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. A biodegradable implant comprising a magnesium or zinc alloy product coated 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; wherein the magnesium alloy is selected form the group consisting of a magnesium silver alloy (MgAg), a MgY-RE alloy containing yttrium and at least one additional rare earth element (RE), and a magnesium alloy comprising calcium and zinc, or wherein the zinc alloy is a selected from the group consisting of a zinc-magnesium alloy with the addition of calcium (ZnCaMg or ZnMgCa), a zinc-silver alloy (ZnAg) with or without the addition of magnesium (ZnAgMg or ZnMgAg), a zinc-strontium alloy with the addition of magnesium (ZnSrMg or ZnMgSr), a zinc-lithium alloy with or without the addition of magnesium (ZnLiMg) or (ZiMgLi), a zinc-calcium alloy with the addition of magnesium (ZnCaMg or ZnMgCa), and a zinc-manganese alloy (ZnMn) with or without the addition of magnesium (ZnMnMg or ZnMgMn).

2. The biodegradable implant according to claim 1, wherein the coated magnesium or zinc alloy product comprises the following characteristic: the metal oxide or metal phosphate forms an amorphous domain within the coating layer.

3. The biodegradable implant according to claim 1, wherein the metal oxide or metal phosphate of the coated magnesium or zinc alloy product forms a crystalline domain within the coating layer.

4. The biodegradable implant according to claim 1, wherein the coated magnesium or zinc alloy product comprises the following characteristic: the coating layer has a thickness of between 2 to 50 m.

5. The biodegradable implant according to claim 1, 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 a distinct metal fluoride enriched zone at the bottom surface of the coating layer.

6. The biodegradable implant according to claim 1, 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 to 800 as measured according to DIN EN ISO 6507-1/4:2018.

7. The biodegradable implant according to claim 1, wherein the coated magnesium or zinc alloy product comprises the following characteristic: the coating layer is generated by plasma electrolytic oxidation.

8. The biodegradable implant according to claim 1, wherein the coating layer is manufactured by a conversion coating.

9. The biodegradable implant according to claim 1, wherein the coating layer is a porous layer, wherein pores at the top of the porous layer have a mean pore size of between 0.1 to 10 m.sup.2.

10. The biodegradable implant according to claim 9, wherein the pores have a mean pore size of between 2 to 8 m.sup.2.

11. The biodegradable implant according to claim 1, wherein the MgY-RE alloy is a MgYNd with or without addition of Zr and the magnesium alloy comprising calcium and zinc is MgCaZn or MgZnCa alloy with or without addition of Zr.

12. The biodegradable implant according to claim 1, wherein the coated magnesium or zinc alloy product after incubation for 100 hours in Minimal Essential Medium at 37 C. under non-turbulent stirring has a hydrogen gas evolution rate of less than 1.0 ml/cm.sup.2, as measured by continuous volumetric measurement of the generated hydrogen gas.

13. The biodegradable implant of claim 4, wherein the coating layer has a thickness of between 5 to 35 m.

14. The biodegradable implant of claim 10, wherein the pores have a mean pore size of 4 to 6 m.

15. The biodegradable implant of claim 11, wherein the magnesium alloy is a MgYNd alloy with a Y content between 3 and 5 wt. %.

16. The biodegradable implant of claim 11, wherein the magnesium alloy comprising calcium and zinc is a MgCaZn or MgZnCa alloy with or without the addition of Zr and having Ca and Zn contents each below 1 wt. %.

17. The biodegradable implant of claim 12, wherein the coated magnesium or zinc alloy product after incubation for 100 hours in Minimal Essential Medium at 37 C. under non-turbulent stirring has a hydrogen gas evolution rate of less than 0.6 ml/cm.sup.2 as measured by continuous volumetric measurement of the generated hydrogen gas.

18. The biodegradable implant of claim 12, wherein the coated magnesium or zinc alloy product after incubation for 100 hours in Minimal Essential Medium at 37 C. under non-turbulent stirring has a hydrogen gas evolution rate of less than 0.2 ml/cm.sup.2 as measured by continuous volumetric measurement of the generated hydrogen gas.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter.

(2) The invention will now be described, by way of example, based on embodiments with reference to the accompanying drawings.

(3) In the drawings:

(4) FIG. 1 shows a schematic drawing of a cell for PEO anodization.

(5) 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 m.sup.2). In B the SEM pictures showing the surface morphology of the test sample S6 together with the EDS spectrum is shown.

(6) FIG. 3 shows the results for the LDH, XTT and BrdU testing of extracts taken from the test samples S1 to S12.

(7) 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.

(8) 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.

(9) 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.

(10) 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.

(11) FIG. 8 shows the results of the EDS analysis using eZAF Smart Quant for four different phases of the PEO coated Mg alloy ZX00.

(12) 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.

(13) 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.

(14) 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.

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

(16) 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.

(17) FIGS. 17, 18 and 19 show the surface of a PEO coated Zn1Mg specimen (1 wt-% Magnesium, remainder 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.

(18) FIG. 20 shows the phase composition of an exemplary resulting PEO coating on Zn1MG specimen (1 wt-% Magnesium, remainder 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 K 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.

(19) In the Figures, like numbers refer to like objects throughout. Objects in the Figures are not necessarily drawn to scale.

DETAILED DESCRIPTION OF EMBODIMENTS

(20) Various embodiments of the invention will now be described by means of the Figures.

(21) 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

(22) The term biodegradable as used in the context of the present invention refers to a device that is degradable under physiological conditions.

(23) 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.

(24) 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).

(25) In the context of the present application the term coating also encompasses the conversion of surface material and surface modification.

(26) A used herein, the terms spark discharge and plasma discharge are synonymous terms.

(27) The term oxide as used in the context of the present invention encompasses also oxide-hydrates.

(28) The term phosphate as used herein denotes to phosphates, diphosphates and polyphosphates.

(29) 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.

(30) 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.

(31) 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 0.

(32) 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.

(33) 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.

(34) 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

(35) a) power source b) electrolyte solution c) counter electrode d) mg ally test piece e) gas aspiration f) encapsulation g) heat exchanger h) electrolyte circulation i) air supply j) filter