RO131564A2 - Biocompatible alloys based on zirconium with controlled titanium addition - Google Patents

Abstract

The invention relates to three biocompatible alloys based on zirconium with controlled titanium addition, meant to be used in structural orthopaedic and dental implants, either temporary or permanent, in human and veterinary medicine. According to the invention, the alloys have the following chemical composition: a. 95% Zr, 5% Ti; b. 75% Zr, 25% Ti and c. 55% Zr, 45% Ti, the percentage being expressed by weight.

Description

FIELD OF THE INVENTION The invention relates to three biocompatible alloys with zirconium base for the manufacture of temporary or permanent implantable products used in human medicine and veterinary medicine. The alloys are characterized by original chemical compositions and properties appropriate to the scope of the invention. Alloys can be used, for example, either in the manufacture of screws, fixing plates, etc., used for temporary fixation of bone tissue fractures (temporary implantable products, implants for osteosynthesis), or in the manufacture of components of the joint prostheses, dental implants , products for permanent fixation of tissue fractures, etc. (permanent implantable products, arthroplasty, dental implantology, orthopedics).

The present state of the art in the field of the object of the invention. Both human medicine and veterinary medicine use to treat implantable device disorders made from materials or material structures synthesized by either natural or artificial means. Artificial materials are inorganic (metallic, ceramic) and organic (polymers), each class being dedicated to specific medical applications. Thus, metallic materials are mainly used for implantable devices for permanent replacement or temporary or permanent support of bone tissues, tissues with a pronounced structural and movement transmission role, or implantable devices intended for the cardiovascular system (stents, cardiac valves, cardiac pacemakers), Currently, the following classes of standardized alloys are used for the manufacture of implantable devices with structural role and motion transmission: 1) stainless steel (ISO 5832-1, ISO 5832-9); 2) CoCrMo alloys (ISO 5832-4, 5832-6,5832-7, 5832-8, 5832-12) and CoCrWNi (ISO 5832-5); 3) titanium alloy (ISO 5832-2) and titanium alloys (ISO 5832-3, 5832-11, 5832-14). In addition to these standardized metal materials, there is a relatively large number of scientifically investigated titanium alloys (Geetha ^ .a., 2009, Li et al., 2014), proposed for patenting (RO127102 A2, RO128388 A2, RO129303 A2, WO1998043550 Al) or patented (W02009145406 Al, US5169597 A, US8512486 B2, US8568540 B2) from the perspective of the scope of the invention. Titanium alloys are of the alpha + beta type, metastable beta or beta, being characterized by chemical compositions consisting of non-toxic elements (Ta, Nb, Mo, Zr, etc.), the elasticity mode as close to that of the bone structure, mechanical resistance and adequate fatigue resistance, in vitro and in vivo corrosion resistance, biocompatibility. The main disadvantage of titanium alloys for medical use is the high wear and tear of the contact surfaces in relative motion, a disadvantage that is currently eliminated by ceramic coatings of titanium alloy metal components or the fabrication of components subjected to friction wear by medical devices made of ceramic materials. for example, zirconium oxide (zirconia) (Geetha et al., 2009). Among the titanium alloy systems investigated for medical use, a special place is occupied by the Ti-Zr binary system (Ikarashi Y. et al., 2005, Grandin

H.M. et al., 2012, US 8168012 B2), the ternary Ti-Nb-Zr system (Song XP et al., 2012) and the Ti-Nb-Zr-Ta quaternary systems (Samoil S. et al., 2008, Nag S. et al., 2009) and Ti-Nb-Mo-Zr (Goîosova OA et al., 2011).

The long-term success of implantable devices for permanent orthopedic applications is dependent on the ability of the implant surfaces to be in contact with the bone tissue to promote the process of osteointegration (Geetha et al., 2009). In contrast, in the case of implantable devices for temporary orthopedic applications, since after a certain period of time they need to be extracted from the bone tissue, it is desirable that this process of

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osteointegration should be inhibited or non-existent to favor implant extraction. Titanium, due to its superficial oxide and its chemical interaction with the fluids of the human body, has the capacity to promote the process of osteointegration (Kobayashi E. et al., 2007, Geetha et al., 2009). Zirconia, unlike titanium, favors slowing or inhibiting the process of osteointegration (Kobayashi E. et al., 2007, Zhao X. et al., 2011). One of the advantages of the Ti-Zr alloy system, which can provide alloys with chemical compositions designed so that the resulting material can be used in the manufacture of implantable devices with different durations, results from the considerations shown. Titanium and zirconium are metals with similar crystalline structures, and the Zr-Ti binary system is characterized by an isomorphic phase diagram with a continuous series of solid solutions (Lo YC et al., 2008, Zhao X. et al., 2011). The magnetic susceptibility of the zirconia is lower than that of the titanium, so alloys in the Ti-Zr system with an appropriate zirconium content have the advantage of improving the images obtained by magnetic resonance, a very useful investigation method in the post-operative examination of patients. with implantable devices (Suyalatu et al., 2010, Suyalatu et al., 2011).

So far, several binary alloys have been studied (Oliviera NTC et al., 2005, Notnura N. et al., 2009, Hsu HC et al., 2009, Suyalatu et al., 2010) respectively ternation (Nie L. et al., 2014, Nie L., 2014) based on zirconium for the manufacture of implantable structural devices. Also, two patents have been applied, one for a Zr-Nb- (Sn, Al) alloy (WO2014034574 Al), and the second for a Zr-Ti-Nb- (Sn, Al) superelastic alloy. The authors of these two patent applications consider that the alloys with the claimed chemical compositions provide a low modulus of elasticity (50-70 GPa respectively 38-49 GPa), a reduced magnetic susceptibility, adequate corrosion resistance, biocompatibility. A number of patent applications concern methods of surface oxidation of zirconium alloys (EP 1789602 A2, EP 1670397 Al, EP 1409760 Al), and several patents of the invention refer to implantable components of oxidized surface zirconium (EP 1030696 Bl), zirconium prosthetic devices and zirconium alloys with oxidized surfaces (EP1395299 Bl, EP1670397 Bl), surface oxidation method of zirconium alloys (EP 1409760 Al). Superficial oxidation of zirconium and zirconium alloys aims to improve wear behavior by rubbing. The surface oxidation was applied to the Zr-2.5 Nb alloy (mass percentages) obtaining obvious increases in the wear resistance of the surfaces of the components of the joint prostheses with contact surfaces in relative motion.

Presentation of the scope of the invention. The purpose of the invention is to improve the properties of zirconium alloys used in the manufacture of temporary or permanent implantable devices by choosing suitable chemical compositions from the binary system of Zr-Ti alloys. It is an object of the invention to design zirconium alloys with properties specific to the field of use, properties that are controllable by the addition of titanium, another object is to provide zirconium alloys that can be superficially oxidized for the purpose of increasing wear resistance, and another objective is to obtain post-operative magnetic resonance imaging of the implantable devices through magnetic resonance imaging.

Exposure of the invention. The problem solved by the invention is to synthesize by known methods alloys from the Zr-Ti binary system dedicated to the medical field, which by the different titanium content of the chemical composition correspond to a certain type of medical application with a structural function.

Zirconium is a transition metal in the IVB group, atomic number 40, atomic mass 91.224 and density 6.52 g / cm ³ . The zircon has an allotropic transformation at 863 ° C, when the low temperature stable phase having a compact hexagonal crystalline structure (alpha phase) turns into the high temperature stable phase which has a cubic crystalline structure with centered volume (beta phase). (Schnell I et al., 2006). The zirconium has a modulus of longitudinal elasticity with a moderate value (88 GPa) which can be an advantage for the structural applications from ^ - 2 0 1 5 - 0 0 4 2 0 -.

9 -06-2015 medical field. The zirconium has a significant corrosion resistance in alkaline, acidic solutions, etc. (Lide DR, ed., 2007-2008), resistance due to the superficial layer of zirconium dioxide formed spontaneously in air.), But dissolves in hydrochloric acid and sulfuric acid, especially in the presence of fluorine (Considine GD, ed. , 2005). The zirconium is non-ferromagnetic (paramagnetic) which allows patients with implants made of zirconium materials to be examined postoperatively by magnetic resonance imaging. The images obtained by magnetic resonance, in the case of the zirconium-based materials, have a better quality compared to the images obtained in the case of the titanium-based materials, due to the lower susceptibility of the zirconium (1.3x10 cm ³ g '') to the ratio with that of the titanium (3.2x10 cm'g ¹ ) (Nomura N. et al., 2009). Zirconium dioxide, known as zirconia, is used as a material in various structural medical applications, being characterized among others by high wear resistance by rubbing.

Titanium is a transition metal from the IVB group, atomic number 22 and atomic mass 47,867 and density of 4,506 g / cm ³ , being included in the light metals category. Titanium has two allotropic forms, alpha titanium having a compact hexagonal structure, stable at temperatures higher than the transition temperature of 882 ° C, and beta titanium having a cubic structure with centered volume, stable at temperatures above the temperature of allotropic transformation. Due to the high value of the mechanical strength / density ratio it is suitable for structural applications, and the moderate value of the longitudinal elasticity mode (approx. 116 GPa) is an advantage for the orthopedic medical applications. The titanium spontaneously oxidizes in the air, on its surface forming a compact and adherent layer of titanium dioxide I a few nanometers thick. This layer of oxide provides titanium with excellent corrosion resistance in eum electrolytic media such as dilute solutions of sulfuric or hydrochloric acid, seawater, chlorine solutions and most organic acids (Lide D. R „ed., 2005). in contrast, its corrosion resistance decreases in concentrated acid solutions (Casillas N. et al., 1994). In contact with the fluids of the human body, a process of increasing the thickness of the oxide layer takes place, the superficial formation of a hydroxide and the incorporation of Ca and P atoms that contribute to the osseointegration of the titanium implants in the bone tissue. improvement of mechanical properties, corrosion resistance and biocompatibility is possible by alloying with elements known to be non-toxic such as Nb, Zr, Ta, Mo, Sn, which have the effect of stabilizing the beta phase of titanium at room temperature, as well as with elements such as Fe, Cr, Mn with the role of hardening by the formation of secondary phases. Because titanium is non-ferromagnetic (paramagnetic), patients with titanium implants and titanium alloys can be examined post-operatively by magnetic resonance imaging. From the perspective of using it materials for components that have surfaces in contact and relative motion, the titanium and its alloys have a low wear resistance, especially by rubbing.

Since the structural states and temperature domains in which the two allotropic forms are stable are similar, the alloys in the Zr-Ti binary system (mass percentages in the range (0-50) for titanium) are structurally characterized by continuous series of solid solutions and a phase transformation whose temperature ranges from 863 ° C (0.0% at. Ti or 0.0% at. Ti) to 605 ° C (50.0% at. Ti or 34.4% mass. Small) (Okamoto H, 1995). Since both metals spontaneously oxidize in air, it is expected that in the case of alloys in the ZrTi system there will be a surface oxide layer spontaneously. Both the corrosion behavior and the process of osteointegration after implantation in the bone tissue depend, besides other factors, on the physico-chemical modifications of the surface oxide, following the contact with the biological fluids, on the surface of the implant devices, both in vivo and in vitro, there is a succession of physico-chemical processes that determine dimensional, structural and compositional changes of the surface layers.

In this context, after immersion in biological fluids of specimens of Ti-Zr alloys having chemical compositions, Ti of technical purity, Ti-25% mas. Zr, Ti-50% mass. Zr, Ti- 60% mass. Zr

ML • 2015-- WHERE-,

19-00-2015 and Ti- 74% mas. Zr, Zr of technical purity, the following were observed: 1) the ratio between Ti and Zr in the oxide layer is similar to that in the base material, 2) in the case of Ti and Ti-25% mass alloy. Zr in the oxide layer were incorporated Ca and P ions, for the other materials the amount of Ca incorporated, decreasing with the increase of the zirconia content, 3) the thickness of the oxide layer increased with the increase of the Zr content, 4) the chemical state of Zr it was more stable than Ti in the case of the oxide layer (Hanawa T. et al., 1992, Hanawa T. et al., 2002).

following electrochemical corrosion tests in simulated biological environments, the following were observed: 1) the oxide layer is composed of a mixture of T1O2 and Z1O2, 2) the susceptibility to localized corrosion decreases with increasing Ti content, 3) thermal oxidation increases the corrosion resistance of all investigated alloys, 4) all alloys investigated under normal physiological conditions of pH and temperature have adequate corrosion resistance (Chelariu R. et al., 2012, Bolat G. et al., 2013 , Bolat G. et al., 2013, Mareei D., 2013, Mareei D., 2013). Following the described, three alloys from the Zr-Ti system are proposed for the manufacture of structural implantable devices having original chemical compositions. The novelty regarding the proposed chemical compositions, which are the subject of the patent, consists in the content of Ti, in mass percentages, of the Zr-Ti alloys, namely: alloy 1) 5% mass. Small, 95% mass. Zr; others 2) 25% mass. Small, 75% Zr; 3) 45% mass. Small, 55% mass. Zr.

The advantages resulting from the application of the invention-the invention have the following advantages:

• Obtaining three biocompatible alloys, as a result of chemical compositions made of elements known as biocompatible * Obtaining alloys with dedicated medical structural applications through the control of titanium content.

• Obtaining some alloys with chemical compositions that allow to increase the performances of use by surface thermochemical treatments.

Presentation of the diagram in the figure. The synthesis process of the proposed alloys for patenting, is that of melting - re-melting the metals in a melting furnace with a flow of electrons in vacuum, a process that ensures the obtaining of an alloy with a strictly controlled composition. Melting in high vacuum excludes impurities of gas alloys, metals entering the composition of alloys, zirconium and titanium being highly reactive to the temperature at which the melting occurs. The patent application contains a diagram with the steps of the process of synthesis of titanium-based zirconium alloys, shown in Figure 1.

Following are some details about the process of obtaining the alloys that are the subject of this documentation.

Analyzing the physical and chemical properties of the elements that make up the alloys, Zr and Ti, the interaction between them and their interaction with the gases in the atmosphere, the following were highlighted:

• Zirconia, titanium, are very reactive metals, gases - oxygen, hydrogen, nitrogen, reacting with them and influencing the mechanical characteristics, both as impurities and as micro or alloying elements;

• Zirconia and titanium have relatively close melting temperatures, being totally miscible throughout the concentration range, after solidification forming solid solutions.

Detailed description of an embodiment of the invention claimed in the following is described in an embodiment of the invention.

The work equipment. The elaboration of the zirconia based alloys was carried out in a vacuum melting furnace with electron flow having the following technical characteristics. The EMO 80 electron flow multi-chamber furnace was built in 1987 by the "Hans Beimler" locomotive electrical plants in Hennigsdorf, RDG. The EMO 80 oven is a melting, alloying and vacuum casting furnace. It is equipped with an electron gun with a power of 80

--2015-- 0042019-16-208 kW, with multi-chamber construction, which also determines the name of the oven. The applied multicameral principle allows the melting process to be carried out in the pressure range of IO ² torr (1.33 Pa). In general, the melting vacuum is at IO ⁴ - IO ' ⁵ tori (1.33 * IO' ² to 1.33 * IO ' ³ Pa).

Due to the application of the construction principle from standardized subassemblies, the installation can meet multiple requirements, being especially indicated for use in the laboratory.

The EMO 80 electron beam is composed of:

• electron gun;

• container (vacuum or melting chamber);

• support;

• working platform;

• vacuum installation for the container;

• vacuum installation for the electron gun;

• control system for cooling water;

• the loading system, two left-hand, and a granulated material loading system;

• ingot extraction plant;

• 80 * 30 viewfinder;

• systems for regulating, measuring and controlling the operating parameters.

Main operating parameters • 3x380 V connection voltage 10% TN-S, 50 Hz +/- 1Hz network;

• installed power 135 kW;

• rated power 80 kW;

• range of electron beam tuning power range 5-80 kW continuous adjustment;

• the acceleration voltage 30 kV DC, continuous adjustment;

• beam current 2.67 A;

• control voltage 220 V, 50 Hz;

• auxiliary voltage 20 V, 50 Hz.

Characteristics of the material introduced at the melting • electrode length max. 1000 mm .;

• electrode rest length (clamping part) approx. 100 mm .;

• max. Section Φ 100 mm., Or circumscribed polygon;

• feed rate 1 0.85 - 10 mm / min, II 8.5 - 100 mm / min;

Characteristics of the molten material • ingot length max. 800 mm;

• ingot section Φ 25 - 150 mm;

• ingestion rate I 0.85 - 10 mm / min, II 8.5 - 100 mm / min.

Vacuum characteristics • Melting vacuum 1 Pa - 5 * 10 ' ³ Pa (8 * 10' ³ 4 * 10 ⁵ Torr), depending on the melting speed and the gas content of the material subject to melting;

• suction capacity of high vacuum pumps

1. container (melting chamber) 8000 1 / s

2. cannon with electrons 2 * 1000 1 / s

3. container leakage rate 1.3 * 10 ' ¹ Pa * l / s

4. 8 * IO ' ² Pa * l / s beam generation chamber.

The technological flux F \\ xxu \ technological elaboration of the Zr-Ti alloys, in vacuum melting furnace, with electron flow, shown in Figurei, comprises the following operations;

you

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9 -06-2015

Preparation of raw materials

Description of raw materials. The following raw materials were used in the elaboration of Zr 5Ti, Zr 25Ti, Zr 45Ti alloys:

1. titanium wire, 3.25 mm in diameter;

2. Zirconium metal, sheet metal waste;

Raw materials Chemical composition, (%, weight) Ti Zr Fe C n ₂ The ₂ Cr The Wire of You 99.72 - 0.050 0.08 0.03 0.180 Plate of Zr - 99.60 0.138 0.01 0.03 0.042! 0.103 4. Physical characteristics of the elements d and alloys: metal Melting temperature (° C) Boiling temperature (° C) Density (g / cm ³ ) Atomic mass zirconium 1852 3580 6.49 91.224 Titanium 1668 3260 4.51 47.867

The preparation of the raw materials had as an objective the cutting of zirconia and titanium (strips of zirconium sheet with dimensions 0.5 x 20 x 40-50 mm were cut, titanium wire was cut in 700 mm segments).

The materials thus minced were degreased with an organic solvent (acetone), and then pickled with a mixture of sulfuric acid solution (25 g / l) and hydrofluoric acid (5 g / l). The milling was done manually, using the chisel, the hammer and a scissors to cut the board.

The pickling was followed by washing with water and drying in the oven at 120 ° C.

The dosing of the components was done using a piezoelectric balance 0-6 kg. When dosing the components, the losses due to vaporization were taken into account, and the fact that two melts are made.

After weighing, the cut materials were bound in bundles, with dimensions 50x40x700 mm ³ . The compositions after which the weighings were made:

Otherwise ZrTi 5% Small 25% Small 45% Small Excess You 20% 15% 10% (G) % (G) % (G) L ^% ........... Titanium 6000 5930 28.750 27.680 49,500 47.340 zirconium 95,000 93.870 75,000 72.210 55,000 52,600 Other 0.199 0,200 0.120 0.110 0.060 0.050 Total 101.199 100,000 103.87 100,000 104.560 100,000

Three bundles were made:

Alloy Zr 5Ti Zr 25Ti Zr 45Ti Total (g) Ti 180 862.5 1485 2527.5 Zr 2850 2250 1650 6750 Beam weight (g) 3030 3112.5 3135 9277.5

The melting was done in a crucible with a diameter of 60 mm.

After cooling the ingot in vacuum, these are subjected to a primer cutting operation (the connection piece between the ingot extraction device and the ingot), and turning on the generators

/

A- -2915--90129

19-OS-2015 for the removal of the superficial layer which generally accumulates impurities. The ingot thus prepared was cut on a generator, the two halves then welded together forming a bar that was fed into the furnace for refolding (melting II a).

Each beam was subjected to the first melt resulting in three ingots that were processed as above, after re-casting resulting in three final ingots. These were cut for the removal of the primers and were turned for finishing, with this occasion being taken samples for chemical characterization.

The actual chemical compositions of the three alloys are presented in the table below. From the table below it can be seen that the titanium losses were higher than estimated .__

Alloy Chemical composition (% mass) Zr Ti Fe Cr Other Zr 5Ti 97.766 4,230 0.199 0.039 0.400 ' Zr 25Ti 77.230 22,120 0.198 0.052 0,400 Zr 45Ti 57.270 42.150 0,140 0,040 0.400 i

Also, the fact that it was used for the synthesis of recyclable material alloys, certain impurities have significant values, these impurities being mainly brought by the zirconia used.

Claims (2)

1. Biocompatible alloys based on zirconia, characterized in that they have original chemical compositions (expressed as a percentage by mass): 1) 95% Zr - 5% Ti; 2) 75% Zr - 25% Ti; 3) 55% Zr - 45% Ti. The alloys are intended for the manufacture of implantable medical devices with orthopedic and dental structural applications in both human and veterinary medicine. 2. Biocompatible alloys based on zirconium (95% Zr-5% Ti, 75% Zr-25% Ti, 55% Zr-45% Ti, weight percent) characterized in that they have a titanium-controlled content and are formed entirely from metals known to be biocompatible.