefore become the materials ideal candidates. PTFE and expanded PTFE (ePTFE) have been used to create cusps of the heart valve. However, PTFE has been shown to harden with repeated flexing, which can lead to unacceptable flow performance. Failure due to the formation of holes and tears in the material was also observed. A variety of polymeric materials have previously been used with prosthetic heart valve cusps. Failure of these cusps due to stiffness and hole formation occurred within two years of implantation. Efforts to improve cusp durability by cusp thickening resulted in unacceptable hemodynamic performance of the valves, that is, the pressure drop across the open valve was too high.
[0005] [005] Therefore, it remains desirable to provide a biocompatible artificial heart valve design that will last at least 10 years in vivo, exhibiting sufficient durability for at least about four hundred million flexion cycles or more. ABSTRACT
[0006] [006] According to embodiments, an implantable article is provided for regulating the direction of blood flow in a human patient. Such an article may include, but is not limited to, a heart valve or a venous valve.
[0007] [007] In one embodiment, the article includes an implantable cusp comprising a composite material with at least one layer of fluorinated polymer having a plurality of pores and an elastomer present in substantially all pores of the layer of at least one fluorinated polymer , wherein the composite material comprises less than about 80% by weight of fluorinated polymer.
[0008] [008] In other exemplary embodiments, the implantable article includes a cusp with a thickness and formed from a composite material having more than one layer of fluorinated polymer having a plurality of pores and an elastomer present in practically all pores of another layer of fluorinated polymer, where the cusp has a ratio of the thickness of the cusp (μm) to the number of layers of fluorinated polymer of less than about 5.
[0009] [009] In other exemplary embodiments, the implantable article includes a support structure, a cusp supported on the support structure, the cusp with a thickness and formed from a composite material that has more than one layer of fluorinated polymer having a plurality of pores and an elastomer present substantially in all pores of more than one layer of fluorinated polymer, wherein the cusp has a ratio of cusp thickness (μm) to the number of layers of fluorinated polymer of less than about 5.
[0010] [010] In other exemplary embodiments, the implantable article includes a cyclable cusp between a closed configuration to substantially prevent blood flow through the implantable article and allowing blood flow in an open configuration through the implantable article. The cusp is formed from a plurality of layers of fluorinated polymer and having a ratio of cusp thickness (μm) to the number of layers of fluorinated polymer of less than about 5. The cusp maintains a substantially unchanged performance after actuation of the cusp at least 40 million cycles.
[0011] [011] In other exemplary embodiments, the implantable article includes a cyclable cusp between a closed configuration to substantially prevent blood flow through the implantable article and allowing blood flow in the open configuration through the implantable article. The implantable article also includes a damping element located between at least a part of the support structure and at least a part of the cusp, where the damping element is formed from a plurality of layers of fluorinated polymer and having a ratio of cusp thickness (μm) for the number of fluorinated polymer layers of less than about 5. The cusp maintains a substantially unchanged performance after the cusp has acted for at least 40 million cycles.
[0012] [012] In exemplary embodiments, a method is provided for forming a cusp of an implantable article for regulating the direction of blood flow in a human patient, which includes the steps of: providing a composite material that has more than a layer of fluorinated polymer having a plurality of pores and an elastomer present in substantially all pores of the layer of more than one fluorinated polymer, and bringing more than one layer of the composite material in contact with other layers of the composite material by wrapping a composite material cusp with a start and end defined as an axial seam adhered to itself.
[0013] [013] In exemplary embodiments, an implantable article is provided for regulating the direction of blood flow in a human patient, which includes a polymer cusp having a thickness of less than about 100 μm.
[0014] [014] In another embodiment, the implantable article includes a support structure of generally annular shape having a first end and an opposite second end. The first end of the support structure has a longitudinally extending post. A cusp of cusp material extends along an outer periphery of the support structure and forms the first and second cusps that extend along opposite sides of the pole. A damping member is attached to the pole and provides damping between the pole and the cusps to minimize stress and wear on the cusps according to the cycles of the cusps between the open and closed positions. BRIEF DESCRIPTION OF THE DRAWINGS
[0015] [015] The accompanying drawings are included to provide a better understanding of the invention and are incorporated and form part of this specification, illustrate exemplary embodiments of the invention and, together with the description, serve to explain the principles of the invention.
[0016] [016] Figures 1A, 1B, 1C and 1D are front, side and top elevation views and a perspective view, respectively, of a tool for forming a heart valve cusp, according to an embodiment ;
[0017] [017] Figure 2A is a perspective view of a damping block being stretched along a cusp tool, according to an embodiment;
[0018] [018] Figure 2B is a perspective view of a release layer being stretched over the damping block covering the cusp tool in Figure 2A, in accordance with an embodiment;
[0019] [019] Figures 3A, 3B and 3C are top, side and front elevation views illustrating a step in the formation of a valve cusp, in which the cusp tool covered by the damping block and the release layer (shown in Figures 2A and 2B, respectively) are positioned on a composite material for cutting and still together, according to an embodiment;
[0020] [020] Figure 4 is a top elevation view of a three-leaf assembly before cutting excess leaf material, according to an embodiment;
[0021] [021] Figure 5A is a perspective view of the tricuspid set and a basic tool, according to an embodiment;
[0022] [022] Figure 5B is a perspective view of the tricuspid assembly and a base tool aligned and assembled to form a base tool set, according to an embodiment;
[0023] [023] Figure 6A is a plan view of a flat stent structure or support structure, according to an embodiment;
[0024] [024] Figure 6B is a flat plan view of the support structure covered by a polymer coating, according to an embodiment;
[0025] [025] Figures 7A, 7B and 7C are digitalized electron micrograph images of expanded fluorine polymer membranes used to form the valve cusps, according to one modality;
[0026] [026] Figure 8 is a perspective view of a valve assembly, according to an embodiment;
[0027] [027] Figures 9A and 9B are seen in top elevation of the heart valve assembly of Figure 8 shown illustratively in the closed and open positions, respectively, according to an embodiment;
[0028] [028] Figure 10 is a graph of the results measured from a heart pulse duplicating system flow used to measure the performance of the valve assemblies;
[0029] [029] Figures 11A and 11B are a graph and a graph of results data measured from a high fatigue rate tester used to measure the performance of valve assemblies;
[0030] [030] Figures 12A and 12B are graphs of measured flow results from the heart flow pulse duplicating system, obtained while testing the valve assemblies according to an embodiment in zero cycles and after about 207 million cycles, respectively;
[0031] [031] Figures 13A and 13B are graphs of measured results of the flow of the heart rate duplicator system obtained while testing the valve assemblies according to embodiments in about 79 million cycles and after about 198 million cycles, respectively;
[0032] [032] Figure 14 is a perspective view of a mandrel for the manufacture of a heart valve assembly, according to an embodiment;
[0033] [033] Figure 15 is a perspective view of a valve structure for a heart valve, according to an embodiment;
[0034] [034] Figure 16 is a perspective view of the valve structure of Figure 15 fitted together with the mandrel of Figure 14, according to an embodiment;
[0035] [035] Figure 17 is a perspective view of a molded valve, according to an embodiment;
[0036] [036] Figure 18 is a perspective view of a molded valve, showing a fixing element to reinforce the connection between the adjacent valve cusps and a post of a valve structure, according to an embodiment;
[0037] [037] Figure 19 is a perspective view of a valve structure, according to an embodiment;
[0038] [038] Figure 20 is a perspective view of the valve structure of Figure 19, with posts that are wrapped in cushioning, according to an embodiment;
[0039] [039] Figure 21 is a perspective view of a mandrel formed by stereolithography, according to an embodiment;
[0040] [040] Figure 22 is a perspective view of the wrapped cushion valve structure of Figure 20 mounted on the mandrel of Figure 21, according to an embodiment;
[0041] [041] Figure 23 is a perspective view of a valve that has valve cusps attached and supported on the wrapped cushion valve structure of Figure 20, according to an embodiment
[0042] [042] Figure 24 is a perspective view of a non-retractable stent structure or support structure, according to an embodiment;
[0043] [043] Figure 25 is a perspective view of a laminated stent structure, according to an embodiment;
[0044] [044] Figure 26A is a perspective view of the tricuspid assembly, the base tool, stent structure encapsulated within a composite strain relief and seam ring, according to an embodiment;
[0045] [045] Figure 26B is a perspective view of a three-leaf cluster, in accordance with an embodiment;
[0046] [046] Figure 27 is a perspective view of a valve, according to an embodiment;
[0047] [047] Figure 28 is a perspective view of a valve and fitting, according to an embodiment;
[0048] [048] Figure 29 is a perspective view of a valve, of fixation and pressure, according to an embodiment;
[0049] [049] Figure 30 is a perspective view of a complete valve, according to an embodiment;
[0050] [050] Figure 31 is a perspective view of a non-retractable stent structure or support structure of Figure 24 with a damping element that covers a perimeter of the structure, according to an embodiment;
[0051] [051] Figure 32 is a perspective view of a complete valve having cusps coupled and supported on a support system or structure with a damping element that covers a perimeter of the support structure, a strain relief, and a flange of sewing, according to an embodiment;
[0052] [052] Figure 33A is a perspective view of a stent structure or demountable support structure of Figure 6A with a damping member that covers the regions of the structure to which cusps are attached, according to an embodiment;
[0053] [053] Figure 33B is a flat plan view of the support structure of Figure 6A, with a polymer coating encapsulating the damping members, according to an embodiment;
[0054] [054] Figure 34 is a perspective view of the folding stent structure and damping members of Figures 33A and 33B with the cusp material rolled as a cylinder over the outside of the structure, with three axial slits, in accordance with one embodiment ;
[0055] [055] Figure 35 is a perspective view of Figure 34, with three flaps of cusp material internalized to the stent structure through individual openings, according to an embodiment;
[0056] [056] Figure 36 is a perspective view of a complete valve having cusps coupled and supported in a folding structure with a damping member in places of fixation of the cusps of the structure and a strain relief, according to an embodiment;
[0057] [057] Figure 37 is a graph of the thickness of the cusp and the numbers of layers for a single composite material, according to embodiments;
[0058] [058] Figure 38 is a graph that compares the thickness of the cusp and the numbers of layers of two different composite materials, according to embodiments;
[0059] [059] Figure 39 is a sample graph of cusp thickness and number of layers with defined limits for hydrodynamic performance, minimum number of layers, minimum strength, maximum composite thickness, and maximum percentage of fluorinated polymer. , according to embodiments;
[0060] [060] Figure 40 is a graph of the cusp thickness and number of layers with the limits defined for hydrodynamic performance, the minimum number of layers, the minimum strength, the maximum composite thickness, and the maximum percentage of fluorinated polymer for the cusp configurations of Examples 1, 2, 3, A, B and 4A, 4B, 4C, 5, 6, 7, and 8, according to embodiments;
[0061] [061] Figure 41A is a graph of the cusp thickness and number of layers that describe the general trends in improved durability observed during the accelerated wear test;
[0062] [062] Figure 41 B is a graph of the cusp thickness and number of layers that describe the general trends of reduced durability observed during the accelerated wear test;
[0063] [063] Figure 42 is a graph of the hydrodynamic performance data (EOA and regurgitation fraction), comparing two valves, according to embodiments;
[0064] [064] Figure 43 is Table 4, which is a table of performance data for example valves, according to embodiments, and
[0065] [065] Figure 44 is Table 6, which is a table of performance data for example of valves, according to embodiments. DETAILED DESCRIPTION OF THE ILLUSTRATED WAYS OF IMPLEMENTATION
[0066] [066] Definitions of some terms used here are provided below in the appendix.
[0067] [067] The embodiments presented here meet a long-felt need for a material that meets the durability and biocompatibility requirements of high-flexion implant applications, such as heart valve cusps. It has been observed that the cusps of the heart valve, formed from porous materials or fluorine polymers, more particularly, from ePTFE, not containing elastomer, suffer from stiffness in a high flexion test and animal implantation cycle.
[0068] [068] In one embodiment, described in more detail below, the flexural durability of the porous fluorinated polymer heart valve cusps has been significantly increased by the addition of a relatively high percentage of elastomer with relatively lower strength to the pores. Optionally, additional layers of the elastomer can be added between the composite layers. Surprisingly, in embodiments in which porous fluorinated polymer membranes are embedded with the elastomer the presence of the elastomer increased the overall thickness of the cusp, the result increased the thickness of the fluorinated polymer members, due to the addition of the elastomer not affecting or decreasing flexural durability. In addition, after reaching a minimum weight percent of elastomer, it was found that fluorinated polymer members in general performed better with increasing elastomer percentages, resulting in a significant increase in the life cycle of more than 40 millions of cycles in vitro, as well as for showing no signs of calcification under certain controlled laboratory conditions.
[0069] [069] A material according to an embodiment includes a composite material comprising an expanded fluorinated polymer membrane and an elastomeric material. It should be quickly understood that various types of fluorine polymer membranes and different types of elastomeric materials can be combined, while in the spirit of the present embodiments. It should also be readily appreciated that the elastomeric material can include various elastomers, various types of non-elastomeric components, such as inorganic fillers, therapeutic agents, radiopaque markers, and at the same time, as within the spirit of the present embodiments.
[0070] [070] In one embodiment, the composite material comprises an expanded fluorinated polymer material made from porous ePTFE membrane, for example, as described generically in US Patent No. 7,306,729.
[0071] [071] The expanded fluorinated polymer, used to form the described expanded fluorinated polymer material, may comprise PTFE homopolymer. In alternative embodiments, mixtures of PTFE, expandable modified PTFE and / or expanded PTFE copolymers can be used. Non-limiting examples of suitable fluorine polymer materials are described, for example, US Patent No. 5,708,044 (White), US Patent No. 6,541, 589, (Baillie), US Patent No. 7,531, 611, (Sabol et al), US Patent Application No. 1 1/906, 877, (Ford), and US Patent Application No. 12/410, 050, (Xu et al.).
[0072] [072] The expanded fluorinated polymer of the present embodiments can comprise any suitable microstructure to achieve the desired performance of the cusp. In one embodiment, the expanded fluorinated polymer may comprise a microstructure of fibril interconnected nodes, such as those described in US Patent No. 3,953,566 (Gore). In one embodiment, the microstructure of an expanded fluorinated polymer membrane comprises nodes interconnected by fibrils, as shown in the scanning electron microscopy image in Figure 7A. The fibrils extend from the nodes in a plurality of directions, and the membrane has a generally homogeneous structure. Membranes with this microstructure can typically exhibit a matrix tensile strength in two orthogonal directions, less than 2, and possibly less than 1.5.
[0073] [073] In another embodiment, the expanded fluorinated polymer may have a microstructure of only substantially fibrils, such as, for example, illustrated in Figure 7B and 7C, as is generally taught in US Patent No. 7,306,729, (Bacino ). Figure 7C is a larger enlargement of the expanded fluorinated polymer membrane shown in Figure 7B, and shows more clearly the homogeneous microstructure having substantially only fibrils. The expanded fluorinated polymer membrane having substantially only fibrils, as shown in Figures 7B and 7C, can have a high surface area, such as greater than 20m2 / g, or greater than 25m2 / g, and in some embodiments it can provide a highly balanced strength material with a matrix tensile strength product in two orthogonal directions of at least 1.5 x 105 MPA2, and / or a matrix tensile strength product in two orthogonal directions of less than 2 , and possibly less than 1.5.
[0074] [074] The expanded fluorinated polymer of the present embodiments can be adapted to have any suitable thickness and mass to obtain a cusp with the desired performance. In some cases, it may be desirable to use a very thin expanded fluorinated polymer membrane with a thickness of less than 1.0 μm. In other embodiments, it may be desirable to use an expanded fluorinated polymer membrane having a thickness greater than 0.1 μm and less than 20 μm. Expanded fluorinated polymer membranes can have a density of less than about 1g / m2 to greater than about 50g / m2.
[0075] [075] Membranes according to embodiments may have a tensile strength of the matrix ranging from about 50 MPa to about 400 MPa or higher, based on a density of about 2.2 g / cm3 for PTFE .
[0076] [076] Additional materials can be incorporated within the pores of the material or within the membranes or between the layers of membranes to improve the desired properties of the cusp. Composites according to one embodiment may include fluorinated polymer membranes having thicknesses ranging from about 500 μm to less than 0.3 μm.
[0077] [077] The expanded fluorinated polymer membrane combined with elastomer provides the elements of the present embodiments with the performance attributes required for use in high flexion implant cycle applications, such as heart valve cusps, in at least several aspects significant. For example, the addition of the elastomer improves cusp fatigue performance, eliminating or reducing the stiffness observed with ePTFE-only materials. In addition, it reduces the likelihood that the material will undergo permanent deformation, such as wrinkling or creasing, which could result in compromised performance. In one embodiment, the elastomer occupies substantially the entire volume of pores or spaces within the porous structure of the expanded fluorinated polymer membrane. In another embodiment, the elastomer is present in substantially all pores of the layer of at least one fluorinated polymer. Having the elastomer substantially fill the pore volume or present substantially in all pores reduces the space in which foreign materials can be undesirably incorporated into the composite. An example of such a foreign material is calcium. If calcium becomes incorporated into the composite material, as used in a heart valve cusp, for example, mechanical damage may occur during the cycle, thus leading to the formation of holes in the cusp and degradation in hemodynamics.
[0078] [078] In one embodiment, the elastomer that is combined with that of ePTFE is a thermoplastic copolymer of tetrafluoroethylene (TFE) and perfluoromethyl vinyl ether (PMVE), as described in US Patent No. 7,462,675. As discussed above, the elastomer is combined with the expanded fluorinated polymer membrane in such a way that the elastomer occupies substantially all of the void space or pores within the expanded fluorinated polymer membrane. This pore filling of the expanded fluorinated polymer membrane with elastomer can be accomplished by a variety of methods. In one embodiment, a method of filling the pores of the expanded fluorinated polymer membrane includes the steps of dissolving the elastomer in a suitable solvent to create a solution with a viscosity and surface tension, which is suitable for the partial or total flow within the pores of the expanded fluorinated polymer membrane and allows the solvent to evaporate, leaving the filler material behind.
[0079] [079] In another embodiment, a method of filling the pores of the expanded fluorinated polymer membrane includes the steps of supplying filler material by means of a dispersion to fill, partially or completely, the pores of the expanded fluorinated polymer membrane.
[0080] [080] In another embodiment, a method of filling the pores of the expanded fluorinated polymer membrane includes the steps of bringing the porous expanded fluorinated polymer membrane into contact with an elastomer cusp, under conditions of heat and / or pressure that allow the elastomer to flow into the pores of the expanded fluorinated polymer membrane.
[0081] [081] In another embodiment, a method of filling the pores of the expanded fluorinated polymer membrane includes the polymerization steps of the elastomer inside the pores of the expanded fluorinated polymer membrane by first filling the pores with an elastomer prepolymer and then at least partially heals the elastomer.
[0082] [082] After reaching a minimum percentage by weight of elastomer, cusps constructed from fluorinated polymer materials or ePTFE generally perform better with increasing elastomer percentages, resulting in a significant increase in life cycle. In one embodiment, the elastomer combined with ePTFE is a thermoplastic copolymer tetrafluoroethylene and perfluoromethyl vinyl ether, as described in US Patent No. 7,462,675, and other references that may be known to those skilled in the art. For example, in another embodiment shown in Example 1, a cusp was formed from a composition of 53% by weight of ePTFE elastomer and was subjected to the cycle test. Some stiffness has been observed around 200 million test cycles, although with only a modest effect on hydrodynamics. When the weight percentage of the elastomer was increased to about 83% by weight, as in the embodiment of Example 2, no hardening or negative changes in hydrodynamics were observed at around 200 million cycles. In contrast, with non-composite cusps, that is, all ePTFE without elastomer, as in Comparative Example B, severe hardening was apparent in 40 million test cycles. As demonstrated by these examples, the durability of the porous fluorinated polymer members can be significantly increased by adding a relatively high percentage of elastomer of relatively less strength than that of the pores of the fluorinated polymer members. The high strength of the fluorinated polymer membrane material also allows specific configurations to be very thin.
[0083] [083] Other biocompatible polymers that may be suitable for use in embodiments may include, but are not limited to, groups of urethanes, silicones (organopolysiloxanes), silicone copolymers - urethane, styrene / isobutylene, polyisobutylene copolymers, polyethylene -co-poly (vinyl acetate), polyester copolymers, nylon copolymers, fluorinated hydrocarbon polymers and copolymers or mixtures of each of the above.
[0084] [084] Cusps constructed from a composite material comprising less than about 55% by weight of fluorinated polymer can be assembled in a variety of configurations based on desired laminations or cusp thickness and number of layers of composite. The thickness of the composite is directly related to the percentage of fluorinated polymer, by weight, and thickness of the membrane. Using a membrane thickness range from about 300 nm to more than 3.556 nm and a percentage range of fluorinated polymer, by weight, from 10 to 55, for example, allowed the formation of composite thicknesses ranging from 0.32 μm more than 13 μm.
[0085] [085] The relationship between the thickness of the cusp and the number of composite layers is shown illustratively in a graph in Figure 37, in which two cusp configurations, indicated as A and B, are shown. In one embodiment, these configurations of A and B can be constructed from a single composite. In another embodiment, there may be a generally linear relationship between the thickness of the cusp and the number of layers, where Y = mX, where Y = the thickness of the cusp, m = slope, and X = number of layers. The slope (m) or the ratio of the thickness of the cusp to the number of layers is equal to the thickness of the composite. Therefore, doubling the number of layers from 20 to 40 for A and B configurations, for example, results in doubling the thickness from 40 μm to 80 μm. It should be noted that the slope of the line, or even the shape of the cusp thickness chart versus the number of layers of composition may vary, depending on the amount of elastomer between the layers and the uniformity of the layers.
[0086] [086] When the percentage of fluorinated polymer, by weight, for the same membrane is reduced, the thickness of the composite is increased. As shown in Figure 38, this increase in composite thickness is indicated by the increase in the slope of the dotted line in relation to the solid line of the previous embodiment. In the embodiment illustrated by the dashed line, a reduction of the percentage of fluorinated polymer, by weight, for the same membrane by about half resulted in an increase in the thickness of the composite by about two, which is reflected in the increase in the slope of the dotted line. Therefore, a cusp, as illustrated by configuration C in Figure 38, can either have the same number of layers as configuration A or the same thickness as the cusp of configuration B, with the weight percentage of fluorinated polymer varying.
[0087] [087] In order to determine which fluorinated polymer configurations by weight, weight, composite thickness and number of layers influence both hydrodynamics and durability performance, the limits were observed, as best seen in the graph in Figure 39 There are five limits that generally define the appropriate cusp settings that have been observed so far. The first limit is defined by the acceptable hydrodynamic performance established by the ISO guide document for cardiovascular implants (5840: 2005) define limits of OAE and regurgitation fraction for a given valve size. Typically, cusps with a thickness greater than 100 μm, formed from these composite materials perform close to these acceptability limits. The second limit is a minimum number of layers (10), as observed by durability flaws still illustrated by the examples provided. Likewise, the third limit is a maximum cusp thickness ratio for the number of layers or the composite thickness of 5 μm. Generally, low numbers of layers constructed from thick composites perform poorly when compared to high layer numbers of one or another of the same fluorinated polymer by weight and thickness of the cusp. The fourth boundary is defined by a minimum number of layers of a given composite, which is determined by the force necessary to resist the fluorinated polymer deformation during hydrodynamic loading of the cusp, when the valve is closed during the cardiac cycle. The strength of the laminate is measured by a dome burst test, where a burst pressure of at least 207 KPa is normally required to ensure that the cusps maintain their shape and function. The fifth frontier is defined by the maximum percentage by weight of fluorinated polymer (55%) necessary to significantly increase the cyclic durability. In Figure 40, a graph illustrating these limits is shown with the cusp settings of all examples provided to further illustrate these findings.
[0088] [088] The maximum number of layers of a given composite can be determined by the thickness of the desired cusp. It has been observed that as the thickness of the cusp increases, the hydrodynamic performance behavior for a given valve geometry decreases, while the bending character increases. "Hydrodynamic performance" generally refers to the combination of OAE and regurgitation fraction represented in a two-dimensional Cartesian coordinate system for a given valve dimension, as shown in Figure 42. "Bending character" generally refers to the qualitative quantity of wrinkles and / or folds developed with the cusp structure during deformations induced by cyclic opening and closing. On the other hand, as the thickness of the cusp is decreased, the hydrodynamic performance behavior for a given geometry increases, while the bending character is reduced. This observation of the differences in bending characteristics as a function of the cusp thickness is further illustrated with examples of two valves with 13 μm and 130 μm of cusp thickness, referred to as valve 42A and valve 42B, respectively. A graph of hydrodynamic performance data (EOA and regurgitation fraction), comparing these two valves is shown in Figure 42, where minimizing the regurgitation fraction and maximizing EOA are desirable.
[0089] [089] It has been observed that thin-film materials exposed to large cyclic deformations over long periods are generally susceptible to wrinkles and creases. It is also generally known to those skilled in the art that the durability of fine materials exposed to large cyclic deformations over long periods is reduced as a result of such wrinkles and folds, which can be formed during the work cycle.
[0090] [090] So it was surprising when cusps of similar thickness (about 16 μm), which were built from ultra-thin composites (0.32 μm) and had five times the number of layers (about 50) versus cusps Conventional models had only the desirable flexion behavior previously achieved by cusps with thicknesses of 75 or greater. Furthermore, when comparing the durability of the low number of layers of composites with a high number of layers, the high number of layers typically outperformed the low number of layers of constructions by orders of magnitude using number of cycles as a comparison. A valve with fifty layers and 16 μm cusp thickness was found to have significantly less wrinkles and folds than a layer of construction of six to approximately the same thickness.
[0091] [091] Comparing cusps of approximately the same thickness in cross section, with 4, 9, 26, 50, and 21 layers, respectively, it was appreciated that the increase in the number of layers facilitates both the ability to have a smaller radius of curvature as well how to accommodate a tight curvature by storing the length of the individual layers through localized deformation.
[0092] [092] The general trends that were observed by varying the thickness and number of layers are illustrated in the graphs of Figures 41A and 41B, and are further supported by the examples provided.
[0093] [093] The following non-limiting examples are provided to further illustrate embodiments. It should also be readily appreciated that other models of valve structure can be used in addition to those illustrated in the examples below and attached Figures. Example 1
[0094] 1) Um espesso, bloco de amortecimento de ferramenta de sacrifício ou camada foi formada pela dobra de uma camada de ePTFE sobre si mesma para criar um total de quatro camadas. A camada de ePTFE foi cerca de 5 cm (2") de largura, cerca de 0,5 milímetros (0,02 ") de espessura e tinha um elevado grau de compressibilidade, formando um bloco de amortecimento. Com referência às Figuras 1 e 2, o bloco de amortecimento 200 foi então alongado (Figura 2) em direção a ferramenta de cúspide, genericamente indicada por 100. A ferramenta cúspide 100 tem uma parte de cúspide 102, uma parte de corpo 104 e uma extremidade inferior 106. A parte cúspide 102 da ferramenta cúspide 100 tem uma superfície final geralmente arqueada, convexa 103. O bloco de amortecimento200 foi esticado e alisado sobre a extremidade da superfície 103 da parte de cúspide 102 da ferramenta cúspide 100 forçando a ferramenta cúspide 100 na direção representada pela seta (Figura 2A). Uma borda periférica 202 do bloco de amortecimento 200 foi esticada sobre a extremidade inferior 106 da ferramenta de cúspide 100 e torcida para segurar a bloco de amortecimento 200 no lugar (Figura 2B). 2) Com referência à Figura 2B, a camada de liberação 204 foi em seguida esticada sobre a parte de cúspide 102 da ferramenta 100, que na etapa anterior foi coberta com a bloco de amortecimento 200. Numa concretização, a camada de liberação 204 foi feita a partir de um ePTFE substancialmente não poroso, possuindo uma camada de etileno propileno fluorado (FEP), dispostos ao longo de uma superfície externa ou um de seu lado. A camada de liberação 204 foi esticada sobre a ferramenta cúspide 100 de tal modo que a camada de FEP faceou na direção do bloco de amortecimento200 e o ePTFE substancialmente não poroso faceou para fora ou para longe do bloco de amortecimento 200. A camada de liberação foi de cerca de 25 µm de espessura e de comprimento e largura suficientes para permitir que a camada de liberação 204 pudesse ser puxada por cima da extremidade inferior 106 da ferramenta de cúspide 100. Tal como acontece com o bloco de amortecimento 200 na etapa anterior, uma borda periférica 206 da camada de liberação 204 foi puxada para a extremidade inferior 106 da ferramenta de cúspide 100 e, em seguida torcida para a extremidade inferior 106 da ferramenta de cúspide 100 para reter ou segurar a camada de liberação 204 no lugar. A camada FEP da camada de liberação 204 foi então derretida e, assim, fixamente presa à bloco de amortecimento 200, conforme necessário, através da utilização de um ferro de solda quente. 3) Os processos das etapas 1) e 2) foram repetidos para preparar três ferramentas cúspide separadas, cada uma tendo um bloco de amortecimento coberto por uma camada de liberação. 4) Um material cúspide de acordo com uma concretização foi formado a partir de um material compósito que compreende uma membrana de ePTFE embebida com fluoro elastômero. Uma parte do material compósito de cerca de 10 cm de largura foi enrolado num mandril circular para formar um tubo. O material compósito foi composto por três camadas: duas camadas externas de ePTFE e uma camada interior de um elastômero fluorado colocada entre elas. A membrana de ePTFE foi fabricada de acordo com os ensinamentos gerais descritos na Patente dos US No. 7.306.729. O elastômero fluorado foi formulado de acordo com os ensinamentos gerais descritos na Patente dos US No. 7.462.675. Elastômeros fluorados adicionais podem ser adequadoss e são descritos na Publicação US No. 2004/ 0024448. [094] Heart valve cusps according to one embodiment were formed from a composite material with an expanded fluorinated polymer membrane and an elastomeric material and joined to a metallic expandable balloon using an intermediate layer of FEP, as described by the following process: 1) A thick, sacrificial tool cushion block or layer has been formed by folding an ePTFE layer over itself to create a total of four layers. The ePTFE layer was about 5 cm (2 ") wide, about 0.5 mm (0.02") thick and had a high degree of compressibility, forming a cushioning block. With reference to Figures 1 and 2, the damping block 200 was then stretched (Figure 2) towards the cusp tool, generally indicated by 100. The cusp tool 100 has a cusp part 102, a body part 104 and a lower end 106. The cusp part 102 of the cusp tool 100 has a generally arched, convex end surface 103. The damping block200 has been stretched and smoothed over the end of the surface 103 of the cusp part 102 of the cusp tool 100 by forcing the cusp tool 100 in the direction represented by the arrow (Figure 2A). A peripheral edge 202 of damping block 200 has been stretched over the lower end 106 of cusp tool 100 and twisted to hold damping block 200 in place (Figure 2B). 2) With reference to Figure 2B, the release layer 204 was then stretched over the cusp portion 102 of the tool 100, which in the previous step was covered with the damping block 200. In one embodiment, the release layer 204 was made from a substantially non-porous ePTFE, having a layer of fluorinated propylene ethylene (FEP), arranged along an external surface or one on its side. The release layer 204 was stretched over the cusp tool 100 such that the FEP layer faced towards the damping block200 and the substantially non-porous ePTFE faced outward or away from the damping block 200. The release layer was about 25 µm thick and of sufficient length and width to allow the release layer 204 to be pulled over the lower end 106 of cusp tool 100. As with damping block 200 in the previous step, a peripheral edge 206 of release layer 204 has been pulled to the lower end 106 of cusp tool 100 and then twisted to the lower end 106 of cusp tool 100 to hold or hold release layer 204 in place. The FEP layer of release layer 204 was then melted and thus fixedly attached to the damping block 200, as needed, using a hot soldering iron. 3) The processes from steps 1) and 2) were repeated to prepare three separate cusp tools, each having a damping block covered by a release layer. 4) A cusp material according to one embodiment was formed from a composite material comprising an ePTFE membrane embedded with fluoro elastomer. A portion of the composite material about 10 cm wide was wound in a circular mandrel to form a tube. The composite material was composed of three layers: two outer layers of ePTFE and an inner layer of a fluorinated elastomer placed between them. The ePTFE membrane was manufactured in accordance with the general teachings described in US Patent No. 7,306,729. The fluorinated elastomer was formulated in accordance with the general teachings described in US Patent No. 7,462,675. Additional fluorinated elastomers may be suitable and are described in US Publication No. 2004/0024448.
[0095] [095] The ePTFE membrane had the following properties: thickness = about 15 µm; MTS in the direction of force majeure = about 400 MPa; MTS force in the orthogonal direction = about 250 MPa; density = about 0.34 g / cm3; IBP = about 660 kPa.
[0096] [096] The copolymer consists essentially of vinyl ether between about 65 and 70 weight percent perfluoromethyl viper ether in addition about 35 and 30 weight percent tetrafluoroethylene.
[0097] [097] The weight percent of fluorinated elastomer in relation to ePTFE was about 53%.
[0098] [098] The multi-layer composite material had the following properties: thickness of about 40 µm, a density of about 1.2 g / cm3, breaking strength / width in the direction of the maximum force = about 0.953 kg / cm , tensile strength in the direction of greatest force = about 23.5 MPa (3400 psi); breaking strength / width in the orthogonal direction = about 0.87 kg / cm, tensile strength in the orthogonal direction = about 2 0.4 MPa (3100 psi), bubble point IPA greater than about 12.3 MPa, Gurley number greater than about 1, 800 seconds and mass / area = about 14 g / m2.
[0099] [099] The following test methods were used to characterize the ePTFE layers and the multi-layer composite.
[0100] [100] The thickness was measured with a Mutitoyo Snap Gage Absolute Gage, 12.7 mm (0.50 ") in diameter, model ID-C112E, Serial # 10299, made in Japan. The density was determined by a calculation of weight / volume using a Mettler PM400 New Jersey, US analytical balance The breaking strength and breaking strength were measured using an Instron Model # 5500R Norwood, MA, 50 kg load cell, standard length = 25.4 centimeters, at crosshead speed = 25 mm / min (deformation speed of 100% = per minute), with flat-faced jaws.The IPA boiling point was measured by an IPA bubble point tester, Data Systems model LG industrial pressure regulator - Apok, Salt Lake City, UT, US, with a ramp rate of 1.38 kPa / s (0.2 psi / s), 3.14 cm2 of test area The Gurley Number was determined as the time in seconds for 100 cm3 of air to flow through a 6.45 cm2 sample at 124 mm of water pressure, using a Gurley tester, Model # 4110, Troy , New York, US.
[0101] [101] Unless otherwise stated, these test methods were used to generate the data in the following examples.
[0102] [102] The layers of composite material, each having two outer layers of ePTFE and an inner layer of a fluorinated elastomer placed between them, were wound in a mandrel that has a diameter of approximately 28 mm (1.1 ") in such a way that the direction of the greatest force of the membrane was oriented in the axial direction of the mandrel. In one embodiment, the four layers of the composite material were wrapped in a non-helical shape, generally circumferential over the mandrel. to the material adhere to itself. While still in the mandrel, the composite material was cut longitudinally, generally along the longitudinal axis of the mandrel, in order to form a cusp of about 10 cm (4 ") by about 90 mm (3 , 5 "). 5) The resulting sheet of the cusp material (or composite material from Step 4) was then cut and wound over the cusp tool 100 having a damping block 200 covered by a release layer 204. More specifically, as shown in Figures 3A - 3C, the material of the cusp 300 was placed on a flat cutting surface. The cusp tool 100 with the damping block 200 and the release layer 204 was then aligned over the cusp material 300 approximately as shown. Four slits 302, 304, 306, 308 were then formed in the cusp material 300 with a razor blade. A pair of slits 302, 304 extends from one side of the cusp tool 100 and ends at an edge 300a of the cusp material 300, and the other pair of slits 306, 308 extends from an opposite side of the cusp tool 100 and ends at an opposite edge 300b from cusp material 300. Slits 302, 304, 306, 308 have been moved away from cusp part 102 of cusp tool 100. Slits 302, 304, 306, 308 do not protrude under the cusp tool 100. It should be appreciated that the widths of the individual slots are not shown to scale. Slits 302, 304, 306, 308 in the cusp material 300 resulted in the formation of a folding part 310, a pair of straps 312, 314 and the excess material of cusp material 315. The folding portions 310 were then folded in the general direction indicated by the arrows 316 in Figure 3 and smoothed over the cusp tool 100, which was covered by the damping block 200 and the release layer 204 in the previous steps. 6) The cusp material 315 was then stretched and smoothed over the cusp portion 102, in particular the end of the surface 103 of the cusp tool 100. Steps 4) and 5) were repeated to form three separate cusp sets . The three cusp sets 402, 404, 406 were then attached together to form a tri-cusp assembly 400, as shown in Figure 4. The three separate cusp sets 402, 404, 406 are shown, each having an excess cusp material 315 that generically extends radially beyond the periphery of the tri-cusp assembly 400. 7) The base tool was then provided with cavities to enclose the final surfaces of the cusp tools of the tri-cusp set, trimming the excess cusp area to form three cusps. Referring to Figure 5A, the base tool is generally indicated by 500 and extends longitudinally between an end 501 and a lower opposite end 503. Three concave cavities 502, 504, 506 are formed at the end 501 of the base tool 500. Each concave cavity 502, 504, 506 is formed to match or lodge on the end surface 103 of one of the three cusp assemblies 402, 404, 406. The three radially extending elements 508, 510, 512 extend outwardly from from the end of the base tool 500. Each of the elements 508, 510, 512 is disposed between an adjacent pair of concave cavities 502, 504, 506.
[0103] [103] The base tool 500 was then prepared having a compression block and a release layer (not shown), similar to the way the cusp tool was prepared in Steps 1 and 2. As described for each tool cusp in Steps 1 and 2, the compression block and release layer were equally stretched and attached to the base tool 500 to form a base tool set. 8) Referring to Figure 5b, the tool base set (illustrated for convenience, as the base tool 500 without showing the damping block and release layer) and the three-leaf set, usually indicated by 400, were then, generally axially aligned together so that the end surface (not shown) of each cusp tool 100 has been fitted into one of the concave cavities (not shown) at the end 501 of the base tool, usually indicated by 500, to form a combined tool set. 9) An expandable metallic balloon was then manufactured. A 316 stainless steel tube having a wall thickness of about 0.5 mm (0.020 ") and a diameter of about 2.5 centimeters (1.0") was laser cut. A pattern was cut within the tube to form an annular cutting stent structure or on the support structure, which is generally indicated at 600 and shown illustratively in a flat surface view in Figure 6a. The support structure 600 includes a plurality of small closed cells 602, a plurality of large closed cells 604, and a plurality of closed cusp cells 606. Note that one of a plurality of closed cusp cells 606 appears as an open cell in Figure 6A, due to the view of the flat surface. Cells 602, 604, 606 are generally disposed along the lines that constitute the annular shape of the support structure 600. 10) polymeric materials were then adhered to the laser-cut stent frame. First, a sacrificial compression layer of the ePTFE membrane was wound without overlapping over a mandrel (not shown), having a diameter of about 2.5 cm (1.0 "). The sacrificial compression layer of the ePTFE membrane ePTFE had a thickness of about 0.5 mm (0.02 ") and a width of about 10 cm (4"), and was compatible and compressible to provide a soft sacrificial compression layer. 11) Four layers of a substantially non-porous ePTFE film were then wound over the mandrel on top of the compression layer membrane. The substantially non-porous ePTFE film has a thickness of about 25 µm (0.001 "), was about 10 cm (4") wide and had a layer of FEP on one side. The substantially non-porous ePTFE film was wrapped with FEP facing the mandrel. The substantially non-porous ePTFE film has the properties of the release layer described earlier in step 2). 12) A thin type 1 FEP film (ASTM D3368) was constructed using extrusion and elongation. 10 additional layers of this type 1 (ASTM D3368) FEP film was added to the mandrel, which was previously wrapped in the compression membrane layer in Step 10 and the four substantially non-porous layers of ePTFE film in Step 11. The type 1 FEP film (ASTM D3368) was about 40 μm (0.0016 ") thick and about 3" (7.7 cm) wide. 13) The coiled mandrel was then heat treated in an air convection oven at about 320 ° C for about 5 minutes and allowed to cool. 14) The support structure (indicated at 600 in Figure 6A), was then placed over the heat treatment and the rolled mandrel. Two additional layers of type 1 FEP film (ASTM D3368) (provided in Step 12) were then wound onto the support structure, which was previously placed over the wound mandrel. 15) The coiled mandrel and the support structure supported therein were then heat treated in an air convection oven at about 320 ° C for about 10 minutes and allowed to cool, forming a polymeric coated support structure. 16) The polymer-coated support structure was then cut with a scalpel to form a trimmed stent frame, which is generally indicated by the 700 and shown illustratively in a flat surface view in Figure 6B. More specifically, in one form, the polymer coating was cut about 2 mm (0.08 ") beyond the ends of the support structure (600, Figure 6A) to form a variety of edge profiles 708. In another form , the polymeric coating was left to cover whole cells to form a web in each cell In both cases, the support structure 600 was fully encapsulated within a polymeric coating 702, to form the structure of the cut stent 700. The structure of the cut stent 700 includes a plurality of cusp openings 704 corresponding in number and generally in the form of a plurality of closed cell cusp 606 (Figure 6A). In addition, a slot 706 is formed in the polymeric coating 702 of each of the small closed cells, as shown in Figure 6B Specifically, each slot 706 is linear and generally parallel to a central longitudinal axis (not shown) of the annular support structure 600. 17) The trimmed stent frame was then placed over the combined tool set from Step 8. The cusp portions (102) of the cusp tools were aligned with the cusp openings (704 in Figure 6B) in the cut stent frame. The three areas of excess dome material (315 in Figure 4) were pulled through the cusp openings in the stent structure. Each of the three pairs of clips (312, 314 in Figure 3A), was pulled through one of the slots (706 in Figure 6B) and wrapped around the structure of the cut stent. Each pair of strips were packed in directions with respect to the other. The six strips were then heated nailed to the cut stent frame using a hot soldering iron. 18) The combined tool assembly (Step 8) and the stent frame cut with the rolled strips and heat nailed were then mounted on a rotary mandrel mechanism. The rotating mandrel mechanism was then adjusted to apply a light longitudinal compression load. The excess areas of cusp material (315 in Figure 4) were then heated nailed to the base tool (500 in Figure 5), using a hot soldering iron. 19) The combined tools from Step 18 were then wrapped with two additional layers of a type 1 FEP film (ASTM D3368) (from Step 12). Three additional layers of the composite (Step 4) were then wrapped and glued to the cut stent structure. 20) In preparation for a final heat treatment, release and sacrifice layers of a compression tape and compression fiber were applied both circumferentially and longitudinally to the set of Step 19. The compression tape / fiber contacts and compresses the assembly both circumferentially and longitudinally during the subsequent heat treatment. A sacrificial layer of compression tape was encircled in a helical fashion over the whole of Step 19. This compression tape had the properties of the ePTFE sacrifice compression layer previously described in Step 10. An ePTFE compression fiber was then wrapped over the compression tape. About 100 loops of compression fiber were applied circumferentially in a spaced helical pattern. The compression ePTFE fiber was about 1 mm (0.04 ") in diameter and was structured to shrink longitudinally when sufficiently heated. The trapped assembly was then removed from the rotary mandrel mechanism. Three layers of Sacrifice compression tape was then wrapped in a longitudinal shape around the assembly.Approximately 20 loops of compression fiber was then wrapped longitudinally over the longitudinal compression tape.
[0104] [104] The assembly of Step 20 was then heat treated in an air convection oven at about 280 ° C for about 90 minutes and then cooled to room temperature. This heat treatment step facilitates the flow of the fluorinated thermoplastic elastomer into the pores of the ePTFE membrane used to create the cusp material described in step 4. 22) The sacrificial compression tapes / fibers were then removed. The polymeric materials were trimmed so that the cusp and base tools were separated. The polymeric stent layers were then cut to allow removal of the stent structure with the cusps attached. The cusps were then trimmed, resulting in a valve assembly, as shown in Figure 8, and generally indicated at 800.
[0105] [105] The resulting assembly valve 800, according to one embodiment, includes 802 cusps formed from a composite material with at least one layer of fluorinated polymer having a plurality of pores and an elastomer present in substantially all pores of the layer of at least one fluorinated polymer. Each cusp 802 is movable between a closed position, shown illustratively in Figure 9A, in which blood is prevented from flowing through the valve assembly, and an open position, shown illustratively in Figure 9B, in which blood is allowed to flow through the valve assembly. Thus, the cusps 802 of the valve assembly 800 of the cycle between the open and closed positions to regulate the general direction of blood flow in a human patient.
[0106] [106] The performance of the valve cusp in the assembly of each valve was characterized by a real-time pulse duplicator that measures typical anatomical pressures and typical anatomical flows through the valve, generating an initial set or "zero fatigue" data for the particular valve assembly. The valve assembly was then transferred to a high-frequency fatigue tester, and underwent about 207 million cycles. After each block of about 100 million cycles, the valve was then returned to the pulse duplicator in real time and the performance parameters measured again.
[0107] 1) O conjunto de válvula foi colocado em um anel anelar de silicone (estrutura de suporte) para permitir que o conjunto de válvula fosse posteriormente avaliado num duplicador de pulsos em tempo real. O processo de encapsulamento foi realizado de acordo com recomendações do fabricante de duplicador de pulso (Vi Vitro Laboratories Inc., Victoria BC, Canadá). 2) O conjunto de válvula de vaso foi então colocado dentro de um sistema de fluxo de impulsos do coração esquerdo duplicador em tempo real. O sistema duplicador de fluxo de pulso incluiu os seguintes componentes fornecidos pelo VSI Vivitro Systems Inc., Victoria BC, Canadá: um Super Pump, Servo Amplificador de Potência Número da peça SPA 3891; uma cabeça Super Pump, Part Number SPH 5891 B, 38,320 cm2 de área cilindro; uma estação de válvula / dispositivo elétrico, um gerador de formulário de onda, Número da peça Tripack TP 2001; um Sensor interface, Número da peça VB 2004; um Sensor Amplificador Componente, Número da peça AM 9991, e uma onda quadrada Electro Magnetic Flow Meter, Carolina Medical Electronics Inc., East Bend, NC, EUA. [107] Flow performance was characterized by the following process: 1) The valve assembly was placed on a silicone ring (support structure) to allow the valve assembly to be subsequently evaluated in a pulse duplicator in real time. The encapsulation process was performed according to the recommendations of the pulse duplicator manufacturer (Vi Vitro Laboratories Inc., Victoria BC, Canada). 2) The vessel valve assembly was then placed inside a left-hand duplicating heart pulse flow system in real time. The pulse flow duplicator system included the following components provided by VSI Vivitro Systems Inc., Victoria BC, Canada: a Super Pump, Power Amplifier Servo Part number SPA 3891; a Super Pump head, Part Number SPH 5891 B, 38,320 cm2 of cylinder area; a valve / fixture station, a waveform generator, Part number Tripack TP 2001; an Interface sensor, Part number VB 2004; a Component Amplifier Sensor, Part Number AM 9991, and a Square Wave Electro Magnetic Flow Meter, Carolina Medical Electronics Inc., East Bend, NC, USA.
[0108] [108] In general, the duplication system uses a fixed displacement pulse flow, the piston pump to produce a desired fluid flow through the valve under test. 3) The flow of the heart pulse duplicator system was adjusted to produce the desired flow rate, mean pressure, and simulated pulse rate. The valve under test was then subjected to a cycle of about 5 to 20 minutes 4) Pressure and flow data were measured and collected during the test period, including ventricular pressures, aortic pressures, flow rates and piston pump position. Illustrated in Figure 10 is a graph of the results of typical flow data from the cardiac pulse duplicator system. 5) The parameters used to characterize the valve and to compare it with the post-fatigue values are the pressure drop through the open valve, during the part of the positive pressure flow forward, the effective area of the orifice, and the fraction regurgitation.
[0109] [109] After characterization, the valve assembly was then removed from the flow pulse doubling system and placed on a high-frequency fatigue tester. The Durability Tester Heart Valve Position Six, Part Number M6 was supplied by Dynatek, Galena, MO, US, and was powered by a Dynatek Dalta DC 7000 Controller. This high fatigue rate of the tester displaces fluid through a valve assembly with a typical cycle rate of about 780 cycles per minute. During the test, the valve assembly can be examined visually using a tuned strobe light. The pressure drop through the closed valve can also be monitored as shown in Figures 11A and 11B. Figures 11A and 11B show a typical set of verification data that the high-rate fatigue tester was producing consistent pressure waveforms.
[0110] [110] The valve assembly has been continuously recycled and monitored periodically for visual changes and pressure drops. After about 200 million cycles, the valve assembly was removed from the high frequency tester and returned to the pulse duplicator in real time. The pressure and flow data were collected and compared with the original data collected.
[0111] [111] A screen capture is shown in Figure 12A showing typical outputs of data measured from the flow of the heart pulse duplicator system in real time. Ventricular pressures, aortic pressures and flow are shown. The initial fatigue or zero data for a particular valve is shown illustratively in Figure 12A. The same measurements were taken and data were collected by the same special valve after 207 million cycles. The 207 million cycle data for the special valve is shown illustratively in Figure 12B. Both sets of measurements were taken at 5 liters per minute flow rate and 70 cycles per minute rate. Comparing Figures 12A and 12B, it should be readily understood that the waveforms are substantially similar, indicating that there were no significant changes in the performance of the cusp valve after about 207 million cycles. The pressure drop, the effective orifice area (EOA), and the regurgitation fraction measured at zero and 207 million cycles are summarized in Table 1 below.
[0112] [112] In general, it has been observed that valve cusps built according to the embodiments described here do not exhibit physical or mechanical degradation, such as tears, holes, permanent deformation and the like, after 207 million cycles. As a result, there was also no observable change or degradation in the closed and open configurations of the valve cusps, even after 207 million cycles. Example 2
[0113] [113] The heart valve having polymeric cusps connected to a rigid metallic structure was constructed according to the following process:
[0114] [114] A mandrel 900 has been machined from PTFE which has a shape shown in Figure 14. Mandrel 900 has a first end 902 and an opposite second end 904, and extends longitudinally therebetween. Mandrel 900 has an outer surface 910 which has three (two shown) generally arched convex lobes 912, each generally for forming cusps (not shown) of a finished valve assembly (not shown). The outer surface 910 also includes a seating frame area 920 for the positioning of a valve structure (930 in Figure 5), in relation to the convex lobes 912 prior to the formation of the valve leaflets on the frame.
[0115] [115] As shown in Figure 15, a valve structure 930 was laser cut from a length of 316 stainless steel tube with an outer diameter of about 25.4 millimeters and a wall thickness of about 0, 5 mm in the shape shown in Figure 15. In the shown embodiment, the structure of valve 930 extends axially between a lower end 932 and an opposite upper end, generally defined by a plurality of which extends axially, generally in the form of poles. spiral 934 corresponding to the number of valve cusps to be terminated (not shown). In the specific embodiment shown, three posts 934 are formed in the structure of valve 930.
[0116] [116] Two layers of thickness of about 4 µm of FEP film (not shown) were wrapped around the 930 valve structure and baked in an oven for about 30 minutes at about 270 ° C and allowed to cool. The resulting covered valve structure (for clarity, shown uncovered and indicated in 930) was then slid upward onto the mandrel 900, so that the complementary features between the valve structure 930 and the mandrel 900 are fitted together, as shown in Figure 16.
[0117] [117] A cusp material was then prepared with a layer of ePTFE membrane embedded with a fluorinated elastomer. More specifically, the ePTFE membrane layer was manufactured in accordance with the general teachings described in US Patent No. 7,306,729. The ePTFE membrane has been tested in accordance with the methods described in the Appendix. The ePTFE membrane had a mass per unit area of about 0.57 g / m2, a porosity of about 90.4%, a thickness of about 2.5 μm, a boiling point of about 458 kPa , a tensile strength of the matrix of about 339 MPa, in the longitudinal direction and about 257 MPa in the transverse direction. This membrane was embedded with the same fluorinated elastomer as described in Example 1. The fluorinated elastomer was dissolved in Novec HFE7500, 3M, St Paul, MN, US, at a concentration of about 2.5%. The solution was covered using a Mayer bar over the ePTFE membrane (while being supported by a polypropylene release film) and dried in a convection oven set at about 145 ° C for about 30 seconds. After two coating steps, the resulting ePTFE / fluorinated composite material had a mass per unit area of about 3.6 g / m2.
[0118] [118] The composite material (not shown) was then wrapped around the assembled mandrel 900 and valve structure 930. In one embodiment, a total of 20 layers of the ePTFE / fluorinated elastomer composite was used. Any excess composite material that extended beyond the ends of the mandrel 900 was twisted and pressed lightly against the ends 902, 904 of the mandrel 900.
[0119] [119] The composite material of the coiled mandrel was then mounted in a pressure vessel so that a discharge port 906 (Figure 14) at the base or second end 904 of mandrel 900 was probed into the atmosphere. The vent 906 extends from the second end 904 axially through the mandrel 900 and communicates with a vent 908 which generally extends perpendicularly through the outer surface 910 of the mandrel 900. The vent ports 906, 908 , in addition to other ventilation ports, which can be provided on the mandrel as needed (not shown), allow the air trapped between the composite material and the mandrel to escape during the molding process.
[0120] [120] About 690 kPa (100 psi) of nitrogen pressure was applied to the pressure vessel, forcing the ePTFE / fluorinated elastomer composite against the mandrel 900 and the valve structure 930. Heat was applied to the pressure vessel until the temperature inside the reactor reached about 300 ° C, about 3 hours later. The heater was turned off and the pressure vessel was allowed to cool to room temperature overnight. This process thermally bonded the ePTFE / fluorinated elastomer composite layers to each other and to the FEP coating of the 930 valve structure. The pressure was released and the mandrel was removed from the pressure vessel.
[0121] [121] The ePTFE / fluorinated elastomer composite was cut circularly at two locations: first, at the lower end 932 of the valve structure 930, and second, near the upper end of the valve structure 930 along a circle intersecting usually near the midpoint of each post 934. The resulting valve assembly 940 consists of the valve structure 930 and the cut composite material has been separated and slid from the mandrel. The molded valve assembly 940, as shown in Figure 17, includes the structure of the valve. valve 930 and a plurality of cusps 950 formed from trimmed composite material. In one embodiment, valve assembly 940 includes three cusps. In another embodiment, each cusp 950 in the 940 valve assembly is approximately 40 μm thick.
[0122] [122] To help control the degree of openness of the valve, adjacent cusps on each post were connected together. As shown in Figure 18, adjacent cusps 950a, 950b were wrapped around post 934 and connected together to form a seam 954. Seam 954 had a depth 956 extending to at least about 2 mm from from post 934. To support the connection between the adjacent cusps 950a, 950b, connecting member 952 was rigidly attached to internal surfaces of the adjacent cusps 950a, 950b thus building the seam 954 between the adjacent cusps 950a, 950b. As shown in Figure 18, the fixture 952 is generally rectangular. It should be appreciated, however, that other shapes for the fastening element can be used. The fixture 952 was formed from the same type of composite material used to form the 950 cusps. The fixture 952 was rigidly attached to the interior surfaces of the adjacent cusps 950a, 950b, using the fluorinated elastomer solution described above. These steps were repeated for the other adjacent cusp pairs in the valve assembly.
[0123] [123] The performance and durability of the valve cusps in this example were analyzed in the same way as described in Example 1. The valve assembly was initially characterized in the same pulse duplicator in real time, as described in Example 1, which measured typical anatomical pressures and flow through the valve, generating an initial "zero fatigue" or data set for that particular valve set. The valve was then subjected to accelerated tests as in Example 1. After about 79 million cycles, the valve was removed from the high rate fatigue tester and the hydrodynamic performance characterized again as in Example 1. The valve was finally removed in about 198 million cycles. The pressure drop, OAE and the regurgitation fraction measured at about 79 million cycles and about 198 cycles are summarized in Table 2 below.
[0124] [124] Figures 13A and 13B show similar results for a similar valve. Figure 13A is a graph of the measured output data from the pulsation doubling system flow made after about 79 million cycles. The same measurements were made for the similar valve after about 198 million cycles, a graph of which is shown illustratively in Figure 13B. Both sets of measures were taken at about 4 liters per minute of flow and at a rate of about 70 cycles per minute. Comparing Figures 13A and 13B, it should again be appreciated that the waveforms are significantly similar, indicating that there were no significant changes in the performance of the valve cusp after about 198 million cycles. The pressure drop, the effective orifice area (EOA), and the regurgitation fraction measured at 0, about 79, and about 198 million cycles are summarized in Table 2 below. These data indicate no substantial change in valve cusp performance after about 198 million cycles.
[0125] [125] A heart valve having polymeric cusps attached to a rigid metal structure was constructed according to the following process:
[0126] [126] The support frame or valve frame 960 has been laser cut from a length of 316 stainless steel tube with an outside diameter of about 25.4 mm and a wall thickness of about 0.5 mm in the form shown in Figure 19. In the embodiment shown, structure 960 extends axially between a lower end 962 and an opposite upper end generally defined by a plurality of axial extensions, generally in the form of spiral posts 964 corresponding to the number of cusps valve that is intended to terminate (not shown). The parabolic top end 968 extends between adjacent posts 964. In the specific embodiment shown, three posts 964 and three top edges 968 form the top end of frame 960. The corners of the frame that would be in contact with the material of the cusp were rounded using a rotary sander and hand polished. The structure was rinsed with water and then cleaned with plasma using a PT2000P plasma treatment system, Tri-Star Technologies, El Segundo, CA, US.
[0127] [127] In one embodiment, a damping member is provided between at least part of the structure and at least part of the cusp to minimize stress related to direct contact between the structure and the cusp. A composite of ePTFE and silicone fiber was created by first embedding an ePTFE membrane with MED -6215 silicone (NuSil, Carpinteria, CA, US), cut to a width of about 25 mm, and a substantially fiber material round. The ePTFE used in this fiber has been tested in accordance with the methods described in the Appendix. The ePTFE membrane had a bubble point of about 217 kPa, a thickness of about 10 µm, a mass per unit area of about 5.2 g / m2, a porosity of about 78%, a tensile strength of the matrix in a direction of about 96 MPa, and a tensile strength of the matrix of about 55 MPa in the orthogonal direction. The fiber composite 966 was wrapped around each of the posts 964 of the structure 960, as shown in Figure 20.
[0128] [128] A mandrel 970 was formed using stereolithography in the form shown in Figure 21. Mandrel 970 has a first end 972 and an opposite second end 974, and extends longitudinally therebetween. Mandrel 970 has an outer surface 980 with three (two shown), in general, arched convex lobes 982, each in general for forming valves (not shown) of a finished valve assembly (not shown). The outer surface 980 also includes a frame seating area 984 for positioning the frame (960 in Figure 19) in relation to the convex lobes 982 prior to the formation of the valve cusps on the valve frame.
[0129] [129] Mandrel 970 was then spray coated with a PTFE mold release agent. Four layers of the ePTFE membrane previously described in this example were wrapped around the mandrel. MED -6215 was swept in the ePTFE and allowed to get wet and to substantially fill the pores of the ePTFE. Excess MED -6215 was erased and frame 960 with fiber composite 966 wrapped posts 964 was positioned on mandrel 970 along structure seating area 984, as shown in Figure 22. MED-4720 silicone, NuSil, Carpinteria, CA , US, was placed along the upper edges 968 of the frame 960 and along the posts 964 of the frame 960 to create strain relief on the cusp (not shown). Eight additional layers of ePTFE were wrapped around frame 960 and mandrel 970. Additional MED -6215 was swept into the ePTFE and allowed to wet to substantially fill the pores of the ePTFE. Another 8 layers of ePTFE were wrapped around frame 960 and mandrel 970. These layers form a blotter to absorb any excess silicone during the molding process and were removed after the silicone was cured.
[0130] [130] Forms of silicone rubber (not shown) molded with a surface exactly matching the reverse shape of the mandrel surface were previously manufactured for each of the three cusp-forming characteristics. These shapes were coated by spraying with PTFE to release the mold and then coupled with the mandrel matching feature. About 50 turns of an ePTFE fiber (not shown), were wrapped around the silicone molds to apply generally radial pressure, to the valve against the mandrel.
[0131] [131] This set was then placed in an oven at about 100 ° C for about 1 hour to cure the silicone. After cooling, the fiber and silicone forms were removed, the eight layers of the ePTFE blotter were peeled off and discarded, and the resulting valve (not shown) was slid out of the mandrel. The posts were cut using pliers and the excess length of the cusp material and the excess length of the material at the base of the structure was carefully trimmed with scissors to form a completed valve assembly, which is shown and usually indicated by 990 in Figure 23. Thus, in one embodiment, the valve assembly 990 was formed having the frame or support structure 960, a plurality of cusps 992 supported on the support structure 960 and movable between the open and closed positions to regulate flow of blood through valve assembly 990, and a fiber composite of 966 wrapped in post 964 located between at least part of the support structure 960 and at least part of each cusp 992 to minimize cusp stress due to coupling and / or proximity of the cusps to the support structure. In another embodiment, the damping element is formed from a composite material with at least one layer of fluorinated polymer having a plurality of pores and an elastomer present in virtually all pores, as described above.
[0132] [132] It should be understood that other support structures, others that as specifically shown in the Figures can be used. In addition, the damping members can be used anywhere along the support structure, as necessary to minimize stress on the cusps due to coupling and / or proximity of the cusps to the support structure. For example, a damping member (s) can be coupled to the support structure along the upper edge in parabolic shape.
[0133] [133] It should also be appreciated that the damping members can be formed as sheets and wrapped around the desired positions along the support structure, or be formed from fibers of various shapes and sizes in cross section.
[0134] [134] It should also be appreciated that the damping members can be formed as tubes and slid along the ends of the support structure, or be cut longitudinally and positioned around the desired location along the support structure.
[0135] [135] The cusps of the complete valve assembly were measured and determined to have an average thickness in the center of each cusp of about 120 µm.
[0136] [136] The valve assembly was then characterized by flow performance and subjected to accelerated testing as in Example 1. After each block of about 50 million cycles, the valve assembly was removed from the fatigue testing device. high rate and hydrodynamic performance again characterized as in Example 1. The valve assembly was finally removed in about 150 million cycles demonstrating acceptable performance and no hole formation. Comparative Example A
[0137] [137] Six valves were constructed in the manner of Example 1 with the exception that the elastomer was not incorporated. The ePTFE material was the same as described in Example 1, but it was not soaked with the fluorinated copolymer and was instead coated with a discontinuous layer of FEP copolymers that served as a thermoplastic adhesive. The valves were constructed as in Example 1, with each cusp comprising three layers of membrane, resulting in a cusp with an average final thickness of about 20 μm. After the hydrodynamic characterization, the valves were mounted on the Dynatek accelerated test device described in Example 1. For about 40 million cycles, delamination of the extremity and formation of holes in the cusps was observed and the test was interrupted. Comparative Example B
[0138] [138] Two valves were constructed in the manner of Example 1, but the elastomer part of the embodiments was not incorporated. The material used was that of the thin ePTFE membrane that has properties similar to the following: a mass per area of about 2.43 g / m2, a porosity of about 88%, an IBP of about 4.8 kPa, a thickness of about 13.8 μm, a tensile strength of the matrix in a direction of about 662 MPa and a tensile strength of the matrix of about 1.2 MPa in the orthogonal direction. The ePTFE membrane has been tested in accordance with the methods described in the Appendix. Ten layers of the membrane were placed in alternating directions for a pile and then placed on the tool set, as described in Example 1. The tool set was then exposed to about 350 ° C in an oven. air convection for about 25 minutes, removed and cooled in a water bath. The three pieces of tools were then inserted into the stent structure and the cusps attached to the valve assembly with FEP as in Example 1.
[0139] [139] Each of the valves was subjected to high flow rate fatigue tests using the real-time heart rate doubling system, as described above. After about 30 million cycles on one valve and about 40 million cycles on another valve, visual degradation, including stiffness and deformation, was observed and measurable decrease in performance was noted. In addition to the visual and measurable degradation in performance, Table 3 below summarizes the pressure drop, the effective orifice area (EOA), and the regurgitation fraction measured after about 40 million cycles.
[0140] [140] The material properties of the following non-limiting examples are provided in FIG. 42, Table 4, by reference to the individual descriptions, where, as parts of the previous exemplary embodiments are listed with the same prime numbers. Example 4a
[0141] [141] In exemplary embodiments, a heart valve having polymeric cusps formed from a composite material with an expanded fluorinated polymer membrane and an elastomeric material and joined with a semi-rigid, non-dismountable metal structure, and a strain relief and a sewing ring was constructed according to the following process:
[0142] [142] The valve frame is manufactured from a MP35N chromium-cobalt tube-length laser with a 26.0 mm outer diameter and a 0.6 mm wall thickness as shown, illustratively and , usually indicated at 1000 in Figure 24. The structure of 1000 was electro-polished, resulting in 0.0127 mm of material removal from each surface and leaving the edges rounded. The 1000 structure was exposed to a superficial roughness step to improve the adherence of the cusps to the 1000 structure, without degrading the fatigue durability performance. Structure 1000 was cleaned by immersion in an acetone ultrasound bath for about five minutes. The surface of the entire metal structure was then subjected to a plasma treatment using methods generally known to those of ordinary skill in the art. This treatment also serves to improve the wetting of the fluorinated ethylene propylene adhesive (FEP).
[0143] [143] FEP powder (Daikin America, Orangeburg NY) was then applied to the structure. More specifically, the FEP powder was stirred to form a "cloud" in the air in a closed mixing apparatus, such as a type of standard kitchen mixer, while the structure is suspended in the cloud. The structure was exposed to a cloud of FEP powder until a uniform layer of powder was adhered to the entire surface of the structure. The structure was then subjected to a heat treatment, placing it in a forced air oven set at 320 ° C for about three minutes. This caused the powder to melt and adhere as a thin coating over the entire structure. The structure was removed from the oven and left to cool to room temperature.
[0144] [144] The strain relief and a sewing ring was attached to the frame as follows. A 23 mm diameter cylindrical shaft was wrapped with a single layer of Kapton ® (El DuPont de Nemours, Inc., Wilmigton, DE) polyimide film and held in place by a strip of Kapton ® tape over the length of the overiapping seam. A two-layer laminate wrapper consisting of a laminated ePTFE membrane for a 25.4 μm thick fluorine layer, as described in Example 1, has been wrapped with the high strength of the membrane aligned along a generally direction parallel to the axis of the Kapton ® mandrel covered with any substantially overlap in the seam. The frame was aligned coaxially over the wrapped mandrel. An additional wrap of the two-layer laminate was wound over the entire frame encapsulation mandrel with the seam oriented 180 ° from the junction line of the single inner wrap. The four-layer laminate was cut end about 135 mm from the base of the encapsulated frame inside. The four-layer laminate was rolled axially towards the base of the frame until the 135 mm material length formed approximately 3 mm in diameter from the outer ring adjacent to the base of the structure. The final four laminated layer was cut approximately 20 mm from the top of the structure and the assembly was helically wound compression with two sacrificial layers of ePTFE membrane embedded with a polyimide, four layers of non-sintered ePTFE membrane, and about a hundred of an ePTFE fiber bandage. The whole set was subjected to a heat treatment, placing it in a forced air oven set at 280 ° C for five minutes and returning to room temperature by quenching water immediately after removal from the oven. The sacrificial layers were removed and the four-layer laminate at the top of the structure cut out to allow about 2 mm in length to extend beyond the perimeter of the upper part of the structure. The Kapton and mandrel were then removed from the interior of the structure, resulting in the frame assembly, generally indicated in 1010 in Figure 25, having the 1012 and 1014 ring seam strain relief with the 1000 laminated inner frame.
[0145] [145] A single female mold or base tool, shown illustratively and indicated at 50 in Figure 5a, is provided with concave cavities (502, 504, 506) generally defining the shape of the tricuspid. Three mold cores or cusp tools (100) are provided with the corresponding end surfaces (103) in shape and contour with the concave cavities in the base tool. The cusp tools are hingedly linked to each other, which helps maintain relative axial and rotational spacing, as illustrated in the tricuspid assembly (400) in Figure 5a. The base tools and a cusp are wrapped with a single layer of non-sintered ePTFE membrane to form a damping layer, and then a layer of substantially non-porous ePTFE membrane with FEP on one side is used to adhere the membranes together and for the chucks with a soldering iron. The sacrificial layers ensure that all contact surfaces between the base and the cusp tools have a cushioning layer when compressed, an additional function that is a release layer to prevent the cusp material from sticking to the tools. The base tools and a cusp are initially combined to create a single cylindrical structure or combined tool set, as shown in Figure 5b, to facilitate construction and cusp attached to the frame with strain relief and the sewing ring component across of a ribbon winding process, as discussed in detail below.
[0146] [146] A cusp material was then prepared. An ePTFE membrane was manufactured in accordance with the general teachings described in US Patent 7,306,729. The ePTFE membrane has a mass per unit area of 1.15 g / m2, a bubble point of 79.7 MPa, a thickness of about 1016 nm, a tensile strength of 410.9 MPa, in the direction longitudinal and 315.4 MPa in the transverse direction. This membrane was embedded with a fluorinated elastomer, as described above in Example 1. The fluorinated elastomer was dissolved in Novec HFE7500 (3M, St. Paul, MN) at a concentration of 2.5%. The solution was coated using a Mayer bar over the ePTFE membrane (while being supported by a polypropylene release film) and dried in a set convection oven at 145 ° C for 30 seconds. After two coating steps, the final fluorinated ePTFE / elastomer or composite had a mass per unit area of 4.08 g / m2, 28.22% by weight of fluorinated polymer, a 15.9 kPa burst strength dome , and thickness of 1.93 µm.
[0147] [147] Three layers of cusp, or the composite material has been wrapped around the tool set combined with a rich elastomer side of the composite back to the tools. In exemplary embodiments, the composite material is oriented to have a predetermined matrix tensile strength along a direction generally parallel to the longitudinal axis of the combined tool set. More specifically, the tensile strength of the predetermined matrix is about 410 MPa.
[0148] [148] Referring to Figures 26a and 26b, the assembly structure 1010 was positioned coaxially over the combined tool set, usually indicated by 1020, along the three internal turns of the composite material. The assembly of frame 1010 has also been rotationally aligned to match the characteristics of the tool base 500 ', as described in Figure 26a. Twenty-three additional layers of the composite material were wrapped around the 1020 combined tool set with the rich elastomer side of each layer facing the tools previously delimited by the three layers of composite material mentioned above. In exemplary embodiments, the additional layers of the composite material were each oriented to have a predetermined matrix tensile strength along a direction generally parallel to the longitudinal axis of the combined tool set. In one embodiment, the tensile strength of the predetermined matrix was about 410 MPa. The cusp tools 100 'were then removed from under the twenty-six layer composite laminate tube.
[0149] [149] Each of the cusp tools 100 'was then rotated around their respective final pivot, as shown in Figure 26b, to allow the composite laminated tube 1015 from the previous step to be positioned between the cusp tools 100' . The cusp tool set was coaxially aligned with the base tool 500 'and the cusp tools 100' were rotated inwardly relative to one another to compress the twenty-six layer composite laminated tube over the mold surface of the triple configuration female cusp of the 500 'base tool. The combined tool set comprising the cusp and base tools, composite laminate, strain relief, frame, and a sewing ring was then mounted between the fixed and translational parts of an electrical device. Both radial and axial compression, were applied by radially tightening to the 100 'cusp tools, while simultaneously applying an axial load with the translational end of the clamping device.
[0150] [150] The combined tool set was then helically compressed with two layers of sacrificial ePTFE-compatible membrane, embedded with a polyimide, four layers of non-sintered ePTFE membrane, and about one hundred wraps of an ePTFE fiber. The entire assembly was removed from the lathe and placed in a fixture to maintain axial compression, when subjected to a heat treatment, placing them in a forced air oven, adjusted to about 280 ° C for about 30 minutes. The assembly was removed from the oven and brought back to room temperature by means of immediate water quenching. The sacrificial layers, cusp and base tools were removed leaving a fully adhered valve in a closed three-dimensional shape.
[0151] [151] The excess cusp material was cut with scissors from the top of the frame posts to the common triple point of each cusp to create three commissures or regions of coapting surface, as shown in Figure 27. The cusps were opened with a mandrel conical ePTFE from 10 mm to 25 mm. Ring seam ring 1014 at the base of frame 1000 was molded on a flange, placing frame assembly 1010 between corresponding halves 1030A, 1030B of an element, as shown in Figures 28 and 29, and placing the assembly on a welder of ultrasound compression (not shown), such as a model # 8400 welder ultrasound compression made by Branson ultrasound, Danbury CT. A welding time of about 0.8 seconds and the holding time of about 3.0 seconds and the pneumatic pressure of about 0.35 MPa, was applied to the assembly. The ultrasound welding process was carried out twice to create a seam ring with a flange thickness of approximately 2 mm with an outside diameter of 33 mm. The final valve assembly is shown, illustratively and, generally indicated at 1100 in Figure 30.
[0152] [152] The final cusp was composed of 28.22% by weight of fluorinated polymer with a thickness of 50.3 μm. Each cusp had 26 layers of the composite and a thickness / number of layers ratio of 1.93 μm.
[0153] [153] The resulting valve assembly 1100 includes cusps 1102 formed from a composite material with more than one layer of fluorinated polymer having a plurality of pores and an elastomer present in substantially all pores of the layer of more than one fluorinated polymer . Each cusp 1102 is movable between a closed position, shown illustratively in Figures 30A, in which blood is substantially prevented from flowing through the valve assembly, and an open position, shown illustratively in Figure 30B, in which blood is allowed to flow through valve assembly. Thus, the cusps 1102 of the valve assembly 1100 cycle between the open and closed positions to regulate the general direction of blood flow in a human patient.
[0154] [154] Hydrodynamic performance was measured before the accelerated wear test. The performance values were: OAE = 1.88 cm2 and regurgitation fraction = 10.86%. No observable damage was recorded during durability tests with the number of cycles approaching 100 million. Example 4b
[0155] [155] In exemplary embodiments, a heart valve was constructed with a strain relief valve structure, the seam ring, and the first three layers of composite material, as described above in Example 4A, and using a composite material comprising a final cusp with a mass per unit area of 11.80 g / m2, 9.74% by weight of fluorinated polymer, a bursting strength of 17.3 kPa, and a thickness of 5.78 μm , after the coating steps.
[0156] [156] Six additional layers of the composite material were wrapped around the combined molds of Figure 26a, with the orientation of the membrane as described in Example 4a.
[0157] [157] The assembly was molded, thermally processed, and trimmed, as described in Example 4a.
[0158] [158] The final cusp was composed of 9.74% by weight of fluorinated polymer with a thickness of 52.0 μm. Each cusp had 9 layers of composite material and a thickness / number of layers ratio of 5.78 μm.
[0159] [159] Hydrodynamic performance was measured before the accelerated wear test. The performance values were: EOA = 2.05 cm2 and regurgitation fraction = 11.71%. Observable damage was recorded as a detachment during durability tests of about 6 million cycles. Example 4c
[0160] [160] In exemplary embodiments, a heart valve was constructed with a valve structure that was laser machined and coated with FEP, as described above in Example 4a, and further provided with a damping element attached to the perimeter of the structure adjacent to the cusp regions to minimize stress related to direct contact between the structure and the cusp.
[0161] [161] The 0.5 mm thick ePTFE fiber was helically wrapped in a 1.143 mm mandrel with a pitch that eliminated space between the windings. Two layers of 2.54 μm FEP film were wrapped over ePTFE fiber spools and then subjected to a heat treatment, placing them in a forced air oven at 320 ° C for about three minutes. The material was brought back to room temperature by cooling the air to room temperature. The ePTFE fiber formed a coil of contiguous tube, once removed from the mandrel. The spiral tube was cut to three lengths of 125 mm and an axial slit leaving only five millimeters intact as a spiral tube. Each of the three lengths was slid from the FEP-coated frame to form the structure 1000'with the damping element 1030 connected to it to minimize the stress related to direct contact between the structure 1000 'and the cusp (not shown), as shown illustrated in Figure 31.
[0162] [162] The valve structure, strain relief, the sewing ring, the cusp material, and the first layer of composite material were prepared, as described in Example 4a, by encapsulating the damping members and the structure. The cusp material was prepared in such a way that after the coating steps, the final composite had a mass per unit area of 25.48 g / m2, 8.91% by weight of fluorinated polymer, a burst strength dome 31.7 kPa, and a thickness of 13.08 µm.
[0163] [163] Three additional layers of the composite material were wound around the molds combined with the membrane orientation, as described in Example 4a.
[0164] [164] The assembly was molded with the damping members, thermally processed, and trimmed, as described in Example 4a, to form the definitive valve assembly 1100'with structure 1000 'and the damping element 1030 connected to it for minimize the stress related to direct contact between the 1000 'structure and the 1102 "cusps, as shown in Figure 32.
[0165] [165] The final cusp was composed of 8.91% by weight of fluorinated polymer with a thickness of 52.3 μm. Each cusp had four layers of the composite and a thickness / number of layers ratio of 13.08 μm.
[0166] [166] Hydrodynamic performance was not measured before the accelerated wear test. Observable damage was recorded as a formation of holes in the cusp during durability tests of about 12.4 million cycles. Example 5
[0167] [167] In exemplary embodiments, a heart valve was constructed having a strain relief valve structure, sewing ring, cusp material, and first three layers of composite material were prepared, as described in Example 4a, and still having the last cusp described immediately below.
[0168] [168] Fifteen additional layers of the composite material were wrapped around the molds and combined with the orientation of the membrane as described in Example 4a.
[0169] [169] The assembly was molded, thermally processed, and trimmed, as described in Example 4a.
[0170] [170] The final cusp was composed of 9.74% by weight of fluorinated polymer with a thickness of 98.3 μm. Each cusp had 18 layers of the composite and a thickness / number of layers ratio of 5.46 μm.
[0171] [171] Hydrodynamic performance was measured before the accelerated wear test. The performance values were: OAE = 1.73 cm2 and regurgitation fraction = 11.71%. Observable damage was recorded as detachment and delamination of the cusp during durability tests in about 100 million cycles. Example 6
[0172] [172] In exemplary embodiments, a heart valve was constructed having a valve structure, the damping layer, strain relief, and a seam ring were prepared, as described in Example 4c, and still having the final cusp as described immediately below.
[0173] [173] A cusp material was then prepared. The ePTFE membrane had a mass per unit area of 0.31 g / m2, a bubble point of 0.11 MPa, a thickness of about 127 nm, a tensile strength of the matrix of 442.0 MPa in the direction longitudinal and 560.0 MPa in the transverse direction. This membrane was embedded with a fluorinated elastomer as described in Example 4a. After the coating steps, the final fluorinated ePTFE / elastomer or composite had a mass per unit area of 1.04 g / m2, 29.9% by weight of fluorinated polymer, a 9.9 KPa burst strength dome , and thickness of 0.52 μm.
[0174] [174] Ninety-five layers of the composite were wrapped around the molds combined with the membrane oriented in such a way that the tensile strength of the 442 MPa matrix is axially oriented and the elastomer enriched next to the membrane facing the molds, as as described in Example 4a.
[0175] [175] The assembly was molded, thermally processed, and trimmed, as described in Example 4a.
[0176] [176] The final cusp was composed of 29.00% by weight of fluorinated polymer with a thickness of 49.7 μm. Each cusp had 95 layers of the composite and a thickness / number of layers ratio of 0.52 μm.
[0177] [177] Hydrodynamic performance was measured before the accelerated wear test. The performance values were: OAE = 2.19 cm2 and fraction of regurgitation = 9.7%. No observable damage was recorded during the durability tests. Example 7
[0178] [178] In other exemplary embodiments, a heart valve having polymeric cusps was formed from a composite material with an expanded fluorinated polymer membrane and an elastomeric material, attached to an expandable stent-shaped metal balloon, and was constructed from according to the following procedure:
[0179] [179] An expandable stent-framed metal balloon was laser machined from an annealed tube segment of MP35N alloy with an external diameter of 26.00 mm and a wall thickness of 0.60 mm. A pattern was cut into the tube to form a cylindrical cut stent structure, also referred to herein as a support structure, as illustrated and generally indicated by 600 in the plan view of Figure 6a. The support structure 600 includes a plurality of small closed cells 602, a plurality of large closed cells 604, and a plurality of closed cusp cells 606. Note that one of a plurality of closed cusp cells 606 appears as an open cell in the Figure 6A, due to the display of the flat surface. Cells 602, 604, 606 are generally disposed along the lines that constitute the annular shape of the support structure 600.
[0180] [180] The surface of the metal structure was prepared as described in Example 4a.
[0181] [181] An ePTFE laminate was attached to the structure with a strain relief, similar to Example 4c. A cylindrical mandrel with a diameter of 24 millimeters was wrapped with a single layer of Kapton ® polyimide film (DuPont), and held in place by a strip of Kapton ® tape over the length of the overlapping seam. Two layers of substantially non-porous ePTFE, having a layer of FEP arranged along an external surface or on one of its sides, were wrapped with the FEP facing away from the surface of the mandrel, two layers of FEP, 3.6 μm in diameter. thickness, were then rolled over this. The expandable stent-framed metal balloon was aligned coaxially over the wrapped mandrel. Two additional layers of FEP were wrapped over the stent in the mandrel encapsulating the stent and strain relief. Two layers of a substantially porous ePTFE were wrapped over FEP, followed by three additional layers of FEP wrapped over ePTFE. The whole set was subjected to a heat treatment, placing it in a forced air oven at 375 ° C for 20 minutes and returned to room temperature by cooling after removal from the oven. The laminate was cut from regions of the structure to expose three windows for fixing the cusp, as shown in Figure 33b.
[0182] [182] A cusp material was then prepared as described in Example 6. The ePTFE membrane had a mass per unit area of 0.29 g / m2, a bubble point of 0.11 MPa, a thickness of about 158 nm, a tensile strength of the matrix of 434.0 MPa in the longitudinal direction and 646.0 MPa in the transverse direction. This membrane was embedded with a fluorinated elastomer as described in Example 4a. After the coating process, the final ePTFE / elastomer or composite had a mass per unit area of 0.94 g / m2, 30.3% by weight of fluorinated polymer, a burst strength dome of 4.14KPa, and thickness 0.44 µm.
[0183] [183] Seventeen layers of the composite were wrapped around a 26 mm mandrel. The composite was oriented so that the tensile strength of the 434 MPa matrix was placed axially and the elastomer-rich side of the membrane was turned towards the mandrel, as described in Example 4a.
[0184] [184] The subset containing the structure and the strain relief was positioned in the mandrel on the 17 layers. An additional 40 layers of composite were rolled up, fitting the structure between the two layers of composite creating a total of 57 layers of composite. The mandrel, cusp layers, and structure were covered with an impermeable layer and sealed at both ends. Using a pressure vessel, the assembly was heated to about 285 ° C at 75 psi for about 23 minutes and then allowed to cool to room temperature under pressure. The valve assembly has been removed from the mandrel. The free end of the cusp was created by cutting the laminate at an angle to each of the three closed cusp cells 606 in the structure, releasing the cusp to open and close under fluid pressure. The cusps were molded in final shape using the molding tools described in FIGs. 5A- 5B. Each cusp molding tool was coaxially aligned with the base tool to allow a cover to be applied to the outside of the structure.
[0185] [185] A structure cover material was then prepared as described in Example 6. The ePTFE membrane with a mass per unit area of 0.86 g / m2, a bubble point of 0.11 MPa, a thickness of about 900 nm, a resistance to the matrix traction of 376.0 MPa, in the longitudinal direction and 501.0 MPa in the transverse direction. This membrane was embedded with a fluorinated elastomer as described in Example 4a. After the coating process, the final fluorinated elastomer / composite ePTFE had a mass per unit area of 7.05 g / m2, 4.1% by weight of fluorinated polymer, a dome of rupture strength of 13.1KPa, and 3.28 μm thickness.
[0186] [186] Fifteen layers of the composite have been wrapped around the valve structure while it is being carried out in the form of joint tools. The composite was oriented so that the 501 MPa matrix tensile strength was placed axially and the elastomer-rich membrane side was turned towards the mandrel, as described in Example 4a. The final cover consisted of 14.1% by weight of fluorinated polymer with a thickness of 49.2 μm.
[0187] [187] The set was molded, thermally processed in an open atmosphere of a convection oven at 250 ° C for 1 hour. The valve was then removed from the molding tool set.
[0188] [188] The final cusp was composed of 30.3% by weight of fluorinated polymer with a thickness of 25.0 μm. Each cusp had 57 layers of the composite and a thickness / number of layers ratio of 0.44 μm.
[0189] [189] A plurality of longitudinally extending slits 1302 have been formed in tube 1300, resulting in the formation of a plurality of flaps 1304. Slits can be formed by any suitable method known to those of ordinary skill in the art, such as by cutting with a blade.
[0190] [190] The cusp tools (not shown) were then slid off the bottom of the 1300 tube.
[0191] [191] The three flaps 1304 created by the formation of cracks 1302 in the tube 1300 were then fed inward through respective windows or cells formed in the frame, as shown in Figure 35. Each of the cusp tools was aligned coaxially with the base to allow the flap-fed interior 1304 of the tube 1300 from the previous step, to be positioned and compressed between the cusp tools and the configuration of the female tri-cusp mold surface of the base tool. The set of combined tools comprising the cusp and basic tools, composite material or cusp, and the structure was then assembled between the fixed and translational parts of an electrical device. Both radial and axial compression were applied by radially tightening the cusp tools while simultaneously applying an axial load with the translational end of the fixture.
[0192] [192] The assembly was molded, thermally processed, and trimmed, as described in Example 4a. The final valve assembly with metallic balloon expandable stent structure 600 ", damping members 1030", and cusps 704 "are shown in Figure 36.
[0193] [193] The final cusp was composed of 33.70% by weight of fluorinated polymer with a thickness of 16.0 μm. Each cusp had fifty layers of the composite and a thickness / number of layers ratio of 0.32 μm.
[0194] [194] Hydrodynamic performance was measured before use. The performance values were: OAE = 2.0 cm2 and fraction of regurgitation = 15.7%. No observable damage was recorded during the durability tests.
[0195] [195] After construction and testing, the valve was sent to Carmeda Corporation (Carmeda AB, Stockholm, Sweden) for the heparin coating. After coating, the complete valve was mounted on a balloon catheter and flattened to a reduced diameter of 20French using a mechanical flattening device. The catheter-mounted valve was sent to Sterigenics corp. (Salt Lake City, UT) for ethylene oxide sterilization. Using a sterile technique, the valve was inserted through a 20F sheath into the surgically exposed iliac artery of an anesthetized 4-month-old, 25 kg Ramboulet sheep. The catheter was advanced through the inferior vena cava, through the right atrium and into the pulmonary artery trunk. It was implanted through the native pulmonary valve and acted by pressurizing the balloon catheter at 4 atmospheres. After angiography and pressure measurements, the catheter was removed and the animal recovered. The valve, referred to below as the explanted valve, remained in place for one month, replacing the function of the native pulmonary valve.
[0196] [196] The hydrodynamic performance of the explanted valve was measured after the explant and compared to a control valve. The valve was explanted, explanted, fixed in formalin solution, digested in sodium hydroxide, washed with ethanol, acetone and distilled water before being tested. The control valve was a duplicate of the explanted valve, which was compressed to the delivery diameter, reimplanted in a balloon catheter and tested. Each valve was tested under both aortic and pulmonary flow conditions in a real-time ViVitro tester. There was no degradation in hemodynamic performance.
[0197] [197] Yield values for explanted and control valves are listed below in Table 5.
[0198] [198] In exemplary embodiments, a heart valve with polymeric cusps attached to a rigid metallic structure was constructed according to the following process:
[0199] [199] The valve support frame or frame 960 has been laser cut from a length of 316 stainless steel tube with an outside diameter of 25.4 mm and a wall thickness of 0.5 mm as shown in Figure 19. In the embodiment shown, structure 960 extends axially between a lower end 962 and an opposite upper end generally defined by a plurality of axial extensions, generally in the form of spiral posts 964 corresponding to the number of valve cusps that intended to end (not shown). The parabolic-shaped upper end 968 extends between adjacent posts 964. In the specific embodiment shown, three posts 964 and three top edges 968 form the upper end of frame 960. The corners of the frame that would be in contact with the material of the cusp were rounded using a rotary sander and hand polished. The structure was rinsed with water and then cleaned by plasma using a PT2000P plasma treatment system, Tri-Star Technologies, El Segundo, CA, US.
[0200] [200] A damping member is provided between at least part of the structure and at least part of the cusp to minimize stress related to direct contact between the structure and the cusp. A composite of ePTFE fiber and silicone was first created by soaking an ePTFE membrane with MED-6215 silicone (NuSil, Carpinteria, CA, US), cutting it to a width of 25 mm and wrapping it in and material in substantially fiber. The ePTFE used in this fiber has been tested in accordance with the methods described in the Appendix. The ePTFE membrane had a bubble point of 217 kPa, a thickness of 10 μm, a mass per area of 5.2 g / m2, a porosity of 78%, a tensile strength of the matrix in a direction of 96 MPa and a tensile strength of matrix 55 MPa in an orthogonal direction. The fiber composite 966 was wrapped around each of the posts of structure 964 of valve 960, as shown in Figure 20.
[0201] [201] A mandrel 970 was formed using stereolithography in a form shown in Figure 21. Mandrel 970 has a first end 972 and an opposite second end 974, and extends longitudinally therebetween. Mandrel 970 has an outer surface 980 with three (two shown), generally arcuate convex lobes 982, each generally for forming cusps (not shown) of a finished valve assembly (not shown). The outer surface 980 also includes a frame seating area 984 for positioning the valve frame (960 in Figure 19) in relation to the lobes 982 prior to the formation of the valve cusps on the valve frame.
[0202] [202] Mandrel 970 was then spray coated with a PTFE mold release agent. Four layers of ePTFE membrane were wrapped around the mandrel. The ePTFE membrane has been tested in accordance with the methods described in the Appendix. The ePTFE membrane had a mass per unit area of 0.57 g / m2, a porosity of 90.4%, a thickness of about 2.5 μm, a bubble point of 458 kPa, a tensile strength of matrix of 339 MPa, in the longitudinal direction and of 257 MPa in the transverse direction. MED-6215 was eliminated in ePTFE and allowed to substantially wet and fill the pores of ePTFE. The excess MED6215 was erased from the valve structure 960 with the fiber composite of 966 wrapped in posts 964 was positioned on mandrel 970 along the seating area of frame 984, as shown in Figure 22. Silicone MED-4720, NuSil, Carpinteria, CA, US, was placed along the upper edges 968 of the frame 960 and along the posts 964 of the frame 960 to create strain relief on the cusp (not shown). Thirty additional layers of the same ePTFE were wrapped around structure 960 and mandrel 970. MED -6215 Additional was swept into ePTFE and allowed to get wet and to substantially fill the pores of the ePTFE. 8 layers of ePTFE membrane were wrapped around structure 960 and mandrel 970. The ePTFE used was tested in accordance with the methods described in the Appendix. The ePTFE membrane had a bubble point of 217 kPa, a thickness of 10 μm, a mass per area of 5.2 g / m2, a porosity of 78%, a tensile strength of the matrix in a direction of 96 MPa and a tensile strength of matrix 55 MPa in an orthogonal direction. These layers absorbed any excess silicone during the molding process and were removed after curing the silicone.
[0203] [203] Forms of silicone rubber (not shown) molded with a surface exactly matching the reverse shape of the mandrel surface were previously manufactured for each of the three cusp-forming characteristics. These shapes were coated by spraying with PTFE to release the mold and then coupled with the chuck tool. About 50 turns of an ePTFE fiber (not shown), were wrapped around the silicone molds to apply generally radial pressure, the valve against the mandrel.
[0204] [204] This set was then placed in an oven at 100 ° C for 1 hour, to cure the silicone. After cooling, the silicone fiber forms were removed, the eight layers of the ePTFE blotter were peeled off and discarded, and the resulting valve (not shown) was slid out of the mandrel. The posts were cut using pliers and the excess length of the cusp material and the excess length of the material at the base of the structure was carefully trimmed with scissors to form a complete valve assembly, which is shown and usually indicated by 990 in Figure 23. Thus, in one embodiment, the valve assembly 990 was formed having the support structure or structure 960, a plurality of cusps 992 supported on the support structure 960 and movable between the open and closed positions to regulate flow of blood through valve assembly 990, and a damping member 1030 located between at least part of the support structure 960 and at least part of each cusp 992 to minimize stress on the cusps due to coupling and / or proximity to the cusps with the support structure. In another embodiment, the damping element is formed from a composite material with at least one layer of fluorinated polymer having a plurality of pores and an elastomer present in virtually all pores, as described above.
[0205] [205] It should be understood that other support structures, as specifically shown in the Figures, can be used. In addition, the damping members can be used anywhere along the support structure, as necessary to minimize stress on the cusps due to coupling and / or proximity of the cusps to the support structure. For example, a damping member (s) can be attached to the support structure along the upper edge in parabolic shape.
[0206] [206] It should also be appreciated that the damping members can be formed as cusps and wound around the desired positions along the support structure, or be formed from fibers of various shapes and sizes in cross section.
[0207] [207] It should also be appreciated that the damping members can be formed as tubes and slid along the ends of the support structure, or be cut longitudinally and positioned around the desired location along the support structure.
[0208] [208] The cusps of the complete valve were measured and determined to have an average thickness in the center of each cusp of about 48 μm.
[0209] [209] The final cusp was composed of 24.00% by weight of fluorinated polymer with a thickness of 48.0 μm. Each cusp had 48 layers of the composite and a thickness / number of layers ratio of 1.07 μm.
[0210] [210] Hydrodynamic performance was measured before the accelerated wear test. The performance values were: OAE = 2.4 cm2 and regurgitation fraction = 12.5%. No observable damage was recorded during the durability tests with the number of cycles of around 150 million.
[0211] [211] The hydrodynamic performance of the valves described in Examples 4a, 4b, 5, 6, 7 and 8 was characterized by a real-time pulse duplicator that measures typical anatomical pressures and flows through the valve, generating an initial set or "zero fatigue" data for that particular valve assembly.
[0212] [212] After characterizing the flow performance, the valve assemblies were then removed from the flow pulse doubling system and placed on a high-frequency fatigue or durability tester. The valves were monitored continuously to ensure that the pressure performed when closed and to assess when any damage in the form of a frame detachment, tears, holes, or delamination occurring. If necessary, the hydrodynamic performance of valves was again measured with post-durability tests in approximately 100 million cycles and recorded.
[0213] [213] The results of the performance characterizations are shown in FIG. 43, table 6.
[0214] [214] The data presented in Examples 4a, 4b, 4c, 5, 6, 7 and 8 and summarized in Tables 4, 5 and 6 support the observation of the overall durability and hydrodynamic performance trends associated with different cusp configurations when thickness, percentage of polymer fluctuated by weight and number of layers are varied. The number of examples presented supports these observations, allowing comparisons to be made when differences due to the type of damping structure and members are used in the construction of the individual valve.
[0215] [215] Examples 4b and 4c are configurations where the cusp thickness and the percentage of fluorinated polymer by weight are the same and show that the number of low layers leads to reduced durability. The failure mode of Example 4b of the detached frame was mitigated by the use of a damping member which in turn doubled the time until failure, however, the failure mode changed from detachment frame to the formation of holes within the cusp. . Both examples 4a and 4b had durability failures well below what is acceptable.
[0216] [216] Examples 4b and 5 provide a comparison, where the percentage of fluorinated polymer by weight is kept constant and the difference in the number of layers and, therefore, the cusp thickness are measured. Both examples have the same valve construction without the damping members, which were shown above, to mitigate detachment. The effect of doubling the number of layers from 9 to 18 and, therefore, increasing the thickness of the cusp from about 52 μm to about 98 μm improved the number of cycles to frame detachment by almost an order of magnitude from 12 to 100 millions.
[0217] [217] Example 4a, which in turn is similar in construction to Examples 4b, where the cusp thickness of about 50 μm is kept constant and the percentage of fluorinated polymer by weight varying from about 10% for the Example 4b at about 30% for Example 4a allowed the creation of a thinner composite and therefore many more layers (26) for the same cusp thickness. Although some free-edge delamination has been observed, for example 4a near the high voltage region of the triple point, the valve is still viable as determined by hydrodynamic characterization studies with 100 million accumulated cycles as shown in Table 5.
[0218] [218] In examples 6 and 7, the improved flexural behavior of these thin and high layer configurations generally indicates that the improvement in durability follows when compared to constructions with lower layer numbers, due to the reduction in creases and wrinkles in the thought cycle. work, as illustrated in Figures 41 A and 41 B.
[0219] [219] In addition, Example 8 illustrates that similar durability can be achieved with elastomers of different high-layer configurations, as demonstrated by Examples 6 and 7.
[0220] [220] It is evident to those skilled in the art that various modifications and variations can be made to the embodiments without departing from the spirit or scope of the embodiments. Thus, it is intended that the present embodiments cover the modifications and variations of this invention as long as they are within the scope of the appended claims and their equivalents. ATTACHMENT
[0221] [221] As used in this application, tensile strength of the matrix refers to the resistance to removal of a sample of porous fluorinated polymer under specified conditions. Sample porosity is accounted for by multiplying the tensile strength by the ratio of the polymer density to the specimen density.
[0222] [222] As used herein, the term "membrane" refers to a porous fluorinated polymer article, "composite" refers to embedded porous fluorinated polymers, and a "cusp" is a component of an implant article for regulating the direction of blood flow. Cusps of the present embodiments are one or more layers of a composite.
[0223] [223] The term "absorb" used here refers to any process used to at least partially fill the pores with a secondary material.
[0224] [224] For porous fluorinated polymer cusps with pores substantially filled with elastomer, the elastomer can be dissolved or degraded and washed with a suitable solvent in order to measure the desired properties.
[0225] [225] As the term "elastomer" is used herein it defines a polymer, mixture of polymers, or a mixture of one or more polymers, with one or more non-polymeric components that have the ability to be stretched at least 1.3 times its original length and rapidly retracting to approximately its original length when released. The term "elastomeric" is intended to describe a property of a polymer according to which it exhibits elastomer-like stretch and recovery properties, although not necessarily to the same degree of elongation and / or recovery.
[0226] [226] With the term "thermoplastic" it is used here to define a polymer that softens when exposed to heat and returns to its original state when cooled to room temperature. Such a polymer can be made to soften, drain or take on new forms, without significant degradation or change in the original state of the polymer, through the application of heat or heat and pressure. In contrast to a thermoplastic polymer, a "thermoset" polymer is defined herein as a polymer that solidifies or "sticks" irreversibly when cured. The determination of whether a polymer is a "thermoplastic" polymer, within the meaning of the present embodiment, can be done by slowly raising the temperature of a stressed specimen and observing deformation. If the polymer can be made to soften, flow, or take on a new shape, without any significant degradation or change in the polymer's original chemical condition, then the polymer is considered to be a thermoplastic. If only a small amount of material is available, it may be necessary to use a hot-stage microscope for this determination.
[0227] [227] A measure of the quality of a valve is the effective orifice area (EOA), which can be calculated as follows: EOA (cm2) = Qrms (51.6 (ΔΡ) 1/2) where Qrms is the square root of the mean systolic / diastolic flow (cm3 / s) and ΔΡ is the systolic / diastolic pressure drop (mmHg).
[0228] [228] Another measure of a valve's hydrodynamic performance is the regurgitation fraction, which represents the amount of liquid or blood regurgitated through the valve, divided by the volume of the stroke.
[0229] [229] As used in this patent application, the surface area per unit of mass, expressed in units of m2 / g, was measured using the Brunauer-Emmett-Teller (BET) method on a Coulter SA3100 Gas Adsorption Analyzer, Beckman Coulter, Inc. Fullerton CA, US. To perform the measurement, the sample was cut from the center of the expanded fluorinated polymer membrane and placed in a small sample tube. The sample mass was about 0.1 to 0.2 g. The tube was placed in the Coulter SA -Prep Surface Area Outgasser (Model SA-Prep, P / n 5102014) from Beckman Coulter, Fullerton CA, US and purged at about 110 ° C for about two hours with helium. The test tube was then removed from the SA -Prep Outgasser and weighed. The test tube was then placed in the SA3100 adsorption gas analyzer and BET surface area analysis was performed in accordance with the instrument's instructions using helium to calculate the free space and nitrogen as the adsorbed gas.
[0230] [230] Boiling point and average pore size flow were measured according to the general teachings of ASTM F31 6-03 using a capillary flow porometer, Model CFP 1500AEXL of porous materials, Inc., Ithaca NY, US. The membrane sample was placed in the sample chamber and wetted with SilWick silicone fluid (available from porous materials, Inc.), with a surface tension of about 20.1 dynes / cm. The bottom clip of the sample chamber was about 2.54 cm in diameter. Using the software version Capwin 7.73.012 the following parameters were established as specified in the table below.
[0231] [231] The thickness of the membrane was measured by placing the membrane between the two plates of a Kafer FZ1000 / 30 thick gauge fitting Kafer Messuhrenfabrik GmbH, Villingen-Schwenningen, Germany. The average of the three measures was reported.
[0232] [232] The presence of elastomer within the pores can be determined by several methods known to those of ordinary skill in the art, such as the surface and / or visual cross section, or other analyzes. These analyzes can be performed before and after removing elastomer from the cusp.
[0233] [233] Membrane samples were cut to form rectangular sections about 2.54 cm by 15.24 cm to measure weight (using a Mettler-Toledo analytical balance model AG204) and thickness (using a pressure gauge Kafer Fz1000 / 30). Using these data, the density was calculated with the following formula: p = m / w * l * t, where: p = density (g / cm3): m = mass (g), W = width (cm), I = length (cm), and t = thickness (cm). The average of three measurements was reported.
[0234] [234] Tensile breaking load was measured using an INSTRON 122 tensile testing machine equipped with flattened grips and a 0.445 kN load cell. The duration was about 5.08 cm and the cross-head speed was about 50.8 cm / min. The dimensions of the samples were about 2.54 centimeters by 15.24 centimeters. For longitudinal measurements, the longest dimension of the sample was oriented in the direction of maximum force. For orthogonal MTS measurements, the largest dimension of the sample was oriented perpendicularly to the direction of the maximum force. Each sample was weighed with a Mettler Toledo model scale AG204, then the thickness measured using the Kafer FZ1000 / 30 pressure gauge. The samples were then individually tested by the tensile tester. Three different sections of each sample were measured. The average of the three maximum loads (that is, the peak force) of the measurements was reported. The longitudinal and transverse matrix tensile strengths (MTS) were calculated using the following equation: MTS = (maximum load / cross-sectional area) * (bulk density of PTFE) / (the density of the porous membrane), where the Bulk density of PTFE was made to be about 2.2 g / cm3. Flexural stiffness was measured following the general procedures established in the ASTM D790 standard. Unless large test samples are available, the test sample must be reduced. The test conditions were as follows. The leaflet specimens were measured in a three-point bending test apparatus employing sharp poles placed horizontally about 5.08 mm from each other. A steel bar about 1.34 mm in diameter, weighing about 80 mg was used to cause deformation in the y (downward) direction, and the samples were not contained in the x direction. The steel bar was placed slowly over the sample point of the central membrane. After waiting about 5 minutes, deflection y was measured. Deflection of elastic beams supported above can be represented by: d = F * L 3/48 EI, where F (in Newtons) is the load applied at the center of the beam length, L (in meters), then L = 1 / 2 distance between suspension posts and El is the flexural stiffness (Nm). From this relationship the value of El can be calculated. For a rectangular cross section that: I = t3 * w / 12, where I = moment of cross-section of inertia, t = thickness of the sample (in meters), w = width of the sample (in meters). With this relationship, the mean modulus of elasticity in the flexural strain measurement range can be calculated.

权利要求:
Claims (11)
[0001]
Implantable article for the regulation of the direction of blood flow in a human patient, characterized by understanding: a cusp (802) with a thickness and formed from a composite material with more than one layer of fluorinated polymer having a plurality of pores and an elastomer or elastomeric material present in substantially all pores of the layer of more than one fluorinated polymer , the cusp with a cusp thickness ratio (µm) to the number of fluorinated polymer layers of less than about 5.
[0002]
Implantable article according to claim 1, characterized in that the relationship between the cusp thickness (µm) and the number of fluorinated polymer layers is less than about 3.
[0003]
Implantable article according to claim 1, characterized in that the relationship between the cusp thickness (µm) and the number of fluorinated polymer layers is less than about 1.
[0004]
Implantable article according to claim 1, characterized in that the relationship between the cusp thickness (µm) and the number of fluorinated polymer layers is less than about 0.5.
[0005]
Implantable article according to claim 1, characterized in that the cusp has at least 10 layers and a composite material comprising less than about 50% by weight of fluorinated polymer.
[0006]
Implantable article, according to claim 5, characterized in that the cusp has a thickness of less than 100 µm.
[0007]
Implantable article according to claim 6, characterized by the cusp having a flexural modulus of less than about 100 MPa.
[0008]
Implantable article, according to claim 1, characterized by the fact that the cusp is cyclable between a closed configuration to substantially prevent blood flow through the implantable article and an open configuration allowing blood flow through the implantable article, and the cusp to be formed from a plurality of fluoro polymer layers.
[0009]
Implantable article, according to claim 8, characterized in that the cusp is operatively coupled to a support and mobile structure between the open and closed configurations in relation to the support structure.
[0010]
Implantable article, according to claim 9, characterized in that the support structure is diametrically selectively adjustable for endovascular delivery and implantation in a treatment site.
[0011]
Implantable article according to claim 8, characterized in that the cusp comprises a radiopaque element.

类似技术:

---

公开号 | 公开日 | 专利标题

---

BR112013030992B1|2021-01-26|durable multi-layer high-strength polymer composite suitable for implant and articles derived from it

---

US10993803B2|2021-05-04|Elastomeric leaflet for prosthetic heart valves

---

US20190269506A1|2019-09-05|Durable high strength composite prosthetic valve leaflets

---

BR112013025114A2|2021-01-05|durable, high-strength polymer composite suitable for implant and articles made from it

---

ES2701197T3|2019-02-21|Durable polymeric compounds of high mechanical strength suitable for implantation and articles produced from them

---

AU2018264049A1|2018-12-06|Elastomeric leaflet for prosthetic heart valves

---

KR20150127222A|2015-11-16|Durable multi-layer high strength polymer composite suitable for implant and articles produced therefrom

---

AU2018203416B2|2019-12-12|Durable multi-layer high strength polymer composite suitable for implant and articles produced therefrom

同族专利:

---

公开号 | 公开日

---

KR20190018734A|2019-02-25|

---

CN105999422B|2020-04-03|

---

US10022219B2|2018-07-17|

---

ES2643173T3|2017-11-21|

---

JP2014524767A|2014-09-25|

---

US20180200050A1|2018-07-19|

---

US20150257876A1|2015-09-17|

---

KR101999508B1|2019-07-11|

---

AU2012261921A1|2014-01-09|

---

US10653518B2|2020-05-19|

---

KR20140034878A|2014-03-20|

---

CA3042538A1|2012-12-06|

---

EP2713954A1|2014-04-09|

---

CN103702636B|2017-06-09|

---

RU2013157353A|2015-07-20|

---

US20150135537A1|2015-05-21|

---

EP2713954B1|2017-08-02|

---

EP3251633A1|2017-12-06|

---

CN103702636A|2014-04-02|

---

US20120323315A1|2012-12-20|

---

CA2837098C|2017-05-09|

---

CA2966238A1|2012-12-06|

---

CA2837098A1|2012-12-06|

---

US8945212B2|2015-02-03|

---

CN105999422A|2016-10-12|

---

HK1246143A1|2018-09-07|

---

KR101946595B1|2019-02-11|

---

WO2012167131A1|2012-12-06|

---

US20130166021A1|2013-06-27|

---

CA2966238C|2019-07-02|

---

JP5785326B2|2015-09-30|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

SE392582B|1970-05-21|1977-04-04|Gore & Ass|PROCEDURE FOR THE PREPARATION OF A POROST MATERIAL, BY EXPANDING AND STRETCHING A TETRAFLUORETENE POLYMER PREPARED IN AN PASTE-FORMING EXTENSION PROCEDURE|

---

US4340091A|1975-05-07|1982-07-20|Albany International Corp.|Elastomeric sheet materials for heart valve and other prosthetic implants|

---

US4339831A|1981-03-27|1982-07-20|Medtronic, Inc.|Dynamic annulus heart valve and reconstruction ring|

---

US4629459A|1983-12-28|1986-12-16|Shiley Inc.|Alternate stent covering for tissue valves|

---

JPH0627216B2|1984-12-11|1994-04-13|ジャパンゴアテックス株式会社|Stretchable moisture-permeable waterproof film for clothing|

---

US5071609A|1986-11-26|1991-12-10|Baxter International Inc.|Process of manufacturing porous multi-expanded fluoropolymers|

---

US4816339A|1987-04-28|1989-03-28|Baxter International Inc.|Multi-layered poly/elastomer materials useful for in vivo implantation|

---

US4955899A|1989-05-26|1990-09-11|Impra, Inc.|Longitudinally compliant vascular graft|

---

EP0705081B1|1994-04-22|2001-10-17|Medtronic, Inc.|Stented bioprosthetic heart valve|

---

EP0773971B1|1994-07-27|1999-06-23|W.L. Gore & Associates, Inc.|High strength porous ptfe sheet material|

---

AU688404B2|1994-09-02|1998-03-12|W.L. Gore & Associates, Inc.|Porous polytetrafluoroethylene compositions|

---

US6428571B1|1996-01-22|2002-08-06|Scimed Life Systems, Inc.|Self-sealing PTFE vascular graft and manufacturing methods|

---

CA2248819C|1996-03-20|2004-04-06|W. L. Gore & Associates, Inc.|Improved flocked articles|

---

US5824050A|1996-12-03|1998-10-20|Atrium Medical Corporation|Prosthesis with in-wall modulation|

---

WO1998026731A2|1996-12-03|1998-06-25|Atrium Medical Corporation|Multi-stage prosthesis|

---

EP1185415B1|1999-05-10|2003-07-02|The Secretary Of State For Defence|Smart porous film or material|

---

US6451396B1|1998-02-13|2002-09-17|Gore Enterprise Holdings, Inc.|Flexure endurant composite elastomer compositions|

---

US7049380B1|1999-01-19|2006-05-23|Gore Enterprise Holdings, Inc.|Thermoplastic copolymer of tetrafluoroethylene and perfluoromethyl vinyl ether and medical devices employing the copolymer|

---

US7628803B2|2001-02-05|2009-12-08|Cook Incorporated|Implantable vascular device|

---

US20030055492A1|1999-08-20|2003-03-20|Shaolian Samuel M.|Transluminally implantable venous valve|

---

US6440164B1|1999-10-21|2002-08-27|Scimed Life Systems, Inc.|Implantable prosthetic valve|

---

US20030097175A1|1999-12-08|2003-05-22|O'connor Bernard|Heart valve prosthesis and method of manufacture|

---

US6652583B2|2000-04-07|2003-11-25|Rhode Island Hospital|Cardiac valve replacement|

---

JP2004510471A|2000-09-21|2004-04-08|セント・ジュード・メディカル・インコーポレーテッド|Valve prostheses with enhanced polymer leaflets|

---

US7374571B2|2001-03-23|2008-05-20|Edwards Lifesciences Corporation|Rolled minimally-invasive heart valves and methods of manufacture|

---

US6761733B2|2001-04-11|2004-07-13|Trivascular, Inc.|Delivery system and method for bifurcated endovascular graft|

---

US7828833B2|2001-06-11|2010-11-09|Boston Scientific Scimed, Inc.|Composite ePTFE/textile prosthesis|

---

DE60205903T3|2001-06-11|2014-10-16|Boston Scientific Ltd.|COMPOSITE EPTFE / TEXTILE PROSTHESIS|

---

US6541589B1|2001-10-15|2003-04-01|Gore Enterprise Holdings, Inc.|Tetrafluoroethylene copolymer|

---

US6726715B2|2001-10-23|2004-04-27|Childrens Medical Center Corporation|Fiber-reinforced heart valve prosthesis|

---

US6752826B2|2001-12-14|2004-06-22|Thoratec Corporation|Layered stent-graft and methods of making the same|

---

EP1465685B1|2001-12-20|2010-03-17|TriVascular2, Inc.|Method and apparatus for manufacturing an endovascular graft section|

---

US6776604B1|2001-12-20|2004-08-17|Trivascular, Inc.|Method and apparatus for shape forming endovascular graft material|

---

US20040002444A1|2002-04-08|2004-01-01|Toshikazu Shiba|Polyphosphate-water soluble collagen complexes and process for preparation thereof|

---

WO2003092554A1|2002-05-03|2003-11-13|The General Hospital Corporation|Involuted endovascular valve and method of construction|

---

US20030211264A1|2002-05-09|2003-11-13|Farnsworth Ted Ray|Expanded polytetrafluoroethylene -reinforced perfluoroelastomers |

---

US7351256B2|2002-05-10|2008-04-01|Cordis Corporation|Frame based unidirectional flow prosthetic implant|

---

EP1507492A1|2002-05-10|2005-02-23|Cordis Corporation|Method of making a medical device having a thin wall tubular membrane over a structural frame|

---

US7789908B2|2002-06-25|2010-09-07|Boston Scientific Scimed, Inc.|Elastomerically impregnated ePTFE to enhance stretch and recovery properties for vascular grafts and coverings|

---

US20040024448A1|2002-08-05|2004-02-05|Chang James W.|Thermoplastic fluoropolymer-coated medical devices|

---

US7448122B1|2003-10-31|2008-11-11|Advanced Cardiovascular Systems, Inc.|Method of compressing a polymeric layer of an expandable medical device|

---

US7261732B2|2003-12-22|2007-08-28|Henri Justino|Stent mounted valve|

---

US20110039690A1|2004-02-02|2011-02-17|Nanosys, Inc.|Porous substrates, articles, systems and compositions comprising nanofibers and methods of their use and production|

---

EA010202B1|2004-06-09|2008-06-30|Пэтоджен Римувал Энд Дайэгностик Текнолоджиз Инк.|Device and method for removing target agents from a sample|

---

GB0414099D0|2004-06-23|2004-07-28|Univ Glasgow|Biocompatible layered structures and methods for their manufacture|

---

US7727271B2|2004-06-24|2010-06-01|Boston Scientific Scimed, Inc.|Implantable prosthesis having reinforced attachment sites|

---

US7919112B2|2004-08-26|2011-04-05|Pathak Holdings, Llc|Implantable tissue compositions and method|

---

US7361189B2|2004-09-10|2008-04-22|Cook Incorporated|Prosthetic valve with pores|

---

US8029563B2|2004-11-29|2011-10-04|Gore Enterprise Holdings, Inc.|Implantable devices with reduced needle puncture site leakage|

---

US7867274B2|2005-02-23|2011-01-11|Boston Scientific Scimed, Inc.|Valve apparatus, system and method|

---

CN101180010B|2005-05-24|2010-12-01|爱德华兹生命科学公司|Rapid deployment prosthetic heart valve|

---

WO2007002320A1|2005-06-27|2007-01-04|The Cleveland Clinic Foundation|Apparatus for placement in the annulus of a tricuspid valve|

---

US7531611B2|2005-07-05|2009-05-12|Gore Enterprise Holdings, Inc.|Copolymers of tetrafluoroethylene|

---

US7306729B2|2005-07-18|2007-12-11|Gore Enterprise Holdings, Inc.|Porous PTFE materials and articles produced therefrom|

---

WO2007016251A2|2005-07-28|2007-02-08|Cook Incorporated|Implantable thromboresistant valve|

---

US20070118210A1|2005-11-18|2007-05-24|Leonard Pinchuk|Trileaflet Heart Valve|

---

WO2007142935A1|2006-05-30|2007-12-13|Cook Incorporated|Artificial valve prosthesis|

---

JP2009542421A|2006-07-07|2009-12-03|アンソニー・ヌネズ|Method and system for monitoring an endoprosthesis implant|

---

US20080125711A1|2006-08-07|2008-05-29|Alpini Alfred A|Catheter balloons with integrated non-distensible seals|

---

US20080220054A1|2006-10-13|2008-09-11|Shastri V Prasad|Modulation of drug release rate from electrospun fibers|

---

WO2008046092A2|2006-10-13|2008-04-17|Creighton University|Implantable valve prosthesis|

---

US20100190254A1|2006-12-05|2010-07-29|Nanyang Technological University|Three-dimensional porous hybrid scaffold and manufacture thereof|

---

US8932619B2|2007-06-27|2015-01-13|Sofradim Production|Dural repair material|

---

US20090187197A1|2007-08-03|2009-07-23|Roeber Peter J|Knit PTFE Articles and Mesh|

---

US20100249922A1|2007-09-19|2010-09-30|St Jude Medical Inc.|Fiber-reinforced synthetic sheets for prosthetic heart valve leaflets|

---

US8637144B2|2007-10-04|2014-01-28|W. L. Gore & Associates, Inc.|Expandable TFE copolymers, method of making, and porous, expended articles thereof|

---

US10364527B2|2007-10-24|2019-07-30|W. L. Gore & Associates, Inc.|Burn protective materials|

---

US9402724B2|2008-05-12|2016-08-02|Mo-Sci Corporation|Dynamic bioactive nanofiber scaffolding|

---

CN202568532U|2008-06-06|2012-12-05|爱德华兹生命科学公司|Implantable artificial valve|

---

DE102008027856A1|2008-06-11|2009-12-24|W. L. Gore & Associates Gmbh|Shoe with ventilation in the lower shaft area and air-permeable spacer construction|

---

EP2337522B1|2008-06-20|2014-06-11|Vysera Biomedical Limited|Esophageal valve|

---

NL1036038C|2008-10-09|2010-04-14|Univ Eindhoven Tech|Multilayer preform obtained by electro-spinning, method for producing a preform as well as use thereof.|

---

US20150265744A1|2008-10-09|2015-09-24|Technische Universiteit Eindhoven|Multilayer preform obtained by electro-spinning, method for producing a preform as well as use thereof|

---

US20160067374A1|2009-01-16|2016-03-10|Zeus Industrial Products, Inc.|Composite prosthetic devices|

---

WO2010085659A1|2009-01-22|2010-07-29|St. Jude Medical|Magnetic docking system and method for the long term adjustment of an implantable device|

---

US9139669B2|2009-03-24|2015-09-22|W. L. Gore & Associates, Inc.|Expandable functional TFE copolymer fine powder, the expandable functional products obtained therefrom and reaction of the expanded products|

---

WO2010120668A1|2009-04-13|2010-10-21|Entegris, Inc.|Porous composite membrane|

---

US10022222B2|2009-10-06|2018-07-17|Adam Groothuis|Systems and methods for treating lumenal valves|

---

US8691543B2|2009-11-25|2014-04-08|Worcester Polytechnic Institute|Nanofibrous scaffold comprising immobilized cells|

---

MX339572B|2009-11-27|2016-05-18|Univ Nac Autónoma De México|Polymeric matrix material with reinforcements of different morphologies and the synthesis process thereof.|

---

EP2544624B1|2010-03-11|2019-01-23|Board Of Regents Of the University Of Texas System|Scaffold system to repair cardiovascular conditions|

---

EP2547285A4|2010-03-17|2017-07-12|Deep Vein Medical, Inc.|Fatigue-resistant flow regulating device and manufacturing methods|

---

US9066997B2|2010-06-02|2015-06-30|The Regents Of The University Of Michigan|Scaffolds and methods of forming the same|

---

US8961599B2|2011-04-01|2015-02-24|W. L. Gore & Associates, Inc.|Durable high strength polymer composite suitable for implant and articles produced therefrom|

---

US9801712B2|2011-04-01|2017-10-31|W. L. Gore & Associates, Inc.|Coherent single layer high strength synthetic polymer composites for prosthetic valves|

---

US8945212B2|2011-04-01|2015-02-03|W. L. Gore & Associates, Inc.|Durable multi-layer high strength polymer composite suitable for implant and articles produced therefrom|

---

US9554900B2|2011-04-01|2017-01-31|W. L. Gore & Associates, Inc.|Durable high strength polymer composites suitable for implant and articles produced therefrom|

---

EP2522308B1|2011-05-10|2015-02-25|Biotronik AG|Mechanical transcatheter heart valve prosthesis|

---

US8945209B2|2011-05-20|2015-02-03|Edwards Lifesciences Corporation|Encapsulated heart valve|

---

EP2736456B1|2011-07-29|2018-06-13|Carnegie Mellon University|Artificial valved conduits for cardiac reconstructive procedures and methods for their production|

---

US9144492B2|2012-12-19|2015-09-29|W. L. Gore & Associates, Inc.|Truncated leaflet for prosthetic heart valves, preformed valve|

---

US9101469B2|2012-12-19|2015-08-11|W. L. Gore & Associates, Inc.|Prosthetic heart valve with leaflet shelving|

---

US9737398B2|2012-12-19|2017-08-22|W. L. Gore & Associates, Inc.|Prosthetic valves, frames and leaflets and methods thereof|

---

US9827094B2|2014-09-15|2017-11-28|W. L. Gore & Associates, Inc.|Prosthetic heart valve with retention elements|

---

US10507101B2|2014-10-13|2019-12-17|W. L. Gore & Associates, Inc.|Valved conduit|

---

US9855141B2|2014-12-18|2018-01-02|W. L. Gore & Associates, Inc.|Prosthetic valves with mechanically coupled leaflets|WO2012122567A2|2011-03-10|2012-09-13|University Of Florida Research Foundation, Inc.|Anti-thrombogenic heart valve and medical implements|

---

CA2900805C|2013-03-13|2019-08-13|W.L. Gore & Associates, Inc.|Elastomeric leaflet for prosthetic heart valves|

---

US20130197631A1|2011-04-01|2013-08-01|W. L. Gore & Associates, Inc.|Durable multi-layer high strength polymer composite suitable for implant and articles produced therefrom|

---

US9744033B2|2011-04-01|2017-08-29|W.L. Gore & Associates, Inc.|Elastomeric leaflet for prosthetic heart valves|

---

US9554900B2|2011-04-01|2017-01-31|W. L. Gore & Associates, Inc.|Durable high strength polymer composites suitable for implant and articles produced therefrom|

---

US9801712B2|2011-04-01|2017-10-31|W. L. Gore & Associates, Inc.|Coherent single layer high strength synthetic polymer composites for prosthetic valves|

---

JP2016514011A|2013-03-13|2016-05-19|ダブリュ．エル．ゴア アンド アソシエイツ，インコーポレイティドＷ．Ｌ． Ｇｏｒｅ ＆ Ａｓｓｏｃｉａｔｅｓ， Ｉｎｃｏｒｐｏｒａｔｅｄ|Durable multilayer high-strength polymer composite suitable for implants and articles made therefrom|

---

WO2014149295A1|2013-03-15|2014-09-25|W. L. Gore & Associates, Inc.|Prosthetic heart valve leaflet adapted for external imaging|

---

US8961599B2|2011-04-01|2015-02-24|W. L. Gore & Associates, Inc.|Durable high strength polymer composite suitable for implant and articles produced therefrom|

---

ES2801328T3|2013-03-13|2021-01-11|Gore & Ass|Prosthetic heart valve comprising durable, high-strength polymer compounds suitable for implantation|

---

EP3256178B1|2015-02-13|2021-01-13|W. L. Gore & Associates, Inc.|Coherent single layer high strength synthetic polymer composites for prosthetic valves|

---

US8945212B2|2011-04-01|2015-02-03|W. L. Gore & Associates, Inc.|Durable multi-layer high strength polymer composite suitable for implant and articles produced therefrom|

---

US10213329B2|2011-08-12|2019-02-26|W. L. Gore & Associates, Inc.|Evertable sheath devices, systems, and methods|

---

WO2013138286A1|2012-03-13|2013-09-19|W.L. Gore & Associates, Inc.|Venting array and manufacturing method|

---

US9345573B2|2012-05-30|2016-05-24|Neovasc Tiara Inc.|Methods and apparatus for loading a prosthesis onto a delivery system|

---

US9283072B2|2012-07-25|2016-03-15|W. L. Gore & Associates, Inc.|Everting transcatheter valve and methods|

---

US10376360B2|2012-07-27|2019-08-13|W. L. Gore & Associates, Inc.|Multi-frame prosthetic valve apparatus and methods|

---

US9144492B2|2012-12-19|2015-09-29|W. L. Gore & Associates, Inc.|Truncated leaflet for prosthetic heart valves, preformed valve|

---

US10321986B2|2012-12-19|2019-06-18|W. L. Gore & Associates, Inc.|Multi-frame prosthetic heart valve|

---

US9398952B2|2012-12-19|2016-07-26|W. L. Gore & Associates, Inc.|Planar zone in prosthetic heart valve leaflet|

---

US9737398B2|2012-12-19|2017-08-22|W. L. Gore & Associates, Inc.|Prosthetic valves, frames and leaflets and methods thereof|

---

US10966820B2|2012-12-19|2021-04-06|W. L. Gore & Associates, Inc.|Geometric control of bending character in prosthetic heart valve leaflets|

---

US9101469B2|2012-12-19|2015-08-11|W. L. Gore & Associates, Inc.|Prosthetic heart valve with leaflet shelving|

---

US9968443B2|2012-12-19|2018-05-15|W. L. Gore & Associates, Inc.|Vertical coaptation zone in a planar portion of prosthetic heart valve leaflet|

---

US10039638B2|2012-12-19|2018-08-07|W. L. Gore & Associates, Inc.|Geometric prosthetic heart valves|

---

US9681951B2|2013-03-14|2017-06-20|Edwards Lifesciences Cardiaq Llc|Prosthesis with outer skirt and anchors|

---

US9504565B2|2013-12-06|2016-11-29|W. L. Gore & Associates, Inc.|Asymmetric opening and closing prosthetic valve leaflet|

---

US9907641B2|2014-01-10|2018-03-06|W. L. Gore & Associates, Inc.|Implantable intraluminal device|

---

US9539089B2|2014-05-09|2017-01-10|Foldax, Inc.|Replacement heart valves and their methods of use and manufacture|

---

US10314697B2|2014-08-18|2019-06-11|W. L. Gore & Associates, Inc.|Frame with integral sewing cuff for prosthetic valves|

---

US9827094B2|2014-09-15|2017-11-28|W. L. Gore & Associates, Inc.|Prosthetic heart valve with retention elements|

---

US10507101B2|2014-10-13|2019-12-17|W. L. Gore & Associates, Inc.|Valved conduit|

---

US9855141B2|2014-12-18|2018-01-02|W. L. Gore & Associates, Inc.|Prosthetic valves with mechanically coupled leaflets|

---

EP3294150B1|2015-05-14|2021-12-15|W. L. Gore & Associates, Inc.|Devices for occlusion of an atrial appendage|

---

US10716671B2|2015-07-02|2020-07-21|Boston Scientific Scimed, Inc.|Prosthetic heart valve composed of composite fibers|

---

ITUB20152409A1|2015-07-22|2017-01-22|Sorin Group Italia Srl|VALVE SLEEVE FOR VALVULAR PROSTHESIS AND CORRESPONDING DEVICE|

---

US10195023B2|2015-09-15|2019-02-05|Boston Scientific Scimed, Inc.|Prosthetic heart valves including pre-stressed fibers|

---

US10022223B2|2015-10-06|2018-07-17|W. L. Gore & Associates, Inc.|Leaflet support devices and methods of making and using the same|

---

US9968447B2|2016-01-22|2018-05-15|Medtronic Vascular, Inc.|Bioprosthetic tissue for use as a prosthetic valve leaflet and method of preparing|

---

US10729542B2|2016-10-26|2020-08-04|Medtronic Vascular, Inc.|Stented prosthetic heart valve having a paravalvular sealing wrap|

---

EP3615097A1|2017-04-25|2020-03-04|Boston Scientific Scimed, Inc.|Biocompatible polyisobutylene-fiber composite materials and methods|

---

CN111263622A|2017-08-25|2020-06-09|内奥瓦斯克迪亚拉公司|Sequentially deployed transcatheter mitral valve prosthesis|

---

US10959842B2|2017-09-12|2021-03-30|W. L. Gore & Associates, Inc.|Leaflet frame attachment for prosthetic valves|

---

AU2018342223B2|2017-09-27|2021-04-01|W. L. Gore & Associates, Inc.|Prosthetic valves with mechanically coupled leaflets|

---

US11020221B2|2017-09-27|2021-06-01|W. L. Gore & Associates, Inc.|Prosthetic valve with expandable frame and associated systems and methods|

---

US11090153B2|2017-10-13|2021-08-17|W. L. Gore & Associates, Inc.|Telescoping prosthetic valve and delivery system|

---

US11173023B2|2017-10-16|2021-11-16|W. L. Gore & Associates, Inc.|Medical devices and anchors therefor|

---

CN111818875A|2017-10-31|2020-10-23|W.L.戈尔及同仁股份有限公司|Pipeline with valve|

---

US11154397B2|2017-10-31|2021-10-26|W. L. Gore & Associates, Inc.|Jacket for surgical heart valve|

---

CN111295156A|2017-10-31|2020-06-16|W.L.戈尔及同仁股份有限公司|Prosthetic heart valve|

---

WO2019089135A1|2017-10-31|2019-05-09|W. L. Gore & Associates, Inc.|Transcatheter deployment systems and associated methods|

---

EP3810038A1|2018-06-20|2021-04-28|W.L. Gore & Associates, Inc.|Support structure for an implantable device with enhanced compressive stiffness region|

---

USD926322S1|2018-11-07|2021-07-27|W. L. Gore & Associates, Inc.|Heart valve cover|

---

WO2021022211A1|2019-08-01|2021-02-04|W. L. Gore & Associates, Inc.|Transcatheter prosthetic valve with multi-part frame subcomponent transverse deformation resistance|

---

WO2021026531A1|2019-08-08|2021-02-11|W. L. Gore & Associates, Inc|Prosthetic valve with asymmetric leaflets|

---

WO2021202916A1|2020-04-01|2021-10-07|Nininger Medical, Inc.|Three-dimensional thin-film leaflet valve device|

---

RU201554U1|2020-08-20|2020-12-21|Федеральное государственное унитарное предприятие "Центральный аэрогидродинамический институт имени профессора Н.Е. Жуковского" |A device for measuring the transverse deformation of a polymer composite sample|

法律状态:
2018-12-11| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

---

2019-10-01| B15K| Others concerning applications: alteration of classification|Free format text: AS CLASSIFICACOES ANTERIORES ERAM: A61F 2/24 , A61L 27/48 Ipc: A61F 2/24 (1985.01), A61L 27/34 (2000.01), A61L 27 |

---

2019-10-08| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

---

2020-12-08| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

---

2021-01-26| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 01/06/2012, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

---

申请号 | 申请日 | 专利标题

---

US201161492324P| true| 2011-06-01|2011-06-01|

---

US61/492,324|2011-06-01|

---

US13/485,823|2012-05-31|

---

US13/485,823|US8945212B2|2011-04-01|2012-05-31|Durable multi-layer high strength polymer composite suitable for implant and articles produced therefrom|

---

PCT/US2012/040529|WO2012167131A1|2011-06-01|2012-06-01|Durable multi-layer high strength polymer composite suitable for implant and articles produced therefrom|

---