WO2006117630A2

WO2006117630A2 - Method for manufacturing a leaflet for heart valve prostheses

Info

Publication number: WO2006117630A2
Application number: PCT/IB2006/001068
Authority: WO
Inventors: Alexander V. Samkov
Original assignee: Samkov Alexander V
Priority date: 2005-04-29
Filing date: 2006-04-28
Publication date: 2006-11-09
Also published as: WO2006117630A3

Abstract

A process for manufacturing a leaflet for an artificial heart valve includes pyrolyzing a carbon-containing precursor, present in a gas having a flow direction, to produce a pyrocarbon deposit on a substrate which has a fixed orientation with respect to the flow direction. A leaflet is formed from the deposit, wherein a conjugate axis of the leaflet is oriented along the flow direction. Also disclosed is a pyrocarbon leaflet for an artificial heart valve that has a flexural strength of at least about 200 MPa.

Description

TITLE OF THE INVENTION

METHOD FOR MANUFACTURING A LEAFLET FOR HEART VALVE PROSTHESES

BACKGROUND OF THE INVENTION

[oooi] One artificial heart valve type includes a titanium-based annulus, or casing, which encloses two leaflets. Pivot, stops, sockets or hinge components ensure proper opening and closing of the leaflets during operation. The leaflets themselves often include protrusions or lugs for attachment to the annulus. Parts in the leaflet that engage with sockets or rub against stops generally are subjected to high frictional forces and can experience a high mechanical load.

[0002] In some designs, leaflets are fabricated from a graphite substrate coated with pyrolytic carbon, also known as pyrocarbon. Generally, the term "pyrocarbon" or "pyrolytic carbon" refers to carbon material deposited from a hydrocarbon at temperatures ranging from 1000 degrees Kelvin (K) to 2500 K. In some instances, the pyrolytic carbon is referred to as "isotropic" carbon, a monolithic carbon material showing no preferred crystallographic orientation in its microstructure.

[0003] The process for producing pyrocarbon deposits on substrates often is conducted in fluidized bed reactors, with the substrates being "levitated" by a gas, often in the presence of small particles. U.S. Patent No. 6,274,191 Bl, issued to Emken on August 14, 2001 describes a deposition process conducted in a fluidized bed with suspended and unordered substrates, followed by fabricating a desired article entirely made from the pyrocarbon deposit.

[0004] With extended use, pyrocarbon coatings on graphite substrates can deteriorate. Wear in the coating is of particular concern at points of high friction and mechanical load, such as the leaflet lug region.

[0005] In the case of articles fabricated entirely from pyrocarbon, existing processes which use random substrate orientaions often result in "isotropic" carbon coatings that are not

Page l entirely isotropic but include regions of anisotropy. Such defects can cause deteriorations, reducing the durability and reliability of the article.

[0006] Since synthetic heart valve prosthetic devices are intended for extended use, a need exists for improving the reliability of heart valve components. A need also continues to exist for processes that result in heart valve leaflets having high wear resistance, in particular in regions of high mechanical load or wear. Articles made of pyrocarbon that have improved flexural strength also are needed.

SUMMARY OF THE INVENTION

[0007] The above and other features of the invention including various novel details of construction and combinations of parts, and other advantages, will now be more particularly described with reference to the accompanying drawings and pointed out in the claims. It will be understood that the particular method and device embodying the invention are shown by way of illustration and not as a limitation of the invention. The principles and features of this invention may be employed in various and numerous embodiments without departing from the scope of the invention.

[0008] The invention generally relates to the manufacture of pyrocarbon-containing articles, hi preferred aspects, the articles are entirely made from pyrocarbon.

[0009] In one embodiment, the invention is directed to a process for manufacturing a heart valve leaflet. In the process, a carbon-containing precursor, present in a gas having a flow direction, is pyrolyzed to produce a pyrocarbon deposit on a substrate. The substrate has a fixed orientation with respect to the flow direction. A leaflet is formed from the deposit wherein a conjugate axis of the leaflet is oriented along the flow direction.

[0010] The leaflet can be formed before, during or after separation of the substrate from the deposit. In preferred examples the substrate is made of graphite.

[0011] In another embodiment, the invention is directed to a pyrocarbon heart leaflet having a flexural strength of at least 200 mega Pascal (MPa). [0012] In a further embodiment, the invention is directed to a leaflet for an artificial heart valve, manufactured by a process comprising the steps of pyrolyzing a carbon-containing precursor, present in a gas having a flow direction, to produce a pyrocarbon deposit on a substrate having a fixed orientation with respect to the flow direction; and forming a leaflet from the deposit, wherein a conjugate axis of the leaflet is orientated along the flow direction.

[0013] The invention has many advantages. For example, practicing the process disclosed herein produces valve leaflets that have good biocompatibility, high flexural strength and increased wear resistance. The invention also can be employed to manufacture other prosthetic devices having good reliability and extended durability, as well as other articles or components thereof. Since the deposition process does not require a fluidized bed, problems associated with substrate levitation, clumping of added particles and operating the fluidized bed are eliminated. At temperatures between about 0 and about 200 degrees centigrade (⁰C), pyrocarbon obtained as disclosed herein has a strength of 180-250 MPa, while the pyrocarbon obtained with the method of fluidized levitation has only about half the strength at the same temperature. Compared to the substrate levitation, the present method provides a pyrocarbon structure that has a softer core, hence the properties of the pyrocarbon generally are uniform throughout the entire volume. Furthermore, the invention can be used to produce improved pyrocarbon coatings on a substrate.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] In the accompanying drawings, reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale; emphasis has instead been placed upon illustrating the principles of the invention. Of the drawings:

[0015] FIG. 1 is a perspective view of six substrate plates oriented in the direction of the gas flow.

[0016] FIG. 2 is a perspective view of a pyrocarbon layer being formed on a substrate plate using gas flowing in the direction of the arrow. [0017] FIG. 3 is a schematic diagram showing the cutting of a leaflet of a tri-leaflet heart valve design and that of a leaflet of a bi-leaflet heart valve design from pyrocarbon formed on a substrate plate using gas flowing in the direction of the arrow.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The invention relates to the manufacture of articles fabricated in whole or in part of pyrocarbon. In specific aspects, the invention relates to producing pyrocarbon medical devices, such as, for instance, leaflets or other components for artificial heart valves. The invention can be practiced in the manufacture of different leaflet designs for both bi-leaflet and tri-leaflet artificial heart valve prostheses.

[0019] In a specific example, the invention is used to manufacture tri-leaflets for an artificial heart valve disclosed in RU 2006110832 filed on April 4, 2006 with the title "Heart Valve Prosthesis" and a PCT Application with the same title, filed concurrently herewith under Attorney Docket No. 105.3 WO. The teachings of both applications are incorporated herein by reference in their entirety. Such leaflets preferably have convexo-concave surfaces, with each of the convex and concave surfaces being a fragment of a toroidal surface. The leaflet thickness preferably is non-uniform and can increase from a symmetry plane towards the regions at or near the hinge mechanisms. In specific examples the thickness increases from the symmetry plane to the hinge mechanisms by a factor within the range of from about 1.13 to about 1.35.

[0020] Pyrocarbon deposits used in the practice of the invention are obtained by decomposing a carbon-containing precursor, for instance a hydrocarbon in gaseous or vapor state. Suitable hydrocarbons include methane, ethane, propane, isopropane, propylene, acetylene, natural gas and so forth. In a specific example, the carbon-containing precursor includes methane and propane. Propane, which decomposes at a temperature lower than methane forms soot particles that act as crystallization seeds or centers for growing the pyrocarbon layer. [0021] Other compounds as well as combinations of carbon-containing precursors also can be used. In many cases, the carbon-containing precursor is pre-mixed with one or more inert gases, which serve as carriers. Examples of inert gases that can be employed include nitrogen, argon, helium and others known in the art. Additives, such as, for example, boron trichloride (BCl₃) or methylchlorosilanes also can be included. BCl₃, for example, is believed to increase the density of the polycarbon deposit.

[0022] The process described herein is conducted in a reactor, preferably a continuous reactor, having an inlet for receiving a gas such as described above and an outlet for exhaust. The reactor can be a continuous tubular reactor. Other suitable reactor types also can be employed.

[0023] The reactor is designed for maintaining a vacuum and can be fabricated from a suitable material capable of withstanding high temperatures. The reactor has a suitable size for producing artificial heart valve leaflets.

[0024] During operation, the reactor is heated to a temperature sufficient for carrying out the decomposition or "pyrolysis" of the carbon-containing precursor. Hydrocarbon precursors, for instance, often are heated to a temperature of at least about 1100 degrees centigrade (°C). Typical pyrolysis temperatures are in the range of from about 1200°C to about 1500°C. Higher temperatures also can be used. The reactor can be heated in a furnace or by heating coils, electrical elements, hot exhaust gases and other means known in the art.

[0025] Reactor temperature, pressure, gas flow parameters, and other reactor conditions can be monitored and/or controlled by valves, flow meters, sensors automated controls and other means.

[0026] The reactor houses one and preferably more than one substrate. As used herein, the term "multiple substrates" or a "plurality of substrates" means that at least two substrates are present. Shown in FIG. 1 is an arrangement using six substrate plates 10. More or less substrates can be processed, depending on factors such as their size, shape, reactor dimensions, desired productivity and others. In preferred examples, substrate plates 10 are fabricated from graphite. Other materials, such as, variations of graphite, also can be employed.

[0027 ] To prepare coated articles, pyrocarbon deposits also can be formed on materials able to withstand pyrolysis temperatures, e.g., HOO⁰C. Examples include refractory metals such as W, Ta, Nb, Hf, Rh.

[0028] Pyrocarbon is deposited or "precipitated" on substrates 10 by decomposing or pyrolyzing a carbon-containing precursor present in gas 12. As described above, in addition to the carbon-containing precursor, gas 12 preferably includes an inert carrier gas, e.g. nitrogen, and optionally one or more additives such as BCl₃.

[0029] Optionally, gas 12 or any component thereof can be preheated to a desired temperature prior to being introduced to the reactor. Preheating can be by heat exchangers or other means known in the art. The flow of gas 12 through the reactor can be continuous or intermittent, e.g., pulsed. Its flow rate can be constant or essentially constant throughout the deposition process or it can be varied. The flow of gas can be interrupted in order to carry out the deposition in stages, to analyze the deposit, for equipment malfunctions or for other reasons.

[0030] The orientation of substrate plates 10 is fixed with respect to the flow direction, indicated by the arrow, of gas 12. In one example, substrate plates 10 are attached in a fixed orientation to the reactor walls, not shown in FIG. 1. In one arrangement, no gap is formed between the substrate plate and the reactor wall. Other substrate plate arrangements can be selected as long as their orientation with respect to the gas flow remains unchanged during the deposition process. Arrangements in which two or more faces or sides of a substrate body are coated with pyrocarbon also can be used.

[0031] With substrate plates 10 fixed in the reactor, directional changes of gas 12 can be minimized or eliminated by avoiding turbulence in the gas flow. A steady and relatively gentle gas flow can be selected, hi preferred examples, gas 12 is swept by plates 12 in a laminar mode, such as can be obtained by using a diffuser or other means known in the art. Also preferred are arrangements in which no gaps are formed between adjacent plates, as shown in the arrangement illustrated in FIG. 1. Other approaches also can be utilized to minimize directional changes in the flow of gas 12.

[0032] Pyrolysis of the carbon-containing precursor and deposition or precipitation of pyrocarbon on substrate plates 12 can be conducted at a desired rate and for a desired time interval. In many cases, the rate of precipitation depends on the gas flow rate. Often, longer deposition times result in thicker deposits. Adjusting the ration of inert gas to carbon- containing precursor can affect flow characteristics, precipitation rates and deposit characteristics. Other parameters that can affect deposition rates and quality of deposits include the nature of the carbon-containing precursor, reactor temperature, the shape and material of substrate plates 10, reactor geometry, impurity content and others.

[ 0033] Deposits also can be prepared in two or more stages. If desired, the deposition process described herein can be preceded and/or followed by other deposition processes, for instance by random orientation depositions.

[ 0034 ] FIG. 2 illustrates the formation of pyrocarbon deposit 14 on plate 10, swept by gas 12. For many applications, pyrocarbon deposit 14 has a final thickness of a few millimeters (mm), e.g., in the range of from a few tenths of a millimeter to about 10 mm. Thinner as well as thicker deposits also can be produced. For instance, if the end product is a graphite article, coated with pyrocarbon, the deposit can be as thin as about 3-4 microns (μm), whereas some articles entirely made of pyrocarbon, may require a deposit thicker than about 10 mm.

[ 0035 ]

[0036] The properties of pyrocarbon deposits obtained by the process described herein can be determined by analytic techniques known in the art. Examples include density measurements, microstructure, microhardness, flexural strength and others.

[0037] Once the pyrolysis is finished, plates 10 coated with pyrocarbon deposit 14 can be cooled, for instance to room tyemperature or to another temperature suitable for forming an end product, e.g., a leaflet for an artificial heart valve. Forming a desired article can be by one or more mechanical operations such as cutting, grinding, and so forth, by selective dissolution of unwanted portions of material, or by other operations.

[0038] FIG. 3 is a schematic diagram illustrating the preferred orientation for forming an end product. Shown in FIG. 3 is substrate plate 10 and pyrocarbon deposit 14, prepared essentially as described above. The arrow indicates the flow direction of gas 12, used in the deposition process. Also shown in FIG. 3, is the orientation of two end articles, tri-leflet 16 and bi-leaflet 18, being formed from deposit 14 grown on substrate 10. Specifically, conjugate axis 20, connecting lugs 22 and conjugate axis 24, connecting lugs 26, are oriented in the same direction, as that of the flow of gas 12. Specifically, conjugate axes 20 and 22 are essentially lined up or essentially parallel to the arrow representing the flow direction of gas 12. Herein,, this orientation also is described as being "along" the direction of the gas flow.

[0039] As seen in FIG. 3, the "conjugate axis" refers to the conjugate axis of the lugs. This axis is a straight line that can be drawn inside, or through the volume of the leaflet, as in the case of a two-leaf valve, as well as outside the leaflet, as in the three-leaf valve. In other articles, the conjugate axis is a straight line between two hinge or flange mechanisms, e.g., lugs or pivots, that can rotate in recesses and that couple a cover or lid to the body of the article.

[0040] In a preferred embodiment of the invention, the pyrocarbon deposit is separated from the material, e.g., graphite, making up substrate 10. Removal of substrate 10, or portion thereof, can be conducted before, during or after the forming of the desired article, e.g., leaflet 16 or IS. Removal can be by one or more mechanical operations, such as boring, grinding, chipping, abrading, sand blasting and so forth. Chemical processes such as etching, also can be used. Finishing operations such as filing or polishing can be carried out to smooth product surfaces.

[0041] Flexural strength of pyrocarbon leaflet samples fabricated by practicing the invention exceeds by about 20% that of samples prepared with no particular (random) orientation with respect to the gas flow. Flexural strength of pyrocarbon leaflet samples fabricated according to the invention also is about 30% higher than the flexural strength of samples orientated in the traverse direction relative to the gas flow. In one example, the flexural strength of a leaflet, measured by known techniques, is within the range of from about 180 Mpa to abput 250 Mpa at a temperature between about 0 degrees (°) Centigrade and about 200° C.

[0042] Other articles that have regions of high mechanical loads also can be manufactured using the orientations of gas flow and axes shown in FIG. 3. In further aspects of the invention, the orientations depicted in FIG 3 can be used to form articles coated with pyrocarbon. For instance pyrocarbon can be depositied on all surfaces of a substrate and the step of separating the deposit from the substrate material can be omitted.

EXAMPLE

[0043] Six graphite plates having the dimensions of 170 x 47 x 5.0 mm were arranged in a tubular continuous reactor as shown in FIG. 1 and were heated to 1400° C - 1500° C. A gas containing 45 % nitrogen, 45% methane and 10% BCl₃ was directed to the reactor in the direction shown in FIG. 1. As described above, the plates were kept in a fixed orientation with respect to the gas flow. Pyrocarbon precipitation was carried out for 10 - 12 hours to form a pyrocarbon deposit having a thickness between 3.5 and 4.5 mm. The pyrocarbon, deposited on the graphite plates, was used to manufacture leaflets following the leaflet orientation shown in FIG. 3, i.e., having the conjugate axis of the leaflet along the direction of the gas flow. Once formed, the pyrocarbon leaflets were separated from the graphite substrate and tested for flexural strength using known measurement techniques.

[0044] Leaflets also were prepared by cutting plates on which deposits were made transverse to the direction of the gas flow. In these samples, the conjugate axis of the leaflet was perpendicular with respect to the direction of the gas flow. [0045] It was found that leaflets prepared according to the invention had a flexural strength of 27 kgf/mm² +/- 0.6 while those made using transverse gas flow had a flexural strength of about 28 % lower.

[0046] While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.

Claims

CLAIMSWhat is claimed is:

1. A process for manufacturing a leaflet for an artificial heart valve, the process comprising: a. pyrolyzing a carbon-containing precursor, present in a gas having a flow direction, to produce a pyrocarbon deposit on a substrate, said substrate having a fixed orientation with respect to the flow direction; and b. forming a leaflet from said deposit, wherein a conjugate axis of the leaflet is oriented along the flow direction.

2. The process of Claim 1 , further comprising separating at least a portion of the substrate from the pyrocarbon deposit.

3. The process of Claim 1 , further comprising separating the leaflet from at least a portion of the substrate.

3. The process of Claim 1 , wherein the substrate is made of graphite.

4. The process of Claim 1 , wherein the carbon-containing precursor is a hydrocarbon.

5. The process of Claim 1 , wherein the gas includes an inert gas carrier.

6. The process of Claim 1, wherein the gas includes an additive.

7. The process of Claim 1 , wherein the carbon-containing precursor is pyrolyzed at a temperature above 1100⁰C.

8. The process of Claim 1 , wherein the substrate is housed in a continuous tubular reactor.

9. The process of Claim 1, wherein pyrocarbon is deposited on multiple substrates.

10. The process of Claim 9, wherein the multiple substrates are in an arrangement without gaps between adjacent substrates.

11. The process of Claim 1 , wherein the leaflet is a leaflet for a bi-leaflet heart valve prosthesis.

12. The process of Claim I₅ wherein the leaflet is a leaflet for a tri-leaflet heart valve prosthesis.

13. The process of Claim 1 , further comprising mounting the leaflet in an artificial heart valve prosthesis.

14. A leaflet for an artificial heart valve manufactured by a process comprising the steps of: a. pyrolyzing a carbon-containing precursor, present in a gas having a flow direction, to produce a pyrocarbon deposit on a substrate having a fixed orientation with respect to the flow direction; and b. forming a leaflet from said deposit, wherein a conjugate axis of the leaflet is orientated along the flow direction.

15. A pyrocarbon leaflet for an artificial heart valve, the leaflet having a flexural strength of at least about 200 MPa.

16. An method for producing a pyrocarbon-containing article, the method comprising: a. pyrolyzing a carbon-containing precursor, present in a gas having a flow direction, to produce a pyrocarbon deposit on a substrate having a fixed orientation with respect to the flow direction; b. forming the article from the pyrocarbon deposit on the substrate, wherein a conjugate axis of the article is oriented along the flow direction; and c. . optionally removing the substrate or a portion thereof.

17. A process for producing a leaflet for an artificial heart valve, the process comprising: forming a shape of the leaflet from a pyrocarbon deposit, wherein a conjugate axis of the leaflet is orientated along a flow direction of a gas sweeping a substrate during pyrolysis, said substrate having a fixed orientation with respect to the flow direction.