Implanted medical device, containing biodegradable alloys

FIELD: medicine.

SUBSTANCE: group of inventions relates to medical devices, containing highly-strong alloy, eventually subjected to degradation in human or animal organism, at adjustable degradation rate, without formation of emboli. Described is device for bone fixation, such as fixer, screw, plate, support or rod, made from alloy, as well as device for tissue fixation, such as staple, made from alloy. Dental implant or stent, made from alloy, is described.

EFFECT: alloy-containing devices possess required steel-associated properties, being simultaneously biodegradable.

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The present invention claims priority on Provisional application for U.S. patent No. 61/143378, filed January 8, 2009; No. 61/168554, filed April 10, 2009; and No. 61/260363, filed November 11, 2009, the contents of which are included in the description by reference.

The technical field to which the invention relates

The present invention relates to biodegradable materials suitable for the production of implantable medical devices, in particular to biodegradable compositions containing metal alloys, which provide high initial strength at implantation and gradually erodium and replaces the tissue of the body.

The level of technology

Medical devices designed for temporary or semi-permanent implant, often made of stainless steel. Stainless steel is durable, can withstand a greater load is sufficiently inert in the body, is not soluble in body fluids, and is a long-term, remaining for many years, if not decades. However, long-term medical implants are not always necessary. Many devices for bone fixation create problems as the bone heals, requiring removal with subsequent operations. Likewise, short-term devices, such as brackets fabric, you need to uninstall after shivlani� tissue, which significantly limits their use.

Attempts to create biodegradable materials traditionally focused on polymer compositions. One example is described in U.S. Patent No. 5932459 towards biodegradable amphiphilic polymer. Another example is described in U.S. Patent No. 6368356 directed to biodegradable polymeric hydrogels for use in medical devices. Biodegradable materials used in bone fixation described in U.S. Patent No. 5425769 sent on a mixture of CaSO4and fibrous collagen. Further, U.S. Patent No. 7268205 describes the application of biodegradable polyhydroxyalkanoates in the production of such bone fasteners like screws. However, none of designed to date, polymeric materials do not demonstrate sufficient strength, in cases when the material must withstand substantial loads when necessary plastic deformation of the material during implantation, or when for any other material required inherent to the metal on the nature of the property. For example, polyhydroxyalkanoate composition described in U.S. Patent No. 7268205, themselves do not possess sufficient strength to withstand the load, and they need to be strengthened by means of temporary fixation of bone segments. In addition, biodegradable polymeric materials has�t trend to a much more rapid loss of strength, what is their degradation, because of the material under stress conditions become more reactive, which contributes to preferential dissolution and destruction of sections under load.

Thus, the metals, particularly steel, are preferred in the design of many medical implants. Performance became closely match the mechanical requirements for many medical devices that carry the load. Although the normal connection, steel, unlike stainless steel, dissolved in biological fluids, they are not suitable for biodegradable medical devices. This is because ordinary steel is not destroyed predictable way, as one molecule or group of molecules per unit time, which can be easily removed by the body. Rather, because of coarse-grained structures, conventional steel collapses first at the grain boundaries, which causes the formation of cracks and fractures in the medical device, followed by a rapid decline in strength and loss of integrity of the partitioning. The fragmentation of medical devices is extremely dangerous because small particles leave the device implantation area and transported to other tissues, which can cause serious damage, including failure funk�AI bodies heart attack and stroke. The use of conventional steel in implantable medical devices is also complicated by the fact that ordinary steel usually contains elements of the alloy, having toxic effects when released into the body.

Thus, in this area there is a need to develop implantable medical devices having the required properties associated with steel, but it is biodegradable.

Disclosure of the invention

The present invention is based, in particular, on the discovery that certain metal alloys having, for example, fine-grained, essentially austenitic structure, biodegraded over time without the formation of emboli. The present invention is also based, in particular, on the discovery that certain metal alloys, for example, with essentially martensitic structure, biodegraded over time without the formation of emboli. Such alloys are suitable for the manufacture of biodegradable implantable medical devices.

Accordingly, in one aspect, the invention relates to implantable medical devices comprising a biodegradable alloy, gradually dissolving from the outer surface. In some embodiments the dissolution rate from the surface of the alloy is essentially homogeneous smooth cha�children of the outer surface (e.g., substantially flat, concave or convex surfaces). In some embodiments, the alloy has a fine-grained, essentially austenitic structure. In some embodiments, the alloy has essentially austenitic structure, preferably not collapsing at the grain boundaries. In other embodiments, the alloy has an essentially martensitic structure.

In some embodiments, an implantable medical device includes an alloy essentially austenitic structure and having an average grain size of about 0.5 microns to 20 microns. For example, in some embodiments, the average grain size is from about 0.5 microns to 5.0 microns, or from about 1.0 microns to 2.0 microns. In some embodiments, an implantable medical device includes an alloy essentially austenitic structure, where the ratio of surface to volume of individual grains is, on average, higher than 0.1 Miron-1. For example, in some embodiments, the ratio of surface to volume of individual grains on average above 1.0 μm-1.

In some embodiments, an implantable medical device includes an alloy that is an alloy of iron (e.g., steel). For example, in some embodiments, the alloy contains from about 55% to 80% iron. In some embodiments, the alloy contains at least two non-ferrous element, where each� of the at least two non-ferrous elements is present in amounts of at least about 0.5%, and where the total number of such at least two elements is more than about 20% of the alloy. In some embodiments more than about 5% of the alloy consists of other elements than iron, chromium, Nickel and carbon. In some embodiments, an implantable medical device includes an alloy containing less than about 0.1% Nickel. In some embodiments, the alloy contains less than about 0.1% vanadium. In some embodiments, the alloy contains less than about 4.0% chromium. In some embodiments, the alloy contains less than about 6.0% cobalt. In some embodiments, the alloy contains less than about 0.1% Nickel, less than about 0.1% vanadium, less than about 4.0% chromium, and less than about 6.0% cobalt. In some embodiments, the alloy contains less than about 0.1% of each of the elements from the group consisting of platinum, palladium, iridium, rhodium, rhenium, rubidium, and osmium. In some embodiments, the alloy contains less than about 0.01% phosphorus.

In some embodiments, an implantable medical device includes an alloy comprising austentatious component. In some embodiments, the number austentatious component in the alloy exceeds about 10%. In some embodiments austentatious component contains one or more elements selected from the group consisting of manganese, cobalt, platinum, palladium, iridium, aluminum, copper�tion, carbon, nitrogen and silicon. In some embodiments austentatious component contains one or more elements selected from the group consisting of manganese, cobalt, platinum, palladium, iridium, carbon and nitrogen, where % platinum + % palladium + % iridium + 0,5·(% manganese + % cobalt) +30·(% carbon + % nitrogen) is greater than about 12% (e.g., greater than about 14%, about 16%, about 18%, about 19%, or about 20%).

In some embodiments, an implantable medical device includes an alloy comprising a corrosion-resistant component. In some embodiments, the number of corrosion-resistant component in the alloy is less than about 10% (e.g., about 0.5% -10%). In some embodiments, the corrosion resistant component comprises one or more elements selected from the group consisting of chromium, molybdenum, tungsten, tantalum, niobium, titanium, zirconium and hafnium. In some embodiments, the corrosion resistant component comprises one or more elements selected from the group consisting of chromium, molybdenum, tungsten, tantalum, niobium, titanium, zirconium and hafnium, where % CR + % molybdenum + % tungsten + 0,5·(% tantalum + % NB) + 2·(% titanium + % zirconium + % hafnium) is from about 0.5% to 7% (e.g., about 6.0%, about 5.5%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, or about 3.0%).

In some embodiments, the alloy content�t austentatious component and corrosion-resistant component. In some embodiments, the number austentatious component in the alloy exceeds about 10%, and the number of corrosion-resistant component in the alloy is from about 0.5% to 10%.

In some embodiments, an implantable medical device is a high strength bone fixation (for example, to restore the divided bone segments). In other embodiments, an implantable medical device is a high strength bone screw (e.g., to strengthen the fractured bone segments). In other embodiments, an implantable medical device is a high-strength device for immobilization of bone (eg, for large bones). In other embodiments, an implantable medical device is a brace to strengthen the fabric. In other embodiments, an implantable medical device is a plate or screws for Craniomaxillofacial reconstruction. In other embodiments, an implantable medical device is a dental implant (e.g., restorative dental implant). In other embodiments, an implantable medical device is a stent (for example, to keep the clearance holes in the body in the body of a person or animal).

In some embodiments, an implantable medical device has a geometric shape of�, increasing the ratio of surface to mass. For example, in some embodiments, an implantable medical device comprises one or several openings (e.g., recesses) on the surface of the device or one or more passes through the device.

In some embodiments of the implantable medical device further comprises a therapeutic agent. In some embodiments therapeutic agent is applied as a coating on the surface of the device. In other embodiments therapeutic agent is implanted in the body of the device (e.g., into the pores of the alloy, which is made of an implantable medical device, into the recesses on the surface of the device or in the passages through the device).

In some embodiments of the implantable medical device further comprises a biodegradable gel. In some embodiments the biodegradable gel covers the surface of the device. In other embodiments the biodegradable gel is introduced into the device (e.g., into the pores of the alloy, which is made of an implantable medical device, into the recesses on the surface of the device or in the passages through the device). In some embodiments the biodegradable gel contains a therapeutic agent.

In another aspect, the invention relates to a container containing implantable �medical device in accordance with the invention. In some embodiments, the container further comprises instructions (e.g. the use of implantable medical devices to medical procedures).

The invention and additional embodiments hereinafter described in more detail in the section implementation of the invention.

The implementation of the invention

Used in the present description, the term "interest" as used in relation to the number of element in the alloy, means mass percent. However, the "weighted percent" corrosion-resistant and austentatious component is calculated so that the weighted percentages do not necessarily correspond to the actual mass percent.

The object of the present invention is to provide a medical device for temporary implantation in the body of a subject (e.g. human or animal), which are fabricated using biodegradable alloy. Biodegradable alloy is stainless steel, but is subjected to reactions with the normal chemistry of the organism for biodegradation or bioabsorable over time, and is removed through the normal processes of the body. Another object of the invention is the provision of implantable medical devices fabricated using biodegradable alloy, non-toxic and/or non-allergenic in degradation and p�zruseni by the body. Another object of the invention is the provision of implantable medical devices fabricated using biodegradable alloy, not possessing or having negligible magnetic susceptibility, and does not distort the image obtained by magnetic resonance imaging (MRI).

Thus, the invention is partly based on the discovery that certain alloys, for example, possessing a fine-grained, essentially austenitic structure, biodegraded over time without the formation of emboli. These austenitic alloys do not possess, or have low magnetic susceptibility and can be made non-toxic and/or non-allergenic by adjusting the quantities of various metals (e.g., chromium and Nickel) included in the alloy. The invention is also based, in particular, on the discovery that certain alloys, for example, with essentially martensitic structure, are biodegradable over time without the formation of emboli. These martensitic alloys can also be made non-toxic and/or non-allergenic by regulating the amounts of various metals (e.g., chromium and Nickel) included in the alloy. The alloys can be used in various implantable medical devices that are used to treat the body of a subject (e.g., human and�and other animal), but become unnecessary when the subject recovers. Alloys can be applied, for example, for the manufacture of biodegradable implantable medical devices that require high strength, such as bone fixators for bones that carry the weight load. These alloys can also be used for the manufacture of biodegradable medical devices that require plasticity, such surgical brackets for fixation of tissues.

Accordingly, in one aspect, the invention provides an implantable medical device comprising a biodegradable alloy, dissolving on the outer surface. Used in the present description, the term "alloy" means a mixture of elements comprising two or more metallic elements. Biodegradable alloys suitable for the manufacture of implantable medical devices in accordance with the invention, can be, for example, iron alloys (e.g., steels). In some embodiments, the iron alloys contain from about 55% to 65%, from about 57.5 per cent to 67.5%, from about 60% to 70%, from about 62.5 percent to 72.5%, from about 65% to 75%, approximately from 67.5% to 77.5%, from about 70% to 80%, approximately from 72.5% to 82.5%, or from about 75% to 85% of iron. Iron alloys additionally contain one or more non-iron metallic elements. One or more of iron IU�allicesia elements may include, for example, transition metals such as manganese, cobalt, Nickel, chromium, molybdenum, tungsten, tantalum, niobium, titanium, zirconium, hafnium, platinum, palladium, iridium, rhenium, osmium, rhodium, etc., or nontransition metals, such as aluminum. In some embodiments, the alloys of iron, contain at least two non-ferrous metal element. At least two non-ferrous metal element may be present in amounts of at least about 0.5% (e.g., at least about 1.0%, about 1.5%, about 2.0%, about 2.5%, about 3.0%, about 4.0%, about 5.0% or more). In some embodiments of the steel alloys contain at least two non-ferrous metal element, where each of the at least two non-ferrous elements is present in amounts of at least about 0.5%, and where the total number of such at least two elements is at least about 15% (e.g., at least about 17.5%, about 20%, about 22.5%, about 25%, about 27.5%, about 30%, about 32.5%, about 35%, about 37.5%, or about 40%). Biodegradable alloys may also contain one or more non-metallic elements. Suitable non-metallic elements include, for example, carbon, nitrogen and silicon. In some embodiments, the iron alloys contain at least about 0.01% (e.g., about 0.01%-0,10%, about 0.05%-0,15%, about 0.10% to -0.20%, OK�lo 0,15%-0,25%, or about 0,20%-0,30%) at least one non-metallic element.

Biodegradable alloys suitable for use in implantable medical devices in accordance with the invention, dissolved from the outer part to the inner, whereby they retain the strength for most of their lives, and not divided into parts and do not form emboli. Without limitation by theory, the applicants believe that this is achieved by ensuring that the structure of the alloy, which has either not significantly reactive grain boundaries, which promotes the degradation on the molecular surface layer, or by providing the alloy with very fine grains, acting as a homogeneous, containing grains of the material. In some embodiments the dissolution rate from the outer surface of a suitable biodegradable alloy is essentially uniform in each point of the outer surface. In this context, "substantially homogeneous" means that the dissolution rate at a specific point on the external surface is ±10% of the speed of dissolution in any other point of the same outer surface. As is clear to experts in the art, the type "external surface", the alleged in these embodiments, is smooth and continuous (i.e., substantially flat, concave, convex �whether the like) and does not include sharp edges or similar irregularities, because in such sites, the dissolution rate is probably much higher. "Essentially" flat, concave or convex surface is flat, concave, convex or the like surface not containing any irregularities, scarring, or furrows, rising or sinking from the surface by more than 0.5 mm.

Steel alloys contain iron as a main component. Depending on the combination of (i) the elements in the alloy with iron and (ii) previous treatment of the alloy steel can have different structural forms, such as ferrite, austenite, martensite, cementite, pearlite and bainite. In some cases, become have the same composition but different structure. For example, martensitic steel is a high-strength steel, which can be obtained from austenitic steel. When heated austenitic steel to a temperature of from 1750°F to 1950°F followed by rapid cooling to a temperature transition in the martensite, face-centered cubic structure of austenite steel is reoriented in a body-centered tetragonal martensitic structure and martensitic structure is locked in place; Martensitic steels do not have a noticeable grain boundaries, and therefore provide no way of dissolving the inner part of steel. It leads to slow dissolution from the outside without the formation of emboli. Metallurgical study of martensitic material shows "pre-austenite grain boundaries, which is where existed austenitic grain boundaries, but they are directionspanel traces of the previous structures.

Accordingly, in some embodiments of the biodegradable medical device in accordance with the invention contain an alloy (for example, an iron alloy) having an essentially martensitic structure. Used in the description, the term "substantially martensitic structure" means an alloy having at least 90% martensite structure. In some embodiments, the alloy has at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%; 99,5%; 99,8%; 99.9% or more of a martensite structure.

Martensitic alloy may have the composition of any alloy described in the present description. For example, in some embodiments martensitic alloy is formed from austenitic alloy described herein. In some embodiments martensitic alloy includes carbon, chromium, Nickel, molybdenum, cobalt, or combinations thereof. For example, in some embodiments of the martensite alloy comprises (i) carbon, (ii) chromium and/or molybdenum, and (iii) Nickel and/or cobalt. In some embodiments martensitic alloy contains approximately from 0.01% to 0.15%, about 0.05% to 0.20%, about 0.10% to 0.25%, about 0.01% to 0.05%, from about 0.05% to 0.10%, and when�Erno from 0.10% to 0.15%, or from about 0.15% to 0.20% carbon. In some embodiments martensitic alloy contains from about 0.1% to 6.0%, from approximately 1.0% to 3.0%, about 2.0% to 4.0%, about 3.0% to 5.0%, or from about 4.0% to 6.0% of chromium. In some embodiments martensitic alloy contains from about 0.1% to 6.0%, from about 0.5% to 2.5%, from approximately 1.0% to 3.0%, from about 1.5% to 3.5%, about 2.0% to 4.0%, about 2.5% to 4.5%, about 3.0% to 5.0%, about 3.5% to 5.5%, or from about 4.0% to 6.0% of molybdenum. In some embodiments of the martensite alloy comprises about 5.0% to 9%, approximately from 6.0% to 10%, from about 7.0% to 11%, from about 8.0% to 12%, from about 9.0% to 13%, from about 10% to 14%, or from about 11% to 15% Nickel. In some embodiments of the martensite alloy comprises approximately 5.0% to 10%, from about 7.5% to about 12.5%, about 10% to 15%, approximately from 12.5% to 17.5%, or from about 15% to 20% of cobalt.

In some embodiments martensitic alloy contains from about 2.0% to 6.0 percent, from about 3.0% to about 7.0%, about 3.5% to 7.5%, from about 4.0% to 8.0 percent, from about 4.5% to 8.5% or about 5.0% to 9.0% corrosion-resistant component. In some embodiments martensitic alloy contains about 2.5%, about 3.0 percent, about 3.5%, about 4.0%, about 4.5%, about 5.0 percent, of about 5.5% or approximately 6.0% of the corrosion resistant component. In some embodiments, the corrosion resistant component count to�to the sum of the percentage of corrosion-resistant elements (e.g., chromium, molybdenum, tungsten, tantalum, niobium, titanium, zirconium, hafnium, etc.) in the alloy. In other embodiments, the corrosion resistant component is calculated as a weighted sum of the corrosion-resistant elements in the alloy. In some embodiments of the individual elements in the weighted sum are counted according to their corrosion-resisting performance comparing with chromium. In some embodiments the weighted content of corrosion-resistant component is determined in accordance with the formula: % CR + % molybdenum + % tungsten + 0,5·(% tantalum + % NB) +2·(% titanium + % zirconium + % hafnium).

In some embodiments martensitic alloy contains at least about 10%, about 15%, about 18%, about 20%, about 22%, or approximately 24% austentatious component. For example, in some embodiments martensitic alloy contains from about 10% to 20%, from about 15% to 25%, from about 20% to 30%, from about 25% to 35%, from about 30% to 40% austentatious component. In some embodiments of the martensite alloy comprises about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, or approximately 28% austentatious component. In some embodiments austentatious component is calculated as the sum of the percentage content austentatious elements (e.g., Nickel, manganese, cobalt, p�tiny, palladium, iridium, aluminum, carbon, nitrogen, silicon, etc.) in the alloy. In other embodiments austentatious component is calculated as a weighted sum austentatious elements in the alloy. In some embodiments of the individual elements in the weighted sum are counted according to their austentatious efficiency, in comparison with Nickel. In some embodiments the weighted content austentatious component is determined in accordance with the formula: % Ni + % platinum + % palladium + % iridium + 0,5·(% manganese + % cobalt) +30·(% carbon + % nitrogen).

In some embodiments of the martensite alloy comprises about 2.0% to 4.0%, about 3.0% to 5.0%, or from about 4.0% to 6.0% of the corrosion-resistant component, and from about 10% to 20%, from about 15% to 25%, from about 20% to 30%, from about 25% to 35%, or from about 30% to 40% austentatious component. For example, in some embodiments of the martensite alloy comprises about 3.0% to 5.0% corrosion-resistant component and from about 20% to 30% austentatious component. In some embodiments, the corrosion resistant and austentatious components calculated as the sum of the percentage of corrosion-resistant and austentatious elements, respectively. In other embodiments, the corrosion resistant and austentatious components R�schityvat as a weighted sum of corrosion resistant and austentatious elements respectively.

While the martensitic alloys have the necessary characteristics to the absence of grain boundaries, austenitic alloys are particularly suitable for medical implants due to its low magnetic susceptibility, which can be useful when the alloy is exposed to a strong magnetic field. For medical implants needed low magnetic susceptibility, because they can be used in patients who subsequently may require magnetic resonance imaging (MRI), which uses a very powerful magnetic field. Responsive to a magnetic field to the alloy in a strong magnetic field may be heated, contributing to the local stress and damage to the tissue surrounding the implant. Responsive to a magnetic field implants also distort MRI images obtained, making them unreadable. In addition, austenitic alloys can provide favorable mechanical properties, as they are subjected to large plastic deformation between the elastic limit (yield point) and final destruction, compared with martensitic alloys. For example, while the martensitic alloy can have a maximum stretch of about 16% to 20%, austenitic alloy can have a maximum stretch of approximately 50% to 60%.

Thus, in some�'s incarnations biodegradable implantable medical device in accordance with the invention contain an alloy (for example, iron alloy) having essentially austenitic structure. Used in the description, the term "substantially austenitic structure" means at least 85% austenitic structure. In some embodiments, the alloy has at least 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%; 99,5%; 99,8%; 99,9% or more austenitic structure. In some embodiments of the austenitic alloy essentially contains martensitic or ferritic structure. Used in the description, the term "essentially does not contain martensitic or ferritic structure" means a content of less than 5% (e.g., less 4%, 3%. 2%, 1%; 0,5%; 0,2%; 0,1% or 0.05%) martensitic or ferritic structure. In some embodiments of the austenitic alloy has the maximum tensile strength of from about 40% to 65% (e.g. from 50% to 60%).

Austenitic steel with defined grain boundaries of irregular shape. Since austenite is a face-centered cubic structure, the grains seem to be cubic when viewed perpendicular to the major plane of the crystal lattice. In the austenitic alloy with very low carbon content, chromium, or you can create a structure with small grain size (e.g., about 0.5 to 5.0 microns on the side). Cubic austenitic grain size of 2.5 microns has a total surface area of 37.5 square microns and the volume of 15,625 cubic microns, with the ratio� of surface to volume of 2.4 μm -1and a total weight of 0.12 ág. Due to the extremely low mass of the grains, the material grains reacts immediately after his placement in a biological environment, allowing the alloy to lose material from the outside. This, in turn, prevents loosening of the material along grain boundaries and segregation of grains of alloy material. However, when the grain size increases, the ratio of surface to volume decreases. Each grain is increased, slowing down the absorption, increasing the likelihood of dissolution along grain boundaries, a deeper penetration into the bulk alloy material, and thus reducing the strength of the alloy.

Accordingly, the biodegradation rate of austenitic alloys can be changed by adjusting the grain size and surface to volume of the individual grains. When grain size increases, with a commensurate decrease in surface to volume biodegradation toward the center of the device is moving faster, increasing the overall biodegradation rate. However, a too large grain size can cause the separation of the grains and side effects.

In some embodiments of the austenitic alloy has an average grain size of about 0.5 microns to 20 microns on each side. For example, in some embodiments, the average grain size is from about 0.5 microns to 5.0 microns, from about 2.5 microns to 7.5 microns, �rimero from 5.0 microns to 10 microns, from about 7.5 microns to about 12.5 microns, about 10 to 15 microns, from about 12.5 microns to 17.5 microns, or about 15 to 20 microns on each side. In some embodiments, the average grain size is from about 0.5 to 3.0 microns, or from about 1.0 microns to 2.0 microns on each side. In some embodiments of the austenitic alloy has a structure in which the ratio of surface to volume of individual grains is, on average, more than 0.1 μm-1. For example, in some embodiments the ratio of surface to volume of individual grains is, on average, more than 0.2 μm-1; 0.3 µm-1; 0.4 mm-1; 0.5 µm-1; 0.6 μm-1; 0.7 μm-1; 0.8 μm-1; 0,9 m-1; 1.0 μm-1; 1.5 mm-1; 2.0 µm-1; 2.5 μm-1; 3.0 mm-1; 3.5 µm-1; 4,0 mm-1; 4.5 µm-1; 5.0 µm-1; 6,0 µm-1; 7,0 µm-1And 8.0 µm-1; 9,0 µm-1; Of 10.0 μm-1; 11,0 μm-1; 12,0 µm-1; Of 13.0 μm-1; 14,0 µm-1; 15,0 µm-1or more.

The grain size of austenite from about 0.5 microns to 20 microns can be achieved using successive machining cycles to fracture of the alloy with subsequent thermal recrystallization. Mechanical processing of materials carried out at cold temperatures (i.e., from room temperature to 200°C) or at elevated those�erature, causes rupture of the crystal structure under the action of deformation, physically giving the alloys a new form. The most common method of mechanical processing of metals is the reduction of the thickness of the metal sheet between two rollers under high pressure, whereby the material at the outlet is substantially thinner (e.g., thinner by 20%-60%) compared to the original thickness. Can also be used other methods, such as extrusion. In the process of mechanical processing of metals large units continuous crystal lattice to collapse of various structures. More importantly, they retain the bulk-induced strain energy in the deformed elements of lattices, by stretching the distances of the crystal structure to a higher energy location. Subsequent low-temperature recrystallization carried out at a temperature of approximately from 0.35 to 0.55 of the absolute melting temperature of the alloy, allows the crystal lattice to undergo rearrangements in low-energy conditions, the General microrasbora. To fit the rearrangement of the crystal structure without much change in size, the size of the individual subunits of the crystal lattice, or grains, is reduced, releasing the main energy Def�rmacie by destruction of the crystal lattice into smaller subunits, and obtain the structure with smaller grains. The machining process followed by recrystallization can be repeated periodically, getting smaller and smaller grains.

In some embodiments of the austenitic alloy contains carbon. For example, in some embodiments, the alloy contains approximately from 0.01% to 0.10%, about 0.02% to 0.12%, about 0.05% to 0.15%, approximately 0.07% to 0.17%, about 0.10% to 0.20%, about 0.12% to 0.22%, or from about 0.15% to 0.25% carbon. In some embodiments of the austenitic alloy comprises one or more (e.g., two or more elements selected from the group comprising Nickel, cobalt, aluminum and manganese. In some embodiments, the alloy contains from about 2.0% to 6.0 percent, from about 3.0% to about 7.0%, about 4.0% to 8.0%, or about 5.0% to 9.0% Nickel. In other embodiments, the alloy is essentially Nickel-free. In some embodiments, the alloy contains from about 10% to 20%, from about 15% to 20%, from about 15% to 25%, from about 18% to 23%, from about 20% to 25%, or from about 20% to 30% cobalt. In some embodiments, the alloy contains less than about 5.0 percent (e.g., less than about 4.5%, about 4.0%, about 3.5%, about 3.0 percent, or approximately 2.5%) of manganese. In some embodiments, the alloy comprises about 0.5% to 1.5%, from approximately 1.0% to 2.0%, or from about 1.5% to 2.5% manganese. In other embodiments, the alloy contains prima�but from 1.0% to 8.0%, approximately from 6.0% to 10%, from about 8.0% to 12%, or from about 10% to 14% manganese. In some embodiments, an austenitic alloy that contains one or more (e.g., two or more elements selected from the group consisting of chromium, molybdenum and tantalum. In some embodiments, the alloy comprises about 0.5% to 1.5%, from approximately 1.0% to 2.0%, from about 1.5% to 2.5%, or from about 2.0 to 3.0% of chromium. In other embodiments, the alloy essentially contains chromium. In some embodiments, the alloy comprises about 0.5% to 1.5%, from approximately 1.0% to 2.0%, from about 1.5% to 2.5%, or from about 2.0% to 3.0% of molybdenum. In some embodiments, the alloy contains from approximately 1.0% to 3.0%, about 2.0% to 4.0%, about 3.0% to 5.0%, or from about 4.0% to 6.0 percent tantalum. In some embodiments of the austenitic alloys contain (i) carbon, (ii) at least two elements selected from the group consisting of Nickel, cobalt, aluminum and manganese, and (iii) at least two elements selected from the group consisting of chromium, molybdenum and tantalum.

In addition to the mode of dissolution, the rate of dissolution and release of potentially toxic elements need to be regulated in the alloys used for the manufacture of implantable medical devices in accordance with the invention. Some of the elements used to alloy manufacturers, help you to determine the physical and chemical WCs�STV finished alloy. For example, the addition of small amounts of carbon to iron changes the structure of iron, creating steel with significantly increased hardness and strength, while changing the relative plasticity of iron. This way, stainless steel is made by adding hardware elements that reduce corrosion (i.e. corrosion-resistant components, such as chromium and molybdenum. Stainless steel, resistant to corrosion in biological systems, may contain, for example, 18% chromium and 1% molybdenum. Titanium, niobium, tantalum, vanadium, tungsten, zirconium, and hafnium also provide a protective effect, inhibiting the fracture of steel in a biological system.

Stainless steel, not collapsing in a biological system, usually not suitable for use in biodegradation the implant. Thus, alloys with large amounts of corrosion-resistant elements, such as chromium, molybdenum, titanium and tantalum, usually cannot be used for the manufacture of biodegradable implantable medical devices in accordance with the invention. However, small quantities of such corrosion-resistant elements are suitable to control the rate of biodegradation of a suitable alloy. Accordingly, in some embodiments the alloy suitable for the manufacture of biodegradable medical device according�accordance with the invention (for example, austenitic alloy), contains at least about 0.5%, about 1.0%, about 1.5%, about 2.0% and about 2.5%, about 3.0 percent, or approximately 3.5%, but less than about 15%, about 12%, about 11%, about 10%, about 9.0% to about 8.0% or approximately 7.0% of the corrosion resistant component. For example, in some embodiments, the alloy contains from about 1.0% to about 7.0%, about 2.0% to 8.0%, or from about 3.0% to 9.0% of the corrosion resistant component. In some embodiments, the alloy (for example, austenitic alloy) contains in excess of 3.0%, about 3.5%, about 4.0%, about 4.5%, about 5.0 percent, of about 5.5%, about 6.0%, about 6.5%, or approximately 7.0% of the corrosion resistant component. In some embodiments, the corrosion resistant component count as the sum of the percentage of corrosion-resistant elements (e.g., chromium, molybdenum, tungsten, tantalum, niobium, titanium, zirconium, hafnium, etc.) in the alloy. In other embodiments, the corrosion resistant component is a weighted sum of all corrosion-resistant elements in the alloy. For example, in some embodiments of the individual elements in the weighted sum are counted according to their corrosion-resisting performance comparing with chromium. In some embodiments, the weight percent of the corrosion-resistant component is determined by the formula: % CR + % molybdenum + % tungsten + 0,5·(% tantalum + niobium) +2·(% titanium + % zirconium + % hafnium).

Corrosion-resistant elements, such as chromium and molybdenum, are territooriumil, causing the formation in ferritic steel structure. To overcome the formation of ferrite and achieve the austenitic structure in the alloy can add austentatious elements. Austentatious elements include, for example, Nickel, manganese, cobalt, platinum, palladium, iridium, aluminum, carbon, nitrogen and silicon. Accordingly, in some embodiments the alloy (for example, austenitic alloy) suitable for the manufacture of implantable medical devices in accordance with the invention comprises austentatious component. In some embodiments, the alloy contains from about 10% to 20%, from about 15% to 25%, from about 20% to 30%, from about 25% to 35%, or from about 30% to 40% austentatious component. In some embodiments, the alloy contains at least about 10%, about 12%, about 14%, about 16%, about 18%, about 20%, about 22%, about 24%, about 26%, about 28%, or about 30% austentatious component. In some embodiments austentatious component is calculated as the sum of the percentage content austentatious elements (e.g., Nickel, cobalt, manganese, platinum, palladium, iridium, aluminum, carbon, nitrogen, silicon, etc.) in the alloy. In other embodiments of Aust�kitoobraznymi component is a weighted sum austentatious elements in the alloy. In some embodiments of the individual elements in the weighted sum are determined according to their austentatious efficiency, in comparison with Nickel. In some embodiments a weighted % austentatious component calculated from the formula: % Ni + % platinum + % palladium + % iridium + 0,5·(% manganese + % cobalt) + 30·(% carbon + % nitrogen). In some embodiments, the alloy contains weighted percentage austentatious component from about 15% to 25% (e.g., about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24% or about 25%). In some embodiments, the alloy contains unweighted percentage austentatious component from about 25% to 35% (e.g., about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, or about 35%).

In some embodiments, the alloy (for example, austenitic alloy) suitable for the manufacture of implantable medical devices in accordance with the invention contains less than about 5.0 percent (e.g., from about 0.1% to 2.5%, about 0.5% to 3.0%, from approximately 1.0% to 3.5%, from about 1.5% to 4.0%, or from about 2.0% to 4,5%) platinum, iridium and osmium, either individually or as a whole. In some embodiments, the alloy essentially does not contain platinum, palladium or iridium. Used in the description, the phrase "substantially not containing" platinum, palladium or iridium means that�love contains less than 0.1% of platinum, palladium or iridium. In some embodiments, the alloy essentially does not contain platinum, palladium or iridium. In some embodiments, the alloy contains less than about 0.05%, or about 0.01% of each of platinum, palladium or iridium. In some embodiments, the alloy contains less than about 0.05%, or less than about 0.01% of each of platinum, palladium or iridium. In other embodiments the total amount of platinum, iridium and osmium in the alloy is approximately 5.0 percent or above, and the alloy further comprises at least one additional metal element other than iron, manganese, platinum, iridium and osmium (e.g., at least about 0.5% or more of the specified at least one metal element). In some embodiments, at least one additional metallic element is corrosion-resistant element (e.g., chromium, molybdenum, tungsten, titanium, tantalum, niobium, zirconium or hafnium) or austenitisation element selected from the group consisting of Nickel, cobalt and aluminum.

Biodegradable alloys, implantable in a human or animal, should be relatively non-toxic, since all the elements in the alloy gradually dissolve in body fluids. Nickel is often used to stabilize the austenitic crystal structure. However, many �employers develop an Allergy to Nickel, and they can't take the Nickel in these systems. The presence of Nickel as part of the biodegradable alloy ensures that all the Nickel in the alloy is gradually absorbed by the body of media that can cause complications in individuals sensitive to Nickel. Similarly, chromium, cobalt and vanadium are shown to have some toxicity in the human body, and needs to be minimized in biodegradation alloy. Accordingly, in some embodiments the alloy suitable for the manufacture of biodegradable medical devices in accordance with the invention (for example, austenitic alloy contains less than about 9.0% to about 8.0 percent, about 7.0 percent, about 6.0%, about 5.0 percent, about 4.0%, about 3.0 percent, about 2.5%, about 2.0% and about 1.5%, about 1.0%, or about 0.5% each of Nickel, vanadium, chromium and cobalt. In some embodiments, the alloy essentially contains Nickel. Used in the description, the phrase "essentially does not contain Nickel" means that the alloy contains 0.1% or less Nickel. In some embodiments, the alloy contains less than about 0.05%, less than approximately 0.02%, or less than about 0.01% Nickel. In some embodiments, the alloy essentially contains no vanadium. Used in the description, the phrase "essentially does not contain vanadium" means that the alloy contains 0.1% or less of vanadium. In some embodiments, the alloy content�t less than about 0.05%, less than approximately 0.02%, or less than about 0.01% of vanadium. In some embodiments, the alloy contains less than about 4.0% chromium (for example, less than about 3.0 percent, about 2.0 percent, or about 1.5%). In some embodiments, the alloy is essentially free of chromium. Used in the description, the phrase "essentially does not contain chromium" means that the alloy contains 0.1% or less of chromium. In some embodiments, the alloy contains less than about 0.05%, less than approximately 0.02%, or less than about 0.01% of chromium. In some embodiments, the alloy contains less than about 6.0% (e.g., less than about 5.0 percent, about 4.0%, about 3.0 percent, about 2.0 percent, or approximately 1.0%) of cobalt.

To remove or minimize the toxic elements from the alloy used to create biodegradable implantable medical devices in accordance with the invention, the toxic elements can be replaced by non-toxic components. For example, as Nickel is used as austentatious element, it can be replaced by other austentatious elements such as manganese, cobalt, platinum, palladium, iridium, aluminum, carbon, nitrogen and silicon. Similarly, since chromium is used as a corrosion-resistant element, it can be replaced with other corrosion-resistant elements such as molybdenum, tungsten, titanium, tantalum, niobium, zirconium and hafnium�rd. However, not all substitutes in the alloy are equivalent. For corrosion-resistant steps molybdenum is as effective as chromium, while niobium and tantalum are only half effective than chromium, and titanium is two times more effective than chromium. For austenitisation of the action of manganese and cobalt in two times less effective than Nickel, while the carbon in 30 times more effective than Nickel, and nitrogen at 25-30 times more effective than Nickel. Accordingly, in some embodiments the biodegradable alloy make non-allergenic or less allergenic by replacing one part of Nickel in two parts manganese, manganese, and one part of cobalt, or two parts of cobalt. In other embodiments the biodegradable alloy make non-toxic or less toxic by replacing one part one part chromium molybdenum, a half parts of titanium, or the two parts of tantalum or niobium. In some embodiments, the total percentage of Nickel, cobalt and manganese is from about 10% to 20%, from about 15% to 25%, or from about 20% to 30%, from about 25% to 35%, or from about 30% to 40%, while the percentage of Nickel is less than about 9.0% to about 8.0 percent, about 7.0 percent, about 6.0%, about 5.0 percent, about 4.0%, or approximately 3.0 percent. In other embodiments, the total percentage of chromium and molybdenum sostavljae� from approximately 1.0% to 7.0%, approximately from 2.0% to 8.0%, about 3.0% to 9.0%, or from about 4.0% to 10%, while the amount of chromium is less than about 2.0% and about 1.5%, about 1.0%, or approximately 0.5%.

Additional elements that may be included in the alloys suitable for the manufacture of biodegradable implantable medical devices in accordance with the invention include rhodium, rhenium and osmium. In some embodiments, the amount of rhodium, rhenium, or osmium in the alloy is less than about 5.0 percent (e.g., from about 0.1% to 2.5%, about 0.5% to 3.0%, from approximately 1.0% to 3.5%, from about 1.5% to 4.0%, or approximately from 2.0% to 4.5%). In some embodiments, the alloy essentially contains rhodium, rhenium, or osmium. Used in the description, the phrase "essentially does not contain rhodium, rhenium or osmium means that the alloy contains less than about 0.1% of rhodium, rhenium, or osmium. In some embodiments, the alloy essentially contains rhodium, rhenium and osmium. In some embodiments, the alloy contains less than about 0.05%, or less than about 0.01% of rhodium, rhenium, or osmium. In some embodiments, the alloy contains less than about 0.05%, or less than about 0.01% of each of rhodium, rhenium and osmium.

In some embodiments, when one or more elements selected from the group consisting of platinum, palladium, iridium, rhodium, rhenium and osmium, are present in the alloy suitable for the manufacture�Oia biodegradable implantable medical devices in accordance with the invention, the amount of manganese in the alloy is less than about 5.0 percent (e.g., less than about 4.5%, about 4.0%, about 3.5%, about 3.0 percent, or approximately 2.5%). In other embodiments, when one or more elements selected from the group consisting of platinum, palladium, iridium, rhenium, rubidium, and osmium, is present in the alloy, and when the amount of manganese in the alloy is approximately a 5.0% or more (e.g., about 5.0% -30%), the alloy additionally contains at least one additional metal element. In some embodiments said at least one additional metallic element is corrosion-resistant element (e.g., chromium, molybdenum, tungsten, titanium, tantalum, niobium, zirconium or hafnium) or austenitisation element selected from the group consisting of Nickel, cobalt and aluminum.

In some embodiments, the alloy suitable for the manufacture of biodegradable implantable medical devices in accordance with the invention essentially does not contain rubidium or phosphorus. Used in the description, the phrase "essentially does not contain rubidium or phosphorus" means the content less than 0.1% of rubidium or phosphorus. In some embodiments, the alloys essentially do not contain rubidium and phosphorus. In some embodiments, the alloys contain less than about 0.05%, or less than about 0.01% of rubidium and�and phosphorus. In some embodiments, the alloys contain less than about 0.05%, or less than about 0.01% of each of rubidium and phosphorus.

In some embodiments, the present invention provides biodegradable implantable medical device comprising a number of biodegradable alloys such as austenitic alloys) that are acceptable non-allergenic, non-toxic, do not possess or have negligible magnetic susceptibility, and provide an acceptable range of speed degradation. The approximate boundaries defining the alloys suitable for the biodegradable implantable medical devices in accordance with the present invention are as follows:

"essentially does not contain Nickel;

- essentially do not contain vanadium;

- contain less than about 6.0 percent chromium;

- contain less than about 10% cobalt;

- contain corrosion-resistant component in an amount of less than about 10% (e.g., about 0.5% -10%); and

- contain austentatious component in the amount of at least about 10% (e.g., about 10%-40%).

In some embodiments, the alloy contains from about 55% to 80% iron. For example, in some embodiments, the alloy contains from about 55% to 65%, from about 60% to 70%, from about 65% to 75%, from about 70% to 80% iron. In some embodiments, the amount of chromium is less than about 0%, and the amount of cobalt is less than about 6.0%. In some embodiments, the amount of chromium is less than about 2.0%, and the amount of cobalt is less than about 4.0%. In some embodiments, the corrosion resistant component is less than about 8.0 percent (e.g., about 0.5%-8,0%), and austentatious component is more than about 12%. In some embodiments, corrosion-resistant component is less than about 7.0 percent (e.g., about 0.5%-7,0%), and austentatious component is more than about 14%. In some embodiments, corrosion-resistant component is less than about 6.0% (e.g., about 0.5%-6,0%), and austentatious component is more than about 16%. In some embodiments, the corrosion resistant and austentatious components is calculated as the sum of the percentage of corrosion-resistant and austentatious elements, respectively. In other embodiments, the corrosion resistant and austentatious components is calculated as a weighted sum of the corrosion-resistant and austentatious elements, respectively. In some embodiments, a weighted percentage of corrosion-resistant component is determined by the formula: % CR + % molybdenum + % tungsten + 0,5·(% tantalum + % NB) + 2·(% titanium + % zirconium + % hafnium). In some embodiments, a weighted percentage of austinites�the next component is determined by the formula: % Ni + % platinum + % palladium + % iridium + 0,5·(% manganese + % cobalt) +30·(%carbon + % nitrogen). In some embodiments, the alloy contains less than about 5.0% of manganese (e.g., less than about 4.5%, about 4.0%, about 3.5%, about 3.0 percent, or approximately 2.5%). In some embodiments, the alloy contains one or more elements selected from the group consisting of platinum, palladium, iridium, rhodium, rhenium and osmium. In some embodiments, the alloy contains from about 0.5% to 5.0% of one or more elements selected from the group consisting of platinum, palladium, iridium, rhodium, rhenium and osmium. In some embodiments, the alloy essentially contains no elements selected from the group consisting of platinum, palladium, iridium, rhodium, rhenium and osmium. In some embodiments, the alloy essentially contains no elements selected from the group consisting of rubidium and phosphorus.

The destruction of the entire implant depends on the mass of the implant compared to the surface area. Implants have many different sizes and shapes. A typical coronary stent, for example, found to be 0.0186 weighs grams and has a surface area of 0,1584 square inches. At a speed of degradation of 1 mg/square inch/day coronary stent needs to lose 50% of its mass within 30 days. In comparison with cannulated bone screw length 12 mm weighs 0,5235 g and has a surface area of 0,6565 square inches. At the very same degradation rate of 1 mg/square inch/day with cannulated screw lose on�owino its mass for 363 days. Thus, as is clear to a person skilled in the technical field, you must have a biodegradable alloy with a speed range of degradation to adapt to various implants used in the body of the subject.

In addition, the rate of degradation of implantable medical devices in accordance with the present invention have a significant impact transport characteristics of the surrounding tissues. For example, the rate of biodegradation of the implant placed into the bone where the transport in the rest of the body is limited by a lack of fluid flow should be slower than vascular stent, which contacts the blood. Similarly, biodegradable dish soap in response, the device is immersed in the fabric and has a lower degradation rate than the device is exposed to blood flow, although more rapid degradation rate than that of the device submerged in the bone. In addition, different ends of the medical device should exhibit different degradation rate of, for example, if one end is in the bone and the other end is located in tissue or blood. Thus, the required modulation of the rate of biodegradation based on the placement of the device and the final requirements of the device.

To adjust the dissolution rate of the medical device independently of changes in the geometry�certification form emerging as the degradation of the device have been developed some methods. The first way to change the profile of the dissolution of metallic devices is changing the geometric shape of the device so as to neutralize large changes in surface area. For example, you can increase or maximize the ratio of surface to mass. Essentially cylindrical device that loses surface area linearly with the loss of diameter as the degradation of the device may have a concentric hole drilled in the center of the device. The resulting cavity will cause a compensatory increase in surface area as the dissolution of the alloy from the surface of the cavity unit. As a result, the change in surface area as degradation of the device over time, and thus change the speed of degradation will be minimized or eliminated. This technique of creating space cavity (e.g., cavity space having a shape similar to the outer surface of the device) can be used essentially for any type of medical device.

Because the rate of biodegradation depends in part on the impact of the flow of body fluid, the biodegradation rate can be modified by coating (e.g., all or a portion of) biodegrad�trolled implantable medical devices from substances protects the surface of the alloy. For example, biodegradable hydrogels, such as those disclosed in U.S. patent 6368356, can be used to slow the impact on any parts of the instrument exposed to moving fluids of the body, thus slowing the dissolution and transport of metal ions from the device. Alternatively, the medical device can be constructed from two or more different alloys described herein, and parts of the instrument exposed to moving fluids are made from a more corrosion-resistant alloys (i.e., alloys that include higher amounts of corrosion-resistant component), while the parts of the device, loaded into the bone or tissue, made of a less corrosion-resistant alloys. In some embodiments, different portions of a device can be manufactured from various alloys. In other embodiments of the device exposed to moving fluids may have a thin layer of an alloy that is more corrosion-resistant than the alloy used for manufacturing the main part of the device.

It is often necessary to incorporate bioactive agents (e.g., drugs) in an implantable medical device. For example, U.S. patent 6649631 describes the medicinal fry�ETS to stimulate the growth of bone tissue, which can be used with orthopedic implants. Bioactive agents can be embedded directly on the surface of the implantable medical device in accordance with the invention. For example, agents can be mixed with a polymeric shell, such as a hydrogel from the US patent 6368356, and a polymer shell can be applied to the surface of the device. Alternatively, the bioactive agents can be administered in cavities or pores of the medical devices that act as storage, so that the agents are slowly released over time. The pores can be on the surface of medical devices, providing relatively rapid release of drugs, or part of the basic structure of the alloy used for the manufacture of medical devices, so that the bioactive agents are released gradually over the main portion or the entire service life of the device. Bioactive agents can be, for example, peptides, nucleic acids, hormones, chemical drugs, or other biological agents, suitable to enhance the healing process.

Specialists in the art it is clear that there is a wide range of implantable medical devices that can be manufactured using alloys disclosed here. In some embodiments, an implantable medical� device is a high strength bone fixation (for example, for healing of segments separated bones). In other embodiments, an implantable medical device is a high strength bone screw (e.g., to strengthen the fractured bone segments). In other embodiments, an implantable medical device is a high-strength device for immobilization of bone (eg, for large bones). In other embodiments, an implantable medical device is a brace to strengthen the fabric. In other embodiments, an implantable medical device is a plate or screws for Craniomaxillofacial reconstruction. In other embodiments, an implantable medical device is a dental implant (e.g., restorative dental implant). In other embodiments, an implantable medical device is a stent (for example, to keep the clearance holes in the body in the body of the animal).

Powder metallurgy technology is well known in the field of medical devices. Bone clamps, shaped, produced by molding under high pressure metal powder in a carrier, with subsequent high-temperature sintering to bind the metal particles and remove any remaining media. The device of powdered metal are usually made of directionsparking �of yellow, such as stainless steel to 316LS. The porosity of the finished device depends partly on the particle size of the metal used for its manufacture. Since metal particles are much larger and structurally independent of the crystal grains of the metal structure, metal particles (and the device is made of such particles) can be made of alloys of any grain size. Thus, the biodegradable implantable medical device in accordance with the invention can be produced from powders obtained from any alloy described in the present description. The porosity caused by the powder metallurgy technique, can be used, for example, by filling the pores with medical devices biodegradable polymers. The polymers can be used to slow the speed of biodegradation of part or all implantable devices, and/or mixing with the bioactive agents (e.g., drugs), speeding up the healing of the tissue surrounding the device. If the pores of the device from powdered metal fills medicine, deliver medicine in degradation of the device is opened, thus providing the drug to the tissue site as the existence and biodegradation of the device.

In some embodiments, an implantable medical�the device is designed for implantation in humans. In other embodiments, an implantable medical device designed for implantation in domestic animals (e.g. dog or cat). In other embodiments, an implantable medical device designed for implantation in farm animal (e.g., cow, horse, sheep, pig, etc.). In other embodiments, an implantable medical device designed for implantation in a wild animal.

In another aspect the invention provides a container containing an implantable medical device in accordance with the invention. In some embodiments the container is a packing container such as a box (e.g., box for storage, sale or transportation of the device). In some embodiments, the container further comprises instructions (e.g., use of implantable medical devices to medical procedures).

The following examples are intended to illustrate but not to limit the invention in any way, shape or form, either explicitly or implicitly. While specific alloys describe exemplary alloys that can be used in implantable medical devices in accordance with the invention, specialists in the art can readily identify other suitable alloys in the light of the present description� invention.

Examples

Example 1

Martensitic steel "brand A", consisting of 0.23 percent carbon, 3.1% of chromium, 11,1% Nickel, 1.2% of molybdenum, 13.4% of cobalt and 70,97% of iron was obtained from Carpenter Steel. The steel was treated by heating in a reducing atmosphere at 1250°C for 12 hours, followed by slow cooling. The material is then tested for Rockwell hardness, having a range of hardness 31-32 on a scale From Rockwell. The steel then cut into pieces of various sizes:

(1) width 0,514 inch, length 0,0315 inch, thickness 0.020 inch, with a ratio of surface to volume is approximately 167,4 and weighing approximately 48,2 mg;

(2) width 0,514 inch, length 0,0315 inch, thickness 0,050 inch, with the ratio of surface to volume is approximately 107,4 and weight around of 119.8 mg; and

(3) width 0,514 inch, length 0,0315 inch, thickness 0,500 inch, with the ratio of surface to volume is approximately 71,4 and weighing approximately 1207,7 mg.

Each piece of steel was immersed in 10 ml of human blood at 37°C with gentle rocking. The slices were extracted at intervals of one week, weighed and tested for Rockwell hardness. Experimental pieces demonstrated the degradation rate corresponding to the linear formula L=0,74·S, where L is the weight loss in milligrams per day, a S is the total surface area. Did not show loss of hardness of the material to the point where t�Lina material became too small to measure, demonstrating the loss from the outer surface of the material without degradation of the inner part of the material.

Example 2

Austenitic steel containing 0.1% carbon, 0.45% of manganese, and 99,45% iron, with the inclusion of not more than 0.05% of the pollutants were obtained from a commercial source. Alloy etched and tested for grain size and Rockwell hardness. The alloy was cut into several pieces with a width of about 0.5 inch, a length of approximately 0.5 inches and a thickness of about 0.005 inches.

Pieces of austenitic steel were tested for hardness, and then immersed in 10 ml of blood at 37°C with gentle stirring. The slices were extracted at intervals of one week, were tested for hardness and re-immersed in fresh blood for the next period. The obtained dissolution in blood samples corresponded to the linear formula L=1,05·S, where L is the weight loss in milligrams per day, and S is the total surface area. Did not show loss of hardness to the point where the thickness of the material became too small to measure the hardness.

In both of the above experiments, the dissolution rate was more dependent on total surface area, which due to the shape of experimental pieces very little changed throughout the experiment. In the forms of devices that are more relevant to practical implant size �poverhnosti device decreases as the dissolution of the device and replacement of body tissues. The reduction in surface area reduces the rate of metal loss, causing loss of geometric dependence of the losses from the remaining surface area of the device. Thus, the specialist in the art it is clear that the rate of loss of implantable devices largely depends on the geometrical shape of the device.

Example 3

Some examples of austenitic alloys that are suitable for use in implantable medical devices in accordance with the invention, are as follows:

Alloy 1:

Carbon0,1%
Nickel6,0%
Cobalt20,0%
Manganese1,0%
Chrome2,0%
Molybdenum2,0%
Iron68,9%

Alloy 2:

Carbon0,1%
Nickel6,0%
Cobalt 20,0%
Manganese8,0%
Chrome2,0%
Tantalum4,0%
Iron59.9% of

Alloy 3:

Carbon0,1%
Nickel0,0%
Cobalt20,0%
Manganese10,0%
Molybdenum2,0%
Tantalum4,0%
Iron63,9%

Alloy 4:

Carbon0,08%
Nickel0,0%
Manganese28,0%
Titanium3,0%
Iron68,92%

As is clear to a person skilled in the art, the above SP�ava may contain some impurities, slightly reducing the actual percentage of each element in the alloy compared with the specified value.

Example 4

Thin flat samples with an area of about 0.5 square inches and a thickness of 0.05 inches was made from martensitic steel consisting of 0.23 percent carbon, 3.1% of chromium, 11,1% Nickel, 1.2% of molybdenum, 13.4% of cobalt, and the rest iron. Flat shape was chosen so as to provide very small changes in surface area as the degradation of the sample. The samples were cleaned and weighed. Then all samples were immersed in buffered saline solution at 37°C with gentle shaking. Half of the samples are left to oxidize in air, forming a protective chromium oxides on the surface before the dive, and the other half was immersed immediately after cleaning. The samples were extracted at intervals of from one week to 136 days, dried and weighed. The samples that were immersed immediately after treatment, showed a continuous weight loss of 1.1 mg per square inch per day throughout the study period. The samples subjected to oxidation before the dive, showed a weight loss of 0.6 mg per day per square inch of surface. The protective effect of chromium oxide reduced the degradation rate by about 50%.

Example 5

Austenitic alloy containing 0.08% carbon, 18% manganese, 5% cobalt, 0.5% molybdenum, 1% tantalum, 2% chromium,melted, stamped draft and was subjected to hot rolling to a thickness of about 0.094 inch. The alloy had a hardness on a scale From Rockwell about 45. The samples were immersed in buffered saline solution at 37°C With gentle shaking. Samples were periodically washed, dried and weighed for three months. Marked by constant loss of mass of samples of 1.07 mg per square inch per day.

Example 6

Austenitic alloy containing 0.08% carbon, 18% manganese, 5% cobalt, 0.5% molybdenum, 1% tantalum, 2% chromium, melted, stamped draft and was subjected to hot rolling to a thickness of about 0.094 inch. The alloy was further calcined at 1800°F, after which the alloy had a hardness scale Rockwell about 25. The samples were immersed in buffered saline solution at 37°C With gentle shaking. Samples were periodically washed, dried and weighed for three months. Marked by constant loss of mass of samples 0,92 mg per square inch per day.

Example 7

Austenitic alloy containing 0.08% carbon, 18% manganese, 5% cobalt, 0.5% molybdenum, 1% niobium, 2% chromium, melted, stamped draft and was subjected to hot rolling to a thickness of about 0.094 inch. The alloy had a hardness on a scale From Rockwell about 45. The samples were immersed in buffered saline solution at 37°C With gentle shaking. Samples periodically ol�mawali, dried and weighed for three months. Marked by constant loss of mass of samples 1.08 mg per square inch per day.

Example 8

Austenitic alloy containing 0.08% carbon, 18% manganese, 5% cobalt, 0.5% molybdenum, 1% niobium, 2% chromium, melted, stamped draft and was subjected to hot rolling to a thickness of about 0.094 inch. The alloy was further calcined at T, after which the alloy had a hardness on a scale From Rockwell about 25. The samples were immersed in buffered saline solution at 37°C With gentle shaking. Samples were periodically washed, dried and weighed for three months. Marked by constant loss of mass of samples of 0.98 mg per square inch per day.

Although the invention is described with reference to the present preferred embodiment, it should be understood that various changes and modifications, obvious to those skilled in the art, may be made without straying from the invention. Accordingly, the invention is limited only by the claims.

1.Implantable medical device comprising a biodegradable alloy, which is essentially austenitic structure and which has an average grain size in the range of from about 0.5 microns to 20 microns, and the ratio of surface to volume of individual grains on average exceed 0.1 Mick�he -1.

2. Implantable medical device according to claim 1, wherein the average grain size is from about 0.5 microns to 5.0 microns.

3. Implantable medical device according to claim 1, wherein the average grain size is from about 1.0 microns to 2.0 microns.

4. Implantable medical device according to claim 1, wherein the ratio of surface to volume of individual grains on average more than 1.0 μm-1.

5. Implantable medical device according to claim 1, which is a bone screw, the bone locking, cloth bracket, a plate for cranio-maxillo-facial reconstruction, latch, restorative dental implant or stent.

6. Implantable medical device according to claim 1, wherein the alloy contains austentatious component, including manganese, cobalt, platinum, palladium, iridium, aluminum, carbon, nitrogen, silicon or any combination thereof, and corrosion-resistant component comprising chromium, molybdenum, tungsten, tantalum, niobium, titanium, zirconium, hafnium or any combination of them, with the total number austentatious component in the alloy exceeds about 10%, and the total number of corrosion resistant component comprises from about 0.5% to 10%.

7. Implantable medical device according to claim 1, wherein the alloy contains less than about 0.1% Nickel and less than about 0.1% VA�adiya.

8. Implantable medical device according to claim 1, wherein the alloy essentially contains chromium.

9. Implantable medical device according to claim 1, wherein the alloy contains less than about 6% cobalt.

10. Implantable medical device according to claim 1, wherein the alloy contains less than about 0.1% Nickel, less than about 0.1% vanadium, less than about 4% chromium and less than about 6% cobalt.

11. Implantable medical device according to claim 1, wherein the alloy contains austentatious component, including manganese, cobalt, platinum, palladium, iridium, aluminum, carbon, nitrogen, silicon, or any combination thereof and in which % platinum + % palladium + % iridium + 0,5·(% manganese + % cobalt) + 30·(% carbon + % nitrogen) is greater than about 12%.

12. Implantable medical device according to claim 1, wherein the alloy comprises a corrosion-resistant component comprising chromium, molybdenum, tungsten, tantalum, niobium, titanium, zirconium, hafnium, or any combination thereof, and in which % chromium + % molybdenum + % tungsten + 0,5·(% tantalum + % NB) + 2·(% titanium + % zirconium + % hafnium) is from about 0.5% to 7%.

13. Implantable medical device according to claim 1, wherein the alloy contains austentatious component, including manganese, cobalt, platinum, palladium, iridium, aluminum, carbon, nitrogen, silicon or any combination of them, where % platinum + % pall�Diya + % iridium + 0,5·(% manganese + % cobalt) + 30·(% carbon + % nitrogen) is greater than about 12%, and wherein the alloy comprises a corrosion-resistant component comprising chromium, molybdenum, tungsten, tantalum, niobium, titanium, zirconium, hafnium or any combination of them, where % CR + % molybdenum + % tungsten + 0,5·(% tantalum + % NB) + 2·(% titanium + % zirconium + % hafnium) is from about 0.5% to 7%.

14. Implantable medical device according to claim 1, which is coated therapeutic agent.

15. Implantable medical device according to claim 1, which is covered with a biodegradable hydrogel.

16. Implantable medical device according to claim 1, which has a geometric shape that increases to a maximum ratio of surface to mass.

17. Implantable medical device according to claim 1, which comprises a hollow hole or passage.

18. Implantable medical device according to claim 1, wherein the biodegradable alloy comprises at least two non-ferrous metal element.

19. Implantable medical device according to claim 1, wherein the biodegradable alloy comprises manganese and niobium.

20. Implantable medical device according to claim 1, wherein the biodegradable alloy comprises from at least 0.01 to 0.1% of a non-metallic element.

21. Implantable medical device according to claim 1, wherein the biodegradable alloy comprises from at least 0.01 to 0.1% carbon.

22. Implantable medical�first device, contains biodegradable alloy, which is essentially austenitic structure and which has an average grain size in the range of from about 0.5 microns to 20 microns, and the ratio of surface to volume of individual grains on average exceeds 0.1 μm-1while recrystallization at a temperature of approximately from 0.35 to 0.55 of the absolute melting temperature of the alloy allows the crystal lattice of the alloy to undergo rearrangements in low-energy state without changing the overall microrasbora.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine. A method of post-loading of ceramic particles with antimicrobial metal cations is described. The post-loaded particles represent zeolites, where the zeolites are includes into resin, and a combination is used as an implanted device. The polymer represents a thermoplastic polymer such as polyaryletheretherketone (PEEK). A source of antimicrobial activity includes ion-exchange cations, contained in zeolite. Described is the method of adding antimicrobial activity to devices by regulating the delivery of certain cations by ionic exchange via zeolite, included into the device.

EFFECT: device makes it possible to reduce bacteria growth and infection risk.

14 cl, 2 ex

FIELD: medicine.

SUBSTANCE: invention describes a composite ceramic bone graft containing a porous ceramic carrier made of zirconium oxide - aluminium oxide; the carrier is coated with a layer of hydroxyl apatite and platelet-rich plasma; the carrier is made by preparing a mixture ceramic powder and foaming agent Al(OH)3 or Zr(OH)4, adding distilled water to give the moulding properties and caking the end product.

EFFECT: composite ceramic bone graft of the ceramic material of zirconium oxide system is effective and applicable in medicine for synthesis of the anatomic continuity and functions of the bone tissue.

1 ex, 14 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, more specifically to absorbable polyether esters that have been found to reduce bacterial adhesion to materials such as medical devices and implants. Amorphous copolymers are used to produce a coating for medical devices and implants to reduce bacterial adhesion.

EFFECT: invention refers to new amorphous copolymers containing polyethylene diglycolate (PEDG) copolymerised with lactide-rich monomers.

15 cl, 4 dwg, 7 tbl, 13 ex

FIELD: medicine.

SUBSTANCE: there are described new reinforced biodegradable frames for soft tissue regeneration; there are also described methods for living tissue support, extension and regeneration, wherein the reinforced biodegradable frame is applied for relieving the symptoms requiring high durability and stability apart from patient's soft tissue regeneration. What is described is using the frames together with cells or tissue explants for soft tissue regeneration in treating medical prolapsed, e.g. rectal or pelvic prolapse, or hernia.

EFFECT: frames are adequately durable to be applicable for implantation accompanying the medical conditions requiring the structural support of the injured tissues.

14 cl, 19 dwg, 2 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: tissue regeneration or healing is stimulated when using a structure comprising a multilayer plate of a collagen membrane material, which contains a lamellated barrier material of pure collagen prepared of a natural collagen tissue; the lamellated barrier material containing a barrier layer with an outer smooth barrier surface and a fibre surface, which is opposite the outer smooth barrier surface. The structure additionally contains a matrix layer of a collagen sponge material adjoining the fibre surface.

EFFECT: matrix layer of the collagen sponge material is absorbed by an individual's body at a higher rate, than the lamellated barrier material.

20 cl, 3 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a method for measuring antimicrobial-coated tubular polyurethane products, including multiple-lumen polyurethane catheters consisting in the three-staged chlorhexidine and/or its salts modification. Chlorhexidine and/or its salts are impregnated on the product surface by processing the products in aqueous-alcohol solutions of chlorhexidine and/or its salts, removing excessive chlorhexidine and/or its salts from the product surface, applying a solution of polyurethane in tetrahydrofurane containing chlorhexidine and/or its salts, and evaporating tetrahydrofurane.

EFFECT: preparing the polyurethane products, eg catheters possessing the prolonged antimicrobial activity being in full accord with the multifunctionality of the multiple-lumen catheters.

9 cl, 1 tbl

FIELD: medicine.

SUBSTANCE: antimicrobial composition for coating a medical device includes a material, which forms a polymer film, and an antimicrobial preparation from the traditional Chinese medicine, selected from a group: extract of Houttuynia cordata, sodium houttuyfonat and sodium new houttuyfonat or their mixtures. The medical device, covered with an antimicrobial composition, is made in the form of an implanted device.

EFFECT: invention provides the antimicrobial effectiveness with respect to microorganisms - causative agents of surgical infections.

19 cl, 2 dwg, 7 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a bioresorbable hydrogel polymer composition for cardiovascular surgery in the form of a film prepared by a reaction of natural polymers, biologically active substances, a solvent and a softening agent wherein the polymers are presented by cross-linked bioresorbable polymers - gelatin, chitosan or a mixture of chitosan and gelatin, chitosan and polyhydroxybutyrate; the biologically active substance or mixtures thereof are presented by the antioxidant L-carnosine, the anticoagulant heparin, the antiaggregant dipyridamole, acetylsalicylic acid, the non-steroid anti-inflammatory preparation acetylsalicylic acid, the antimicrobial preparations - ciprofloxacin, metronidazole; mechanical strength of the film is not less than 1.2 MPa, the relative elongation is no more than 160%, and the elasticity modulus is 0.4-5 MPa.

EFFECT: there are used hydrogel polymer compositions with the control bioresorption period, prolonged length of biologically active substance release, having biocompatible and thrombus-resistant properties and improved mechanical characteristics - higher softness and elasticity.

7 cl, 12 dwg, 2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and tissue engineering, and may be used in cardiovascular surgery for small-vessel bypasses. A vascular graft is made by two-phase electrospinning with the staged introduction of the ingredients into the polymer composition.

EFFECT: making the bioresorbed small-diameter vascular graft possessing the improved biocompatibility ensured by using the polymer composition of polyhydroxybutyrate (PHBV) with oxyvalerate, and epsilon-polycaprolactone with type IV collagen, human fibronectin and human fibroblast growth factor (hFGF) additionally introduced into the composition.

2 cl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine. What is described is a biomaterial on the basis of calcium phosphate, preferentially on the basis of hydroxyapatite, or on the basis of a material containing hydroxyapatite, such as diphase calcium phosphates and calcium phosphate cements, and using it for making an implant or for positioning prosthesis for the purpose of osteoanagenesis.

EFFECT: biomaterial provides the excellent properties of biological compatibility and fast osteoneogenesis.

17 cl, 4 dwg, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to medicinal hydrogel polymer materials, used as a base for the creation of polymer implants and products, contacting with blood. Described is a non-porous hydrogel material based on a modified polyvinyl alcohol, which contains unsaturated radicals in side chains, obtained by polymerisation at 0-250°C in a solution or in polymer powder sintering at 100-180°C. Also described is a combined material, containing a matrix of the porous hydrogel polymer material and reinforcing filler, filling the matrix, of the non-porous hydrogel material obtained by the said method.

EFFECT: materials are liquid-impermeable, possess biocompatibility, high strength characteristics and high stability at heating.

3 cl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine. Described are biomaterials prepared by mixing an autocross-linked derivative of hyaluronic acid with hyaluronic acid derivative cross-linked with 1,4-butandiol diglycidyl ether (BDDE) in a weight ratio from 10:90 to 90:10, as new fillers.

EFFECT: biomaterials make is possible to promote the immediate regeneration/restoration of dermal/skin tissue, which has lost its initial tightness.

7 cl, 2 dwg, 16 ex

FIELD: medicine.

SUBSTANCE: there are described compositions containing hyaluronic acid with a low degree of modification of functional groups, and mixtures prepared by a controlled reaction of this slightly modified hyaluronic acid with applicable difunctional or polyfunctional cross-linking agents. The compositions possess the low anti-inflammatory properties in injection in vivo and can be used as medical devices, biomedical adhesives and sealing matters.

EFFECT: targeted delivery of the bioactive substances.

49 cl, 14 dwg, 24 tbl, 45 ex

FIELD: medicine.

SUBSTANCE: bioactive porous 3D-matrix for tissue engineering involves a resorbed partially crystalline polymer having a porosity of 60-80% and a pore size of 2 to 100 mcm. A biopolymer gel having a particle size of 30-100 mcm is incorporated into a portion of the pores. A polymer/gel ratio makes 99:1 to 50:50 wt %. The matrix is prepared by grinding a mixture of gel and polymer powder having an average particle size of 100 mcm, and the prepared mixture fills prepared moulds to be placed in a high-pressure chamber wherein the temperature is increased to 25-40°C first, and then the CO2 pressure is increased to 4.0-25.0 MPa. The system is kept in the above environment for 1 hour, and then the chamber pressure is discharged to an atmospheric one for 30-120 minutes; thereafter the temperature is decreased to a room value, and the patterns are removed.

EFFECT: ensuring flexibility of using the matrix in various organs and systems, no toxicity, higher ability to tissue regeneration stimulation, prolonged effect of biostimulation.

6 cl, 5 ex, 1 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: conduit wall is presented by a material of random micro- and nanofibres of a bioresorptive polymer of poly(ε-caprolactone), and the content is presented by a self-assembled nanostructured hydrogel of acetyl-(Arg-Ala-Asp-Ala)4-CONH2(PuraMatrix™) oligopeptide. The above conduit is implanted in a complex with the direct local delivery of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) genes to be introduced into the proximal and distal nerve segments, while the formed conduit is implanted into a nerve rupture, and its ends are fixed with epineural sutures.

EFFECT: invention provides a stimulating effect on the invasion of regenerative medullated fibres, on the recovery of motor and sensitive nerve function, and enables improving the effect of the recovery of the nerve structure and function after the extended ruptures.

4 cl

FIELD: medicine.

SUBSTANCE: claimed invention is aimed at manufacturing intraocular lens (IOL), for introduction of posterior eye chamber in form of PC Phakic lens. IOL is formed from hydrogel material, formed by cross-linked polymer and copolymer component. Lens includes UV chromophore, which is benzotriazole.

EFFECT: IOL hydrogel material usually has relatively high index of refraction and/or possesses desirable degree of protection against irradiation.

12 cl, 3 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine. Described is implant, which can be injected in subcutaneous or intracutaneous way in form of monophase hydrogel, which contains gel, obtained from cross-linked hyaluronic acid and one of its physiologically acceptable salts.

EFFECT: obtaining subcutaneous implant used for filling wrinkles and stimulation of epidermal cells and/or supporting mechanical properties of skin density and elasticity.

15 cl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, in particular to method of obtaining form-preserving aggregates of gel particles, in which aggregates are held together by physical forces of non-covalent bonds, such as hydrophobic-hydrophilic interactions and hydrogen bonds. Method of obtaining form-preserving aggregates of gel particles includes introduction of preliminarily obtained suspension of gel particles in polar liquid, where gel particles have absolute electrochemical potential, into receiving medium, in which absolute electrochemical potential of gel particles decreases, which results in fusion of gel particles into form-preserving aggregate.

EFFECT: invention allows to obtain form-preserving gel aggregates in situ so that form of aggregate is determined by place of application.

49 cl, 35 ex, 11 tbl, 33 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, more specifically to biocompatible alginate systems with the delayed gelatinisation process. There are offered sets and compositions for making a self-gelatinised alginate gel containing sterile water-soluble alginate and particles of sterile water insoluble alginate with a gelling ion. There are offered methods for dosing self-gelatinised alginate dispersion for making the self-gelatinised alginate gel. The methods can include dosing the dispersion in an individual. There is offered the self-gelatinised alginate gel of the thickness more 5 mm and not containing one or more sulphates, citrates, phosphates, lactates, EDTA or lipids. There are offered implanted devices coated with the homogeneous alginate gel. There are offered methods for improving viability of pancreatic islets or other cell aggregate or tissue, after recovery and while stored and transported.

EFFECT: group of inventions provides creation of the alginate gelling system which contains alginate and the gelling ions with high biological compatibility; enables the gelatinisation process without pH variations, connected with the other systems, and requires minimum ingredients, thus provides variation of gelatinisation time and gel strength depending on the specific requirements.

62 cl, 11 dwg, 2 tbl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing biologically compatible gel which is thickened with cross-linked polymer by cross-linking a given amount of at least one biologically compatible natural polymer in a solution by adding a defined amount of cross-linking agent, an additional amount of polymer with molecular weight over 500000 dalton in a solution, in which the reaction mixture is diluted to reduce concentration of polymer in the solution, and the cross-linking reaction is stopped by removing the cross-linking agent.

EFFECT: gel and its use for separating, replacing or filling biological tissue or for increasing volume of such tissue, or supplementing or replacing biological fluid.

11 cl, 1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to an orthopaedic product and an orthopaedic pad, particularly an amputation stump pad, a contact pad, a prosthesis cover, an orthesis cover, a prosthesis collar, a shoe sole or orthopaedic socks, i.e. polymer materials used in direct skin contact. The polymer material is applicable for direct skin contact and contains a fine-distributed silver as an antibacterial agent and is additionally provided with fine-dispersed particles of other metal. The metals of the group containing aluminium or aluminium alloy, magnesium, bronze, titanium and/or platinum are applicable.

EFFECT: invention enables concealing the discoloration when using the orthopaedic pad on the skin, and hence when using the orthopaedic product provided with this pad, also including for masking the discoloration in the pigmented or coloured polymer materials applicable in air or skin contact.

7 cl, 1 tbl

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