Background
Cerebral apoplexy is commonly called cerebral apoplexy, including hemorrhagic stroke and ischemic stroke, is a very common epidemic disease which endangers life and is the disease with the highest fatality rate in China. Intracranial aneurysms are the major cause of hemorrhagic stroke, while intracranial arterial stenosis is the major cause of ischemic stroke. Intracranial stent systems provide effective treatment of both of these diseases.
The existing intracranial braided stent in the world has the characteristics that the metal wire size is extremely small (the diameter of the metal wire of the traditional cardiac stent is 0.07-0.12 mm, and the diameter of the metal wire of the intracranial stent is not more than 0.06mm basically), the memory metal wire is used for braiding, and the like. The traditional intracranial braided stent is made of memory alloy by braiding, usually cobalt-chromium alloy or nickel-titanium alloy, and after braiding, the shape of the product is shaped by a heat treatment mode so as to adapt to the shape of a blood vessel. At present, the final stent product is obtained by carrying out surface treatment on the common intracranial braided stent after carrying out heat treatment.
Disclosure of Invention
The technical problem that this disclosure will solve is: on the one hand, patients are easy to generate thrombus after the intracranial stent is implanted; on the other hand, when the prior art carries out surface treatment on the extremely fine metal wires of the intracranial stent, the lapping parts among the metal wires are easy to cause the condition that the surface treatment does not reach the standard or is excessive, and the treated metal wires are extremely easy to break, so that the mechanical property of the stent is seriously reduced.
The inventor finds that a heat treatment oxidation layer is generated on the surface of the metal wire of the heat treatment-shaped woven stent product, when the woven stent is compressed and expanded, the heat treatment oxidation layer is easy to fall off due to friction and blood flow scouring among the metal wires, the fallen oxide is easy to excite a blood coagulation mechanism in blood to form thrombus, and the thrombus easily enters peripheral cerebral tissue arterioles along with the flow of the fallen oxide in the blood to easily cause acute ischemic stroke and secondary subarachnoid hemorrhage so as to endal the life of a patient. Therefore, the heat treatment oxide layer on the surface of the metal wire can be removed, so that the risk of thrombus generation after the stent is implanted can be effectively reduced.
The invention aims to solve the technical problems, removes the heat treatment oxide layer on the surface of the metal wire by carrying out surface treatment on the stent and avoids generating serious corrosion on the metal wire matrix, and further forms a passive film on the surface of the metal wire to prepare the low-thrombus intracranial intravascular braided stent.
Specifically, the present disclosure proposes the following technical solutions:
in one aspect, some embodiments of the present disclosure provide a low thrombogenicity intracranial vascular woven stent comprising a cylindrical tubular mesh structure body including a plurality of woven wires woven with one another to form a coherent mesh structure, the woven wires including warp and weft; the weaving point is formed after the warp and the weft are intersected, the weaving point comprises a forward weaving point and a backward weaving point, the weaving point pressed above the weft at the warp position is the forward weaving point, the weaving point pressed below the weft at the warp position is the backward weaving point, the weaving line is selected from one or more than two metal wires, and a heat treatment oxidation layer is removed from the surface of at least one metal wire.
In some embodiments of the present disclosure, the cross-section of the braided wire is circular or oblate, including elliptical or racetrack; optionally, the round braided wire has a diameter of 0.001-0.06mm, optionally the diameter is 0.02-0.04mm, such as 0.025mm, 0.030mm or 0.035 mm; the length of the long axis of the oblate braided wire is as follows: the minor axis length is 3-10:1, optionally the minor axis length is 0.001-0.06mm, optionally the minor axis length is 0.02-0.04mm, for example 0.025mm or 0.035 mm.
In some embodiments of the present disclosure, the at least one wire surface has a passivation film;
optionally, the metal wire comprises a cobalt-chromium alloy wire, and the surface of the cobalt-chromium alloy wire is provided with a passivation film;
optionally, the passivation film is a chromium oxide film.
In some embodiments of the present disclosure, one warp thread is adjacent to the forward weaving point and the backward weaving point formed by the weft thread crossing the one warp thread, and one weft thread is adjacent to the forward weaving point and the backward weaving point formed by the warp thread crossing the one weft thread.
In some embodiments of the present disclosure, one warp thread and four adjacent weft threads crossing over the warp thread are a weaving thread, and the weaving thread includes four weaving points, which are two forward weaving points and two backward weaving points, respectively, where the two forward weaving points are adjacent or the two backward weaving points are adjacent.
In some embodiments of the present disclosure, every two warps form a group of warps, every two wefts form a group of wefts, a distance between two warps in each group of warps is a first distance, a distance between two wefts in each group of wefts is a second distance, a distance between two adjacent groups of warps is a third distance, and the distance of the third distance is greater than the distance of the first distance and the second distance; and/or the distance between two adjacent weft groups is a fourth distance, and the distance of the fourth distance is greater than the distance of the first distance and the distance of the second distance.
In some embodiments of the present disclosure, the stent is subjected to a corrosion treatment and a passivation treatment;
optionally, wherein the etching treatment comprises a step of performing a pre-etching treatment with a pre-etchant; optionally, the pre-etchant contains water, an acid, a corrosion inhibitor, and a surfactant; optionally, the pre-etchant contains water, 15-45 wt.% acid, 0.1-5 wt.% corrosion inhibitor, and 0.25-2.8 wt.% surfactant; optionally, the pre-etchant contains water, 28-40 wt% acid, 0.15-1 wt% corrosion inhibitor, and 0.45-2.15 wt.% surfactant;
optionally, the acid is selected from hydrochloric acid and/or hydrobromic acid, the corrosion inhibitor is selected from alkynols, the surfactant is selected from sodium dodecyl sulfate and/or o-benzoylsulfonimide; optionally, the alkynol is selected from propargyl alcohol, butynol, methylpentylynol and/or 1, 4-butynediol; optionally, the pre-etchant comprises water, hydrochloric or hydrobromic acid, sodium dodecyl sulfate, o-benzoylsulfonimide, and 1, 4-butynediol;
optionally, the pre-etching treatment step temperature is 40-60 ℃, optionally, the temperature is 43-53 ℃;
optionally, the time of the pre-etching step is more than 10min, optionally, the time is 10-15min, optionally, the time is 10-12 min.
In some embodiments of the present disclosure, the etching treatment includes a step of performing a first etching treatment with a first etchant;
optionally, the first etchant comprises a solution A and a solution B, wherein the solution A contains sodium permanganate and/or potassium permanganate, and the solution B contains sodium hydroxide and/or potassium hydroxide; optionally, the solution a is a 20-40 wt.% sodium permanganate solution, and the solution B is a 15-30 wt.% sodium hydroxide and/or potassium hydroxide solution;
optionally, the first etching treatment step temperature is 55-70 ℃, optionally, the temperature is 60-65 ℃; optionally, the first etching treatment step time is 4-5 h;
optionally, the etching treatment includes a step of performing a second etching treatment with a second etchant;
optionally, the second etchant contains water, an acid, and a surfactant; optionally, the acid is selected from hydrochloric acid and/or hydrobromic acid, the surfactant is selected from sodium dodecyl sulfonate, sodium dodecyl sulfate and/or o-benzoylsulphonimide;
optionally, the second corrosive agent contains water, hydrochloric acid and sodium dodecyl sulfate; optionally, the second caustic comprises water, 15 to 30 wt.% hydrochloric acid, and 0.1 to 0.5 wt.% sodium dodecyl sulfate;
optionally, the temperature of the second corrosion treatment step is 40-55 ℃; optionally, the second etching treatment step time is 10-15 min.
In some embodiments of the present disclosure, the passivating solution for passivating treatment contains 20 to 50 vol.% nitric acid; optionally, the passivating liquid is a 30-45 vol.% nitric acid solution; optionally, the temperature of the passivation treatment step is 20-70 ℃, optionally, the temperature is 25-50 ℃; optionally, the time of the passivation treatment step is 20-60min, and optionally, the time is 20-55 min.
In another aspect, the present disclosure provides a method for treating a low thrombogenicity intracranial vascular braided stent provided in any one of the above embodiments, comprising the steps of:
step 1, pre-corroding the bracket after heat treatment and shaping by using a pre-corrosive agent,
step 2, carrying out first corrosion treatment on the support subjected to the pre-corrosion treatment by using a first corrosive agent,
step 3 subjecting the first etching-treated stent to a second etching treatment with a second etchant, and
step 4, passivating the bracket subjected to the second corrosion treatment by using a passivation solution;
optionally, the pre-corrosion agent in the step 1 contains water, acid, corrosion inhibitor and surfactant, and optionally, the temperature of the pre-corrosion treatment step is 40-60 ℃;
optionally, in step 2, the first etchant comprises a solution A and a solution B, the solution A contains sodium permanganate, the solution B contains sodium hydroxide and/or potassium hydroxide, and optionally, the temperature of the second etching treatment step is 40-55 ℃;
optionally, in step 3, the second corrosive agent contains water, acid and surfactant, and optionally, the temperature of the second corrosion treatment step is 40-55 ℃;
optionally, in step 4, the passivation solution contains 20-50 vol.% nitric acid, and optionally, the temperature of the passivation treatment step is 20-70 ℃.
The beneficial effects of the invention include:
1. the intracranial vascular braided stent in some embodiments of the present disclosure removes the heat-treated oxide layer that is formed during the processing of the wire. The falling of the oxide layer can be avoided, so that acute ischemic stroke and secondary subarachnoid hemorrhage which endanger the life of a patient are avoided.
2. The intracranial vascular braided stent in some embodiments of the present disclosure is subjected to surface treatment to form a very thin and dense passivation layer on the metal surface, so that the metal surface has fewer defects, and the possibility of breaking of the metal wire is reduced.
3. Some embodiments of the present disclosure provide methods for surface treatment of an intracranial braided stent, which can remove a heat-treated oxide layer on the surface of the stent while preventing the mechanical properties of the stent from being greatly reduced.
Detailed Description
The technical scheme of the disclosure is clearly and completely described in the following with reference to the accompanying drawings. Obviously, all other embodiments obtained by a person of ordinary skill in the art without making creative efforts based on the specific embodiments in the present disclosure belong to the protection scope of the present disclosure.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. Unless otherwise specified, the terms "left", "right", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are merely for convenience in describing the present invention and simplifying the description, and do not indicate or imply that the referred devices or elements must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present disclosure. The terms "first" and "second" are used for descriptive purposes only and are not to be construed as being of relative importance.
In the description, when the outer surface of the bracket is observed based on the attached drawings, the warp yarns are the weaving yarns with the lower left and the higher right, and the weft yarns are the weaving yarns with the higher left and the lower right. The outer surface of the bracket is taken as the upper part, and the inner surface of the bracket is taken as the lower part. The positive weaving point is formed when the warp threads at the weaving point are on the outer surface of the bracket and the weft threads are on the inner surface (i.e. when the warp threads are pressed above the weft threads), and the negative weaving point is formed when the warp threads at the weaving point are on the inner surface of the bracket and the weft threads are on the outer surface (i.e. when the warp threads are pressed below the weft threads).
The current common stent braided wires comprise circular or oblate (including oval or racetrack) cross-sections. Whereas stent braids for intracranial vessels are thin in diameter, generally round braids are 0.001-0.06mm in diameter, e.g., 0.02mm, 0.025mm, 0.03mm, 0.035mm, or 0.04 mm. Long axis length of the oblate braided wire: the length of the short axis is 3-10: 1. The short axis length of the usual flattened round braided wires is 0.001-0.06mm, e.g. 0.02mm, 0.025mm, 0.035mm, 0.04 mm.
As described above, the present disclosure aims to provide a low thrombus-causing intracranial vascular braided stent to solve the technical problem that the current stent is easy to cause thrombus.
In some embodiments of the disclosure, the intracranial vascular braided stent is subjected to a corrosion treatment to remove the heat-treated oxide layer on the surface of the wire, thereby preventing oxide debris from rapidly entering the tiny arteries of the surrounding brain tissue, including capillaries, with the blood flow, causing acute ischemic stroke and secondary subarachnoid hemorrhage, which endangers the life of the patient. In some embodiments, the etching treatment includes a pre-etching treatment, a first etching treatment, and a second etching treatment step, wherein the pre-etching treatment is performed with a pre-etchant containing water, an acid, a corrosion inhibitor, and a surfactant to remove an outermost oxide layer; the first corrosion treatment adopts a first corrosion solution containing sodium permanganate and strong base, the sodium permanganate is decomposed under the action of metal catalysis to release oxygen, and a mechanical stripping effect is performed on an oxide layer on the surface of the metal wire, so that the oxide layer on the inner part of the surface of the metal wire is loosened and corroded; the second corrosion treatment adopts the simultaneous action of acid and surfactant to dissolve and remove the residual oxide on the surface of the metal wire.
In some embodiments of the present disclosure, the intracranial vascular braided stent is further subjected to a passivation treatment step. The metal wire of the intracranial vascular stent is extremely thin and is to be permanently implanted into a human body, so the state of the metal surface of the stent is directly related to the long-term use performance of the stent after implantation, a compact and continuous passivation layer is formed on the metal surface through passivation treatment, the metal surface is more stable, and the long-term use capability of the stent is improved.
The low thrombogenic intracranial vascular braided stent of the present disclosure and its method of treatment are illustrated by the following specific examples. The reagents or equipment or procedures used in the following examples are those routinely determined by one of ordinary skill in the art.
Example 1
As shown in figure 1, the embodiment is a surface-treated intracranial vascular braided stent, the stent is braided by a cobalt-chromium alloy wire and a platinum-based alloy developing wire, and a layer of dense chromium oxide passive film (the main component is Cr) is formed on the surface of the cobalt-chromium alloy wire2O3). The intracranial vascular knitted stent comprises a cylindrical tubular net-shaped structure body, wherein the net-shaped structure body comprises a plurality of knitting lines which are mutually knitted to form a continuous mesh structure 3, and each knitting line comprises a warp 1 and a weft 2; the warp and the weft intersect to form a weaving point, the weaving point comprises a forward weaving point 4 and a backward weaving point 5, wherein the weaving point pressed above the weft 2 at the position of the warp 1 is the forward weaving point 4, the weaving point pressed below the weft 2 at the position of the warp 1 is the backward weaving point 5, one warp 1 is adjacent to the forward weaving point 4 and the backward weaving point 5 formed by the weft 2 crossed on the one warp 1, and one weft 2 is adjacent to the forward weaving point 4 and the backward weaving point 5 formed by the warp 1 crossed on the one weft 2. The intracranial vascular braided stent of the embodiment has higher flexibility and lower support property, and is suitable for positions with smaller vessel diameter (D is less than or equal to 2.5mm), such as anterior cerebral artery, posterior cerebral artery, anterior communicating artery, posterior communicating artery, superior cerebellar artery and inferior cerebellar artery.
Example 2
As shown in fig. 2, the intracranial vascular braided stent of the embodiment is subjected to surface treatment, the stent is braided by a cobalt-chromium alloy wire and a platinum-based alloy developing wire, and a layer of dense chromium oxide passive film (the main component is Cr) is formed on the surface of the cobalt-chromium alloy wire2O3). The intracranial vascular knitted stent comprises a cylindrical tubular net-shaped structure body, wherein the net-shaped structure body comprises a plurality of knitting lines which are mutually knitted to form a continuous mesh structure 3, and each knitting line comprises a warp 1 and a weft 2; warp with form after the weft intersects and weave the point, it includes just weaving point 4 and reverse weaving point 5 to weave the point, and wherein 1 position of warp is pressed the weaving point above weft 2 and is woven point 4 just, and 1 position of warp is pressed the weaving point below weft 2 and is reverse weaving point 5, a warp 1 with cross in a warp 1 with it is in a warp 2The four adjacent weft threads 2 on the weft thread 1 are a weaving thread, the weaving thread comprises four weaving points, namely two forward weaving points 4 and two backward weaving points 5, wherein the two forward weaving points 4 are adjacent or the two backward weaving points 5 are adjacent. The intracranial vascular braided stent of the embodiment has moderate flexibility and support property, and is suitable for positions with the diameter of the blood vessel being 2.5mm and D being less than or equal to 4.0mm, such as the distal ends of the middle cerebral artery, the vertebral artery and the internal carotid artery.
Example 3
As shown in fig. 3, in this embodiment, the surface-treated intracranial vascular braided stent is formed by braiding a cobalt-chromium alloy wire and a platinum-based alloy developing wire, and a layer of dense chromium oxide passivation film is formed on the surface of the cobalt-chromium alloy wire. The intracranial vascular knitted stent comprises a cylindrical tubular net-shaped structure body, wherein the net-shaped structure body comprises a plurality of knitting lines which are mutually knitted to form a continuous mesh structure 3, and each knitting line comprises a warp 1 and a weft 2; the warp and the weft are intersected to form a weaving point, the weaving point comprises a positive weaving point 4 and a negative weaving point 5, wherein the weaving point, pressed above the weft 2, at the position of the warp 1 is the positive weaving point 4, the weaving point, pressed below the weft 2, at the position of the warp 1 is the negative weaving point 5, every two warps 1 form a group of warp groups, every two wefts 2 form a group of weft groups, the distance between every two warps 1 in each group of warp groups is a first distance, the distance between every two wefts 2 in each group of weft groups is a second distance, the distance between every two adjacent groups of warp groups is a third distance, and the distance of the third distance is greater than the distance between the first distance and the second distance; and the distance between two adjacent weft groups is a fourth distance, and the distance of the fourth distance is greater than the distance of the first distance and the distance of the second distance. The intracranial vascular braided stent of the embodiment has lower flexibility and higher support property, and is suitable for positions with larger vessel diameter (D is more than 4mm), such as the proximal end of an internal carotid artery and a basilar artery.
Example 4
This example provides a method for surface treatment of an intracranial vascular braided stent (formed by braiding 0.03mm diameter cobalt-chromium alloy wire according to the braiding method of example 1), which is performed by first immersing the stent in a pre-corrosive solution (containing 28 wt.% hydrochloric acid, 0.15 wt.% 1, 4-butynediol, 0.15 wt.% sodium dodecyl sulfate, 2 wt.% o-benzoylsulfimide, and the remaining percentage of water) at 53 ℃ for 12min to perform pre-corrosion treatment, and then the cobalt-chromium alloy wire surface becomes blue and lighter. Taking out the bracket, washing with water, and air drying. Mixing the solution A (20 wt.% of sodium permanganate and 80 wt.% of water) and the solution B (20 wt.% of sodium hydroxide and 80 wt.% of water) to prepare a first corrosion solution, soaking the support in the first corrosion solution at 65 ℃ for 4 hours to perform first corrosion treatment, and changing the surface of the cobalt-chromium alloy wire from light blue to light brown through the first corrosion treatment. Taking out the bracket, washing with water, and air drying. Preparing a second corrosive liquid (containing 15 wt.% of hydrochloric acid and 0.1 wt.% of sodium dodecyl sulfate aqueous solution), placing the support in the second corrosive liquid, soaking for 15min at 40 ℃ for second corrosion treatment, and performing second corrosion treatment to enable the surface of the cobalt-chromium alloy wire to become bright. Taking out the bracket, washing with water, and air drying. And (3) placing the corroded bracket in a nitric acid solution (containing 30 vol.% of nitric acid and 70 vol.% of water), soaking for 20min at 50 ℃ for passivation treatment to form a passivation film, and detecting that the pitting potential Eb of the passivation film is more than 800 mv.
The passivated stent is subjected to in vitro testing for ten-year fatigue cycles (the testing method is referred to the YY/T0808-2010 intravascular stent in vitro pulsation durability standard testing method), and the results are shown in FIG. 4, wherein it can be seen that the metal wires of the stent are not corroded and broken.
Example 5
This example provides a method for surface treatment of an intracranial vascular braided stent (formed by braiding 0.03mm diameter cobalt-chromium alloy wire according to the braiding method of example 2), which is performed by first immersing the stent in a pre-etching solution (containing 40 wt.% hydrobromic acid, 0.15 wt.% 1, 4-butynediol, 0.3 wt.% sodium dodecyl sulfate, 0.15 wt.% o-benzoylsulfimide, and the remaining percentage of water) at 43 ℃ for 12min, and then the surface of the cobalt-chromium alloy wire is blue-colored. Taking out the bracket, washing with water, and air drying. Mixing the solution A (40 wt.% of sodium permanganate and 60 wt.% of water) and the solution B (30 wt.% of sodium hydroxide and 70 wt.% of water) to prepare a first corrosion solution, soaking the support in the first corrosion solution at 60 ℃ for 5 hours to perform first corrosion treatment, and changing the surface of the cobalt-chromium alloy wire from light blue to light brown through the first corrosion treatment. Taking out the bracket, washing with water, and air drying. Preparing a second corrosive liquid (containing 30 wt.% of hydrochloric acid and 0.5 wt.% of sodium dodecyl sulfate aqueous solution), placing the support in the second corrosive liquid, soaking for 10min at 55 ℃ for second corrosion treatment, and performing the second corrosion treatment to enable the surface of the cobalt-chromium alloy wire to be bright. Taking out the bracket, washing with water, and air drying. And (3) placing the corroded bracket in a nitric acid solution (containing 45 vol.% of nitric acid and 65 vol.% of water), soaking for 55min at 25 ℃ for passivation treatment to form a passivation film, and detecting that the pitting potential Eb of the passivation film is more than 800 mv.
The passivated stent was subjected to in vitro testing for ten-year fatigue cycles (the test method is referred to as YY/T0808-2010 intravascular stent in vitro pulsation durability standard test method), and the results are shown in FIG. 5, wherein it can be seen that the wires of the stent are not corroded and broken.
Comparative example 1
The comparative example adopts an electrochemical method to remove the heat treatment oxide layer on the surface of the bracket, and takes the bracket as an anode to carry out electrochemical corrosion. Partial discharge at the conductive contact of the stent causes the wire to fuse or melt.
Comparative example 2
In the comparison example, the intracranial vascular stent is subjected to surface treatment by adopting a traditional cardiovascular stent treatment method, the surface of the cobalt-chromium alloy wire is observed after the intracranial vascular stent is subjected to corrosion treatment by using a corrosive liquid (containing hydrofluoric acid, nitric acid and hydrogen peroxide), and the fact that although a heat treatment oxide on the surface of the cobalt-chromium alloy wire is corroded, an alloy wire matrix positioned under the oxide is also corroded, is easy to break and cannot bear ten-year fatigue cycle tests is found.
It can be seen from the above examples and comparative examples that the surface treatment method provided by the present disclosure can remove the heat-treated oxide layer on the surface of the intracranial vascular stent, form a passivation layer on the surface of the metal wire, and simultaneously keep the mechanical properties of the stent metal wire from being greatly reduced, while the electrochemical method or the traditional treatment cardiovascular stent treatment method is used for treating the intracranial vascular stent, which is prone to wire breakage.