US20090285714A1

US20090285714A1 - Implantable medical Devices Composed of a Radiopaque Alloy and Method of Making the Alloy

Info

Publication number: US20090285714A1
Application number: US12/349,649
Authority: US
Inventors: Andrew Fisk; Robert S. Walsh, SR.; Francis E. Hanofer, JR.; Joseph C. Rosato, JR.; Anatolii Demchyshyn; Leonid Kulak; Sergei Firstov; Mykola Kumenko
Original assignee: Pulse Technologies Inc
Current assignee: Pulse Technologies Inc
Priority date: 2008-05-19
Filing date: 2009-01-07
Publication date: 2009-11-19
Also published as: WO2009142780A1

Abstract

Implantable medical devices made from a single beta phase Tantalum alloy utilizing Titanium as an alloying agent that are biocompatible, radiopaque and visible under x-ray and fluoroscopy, the alloy having mechanical properties that allow it to be machined by conventional, machining methods for forming the devices, and a method for making the alloy. The alloy is between approximately 10 percent and 25 percent Ti by weight and preferably has a density of 12 g/cm³or greater.

Description

RELATED APPLICATIONS

This application claims the benefit of U.S. provisional application 61/054,307, filed May 19, 2008 and entitled “Biocompatible Alloy Having Radiopaque Properties.”

FIELD OF THE INVENTION

This invention relates generally to a biocompatible medical devices used for chronic or acute implant, and, in particular, to such devices which must be radiopaque, such as to be visible under x-ray fluoroscopy.

BACKGROUND OF THE INVENTION

Biomedical devices such as those used in cardiac surgeries must be visible under fluoroscopy and x-ray. Examples of such devices include, for example, stimulation or sensing electrodes used with pacemakers, ablation catheters or permanently implanted defibrillators.
Examples of electrodes used for stimulation (“stimulation electrodes”) and sensing of electrical signals in the body (“sensing electrodes”) include (but are not limited to) a “tip” electrode having a blunted leading edge which is contacting tissue, a “ring” electrode having generally a cylindrical shape, a “helical” electrode or active fixation electrode comprising a coiled section, a “pin” electrode having a sharpened tip for insertion into tissue and a “disk” electrode comprising a flat disk for direct contact with tissue. These would also include a device known as a “shock coil,” which is a generally spring-shaped device used for the delivery of high energy stimulation by internal cardiac defibrillators.
Another type of electrode is a device for connecting wires, known as a “crimp” or “connector” which houses one or more wires and makes electrical connection by mechanical deforming, welding, brazing or soldering.
Also included are devices for locating the position of a medical device under x-ray fluoroscopy, know as a “marker” or “marker band”. This device is generally cylindrical in shape, or disk or tab shaped.
Such implanted electrodes are necessarily in a variety of shapes, such as coil- or screw-shaped, cylindrically-shaped or mushroom-shaped, and are typically machined into the desired shape, or, in the case of a coil-shaped device, are wound into the correct shape.
Current state of the art devices utilize platinum as the major constituent in the alloys used to form the devices. Platinum is both radiopaque and highly biocompatible and also possesses the necessary mechanical properties to be readily machined. Another material often used as a primary constituent is palladium, which has similar properties to platinum.
Typical x-ray fluoroscopy used to locate medical devices implanted in tissue relies on energy potentials in the range of 50 KeV to 150 KeV, and more typically in the range of 80 KeV to 120 KeV, with the majority of procedures done in the range of 100 KeV to 110 KeV. The ability of a material to absorb energies in this range is known as the mass energy absorption coefficient (μ_en/ρ) in units cm²/g. The mass energy absorption coefficient is the predominant characteristic which determines whether a material can be seen under x-ray fluoroscopy.
U.S. Pat. No. 7,354,488 describes a palladium-based material which is radiopaque, biocompatible and workable via machining. The patent describes radiopacity as tending to follow density and presents an alloy having half the density of platinum, but having the same radiopacity as platinum.
In U.S. Pat. No. 7,354,488 the alloys are subjected to radiation in the order of 50 KeV and 60 Kev, which is lower than that typically used for medical fluoroscopy. Typical energies for medical fluoroscopy are 80 KeV to 150 KeV and more typically from 90 KeV to 110 KeV. The mass energy absorption of the alloy disclosed in U.S. Pat. No. 7,354,488 is shown to be equal to platinum in radiopacity at 50 KeV and 60 KeV but has a radiopacity which is considerably lower than that of Pt-20% Ir in the range of 90 KeV to 110 KeV.
U.S. Pat. No. 6,027,585 describes a method for producing an Ta—Ti alloy by combining mixtures of Ta and Ti powder and subsequently melting them under a pressure of greater then 1 atm. The present invention differs in that the alloys are produced by melting separated ingots of Ta and Ti in a vacuum arc furnace at a pressure of less then 0.75 atm and greater then 0.1 atm. This range of pressures is sufficient to produce a homogeneous ingot of Ta—Ti alloy in the ranges of 10-20 wt % Ti. The present invention also differs in that the mechanical properties of the alloy are dependant on obtaining a single phase alloy where the material substantially Beta phase (>98%).
Patent App 2005/0070990 presents various Ta alloys, some containing Ti and a method for manufacturing the alloys. According to the application, the Ta and Ti materials (or other materials of differing vapor pressures) are mechanically bonded or formed together to create a solid body which is melted in a vacuum arc furnace of similar construct.
An alloy of Pd and Re is described in literature found on the website of Johnson Matthey Inc. This alloy, sold under the trade name Biomed® 1400, is a radiopaque material having the necessary properties to replace platinum alloys for medical uses. FIG. 3 shows the relative radiopacity of Biomed® 1400 against the present invention. In the ranges of 90 KeV to 110 KeV the alloy has an inferior radiopacity as compared to the alloy of the present invention.
Platinum and palladium are elements in the family of the precious metals group (PGM). While these elements possess optimum material characteristics, they have high market volatility and in recent years the price of platinum has doubled. The value of palladium is lower but still remains at an elevated level compared to other elements used in medical devices such as titanium, tantalum, cobalt and nickel.
The inventors of the present invention have realized that the radiopacity of the material is based on mass energy absorption and that the radiopacity of an object depends not only on the material but also the excitation energies used.
An ideal alloy for use in a medical implant which requires visibility under x-ray fluoroscopy would have a mass energy absorption (μ_en/ρ) equal to or greater then that of palladium (1.15 cm²/g) for the energies typically used for fluoroscopy (100 KeV). The alloy would also be biocompatible and non-corrosive during implant. The alloy would also be readily machinable with conventional techniques, having a tensile strength of greater then 550 MPa and less then 1380 MPa. The ideal alloy would also be made of primarily abundant materials with low market volatility and relatively low cost.

SUMMARY OF THE INVENTION

The present invention is an alloy and an implantable medical device composed of the alloy, which may be implanted into a body chronically or acutely. The implantable medical device may be an electrode, and, depending on the application, may be a stimulating or sensing electrode. The properties of the alloy allow for the medical device to be viewed under x-ray and fluoroscopy, having an x-ray signature similar to that of Pt.
The device consists of a metal alloy containing primarily Ta and Ti. The ratios of Ta and Ti, as well as the manner in which the alloys is produced, results in a radiopaque alloy which is machinable through conventional means. These conventional means include, but are not limited to turning, milling and drilling. It is preferred that the alloy be in the range of Ta-10% Ti to Ta-25% Ti and that the alloy be a single beta phase alloy.
Also disclosed is a process for manufacturing the alloy which involves creating various conditions under which the alloy will be homogeneous and of the proper phase.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an x-ray fluorescent photograph of different alloys, with the alloys being covered with a bag of saline solution to simulate visibility of devices made from these alloys when implanted into a human body.

FIG. 2 is a graph of the ultimate tensile strength, yield strength and elongation at break for Ta—Ti alloys having varying ratios of Ta and Ti.

FIG. 3 shows mass energy absorption coefficients for various materials over the useable fluoroscopy range of 80 KeV to 150 KeV.

DETAILED DESRIPTION OF THE INVENTION

Medical devices of the type which would be made from the Ta—Ti alloy of the present invention rely heavily on conventional machining techniques to provide small precision parts with dimensional tolerances of less than ±30 micron and, ideally, less than ±10 micron. Surface finish properties of current art devices are less than 0.8 micron Ra and ideally less than 0.5 micron Ra. These properties require the medical device to be made from materials having certain mechanical properties. Typical properties are ultimate tensile strength, yield strength and elongation at break.
Materials known to provide the required dimensional tolerances using conventional machining have ultimate tensile strengths in the range of 550 MPa to 1380 MPa and are ideally in the range of 690 MPa to 1170 MPa. Materials known to provide the above tolerances using conventional machining have yield strengths in the range of 550 MPa to 1030 MPa and are ideally in the range of 620 MPa to 900 MPa and elongation at break in the range of 2% to 15% and are ideally in the range of 6% to 14%.
Regarding the radiopacity of the alloy, FIG. 1 is an x-ray fluorescent photograph of different alloys, showing their relative visibilities when implanted into a body.
A range of alloys ranging from Ta-10% Ti to Ta-40% Ti were melted using a laboratory vacuum arc melting furnace at a pressure of less then 1 atm and greater then 0.1 atm.
The mechanical testing results of the alloys is found in FIG. 2. As can be seen, the optimal range to maximize the mechanical properties of the alloy lie between approximately Ta-10% Ti and Ta-25% Ti.
Mechanical testing of the alloys was performed on an annealed sample which was heated at 1200° C. for 20 hours and a formed sample with 82% deformation. The results are shown in the table below.


UTS	YS	Elongation
(Mpa)	(Mpa)	(%)

Formed	884	627	9.6
Annealed	662	627	3

Annealed and deformed sample were tested using dilatometric analysis. Three analysis were performed to a temperature of 1455° C. at rates of 80° C./min, 40° C./min and 20° C./min. Samples were subsequently cooled to room temperature. Dilatometric analysis did not show the presence of phase changes in the material upon heating or cooling.
The manufacture of the alloy occurs in a vacuum arc furnace at an atmospheric pressure less than 1 atm, preferably less than 0.75 atm, and most preferably at about 0.5 atm. This results in a homogeneous alloy in single beta phase, which was confirmed by x-ray diffraction analysis. The single beta phase material has the desired properties conducive to machining, radiopacity and biocompatibility. To obtain the desired properties, it is desirable that the alloy be primarily a single phase alloy containing 98% or greater beta phase.
The present invention creates the alloy by vacuum arc melting separated powders or nuggets at a pressure of 0.1-0.75 atm. This suppresses the evaporation of the titanium such that the titanium and the tantalum can be in liquid state sat the same time. Normally, because the melting point of the tantalum is much higher than that of titanium, the titanium would be evaporated before the tantalum reached it melting point.
The specific method for creating the alloy is as follows. First the pressure in the vacuum arc furnace is lowered to approximately 10⁻³Torr, and 99.99% pure argon is introduced via a constant flow to raise the pressure to approximately 230 Torr (˜0.3 ATM). The pressure is maintained between 150 Torr (˜0.2 ATM) and 300 Torr (˜0.4 ATM) throughout the rest of the procedure.
A getter may optionally be used to remove traces of oxygen in the chamber. Nuggets of pure titanium or zirconium may be used for this purpose. The getters are introduced into the chamber and an electric arc is applied to the getters to raise them to their melting points.
Because the melting point of Ta (3017° C.) is much higher than that of Ti (1668° C.), the Ti and Ta are placed into the furnace in the desired weight ratio, and are situated such that the electric arc will strike the nuggets of Ta rather than the Ti. This will cause The Ta to be raised to its melting pint before the Ti. The molten Ta will then cause the Ti to melt. One way to accomplish this is to place the solid Ti in a hearth covered by the solid Ta. Preferably, the hearth will be composed of a water-cooled metal, such as copper, but any suitable receptacle could be used.
The arc is then struck between the electrode and the Ta, using 40V at 1000 A -1500 A. Once the arc is struck, the current may be reduced to between approximately 700 A -900 A, preferably around 800 A. Other combinations of voltage and current may be used to achieve the same results. The arc is maintained until the Ti starts to evaporate, which will be evidenced by Ti vapor rising through the molten Ta, forming “stalagmites” in the Ta. At this point the alloy is formed and the arc is turned off, causing rapid solidification of the alloy.
To make the alloy more homogeneous, the melting and solidifying procedure can be performed multiple times by applying the arc to heat the ally to above the melting point of both materials and then discontinuing the arc or reducing the power of the arc to allow the rapid solidification of the alloy. To promote a thorough mixing of the metals in the alloy to achieve a homogeneous sample, the sample may be flipped over between applications of the arc. Alternatively, a series of cascading receptacles may be used to promote mixing of the metals. In this configuration, the alloys would be melted in the upper receptacle by application of the electric arc, and allowed to pour down to the next receptacle, where it solidifies. The arc is then re-applied until the alloy melts and pours down to the next receptacle, etc. Although two methods have been described, any method of mixing the metals in the alloy may be used.
The alloy is then drawn out of the furnace and allowed to cool rapidly, promoting formation of a single Beta phase material. The alloy may be cooled rapidly in a water cooled crystallizer to bring it to a single Beta phase.
To form rods suitable for machining into the required shapes for the medical devices described above, ingots of the alloy may first be mechanically treated (i.e., by forging or swaging) to form them into the necessary shape. The rods are then fractionally deformed, with a total degree of deformation greater than 40% at the first step. The rods are then interannealed by exposure to heat at a temperature between 800° C.-1600° C. for 15 minutes-24 hrs, but preferably a temperature between 1100° C.-1300° C. for 30-90 minutes, to reduce the possibility of oxidation. The rods are again fractionally deformed. The process is repeated until a rod having a total deformation of 70% or greater is achieved.
The interannealed rods may then be drawn into a wire by passing through a die with a maximum step size of about 0.05 mm. The wire can then be cut and machined or worked into the desired shapes for the various medical applications.
It should be recognized by one of skill in the art that variations on the described manufacturing process may be utilized and will render the same result, and that the method is not meant to be limited to the specific parameters provided.
The various sample alloys produced are described below.

EXAMPLE 1

An alloy of Ta-10% Ti was created by vacuum arc melting nuggets of high purity Ta and Ti in an atmosphere of 0.5 atm. The subsequent alloy was cold rolled to a total deformation of 82%. The alloy presented an ultimate tensile strength of 815 MPa and a yield strength of 702 MPa with an elongation of 3%. The resulting samples were found to be a single phase, containing more the 98% beta.

EXAMPLE 2

An alloy of Ta-16% Ti was created by vacuum arc melting nuggets of high purity Ta and Ti in an atmosphere of 0.5 atm. The subsequent alloy was cold rolled to a total deformation of 82%. The alloy presented an ultimate tensile strength of 943 MPa and a yield strength of 790 MPa with an elongation of 11%. The resulting samples were found to be a single phase, containing more the 98% beta. The alloy was then annealed at 1455° C. for 24 hours and cooled in air to room temperature. The resulting ultimate tensile strength was 662 with a yield strength of 667 and an elongation of 3%. Further deformation of this ingot caused a rise in the ultimate tensile strength and yield strength.

EXAMPLE 3

An alloy of Ta-24% Ti was created by vacuum arc melting nuggets of high purity Ta and Ti in an atmosphere of 0.5 atm. The subsequent alloy was cold rolled to a total deformation of 82%. The alloy presented an ultimate tensile strength of 822 MPa and a yield strength of 706 MPa with an elongation of 12%. The resulting samples were found to be a single phase, containing more the 98% beta.

EXAMPLE 4

An alloy of Ta-30% Ti was created by vacuum arc melting nuggets of high purity Ta and Ti in an atmosphere of 0.5 atm. The subsequent alloy was cold rolled to a total deformation of 82%. The alloy presented an ultimate tensile strength of 751 MPa and a yield strength of 656 MPa with an elongation of 9%. The resulting samples were found to be a single phase, containing more the 98% beta.

EXAMPLE 5

An alloy of Ta containing 40Wt % Ti was created by vacuum arc melting nuggets of high purity Ta and Ti in an atmosphere of 0.5 atm. The subsequent alloy was cold rolled to a total deformation of 82%. The alloy presented an ultimate tensile strength (UTS) of 1127 MPa and a yield strength (YS) of 542 MPa with an elongation of 4%. The resulting samples were found to be a single phase, containing more the 98% beta.
Note that other alloying agents may be utilized in place of titanium including, but not limited to, niobium, cobalt, molybdenum or zirconium.
FIG. 2 shows a graph of the mechanical properties of various Ta—Ti alloys from 10% Ti by weight to 40% Ti by weight. As can be seen, the desired mechanical properties previously mentioned are maximized in the alloys having between 10% and 20% Ti by weight.
As it is now known that the mass energy absorption changes with different ranges of applied fluoroscopy energy, FIG. 3 shows a graph of mass energy absorption versus fluoroscopy energy (KeV) for various alloys and substances. In the ranges typically used for medical fluoroscopy, it can be seen that the Ta-10% Ti and Ta-20% Ti alloys of the present invention perform well and are close enough to the performance the platinum alloy (Pt-20% Ir) to act as a very suitable substitute for the more expensive material.

Claims

1. An implantable medical device comprising a body composed of an alloy of tantalum and an alloying agent, said alloy having a mass energy absorption coefficient sufficient such that said medical device is visible under x-ray and fluoroscopy.

2. The device of claim 1 wherein the mass energy absorption coefficient of said Ta alloy is at least 75% that of platinum.

3. The device of claim 1 wherein said alloying agent is chosen from a group consisting of titanium, niobium, cobalt, molybdenum or zirconium.

4. The device of claim 1 wherein said alloying agent is titanium.

5. The device of claim 2 wherein said alloy is a homogeneous solid solution of tantalum and titanium.

6. The device of claim 3 wherein said alloy is in a single beta phase.

7. The device of claim 4 wherein said alloy exhibits an ultimate tensile strength between 550 Mpa and 1380 Mpa.

8. The device of claim 7 wherein said alloy exhibits an ultimate tensile strength between 690 Mpa and 1040 Mpa.

9. The device of claim 4 wherein said alloy exhibits a yield strength between 550 Mpa and 1030 Mpa.

10. The device of claim 4 wherein said alloy exhibits an elongation at break between 2% and 15%.

11. The device of claim 8 wherein said alloy exhibits an elongation at break between 6% and 14%.

12. The device of claim 4 where said alloy is between 10 and 25 percent titanium by weight.

13. An alloy of tantalum and titanium comprising:

a. said alloy being between 10 and 25 percent titanium by weight;

b. said alloy having being homogeneous and in a single beta phase; and

c. said alloy having a mass energy absorption coefficient of at least 75% that of platinum.

14. The alloy of claim 13 further comprising:

a. said alloy having an ultimate tensile strength between 550 Mpa and 1380 Mpa;

b. said alloy having a yield strength between 550 Mpa and 1030 Mpa.; and

c. said alloy exhibiting an elongation at break between 2% and 15%.

15. An implantable medical device composed of the alloy of claim 13 further comprising said implantable medical device being formed from a sample of said alloy that has been plastically deformed and annealed.

16. The device of claim 15, wherein said device is selected from a group consisting of a stimulation electrode, a sensing electrode a connector and a marker.

17. the device of claim 15, wherein said device is in the shape of a helix.

18. A method of producing an alloy of Ta and Ti comprising the steps of:

a. inserting nuggets of Ta and Ti in a vacuum arc furnace, wherein the Ti is between 10% and 25% of the total weight of said Ta and Ti;

b. dropping the pressure in said vacuum arc furnace to 0.75 atm or less;

c. applying an electric arc to said Ta and Ti nuggets to raise them to their respective melting points;

d. allowing said melted Ta and Ti to mix, forming a homogeneous mixture; and

e. drawing said mixture out of said furnace and allowing said mixture to cool rapidly to form a single beta phase alloy.

19. The method of claim 18 wherein said pressure is dropped to at least 10⁻³Torr.

20. The method of claim 19 further comprising the step of placing getters into said furnace and applying an electric arc to said getters to raise them to their melting points, to remove any trace oxygen from said furnace.

21. The method of claim 20 wherein said getters are nuggets of a material selected form a group consisting of Ti and Zr.

22. The method of claim 19 further comprising the step of introducing argon into said furnace at a constant rate to raise the pressure to between 150 Torr and 300 Torr.

23. The method of claim 22 wherein said argon is not less then 99% pure.

24. The method of claim 22 wherein said Ta and Ti are situated such that the electric arc contacts said Ta, thereby allowing said Ta to melt and further wherein said Ti is melted by the heat from said molten Ta.

25. The method of claim 24 further comprising the steps of:

a. melting a percentage of the total volume of Ta and Ti

b. stopping the melting by reducing the power of the arc

c. repeatedly increasing and decreasing the power of the arc until all of the Ti and Ta has been melted; and

d. allowing said melted Ta and Ti to mix, forming a homogeneous mixture.

26. The method of claim 24 further comprising the steps of

a. applying an arc to said Ta and Ti until said Ti starts to evaporate;

b. removing said arc and allowing the mixture of molten Ta and Ti to solidify;

c. reapplying said arc until the solidified alloy is re-melted; and

d. repeating steps a, b, and c until the desired degree of homogeneity is achieved.

27. The method of claim 26 further comprising flipping said solidified mixture after step b prior to re-establishing the arc.

28. The method of claim 24 further comprising the steps of:

a. providing two or more cascading receptacles;

b. melting the alloy in a first receptacle and allowing the molten mixture to flow from the first receptacle to the next receptacle in the cascade and solidify;

c. repeating step b until the desired degree of homogeneity is achieved.

29. The method of claim 24 wherein said arc is establish by applying 40V at 1000 A -1500 A and thereafter reducing the current to approximately 700-900 A.

30. The method of claim 25 further comprising the step of removing the alloy from the furnace and allowing it to cool quickly such that a single beta phase material is formed.

31. The method of claim 30 said cooling step further comprises the step of placing the alloy in a water cooled crystallizer.

32. A method of preparing the alloy of claim 13 for use in a medical device to achieve a two-staged plastic deformation of the alloy with a total degree of deformation of 70% or greater comprising the steps of:

a. mechanically treating ingots of said alloy to shape said ingots for subsequent deformation;

b. fractionally deforming the ingots into rods with a total degree of deformation of 40% or greater at first step;

c. interannealing the deformed ingots; and

d. fractionally deforming the ingots into rods with a total degree of deformation of 40% or greater at second step.

33. The method of claim 32 wherein said interannealing step further comprises the step of heating the alloy to between 1100° C. and 1300° C. for 30 to 90 minutes.

34. The method of claim 32 further comprising repeating steps c and d until a total deformation of 70% or greater is achieved.

35. The method of claim 34 wherein said deformed ingots are annealed at a temperature between 1100° C. and 1300° C. for 30-90 minutes to increase percent elongation at break.

36. The method of claim 34 further comprising the steps of

a. drawing said rod-shaped ingot of alloy through dies with the maximum step size of 0.05 mm; and

b. repeating step a until a wire of the desired diameter is achieved