Processes for regulating NITI properties

Abstract

An alloy that includes Ni and Ti is provided. The alloy has an austenite finish temperature (Af) of about 20 °C or less and a radial force (RF) of about 3.0 gf to 4.5 gf average per 3 mm capsule, or an RF of about 1.5 gf to 3.0 gf average per 4 mm or 6 mm capsules.

Description

1956788.00381 PROCESSES FOR REGULATING NITI PROPERTIES RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional patent application 63 / 624,141 filed January 23, 2024, the entire contents of which are incorporated by reference herein. FIELD

[0002] The present disclosure relates to nitinol compositions. BACKGROUND

[0003] Nickel titanium, also known as nitinol is a metal alloy that contains nickel and titanium. Nitinol is a common engineering material in the medical industry. Nitinol is sometimes referred to as the “metal with a memory” or as an alloy with a “thermal memory effect.” These alloys exhibit a combination of properties that make them particularly suited for self-expanding stents. The “thermal memory effect” of nitinol causes the released stent to unfold into its predetermined dimensions at body temperature. It therefore adapts to the anatomy and achieves the desired dilation of the stenosis in an optimum manner.

[0004] Despite the advantageous properties of nitinol, there is still a need for an alloy with a lower austenite finish temperature (Af). SUMMARY

[0005] The present disclosure solves the above shortcoming. Having the lower Af temperature increases the radial force (RF) of the device and permits the desired shape created during the heat setting process to become fully realized at lower ambient temperatures. Thus, a user may see how a device is intended to look while the device is being used in its vessel. In addition, the lower Af temperature results in a higher RF without making changes to the device dimensions. The present disclosure provides processes for achieving an alloy with these desired properties. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] The following figures are included to illustrate certain aspects of the present disclosure and should not be viewed as exclusive embodiments. The subject matter disclosed is capable of considerable modifications, alterations, combinations, and equivalents in form and function, as will occur to one having ordinary skill in the art and having the benefit of this disclosure. 508933170.111956788.00381

[0007] FIG.1. Differential scanning calorimetry (DSC) testing: Af temperature of heat set 570 °C 5-5-5-5-8 min.

[0008] FIG.2. DSC testing: Af temperature of heat set 570 °C 2-5-5-5-8 min.

[0009] FIG.3. DSC testing: Af temperature of expanded capsules vs. unexpanded.

[0010] FIG.4. DSC testing: Af temperature results of no heat set and laser cut hypotube vs raw hypotube without laser cut.

[0011] FIG.5. Load dependency of the Af temperature. DETAILED DESCRIPTION

[0012] A lower Af temperature increases the RF of the device and allows the desired shape created during the heat set process to become fully realized at lower ambient temperature. Previous Af temperatures between 22-37 °C would show the desired shape at body temperature when deployed in a vessel, but would not show the desired shape at room temperature. Lowering the Af temperature below 20 °C allows the desired shape to be fully realized at room temperature and body temperature, so if a user looks at the device at room temperature they can see how it is intended to look while being used in the vessel. A lower Af temperature also results in a higher RF without making changes to the device dimensions.

[0013] RF spec is ≥ 3.0 gf average per capsule (Hoop Force) for the 3 mm size and ≥ 1.5gf average per capsule (Hoop Force) for the 4 and 6mm sizes. These are measured as Chronic Outward Force at ~50% max OD.

[0014] Af temperature spec is ≤ 20 °C. 508933170.121956788.00381 Table 1. Sample specifications for example NiTi tube size one. Characteristic Properties Unit Requirement Test Results Chemical Composition 5 4 4 0 8 6 0 0Ingot Properties Units Requirement Results Mi M Mi M 9 3 % % 75ts508933170.131956788.00381 Table 3. Before and after dimensions for capsules. Size Dimension Before shape setting After shape setting process (mm) process (mm) [00ample, DSC, X-ray diffractometry (XRD) and transmission electron microscopy (TEM). These techniques are well known to those skilled in the art and are described, for example, in Y. Liu, S. Miyazaki, and J.I. Kim, "Ageing-induced Two-stage R-phase Transformation in Ti-50.8at.%Ni," vol.52, pp. 487-499, 2004.

[0016] The percentage of nickel in nitinol may similarly be determined by techniques that are well known to those skilled in the art. These techniques may include energy dispersive x-ray analysis (EDX) and scanning electron microscope (SEM).

[0017] Experiments were performed with a goal being to decrease the Af temperature and increase the RF.

[0018] An Af temperature of NiTi may be altered by subjecting the NiTi material to heat for a specific period of time and quenching the material in water after that time has elapsed. An initial experiment was conducted in which the heat setting was accomplished in four steps. A quench in water was performed after each step.

[0019] The four steps were as follows: Step 1: 550 °C for 5 minutes; Step 2: 550 °C for 3 minutes; Step 3: 550 °C for 3 minutes; and Step 4: 550 °C for 8 minutes.

[0020] This process resulted in a higher than desired Af temperature, and a lower RF of the device. To remedy this issue, further experiments were performed to determine the optimal temperatures and times for heat setting steps. It was determined that raising the temperature and time, in some steps, resulted in a lower Af temperature and a higher RF. 508933170.141956788.00381

[0021] Increasing the temperature to 570 °C and 580 °C and increasing the time in Steps 2 and 3 to 5 minutes provided more desirable Af temperatures and RF results.

[0022] One of the best performing processes was found to be: Step 1: 570 °C for 5 minutes; Step 2: 570 °C for 5 minutes; Step 3: 570 °C for 5 minutes; and Step 4: 570 °C for 8 minutes.

[0023] And another of the best performing processes was found to be: Step 1: 570 °C for 5 minutes; Step 2: 570 °C for 5 minutes; Step 3: 570 °C for 5 minutes; and Step 4: 580 °C for 8 minutes.

[0024] The following figures show the results of DSC testing under a variety of conditions.

[0025] FIG. 1 shows Af temperature of heat set 570 °C 5-5-5-5-8 min. Af Temperature is consistently lower when expanded (compared to non-expanded) for both 6 mm and 3 mm spheres. The stress / strain applied when using fixtures during heat set process affects the Af temperature.

[0026] FIG.2 shows Af temperature of heat set 570 °C 2-5-5-5-8 min.

[0027] FIG. 3 shows Af temperature of expanded capsules vs. unexpanded. The different heat steps did not significantly alter the Af temperature for the 6 mm samples. There was a difference between Af temperature for the 3 mm samples with different heat set steps.

[0028] FIG. 4 shows Af temperature results of no heat set and laser cut hypotube vs raw hypotube without laser cut. 508933170.151956788.00381 Table 4. Raw data from the foregoing experiments. 6 mm Heat Set 5-5-5-8 min 3 mm Heat Set 5-5-5-8 min Size Sample Shape Af Size Sample Shape Af 1 1 7 f 0 9 f 3 2 1508933170.161956788.00381 Size Sample Shape Af Size Sample Shape Af # # 8 3is not greatly affected by the addition of 2 or 5 minutes to the existing heat set time for 6 mm capsules. However, this time has a greater effect on the 3 mm capsules. Heat set at 570 °C is sufficient to lower Af temperature to capsules visually expanded at room temperature with heat setting 5-5-5- 8.

[0030] The studies of the present disclosure have applications to stent transformation modification and shape recovery. The best performing processes described above (i.e., Step 1: 570 °C for 5 minutes; Step 2: 570 °C for 5 minutes; Step 3: 570 °C for 5 minutes; and Step 4: 570 °C for 8 minutes; and Step 1: 570 °C for 5 minutes; Step 2: 570 °C for 5 minutes; Step 3: 570 °C for 5 minutes; and Step 4: 580 °C for 8 minutes) were shown to i) result in an Af temperature reduction and an RF increase; and ii) remove / minimize the retained strain / deformation caused during the expansion process. In the presence of retained stress-strain / deformation, it was shown that it was difficult to cause an Af temperature reduction and an increase in RF.

[0031] In the stent transformation modification and shape recovery process, it was shown that the heat treatment and quenching resulted in removing substantially all the remaining stress / strain. This was followed by shape recovery to the nominal specifications after crimp- reopening. After the heat treatment and quenching resulted in removing substantially all the remaining stress / strain, no extra stress was added and / or built up in the subsequent crimping step. In the crimping step, the deformation / strain left was below 8%.

[0032] If any type of mechanical loading (the force applied for the capsule expansion) exists during the heat treatment / annealing process, it does have a considerable effect on the Af temperature. The force applied on the capsule to expand it and the heat treatment / annealing is accomplished as quickly as possible. This causes a double effect on Af temperature changes. This double effect event (mechanical and thermal effects) causes significant changes to the Af 508933170.171956788.00381 temperature, compared to, for example, the raw hypotube in which the Af temperature response is only thermally driven (heat setting parameters). This phenomena is called “Load-dependency of Af temperature” and it happens when the applied load and the heating process occur almost at the same time (The stress-strain stays inside the capsule during / after the expansion).

[0033] FIG.5 shows the load dependency of the Af temperature.

[0034] Aspects of the present disclosure are directed to alloys that include Ni and Ti. In some embodiments, the alloy has an austenite finish temperature (Af) of about 20 °C or less and a radial force (RF) of about 3.0 gf to 4.5 gf average per 3 mm capsule and / or an RF of about 1.5 gf to 3.0 gf average per 4 mm or 6 mm capsules. In some embodiments, the alloy has an Af of 20 °C or less and a radial force (RF) of 3.0 gf to 4.5 gf average per 3 mm capsule and an RF of 1.5 gf to 3.0 gf average per 4 mm or 6 mm capsules. In some embodiments, the alloy has an Af of about 0 °C to about 20 °C. In some embodiments, the alloy has an Af of about 10 °C to about 20 °C. In some embodiments, the alloy has an Af of about 5 °C to about 15 °C.

[0035] In some embodiments, the alloy includes about 52 to 60 % Ni and about 40 to 48 % Ti.

[0036] In some embodiments, the alloy includes about 54 to 58 % Ni and about 42 to 46 % Ti.

[0037] In some embodiments, the alloy includes about 55 to 57 % Ni and about 43 to 45 % Ti.

[0038] In some embodiments, the alloy includes about 55 to 56 % Ni and about 44 to 45 % Ti.

[0039] In some embodiments, the alloy includes about 56 % Ni and about 44 % Ti.

[0040] In some embodiments, the alloy includes about 55.8 % Ni and about 44.2 % Ti.

[0041] In some embodiments, the alloy includes about 55.9 % Ni and about 44.1 % Ti.

[0042] In some embodiments, the alloy has been sequentially treated. Prior to sequential treatment the untreated alloy had an Af temperature of greater than about 20 °C and an RF less than that of the alloy (e.g., an RF of less than about 3.0 gf to 4.5 gf average per 3 mm capsule, or an RF of less than about 1.5 gf to 3.0 gf average per 4 mm or 6 mm capsules). The sequential treatment includes one of A or B: A) includes: a first heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a first quench; a second heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a second quench; a third 508933170.181956788.00381 heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a third quench; and a fourth heat treatment at 570 ± 2 °C for 8 ± 0.5 minutes, followed by a fourth quench; or B) includes: a first heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a first quench; a second heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a second quench; a third heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a third quench; and a fourth heat treatment at 580 ± 2 °C for 8 ± 0.5 minutes, followed by a fourth quench.

[0043] In some embodiments, provided herein are methods of making the alloys disclosed herein comprising a sequential treatment of an untreated alloy. Thus, in some embodiments, provided herein are methods of making the alloys provided herein, comprising: a sequential treatment of an untreated alloy to make the alloy, the sequential treatment including one of A or B: A) includes: a first heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a first quench; a second heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a second quench; a third heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a third quench; and a fourth heat treatment at 570 ± 2 °C for 8 ± 0.5 minutes, followed by a fourth quench; or B) includes: a first heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a first quench; a second heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a second quench; a third heat treatment at 570 ±2 °C for 5 ± 0.5 minutes, followed by a third quench; and a fourth heat treatment at 580 ±2 °C for 8 ± 0.5 minutes, followed by a fourth quench; wherein the untreated alloy has an Af temperature greater than the alloy (e.g., an Af temperature of greater than 20 °C) and an RF of less than the alloy (e.g., an RF of less than about 3.0 gf to 4.5 gf average per 3 mm capsule, and / or an RF of less than about 1.5 gf to 3.0 gf average per 4 mm or 6 mm capsules). 508933170.191956788.00381

[0044] In some embodiments, the sequential treatment results in a reduction of retained strain in the alloy.

[0045] In some embodiments, the sequential treatment results in a reduction of strain imparted to the alloy during the heat treatment steps.

[0046] In some embodiments, the alloy is in the form of a medical device.

[0047] In some embodiments, the alloy is in the form of an expandable medical device.

[0048] In some embodiments, the alloy is in the form of a stent.

[0049] In some embodiments, the alloy is located within a cannula.

[0050] Another aspect of the present disclosure is directed to methods that include translocating a device that includes the alloy of one of the foregoing embodiments from within a delivery device to a location outside of the delivery device.

[0051] Another aspect of the present disclosure is directed to methods of delivering a medical device to a vascular site in a subject in need thereof. The method includes directing the medical device through the subject’s vasculature. The medical device includes the alloy of one of the foregoing embodiments.

[0052] Another aspect of the present disclosure is directed to methods of treating a vasculopathy in a subject in need thereof. The method includes administering a medical device to the subject. The medical device includes the alloy of one of the foregoing embodiments.

[0053] In some embodiments, the vasculopathy is a pseudoaneurysm.

[0054] In some embodiments, the vasculopathy is a dissecting aneurysm.

[0055] In some embodiments, the vasculopathy is an aneurysm.

[0056] In some embodiments, the aneurysm is a fusiform aneurysm.

[0057] In some embodiments, the aneurysm is a saccular aneurysm.

[0058] In some embodiments, the aneurysm is an aortic aneurysm, a cerebral aneurysm, a popliteal aneurysm, a femoral aneurysm, a mesenteric aneurysm, or a splenic aneurysm. 508933170.1101956788.00381 Definitions

[0059] As used herein, the term “individual”, “patient”, or “subject” used interchangeably, refers to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans.

[0060] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” As used herein the terms "about" and “approximately” means within 10 to 15%, preferably within 5 to 10%. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0061] The terms “a,” “an,” “the” and similar referents used in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0062] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. 508933170.1111956788.00381 It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[0063] Certain embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

[0064] Specific embodiments disclosed herein may be further limited in the claims using consisting of or consisting essentially of language. When used in the claims, whether as filed or added per amendment, the transition term “consisting of” excludes any element, step, or ingredient not specified in the claims. The transition term “consisting essentially of” limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s). Embodiments of the invention so claimed are inherently or expressly described and enabled herein.

[0065] Furthermore, references to patents and printed publications may have been made in this specification. Each of the above-cited references and printed publications are individually incorporated herein by reference in their entirety.

[0066] In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, the present invention is not limited to that precisely as shown and described. 508933170.112

Claims

1956788.00381 CLAIMS We claim:

1. An alloy, comprising Ni and Ti, wherein the alloy has an austenite finish temperature (Af) of 20 °C or less and a radial force (RF) of about 3.0 gf to 4.5 gf average per 3 mm capsule, or an RF of about 1.5 gf to 3.0 gf average per 4 mm or 6 mm capsules.

2. The alloy of claim 1, comprising about 52 to 60 % Ni and about 40 to 48 % Ti.

3. The alloy of claim 1, comprising about 55 to 56 % Ni and about 44 to 45% Ti.

4. The alloy of claim 1, having been sequentially treated, wherein prior to sequential treatment the untreated alloy had an Af temperature of greater than about 20 °C and an RF of less than about 3.0 gf to 4.5 gf average per 3 mm capsule, or an RF of less than about 1.5 gf to 3.0 gf average per 4 mm or 6 mm capsules, and wherein the sequential treatment includes one of A or B: A) a first heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a first quench; a second heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a second quench; a third heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a third quench; and a fourth heat treatment at 570 ± 2 °C for 8 ± 0.5 minutes, followed by a fourth quench; or B) a first heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a first quench; a second heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a second quench; a third heat treatment at 570 ±2 °C for 5 ± 0.5 minutes, followed by a third quench; and a fourth heat treatment at 580 ±2 °C for 8 ± 0.5 minutes, followed by a fourth quench.

5. The alloy of claim 4, wherein the sequential treatment results in a reduction of retained strain in the alloy.

6. The alloy of claim 4, wherein the sequential treatment results in a reduction of strain imparted to the alloy during the heat treatment steps. 508933170.1131956788.00381 7. The alloy of claim 1, in the form of a medical device.

8. The alloy of claim 1, in the form of an expandable medical device.

9. The alloy of claim 1, in the form of a stent.

10. The alloy of claim 1, located within a cannula.

11. A method, comprising translocating a device comprising the alloy of one of claims 1–10 from within a delivery device to a location outside of the delivery device.

12. A method of delivering a medical device to a vascular site in a subject in need thereof, comprising directing the medical device through the subject’s vasculature, wherein the medical device comprises the alloy of one of claims 1–10.

13. A method of treating a vasculopathy in a subject in need thereof, comprising administering a medical device to the subject, wherein the medical device comprises the alloy of one of claims 1–10.

14. The method of claim 13, wherein the vasculopathy is a pseudoaneurysm.

15. The method of claim 13, wherein the vasculopathy is a dissecting aneurysm.

16. The method of claim 13, wherein the vasculopathy is an aneurysm.

17. The method of claim 16, wherein the aneurysm is a fusiform aneurysm.

18. The method of claim 16, wherein the aneurysm is a saccular aneurysm.

19. The method of claim 16, wherein the aneurysm is an aortic aneurysm, a cerebral aneurysm, a popliteal aneurysm, a femoral aneurysm, a mesenteric aneurysm, or a splenic aneurysm.

20. A method of making the alloy of claim 1, comprising: 508933170.1141956788.00381 a sequential treatment of an untreated alloy to make the alloy, the sequential treatment including one of A or B: A) includes: a first heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a first quench; a second heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a second quench; a third heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a third quench; and a fourth heat treatment at 570 ± 2 °C for 8 ± 0.5 minutes, followed by a fourth quench; or B) includes: a first heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a first quench; a second heat treatment at 570 ± 2 °C for 5 ± 0.5 minutes, followed by a second quench; a third heat treatment at 570 ±2 °C for 5 ± 0.5 minutes, followed by a third quench; and a fourth heat treatment at 580 ±2 °C for 8 ± 0.5 minutes, followed by a fourth quench; wherein the untreated alloy has an Af temperature of greater than 20 °C and an RF of less than about 3.0 gf to 4.5 gf average per 3 mm capsule, or an RF of less than about 1.5 gf to 3.0 gf average per 4 mm or 6 mm capsules. 508933170.115

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