CN110090094A - The method of artificial valve and manufacture of intraocular valve - Google Patents

Abstract

The present invention relates to the methods of artificial valve and manufacture of intraocular valve.The present invention relates to artificial valves, it includes leaflet assemblies, there is the leaflet assembly at least one to be connected to the leaflet (3) of support component (2), the leaflet has the free edge that can be moved between the first position and the second position, wherein at first position, the free edge is bent far from closing surface (700) to allow body fluid to flow by the valve；At the second position, for the adjacent closing surface of the free edge to close the valve, and wherein when not having pulsating load on the valve, the leaflet can form the jointing altitude for being greater than 0.1mm along the length of the free edge.This artificial valve can be provided for a long term superperformance, and be able to use a variety of materials of suitable leaflet to manufacture.The invention further relates to the methods for leaflet assembly and manufacture of intraocular valve in artificial valve, including manufacture leaflet assembly.

Description

The method of artificial valve and manufacture of intraocular valve

The present invention be the applying date be on May 6th, 2015, application No. is 201580023424.2 (international application no PCT/ EP2015/059982 the divisional application of application for a patent for invention " method of artificial valve and manufacture of intraocular valve ").

Technical field

The present invention relates to the method for implantable medical instrument and the manufacture medical instrument, the medical instrument examples Such as artificial valve (prosthetic valve), more specifically two leaflet formulas or three leaflet formula heart valve prosthesises.

Background technique

The typical natural valve of mammal is aorta petal, is one of four kinds of heart valves.Aorta petal include with Three connected leaflets (also referred to as cusp) of aortic root, the aortic root serve as the support component of these leaflets.Aorta The edge that each of three leaflets of valve are all had free edge and are connected in a manner of semilune with aortic root.Work as valve When film is opened, leaflet, which falls back in their sinus, blocks any tubulose aperture without potential.The hinge of neighbouring leaflet exists Sinus pipe boundary level is converged, to form at least part of joint (commissure).The main body of leaflet is soft, can expand Exhibition and the thin flexibility required with offer, although its is in uneven thickness.Leaflet is slightly thicker towards its free edge.Its room property Surface is the region juxtaposition (apposition) (also known as planum semilunatum (lunule)), which occupies the overall with along free edge And cross over the about one third of leaflet depth.This is in place of valve down periods leaflet meets with neighbouring leaflet.When valve is in It when closed position, the edge join of planum semilunatum or merges together, thus by the blood and aorta in heart left chamber chamber Blood separate.For the valve of this seed type or respective type, during opening and closing, highest mechanical stress, which is appeared in, connects At conjunction, and mechanical stress appears in the free edge of leaflet in lesser degree.

Artificial valve is implanted in human body or animal body and can for example be used as intravascular or near vessels quilts Dynamic, unidirectional artificial valve.They can be completely preforming and be implanted into as former state, or can be used and be used to form functional people Artificial elements needed for work valve and/or natural elements are formed in situ.Suitable artificial valve is in the pressure to valve either side It needs to readily open and close when difference response, does not lead to or cause few non-physiologic turbulent flow in blood flow, and avoided More reflux.Therefore, to the loading condition of cardiovascular products (such as heart valve prosthesis) (at two aspect of magnitude and recurring number) It is required that very high.In general, heart valve leaflets can be subjected to more than 1,000,000,000 load cycles during its service life.Therefore, artificial valve The durability of (especially movable leaflet) is important requirement.

Practical machine during any artificial valve all should be able to be resistant to valve surgery on joint and leaflet free edges edge Tool load, and preferably, maintain this repeated loading of tolerance to continue many years.For this purpose, not only initial strength is important ginseng Number, but also to reduce a possibility that (unobvious) production is lopsided when manufacturing valve.

Now, valve used in valve surgery is usually to have by biological tissue's (often chemically treated cattle heart Packet) made of leaflet bioprosthetic valves.This is a kind of elastic material, shows quite excellent and can simulate natural Valve.But it would ordinarily be encountered initial failure, and initial failure is considered and posterior leaflet is continuously stretched and shunk under pulsating load High stress on material is related.It has been presented for various synthetic materials and is configured as the substitute of manufacture of intraocular valve leaflet.

Such as it is described in NL1008349 using valve prosthesis made of synthetic fibers (prosthesis).This valve Support component comprising having some leaflets, the leaflet is by with corresponding with the stress in the presence of leaflet specific Reinforcing fiber is wrapped on mandrel by direction to be manufactured.Since fiber must be placed according to maximum stress line, so this valve Film prosthese is difficult to manufacture and adjusts stress using many winding layers, to increase quality and can damage flexibility.

Similarly, US6726715 is described for valvular leaflet, it includes have with during valve operation The flexible sheets of the consistent fibre element for eliminating stress of predetermined stress line in leaflet.Sheet material is usually PTFE or PVF, wherein Use high strength/high modulus fiber as reinforcing element.Fiber such as carbon fiber, aramid fiber or polyethylene fiber can be used Dimension is such asUHMWPE fiber.

WO2010/020660 is described by such as uniform hollow braided fabric made of polyolefine fiber come manufacture of intraocular Valve.Make its molding to form valve by the way that hollow braided fabric to be placed on mold, the mold includes tubular part and star Shape component.By the way that then using heat and pressure, hollow braided fabric is in the shape of mold and produces different piece.In mold Around tubular part, the part of support component of the hollow braided fabric formation corresponding to valve, and the offer pair of the star member of mold It should be in the part of multiple valve leaflets.Before removing valve in mold, front side and rear side to valve prosthesis carry out edge and repair It cuts.Destroy pruned edge in order to prevent, edge can be treated with heat such that yarn be fused to each other, be equipped with suture needle or Processing is so that edge is mechanically stable in other ways.

Heim et al. is in Materials and Manufacturing Processes, 26:1303-1309,2011 A kind of method is disclosed, wherein by woven polyester yarn by the way that textile thermoplastic is caused tricuspid valve geometry on mold To manufacture Synthetic leaflets；It is applicable to form valve prosthesis which show woven polyester.PE yarn have extension property so that The natural elastic extension (elongation is about 15%) of people's valve can be simulated by obtaining textile, this is because its typical extension at break Rate is about 14-17%.In order to during obtaining good accessible leaflet between leaflet in the closed position and limiting working cycles Stress, the shape of leaflet is moulded in author's introduction so that there are sizable intrinsic openings at valve center, and in heart arteries and veins Under dynamic load, sufficient engagement is created in the overall length of leaflet free edges edge, to prevent backflow or at least making to flow back reduces to most It is small.

Describe implantable valve prosthesis in US2008/0200977, it includes frames and at least one by synthesizing Leaflet made of biocompatible polymer.Leaflet is designed so that its movement helps prevent sludging in valve bag, Prevent thrombosis.Usually it is formed by the following method leaflet: the solution of cast polymer (preferably block type polyurethane), It can be moved to open position and closed position without restriction when then providing two slits to be limited to fluid flow response Free portion.

Heart valve prosthesis is disclosed in US2003/0114924, is to pass through it includes valve bodies and multiple leaflets What molded silicone or polyurethane were formed with single piece type.Valve is molded to free comprising the leaflet in neutral position (neutral) Gap between edge, and the leaflet along free edge with specific curvature；So that under fluid flowing load, gap Closing and the face bonding of leaflet simultaneously form engaging zones.

US2009/027039 describes implantable artificial valve, has at least one leaflet and for temporarily preventing Leaflet is substantially moved to the inhibition component of closed position from open position.Leaflet can by a variety of materials (such as biomaterial or Synthetic polymer) it is made, it is preferred that thin metal film.

The vein valve with tubular frame and covering is disclosed in US2005/0137681, the covering includes It limits the surface of reversible enclosed type opening and therefore serves as leaflet.Leaflet can have various sizes and shape, including arcuate edge Edge, curved surface, concave structure, or including bent support structure effectively to close valve and limit fluid flowing of driving in the wrong direction.It is small Leaf can be made by the material (including ePTFE, PET, carbamate and polyethylene) of impermeable fluid that is biology or synthesizing At.

WO2000/62714 discloses heart valve prosthesis, and it includes single piece type moulding bodies and multiple by silicone or poly- ammonia Leaflet made of ester.In neutral position or rest position, the free edge convergence of leaflet is non-uniform to be formed between them Gap.There is scalloped shaped edge (scallop) at the free edge of leaflet, to provide foot with the smallest be bonded at center Enough materials flow to seal reverse fluid.

US4191218 is disclosed for the fabric in artificial blood vessel and heart valve, the fabric be by comprising diameter about For multifilament (polyester) yarn weaving of 10 μm of long filament, and it is heat-shrinked the fabric to generate 20-40 μm of open space Space and at least one direction at least 10% elongation.Fabric preferably has woven selvedge (selvedge), Form the free edge of heart valve leaflets.

US2012/0172978 describes artificial valve, it includes the leaflet made of filtering screening material, the filtering Screening material has 15-60 μm of uniform small pores and 10-100 μm of thickness and is knitted by such as polyester or polypropylene monofilament Made of making.When pressing response to the flowing of closing, leaflet can be pushed together to engage in outflow edge, and then produce The engagement of 3-9mm is given birth to.The method for manufacturing this valve includes: to independently form each leaflet by screening material, along connecting line They are linked together, and is optionally coupled on suture ring or suture frame/stand.

The method of manufacture heart valve prosthesis is disclosed in US2005/177227, wherein to weaving film (preferably by polyester Or film of weaving made of PTFE) moulding is carried out to form leaflet；This is for example realized by the following method: being cut into segment And using there is formed parts duplication in the valvular geometry for closing artery position, heat fixation is then carried out.

Summary of the invention

The present invention relates to artificial valve (400), and it includes leaflet assembly, the leaflet assembly has at least one It is connected to the leaflet (3) of support component (2), the leaflet has oneself that can be moved between the first position and the second position By edge (5), wherein free edge is bent to allow body fluid to pass through valve stream far from closing surface (700) at first position It is dynamic；At the second position, free edge abuts closing surface to close valve, and wherein when not having pulsating load on valve, Leaflet can form the jointing altitude (coaptation height) for being greater than 0.1mm along the length of free edge.

The present invention is at least partially based on following cognition: the known artificial valve made of flexible sheet material, such as in natural valve In the case where, the substantially elongation (extension) of the sheet material dependent on manufacture leaflet, to provide sufficient engagement, the engagement is small Leaf is contacted along its free edge with closing surface with closing surface, and is properly opened during closing and opening circulation Valve.In general, elongation must be up to about 15% to provide sufficient engagement, at the center of leaflet (for asymmetric cylinder It is consistent with valve center for three leaflet configuration of shape) at it is especially true.This in turn means that sheet material must satisfy sternly The mechanical property requirements of lattice are can and persistently simulate native leaflet.Applicants have appreciated that: is especially causing immune and can cause In the natural surroundings of neoplasm and other exception procedures, it is difficult to a large amount of extensions of combination and durability.Based on this cognition, application People devises a kind of artificial valve, wherein, equally in neutral position, leaflet can be along it when not having pulsating load on valve Closing surface of the free edge in entire specific lowest splice height in adjacent valve.This jointing altitude and the prior art On the contrary, in the prior art, engagement usually only generates during practical pulsating load on valve and therefore depends on leaflet material The elongation of material and the dynamics of process, rather than generate the valve itself for meeting particular space limitation.To sum up, this anticipates Taste the material of manufacture leaflet must satisfy less strict extensibility requirement, therefore this artificial valve and its manufacturing method can It at least provides more sheet materials to use freely, and the option for manufacturing more durable artificial valve is provided.Other advantage includes: can Using textile structural made of the biocompatible fibres high-intensitive, low elongation, and therefore use thin flexible fabric (preferably Woven fabric) carrys out manufacture of intraocular valve.

It should be noted that the present invention is not excluded for: along free edge after the engagement of certain point, such as due to pulsing The dynamics of journey can be temporarily present passage aisle or other openings.Fold is formed in sheet material or other persistent errors do not interfere valve Film operates normally, as long as leaflet, which has, inherently to allow to close valve along free edge length in no pulsating load Geometry does not need leaflet stretching, extension.In other words, one or more leaflets have such geometry: having When pulsating load, certain minimum engaging zones be it is possible, limited by the free edge length and jointing altitude of leaflet This area adjacency closing surface, to prevent from largely flowing back in valve during actual use.This geometry also results in There is sufficient engagement and effective valve in pulsating load to close, even if free edge itself part is endless during use Full adjacent closing surface is also such.

The invention further relates to for the leaflet assembly in artificial valve, as further described herein.The present invention also relates to And the method for manufacture of intraocular valve, the method including manufacturing leaflet assembly.More particularly it relates to manufacture of intraocular valve The method of film, the artificial valve include that at least one is connected to the leaflet of support component, and the leaflet has can be first The free edge moved between position and the second position, wherein at first position, closing surface of the free edge far from valve Bending is to allow body fluid to flow by valve；At the second position, the adjacent closing surface of free edge is described to close valve Method includes:

Sheet material is provided, and

Leaflet assembly is formed by the sheet material, the leaflet assembly includes at least one leaflet and support component,

Wherein forming leaflet assembly includes: to carry out moulding to apply geometry, wherein not having on valve to leaflet When pulsating load, leaflet can form the jointing altitude for being greater than 0.1mm along the length of free edge.

For example leaflet is carried out it should be noted that " forming leaflet assembly by the sheet material " can comprise the following steps that It folding, cutting, moulding in a mold assembles plurality of sheets, it is connected by suture, gluing, etc...

Definition

Artificial valve is the construction at least one leaflet and support component, wherein leaflet be connected to support component with Leaflet is enabled to be bent or be twisted to provide open position and closed position for valve, and optionally including rigidity Or semi-rigid supports (also referred to as frame or bracket).

Leaflet assembly is the combination of at least one leaflet and the respective support elements in general tubular configuration, can To be made of the more sheets linking together or be made of a kind of individually textile structural (such as Woven fabric).Leaflet is can Dynamic component is simultaneously connected to support component (also referred to as grafting or skirt), they collectively define fillable fluid to close valve The bag of film.

Joint is usually two things along its connected line or point；In the anatomy of native heart valve, engagement Place is unique join domain between two adjacent valve leaflets and their support blood vessels wall.In this application, joint refers to Be between leaflet and support component (in the case where no stent valve) and leaflet and bracket and optionally support component Between side outflow (outflow) (for standoff valve) connecting line or region.In addition to formed joint connection it Outside, other connection, such as the shape for further limiting leaflet also may be present between leaflet, support component and/or bracket Shape.

The edge of leaflet is a kind of edge.

Engagement indicates that leaflet abuts with closing surface (such as another leaflet), contacts or converges, to close valve；It connects Close height or length that height refers to the engagement measured on valve is longitudinal from free edge (that is, towards leaflet bottom).

The center line of leaflet be from the free edge at valve center to leaflet bottom minimum point (i.e. by with support member Part connection is to limit the minimum point of leaflet) hypothesis line.In the case where the asymmetric valve with such as three leaflets, The center line of leaflet is from the contact points of three free edges or junction to the line of minimum point.

Bending height characterizes the bending of valve leaflet are as follows: center line and the free margins for connecting minimum point and valve center Maximum orthogonality distance between the straight line of edge.

The radius of curvature of leaflet is best suitable for the orthogonal cross-sections of the curved surface in the leaflet for closing position of valve Round radius.

Elastic material is the material that its original-shape can be restored to after deforming.

Applying (impose) geometry on object indicates: the geometry of the object is built by object generation Vertical, since the geometry that the external force being applied to thereon can generate is completely contradicted after being generated with object.

The inflow side of valve or bottom indicate: when valve is in an open position, fluid enters that side of valve, on the contrary Side is referred to as outflow side or the top side of valve.

A certain things and another things run parallel or extend in parallel expression: both things are mainly in the same direction Stretching, extension.

The elongation at break of sample is: under the load of application, the elongation of the sample recorded in specimen breaks Rate is represented as the percentage of sample original length.For sheet material, elongation at break is also generally referred to as ultimate elongation rate Or the elongation that fractures.

Yarn is the slender bodies that length is much larger than its cross-sectional width, is generally comprised a variety of continuous and/or discontinuous Filament, the filament is preferably essentially parallel to each other arrangement.

It is recently or adjacent on neighbouring expression position.

Selvedge is the edge of weaving structure, wherein not stretching out knot in spinning of running up of the side perpendicular to structure edge It is configured to free terminal, but by returning in structure to continuous in edge.Selvedge usually during tatting technique by (also referred to as weft) formation that spins is filled, but also can use other technologies or be made of warp.

Detailed description of the invention

Fig. 1, which is schematically illustrated, utilizes each step for forming valve prosthesis according to the method for the present invention.

Fig. 2 schematically illustrates the various views for being suitable for manufacturing the textile structural of valve prosthesis according to the present invention.

Fig. 3 schematically illustrates the geometry applied according to the present invention compared with prior art.

Fig. 4 schematically illustrates each step in the variant in conjunction with Fig. 3 the method.

Fig. 5 schematically illustrates how selvedge is weaved on the edge perpendicular to warp direction.

Fig. 6 schematically illustrates each step in another embodiment according to the method for the present invention.

Specific embodiment

In the first embodiment, at least one leaflet of artificial valve is formed to have the geometry knot so applied Structure: when not having pulsating load, jointing altitude is that the engagement of 1-15mm is possible.It has been found that this height produces suitably Engaging zones, flow back after reverse fluid flow can be effectively prevent, at the same allow quickly, fully open fluid channel. Preferably, the geometry of leaflet be manufactured so that jointing altitude be at least 2mm, 3mm, 4mm or 5mm and at most 15mm, 13mm, 11mm, 10mm, 9mm, 8mm or 7mm, such as between 3-10mm, between preferably 5-7mm.

It in another embodiment, include that convex surface (enters relative in valve bottom to the geometry that leaflet applies Fluid), the radius of curvature at centrilobular line between 1-20mm, such as 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18 mm, 19mm or 20mm, it is excellent Selection of land about 12mm.It has been recognised by the inventors that having this specific minor radius (with known artificial valve 50mm or bigger typical radius Completely contradict) the convex surface geometry applied lead to stress in leaflet material and deformation is smaller and the tension of joint It may be smaller.This geometry is also resulted in the relatively large volume of bag as defined by leaflet and support component, is being closed The bag will be filled with a fluid during closing.This can be conducive to effectively empty again after opening, prevent such as blood from staying in bag And reduce thrombosis risk.

In another embodiment, the geometry of the leaflet applied includes bending convex surface, wherein in centrilobular The bending height of this curved surface is the most preferably about 5mm greater than 1mm, preferably more than 2mm, 3mm or 4mm at line.Most Big value inherently depends on the external dimensions of valve itself, but typically about 10-15mm, for example, 10mm, 11mm, 12mm, 13mm, 14mm or 15mm.It has been recognised by the inventors that (being cut with the exemplary height of prior art valve 0-1mm with this specific shape The convex surface geometry applied so on the contrary) causes the stress in leaflet material smaller and the tension of joint may be smaller. It should be noted that the curvature of leaflet surfaces may depend on the diameter of valve, i.e., larger-diameter valve can have corresponding larger Curvature.

In another embodiment, leaflet is formed so that the free edge of leaflet has relative to closing valve institute Need theoretical length (for example, at least two leaflets general cylindrical valve in the case where, relative to via valve The distance between the both ends of free edge of joint at center) additional length.It is long along leaflet free edges edge in order to generate The preferred jointing altitude of at least 1mm or at least 3mm of degree, it is found by the applicant that (such as with the conventional design of pericardium material The design of Carpentier-Edwards PERIMOUNT or fabric pattern design Frederic Heim as described above are opposite) Additional free edge length is generated to be advantageous.This extra length can be generated in different ways.For example, being in radius R and the general cylindrical for having the leaflet for being connected to support component and being evenly distributed between joint there are three identical size In the case where valve, required theoretical free edge length is 2R.By making leaflet that there is size at least identical as support component Leaflet, free edge length will be at least 2 π R/3；To produce at least about 1.05 excessive (oversize) factor. By the way that leaflet and optional support component are designed as can get more greatly more than the actual size of valve during use or its bracket Add excessive.This can for example realize that the artificial valve includes to pass through compressed stent by reducing the diameter of artificial valve Leaflet assembly and bracket with matching diameter.Inventor notices that US2005/177227 is described with 3 leaflets Cylindrical valve, and indicate that leaflet free edges edge length is equivalent to 2 times of radius R length, therefore than pair of 2 peripheries π R/3 Answer part small, to ensure that the closing of valve during diastole.In general, inventor has found that manufacturing following valves is It is advantageous, wherein relative to close valve needed for theoretical length (for example, relative to via valve center bridge joint joint it Between distance needed for minimum length), leaflet free edges edge have at least 1.07, preferably at least 1.09,1.11,1.13 or 1.15, and the total excessive or extra length factor preferably no more than about 1.4, more preferably up to 1.3.In other words, free edge Preferably there is at least 7%, more preferably at least 10% or 15%, and at most 40% or 30% extra length.

In another embodiment, the extra length of leaflet, the side are generated by one or more method and steps Chosen from the followings group of method step: for example by forming trapezoidal print material (that is, wherein being formed corresponding to the part of leaflet trapezoidal Wider lower half portion and correspond to support component part formed sheet material smaller upper semisection form), or formed taper or Conical tubular material, to make sheet material be preformed into specific shape；Such as by using retaining ring or the valve of compression belt supporting frame Reduce the outer perimeter of valve, and change leaflet surfaces, then leaflet is finally fixed in valve.

In another embodiment, manufacture such valve: wherein leaflet is connected to support component along joint, The joint is parallel to body fluid flow (that is, the longitudinal axis with valve is parallel) since free edge and at least extends certain length.With This mode, the stress on joint concentrated on unlike in conventional design upper edge a bit, but throughout the length Distribution, this can increase durability.If valve includes rigid support object or bracket, bracket preferably has to be assembled with leaflet The connected column of body is as a part of joint is formed, to generate stable and durable joint.Joint may extend over The height of leaflet assembly or bracket extends, but preferably has the length apart from outflow side 1-9mm or 1-6 mm.Obviously engagement The length at place can be proportional to size (height) of valve.

In another embodiment, wherein sheet material is elastic material, and the elongation at break of sheet material is 10% or smaller. An advantage of the present invention is low extension sheet material (that is, extendability substantially lowers and has much lower elongation at break Material) can also be used for being formed the leaflet of valve prosthesis, the introduction of this and the prior art deviates from completely, prior art religion It leads using the material (extension property of simulation native leaflet material) for allowing about 15% or more elastic extension.During use compared with Few extend is considered providing more durable leaflet and valve after the implantation, be in terms of mechanical visual angle not only in this way, but also due to Object extension can cause collagen to spread on the object.Therefore, the low extended characteristics of leaflet of the present invention can reduce potential collagen Connection tissue overgrowth power or minimize it, otherwise this will lead to leaflet thicken with mobility loss and can It can cause Focal thrombus or other neoplasms.In general, tissue overgrowth or fibrosis can lead to leaflet compression, this It will lead to valve insufficiency.Preferably, in surface made according to the present invention, the elongation of sheet material during use is small In 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or even 1%.Similarly, higher than during being used as leaflet Load under when occurring, the elongation at break of this sheet material is less than 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or even 1%.It is not intended to be limited to any theory, it has been recognised by the inventors that applying geometry under no load to leaflet can mention For certain minimum jointing altitude, this obviously allows using extensibility is low or sheet material with high mechanical stretching resistance；Have The sheet material of high tensile modulus (also referred to as Young's modulus).

Although such as chitling submucosa (CorMatrix^TM) it is the natural bullet that can be used for generating the leaflet in valve prosthesis Property sheet material (see, for example, Zaidi et al., doi:10.1016/j.jtcvs.2014.02.081), but in a kind of embodiment In, it is 10% or the textile structural of lower elastomeric yarn that sheet material, which is comprising one or more elongation at break,.It is such as some above Shown in cited patent publications, textile structural is readily applicable to manufacture leaflet.Textile material is easy industrially with big And controllable large-scale production.By using elongation at break less than 10%, preferably less than 9%, 8%, 7%, 6% or 5%, the yarn being preferably ranges between 1-5% can be easy to get low stretching advantage described above.It can use such as needle It knits, weave or woven technology manufactures textile structural or fabric.

In another embodiment, textile structural be it is one or more spin or yarn made of Woven fabric.Weaving The advantages of structure is compared to such as knitted structure or braiding structure are as follows: by the various weaving technologies of application, and by using various Yarn spins (or weft) as warp and filling, can easily include desired (non-stretching or low stretching) tensile property With shape or form.Do not find that weave patterns are particularly critical, those skilled in the art can combine selected spinning using some experiments Line carrys out selection mode to obtain desired property.It is typical to find that having common pattern, (such as plain weave, twill or volume basket line are knitted The combination of modeling formula or different mode) Woven fabric be capable of providing superperformance.

One or more textile structurals are used as forming the sheet material of leaflet and leaflet assembly.Suitable method includes: Each leaflet and support component are formed by individual sheet sheet material or textile structural, then each connects together；By one kind Textile structural forms multiple leaflets and forms multiple support components by individual textile structural, and then two parts connect together； With so that multiple leaflets and support component from a kind of textile structural is formed leaflet assembly.For example, there are three leaflet and branch for tool Therefore the leaflet assembly for supportting element can be made of 6,4,2 or 1 textiles (preferably Woven fabric).By a kind of Woven fabric The appropriate method for forming leaflet assembly includes: to generate multi-layer woven using duplex weave (double weaving) technology Fabric, such as open in side so-called double width fabric or flattening tubing, as described further below.

In another embodiment, the free edge of leaflet is made into selvedge.Weaving selvedge or simple selvedge are that weaving is spun Knit the self-training edge of structure.Selvedge avoids textile structural from scattering or wear, but with other types of stabilisation edge or through repairing Treating selvedge is along completely contradicting, and selvedge is practical weaving process as a result, rather than additional process steps (such as cutting, fusing, seam Close or for provides stabilisation edge other techniques) result.In woven textile structure, selvedge is usually (but not necessarily) Warp is parallel to extend and be to be spinned around filling of last root warp winding into fabric by exiting back wall to be formed.Such as Fruit continuously supplies filling as in tatting technique and spins, then inherently generates selvedge, but can also be in no tatting Selvedge is generated by filling in boundary (fringed) end that filling spins after each intertexture and cutting in operation.Another kind side Method is: spinning using the design introducing of so-called leno edges is additional, the leno edges design locks most at the edge of fabric The end that spins of outside.By weaving free edge at selvedge, this free edge is provided as intrinsic mechanically stable side Edge, without using additional process steps (such as fusing or suture).Additional process steps can make valve manufacturing process whole Complicate, and also can produce side effect, for example, after fusing loose yarn end the engineering properties of yarn change (for example, Rigidity improve, wearability reduce or strength reduction) or edge suture after the reduction of pliability of partial thickening and fabric.Although such as This, this additional side can be still appropriately used for marginal steady using the Woven fabric for carrying out manufacture of intraocular valve along finishing；Example Such as, in the case where manufacture continuous or endless woven fabrics by desired length is cut into form such as leaflet later just It is such.Manufacture, which stabilizes edge or the suitable example at trimmed edge, thermal cutting Woven fabric, such as utilizes laser or benefit With electronics heat-cutting machine, (also referred to as hot knife allows to cut and melt simultaneously thermoplastic fibre in controllable single step Fabric) thermal cutting Woven fabric.Alternatively, can will include that there is leno design in place of cutting fabric during Woven fabric Spin.

Particularly, it was found that textile structural is weaved and is advantageous at the multilayered structure comprising lamination, the layer is preferred Ground is interconnected by and desired locations crossing warp or filling spin, or mutual by sewing after weaving or suture It is connected.Applicants have appreciated that wherein generating weaving process (this of the woven textile structure comprising multiple laminations by application Kind of technique is commonly known as " duplex weave " technique and commonly used to manufacture decorative fabric), support component and leaflet can be It is formed in one weaving process with identical textile structural, i.e., as the different layers of this textile structural (or as difference Segment in layer).Meanwhile leaflet and support component can obtain common structure in the structure or subsequent leaflet assembly Type, the common configuration correspond to the common configuration that the leaflet having and support component are needed in final valve, and joint It (at least partly) can also be obtained as the direct result of weaving process.It, can be to open edge in this multi-layer woven The form of (usually with selvedge) manufactures the longitudinal direction side of each layer, or can be made respectively by connecting two layers at the edge of two layers The longitudinal direction side of layer becomes enclosed edge edge.In view of the size for the valve being used in bodily conduit (such as blood vessel or artery), it is used to The width for manufacturing the textile structural of leaflet assembly will be in centimetre scale.For the production of (industry) Woven fabric, this Kind size may seem relatively small, but be suitble to method for weaving, weave patterns and the machine of this purpose known in the art 's；The smallware that is commonly referred to as such as being commonly used for manufacture adhesive tape and ribbon weaves those of (system).It is knitted this In manufacturing apparatus, the movement of every kind of warp can be controlled separately usually to manufacture the various connections between multiple layers and each layer.About The other information of this method for weaving can obtain on the internet, such as the other information about duplex weave can pass through The text that http://www.cs.arizona.edu/patterns/weaving/webdocs/opr_rgdw.pdf can be obtained It is obtained in part.

In one embodiment, leaflet assembly is manufactured by a piece of flat Woven fabric by the following method: being folded flat Flat Woven fabric itself forms tubular configuration by connection end, and generates other connection between the two layers to limit leaflet And support component.

In another embodiment, single woven textile structure is manufactured by duplex weave technique, to generate Double woven fabric, such as so-called double width fabric, open sides tool is there are two selvedge and opposite closed side has and connects Continuous fold line.In this configuration, support component will be formed and the other side will form leaflet for one layer.The width of layer is by through line number Mesh and end size determine, and can make to have identical or different width two layers by changing the respective number of every layer of middle longitude Degree or size.In this weaving process, can by make from one layer to another layer warp and/or filling spin intersection to Other connection is generated between layers；This mode is for example at least partially defined by connecting line (it can be joint) Leaflet.Connect shape and size and respective support elements that the spatial arrangement of each line will limit leaflet and its free edge Shape and size.Leaflet, which can be manufactured such that, has the size bigger than respective support elements, to generate freely in final valve The extra length at edge, this is to increase to fill out in leaflet (layer for forming leaflet) by the support component (part) relative to leaflet Fill the number to spin.

It is long with uniqueness (warp being connected with warp beam (beam) can be utilized such as on conventional textile loom) in discontinuous technique The form of the fabric of degree manufactures Woven fabric (including double width fabric as described above), can also be by by warp continuous feeding Woven fabric (including double width as described above is manufactured in the form of the fabric of unique length in continuous weaving operation to warp beam Fabric).In the latter case, continuous (or cyclic annular) fabric is produced, desired length can be cut into.In both feelings It, can be by the way that fabric edges and warp (or cutting) end be connected together the piece of cloth obtained tubulose is made under condition Structure.Then double woven fabric leads to tubular structure, wherein support component will form external and leaflet in the inside of structure. In these embodiments, warp is parallel to free edge operation/extension, and the free edge is that the selvedge of fabric (is similar to The upper edge of support component).

In another embodiment, by generating seamless tubing (also referred to as flattening tubing, flat Weaving tubing or hollow elongated fabric) duplex weave technique generate woven textile structure；Because of the woven textile Structure is by continuously filling the generation that spins, and the continuous filling spins after each interweave in each side edge from formation A set of warp of first layer is to the another set of yarn crossovers for forming another layer.It should be noted that in this case, using Non-uniform warp sum come exclude weaving mistake, this be commonly referred in the art as " weaving of error correction tubulose " (error corrected tubular weaving)。

In a kind of alternative embodiment, knitted using cyclic annular warp beam (such as round or triangle warp beam) to manufacture tubulose Make fabric.In addition, other than single tube structure or single-pass configuration, more set warps and warp beam, particular design can also be used Cyclic annular warp beam (that is, there is the warp beam for the end that is connected, such as annulus), and/or between layer or tubular structure specific cross-mode It spins to manufacture multichannel or multilayer tubular Woven fabric.

Similarly, as described above, tubing can be manufactured in continuous weaving process or in discontinuous manufacturing operation. In one embodiment of the invention, method includes: continuous weaving, and then knits the ring-type of generation (more) tubulose Object is cut into desired length.One incision tip of pipe will form the free edge of leaflet, but due to it is longitudinally running in pipe/ The warp of extension will stretch out fabric edges after dicing, so using pre-shaping step so that incision tip stabilizes.For tubulose For the both ends of structure, various dressing methods can be used, preferably to the Woven fabric made of thermoplastic polymer fibers Using heat treatment.It is highly preferred that combining cutting and finishing by using hot knife or other method for hot cutting.Finishing cutting After edge, partly inversion tube, i.e. a part of pipe it will can be formed in the tube pipe；It is external by generating connection between the tubes Support component will be formed and internal through the one or more valve leaflets of formation.

In another embodiment, tubulose Woven fabric is manufactured by discontinuous weaving process one by one.This has Following advantages: can by not by warp be directly connected in warp beam but by it is additional spin and/or bending part connect Onto warp beam, such as using Pueblo-Navajo known in the art or warp selvedge system, selvedge is weaved in warp.

In one exemplary embodiment, the pipe of general cylindrical is manufactured, optionally makes its end stabilizing, then Partly inversion tube in pipe to generate pipe.In this case, the free edge of leaflet will have big with respective support elements The identical length of body；This method has about 5% extra length.In other embodiment, conical pipe is manufactured, preferably By using including gradually changing knitting for Woven fabric middle longitude number as described in US5800514 or US2014/0135906 Technique is made to carry out.The tubing of certain length is provided, the first diameter of one end is bigger than the second diameter of opposite end, It is preferred that big at least 2% or 5%, and its gradually transformation with first diameter to second diameter, optionally make end stabilizing. Then partly inversion tube so that inner tube is bigger than the internal diameter of outer tube；This means that the free edge of leaflet will have more than 5% Extra length.The multilayer tubular structures further described below with attached drawing can be processed in a similar manner to be formed and be used Leaflet assembly in the method for the present invention.

Preferably, using the textile structural for comprising one or more elongation at break being 10% or lower elastomeric yarn Sheet material as manufacture leaflet assembly.In other embodiment, the line density of elastomeric yarn is less than 120dtex, preferably The line density of ground elastomeric yarn is less than 100dtex, 80dtex, 60 dtex, 50dtex, 40dtex, 30dtex, 20dtex or very To 15dtex, the line density of preferably elastomeric yarn is at least 5dtex, 7dtex or 10dtex；Such as the line of elastomeric yarn is close Degree is between 5dtex and 30dtex or between 7dtex and 15dtex.It has been found that using by thin yarn Manufactured textile structural, which carrys out manufacture of intraocular valve, can have an important advantage (note that while dtex to be not representing practical ruler Very little or space length parameter, but actually it is equivalent to yarn diameter, because of most of synthetic material for manufacturing yarn Density with natural material is about 1kg/dm³).Particularly, it has been found that using this thin yarn in textile structural Lead to very flexible fabric, so that leaflet is enable to respond quickly under pulsating load.Flexible leaflets can also be easily It arranges consistently with support component, to generate big effective aperture；And also cause less load in joint.This Outside, it has been found that tending to the textile structural with relatively low aperture and low-permeability using this thin yarn, is knitting It makes especially true in the case where structure.It is reduced together with thrombosis risk mentioned above, this can help to the good life of valve Object compatibility, high-effect and durability.

Similarly, it is found by the applicant that following situations is advantageous optimum performance: single-layer woven structure (is preferably knitted Object) thickness be preferably at most 200 μm, 150 μm, 120 μm or 100 μm and at least 20 μm, 30 μm, 40 μm or 50 μm, such as 40-150 μm, preferably 50-100 μm of thickness.In the case of woven fabrics, this thickness degree generally correspond in warp and Line density is the plain weave of (UHMWPE) filament of 5-50dtex, compiles basket tissue or twill-weave in filling direction.

In another embodiment, textile structural includes high-performance polymer filament, and the filament preferably has at least The high-tensile or toughness of 1Gpa and the high tensile modulus of at least 30GPa.Example include carbon fiber, aramid fibre, Aromatic polyester fibres and ultrahigh molecular weight polyolefin fibers.Preferably, textile structural includes ultra-high molecular weight polyethylene (UHMWPE) fiber, more preferably textile structural include the UHMWPE filament that the toughness of at least 80 mass % is at least 2GPa, more It is preferred that mainthread and/or filling spin and are substantially made of UHMWPE filament.It has been found that this polyfilament yarn is preferably suited In the Woven fabric of leaflet and support component for manufacturing valve prosthesis.UHMWPE yarn is durable, can be made with Desired engineering properties and medical grade be it is available commercial, the medical grade is hardly immunogenic.In particular it is preferred to The UHMWPE yarn for the use of intrinsic viscosity (IV) being at least 5dl/g, preferably at least 10dl/g, more preferably at least 15dl/g. Preferably, IV is at most 40dl/g, more preferably up to 30dl/g, even more preferably at most 25dl/g or 20dl/g.IV It is to be measured in decahydronaphthalenes at 135 DEG C according to method PTC-179 (Hercules Inc.Rev.1982 April 29) , dissolution time is 16 hours, and usage amount is the DBPC of 2g/l solution as antioxidant, wherein will survey under various concentration The viscosity of amount is extrapolated to the viscosity under zero-dose.Particularly preferably gel is spun into UHMWPE yarn, and Young's modulus is usually 30GPa or 50GPa.Preferably, the toughness of UHMWPE yarn is at least 1.2GPa.Preferably, yarn used according to the invention Include at least UHMWPE yarn of 90 weight %；Most preferably, yarn used according to the invention is made of UHMWPE yarn, And there is at least Young's modulus of 50GPa.One preferred embodiment of UHMWPE yarn is can to obtain from the DSM of Holland DyneemaYarn.Such UHMWPE yarn is particularly preferred, is the available doctor of low dtex version 2-4% is typically about with the elongation at break of grade yarn, the yarn.Under room temperature (i.e. about 20 DEG C), the institute in ASTMD885M Fiber, the crosshead speed and " Fibre of 50%/minute on specified polyfilament yarn, using nominal gauge length for 500mm 2714 fixture of Grip D5618C " type Instron defines and measures the tensile strength (or intensity) and anti-tensile of UHMWPE yarn Modulus (or modulus).Load-deformation curve based on measurement, modulus are measured as the gradient between 0.3-1% strain. In order to calculate modulus and intensity, by the tension of measurement divided by fiber number (measuring fiber number by weighing 10 meters of yarns)；Assuming that close Degree is 0.97g/cm³To calculate the value in terms of GPa.Ultra-high molecular weight polyethylene can be linear or branch, but preferably make With linear polyethylene, very high toughness and modulus can get because passing through to stretch during manufacture yarn.Linear polyethylene is at this Be understood to mean in text: every 100 carbon atoms having less than 1 side chain, preferably every 300 carbon atoms are having less than 1 The polyethylene of side chain；Side chain or branch usually contain at least ten carbon atom.Through FTlR on the compression forming film of 2mm thickness The number of side chain in UHMWPE sample is measured, wherein the calibration curve based on NMR measured value is used to quantify the suction at 1375cm It receives (such as in such as EP0269151).

In another embodiment, it usually in the case where sheet material is formed by semi-crystalline thermoplastic polymer, is formed Leaflet assembly can further include: the shape of leaflet is moulded by contacting leaflet with the mold of intended shape, optionally by mould Tool is heated to the fusing point than sheet material (that is, the fusing point of the polymer of sheet material is made；Melting point polymer measurement refers to ISO11357- 3) temperature of 3-60 DEG C low (preferably 5-40 DEG C) optionally makes sheet material creep forming (that is, changing its size), and makes its warp By controlled relaxation and/or plastic stretching at least partly consistent with mold.Such as this is described in WO2010/020660 Kind thermoforming process.Using this embodiment, the geometry of leaflet can be further finely tuned, such as to generate a certain curvature Or to meet certain clinical requirements.

In another embodiment, equally usually in the case where sheet material is substantially formed by semi-crystalline polymer, institute It is further comprising the steps of to state method: by applying coating or optionally arrangement sheet material (preferably textile structure) is dropped in a mold The permeability of low sheet material, is heated to the temperature of 15 DEG C of 3- lower than the fusing point of polymer, and is maintained at 3- lower than the fusing point of polymer It is connected with assigning the part in textile between adjacent filaments and/or yarn within -2 hours for 10 seconds at a temperature of 15 DEG C.Depend on In the cross section of yarn and its arrangement (such as type of weave) in textile structural, the permeability for reducing textile structural can be with It is advantageous.In this embodiment, the thermomechanical property for manufacturing the polymer of yarn can be used to improve the infiltration of textile structural Permeability.

In another embodiment, artificial valve further includes bracket (also referred to as rigid bearing structure or frame) and institute State method further include: at least one leaflet and support component is made to be connected to bracket.It can be by using one or more fastening means It is attached, is preferably attached by application suture.Suitable suture has such strength character, so that being used as Lasting connection can be obtained during artificial valve under a load.Preferably, suture be by using in leaflet and support component The similar suture material and yarn of yarn strength made of, more preferably by the yarn for using suitable dimension or line density Made of line or sutures, the yarn or sutures include at least 80 mass % with the yarn in leaflet and support component The identical yarn of type is substantially made of the yarn of this type.

About the use of rigid bearing structure or bracket, this bracket generally comprises rigid member, and often for annular or It is cylindrical.Be suitble to manufacture bracket material include rigid polymer, fiber-reinforced polymer, metal and metal alloy, ceramics and A combination thereof.Suitable rigid polymer includes polyacetals, dextroplast, polyurethane, polyethylene, polysulfones, polyether sulfone, poly- virtue Base sulfone, polyether-ether-ketone and polyetherimide.Suitable metal includes biocompatibility metal, such as stainless steel, titanium, cobalt alloy Such as(cobalt-chromium-nickel alloy) and MP35N (nickel-cobalt-chromium-molybdenum alloy), and(Ni-Ti is closed Gold).Furthermore, it is possible to produce bracket, the ceramic material such as pyrolytic carbon, silicon carbide or metal-carbide, hydroxyl phosphorus by ceramic material Lime stone and aluminium oxide.Suitable bracket can also be produced by carbon such as graphite.Preferably, bracket is at least partly closed by super-elasticity Gold or marmem are made, such as(Ni-Ti alloy) both can be used as elastic material, also can be used as shape Shape memory alloys.This bracket allows that valve prosthesis is easily inserted into intracorporal desired locations.Before insertion, making can be from swollen Swollen bracket reaches first (relatively low) temperature, it is with tight configuration at such a temperature.This tight configuration allow using It easily will be in bracket (and coupled valve) insertion body when Minimally Invasive Surgery.After placing bracket, due to body temperature, shape note Recalling alloy will heat up and change phase, to change its shape.Such asIt will be in austenite phase and martensitic phase Between undergo phase transition.Therefore, bracket will expand and thereby generate the clamping force to surrounding tissue.In another configuration,It is elastic material and can be resiliently deformable until material strain is about 10%, therefore valve is towards close shape Shape deformation be it is possible, still allow for after placement elasticity be expanded to final shape.

The artificial valve manufactured by means of the present invention can be without bracket or may include being connected with leaflet assembly Bracket.No stent valve or leaflet assembly also serve as the grafting of valve or have the valve of grafting；This means that it is propped up Support element layer may be coupled to vascular wall or arterial wall and play grafting, and fragile vascular is substituted or reinforced with (part) Or aneurysm vascular.In this embodiment, the outside (support component layer) of leaflet assembly can be further processed to reduce Permeability, such as handled by providing coating or another layer material.It is some other to have standoff artificial valve offer Advantage can be used for example conduit system and is implanted by minimal invasive techniques.In one embodiment, method is therefore further include: will Leaflet assembly is connected to bracket.

In another embodiment, artificial valve includes two leaflets defined above, and wherein accessory flocculus serves as The closing surface of first leaflet, vice versa.Artificial valve also may include three leaflets, in this case, each leaflet Serve as the closing surface of other two leaflet.

Artificial valve described herein can be used for replacing mammal valve (such as people's vein valve or heart valve), depend on The type of the bracket optionally employed in artificial valve by operative treatment, passes through traditional operation or passes through minimally invasive and percutaneous skill Art carries out.

Other than above embodiment, artificial valve will be explained further using some schematic diagrames now and manufacture this The method of kind valve, the schematic diagram is not necessarily to scale, and may for the sake of clarity not show all features or group Part.Similar reference number refers to similar features in different figures.

Fig. 1 includes subgraph 1A-1I, schematically illustrates a kind of each of the embodiment for the method to form artificial valve A step.Loom 100 is depicted in Figure 1A, which has 4 101,102,103 and of warp beam (or changing winding weft bar) 104.Warp thread 10 is connected between two warp beams 101 and 103 at top and between two warp beams 102 and 104 of bottom.With A kind of loom device can be used in this mode, and tool is formed in a kind of weaving process, and there are two the textile structurals of lamination. For clarity, the common other parts of loom, such as heald frame (or harness cord tool) are not shown, wherein heald and one The warp thread of preassigned pattern is separated to be formed and (can be taken across filling yarn (also referred to as weft) in (or in all two layers) layer With filling yarn shuttle or throw a spear) clear space (or Warp opening)；Push fell to for yarn will to be filled with optional Stub (bat) (or reed).Warp thread may be connected in warp beam (commonly used in discontinuous technique), or using 101 He of warp beam 102 is without interruption as guide member, and in this case, and 103 and 104 represent for receiving manufactured two-layer fabric Single fabric axis.Shown in Figure 1A filling yarn 11 be in the upper layer of textile structural 13 by make fill yarn with above Warp thread interweave (such as formed plain weave) and woven, and back transmitted on the edge of layer 35 towards fold line 12, It herein, is woven in lower layer 2 until its edge 4 for reaching the lower layer and back being transmitted towards fold line 12.It please infuse Meaning, for the sake of clarity, so that fold line is in figure than seeming bigger in practice.In this way, the formation of edge 5 and 4 Selvedge.Weaving process continues until textile structural has desired size.The result is that two-layer weave textile structural, it includes tools First unique (distinct) layer 2 for having selvedge 4 and the second distinct layer 3 with selvedge 5.By making to fill yarn from one layer It is transmitted to another layer, layer 2 is connected along fold line 12 with layer 3.These layers 2 and 3 will be respectively formed the support component of final valve And leaflet, and fold line 12 can form a part connected between support component and leaflet.A kind of alternative embodiment is also wrapped It includes: by intersecting the yarn between each layer rather than at fold line come interlaced plies 2 and 3, to generate other connection and in layer Middle formation such as more multi-segmental (sections).

On loom 100 after woven textile structure 1, as shown in fig. 1b, textile structural 1 is discharged from loom.It is existing It is clear that textile structural is woven to double-layered structure (or double width) cloth, with distinct layer 2 and 3, each layer is respectively provided with Selvedge 4 and 5.Warp thread 10 extends on exceeding a small amount of length of actual woven structure in non-selvedge edge.At this stage or slightly Afterwards, these edges are stabilized.

In next step, as is shown in fig. 1C, suture 22 (being located next to fold line 12) is added further with 3 He of articulamentum 2.By adding two sutures 22 into this structure, layer 3 is divided into three individual segments, they correspond to single in valve Only leaflet.

In next step, as shown in figures 1D and 1E, two non-selvedge edges are put together (that is, the proximal end of structure and Distal end is configured in top of each other) so that textile structural forms tubular structure.It can be seen that layer 3 in Fig. 1 D and 1E Leaflet be located inside configuration, and the support component of layer 2 is located at structural outer.At ring seal object 9, the two of textile structural The warp thread 10 at a edge converges.Then, processing ring seal object 9 with ensure using when the closure can keep out and be applied to people Mechanical force on work valve.Firstly, then as shown in fig. 1E cleavable loose warp thread end is rolled over towards the surface of layer 2 Folded closure 9, reinforces closure 9 using suture 30 later.Alternatively, rolling longitudinal folded ends first, then folded towards layer 2.With This mode, any loose warp thread end no longer freely expose, but the disadvantage is that: the closure 9 rolled is than the non-envelope rolled It is slightly thicker to close object.Other alternative is: stabilizing edge, is then stitched to layer 2.

In a further step, as shown in figure iF, add additional suture 31, such as along U-shaped line, the suture into Corresponding segment in the segment and layer 2 of one step articulamentum 3, preferably to limit leaflet or manufacture 3D sample shape.It is shown in Fig. 1 F One section of tubular structure, the tubular structure illustrate a kind of combination of support component and leaflet.It can be seen that the freedom of leaflet Edge is formed by selvedge 5.Since free edge, the connection of generation includes suture 22 and suture 31.Suture 22 and 31 can also Be it is continuous, i.e., suture 22 with deflection and can not can continuously form throughout the entire height of valve and be denoted as 31 The U-shaped curve of suture.In this way, bag is collectively formed in leaflet and support component.By the position for occupying neighbouring support component It sets, the openable final valve of leaflet；By occupying the position extended far from support component, leaflet can close final valve.

Mold 37 can be used in order to mould the shape of leaflet and bag even betterly referring now to Fig. 1 G.Suture connects Before wiring 31, the shape of the convertible leaflet of mold 37 is carried out optionally by leaflet is pulled up at edge 5.With this Mode produces extra length between the center and minimum point of valve along leaflet.Generate the another kind of this extra length Method is: the layer 3 bigger than in layer 2 (in segment) has been weaved than warp thread more in layer 2 by using in layer 3.Figure The step of 1F and 1G illustrated, can also carry out during or after being connected to bracket.

Referring now to Fig. 1 H and 1I, make the textile structural generated or leaflet assembly be connected to round wire bracket 40 with Manufacture valve 400.Leaflet assembly is placed in bracket and is sewn on bracket using suture 33 in its bottom, and benefit With suture 32 in top stitch to connect support component 2.This suture 32 is preferably continued to leaflet and support component and three Trestle 41 (see Fig. 1 I) connects together, and this connection also forms final joint.The freedom of three leaflets is further depicted in Fig. 1 H Edge 5.In this form, the engagement that valve 400 is in the leaflet of neutral position is closed.If the neighbouring branch of free edge 5 It supports element 2 (that is, wall of near bracket 40), then valve 400 will be opened.The one of stent configuration and its column 41 is depicted in Fig. 1 I A little more details.After circumference connects fabric, tie point of the knot 36 as the suture is generated in suture 32.In one kind It substitutes in sexual approach, suture 33 can be generated at this stage；Then interim connection 35 can be used to keep structure being sewn onto It is in appropriate position during column 41, can remove it later.Fig. 1 I shows a kind of alternative embodiment, wherein leaflet Assembly stretches out frame bottom, and this part can be folded in a further step except bracket and be connected thereto.Its is excellent Point more successfully adapts to vascular or artery after may is that implantation.

In a kind of alternative embodiment, not in forming process early application suture 22 (as is shown in fig. 1C), but It is tightly wound around bracket 40 (at this stage, bracket is covered by protectiveness plastic sheet) or another formed parts (such as stub) Duplex weave textile structural itself (as shown in fig. 1b), and by closure 9 it is four-layer seamed together.Later, it carefully removes Bracket, and tubular structure is placed in bracket.Then, the suture (suture) corresponding to suture 31,32 and 33 is provided with shape At leaflet cusp and textile structural is fixed on bracket.

Fig. 2 is made of subgraph 2A, 2B and 2C, is schematically illustrated for manufacturing artificial valve according to the present invention The various views of textile structural.In the embodiment of Fig. 2A, give and textile structural as shown in Figure 1A in s direction The parallel cross section of 1 filling yarn.It can be seen that filling yarn 11 interweaves in layer 2 and 3 with warp thread 10, so as to form Plain weave.By using duplex weave method described in Fig. 1, layer 2 and 3 is respectively provided with longitudinal (that is, being parallel to warp thread) Selvedge 4 and 5.Filling yarn at fold line 12 is transmitted from layer 2 to layer 3, and vice versa, so as to form leaflet and support member A part finally connected between part.In fig. 2b, this weaving knot as shown in Figure 2 A on the direction V is given The side view of structure.In this view, selvedge 4 and 5 is only schematically depicted.

In a kind of alternative embodiment, as depicted in fig. 2c and represent with Fig. 2 B in similar visual angle, make to fill Yarn and warp thread interweave so that forming cross spider 220 in textile structural.Textile structural 1 includes totally 6 in two layers now A segment, i.e., the segment 2 ', 2 " and 2 ' in top layer " and bottom in segment 3 ', 3 " and 3 ' ".In left cross spider 220, four Segment 2 ', 2 ", 3 ' and 3 " meets a line, which will correspond to the joint (a part) of final valve.For this purpose, warp thread It is transmitted from segment 2 ' to segment 3 " and warp thread is transmitted from segment 3 ' to segment 2 ", this is by heald and warp thread during weaving Move Mode control.By this method, common (mutual) configuration is not only obtained, wherein each segment corresponds to Support component or leaflet, and the direct result as weaving process form leaflet-support component connection, and have and knit The similar intensity of object itself.This also means: it is final to be formed to need to add less suture (or even without addition suture) Joint, including it is connected to bracket.Corresponding weaving process occurs in right hand cross spider 220.By connecting as retouched in Fig. 2 C The end of structure drawn and obtained, obtains three leaflet structures of tubulose.

Fig. 3 is made of subgraph 3A, 3B and 3C, schematically illustrates the geometry and root applied according to the present invention According to the geometry of the prior art.In each schematic diagram, depict across the valve having there are two opposed leaflet 3 and 3 ' The cross section of the center line of film, the valve is when not loading in closing but neutral position, and the leaflet is in discribed cross It is connected in respective minimum point 120 and 120 ' with its respective support component 2 and 2 ' in section.Note that for tool there are three The valve of leaflet, the plane across the center line of a leaflet can be in 60 degree of angle with the central plane of opposed leaflet.

Fig. 3 A, which is shown, for example (to see above the bibliography Materials and mentioned according to the method for Heim Manufacturing Processes) manufacture when, when there is no pulsating load, the geometry that is applied to two leaflets.? Valve center, when not loading, there are wide arc gap G in neutral position.Under pulsating load, which will close and passes through extension Leaflet material (about 15%, partially due to the extension of PE yarn, partially due in textile yarn rearrangement) and further beat It opens, to imitate the dynamics of natural valve.When not having pulsating load, the radius of curvature of leaflet is about 50mm.

Fig. 3 B shows the cross section of the leaflet assembly in artificial valve according to the present invention.It is loaded in no artery When in neutral position, opposed leaflet 3 and 3 ' has the geometry applied, this makes them along free edge length It is adjacent to each other therefore also adjacent to each other at valve center, so that the jointing altitude being formed on the cross section is the engagement of H 700.In this embodiment, jointing altitude H is 6mm and across the free edge length of each leaflet at least at center 0.1mm extends (its bottom is indicated with reference number 300), can also even larger court wherein depend on the length of joint To joint.The geometry of each leaflet further includes at the top of closing surface H and respectively between the connection of support component The convex surface of extension wherein shows minimum point 120 and 120 ' in the cross section of the valve in Fig. 3 B.Each convex surface is far from respectively The protrusion of support component 2 and 2 '.

It is shown in Fig. 3 C: by small fluid pressure (it is generated as 600 filling baggy fabric of water shown in), It can more easily check applied geometry and the jointing altitude (shape including the closing " band " with free edge length At) and estimate its size.It should be noted that since the extra length of free edge is (than crossing over the distance between support component And connect the actually required more weaving length in jail), at some when by filling valve with water to make its closing, close Fold or small opening (channel) may be present in surface.But it is this opening be not it is lasting, arteries and veins will be passed through in actual use It is dynamic to be closed.The curvature of leaflet can also be characterized by bending height h, bending height h is defined as connecting minimum point and valve Maximum orthogonality distance between the straight line and center line of the free edge of center membrane.

Fig. 4 is made of subgraph 4A and 4B, schematically illustrates the continuous structure generated according to another embodiment, The embodiment is consistent with the method in conjunction with described in Fig. 2 C.In this embodiment, two kinds of (every layer of yarn of fillings are utilized It is a kind of) woven textile structure 1, so that top layer 2 and bottom 3 have selvedge in two sides (4,4 ', 5 and 5 ').In width direction On, layer 2 is bigger than layer 3, this is realized by using more warp thread；It note that for this two layers, only describe in edge Warp thread 10.In the leaflet assembly of generation, support component will be therefore longer and be extended far from leaflet；And therefore it can be used for Such as around support-folding.Selvedge 5 or 5 ' it may be formed at the free edge of leaflet in produced valve.In a kind of alternative reality It applies in mode, the support component layer of extension can be used for leaflet assembly being connected to blood vessel wall or arterial wall, to play grafting Effect is substituted or is reinforced fragile vascular or aneurysm vascular with (part).This leaflet assembly (also without bracket) can Therefore play valve and grafting, and be referred to alternatively as the grafting of valve or have the valve of grafting.In this embodiment In, the outside (support component layer) of leaflet assembly can be further processed to reduce permeability, such as by provide coating or Person another layer material is handled.

Increase the size of leaflet (free edge) using additional filling yarn extension bottom.When reaching leaflet It is expected that retracting layer 3 using holding rod 105 so that the filling line of top layer and the filling line of bottom are consistent, as schemed when extra length Shown in 4A.Then intersect the warp thread of bottom warp yam and top layer corresponding part to form cross spider 220；This is additionally shown in Fig. 4 B In.These cross spiders provide joint, and the joint at least in the length formed by cross spider 220, is opened from free edge Begin, the longitudinal axis being parallel in the final valve formed by structure 1 extends (corresponding to the method summarized in Fig. 1).Weaving Afterwards, product can be cut into desired length, then connected to form tubular structure, and be optionally coupled to bracket.

Alternatively, leaflet can be made into bigger than support component.In other alternative, by make fill yarn with Another set of warp thread intersects to form fold line an edge.

Fig. 5 schematically illustrates how to weave selvedge, or even weaves selvedge at the edge perpendicular to warp direction WA.? In this case, what is be connected with warp beam 101 is to stop object (stay), and it includes multiple bending parts 62.Each self-forming of warp thread 10 One ring, and each of these rings are connected to warp beam using the bending part for stopping object, therefore the stop object is passing through Extend between axis 101 and the ring.Filling yarn 11 interweaves on filling direction WE with warp thread 10.In this particular implementation side In formula, the ring is fixed on bending part 62 using rope 60.For this purpose, rope 60 pass through warp thread each ring along Edge 13 extends, and is connected to warp beam using stop object illustrated above.In this case, rope 60 is one section of warp thread And it is continued to as filling yarn 11, therefore adjacent with edge 13 without loose ends.

By using this method, the warp thread at edge 13 forms ring, therefore is continuous, the edge in the edge Therefore selvedge is formed.In this case, selvedge extends on the filling direction WE perpendicular to warp direction WA.Therefore, it is produced Raw flat fabric at least has selvedge in three of them edge.This method that selvedge is formed in warp can also be suitably It is used to form non-flat structure but such as tubular textile structure, wherein the edge or edge correspond to the leaflet of final valve Free edge.The example of this tubular textile structure is schematically depicted in attached drawing below.

In another embodiment, bending part is connected directly warp beam with warp thread ring.Yarn is filled in order to prevent Free end, preferably to surround one of warp thread (if fabric is flat fabric, the yarn close to fabric side is advantageous) Mode wind filling yarn, then use filling yarn both ends as individually fill yarn weaved.

Inventors have found that being made when preparation has the Woven fabric for the selvedge for being parallel to filling yarn using UHMWPE yarn It is particularly advantageous for filling yarn, because this yarn tends to laterally adjust, when removing stop object or bending part The ring of stuffer warp.It can theoretically be inferred to and (be not intended to be limited to this): about the yarn with very high strength and modulus For it is this it has unexpectedly been discovered that the flexible combination of bending with the low-friction coefficient and UHMWPE yarn of UHMWPE It is related.

Fig. 6 is made of subgraph 6A-6F, each step in another embodiment is schematically illustrated, in this side In method, the leaflet assembly for valve is manufactured using tubulose (ring-type) woven textile structure.

Fig. 6 A (warp direction is represented as " WA ", and filling direction is represented as " WE ") shows woven tubular textile Structure 1, as tubular inner layer 2 (support component corresponding to final valve described in Fig. 6 E) and tool there are three segment Outer layer 3 (it will correspond to the leaflet for having extra length in free edge) composition.Outer layer and internal layer connect along three lines 220 It connects.In this embodiment, tubular inner layer 2 is with selvedge 4 and layer 3 has selvedge 5, this is the method as described in such as Fig. 5 The textile structural generated using the warp beam of particular design.Alternatively, this structure is manufactured in continuous weaving process, then by it It is cut into desired length and generates stabilized edge.Leaflet segment in layer 3 (corresponds to institute in Fig. 2 C by cross spider 220 The cross spider 220 of description, but fill yarn crossovers in this case, and warp thread intersects in fig. 2 c) with the support in layer 2 Element is connected.

Fig. 6 B gives the top view (or cross-sectional view strength) (on warp direction) of the textile structural of Fig. 6 A.Fig. 6 C gives Identical view is gone out, but has wherein been configured such that layer 2 forms ring-type now by the textile structural of its original flat form Pipe.The leaflet segment of layer 3 extends throughout the surface of this pipe and converges in cross spider 220.It, will in next processing step The textile structural of Fig. 6 C is turned inside out, this causes such as structure discribed in Fig. 6 D.At this stage, textile structural is carried out Processing is so that support component 2 is in outside, and leaflet 3 is in inside, to form the leaflet shown in Fig. 6 E with isometric view Assembly or valve 400 (in valve configuration is closed).

One kind that the textile structural of the method using method similarly as described above is schematically depicted in Fig. 6 F is alternative Embodiment, in this embodiment, layer 2 (being different from structure shown in Fig. 6 A) extend longer distance than layer 3.At this In kind of embodiment, the edge 5 of the leaflet segment in layer 3 forms selvedge (for example, using cyclic annular warp beam and using being retouched in Fig. 5 The method drawn), and the edge of layer 2 is woven to regular edge, and wherein warp thread is discontinuous (such as discontinuous at the edge , because they are cut to discharge structure from loom).For simplicity, it is similar to Fig. 6 A, depicts only warp thread 10 Some ends.With method identical with the structure of Fig. 6 A (that is, passing through reversion), this textile structural can be made to form valve.Institute The advantages of generating leaflet assembly are as follows: support component is longer, extends far from practical leaflet, therefore can be used for for example being connected to Leaflet assembly is connected to artery as the grafting for having valve by the outside of the bracket used when manufacture of intraocular valve.Class As, layer 2 can extend in the opposite end of structure or layer 3 can be made into bigger.

It will be by following exemplary experiment come the present invention is further explained.

Embodiment 1

This embodiment describes artificial valve according to the present invention and experiment is manufactured, in the experiment, this valve exists Testing in vitro is simultaneously used as lung valve prosthesis by being implanted into sheep.In this embodiment, it is manufactured using process described below Each valve, the method are substantially consistent with the method in conjunction with described in Fig. 1 and Fig. 3 B.

By DyneemaTG 10dtex UHMWPE polyfilament yarn (can obtain from the DSM of Holland) is passed through with 458 Yarn/inch and 223 filling yarn/inch density manufacture Woven fabric shown in Figure 1B.The double-layer structure of folding has The thickness degree of the length of 90mm, the width of 21.5mm and 0.00314 inch (80 μm), and it is woven to have the 2 of longitudinal selvedge × 2 twill-weaves.Used cylindrical stent has to be designed shown in Fig. 1 I, and is made by electromagnetism polishing stainless steel 304 At.Its overall diameter is 25mm, and interior diameter is 23mm and height is 17mm.For suture, two kinds of sutures are used: with taper The Maxbraid PE 3-0 blue suture (suture blue) of needle (can be from BIOMET MERCK LTD with MPC 900252 Obtain), it is hereinafter referred to as suture A；It (can be from same with the Maxbraid PE 4-0 blue suture with taper needle Supplier is with the acquisition of MPC 900244), it is hereinafter referred to as suture B.Both sutures include UHMWPE yarn.

Manufacture lung valve as described below.In order to generate the jointing altitude of 6mm in leaflet free edges edge length, generate big Measure free edge length.Keep free edge length excessive by following steps:

1. leaflet free edges edge length in woven textile structural will inherently be equal to support element length, two Layer has equal length.The distance between formed among edge and valve of the support component of cylindrical body be valve radius R, 3 It is 6R that a leaflet, which bridges this apart from required total length, and the length of support component is 2 π R.This creates 2 π R/6R for leaflet =1.05 intrinsic extra length factor.

2. double woven fabric then will be perpendicular to round the winding of 25mm bracket (that is, being wound into outside bracket) first The end of leaflet free edges edge is stitched together.Then, cylindrical textile structural is placed on the internal stent of internal diameter 23mm simultaneously It is fixed on bracket using UHMWPE suture.This create the extra length factors of 25/23=1.09.

3. in this example, for the final heart valve prosthesis of implantation having a size of 23mm, therefore the bracket of outer diameter 25mm It is radially compressed to 23mm.In this way, the internal diameter for being fixed with the bracket of support component and leaflet is decreased to from 23mm 21mm.This create the extra length factors of 23/21=1.10.

The total extra length factor for the leaflet free edges edge created in this way is π x25/3x21=1.25.So wound The extra length made is about 25%.

As indicated above, Woven fabric is closely wound round bracket (being initially used as mold), then utilizes suture Line A begins through following methods for four layers at closure (corresponding to 9 in Fig. 1 D) from fabric/holder combination outflow side It is stitched together: generating knot 36, reserve about 2cm loose ends and long end, the long end is for generating towards fabric/valve The suture of film combination entrance side.Bracket/mold is carefully removed, then tubular textile structure is placed in bracket.Leaflet and Therefore filled during yarn is parallel to perpendicular to the vertical central axis and engagement stent strut of bracket in the direction of the warp of support component Mandrel and and engagement stent strut.Then guidance suture A passes through edge and bracket post holes (as schemed from entrance side towards outlet side Shown in 1I), so that stent strut 41 is fixed to support component and leaflet with the length of about 9mm.In the top (outflow of column Side), using suture A in a continuous manner by occupying the closed bite (locked bite) of bracket bent end to prop up The edge for supportting element is fixed to bracket (known " the Blalock method " that uses illuminated (festooning) suture).In knot 36 Loose ends at, by the end system of suture A to its starting point.Textile structural is temporarily fixed in a manner of 120 degree remaining Engagement stent strut 41, so that the three parts with roughly the same free edge length are divided into, during keeping next step Structure is in position；Then, it can be removed and be fixed temporarily object.

The connection of textile structural is completed by following procedure using the second suture B and generates practical leaflet in bracket Assembly: two remaining stent struts 41 are sewn into the length of about 9mm, and leaflet layer is sewn onto support component layer and branch Frame is to generate valve cusps.Before quilting, using in inflow side support element length as cost, by all 3 independent leaflets Free edge pulls up 3mm in the middle part of free edge, to produce between the bond post improved in the entire plane in bracket outflow side Raw arch Woven fabric.Together with extra length mentioned above, this generates about 6mm jointing altitude at heart valve center, and It is likely to even higher towards joint: being about 9mm.Mold (is derived from the negative form (negative of human aorta valve Form it)) be used to further mould the size and shape of the protrusion part (belly) of leaflet shown in Fig. 1 G.Leaflet is assembled Body sutures the middle part of (35) between the column for being located at inflow side temporarily to maintain this configuration during next step.From this point, Start to suture according to Fig. 1 I.In column top, using two around occlusion, dual fixed leaflet and support component.In cradle top On by leaflet sheet material pull back little by little and fixed by suture.The route of (U-shaped) leaflet suture is also by bracket and mould The shape of tool controls.Suture ends are tied up into remaining loose ends at the knot of suture B starting point.Generated leaflet exists Its center line has convex surface, and when not having pulsating load, radius of curvature is about 12mm.It is expected that this represent shown in Fig. 3 C along The distance h that centerline height h is about 5mm.Textile structural extends several millimeters from the bracket for being located at inflow position and (is also shown in figure In 1I), can be used for that valve is made to be connected to blood vessel wall or arterial wall after the implantation.Using suture by leaflet assembly into One step is connected to bracket lower part, and removes interim suture 35.

It from diameter is that be compressed to diameter be 23mm to 25mm by the bracket 40 of valve, so after leaflet assembly fixed in this way It is sterilized by using ethylene oxide sterilization afterwards.

The performance of valve as described above and manufactured is tested in vitro and in vivo.It is carried out in simplified simulation loop The mechanical test of heart valve prosthesis and functional test.5000 circulatory aid of BVS (Abiomed, Danvers, MA, beauty State) it is comprised in the closed loop with liquid storage device and return pipe.Heart pump capsule by frequency be 80 heartbeats/point and Intra Aortic Balloon Pump (Maquet, Rastatt, Germany) driving that output is 3600cc/ points, uses simultaneously The afterload of heart pump outflow side is set 80mmHg by water column.In initial test, the standard valve quilt of outflow side heart pump The valve institute that individually leaflet made of 55dtex UHMWPE yarn constructs of utilization three being mounted in lucite pipe Substitution, to study its opening performance and close performance.The guiding valve is competent at and is maintained in the case where weaving leaflet and not degenerating > 4 weeks (3571200 circulations).Based on the experience, as above building is tested under the conditions of the same loadings of mankind's body circulation Valve (based on leaflet made of the Woven fabric 10dtex UHMWPE yarn), accumulation be continued above 120 days (13824000 circulations).Valve, which is sufficiently opened, becomes best available hole, wherein being parallel to the swing leaflet of liquid stream has public affairs The upright position known, and close and do not observed visually (other than the small centre bore of about 0.5mm) simultaneously along converging The closing defect of the closing line of leaflet free edges edge.Visual inspection after test shows intact valve geometry；It is small Free edge abrasion or any other destruction or defect is not shown in leaf.All sutures and knot as described above are complete 's.

Also lung artificial valve is implanted into adult sheep model (bread " swifter ", weight are 55-70 kg) and is not stopped On the heart of jump, while using cardiopulmonary bypass unit.It is realized by left thoracotomy 3-4 i.c.s. close to pulmonary artery.It is longitudinal Pulmonary artery is cut, primary leaflet is then cut off.Use 3 5-0Location slit zygonema, which tenses, engages primary column.It uses 5-0In ring epivalve (supra annular) level that valve is sewn onto pulmonary artery (primary joint it is flat At the top of face) on.Pulmonary artery is closed in a linear fashion.

Echocardiography shows normal lobules function, in addition to some accidental bottom line reflux at valve center Except, no valve regurgitation or paravalvular regurgitation.Sheep is simultaneously taken back animal house recovery by closing wound.

Sheep keeps stablizing, without any bad clinical symptoms until 6 months observation periods.The period and then secondary assessment Leaflet function.Echocardiography shows leaflet function competent enough, has more medium valve regurgitation but without valve Reflux by film, and effectively hole does not change from implantation certainly.Hereafter, valve is taken out from sheep to be checked.Leaflet and branch Element and tissue together undue growth are supportted, but this shows very thin fibroblast and endothelial layer, without organizing The histological signs and radiology sign of calcification, and the maximum gauge (including leaflet) at free edge with 250 μm, And the amount of streamlined repair tissue increases to minimum point.The structure of valve appears not to change, and all sutures are suitable When position without be broken and the free edge of leaflet look like it is initially manufactured as it is intact.Fail to detect Wear sign or other abnormal phenomenon.According to the inventors knowledge, small made of fabric using having without with the following characteristics Other researchs of the artificial valve of leaf, the fabric are weaved by synthetic fibers, and the animal dis wherein with this implantation valve 6 months living without complication.

Embodiment 2

The aortic valve prosthesis that will be implanted into body circulation is manufactured similar to embodiment 1 but there are some variations.Following system Standby support component: three pieces semilune fabric (towards the Fo Shi sinus in human or animal's aorta) is taken out to allow blood supply stream Enter coronary ostium.According to the correspondence suture (towards Fo Shi sinus) of U-shaped cusp suture by the remaining sides of support component along solid Surely leaflet is arrived.The connection of textile structural is completed by following procedure using the second suture and generates practical leaflet in bracket Assembly: stent strut 41 is sewn into the length of about 9mm, and leaflet layer is sewn onto support component layer and bracket to generate valve Film cusp.

Then the valve is constructed above for mode described in lung valve to be similar to.When completion, utilize MaxBraid^TM3-0UHMWPE (available from Teleflex, Limerick, Ireland) is used in a manner of (everted) by turning up Blalock suture configuration sutures the additional sewing flange (sewing cuff) of woven UHMWPE yarn.

Under the support recycled in vitro, by valve implantation adult sheep model, (bread " swifter ", weight are On the heart stoped jumping in 65kg).It is realized by left thoracotomy 3-4i.c.s. close to aortic root.Pulmonary artery is cut It opens and draws to side to allow crosscutting aorta.Use continuous suture5-0 in asystolic situation into Row tradition implantation.Aorta is closed using pericardium sticking patch, makes cardiac defibrillation later.Disconnect heart-lung machine.Echocardiography Show normal lobules function, no valve regurgitation or paravalvular regurgitation.

Embodiment 3

By a piece of chemical preparation pig intestinal mucosa lower layer flat sheet (Roswell, the U.S.) it is built with The conduit of valve or the grafting for having valve.It is respectively the valve of 25mm and 18mm by diameter in a series of sheep and lamb It is grafted as insertion between the efferent tract and distal end main pulmonary artery of implantation right ventricle.Operation method is identical as described in embodiment 1 And it is implanted into using extracorporal circulatory system supporter.Crosscutting pulmonary artery, then removes pulmonary valve on pulmonary valve.For Diameter is conduit/valve of 25mm, prepares trapezoidal sheet material, width (A) and about 14 cm with an about 12cm The side (C and D) of width (B) and tool there are two length greater than 10cm.It is freely oblique by being incited somebody to action in a manner of turning up for flat sheet Side C and D and illuminated 4-0Suture is stitched together to construct conical tube.Additional materials are cut off, then folds and inverts Pipe is so that the tubular part with larger circular edge B is located at circular edge A (outflow side) and leaves folding in inflow side The inside of the pipe on folded side.The circular edge B for forming leaflet free edges edge is divided into the three parts with equal length, then benefit Outer tube is fixed to the suture (Prolene 4-0) with absorbent cotton with respective 120 °.Therefore, 3 are produced in valve The longitudinal joint 3-4mm of film, and when not loading, there are free edge 3 independent leaflets of extra length to engage, Jointing altitude at least 7mm.Flange is remained in the outflow side of A, the flange is used for during being implanted to crosscutting pulmonary artery Connect valve.The inflow side of pipe with folded edge is connected to the residual branch of pulmonary artery.After implantation, echocardiography is shown Normal lobules functions, other than some accidental bottom lines reflux at valve center, no valve insufficiency.

It is unless otherwise indicated or to those skilled in the art technically obvious infeasible, otherwise institute in the application It is disclosed about the method for manufacture of intraocular valve or using the method obtain valve embodiment, in terms of and preferably Any of feature or range can be combined in any combination.This is further summarized in following embodiment set Invention.

Artificial valve (400), it includes leaflet assembly, there is the leaflet assembly at least one to be connected to support The leaflet (3) of element (2), the leaflet have the free edge (5) that can be moved between the first position and the second position, Wherein at first position, free edge is bent to allow body fluid to flow by valve far from closing surface (700)；Second When position, for the adjacent closing surface of free edge to close valve, and wherein when not having pulsating load on valve, leaflet can The jointing altitude for being greater than 0.1mm is formed along the length of free edge.

According to the artificial valve in preceding embodiment, wherein the jointing altitude is 1-15mm, preferably 3-10mm, more Preferably 5-7mm.

According to the artificial valve in preceding embodiment, wherein the geometry of the leaflet includes convex surface, the convex surface exists Radius of curvature at centrilobular line is 1mm, 2mm, 3mm, 4mm, 5 mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14 mm, 15mm, 16mm, 17mm, 18mm, 19mm or 20mm.

According to the artificial valve in preceding embodiment, wherein the radius of curvature is 1-20mm, preferably about 12mm.

According to any artificial valve in preceding embodiment, wherein the geometry of the leaflet includes convex surface, institute The bending height for stating convex surface is greater than 1mm, preferably more than 2mm, 3mm or 4mm and at most 15mm, 14mm, 13mm, 12mm, 11mm Or 10mm, most preferably about 5 mm, the bending height are center line and the free edge that connect minimum point and valve center Maximum orthogonality distance between straight line.

According to any artificial valve in preceding embodiment, wherein the free edge of the leaflet is relative to closing Theoretical length needed for valve have extra length, the preferably described extra length be at least 7%, preferably 10-40% or 15-30%.

According to any artificial valve in preceding embodiment, wherein the leaflet is connected to support along joint Element, the longitudinal axis that the joint is parallel to valve since free edge extend, and the length of the preferably described joint is extremely Few 1mm and at most 9mm, preferably 1-6mm.

According to any artificial valve in preceding embodiment, wherein it is 10% that the leaflet, which includes elongation at break, Or smaller, preferably less than 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or even 1% elastic sheet material.

According to any artificial valve in preceding embodiment, wherein the leaflet includes such textile structural, institute State textile structural include one or more elongation at break be 10% or smaller, preferably less than 9%, 8%, 7%, 6% or 5%, the more preferably elastomeric yarn of 1-5%.

According to the artificial valve in preceding embodiment, wherein the textile structural is by one or more elastomeric yarn systems At Woven fabric, and the preferably described Woven fabric include plain weave, twill or compile basket line weave patterns.

According to the artificial valve in preceding embodiment, wherein the textile structural is a piece of Woven fabric, it is preferably a piece of Woven fabric comprising multiple laminations.

According to the artificial valve in preceding embodiment, wherein the free edge of the leaflet is knitting for the Woven fabric Side.

According to the artificial valve in preceding embodiment, wherein the textile structural is the multi-layer woven fabric comprising lamination, The layer is connected with each other in desired position, is preferably connected with each other by crossing warp or filling yarn, to limit leaflet And support component.

According to the artificial valve in preceding embodiment, wherein the Woven fabric is two-layer fabric, it includes in opening side Two selvedges and continuous fold line in opposed close side.

According to the artificial valve in preceding embodiment, wherein the woven textile structure is seamless tubing, optionally Multichannel or multilayer tubular fabric.

It is manufactured by the following method according to the artificial valve in preceding embodiment: continuously weaves the weaving knot The structure of generation is then cut into desired length, and optionally stabilizes cutting edge by structure.

According to the artificial valve in preceding embodiment, wherein the line density of the elastomeric yarn is less than 120 dtex, preferably The line density of the ground elastomeric yarn be less than 60dtex, be preferably ranges between 5dtex and 30 dtex, more preferably between Between 7dtex and 15dtex.

According to the artificial valve in preceding embodiment, wherein the thickness of one layer of textile structural (preferably Woven fabric) Degree is 20-200 μm, preferably 40-150 μm or 50-100 μm.

According to the artificial valve in preceding embodiment, wherein the textile structural includes polymer filaments, preferably UHMWPE filament, the more preferably described textile structural include that the toughness of at least 80 mass % is at least UHMWPE of 20cN/dtex Filament, more preferably warp and filling spin and are substantially made of UHMWPE filament.

It also include the branch for being connected to the leaflet assembly according to any artificial valve in preceding embodiment Frame (40).

According to the artificial valve in preceding embodiment, wherein by suture, preferably by being assembled using with the leaflet Yarn in body has suture made of the suture of similar intensity, is made more preferably by using the yarn of same type Suture or the suture that is made from it, connect the bracket.

According to any artificial valve in preceding embodiment, wherein the valve includes two leaflets, accessory flocculus The closing surface of the first leaflet is served as, vice versa.

According to the artificial valve in preceding embodiment, wherein the valve includes three leaflets, in addition each leaflet is served as The closing surface of two leaflets.

It is implantable heart valve prosthesis according to any artificial valve in preceding embodiment.

Leaflet assembly for the artificial valve any in preceding embodiment.

The method of manufacture of intraocular valve (400), the valve include that at least one is connected to the leaflet of support component (2) (3), the leaflet has the free edge (5) that can be moved between the first position and the second position, wherein in first position When, free edge is bent to allow body fluid to flow by valve far from closing surface (700)；At the second position, free edge Adjacent closing surface is to close valve, which comprises

Sheet material is provided,

Leaflet assembly is formed by the sheet material, the leaflet assembly includes at least one leaflet and support component, With

Valve is consequently formed,

Wherein forming leaflet assembly includes: to carry out moulding to apply geometry, wherein not having on valve to leaflet When pulsating load, leaflet can form the jointing altitude for being greater than 0.1mm along the length of free edge.

According to the method in preceding embodiment, wherein the jointing altitude is at least 2mm, 3mm, 4 mm or 5mm and at most 15mm, 13mm, 11mm, 10mm, 9mm, 8mm or 7mm.

According to the method in preceding embodiment, wherein the jointing altitude is 1-15mm, preferably 3- 10mm, more preferably Ground 5-7mm.

According to any method in preceding embodiment, wherein the geometry includes convex surface, the convex surface is small The radius of curvature of leaf centerline be 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm or 20mm.

According to the method in preceding embodiment, wherein the radius of curvature is 1-20mm, preferably about 12mm.

According to any method in preceding embodiment, wherein the geometry includes convex surface, the convex surface it is curved Qu Gaodu is greater than 1mm, preferably more than 2mm, 3mm or 4mm and at most 15 mm, 14mm, 13mm, 12mm, 11mm or 10mm, most Preferably about 5mm.

According to any method in preceding embodiment, wherein forming the freedom that such leaflet makes the leaflet Edge has extra length relative to theoretical length needed for closing valve, and the preferably described extra length is at least 7%, excellent Selection of land 10-40% or 15-30%.

According to the method in preceding embodiment, wherein the extra length is generated by one or more method and steps, Chosen from the followings group of the method step: for example being made by forming trapezoidal print material or taper or conical tubular material Sheet material is preformed into specific shape, reduces the outer perimeter of valve, and changes leaflet surfaces, and then leaflet is fixed in valve.

According to any method in preceding embodiment, wherein the leaflet is connected to support component along joint, The longitudinal axis that the joint is parallel to valve since free edge extends, and the length of the preferably described joint is at least 1mm And at most 9mm, preferably 1-6mm.

According to any method in preceding embodiment, wherein it is 10% or smaller that the sheet material, which is elongation at break, Preferably less than 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or even 1% elastic material.

According to any method in preceding embodiment, wherein the sheet material is such textile structural, the weaving Structure includes that one or more elongation at break are 10% or smaller, and preferably less than 9%, 8%, 7%, 6% or 5% are more excellent The elastomeric yarn of selection of land 1-5%.

According to the method in preceding embodiment, wherein the textile structural is woven by one or more elastomeric yarns Structure, and the preferably described Woven fabric includes plain weave, twill or volume basket line weave patterns.

According to the method in preceding embodiment, it is characterised in that: wherein the textile structural is a kind of weaving structure, excellent Selection of land includes the weaving structure of multiple laminations.

According to the method in preceding embodiment, wherein the free edge of the leaflet is woven to selvedge.

According to the method in preceding embodiment, wherein the textile structural is woven to the multilayered structure comprising lamination, institute Layer is stated to be connected with each other in desired position, preferably by crossing warp or filling yarn be connected with each other, with limit leaflet and Support component.

According to the method in preceding embodiment, wherein the textile structural is manufactured by duplex weave technique, to generate Two-layer fabric has in two selvedges of opening side and in the continuous fold line of opposed close side.

According to the method in preceding embodiment, wherein the textile structural is manufactured by duplex weave technique, to generate Seamless tubing, optionally multichannel or multilayer tubular fabric.

According to the method in preceding embodiment comprising: the textile structural is continuously weaved, then by the structure of generation It is cut into desired length, and optionally stabilizes cutting edge.

According to the method in preceding embodiment, wherein the line density of the elastomeric yarn is less than 120dtex, preferably institute State elastomeric yarn line density be less than 60dtex, be preferably ranges between 5dtex and 30dtex, more preferably between 7dtex and Between 15dtex.

According to the method in preceding embodiment, wherein one layer of textile structural (preferably Woven fabric) with a thickness of 20-200 μm, preferably 40-150 μm or 50-100 μm.

According to the method in preceding embodiment, wherein the textile structural includes polymer filaments, preferably UHMWPE is thin Silk, the more preferably described textile structural include the UHMWPE filament that the toughness of at least 80 mass % is at least 20cN/dtex, more It is preferred that mainthread and/or filling spin and are made of UHMWPE filament.

According to any method in preceding embodiment, the method also includes: the leaflet assembly is connected to Bracket (40).

According to the method in preceding embodiment, wherein preferably being assembled by using with the leaflet by applying suture Yarn in body has the suture of similar intensity, more preferably by the seam for using the yarn of same type or being made from it Zygonema is attached.

According to any method in preceding embodiment, wherein the valve includes two leaflets, accessory flocculus is served as The closing surface of first leaflet, vice versa.

According to any method in preceding embodiment, wherein the valve includes three leaflets, each leaflet is served as The closing surface of other two leaflet.

The method for manufacturing the leaflet assembly for the artificial valve any in preceding embodiment.

Pass through the leaflet assembly or artificial valve that can be obtained according to method any in preceding embodiment.

Claims (26)

1. artificial valve, it includes leaflet assembly, there are three the leaflets for being connected to support component for the leaflet assembly tool, often A leaflet serves as the closing surface of other two leaflet, and the leaflet has and can move between the first position and the second position Free edge, wherein at the first position, the free edge is bent to allow body fluid logical far from the closing surface Cross the valve flowing；In the second position, the adjacent closing surface of the free edge to be to close the valve, The free edge of middle leaflet has at least 10% extra length relative to theoretical length needed for closing the valve, and Wherein when not having pulsating load on the valve, the leaflet can form 1-15mm's along the length of the free edge Jointing altitude.

2. artificial valve according to claim 1, wherein the jointing altitude is 3-10mm.

3. artificial valve according to claim 1, wherein the jointing altitude is 5-7mm.

4. artificial valve according to any one of claim 1-3, wherein the free edge of the leaflet has 15-30% Extra length.

5. artificial valve according to any one of claim 1-3, wherein the leaflet be connected to along joint it is described Support component, the longitudinal axis that the joint is parallel to the valve since the free edge extends, and the joint Length be at least 1mm.

6. artificial valve according to claim 5, wherein the length of the joint is 1-6mm.

7. artificial valve according to any one of claim 1-3, wherein it is 10% that the leaflet, which includes elongation at break, Or smaller elastic sheet material.

8. artificial valve according to claim 7, wherein the elastic sheet material has the elongation at break less than 5%.

9. artificial valve according to any one of claim 1-3, wherein the leaflet includes such textile structural, institute It is 10% or smaller elastomeric yarn that textile structural, which is stated, comprising one or more elongation at break.

10. artificial valve according to claim 9, wherein the elastomeric yarn has the elongation at break of 1-5%.

11. artificial valve according to claim 9, wherein the textile structural is made of one or more elastomeric yarns Woven fabric.

12. artificial valve according to claim 9, wherein the textile structural is piece of fabric.

13. artificial valve according to claim 11, wherein the free edge of the leaflet is the selvedge of Woven fabric.

14. artificial valve according to any one of claim 1-3, wherein the textile structural is the multilayer comprising lamination Weaving structure, the layer are connected with each other in desired position, to limit leaflet and support component.

15. artificial valve according to claim 14, wherein the Woven fabric is two-layer fabric, it includes in opening side Two selvedges and continuous fold line in opposed close side.

16. artificial valve according to any one of claim 1-3, wherein woven textile structure is seamless tubing.

17. artificial valve according to any one of claim 1-3, wherein the line density of the elastomeric yarn is less than 120dtex。

18. artificial valve according to claim 17, wherein the line density is between 5dtex and 30dtex.

19. artificial valve according to any one of claim 1-3, wherein one layer of textile structural with a thickness of 40- 150μm。

20. artificial valve according to claim 9, wherein the textile structural includes UHMWPE filament.

21. artificial valve according to claim 20, wherein the toughness that the textile structural includes at least 80 mass % is The UHMWPE filament of at least 20cN/dtex.

22. artificial valve according to any one of claim 1-3 also includes the branch for being connected to the leaflet assembly Frame.

23. artificial valve according to any one of claim 1-3 is implantable heart valve prosthesis.

24. the leaflet assembly for artificial valve described in any one of claim 1-23.

25. the method for manufacture of intraocular valve, the valve includes three leaflets for being connected to support component, and each leaflet serves as separately The closing surface of outer two leaflets, the leaflet have the free edge that can be moved between the first position and the second position, Wherein at the first position, the free edge is bent to allow body fluid to pass through the valve stream far from the closing surface It is dynamic；In the second position, the adjacent closing surface of the free edge is to close the valve, which comprises

Sheet material is provided,

Leaflet assembly is formed by the sheet material, the leaflet assembly includes at least three leaflets and support component,

The valve is consequently formed,

Wherein forming the leaflet assembly includes: to carry out moulding to the leaflet to apply geometry, and each leaflet has The free edge that extra length relative to theoretical length needed for closing the valve is at least 10%, wherein in the valve On when there is no pulsating load, the leaflet can form the jointing altitude for being greater than 1-15mm along the length of the free edge.

26. passing through the leaflet assembly or artificial valve that can obtain according to the method for claim 25.