WO2011084240A1

WO2011084240A1 - Method of improving the properties of a component of a medical device comprising a nickel-titanium-chromium alloy

Info

Publication number: WO2011084240A1
Application number: PCT/US2010/056938
Authority: WO
Inventors: James M. Carlson
Original assignee: Cook Inc
Current assignee: Cook Inc
Priority date: 2009-12-17
Filing date: 2010-11-17
Publication date: 2011-07-14
Anticipated expiration: 2012-06-17
Also published as: US20120255657A1

Abstract

A method of improving the properties of a component of a medical device entails constraining the component, which comprises about 45-55 at.% Ni, about 45-55 at.% Ti, and about 0.3 at.% Cr, into a predetermined configuration. The component also includes at least about 35% cold work. The component is heated during the constraining at a temperature of between about 425°C and about 500°C for a time duration of between about 5 minutes and about 30 minutes, thereby improving the superelastic and mechanical properties of the component. A medical device includes a superelastic component for use in a body vessel that comprises about 45-55 at.% Ni, about 45-55 at.% Ti, and about 0.3 at.% Cr, where the component has an upper plateau strength of at least about 75 ksi, a residual elongation of about 0.1 % or less, and an austenite finish temperature (Af) of about 30°C or less.

Description

METHOD OF IMPROVING THE PROPERTIES OF A COMPONENT OF A MEDICAL DEVICE COMPRISING A NICKEL-TITANIUM- CHROMIUM ALLOY

RELATED APPLICATION

[0001] The present patent document claims the benefit of the filing date under 35 U.S.C. §1 19(e) of Provisional U.S. Patent Application Serial No. 61/287,499, filed December 17, 2009, which is hereby incorporated by reference in its entirety.

TECHNICAL FIELD

[0002] The present disclosure is directed generally to processing methods for medical device components and more particularly to a method of improving the properties of a medical device component comprising a Ni-Ti-Cr alloy.

BACKGROUND

[0003] Nickel-titanium alloys are commonly used for the manufacture of endoluminal biomedical devices, such as self-expandable stents, stent grafts, embolic protection filters, and stone extraction baskets. These devices may exploit the superelastic or shape memory behavior of equiatomic or near- equiatomic nickel-titanium alloys. Such alloys, which are commonly referred to as Nitinol or Nitinol alloys, undergo a phase transformation between a lower temperature phase (martensite) and a higher temperature phase (austenite) that allows a previous shape or configuration to be "remembered" and recovered.

[0004] For example, strain introduced into a Nitinol stent in the martensitic phase to achieve a compressed configuration may be substantially recovered upon completion of a reverse phase transformation to austenite, allowing the alloy to elastically spring back to an expanded configuration. The strain recovery may be driven by the removal of an applied stress (superelastic effect) and/or by a change in temperature (shape memory effect). Typically, strains of up to 8-10% may be recovered during the phase transformation. [0005] To set the remembered shape, a superelastic component may undergo a heat setting treatment during processing. During heat setting, the component is constrained in the desired configuration and heated for a certain time and temperature. During this process, a "memory" of the desired configuration is imparted to the alloy. For conventional nickel-titanium alloys, different heat setting treatments have been evaluated and general guidelines regarding heat setting conditions are known in the art.

[0006] For some medical device applications (e.g., stents employed in the superficial femoral artery (SFA)), an enhancement of the properties of conventional binary Nitinol alloys is desired. For example, due to its location in the vicinity of the hip joint, the SFA may experience repetitive axial strains that can cause the artery to elongate or contract up to 10-12%. Stents placed in the SFA may thus be prone to fatigue failure. In addition, a stent deployed in the SFA or other superficial arteries may be subjected to crushing loads due to the proximity of the artery to the surface of the skin. A major challenge of treating the SFA is providing a stent having sufficient elasticity, crush resistance, and fatigue properties to withstand the strains of the arterial environment.

[0007] One approach to improving the properties of a metal is alloying. For example, Ni-Ti-X alloys, where X is another metallic alloying element, have been proposed for the purpose of improving the mechanical properties of binary Nitinol alloys. To gain maximum advantage from alloying additions, changes in the procedure used to fabricate and heat set the binary alloy may be required. A challenge is to formulate a processing regime for the desired Ni-Ti-X alloy so as to achieve the mechanical properties without sacrificing the superelastic behavior and characteristics. Such information is not generally available in the literature, nor is it predictable or obvious given the often complicated microstructural effects of alloying additions as well as the numerous processing and properties variables involved. BRIEF SUMMARY

[0008] A method of improving the superelastic and mechanical properties of a component of a medical device is set forth herein. Also described is a medical device including a superelastic component with improved properties. Both the method and the medical device are directed to a component including a Ni-Ti-Cr alloy.

[0009] The method of improving the properties of the medical device entails constraining the component, which comprises about 45-55 at.% Ni, about 45-55 at.% Ti, and about 0.3 at.% Cr, into a predetermined

configuration. The component also includes at least about 35% cold work. During the constraining, the component is heated at a temperature of between about 425°C and about 500°C for a time duration of between about 5 minutes and about 30 minutes. The superelastic and mechanical properties of the component are thereby improved.

[0010] The medical device includes a component comprising about 45-55 at.% Ni, about 45-55 at.% Ti, and about 0.3 at.% Cr, where the component has an upper plateau strength of at least about 75 ksi, a residual elongation of about 0.1 % or less, and an austenite finish temperature (A_f) of about 30°C or less.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 is a plot of austenite finish temperature (A_f) as a function of heat setting temperature (deg C) for a Ni-Ti-0.25 at.% Cr wire specimen;

[0012] Figure 2 is a plot of upper plateau strength, tensile strength and lower plateau strength (psi) as a function of heat setting temperature (deg C) for a Ni-Ti-0.25 at.% Cr wire specimen;

[0013] Figure 3 is a plot of residual elongation (%) as a function of heat setting temperature (deg C) for a Ni-Ti-0.25 at.% Cr wire specimen;

[0014] Figure 4 is a plot of uniform elongation (%) as a function of heat setting temperature (deg C) for a Ni-Ti-0.25 at.% Cr wire specimen;

[0015] Figure 5 is a plot of austenite finish temperature (A_f) as a function of cold work (%) imparted to a Ni-Ti-0.25 at.% Cr wire specimen; [0016] Figure 6 is a plot of upper plateau strength, tensile strength and lower plateau strength (psi) as a function of cold work (%) imparted to a Ni-Ti- 0.25 at.% Cr wire specimen;

[0017] Figure 7 is a plot of residual elongation (%) as a function of cold work (%) imparted to a Ni-Ti-0.25 at.% Cr wire specimen;

[0018] Figure 8 is a plot of uniform elongation (%) as a function of cold work (%) imparted to a Ni-Ti-0.25 at.% Cr wire specimen;

[0019] Figure 9 is a plot of austenite finish temperature (A_f) as a function of heat setting time (min) for a Ni-Ti-0.25 at.% Cr wire specimen;

[0020] Figure 10 is a plot of upper plateau strength, tensile strength and lower plateau strength (psi) as a function of heat setting time (min) for a Ni-Ti- 0.25 at.% Cr wire specimen;

[0021] Figure 1 1 is a plot of residual elongation (%) as a function of heat setting time (min) for a Ni-Ti-0.25 at.% Cr wire specimen;

[0022] Figure 12 is a plot of uniform elongation (%) as a function of heat setting time (min) for a Ni-Ti-0.25 at.% Cr wire specimen;

[0023] Figure 13 is a plot of radial force per unit length of 7 Fr Ni-Ti-Cr alloy stents having the Zilver® geometry;

[0024] Figure 14 is a plot of radial force per unit length of 7 Fr Ni-Ti binary alloy stents having the Zilver® geometry; and

[0025] Figure 15 is a plot overlaying the radial force per unit length for representative test articles of ternary and binary alloy stents.

DETAILED DESCRIPTION

[0026] Definitions

[0027] Binary Nitinol alloy - an alloy including about 45-55 at.% Ni and about 45-55 at.% Ti and no additional alloying elements, with the exception of any incidental impurities.

[0028] Austenite finish temperature (A_f) - the temperature at which, for a shape memory alloy having a higher temperature phase (austenite) and a lower temperature phase (martensite), a phase transformation to the austenitic phase is complete. [0029] Cold work - plastic deformation imparted to a component without applying heat to alter the size, shape and/or mechanical properties of the component.

[0030] Percent (%) cold work - a measurement of the amount of plastic deformation imparted to a component, where the amount is calculated as a percent reduction in a given dimension. For example, in wire and/or tube drawing, the percent cold work corresponds to the percent reduction in wire or tube cross-sectional area resulting from a drawing pass.

[0031] Upper plateau strength - the stress at 3% strain during loading of a superelastic Ni-Ti alloy specimen undergoing a tensile test in accordance with

ASTM Standard F 2516. This property is an indicator of the radial force that may be obtained from an expandable stent in use in a body vessel.

[0032] Lower plateau strength - the stress at 2.5% strain during unloading of the superelastic Ni-Ti alloy specimen, after loading to 6% strain during a tensile test in accordance with ASTM Standard F 2516.

[0033] Ultimate tensile strength (or "tensile strength") - the maximum load applied in breaking the specimen during the tensile test divided by the original cross-sectional area of the specimen.

[0034] Uniform elongation - the % elongation of the specimen at the maximum force sustained just prior to necking, or fracture, or both during the tensile test.

[0035] Residual elongation - the % difference between the strain at a stress of 7.0 MPa during unloading and the strain at a stress of 7.0 MPa during loading during the tensile test.

[0036] Described here is a method of improving the superelastic and mechanical properties of a medical device component including a Ni-Ti-Cr alloy. The method entails constraining the component, which contains about 45-55 at.% Ni, about 45-55 at.% Ti, and less than about 1 at.% Cr, into a predetermined configuration, such as a deployed configuration if the component is a stent or another endoluminal medical device. The component also includes at least about 35% cold work. Once constrained, the component is heated at a temperature in the range of about 425°C to about 500°C for a time duration of from about 5 to about 30 minutes so as to improve the superelastic and mechanical properties of the component.

[0037] Experiments to Determine Optimal Processing Conditions

[0038] To determine the optimal set of processing conditions for Ni-Ti-Cr alloy components, tensile tests and differential scanning calorimetry (DSC) experiments were carried out on a series of cold worked Ni-Ti-Cr wire specimens. Each specimen contained 0.25 at.% Cr and was processed according to a different regimen of heat setting conditions, as described below.

[0039] Tensile Tests

[0040] Prior to tensile testing, wire specimens drawn to a diameter of 0.01 inch and including either a low (-30%) or high (-45%) level of cold work underwent heat setting at temperatures ranging from 350°C to 550°C for time durations of 5 to 70 minutes. In particular, the wire specimens were heated at 350, 400, 450, 500, or 550°C for 5, 20, 60, or 70 minutes followed by water quenching. A total of 74 wire specimens having a gage length of 150 mm and an additional 13 specimens having a gage length of 102 mm underwent tensile testing at 37°C (body temperature) to simulate the conditions a medical device might experience in vivo. A summary of the wire specimens tested, including the amount of cold work and the heat setting conditions employed for each specimen, is provided in Table 1 .

Table 1 . Summary of Process Conditions for Ni-Ti-0.25 at.% Cr Wire

Specimens

Specimen Cold work level Heat setting Heat setting

ID LOW: 30% time (min) temperature (°C)

HIGH: 45%

1 LOW 20 500

2 LOW 20 500

3 LOW 20 500

4 HIGH 20 500

5 HIGH 20 500

6 HIGH 20 500

7 LOW 5 500 Specimen Cold work level Heat setting Heat setting ID LOW: 30% time (min) temperature (°C)

HIGH: 45%

8 LOW 5 500

9 LOW 5 500

10 HIGH 5 500

1 1 HIGH 5 500

12 LOW 70 500

13 LOW 70 500

14 LOW 70 500

15 HIGH 70 500

16 HIGH 70 500

17 HIGH 70 500

18 LOW 5 550

19 LOW 5 550

20 LOW 5 350

21 LOW 5 350

22 LOW 5 350

23 HIGH 5 350

24 HIGH 5 350

25 HIGH 5 350

26 LOW 20 350

27 LOW 20 350

28 LOW 20 350

29 HIGH 20 350

30 HIGH 20 350

31 HIGH 20 350

32 LOW 60 350

33 LOW 60 350

34 LOW 60 350

35 HIGH 60 350

36 HIGH 60 350

37 HIGH 60 350

38 LOW 5 400

39 LOW 5 400

40 LOW 5 400

41 HIGH 5 400

42 HIGH 5 400

43 HIGH 5 400

44 LOW 20 400

45 LOW 20 400

46 LOW 20 400

47 HIGH 20 400

48 HIGH 20 400

49 HIGH 20 400

50 LOW 60 400 Specimen Cold work level Heat setting Heat setting ID LOW: 30% time (min) temperature (°C)

HIGH: 45%

51 LOW 60 400

52 LOW 60 400

53 HIGH 60 400

54 HIGH 60 400

55 HIGH 60 400

56 LOW 5 450

57 LOW 5 450

58 LOW 5 450

59 HIGH 5 450

60 HIGH 5 450

61 HIGH 5 450

62 LOW 20 450

63 LOW 20 450

64 LOW 20 450

65 HIGH 20 450

66 HIGH 20 450

67 HIGH 20 450

68 LOW 60 450

69 LOW 60 450

70 LOW 60 450

71 HIGH 60 450

72 HIGH 60 450

73 HIGH 60 450

74 HIGH 5 550 r HIGH 5 550

2' LOW 20 550

3' LOW 20 550

4' LOW 20 550

5' HIGH 20 550

6' HIGH 20 550

T HIGH 20 550

8' LOW 60 550

9' LOW 60 550

10' LOW 60 550

1 1 ' HIGH 60 550

12' HIGH 60 550

13' HIGH 60 550

[0041] The tensile tests on the Ni-Ti-0.25 at.% Cr wire specimens were conducted in accordance with ASTM F2516 "Standard Test Method for Tension Testing of Nickel-Titanium Superelastic Materials" using an Instron 5569 test machine with a 1 -kN load cell. Crosshead displacement was monitored for strain determination, and crosshead rates of 3 mm/min and 30 mm/min were employed for testing. Table 2 provides a summary of the results from the tensile tests, including the ultimate tensile strength, % elongation, upper and lower plateau strength, and residual elongation for each specimen. Graphical representations of the tensile test data are provided in Figures 1 -6.

Table 2. Summary of Tensile Test Results for Ni-Ti-0.25 at.% Cr Wire

Specimens

[0042] The tensile test data obtained in the preceding table may be analyzed according to the protocol set forth below, along with data from differential scanning calorimetry (DSC) experiments, in order to determine optimal processing conditions for the Ni-Ti-Cr wire specimens.

[0043] Differential Scanning Calorimetry (DSC) Experiments

[0044] In addition to the tensile tests, a series of DSC experiments were carried out on a subset of the wire specimens, in particular, those heat set at temperatures of 350, 400, 450, 500, or 550°C for 5, 20, or 60 minutes and including either about 30% or 45% cold work. The objective was to evaluate the impact of the process variables (heat setting conditions and amount of cold work) on the austenite finish temperature (A_f) of the Ni-Ti-0.25 at.% Cr alloy specimens. A double loop DSC experiment performed according to the protocol set forth in U.S. Patent Application Serial No. 12/274,556, which is hereby incorporated by reference in its entirety, was employed for the testing. The A_f temperature obtained for each specimen based on the testing is provided in Table 3.

Table 3. Summary of Results of DSC Experiments

Temp. Time Cold work A_f (°C) Phase transformation (°C) (minutes) Low (L): 30% Two stage (2)

High (H): 45% Single stage (1 )

350 5 L 23.7 2

H 18.5 1

20 L 33 2

H 27.1 1

60 L 34.1 2

H 36.2 1

400 5 L 26.7 2

H 20.6 2

20 L 32.1 2

H 30.4 1

60 L 34.8 2

H 34.3 1

450 5 L 23.3 2

H 22.7 1

20 L 26.4 2

H 24.1 2

60 L 28.7 2

H 27.8 2

500 5 L 14.2 2

H 14.1 2

20 L 23.2 2

H 22.2 2

60 L 20.3 2

H 18.9 2

550 5 L -18.9 2

H -17.9 2

20 L -20.9 2

H -1 1 .6 2

60 L 8.7 2

H 10.7 2 [0045] Analysis

[0046] To identify the preferred processing conditions, specifically, the preferred amount of cold work and desired heat setting temperature and time, the results of the tensile tests and DSC experiments may be evaluated according to the following criteria and generally in the order indicated:

[0047] (1 ) A_f, where a value of about 30°C or less is desired and lower values (e.g., about 25°C or less) are generally preferred to ensure

superelasticity at body temperature;

[0048] (2) upper plateau strength, where a minimum value lies in the range of 62.4 ± 7.3 ksi and higher values {e.g., about 75 ksi or greater, or about 90 ksi or greater) are preferred;

[0049] (3) residual elongation, where a value of about 0.5% or less is desired and lower values (e.g., about 0.2% or less, or about 0.1 % or less) are preferred;

[0050] (4) ultimate tensile strength, where a value of at least about 145 ksi is desired and higher values {e.g., about 175 ksi or greater, or about 200 ksi or greater) are preferred;

[0051] (5) percent elongation, where a value of at least 10% is desired and higher values are preferred;

[0052] (6) lower plateau strength, where a value of at least about 25 ksi is desired and higher values {e.g., about 40 ksi or greater, or about 50 ksi or greater) are preferred.

[0053] Referring to Figure 1 , the data show that lower heat setting temperatures {e.g., 350°C and 400°C) lead to specimens with A_f values that are higher than desired for medical device components deployed

superelastically in the body, although the strength of these specimens (see Figure 2) is advantageously high. As shown in Figures 1 -3, at the second highest heat setting temperature of 500°C, the Ni-Ti-0.25 at.% Cr wire specimens yield satisfactory residual elongation (less than about 0.1 %) and good A_f values (14-23°C), but the tensile and upper plateau strengths are diminished compared to those of wire specimens heat set at lower temperatures. Specimens heat set at the highest temperature (550°C) show drastically decreased tensile strength and excessive residual elongation compared to specimens heat set at lower temperatures, despite having desirably low A_f values. And, as will be seen below, the radial force per unit length of Ni-Ti-0.35 at.% Cr stent specimens heat set at 500°C is lower than that of stent specimens heat set at 450°C.

[0054] Referring to Figures 5-8, a higher level of cold work seems to favorably impact the properties of the alloy. In general, specimens including about 45% cold work compared to about 30% cold work show higher strengths (see Figure 6) and lower residual elongations (see Figure 7).

[0055] Additionally, Figures 9-12 suggest that shorter heat setting time durations {e.g., 5-20 minutes compared to 60 minutes or more) may be associated with lower values of A_f and higher strengths.

[0056] Overall, the tensile data presented herein for 87 Ni-Ti-0.25 at.% Cr wire specimens combined with the DSC data for 30 of these samples indicate that a good combination of strength, elongation, and austenite finish temperature (A_f) may be attained for Ni-Ti-0.25 at.% Cr specimens with 45% cold work that undergo heat setting at a temperature of about 450°C-475°C for a time duration of from about 5-20 minutes.

[0057] In general, the Ni-Ti-Cr alloy specimen may be heat set at a temperature in the range of from about 425°C to about 500°C. As indicated, a temperature in the range of from about 450°C to about 475°C may be particularly effective. The heat setting temperature preferably does not exceed 500°C, and is no lower than 425°C. The heat setting may occur for a time duration of from about 5 min to about 30 min, or from about 5 min to about 20 min.

[0058] Since the Ni-Ti-0.25 at.% Cr specimens having a higher level of cold work generally show better performance, a cold work level of at least about 35% is preferred, with the range of from about 35% to about 45% being particularly suitable for the Ni-Ti-0.25 at.% Cr wire specimens. The

specimens may be cold worked up to 60% reduction in area provided that they have been properly annealed prior to drawing. However, fracture of the cannula or wire is possible as the cross section becomes smaller if defects are present, such as large carbides, oxides, nitrides, drawing defects, pits, etc. Accordingly, a cold work level of between about 40% and about 45% is expected to be a maximum preferred range.

[0059] Because of the different precipitation chemistry and phase structure of the ternary Ni-Ti-0.25 at.% Cr alloy compared to binary Nitinol alloys, what is known to be effective for the latter may not be effective for the former. This is clear when one considers that it is known in the art to heat set binary Nitinol at temperatures ranging from about 350°C to about 550°C, while

temperatures from both the low and high ends of this range are shown here to result in nonoptimal superelastic and mechanical properties for Ni-Ti-0.25 at.% Cr wire specimens.

[0060] Fatigue Life and Radial Force of Ni-Ti-0.25 at.% Cr Stents

Fabricated Under Preferred Processing Conditions

[0061] Experiments were carried out to evaluate the fatigue life and radial force capability of Ni-Ti-0.25 at.% Cr stents prepared from tubing including from 35%-45% cold work and processed using optimized heat setting conditions. In particular, cold worked Ni-Ti-0.25 at.% Cr tubing was laser cut to have the Zilver® stent pattern, and the stents were heat set at 450°C for 15-30 minutes and electropolished.

[0062] The results of the axial fatigue and radial force tests were compared to those obtained from conventional Zilver® stents based on binary Ni-Ti alloys (50.8 at.% Ni; 49.2 at.% Ti). The conventional Zilver® stents included about 35-45% cold work and were heat set at 425-475°C for a time duration of 10-20 min. A general description of the Ni-Ti-0.25% Cr test articles is provided in Tables 4 and 5, and the experiments are described below.

Table 4. Test Article Description for Axial Fatigue Experiments

Delivery system Stent diameter (mm) x Quantity of Sterilization

size length (mm) test articles

5 Fr 6 x 60 14 N/A

7 Fr 6 x 60 15 100% EtO Table 5. Test Article Description for Radial Force Experiments

[0063] Axial Fatigue Experiments

[0064] Each stent was deployed from its delivery system and attached to an EnduraTEC ELF tester using suitable fixtures. The gage length (distance between the mandrels on the tester) was set to 15 mm ± 0.5 mm and the stent was subjected to time accelerated, displacement-controlled longitudinal fatigue that corresponded to the desired percent change in gage length.

[0065] Testing was performed at 70 Hz in 37°C ± 2°C water until "run-out" (equivalent of 10 years or 10 million cycles) was reached or until fractures were observed. The temperature of the testing solution was measured at the beginning and end of each test at minimum. Each stent was visually monitored for fractures in the gage section. In the event of a fracture, the approximate number of cycles at which fracture occurred and location of the fracture were recorded.

[0066] The axial endurance limit of two designs of 6 mm (nominal diameter) stents cut from Ni-Ti-Cr alloy tubing was determined. The axial endurance limit is defined as the percent change in gage length at which six out of six test articles achieve run-out, whereas at least one test article out of four tested at higher percent changes in length (in increments of 1 %) exhibited fractures prior to reaching 10 million cycles.

[0067] A summary of the results is presented in Tables 6 and 7. The 5 Fr and 7 Fr Ni-Ti-Cr alloy stents achieved an endurance limit of ±3% and ±7%, respectively. For comparison, the endurance limit of a 5 Fr Zilver® stent has been previously determined to be ±2%, and the endurance limit of the 7 Fr Zilver® stent has been previously determined to be ±7%. The present study shows an improvement of 1 % for the 5 Fr stent produced from a Ni-Ti-Cr cannula as compared to the current 5 Fr Zilver® device, and no change in the endurance limit of the Ni-Ti-Cr stent compared to the current material. In summary, Ni-Ti-Cr stents laser cut to have the same pattern as Zilver® stents have the same or slightly better fatigue resistance than the current binary Nitinol alloy Zilver® stents.

Table 6. Summary of Results of Axial Fatigue Tests for 5 Fr Stents

Specimen Displacement No. of Cycles at which Fracture ID (5 Fr) Limits (%) Fracture(s) Observed Location

3 +5/-5 497,904 4 in gage region

4 542,024 Multiple in gage region

5 4.5/-4.5 >10,000,000 (runout) None observed

6 5,635,642 2 in gage region

1 >10,000,000 (runout) None observed

2 +4/-4 >10,000,000 (runout) None observed

7 3,822,066 3 in gage region

8 9,999,991 2 in gage region

10 >10,000,000 (runout) None observed

1 1 >10,000,000 (runout) None observed

12 +3/-3 >10,000,000 (runout) None observed

13 >10,000,000 (runout) None observed

14 >10,000,000 (runout) None observed

Table 7. Summary of Results of Axial Fatigue Tests for 7 Fr Stents

Specimen Displacement No. of Cycles at which Fracture ID (7 Fr) Limits (%) Fracture(s) Observed Location

1 >10,000,000 (runout) None observed

2 217,190 3 in gage region

3 +9/-9 157,800 3 in gage region

4 241 ,485 Multiple in gage region

5 678,129 Multiple in gage Specimen Displacement No. of Cycles at which Fracture ID (7 Fr) Limits (%) Fracture(s) Observed Location region

6 5,138,350 2 fractures in gage region

7 +3/-3 >10,000,000 (runout) None observed

14 >10,000,000 (runout) None observed

15 <10,000,000 Multiple in gage region

8 >10,000,000 (runout) None observed

9 >10,000,000 (runout) None observed

10 +11-1 >10,000,000 (runout) None observed

1 1 >10,000,000 (runout) None observed

12 >10,000,000 (runout) None observed

13 >10,000,000 (runout) None observed

[0068] Radial Force Experiments

[0069] Experiments were conducted to determine the radial force exerted by a Ni-Ti-0.25 at.% Cr alloy stent when its diameter is reduced by

mechanical constriction and compare the results to the behavior of a binary Nitinol alloy stent under the same conditions. Test articles having the geometry of Zilver® stents and processed as described above were employed in the experiments. The Ni-Ti-Cr alloy stent underwent heat setting at 450°C for 15-30 minutes.

[0070] The test articles were placed in a low-friction, stainless steel Machine Solutions radial expansion force gage. The temperature within the tester was maintained at 37°C ± 2°C during testing. Each test article was compressed from an initial, fully expanded diameter to a final diameter of 5 mm at a rate of 0.2 mm/s. The test article was then allowed to expand back to the initial diameter at the same rate. The compression and expansion were repeated for three cycles. Hoop force, diameter, and time were captured via the Machine Solutions software. Radial force was calculated from the hoop force at 5, 6, 7, 8, and 9 mm during the third cycle and recorded. These diameters are in the range of expected in vivo conditions. The third compression and expansion cycle of the test was used for data analysis to ensure that the stent equilibrated to the compression and expansion cycles.

[0071] The radial force data calculated at 5, 6, 7, 8, and 9 mm were normalized per unit length for the ternary and binary alloy stents. A summary of the results is presented in Tables 8 and 9, where Table 8 shows radial force per unit length vs. stent diameter for 10 mm x 40 mm Ni-Ti-Cr alloy stents, and Table 9 shows radial force per unit length vs. stent diameter for 10 mm x 80 mm Ni-Ti binary alloy stents. The radial force per unit length data are plotted and shown in Figures 13, 14, and 15. Figure 13 shows the radial force per unit length of the Ni-Ti-Cr alloy stents, and Figure 14 shows the radial force per unit length of the binary Nitinol alloy stents. Figure 15 provides an overlay of the radial force per unit length for representative Ni-Ti- Cr alloy and binary Nitinol alloy test articles.

Table 8. Summary of Results of Radial Force Experiments for 10 x 40 mm Ni- Ti-Cr Stents

Table 9. Summary of Results of Radial Force Experiments for 10 x 80 mm Ni- Ti Binary Alloy Stents

Radial Force/Length (N/mm)

Diameter 5 mm 6 mm 7 mm 8 mm 9 mm

Loading Mean 0.53 0.51 0.48 0.42 0.27 S.D. 0.01 0.01 0.01 0.01 0.01

Min. 0.52 0.50 0.46 0.40 0.25

Max. 0.54 0.52 0.49 0.43 0.28

Unloading Mean 0.53 0.36 0.27 0.22 0.17

S.D. 0.01 0.00 0.01 0.00 0.01

Min. 0.52 0.35 0.26 0.22 0.15

Max. 0.54 0.37 0.28 0.23 0.18

[0072] A t-test was performed comparing the radial force per unit length of the Ni-Ti-Cr alloy stents versus the binary alloy stents. The t-test showed that the radial force per unit length of the ternary alloy stents was significantly higher than that of the binary alloy stents during loading and unloading at each diameter (p < 0.05 in each case). In addition to the t-tests, a 95% confidence interval for the difference in means was constructed. Margins of superiority for the increase in radial force per unit length for the Ni-Ti-Cr alloy stents were subsequently calculated from the difference in means and are shown in Table 10.

Table 10. Summary of the Range of Increase in Radial force for Ni-Ti-Cr Stents Compared to Binary Ni-Ti Stents

[0073] Similar experiments were carried out with Ni-Ti-0.25 at.% Cr stents that were heat set at 500°C for 15-30 minutes. The radial force values obtained for these specimens were about 25% lower than those observed for the Ni-Ti binary alloy stents, and about 35% lower than the radial force values obtained for the Ni-Ti-0.25 at.% Cr stents heat set at 450°C for 15-30 minutes. The radial force data provide further support for a preferred Ni-Ti-Cr heat setting temperature range of from about 450°C to about 475°C.

[0074] The experiments described here show that stents based on Ni-Ti- 0.25 at.% Cr alloys processed under appropriate conditions may outperform stents based on binary Ni-Ti in terms of radial force, and they may exhibit equivalent or better axial fatigue properties.

[0075] Although the present invention has been described in considerable detail with reference to certain embodiments thereof, other embodiments are possible without departing from the present invention. The spirit and scope of the appended claims should not be limited, therefore, to the description of the preferred embodiments contained herein. All embodiments that come within the meaning of the claims, either literally or by equivalence, are intended to be embraced therein. Furthermore, the advantages described above are not necessarily the only advantages of the invention, and it is not necessarily expected that all of the described advantages will be achieved with every embodiment of the invention.

Claims

1 . A method of improving the properties of a component of a medical device comprising a Ni-Ti-Cr alloy, the method comprising:

constraining a component comprising about 45-55 at.% Ni, about 45-55 at.% Ti, and about 0.3 at.% Cr into a predetermined configuration, the component comprising at least about 35% cold work;

heating the component during the constraining at a temperature of between about 425°C and about 500°C for a time duration of between about 5 minutes and about 30 minutes, thereby improving the superelastic and mechanical properties of the component.

2. The method of claim 1 wherein the component includes about 0.25 at.% Cr.

3. The method of claim 1 wherein the temperature of the heating is between about 450°C and about 475°C.

4. The method of claim 1 wherein the time duration of the heating is about 20 minutes.

5. The method of claim 1 wherein the component includes between about 35% and about 45% cold work.

6. The method of claim 5 wherein the component includes about 45% cold work.

7. The method of claim 1 further comprising, prior to constraining the component, drawing an elongate body having a first cross-sectional area to a second cross-sectional area at least about 35% smaller than the first cross-sectional area, thereby forming the component.

8. The method of claim 1 wherein the component is a wire.

9. The method of claim 1 wherein the component is a thin-walled cannula.

10. The method of claim 1 wherein the component includes about 0.25% Cr and between about 35% and about 45% cold work, and wherein the temperature of the heating is between about 450°C and about 475°C and the time duration of the heating is about 20 minutes.

1 1 . The method of claim 10 wherein the component includes about 45% cold work and the temperature of the heating is about 450°C.

12. A medical device comprising a superelastic component for use in a body vessel, the medical device comprising:

a component comprising about 45-55 at.% Ni, about 45-55 at.% Ti, and about 0.3 at.% Cr, wherein the component has an upper plateau strength of at least about 75 ksi, a residual elongation of about 0.1 % or less, and an austenite finish temperature (A_f) of about 30°C or less.

13. The medical device of claim 12, wherein the component further comprises an ultimate tensile strength of at least about 200 ksi.

14. The medical device of claim 12 wherein the component further comprises a lower plateau strength of at least about 40 ksi.

15. The medical device of claim 12 wherein the component further comprises a radial force per unit length exceeding that of a component comprising a binary Nitinol alloy.

16. The medical device of claim 12 wherein the austenite finish temperature (A_f) is about 25°C or less.

17. The medical device of claim 12 wherein the upper plateau strength is at least about 90 ksi.

18. The medical device of claim 12, wherein the component comprises an upper plateau strength of at least about 90 ksi, a lower plateau strength of at least about 40 ksi, an ultimate tensile strength of at least about 200 ksi, a residual elongation of about 0.1 % or less, an austenite finish temperature (A_f) of about 25°C or less, and a radial force per unit length exceeding that of a component comprising a binary Nitinol alloy.