CN101623218A - Blood vessel covered stent and manufacturing method thereof - Google Patents
Blood vessel covered stent and manufacturing method thereof Download PDFInfo
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- CN101623218A CN101623218A CN200910304010A CN200910304010A CN101623218A CN 101623218 A CN101623218 A CN 101623218A CN 200910304010 A CN200910304010 A CN 200910304010A CN 200910304010 A CN200910304010 A CN 200910304010A CN 101623218 A CN101623218 A CN 101623218A
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Abstract
The invention relates to a blood vessel covered stent and a manufacturing method thereof. The blood vessel covered stent comprises a tubular nickel-titanium alloy framework and an isolation membrane; the isolation membrane is arranged on at least most tubular surface of the nickel-titanium alloy framework as a tube wall and used for preventing blood in the blood vessel covered stent from permeating through the tube wall; and a shielding layer for preventing nickel ions from releasing and entering into blood is formed on the surface of the material which forms the nickel-titanium alloy framework. The manufacturing method of the nickel-titanium alloy framework comprises the following steps: manufacturing the tubular nickel-titanium alloy framework with the shielding layer; and arranging the isolation membrane onto the tubular surface of the nickel-titanium alloy framework as the tube wall. In the blood vessel covered stent, the shielding layer is formed on the surface of the material forming the nickel-titanium alloy framework and can prevent the nickel ions from releasing and accumulating in a human body.
Description
Technical field
The present invention relates to a kind of blood vessel covered stent and manufacture method, relate in particular to a kind of blood vessel covered stent and manufacture method that is used for aortal band screen layer.
Background technology
In the existing Therapeutic Method, mainly adopt endovascular graft to treat to the very harmful aortic aneurysm of human body.Aortic aneurysm endovascular graft exclusion carries out image checks such as CT angiography earlier to the aortic aneurysm patient, obtain the precise information of aortic disease position, selects the blood vessel covered stent of corresponding specification size then in view of the above.During operation, under X line fluoroscopic monitoring, blood vessel covered stent is delivered to the aortic disease position, then blood vessel covered stent is discharged at the lesion vessels place, blood vessel covered stent expands into design shape automatically, contacts with the blood vessel wall of aortic disease position, makes blood and aortic disease position isolated, blood flows through in the blood vessel covered stent interior lumen, and the aortic aneurysm intracavity blood solidifies and fleshization because of flow velocity descends.The use of blood vessel covered stent, it is unobstructed both to have kept aortal blood flow, has reached the purpose of prevention and treatment aortic aneurysm again.Aortic aneurysm endovascular graft exclusion has become the first-selected Therapeutic Method of aortic aneurysm because its wound is little, operating time is short, the success rate advantages of higher.
One of core technology of aortic aneurysm intracavitary therapy is the blood vessel covered stent technology, and the research of blood vessel covered stent is a wherein most important link.Blood vessel covered stent of the prior art is a species complex, adopts the high-performance medical metal material to be woven into the mesh duct skeleton earlier, then artificial medical thin-film material is coated or is sewn on the metallic framework.Nickel-titanium alloy material can guarantee good resilience of support and enough radial support power, therefore makes the main flow that skeleton has become existing blood vessel covered stent technology with nickel-titanium alloy material.But the nickel content in the Nitinol is than higher, and nickel ion discharges in human body, assembles in human body easily, causes secular biocompatibility issues, causes inflammation simultaneously or forms thrombosis.
Summary of the invention
The technical problem that the present invention solves is: behind the intravascular stent implant into body with the Nitinol making, nickel ion can cause secular biocompatibility issues in intravital release of people and gathering.
The technical scheme that the present invention addresses the above problem is: make up a kind of blood vessel covered stent, comprise nickel-titanium alloy framework and secluding film, described nickel-titanium alloy framework becomes tubulose, described secluding film is arranged on most of at least tubular surface of described nickel-titanium alloy framework as tube wall, described secluding film is used to stop the blood penetration in the blood vessel covered stent to cross tube wall, forms at the material surface that constitutes described nickel-titanium alloy framework and prevents that nickel ion from discharging into the screen layer of blood.
Further technical scheme of the present invention is: the material of described nickel-titanium alloy framework screen layer is any in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum or the rustless steel.Form screen layer at the material surface that constitutes described nickel-titanium alloy framework, can adopt vacuum filtration arc ion plating, magnetron sputtering, ion beam-assisted build up or ion implantation in any method.
Further technical scheme of the present invention is: described nickel-titanium alloy framework is bent by nitinol alloy wire and forms, and contains a plurality of wavy bending rings.Described nickel-titanium alloy framework can adopt a nitinol alloy wire to be bent into a plurality of wavy bending rings that connect in succession; Also can adopt a nitinol alloy wire to be bent into an independent ring, and then a plurality of independently wavy bending rings are connected to form duct-like nickel-titanium alloy framework with nitinol alloy wire.Described nickel-titanium alloy framework can also be formed by laser engraving by the Nitinol pipe, has wavy decorative pattern after the expansion.
Further technical scheme of the present invention is: described nickel-titanium alloy framework is a mesh duct, comprises straight tubular, taper and Y-shaped.
Further technical scheme of the present invention is: the material that described secluding film adopts is politef, polyester or terylene.Secluding film can be arranged on the tubular outer surface of described nickel-titanium alloy framework, and wherein, poly tetrafluoroethylene can be arranged on the tubular inner surface and the outer surface of described nickel-titanium alloy framework.When adopting poly tetrafluoroethylene to make, earlier described poly tetrafluoroethylene is prefabricated into tubulose, then polyfluortetraethylene pipe is made, form secluding film at described nickel-titanium alloy framework outer surface.When adopting adherent method, with poly tetrafluoroethylene parcel nickel-titanium alloy framework outer surface and inner surface, the several layers poly tetrafluoroethylene is bonded together, and forms secluding film.When adopting polyester or dacron membrane, polyester or dacron membrane directly are sewn to described nickel-titanium alloy framework outer surface formation tube wall.
Technical scheme of the present invention is: described nickel-titanium alloy framework comprises skeleton body, at least one end and connecting rod, and described skeleton body is connected by at least two connecting rods with each end, and described secluding film is arranged on the described skeleton body.
The invention provides a kind of method of making above-mentioned blood vessel covered stent, comprise the steps: to make described tubulose nickel-titanium alloy framework; Material surface in nickel-titanium alloy framework forms screen layer with any material in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum, the rustless steel; Secluding film is arranged on most of at least tubular surface of nickel-titanium alloy framework as tube wall.
The invention provides a kind of method of making above-mentioned blood vessel covered stent, comprise the steps: nickel-titanium alloy material is made filamentation, form screen layer with any material in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum, the rustless steel on the nitinol alloy wire surface; The nitinol alloy wire of band screen layer is woven into described tubulose nickel-titanium alloy framework; Secluding film is arranged on most of at least tubular surface of nickel-titanium alloy framework as tube wall.
Technique effect of the present invention is: in the blood vessel covered stent of the present invention, form screen layer at the material surface that constitutes nickel-titanium alloy framework, the material of described screen layer has better biocompatibility, and can prevent that the nickel ion in the intravascular stent from discharging accumulation in human body.
Description of drawings
Fig. 1 is the blood vessel covered stent structure chart of band screen layer of the present invention.
Fig. 2 is the nickel-titanium alloy framework wire rod drawing in side sectional elevation of band screen layer of the present invention.
Fig. 3 forms structure chart for nickel-titanium alloy framework of the present invention by a plurality of wave bending rings.
Fig. 4 is a taper nickel-titanium alloy framework profile of the present invention.
Fig. 5 is a band bifurcated nickel-titanium alloy framework profile of the present invention.
Fig. 6 is exposed part nickel-titanium alloy framework end construction figure of the present invention.
Fig. 7 is a fixedly skeleton structure diagram of nickel-titanium alloy framework band of the present invention
Fig. 8 is the flow chart of a kind of production method of blood vessel covered stent of the present invention.
Fig. 9 is the flow chart of the another kind of production method of blood vessel covered stent of the present invention.
The specific embodiment
Below in conjunction with specific embodiment, technical solution of the present invention is further specified.
As shown in Figure 1 and Figure 2, a kind of blood vessel covered stent of the present invention, comprise nickel-titanium alloy framework 2 and secluding film 4,2 one-tenth tubuloses of nickel-titanium alloy framework, described secluding film 4 is arranged on most of at least tubular surface of nickel-titanium alloy framework 2 as tube wall, described secluding film 4 is used to stop the blood penetration in the blood vessel covered stent to cross tube wall, forms at the material surface that constitutes described nickel-titanium alloy framework 2 and prevents that nickel ion from discharging into the screen layer 1 of blood.The blood vessel covered stent that nickel-titanium alloy material is made has good resilience and radial support power.Make in the support process, nickel-titanium alloy framework 2 heat treatments are shaped, make default profile.During use, support is compressed in the induction system, sends into again in the blood vessel, discharge the state when support returns to molding in the precalculated position.The screen layer 1 of blood vessel covered stent of the present invention can prevent that nickel ion from discharging into blood, overcome that nickel ion discharges into blood and the problem that causes the human-body biological intermiscibility.Screen layer 1 of the present invention can also prevent that blood and nickel-titanium alloy framework 2 from chemical reaction taking place, and reduces the infringement to human body, also strengthens the anti-fatigue performance of nickel-titanium alloy framework 2 simultaneously.
Preferred implementation of the present invention is: the material of screen layer 1 is any in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum or the rustless steel, can prevent effectively that nickel ion is discharged in the blood.When these materials contact with blood in human body, show better biocompatibility, therefore, these materials can be used as screen layer.As shown in Figure 2, screen layer 1 is formed at nickel-titanium alloy framework 2 surfaces that wire rod or other shape materials are made; The method of formation screen layer 1 has multiple, as: vacuum filtration arc ion plating, magnetron sputtering, ion beam-assisted are built up or are ion implantation.
As shown in Figure 3, preferred implementation of the present invention is: nickel-titanium alloy framework 2 is bent by nitinol alloy wire and forms, and contains a plurality of wavy bending rings 221.Bending ring 221 adopts the nitinol alloy wire bending to form, and preferably becomes the bending of a plurality of " Z " font.Between a plurality of wavy bending ring 221 in the nickel-titanium alloy framework 2 space is arranged, be convenient to blood vessel covered stent along the shape of aortic arch and bending, guarantee the pliability of support.
As shown in Figure 3, preferred implementation of the present invention can also be made a plurality of wavy bending rings for: nickel-titanium alloy framework 2 adopts a nitinol alloy wire, extend to the starting position of next ring from the closure of a last ring, continue to be bent into ring-type, and the like, till the length of tubulose nickel-titanium alloy framework 2 meets the requirements.Another kind of optionally embodiment is, each wavy bending ring 221 all is to be formed by a nitinol alloy wire bending, and a plurality of wavy bending rings are connected to form nickel-titanium alloy framework 2 by nitinol alloy wire 5.
Preferred implementation of the present invention can also for: nickel-titanium alloy framework 2 is formed by laser engraving by the Nitinol pipe, has wavy decorative pattern through heating behind the expanding and shaping.
As Fig. 4, shown in Figure 5, preferred implementation of the present invention is: according to vascular function, pathological changes with branchiess situation is arranged, nickel-titanium alloy framework 2 is made into such as different shapes such as tubular, taper and Y-shapeds.The diameter difference of the bending ring 221 that tapered tubular skeleton two ends form is respectively D1 and D2.The tubular bracket of band bifurcated comprises straight tube stent 8 and the bifurcated stent that is connected with straight tube stent 8, and described bifurcated stent comprises first branch 81 and second branch 82.
Preferred implementation of the present invention is: the material that secluding film 4 adopts is politef, polyester or terylene.Secluding film 4 can be arranged on the tubular outer surface of described nickel-titanium alloy framework 2, and wherein, poly tetrafluoroethylene can be arranged on the tubular inner surface and the outer surface of described nickel-titanium alloy framework 2.Secluding film 4 can adopt the method for making to form, and when adopting poly tetrafluoroethylene to make, earlier poly tetrafluoroethylene is prefabricated into tubulose, and then the outer surface that the tubulose poly tetrafluoroethylene is made in nickel-titanium alloy framework 2 forms tube wall; When adopting polyester or dacron membrane to make, polyester or dacron membrane directly can be sewn to nickel-titanium alloy framework outer surface formation tube wall.Secluding film 4 can also adopt adherent method to form, and promptly with poly tetrafluoroethylene parcel nickel-titanium alloy framework outer surface and inner surface, the several layers poly tetrafluoroethylene is bonded together.
As shown in Figure 6, another embodiment of the invention is: the radical length of nickel-titanium alloy framework 2 is longer than secluding film 4, forms not the end 21 with secluding film in the one or both ends of blood vessel covered stent.This place that is not fixed on branch vessel with the end 21 of secluding film can block blood not flow to branch vessel from aorta.
As shown in Figure 7, preferred implementation of the present invention is: nickel-titanium alloy framework 2 comprises skeleton body 22, at least one end 23 and connecting rod 6, skeleton body 22 is connected by at least two connecting rods 6 with each end 23, and secluding film 4 is arranged on the skeleton body 22.In the present embodiment, secluding film is not with in end 23, and each end 23 is connected with skeleton body 22 by at least two connection extension bars 6.End 23 is fixed on the place of branch vessel, can block blood not flow to branch vessel from aorta.
As shown in Figure 8, the manufacture method of blood vessel covered stent of the present invention comprises the steps: step 110, makes nickel-titanium alloy framework,, nickel-titanium alloy material is made into piped nickel-titanium alloy framework 2 that is.Step 210 plates screen layer 1 at the material surface of nickel-titanium alloy framework 2, and the material of screen layer 1 is any in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum or the rustless steel (for example SUS316L rustless steel).When these materials contact with blood, show better biocompatibility in human body.Simultaneously, adopt the screen layer 1 of these material can prevent that the nickel ion in the nickel-titanium alloy framework 2 from discharging into human body.Step 310 is made blood vessel covered stent,, secluding film is arranged on most of at least tubular surface of nickel-titanium alloy framework as tube wall that is.
As shown in Figure 9, the manufacture method of blood vessel covered stent of the present invention comprises the steps: step 120, nickel-titanium alloy material is made filamentation, plate screen layer 1 on the nitinol alloy wire surface, the material of screen layer 1 is any in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum or the rustless steel (for example SUS316L rustless steel).When these materials contact with blood, show better biocompatibility in human body.Simultaneously, adopt the screen layer 1 of these material can prevent that the nickel ion in the nickel-titanium alloy framework 2 from discharging into human body.Step 220 will be with the nitinol alloy wire of screen layer 1 to be made into piped nickel-titanium alloy framework 2.Step 320 is made blood vessel covered stent,, secluding film is arranged on most of at least tubular surface of nickel-titanium alloy framework as tube wall that is.
The screen layer 1 of blood vessel covered stent of the present invention can prevent that nickel ion from discharging into blood, overcome nickel ion and discharged into blood and cause problem with the biocompatibility of human body.Screen layer 1 of the present invention can also prevent nickel-titanium alloy framework 2 and blood generation chemical reaction, reduces the infringement to human body, also strengthens the anti-fatigue performance of nickel-titanium alloy framework 2 simultaneously.
Above content be in conjunction with concrete preferred implementation to further describing that the present invention did, can not assert that concrete enforcement of the present invention is confined to these explanations.For the general technical staff of the technical field of the invention, without departing from the inventive concept of the premise, can also make some simple deduction or replace, all should be considered as belonging to protection scope of the present invention.
Claims (10)
1. blood vessel covered stent, comprise nickel-titanium alloy framework and secluding film, described nickel-titanium alloy framework becomes tubulose, described secluding film is arranged on most of at least tubular surface of described nickel-titanium alloy framework as tube wall, described secluding film is used to stop the blood penetration in the blood vessel covered stent to cross tube wall, it is characterized in that, form at the material surface that constitutes described nickel-titanium alloy framework and prevent that nickel ion from discharging into the screen layer of blood.
2. blood vessel covered stent according to claim 1 is characterized in that, described screen layer be by vacuum filtration arc ion plating, magnetron sputtering, ion beam-assisted build up or ion implantation in any method form.
3. blood vessel covered stent according to claim 1 is characterized in that, the material of described screen layer is any in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum or the rustless steel.
4. blood vessel covered stent according to claim 3 is characterized in that, described nickel-titanium alloy framework is bent by nitinol alloy wire and forms, and contains a plurality of wavy bending rings.
5. blood vessel covered stent according to claim 3 is characterized in that described nickel-titanium alloy framework is formed by laser engraving by the Nitinol pipe, has wavy decorative pattern after the expansion.
6. blood vessel covered stent according to claim 3, it is characterized in that, described nickel-titanium alloy framework comprises skeleton body, at least one end and connecting rod, and described skeleton body is connected by at least two connecting rods with each end, and described secluding film is arranged on the described skeleton body.
7. blood vessel covered stent according to claim 3 is characterized in that described nickel-titanium alloy framework is a mesh duct, comprises straight tubular, taper and Y-shaped.
8. blood vessel covered stent according to claim 3 is characterized in that, the material that described secluding film adopts is politef, polyester or terylene.
9. a method of making the described blood vessel covered stent of claim 1 comprises the steps:
Make described piped nickel-titanium alloy framework;
Described nickel-titanium alloy framework is plated any material in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum or the rustless steel as described screen layer;
Described secluding film is arranged on most of at least tubular surface of described nickel-titanium alloy framework as tube wall.
10. a method of making the described blood vessel covered stent of claim 1 comprises the steps:
Nitinol alloy wire is plated any material in titanium nitride, titanium carbide, titanium oxide, titanium, carborundum or the rustless steel as described screen layer;
The nitinol alloy wire of band screen layer is made into piped described nickel-titanium alloy framework;
Described secluding film is arranged on most of at least tubular surface of described nickel-titanium alloy framework as tube wall.
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| CN200910304010A CN101623218A (en) | 2009-07-03 | 2009-07-03 | Blood vessel covered stent and manufacturing method thereof |
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| CN200910304010A CN101623218A (en) | 2009-07-03 | 2009-07-03 | Blood vessel covered stent and manufacturing method thereof |
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| CN102166143A (en) * | 2011-05-23 | 2011-08-31 | 先健科技(深圳)有限公司 | Device for conveying bracket in operation and method for mounting and releasing bracket in aortic arch operation |
| CN102286685A (en) * | 2011-08-26 | 2011-12-21 | 重庆科技学院 | Preparation method of SiC/stainless steel composite blood vessel stent material |
| CN102670338A (en) * | 2012-06-11 | 2012-09-19 | 上海中山医疗科技发展公司 | Pre-bent aortic membrane-covered stent and manufacturing method thereof |
| CN102784019A (en) * | 2012-08-07 | 2012-11-21 | 湖南瑞康通科技发展有限公司 | Cerebral aneurysm scaffold system and preparation method thereof |
| CN103720529A (en) * | 2013-12-30 | 2014-04-16 | 先健科技(深圳)有限公司 | Arcus aortae intraoperative stent and method for manufacturing stent |
| CN104099609A (en) * | 2014-06-26 | 2014-10-15 | 华中科技大学 | Surface modification method for medical titanium alloy |
| CN106073958A (en) * | 2016-07-13 | 2016-11-09 | 余少恒 | A kind of Medical rack and manufacture method thereof |
| CN106137459A (en) * | 2015-08-20 | 2016-11-23 | 上海市浦东医院 | The interim film covering device of intravascular stent and the method for the interim overlay film of intravascular stent |
| CN106137483A (en) * | 2016-07-21 | 2016-11-23 | 成都嘉宝祥生物科技有限公司 | A kind of coronary vessel stent manufacture method |
| CN106175981A (en) * | 2016-03-04 | 2016-12-07 | 上海沐春投资管理有限公司 | A kind of part band film intravenous type support |
| CN106267356A (en) * | 2015-05-22 | 2017-01-04 | 先健科技(深圳)有限公司 | Implanted medical device prefabricated component, implanted medical device and preparation method thereof |
| CN106310376A (en) * | 2015-06-30 | 2017-01-11 | 先健科技(深圳)有限公司 | Implantable medical appliance prefabricated part, implantable medical appliance and manufacturing method of implantable medical appliance |
| CN107530176A (en) * | 2015-04-15 | 2018-01-02 | M.I.泰克株式会社 | Support manufacturing method |
| CN108785754A (en) * | 2017-05-05 | 2018-11-13 | 赛诺医疗科学技术股份有限公司 | Medical overlay film frame |
| CN109773820A (en) * | 2017-11-14 | 2019-05-21 | 先健科技(深圳)有限公司 | A kind of fixture |
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- 2009-07-03 CN CN200910304010A patent/CN101623218A/en active Pending
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| CN102166143B (en) * | 2011-05-23 | 2014-04-09 | 先健科技(深圳)有限公司 | Device for conveying bracket in operation |
| CN102166143A (en) * | 2011-05-23 | 2011-08-31 | 先健科技(深圳)有限公司 | Device for conveying bracket in operation and method for mounting and releasing bracket in aortic arch operation |
| CN102286685A (en) * | 2011-08-26 | 2011-12-21 | 重庆科技学院 | Preparation method of SiC/stainless steel composite blood vessel stent material |
| CN102286685B (en) * | 2011-08-26 | 2014-01-15 | 重庆科技学院 | Preparation method of SiC/stainless steel composite blood vessel stent material |
| CN102670338A (en) * | 2012-06-11 | 2012-09-19 | 上海中山医疗科技发展公司 | Pre-bent aortic membrane-covered stent and manufacturing method thereof |
| CN102784019A (en) * | 2012-08-07 | 2012-11-21 | 湖南瑞康通科技发展有限公司 | Cerebral aneurysm scaffold system and preparation method thereof |
| CN103720529B (en) * | 2013-12-30 | 2017-02-08 | 先健科技(深圳)有限公司 | Arcus aortae intraoperative stent and method for manufacturing stent |
| CN103720529A (en) * | 2013-12-30 | 2014-04-16 | 先健科技(深圳)有限公司 | Arcus aortae intraoperative stent and method for manufacturing stent |
| CN104099609A (en) * | 2014-06-26 | 2014-10-15 | 华中科技大学 | Surface modification method for medical titanium alloy |
| CN107530176A (en) * | 2015-04-15 | 2018-01-02 | M.I.泰克株式会社 | Support manufacturing method |
| CN107530176B (en) * | 2015-04-15 | 2019-08-16 | M.I.泰克株式会社 | Support manufacturing method |
| CN106267356B (en) * | 2015-05-22 | 2020-01-03 | 先健科技(深圳)有限公司 | Implanted medical device prefabricated part, implanted medical device and preparation method thereof |
| CN106267356A (en) * | 2015-05-22 | 2017-01-04 | 先健科技(深圳)有限公司 | Implanted medical device prefabricated component, implanted medical device and preparation method thereof |
| CN106310376A (en) * | 2015-06-30 | 2017-01-11 | 先健科技(深圳)有限公司 | Implantable medical appliance prefabricated part, implantable medical appliance and manufacturing method of implantable medical appliance |
| CN106137459B (en) * | 2015-08-20 | 2018-02-23 | 上海市浦东医院 | The method of the interim film covering device of intravascular stent and the interim overlay film of intravascular stent |
| CN106137459A (en) * | 2015-08-20 | 2016-11-23 | 上海市浦东医院 | The interim film covering device of intravascular stent and the method for the interim overlay film of intravascular stent |
| CN106175981A (en) * | 2016-03-04 | 2016-12-07 | 上海沐春投资管理有限公司 | A kind of part band film intravenous type support |
| CN106073958A (en) * | 2016-07-13 | 2016-11-09 | 余少恒 | A kind of Medical rack and manufacture method thereof |
| CN106073958B (en) * | 2016-07-13 | 2019-04-16 | 余少恒 | A kind of Medical rack and its manufacturing method |
| CN106137483A (en) * | 2016-07-21 | 2016-11-23 | 成都嘉宝祥生物科技有限公司 | A kind of coronary vessel stent manufacture method |
| CN108785754A (en) * | 2017-05-05 | 2018-11-13 | 赛诺医疗科学技术股份有限公司 | Medical overlay film frame |
| CN109773820A (en) * | 2017-11-14 | 2019-05-21 | 先健科技(深圳)有限公司 | A kind of fixture |
| CN109773820B (en) * | 2017-11-14 | 2022-09-20 | 元心科技(深圳)有限公司 | Clamp |
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Open date: 20100113 |