WO2021066667A1

WO2021066667A1 - Method for applying a vacuum ion-plasma coating of titanium oxynitride to the surface of intravascular stents

Info

Publication number: WO2021066667A1
Application number: PCT/RU2019/000694
Authority: WO
Inventors: Олег Станиславович КУЗЬМИН; Дмитрий Анатольевич ПЛЕХАНОВ; Михаил Викторович ЯКОВЛЕВ
Priority date: 2019-09-30
Filing date: 2019-09-30
Publication date: 2021-04-08

Abstract

The invention relates to the field of applying coatings by vacuum ion-plasma deposition, and more particularly to the application of titanium oxynitride coatings to the surface of metallic intravascular stents by magnetron sputtering, and can be used in various technical fields for applying thin films of metals and metal compounds. In terms of properties, intravascular stents having a coating applied using the proposed method should exhibit an improved effect by the artificial materials (nitrogen-alloyed coatings based on titanium oxide) on their thromboresistance by virtue of the uniformity of the functional properties of the coating, including on the inner surface of stents, and the excellent deformation properties of the coating during stenting. An article produced using this method (a coated metallic intravascular stent) contains a coating that includes an inner layer of high-purity titanium metal with a thickness of 15-40 nm, a gradated transition layer from titanium metal to titanium dioxide with a thickness of 5-15 nm, and an upper functional layer of oxynitride coating with a thickness of 100-200 nm.

Description

METHOD FOR APPLYING VACUUM ION-PLASMA COATING OF TITANIUM OXYNITRIDE ON THE SURFACE OF INTRAVASCULAR STENTS

FIELD OF TECHNOLOGY

The invention relates to the field of coating using vacuum ion-plasma spraying, in particular to the coating of titanium oxynitride on the surface of metal intravascular stents by magnetron sputtering, and can be used for the deposition of thin films of metals and their compounds in various fields of technology.

PRIOR ART.

A known method for growing a layer of oxynitrides of metals and transition metals (M _x (ON) _y ) on glass and flexible substrates using reactive radiothermal magnetron sputtering without heating the substrate, disclosed in the US application [US20090026065 A1, publ. 29.09. 2009 "Gas-timing method for depositing oxynitride films by reactive RF magnetron sputtering"].

The method consists in regulating the reaction time of the reagent gas for growing the metal and transition oxynitride (M _x (ON) _y ) layer and includes the following steps:

- providing a vacuum chamber for sputtering, equipped with a holder for ceramic and / or flexible substrates and a planar target cathode made of metal, transition metal or transition metal alloy;

- supply of gases to the spraying chamber in successive portions at appropriate flow rates: argon, oxygen, nitrogen;

- formation of a gas plasma in the sputtering chamber by a high-frequency generator (13.56 MHz), argon ions from which sputter the target cathode, and the oxygen and nitrogen activated by the discharge react with the forming film;

Argon is fed into the atomization chamber for ion bombardment, and nitrogen and oxygen form a reactive gas plasma generated by radio frequency, while the oxygen + nitrogen / argon flow rate ratio is at least 0.02, the oxygen / nitrogen flow rate ratio is at least 0.01, and the gas synchronization time (gas flow sequence control): argon, nitrogen and oxygen alternately or a mixture in a spray chamber for at least 1 s.

The disadvantages of this method are the planar geometry of the sputtered target, the low effective sputtering process with an HF discharge, the large values of the time constants for changing the composition of the gaseous medium, which limits the deposition rate and can lead to a layered structure of the grown coating.

Known products of the company Hexacath and the technology used to obtain these products. The information provided on the company's website https://www.hexacath.com/technology-device-description/ notes that it is generally accepted that a film of nitrogen-containing titanium oxide synthesized by the method of reactive magnetron sputtering (RMP) combines the properties of the following components : bioinert titanium oxide and nitric oxide. From the point of view of biological properties, the existing concept associates biological activity with the oxide forms of nitrogen compounds in the coating. A pioneer in the medical application of this type of coatings, the NEHASATN company has put forward just such an approach to the biomedical parameters of the interaction of Ti-0-N films with living tissues. The process is carried out in a high-vacuum unit with a cryogenic vacuum pump. The titanium atoms used for deposition are obtained by sputtering an electrode from a high-purity metal (99.99%). The synthesis of a coating of titanium nitride oxides is carried out from the products of HF plasma formed in a special configuration of the magnetic field at a low pressure of working gases: argon, oxygen, nitrogen. Titanium oxynitride (TΪ-NO) is applied to both the external and internal surfaces of the stent using the patented Hexacath process, which ensures the presence of NO compounds on the surface. The high hardness and absence of defects in the coating ensures successful direct stenting and protects the stent from damage by calcites. Also known is the EPO patent of this company, which protects the products of this company [EP1674117 (A1) - 2006-06-28], which notes that the main problem in the formation of the coating is to ensure high adhesion strength and the ability of the film to withstand high plastic deformations (up to 200% ) arising from angioplasty. To solve this problem, the authors have proposed a multilayer (from 7 to 13 layers) nanostructure, the deposition technology of which consists in alternating plastic metal, transition and solid nitride and oxynitride layers. Obviously, one of the main reasons for this problem is the one-zone model of the processing process: cleaning operations, bringing the magnetron to operating parameters, intermediate operations in a planar single-chamber architecture will not provide controlled purity of layers during HF sputtering, even in the presence of various shielding elements. It is this, first of all, that affects the plastic properties of such an intermediate layer material as titanium, which has the property of embrittlement with minimal contamination by impurities.

In addition, the deposition process is controlled by external parameters: the flow rate of the working gases, the operating modes of the RF plasma and bias power supplies, the procedure time or similar values for other proposed film deposition technologies (arc evaporation, thermochemical deposition). However, the stability of the HF sputtering mode, and hence the structure of the coating, is largely determined by the presence of secondary factors, such as the amount of erosion of the electrodes, the degree of contamination of the chamber with spraying products, and the chemical state of the electrode surface. The lack of feedback, fixing the parameters in the deposition zone, as well as diffusion thermal effects accompanying the methods of filtered arc evaporation or the thermochemical CVD process will lead to an uncontrolled change in the properties of the coating. This, first of all, affects the concentration and localization of NO compounds, which have a bioactive effect on the tissues of the body, and not the total content of oxygen and nitrogen in the surface layer.

As shown in the work [A.A. Barybin, A.V. Zavyalov and V.I. Shapovalov. A non-isothermal model of the synthesis of oxynitride films by the method of reactive magnetron sputtering [Physics and chemistry of glass, 2012, Volume 38, · N ° 4, pp. 515-522] the evolution of the structure of titanium oxynitride with increasing nitrogen content in the magnetron discharge is consistently described in terms of the modified Thornton model (SZM) N-T1O2 films. In the process of deposition, T1O2 grains are formed, which, with an increase in nitrogen, form a dispersed, randomly oriented compacted structure. This is due to the fact that, during growth, nitrogen is localized on low-index planes bounding nanocrystals titanium oxide, forming a 2D layer of nitric oxide [Alla A. Pustovalova, Vladimir F. Pichugin, Nina M. Ivanova, Michael Bruns. Structural features of N-cjntaining titanium dioxidt thin films dehjsited by magnetron sputtering // Thin Solid Films 627 (2017) 9-16 http://dx.doi.Org/10.1016/j.tsf.2017.02.056], which limits the epitaxial the growth of TiO2 crystallites, the growth of the film occurs due to repeated nucleation. Thus, the bioactivity of the coating (the ability to release NO) is determined by the dispersion of the nanocrystalline structure, i.e. the surface area of the crystallites of the ceramic layer [V.F. Pichugin, A.A. Pustovalova, K.E. Evdokimov et al. Structural features and physicochemical properties of nitrogen-containing titanium dioxide films grown by reactive magnetron sputtering. Films and coatings-2019, St-Peterburg. 507-510]. The deposition technologies proposed in the EPO patent [EP 1674117 (A1) - 2006-06-28] do not allow controlling this process through physical parameters.

In addition, the planar geometry of the process, as shown by the analysis of HEXATH stents, does not provide a film coverage of the surface of more than 75-80%.

DISCLOSURE OF THE INVENTION

The present invention seeks to overcome the aforementioned problems and overcome one or more of the discussed disadvantages.

The basis of the invention is the task of applying uniform coatings by the method of vacuum ion-plasma (magnetron) deposition with high adhesive strength and the ability to withstand high plastic deformations (up to 200%) on such products, for example, as intravascular stents.

The technical result is to obtain long-lasting titanium oxynitride coatings on metal intravascular stents, which combine the properties of bioinert titanium oxide and bioactive nitric oxide.

In terms of properties, intravascular stents coated with the proposed method should provide an improved effect of artificial materials (titanium oxide-based coatings doped with nitrogen) on their thromboresistance by ensuring uniformity of functional properties, including the inner surface of stents, high deformation properties of the coating during stenting. products. The problem is solved by the fact that the proposed method of applying a vacuum ion-plasma coating of titanium oxynitride (Ti-0-N) on the surface of metal intravascular stents (products) includes:

- placing and fixing the above-mentioned products on a rotating planetary working table of a vacuum ion-plasma installation, which includes separate airlock and vacuum (working) chambers;

- sealing the working table in the airlock equipped with a plasma generator;

- evacuation of the atmosphere and subsequent cleaning of products in the airlock with argon ions from the gas plasma due to the displacement potential on the work table;

- preliminary cleaning (training) of the electrodes of the dual magnetron sputtering system (DMS), located in the working chamber, in an argon atmosphere;

- moving the working table into a vacuum chamber with the placement of products inside the LCA, the electrodes of which have a cylindrical shape, in which:

- - first, a layer of high-purity titanium metal with a thickness of 15 - 40 nm, preferably 30 ± 5 nm, is deposited onto the surface cleaned with argon ions, which provides increased adhesion and high plastic characteristics of the said coating;

- then, in an atmosphere of argon and oxygen, a gradient transition layer from metal to titanium dioxide is formed with a thickness of 5-15 nm, preferably 10 ± 2 nm,

- - and finally carry out the deposition of the functional oxynitride coating in an atmosphere of argon, oxygen and nitrogen at a ratio of N2 / O2 equal to from 0.5 to 2.5 with a thickness of 100-200 nm, preferably 160 ± 15 nm.

In addition, the preliminary ion-plasma treatment of articles (stents) with a gas plasma generator is carried out at a pressure of 0.4-0.8 Pa, preferably 0.6 Pa, a discharge current of 5-10 A, preferably 7 A, and a pulse bias potential at the working table with parameters: pulse duration 3-25 μs with an amplitude of 500-700 V and a frequency of 10-80 kHz.

In addition, preliminary training of the dual magnetron sputtering system is carried out at an argon pressure of 0.07-0.15 Pa, a magnetron discharge power of 1.5-2.5 kW for 2-4 minutes. In the course of its implementation, the surface of the cathodes of the dual magnetron sputtering system (DMS) is cleaned; coating of open surfaces inside the working chamber with titanium metal; the residual pressure is reduced due to heterogeneous absorption by sputtered titanium, which ensures the absence of impurities and the ductility of the subsequently deposited metal layer on the products.

In addition, the deposition of the coating is carried out in the internal volume of the dual magnetron sputtering system formed by two cylindrical electrodes, with the planetary rotation of the products and supplying them with a pulse bias potential of 100-300 V with a frequency twice the frequency of the power supply pulses of the dual magnetron sputtering system, and pulse synchronization with polarity reversal on the electrodes.

When depositing a coating, it is preferred that:

- the deposition of a metal adhesive sublayer (deposition of a titanium film) is carried out in an argon atmosphere at a pressure of 0.10-0.15 for 3-7 minutes;

- the formation of an intermediate gradient transition layer from metal to titanium dioxide is carried out at a magnetron discharge power of 1.0-1.5 kW, while the oxygen consumption is selected in such a way that the beginning of the formation of amorphous titanium dioxide on the surface of the products occurs within 3-4 minutes, (accompanied, as a rule, by an increase in the total gas pressure from 0.10 Pa to 0.20 Pa);

- the deposition of a functional oxynitride layer is carried out in an argon, oxygen and nitrogen atmosphere at a ratio of nitrogen and oxygen consumption from 0.5 to 2.5, a total pressure of 0.17 0.25 Pa and a discharge power of 3.0 3.5 kW at a frequency power supply 10 - 40 kHz.

In addition, after the expiration of the time allotted for the establishment of the gas balance in the system from 20 to 40 s from the beginning of the titanium oxynitride deposition process, the spectral characteristics of the radiation of the cathode plasma of the dual magnetron sputtering system are monitored and the flow rate of the gas components is adjusted in order to maintain the ratio integrated radiation intensity of titanium to oxygen, in order to stabilize the deposition parameters of a functional oxynitride coating

In this case, to adjust the flow rate of gas components in order to stabilize the deposition parameters of the functional oxynitride coating the control signal of the spectrometer is used, the optical axis of the recorded radiation of which is located in the cathode region parallel to the cylindrical surface of the electrodes.

The automatic control system regulates the oxygen consumption and, proportionally, the nitrogen consumption in order to stabilize the given relative intensity of the radiation of oxygen atoms of the plasma to the emission line of titanium atoms at a stabilized discharge power.

BRIEF DESCRIPTION OF DRAWINGS.

Hereinafter, the present invention will be described by way of examples with reference to the accompanying drawings, in which:

- in Fig. 1 shows a block diagram of the installation of vacuum ion-plasma deposition of coatings;

- in Fig. 2 shows a block diagram of the N-T1O2 coating on a metal stent;

- in Fig. 3 shows a data exchange diagram for the entire software package of the installation.

- in Fig. 4 shows a PEM image of the stent surface after testing in the zone of maximum plastic flow.

CARRYING OUT THE INVENTION

To implement the method proposed in the present invention, a device was developed (Fig. 1).

The installation (Fig. 1) contains a vacuum chamber 1 with a dual magnetron sputtering system (MS) 2 located in it with titanium cylindrical cathodes 3 to which a lock chamber 6 is connected through a gate 5 with a gas plasma generator 7 installed in it for preliminary ion-plasma treatment and a transport planetary work table 8 for loading products; high-vacuum pumping system including oil-free pumping means; three-channel gas supply system 11; a power supply for the magnetron sputtering system 12, a power supply for the bias potential of the working table 13, power supplies for the gas discharge 14, 15 of the plasma generator 7; an automatic control system 16 and means for monitoring the technological process, including a spectrometric analyzer of plasma radiation 17, pressure and cooling sensors, and a control computer 18. The electromechanical drive M provides a linear movement of the working table 8 into the vacuum chamber 1 using a telescopic screw device 21. The working table 8 is equipped with planetary satellites and has attachments for the workpieces.

Vacuum chamber 1 is a sealed vacuum volume, inside of which there is a dual magnetron system 2 with a working area for processing along the axis of cylindrical titanium electrodes (cathodes) 3.

The vacuum chamber 1 has an optical channel for transmitting the radiation of the magnetron discharge to the automatic spectrometer 17. The optical axis of the probe 27 is parallel to the surface of the cylindrical cathodes 3 in the area of the near-cathode plasma. For example, an AvaSpec-Mini 4096CL-UV-5 spectrometer can be used as a spectrometer, and an FC-UVIR600-2-ME fiber optic cable can be used as a probe.

The MS magnetron sputtering system consists of two, one above the other, identical cylindrical magnetron electrodes (or electrode devices) 2 with their own magnetic systems.

The control and monitoring system 16 is designed to control the units and mechanisms of the installation in accordance with the specified algorithms for conducting the technological process.

The products, after ion treatment in the lock chamber 6, are moved into the vacuum chamber 1 by a telescopic transport system (telescopic screw device 21) of the working table 8, and during the spraying of coatings, a circular planetary motion of the processed products is carried out.

Symmetrical bipolar power from the power supply 12 is fed to magnetron electrodes 2, deposition is accompanied by a pulsed bias potential on the products, synchronized with the polarity change on the electrodes 3. The stability of the film synthesis process is ensured by monitoring the intensity of the spectral lines of radiation of titanium, nitrogen and oxygen atoms in the magnetron discharge plasma, moreover, the control signal to the regulators of the oxygen and nitrogen gas consumption is normalized to the intensity of the titanium emission line, and the power of the magnetron discharge and the argon consumption are stabilized.

EXAMPLES OF SPECIFIC IMPLEMENTATION OF THE METHOD

According to the technological program shown in Table 1, the processing of pilot batches of intravascular implants made of steel 316L (AISI) and flat samples-witnesses with different ratio of gas consumption N2 / O2 for further physico-mechanical and medico-biological studies, including both the determination of the reaction of the obtained coatings to various modeling media, and interactions with living tissues. Table!.

The structural diagram of the applied coatings is shown in figure 2, where 1 is the stent material, 2 is the titanium sublayer, 3 is a transition gradient layer, 4 is a functional layer of titanium oxynitride. Example 1. Deposition of the surface layer at a ratio of consumption of gas reagents N2 / O2 equal to 1.5 (with the parameters indicated in Table 1).

Preparation of products for coating.

Loading of products - pre-defatted metal stents (20 metal cardiostents 1.6x18 mm manufactured by "Balton" Ltd.) - is carried out by suspension on the planetary satellites of the desktop 8 of the vacuum ion-plasma installation (Fig. 1) by a method that minimizes the contact area with samples. Samples-witnesses (2 pcs. - glass, 2 pcs. - steel 316L (AISI) are placed in identical positions. Loops of a silver-plated copper conductor MC16-13 0.02 wire were used as a material for suspension. Diameter 45 microns provides a small contact area with the sample and has sufficient rigidity for fixation. Processing of products in a vacuum ion-plasma installation.

Pumping out the lock chamber to a predetermined level of residual pressure (- 6.7x10-3 Pa).

Further, the processing of products is carried out automatically in accordance with the technological program (TP), which assumes, in accordance with the parameters given in Table 1, the sequential execution of the following operations:

- Ion-plasma cleaning of products in a gas discharge of a plasma generator due to bombardment of the surface with charged particles, accelerated by the supply of a pulsed displacement potential to the working table.

To perform the operation, the working gas is supplied to the plasma generator - argon (position No. 2: 1.08 ± 0.05 l / h (30% of the maximum range of 3.6 l / h)); the drive of the working table is switched on in reverse mode (position N ° 3: M - out); processing parameters are set and switched on (positions N ° 4-9): cathode heating (PS1 40 A, on) and generator discharge power (PS2 7.5A, on); Bias voltage pulses are applied to the desktop (PS3 600 V, 6 μs, 40 kHz, on); the timer for the operation is started (position ° 10: Pause 300 s). At the end of the timer, the power supply from the plasma generator is turned off (position N ° 10: PS1 off, position Nell: PS2 off) and reverse is turned off (position N ”12: M - off).

- Training of a dual magnetron sputtering system (DMS).

For these purposes, the program corrects the flow of the working gas-argon into the working chamber (position N ° 14: VF1 - 12%); the bipolar power supply is switched on to the DMS electrodes in the specified mode (positions N ° 15-16: PS4 - 2.0 kW, 10 kHz, on); the magnetron is trained for the time specified by the program parameter (position N ° 17: PAUSE 180 s), after which the discharge voltage is removed (position N ° 18: PS4 - off).

- Transportation of the work table from the airlock to the processing area

LCA.

For this, the drive of the desktop is switched on in the direction of transportation from the lock (position Nel9: M - in); the bias potential is reduced to values suitable for deposition of coatings (position N ° 20: PS3 250 V, 20 kHz); the operation of the inductive position sensor in the working chamber is expected, after which the next operation starts.

- Deposition of a metal adhesive sublayer (position 2 in figure 2). When performing the operation, the trained LCA is switched on in the metal deposition mode (position 1 21: VF1 - 6.5 N ° 22: PS4 - on) and the titanium film is deposited within the time specified by the program (position N ° 24: PAUSE - 300 s) , which determines the thickness of the metal sublayer 30 ± 5 nm. Products installed on the working table make planetary motion in the working area of the LCA.

- Transfer of the parameters of the DMS operation to the oxide deposition mode with the formation of a gradient transition layer from metal to titanium dioxide (pos. 3 in Fig. 2). Physically, the process is accompanied by a change in the discharge parameters at a stabilized power: a decrease in potential and an increase in current, as well as a gradual increase in the total pressure from ~ 0.1 to ~ 2.0 Pa. This approach ensures the stable subsequent operation of the DMS on the descending branch of the hysteresis loop of the discharge in the medium of reactive gases: argon - oxygen - nitrogen.

For these purposes, the discharge power is reduced (position N ° 25: PS4 - 1.0 kW, 80 kHz) and the oxygen supply (position N ° 26: VF2 - 12%) is switched on at a given flow rate, which ensures a smooth transition to the oxide deposition mode within 3-4 minutes ... The spread in the formation time of the required parameters, and hence the thickness of the transition layer, depends on various secondary factors, therefore the operation timer is set deliberately exceeding the maximum required procedure time (position N ° 27: Pause 240 s). During this time, in the specified mode, a gradient layer (position 3 in Fig. 2) is formed from titanium metal to amorphous dioxide with a thickness of about 10 ± 2 nm.

- Directly deposition of a functional oxynitride coating (position 4 in Fig. 2).

In the course of this operation, the following is performed: oxygen consumption correction (position N ° 28: VF2 - 3.40%); inclusion of leakage into the nitrogen chamber (position N ° 29: VF3 - 5.10%) in accordance with the preset starting values (VF2, VF3); output of LCA parameters to a given discharge power (position 30: PS4 - 3.0 kW); and then, after the expiration of the time allotted for the stabilization of the gas balance (position I: Pause - 30 s), the monitoring of the spectral characteristics of the radiation of the cathode plasma is switched on (position N ° 30: As - on). The processed control signal of the spectrometer is used to correct oxygen and nitrogen in order to stabilize the deposition parameters of the functional coating. The software (software) of the spectrometer is an integral part of the software of the installation.

For data exchange with external equipment, Simle-Scada is an OPC client that connects to the OPC server.

Figure 3 shows a data exchange diagram of the entire software package. Functionally, the spectrometer software can be divided into three modules:

- AvaSpec DLL library;

- spectrometer data processing program;

- OPC server.

The data processing program interacts with the spectrometer through the AvaSpec DLL, processes the received data in accordance with the radiation peak integration algorithm, and interacts with the OPC server to receive commands and issue the calculation results.

The OPC server exchanges data with the Simple-Scada system of the plant control program.

The OPC server interface includes a set of variables with fixed names and data types.

The control signal implements the following function of the measured spectrum of the DMS plasma:

where Ii is the integrated intensity of the signal from the ROM of the matrix

spectrometer corresponding to the peak of the radiation wavelength of titanium atoms Tί _h, and g I

* ί corresponds to the emission of molecular oxygen. The quantity '

Thus, by correcting the current oxygen consumption, the system maintains a constant ratio of the radiation peaks of the plasma components at a stabilized discharge power. After a predetermined time interval (position N ° 33: Pause 1800 s), the power supply to the magnetron is turned off, the potential is removed from the working table, the supply of working gases to the vacuum system is shut off (positions N «34 - Ke41). During the time (1800 s), the deposition of a layer of N-T1O2 (position 4 in Fig. 2) with a thickness of 160 ± 15 nm occurs.

The technological program has been completed.

- When the next command "START UP" is given, the working table is transported to the airlock, the working chamber is sealed and the atmosphere is released into the volume of the airlock.

The unit is ready for the next machining cycle.

The given technological program corresponds to the mode of deposition of the surface layer with the ratio of the consumption of gas reagents N2 / O2 equal to 1.5, set by the regulators VF2, VF3 (Fig. 1) at the program step 28, 29.

The mechanical properties of the coatings were investigated by the method of dynamic nanoindentation using an NHT-S-000X device at a load of 5 mN, as well as using a NanoScan scanning nanohardness tester. Nanohardness, Young's modulus, and contact stiffness were determined by the Oliver-Pharr method. Elastic recovery was determined from load-unload curves.

Tests for plastic deformation of the treated stents were carried out by the method of balloon expansion to the maximum diameter at a test pressure in the standard system up to 2.0 MPa, followed by electron microscopy of the zones of tension and compression.

The thickness of the Ti – O – N coating was determined by the method of optical ellipsometry of flat witness specimens treated simultaneously with stents. The spectroanalytical complex "SAG-1891" was used. The calculation was carried out using the Cauchy dispersion equation for transparent or semitransparent films.

To assess the biological properties of coatings, methods were used that simulate the interaction of samples in vitro with biological media.

Automated chromatic infrared microscopy was performed using a Thermo Nicolet ™ iN ™ 10 instrument. Coated samples were placed in cuvettes containing body fluid (SBF) and albumin. To study the dynamic characteristics of stents, we used a device that simulates their behavior in a vessel. The special system included an artificial vessel, a peristaltic pump type MCP Process IP 65 (ISMATEC GmbH), sensors for monitoring temperature, flow rate and pH values. Simulated blood plasma (SBP) was used as a test medium. The stents were placed in silicone tubes (r = 1.5 mm) under conditions of simulating the blood vessel system.

The morphological properties of the surface of the samples were analyzed before and after exposure using a scanning microscope (XL 30 ESEM-FEG Philips, voltage 3.0 kV). Elemental and chemical analysis - using EDS and FTIR microscopy.

The hydrophilicity / hydrophobicity of the coating surface was determined by measuring the contact angles using an OSA 20 instrument (DataPhysics Instrument Gmbh) with the appropriate SCA 202 software.

The electrochemical corrosion resistance of the stent samples was determined from the linear sweep current-voltage characteristic (LSW) with an IviumStat.h potentiostat. SBP was used as the test solution (pH = 7.4).

The analysis of the interaction of living tissues with the coating was carried out by in vitro testing of the reaction of human mesenchymal stem cells (MMSC) isolated from lipoaspirate of adipose tissue of a conventionally healthy donor.

The complex of studies performed shows that functional oxynitride films have a quasi-uniform nanocrystalline structure N—

T1O2 and consist of an amorphous phase with the presence of anatase and rutile nanocrystallites.

With an increase in the bias potential and an increase in the nitrogen content, the crystallite sizes decrease, the fraction of rutile increases, up to complete amorphization of the ceramic layer. The average size of coherent scattering regions (CSR) is less than 10 nm. Analysis shows that anatase nanoparticles are limited by the (101) and (100) planes, and rutile, by the (110) planes.

Using high-resolution X-ray photoelectron spectroscopy (XPS HR), it was shown that titanium is oxidized to Ti ⁴⁺ (T1O2 stoichiometry) regardless of the N2 ratio in the working gas. The 01 S oxygen spectra contain peaks corresponding to the bonds Ti-0 (529.9 eV), Ti-ON (531.3 eV), and Ti-OH (532.4 eV), respectively. X-ray shifts of the Nls spectrum peaks of nitrogen refer to chemisorbed molecular nitrogen N ₂ (399.9 eV) and nitrogen oxides NO (402.0 eV) and NO2 (406.2 eV). The Gibbs free energy of formation of titanium nitride is AGTiN = -308/9 kJ / mol and AGTi02 = -888.9 kJ / mol, because of this difference, TiN is not formed in the film structure until the 2 / O2 ratio exceeds 2.0. This suggests the localization of nitrogen oxide forms along grain boundaries in the N-Tίq2

The results of studies of the physical and mechanical properties of coatings are presented in table a 2.

Table a 2

Nitrogen-containing N-T1O ₂ films deposited by reactive magnetron sputtering have high values of nanohardness (up to 28 GPa), Young's modulus (up to 231 GPa), elastic recovery (up to 70%), and high adhesive strength (up to 376 MPa), and this determines good elastic properties and crack resistance. The deformation of the stents by the test pressure showed that the process occurs without cracking and detachment.

Figure 4 shows a PEM image of the surface after testing in the zone of maximum plastic flow, where a is an uncoated stent; b - stent coated with Ti + N-T1O ₂ (example) after balloon deformation of 2.0 MPa.

Tests of dynamic stability during imitation of vascular implantation in the SBP flow medium simulating blood plasma showed that the presence of deposits was observed in individual nodes of plastic deformation of the opened stents. Moreover, the number of defective areas decreased with an increase in the ductility of the coating caused by a decrease in the grain size of the realized structure with an increase in the nitrogen concentration and displacement potential. The main types of sediments are identified as apatite, calcite and phosphate.

Incubation of HUVEC cells after 24 and 48 hours showed no toxic effect of the Ti + N-T1O ₂ surface on the cultures. However, samples with increased nitrogen content showed a slight but clearly detectable increase in metabolic activity. They also showed the lowest protein adsorption, and minimal salt deposition from model living body fluids. A variation in the ratio of reactive gases during deposition towards nitrogen dominance leads to a decrease in the roughness of the coating, a decrease in the grain size and, as a consequence, an increase in the plasticity of the film, and hence a decrease in defectiveness during implantation of stents.

Evaluation of the differentiation of the culture of multipotent mesenchymal stromal cells (MMSC) after 21-day contact with the test samples by selective cytological staining, showed that the coated samples

Ti + N-T1O ₂ does not cause differentiation of the culture into osteoblasts, cartilage cells and fat cells. In the context of the 7 day coculture samples s_napyleniem Ti + N-T1O ₂ significantly reduced (by 40%, p <0.05) mean number MMSC (due to migration and cell division) in comparison with the coated hm _2.

Based on the analysis of the results obtained on in vitro assessment of the effect of active forms of nitrogen oxides in the magnetron coating Ti + N-T1O ₂ , the following conclusions can be drawn: - The coatings are bioinert, which leads to a low risk of ectopic transformation of the vascular wall MMSC into other cell types around the coated stents and the formation of calcifications.

- Ti + N-T1O ₂ coating, especially for the sample with N2 / O2 - 1.5, reduce the risk of restenosis due to excessive cell regeneration.

Thus, according to the results of biomedical studies, it was concluded that the developed method of deposition of coatings based on titanium oxynitride favors the adaptation of implants to the biological environment. INDUSTRIAL APPLICABILITY

The proposed method provides the application of uniform nanocomposite multicomponent (Ti-0-N) coatings on vascular stents, due to the uniform deposition of the material in argon and reaction gases: oxygen, nitrogen. The effectiveness of the method is achieved by sluicing products, dividing the zones of ion-plasma cleaning of the surface of products and spraying, moving the working table for transporting products from the sluice to the working chamber with their planetary rotation inside a special cylindrical dual magnetron system in combination with synchronized pulse modes of supply of the displacement potential of the working table, control of the deposition process based on the spectral characteristics of the plasma, the use of modern vacuum equipment and controls, automation of the technological process.

Claims

CLAIM

1. The method of applying a vacuum ion-plasma coating of titanium oxynitride (Ti-N-O) on the surface of metal intravascular stents includes:

- placing and fixing the mentioned stents on a rotating planetary working table of a vacuum ion-plasma installation with a dual magnetron sputtering system, including separate airlock and vacuum (working) chambers;

- sealing the working table in the airlock equipped with a plasma generator; - pumping out the lock chamber to a predetermined level of residual pressure and subsequent cleaning of the stents in the lock chamber with argon ions from the gas plasma by supplying the bias potential to the working table;

- preliminary cleaning (training) of the electrodes of the dual magnetron sputtering system, located in the working chamber, in an argon atmosphere;

- moving the working table into the vacuum chamber, with the placement of stents inside a dual magnetron sputtering system, the electrodes of which have a cylindrical shape, in which the deposition of the mentioned coating is sequentially carried out, and: - first, a layer of metal - titanium (Ti) high purity with a thickness of 15-40 nm, providing increased adhesion and high plastic characteristics of the coating;

- then, in an atmosphere of argon and oxygen, the formation of a gradient transition layer from metal to titanium dioxide (TiOr) with a thickness

5-15 nm,

- and finally, in an atmosphere of argon, oxygen and nitrogen with a gas consumption ratio N2 / O2 equal to 0.5-2.5, a functional oxynitride layer (N-T1O2) with a thickness of 100-200 nm is deposited.

2. The method according to claim 1, characterized in that the preliminary ion-plasma treatment of products by a gas plasma generator is carried out at a pressure of 0.4-0.8 Pa, preferably 0.6 Pa, a discharge current of 5-10 A, and a pulse potential displacement on the desktop with parameters: pulse duration 3 - 25 μs, amplitude 500 - 700 V, frequency 10 - 80 kHz.

3. The method according to claim 1, characterized in that the training of the dual magnetron sputtering system is carried out in an argon atmosphere at a pressure of 0.08 - 1.5 Pa, a magnetron discharge power of 1.5 - 2.5 kW for 2-4 minutes.

4. The method according to claim 1, characterized in that the deposition of the coating is carried out in the internal volume of the dual magnetron sputtering system formed by two cylindrical electrodes, with the planetary rotation of the products and supplying them with a pulsed bias potential of 100-300 V with a frequency twice the frequency power supply of the dual magnetron sputtering system and synchronization of pulses with polarity reversal on the electrodes.

5. The method according to claim 1, characterized in that the deposition of the titanium metal adhesive layer is carried out in an argon atmosphere at a pressure of 0.07-0.15 Pa for 3-7 minutes and a magnetron discharge power of 1.5-3.5 kW.

6. The method according to claim 1, characterized in that the formation of an intermediate gradient transition layer from metal to titanium dioxide is carried out at a magnetron discharge power of 1.0-1.5 kW, while the oxygen consumption is selected in such a way that the beginning of formation on the surface of the products amorphous titanium dioxide occurred within 3-4 minutes.

7. The method according to claim 1, characterized in that the deposition of the functional oxynitride layer is carried out at a total pressure of 0.17-0.25 Pa and a discharge power of 3.0-3.5 kW at a power frequency of 10-40 kHz.

8. The method according to claim 1, characterized in that when the functional oxynitride layer is deposited, 20-40 s after the gas mixture is supplied, the plasma radiation spectrum from the cathode region of the magnetron discharge is monitored and the current flow rate of oxygen and, proportionally, nitrogen is adjusted in order to stabilize the ratio of the integral intensity of radiation by the plasma of the spectral line of titanium to oxygen at a constant power of the magnetron discharge.

9. Metal intravascular stent, characterized by the fact that it contains on the surface an oxynitride coating (Ti — N — O) obtained by the method according to any one of paragraphs 1-8, and the said coating contains a lower, adjacent to the surface, a layer of metal (Ti) - titanium thickness from 15-40 nm, a gradient transition layer from metal (Ti) to titanium dioxide (TiOr) with a thickness of 5-15 nm and an upper functional layer of titanium oxynitride (N-TiOr) with a thickness of 100-200 nm with a nitrogen content in the form of N-0 compounds.

10. A metal intravascular stent according to claim 9, characterized in that preferably the inner titanium layer has a thickness of 30 ± 5 nm, the gradient transition layer from metal to titanium dioxide has a thickness of preferably 10 ± 2 nm and the upper functional layer of titanium oxynitride, preferably - 160 ± 15 nm.