Method for making antimicrobial implants of polyetheretherketone
SUBSTANCE: invention refers to medicine. There are described methods for making implantable medical devices, preferentially of PEEK, having antimicrobial properties. The antimicrobial action is ensured by implantation of ceramic particles containing antimicrobial metal cations into the molten PEEK resin to be cooled and finally shaped by injection moulding, cutting and mechanical treatment or by other processing methods.
EFFECT: implants possess effective antimicrobial action for reducing a bacterial growth and a risk of infection.
12 cl, 1 dwg, 3 tbl
This application has a priority based on provisional application for U.S. patent number 61/285,719, registered on December 11, 2009, and the number 61/300,629 registered 2 February 2010, the descriptions of which are incorporated herein by reference.
The LEVEL of TECHNOLOGY
Implantable medical devices implanted in the body for a variety of reasons, including orthopedic (e.g. replacement of the hip, spine surgery, knee replacement, plastic, bone fractures and other). Taking into consideration the requirements for structural integrity of such products, materials for their production is limited and traditionally include metal, plastic and composite materials.
The benefits derived from the use of these products, often neutralized infection, which can lead to infection and death. The most common organisms causing infection are epidermal Staphylococcus (Staphylococcus epidermidis and Staphylococcus aureus (Staphylococcus aureus). Other gram-positive bacteria, gram-negative bacteria and fungal organisms are also problematic. Of particular importance is methicillin-resistant Staphylococcus aureus (MRSA), a genus of bacteria of the Staphylococcus that is resistant to many antibiotics. As a result, MRSA infection more difficult the treatment, than ordinary staph infections, and they have become a serious problem.
Many pathogenic bacteria can form on bioengineered implants multicellular covering layers called biofilms. Biofilms may contribute to the proliferation and spread of microorganisms by providing a protective environment. These biofilms, if they are well developed and can spread bacterial planktonic precipitation that can lead to extensive systemic infection.
Bioengineered materials serve as excellent carriers for the formation of bacterial biofilms. Sometimes the implant carries the infective organism, and the implants are developing very resistant biofilms sown infective organisms. When this happens, typically, the implant must be removed, the patient must undergo a long course of treatment for one or more antibiotics to eliminate the infection, and then implanted the new implant. This obviously exposes the patient to additional trauma and pain and is extremely expensive.
Accordingly, many studies have been devoted to preventing the formation of colonies of bacterial and fungal microorganisms on the surfaces of orthopedic implants by approx the various antimicrobial agents, such as antibiotics, communicating with the surface of the materials used in these products. For example, silver is a powerful natural antibiotic and preventative measure against infections. Acting as a catalyst, it deactivates enzymes (enzymes)that need single-celled bacteria, viruses and fungi for their oxygen metabolism. They are suppressed without proper damage enzymes person or components of metabolism in the human body. The result is the destruction of pathogenic microorganisms in the body. Silver destroys the membrane of the bacteria, intermembrane enzymes and DNA biosynthesis.
Ceramic materials, such as zeolite, functioning as a cationic lattice, having the opportunity to feast upon the silver and other cations having antimicrobial properties. Metallocyanide can be used as an antimicrobial agent, for example, by mixing with the resin used as thermoplastic materials, in the manufacture of implantable products, or as a covering layers are applied to products; see, for example, U.S. patent number 6582715, the description of which is incorporated herein by reference. Antimicrobial metallocyanide can be prepared by replacing all or part of the ion-exchange ions in the zeolite by ion is ammonium ions and antimicrobial metals. Preferably, replaced not all ion-exchange ions.
One specific example of thermoplastic resin, which is recognized as applicable to implants is polyetheretherketone (Cape peek). This thermoplastic polymer is an aromatic main chain connected with ketone and ether functional groups. Cape peek is suitable for implants, because its modulus of elasticity is practically coincides with the modulus of elasticity of the bone, and it is resistant to chemical and radiation damage. Varieties Cape peek approved for implantation, are very clean and inert and must undergo stringent testing for cytotoxicity, prior permission for their implantation in the body of mammals.
Set ISO 10993 sets a number of standards for evaluating the biocompatibility of a medical product prior to beginning clinical trials. These documents was preceded by a tripartite agreement and are part of the harmonisation of the assessment of the safe use of medical devices. These standards include:
ISO 10993-1:2003 Biological evaluation of medical devices. Part 1: Evaluation and testing
ISO 10993-2:2006 Biological evaluation of medical devices. Part 2: Requirements for animal health
ISO 10993-3:2003 Biological evaluation of medical devices. Part 3: Tests on genotoxin the face, Carcinogenicity and toxicity that affect fertility
ISO 10993-4:2002/Amd 1:2006 Biological evaluation of medical devices. Part 4: Selection of tests relating to interactions with blood. Change 1
ISO 10993-5:2009 Biological evaluation of medical devices. Part 5: Tests for cytotoxicity in vitro
ISO 10993-6:2007 Biological evaluation of medical devices. Part 6: Tests for local effects after implantation
ISO 10993-7:1995, Biological evaluation of medical devices. Part 7: the Remains at the time of sterilization with ethylene oxide
ISO 10993-8:2001 Biological evaluation of medical devices. Part 8: Selection and evaluation of reference materials for biological tests
ISO 10993-9:1999 Biological evaluation of medical devices. Part 9: Structure identification and quantification of potential degradation products
ISO 10993-10:2002/Amd 1:2006 Biological evaluation of medical devices. Part 10: Tests for irritation and allergic reaction of the delayed type. Change 1
ISO 10993-11:2006 Biological evaluation of medical devices. Part 11: Tests for systemic toxicity
ISO 10993-12:2007 Biological evaluation of medical devices. Part 12: sample Preparation and reference materials (available in English only)
ISO 10993-13:1998 Biological evaluation of medical devices. Part 13: Identification and quantification of products is impressive decomposition in polymer medical devices
ISO 10993-14:2001 Biological evaluation of medical devices. Part 14: Identification and quantification of degradation products ceramics
ISO 10993-15:2000 Biological evaluation of medical devices. Part 15: Identification and quantification of degradation products of metals and alloys
ISO 10993-16:1997 Biological evaluation of medical devices. Part 16: the Concept toxicokinetics studies of degradation products and leachables
ISO 10993-17:2002 Biological evaluation of medical devices. Part 17: Establishment of allowable limits leachables
ISO 10993-18:2005 Biological evaluation of medical devices. Part 18: Determination of chemical characteristics of materials
ISO/TS 10993-19:2006 Biological evaluation of medical devices. Part 19: Physico-chemical, morphological and topographical characterization of materials
ISO/TS 10993-20:2006 Biological evaluation of medical devices. Part 20: Principles and methods immunotoxicological testing of medical products
During high temperature processing metallocyanide can release moisture, if you are not extremely dry. This moisture can cause the formation of voids in the polymer melt and may contribute to the destruction of Cape peek-polymer and oxidation of metals, such as silver, copper and/or zinc embedded in zeolite antimicrobial preparation is so Despite the fact that the presence of voids may be negligible for some applications, no load, no voids is of particular importance for applications with load, for example, when the plastic spine.
If the process of implementation of metallothionien is in the air, can be severe oxidation as the temperature is increased and the moisture and oxygen come into contact with metal ions. Silver is rapidly darken to dark brown or black. Also, the introduction of significant quantities of metallothionien in Cape peek-polymer can affect the viscosity and rheology of the composition.
The present description is based on the idea of the possibility, under the conditions of high temperature and high shear effort to implement antimicrobial zeolite, such as silver zeolite, in Cape peek, for example, by mixing alloy metallothionien with melt temperature peek cages (melting point between 300 and 400°C, depending on purity), followed by forming and processing a composite mixture. In the result are provided with medical devices such as implants, with effective antimicrobial action to reduce the growth of bacteria and the risk of infection.
The defect of the prior art are eliminated by using the present invention, which relates to the FPIC of the BAM receiving implantable medical device preferably from Cape peek, having antimicrobial properties. The antimicrobial effect is achieved by the introduction of ceramic particles containing cations of antimicrobial metals in the melt Cape peek resin, which is then cooled and takes its final shape, provide injection molding, cutting and machining or other processing methods.
The rate of release of metal ions is determined by the degree of saturation of the plastic ceramic particles containing antimicrobial metal cations, and the dosage of the metal in the ceramic material. Electrolytic concentration in blood and biological fluids is relatively constant and causes ion exchange ions such as silver ions, copper, zinc and others, with the implant surface, which inactivate or kill gram-positive and gram-negative microorganisms, including Escherichia coli (E. coli) and Staphylococcus aureus (Staphylococcus aureus). Effective antimicrobial control reduction of microorganisms by six orders of magnitude (a million times) is achieved, for example, at concentrations of metallocyanide 4% or more. Products are implanted in the animal body, in particular the human body. Specifically discusses spinal implants.
BRIEF DESCRIPTION of DRAWING
1 shows a perspective view of cervical the second spacers, in accordance with some of the options for implementation.
Embodiments of disclosed herein relate to processing of ceramic materials, preferably zeolites as cation lattice, in combination with medical implants for delivery and dispensing one or more antimicrobial cations. In addition to zeolites, other suitable ceramic antimicrobial materials include hydroxyapatite, zirconium phosphates and other ion-exchange ceramic materials.
Suitable cations include ions of silver, copper, zinc, mercury, tin, lead, gold, bismuth, cadmium, chromium and thallium, and combinations thereof, most preferably silver ions, zinc and/or copper. Either natural or synthetic zeolites can be used as zeolites used in variants of the implementation disclosed in this document.
"Zeolite" is an aluminosilicate having a three dimensional skeletal structure, which is represented by the formula: XM2/nO∙Al2O3∙YsiO2∙ZH2O, in which M represents an ion-exchange ion, typically ion is monovalent or divalent metal, n is the atomic valence of the ion (metal), X and Y represent coefficients of metal oxide and silicon, respectively, and Z represents the t amount of water of crystallization. Examples of such zeolites include zeolite A-type zeolites, X-type zeolites, Y-type zeolites T-type, high-silicon zeolites, sodalites and others.
In addition, silicate materials, such as phosphate glass doped with metal, bioactive glass, such as 45S5 and BG can be processed to deliver an appropriate dose of antimicrobial cations.
The following terms of handling and manipulation required for processing antimicrobial Cape peek-implants with desirable properties.
Manipulation of materials
Cape peek is a refractory material which has a melting point of about 340°C and must be processed at a temperature of from 360°C to 400°C, to the possibility of introducing powders metallothionien and forming by extrusion or casting of the composite mixture. Under these high temperatures, the release of any trapped moisture can cause the formation of voids in the polymer melt. This may contribute to the destruction of Cape peek-polymer and oxidation of metals embedded in zeolite antimicrobial agent, reducing the effectiveness of antimicrobial action. In addition, the presence of voids can significantly weaken the properties of the final product. In the case of material produced for spinal implants used with the load, minimizing the sizes and quantities is any voids is of particular importance for the preservation of the mechanical properties of the final product. Therefore, the removal of residual moisture from the raw materials used in the manufacture of implants, Cape peek and antimicrobial powder (component composite mixture), is a sine qua non. Powder silver zeolite must be heated to a temperature of about 400°C at atmospheric pressure and is thus in sufficient time for the release of adsorbed water. If you distribute the powder in a thin layer, the release of water will be more effective and appropriate aging time will be from 30 to 60 minutes. Silver zeolite can be dried at lower temperatures and reduced pressure. Preferably, the components of the composite mixtures were dried in a clean environment to less than 0.1% moisture by weight before processing. In addition, it is extremely important to keep the material in a dehydrated conditions before and during processing.
Antimicrobial powder is very hygroscopic, requiring hermetic sealing material in its original packaging prior to any use. During action on the preliminary mixing contact with atmospheric air should be minimal. As an additional precaution, the tank powder feeder boot device must be very the puppy with dry nitrogen immediately before and after loading.
Cape peek-material should be dried at a temperature of from 120°C to 130°C for 12 hours (or equivalent to the ratio of time/temperature) before any blending operation. This ensures that the content of residual moisture in Cape peek-pellets less than 0.1% by weight before processing.
Packing after treatment: the materials should be Packed in moisture-proof containers immediately after mixing.
Equipment for mixing
To achieve a high degree of viscosity can be used twin screw extruder for mixing Cape peek with other additives. The additive is dosed gravimetrically in the melt Cape peek right before the introduction of the screw of the extruder with the aim of obtaining the desired saturation additives. The use of co-rotating twin screw extruder improves the distribution of filler in the mixture and the impregnation and results in a more reproducible rheological properties.
A specific example of the preferred equipment used for mixing, is described below:
Line extruder: 30 mm
Set auger: 30-3
Scheme matrix: 2-channel
The range of acceptable values of the length of the pellet (inches): 0,100-is 0.135
The range of acceptable values of the diameter of the pellet (inches): 0,085-0,120
One of the suitable extruder is a twin screw extruder Leistritz ZSE.
Rich Cape peek-procurement, having a form close to the set, and suitable for secondary machining, can be manufactured through a process of compression molding. Compression molding is a method of forming a pre-heated saturated Cape peek polymer pellets or preforms in a pre-defined form under pressure a heated mold cavities. Compression molding is a multi-step method that uses high pressure and which is suitable for forming complex shapes. In this process you lose a relatively small amount of material compared to machining products from extruded rods.
Cape peek implants can be made to finishing profile by removal of material in the machining process such as turning, boring, boring, rolling, drawing, cutting, crimping, obstrusive and/or deployment. These machining processes can be performed manually or automatically through the use of multi-purpose CNC machines.
The conductivity of all polymeric materials is lower than that of metals, so that the heat generated during machining is fast. A cleaner cut and more open poverhnostnogo to be obtained, if the cutting plate is cooled and operates more slowly. Cape peek-surface subjected to machining, can come off preprinted paper and form a defect called "skin", if the temperature of the Cape peek-surface increases significantly during the machining material of the future implant, possibly affecting the release of cations. In order to achieve the highest efficiency of surface finishing, require clean cut and "open" the surface structure. One way of achieving the required quality of surface treatment is to cool the cutting tool cold, clean compressed air, in combination with optimized speed of the cutting tool and the rate of feed. In addition, the cooling rate can have a strong impact on the degree of crystallinity Cape peek that may be essential to optimize the speed of release of metal ions. By adjusting the cooling rate during production crystallinity percentage of the material of the implant is carefully monitored.
When the operations of machining and finishing at Cape peek materials often develop residual stresses. Before machining, it is recommended to expose the annealing components formed from Cape peek, for h is usually used to relieve stress. During mechanical or finishing additional voltage can accumulate inside the material by means of local heating on the cutting edge of the tool. Therefore, if the component is subject to significant mechanical or finishing process, you may need a second annealing procedure. On the basis of the desired result of the process of annealing (stress relieving, or thermal prehistory, or optimization of the crystal structure) the annealing of manufacturer's recommended Cape peek material, must be requested and followed.
Additional precautions can be taken to prevent contamination of surfaces Cape peek-products subjected to mechanical processing, by placing the machines marked "only for Cape peek and location of machines in places of production areas specially designated for machining Cape peek for medical devices.
Ready or almost ready-made saturated temperature peek cages can be manufactured using a molding process. During the molding process produces parts from saturated Cape peek polymer by feeding pellets saturated Cape peek into the heated barrel of the extruder (400°C), where the melt is saturated Cape peek mixed and wdwlive is conducted in a heated cavity of the mold, which is maintained at temperatures of from about 175°C to 205°C. Immediately after being pressed into the mold, the melt is saturated Cape peek is cooled to a temperature below 343°C and hardens, acquiring the shape of the cavity of the mold. Through careful monitoring and control of the preset value of the desired temperature (from about 175°C to 205°C) mold can be achieved a significant improvement of the control parameters and durability of parts and to minimize the generation of surface defects.
The optimal dosage of zeolite
The number of metallocyanide introduced into the resin must also be an amount effective to stimulate antimicrobial activity; for example, a sufficient amount of to prevent or block the growth of bacterial and fungal organisms and destroy them. At the same time, the introduction of significant quantities of metallothionien in the melt Cape peek-polymer can affect the viscosity and rheology of the mixture. So was established the processing interval, allowing sufficient dosage of zeolite without adverse effects on the properties of the final product throughout the sample volume.
The appropriate amount of zeolite in the resin are in the range from 0.01 to 20.0 percent by weight. It was found that the optimal dosage is in the range from 0.1 to approx the tion of 10.0 weight percent. Carefully controlled and monitored the size of the pellets obtained under conditions of optimal dosage, shown below in table 1. The color of the final pellets is an important indicator in case, if there is a strong oxidation or moisture to come into contact with metal ions during the high temperature process. Clean Cape peek has a glow, while properly treated zeolite Cape peek is brown in color. When oxidation has occurred, silver quickly darkens to dark brown or black color.
|Length and the average diameter of the pellets|
|Dosage of zeolite||The average diameter of the pellets (inches)||Length medium pellet (inches)||Color|
Confirmation inclusions zeolites
Images of samples obtained with a scanning electron microscope (SEM)revealed that the particles of the zeolite in the mixture are dispersed satisfactorily homogeneous. The images of SEM show that the samples are a highly saturated, in accordance with the set norms of saturation.
For the quantitative determination of saturation silver metallothionien was used pyrolysis. Small, accurately weighed quantity of the sample mixture Cape peek/silver zeolite was placed in a ceramic crucible and fired in a propane burner. While using this method the usual Cape peek burns completely, leaving no residue, Cape peek, rich metalloceramic, will burn with the formation of a powdery residue. The magnitude of the saturation silver zeolite can then be determined gravimetrically. The amount present of silver can be confirmed by extracting the silver from the residue and determine the amount of silver in the extract solution using graphite furnace AA or ICP.
Quantitative indicators for the silver recovered from the adsorbent
The proportion of extractable ionic took silver at the and in samples with different norms saturation was established by chemical analysis using the method of atomic absorption spectrometry with graphite furnace. Cut samples of size 1”x1” were immersed in 40 ml of 0.8%aqueous solution of sodium nitrate for a period of 24 hours. The amount of silver extracted from the various doses are shown in table 2.
|The amount of silver extracted from various dosage regimes|
|The concentration of the extracted silver (ug/l)|
|Dosage of zeolite||Cycle 1||Cycle 2||Cycle 3|
The extract from the adsorbent other antimicrobial metals may be determined in a similar manner.
Antimicrobial action is e
Is not certain that the zeolite of silver or other metal, is embedded in the melt Cape peek, demonstrate appropriate antimicrobial effects when the surface of the material exposed to microbial contamination. Samples with bacterial infection were performed on gram-negative (E. coli) and gram positive (Staphylococcus aureus) microorganisms at two different test doses (2% and 4%). The results show that for both microorganisms dosage of 4% was effective in combating colony forming units (CFU) of bacteria after 24-hour period. As shown in table 3, control samples without zeolite showed no bacterial reduction, whereas a dosage of 4% showed at least a reduction of microorganisms by six orders of magnitude (a million times) for a specified period of time.
|Antimicrobial action against gram-negative and gram-positive microorganisms|
|Dosage of zeolite||The tested microorganism||The average reduction in CFU|
|0% (control sample)||E. coli||No reduction|
|0% (control sample)||S. aureus||No reduction|
Proof for x-ray
One of the drawbacks of Cape peek-implant is that due to the transparency Cape peek for x-ray implantable products from Cape peek not appear sufficiently well on x-rays. Thus, the detection of the exact location and integrity of the implant and the monitoring of other important characteristics using x-rays can be difficult. One of the methods used to overcome this drawback is the addition of barium sulfate to the cooking mixture. Although products can be impervious to radiation due to the introduction of barium sulfate to Cape peek, adding the required amounts of barium sulfate to the desired degree of tightness about what a rule weakens the strength of the resulting product. Therefore, the use of an implant made from a mixture of barium sulfate and Cape peek, provides an undesirable relationship between the required mechanical properties of the product and its proof for x-rays. The materials described in this document, when observed under x-rays demonstrate properties impermeable to radiation, even at low dosage levels of silver zeolite. This is an important additional advantage that can be obtained without compromising the antimicrobial efficiency or mechanical integrity of the material.
Increased binding of cells
The zeolite on the surface of the implant can significantly increase the binding osteoblastic cells, due to the presence of negatively charged silicates present in the zeolite. An important drawback of the Cape peek-products is often a lack of proper adhesion of cells in the bed of the implant due to the inherent Cape peek inertia. This problem can be sufficiently reduced by the presence of negatively charged silicates on the surface of the implant. The structure of the zeolite is from nature negatively charged. These silicates attract proteins containing the sequence RGD-peptides with the relevant confirmation, resulting in St the statements and proliferation osteoblastic cells, bone-forming. This starts a cascade process, eventually leading to a significant growth of bone tissue.
Optimization of surface roughness
Cape peek is impervious to moisture, so that only the material of the surface layer, no deeper than the diameter of the zeolite particles, will be available for the recovery of silver. If the silver in this field was deactivated or otherwise converted into insoluble complexes, it is quite likely that the materials would not be suitable as antimicrobial materials. Therefore, the process conditions must be carefully monitored and followed to maintain the effectiveness of silver on the surface of the implant. Efficiency can be monitored quantitatively by measuring the recoverable silver using atomic emission spectroscopy with inductively coupled plasma (ICP) and provide a level much higher than the published minimum concentration that blocks the growth of biofilms, a value of 0.1 g/t (ppm) silver. It has been proven that 20 mg/t silver are active in laboratory conditions, and the components of the mixture show antimicrobial activity below 5 mg/I. in Addition, while the concentration of the bulk of the solution may be 5 mg/t, the activity of cations near the surface must be higher./p>
Surface color can also be used as quantitative measures for the control of process conditions. Deactivated or otherwise converted silver will change color from brown to black or a mixture of black and brown.
In addition, the surface roughness can be optimized to improve the osteogenic properties of the implant. Studies in the laboratory showed that all parameters (adhesion, proliferation, alkaline phosphatase activity, protein synthesis of bone matrix and mineralization), affecting the growth of bone tissue are influenced by the cleanliness of the surface finish of the material. Conventional production techniques, such as blasting (shot blasting, sand blasting, soda blasting, dry ice cleaning, etc.), scraping or grinding inert materials, can be used to control the surface roughness for optimization of the extraction of silver, and cell growth. Atomic force microscopy (AFM) or profilometry can be used to compute the average value of the parameter of surface roughness in nanometers, and this value can be correlated with growth parameters of bone taken from the results of laboratory of cell samples to obtain optimally the range of surface roughness.
The increase in tumor blood vessels (vascularization)
Early lumbar (lumbar) and cervical (neck) spacers had a monolithic structure in most cases. The goal was to create a polymer imitators allotransplantation bones, which were previous gold standard for osteosynthesis. Modern development of implants designs aimed at the holes between the inner and outer surfaces for the formation of new blood vessels (vascularization) new bone mass. The cavity of the spacer is important because it accommodates outer material (fillers) and may be a carrier of disease-causing microorganisms (pathogens). The columnar structure of the implants disclosed herein was designed in such a way that it provides a mechanically stable implant and at the same time increases the length of newly formed blood vessels and provides a large area for the extraction of silver.
A specific example of this design is depicted in figure 1. As can be seen from figure 1, column design makes it possible to significantly increase the surface area compared to a monolithic design. This provides significantly increased the profile of elution of silver, as well as the lengthening of the newly formed cravino the different vessels.
Giving a porosity of
Optionally, in some embodiments, the implementation of the Cape peek can be made porous with appropriate porosity, including porosity from 50% to 85% by volume. Porosity can be given through a pore-forming agents, such as sodium chloride, to obtain a porous polymer containing many interconnected voids, through processes known in the art. The average pore size is usually greater than 180 microns in diameter, respectively, from about 300 to about 700 microns.
Optionally, in some embodiments, the implementation of the Cape peek can be reinforced with a reinforcing material such as ceramics or graphite fiber. This can be done by distributing reinforcing material in polymer matrix Cape peek, for example twin-screw mixing implantable Cape peek-polymer with graphite fibers. The resulting product, reinforced graphite fiber, can be used for direct injection molding of the final products or forms of products that are close to the given one, or it can be molded in the form of workpieces for machining. The introduction of fiber or other suitable reinforcing material(s) provides a high symptom is sostonol, the modulus of elasticity of the value of 12 HPa (corresponding to the modulus of elasticity of bone), and sufficient tensile strength to enable its use in very thin structures implants, which are more efficiently distribute the load on the bone. The amount of reinforcing material, such as graphite fibers embedded in Cape peek, can vary, for example, to adjust the modulus of elasticity and tensile strength in bending. Such appropriate amount of 30 weight percent graphite fibers.
1. The method of obtaining antimicrobial carrying a load of spinal implant, comprising drying polyetheretherketone resin until a residual moisture of less than 0.1 wt. -%, heating the dried specified polyetheretherketone resin to a temperature effective to melt the specified resin, the melt mixing of the specified resin with metallothionien, which dried to a residual moisture of less than 0.1 wt. -%, the mentioned cooling the mixture and molding the above-mentioned mixture in a spinal implant.
2. The method according to claim 1, wherein the specified temperature effective to melt the said resin is from about 360°C to 400°C.
3. The method according to claim 1, wherein said metallocenic includes silver metallocenic.
4. The method according to claim 1, where the specified resin is dried put the m heating to a temperature of approximately 120°C to 130°C.
5. The method according to claim 1, where the specified zeolite is dried at a temperature of approximately 400°C.
6. The method according to claim 1, in which the specified stage mixing is carried out in a twin screw extruder.
7. The method according to claim 1, wherein the amount of zeolite mixed with the above resin, approximately from 0.01 to 20.0 weight percent.
8. The method according to claim 1, wherein said peek is porous.
9. The method of claim 8, wherein said seats has a coefficient of porosity from 50% to 85% by volume.
10. The method according to claim 1, wherein said seats is increased.
11. The method according to claim 10, wherein said peek is reinforced graphite fiber.
12. The method according to claim 1, wherein said metallocenic selected from the group consisting of silver, copper, zinc, mercury, tin, gold, bismuth, cadmium, chromium and thallium.
SUBSTANCE: invention refers to medicine. What is described is a method for preparing a cell-free organic tissue of a human or animal origin for the vitality recovery, particularly for introducing living cells, involving a stage of making a number of holes (4; 14) in the cell-free organic tissue (2; 12) through its surface (8; 18) and setting in the tissue (2; 12); wherein the said number of holes (4; 14) is formed using a needle or a kit of needles. The holes (4; 14) are partially intersected thereby forming partially connected holes (4; 14).
EFFECT: invention also refers to a respective cell-free organic tissue (2; 12) of the human or animal origin.
17 cl, 3 dwg
FIELD: process engineering.
SUBSTANCE: invention relates to medicine. Proposed method can be used in stomatology and orthopedics for production of medical materials stimulating recovery of bone tissue defects, for making dental stopping and dental pastes. It comprises preparation of mix containing compounds of calcium, phosphorus, silicon and sodium, impregnation of bioinertial incombustible porous matrix with made mix, matrix is composed of ceramics from aluminium or zirconium oxides followed by calcination. Note here that silicon compound represents tetraethoxysilane. Note also that phosphoric acid ether is used as phosphorus compound. Calcium and sodium compounds are represented by their carboxylates in polar organic solvent. This method includes making the thin layers on more strong bioinertial porous ceramics. Note also that said process involves no special complicated equipment and expensive reagents.
EFFECT: production of glass ceramics directly from solution omitting sol preparation stage, simplified and accelerated process.
7 cl, 5 ex
SUBSTANCE: invention refers to porous microsphere granules with the adjusted particle size for bone tissue regeneration. The above microspheres have a size within the range of 1-1000 mcm, have through pores of the size of 1-100 mcm and total porosity 40-75%. The declared microsphere granules are prepared by granulation by electrospinning, and heat-treated. A mixture used to form the granules by electrospinning contains a mixture of magnesium orthophosphate and biological hydroxyapatite of bovine demineralised bones in ratio 0.5:1.0, as well as 1-3% sodium alginate in distilled water and a hardener representing saturated calcium chloride.
EFFECT: invention provides preparing the microsphere granules possessing biocompatibility, biodegradation, osteoinduction and osteoconduction properties and able to be substituted by the bone tissue.
SUBSTANCE: invention relates to medicine, namely to ophthalmosurgery, and in particular to scleroplasty. Transplant for scleroplasty has polymeric base, covered with porous layer of the same polymer. As polymer base, transplant includes layer, made from porous stretched polytetrafluoroethylene, which has nodular-fibrillar structure. As porous layer, it includes layer of porous polytetrafluoroethylene, which has volume fraction of void space 15-40%, specific surface of void space 0.25-0.55 mcm2/mcm3, average distance between voids in volume 25-30 mcm and average chord volume 8-25 mcm, with the total width of transplant constituting 0.15-0.35 mm (first version). Transplant for scleroplasty can also include porous layer of polymer, whose surface is processed to add compatibility with sclera tissue. Transplant surface is processed by application of allogenic dermal fibroblasts of 3-5 passages of culturing, with the total width of transplant being 0.15-0.35 mm (second version).
EFFECT: chemically and biologically inert transplant, which ensures effect of invasion of sclera tissues, is obtained.
SUBSTANCE: invention relates to chemical-pharmaceutical industry and represents artificial dura mater, produced from electrospinning layers by technology of electorspinning, with electrospinning layer, consisting of, at least, hydrophobic electrospining layer, which is produced from one or several hydrophobic polymers, selected from polylatic acid and polycaprolactone.
EFFECT: invention ensures creation of artificial dura mater, which has good tissue compatibility, anti-adhesiveness and possibility of introducing medications, preventing cerebrospinal fluid outflow during regeneration of person's own dura mater.
30 cl, 7 ex, 11 dwg
SUBSTANCE: invention refers to medicine, particularly to ophthalmic and maxillofacial surgery, and aims at repairing post-traumatic defects and deformations of the eye-pit bottom and walls. What is described is an implant in the form of a solid perforated plate which is formed by photocuring of a light curing composition; when heated the implant (a cure temperature 70-90°C) keeps the shape after self-cooling that provides high strength and biocompatible properties of the material. The cure temperature of the material is much higher than a temperature of a human body that ensures maintaining the physical and mechanical properties of the implant inserted in the human body, namely the material remains strong, when fixed it shows no cutting and breaking. Before the implantation, the plate is heated to the required temperature and bent so that it is congruently repeats the eye-pit shape in a place of the defect, overlaps the defect and supports the eye in the right anatomical position.
EFFECT: reducing the likelihood of graft rejection and reducing a quantity of various complications by improving the biocompatible properties of the material.
1 tbl, 5 ex
SUBSTANCE: group of inventions refers to medicine. In a method for making an antimicrobial silver-containing endoprosthesis according to the 1 version, a mesh material is made of synthetic polymer fibres with a silver-containing composition in a solution, dried; the endoprosthesis made of polyvinylidene fluoride monofilaments of the diameter of 0.09-0.15 mm in the form of a form-stable combined weaved knitted cloth at surface density of the endoprosthesis 80-200 g/m2, processed for 2-4 hours in 3-15% silver nitrate solution in dimethylsulphoxide, dried in air for 17-20 hours, processed again, dried, additionally processed in the composition consisting of 4-8 wt % of aqueous sodium hydroxide, 6-10 wt % of aqueous ammonium and 0.3-0.7 wt % of aqueous glucose in proportions 100:4:4, at temperature 20-25°C, and then washed in water, and dried. According to the 2 version, the endoprosthesis made of polypropylene monofilaments of the diameter of 0.07-0.15 mm, at surface density 20-120 g/m2, processed in 5-15% silver nitrate solution in dimethylsulphoxide, dried for 5-8 hours, processed again, dried, processed in the composition (as provided by the first version) in proportions 100:7:9 at temperature 20-25°C, and then washed in water, and dried.
EFFECT: group of inventions provides prolonged antimicrobial action of the endoprosthesis.
2 cl, 2 tbl, 3 dwg
SUBSTANCE: invention refers to medicine, particularly traumatology and orthopedics, and can find application in treating false joints of long bones. What is described is a method for preparing a non-toxic porous implant of polylactic acid with controlled pore size for building of long bone defects involving melting the polylactic acid granules in a melting pot immersed in thermally stable oil with porogen presented by sodium chloride crystals 100-250 nm to be washed out by aqueous solutions of antiseptics. The implant is prepared with no toxic solvents added and has a pre-set pore diameter.
EFFECT: improved efficiency of the method.
SUBSTANCE: invention relates to a method of producing composite material from titanium nickelide-based alloys. The disclosed method involves process connection of a basic semi-finished product and porous components via self-propagating high-temperature synthesis, wherein titanium nickelide is additionally introduced into the structure of the composite material on selected areas of the semi-finished product. Titanium nickelide is a powder with the following grain-size distribution: 50-100 mcm - 60 wt %, 100-150 mcm - 40 wt %, and is introduced into said structure by sintering at 1260-1280°C for 1-5 minutes.
EFFECT: widening the pore size interval towards small values.
4 dwg, 1 ex
SUBSTANCE: invention relates to field of medicine. Described is method of biocompatible coating on implant surface which lies in precipitation on implant surface of polysilicon film in reactor. Obtained polysilicon film is subjected to chemical etching to form nanostructured superficial layer of porous polysilicon. Etching of polysilicon film nis carried out submerging implant into mixture which contains 50-55% water solution of tetrafluoroboric acid (HBF4), 70-90% water solution of nitric acid (HNO3) and anionic surface active substance on the basis of ammonium salt of perfluorsulfonic acid RfSO3NH4 in amount 5·10-3-10-2 (wt %), where Rf - C8F17 or C2F5OC3F6OC2F4, or C6F13CH2CH2. Used are water solution of acids with ratio of their volume parts: HBF4:HNC3, as (100-800):(1:1.1), with further washing of implant with deionised water and drying.
EFFECT: extension of technological possibilities of the method irrespective of materials used and constructive abilities of implants.
2 cl, 1 dwg, 2 ex
SUBSTANCE: what is described is an umbrella device (occluder) with a modified coating layer for the left atrial appendage occlusion. The umbrella device (occluder) with the modified coating layer is made from a titanium nickelide alloy. It has the coating modified layer having a thickness of 80-95 nm which consists of at least two sub-layers: an external sub-layer having a thickness of 20-25 nm contains oxygen, carbon, silicone and titanium in the following ratio, at %: oxygen 25-65, carbon 1-5, silicone 1-10, titanium - the rest; an intermediate sub-layer having a thickness of 60-70 nm contains oxygen, carbon, silicone, titanium and nickel in the following ratio, at %: oxygen 5-30, carbon 1-5, silicone 10-30, nickel 1-50, titanium - the rest, with silicone reaching its maximum concentration at a depth of 30-35 nm from the surface. The modified coating layer of the umbrella device (occluder) has no evident interface of the sub-layers specific for a deposited layer.
EFFECT: umbrella device with the modified coating layer possesses biocompatibility, corrosive resistance and no toxicity.
9 cl, 2 dwg
SUBSTANCE: group of inventions relates to ophthalmology and is intended for delivery of a therapeutic preparation into an eye. An eye device contains a non-biodegradable mass of material, which includes a hydrophobic component, represented in an amount, sufficient for contact angle of the material to be larger than 50° and formed of at least 80% by weight of acryl material. The device also contains the therapeutic preparation, located on the peripheral surface of the material mass. The therapeutic preparation is hydrophobic and has a coefficient of distribution in the system octane/water PC Log P, equal at least to 1.0. The material mass is formed for introduction into the human eye. Attraction of the therapeutic agent to the hydrophobic part controls a delayed release of the therapeutic preparation in such a way that less than 50 wt % of the therapeutic preparation is released from the eye device into the basic salt solution (BSS) within at least three days. The method of the eye device obtaining includes submergence of the material mass into the solution, which contains a solvent and the therapeutic preparation.
EFFECT: application of the group of inventions ensures delivery of the therapeutic preparation into the eye within long period of time.
19 cl, 12 dwg, 1 tbl, 12 ex
FIELD: process engineering.
SUBSTANCE: invention relates to production of cardio implants from titanium nickelid-based alloy with shape memory and superelasticity effects modified surface layer. Said implants are intended for long-term operation in cardiovascular system and feature corrosion resistance, biocompatibility and nontoxicity in biological media. Proposed method comprises making said cardio implant, chemical and electrochemical surface cleaning, surface cleaning by silicon ion flows produced by spraying silicon cathode in vacuum under conditions of high-dose ion implantation with fluence of (0.5÷6.0)×1017 cm-2 to obtain modified 80-95 nm-thick surface layer. The latter consists of at least two sublayers. Outer 20-25 nm-thick sublayer contains oxygen, carbon, silicon and titanium at the following ratio of components, at.%: oxygen - 25-65, carbon - 1-5, silicon - 1-10, titanium making the rest. Mid 60-70 nm-thick sublayer contains oxygen, carbon, silicon, titanium and nickel at the following ratio of components, at.%: oxygen - 5-30, carbon - 1-5, silicon - 10-30, nickel - 1-50, titanium making the rest. Note here that maximum concentration of silicon is reached at 30-35 nm from the surface.
EFFECT: modified surface layer features no apparent interface between sublayers.
9 cl, 1 dwg
SUBSTANCE: invention refers to medicine, more specifically to artificial biomaterials, methods for making and using them. There are described collagen biopolymers and biocomposites. Making an oriented fibre biopolymer material is ensured by preparing a solution of fibre biopolymer gel in a liquid crystal phase; a uniform layer of the solution is applied on a substrate and dried by fibre biopolymer orientation. If necessary, the biopolymer is removed from the substrate as a film. For making the biopolymer fibre, a tape of the oriented biopolymer material is immersed into the solution, then removed from the solution so that the biopolymer material is rolled as a fibre at the boundary of air and liquid.
EFFECT: simplifying and cheapening the method for making the oriented biopolymer materials, improving producibility, enhancing biocompatibility of such materials with living tissues.
38 cl, 4 tbl, 14 dwg
SUBSTANCE: invention refers to using a tracer agent for magnetic particle imaging (MPI) for the purpose of visual monitoring of a biocompatible product. The biocompatible product contains the tracer agent for magnetic particle imaging (MPI) by imaging technique using magnetic particles. The biocompatible product represents a microcontainer comprising a solid or semi-solid material applicable for cell culture support. The invention also refers to a method for visual monitoring of the biocompatible product. The declared method involves the stages of providing the biocompatible product containing the tracer agent for MPI, introducing the biocompatible product into a target area, and detecting signals generated by the tracer agent for MPI by imaging technique using magnetic particles.
EFFECT: invention provides monitoring of the targeted cell or active agent delivery into the target area.
10 cl, 2 ex
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
SUBSTANCE: invention relates to medicine and pharmaceutical industry, in particular to method of manufacturing elongated hollow body (1). Body, containing crystalline cellulose, has multiple projections (3, 4), which project into lumen of hollow body (1), on internal wall. Method of manufacturing elongated hollow body (1), includes stages: manufacturing hollow form (12), cultivation of cellulose-forming organisms in internal space, formed by hollow form (12), aimed at providing growth of hollow body (1) in internal space; operation of removal of hollow body from form (12). At the stage of removal from form (12), at least, part of hollow form (12) is irreversibly deformed.
EFFECT: increased efficiency of manufacturing method.
16 cl, 8 dwg
SUBSTANCE: group of inventions refers to surgery and may be used for making external osteosynthesis implants. An osteosynthesis system comprises a piece part on an external surface of which there is a layer of a polymer film in the electret state with the layer of the polymer film made of a fusible element. The group of inventions refers to a method for making the osteosynthesis system involving preparation the layer of the polymer film on an external surface of the piece part by coating the surface of the piece system with a fine fusible polymer powder, fusion thereof on the surface of the piece part and electrostatic charging of the prepared film.
EFFECT: group of invention provides making a uniform coating of the electret layer on the surface of the piece part of the osteosynthesis system firmly attached to the surface of the piece part that enables faster fusion of bone fragments due to electric stimulation and prevented implant corrosion.
10 cl, 1 ex
SUBSTANCE: described are soft, having high index of refraction acrylic materials for devices. Materials include di-block or tri-block macromers, containing hydrophilic side chains.
EFFECT: materials have improved stability to reflections.
17 cl, 6 tbl, 12 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine. There are described soft acrylic materials having a high refraction coefficient for apparatuses. The materials contain diblock- or triblock-marcomers containing a hydrophilic block in a polymer backbone.
EFFECT: materials have better gloss resistance.
17 cl, 3 tbl, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: implant represents a medicated polymer device, e.g. in the form of a rod, designed for release control of a biologically active substance clonidine and derivatives thereof, such as clonidine HCl, for a long period of time, e.g. for 2 months, 3 months, 4 months and even 4.5 months. The above polymer preferentially represents a biodegradable polymer, such as poly(lactide-co-glycolide) or poly(lactic acid). A challenge of using medicated salt forms HCl, such as clonidine consists in release control of the high water-soluble medication up to 4.5 months. It has been found that a particle size distribution control in the medicated powder can provide more uniform medication distribution in a polymer carrier which can be regulated. This enables avoiding formation of aggregates causing faster medication release.
EFFECT: invention refers to medical devices able to release the biologically active substances.
5 cl, 10 dwg, 8 ex