Stent made of a bio-degradable magnesium alloy with a magnesium fluoride coating and an organic coating

Abstract

The present invention relates to stents made of a magnesium alloy degradable under physiological conditions having an inorganic coating comprising magnesium fluoride and having an organic coating. The stents according the invention can additionally be coated with at least one antiinflammatory, antiproliferative, antiangiogenic, antirestenotic, and/or antithrombogenic active agent.

Claims

1. A stent of biodegradable magnesium alloy having two coatings, wherein the first coating is an inorganic coating comprising magnesium fluoride and the second coating is an organic coating, the magnesium alloy containing at least 80% by weight magnesium, and wherein the inorganic coating covers the stent and the organic coating covers the inorganic coating, wherein the organic coating comprises one or more substances of the following group: poly(ε-caprolactone), poly(L-lactide-co-glycolide), poly(L-lactide), and parylene, wherein the organic coating is metal-free and does not contain metal-containing compounds and/or organometallic compounds, metal alkoxides or polymeric metal alkoxides, wherein the layer thickness of the organic coating is 0.5 μm to 10 μm; or in case of parylene, wherein the layer thickness of the organic coating is 0.001 μm to 10 μm; and wherein the layer thickness of the inorganic coating is 0.1 pm to 10 μm; wherein the biodegradable magnesium alloy comprises 5.0% by wt.-13.0% by wt. dysprosium, 0.01% by wt.-1.5% by wt. neodymium and/or europium, 0.0% by wt.-2.0% by wt. zinc, 0.0% by wt.-1.0% by wt. zirconium, and at least 80.0% by wt. magnesium.

2. The stent according to claim 1, wherein the organic coating has no micropores, holes, openings or channels.

3. The stent according to claim 1, wherein at least one anti-inflammatory, antiproliferative, antiangiogenic, antirestenotic, antineoplastic, antimigrative and/or antithrombogenic active agent is present in or on the organic coating.

4. The stent according to claim 3, wherein the at least one anti-inflammatory, antiproliferative, antiangiogenic, antirestenotic, antineoplastic, antimigrative and/or antithrombogenic active agent is selected from the group consisting of paclitaxel, sirolimus, biolimus A9, myolimus, novolimus, pimecrolimus, tacrolimus, temsirolimus, zotarolimus, everolimus and ridaforolimus.

5. The stent according to claim 1, wherein the stent is a stent for blood vessels, urinary tracts, respiratory tracts, biliary tracts or digestive tract.

6. The stent according to claim 1, wherein the stent is a stent for blood vessels, urinary tracts, respiratory tracts, biliary tracts or digestive tract.

7. A stent of biodegradable magnesium alloy, comprising: an inorganic coating comprising magnesium fluoride; and an organic coating, the magnesium alloy containing at least 80% by weight magnesium, wherein the inorganic coating covers the stent and the organic coating covers the inorganic coating, wherein the organic coating comprises an organic polymer selected from the group consisting of: polyvinyl pyrrolidone, poly hydroxyethyl methacrylates, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvalerolactones, poly-ε-decalactones, polylactonic acid, poly(glycolic acid), polylactides, poly(L-lactide), poly(D,L-lactide), and copolymers, poly(L-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-trimethylene carbonate)] (PTMC), poly(ε-caprolactone), polyhydroxybutyric acid, polyhydroxyvalerates, polyhydroxybutyrate-co-valerates, poly(1,3-dioxane-2-one), poly(para-dioxanones), poly(maleic anhydrides), polyhydroxy methacrylates, fibrin, polycyanoacrylates, polycaprolactone dimethylacrylates, polycaprolactone butyl acrylates, polycaprolactone glycolides, poly(methyl methacrylate), poly(butyl methacrylate), polyacrylamide, polyamides, polyetheramides, polyethylene amine, polyimides, polycarbonates, polycarbourethanes, polyvinyl ketones, polyvinyl ethers, polyisobutylenes, polyvinyl aromatic compounds, polyvinyl esters, polyoxymethylenes, polytetramethylene oxide, polyethylene, polypropylene, polytetrafluoroethylene, polyurethanes, polyetherurethanes, polyolefin elastomers, parylene (poly-para-xylylene), parylene N, and parylene C, wherein the layer thickness of the organic coating is 0.001 μm to 10 μm in a case of the organic polymer being poly-para-xylylene (parylene), parylene N or parylene C, wherein the layer thickness of the organic coating is 0.5 μm to 10 μm in a case of the organic polymer being any other organic polymer; and wherein the biodegradable magnesium alloy comprises 91.0% by wt. to 92.0% by wt. of magnesium, 0.7% by wt. to 0.8% by wt. of dysprosium, 0.6% by wt. to 0.8% by wt. of gadolinium, 1.9% by wt. to 2.1% by wt. of neodymium, 0.6% by wt. to 0.8% by wt. of zirconium, and 3.9% by wt. to 4.2% by wt. of yttrium.

8. The stent according to claim 7, wherein the organic coating comprises one or more substances of the following group: poly(ε-caprolactone), poly(L-lactide-co-glycolide), poly(L-lactide) and parylene.

9. The stent according to claim 8, wherein the organic coating has no micropores, holes, openings or channels.

10. The stent according to claim 8, wherein at least one anti-inflammatory, antiproliferative, antiangiogenic, antirestenotic, antineoplastic, antimigrative and/or antithrombogenic active agent is present in or on the organic coating.

11. The stent according to claim 9, wherein the at least one anti-inflammatory, antiproliferative, antiangiogenic, antirestenotic, antineoplastic, antimigrative and/or antithrombogenic active agent is selected from the group consisting of paclitaxel, sirolimus, biolimus A9, myolimus, novolimus, pimecrolimus, tacrolimus, temsirolimus, zotarolimus, everolimus and ridaforolimus.

Description

DESCRIPTION OF THE FIGURES

(1) FIG. 1 shows a graphic representation of the results of the corrosion tests with binary magnesium alloys containing between 5 and 20% dysprosium and magnesium as balance. The corrosion was measured in 0.9% saline solution in a eudiometer. The data in % refer to the content of dysprosium in % by weight.

(2) FIG. 2 shows a graphic representation of the dependence of the tendency for hot crack formation in connection with the amount of zinc in the alloy. Magnesium alloys containing 10% dysprosium, 1.0% by weight neodymium, increasing % by weight zinc, 0.2% by weight zirconium and the balance of magnesium were tested. The data in % refer to the content of zinc in % by weight.

(3) FIG. 3 shows a comparison of the photometric measurements to the degradation rates of the O.sub.2 ion-implanted stent, stent of uncoated magnesium alloy A (bare metal stent (BMS)) and magnesium fluoride coated stent of magnesium alloy A. The dissolved masses of magnesium in PBS are applied over time. Sample A is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without further treatment. The average values of dissolved magnesium over the time of three equal stents of sample A are shown.

(4) Sample B is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) followed by oxygen ion implantation. During ion implantation, oxygen ions are shot (implanted) into the surface to form a magnesium oxide layer.

(5) Sample C is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) followed by surface transformation, wherein a magnesium fluoride (MgF.sub.2) layer is formed. The average values of dissolved magnesium over the time of three equal stents of sample C are shown.

(6) FIG. 4 shows camera images of the degradation of individual stents of samples A, B and C according to FIG. 3 and corresponding description.

(7) The first line shows a stent of sample B (magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent oxygen ion implantation). The first image (from left) is taken at the start of the degradation test. The second image shows the stent after 24 hours and the third image shows the stent after 36 hours in the PBS traversed tube.

(8) The second line shows a stent of sample A (magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without further treatment). The first image (from left) is taken at the start of the degradation test. The second image shows the stent after two hours and the third image shows the stent after six hours in the PBS traversed tube.

(9) The third line shows a stent of sample C (magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent surface transformation to produce MgF.sub.2). The first image (from left) is taken at the start of the degradation test. The second image shows the stent after 13 hours and the third image shows the stent after 24 hours in the PBS traversed tube.

(10) FIG. 5 shows a comparison of the photometric measurements to the degradation rates of MgF.sub.2—, MgCO.sub.3— and Mg.sub.3(PO.sub.4).sub.2 coated stents. The dissolved masses of magnesium in PBS are applied over time. Three stents with the same coating were measured and the average values of these measurements are shown in FIG. 5.

(11) Sample A is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium phosphate layer (Mg.sub.3(PO.sub.4).sub.2). For generation of this layer, the stent was immersed in a 10% sodium phosphate solution (50 ml) for 24 hours at a temperature below 50° C. The container with the sodium phosphate solution in turn was immersed in a heated water bath to ensure the temperature of 50° C. After 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The average values of dissolved magnesium over the time of three equal stents of sample A are shown.

(12) Sample B is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium fluoride layer (MgF.sub.2). For generation of this layer, the stent was immersed in a 40% hydrofluoric acid (50 ml) for 24 hours at a temperature below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The average values of dissolved magnesium over the time of three equal stents of sample B are shown.

(13) Sample C is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium carbonate layer (MgCO.sub.3). For generation of this layer, the stent was immersed in an alkaline 10% sodium carbonate solution (50 ml) for 26 hours at a temperature below 50° C. Sodium hydroxide was added to alkalize the solution. The container with the sodium carbonate solution in turn was immersed in a heated water bath to ensure the temperature of 50° C. After 26 hours, the stent was removed and rinsed with deionized water and then dried in air. The average values of dissolved magnesium over the time of three equal stents of sample B are shown.

(14) Sample D is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without further treatment. The average values of dissolved magnesium over the time of three equal stents of sample D are shown.

(15) FIG. 6 shows individual stents of samples A, B, C and D according to FIG. 5 and corresponding description.

(16) The first line shows a stent of sample B (magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent MgF.sub.2 surface transformation). The first image (from left) is taken at the start of the degradation test. The second image shows the stent after 10 hours and the third image shows the stent after 20 hours in the PBS traversed tube. The second line shows a stent of sample A (magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent Mg.sub.3(PO.sub.4).sub.2 surface transformation). The first image (from left) is taken at the start of the degradation test. The second image shows the stent after ten hours and the third image shows the stent after 20 hours in the PBS traversed tube. The third line shows a stent of sample C (magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent MgCO.sub.3 surface transformation). The first image (from left) is taken at the start of the degradation test. The second image shows the stent after four hours and the third picture shows the stent after ten hours in the PBS traversed tube. The fourth line shows a stent of sample D (magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without further treatment). The first image (from left) is taken at the start of the degradation test. The second image shows the stent after four hours and the third image shows the stent after ten hours in the PBS traversed tube.

(17) FIG. 7 shows a comparison of photometric measurements to the degradation rates of MgF.sub.2, MgCO.sub.3 and Mg.sub.3(PO.sub.4).sub.2 coated stents as well as after a heat treatment, the annealing or an oxygen plasma treatment. The dissolved masses of magnesium in PBS are applied over time. The average values of two measurements (n=2) are shown.

(18) Sample A is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium fluoride layer (MgF.sub.2). For generation of this layer, the stent was immersed in a 40% hydrofluoric acid (50 ml) for 24 hours at a temperature below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The stent was then annealed in air for 24.5 hours. The average values of dissolved magnesium over the time of two equal stents of sample A are shown.

(19) Sample B is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium oxide layer (MgO). For generation of this layer, the stent was placed in an oxygen plasma for 1.5 hours. The plasma is supposed to oxidize the surface of the stent to form a MgO layer. The stent was then annealed in air for 24.5 hours. The average values of dissolved magnesium over the time of two equal stents of sample B are shown.

(20) The sample C is a stent of the magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium carbonate layer (MgCO.sub.3). For generation of this layer, the stent was immersed for 24 hours at room temperature in an alkaline 10% sodium carbonate solution (50 ml). Sodium hydroxide was added to alkalize the solution. After the 24 hours the stent was removed and rinsed with deionized water and then dried in air. The stent was then annealed in air for 24.5 hours. The average values of dissolved magnesium over the time of two equal stents of sample C are shown.

(21) Sample D is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium phosphate layer (Mg.sub.3(PO.sub.4).sub.2). For generation of this layer, the stent was immersed for four days at room temperature in a 10% sodium phosphate solution (50 ml). After the four hours, the stent was removed and rinsed with deionized water and then dried in air. The stent was then annealed in air for 24.5 hours. The average values of dissolved magnesium over the time of two equal stents of sample D are shown.

(22) Sample E is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a plasma treatment for generation of a magnesium oxide layer (MgO) and subsequent surface transformation for generation of a MgF.sub.2 layer. For generation of this layer, the stent was placed in an oxygen plasma for 1.5 hours. The plasma is supposed to oxidize the surface of the stent to form a MgO layer. Subsequently the stent was immersed in a 40% hydrofluoric acid (50 ml) for 24 hours at a temperature of below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The average values of dissolved magnesium over the time of two equal stents of sample E are shown.

(23) Sample F is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without further treatment. The average values of dissolved magnesium over the time of three equal stents of sample F are shown.

(24) FIG. 8 shows the degradation rate in PBS for an annealed MgF.sub.2-coated stent and an annealed and plasma-treated stent.

(25) The dissolved masses of magnesium in PBS, which are photometrically determined, are applied over time.

(26) Samples A and B are each stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium fluoride layer (MgF.sub.2). MgF.sub.2 layer at 50° C. with hydrofluoric acid and then annealed.

(27) Samples C and D are each stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a plasma treatment for generation of a magnesium oxide layer (MgO) and then annealed.

(28) FIG. 9 shows the degradation rate in PBS for MgF.sub.2-coated stents that are heat-treated, annealed or plasma-treated. The dissolved masses of magnesium in PBS, which are photometrically determined, are applied over time.

(29) Sample A is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a plasma treatment for generation of a magnesium oxide layer (MgO) and subsequent surface transformation for generation of an MgF.sub.2 layer. For generation of this layer, the stent was placed in an oxygen plasma for 1.5 hours. The plasma is supposed to oxidize the surface of the stent to form a MgO layer. Subsequently the stent was immersed in a 40% hydrofluoric acid (50 ml) for 24 hours at a temperature of below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The average values of dissolved magnesium over the time of two equal stents of sample A are shown.

(30) Sample B is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a surface transformation for generation of a magnesium fluoride layer (MgF.sub.2). For generation of this layer, the stent was immersed in a 40% hydrofluoric acid (50 ml) for 24 hours at a temperature below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The stent was then annealed in air for 24.5 hours. The average values of dissolved magnesium over the time of two equal stents of sample B are shown.

(31) The sample C is a stent of the magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent surface transformation, wherein a layer of magnesium fluoride (MgF.sub.2) is formed. For generation of this layer, the stent was immersed in 40% hydrofluoric acid (50 ml) for 24 hours at a temperature of below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The average values of dissolved magnesium over the time of three equal stents of sample C are shown.

(32) FIG. 10 shows the degradation rate in PBS for MgF.sub.2-coated stents. The coating is produced under exposure of ammonium fluoride for 5 or 24 hours. On the other hand, 40% hydrofluoric acid for 5 and 24 hours is allowed to act on the stent to generate the coating. The dissolved masses of magnesium in PBS, which are photometrically determined, are applied over time. A=MgF.sub.2-coated stent by treatment with hydrofluoric acid for 24 h; B=MgF.sub.2-coated stent by treatment with ammonium fluoride for 24 h; C=MgF.sub.2-coated stent by treatment with hydrofluoric acid for 5 h; B=MgF.sub.2-coated stent by treatment with ammonium fluoride for 5 h.

(33) Sample A is stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent surface transformation, wherein a magnesium fluoride (MgF.sub.2) layer is formed. For generation of this layer, the stent was immersed in 40% hydrofluoric acid (50 ml) for 24 hours at a temperature of below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The measured values of dissolved magnesium over the time of a stent of sample A are shown.

(34) Sample B is a stent of the magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent surface transformation, wherein a layer of magnesium fluoride (MgF.sub.2) is formed. For generation of this layer, the stent was immersed in a 10% ammonium fluoride solution (50 ml) for 24 hours at a temperature below 50° C. The container with the solution in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The measured values of dissolved magnesium over the time of a stent of sample B are shown.

(35) The sample C is a stent of the magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent surface transformation, wherein a layer of magnesium fluoride (MgF.sub.2) is formed. For generation of this layer, the stent was immersed in 40% hydrofluoric acid (50 ml) for five hours at a temperature below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After five hours, the stent was removed and rinsed with deionized water and then dried in air. The measured values of dissolved magnesium over the time of a stent of sample C are shown.

(36) The sample D is a stent of the magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and subsequent surface transformation, wherein a layer of magnesium fluoride (MgF.sub.2) is formed. For generation of this layer, the stent was immersed a 10% ammonium fluoride solution (50 ml) for five hours at a temperature below 50° C. The container with the solution in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the five hours, the stent was removed and rinsed with deionized water and then dried in air. The measured values of dissolved magnesium over the time of a stent of sample D are shown.

(37) FIG. 11 shows the degradation rate of magnesium alloys treated by ion implantation (oxygen, fluorine and carbon).

(38) Sample A is a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an oxygen implantation.

(39) Sample B is stent of a magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a fluorine implantation.

(40) Sample C is a stent of the uncoated magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr).

(41) FIG. 12 shows the degradation rate of stents after additional heat treatment and subsequent fluoridation.

(42) Group A: Previously additionally heat-treated stents of magnesium alloy A were treated with 38-40% hydrofluoric acid.

(43) Group B: Previously heat-treated stents of magnesium alloy A were treated with 48% hydrofluoric acid.

(44) Group C: Untreated stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with the same design and same material lot as group A and B.

(45) FIG. 13 shows the degradation rate of stents having an intermediate layer of magnesium fluoride and a further coating of parylene C.

(46) Sample A: Stents of magnesium alloy A treated with hydrofluoric acid and then coated with parylene C polymer.

(47) Sample B: Stents coated with parylene C polymer but not fluoridated.

(48) FIG. 14 Degradation tests of stents having an intermediate layer of magnesium fluoride and a further coating of a resorbable polymer

(49) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly(L-lactide) (PLLA), which was applied to the stent by spraying method.

(50) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method.

(51) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly(L-lactide) (PLLA), which was applied to the stent by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(52) Group D: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(53) FIG. 15 shows the degradation rate of stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an intermediate layer of magnesium fluoride and a further coating of bioresorbable polymer (PCL) of different layer thickness and introduced antirestenotic active agent (rapamycin).

(54) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 4 μm layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method.

(55) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 7 μm layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method.

(56) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 4 μm layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(57) Group D: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 7 μm layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(58) FIG. 16 shows the degradation rate of stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with and without an intermediate layer of magnesium fluoride and a further coating of bioresorbable polymer (PLLA) and introduced antirestenotic active agent (rapamycin).

(59) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 7 μm layer of poly-L-lactide (PLLA) with introduced drug (rapamycin) applied by spraying method and an intermediate layer of magnesium fluoride.

(60) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 7 μm layer of poly-L-lactide (PLLA) with introduced drug (rapamycin) applied to the stent by spraying method.

(61) FIG. 17: shows the degradation rate of stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic intermediate layer and a further coating of PLLA (with different composition of the inorganic intermediate layer).

(62) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium hydroxide and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium hydroxide surface was applied to the stents in a wet chemical process. For this purpose the polished stents were immersed for 2 min in 30% H.sub.2O.sub.2 solution at room temperature. Subsequently they were then rinsed with H.sub.2O and immersed in ethanol and dried at 80° C. for one hour in a drying chamber.

(63) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium carbonate/magnesium hydroxide and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The surface transformation was realized by means of a wet chemical process. Thereby the polished stents were immersed in saturated NaHCO.sub.3 solution for 5 min and at 37° C. Subsequently the stents were then rinsed with H.sub.2O and immersed in ethanol. Afterwards the stents were dried at 100° C. for one hour in a drying chamber.

(64) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium phosphate/magnesium hydroxide and a 10 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The surface transformation was realized by means of a wet chemical process. Thereby the polished stents were immersed in saturated Na.sub.2HPO.sub.4 solution for one hour at 37° C. The stents were then rinsed with H.sub.2O and immersed in ethanol. This was followed by drying at 100° C. for one hour in a drying chamber.

(65) Group D: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(66) Group E: Stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(67) FIG. 18 shows the degradation rate of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) stents with and without an inorganic intermediate layer and a further coating of parylene N.

(68) Group A: Two stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) were treated as in example 13 group B to obtain a magnesium fluoride layer. The stents were then coated with the polymer parylene N (poly-p-xylylene). Parylene N can be deposited directly from the gas phase by condensation on the substrate, resulting in a very uniform coating. The layer thickness can be varied over the duration of the treatment.

(69) Group B: The two stents of group B were coated directly (thus without an intermediate layer of magnesium fluoride) with the polymer parylene N. The layer thickness of the polymer was the same as these were coated in the same coating cycle as the stents of group A.

(70) Group C: The two stents were treated as in group A, but no polymer was applied.

(71) Group D: The three stents had no coating (no magnesium fluoride layer and no polymer layer).

(72) FIG. 19: shows the degradation rate of stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with and without an inorganic intermediate layer and a further double coating of polyethyleneimine (PEI) and polyacrylic acid (PAA).

(73) Group A: A stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and a layer of PEI and PAA. The double layer of PEI and PAA was applied in a layer by layer process. The stent was immersed successively in an aqueous solution of 5 mg/ml PAA for two minutes, then in deionized water for one minute, then in an aqueous solution of 5 mg/ml PEI for two minutes and finally in deionized water for one minute. This sequence was repeated five times and the stent dried in air afterwards.

(74) Group B: A stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr), which was treated as in example 13 Group B to generate an intermediate layer of magnesium fluoride. This was followed by the same coating sequence as for Stent A (5×PEI and PAA).

(75) Group C: Similarly coated stent as stent A but with 10 coating rounds for generation of the PEI and PAA layer.

(76) Group D: Similarly coated stent as stent B but with 10 coating rounds for generation of the PEI and PAA layer.

(77) Group E: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without any further coating.

(78) FIG. 20 shows the degradation rate of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) stents with and without an inorganic intermediate layer and a further coating of poly-L-lactide (PLLA) compared to similarly coated stents of alloys L37 and AZ91 (Mg9Al1Zn).

(79) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method.

(80) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium fluoride layer was applied to the stents as in example 13 (group B).

(81) Group C: Stents of magnesium alloy L37 with a 5 μm layer of Poly-L-Lactide (PLLA), which was applied by spraying method.

(82) Group B: Stents of magnesium alloy L37 having an inorganic coating (surface transformation) of magnesium fluoride and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium fluoride layer was applied to the stents as in example 13 (group B).

(83) Group E: Stents of magnesium alloy AZ91 with a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method.

(84) Group F: Stents of magnesium alloy AZ91 having an inorganic coating (surface transformation) of magnesium fluoride and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium fluoride layer was applied to the stents as in example 13 (group B).

(85) FIG. 21 shows the degradation rate of stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with and without an inorganic intermediate layer of magnesium fluoride and a further coating of poly(lactide-co-glycolide).

(86) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly(lactid-co-glycolide) (PLGA), which was applied by dip coating. Thereby the stent was immersed in a solution of PLGA (85:15) and trichloromethane (5 mg/ml), pulled out of the solution at 20 mm/min and then dried in air at 40° C.

(87) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and an overlying layer of PLGA. The magnesium fluoride coating has been applied as in example 13 group B. The PLGA coating was applied as in group A.

(88) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without any coating.

(89) FIG. 22 shows the degradation rate of stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with and without an inorganic intermediate layer of magnesium fluoride and a further coating of polymethacrylamide (PMAA) in comparison to uncoated stents.

(90) Group A: Three stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of PMAA, which was applied by dip coating (A1, A2, A3).

(91) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and an overlying layer of PMAA (B1, B2, B3).

(92) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without any coating.

(93) FIG. 23 shows the degradation rate of stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with and without an inorganic intermediate layer of magnesium fluoride and a further coating of poly-L-lactide (PLLA) with introduced drug (rapamycin, 1.4 μg/mm.sup.2) in comparison to stents of alloy L37 and a coating of PLLA as well as introduced drug (sirolimus, 1.4 μg/mm.sup.2).

(94) Group A: Two stents (A1 and A2) of magnesium alloy L37 having a PLLA coating and an abluminal layer thickness of 6-12 μm.

(95) Group B: Two stents (B1 and B2) of magnesium alloy A having a coating of 7.5 μm PLLA. The PLLA coating was applied by spraying method.

(96) Group C: Two stents (C1 and 02) of magnesium alloy A having an inorganic coating (surface transformation) of magnesium fluoride and an overlying layer of 7.5 μm PLLA. The magnesium fluoride coating was applied as in example 13 group B. The PLLA coating was applied by spraying method.

EXAMPLES

Example 1: Production of the Alloys

(97) The alloys were produced in the so-called permanent molt direct chill casting (“Tütengußverfahren”). This method serves for the production of precursors for the later extrusion and is characterized in that the material can be produced with a homogeneous microstructure and a homogeneous distribution of alloying elements in the ingot. Therefore it is exceptionally suitable to produce smaller quantities of high quality pins for the reshaping.

(98) With this method, the magnesium alloys (L1, L2, . . . , L44) are melted in a smoothed steel crucible. As material of the crucible practically any nickel-free steel may be used. Graphite would be another possibility. All melting operations are carried out under inert gas. The temperatures of the molten bath are in the range of 660-740° C. Upon reaching the temperature of the molten bath, the alloying elements in form of pure elements or as master alloys were added. After addition of the alloying elements the melt was stirred mechanically. The stirring time depends on how long the elements or master alloys need to dissolve completely in the melt. After this preparation, the melt was transferred to a thin-walled coquille which was preheated to a temperature of 600° C. After a period of about 60 minutes, the coquille was immersed in a water bath having a temperature of 15-20° C. Due to the immersion the coquille completely solidified.

(99) Prior to extrusion the surface of the cast part was turned to the diameter of the recipient of the extrusion press. In addition, prior to extrusion the casting pin was heated to a temperature of 250-500° C. and kept for 3-6 hours at this temperature to dissolve intermetallic phases or to homogenize segregations. This was followed by extrusion and the billet produced in this manner was cooled in air to room temperature. Wires were obtained which were then transformed into tubes.

(100) The following alloys were prepared:

(101) TABLE-US-00075 Alloy L1: 87.8% by wt. magnesium 10.0% by wt. dysprosium  1.0% by wt. neodymium  1.0% by wt. zinc  0.2% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L2: 88.6% by wt. magnesium 10.0% by wt. dysprosium  1.0% by wt. neodymium  0.2% by wt. zirconium  0.2% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L3: 87.6% by wt. magnesium 10.0% by wt. dysprosium  1.0% by wt. neodymium  1.0% by wt. zinc  0.2% by wt. zirconium  0.2% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L4: 89.7% by wt. magnesium  6.0% by wt. dysprosium  2.0% by wt. neodymium  2.0% by wt. zinc  0.3% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L5: 90.7% by wt. magnesium  5.5% by wt. dysprosium  3.0% by wt. neodymium  0.5% by wt. zirconium  0.3% by wt. Impurities comprising Si, Ni. Fe, Cu and other metals and non-metals. Alloy L6: 87.4% by wt. magnesium  8.0% by wt. dysprosium  2.2% by wt. neodymium  1.8% by wt. zinc  0.3% by wt. zirconium  0.3% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L7: 82.7% by wt. magnesium 12.0% by wt. dysprosium  2.5% by wt. neodymium  2.5% by wt. zinc  0.3% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L8: 85.2% by wt. magnesium 11.5% by wt. dysprosium  2.6% by wt. neodymium  0.4% by wt. zirconium  0.3% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L9: 83.1% by wt. magnesium 15.2% by wt. dysprosium  1.2% by wt. neodymium  0.2% by wt. zirconium  0.3% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L10: 88.9% by wt. magnesium  8.0% by wt. dysprosium  1.4% by wt. neodymium  1.2% by wt. zinc  0.2% by wt. zirconium  0.3% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L11: 90.6% by wt. magnesium  8.0% by wt. dysprosium  1.0% by wt. neodymium  0.2% by wt. zinc  0.2% by wt. zirconium Alloy L12: 89.3% by wt. magnesium  8.0% by wt. dysprosium  1.0% by wt. neodymium  1.0% by wt. europium  0.5% by wt. zinc  0.2% by wt. zirconium Alloy L13: 86.0% by wt. magnesium 12.0% by wt. dysprosium  1.0% by wt. neodymium  0.8% by wt. zinc  0.2% by wt. zirconium Alloy L14: 90.1% by wt. magnesium  6.0% by wt. dysprosium  1.0% by wt. neodymium  1.0% by wt. europium  1.5% by wt. zinc  0.4% by wt. zirconium Alloy L15: 86.8% by wt. magnesium 10.0% by wt. dysprosium  1.0% by wt. neodymium  1.0% by wt. europium  1.0% by wt. zinc  0.2% by wt. zirconium Alloy L16: 82.8% by wt. magnesium 14.0% by wt. dysprosium  0.5% by wt. neodymium v0.5% by wt. europium  2.0% by wt. zinc  0.2% by wt. zirconium Alloy L17: 87.3% by wt. magnesium 10.0% by wt. dysprosium  1.5% by wt. neodymium  1.0% by wt. zinc  0.2% by wt. zirconium Alloy L18: 87.45% by wt. magnesium 10.0% by wt. dysprosium  1.5% by wt. neodymium  1.0% by wt. zinc  0.05% by wt. iron Alloy L19: 83.1% by wt. magnesium 15.0% by wt. dysprosium  0.9% by wt. neodymium  1.0% by wt. zirconium Alloy L20: 95.0% by wt. magnesium  4.5% by wt. dysprosium  0.5% by wt. neodymium Alloy L21: 83.7% by wt. magnesium 10.0% by wt. dysprosium  5.0% by wt. neodymium  1.0% by wt. zinc  0.3% by wt. zirconium Alloy L22: 87.25% by wt. magnesium 10.0% by wt. dysprosium  1.5% by wt. neodymium  1.0% by wt. zinc  0.05% by wt. iron  0.2% by wt. zirconium Alloy L23: 85.8% by wt. magnesium 12.0% by wt. dysprosium  1.0% by wt. neodymium  1.0% by wt. zinc  0.2% by wt. zirconium Alloy L24: 82.1% by wt. magnesium 15.0% by wt. dysprosium  0.9% by wt. neodymium  1.0% by wt. zinc  1.0% by wt. zirconium Alloy L25: 80.1% by wt. magnesium 19.0% by wt. yttrium  0.9% by wt europium Alloy L26: 92.5% by wt. magnesium  5.0% by wt. dysprosium  2.5% by wt. europium Alloy L27:  82.1% by wt. magnesium  15.5% by wt. dysprosium  1.2% by wt. neodymium  1.0% by wt. zinc  0.2% by wt. zirconium 0.001% by wt. Impurities comprising Si, Ni, Fe, Cu and other metals and non-metals. Alloy L28: 82.0% by wt. magnesium 10.0% by wt. gadolinium  5.0% by wt. neodymium  1.0% by wt. zinc  2.0% by wt. zirconium Alloy L29: 88.8% by wt. magnesium  6.0% by wt. dysprosium  4.0% by wt. europium  1.0% by wt. zinc  0.2% by wt. zirconium Alloy L30: 89.8% by wt. magnesium  8.0% by wt. dysprosium  1.0% by wt. europium  1.0% by wt. zinc  0.2% by wt. zirconium Alloy L31: 83.2% by wt. magnesium 15.0% by wt. dysprosium  0.4% by wt. neodymium  1.4% by wt. europium Alloy L32: 87.4% by wt. magnesium 10.0% by wt. dysprosium  1.0% by wt. europium  0.5 by wt. neodymium  1.0% by wt. zinc  0.1% by wt. zirconium Alloy L33: 87.0% by wt. magnesium 10.0% by wt. dysprosium  0.3% by wt. europium  1.5% by wt. neodymium  1.0% by wt. zinc  0.2% by wt. zirconium Alloy L34: 86.0% by wt. magnesium 12.0% by wt. dysprosium  1.0% by wt. europium  0.8% by wt. zinc  0.2% by wt. zirconium Alloy L35: 93.24% by wt. magnesium  0.35% by wt. dysprosium  2.05% by wt. neodymium  0.40% by wt. gadolinium  0.35% by wt. zirconium  3.60% by wt. yttrium  0.01% by wt. erbium Alloy L36: 92.2% by wt. magnesium  0.5% by wt. dysprosium  0.5% by wt. gadolinium  2.2% by wt. neodymium  0.5% by wt. zirconium  4.1% by wt. yttrium Alloy L37: 91.8% by wt. magnesium  0.7% by wt. dysprosium  0.7% by wt. gadolinium  2.0% by wt. neodymium  0.7% by wt. zirconium  4.1% by wt. yttrium Alloy L38: 95.1% by wt. magnesium  1.2% by wt. gadolinium  2.5% by wt. neodymium  0.6% by wt. zirconium  0.3% by wt. calcium  0.3% by wt. zinc Alloy L39: 96.9% by wt. magnesium  2.5% by wt. neodymium  0.4% by wt. zirconium  0.2% by wt. zinc Alloy L40: 97.45% by wt. magnesium  0.75% by wt. neodymium  1.80% by wt. manganese Alloy L41: 97.45% by wt. magnesium  0.75% by wt. cerium  1.80% by wt. manganese Alloy L42: 90.0% by wt. magnesium  3.0% by wt. gadolinium  2.4% by wt. yttrium  0.4% by wt. zirvonium  4.2% by wt. scandium Alloy L43: 90.0% by wt. magnesium  3.0% by wt. neodymium  2.4% by wt. yttrium  0.4% by wt. zirconium  5.2% by wt. scandium  2.0% by wt. indium Alloy L44: 96.0% by wt. magnesium  4.0% by wt. lithium

(102) The alloys L1 to L44 were produced with an inorganic magnesium fluoride coating on the one hand and with an inorganic magnesium fluoride coating and an organic parylene C coating on the other hand. All alloys L1 to L44 show a decelerated dissolution kinetics of the inorganic magnesium fluoride coated stents compared to the uncoated stents. Furthermore, stents having an inorganic magnesium fluoride coating and an organic parylene C coating show once again decelerated dissolution kinetics compared to stents having an inorganic magnesium fluoride coating and without an organic parylene C coating. In addition, the dissolution kinetics is significantly decelerated compared to a stent having an organic parylene C coating only. The presence of an antirestenotic active agent in or on the organic parylene C coating does not appear to have a noticeable effect on the resorption kinetics. The following examples exemplarily describe the production and investigation of such stents.

Example 2: Tube Production

(103) From the alloys L1 to L10 according to example 1 extruded wires were prepared. In these extruded wires, a precision drill-hole is introduced in longitudinal direction, which already co-determines the wall thickness of the later stents. By several forming steps, a tube of predetermined diameter and certain wall thickness is made. Between the individual forming steps repeating heat treatment takes place.

Example 3: Stent Production

(104) A tube produced according to Example 2 is fixed into an adapter in the laser machine. A pulsed solid-state laser (FKL) cuts the contours of the stent design out of the tube. The laser cutting is performed under an inert gas atmosphere.

(105) The stent design is stored in a NC program (numerical control). This predefines the traverse path (cutting pattern) to the laser, after which the tube is structured. By the laser beam cutting burr formation occurs, especially on the inside of the tube, along the entire cutting contour. This can cause that off-cuts and cut-outs remain adhered to the contour after the termination of the cutting process. The off-cuts and cut-outs are mechanically removed and the stent is cleaned from manufacturing residues. In a first optical visual control an inspection of the cutting contour is performed.

(106) In the following, the stent is electrochemically polished. The stent is anodically connected and immersed in an acid bath. Via a cathode fixed in the bath, an electric circuit is closed. The electric circuit is maintained for several minutes. The electropolishing is an inverted galvanic process where material is removed in a controlled manner from the surface of the anodically connected component. Due to the method ablation preferably takes place at sharp corners and edges. The stent obtains a smooth surface and rounded edges along the contours. After polishing, the stent is cleaned and freed from acid residues. During the final cleaning all still remaining manufacturing residues are removed from the stent surface. In a last optical visual control the stent geometry is measured and the surface is tested on purity

Example 4: Determination of Grain Size

(107) The counting of the grain size was made using linear intercept method. Grains which are only half cut at the end of the line were hereby counted as half grains. The magnification was selected such that at least 50 grains were cut by the grid. At least 5 sites with a total of at least 250 points of intersection were evaluated on the sample.

Example 5: Determination of the Corrosion Rate

(108) At room temperature, the corrosion rates of various alloys were determined for a period of 3 days in a physiological saline solution (see Table 1). An alloy was tested containing 90.8% by wt. Mg, 8% by wt. Dy, 1% by wt. Nd and 0.2% by wt. Zr, an alloy containing 89.8% by wt. Mg, 8% by wt. Dy, 1% by wt. Nd, 1% by wt. Eu and 0.2% by wt. Zr, an alloy containing 86.8% by wt. Mg, 12% by wt. Dy, 1% by wt. Nd, and 0.2% by wt. Zr, and an alloy containing 87.8% by wt. Mg, 10% by wt. Dy, 1% by wt. Nd, 1% by wt. Eu and 0.2% by wt. Zr. In addition alloys containing 1.0% by wt. neodymium, 1.0% by wt. zinc, 0.2% by wt. zirconium, between 5 and 20% dysprosium and the balance magnesium (see FIG. 7) were tested. Corrosion products were removed by immersion of the samples in chromic acid (180 WO for 20 min at room temperature. The average corrosion rate was calculated in millimeter per year by the following equation:

(109) $\mathrm{CR}=\frac{8.76\times {10}^4\times \Delta g}{A.Math.t.Math.\rho }$

(110) TABLE-US-00076 TABLE 1 Corrosion rate of alloys according to the invention, measured over 3 days at room temperature, and in 0.9% NaCl; the specification of the components of the alloys are in % by weight and Mg as major component adds always up to 100% of the alloy. The alloys were tested after casting, without heat treatment, the average values and standard deviations of the various alloys are listed. Corrosion rate No. Composition (mm/year) L11 Mg8Dy1Nd0.2Zn0.2Zr 9.25 ± 0.38 L15 Mg10Dy1Nd1Eu1Zn0.2Zr 0.81 ± 0.06 L23 Mg12Dy1Nc1Zn0.2Zr 2.94 ± 1.88 L16 Mg8Dy1Nd1Eu1Zn0.1Zr  4.9 ± 1.62 L14 Mg6Dy1Nd1Eu1.5Zn0.4Zr 9.56 ± 0.29 L16 Mg14Dy0.5Nd0.5Eu2Zn0.2Zr 1.25 ± 0.12 L18 Mg10Dy1.5Nd1Zn0.05Fe 12.41 ± 2.16  L20 Mg4.5Dy0.5Nd 25.56 ± 2.34  L24 Mg15Dy0.9Nd1Zr1Zn 2.98 ± 1.78 L25 Mg20Y0.9Eu 44.71 ± 3.22  L28 My20Gd5Nd1Zn2Zr 38.96 ± 1.34  L30 Mg8Dy1Eu1Zn0.2Zr 3.88 ± 1.87 L22 Mg10Dy1.5Nd1Zn0.2Zr0.05Fe 4.47 ± 2.11 L34 Mg12Dy1Eu0.8Zn0.2Zr 5.46 ± 1.22 L29 Mg6Dy4Eu1Zn0.2Zr 12.20 ± 11.36 L33 Mg10Dy0.3Eu1.5Nd1Zn0.2Zr 1.25 ± 0.67 L26 Mg5Dy2.5Eu 23.56 ± 1.56  L31 Mg25Dy0.4Nd1.4Eu 48.71 ± 1.87 

Example 6: Mechanical Characteristics of the Alloys

(111) The alloys and cast parts were produced according to Example 1 and extruded. The heat treatment T4 was carried out at 510° C. over 8 hours and eventually afterwards the heat treatment T6 at 200° C. over a period of time of 72 hours. After the T4 heat treatment the samples were immediately quenched in water. All samples were taken from the same position of the blocks.

(112) The tensile tests were performed at room temperature according to DIN EN 10002-1 (corresponds to ISO 6892 and ASTM E8) and pressure tests were performed at room temperature according to DIN 50106 (corresponds to ISO 604 and ASTM D695). At least 3 samples were tested for each value. The tensile strength was calculated in terms of the maximum tensile force achieved in the tensile test in regard to the initial cross-section of the sample.

(113) TABLE-US-00077 TABLE 2 Mechanical characteristic values of inventive alloys. Alloys were tested as a sample after the extrusion (ST, without heat treatment) and after different heat treatments, T4 (solution annealed), and T6 (a further heat treatment after T4, also known as “aging”). The information on the components of the alloys are given in % by wt. and Mg as the main component always fills the quantity up to 100% of the alloy. SD means standard deviation of the average values, which are indicated in the left column (n = 3). Yield Tensile elongation strength strength at break Composition (MPa) SD (MPa) SD (%) SD ST Mg8Dy1Nd0.2Zn0.2Zr 107.33 1.8 208.5 0.85 28.12 3.41 T4 87.54 0.46 176.84 2.03 18.83 1.79 T6 97.95 1.67 194.11 1.1 19.33 0.68 ST Mg10Dy1Nd1Eu1Zn0.2Zr 169.30 0.74 283.89 0.68 16.96 1 T4 151.97 1.77 259.50 2.57 18.02 0.29 T6 159.23 2.23 275.55 1.78 18.15 2.77 ST Mg12Dy1Nd1 Zn0.2Zr 126.07 11.8 226.04 0.35 28.55 0.08 T4 98.38 0.43 188.45 0.5 20.47 0.91 T6 114.6 1.69 205.2 1.25 17.99 0.79 ST Mg8Dy1Nd1Eu1Zn0.1Zr 132.24 1.1 227.21 0.59 19.75 1.11 T4 114.93 1.25 210.73 1.51 20.89 1.01 T6 136.77 1.77 223.28 0.67 23.64 2.01 ST Mg6Dy1Nd1Eu1.5Zn0.4Zr 128.14 8.02 202.74 2.91 24.62 2.09 T4 80.97 2.27 173.47 2.02 23.78 3.52 T6 84.26 2.57 178.26 1.35 26.32 2.5 ST Mg14Dy0.5Nd0.5Eu2Zn0.2Zr 165.64 4.95 218.17 3.07 18.9 1.14 T4 110.78 1.87 201.28 1.19 21.62 1.07 T6 153.15 3.55 264.09 0.71 17.66 1.33 ST Mg10Dy1.5Nd1Zn0.05Fe 145.46 3.55 237.21 0.75 28.9 1.73 T4 102.78 4.38 193.36 5.84 27.57 0.88 T6 108.84 1.68 200.16 2.97 25.56 1.66 ST Mg4.5Dy0.5Nd 68.39 7.9 208.48 2.03 28.4 0.72 T4 60.31 1.71 179.04 0.83 23.17 0.38 T6 75.13 1.32 250.34 1.42 13.34 0.74 ST Mg15Dy0.9Nd1Zr1Zn 136.93 1.6 227.07 0.42 22.9 3.03 T4 95.79 1.94 200.59 2.59 21.57 0.34 T6 112.09 0.41 206.11 0.19 19.56 0.66 ST Mg20Y0.9Eu 159.75 11.99 238.55 0.76 11.57 0.58 T4 123.19 4.83 214 1.42 19.62 2.74 T6 144.08 4.37 220.2 2.58 15.58 0.94 ST Mg20Gd5Nd1Zn2Zr 297.75 8.12 338.53 5.67 1.53 0.27 T4 195.82 15.65 276.89 0.91 6.58 0.95 T6 327.07 17.57 378.45 14.94 0.76 0.32 ST Mg8Dy1Eu1Zn0.2Zr 112.85 1.15 198.9 0.43 24.07 1.05 T4 93.5 1.01 182.38 0.91 24.02 0.81 T6 99 0.99 185.7 0.4 25.9 1.16 ST Mg10Dy1.5Nd1Zn0.2Zr0.05Fe 127.8 4.62 215.84 1 19.39 1.4 T4 96.72 4.02 192.99 2.87 25.92 0.98 T6 112.34 3.1 201.35 2.18 24.44 1.91 ST Mg12Dy1Eu0.8Zn0.2Zr 182.30 1.52 293.62 1.37 22.39 2.06 T4 164.48 1.44 268.66 0.45 23.70 1.63 T6 172.34 2.12 271.35 1.82 23.34 1.79 ST Mg6Dy4Eu1Zn0.2Zr 115.09 1.39 208.3 1.68 2.30 0.51 T4 97.55 0.74 189.39 0.84 4.78 1.71 T6 112.58 1.59 196.71 2.31 3.41 0.69 ST Mg10Dy0.3Eu1.5Nd1Zn0.2Zr 168.54 6.15 277.11 2.09 16.46 2.33 T4 136.36 5.11 244.89 2.37 20.67 3.15 T6 152.22 2.42 253.91 2.33 18.56 1.87 ST Mg5Dy2.5Eu 74.25 1.63 283.50 1.44 21.60 1.27 T4 60.19 1.69 264.46 0.91 23.16 1.43 T6 65.38 1.83 266.64 1.36 22.85 1.64 ST Mg25Dy0.4Nd1.4Eu 106.34 2.98 211.15 1.65 18.90 1.55 T4 88.74 1.69 178.56 2.03 20.03 2.31 T6 94.21 1.34 191.25 1.67 19.54 1.99

Example 7: Animal Study

(114) 8 stents produced according to Example 2 and 3 were implanted in the coronary arteries of 4 domestic pigs. The stents had a diameter of 3.0 mm and a length of 14 mm (length of the catheter balloon 15 mm), were uncoated and were made of an alloy of the following composition:

(115) TABLE-US-00078 87.8 Gew.-% magnesium 10.0 Gew.-% dysprosium  1.0 Gew.-% neodymium  1.0 Gew.-% zinc  0.2 Gew.-% zirconium

(116) The “follow up” period for all 4 animals was 4 weeks after implantation. One day prior to stent implantation a single dose of clopidogrel (300 mg) and aspirin (250 mg) were administered orally to the pigs. Under general anaesthesia, an access to the femoral artery was surgically placed and a bolus of heparin sodium (10 000 IU) was administered. A 6F coronary guiding catheter was inserted through the femoral artery into the aorta descendens. Coronary angiography was performed by using hand injection of a non-ionic contrast agent to obtain the anatomic conditions for the performance of the procedure.

(117) The stents were implanted in the ramus interventricularis anterior (RIVA or LAD) and ramus circumflexus (RCX or LCx). Dilatation pressure of the balloon for stent implantation was chosen to achieve a stent balloon to artery ratio of 1.2 to 1. The pigs were then allowed to recover. During the entire 4 weeks “follow up”, the animals daily received orally a dose of 100 mg aspirin and 75 mg clopidogrel per 30 g body weight.

(118) After 4 weeks “follow up”, control angiography and optical coherence tomography (OCT) were performed.

(119) In the OCT procedure a 0.014 inch guidewire is inserted into the LAD and the LCx and guided through the implanted stents into the distal part of the vessel. An OCT catheter was subsequently advanced distal to the stent over the guide wire. The injection pump was turned on to inject contrast agent at a speed of 3.0 ml/s and thus to temporarily displace the blood. The entire length of the lesion was imaged by using an automatic pullback device at 10 mm/s. After imaging, the OCT catheter was withdrawn, and the images were saved. The animals were then euthanized, and the coronary arteries were explanted.

(120) The explanted arteries were fixed by perfusion with a pressure of 100 mmHg for 1 h using 7% formalin. The stents were processed for light microscopy. For light microscopy, the arteries were cut into 3 sections: proximal, mid and distal stent segments. These segments were embedded in methyl metacrylate (Technovit 9100). The segments of the stented arteries were cut into 4-6 μm slices using a rotary microtome, and stained with hematoxylin and eosin.

(121) As part of the analysis details of the study were listed such as the stent position, the dilatation pressure and the dilatation time, as well as any complications during the implantation.

(122) Quantitative Coronary Angioplasty (QCA)

(123) A QCA was performed to analyze the in-stent restenosis. Thereby, the following parameters were determined: vessel diameter pre and post stent implantation, minimal lumen diameter (MLD) after stent implantation and at follow up and the diameter of a reference segment (RD) at follow up. Here, the minimal lumen diameter is the smallest absolute internal vessel diameter in the region of the dilated segment, averaged from the two orthogonal projection planes. LLL (late lumen loss) is a measure of the narrowing of the lumen by neointimal hyperplasia. The lumen diameter is measured directly after the intervention and 4 weeks post interventional, the difference between the two is given as LLL. The length of the stenosed or dilated segment was monitored and the stenosis in percent was calculated.

(124) Optical Coherence Tomography (OCT)

(125) The images of the optical coherence tomography were analyzed in accordance with the relevant guideline (JACC, 2012). The following parameters were gathered: stent malapposition, stent strut coverage, tissue protrusion, the arterial dissection, thrombosis. The quantitative analysis of the OCT images comprises the minimal and maximal stent diameter and the lumen area. The following parameters were calculated: maximal area stenosis and stent symmetry. For the quantitative analysis the “worst” cross-section per test group was determined.

(126) Calculation of Area Stenosis (% AS):
% AS=intimal area/stent area=(stent area−lumen area)/stent area
Calculation of Stent Symmetry:
Stent symmetry=(maximal stent diameter−minimal stent diameter)/maximal stent diameter

(127) Fibrin deposition, degree of inflammation (intima and adventitia), haemorrhages and necrosis were analyzed in accordance with the published guidelines.

(128) Histomorphometry

(129) Histomorphometry was carried out by using computer-assisted planimetry. The lumen, the area of the internal elastic lamina and external elastic lamina and the maximum neointimal thickness were measured. The extension of the neointima and the tunica media as well as the percentage of stenosis was calculated.

(130) Results

(131) The dilatation pressure used was between 12 and 18 atm. The balloon inflation took 30 sec. In general, the handling of the stents and balloons were excellent; very good pushability and very short deflation time was recorded.

(132) TABLE-US-00079 TABLE 3 Results of the quantitative coronary angioplasty (QCA), the average values and standard deviations (SD); MLD = minimal lumen diameter, RD = diameter of a reference segment, % DS = percentage of diameter of stenosis, FUP = follow-up, LLL = late lumen loss Pre- Post- FUP- FUP- FUP- MLD MLD MLD RD % DS LLL (mm) (mm) mm (mm) (%) mm Uncoated Stents (BMS) 2.68 2.93 2.08 2.92 28.75 0.85 SD 0.11 0.07 0.53 0.20 16.79 0.47

(133) TABLE-US-00080 TABLE 4 Qualitative analysis of the optical coherence tomography (OCT) per implanted stent animal stent- tissue in-stent in-stent edge endothelial- No. artery group malapposition protrusion thrombosis dissection dissection ization MEKO-1 LAD BMS 0 0 0 0 0 complete MEKO-1 LCx BMS 0 0 0 0 0 incomplete MEKO-2 LAD BMS 0 0 0 0 0 complete MEKO-2 LCx BMS 0 0 0 0 0 complete MEKO-3 LAD BMS 0 0 0 0 0 complete MEKO-3 LCx BMS 0 0 0 0 0 complete MEKO-4 LAD BMS 0 0 0 0 0 complete MEKO-4 LCx BMS 0 0 0 0 0 complete

(134) TABLE-US-00081 TABLE 5 Qualitative analysis of the optical coherence tomography (OCT) in relation to the number of implanted stents (n = 8; all values in percent) stent- tissue in-stent in-stent edge endothelial- malapposition protrusion thrombosis dissection dissection ization BMS n = 8 0 0 0 0 0 87.5

(135) From Tables 3, 4 and 5 can be obtained that on the one hand none of the tested complications occurred when using a stent according to the invention and, on the other hand, that an endothelialization was almost always completed after 4 weeks, which meant that the increased risk of in-stent thrombosis due to not completed endothelialization or inflammation reactions was no longer present. Comparable results were also obtained with stents of a magnesium alloy containing europium instead of neodymium.

(136) TABLE-US-00082 TABLE 6 Further results of the qualitative analysis of the optical coherence tomography (OCT), listed are the average values and standard deviations (SD). min. stent max. stent stent lumen diameter diameter r area area % AS stent Type (mm) (mm) (mm.sup.2) (mm.sup.2) (%) symmetry BMS n = 8 2.54 2.72 7.58 5.08 34.0 0.07 SD 0.34 0.35 1.80 1.69 13.2 0.02

Example 8: Coating of Stents According to the Invention by Surface Transformations

(137) Magnesium Fluoride Layer (MgF.sub.2)

(138) For generation of this layer, the stent was immersed in 40% hydrofluoric acid (50 ml) for 24 hours at a temperature below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air.

(139) Magnesium Fluoride Layer (MgF2) and Annealing

(140) For generation of this layer, the stent was immersed in 40% hydrofluoric acid (50 ml) for 24 hours at a temperature below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The stent was then annealed in air for 24.5 hours.

(141) Magnesium Fluoride Layer (MgF.sub.2)

(142) For generation of this layer, the stent was placed in an oxygen plasma for 1.5 hours. The plasma is supposed to oxidize the surface of the stent to form a MgO layer. The stent was then immersed in a 40% hydrofluoric acid (50 ml) for 24 hours at a temperature below 50° C. The container with the hydrofluoric acid in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air.

(143) Magnesium Fluoride Layer (MgF.sub.2) with an Ammonium Fluoride Solution

(144) For generation of this layer, the stent was immersed in a 10% ammonium fluoride solution (50 ml) for 24 hours below 50° C. The container with the solution in turn was immersed in a heated water bath to ensure the temperature of 50° C. After the 24 hours, the stent was removed and rinsed with deionized water and then dried in air. The measured values of dissolved magnesium over the time of a stent of sample B are shown.

Example 9: Degradation Test of Stents Subjected to Oxygen Ion Implantation

(145) The coated stents of example 8 were examined in a degradation test.

(146) The degradation tests were carried out with a degradation test machine (DTM) from MeKo Laserstrahl-Materialbearbeitungen e.K. The DTM is equipped with a peristaltic pump, a temperature sensor, heating system, flow sensor and a camera system.

(147) The coronary stent used for the tests was manufactured by MeKo Laserstrahl-Materialbearbeitungen e.K. The stent material is magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr).

(148) The stent of the magnesium alloy A was subjected to an oxygen ion implantation. Oxygen ions are shot into the surface, where they should modify the surface or form a magnesium oxide layer. The mass of the stent after ion implantation was 5.97 mg (measured with the Sartorius CPA225D precision scale (Serial Number: 31906122)).

(149) The filling quantity of the test fluid PBS (phosphate buffered saline) was 300 ml. The temperature of the fluid is maintained at 37±2° C. The flow rate [ml/min], the temperature of the fluid [° C.] and the digital images [1 image/min] are continuously recorded and stored by the system. The test fluid PBS consists of: 8.0 [g/l] NaCl, 0.2 [g/l] KCl, 1.15 [g/l] Na.sub.2HPO.sub.4 and 0.2 [g/l] KH.sub.2PO.sub.4.

(150) The pH values were measured at different times by using the Mettler Toledo SevenGo SG2, Serial No. B426752831 measuring instrument and the Mettler Toledo InLab 413 SG/2m IP67, No. 51340288 measuring probe.

(151) The pH values were periodically adjusted to 7.40 by adding HCl or NaOH. Thus, these could be kept within the limits of 7.2 to 7.6.

(152) Photometry Measurement

(153) The photometry measurement for the concentration measurement of the magnesium concentrations over the test period was carried out with a spectrophotometer.

(154) The measurement results are shown graphically in FIG. 3. Compared to the average of three uncoated stents of magnesium alloy A (BMS) the degradation was also shown to be decelerated. Initially (within the first two hours), about the same amount of magnesium dissolved in the O.sub.2 ion implanted as well as in the BMS, after that less magnesium dissolved in the ion implanted. Furthermore, in comparison to the hydrofluoric acid treated stent a faster dissolution is shown for the ion-implanted stents.

(155) The comparison of the camera images in FIG. 4 shows that the oxygen implantation (sample B, first line) makes the stent significantly more durable in the corrosive environment (PBS) than the untreated stent (sample A, second line). Also, the stent having MgF.sub.2 surface (sample C, third line) degraded significantly slower than the untreated stent.

(156) Camera Shots

(157) The images in FIG. 4 confirm the photometric measurements. However, it cannot be derived from the pure measured values that the O.sub.2 ion-implanted stent withstands so much longer before the first strut breaks (bare metal stent: after 2 hours; MgF.sub.2 coated stent: 12 hours; O.sub.2 ion-implanted stent: 25 hours) and until the stent is completely degraded in front of the camera.

(158) One explanation could be that up to the protective oxide layer (magnesium oxide), which is generated by the implanted oxygen ions, the magnesium dissolves as quickly as in case of an untreated stent. Then, at the point the magnesium oxide layer has been reached, the magnesium dissolves much more slowly. Furthermore, the magnesium seems to dissolve much more homogeneously, i.e. over the entire stent surface. The magnesium oxide layer of a bare metal stent is probably much thinner. It constitutes only a kind of barrier for the first two hours. Subsequently, more and more struts break at arbitrary points.

(159) The fluoride layer inhibits the degradation the strongest in the first time (up to approx. 25 hours). However, earlier strut fractures still occur. The magnesium fluoride layer is very brittle and can partially break when dilating the stent. At these sites the stent degrades faster.

(160) Conclusion

(161) In case of oxygen ion-implanted stents, magnesium goes into solution from the very beginning. However, this seems to be more homogeneous as the first strut fractures occur much later (after about 25 hours) than in case of comparable stents. For comparison: First strut fractures in bare metal stents occur after about 2 hours, in hydrofluoric acid treated stents after about 11-18 hours.

Example 10: Degradation Tests of Stents after Different Surface Treatments

(162) 3 stents of magnesium alloy A (Mg10Dy1 Nd1Zn0.2Zr) were treated in three solutions (38-40% HF solution, 10% Na.sub.2CO.sub.3 solution and 10% Na.sub.3PO.sub.4 solution).

(163) Treatment in 38-40% hydrofluoric acid was performed as follows:

(164) The 3 stents were each placed in a plastic container. The plastic containers with lids (made of PP) were each filled with 50 ml 38-40% hydrofluoric acid and then placed in a tempered water bath at a temperature of 50° C. The water was heated to 50° C. in a glass reservoir by a heating plate and kept at 50° C. during the treatment process. An agitator in the reservoir made it possible to easily move the plastic containers in the water bath. After 24 hours, the plastic containers were removed from the water bath.

(165) The stents in turn were removed from the hydrofluoric acid, rinsed with deionized water, dried with compressed air and packed in a glass tube.

(166) The treatment in 10% sodium carbonate (Na.sub.2CO.sub.3) solution was carried out as follows:

(167) First, sodium carbonate (Na.sub.2CO.sub.3) was dissolved in deionized water to give a 10% solution. The pH was adjusted by adding sodium hydroxide (NaOH). The stents were then each placed in a plastic container with a lid (made of PP) and each filled with 50 ml of 10% Na.sub.2CO.sub.3 solution. The containers were also placed in a tempered water bath at a temperature of 50° C. and kept there for 26 hours. The further procedure is identical to the hydrofluoric acid treatment (see above).

(168) The treatment in 10% sodium phosphate (Na.sub.3PO.sub.4) solution was carried out as follows:

(169) First, sodium phosphate (Na.sub.3PO.sub.4) was dissolved in deionized water to give a 10% solution. The stents were then each placed in a plastic container with a lid (made of PP) and each filled with 50 ml of 10% Na.sub.3PO.sub.4 solution. The containers were also placed in a tempered water bath at 50° C. and kept there for 24 hours. The further procedure is identical to the hydrofluoric acid treatment (see above).

(170) The degradation measurements were carried out as in example 9.

(171) Photometric Measurement

(172) The results of the photometric measurement are shown graphically in FIG. 5. The differences in the degradation rate in case of MgCO.sub.3 or Mg.sub.3(PO.sub.4).sub.2 samples are rather small. A clear delay of the degradation could only be achieved by hydrofluoric acid treatment at 50° C. for 24 hours (MgF.sub.2 samples).

(173) It is also noticeable that the values of the dissolved masses of magnesium among each other in case of hydrofluoric acid treatment do not have a large scatter.

(174) The samples treated in sodium phosphate show the strongest differences of the degradation rates among each other, which could already be assumed by examination of the microscope images before the beginning of degradation.

(175) Camera Shots

(176) FIG. 6 illustrates the degradation very well. Each line contains three camera shots of the same sample.

(177) In principle, the observations from the photometric measurements are confirmed. The stent with hydrofluoric acid treatment (first line) dissolves much more slowly than the other stents. In this stent, the first strut fracture occurs after 11 to 19 hours. A sample of the Mg.sub.3(PO.sub.4).sub.2 group dissolved completely in front of the camera after 6 hours, which confirms the photometric measurement of this sample.

(178) Conclusion

(179) A significant improvement of the degradation rate could only be achieved with hydrofluoric acid treatment. The time until the first strut break could be increased at least fivefold (from 2 h to 11-19 h). The course of degradation of MgF.sub.2 surface-treated stents is also better for maintaining the radial strength of the stent. Initially, the stents degrade slowly (compared to bare metal stents and MgCO.sub.3 and MgPO.sub.4 modifications).

(180) The comparison of the images shows that due to the magnesium fluoride surface transformation (sample B, first line) the stent is significantly more durable in the corrosive environment (PBS) than the untreated stent (sample D, fourth line). The magnesium phosphate and magnesium carbonate layer does not seem to significantly slow down degradation, which is consistent with the photometric measurements of dissolved masses of magnesium over time (FIG. 5).

Example 11: Degradation Experiments of MgF.SUB.2 .Coating, Produced with Ammonium Fluoride and Hydrofluoric Acid, Each with a Different Exposure Time

(181) The stents were treated in different ways (specifications are based on FIG. 10).

(182) Sample A and C: Two stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) were each placed in a plastic container. The plastic containers with lids (made of PP) were each filled with 50 ml 38-40% hydrofluoric acid and then placed in a tempered water bath at a temperature of 50° C. The water was heated to 50° C. in a glass reservoir by a heating plate and kept at 50° C. during the treatment process. An agitator in the reservoir allows to easily move the plastic containers in the water bath. After 5 hours (sample C) or after 24 hours (sample A), the plastic containers were removed from the water bath. The stents in turn were removed from the hydrofluoric acid, rinsed with deionized water, dried with compressed air, and packed in a glass tube.

(183) Sample B and D: Ammonium fluoride (NH.sub.4F) was first dissolved in deionized water to give a 10% solution. Then, the two stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) were each placed in a plastic container with lid (made of PP) and each filled with 50 ml of 10% NH.sub.4F solution. The containers were also placed in a tempered water bath at 50° C. and kept there for 5 hours (sample D) or 24 hours (sample B). The further procedure is identical to the hydrofluoric acid treatment (see samples A and C).

(184) Stents of magnesium alloy A were treated in two different solutions (40% hydrofluoric acid and 10% ammonium fluoride) at 50° C. for 5 and 24 hours respectively. The stents were stored in a closed plastic container and swivelled by means of a stirring plate.

(185) Subsequently, the composition of the surface coating was determined with the scanning electron microscope (SEM) “Tescan Vega 3” with integrated EDX from Thermo Fischer. The surface layer was examined under an electron acceleration voltage of 15 kV.

(186) Stents having the following surface coatings were obtained:

(187) 5 h with ammonium fluoride: 48.8% F, 32.4% Mg, 11.0% 0, 7.7% C

(188) 24 h with ammonium fluoride: 50.3% F, 24.5% Mg, 19.7% 0, 0.5% Dy, 5.1% C

(189) 5 h with hydrofluoric acid: 54.7% F, 24.6% Mg, 10.2% 0, 10.6% C

(190) 24 h with hydrofluoric acid: 57.8% F, 24.0% Mg, 9.5% 0, 8.8% C

(191) The degradation measurements were carried out as in example 9.

(192) The results are shown in FIG. 10. The stent which was treated for 24 hours in hydrofluoric acid shows the slowest degradation in this comparison. In the first 10 hours only half amount of magnesium is dissolved as in the stent which was only treated for 5 hours. Stents treated with ammonium fluoride do not differ significantly from each other. In comparison to the 24-hour hydrofluoric acid treatment, the other treatments are less effective in decelerating the degradation.

Example 12: Degradation Tests with Ion-Implanted Stents

(193) During ion implantation, ions (oxygen, fluorine and carbon) were introduced into stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr). The corresponding ions, which are generated by an ion source, are strongly accelerated by an electric field and shot into the substrate (in this case the stent) with high energy. In this way, a protective layer is supposed to be created to protect the stent from degradation.

(194) For the degradation experiments, stents were bombarded with carbon, oxygen and fluorine ions. For the degradation comparison, the stents were divided into three groups. For the test, the same design and substrate material (magnesium alloy A) was always used for the stents. All stents were laser cut, heat treated and electropolished. The group specifications refer to FIG. 11: Sample A: 3 stents having an oxygen implantation (2×10.sup.17 O-ions per cm.sup.2) Sample B: 2 stents having a fluorine implantation (6×10.sup.16 F ions per cm.sup.2) Sample C: 3 stents without any coating (reference)
Photometric Measurement

(195) The degradation measurements were carried out as in example 9 and are shown in FIG. 11. The mean values (for group A: mean value of 3 measured values, for group B: mean value of 2 measured values) are shown at the corresponding times. Group C was used as a reference as in the previous examples.

(196) Group A and group B show a delay of the degradation rates compared to the uncoated stents (group C).

(197) Conclusion

(198) Bombarding magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) stents with fluorine and oxygen ions (ion implantation) can significantly reduce degradation rates compared to uncoated stents.

Example 13: Degradation Tests of Stents after Additional Heat Treatment and Subsequent Fluoridation

(199) In contrast to example 10, in this method stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) were first annealed and then treated with hydrofluoric acid. The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished.

(200) Five stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) were first annealed (in addition to the first annealing) in air for four hours at 400° C. in a tube furnace. The stents were then divided into two groups and treated differently.

(201) Group A: Two of the previously additionally heat-treated stents were each placed in a plastic container. The plastic containers with lids (made of PP) were each filled with 50 ml 38-40% hydrofluoric acid and closed. The plastic containers were fixed in a shaking incubator and shaken at 50° C. and for 24 hours at 120 rpm. After treatment, the stents were removed from the hydrofluoric acid, rinsed with deionized water and swivelled into ethanol. The stents were then dried in a drying chamber at 80° C. for 30 minutes.

(202) Group B: Three of the previously additionally heat-treated stents were treated identically to the group A stents, but a 48% hydrofluoric acid was used for fluoridation.

(203) Group C: Untreated stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with the same design and material lot as group A and B.

(204) Photometric Measurement

(205) The degradation measurements were carried out as in example 9 and are shown in FIG. 12. For sample specification A, the mean values were measured for the two stents treated as described above. Sample B is a reference for mean values from the measurements of three uncoated stents of the same design and magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr).

(206) The mass of magnesium ions dissolved over time (FIG. 12) shows that the fluoridated stents of group A and B have a significantly lower rate of degradation than the uncoated stents of Group C. Particularly within the first 5 hours is shown that the stents of group A and B released only about one third of the mass of magnesium ions than the uncoated stents. In addition, the degradation time of group B was significantly extended than that of group C as a whole.

(207) Conclusion

(208) Additional annealing in air and subsequent fluoridation could significantly reduce the degradation rate of the stents during the first hours, which could be advantageous with regard to the in vivo ingrowth of the stent. The fluoridation of the stents in 48% hydrofluoric acid not only reduced the initial degradation rate, but also slowed down the overall degradation time.

Example 14: Degradation Tests of Stents Having an Intermediate Layer of Magnesium Fluoride and a Further Coating of Parylene C

(209) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished.

(210) The purpose of this experiment was to demonstrate the influence of a magnesium fluoride interlayer below a 2.5 μm parylene C layer.

(211) Two groups of coated stents were compared:

(212) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) were placed in a plastic container. The plastic containers with lids (made of PP) were each filled with 50 ml 38-40% hydrofluoric acid and then placed in a tempered water bath at a temperature of 50° C. The water was heated to 50° C. in a glass reservoir by a heating plate and kept at 50° C. during the treatment process. An agitator in the reservoir allows to easily move the plastic containers in the water bath. After 24 hours, the plastic containers were removed from the water bath. The stents in turn were removed from the hydrofluoric acid, rinsed with deionized water, dried with compressed air and packed in a glass tube. The layer thickness of the fluoride layer was 1-2 μm.

(213) The stents were then coated with chlorinated poly-p-xylylene (parylene C). Parylene C can be deposited directly from the gas phase on the substrate, resulting in a very uniform coating. The thickness of the coating can be varied over the duration of the treatment.

(214) Group B: The stents of group B were coated directly (i.e. without an intermediate layer of magnesium fluoride) with the polymer parylene C. The layer thickness of the polymer was the same because they were coated in the same coating cycle as the stents of group A.

(215) Photometric Measurement

(216) The degradation measurements were carried out as in example 9 and are shown in FIG. 13. The sample specification A is the mean of the dissolved mass values of magnesium of two stents of group A.

(217) Sample B is the mean value of the dissolved mass of magnesium of two stents of group B.

(218) The measurement of dissolved magnesium ions shows that the stents of group A (stents having an intermediate layer of magnesium fluoride) degrade much more slowly than stents of group B (without an intermediate layer of magnesium fluoride). The degradation rate is roughly halved.

(219) Conclusion

(220) The layer thickness, the layer application and the layer homogeneity of the polymer were identical for both groups as these were coated in parallel in the same coating cycle. This means that the slower degradation rate of stents of group A compared to group B can be attributed solely to the magnesium fluoride interlayer. The magnesium fluoride layer is therefore also suitable as an intermediate layer for other coatings (such as polymer coatings).

Example 15: Degradation Tests of Stents Having an Intermediate Layer of Magnesium Fluoride and a Further Coating of an Resorbable Polymer

(221) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished. The layer thicknesses of the applied polymer were the same for all groups.

(222) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly-L-lactide (PLLA), which was applied to the stent by spraying method.

(223) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method.

(224) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly-L-lactide (PLLA), which was applied to the stent by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(225) Group D: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(226) Photometric Measurement

(227) The degradation measurements were carried out as in example 9 and are shown in FIG. 14. The sample specification A is the dissolved mass of magnesium of a stent of group A.

(228) Sample B is the dissolved magnesium mass of a stent of group B.

(229) Sample C is the mean value of the dissolved mass of magnesium of two stents of group C.

(230) Sample D is the mean value of the dissolved mass of magnesium of two stents of group D.

(231) The measurement of dissolved magnesium ions (FIG. 14) shows that the stents having an intermediate layer of magnesium fluoride (groups C and D) degrade much more slowly than the stents without an intermediate layer. The combination of magnesium fluoride and poly-ε-caprolactone (group D) shows the slowest degradation rate followed by magnesium fluoride and poly(L-lactide) (group C).

(232) Conclusion

(233) In this experiment, it could be shown that the degradation time of stents of magnesium alloy A having a resorbable polymer coating can considerably be further slowed down by an intermediate layer of magnesium fluoride. The layer thickness of the respective polymer was identical for all stents (10 μm). The intermediate layer of magnesium fluoride decelerated the degradation time both for PLLA-coated stents (group A vs. group C) and for PCL-coated stents (group B vs. group D).

(234) A layer of magnesium fluoride on a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) is therefore also suitable as an intermediate layer for a resorbable polymer coating to significantly decelerate the rate of degradation.

Example 16: Degradation Tests of Stents Having an Intermediate Layer of Magnesium Fluoride and an Additional Coating of Poly(L-Lactide) (PLLA) and Introduced Drug

(235) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished.

(236) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 7 μm layer of poly-L-lactide (PLLA) with an introduced drug (rapamycin), which was applied by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(237) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 7 μm layer of poly-L-lactide (PLLA) with an introduced drug (rapamycin) applied to the stent by spraying method.

(238) Photometric Measurement

(239) The degradation measurements were carried out as in example 9 and are shown in FIG. 16. The sample specification A is the mean of the measurements of dissolved mass of magnesium of two stents of group A.

(240) Sample B is the mean value of the dissolved mass of magnesium of three stents of group B.

(241) The photometric concentration measurement (FIG. 16) shows that the stents having an intermediate layer of magnesium fluoride degrade more slowly than the stents without such a layer at same layer thickness of the polymer coating (7 μm).

(242) Conclusion

(243) In this experiment it could be shown that the degradation time of stents of magnesium alloy A having a resorbable polymer coating of poly-L-lactide (PLLA) and a layer thickness of 7 μm can considerably be slowed down by an intermediate layer of magnesium fluoride.

Example 17: Degradation Tests of Stents Having an Intermediate Layer of Magnesium Fluoride and a Further Coating of Poly-ε-Caprolactone (PCL) with Introduced Drug and Different Layer Thicknesses

(244) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated, and electropolished.

(245) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 4 μm layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method.

(246) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 7 μm layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method.

(247) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 4 μm layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(248) Group D: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 7 μm layer of poly-ε-caprolactone (PCL), which was applied to the stent by spraying method and an intermediate layer of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(249) Photometric Measurement

(250) The degradation measurements were carried out as in example 9 and are shown in FIG. 15. The sample specification A is the dissolved mass of magnesium of a stent of group A.

(251) Sample B is the dissolved magnesium mass of a stent of group B.

(252) Sample C is the mean value of the dissolved mass of magnesium of two stents of group C.

(253) Sample D is the mean value of the dissolved mass of magnesium of two stents of group D.

(254) The photometric concentration measurement (FIG. 15) shows that the stents having an intermediate layer of magnesium fluoride degrade more slowly than the stents without such a layer at the same layer thickness of the polymer coating (4 μm or 7 μm).

Example 18: Degradation Tests of Stents Having an Inorganic and a Further Coating of an Resorbable Polymer with Different Composition of the Inorganic Coating

(255) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished.

(256) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium hydroxide and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium hydroxide surface was applied to the stents in a wet chemical process. The polished stents were immersed for 2 min in 30% H.sub.2O.sub.2 solution at room temperature. Afterwards these were rinsed with H.sub.2O and immersed in ethanol and dried at 80° C. for one hour in a drying chamber.

(257) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium carbonate/magnesium hydroxide and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The surface transformation was realized by means of a wet chemical process. Thereby the polished stents were immersed in saturated NaHCO.sub.3 solution for 5 min and at 37° C. The stents were then rinsed with H.sub.2O and immersed in ethanol. Afterwards the stents were dried at 100° C. for one hour in a drying chamber.

(258) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium phosphate/magnesium hydroxide and a 10 μm layer of poly-L-lactide (PLLA), which was applied by spraying method.

(259) The surface transformation was realized by means of a wet chemical process. Thereby the polished stents were immersed in saturated Na.sub.2HPO.sub.4 solution for one hour at 37° C. Afterwards the stents were rinsed with H.sub.2O and immersed in ethanol. The stents were then dried at 100° C. for one hour in a drying chamber.

(260) Group D: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(261) Group E: Stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride. The magnesium fluoride layer was applied to the stents as in example 13 (group A).

(262) Photometric Measurement

(263) The degradation measurements were carried out as in example 9 and are shown in FIG. 17. The sample specification A is the measurement of the dissolved mass of magnesium relative to the initial surface of a stent of group A (A1 and A2).

(264) Sample B is the dissolved mass of magnesium relative to the initial surface of a stent of group B (B1 and B2).

(265) Sample C is the dissolved mass of magnesium relative to the initial surface of two stents of group C (C1 and C2).

(266) Sample D is a measurement of the dissolved mass of magnesium relative to the initial surface of two stents of group D (D1 and D2).

(267) Sample E is a measurement of the dissolved mass of magnesium relative to the initial surface of a stent of group E.

(268) The photometric concentration measurement (FIG. 17) shows that the stents having an intermediate layer of magnesium fluoride degrade more slowly than stents with other intermediate layers.

(269) Conclusion

(270) In this experiment it could be shown that an inorganic coating of magnesium fluoride on the stent significantly decelerates the degradation time of stents of magnesium alloy A having an resorbable polymer coating compared to inorganic coatings consisting of magnesium hydroxide, magnesium carbonate and magnesium phosphate.

(271) A coating of magnesium fluoride and an overlying coating of poly-L-lactide (PLLA) on a stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) is particularly suitable to decelerate the degradation rate considerably.

Example 19: Coating of Stents with a Bioresorbabie Polymer and an Overlying Magnesium Fluoride Layer

(272) The stents (magnesium alloy A) were laser cut, heat treated, and electropolished. The polymer (PLLA) was then applied with embedded drug (rapamycin, 1.4 μg/mm.sup.2) in a spraying method. The subsequent application of a magnesium fluoride layer was carried out with IBAD (ion beam assisted deposition). The IBAD process comprises a thin layer formation with simultaneous ion bombardment of this layer from an ion source. In this case the coating was formed by evaporating magnesium fluoride from a molybdenum crucible at a pressure of e.g. 1 E-05 Pa. The application rate can be varied and is e.g. between 0.3 and 1.5 nm/s. The layer thickness can also be adjusted over time. In the present case, the layer thickness was about 800 nm. The temperature of the sample always remained below 70° C. so that the properties of the polymer and the drug were not influenced. The magnesium fluoride layer proved to be brittle. During crimping of the stents from the initial diameter of 1.8 mm to 1.1 mm, cracks and even detachments of the MgF.sub.2 layer were already detected by using light microscopes. During subsequent dilatation to a diameter of 3.2 mm, it was found that the MgF.sub.2 layer detached from the polymer in areas of greatest deformation of the stent. It can therefore be assumed that this layer does not lead to a degradation delay in this combination. In addition, spalling of the MgF.sub.2 layer from the polymer can lead to a local and thus non-uniform release of the drug. Flaking parts could also lead to an embolism.

Example 20: Degradation Tests of Stents Having an Intermediate Layer of Magnesium Fluoride and a Further Coating of Parylene N

(273) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished.

(274) The purpose of this experiment was to demonstrate the influence of a magnesium fluoride interlayer below a 0.1 μm parylene N layer.

(275) Two groups of coated stents were compared:

(276) Group A: Two stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) were treated as in example 13 group B to obtain a magnesium fluoride layer.

(277) The stents were then coated with the polymer parylene N (poly-p-xylylene). Parylene N can be deposited directly from the gas phase by condensation on the substrate, resulting in a very uniform coating. The layer thickness can be varied over the duration of the treatment.

(278) Group B: The two stents of group B were coated directly (i.e. without an intermediate layer of magnesium fluoride) with the polymer parylene N. The layer thickness of the polymer was the same as these were coated in the same coating cycle as the stents of group A.

(279) Group C: The two stents were treated as in group A, but no polymer was applied.

(280) Group D: The three stents had no coating (no magnesium fluoride layer and no polymer layer).

(281) Photometric Measurement

(282) The degradation measurements were carried out as in example 9 and are shown in FIG. 18. The sample designation A is the mean of the dissolved mass values of magnesium of two stents of group A.

(283) Sample B is the mean value of the dissolved mass of magnesium of two stents of group B. Sample C is the mean value of the dissolved mass of magnesium of two stents of group C. Sample D is the mean value of the dissolved mass of magnesium of three stents of group D.

(284) The measurement of the dissolved magnesium ions shows that the stents of group A (stents having an intermediate layer of magnesium fluoride) degrade much more slowly than stents of group B (without an intermediate layer of magnesium fluoride). The degradation rate is reduced by a factor of 2.5. The stents of group A degrade at about the same rate as the stents of group C. The stents of group D degrade the fastest.

(285) Conclusion

(286) The layer thickness, the layer application and the layer homogeneity of the polymer were identical for both groups as these were coated in parallel in the same coating cycle. This means that the slower degradation rate of the stents of group A compared to group B can be attributed solely to the magnesium fluoride interlayer. The comparison with uncoated stents and stents having only a magnesium fluoride layer shows that only the combination of the intermediate layer (magnesium fluoride) and the polymer (in this case parylene N) allows such a reduction in degradation. The individual coatings applied alone do not show the corresponding degradation inhibition.

Example 21: Degradation Tests of Stents Having an Intermediate Layer of Magnesium Fluoride and a Further Coating of Polyethyleneimine (PEI) and Polyacrylic Acid (PAA)

(287) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished.

(288) The aim of this experiment was to demonstrate the influence of an intermediate layer of magnesium fluoride below a double layer of polyethyleneimine (PEI, Mw 25,000) and polyacrylic acid (PAA, My 450,000). Stents with and without an intermediate layer of magnesium fluoride were compared. The magnesium fluoride layer was applied as in example 20 (group A).

(289) The double layer of PEI and PAA was applied by a layer by layer method. The stents (uncoated and coated with magnesium fluoride) were successively immersed in an aqueous solution of 5 mg/ml PAA for two minutes, then in deionized water for one minute, then in an aqueous solution of 5 mg/ml PEI for two minutes and finally in deionized water for one minute. This sequence was repeated five and ten times, respectively, and the stents were then dried in air.

(290) Group A: A stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) and a layer of PEI and PAA. The double layer of PEI and PAA was applied by layer by layer method. The stent was immersed successively in an aqueous solution of 5 mg/ml PAA for two minutes, then in deionized water for one minute, then in an aqueous solution of 5 mg/ml PEI for two minutes and finally in deionized water for one minute. This sequence was repeated five times and the stent was dried in air afterwards.

(291) Group B: A stent of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr), which was treated as in example 13 group B to generate an intermediate layer of magnesium fluoride. This was followed by the same coating sequence as for Stent A (5×PEI and PAA).

(292) Group C: Similarly coated stent as in group A but with 10 coating rounds for generation of the PEI and PAA layer.

(293) Group D: Similarly coated stent as in group B but with 10 coating rounds for generation of the PEI and PAA layer.

(294) Group E: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without any further coating.

(295) Photometric Measurement

(296) The degradation measurements were carried out as in example 9 and are shown in FIG. 19. The specification of the measured values corresponds to those of the stent specifications. The values of group E are mean values from the values of three stents.

(297) The stents having a triple coating of magnesium fluoride and PEI and PAA degrade more slowly than those with only a PEI and PAA layer.

(298) Conclusion

(299) In this experiment it could be shown that an intermediate layer of magnesium fluoride also has an additional degradation-inhibiting effect, even if polyacrylic acid and polyethyleneimine are used as coatings, when compared with stents without an intermediate layer of magnesium fluoride.

Example 22: Degradation Tests of Stents of Different Alloys with and without an Intermediate Layer of Magnesium Fluoride and a Further Coating of Poly-L-Lactide

(300) For the experiment the same design was used for all stents. An stents of the following groups were laser cut, heat treated and electropolished. Some of the stents differed in the magnesium alloy used.

(301) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) with a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method.

(302) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium fluoride layer was applied to the stents as in example 13 (group B).

(303) Group C: Stents of magnesium alloy L37 having a 5 μm layer of Poly-L-Lactide (PLLA), which was applied by spraying method.

(304) Group D: Stents Magnesium alloy L37 having an inorganic coating (surface transformation) of magnesium fluoride and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium fluoride layer was applied to the stents as in example 13 (group B).

(305) Group E: Stents of magnesium alloy AZ91 (Mg9Al1Zn) having a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method.

(306) Group F: Stents of magnesium alloy AZ91 (Mg9Al1Zn) having an inorganic coating (surface transformation) of magnesium fluoride and a 5 μm layer of poly-L-lactide (PLLA), which was applied by spraying method. The magnesium fluoride layer was applied to the stents as in example 13 (group B).

(307) Photometric Measurement

(308) The degradation measurements were carried out as in Example 9 and are shown in FIG. 20.

(309) The sample specification A is the mean value of the dissolved mass of magnesium relative to the time of two samples from group A each.

(310) The same applies to the other samples (B, C, D, E, F).

(311) Here, for all alloys used, stents of this alloy corrode more slowly in case an intermediate layer of magnesium fluoride is applied (compare A and B, as well as C and D, and E and F). Stents of alloy L37 degraded faster than those of alloys A and AZ91 (Mg9Al1Zn).

(312) Conclusion

(313) In this experiment, it could be shown that an intermediate layer of magnesium fluoride in combination with an organic coating significantly decelerates the degradation even in case of different alloys as stent material. If no intermediate layer is applied, the degradation rate is significantly faster.

(314) This experiment shows that an intermediate layer of magnesium fluoride can also be applied to magnesium alloys other than alloy A.

Example 23: Degradation Tests of Stents with and without an Intermediate Layer of Magnesium Fluoride and a Further Coating of Poly(Lactid-Co-Glycolide) (PLGA)

(315) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished.

(316) Group A: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of poly(lactid-co-glycolide) (PLGA), which was applied by dip coating. The stent was immersed in a solution of PLGA (85:15) and trichloromethane (5 mg/ml), pulled out of the solution at 20 mm/min and then dried in air at 40° C.

(317) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and an overlying layer of poly(lactid-co-glycolide) (PLGA). The magnesium fluoride coating has been applied as in example 13 group B. The PLGA coating was applied in the same way as group A.

(318) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without any coating.

(319) Photometric Measurement

(320) The degradation measurements were carried out as in Example 9 and are shown in FIG. 21.

(321) The sample specification A is the mean value of the dissolved mass of magnesium relative to the time of two samples from group A each.

(322) The same applies to the other samples (B,C).

(323) The coated stents degrade more slowly than the uncoated ones, the ones with an intermediate layer of magnesium fluoride degrading most slowly.

(324) Conclusion

(325) In this experiment it could be shown that an intermediate layer of magnesium fluoride in combination with an organic coating (in this case PLGA) degrades much more slowly than stents without such or without any coating. The experiment shows that the combination of magnesium fluoride as intermediate layer and PLGA as overlying organic layer is particularly suitable to decelerate the degradation.

Example 24: Degradation Tests of Stents with and without an Intermediate Layer of Magnesium Fluoride and a Further Coating of Polymethacrylamide (PMAA)

(326) The same design and substrate material (magnesium alloy A) was used for all stents. All stents of the following groups were laser cut, heat treated and electropolished.

(327) Group A: Three stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a layer of PMAA, which was applied by dip coating (A1, A2, A3).

(328) Group B: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and an overlying layer of PMAA (B1, B2, B3).

(329) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) without any coating.

(330) Photometric Measurement The degradation measurements were carried out as in Example 9 and are shown in FIG. 22.

(331) The sample specification C is the mean value of the dissolved mass of magnesium relative to the time of three samples from group C.

(332) The double-coated stents (magnesium fluoride and PMAA) degrade more slowly than the uncoated ones. The stents coated with PMAA only show no delay in degradation rate compared to uncoated stents.

(333) Conclusion

(334) In this experiment it could be shown that an intermediate layer of magnesium fluoride in combination with an organic coating (in this case PMAA) degrades more slowly than stents without such or without any coating. The experiment shows that the combination of magnesium fluoride as intermediate layer and PMAA as overlying organic layer is suitable to decelerate the degradation (at least in the first hours of the experiment). However, other polymers are more suitable as overlying layers.

Example 25: Degradation Tests of Stents with and without an Intermediate Layer of Magnesium Fluoride and a Further Coating of Poly-L-Lactide in Comparison to Stents of Alloy L37 Having a Coating of Poly-L-Lactide

(335) The same design and substrate material (magnesium alloy A) was used for all stents of groups B and C for the experiment. The material used for the stents of group A was L37 alloy. All stents were laser cut, heat treated and electropolished and then coated.

(336) Group A: Two stents of L37 magnesium alloy having a PLLA coating and an abluminal layer thickness of 6-12 μm.

(337) Group B: Two stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having a coating of 7.5 μm PLLA and an introduced drug (rapamycin, 1.4 μg/mm.sup.2). The PLLA coating was applied by spraying method.

(338) Group C: Stents of magnesium alloy A (Mg10Dy1Nd1Zn0.2Zr) having an inorganic coating (surface transformation) of magnesium fluoride and an overlying layer of 7.5 μm PLLA with introduced drug (rapamycin, 1.4 μg/mm.sup.2). The magnesium fluoride coating was applied as in example 13, group B. The PLLA coating was applied by spraying method.

(339) Photometric Measurement

(340) The degradation measurements were carried out as in example 9 and are shown in FIG. 23. Since stents with different designs were compared, the mass of dissolved Mg ions was related to the initial surface of the respective stents.

(341) The specifications A1 and A2 refer to the measured values of the two stents in group A. The same applies to groups B and C.

(342) Both stents of group B and stents of group C degrade much more slowly than stents of group A. Stents having an intermediate layer of magnesium fluoride (group C) degrade the slowest.

(343) Conclusion

(344) In this experiment it was shown that stents of magnesium alloy A having an intermediate layer of magnesium fluoride in combination with an organic coating (in this case PLLA) with an introduced drug degrade more slowly than stents without such an intermediate layer. In addition, stents of magnesium alloy A degrade much more slowly than stents of alloy L37 having a comparable coating without an intermediate layer. The experiment shows that the combination of magnesium fluoride as the intermediate layer and PLLA as the overlying organic layer is suitable to significantly decelerate degradation. The measured values within group C scatter the least in this comparison, which indicates a very homogeneous layer (double layer).