Absorbable high-strength zinc alloy for medical implants

Abstract

An absorbable high-strength zinc alloy implant material includes a first tier material selected from the group consisting of Zn, Fe, and Mg, wherein Zn is in a range between about 90% and about 99% by weight and Fe and Mg is in a combined range between about 1% and about 10% by weight. The implant material can also include a second tier material being one or more element selected from the group consisting of Ag, Cu, Ce, Li, Sr, Mn, and rare earth elements, wherein the second tier material is between about 0.001% and about 10% by weight.

Claims

1. An absorbable zinc alloy medical implant material consisting of: a first material consisting of Fe; and Mg, wherein Fe and Mg is in a combined range between greater than 1.0% and less than 10% by weight of the alloy; and a second material consisting of cesium, the cesium being between 0.01% and 1% by weight of the alloy, and one or more element selected from the group consisting of silver, copper, manganese, lithium, and rare earth elements, wherein the total percentage of the second material is between greater than 0.01% and less than 9% by weight of the alloy; and a remainder Zn.

2. The implant material according to claim 1, wherein the Mg is up to 0.1% by weight of the alloy.

3. The implant material according to claim 1, wherein the Fe is up to 0.1% by weight of the alloy.

4. The implant material according to claim 1, wherein the second material is between 0.1% and 9% by weight of the alloy.

5. The implant material according to claim 1, wherein the implant material has a tensile strength greater than 250 MPa.

6. The implant material according to claim 5, wherein the implant material has a tensile strength less than 500 MPa.

7. The implant material according to claim 1, wherein the implant material has an elongation factor of between about 6% and about 36%.

8. The implant material according to claim 1, wherein the implant material has a tensile strength greater than 280 MPa.

9. The implant material according to claim 8, wherein the implant material has a tensile strength less than 450 MPa.

10. The implant material according to claim 1, wherein Fe is <0.002% by weight of the alloy.

11. An absorbable zinc alloy medical implant material consisting of: a first material consisting of Fe; and Mg, wherein Fe and Mg is in a combined range between 1.0% and less than 9.88% by weight of the alloy; a second material consisting of cesium, the cesium being between 0.01% and 1% by weight of the alloy, and one or more element selected from the group consisting of copper, manganese, and rare earth elements, wherein the one or more element of the second material is between 0.01% and 8.89% by weight of the alloy; and a third material consisting of Ca being between 0.1% and 1% by weight of the alloy; and a remainder Zn.

12. An absorbable zinc alloy medical implant material consisting of: a first material consisting of Zn and Fe; and a second material, wherein the second material consists of cesium, the cesium being between 0.01% and 1% by weight of the alloy, copper, and silver, wherein the first material is between 90% and less than 99.99% by weight of the alloy; and wherein the second material is between greater than 0.01% and 10% by weight of the alloy.

13. The implant material according to claim 12, wherein the implant material has a tensile strength greater than 280 MPa.

14. The implant material according to claim 13, wherein the implant material has a tensile strength less than 500 MPa.

15. The implant material according to claim 12, wherein the implant material has an elongation factor of between about 6.0% and about 40%.

16. The implant material according to claim 12, wherein the implant material has a biodegradation rate between 0.15 mm/year, and about 0.12 mm/year based in simulated body fluid (SBF) immersion testing.

17. An absorbable zinc alloy medical implant material consisting of: a first material consisting of Mg; a second material consisting of cesium, the cesium being between 0.01% and 1% by weight of the alloy, and two or more elements selected from the group consisting of copper, silver, lithium, manganese, and rare earth elements, wherein the total weight of the Mg and the second material is between greater than 0.01% and 10% by weight of the alloy; and a remainder Zn.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate the presently preferred embodiments of the invention, and, together with the general description given above and the detailed description given below, serve to explain the features of the invention. In the drawings:

(2) FIG. 1A is an SEM picture showing cast Zn-1Mg;

(3) FIG. 1B is an SEM picture showing extruded Zn-1Mg;

(4) FIG. 2A is a top plan view of a plate with screws using an alloy according to the present invention at the time of implantation; and

(5) FIG. 2B is a top plan view of the plate with screws of FIG. 2A six months after implantation.

DETAILED DESCRIPTION

(6) In the drawings, like numerals indicate like elements throughout. Certain terminology is used herein for convenience only and is not to be taken as a limitation on the present invention. The terminology includes the words specifically mentioned, derivatives thereof and words of similar import. The embodiments illustrated below are not intended to be exhaustive or to limit the invention to the precise form disclosed. These embodiments are chosen and described to best explain the principle of the invention and its application and practical use and to enable others skilled in the art to best utilize the invention.

(7) Reference herein to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one embodiment of the invention. The appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments necessarily mutually exclusive of other embodiments. The same applies to the term “implementation.”

(8) As used in this application, the word “exemplary” is used herein to mean serving as an example, instance, or illustration. Any aspect or design described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs. Rather, use of the word exemplary is intended to present concepts in a concrete fashion.

(9) The word “about” is used herein to include a value of +/−10 percent of the numerical value modified by the word “about” and the word “generally” is used herein to mean “without regard to particulars or exceptions.”

(10) Additionally, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or”. That is, unless specified otherwise, or clear from context, “X employs A or B” is intended to mean any of the natural inclusive permutations. That is, if X employs A; X employs B; or X employs both A and B, then “X employs A or B” is satisfied under any of the foregoing instances. In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from context to be directed to a singular form.

(11) Unless explicitly stated otherwise, each numerical value and range should be interpreted as being approximate as if the word “about” or “approximately” preceded the value of the value or range.

(12) The use of figure numbers and/or figure reference labels in the claims is intended to identify one or more possible embodiments of the claimed subject matter in order to facilitate the interpretation of the claims. Such use is not to be construed as necessarily limiting the scope of those claims to the embodiments shown in the corresponding figures.

(13) It should be understood that the steps of the exemplary methods set forth herein are not necessarily required to be performed in the order described, and the order of the steps of such methods should be understood to be merely exemplary. Likewise, additional steps may be included in such methods, and certain steps may be omitted or combined, in methods consistent with various embodiments of the present invention.

(14) Although the elements in the following method claims, if any, are recited in a particular sequence with corresponding labeling, unless the claim recitations otherwise imply a particular sequence for implementing some or all of those elements, those elements are not necessarily intended to be limited to being implemented in that particular sequence.

(15) The present invention provides zinc-based alloys for medical implant and coronary heart stent purposes. A stent manufactured by the inventive zinc-based alloy is absorbed by the patient's body. Such absorption may make vessel recovery possible when treating coronary heart disease, which is impossible when using a traditional metal stent. Because there is no permanent metal left in the body, the patient's vessel being treated by the absorbable stent may be able to move, stretch and pulse, like a new one.

(16) Hot extrusion of Zn—Mg alloys under various processing conditions were compared with casting. Metallurgical analysis revealed significant grain size reduction, and immersion testing found that corrosion rates of Zn—Mg alloys were substantially reduced by hot extrusion. One example comparison of morphology before and after hot extrusion of Zn-1Mg is shown in FIGS. 1A and 1B. After hot extrusion, the phase size is refined by orders of magnitude. The corrosion rate in simulated body fluid (SBF) reduced from 0.28 mm/year to 0.12 mm/year. The mechanical strength increased from 140 MPa to 280 MPa. Therefore, hot extruded Zn-1Mg alloys with homogenously refined microstructure and uniform as well as slow degradation, improved mechanical properties, and good biocompatibility are believed to be an excellent candidate material for loadbearing and biodegradable implant applications.

(17) Plates and screws were manufactured from a Zn—Mg alloy and studied in vivo degradation in animal tests (dogs). The plates and screws were produced by machining of an alloy cast. The designs were taken from the common ones used by conventional titanium counterparts for fixation of mandible fractures illustrated in FIG. 2A. The weight loss of the implants in dog was monitored. After 6 months, the weight loss was about 12% for the plate and 10% for the screw. Better healing results were observed with Zn—Mg alloys; furthermore, the Zn—Mg implants can degrade in vivo. Cell cytotoxicity tests did not show formation of teratomas; nor was tissue inflation observed. Toxic substances were not detected in dog urine samples. Ingrowth of tissue was also observed at sites with degradations (FIG. 2B). These results indicate that biodegradable and resorbable Zn—Mg alloys may replace traditional non-degradable titanium alloys in implant devices.

(18) Exemplary formulations of the inventive zinc alloy are provided below.

(19) In order to obtain the best mechanical property and biological corrosion resistance, it is desired that the elements used have high purity: Zn purity is greater than or equal to 99.999%; Cs purity is greater than or equal to 99.99%; Mg purity is greater than or equal to 99.99%; Ca purity is greater than or equal to 99.99%; Cu purity is greater than or equal to 99.99%; the remaining elements have total impurities less than 0.1%.

(20) The inventive alloy is constructed from elements that have been categorized in different tiers, with a first tier of elements having properties of being biocompatible, biodegradable, bioabsorbable, and biofunctional, with relatively high strength. Exemplary elements in the first tier include zinc (Zn), iron (Fe), and magnesium (Mg).

(21) A second tier of elements has properties of being bio-benign and at least partly biofunctional. Exemplary second tier elements include silver (Ag), copper (Cu), cesium (Cs), lithium (Li), strontium (Sr), manganese (Mn), the rare earth elements, and combinations thereof.

(22) A third tier of elements has properties of being biocompatible, biodegradable, bioabsorbable, and biofunctional, but with relatively low strength and low elongation as compared to the first tier elements. An exemplary element in the third tier is calcium (Ca).

(23) The present invention can be used to manufacture screws, plates, and coronary heart stents. These implants have different uses and have different structural requirements. For example, a screw requires high strength (greater than 320 MPa) and low elongation (at least 6%); a plate requires moderate strength (greater than 230 MPa and high elongation (at least 20%); and a stent requires high strength (greater than 300 MPa) and high elongation (at least 25%).

(24) In an exemplary embodiment, the first tier material is between about 90% and about 99.99% by weight of the inventive alloy and the second tier material is between about 0.01% and about 10% by weight.

(25) In an exemplary embodiment, Zn is in a range between about 90% and about 99% by weight and Fe and Mg is in a combined range not more than 10% by weight, and can be between about 1% and about 10% by weight. Mg can be less than about 0.1% by weight and can be between about 0.01% and about 0.1% by weight, making Mg a micro-alloy. The amount of Mg in the alloy can also be 0%. Alternatively, the amount of Fe in the alloy can be between about 0.01% and about 0.1% by weight, making Fe a micro-alloy; and also Fe can be 0%.

(26) Additionally, the second tier material can be between about 0.001% and about 10% by weight, or, alternatively, between about 0.01% and about 10% by weight.

(27) In an exemplary alloy wherein first and second tier elements are used, the first tier material is between about 90% and about 99.99% by weight and the second tier material is between about 0.01% and about 10% by weight. Further, when the third tier material is also used, the third tier material is between about 0.1% and about 1% by weight of the alloy.

(28) Table 1 below lists different alloy compositions according to the present invention, with the values for each composition reflecting average actual test results.

(29) TABLE-US-00001 TABLE 1 Material Yield UTS Elongation Tier Zn1.5Mg0.015Fe** 328 408 6.9 First tier Zn2Mg0.01Li** 337 411 6.5 First and Second tiers Zn0.015Mg1.56Cu* 326 336 40 First and Second tiers Zn0.015Mg3Cu* 337 403 31.5 First and Second tiers Zn0.45Mg0.03Fe** 324 427 6 First tier Yield = yield strength, in MPa UTS = Ultimate Tensile Strength, in MPa Elongation = elongation factor of material before rupture, in percent *Good for stents, plates and screws. **Good for surgical screws.

(30) Yield=yield strength, in MPa

(31) UTS=Ultimate Tensile Strength, in MPa

(32) Elongation=elongation factor of material before rupture, in percent

(33) * Good for stents, plates and screws.

(34) ** Good for surgical screws.

(35) As can be seen from Table 1, for the tested alloys, tensile strength ranges between about 336 MPa and about 427 MPa, with an elongation between about 6 percent and about 40 percent.

(36) Table 2 below lists different compositions for a rod having a 12 mm diameter to simulate surgical plates and screws.

(37) TABLE-US-00002 TABLE 2 Yield Materials Strength UTS Elongation Tier Zn0.015Mg0.6Cu** 215 260 26 First and Second tiers Zn0.01Mg0.15Ca** 227 261 36.5 First and Third tiers Zn0.02Mg0.9Cu** 248 283 26.5 First and Second tiers Zn0.02Mg0.3Cu** 192 250 36.5 First and Second tiers Zn0.015Mg1.56Cu* 313 328 36.5 First and Second tiers Zn0.015Mg3Cu* 337 403 31.5 First and Second tiers Yield = yield strength, in MPa UTS = Ultimate Tensile Strength, in MPa Elongation = elongation factor of material before rupture, in percent *Good for stents, plates, and screws. **Good for plates.

(38) Yield=yield strength, in MPa

(39) UTS=Ultimate Tensile Strength, in MPa

(40) Elongation=elongation factor of material before rupture, in percent

(41) * Good for stents, plates, and screws.

(42) ** Good for plates.

(43) For these alloys consisting of first tier and second tier materials, minimum tensile strength was about 250 MPa and maximum tensile strength was about 403 MPa, with a minimum elongation of about 26 percent and a maximum elongation of about 36.5 percent.

(44) It will be further understood that various changes in the details, materials, and arrangements of the parts which have been described and illustrated in order to explain the nature of this invention may be made by those skilled in the art without departing from the scope of the invention as expressed in the following claims.