Resorbable Implant Material Made From Magnesium Or A Magnesium Alloy

Abstract

The present invention relates to a resorbable implant material made of magnesium or magnesium alloy and to a process for the production thereof. A disadvantage of the known resorbable implants is that their resorption has hitherto only been trackable using x-ray or CT examinations. The invention provides a resorbable implant material comprising homogeneously distributed fluorescent nanodiamonds in a matrix of magnesium or a magnesium alloy. Fluorescent nanodiamonds are biologically nonhazardous and provide a stable emission in the near infrared range due to nitrogen-vacancy centers (NV centres). This allows detection of the implant material in the blood plasma of the patient.

The resorbable implant material according to the invention is produced by a process wherein magnesium or a magnesium alloy is melted, nanodiamonds are added to the melt and the melt of magnesium or a magnesium alloy provided with nanodiamonds is subjected to an ultrasound treatment.

Claims

1. An implant material comprising homogeneously distributed fluorescent nanodiamonds having nitrogen-vacancy centers in a matrix of magnesium or a magnesium alloy, wherein the fluorescent nanodiamonds have nitrogen-vacancy centers (NV centers) which after excitation by a 532 nm laser beam have a detectable fluorescence band centered at a wavelength between 650 nm and 700 nm.

2. The implant material as claimed in claim 1, wherein the fluorescent nanodiamonds have a concentration of nitrogen-vacancy centers of more than 10 ppm, preferably more than 20 ppm, determined by epifluorescence after excitation by a 532 nm laser beam.

3. The implant material as claimed in claim 1, wherein the homogeneously distributed fluorescent nanodiamonds are present in an amount of 0.1% to 5% by weight based on the weight of magnesium/of the magnesium alloy in the matrix.

4. The implant as claimed in claim 3, wherein the homogeneously distributed fluorescent nanodiamonds are present in an amount of 0.5% to 1.5% by weight based on the weight of the magnesium/of the magnesium alloy in the matrix.

5. The implant as claimed in claim 1, wherein the fluorescent nanodiamonds have a particle size of 1 to 20 nm.

6. The implant as claimed in claim 5, wherein the fluorescent nanodiamonds have a particle size of 3 to 8 nm.

7. The implant as claimed in claim 1 for use in fracture treatment or for the treatment of stenoses, wherein the degradation of the implant material is determined by fluorescence measurements.

8. A method for producing an implant material according to claim 1, wherein magnesium or a magnesium alloy is melted, nanodiamonds are added to the melt and the melt of magnesium or a magnesium alloy provided with nanodiamonds is subjected to an ultrasound treatment.

9. The method as claimed in claim 8, wherein the magnesium or the magnesium alloy is melted in a permanent mold in a furnace under protective gas and with stirring in a first step, the melt is stirred mechanically, the fluorescent nanodiamonds are then added to the melt and after addition of the fluorescent nanodiamonds the melt is treated with ultrasound.

10. The method as claimed in claim 9, wherein the ultrasound treatment is carried out using a sonotrode introduced into the melt.

11. The method as claimed in claim 8, wherein the ultrasound treatment is carried out over a period of 1 min to 10 min.

12. The method as claimed in claim 11, wherein the ultrasound treatment is carried out over a period of 2 min to 5 min.

13. The method as claimed in claim 9, wherein after the ultrasound treatment the mold is transferred into a water bath where the melt solidifies.

14. The method as claimed in claim 8, wherein the implant material is remelted and subsequently poured into the desired mold to afford a metallic implant.

15. The method as claimed in claim 8, wherein the implant material is extruded and the extrudate serves as a precursor for fabrication of an implant.

16. The method as claimed in claim 8, wherein the implant material is converted into a metallic implant using MIM technology.

17. A method for determining the degree of resorption of an implant material in a patient comprising detecting a fluorescence signal in the patient's blood, wherein the implant material comprises homogeneously distributed fluorescent nanodiamonds having nitrogen-vacancy centers in a matrix of magnesium or a magnesium alloy, wherein the fluorescent nanodiamonds have nitrogen-vacancy centres (NV centers) which after excitation by a 532 nm laser beam have a detectable fluorescence band centered at a wavelength between 650 nm and 700 nm.

18. The method of claim 17, wherein the fluorescent nanodiamonds have a concentration of nitrogen-vacancy centers of more than 10 ppm, preferably more than 20 ppm, determined by epifluorescence after excitation by a 532 nm laser beam.

19. The method of claim 17, wherein the homogeneously distributed fluorescent nanodiamonds are present in an amount of 0.1% to 5% by weight based on the weight of magnesium/of the magnesium alloy in the matrix.

20. The method of claim 17, wherein the fluorescent nanodiamonds have a particle size of 1 to 20 nm.

Description

[0015] FIG. 1 shows the fluorescence spectrum of an NV-center in a nanodiamond at room temperature, excited by a 532 nm laser beam. The FIGURE shows a broad fluorescence band centered at a wavelength of about 700 nm.

[0016] The inventive implant material made of magnesium or magnesium alloy and containing homogeneously distributed fluorescent nanodiamonds may be produced by casting. It may subsequently be extruded or processed into implant articles by powder metallurgy processes such as MIM technology. Resorption of the implant material in the body of the patient causes the fluorescent nanodiamonds to pass into the blood circulation where they may be detected by fluorescence spectroscopy or by other means. The fluorescent nanodiamonds are gradually excreted from the body. This affords a wash-in/wash-out profile in the plasma which after calibration allows conclusions to be drawn about the resorption of the implant material.

[0017] When magnesium alloy is used as the matrix material it is preferable to employ alloying elements not considered hazardous to health. It is preferable to employ magnesium alloys with alloying elements selected from the group consisting of lithium, calcium, potassium, strontium, barium, scandium, yttrium, lanthanum, praesodymium, neodymium, samarium, europium, gadolinium, dysprosium, silicon, copper, zinc, gallium, gold, silver, bismuth, iron and combinations thereof. It is more preferable to employ magnesium alloys such as are described in DE 10 2016 007 176 A1 or DE 10 2016 119 227 A1 which are hereby fully incorporated by reference.

[0018] According to the invention the implant material is produced when magnesium or magnesium alloy is melted, nanodiamonds are added to the melt and the melt of magnesium or a magnesium alloy provided with nanodiamonds is subjected to an ultrasound treatment.

[0019] Such a process for homogeneous distribution of nanoparticles in a melt of magnesium or magnesium alloy is described in the article by H. Dieringa et al. Ultrasound Assisted Casting of an AM60 Based Metal Matrix Nanocomposite, Its Properties, and Recyclability in Metals 2017, 7, 338 which is hereby fully incorporated by reference.

[0020] In a preferred process for producing the implant material according to the invention magnesium or a magnesium alloy is preferably melted in a permanent mold in a furnace under protective gas and with stirring in a first step, the melt is admixed with the nanodiamonds in a second step and the nanodiamonds introduced into the melt are dispersed and deagglomerated using a sonotrode in a third step. It is further preferred when after removing the stirrer and the sonotrode the permanent mold containing the melt is immersed in a water bath. This brings about solidification of the melt from bottom to top, thus avoiding cavity formation.

[0021] The thus produced implant material may subsequently be subjected to further processes by conventional means. For example the implant material may be remelted and then poured into the desired mold to form an implant article. Material may also be extruded to fabricate implants from the extrudate. The implant material may also be further processed into powder and then further processed into an implant article by metal injection molding (MIM).

[0022] The implant material according to the invention preferably comprises homogeneously distributed fluorescent nanodiamonds in a matrix of magnesium or magnesium alloy in an amount of 0.1% to 5% by weight, preferably 0.5% to 1.5% by weight, based on the weight of magnesium/magnesium alloy. The nanodiamonds preferably have a particle size of 1 to 20 nm, preferably 3 to 8 nm.

[0023] As described, to produce the implant material according to the invention the magnesium or the magnesium alloy is preferably melted in a permanent mold in a furnace under protective gas and with stirring in a first step, as described in H. Dieringa et al. Ultrasound Assisted Casting of an AM60 Based Metal Matrix Nanocomposite, Its Properties, and Recyclability in Metals 2017, 7, 338. The melt is preferably stirred mechanically, preferably at 150 to 250 rpm. The fluorescent nanodiamonds are then added to the melt. After addition of the fluorescent nanodiamonds the melt is treated with ultrasound. This is preferably achieved by introducing a sonotrode into the melt. The ultrasound treatment is preferably carried out over a period of 1 min to 10 min, more preferably 2 min to 5 min.

[0024] It is preferable when after the mixing and the ultrasound treatment the stirrer and the sonotrode are removed and the permanent mold is slowly lowered from the furnace into a water bath where the melt solidifies.

[0025] The thus produced implant material may subsequently be subjected to further processing by conventional means. For example the implant material may be remelted and then poured into the desired mold to provide a metallic implant article. The implant material according to the invention may also be extruded and an implant article may be fabricated from the extrudate.

[0026] The implant material according to the invention may also be processed into a metallic implant article using MIM technology. Use of MIM technology allows small, complex and precisely shaped metal components to be fabricated in near net shape. MIM technology belongs to the group of so-called powder metallurgy processes in which the starting material for the component to be produced is fine metal powder rather than a solid metal body. MIM stands for metal injection molding. In the MIM process the metal powder is made flowable by addition of thermoplastic binders and the flowable mixture is introduced into an injection mold. After molding the binder fraction is removed again and the component is sintered. Magnesium components may be produced using MIM technology by the process described in M. Wolff et. al. Magnesium powder injection moulding for biomedical application, Powder Metallurgy, 2014 (Vol. 57, No. 5), 331-340 which is hereby fully incorporated by reference.

[0027] When using MIM technology the binder provides for temporary bonding during the primary shaping/molding and ensures the stability of the component until final compacting of the metal powder by sintering. A portion of the binder is generally already removed before sintering, for example using a solvent (solvent debindering). The remainder of the binder decomposes at temperatures of about 300 C. to 500 C. and escapes in gaseous form during thermal debindering.