WO2015162306A1

WO2015162306A1 - Method for the surface treatment of a biocorrodable implant

Info

Publication number: WO2015162306A1
Application number: PCT/EP2015/061210
Authority: WO
Inventors: Volkmar Neubert
Original assignee: Syntellix Ag
Priority date: 2014-04-23
Filing date: 2015-05-21
Publication date: 2015-10-29
Also published as: DE102014105732B3; WO2015162306A8; KR20170023799A; EP3134563A1; RU2016144709A; JP2017519538A; CA2946676A1; BR112016024664A2; IL248450A0; AU2015250774A1; SG11201608850RA; CN106456839A

Abstract

The subject of the present invention is a method for the surface treatment of a biocorrodable implant by means of electrochemical reactions, comprising the steps of: a) providing an implant of a biocorrodable magnesium alloy; b) introducing the implant into an electrolyte with a pH of 9-13; c) electrochemically treating the surface of the implant, wherein the implant serves as the working electrode and there is also a counterelectrode, and wherein the working electrode is alternately polarized cathodically and anodically, the current density being set to -0.1 to -7 mA/cm² for the cathodic polarization and to 0.1 to 2 mA/cm² for the anodic polarization. A corresponding implant is also the subject of the invention.

Description

Process for the surface treatment of a biocorrodible implant

The present invention relates to a method for surface treatment of a biocorrodible implant by means of alternating cathodic and anodic polarization and a corresponding implant.

Implants have the task of supporting or replacing body functions and have found application in various applications in medical technology. In addition to implants for attachment of tissues, endovascular implants, dental prosthesis implants, joint replacement implants also find implants for the treatment of bone damage, such as screws, nails, plates, or as a bone substitute application.

Implants used on the bone are nowadays mostly made of titanium. Despite the relatively good biocompatibility of titanium implants compared to other permanent implants, efforts are being made to further improve them. Often, coatings are applied to the implant surface to improve biocompatibility.

A disadvantage of applying layers to the implant surface is on the one hand a geometry change of the implant, even with small layer thicknesses. In addition, the adhesion of the applied layers is usually not optimal.

DE 195 04 386 C2 discloses a method for producing a graded coating of calcium phosphate phases and metal oxide phases on metallic implants, preferably of titanium. In the electrochemical method with a substrate electrode formed by the metal implant and a counter electrode, an aqueous solution with calcium and phosphate ions in the weakly acidic to neutral range is used as the electrolyte and the substrate electrode formed by the implant is alternately anodically and cathodically polarized. Due to the solid incorporation of calcium phosphate phases into the implant Surface is achieved a good growth of the bone to the implant.

DE 100 29 520 A1 describes a coating for a metallic implant surface for improving osteointegration. The implant is cathodically polarized in an electrolytic cell in a calcium, phosphate and collagen-containing electrolyte. The method forms a mineralized collagen layer on the implant surface. Often, only a temporary retention of the implant in the body is necessary, especially in cardiovascular and orthopedic implants. Implants made of a permanent material must then be removed by another operation. For this reason biocorrodible materials are used for implants. Under biocorrosion in the present case, the gradual degradation of the material is understood due to the body's own media. Even with biocorrodible materials influencing the corrosion process is advantageous.

However, in the case of biocorrodible implants, in most cases no complete inhibition of the corrosion is to be achieved since it is ultimately desirable for the implant to dissolve in the body after a certain time. Rather, only an influence on the corrosion rate is to be achieved, which allows a delayed degradation of the implant in the body as needed. One approach to improve corrosion protection, as with permanent implants, is to apply a corrosion inhibiting coating.

By way of example, DE 103 57 281 A1 is cited, which discloses a degradable stent made of a magnesium material which is provided with a coating which retards the degradation. For this purpose, the uncoated implant surface, which has a natural mixed oxide layer, is converted into a mixed fluoride layer. The coating can be done by dipping in fluoride-containing media with or without electrolytic support. The object of the present invention was to provide an alternative method for surface treatment of a biocorrodible implant, whereby the degradation rate of the implant can be adjusted as needed.

The object is achieved by the method according to the invention for the surface treatment of a biocorrodible implant according to claim 1.

The method according to the invention for the surface treatment of a biocorrodible implant by means of electrochemical reactions comprises the steps of: a) providing an implant of a biocorrodible magnesium alloy;

b) introducing the implant into an electrolyte having a pH of pH 9 to pH 13;

c) electrochemical treatment of the implant surface,

wherein the implant serves as a working electrode and further a counter electrode is present, and

wherein the working electrode is alternately cathodically and anodically polarized, wherein the current density in the cathodic polarization to -0.1 to -75 mA / cm ² and the current density in the anodic polarization to 0.1 to 25 mA / cm ^{2 is} set.

The inventive method results in a magnesium hydride layer that grows from the implant surface into the implant. Hydrogen ions are cathodically deposited from the electrolyte and implanted in the implant surface.

A metal hydride layer is formed which, starting from the implant surface, virtually grows into the implant. Thus, the method has the advantage that no geometry change takes place on the implant, since the metal hydride layer grows into the implant.

In the context of the present invention, an implant is to be understood as meaning an artificial material implanted in the body. Due to the use of a biocorrodible alloy for the implant body, the material used is gradually degraded by the body's own media. It is envisaged that the implant, in whole or in part, consists of a biocorrodible alloy. The implants can fulfill different purposes and functions as required, such as interference screws, screws and plates for fixation of bones, implants as a drug depot, joint prostheses, stents, jaw and dental implants. The list is only an example and by no means exhaustive.

The hydride layer slows down the corrosion of the implant. The corrosion rate of the hydride layer is lower than that of the actual material without hydride layer. As long as a closed hydride layer is present on the surface of the implant, the corrosion rate of the implant is thus determined by the corrosion reaction of the magnesium hydride. Once this hydride layer is degraded by corrosion, the rate of corrosion of the implant corresponds to the rate of corrosion of the actual biocorrodible magnesium alloy. After degradation of the hydride layer by corrosion, the alloy is thus degraded by corrosion as further as would be the case with an untreated implant. Due to the formation of the hydride layer, a two-stage corrosion behavior is present.

Preferably, the process according to the invention is carried out as follows:

An implant, for example a compression screw made of a biocorrodible metal alloy, preferably a biocorrodible magnesium alloy, is threaded onto a platinum wire. Subsequently, the surface of the screw is activated by a bath in aqueous citric acid solution, preferably a 1 -10% solution, for 1 to 10 seconds. Subsequently, the specimen is rinsed in deionized water, preferably for about 5 to 30 seconds. For further treatment, the screw is fixed on a non-metallic slide. The platinum wire is pulled out afterwards. Notches in the slide prevent later slippage of the screw. Alternatively, the screw can be inserted through a plate with a hole, whereby the ends of the screw are free, in order to later make contact eg with clamps.

The screw is contacted with terminals to make conductive contact. The clamps are preferably attached to the outer ends of the screw.

If very small implants such as very small screws or pins are to be used, no terminals are used, since contact by terminals can not be realized. Rather, a fine metallic grid is preferably used, on which the screws or pins grid are placed. The grid then establishes the conductive contact with the implant. The activation in the citric acid solution as well as the rinsing with water are also preferably carried out using the grid. Subsequently, the implant is introduced into the electrolyte. The electrolyte has a basic pH of from pH 9 to pH 13, preferably from pH 9 to pH 10. It is further preferred that the electrolyte contains 0.01 M NaOH and 0.2 M Na ₂ SO ₄ . The basic pH enables the formation of the magnesium hydride layer. At a pH below pH 9, the magnesium material would corrode due to its base character.

First, a cleaning of the surface of the implant by the action of positive pulses. The implant forms the working electrode. Furthermore, in the arrangement, a counter electrode is present. The counterelectrode preferably consists of a corrosion-resistant metallic material, for example of platinum, chromium-nickel steel, etc. Glass vessels are preferably used as electrolysis cell. For cleaning the surface, a positive pulse of 15 mA / cm ² to 35 mA / cm ² is preferred for a pulse length (pulse duration) of 0.10 s to 0.50 s (seconds) and a total duration of the pulses of a total of 5 min 40 min. Particularly preferred is a positive pulse of 25 mA / cm ² with a pulse length of 0.20 s and a total duration of 20 min.

Subsequently, the hydrogenation of the implant is carried out by alternating negative and positive pulse changes. It is preferred for the method according to the invention that the working electrode is repeatedly alternately cathodically and anodically polarized, starting with a cathodic polarization and terminating the deposition with a cathodic polarization. In a preferred embodiment, the current density in the cathodic polarization is adjusted to -35 to -55 mA / cm ² and the current density in the anodic polarization to 5 to 25 mA / cm ² .

Furthermore, it is preferred that the current density and the total duration of the pulses are lower in an anodic polarization step than in a previous anodic polarization step.

For the purposes of the present invention, a polarization step is to be understood as a sequence of positive or negative pulses of a specific current density and pulse length.

Furthermore, it is preferred that the pulse length in the cathodic polarization 0.40 s to 2.5 s and in the anodic polarization 0.10 s to 0.50 s.

In a preferred embodiment of the method according to the invention, the total duration of the pulses in a cathodic polarization step is 5 minutes to 90 minutes and the total duration of the pulses in an anodic polarization step is 1 minute to 20 minutes. In a further preferred embodiment, the total duration of all pulses of the cathodic and anodic polarization steps is 20 minutes to 300 minutes, preferably 1 minute to 240 minutes, particularly preferably 195 minutes. In a preferred embodiment, the method according to the invention consists of an alternating sequence of five polarization steps:

1 . Polarization step: cathodic polarization (negative pulse)

Current density: - 0.1 to - 75 mA / cm2

Pulse length: 0.50 to 2.5 s

Total for 60 min (3.6 ks)

2nd polarization step: anodic polarization (positive pulse)

Current density: + 0.1 to + 25 mA / cm2

Pulse length: 0.20 to 0.5 s

Total for 10 min (0.6 ks)

3. Polarization step: cathodic polarization (negative pulse)

Current density: - 0.1 to - 75 mA / cm2

Pulse length: 0.50 to 2.5 s

Total for 60 min (3.6 ks)

4. Polarization step: anodic polarization (positive pulse)

Current density: + 0.1 to + 15 mA / cm2

Pulse length: 0.20 to 0.5 s

Total for 5 min (0.3 ks)

5. Polarization step: cathodic polarization (negative pulse)

Current density: - 0.1 to - 75 mA / cm2

Pulse length: 0.50 to 2.5 s

Total for 60 min (3.6 ks)

It is achieved with the inventive method advantageously a deposition rate of 5 to 8 nm / h.

For the purposes of the present invention, the term deposition rate is to be understood as the growth of the metal hydride layer from the implant surface into the implant. After alternating cathodic and anodic polarization, the implant is removed from the electrolyte and rinsed with deionized water for about 30 to 60 seconds. For passivation, the implant is introduced into a stream of hot air, preferably at a temperature of 60 ° C. for 10 to 100 seconds. Until further use, the implant is preferably packaged airtight to prevent oxidation.

With the aid of the method according to the invention, a magnesium hydride layer is formed on the implant surface, which increases the corrosion resistance of the implant. Although higher current intensities than those specified for the method according to the invention can lead to a faster formation of the hydride layer in a defined time interval. However, the faster growth of the hydride layer, which results in a different penetration depth of the hydride layer, can lead to an inhomogeneous surface and thus uneven corrosion. With an inhomogeneous layer thickness of the magnesium hydride layer formed, thinner layer regions are completely degraded faster than thicker regions. If the magnesium hydride layer is already degraded in some areas, but not yet in others, it can lead to a sudden increase in the corrosion rate, since in these places no more hydride corrosion takes place, but the corrosion of the actual material. The implant is thus degraded unevenly and can lose its stability. The parameters described lead to an optimal surface with a reasonable amount of time.

The growth of the hydride layer occurs during the cathodic polarization steps. Longer or shorter pulse lengths only have an indirect influence on the growth of the hydride layer. In addition to the electrochemical reaction, the impulse serves above all to release the hydrogen (H2) formed at the working electrode uniformly and at short intervals. Additions of hydrogen bubbles can lead to slowing down or interrupting the formation of the hydride layer at this point, since in extreme cases no contact between material (working electrode) and electrolyte takes place more.

Within a polarization step, there is a short break between the individual pulses, ie, this resting phase between "current is applied" and "current is not applied" and should preferably be long enough for the hydrogen bubbles to rise from the working electrode ,

Particularly rectangular pulse currents are advantageous for the method according to the invention, since they provide enough time for the hydrogen to rise. A rectangular pulse current in the sense of the present invention is to be understood as meaning a current with a steep rise and drop and a constant plateau located therebetween. The same applies to the pulse length. With short and many pulses in a time interval, the rest phase is too short and there is a strong hydrogen gas accumulation in the form of bubbles at the working electrode.

In an advantageous embodiment of the method according to the invention, there is a rest period of at least 0.1 s between two pulses.

The geometry of the implant (working electrode) also has an influence on the optimal pulse length. A smooth or uniform surface promotes the bubbling of the hydrogen bubbles. Here the pulse length can be shortened. Samples with uneven surfaces or threads, such as screw-type implants, or a support grid as an electrode used on small implants will cause the hydrogen bubbles to take more time to bead off.

Thus, the pulse length is adjustable depending on the geometry of the implant. If too many hydrogen bubbles are accumulated on the working electrode, the pulse length is extended.

In this way, the individual process parameters can be adapted to different implant sizes and geometries. In addition, the degradation speed of the implant can be adjusted as needed. If a rapid degradation is desired, the total duration of the pulses, ie the duration of the respective cathodic polarization step, is reduced in order to limit the formation of the hydride layer to a low penetration depth and thus a small layer thickness. With a longer total duration of the pulses, however, the penetration depth and thus the layer thickness is increased.

In a further embodiment of the method according to the invention, it is preferred that the implant provided consists of a biocorrodible magnesium alloy which has a magnesium content of at least 50%. Particularly preferred is the following composition:

a rare earth metal content of 2.5 to 5% by weight,

an yttrium content of 1, 5 to 5 wt .-%,

a zirconium content of 0.1 to 2.5 wt .-%,

a zinc content of 0.01 to 0.8% by weight,

and unavoidable impurities, the total content of possible impurities being less than 1% by weight and the aluminum content being less than 0.5% by weight, preferably less than 0.1% by weight.

and the balance is 100% by weight of magnesium.

Furthermore, it is preferred that the implant consists in whole or in part of a biocorrodible magnesium alloy.

Further advantages result from an implant with a corrosion-inhibiting coating, obtained or obtainable by the process according to the invention.

After carrying out the method according to the invention, the surface of the implant has a hydrogenated outer layer, which increases the corrosion resistance. It is preferred that the corrosion-inhibiting hydride layer has a layer thickness of at least 10 nm, preferably at least 15 nm, particularly preferably 20 nm. In a further preferred embodiment, the provided implant made of a biocorrodible magnesium alloy has a magnesium content of at least 50%. The biocorrodible magnesium alloy from which the implant is made preferably contains the following composition:

a rare earth metal content of 2.5 to 5% by weight,

an yttrium content of 1, 5 to 5 wt .-%,

a zirconium content of 0.1 to 2.5 wt .-%,

a zinc content of 0.01 to 0.8% by weight,

and the balance is 100% by weight of magnesium.

Due to the low, almost negligible content of aluminum, the biocorrodible magnesium alloy is suitable for the use of implants in human medicine, because aluminum putatively attributed to harmful properties, such as the promotion of Alzheimer's or cancer.

The inventive method will be explained in more detail with reference to an embodiment.

Working Example

A round material of the magnesium alloy ZfW 102 PM F is treated by the method according to the invention.

The magnesium alloy ZfW 102 PM F consists of a rare earth metal content (including neodymium) of 4.05 wt.%, The neodymium content corresponds to 2.35 wt.%, An yttrium content of 1. 56 wt. a zirconium content of 0.78 wt .-%, a zinc content of 0.4 wt .-%, an aluminum content of 0.0032 wt .-%. The remainder to 100% by weight is magnesium. The round material is a solid cylinder with a diameter of 6 mm and a length of 3 cm. This solid cylinder acts as a working electrode. The counter electrode used is a platinum electrode with titanium core with a diameter of 6 mm and a length of 7 cm.

As electrolysis cell, a 500 ml beaker is used. The electrolyte consists of 0.01 M NaOH and 0.2 M Na2SO4 and has a pH of 9.4. The process is carried out at 24 ° C. To clean the surface, a positive pulse of 25 mA / cm ^{2 is used} with a pulse length of 0.20 s and a total duration of 20 min.

Subsequently, the hydrogenation of the round piece takes place by repeatedly alternating negative and positive pulse changes. The method according to the invention is carried out in an alternating sequence of five polarization steps:

1 . Polarization step: cathodic polarization (negative pulse)

Current density: -50 mA / cm2 3

Pulse length: 0.50 s

Total for 60 min (3.6 ks)

2nd polarization step: anodic polarization (positive pulse)

Current density: +20 mA / cm2

Pulse length: 0.20 s

Total for 10 min (0.6 ks)

3. Polarization step: cathodic polarization (negative pulse)

Current density: -50 mA / cm2

Pulse length: 0.50 s

Total for 60 min (3.6 ks)

4. Polarization step: anodic polarization (positive pulse)

Current density: + 1 0 mA / cm2

Pulse length: 0.20 s

Total for 5 min (0.3 ks)

5. Polarization step: cathodic polarization (negative pulse)

Current density: -50 mA / cm2 Pulse length: 0.50 s

Total for 60 min (3.6 ks)

After a total of 195 minutes, a layer thickness of 18 nm is achieved.

The treatment success is determined by means of X-ray diffractometry (RDA), secondary mass spectrometry (SIMS) and determination of the free corrosion potential. As a comparison serves an identical round material of the magnesium alloy ZfW 102 PM F, which was not treated with the inventive method.

The results are shown in FIGS. 1 to 4.

1 shows the hydride detection by means of X-ray diffractometry (RDA).

2 shows the hydride detection by means of secondary ion mass spectrometry (SIMS).

3 shows the determination of the free corrosion potential.

Fig. 4 shows the corrosion rate in a Ringer's lactate solution. A round piece, which was treated according to the inventive method according to Example 1, was examined by means of X-ray diffractometry. In Fig. 1, the phases located in the material are shown. The occurrence of magnesium hydride phases (MgH2) is evidence of the hydride layer formed by the process of the present invention.

A round piece, which was treated according to the inventive method according to Embodiment 1, was also examined by means of SIMS. 2 shows the hydride detection as a function of the penetration depth of the hydrogen ions into the workpiece.

In addition, the free corrosion potential was determined by a round piece treated according to the inventive method according to Example 1 and an untreated round piece. Fig. 3 shows that the treated Round piece (H-EIR, H electrochemical induced reaction) with 1 680 mV has a more positive corrosion potential than the untreated round piece.

FIG. 4 shows the corrosion rate of an untreated round piece and a round piece which has been treated according to the inventive method according to exemplary embodiment 1. The corrosion rate under body-like conditions was determined in each case at 37 ° C. in a Ringer's lactate solution (125-134 mmol / l Na ⁺ , 4.0-5.4 mmol / l K ⁺ , 0.9-2.0 mmol / l Ca ²⁺ , 106-1 17 mmol / l CI ^" , 25-31 mmol / l lactate ^" ). A Ringer's solution has a similar composition as the blood plasma and the extracellular fluid. It turns out that the treated round piece has a lower corrosion rate than the untreated round piece. Thus, for example, the untreated round piece has a corrosion rate of 0.415 mm / year after 432 h and a corrosion rate of 0.399 mm / year after 624 h, whereas the round piece treated according to the inventive method according to Example 1 has a corrosion rate of 0.244 mm after 432 h / Year and after 624 h a corrosion rate of 0.153 mm / year (see Fig. 4).

A biocorrodible implant, which is treated with the method according to the invention, thus has a longer life after implantation into the human body due to a delayed degradation rate than an untreated implant of identical construction. With the aid of the method according to the invention, it is thus possible to adapt the rate of degradation to the respective purpose and the necessary residence time of the implant in the body. If a longer residence time in the body is necessary than the actual material would allow, by treating an implant with the method according to the invention, the corrosion resistance can be increased. An increased corrosion resistance also gives the implant increased stability, since corrosion is associated with loss of mass of the implant. If the implant breaks down too quickly in the body, the bone may not have enough time to grow into the implant and replace the material with bone material. The choice of corrosion resistance is thus dependent on the position of the implant in the body or by the patient. This may be the case in older people who have slower bone growth biocorrodible implant can be used with a greatly retarded degradation rate. If, however, only a small implant is inserted into the bone, which is not subject to strong mechanical stress, an implant with a lower hydride layer thickness can be used.

Claims

claims

1 . Process for the surface treatment of a biocorrodible implant by means of electrochemical reactions, comprising the steps:

a) providing an implant of a biocorrodible magnesium alloy;

b) introducing the implant into an electrolyte having a pH of pH 9 to pH 13;

c) electrochemical treatment of the implant surface,

2. The method according to claim 1, characterized in that the working electrode is repeatedly alternating cathodic and anodically polarized, starting with a cathodic polarization and the deposition is terminated with a cathodic polarization.

3. The method according to claims 1 or 2, characterized in that the current density and the total duration of the pulses are lower in an anodic polarization step than in a previous anodic polarization step.

4. The method according to any one of the preceding claims, characterized in that the pulse length in the cathodic polarization 0.40 s to 2.5 s and in the anodic polarization 0.10 s to 0.50 s.

5. The method according to any one of the preceding claims, characterized in that the total duration of the pulses in a cathodic polarization step 5 min to 90 min and the total duration of the pulses at an anodic polarization step 1 min to 20 min.

6. The method according to any one of the preceding claims, characterized in that the total duration of all pulses is 20 minutes to 300 minutes.

7. The method according to any one of the preceding claims, characterized in that a hydride layer of at least 10 nm, preferably at least 15 nm is achieved on the implant surface.

8. By the method according to any one of claims 1 to 7 received implant with a corrosion-inhibiting coating.

9. Implant according to claim 8, wherein the corrosion-inhibiting hydride layer has a layer thickness of at least 10 nm, preferably at least 15 nm.

10. Implant according to claims 8 or 9, characterized in that the biocorrodible magnesium alloy

a rare earth metal content of 2.5 to 5 wt .-%,

an yttrium content of 1, 5 to 5 wt .-%,

a zirconium content of 0.1 to 2.5% by weight,

a zinc content of 0.01 to 0.8% by weight,

and unavoidable impurities, the total content of impurities being below 1% by weight and the aluminum content being less than 0.5% by weight,

and the balance is 100% by weight of magnesium.