Magnesium-based absorbent alloy

Abstract

Magnesium alloys contain small amounts of lithium, zinc, calcium, and manganese. For example, a magnesium alloy may contain 1-5 wt.% lithium, 0.2-2.0 wt.% zinc, 0.1-0.5 wt.% calcium, and 0.1-0.8 wt.% manganese. Because these alloying elements are all nutritional, the alloys of the present invention are safely degraded in vivo and absorbed and / or excreted from the body. Li, Zn, Ca, and Mn each contribute to solid-solution strengthening of the alloy. Ca also acts as a grain refiner, and both Zn and Ca form intermetallic compounds for strengthening and corrosion control. Optionally, the alloy may contain small amounts of yttrium for additional strength and corrosion resistance.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 856,293, filed on June 3, 2019, with the title "MAGNESIUM - BASED ABSORBABLE ALLOYS", the entire disclosure of which is hereby expressly incorporated by reference herein.

[0002] The present invention relates to wires used in biomedical applications, and in particular to biodegradable wires for use in medical devices such as stents.

Background Art

[0003] Special absorbable materials are the focus of ongoing development for surgical implant applications. For example, design efforts to create absorbable stents have mainly focused on balloon - expandable techniques for coronary artery lesions, and may include polymeric materials such as poly - L - lactic acid (PLLA) or poly - L - glycolic acid (PLGA), or metallic materials such as magnesium (Mg), iron (Fe), or zinc (Zn) - based alloys. Some research methods have also focused on hybrids containing various combinations of absorbable polymers and metals. Such materials are absorbable, but their functional properties such as mechanical strength and ductility, corrosion rate, or biocompatibility may be insufficient for specific applications.

[0004] Other uses of absorbable materials such as nutrient - metal absorbable materials include temporary fracture - fixation devices such as bone plates. In some cases, during the regrowth of bone after a fracture, the bone plate needs to provide a specified level of mechanical strength, but the presence of the plate after fracture healing can cause complications and / or may require surgical removal.

[0005] Many magnesium-based alloys have been investigated for their usefulness in such absorbable implant applications. For example, WE43 is an alloy containing nominally 4 wt% Y, 3 wt% other rare earths (mainly Nd), and 0.5% Zr. This alloy has relatively high strength, moderate ductility, and generally acceptable corrosion rates. However, it contains a relatively large amount of rare earth elements that can have a long residence time in the body.

[0006] Other magnesium-based alloys that do not contain rare earth elements and instead contain native additive elements such as Zn, Ca, and / or Mn have been studied. These alloys generally have lower strength than rare earth-containing alloys, combined with comparable ductility. Their corrosion rates can be adjusted based on specific precipitates formed by heat treatment. These alloys may not have sufficient strength for certain applications, such as wire-based medical devices.

[0007] Furthermore, the ductility of the above-known rare earth and magnesium-based alloys is slightly moderate, and for some devices that require large plastic deformation (such as staples, clips, or stents), higher ductility is desirable. Increasing the ductility also improves the manufacturability of semi-finished products of such devices.

[0008] It is known that adding lithium (Li) to Mg improves the ductility of the alloy. When Li exceeds 11 wt%, the crystal structure of the alloy changes from brittle hexagonal close-packed (HCP) to ductile body-centered cubic (BCC). Between about 6 wt% and about 11 wt%, a two-phase structure of both HCP and BCC exists, and below 6 wt% Li, the native HCP is retained. As potential absorbable metals, Mg-Li binary alloys, Mg-Li-Ca alloys, and Mg-Li-Al-rare earth alloys have been investigated. Although Li has been found to increase ductility, it can also decrease strength and corrosion rate. Also, Li is a psychotropic element, and a large amount of Li in the alloy can have related adverse effects. SUMMARY OF THE INVENTION

Problems to be Solved by the Invention

[0009] Therefore, known absorbable magnesium-based alloys can have various combinations of strength, ductility, biocompatibility, and corrosion resistance. However, none of the known absorbable alloys have an optimal combination of these parameters for devices that require significant plastic deformation.

[0010] Improvements beyond those described above are needed.

[0011] The present disclosure relates to magnesium alloys containing small amounts of lithium, zinc, calcium, and manganese. For example, the magnesium alloy can contain 1 to 5 wt% lithium, 0.2 to 2.0 wt% zinc, 0.1 to 0.5 wt% calcium, and 0.1 to 0.8 wt% manganese. Since all of these alloying elements are nutrient elements, the alloys of the present invention can be safely decomposed, absorbed, and / or excreted in vivo. Li, Zn, Ca, and Mn each contribute to solid solution strengthening of the alloy. Ca also acts as a grain refinement agent, and both Zn and Ca form strengthening of intermetallic compounds and corrosion control. Optionally, the alloy can include a small amount of yttrium for additional strength and corrosion resistance.

Means for Solving the Problems

[0012] In one form, the present disclosure provides an alloy for use within an absorbable medical device, the alloy comprising 1.0 to 5.0 wt% lithium, 0.2 to 2.0 wt% zinc, 0.1 to 0.5 wt% calcium, 0.1 to 0.8 wt% manganese, with the balance being magnesium and inevitable impurities.

[0013] The above and other features and objects of the present invention, and the manner of achieving them, will become more apparent, and the invention itself will be better understood by reference to the following description of embodiments of the invention taken in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0014]

Figure 1

Figure 1A

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6A

Figure 6B

Figure 6C

Figure 7

Figure 8

DETAILED DESCRIPTION OF THE INVENTION

[0015] Corresponding reference characters indicate corresponding parts throughout several views. The illustrative examples described herein illustrate embodiments of the invention, but the embodiments disclosed below are not intended to be exhaustive or to limit the invention to the exact forms disclosed.

[0016] 1. Introduction The alloys of the present disclosure are magnesium-lithium-zinc-calcium-manganese (Mg-Li-Zn-Ca-Mn) alloys, which exhibit absorbable alloys with a combination of high ductility and workability, high strength, and a suitable in vivo degradation profile. Yttrium may also be included in some applications where improvement in strength and / or corrosion resistance is desired.

[0017] 2. Terms As used herein, "wire" or "wire product" includes continuous wires and wire products that are continuously produced and wound onto spools for subsequent distribution and use, such as wires having a circular cross-section and wires having non-circular cross-sections, such as flat wires or ribbons. "Wire" or "wire product" also includes other wire-based products such as strands, cables, coils, and tubes, which may be produced in specific lengths depending on the particular application. In some exemplary embodiments, the wire or wire product according to the present disclosure may have a diameter of up to 2.5 mm. In addition to wires and wire products, other material forms can be manufactured using the principles of the present disclosure, such as rod materials having a diameter greater than 2.5 mm and up to 20 mm. Thin material sheets can also be made. An exemplary tube structure can be in wire or rod form with an inner diameter in the range of 0.5 mm to 4.0 mm and a wall thickness in the range of 0.100 mm to 1.00 mm. "Fine wire" refers to a wire having an outer diameter of less than 1 mm.

[0018] As used herein, "fatigue strength" refers to the load level at which a material meets or exceeds a given number of load cycles before failure. In this specification, the load level is given as alternating strain, as is standard in displacement or strain controlled fatigue testing, such that these terms are consistent with those set forth in ASTM E606, which is hereby incorporated by reference in its entirety.

[0019] "DFT®" is a registered trademark of Fort Wayne Metals Research Products Corp., Fort Wayne, IN, and refers to a bimetallic or polymetallic composite wire product including at least one outer layer disposed on a core filament formed by drawing one tube or a plurality of tube layers over two or more concentric layers of metal or alloy, typically on a solid metal wire core element.

[0020] "Impurities", "inevitable impurities", and "trace impurities" are material constituents present in a material in amounts of 500 ppm or less than 0.05 wt% in any given element.

[0021] 3. Magnesium Alloys The magnesium-based alloys of the present invention may contain 1 to 5 wt% lithium, 0.2 to 2.0 wt% zinc, 0.1 to 0.5 wt% calcium, and 0.1 to 0.8 wt% manganese, with the balance being magnesium and inevitable impurities. In some applications, yttrium may be added in amounts up to 2.5 wt%. All other elements are excluded from the alloy such that magnesium is at least 89 wt% and at most 98.6 wt% of the total alloy.

[0022] These alloys have been found to provide magnesium-based alloys that exhibit both high ductility and high strength while using only elements that are inherent to the human body or are easily processed by the human body. As will be explained in more detail below, this combination of material properties provides absorbable alloys with predictable and favorable in vivo degradation profiles that can be efficiently mass-produced.

[0023] As will be further explained below, the Mg-Li-Zn-Ca-Mn material of the present invention exhibits high ductility. This ductility facilitates the fabrication and processing of the alloy. This enables a large amount of cold working, and thus the diameter can be reduced to a desired diameter with fewer cold drawing and annealing cycles and less energy required for cold working. Also, the high ductility of the material of the present invention expands the range of potential medical device applications by suppressing the possibility of breakage, particularly in devices that require high levels of compressive strain, such as stents, staples, or ligating clips.

[0024] The Mg-Li-Zn-Ca-Mn material of the present invention also exhibits relatively high strength, which can be enhanced by cold working to a desired level. Such high strength also facilitates the use of the alloy in certain medical devices. For example, strength may be required for vascular support in stent applications or for bone support in orthopedic device applications or dental orthodontic device applications.

[0025] The alloys of the present invention also corrode predictably and advantageously in the in vivo environment.

[0026] Lithium is included to improve the ductility of the Mg-based alloys of the present invention and at the same time be easily and safely processed by the body. Lithium is an essential nutrient metal, and the typically recommended dietary intake per day is 1 mg. Thus, relatively large amounts of lithium can be included as part of wire 730 or 731 or other materials made in accordance with the present disclosure without adverse effects. To obtain a desirable increase in ductility, at least 1.0 wt% lithium is required, but if the lithium exceeds 5.0 wt%, it can cause a loss of strength, an increased corrosion rate, and an undesirably high dosage of lithium to the body.

[0027] Zinc is included as a contributing factor to solid solution strengthening of the alloy and can also form intermetallic compounds that help regulate and control corrosion in the materials of the present invention. In particular, when zinc is present in a desired amount together with calcium and after a specific heat treatment, zinc contributes to the formation of the Mg6Zn3Ca2 intermetallic compound, which is nobler than the base metal, and can increase the corrosion rate. Zinc is an essential nutrient metal that is easily and safely processed by the body and can be included in relatively large amounts as part of wire 730 or 731 or other materials made in accordance with the present disclosure without adverse effects. To obtain a desirable increase in strength, at least 0.2 wt% zinc is required, but if the zinc exceeds 2.0 wt%, it can cause the formation of excessive Mg6Zn3Ca2, which can result in a corrosion rate that is too fast for most applications.

[0028] Calcium is included as another contributing factor to the solid solution strengthening of the alloy and can also form intermetallic compounds that help regulate and control corrosion in the materials of the present invention. Mg2Ca is not nobler than the base metal and acts as a microgalvanic sacrificial anode to reduce bulk corrosion. As described above, since the Mg6Zn3Ca2 phase can assist in increasing bulk corrosion, calcium can control the corrosion rate of the Mg alloy to some extent. Calcium is also a grain refiner that contributes to the strength, ductility, and workability of the finished material. Similar to zinc, calcium is a nutrient metal that is easily and safely processed by the body and can be included in relatively large amounts without adverse effects as part of wire 730 or 731 or other materials made in accordance with the present disclosure. To obtain a desirable increase in strength, at least 0.1 wt% of calcium is required, but when calcium exceeds 0.5 wt%, an excessive amount of the Mg2Ca phase is formed at the grain boundaries, which can reduce ductility and workability.

[0029] Manganese is included as yet another contributing factor to the solid solution strengthening of the alloy. Manganese can reduce the harmful effects of iron impurities in the material on the corrosion behavior of the alloy. Manganese is also a nutrient metal that is easily and safely processed by the body and can be included in relatively large amounts without adverse effects as part of wire 730 or 731 or other materials made in accordance with the present disclosure. To obtain a desirable increase in strength, at least 0.1 wt% of manganese is required, but when manganese exceeds 0.8 wt%, excessive precipitation of alpha-Mn particles is caused, which can have an adverse effect on corrosion resistance.

[0030] Yttrium can also be optionally added to the Mg-Li-Zn-Ca-Mn alloy of the present invention. Yttrium is a rare earth element known to have good tolerance to the body. Yttrium (or its salts) has relatively high water solubility, which means it is more easily processed by the body than some other rare earths. The addition of yttrium can improve both the strength by solid solution strengthening and the ductility by reducing the texture and refining the grain size. However, when the yttrium exceeds 2.5 wt%, the ductility decreases and the number of Y-containing intermetallic compound particles that can have a relatively long residence time in vivo increases.

[0031] The foregoing elements are an exhaustive list of the materials used in connection with the magnesium-based materials of the present invention. Other elements are specifically excluded, except for the presence of the inevitable impurities noted above.

[0032] 4. Wire constructs containing Mg-Li-Zn-Ca-Mn-(Y) In an exemplary embodiment, the Mg-Li-Zn-Ca-Mn material fabricated in accordance with the present disclosure can be formed into thin medical-grade wires 730, 731 as shown in FIG. 1. Next, these wires 730, 731 can be formed or integrated into a medical device by braiding, for example, into a stent 700 having an overall diameter D of the device S (FIG. 1). The wires 730, 731 can each have a wire outer diameter D of, for example, 1 mm or less. W

[0033] The alloys according to the present disclosure can first be formed in bulk by conventional casting methods or the like. Next, this bulk material is formed into a suitable preform material (e.g., rod, plate, or hollow tube) by hot working the bulk material to the desired preform size and shape. For the purposes of the present disclosure, hot working is achieved by heating the material to a temperature above room temperature and performing the desired shaping and forming operations while the material is maintained at the elevated temperature. Next, the resulting preform material, such as a billet or rod, is further processed by repeated cold forming and annealing cycles to an intermediate form such as a rod, wire, tube, sheet, or plate product. Examples of methods for forming the material can include pressing, extrusion, rolling, drawing, swaging, ECAP, ECAP conforming, high-pressure torsion, severe plastic deformation, forging, pilgering, and the like.

[0034] This intermediate material can be produced, for example, by a drawing and annealing schedule to create an initial rough wire structure that is ready for final processing. Thereafter, the wire 730 or 731 (Figs. 1 - 5) can be subjected to a final cold working conditioning step, and optionally a final heat treatment step, to impart the desired mechanical properties to the finished wire product, as further described below.

[0035] In one exemplary embodiment shown in Fig. 2, a monolithic wire 731 made of an Mg - Li - Zn - Ca - Mn material (such as those further alloys described herein) can first be produced using conventional methods including a drawing and annealing schedule to convert a preform material (such as an ingot or rod) into a wire of the desired diameter. That is, the preform material is drawn through a die 736 (Fig. 2), the outer diameter of the intermediate material is slightly reduced, and at the same time the material is elongated. Thereafter, the material is annealed to relieve the internal stresses imparted to the material by the drawing step (i.e., the retained cold worked portion)is relaxed. Next, this annealed material is drawn through a new die 736 having a smaller finishing diameter to further reduce the diameter of the material and further elongate the material. Further annealing and drawing of the material are repeatedly performed until the material is formed into a wire structure ready for final processing into wire 731.

[0036] To form a composite wire 730 (FIG. 3) such as DFT (registered trademark), a core 734 is inserted into a shell 732 to form an intermediate structure, and then the end of this intermediate structure is tapered to facilitate installation of its end in a drawing die 736 (FIG. 3). Next, the end protruding through the drawing die 736 is gripped and pulled through the die 736 to reduce the diameter of the structure and physically ensure reliable contact between the inner surface of the shell 732 and the outer surface of the core 734. More specifically, in the initial drawing process, the inner diameter of the shell 732 is reduced such that the shell 732 approaches the outer diameter of the core 734 and the inner diameter of the shell 732 becomes equal to the outer diameter of the core 734, whereby, when viewed in cross-section, the inner diameter core 734 completely occupies the outer shell 732 as shown in FIG. 3.

[0037] The exemplary composite wire 730 can be formed using an Mg-Li-Zn-Ca-Mn alloy made in accordance with the present disclosure (for another material for the shell 732 and the core 734). Exemplary materials for the core 734 can include Mg and Mg alloys, Zn and Zn alloys, Fe and Fe alloys, non-absorbable alloys, or polymers.

[0038] In the drawing step, the wire 730 or 731 is subjected to cold working. For the purposes of the present disclosure, the cold working method causes deformation of the material at room temperature or near it, for example, at 20 - 30 °C. In the case of the composite wire 730, drawing imparts a cold worked portion to both the materials of the shell 732 and the core 734 and simultaneously reduces the cross-sectional area of both materials. The cold worked portion imparted to the wire 730 or 731 during the drawing step cold can be characterized by the following formula (I).

[0039]

Number

[0040] In the formula, "cw" is cold working defined by the reduction of the original material area rate and "D 2S " is the outer diameter of the cross-section of the wire after drawing (multiple possible), and "D 1S " is the outer diameter of the cross-section of the wire before the drawing (multiple possible).

[0041] As shown in FIGS. 2 and 3, the cold working step can be carried out by the illustrated drawing process. As shown, the wire 730 or 731 is drawn through a lubricated die 736 having an output diameter D 1S smaller than the diameter D 2S of the wire 730 or 731 before the drawing step. Thus, the outer diameter of the wire 730 or 731 decreases from the diameter D 1S before the drawing to the drawn diameter D 2S , thereby obtaining the cold working rate cw.

[0042] Alternatively, the net cold working portion can be accumulated in the wire 730 or 731 by other processes such as cold swaging, rolling of the wire (e.g., into a flat ribbon or other shape), extrusion, bending, flow forming, severe plastic deformation, or pilgering. The cold working portion can also be imparted by any combination of techniques such as the techniques described herein, e.g., cold swaging and subsequent drawing through a lubricated die, cold rolling to finish into a ribbon or sheet form or other shaped wire form. In one exemplary embodiment, the cold working step of reducing the diameter of the wire 730 from D 1S to D 2S is carried out in one draw, and in another embodiment, the diameter of the wire 730 is reduced from D 1S to D 2SThe cold working step of reducing to is carried out by multiple drawing operations. These drawing operations are sequentially carried out without any annealing step in between. When calculating cw using the above formula (I), it is assumed that no annealing has been carried out after the process of imparting a cold worked portion to the material. rate When calculating cw using the above formula (I), it is assumed that no annealing has been carried out after the process of imparting a cold worked portion to the material.

[0043] In the case of a process where the drawing process is repeated on the composite wire 730 without any intervening annealing, in each subsequent drawing step, as the total cross-sectional area of the wire 730 shrinks, the cross-sectional area of the shell 732 and the core 734 relative to the total cross-sectional area of the wire 730 is proportionally reduced so that the ratio is nominally maintained. Referring to FIG. 3, the ratio of the core outer diameter D before drawing 1C to the shell outer diameter D before drawing 1S is the same as the corresponding ratio after drawing. In other words, D 1C / D 1S =D 2C / D 2S That is.

[0044] Using thermal stress relaxation (also known as annealing in the art) at a nominal temperature that does not exceed the melting point of the wire material (or, in the case of a composite wire, either the first or second material) improves the ductility of the fully dense composite material between the drawing steps, thereby enabling further plastic deformation by subsequent drawing steps. Further details regarding the drawing of wires are discussed in U.S. Patent No. 7,989,703, entitled "Alternating Core Composite Wire," issued on August 2, 2011, and assigned to the assignee of the present invention, the entire disclosure of which is incorporated herein by reference.

[0045] By heating the wire 730 to a temperature sufficient to cause recrystallization of the crystal grains, the accumulation of the cold-worked portion becomes unnecessary. The cold-worked portion obtained by each repeated cold working process is reduced by completely annealing the material during drawing, thereby enabling the next repeated cold working process. In full annealing, the cold-worked material is heated to a temperature sufficient to substantially completely relieve the internal stress stored in the material, thereby relaxing the stored cold-worked portion and "resetting" the cold-worked portion to zero.

[0046] On the other hand, the wire 730 or 731 that undergoes drawing or other mechanical processing without a subsequent annealing process retains a certain amount of cold-worked portion. The amount of the retained worked portion depends on the overall reduction in diameter from D 1S to D 2S and can be quantified based on the deformation of the individual crystal grains in the material as a result of the obtained cold-worked portion. Referring to FIG. 4, for example, the wire 731 is shown in the post-annealing state with crystal grains 12 that are substantially equiaxed, that is, the crystal grains 12 define a substantially ellipsoidal shape of revolution in which the measured value of the total length G1 of the crystal grains 12 is substantially the same regardless of the measurement direction. (As described above) After drawing the wire 731, the equiaxed crystal grains 12 are converted into elongated crystal grains 14 (FIG. 5), whereby the crystal grains 14 become a longitudinal structure defining the length G2 of the elongated crystal grains (i.e., the longest dimension defined by the crystal grains 14) and the crystal grain width G3 (i.e., the shortest dimension defined by the crystal grains 14). The elongation of the crystal grains 14 is obtained from the cold working process, and as shown in FIG. 5, the longitudinal axis of the crystal grains 14 is substantially aligned with the drawing direction.

[0047] The cold-worked portion retained in the wire 731 after drawing can be expressed as the ratio of the elongated grain length G2 to the width G3. The larger the ratio, the more the grains are "stretched", and thus the larger the amount of the retained cold-worked portion. In contrast, the annealed wire 731 after the intermediate drawing process recrystallizes the material, returns the elongated grains 14 to equiaxed grains 12, and "resets" the ratio of the retained cold-worked portion to 1:1 (i.e., has no retained cold-worked portion).

[0048] In the case of the Mg-Li-Zn-Ca-Mn material of the present invention, full annealing can be achieved at a temperature of about 200 to 350 °C for at least several seconds for thin wires (i.e., having a small cross-sectional area of 0.000127 sq.mm to 0.5 sq.mm), and for several tens of minutes for thick materials (i.e., having a large cross-sectional area of 1 sq.mm to 125 sq.mm). Alternatively, full annealing can also be achieved at a higher temperature such as 350 °C to 450 °C for a shorter time such as from several milliseconds to less than 5 minutes, depending on the cross-sectional area of the material. Naturally, a relatively high-temperature annealing process can utilize a relatively short time to achieve full annealing, while at a relatively low temperature, typically a relatively long time is utilized to achieve full annealing. Further, the annealing parameters are expected to change as the diameter of the wire changes, and the smaller the diameter, the shorter the annealing time at a given temperature. Whether full annealing has been achieved can be verified by a plurality of methods well-known in the art, such as microstructure inspection using a scanning electron microscope (SEM), mechanical tests such as ductility, strength, elasticity, and other methods. Further, when designing the manufacturing process of a specific device, the influence of the annealing parameters on the precipitation of the intermetallic compound phase of either Mg2Ca or Mg6Zn3Ca2 can be considered.

[0049] Further discussion of the cold working and annealing method can be found in U.S. Patent No. 8,840,735, issued September 23, 2014, and entitled "FATIGUE DAMAGE RESISTANT WIRE AND METHOD OF PRODUCTION THEREOF", the entire disclosure of which is incorporated herein by reference.

[0050] The resulting coarse wire material can ultimately be processed into a final form, such as a thin wire suitable for integration into a stent or other medical device. Exemplary wire constructs are described in more detail below.

[0051] 5. Wire Characteristics As will be described in more detail in the following examples, the Mg-Li-Zn-Ca-Mn materials of the present disclosure exhibit a combination of high strength and high ductility not found in other combinations of trace metals. When alloyed with yttrium, the Mg-Li-Y-Zn-Ca-Mn materials of the present invention are superior to other combinations of trace metals and yttrium.

[0052] As discussed herein, elongation to failure is used as a surrogate for the ductility of wires 730, 731, but elongation to failure of a material does not necessarily indicate the functional ductility of the material. If ductility is considered the ability to withstand high bending strains or significant cold reduction (e.g., by drawing) without failure, a material with a relatively low elongation to failure may have a relatively high ductility.

[0053] Mg-Li-Zn-Ca-Mn fabricated in accordance with the present disclosure and having no preserved cold worked portion exhibits sufficient ductility to allow for at least 10%, 15%, 20%, or 25% elongation prior to fracture, and a high lithium level at the upper limit of the range of 1.0 to 5.0 wt% is associated with high ductility and vice versa. This high ductility allows the material to be substantially cold worked as a processing step (followed by annealing) or to strengthen the material for the final construct. The cold working ability of the Mg-Li-Zn-Ca-Mn material of the present invention can be, for example, 60%, 75%, or 90%, and the cold working ability corresponds to the ductility. By adding yttrium, the crystal grain size becomes finer and the crystallographic texture decreases, so that the ductility of the material, particularly the annealed (i.e., having no preserved cold worked portion) material, can be improved.

[0054] Mg-Li-Zn-Ca-Mn fabricated in accordance with the present disclosure and having no preserved cold worked portion also exhibits high strength and can be made even stronger by cold working treatment. In the as-annealed state, the Mg-Li-Zn-Ca-Mn material of the present invention exhibits an ultimate strength of at least 25 ksi, 32 ksi, or 40 ksi, and higher strength is associated with the levels of zinc, calcium, and manganese at the upper limits of the respective ranges of 0.2 to 2.0 wt%, 0.1 to 0.5 wt%, and 0.1 to 0.8 wt%, and vice versa. For example, FIG. 6A shows the stress-strain curve of an Mg-2Li-1.2Zn-0.4Ca-0.4Mn alloy fabricated in accordance with the present disclosure, as further described in the following examples. Compared to the binary Mg-4Li alloy also shown in FIG. 6A, the alloy of the present invention exhibits an increase in yield strength and ultimate strength. FIG. 6B shows additional properties of the same Mg-2Li-1.2Zn-0.4Ca-0.4Mn alloy before and after cold working, and properties of an Mg-2Li-2Y-1.2Zn-0.4Mn-0.4Ca alloy both before and after cold working. FIGS. 6A and 6B are drawn to a consistent scale. The nominal strength value of the Mg-Li-Zn-Ca-Mn alloy of the present invention can be increased by 25%, 50%, or 100% by cold working, and the cold working potential corresponds to the ductility of the material as described above.

[0055] Similarly, the Mg-Li-Zn-Ca-Mn material of the present invention exhibits a yield strength of at least 20 ksi, 25 ksi, or 30 ksi, exhibits a corresponding relationship similar to the levels of zinc, calcium, and manganese, and with the addition of yttrium, a similar increase in strength is achieved.

[0056] Looking at FIG. 6C, the Mg-Li-Zn-Ca-Mn material of the present invention also exhibits a high in-vivo survival rate and a predictable long degradation profile. The time-to-failure while under load in a corrosive environment (specifically described in Example 4 below) far exceeds that of known binary Mg-Li alloys such as Mg-4Li as shown in FIG. 6C and is approximately comparable to Mg-Zn-Ca-Mn alloys that do not include the advantages of lithium discussed herein. The Mg-Li-Zn-Ca-Mn material of the present invention has a slightly shorter time-to-failure than WE43, but may be sufficient for many applications and has an improved in-vivo biocompatibility profile compared to WE43.

[0057] Within the range of alloy components of the present invention discussed herein, the time-to-failure of an annealed state wire with a diameter of 0.010 inches (0.0254 centimeters) can be expected to exhibit an average survival of at least 30 hours in Hank's balanced salt solution maintained at 37°C and 7.4 pH, with the initial stress also held at 110 MPa. Similarly, the time-to-failure of a cold-worked state wire with a diameter of 0.010 inches (0.0254 centimeters) having 50% retained cold work can be expected to exhibit an average survival of at least 30 hours in Hank's balanced salt solution maintained at 37°C and 7.4 pH, with the initial stress also held at 110 MPa. Further, any wire fabricated in accordance with the present disclosure and suitable for in vivo use can be expected to exhibit an average survival of at least 24 hours under typical in vivo conditions (i.e., at body temperature, located within the body, and exposed to typical stresses associated with the medical devices described herein).

[0058] 6. Medical device applications Multiple medical devices can be made of the materials of the present invention, which are beneficial for any device whose function and presence in the body can change and decrease over time. Some exemplary such devices are described below, but it is understood that the materials of the present invention can also be used for any other suitable medical device applications.

[0059] As described above, wires 730, 731 can be used in vascular devices such as stent 700 (FIG. 1) or 700A (FIG. 1A). Stent 700 can provide a high degree of initial vascular support, which can then gradually decrease in vivo over time as wires 730, 731 degrade. Other wire-based vascular devices suitable for use with wires 730, 731 include aneurysm occlusion devices, septal occluders such as occluder 900 (FIG. 8), shunts, filters, and grafts.

[0060] Wires 730, 731, or other constructs can also be used for orthopedic fixation. Exemplary uses include screws such as screw 800 (FIG. 7), pins, nails, k-wires, and cerclage cables (e.g., for sternal closure), all of which can be implanted at the surgical site to provide a high level of mechanical support to adjacent tissues and can degrade over time as the tissue itself heals.

[0061] Still other medical device applications of wires 730, 731 include surgical intervention devices such as surgical staples, ligating clips, and tacks. These devices can be used to temporarily close a portion of an associated anatomical structure, and this closure can be released over time as the device degrades. Still other applications can include devices used in renal therapy, temporary pacing leads, and many other indications.

Examples

[0062] The following non-limiting examples illustrate various features and characteristics of the present invention and should not be construed as limiting the present invention.

[0063] In these examples, exemplary monolithic Mg-Li-Zn-Ca-Mn and Mg-Li-Y-Zn-Ca-Mn alloy wires according to the present disclosure were produced, tested, and characterized, particularly with respect to the workability and mechanical strength of the materials.

[0064] The following examples show that the MgLiZnMnCa alloy of the present invention has an optimal combination of strength, ductility, corrosion resistance, and biocompatibility for applications of absorbent wires that require high ductility, such as staples, ligatures, stents, and the like.

[0065] Mechanical properties were evaluated for each wire sample by uniaxial tensile testing on an Instron model 5565 testing machine available from Instron (Norwood, Massachusetts, USA). More specifically, using the destructive uniaxial tensile test of the wire material, the ultimate strength, yield strength, axial stiffness, and ductility of the candidate materials were quantified using the method described in Structure-Property Relationships in Conventional and Nanocrystalline NiTi Intermetallic Alloy Wire (Journal of Materials Engineering and Performance 18, 582-587 (2009) (Jeremy E. Schaffer)), the entire disclosure of which is hereby expressly incorporated by reference. These tests were performed using a servo-controlled Instron load frame in accordance with industry standards for tensile testing of metallic materials.

[0066] In the rotational beam fatigue test according to the embodiments of the present specification, a wire sample is cut to a length of about 118 mm (for example, in the case of a wire with a diameter of 0.33 mm), and then fixed to a rotary jaw at its axial ends. The free portion of the wire between the jaws is bent to introduce a desired tensile strain at the "peak" or outermost portion of the bend. Opposite this peak of the bend, the wire experiences a compressive strain equal to the tensile strain, and the nominal values of both the tensile strain and the compressive strain are referred to herein as the "strain amplitude". Next, the jaws rotate in coordination (i.e., each jaw rotates in the same direction at the same speed), whereby the region of maximum tensile strain rotates about the "peak" of the wire and transitions to the region of maximum compressive strain each time the jaws and the wire rotate 180 degrees. The rotational beam fatigue test is further described in ASTM E2948-14, the entire disclosure of which is hereby expressly incorporated by reference into this specification.

Example

[0067] The Mg-Li-Zn-Mn-Ca alloy of the present disclosure has 2 wt% Li, 1.2 wt% Zn, 0.4 wt% Mn, and 0.4 wt% Ca, and the balance is produced from magnesium and unavoidable impurities. This alloy was made into an ingot by first vacuum induction melting the material components and then casting the material into a 2-inch (5.08 cm) mold.

[0068] Next, the ingot was hot worked by extruding it to a diameter of 0.5 inches (1.27 cm) at a temperature of 325 °C using a ram speed of 10 inches (25.4 cm) per minute. The extruded rod was then centerless ground and processed into a monolithic round wire with a final diameter of 0.0079 inches (0.020 cm) through a series of cold drawing using the standard wire drawing method as described above.

[0069] Next, the wire was fully annealed as described above to produce a first final wire construct, which was subjected to a uniaxial tensile test as described above. The wire exhibited an ultimate tensile strength of 37 ksi and a yield strength of 30 ksi. The wire was capable of 14% elongation before failure. These results are shown in FIG. 6B as the line "A" below the dashed line.

[0070] Another sample of the monolithic wire was further cold drawn to a final diameter of 0.005 inches (0.0127 centimeters) to produce a second final wire construct having 75% retained cold work without annealing. This wire was subjected to the same uniaxial tensile test as the first final wire construct and exhibited an ultimate tensile strength of 64 ksi and a yield strength of 56 ksi. The wire was capable of 7% elongation before failure. These results are shown in FIG. 6B as the line "B" above the solid line.

Example

[0071] An Mg-Li-Y-Zn-Mn-Ca alloy of the present disclosure having 2 wt% Li, 2 wt% Y, 1.2 wt% Zn, 0.4 wt% Mn, and 0.4 wt% Ca, with the balance being magnesium and unavoidable impurities, was produced. Thus, this alloy has the same chemical properties as the alloy of Example 1 above, but further contains 2 wt% yttrium. This alloy was first vacuum induction melted of the material components and then ingoted by casting the material into a 2-inch (5.08 centimeter) mold.

[0072] Next, the ingot was hot worked by extruding it to a diameter of 0.5 inches (1.27 centimeters) at a temperature of 325°C using a ram speed of 10 inches (25.4 centimeters) per minute. Next, the extruded rod was processed into a monolithic round wire with a final diameter of 0.0099 inches (0.0251 centimeters) through a series of cold drawing and annealing using a standard wire drawing method as described above.

[0073] The Mg-Li-Y-Zn-Mn-Ca material of an embodiment of the present invention is proven to have reduced ductility and workability compared to the Mg-Li-Zn-Mn-Ca material of Example 1 and requires additional annealing to achieve a given diameter reduction. However, when compared to other magnesium alloys such as WE43 and Mg-Zn-Ca, less annealing is required to reduce a specific diameter.

[0074] Next, the wire was fully annealed as described above to produce a first final wire construct, which was subjected to the uniaxial tensile test described above. The wire exhibited an ultimate tensile strength of 39 ksi and a yield strength of 33 ksi. The wire was capable of 19% elongation before failure. These results are shown in FIG. 6B as the line "C" above the dashed line. Thus, it can be confirmed that the addition of yttrium increased both the strength and ductility in the annealed state (i.e., having no retained cold work) compared to the annealed Mg-Li-Zn-Mn-Ca material described in Example 1 above.

[0075] Another sample of the monolithic wire was further cold drawn to a final diameter of 0.005 inches (0.0127 centimeters) to produce a second final wire construct having 75% retained cold work without annealing. This wire was subjected to the same uniaxial tensile test as the first final wire construct and exhibited an ultimate tensile strength of 61 ksi and a yield strength of 45 ksi. The wire was capable of 9% elongation before failure. These results are shown in FIG. 6B as the line "D" below the solid line. Thus, it can be confirmed that the addition of yttrium increased the ductility but did not increase the strength compared to the cold-worked Mg-Li-Zn-Mn-Ca material described in Example 1 above.

Example

[0076] A conventional Mg-Li alloy having 4 wt% Li and the balance being magnesium and unavoidable impurities was produced. This alloy was made into an ingot by first vacuum induction melting the material components and then casting the material into a 2-inch (5.08 cm) mold.

[0077] Next, the ingot was hot worked by extruding it to a diameter of 0.5 inches (1.27 cm) at a temperature of 300 °C using a ram speed of 10 inches (25.4 cm) per minute. Next, the extruded rod was processed into a monolithic round wire with a final diameter of 0.0079 inches (0.020 cm) through a series of cold drawing and annealing via the standard wire drawing method as described above.

[0078] As shown by the dashed line in Figure 6A, the conventional Mg-Li material of the embodiment of the present invention has been proven to have equivalent or increased ductility and workability compared to the material of Example 1 that requires equal or less annealing to achieve a given diameter reduction. However, the strength of the alloy was very low compared to the material described in Example 1, as shown in Figures 6A and 6B.

[0079] Next, the wire was fully annealed as described above to produce a first final wire construct, which was subjected to the uniaxial tensile test described above. The wire exhibited an ultimate tensile strength of 28 ksi and a yield strength of 17 ksi. The wire was capable of 16% elongation before failure.

[0080] Therefore, it can be confirmed that the addition of Zn, Mn, Ca, and optionally Y results in an increase in the annealed yield strength of 76% - 94% while maintaining good ductility compared to the annealed Mg-Li-Zn-Mn-Ca material described in Example 1 above or the Mg-Li-Y-Zn-Mn-Ca material described in Example 2.

Example

[0081] To evaluate the corrosion behavior of the alloys of the present invention as compared to other known alloys, the following experiments were conducted. Wires having a finished diameter of 0.010 inches (0.0254 centimeters) were produced from the following four different alloys: - Mg - 2Li - 1.2Zn - 0.4Mn - 0.4Ca (as discussed in Examples 1 and 2 above according to the present disclosure), - Mg - 1Zn - 0.3Ca - 0.1Mn (as a control sample of a similar eutectic alloy without lithium), - Conventional WE43 (as a control sample of a rare earth-containing alloy), - Conventional Mg - 4Li (as a control sample, also described in Example 3 above).

[0082] Four wires were each produced as annealed wires (i.e., having no retained cold work) and cold worked wires (i.e., having 45 - 75% retained cold work), resulting in a total of eight individual alloy / condition combinations. As described below, at least two samples of each alloy / condition combination were tested. For the cold worked wires, the WE43 wire had 75% retained cold work, the Mg - 1Zn - 0.3Ca - 0.1Mn had 50% retained cold work, the Mg - 2Li - 1.2Zn - 0.4Mn - 0.4Ca had 50% retained cold work, and the MgLi had 45% retained cold work. These cold work levels were designed to achieve the mechanical properties of each wire typically desired for medical device applications.

[0083] Each wire sample was exposed to corrosion in Hank's balanced salt solution (HBSS) maintained at 37 °C and 7.4 pH, while simultaneously being held at an initial stress of 16 ksi (110 MPa) by its own weight. HBSS is a physiologically relevant inorganic salt solution and is considered to be a suitable Mg corrosion medium for in vitro testing. HBSS is commercially available and can be purchased from MilliporeSigma (formerly Sigma Aldrich) (St. Louis, Missouri, United States). In this example, this commercially available HBSS was modified with 1.6 g / L of sodium bicarbonate and 0.265 g / L of calcium chloride, which are also commercially available and were purchased from Sigma Alrdrich.

[0084] The wire fracture time of each sample was measured to provide a measure of relative corrosion resistance.

[0085] The experimental results are shown in FIG. 6C. The MgLiZnMnCa alloy of the present invention exhibited an average survival of at least 40 hours in the cold-worked form and at least 33 hours in the annealed form. As expected, this failure time was shorter than that of the rare-earth-containing WE43, which has an average survival time exceeding 50 hours in both the cold-worked and annealed forms. However, the survival of the MgLiZnMnCa alloy was substantially longer than that of the Mg4Li binary alloy, which failed after approximately 20 hours and 11 hours in the cold-worked and annealed forms, respectively. This suggests that the in-vivo survival period of the alloy of the present invention is much longer compared to the baseline binary alloy.

[0086] When the MgLiZnMnCa alloy of the present invention was compared with the conventional MgZnCaMn alloy, the survival time under cold working conditions was slightly shortened by the addition of Li. For the MgZnCaMn alloy at about 45 hours, the MgLiZnMnCa alloy of the present invention was about 40 hours. Surprisingly, the survival time in the annealed state was longer for the MgLiZnMnCa alloy (about 33 hours) than for the MgZnCaMn alloy (about 28 hours), which was not expected due to the high reactivity of Li. Therefore, the MgLiZnMnCa alloy of the present invention exhibits an in-vivo survival time that is superior to or comparable to that of similarly biocompatible alloys, while also showing excellent strength and ductility.

[0087] The present invention has been described as having an exemplary design, but the present invention can be further modified within the spirit and scope of the present disclosure. Accordingly, this application is intended to cover any variations, uses, or adaptations of the present invention using its general principles. Further, this application is intended to cover departures from the present disclosure within the scope of known or customary practices in the art to which this invention pertains and within the scope of the limitations of the appended claims.

Claims

1. An alloy for use in an absorbent medical device, comprising: 1.0 to 5.0 wt% lithium; 0.2 to 2.0 wt% zinc; 0.1 to 0.5 wt% calcium; 0.1 to 0.8 wt% manganese, and the balance being magnesium and inevitable impurities, the alloy.

2. A wire formed from the alloy according to Claim 1.

3. The wire according to Claim 2, having no cold worked portion being retained and exhibiting an ultimate tensile strength reaching 37 ksi.

4. The wire according to Claim 2, having a cold work rate of 75% and exhibiting an ultimate tensile strength reaching 64 ksi.

5. The wire according to Claim 2, having no cold worked portion being retained and exhibiting a yield strength reaching 30 ksi.

6. The wire according to Claim 2, having a cold work rate of 75% and exhibiting a yield strength reaching 56 ksi.

7. The wire according to Claim 2, having no cold worked portion being retained and exhibiting sufficient ductility to allow 14% elongation before fracture.

8. The wire according to Claim 2, having a cold work rate of 75% and exhibiting sufficient ductility to allow 7% elongation before fracture.

9. The wire according to Claim 2, having no cold worked portion being retained, in Hank's balanced salt solution maintained at 37 °C and 7.4 pH, and also with an initial stress maintained at 110 MPa, exhibiting an average survival of at least 30 hours.

10. The wire according to Claim 2, having a cold work rate of at least 50%, in Hank's balanced salt solution maintained at 37 °C and 7.4 pH, and also with an initial stress maintained at 110 MPa, exhibiting an average survival of at least 30 hours.

11. The wire according to Claim 2, having no cold worked portion being retained, an ultimate tensile strength reaching 37 ksi; a yield strength reaching 30 ksi; sufficient ductility to allow 14% elongation before fracture; and in Hank's balanced salt solution maintained at 37 °C and 7.4 pH, and also with an initial stress maintained at 110 MPa, exhibiting an average survival of at least 30 hours.

12. The wire according to Claim 2, having a cold work rate of 75%, an ultimate tensile strength reaching 64 ksi; a yield strength reaching 56 ksi; sufficient ductility to allow 7% elongation before fracture; The wire according to claim 2, which is maintained in Hank's balanced salt solution maintained at 37 °C and 7.4 pH, and also has an initial stress maintained at 110 MPa and exhibits an average survival of at least 30 hours.

13. The alloy according to claim 1, further comprising yttrium in an amount of up to 2.5% by weight.

14. A wire formed from the alloy according to claim 13.

15. The wire according to claim 14, wherein the wire has no retained cold-worked portion and exhibits an ultimate tensile strength reaching 39 ksi.

16. The wire according to claim 14, wherein the wire has a cold work rate of 75% and exhibits an ultimate tensile strength reaching 61 ksi.

17. The wire according to claim 14, wherein the wire has no retained cold-worked portion and exhibits a yield strength reaching 33 ksi.

18. The wire according to claim 14, wherein the wire has a cold work rate of 75% and exhibits a yield strength reaching 45 ksi.

19. The wire according to claim 14, wherein the wire has no retained cold-worked portion and exhibits sufficient ductility to allow an elongation of 19% before fracture.

20. The wire according to claim 14, wherein the wire has a cold work rate of 75% and exhibits sufficient ductility to allow an elongation of 9% before fracture.

21. A medical device formed from the alloy according to claim 1 or 13.

22. A medical device formed from the wire according to any one of claims 2 - 12, 14 - 20.

23. The medical device according to claim 21 or 22, which is a vascular device.

24. The medical device according to claim 21 or 22, which is an orthopedic fixation device.

25. The medical device according to claim 21 or 22, which is a surgical intervention device.

Images