WO2022113015A1

WO2022113015A1 - Organic material with pore-forming, anti-inflammatory and anticoagulant properties and the method of its preparation

Info

Publication number: WO2022113015A1
Application number: PCT/IB2021/061010
Authority: WO
Inventors: Andrzej Swinarew; Jadwiga Gabor; Hubert Okła; Szymon Skoczyński; Ewa Trejnowska; Barbara SZPIKOWSKA—SROKA; Magdalena Popczyk; Arkadiusz Stanula
Original assignee: Uniwersytet Śląski W Katowicach
Priority date: 2020-11-27
Filing date: 2021-11-26
Publication date: 2022-06-02
Also published as: EP4251695A1

Abstract

The object of the invention is an organic material with blowing, anti-inflammatory and anticoagulant properties characterized in that it comprises a base polymeric material and an active admixture in the form of albumin or argatroban or bivalirudin or fondaparinux or heparin, embedded in the microstructure of the base material in a base-active admixture ratio from 80÷1 to 1200÷1 and, in case of some types of base polymer materials, also from 4- (diphenylamino)benzaldehyde admixture in a base-active admixture ratio from 50÷1 to 5000÷1 and 1,3-indandione admixture in a base-active admixture ratio from 50÷1 to 5000÷1. The object of the invention is also a method for obtaining an organic material having blowing, anti-inflammatory and anticoagulant properties based on the fact that the base polymeric material is extruded on a linear head in the form of a string, or on a cross head in the form of a tube, or on a flat head in the form of a film, Then the process of immobilization of active admixture in the form of albumin, argatroban, bivalirudin, fondaparinux or heparin to the steric structure of the material obtained in such a way that its content in the material in the base-active admixture ratio is from 80÷1 to 1200÷1. The method according to the invention makes it possible to obtain materials with blowing, anti-inflammatory and anticoagulant properties, especially for the construction of medical equipment, in particular for components which are in direct contact with blood. Among other applications, the solution can be used to obtain blood oxygenation membranes and other gas-selective membranes.

Description

ORGANIC MATERIAL WITH PORE-FORMING, ANTI-INFLAMMATORY AND ANTICOAGULANT PROPERTIES AND THE METHOD OF ITS PREPARATION

The object of the invention is an organic material with pore-forming, anti inflammatory and anticoagulant properties, intended in particular for the construction of medical devices, in particular for the construction of components in direct contact with blood, and a method for obtaining it.

Materials with pore-forming properties are used to make selective membranes, that is, membranes that only allow particles of a certain size to pass through. Such materials are used, among other things, to make membranes for use in the manufacture of everyday objects such as: tents, jackets, filters, but also osmotic membranes for medical applications: in filters for renal replacement therapy and in oxygenators for blood oxygenation.

The most common, high-tech - in non-medical applications - pore-forming material (used, for example, in the manufacture of jackets), from which membranes were made is poly (tetrafluoroethylene) .

However, in medical applications, i.e. for the construction of medical devices, from the current state of the art various materials are known, including materials for the construction of porous membranes used in devices having direct contact with body fluids.

For example, PL225257 patent description presents a membrane system for local immobilization of eukaryotic cells, having a support and at least one bilayer formed successively from one polyelectrolyte layer comprising polysaccharide hydrogels, especially sodium alginate containing in its structure incorporated fullerenol and protein A, characterized in that the first layer is applied directly to the group of isolated cells then seated on a support made of the same material in terms of composition, and a second polymeric layer of aliphatic secondary and tertiary amines - containing ethyl or methyl groups with incorporated fullerenol. In this system, a single layer is applied directly to a group of isolated eukaryotic cells, and it allows eukaryotic cells to be isolated from the external environment, particularly microorganisms, while not restricting nutrient transport across the membrane, allowing for directed growth.

PL212620 patent description presents a specially modified polyolefin membrane (PP, PE) and a method of modifying microporous polyolefin membranes intended for the isolation of Gram(+) bacteria, consisting in that a solution of polycation, selected from the group consisting of aliphatic amino acids, especially protein amino acids, preferably polar and dissolved in NaCl solution, is introduced into the structure of polyolefin membrane of high porosity in a known way, preferably by soaking, and then the solution of polyanion, selected from the group consisting of polymeric secondary and tertiary amines, especially methylamine and ethylamine, preferably containing 100% methyl or ethyl groups, dissolved in a solution of NaCl.

Also PL197199 patent description presents a polymeric proton-conducting membrane based on hydrated poly(perfluorosulfonic acid), characterized in that it is a reaction product of radiation-induced grafting of poly(perfluorosulfonic acid) with vinylphosphonic acid used in an amount of 1 to 40% by weight or 2-acrylamido-2-methylpropanesulfonic acid used in an amount of 1 to 40% by weight.

PL165872 patent description presents a method for producing a multilayer porous membrane of polytetrafluoroethylene containing at least two layers having pores of different average diameters, which includes the steps of: filling the extruder barrel with at least two different types of fine polytetrafluoroethylene powders, with a liquid lubricant mixed with each.

EP0409496 patent description presents a process for preparing microporous membranes containing at least a partially crystalline aromatic polymer containing ether or thioether and ketone bonds in the chain. The process allows membranes to be made from certain aromatic polymers with high melting points, such as PEDK.

The type of materials from which the membranes known from the above solutions were made allows - for steric reasons - their use for blood oxygenation, however their significant biochemical limitations significantly limit this application. This is because these membranes did not contain additives to provide anticoagulant release, which was a significant disadvantage in such applications. Moreover, due to their structure, they are characterized by developed surface topography on the micrometer scale, which was the reason for their negative effects on living organisms. At the cellular level, these membranes cause steric damage to cell membranes, resulting in cell destabilization. Furthermore, membranes cannot inhibit thrombus formation and do not protect against bacterial biofilm formation.

So far, polypropylene (PP) and polyurethane (PU) have mainly been used as pore forming materials in medical applications. For example, in devices used in the process of oxygenation of blood, polyurethane was used as a porous material for the construction of membranes, and polypropylene was used for the construction of elements for separation of membrane layers (spacers). Despite the high efficiency of such membranes in terms of gas exchange, they have limitations mainly related to the initiation of inflammatory reaction from the low bioinertness of these materials. This affected the formation of progressively growing thrombi on the membrane surface. In this case, in order to maintain the effectiveness of blood oxygenation, it was necessary to increase the oxygen concentration, which induces oxidative stress and intensifies the clotting process, triggering an unfavorable cascade of rapidly consecutive adverse factors, because the oxygen concentration must be constantly increased to maintain the blood saturation level, and this intensifies oxidative stress and enhances clotting.

After crossing a certain threshold, the amount of thrombi is already so high that the device is no longer suitable for further operation (does not perform its function) and the entire oxygenator system must be replaced.

Consequently, there was a need to develop new membrane materials, especially for medical applications, that would allow for a high level of pore-forming properties, while also ensuring their biocompatibility and bioinertness (neutrality) when in contact with patient blood. The reason for using new materials for the membrane in the oxygenator is the need to reduce the risk of inducing inflammation, thereby slowing down the clotting process on the membrane and extending the life of the device. Various compounds with anticoagulant activity are known from the state of the art. Among others, we know albumins - blood proteins produced in the liver and responsible for maintaining oncotic pressure in blood vessels, transport of substances poorly soluble in plasma (fatty acids, some hormones, calcium ions) and buffering blood. The anti inflammatory effects of albumins include inhibition of leukotriene production by neutrophils and thrombocytes and decreased sensitivity of neutrophils to inflammatory cytokines. On the other hand, their anticoagulant effect is through activation of antithrombin III and inhibition of thrombocyte aggregation. Also known is argatroban, a synthetic analogue of hirudin, which is a small-molecule direct thrombin inhibitor (DTI) used for anticoagulant therapy in patients with heparin-induced thrombocytopenia type II who require parenteral anticoagulant therapy. The first mechanism of DTI action involves blocking the active site of thrombin, whereas the second involves inhibition of the fibrin binding site, where the substrate is recognized and spatially correctly oriented. The action of these inhibitors is direct and does not depend on the presence of antithrombin. Unlike indirect DTI inhibitors, they can inhibit fibrin-bound thrombin. Bivalirudin is also known - an anticoagulant from a group of direct specific thrombin inhibitors (DTI). DTIs block the active site responsible for the main thrombin action and/or the external site where the substrate is recognized and spatially correctly oriented. The action of these inhibitors is direct and does not depend on the presence of antithrombin. Unlike indirect DTI inhibitors, they can inhibit fibrin-bound thrombin, which prevents thrombin from splitting fibrinogen to fibrin monomers, activating factors XIII, V, VIII, and stimulating thrombocytes to aggregate. A compound with an anticoagulant effect is also fondaparinux - an organic chemical compound, an oligosaccharide. It is a synthetic pentasaccharide with a sequence identical with the pentasaccharide hydrolysis products of fondaparinux, and contains an additional methyl group at the reducing end. It is a selective inhibitor of factor Xa. Fondaparinux is used as an anticoagulant to prevent the formation of thrombi and is used as standard in patients undergoing surgery and immobilized due to disease, in venous thromboembolism, acute coronary syndromes. Heparin, an organic chemical compound, a polysaccharide composed primarily of N-sulfate and O-sulfate of glycosaminoglycan made up of D-glucosamine and L-iduronic acid radical linked into an unbranched chain, also exhibits anticoagulant activity. Heparin is a natural agent that, by inhibiting the transition of prothrombin to thrombin, causes a potent blood anticoagulant effect and, due to its effect on lipids through lipase activation, is also used as an anticoagulant used for anticoagulant coatings. When released in a controlled manner, it can also inhibit thrombocyte aggregation and adhesion (sticking to surfaces) to blood vessel walls. Heparin is trapped by the vessel walls and increases their negative charge, making it difficult for thrombocytes to adhere and preventing the formation of wall clots. Heparin is used as an anticoagulant to prevent thrombus formation, standard treatment for patients undergoing surgery and immobilized due to disease, in venous thromboembolism, acute coronary syndromes.

So far, however, there are no known materials with pore-forming, anti-inflammatory and anticoagulant properties, containing immobilized in their composition active admixtures of albumin, argatroban, bivalirudin, fondaparinux or heparin, semi -permeable to gases, especially for the construction of membranes used in medical gas exchange systems, especially for blood oxygenation (oxygenators) and effective ways of obtaining such materials, and their development has become the aim of the authors of the present invention.

In a first variation of the invention, the essence of the invention is an organic material with pore-forming, anti-inflammatory and anticoagulant properties, comprising:

- base in the form of a fluoropolymer, preferably poly(tetrafluoroethylene) (PTFE, Teflon) or polyvinylidene fluoride (PVDF) or a copolymer of tetrafluoroethylene and hexafluoropropylene (FEP), and

- active admixture in the form of albumin or argatroban or bivalimdin or fondaparinux or heparin, embedded in the micro structure of the base material, in the proportion base-active admixture from 80÷1 to 1200÷1, preferably 150÷1.

In a second variation of the invention, the essence thereof is an organic material with pore-forming, anti-inflammatory and anticoagulant properties, comprising:

- base in the form of polypropylene (PP) or polyurethane (PU) or polyethylene terephthalate (PET) or polycarbonate (PC) or polyoxymethylene (POM) or polysulfone (PSU) or silicone or fluoropolymer, preferably poly (tetrafluoroethylene) (PTFE) or polyvinylidene fluoride (PVDF) or a copolymer of tetrafluoroethylene and hexafluoropropylene (FEP),

- 4-(diphenylamino)benzaldehyde admixture in a base-to-admixture ratio from 50÷1 to 5000÷1, preferably 100÷1,

- admixture of 1,3-indandione in a base-to-admixture ratio from 50÷1 to 5000÷1, preferably 100÷1, and

The essence of the invention also comprises a method for obtaining an organic material with pore-forming, anti-inflammatory and anticoagulant properties, in the first variant, characterized in that a base material in the form of a fluoropolymer, preferably poly(tetrafluoroethylene) (PTFE) or polyvinylidene fluoride (PVDF) or a copolymer of tetrafluoroethylene and hexafluoropropylene (FEP) is extruded on a linear head in the form of a string, preferably with a diameter of 2 to 10 mm, or on a cross head in the form of a tube, preferably with an outer diameter of 2 to 10 mm, or on a flat head in the form of a foil preferably with a thickness of 0.1 to 3 mm, then the process of immobilization of active admixture in the form of albumin or argatroban or bivalimdin or fondaparinux or heparin to the steric structure of the material thus obtained is carried out in a manner ensuring its content in the material in the ratio base-active admixture from 80÷1 to 1200÷1, preferably 150÷1, in such a way, that after initial cooling in a bath containing a supersaturated aqueous solution of the active admixture to a temperature ±30°C from the plastic transition temperature, preferably below the plastic transition temperature, it is stretched on calenders (by known methods of forming fibers or foils) to obtain an elongation of 5÷20 times, preferably 10 times, which results in the formation of micropores in which the active admixture immobilizes, whereby in a variant with an extruded string, the elongation process is carried out linearly - maintaining the string form, or in two directions - forming a flat foil from the string.

The essence of the invention also comprises a method for obtaining an organic material with pore-forming, anti-inflammatory and anticoagulant properties, in a second variation, characterized in that a polar solvent and an acid selected from the following ones are introduced into a reactor of a non-reactive material in an inert gas atmosphere: sulfuric acid VI, hydrochloric acid or acetic acid, in proportions from 2÷0.002 to 7÷0.002, preferably 5÷0.002, and then per 50 mL of a mixture thus formed, 4-(diphenylamino)benzaldehyde in an amount from 0.2 g to 0.7 g and 1.3-indandione in a quantity of 0.01 g to 0.08 g are added and stirred until a homogeneous mixture is obtained in no less than 1 minute, after which the suspension is washed with inert gas for at least 5 minutes, preferably not more than 60 minutes, heated to boiling under a reflux condenser in an inert gas atmosphere and stirred intensely at 100-1000 rpm, preferably 350-450 rpm for at least 18 hours, preferably not more than 30 hours. After the mixing process, the resulting mixture is cooled to 20 to 35°C and subjected to column chromatography in a S1O2 bed and in the mobile phase of the mixture of hexane and methylene chloride, in amounts of hexane from 0.5 to 2 times the volume of the mixture, and methylene chloride from 0,5 to 2 times the volume of the reaction mixture. It is then vacuum-dried for at least 20 hours, preferably 24 hours to a constant weight, after which it is recrystallized from chloroform. The product after recrystallization from chloroform (recry stallizate) is placed in a homogenizer and the base is introduced as: polypropylene (PP) or polyurethane (PU) or polyethylene terephthalate (PET) or polycarbonate (PC) or polyoxymethylene (POM) or polysulfone (PSU) or silicone or fluoropolymer, preferably poly(tetrafluoroethylene) (PTFE) or polyvinylidene fluoride (PVDF) or a copolymer of tetrafluoroethylene and hexafluoropropylene (FEP), in the proportion of the base- recrystallizate from 50÷2 to 5000÷2, preferably 100÷2, and then mixed to a homogeneous mixture and dried for at least 20 hours at 80-110°C, after which the material is extruded on a linear head is extruded on a linear head in the form of a string, preferably with an outer diameter of 2 to 10 mm, or on a cross head in the form of a tube, preferably with an outer diameter of 2 to 10 mm, or on a flat head in the form of a foil preferably with a thickness of 0.1 to 3 mm, and in the next step the process of immobilization of active admixture in the form of albumin or argatroban or bivalirudin or fondaparinux or heparin to the steric structure of the material thus obtained is carried out in a manner ensuring its content in the material in the ratio base-active admixture from 80÷1 to 1200÷1, preferably 150÷1, in such a way, that after initial cooling in a bath containing a supersaturated aqueous solution of the active admixture to a temperature ±30°C from the plastic transition temperature, preferably below the plastic transition temperature, it is stretched on calenders (by known methods of forming fibers or foils) to obtain an elongation of 5÷20 times, preferably 10 times, which results in the formation of micropores in which the active admixture immobilizes, whereby in a variant with an extruded string, the elongation process is carried out linearly - maintaining the string form, or in two directions - forming a flat foil from the string.

Preferably, the method according to the invention in the second variant is carried out in a glass, ceramic or stainless steel reactor.

Preferably, the method according to the invention in the second variant is carried out in a reactor in the form of a round-bottomed three-necked flask, due to its good functional properties.

Preferably, in the method according to the invention in the second variant, argon or nitrogen or xenon is used as the inert gas. Preferably, in the method according to the invention in the second variant, anhydrous ethanol is used as the polar solvent.

Preferably, in the method according to the first or second variant, the base material is added in the form of a crushed material or aggregate or most preferably granulate.

Preferably, in the method according to the first or second variant, during the calendering step during the immobilization of the active admixture, a cyclic decrease and increase of the stress is applied, which increases the efficiency of the immobilization of the active admixture in the pores of the material.

The chemical structure of macromolecules of materials obtained by the method according to the invention affects their good pore-forming properties and at the same time ensures its biocompatibility and bioinertness (full neutrality). When these materials are used to manufacture membranes for oxygenators, the risk of inducing inflammation is reduced, and thus the process of coagulation on the membrane slows down. The method according to the invention makes it possible to obtain materials with a pore size in the nano range so that a single molecule of oxygen and carbon dioxide is able to penetrate the pores, and at the same time so that the pores are smaller than the macromolecular packets of which body fluids are composed, which in effect makes it possible to effectively oxygenate the blood without the risk of blood molecules penetrating the pores.

In addition to the above advantages, the solution according to the invention makes it possible to obtain membranes with a very wide range of pore sizes from nano/micro scale (application especially for oxygenation, gas exchange) to macro pore size of even tenths of a millimeter (application as waterproof, breathable materials). The method according to the invention makes it possible to precisely control the size of the pores formed.

The use of an immobilized active admixture allows its concentration on the piece contact surface to remain constant throughout the application of the materials (planned product life). The possibility of excessive leaching of the active admixture is minimized, and because of the diffusion-controlled release of the active admixture, its contact concentration on the product surface is constant.

Introduction of the active admixture into the material according to the invention also gives the material the desired anti-coagulant and anti-inflammatory properties. Substances used as active admixture, as noted above, have strong anticoagulant effect. The active admixture is embedded both in the pores of the material and in microcracks formed as equilibrium defects during the material formation stage. This significantly improves the surface continuity of the material structure and thus prevents organic material from depositing in pores and microcracks and significantly reduces coagulation.

The introduction of 4-(diphenylamino)benzaldehyde and 1,3-indandione admixtures in the second variant of the invention results in a reduction of the internal stresses of the material which results in a better orientation of the macromolecules during processing and pore formation, which is ultimately observed as a smooth outer structure so that there are no mechanical steric centers for thrombus formation due to the uniformity of the material as well as the absence of sharp edges around the pores and cracks.

A method for preparing an organic material with pore-forming, anti-inflammatory and anticoagulant properties with the addition of an active admixture according to the invention will be further explained by means of the following examples. Example 1

The material in the form of PTFE granules is extruded on a linear head in the form of a string, with a diameter of 2 mm and then after initial cooling in a bath containing a supersaturated aqueous solution of albumin to a temperature 20°C lower than the plastic transition temperature, it is stretched on calenders to obtain a 10-fold elongation. During calendering, cyclic decreasing and increasing of tension in the range of 60÷90% of tension is used to obtain a 10-fold elongation. Its elongation process is carried out in two directions to form a flat foil from the string. This type of process yields an albumin-to-base ratio of 1:100.

The Teflon-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility. The resulting pores are characterized by sizes ranging from 1 nanometer to 300 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for cell culture. Systems with pores in the order of nanometers can be used to create gas-permeable membranes for example in a blood oxygenation and oxygenation process.

Example 2

The material in the form of PVDF granules and aggregate is extruded on a flat head in the form of a foil with a thickness of 0,1 mm, after which the process of immobilization of argatroban to the steric structure of the material so obtained is carried out in such a way that, after initial cooling in a bath containing a supersaturated aqueous solution of argatroban to a temperature of 20°C lower than the plastic transition temperature, it is elongated on calenders so as to obtain a 15-fold elongation. The elongation process is carried out in two directions to obtain a foil. This type of process yields an argatroban-to-base ratio of 1:140.

The polyvinylidene fluoride -based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility. The resulting pores are characterized by sizes ranging from 1 nanometer to 300 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for cell culture. Systems with pores in the order of nanometers can be used to create gas-permeable membranes for example in a blood oxygenation and oxygenation process.

Example 3

The material in the form of crushed FEP is extruded on a cross head in the form of a tube with an outer diameter of 3 mm, after which the process of immobilization of bivalimdin to the steric structure of the material so obtained is carried out in such a way that, after initial cooling in a bath containing a supersaturated aqueous solution of bivalimdin to a temperature 15°C higher than the plastic transition temperature, it is stretched on calenders so as to obtain a 5-fold elongation. During calendering, cyclic decreasing and increasing of tension in the range of 60÷90% of tension is used to obtain a 5-fold elongation. This type of process yields a bivalimdin-to-base ratio of 1:1200.

The material thus obtained, based on a copolymer of tetrafluoroethylene and hexafluoropropylene can be used as a thrombus filter in medical equipment due to its high biocompatibility. The resulting pores are characterized by sizes ranging from 1 nanometer to 300 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for cell culture. Systems with pores in the order of nanometers can be used to create gas- permeable membranes for example in a blood oxygenation and oxygenation process.

Example 4

The PTFE granules are extruded on a flat head in the form of a 1 mm thick foil, after which the process of immobilization of the fondaparinux into the steric structure of the material so obtained is carried out, in such a way that, after initial cooling of the material in a bath containing a supersaturated aqueous solution of the fondaparinux to a temperature 20°C lower than the plastic transition temperature, it is stretched by cyclically increasing and decreasing the tension in the range of 60÷90% on the calenders until a 15-fold elongation is obtained and fondaparinux is incorporated into the steric structure of the material. This type of process yields a fondaparinux-to-base ratio of 1:1200.

The poly(tetrafluoroethylene)-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility, or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties, or as a breathable material in contact with skin, for example for making wound dressing plasters, kinesiology tapes, orthopedic insoles, etc. The resulting pores are characterized by sizes ranging from 1 nanometer to 150 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for culturing skin cells. Systems having pores in the order of nanometers can be used to create gas-permeable membranes in blood oxygenation and oxygenation process, for example.

Example 5

The PVDF granules are extruded on a flat head in the form of a 0.1 mm thick foil, followed by a process of immobilization of heparin into the steric structure of the material so obtained, in such a way that, after the material is initially cooled in a bath containing a supersaturated aqueous solution of heparin to a temperature of 20°C below the plastic transition temperature, it is stretched on calenders until a 5-fold elongation and incorporation of heparin into the steric structure of the material. The elongation process is carried out in two directions to obtain a foil. This type of process yields a heparin-to-base ratio of 1:800.

The PVDF-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties or as a breathable material in contact with the skin, for example for the manufacture of wound dressing plasters, kinesiology tapes, orthopedic insoles, etc. The resulting pores are characterized by sizes ranging from 1 nanometer to 150 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for culturing skin cells. Systems having pores in the order of nanometers can be used to create gas-permeable membranes in blood oxygenation and oxygenation, for example.

Example 6

The crushed FEP is extruded on a linear head in the form of a string with a diameter of 5 mm, and then the process of immobilization of heparin into the steric structure of the material so obtained is carried out in such a way that, after initial cooling of the material in a bath containing a supersaturated aqueous solution of heparin to a temperature of 30°C below the plastic transition temperature, it is stretched by cyclically increasing and decreasing the tension in the range of 60÷90% on the calenders until a 5-fold elongation is obtained and heparin is incorporated into the steric structure of the material. The elongation process is carried out in two directions to form a flat foil from the string. This type of process yields a heparin-to-base ratio of 1 :200.

The FEP-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties or as a breathable material in contact with the skin, for example for the manufacture of wound dressing plasters, kinesiology tapes, orthopedic insoles, etc. The resulting pores are characterized by sizes ranging from 1 nanometer to 150 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for culturing skin cells. Systems having pores in the order of nanometers can be used to create gas-permeable membranes in blood oxygenation and oxygenation, for example.

Example 7

The PVDF granules are extruded on a flat head in the form of a 0.1 mm thick foil, after which the process of immobilizing the fondaparinux into the steric structure of the material so obtained is carried out, in such a way that, after the material is initially cooled in a bath containing a supersaturated aqueous solution of fondaparinux to a temperature 25 °C below the plastic transition temperature, it is stretched on calenders until a 5-fold elongation is obtained and the fondaparinux is incorporated into the steric structure of the material. This type of process yields a fondaparinux/base ratio of 1:800.

The PVDF-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties or as a breathable material in contact with the skin, for example for the manufacture of wound dressing plasters, kinesiology tapes, orthopedic insoles, etc. The resulting pores are characterized by sizes ranging from 1 nanometer to 150 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for culturing skin cells. Systems having pores in the order of nanometers can be used to create gas-permeable membranes, for example, in blood oxygenation and oxygenation.

Example 8

50 mL of a mixture of anhydrous ethanol and sulfuric acid (VI) in proportions of 5÷0.002 is introduced into a glass reactor in the form of a dried round-bottomed triple-necked flask in an argon atmosphere and 0.2 g of 4-(diphenylamino)benzaldehyde and 0.01 g of 1,3-indandione are added. The whole mixture is stirred for 5 minutes and washed with argon for 10 minutes. It is then heated to boiling under a reflux condenser in an argon atmosphere and stirred intensely at 400 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 20°C and subjected to column chromatography in a S1O2 bed and in the mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 0.5 times the volume of the reaction mixture and methylene chloride equal to 0.5 times the volume of the reaction mixture. The product is then vacuum-dried for 24 hours to a constant mass, after which it is recrystallized from chloroform, the recry stallizate is placed in a homogenizer and 25 g of crushed PTFE is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 80°C. The material is extruded on a linear head in the form of a string with a diameter of 3 mm, after cooling in a bath containing a supersaturated aqueous solution of albumin to a temperature 20°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on calenders until an 8 -fold elongation is obtained and albumin is incorporated into the steric structure of the material. The elongation process is carried out linearly maintaining the form of the string. This type of process yields an albumin-to-base ratio of 1:150.

The poly(tetrafluoroethylene) based material thus obtained can be used as a thrombus filter in medical equipment or as a semi-permeable coating for rain protection with high single molecule water vapor separation properties. The material obtained in this way makes it possible to create pores with a range of 150 micrometers.

Example 9

50 mL of a mixture of anhydrous ethanol and acetic acid in proportions of 6÷0.002 is introduced into a glass reactor in the form of a dried round-bottomed triple-necked flask in a xenon atmosphere and 0.7 g of 4-(diphenylamino)benzaldehyde and 0.01 g of 1,3-indandione are added. The whole mixture is stirred for 3 minutes and washed with xenon for 30 minutes. It is then heated to boiling under a reflux condenser in xenon atmosphere and stirred intensely at 100 rpm for 30 hours. After obtaining a homogeneous mixture, the system is cooled down to 25°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 1 times the volume of the reaction mixture, and of methylene chloride equal to 1 times the volume of the reaction mixture. The product is then vacuum-dried to a constant mass for 24 hours, followed by recrystallization from chloroform, the recry stallizate is placed in a homogenizer and 50 g of PP aggregate is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 100°C. The material is extruded on a cross head in the form of a tube with a diameter of 9 mm, after cooling in a bath containing a supersaturated aqueous solution of albumin to a temperature of 25°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on calenders until 7-fold elongation is obtained and albumin is incorporated into the steric structure of the material. This type of process yields an albumin-to-base ratio of 1:350.

The polypropylene-based material thus obtained can be used as a thrombus filter in medical equipment or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties. The material obtained in this way makes it possible to create pores of 30 micrometers.

Example 10

50 mL of a mixture of anhydrous ethanol and hydrochloric acid in a ratio of 5÷0.002 is introduced into a dried ceramic reactor in an argon atmosphere and 0.2 g of 4- (diphenylamino)benzaldehyde and 0.08 g of 1,3-indandione are added. The whole mixture is stirred for 2 minutes and washed with argon for 60 minutes. It is then heated to boiling under a reflux condenser in an argon atmosphere and stirred intensely at 1000 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 30°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 2 times the volume of the reaction mixture, and of methylene chloride equal to 2 times the volume of the reaction mixture. The product is then vacuum-dried for 24 hours to a constant mass, after which it is recrystallized from chloroform, the recry stallizate is placed in a homogenizer and 28 g of PU granulate is added. The system is mixed until a homogeneous mixture is obtained and dried for 24 hours at 110°C. The material is extruded on a flat head in the form of a foil with a thickness of 0.1 mm, after cooling in a bath containing a supersaturated aqueous solution of albumin to a temperature 20°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on calenders until a 15-fold elongation is obtained and albumin is incorporated into the steric structure of the material. The elongation process is carried out in two directions to obtain a foil. This type of process yields an albumin-to-base ratio of 1:150.

The resulting polyurethane -based material can be used as a thrombus filter in medical equipment due to its high biocompatibility or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties or as a breathable material in contact with the skin for example: wound dressing plasters, kinesiology tapes, orthopedic insoles, etc. The resulting pores are characterized by sizes ranging from 1 nanometer to 150 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for culturing skin cells. Systems with pores in the order of nanometers can be used to create gas- permeable membranes for example in a blood oxygenation and oxygenation process.

Example 11

50 mL of a mixture of anhydrous ethanol and sulfuric acid (VI) in proportions of 2÷0.002 is introduced into a glass reactor in the form of a dried round-bottomed triple-necked flask in an argon atmosphere and 0.2 g of 4-(diphenylamino)benzaldehyde and 0.01 g of 1,3-indandione are added. The whole mixture is stirred for 3 minutes and washed with argon for 10 minutes. It is then heated to boiling under a reflux condenser in an argon atmosphere and stirred intensely at 500 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 25°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 1.5 times the volume of the reaction mixture, and of methylene chloride equal to 1.5 times the volume of the reaction mixture. The product is then vacuum-dried to a constant mass for 24 hours, followed by recrystallization from chloroform, the recry stallizate is placed in a homogenizer and 42 g of crushed PET is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 80°C. The material is extruded on a flat head in the form of a foil with a thickness of 1 mm and after cooling in a bath containing a supersaturated aqueous solution of argatroban to a temperature 30°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on calenders until a 10-fold elongation is obtained and argatroban is incorporated into the steric structure of the material. This type of process yields an argatroban-to-base ratio of 1:150. The poly(ethylene terephthalate) -based material thus obtained can be used as a thrombus filter in medical equipment or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties. The material obtained in this way makes it possible to create pores in the range of 150 micrometers.

Example 12

50 mL of a mixture of anhydrous ethanol and acetic acid is introduced in a xenon atmosphere in proportions of 7÷0,002 is introduced to a dried stainless steel reactor and 0.7 g of 4- (diphenylamino)benzaldehyde and 0.01 g of 1,3-hidandione are added. The whole mixture is stirred 4 minutes and washed with xenon for 30 minutes. It is then heated to boiling under a reflux condenser in xenon atmosphere and stirred intensely at 750 rpm for 30 hours. After obtaining a homogeneous mixture, the system is cooled down to 25°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 1 times the volume of the reaction mixture, and of methylene chloride equal to 1 times the volume of the reaction mixture. The product is then vacuum-dried to a constant mass for 24 hours, followed by recrystallization from chloroform, the recry stallizate is placed in a homogenizer and 40 g of PC aggregate is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 100°C. The material is extruded on a linear head in the form of an 8 mm diameter string, and after cooling in a bath containing a supersaturated aqueous argatroban solution to a temperature 10°C lower than the plastic transition temperature, it is stretched by cyclically increasing and decreasing the tension in the range of 60÷90% on calenders until a 10-fold elongation is obtained and argatroban is incorporated into the steric structure of the material. Its elongation process is carried out in two directions to form a flat foil from the string. This type of process yields an argatroban-to-base ratio of 1:150.

The polycarbonate-based material thus obtained can be used as a water filter or as a semi-permeable coating for rain protection with high single molecule water vapor separation properties. The resulting pores are characterized by sizes ranging from 1 to 300 micrometers.

Example 13

50 mL of a mixture of anhydrous ethanol and hydrochloric acid in proportions of 5÷0.002 is introduced into a glass reactor as a dried round -bottomed triple-necked flask in an argon atmosphere and 0.2 g of 4-(diphenylamino)benzaldehyde and 0.08 g of 1,3-indandione are added. The whole mixture is stirred for 5 minutes and washed with argon for 60 minutes. It is then heated to boiling under a reflux condenser in an argon atmosphere and stirred intensely at 450 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 30°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 2 times the volume of the reaction mixture, and of methylene chloride equal to 2 times the volume of the reaction mixture. The product is then vacuum-dried for 24 hours to a constant mass, after which it is recrystallized from chloroform, the recry stallizate is placed in a homogenizer and 28 g of POM granulate. The system is mixed until a homogeneous mixture is obtained and dried for 24 hours at 110°C. The material is extruded on a linear head in the form of an 2 mm diameter string, and after cooling in a bath containing a supersaturated aqueous argatroban solution to 15°C below the plastic transition temperature, it is stretched by cyclically increasing and decreasing the tension in the range of 60÷90% on calenders until a 15-fold elongation is obtained and argatroban is incorporated into the steric structure of the material. Its elongation process is carried out in two directions to form a flat foil from the string. This type of process yields an argatroban-to-base ratio of 1:350.

The polyoxymethylene -based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility. The resulting pores are characterized by sizes ranging from 1 nanometer to 300 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for cell culture. Systems with pores in the order of nanometers can be used to create gas-permeable membranes for example in a blood oxygenation and oxygenation process.

Example 14

50 mL of a mixture of anhydrous ethanol and sulfuric acid (VI) is introduced into a dried stainless steel reactor in proportions of a 5÷0.002 in an argon atmosphere and 0.2 g of 4- (diphenylamino)benzaldehyde and 0.01 g of 1,3-indandione are added. The whole mixture is stirred for 6 minutes and washed with argon for 10 minutes. It is then heated to boiling under a reflux condenser in an argon atmosphere and stirred intensely at 400 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 30°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 0.5 times the volume of the reaction mixture and of methylene chloride equal to 0.5 times the volume of the reaction mixture. The product is then vacuum-dried for 24 hours to a constant mass, after which it is recrystallized from chloroform, the recrystallizate is placed in a homogenizer and 25 g of ground PSU is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 80°C. The material is extruded on a linear head in the form of a string with a diameter of 3 mm, and after cooling in a bath containing a supersaturated aqueous solution of bivalirudin to a temperature 20°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on calenders until a 10-fold elongation is obtained and bivalirudin is incorporated into the steric structure of the material. The elongation process is carried out linearly maintaining the form of the string. This type of process yields a bivalirudin-to-base ratio of 1:250.

The polysulfone-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility. The resulting pores are characterized by sizes ranging from 1 nanometer to 300 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for cell culture. Systems with pores in the order of nanometers can be used to create gas-permeable membranes for example in a blood oxygenation and oxygenation process.

Example 15

50 mL of a mixture of anhydrous ethanol and acetic acid in proportions of 5÷0.002 is introduced into a dried round-bottomed triple-necked flask in nitrogen atmosphere and 0.7 g of 4-(diphenylamino)benzaldehyde and 0.01 g of 1,3-indandione are added. The whole mixture is stirred for 8 minutes and washed with nitrogen for 30 minutes. It is then heated to boiling under a reflux condenser in nitrogen atmosphere and stirred intensely at 350 rpm for 30 hours. After obtaining a homogeneous mixture, the system is cooled down to 25°C and subjected to column chromatography in a S1O2 bed and in the mobile phase of the mixture of hexane and methylene chloride in a quantity of hexane equal to 1 times the volume of the reaction mixture and methylene chloride equal to 1 times the volume of the reaction mixture. The product is then vacuum-dried for 24 hours to a constant mass, after which it is recrystallized from chloroform, the recry stallizate is placed in a homogenizer and 25 g of ground PVDF is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 100°C. The material is extruded on a linear head in the form of a string with a diameter of 2 mm, and after cooling in a bath containing a supersaturated aqueous solution of bivalimdin to a temperature 20°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on the calenders until a 20-fold elongation is obtained and bivalimdin is incorporated into the steric structure of the material. The elongation process is carried out linearly maintaining the form of the string. This type of process yields a bivalirudin-to-base ratio of 1:80.

The PVDF-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility, or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties, or as a breathable material in contact with skin, for example for making: wound dressing plasters, kinesiology tapes, orthopedic insoles, etc. The resulting pores are characterized by sizes ranging from 1 nanometer to 150 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for culturing skin cells. Systems with pores in the order of nanometers can be used to create gas-permeable membranes for example in a blood oxygenation and oxygenation process.

Example 16

50 mL of a mixture of anhydrous ethanol and hydrochloric acid in proportions of 4÷0.002 is introduced into a dried round-bottomed triple-necked flask in nitrogen atmosphere and 0.2 g of 4-(diphenylamino)benzaldehyde and 0.08 g of 1,3-indandione are added. The whole mixture is stirred for 1 minute and washed with nitrogen for 60 minutes. It is then heated to boiling under a reflux condenser in nitrogen atmosphere and stirred intensely at 450 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 30°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 2 times the volume of the reaction mixture, and of methylene chloride equal to 2 times the volume of the reaction mixture. The product is then vacuum-dried for 24 hours to a constant mass, after which it is recrystallized from chloroform, the recry stallizate is placed in a homogenizer and 28 g of FEP granulate. The system is mixed until a homogeneous mixture is obtained and dried for 24 hours at 110°C. The material is extruded on a cross head in the form of a tube with an outer diameter of 10 mm, after cooling in a bath containing a supersaturated aqueous solution of fondaparinux to a temperature of 15°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on calenders until a 5-fold elongation is obtained and fondaparinux is incorporated into the steric structure of the material. This type of process yields a fondaparinux-to-base ratio of 1:1200. The FEP-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties or as a breathable material in contact with the skin, for example for: wound dressing plasters, kinesiology tapes, orthopedic insoles, etc. The resulting pores are characterized by sizes ranging from 1 nanometer to 150 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for culturing skin cells. Systems with pores in the order of nanometers can be used to create gas-permeable membranes for example in a blood oxygenation and oxygenation process.

Example 17

50 mL of a mixture of anhydrous ethanol and sulfuric acid (VI) in proportions of 5÷0.002 is introduced into a glass reactor in the form of a dried round-bottomed triple-necked flask in an argon atmosphere and 0.2 g of 4-(diphenylamino)benzaldehyde and 0.01 g of 1,3- indandione are added. The whole mixture is stirred for 5 minutes and washed with argon for 10 minutes. It is then heated to boiling under a reflux condenser in an argon atmosphere and stirred intensely at 400 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 20°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 0.5 times the volume of the reaction mixture, and of methylene chloride equal to 0.5 times the volume of the reaction mixture. The product is then vacuum-dried for 24 hours to a constant mass, after which it is recrystallized from chloroform, the recrystallizate is placed in a homogenizer and 21 g of PTFE granulate is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 80°C. The material is extruded on a linear head in the form of a 3 mm diameter string, and after cooling in a bath containing a supersaturated aqueous fondaparinux solution to 20°C below the plastic transition temperature, it is stretched by cyclically increasing and decreasing the tension in the range of 60÷90% on calenders until a 7-fold elongation is obtained and fondaparinux is incorporated into the steric structure of the material. Its elongation process is carried out in two directions to form a flat foil from the string. This type of process yields a fondaparinux/base ratio of 1:150.

The poly(tetrafluoroethylene) based material thus obtained can be used as a thrombus filter in medical equipment or as a semi-permeable coating for rain protection with high single molecule water vapor separation properties. The material obtained in this way makes it possible to create pores in the range of 150 micrometers.

Example 18

50 mL of a mixture of anhydrous ethanol and acetic acid in proportions of 6÷0.002 is introduced into a glass reactor in the form of a dried round-bottomed triple-necked flask in a xenon atmosphere and 0.7 g of 4-(diphenylamino)benzaldehyde and 0.01 g of 1,3-indandione are added. The whole mixture is stirred for 3 minutes and washed with xenon for 30 minutes. It is then heated to boiling under a reflux condenser in a xenon atmosphere and stirred intensely at 100 rpm for 30 hours. After obtaining a homogeneous mixture, the system is cooled down to 25°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 1 times the volume of the reaction mixture, and of methylene chloride equal to 1 times the volume of the reaction mixture. The product is then vacuum-dried to a constant mass for 24 hours, followed by recrystallization from chloroform, the recry stallizate is placed in a homogenizer and 45 g of PP aggregate is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 100°C. The material is extruded on a linear head in the form of an 8 mm diameter string, and after cooling in a bath containing a supersaturated heparin solution to 10°C below the plastic transition temperature, it is stretched by cyclically increasing and decreasing the tension in the range of 60÷90% on calenders until a 10-fold elongation is obtained and heparin is incorporated into the steric structure of the material. The elongation process is carried out linearly maintaining the form of the string. This type of process yields a heparin-to-base ratio of 1:350.

The polypropylene-based material thus obtained can be used as a thrombus filter in medical equipment or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties. The material obtained in this way makes it possible to create pores in the range of 30 micrometers.

Example 19

50 mL of a mixture of anhydrous ethanol and hydrochloric acid in a ratio of 5÷0.002 is introduced into a dried ceramic reactor in an argon atmosphere and 0.2 g of 4- (diphenylamino)benzaldehyde and 0.08 g of 1,3-indandione are added. The whole mixture is stirred 2 minutes and washed with argon for 60 minutes. It is then heated to boiling under a reflux condenser in an argon atmosphere and stirred intensely at 1000 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 30°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of a mixture of hexane and methylene chloride, in an amount of hexane equal to 2 times the volume of the reaction mixture, and of methylene chloride equal to 2 times the volume of the reaction mixture. The product is then vacuum-dried for 24 hours to a constant mass, after which it is recrystallized from chloroform, the recry stallizate is placed in a homogenizer and 28 g of PU granulate is added. The system is mixed until a homogeneous mixture is obtained and dried for 24 hours at 110°C. The material is extruded on a flat head in the form of a foil with a thickness of 0.1 mm and after cooling in a bath containing a supersaturated aqueous heparin solution to a temperature 30°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on calenders until a 15- fold elongation is obtained and heparin is incorporated into the steric structure of the material. The elongation process is carried out in two directions to obtain a foil. This type of process yields a heparin-to-base ratio of 1:150.

The polyurethane-based material thus obtained can be used as a thrombus filter in medical equipment due to its high biocompatibility, or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties, or as a breathable material in contact with skin, for example for making: wound dressing plasters, kinesiology tapes, orthopedic insoles, etc. The resulting pores are characterized by sizes ranging from 1 nanometer to 150 micrometers. Systems having pore sizes between 75 and 150 micrometers are ideal for culturing skin cells. Systems with pores in the order of nanometers can be used to create gas-permeable membranes for example in a blood oxygenation and oxygenation process.

Example 20

50 mL of a mixture of anhydrous ethanol and sulfuric acid (VI) in proportions of 2÷0.002 is introduced into a glass reactor in the form of a dried round-bottomed triple-necked flask in an argon atmosphere and 0.2 g of 4-(diphenylamino)benzaldehyde and 0.01 g of 1,3-hidandione are added. The whole mixture is stirred 3 minutes and washed with argon for 10 minutes. It is then heated to boiling under a reflux condenser in an argon atmosphere and stirred intensely at 500 rpm for 24 hours. After obtaining a homogeneous mixture, the system is cooled down to 25°C and subjected to column chromatography in a S1O2 bed and in a mobile phase of the mixture of hexane and methylene chloride, in an amount of hexane equal to 1.5 times the volume of the reaction mixture, and of methylene chloride equal to 1.5 times the volume of the reaction mixture. The product is then vacuum-dried to a constant mass for 24 hours, followed by recrystallization from chloroform, the recry stallizate is placed in a homogenizer and 50 g of crushed PET is added. The system is mixed until a homogeneous mixture is obtained and dried for 20 hours at 80°C. The material is extruded on a flat head in the form of a foil with a thickness of 1 mm and after cooling in a bath containing a supersaturated aqueous heparin solution to a temperature 30°C lower than the plastic transition temperature, it is stretched by cyclic increasing and decreasing the tension in the range of 60÷90% on calenders until a 10-fold elongation is obtained and heparin is incorporated into the steric structure of the material. The elongation process is carried out in two directions to obtain a foil. This type of process yields a heparin-to-base ratio of 1:150.

The poly(ethylene terephthalate) -based material thus obtained can be used as a thrombus filter in medical equipment or as a semi-permeable coating for rainproofing with high single molecule water vapor separation properties. The material obtained in this way makes it possible to create pores in the range of 150 micrometers.

The method according to the invention makes it possible to obtain materials with pore forming, anti-inflammatory and anticoagulant properties, especially for the construction of medical equipment, in particular for components which are in direct contact with blood. Among other applications, the solution can be used to obtain blood oxygenation membranes and other gas-selective membranes.

Claims

PATENT CLAIMS

1. An organic material with pore-forming, anti-inflammatory and anticoagulant properties, characterized in that it comprises:

- base in the form of a fluoropolymer, preferably poly(tetrafluoroethylene) or polyvinylidene fluoride or a copolymer of tetrafluoroethylene and hexafluoropropylene, and

- active admixture in the form of albumin or argatroban or bivalimdin or fondaparinux or heparin, embedded in the microstmcture of the base material, in the proportion base-active admixture from 80÷1 to 1200÷1, preferably 150÷1.

2. An organic material with pore-forming, anti-inflammatory and anticoagulant properties, characterized in that it comprises:

- base in the form of polypropylene (PP) or polyurethane (PU) or poly(ethylene terephthalate) (PET) or polycarbonate (PC) or polyoxymethylene (POM) or polysulfone (PSU) or silicone or fluoropolymer, preferably poly(tetrafluoroethylene) (PTFE) or polyvinylidene fluoride (PVDF) or a copolymer of tetrafluoroethylene and hexafluoropropylene (FEP),

3. A method for obtaining an organic material with pore-forming, anti-inflammatory and anticoagulant properties characterized in that a base material in the form of a fluoropolymer, preferably poly(tetrafluoroethylene) or a copolymer of tetrafluoroethylene and hexafluoropropylene is extmded on a linear head in the form of a string, preferably with a diameter of 2 to 10 mm, or on a cross head in the form of a tube, preferably with an outer diameter of 2 to 10 mm, or on a flat head in the form of a foil preferably with a thickness of 0.1 to 3 mm, then the process of immobilization of active admixture in the form of albumin or argatroban or bivalirudin or fondaparinux or heparin to the steric structure of the material thus obtained is carried out in a manner ensuring its content in the material in the base-active admixture ratio from 80÷1 to 1200÷1, preferably 150÷1, in such a way, that after initial cooling in a bath containing a supersaturated aqueous solution of the active admixture to a temperature ±30°C from the plastic transition temperature, preferably below the plastic transition temperature, it is stretched on calenders to obtain an elongation of 5÷20 times, preferably 10 times, whereby in a variant with an extruded string, the elongation process is carried out linearly - maintaining the string form, or in two directions - forming a flat foil from the string.

4. A method for obtaining an organic material with pore-forming, anti-inflammatory and anticoagulant properties, characterized in that a polar solvent and an acid selected from the following ones are introduced into a reactor of a non-reactive material in an inert gas atmosphere: sulfuric acid VI, hydrochloric acid or acetic acid, in proportions from 2÷0.002 to 7÷0.002, preferably 5÷0.002, and then 4-(diphenylamino)benzaldehyde in an amount from 0.2 g to 0.7 g and 1,3-indandione in an amount from 0.01 g to 0, 08 g is added to the resulting mixture and stirred until a homogeneous mixture is obtained for not less than 1 minute, after which the suspension is washed with inert gas for at least 5 minutes, preferably not more than 60 minutes, heated to boiling under a reflux condenser in an inert gas atmosphere and stirred intensely at 100-1000 rpm, preferably 350 to 450 rpm, for at least 18 hours, preferably not more than 30 hours, and after the mixing process the resulting mixture is cooled to a temperature of 20 to 35°C and subjected to column chromatography in a S1O2 bed and in the mobile phase of a mixture of hexane and methylene chloride, in an amount of hexane from 0.5 to 2 times the volume of the mixture, and methylene chloride from 0.5 to 2 times the volume of the reaction mixture, then vacuum-dried for at least 20 hours, preferably 24 hours to constant weight, followed by recrystallization from chloroform, after which the product after recrystallization from chloroform (recry stallizate) is placed in a homogenizer and the base is introduced as: polypropylene (PP) or polyurethane (PU) or poly (ethylene terephthalate) (PET) or polycarbonate (PC) or polyoxymethylene (POM) or polysulfone (PSU) or silicone or fluoropolymer, preferably poly(tetrafluoroethylene) (PTFE) or polyvinylidene fluoride (PVDF) or a copolymer of tetrafluoroethylene and hexafluoropropylene (FEP), in the proportion of the base-recrystallizate from 50÷2 to 5000÷2, preferably 100÷2, and then mixed to a homogeneous mixture and dried for at least 20 hours at 80-110°C, after which the material is extruded on a linear head in the form of a string, preferably with an outer diameter of 2 to 10 mm, or on a cross head in the form of a tube, preferably with an outer diameter of 2 to 10 mm, or on a flat head in the form of a foil preferably with a thickness of 0.1 to 3 mm, and in the next step the process of immobilization of active admixture in the form of albumin or argatroban or bivalirudin or fondaparinux or heparin to the steric structure of the material thus obtained is carried out in a manner ensuring its content in the material in the ratio base-active admixture from 80÷1 to 1200÷1, preferably 150÷1, in such a way, that after initial cooling in a bath containing a supersaturated aqueous solution of the active admixture to a temperature ±30°C from the plastic transition temperature, preferably below the plastic transition temperature, it is stretched on calenders to obtain an elongation of 5÷20 times, preferably 10 times, whereby in a variant with an extruded string, the elongation process is carried out linearly - maintaining the string form, or in two directions - forming a flat foil from the string.

5. A method according to claim 4 characterized in that it is conducted in a glass, ceramic or stainless steel reactor.

6. A method according to claim 4 characterized in that it is carried out in a round-bottomed triple-neck flask reactor.

7. A method according to claim 4 characterized in that argon or nitrogen or xenon is used as inert gas.

8. A method according to claim 4 characterized in that anhydrous ethanol is used as polar solvent.

9. A method according to claim 3 or 4 characterized in that the base material is added in the form of crushed fraction or aggregate or most preferably granulate.

10. A method according to claim 3 or 4 characterized in that at the calendering stage during the immobilization of the active admixture, a cyclic decrease and increase of tension is applied.