BIODEGRADEABLE IMPLANT COMPRISING COATED METAL ALLOY PRODUCT

Abstract

The invention relates to a biodegradable implant comprising a surface coated magnesium alloy or zinc alloy product, whereby the coating layer comprises oxides and/or phosphates of from rare-earth elements, Mg, Ca, Zn, Zr, Cu, Fe, Sr, Li, Mn or Ag wherein the coating is preferably generated by plasma electrolytically oxidation (PEO). The invention further comprises a method for preparing the coated magnesium or zinc alloy product of the implant.

Claims

1-13. (canceled)

14. Biodegradable implant comprising a magnesium or zinc alloy productcoated on its surface with a coating layer comprising at least three substances being a. a metal oxide of a metal selected from rare-earth elements, Mg, Ca, Zn, Zr, Cu, Sr, Li, Mn or Ag; and/or b. a metal phosphate of a metal selected from rare-earth elements, Mg,Ca, Zn, Zr, Cu, Sr, Li, Mn or Ag.

15. Biodegradable implant according to claim 14, wherein the coated magnesiumor zinc alloy product comprises the following characteristic: the metal oxide or metal phosphate forms an amorphous domain within the coating layer.

16. Biodegradable implant according to claim 14, wherein the metal oxide ormetal phosphate of the coated magnesium or zinc alloy product forms a crystalline domain within the coating layer.

17. Biodegradable implant according to claim 14, wherein the coated magnesium or zinc alloy product comprises the following characteristic: the coating layer has a thickness of between 2 to 50 μm, preferably 5 to 35 μm, particularly preferably of between 8 to 24 μm and especially of between 12 to 18 μm.

18. Biodegradable implant according to claim 14, wherein the coated magnesium or zinc alloy product comprises the following characteristic: the coating layer comprises metal fluorides which increase in their concentration starting from the top surface of the coating layer down to the bottom, alloy-product oriented surface of the coating layer, building preferably a distinct metal fluoride enriched zone at the bottom surface ofthe coating layer.

19. Biodegradable implant according to claim 14, wherein the coated magnesium or zinc alloy product comprises the following characteristic: the top surface of the coating layer has a mean Vickers hardness from 150 to800, preferably from 200 to 600, and more preferably from 250 to 400, asmeasured according DIN EN ISO 6507-1/4:2018.

20. Biodegradable implant according to claim 14, wherein the coated magnesium or zinc alloy product comprises the following characteristic: thecoating layer comprises at least two sub layers being a bottom, alloy-product oriented barrier layer and a porous top layer.

21. Biodegradable implant according to claim 14, wherein the coated magnesium or zinc alloy product comprises the following characteristic: thecoating layer is generated by plasma electrolytically oxidation (PEO).

22. Biodegradable implant according to claim 14, wherein the coating layer is manufactured by a conversion coating, preferably an anodizing treatment,more preferably a PEO.

23. Biodegradable implant according to claim 14, wherein the coating layeris a porous layer, which preferably has a porosity of 2 to 50%, more preferably of between 3 to 25%, and particularly preferable of 4 to 12%.

24. Biodegradable implant according to claim 23, wherein the pores of at thetop surface of the coating layer have a mean pore size of between 0.1 to 10, preferably of 2 to 8, particularly preferably of 4 to 6 μm.sup.2.

25. Biodegradable implant according to claim 14, wherein the magnesium alloy is selected from the group consisting of a Magnesium silver alloy (Mg—Ag), a Mg alloy containing rare elements (RE), preferably a Mg—Y-RE alloy and more preferably a Mg—Y—Nd with or without addition of Zr, even more preferred with a Y content between 3 and 5% wt.-% and a Nd content between 2 and 4% wt.-%; or a Mg alloy comprising Calcium and Zink, preferably Mg—Ca—Zn or Mg—Zn—Ca with or without addition of Zr,even more preferably with Ca and Zn contents each below 1 wt.-%.

26. Biodegradable implant according to claim 14, wherein the zinc alloy is selected from the group consisting of a zinc-magnesium alloy (Zn—Mg) with or without the addition of calcium (Zn—Ca—Mg or Zn—Mg—Ca), azinc-silver alloy (Zn—Ag) with or without the addition of magnesium (Zn—Ag—Mg or Zn—Mg—Ag), a zinc-strontium alloy (Zn—Sr) with or without the additionof magnesium (Zn—Sr—Mg or Zn—Mg—Sr), a zinc-lithium alloy (Zn—Li) with or without the addition of magnesium (Zn—Li—Mg or Zn—Mg—Li), a zinc-calcium alloy (Zn—Ca) with or without the addition of magnesium (Zn—Ca—Mg or Zn—Mg—Ca) or a zinc-manganese alloy (Zn—Mn) with or without the addition of magnesium (Zn—Mn—Mg or Zn—Mg—Mn).

27. Biodegradable implant according to claim 14, wherein implantis manufactured by conventional (subtractive) or additive manufacturingmethods.

28. Biodegradable implant according to claim 14, wherein the implant comprises at least 2 or more sublayers, which can be separated by analytical measurements of the phase composition, crystalline content or visible features.

29. Biodegradable implant according to claim 14, wherein the coated magnesium or zinc alloy product after incubation for 100 hours in Minimal Essential Medium (MEM) at 37° C. under non-turbulent stirring has ahydrogen gas evolution rate of less than 1.0 ml/cm.sup.2, preferably of less than 0.6 ml/cm.sup.2, more preferably of less than 0.2 ml/cm.sup.2, and even more preferably of less than 0.1 ml/cm.sup.2, as measured by continuous volumetricmeasurement of the generated hydrogen gas.

30. Method for generating a coating layer on the surface of a magnesium or zinc alloy product, preferably of a magnesium alloy product according to claim 26, comprising the following steps: Providing an aqueous electrolyte solution comprising an inorganicphosphate, (ii) subjecting a magnesium alloy or zinc alloy product to the aqueouselectrolyte solution so that the surface of the magnesium alloy product or the zinc alloy product which is to be treated is immersed in the electrolyte solution, (iii) applying an voltage difference between the magnesium or zinc alloy product and a second electrode positioned in the aqueous electrolyte system for generating a plasma electrolytic oxidation onthe immersed surface of the magnesium alloy product or the zinc alloy product, (iv) so that the immersed surface is converted to a mixedoxide/phosphate film.

31. Method for treating a surface of magnesium or zinc alloy product according to claim 30, wherein the aqueous electrolyte solution has one or more of the following characteristics: a. The aqueous electrolyte solution comprises an inorganic phosphate which is preferably selected from the list consisting of phosphoric acid, Na.sub.3PO.sub.4, Na.sub.4P.sub.2O.sub.7, Na.sub.5P.sub.3O.sub.10, Na.sub.6P.sub.6O.sub.18, Na.sub.2HPO.sub.4, NaH.sub.2PO.sub.4, and K.sub.2P.sub.2O.sub.7; b. The aqueous electrolyte solution comprises an inorganic phosphatein a concentration of between 1 and 250 g/L.

32. Method for treating a surface of magnesium or zinc alloy product according to claim 31, wherein the aqueous electrolyte solution comprises in addition to an inorganic phosphate one or more alkaline compounds, preferably selected from the list consisting of ammonium hydroxide, sodium hydroxide,potassium hydroxide and lithium hydroxide.

33. Method for treating a surface of magnesium or zinc alloy product according to claim 31, wherein the aqueous electrolyte solution further comprises one or more additives selected from hydrogen fluoride, urotropinand boric acid.

34. Method for treating a surface of magnesium or zinc alloy product according to claim 31, wherein the voltage and/or current as applied in step (iii) is unipolar or bipolar pulsed with a pulse frequency which is preferably between 1 and 5 kHz, more preferably between 10 and 1.500 Hz and most preferably between 50 and 500 or between 100 and 1.000 Hz.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0145] These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter.

[0146] The invention will now be described, by way of example, based on embodiments with reference to the accompanying drawings.

[0147] In the drawings:

[0148] FIG. 1 shows a schematic drawing of a cell for PEO anodization.

[0149] FIG. 2 A shows the results of the digital analysis of the coated test specimens S1 to S12 with regard to porosity (in %) and pore size (area of the pore in μm.sup.2). In B the SEM pictures showing the surface morphology of the test sample S6 together with the EDS spectrum is shown.

[0150] FIG. 3 shows the results for the LDH, XTT and BrdU testing of extracts taken from the test samples S1 to S12.

[0151] FIG. 4 shows the cumulative results of the in vitro toxicity testing of samples S1 to S12 including a negative control (NK) and a positive control (PK) after direct plating of CCL1 cells on the coated test samples S1 to S12.

[0152] FIG. 5 shows the cross section of the PEO coated ZX00 Mg alloy in the SEM picture (right) and with a colour coded picture showing the distribution of the different coating phases as a so called live map (left). The figure legend for the color-coded phases with their elemental composition is shown in the bottom.

[0153] FIG. 6 shows the cross section of the PEO coated ZX00 Mg alloy with colour coded element overlays for all elements at top left with the element-colour allocation as depicted top right. In the following the separated element presentation for Fluor, Magnesium, Aluminium and Phosphor is shown.

[0154] FIG. 7 shows the cross section of the PEO coated ZX00 Mg alloy with colour coded separated element presentation for Calcium, Iron, Nickel, Zink and Zirconium.

[0155] FIG. 8 shows the results of the EDS analysis using eZAF Smart Quant for four different phases of the PEO coated Mg alloy ZX00.

[0156] FIG. 9 shows the results of the EDS analysis using eZAF Smart Quant for two different phases of the PEO coated Mg alloy ZX00. In the bottom an exemplary EDS spectrum (here for the phase P K/MgK/C K) is shown.

[0157] FIG. 10 shows the cross section of the PEO coated ZX00 Mg alloy with selection of two different EDS spots, for which the elemental composition as determined by eZAF Smart Quant is shown below.

[0158] FIG. 11 shows the cross section of the PEO coated WE43 Mg alloy with selection of two different EDS spots, for which the elemental composition as determined by eZAF Smart Quant is shown below.

[0159] FIGS. 12 and 13 show the results of the x-ray crystallographic analysis for an PEO-coated Mg alloys with two different impulse presentations.

[0160] FIGS. 14 and 15 show the results of the x-ray crystallographic analysis for an PEO-coated Mg alloy WE43 and ZX00 under different angles.

[0161] FIGS. 17, 18 and 19 show the surface of a PEO coated Zn1Mg specimen (1 wt-% Magnesium, remainer is Zinc) analysed with scanning-electron microscopy (SEM). FIG. 17 depicts the surface in small, FIG. 18 in middle and FIG. 19 in high magnification. A typical PEO coating can be observed comprising an open porosity on top of the surface and in this case also small coating spheres additionally bound to the surface.

[0162] FIG. 20 shows the phase composition of an exemplary resulting PEO coating on Zn1MG specimen (1 wt-% Magnesium, remainer is Zinc) in dependency of the applied current densities using Phosphate and KOH containing electrolyte. The phase composition was characterized using a Bruker D8 Advances XRD at room temperature. Ni-filtered Cu Kα radiation was used. Following settings were applied during the measurements: 0.02° step size, 2 s dwell time, 3° glancing angle and 20 s.sub.−1 sample rotation rate. Apparently different Phosphates and Oxides further containing entities of the base materials (Magnesium and Zinc) could be created during conversion of the surface and determined by the measurements. Thus, being in accordance with the present invention.

[0163] In the Figures, like numbers refer to like objects throughout. Objects in the Figures are not necessarily drawn to scale.

Detailed Description of Embodiments

[0164] Various embodiments of the invention will now be described by means of the Figures.

[0165] FIG. 1 shows a principal sketch of the PEO cell for coating of the Mg alloy products. The electrolyte circulation helps to removes gas bubbles from the surface of the Mg alloy product, which might impair the growth of a homogenous layer. By blowing in fine air bubbles (i) the laminar boundary layer will be removed continuously so that an increased exchange with the electrolyte is achieved.

Definitions

[0166] The term “biodegradable” as used in the context of the present invention refers to a device that is degradable under physiological conditions.

[0167] The term “biodegradation” as used herein for the degradation of the implant within the organism of the recipient is synonymous to the terms “degradation”, “absorption”, “resorption“, “corrosion” and “biocorrosion”.

[0168] The term “plasma anodisation” as used herein is synonymous to the following terms: “anodic sparc oxidation (ANOF)”, “microarc oxidation (MAO)”, “anodic spark deposition (ASD)”, “microplasma oxidation (MPO)”, “plasma chemical oxidation (PCO)” and “micro-arc discharge oxidation (MDO)“.

[0169] In the context of the present application the term coating also encompasses the conversion of surface material and surface modification.

[0170] A used herein, the terms “spark discharge” and “plasma discharge” are synonymous terms.

[0171] The term oxide as used in the context of the present invention encompasses also oxide-hydrates.

[0172] The term “phosphate” as used herein denotes to phosphates, diphosphates and polyphosphates.

[0173] As used herein, a metal phosphate is a chemical compound of a metal and at least one phosphate being a chemical derivative of a phosphoric acid. A phosphoric acid is hereby defined as a proton-donating phosphor-oxygen compound and thereby encompasses all types of HxPyOz compounds, such as orthophosphoric acid, metaphosphoric acid, polyphosphoric acid, phosphonic acid and phosphorous acid.

[0174] In the context of the present invention a metal oxide is a chemical compound containing at least one oxygen atom and a metal cation as further element. Examples are MgO, ZnO, CaO, ZrO.sub.2, or ZnO.

[0175] Of note, a change in quantity of atoms within an entity in the surface layer either consisting of oxygen, phosphate or a metal is considered a different substance. For example, ZnO and ZnO.sub.2 will be considered different substances, as they exhibit a different amount of oxygen atoms. In another example, ZnO.sub.2 and ZnMgO.sub.2 will be considered different substances, as they exhibit different amounts of magnesium atoms. The absence of an element in this sense will be considered as having a quantity of O.

[0176] Of note, a “rare earth element” is an element selected from the list consisting of Y, Sc, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu or any other element being considered a rare earth by general technical knowledge as also described in standard text books.

[0177] Of note, the term “coated on its surface” refers to the fact that at least one part of the surface of the implant is coated.

[0178] As used in the context of the invention, the term “biocompatible” relates to a device that is substantially non-toxic in an in vivo environment, and is not substantially rejected by a recipient's physiological system.

LIST OF REFERENCE NUMERALS

[0179] a) power source [0180] b) electrolyte solution [0181] c) counter electrode [0182] d) mg ally test piece [0183] e) gas aspiration [0184] f) encapsulation [0185] g) heat exchanger [0186] h) electrolyte circulation [0187] i) air supply [0188] j) filter