RU2723737C1 - Chitosan application method and chitosan coated antimigration stent-endoprosthesis - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine, namely to a method for applying biopolymer coating from chitosan, preventing ingrowth of stent-endoprosthesis into walls of hollow organ and device with biopolymer coating for introduction into hollow organs to increase their lumen, in particular, to antimigration stent-endoprosthesis. Method of applying a chitosan coating on an antimigration stent-endoprosthesis is characterized by dissolving chitosan in an acid, immersing the stent into the obtained solution, fixing the obtained coating and drying. Method comprises preparing 5 wt% solution of chitosan in 5 % aqueous solution of citric acid, stents-endoprosthesis are placed on a holder frame, made with possibility of rotation around its axis of symmetry, frame of holder with stents is lowered into solution of chitosan in acid and rotating frame is maintained in obtained solution for 3 minutes. Then the frame is immersed in 10 % water solution of triethanolamine for 5 minutes, dehydrated by immersion into pre-cooled ethanol with supersaturated sodium hydroxide for 30 minutes, and dried in vacuum for 1 hour until complete evaporation of solvent. Antimigratic stent-endoprosthesis for hollow organs is made of alloy with shape memory, with possibility of change of configuration when hollow organ is introduced into cavity. Stent-endoprosthesis contains the sections made with possibility of their opposite unwinding. Stent-endoprosthesis is made in the form of a hollow mesh cylinder formed by an interlacing of wire from alloy with memory of the form and consists of alternating belts of a grid of two types: belt of the first type, consisting of one row of compressed wire grid cells, uniformly expanding when heated in transverse direction, belt of the second type, consisting of one row of mesh squeezed in compressed condition of wire mesh, swirled relative to longitudinal stent axis and untwisted at heating in place of installation. Each next belt of wire cells of the grid of the second type is twisted oppositely in relation to the previous belt of the second type, which realizes possibility of opposite shift movements of belts of the first type relative to each other at expansion of stent in the place of installation. Stent-endoprosthesis is coated with chitosan by the method described above.EFFECT: wider range of hollow organs recovery means, as well as a range of methods for applying biocompatible polymer materials on nitinol, for example, chitosan.2 cl, 4 dwg

Description

The invention relates to medicine, namely to a method for applying a biopolymer coating of chitosan to prevent the stent-endoprosthesis from growing into the walls of a hollow organ and a device with a biopolymer coating for insertion into hollow organs in order to increase their lumen.

From the patent of the Russian Federation for the invention No. 2319797 [C25D 11/26, priority of 08/14/2006] there is a known method for producing protective coatings on products made of nitinol. The invention relates to electrolytic methods for producing protective coatings. The method includes an electrochemical treatment, which is carried out in an aqueous electrolyte solution containing, g / l: NaAlO₂- 15-30; Na₂CO₃- 10-20; Na₃PO₄12N₂O - 10-25; dimethylglyoxime - 1.0-1.5, in the anode mode for 10-20 minutes at a formation voltage varying from 0 to 180-200 V. at a speed of 0.2-0.3 V / s, and then in bipolar mode within 5-10 minutes at a constant anode voltage of formation in the range of 180-200 V and a density of the cathode component of the current of 1.0-1.5 A / cm². The disadvantages of the coatings obtained by this method on products made of nitinol (titanium nickelide) include their low elasticity and adhesion under conditions of shear deformation and, as a consequence, low anticorrosive and electrical protective properties.

From the patent for the invention of the Russian Federation No. 2461575 [IPC C08B 37/08, priority 2010-0802], a method for producing a film coating based on chitosan having a bactericidal effect is known, including dissolving chitosan in an organic acid to obtain a molding solution, applying the resulting molding solution on a substrate, followed by keeping the solution on the substrate until a film structure is achieved in which an aqueous solution of 4-6% citric or 2-8% lactic acid is used as the organic acid with a ratio of chitosan: organic acid 1: 2-1 :4. A film coating based on chitosan having a bactericidal effect obtained by the described method is interesting in that the elongation at break of the film coating is from 42 to 470%. The advantage of the invention are highly elastic films of citrate or chitosan lactate, which have a bactericidal effect.

From the patent for the invention of the Russian Federation No. 2585576 [IPC A61K 9/00, priority dated 05/06/2015], a method is known for producing a biodegradable polymer coating with a controlled drug release for minimally invasive surgery, including dissolving chitosan in acids, adding a drug, dipping titanium nickelide wire into the resulting solution, coating fixation and drying, characterized in that phosphoric, or hydrochloric, or glutamic, or acetic acid with a concentration of from 1 to 4% by weight are used as a solvent for dissolving chitosan, lincomycin or gentamicin is used as a medicine or cefotoxime with a concentration of from 0.9 to 7% by weight., the coating is fixed in an alcoholic ammonia solution in a ratio of 1: 2, followed by drying at a temperature of 40-45 ° C for 24 hours.

The RF patent for invention No. 2564921 [IPC A61L 27/20, priority dated 04.17.2014] describes a method adopted as a prototype for applying chitosan to a metal rod, which consists in preparing a solution of chitosan in an organic acid, lowering the rod into a chitosan solution in organic acid, dried in an oven at 45-50 C until the solvent evaporates, while 1.5% aqueous solution of lactic or glycolic acid is taken as acid, moreover, the solution contains chitosan in an amount of 2.5-4 wt.%; before drying, the core with a layer of chitosan solution applied to it is immersed in a 50% aqueous solution of triethanolamine or in a 0.1 M aqueous solution of sodium dodecylbenzosulfate for 1 min, and after drying, the core with a layer of chitosan applied to it is immersed in a 5% aqueous solution of NaOH or 0.1 M an aqueous solution of sodium dodecylbenzene sulfate for 10-20 minutes. The chitosan tubes obtained by this method on a metal rod had good elasticity and extensibility.

Common essential features of the prototype with the claimed method of applying chitosan to a stent is the dissolution of chitosan in organic acid, immersion of the base in the resulting solution, fixing the coating in an aqueous solution of triethanolamine and drying.

From patent JP5876019B2 [IPC A61F2 / 90, priority 2013-10-09], an anti-migration stent prosthesis is known, consisting of a hollow cylindrical body formed by interlacing a metal nitinol wire and a plurality of protruding locking elements located at regular intervals over the surface of this body. The advantages of this device include its ability to hold for a long time at the installation site, the disadvantages are the difficulties of its extraction, due to the design with protruding elements and the germination of tissues in the mesh structure.

Common essential features with the claimed device is the implementation of the stent in the form of a hollow cylinder formed by interlacing an alloy wire with a shape memory of nitinol, realizing the possibility of changing the stent configuration when it is inserted into the organ cavity.

From the patent RU No. 2429804 [IPC A61F2 / 88, priority 01.12.2006] a stent is made made of an alloy with shape memory and changing its configuration when introduced into the cavity of an organ of a human body (prototype), consisting of at least one retaining part, designed to preserve the lumen in the body cavity, and at least one expanding part, designed to hold the stent in a position. Moreover, the expanding part consists of at least one spiral coil twisted in a clockwise direction, and at least one spiral coil twisted in a counterclockwise direction. When the stent expands at the installation site, some turns from the expanding part rotate counterclockwise while spinning, while other turns, untwist, turn clockwise, thereby fixing the expanding part of the stent on the organ walls and allowing the entire stent to maintain its position without migration.

An advantage of the invention is to reduce the risk of stent migration. The disadvantages include insufficiently stent fixation of the stent at the installation site due to its division into expanding (holding) and preserving the lumen of the part.

Common essential features with the claimed device is the implementation of a stent made of an alloy with shape memory, realizing the possibility of changing the configuration of the stent when it is inserted into the cavity of the organ, as well as the presence in the design of sections made with the possibility of oncoming unwinding.

The main objective of the claimed group of inventions is to expand the arsenal of methods for applying a biopolymer coating of chitosan to a stent-endoprosthesis, as well as the creation of a stent-endoprosthesis with enhanced anti-migration properties and properties that reduce the growth of organ tissue in its structure.

The technical result of the claimed group of inventions is to expand the arsenal of means for restoration of hollow organs, as well as an arsenal of methods for applying biocompatible polymer materials onto nitinol, for example chitosan.

The problem is solved in that in the method of applying a coating of chitosan to an anti-migration stent endoprosthesis, chitosan is dissolved in acid, the stent is immersed in the resulting solution, the resulting coating is fixed and dried, while a 5 wt.% Solution of chitosan in 5% aqueous citric acid solution is prepared , endoprosthesis stents are placed on a holder frame that can rotate around its axis of symmetry, lower the holder frame with stents into a solution of chitosan in acid and rotating the frame keep it in the resulting solution for 3 minutes, then immerse the frame in a 10% aqueous solution triethanolamine for 5 min, dehydrated by immersion in pre-cooled ethanol with supersaturated sodium hydroxide for 30 min, and dried in vacuum for 1 hour until the solvent evaporates completely.

The problem was also solved by the fact that the anti-migration stent endoprosthesis for hollow organs made of an alloy with shape memory, with the possibility of changing its configuration when a hollow organ is inserted into the cavity, and containing sections made with the possibility of their counter unwinding, is made in the form of a hollow mesh a cylinder formed by interweaving an alloy wire with shape memory and consists of alternating two kinds of mesh belts, a first kind belt consisting of one row of compressed wire mesh cells expanding uniformly when heated in the transverse direction, a second kind belt consisting of one row deformed into the compressed state of the wire mesh cells twisted with respect to the longitudinal axis of the stent and untwisted when heated at the installation site, with each subsequent belt of wire mesh cells of the second type twisted counter to the previous belt of the second type, which makes it possible for counter shear feathers room of the belts of the first type relative to each other when the stent expands at the installation site, while the stent has a biopolymer coating of chitosan.

The claimed technical solution allows to eliminate the presence of the above negative factors inherent in the prototypes, and allows to achieve the following results:

1) to ensure uniform fixation of the stent on the walls of the hollow organ along its entire length;

2) to eliminate the dependence of the position of the installed stent on the change in the shape of the restored hollow organ;

3) to reduce the germination of soft tissues in the mesh structure of the stent;

4) to ensure the application of a uniform, resistant to deformation biopolymer coating of the stent-endoprosthesis from chitosan.

The main difference between the method of coating chitosan on an anti-migration stent-endoprosthesis is the production of a highly elastic biocompatible chitosan coating for a stent-endoprosthesis with counter shear movements of adjacent belts as a result of its implementation.

The main difference between the claimed device of the stent-endoprosthesis from the prototype is that the device uses counter-shear movements of adjacent stent belts when it is installed in order to prevent migration and a biocompatible coating in order to reduce the growth of soft tissues in it.

A brief description of the graphic materials.

In FIG. 1 schematically shows the design of an anti-migration-stent endoprosthesis in a compressed state.

In FIG. Figure 2 presents one of the design options for the anti-migration stent of the endoprosthesis before and after installation.

In FIG. Figure 3 shows the location of chitosan-coated anti-migration stent cells in contact with the wall of the hollow organ.

Figure 4 shows the holder of anti-migration stents-endoprostheses for implementing the method of coating them with chitosan.

In the initial (compressed) state, the anti-migration stent-endoprosthesis is a cylindrical mesh surface with cells and consists of two types of cell belts, (Figure 1). The belts of the first type 1 alternate with the belts of the second type 2 (Figure 1.2). In the belt 1, in the initial state, there are cells which, when heated at the installation site, uniformly expand in the transverse direction. In the belts of the second type in the initial state, the cells are deformed and are in a state twisted relative to the longitudinal axis of the stent, and the direction of twisting of the adjacent belts of the second type is opposite to each other (Figure 1). When heated at the installation site, the cells of the belt of the first type uniformly expand in the transverse directions, and the twisted cells of the belts of the second type expand and unwind (Figure 2) while unfolding the belts of the first type around the axis in the opposite direction to each other. The stent cells come into contact with the walls of the hollow organ at the installation site at a small angle (Figure 3), and this angle changes to the opposite for neighboring belts. Due to this configuration, the stent is firmly held on the walls of the hollow organ.

From the point of view of preventing soft tissue ingrowth and deformation resistance of the coating on the anti-migration stent, an endoprosthesis with shear deformations of its parts, the most effective direction was the application of a coating on its surface consisting of biocompatible, polymeric materials, for example chitosan.

The method of applying chitosan to an anti-migration stent-endoprosthesis is implemented as follows. For applying chitosan to the stent endoprosthesis, a holder (Figure 4) was developed in the form of a frame, which allows processing of several stents simultaneously and made with the possibility of its rotation around the vertical axis of symmetry. After fixing on the frame of the holder several stent-endoprostheses, it is fixed over a capacity of 5 wt. % solution of chitosan in a 5% aqueous solution of citric acid. Then, the holder frame with stents is lowered into a solution of chitosan in acid and the stents are kept in the solution for 3 minutes by slowly rotating the frame. Then, the stent holder frame is successively immersed in a 10% aqueous solution of triethanolamine (used as an additive that inhibits corrosion manifestations) for 5 min, dehydrated in pre-cooled ethanol with supersaturated sodium hydroxide for 30 min, and dried in a vacuum dryer for 1 hour until the solvent evaporates completely.

An example of practical implementation. 10 nitinol stents of mesh-type endoprostheses consisting of alternating belts of two types were manufactured. The resulting chitosan-coated endoprostheses were placed on a sliding member of the delivery vehicle. To test the design of the stent, hollow-body imitating devices were made of silicone tubes with an inner diameter of 16 mm and internally coated with a thin layer of gelatin silicone, in which a test installation of the stent-endoprosthesis of the developed mesh construction made of nitinol wire was carried out. The experiment showed that the stents of the claimed design were firmly held on the surface of the tube coated with gelatin silicone with its various bends. Examination of the surface of stents extracted from hollow organ imitating devices under a microscope showed the absence of cracks and other damage in the chitosan coating.

Thus, the claimed group of inventions significantly expands the arsenal of technical means for the restoration of hollow organs, as well as methods for applying biocompatible polymer materials onto nitinol, such as chitosan.

Claims (2)

1. The method of coating chitosan on an anti-migration stent-endoprosthesis, in which chitosan is dissolved in acid, the stent is immersed in the resulting solution, the coating obtained is fixed and dried, characterized in that a 5 wt.% Solution of chitosan in a 5% aqueous solution is prepared of citric acid, endoprosthesis stents are placed on a holder frame that can rotate around its axis of symmetry, lower the holder frame with stents in a solution of chitosan in acid and rotating the frame keep it in the resulting solution for 3 minutes, then immerse the frame in 10% an aqueous solution of triethanolamine for 5 minutes, dehydrated by immersion in pre-cooled ethanol with supersaturated sodium hydroxide for 30 minutes, and dried in vacuum for 1 hour until the solvent was completely evaporated. 2. Anti-migration stent endoprosthesis for hollow organs made of an alloy with shape memory, with the possibility of changing the configuration when introduced into the cavity of a hollow organ, and containing sections made with the possibility of their counter-unwinding, characterized in that it is made in the form of a hollow mesh cylinder, formed by interlacing a wire made of an alloy with shape memory and consists of alternating mesh belt of two types, a belt of the first type, consisting of one row of compressed wire mesh cells, uniformly expanding when heated in the transverse direction, a belt of the second type, consisting of one row deformed in a compressed state wire mesh cells twisted with respect to the longitudinal axis of the stent and untwisted when heated at the installation site, with each subsequent belt of wire mesh cells of the second kind being twisted counter to the previous belt of the second kind, which makes it possible to counter-shift the belts of the first type of relative to each other during the expansion of the stent at the installation site, while the stent endoprosthesis is covered with chitosan by the method according to claim 1.

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