Multipurpose biocompatible nanostructue membranulas for medicine

FIELD: medical equipment.

SUBSTANCE: the invention refers to biocompatible wearproof nanostructure thin-film materials on the basis of titan carbonitride, used as membranulas for manufacturing imlants, working under load. Total concentration of the basic and additional elements in a covering has the following ratio: where X_i - total concentration of basic elements Ti, Ta, C, N in the covering, Y_j - total concentration of additional elements Ca, Zr, Si, K, Mn, O, P in a covering, concentration of elements in the covering being chosen at the following ratio of components, at.wt%: Ti - 30-50; Ta 6-50; C - 15-40; N - 0-35; O - 5-25; Ca - 0-7; Zr - 0-20; Si - 0-30; P - 0-1.5; Mn - 0-1.0; K - 0-1.0.

EFFECT: high hardness of covering; low elasticity module; high durability of coupling with a substrate; low factor of friction and rate of deterioration; high firmness to elastic deformation of destruction and plastic deformation; low roughness of the surface; negative charge of the surface in physiological mediums; bioactive surface; biocompatibility and absence of toxicity.

16 ex, 1 tbl

The invention relates to medical equipment, namely to multifunctional biocompatible nanostructured films used as the modifier of the films in the fabrication of implants, working under load: orthopedic and dental implants, dental crowns, implants, used in maxillofacial surgery, artificial joints, clamps, etc. These materials should possess high hardness, fatigue strength, wear and corrosion resistance, biocompatibility and lack of toxicity.

Known medical implant coated with an amorphous layer of hydroxyapatite and titanium, which has a high bonding strength of the film substrate and the low dissolution rate of the film material. The implant consists of a substrate and a film deposited on the surface of the substrate from composite targets containing 10-75% titanium and 90-25% of hydroxyapatite (US 6344427, published. 5.02.02).

Method of production of such an implant includes the following steps: production of the substrate, the production of a composite target consisting of 10-70% by volume of titanium and 90-25% by volume of hydroxyapatite; coating the substrate with a composition of the target surface film by the method of ion sputtering, laser removal or physical method steam application.

However, Dunn is e coating can not be used for implants, working under load (dental implants, implants for reconstructive and bone-plastic surgery of the facial skeleton, astrogirl, implants for fixation of the cervical and lumbar spine, and others), due to low values of the mechanical and tribological properties.

Known low-modulus alloy containing niobium, tantalum and at least one metal from the group composed of zirconium, tungsten and molybdenum. Manufactured from this alloy medical materials have high functional characteristics, are biocompatible, radiopaque and is suitable for use with a magnetic resonance imaging system (EP 1444993, published. 11.08.04).

However, this biocompatible alloy has a low bioactivity, i.e. slow the rate and extent of osseointegration of the implant in the tissue environment, and niobium may cause toxic reactions.

Known composite material (EN 2227011, published. 20.04.04), including Apatite in the amount of less than 90 vol.%, preferably 5-80 vol.%, even more preferably 10-50 vol.% and most preferably 25-45%. Phase Apatite can be a pure hydroxyapatite or mixtures of phases Apatite, i.e. hydroxyapatite and fluorapatite. The main biologically inert mass in the composite material preferably has the structural ceramics, preferably one or more oxide, for example, aluminum oxide, zirconium oxide and/or titanium oxide. The main biologically inert mass can be a structural metal, preferably based on Fe and Co-Cr, or structural metal on the basis of Ti, TA or Zr. The content of structural metal may be 10-95%, preferably 40-95% vol. and more preferably 55-85%, and, accordingly, to prevail in the material. In addition to the Apatite and the main biologically inert mass basis may also be present content is low (preferably below 10 vol.%) other phases.

However, this composite material is nanostructured coating and does not possess the whole set of service properties required for implants, working under load, and high values of biocompatibility, bioactivity, corrosion resistance in biological environments, fatigue and breaking strength, wear resistance and low modulus of elasticity and coefficient of friction.

The prototype of the claimed invention is biocompatible multicomponent nanostructured films for implants (EN 2281122, 10.08.06), working under load, based on titanium carbonitride with the introduction of additional elements which improve the mechanical and tribological properties of the films, and the e ensure its bioactivity, biocompatibility and non-toxicity, at a certain ratio of the total concentrations of major and minor elements. The concentration of elements in the coating is selected when the following ratio of components, at.%: Ti 30-50, With 15-40, N 0.5-30, O 5-25, Sa 0-7, Zr 0-20, Si 0-30, P 0-1 .5, Mn 0-1 .0, 0-1 .0

The invention achieves the technical result consists in the creation of multifunctional biocompatible nanostructured films with compared to prototype a higher passivation characteristics and a lower corrosion rate. Increased corrosion resistance of the films in the first place, is determined by tantalum. In addition, the films have a high hardness, a low elastic modulus, high adhesive strength, low friction coefficient and wear rate of both on air and in different physiological environments, high resistance to elastic deformation, fracture and plastic deformation, low surface roughness, a negative surface charge at the pH of the medium (4,5<pH<9), increased bioactivity; biocompatibility and lack of toxicity. This technical result is achieved as follows.

Biocompatible multicomponent nanostructured films for implants operating under load, is made on the basis of the carbonitride titans the introduction of additional elements, to improve the mechanical and tribological properties of the films, as well as providing its bioactivity, biocompatibility and non-toxicity. Total concentrations of major and minor elements in the coating have the following relationship:

where X_i- the total concentration of major elements Ti, TA, C, N in the floor,

Y_j- total concentration of the additional elements (CA, Zr, Si, K, Mn, O, P in the floor.

The concentration of elements in the coating is selected when the following ratio of components, at.%:

Ti - 30-50

TA - 6-50

- 15-40

N - 0-35

O - 5-25

Sa 0-7

Zr - 0-20

Si - 0-30

R - 0-1 .5

Mn - 0-1 .0

K - 0-1 .0

High complex of physical, chemical, mechanical, tribological and biological properties of the films according to the invention is achieved by inclusion in the composition of the films of the components in the proportions specified above.

The titanium carbonitride has a high hardness, wear and corrosion resistance.

The deposition of films in argon leads to the formation of coarse columnar structure with high porosity. The content in the composition of the film of nitrogen leads to grinding and compaction patterns, and in some cases to a complete suppression of the column structure. The crystallite size, as a rule, does not exceed 20 nm. The roughness of the films SN is supplied with the introduction of nitrogen in the composition of the film.

Optimal is the ratio of the metal (Me) to nonmetallic elements (NMe) Me/NMe=1.0-1.7, in which the film had a cubic NaCl-type structure.

While the introduction of the films additional element of tantalum in the number of 6-50% has a positive effect on the whole range of mechanical, chemical, tribological and biological properties due to the formation of a complex carbonitride of titanium and tantalum (Ti,Ta)C_xN_y. Dissolution of tantalum in the carbide (or carbonitride) titanium leads to the increase of microhardness and corrosion resistance. A unique advantage of tantalum carbonitride TaC_xN_yis that it is more chemically stable and bioactive compared to other known dual carbides and nitrides. Biocompatible film tantalum have parameter values N/E, describing the resistance to elastic deformation of destruction and N³/E²describing the resistance to plastic deformation, respectively, 0.1-0.15 and 0.5-0.9 GPA, which is significantly higher than that of metals, alloys and ceramics used as orthopedic and dental implants. The film showed consistently low coefficient of friction in the range of 0.17-0.22 (air) and 0.24-0.25 (physiological solution). Film doped with tantalum passivation have the characteristics above, and corrosion rate lower is, than films of the same composition, but without tantalum, they have also increased bioactivity, biocompatibility and lack of toxicity.

When the concentration of tantalum in films less than 6% not observed quantitative advantages in comparison with the prototype because of the small content of complex carbonitride (Ti,Ta)C_xN_y. When the concentration of tantalum over 50% increase of the residual stress in the films, resulting in delamination of the film from the substrate of the implant.

The formation of a layer of Apatite is associated with the formation of hydroxypentanal of negatively charged groups on the surface of bioactive ceramics in the internal environment of the organism. This film introduces elements such as CA, P and O in the claimed amount. The presence of calcium ions stimulates the growth of cells on the implant surface. The increase in the content of CA, P and About more than the claimed amount leads to reduction of mechanical and tribological properties of the films, and also to the destruction of the actin cytoskeleton of cells and deterioration of the adhesion properties of the surface (table 1).

In the whole investigated range of pH values (4,5<pH<9) the surface of the films has a negative charge. Films with nitrogen, as a rule, have a more negative surface charge. This means that the surface films can attract positively charged the ons CA ²⁺that are in the internal environment of the body that promotes formation of the first intermediate, calcium-bearing phases, and then a layer of hydroxyapatite, which is a stable phase in the physiological environment.

Introduction to the film elements (CA, Zr and leads to a significant reduction of the friction coefficient to 0.17-0.25 compared to plunkie-based carbide (0.85) or nitride (0.55) titanium.

Attachment of cells to the implant surface is determined by the formation of integrin-mediated focal contacts in cells from the subject surface. The addition of Mn in the amount of <1 at.% leads to activation of integrins and improve adhesion of cells. Further increase in the Mn content leads to a decrease of mechanical properties of films and reduce rasplastyvanija and cell multiplication. Silicon increases the activity of osteoblasts and the formation of a layer of Apatite. When its content is less than 30 at.% films possess single-phase face-centered cubic NaCl-type structure, which has a positive effect on the mechanical and tribological properties.

Composite target and the electrodes can be obtained by the method of self-propagating high temperature synthesis (SHS). Unlike other known methods of producing composite cathodes of high-melting compounds (pressing-sintering, the gas is static pressing, thermal spraying and other) technology SVS has the following advantages: self-cleaning of combustion products from harmful soluble and adsorbed impurities as a result of the high temperatures (2500-3000° (C) and the rate of burning (2-10 cm/s)developed in the combustion wave SHS-systems, achieving high values of relative density (97-99%) of ceramic materials and refractory compounds at relatively low pressing pressures; obtaining metastable States is supersaturated solid solutions; obtaining functional gradient materials (Levashov E.A., Rogachev A.S., Yukhvid VI, Borovinskaya I.P. Physico-chemical and technological bases of self-propagating high temperature synthesis, M., BEAN, 1999, 174 S.).

Inorganic additives, for example, hydroxylapatite (CA₁₀(PO₄)₆(OH)₂), CaO, ZrO₂, KMnO₄and TiO₂etc. can be entered on the stage of production of composite cathodes targets for ion-plasma and/or ion-beam sputtering and electrodes for spark deposition.

The main technological advantage of the material films according to the invention is the presence of a complex of properties required for the surface modification of implants operating under load:

- high hardness N=20-40 GPA;

- low is the modulus of elasticity E=150-300 HPa;

- high adhesion of the film to the substrate, the measured value of the critical load L_c- more than 40 N;

- low coefficient of friction with Al₂About₃in physiological environments μ=0.1-0.25;

low speed wear V_wless than 10^-5mm³/Nm;

- high resistance to elastic deformation, fracture and plastic deformation of 0.5<H³/E²<0.9 GPA;

negative surface charge at physiological environments;

- potential corrosion of the positive - 0.2 when carrying out electrochemical tests according to GOST R ISO 10993-15-2001;

the corrosion rate of less than 0.05 μm/year in various biological environments;

- contact wetting angle <90°;

- no destruction of the actin cytoskeleton of the cells in the presence of surface bioactivity, biocompatibility and lack of toxicity.

The deviation of at least one of the above properties of the film causes deterioration of the performance characteristics of the entire product (implant) in General.

Low modulus of elasticity of the films is favorable from the viewpoint of reducing stresses between the coating and the implant, which is often used stainless steel E=190-200 HPa or titanium E=116 GPA. The low young's modulus also leads to better transfer of bone functional loads and stimulates the growth of costs the th tissue. The combination of high hardness and elastic recovery characterizes the proposed biocompatible film as a new, unique, solid, and at the same time, the elastic material that is the most important factor for medical supplies, working under load.

The invention is as follows.

Example 1.

Technological cycle of being prompted biocompatible films of Ti-Ta-Ca-P-C-O-N consists of two main stages: the production of composite targets (Ti,TA)C_x+CA₃(PO₄)₂for example by the method of self-propagating high temperature synthesis (SHS), and its subsequent magnetron sputtering on a substrate.

The deposition of the film Ti-Ta-Ca-P-C-O-N was carried out in the gas mixture of argon with nitrogen Ar+N₂at a partial pressure of nitrogen, equal to 14%. The result is a coating of the following composition, at.%:

C - 26.0

O - 11.3

N - 6.0

Ca - 1.3

P - 0.6

Ti - 46.0

Ta - 8.8

For measuring physico-mechanical and tribological properties of the films deposited on the substrate made of titanium alloy grades W 1-0, Nickel alloy Celite-N, cobalt alloy Celite, and Nickel-titanium.

Physico-mechanical and tribological properties of the films were determined using the following high-precision devices: Anotherdomain (Nano-Hardness Tester, CSM Instruments, Switzerland); Scratch-test is p (Revetest, CSM Instruments, Switzerland); friction Machine (Tribometer, CSM Instruments, Switzerland); a Scanning force microscope, equipped with a module for measuring the hardness of materials by the method scleroscopy with needles from ultratango fullerite₆₀(NanoScan, Russia); Optical AXIOVERT microscope equipped with digital camera and image analysis (Karl Zeiss, Germany). The hardness and elastic modulus were determined according to the method of Oliver and Headlight [G.M. Pharr, W.C. Oliver, F.R. Brotzen. J. Mater. Res. 3, 613 (1992)] using the indenter of the named Berkovich. The amount of elastic recovery (W_e) films was calculated by curve loading-unloading by the formula: W_e=(h_max-h_r)/h_maxwhere h_max- the maximum depth of penetration of the indenter, a h_rresidual depth after removal of the load. The friction coefficient and wear rate of the films was measured using a friction machine according to the scheme "ball drive" at a load of 1 N and a linear velocity of 10 cm/s Tests were carried out in saline solution (100 ml H₂O + 0.9 g NaCl). As counterbody was used stationary ball of sintered Al₂About₃with a diameter of 3 mm.

The resulting coating had a hardness of 39 GPA, the modulus of 330 GPA, elastic recovery of 70%, the friction coefficient and wear rate of physiological solution, respectively, 0.24 and 7×10^-7mm³N /m

Razrusheny the actin cytoskeleton of the cells was not detected. Rat fibroblasts Rat-1 and epithelial cells IAR-2 dissipated on the surface of the films deposited on glass. Cells were incubated for 24, 48 and 72 hours at a temperature of 37°C. Glass were fixed in 3.7% paraformaldehyde in phosphate buffer for 10 min, and then were stained with Hema-taxiline and concluded in a mixture of glycerol and phosphate buffer. Using light microscopy were counting the number of cells in field of view. Cells were sprawled and multiplied equally well as on the control glass and tested plancich, which suggests that the film of adhesive and non-toxic to cells.

The in vivo experiments were performed on mice. Samples of Teflon with the besieged them plancii was injected under the skin of mice. After 16 weeks, the implant formed around the capsule was removed and examined for biocompatibility. The results showed the absence of an inflammatory reaction inside the capsule, and the cells of the tissue tightly to the surface of the films.

Example 2.

The deposition of the films was carried out by magnetron sputtering of composite SHS targets (Ti,Ta)C_x+CaO in an argon atmosphere. The resulting coating of the following composition, at.%:

With-34.2

0-15 .0

N-0.1

Ti-40.6

TA-7.9

Sa-2.1

The resulting coating had a hardness of 40 GPA, the modulus of 340 GPA, elastic recovery of 72% and the ratio of the rhenium in the physiological solution of 0.24.

The destruction of the actin cytoskeleton of the cells was not detected. Studies in vitro and in vivo showed that the coating Ti-Ca-C-O-N is biocompatible, bioactive, non-toxic, does not cause an inflammatory reaction at the implantation under the skin of mice. Cells, fibroblasts and epithelial cells is well bred and has a high adhesion to the surface of the film.

Examples 3-16.

To optimize the composition of the films numerous experiments have been conducted to obtain a cathode targets of different compositions and deposition of films by magnetron sputtering technology. Table 1 summarizes the research results and properties of films, confirming the validity of the claimed compositions.

Films of the proposed structure have several competitive advantages necessary for implant materials, working under load: high hardness; low modulus; high adhesion; low friction coefficient and wear rate of; high resistance to elastic deformation, fracture and plastic deformation; low surface roughness; a negative surface charge in physiological environments (4,5<pH<9); bioactive surface; biocompatibility and lack of toxicity.

Biocompatible multicomponent nanostructured films for implants, working under load is th, based carbonitride with the introduction of additional elements which improve the mechanical and tribological properties of the films, as well as providing its bioactivity, biocompatibility and non-toxicity, in the following ratio of the total concentrations of major and minor elements:

where X_i- the total concentration of major elements Ti, TA, C, N in the floor,

Y_j- total concentration of the additional elements (CA, Zr, Si, K, Mn, O, P in the coating, the concentration of elements in the coating is selected when the following ratio of components, at%: