CN101370432A

CN101370432A - Medical self-expansion plugging device

Info

Publication number: CN101370432A
Application number: CNA2005800524932A
Authority: CN
Inventors: 汉斯-任娜·菲格拉; 苏姗·克里邦; 弗里德里希·墨桑纳; 罗伯特·墨桑纳; 罗蒂格·奥特玛
Original assignee: Occlutech GmbH
Current assignee: Occlutech GmbH
Priority date: 2005-11-11
Filing date: 2005-11-11
Publication date: 2009-02-18
Also published as: EP1965706A1; JP2009514625A; CA2627196A1; WO2007054117A1

Abstract

The invention relates to a medical self-expandable occlusion device for treating heart defects of a patient, especially for closing abnormal holes in the tissue. The occlusion device (1) can be inserted into the body of a patient by means of a catheter system in a minimally invasive manner. The occlusion device (1) consists of an interlaced structure (1) of thin threads, the interlaced structure (10) having a first shape during insertion of the occlusion device into the body of the patient, which shape can be previously determined, and a second shape in the implanted position of the occlusion device, which shape can be previously determined, the occlusion device in the first shape of the interlaced structure (10) being in a folded condition and in the second shape of the interlaced structure (10) being in an expanded condition. The aim of the invention is to provide an occlusion device which can be implanted in as gentle a manner possible for the patient. For this purpose, the threads of the interlaced structure (10) consist of a shape memory polymer composition so that the interlaced structure (10) is deformed under the effect of an external stimulus from a temporary shape to a permanent shape, the temporary shape being the first shape of the interlaced structure (10) and the permanent shape being the second shape of the interlaced structure (10).

Description

Medical self-expansion plugging device

Technical field

The present invention relates to be used for the treatment of damaged, the self-expanding medical treatment stopper of unusual breach in the sealing tissue especially of heart of patient, thereby this stopper utilizes conduit system to be introduced into patient body by Wicresoft's mode and comprises the fabric of fine rule, thereby this fabric manifests the first confirmable in advance shape when stopper is inserted into patient body, and the second confirmable in advance shape under the stopper implanting state, thereby the fabric of described stopper is to be in folded state at first contour shape, and this fabric is to be in expanded state at second contour shape.

Background technology

The principle of known this type of stopper at least to a certain extent on medical skill.For example, the stopper of known treatment septal defect from the DE 10 338 702 on August 22nd, 2003, it comprises the fabric of thin silk or line and given suitable profile in molded and heat treatment process.This known stopper has obvious especially smooth near-end and keeps the district, and far-end keeps district and the columniform crosspiece between described near-end and far-end maintenance district.Assemble in the support of the end of the silk of formation fabric in far-end keeps distinguishing.From then on, this structure makes two of known stopper to keep the district to be arranged at the both sides for the treatment of the siphunculus of shutoff in barrier film, utilize endovascular surgical procedures usually, and crosspiece will cross this siphunculus.

Attempt can be by the operation of non-surgery venous duct for medical skill for a long time, in other words needn't carry out operation on the letter and the shutoff septal defect, and for example interatrial septum (atrioseptal) is damaged.Various plugging system has been proposed, every kind of pluses and minuses with self, however be widely accepted without any a concrete plugging system.In with reference to these different systems, will use term " plugging device " or " stopper " below.In all got involved plugging systems, the umbrella system of self-expanding was treated through the introducing of vein ground in shutoff damaged in barrier film.This type systematic can comprise two umbrella: for example, one is arranged on the membranous distal side midplane side farthest of health/heart (promptly apart from), with one in membranous proximal lateral (promptly apart from the midplane of health than nearside), thereby two umbrella prostheses are fixed on the dual umbrella in the septal defect subsequently.Therefore, under assembled state, utilize and cross this damaged short screw, this plugging system generally includes the umbrella of two clampings connected to one another.

Yet the disadvantage of this prior art stopper is relative trouble, difficulty and complicated implantation process.Except that the complexity of plugging system in treating the septal defect of shutoff was implanted, the umbrella of employing was subjected to easily along the influence of the fatigue of materials of fragmentation fracture.And, can anticipate thromboembolic complication continually.

Can utilize surgical operation insertion instrument and/or seal wire to introduce stopper of the present invention in order to make, far-end keeps the end in district that support is set, and this far-end keeps the district to engage with insertion instrument and/or seal wire.Thereby, stopper is arranged on this damaged in after, the intention this joint can be broken away from easily.For example, the end of this fabric in the far-end maintenance district of stopper might be set, so mode is arranged so that and produces female thread to engage with the insertion instrument in support.Certainly, also can expect other embodiment naturally.

Under the stopper situation of another kind of type, so-called lock-Concha Meretricis Seu Cyclinae (Lock-Clamshell) umbrella system is provided, two rustless steels, the umbrella that preferred terylene covers, each is stable by four arms.The plugging device of this type is by in the vein implant patient body.Yet, be considered as locking-problem of Concha Meretricis Seu Cyclinae plugging device is to have big relatively size for implanting the necessary insertion appliance requires of this device.The further disadvantage of other system is that for example the Amplatz plugging device needs many different plugging device sizes, so that handle the size separately of the septal defect for the treatment of shutoff.Therefore, not optimum coupling if insert the length or the diameter of the crosspiece in damaged, the result is that umbrella can not flatten under implanting state fully.This can cause incomplete endothelialization.What also demonstrated is because under a large amount of mechanical stress effects in over a long time, many systems of implant patient health present in fatigue of materials and metal structure and rupture.Especially between implant and barrier film, be subjected to permanent stress in this case.

In order to overcome these disadvantages, produced the stopper of self centering, utilize Minimally Invasive Surgery for example to utilize conduit and seal wire, it is inserted in patient's the health and is incorporated in the septal defect for the treatment of shutoff.These designs are based on following principle, and stopper can taper to the insertion instrument that is used for the blood vessel internal procedure and/or the size of conduit.This stopper that is tapered is introduced by conduit and is treated to enter respectively among the siphunculus of the septal defect for the treatment of shutoff in the septal defect of shutoff then.This plugging device is discharged from conduit then, the umbrella of self-expanding thereon, and launch the respectively membranous relatively subsequently both sides of holding plate.This umbrella comprises successively that by the fabric dummy slider of making or covering such as terylene this damaged/siphunculus is by shutoff under this fabric dummy slider effect.After several weeks or some months, the implant of staying in the health is fully given birth in the meat by being organized in varying degrees of health oneself.

The stopper example of the self centering of specified type is known from WO 99/12478 A1, and it is further developing according to " Amplatz plugging device " the known stopper in the U.S. Patent number 5,725,552 of U.S.'s announcement still.This stopper comprises the meticulous of a plurality of employing yo-yos (yo-yo) shape, the fabric of the Nitinol thread of winding.Each fabric produces with its primitive form as the circle braid, and (their proximal laterals, (its distal side has line end freely respectively) respectively) and in its rear end at its front end.During the following process of circle braid, these free-ended each must be aggregated in the collar then and weld together.After suitable processing procedure, both present the outstanding axle collar proximal lateral of the plugging device of finishing and distal side.Dacron patch is stitched among the crosspiece of the maintenance umbrella of into far-end and near-end and insertion.Because memory effect by the nickel-titanium alloy material demonstration of using, two keep umbrella self to launch when withdrawing from conduit, initially be intergrade, thereby keep umbrella finally to be arranged on the membranous both sides, present flattening shape in various degree at last for balloon-like.Between the fixation phase of umbrella, this crosspiece enters among the siphunculus of shutoff with itself centering automatically.

The nickel-titanium alloy material of this shape memory is known from the stopper of prior art, yet, verified some disadvantage that has with respect to stopper as discussed previously.Nitinol, it is the atom alloy of nickel and titanium, only be suitable for shape-memory material conditionally, because the first confirmable in advance shape among stopper just is being inserted into patient body time the and the maximum distortion of the Nitinol between the second confirmable in advance shape when stopper is in implanting state only equal about 8% as medical stopper.In other words, this means that the nickel-titanium alloy material of shape memory only is suitable for as far as possible little folding stopper conditionally for implantation process.Therefore, when use had the medical stopper of the fabric of being made by Nitinol, this implantation process was not mild especially on one's body patient.In a single day and as the alloy of nickel and titanium, Nitinol constitutes permanent foreign body, makes to be in implanting state, can anticipate corresponding system of defense reaction can take place on health.

Based on described problem condition, it is special in the utilization as the Nitinol of shape-memory material that is used for medical stopper, task of the present invention is the stopper of the self-expanding medical treatment of the sort of type that describes in detail is at the beginning made improvements, to offer the mild implantation process of this stopper of patient.

Summary of the invention

This task is to solve according to the medical stopper of the self-expanding of the sort of type that describes in detail at the beginning, it creatively has the line of fabric, this fabric comprises the polymer composites of shape memory, so that this fabric by environmental stimuli from interim warpage to permanent shape, thereby this interim shape is given as first contour shape and permanent shape is given as second contour shape.

Solution of the present invention has a plurality of significant advantages than the medical stopper of known and above-mentioned prior art.Special because the polymer composites of shape memory shows obviously better memory performance than Nitinol, milder implantation process is provided when implanting described medical stopper.Compare with known shape-memory material, for example the Nitinol marmem; That is, the atom alloy of nickel and titanium, shape-memory polymer is preponderated far away with regard to their memory performances.In (heating/cooling) process, only need less effort handle respectively interim shape or, to recover permanent shape.And under the situation of Nitinol, for example, the maximum distortion between permanent and interim shape just in time equals 8%.By contrast, the shape-memory polymer demonstration reaches 1100% remarkable higher deformability.

Than using later manufacture process from conventional treatment method, polymer composites of the present invention also shows the advantage than prior art.For example, utilize such as injection mo(u)lding or the conventional treatment method extruded, this polymer can obtain the permanent shape of initial given it.Then, this synthetic can and be fixed on its required interim shape with after strain, and this is the process that is called as " programming ".This process can make this sample heat to the polymer effect, and distortion is cooling then.Perhaps this polymer/synthetic also can be out of shape at a lower temperature, is called the process of " cold stretch (clod drawing) ".Therefore, this permanent shape becomes the shape memory of remembeing still for interim shape the time.In case environmental stimuli acts on the polymer body of this mold, then cause shape memory effect to trigger and therefore cause the recovery of permanent memory shape.Cooling meeting to sample is implemented irreversible degeneration to interim shape, and why Here it is is called the reason of so-called one-way shape memory effect.This original interim shape and other shape can implement to carry out reprogramming on the new mechanically deform basis.

The polymer of shape memory is included in the group that is called intelligent polymer in English, and is the polymer of display shape memory effect; That is, it can be in response to environmental stimuli, such as variations in temperature, and changes their external shape.The process that said procedure design and shape are recovered is illustrated to describe in Fig. 1.

The preferred embodiment of the present invention's medical treatment stopper provides in the dependent claims.

What offer environmental stimuli particularly preferredly is embodied as confirmable inversion temperature.Therefore conceivable is in order to trigger the recovery of shape memory effect and permanent memory shape therefore, and the fabric of the polymer body of mold must be heated to the temperature higher than inversion temperature.Suitably select chemical constituent to allow the initial regulation of this concrete transition temperature to polymer composites.

Therefore, particularly preferably be and this inversion temperature be set within the scope of room temperature and patient temperature.It has the advantageous particularly part application facet in stopper is implanted to patient body.Thereby when implanting stopper, what all must be guaranteed is the body temperature (36 ℃) that this stopper can not be heated and reach patient, and the shape memory effect of this meeting trigger polymers is up to being in implanting state.

A possible enforcement of stopper of the present invention offers polymer composites, to comprise the polymer conversion element, wherein environmental stimuli is confirmable inversion temperature, thereby the interim shape of fabric is stabilized in below the confirmable inversion temperature based on the characteristic phase transformation of polymer conversion element.

For example, therefore conceivablely be, if polymer composites is revealed as and has crystalline state and change segmental crystalline state or semi-crystalline polymer network, then the interim shape of fabric is fixed and stablizes by solidifying crystalline state conversion segment when crystalline transition, thereby this inversion temperature is respectively a crystallization temperature, and crystalline state is changed the function of segmental inversion temperature.

On the other hand, under situation with the segmental polymer composites such as the amorphous polymer network of amorphous state conversion, by segmental the solidifying of amorphous state conversion, it is feasible when glass transition the interim shape of fabric being fixed and stablized, thereby inversion temperature is the function of the glass transition temperature of amorphous state conversion chains link section.

According to these preferred embodiments, therefore, the characteristic phase transformation can be used to the interim shape of stable shaped memory polymer; That is, crystallization under crystalline state or semi-crystalline polymer situation or the glass transition under the amorphous polymer situation.Therefore, under the elastomeric polymer situation of forming by the covalent bond polymer network, the mechanism of shape memory conversion is to stablize this permanent shape based on the chemical bond of polymer chain on the one hand, on the other hand by the fixing interim shape of segmental crystallization (semi-crystalline polymer network) or by solidify the conversion segment under glass transition (amorphous polymer network) situation.So in corresponding temperature range, this T _TransInversion temperature (surpassed this temperature and just triggered shape memory effect) is looked synthetic T respectively _mMelting temperature, T _gGlass transition temperature and deciding.

Fig. 2 has schematically described the molecular mechanism of the thermoinducible shape memory transformation of semi-crystalline polymer network.When being higher than crystalline solid, ambient temperature changes segmental T _Trans(T _m), these segments are flexible and elastically deformable then, for example stretch.

By being lower than T _Trans(T _m) cooling; Promptly by cooling off the crystalline state zone that forms, the crosslinked action of taking on analog Neo-Confucianism, the fixedly interim shape of formation.When polymer is heated to T _Trans(T _m) when above, this permanent shape is recovered once more.Thereby the thermodynamics active force that drives permanent shape recovery is the increment of attainable entropy.Amorphous polymer network class with shape memory effect function is similar to the semi-crystalline polymer network with shape memory effect, thereby inversion temperature is represented glass transition temperature and can be fixed interim shape by the segmental flowability of solidifying amorphous conversion.

Another favourable enforcement or the improvement of the embodiment that had before quoted of stopper of the present invention are to provide polymer composites, can manifest at least two out of phase linearities to comprise, the segmented copolymer network is separated, thereby first is that hard segment forms phase mutually, wherein be used for the physical crosslinking of polymer architecture and determine and a plurality of hard segments of the permanent shape of stable fabric form blocks and are formed on polymer, and thereby second be that the conversion segment forms phase mutually, the a plurality of conversion segments that wherein are used for fixing the interim shape of fabric form block and are formed in the polymer, thereby forming mutually the transition temperature that hard segment forms phase by the conversion segment is inversion temperature, thereby can use the contour shape of the conventional method setting fabric of for example injection mo(u)lding or expressing technique on the transition temperature that is higher than hard segment formation phase.

The chemical constituent of the polymer composites that comprises with respect to the fabric of the present invention medical treatment stopper, the preferred enforcement of medical stopper of the present invention, this stopper has the fabric that comprises shape memory polymer composite material, can offer the polymer composites of Polyurethane Thermoplastic Elastomer with many block structures, it is by vulcabond especially di-2-ethylhexylphosphine oxide (4-phenyl isocyanate) or hexamethylene diisocyanate and glycol especially 1 mutually that thereby hard segment forms, the 4-butanediol transforms and forms, thereby and change segment formation by oligomeric polyether/polyester glycol, especially based on OH end capped poly-(oxolane), poly-(6-caprolactone), poly-(ethylene glycol adipate), poly-(ethylene glycol) or poly-(propylene glycol) produces.

Also in selectable favourable enforcement, conceivable is that the diblock copolymer that is separated of polymer composites shows amorphous A-block and hemicrystalline B-block, thereby the glass transition of amorphous A-block constitutes hard segment forms phase, thereby and the melting temperature of the B-block of semi-crystalline state as the inversion temperature that is used for hot shape memory effect.

In the preferred enforcement of back, advantageously has polystyrene as amorphous A-block and poly-(1, the 4-butadiene) B-block as semi-crystalline state for this synthetic with respect to polymer composites.

Consequently, the segmented copolymer that is separated of linearity constitutes the important set of shape-memory polymer.These polymer have two isolating phases, thereby have of high transition temperature more as physical crosslinking and be used for determining this permanent shape.On these melting temperatures, can adopt such as injection mo(u)lding or the conventional treatment process that is used for the profile configuration extruded.As noted before, second is that interim shape is changed and be used for fixing to molecule mutually then, thus the transition temperature (T of conversion phase _Trans) can for unwind or glass transition temperature.

Being included among the shape-memory polymer is the Polyurethane Thermoplastic Elastomer with many block structures, and this polymer works according to the operation principle based on linear block copolymers.

Shown in Fig. 3 and 4, hard segment form mutually normally industrial vulcabond such as di-2-ethylhexylphosphine oxide (4-phenyl isocyanate) (MDI) or hexamethylene diisocyanate (HMDI) and industrial glycol as 1, the conversion process of 4-butanediol.This conversion segment forms and produces from industrial available oligomeric polyether/polyester glycol then, for example, and based on OH end capped poly-(oxolane), poly-(6-caprolactone), poly-(ethylene glycol adipate), poly-(ethylene glycol) or poly-(propylene glycol).

From form the MDI/1 of phase as hard segment, the example that produces in 4-butanediol and poly-(6-caprolactone) is the linear block copolymers of semi-crystalline state, and it has shape memory effect and from 1600 to 8000g/mol molecular weight, T _m=44-55 ℃ inversion temperature.By contrast, have amorphous phase with from the MDI/1 that forms as hard segment mutually, the T of 4-butanediol and flexible poly-(ethylene glycol adipate) _gThe linearity configuration memory block copolymer of=-5 to 48 ℃ inversion temperature can have from 300 to 2000g/mol molecular weight.

In one embodiment, the polymer composites of forming the fabric of the present invention's medical treatment stopper manifests the diblock copolymer that is separated, and alternative this embodiment provide polymer composites manifesting the center B-block with semi-crystalline state and the triblock copolymer that is separated of two amorphous terminal A-blocks, thereby the A-block constitutes hard segment and the B-block is determined inversion temperature.

Conceivable at this is that polymer composites has as the semi-crystalline state of center B-block poly-(oxolane) with as the amorphous poly (2-Jia oxazolin) of far-end A-block.

In addition; based on linear block copolymers with according to other the shape-memory polymer that works of above-mentioned operation principle is diblock copolymer that is separated required for protection or triblock copolymer; it comprises; for example the AB block copolymer of 34wt.% polystyrene (PS) gathers (1, the 4-butadiene) (PB) as hypocrystalline B-block as amorphous A-block and 66wt.%.

Fig. 5 shows this structure with diblock or triblock copolymer of shape memory effect.The glass transition of PS is known to be 90 ℃ and formation hard segment formation phase.The melting temperature of PB crystallite is served as the inversion temperature of hot shape memory effect and between 45 and 65 ℃.

In another example shown in Figure 5, described equally as the ABA triblock copolymer as poly-(oxolane) of the semi-crystalline state of center B block (PTHF) and (POX) as amorphous poly-(the 2-Jia oxazolin) of far-end A-block.A-block with mean molecule quantity of 1500g/mol shows 80 ℃ glass transition temperature and constitutes hard segment.Have 4100 and 18800g/mol between the B-block of molecular weight be hypocrystalline and between 20 and 40 ℃, unwind according to molecular weight.Therefore, this inversion temperature can change in this scope.

Have polynorbornene, the polymer of polyethylene/nylon-6-graft copolymer and/or crosslinked gathering (ethylene-be total to-vinylacetate) copolymer has determined that be favourable with respect to use in the chemical constituent of the polymer composites of medical stopper of the present invention.

Proving advantageously equally for polymer composites, polymer composites manifests the covalent cross-linking polymer network, it is formed with ternary or the polymerization of higher official energy crosslinking additives, polycondensation and/or addition polymerization by bifunctional monomer or big monomer, thereby give the suitable selection of the ratio of order body, their degree of functionality and cross-linking agent, then the chemistry of this polymer network of Xing Chenging, heat and mechanical performance can be set particularly and optionally.Therefore, from the transformation of confirmable contour shape in advance of the first in advance confirmable contour shape to the second, this can make the characteristic of stopper accurately and in advance set up, especially, under the expansible situation of stopper, the accurate and foundation in advance of the process of this incident.

It is the covalent polymer network that the particularly preferred enforcement of back embodiment provides polymer composites; it is by octadecyl acrylate and methacrylic acid and N; the copolymerzation with cross-linking of N '-methylene-bisacrylamide constitutes cross-linking agent, thereby the shape memory effect of polymer composites is based on crystallization stearyl side chain.

For polymer composites same feasible be the follow-up covalent cross-linking polymer network that is cross-linked to form that manifests by linearity or branched polymer.

For example, can be envisioned as the thermal fission that forms group by ionizing radiation or free radical in addition at this and can activate that this is crosslinked.

Therefore, the big group of shape-memory polymer constitutes the crosslinking polymer network of covalency, as initially noted earlier.Based on their structure, being used for synthetic two different strategies can advantageously follow:

A) bifunctional monomer or big monomer and have ternary or polymerization, polycondensation or the addition polymerization of the additive that higher official can be crosslinked.Give monomer suitable selection, then their sense of cross-linking agent and ratio, the chemistry of the polymer network of formation, heat and mechanical performance can be specifically and optionally setting.

B) the second synthetic variant that is used for the shape memory polymer networks of covalency can provide by the crosslinked of follow-up linearity or branched polymer.Therefore, crosslink density importantly depends on the reaction condition of selection.At this, crosslinked usually by ionizing radiation or form the thermal fission activation of group by free radical.For example, polyethylene film receives the folding character of heat from the irradiated polyethylene with γ-steel, and perhaps crosslinked polyethylene polyvinyl acetate ester copolymer adds the acquisition shape memory effect by the homogeneity of the radical initiator of cumyl peroxide.

Fig. 6 shows the feasible monomer of the polymer network of the shape memory that is used for covalency.At this, for example, the polymer network of covalency has by octadecyl acrylate STA and the N that has as cross-linking agent, the shape memory effect that the crosslinked copolymerisation of the methacrylic acid MAA of N '-methylene-bisacrylamide MBA obtains, this shape memory effect is based on crystalline stearoyl side chain.Based on relative octadecyl acrylate ratio, cause unwinding or inversion temperature between 35 and 50 ℃.

Can be based upon the shape-memory polymer of two kinds of fundamental types in a word; That is, the polymer network of thermoplastic elastomer (TPE) and covalency, their character, their processing method and their programming procedure are different.This thermoplastic elastomer (TPE) needs the minimum weight portion of hard segment formation polymer chain, to guarantee physical crosslinking.Under the situation of the network of covalency, hard segment forms the ratio of polymer chain can be higher.Certainly, can imagine the potential application of described shape-memory polymer in technology on a large scale, for example with respect to self repairing automatic main body, conversion element, pick off and reach the right of intelligent packaging.

All shape-memory polymers of enumerating are prescriptions, in the biomedicine that is applied in the sort of stopper that the present invention describes in detail at the beginning.And the use of the biodegradable shape-memory polymer of prescription will be described below more accurately.

The advantageous particularly part with respect to medical stopper utilization is that but embedded material is the synthesising biological degraded.Degradable material, each geopolymer has the fissionable binding agent under physiological conditions.The term degradability uses in this case following, if material because or the loss of the mechanical performance of biosystem inside degrade.Profile and the size implanted in fact are undamaged during decomposing.This means with respect to ageing time, not given additional quantitative data is provided, is to be used for mechanical performance to finish the time that loss spends.The Biostatic material is meant that material remains on the firm of biosystem inside, and its at least only part degraded in long-term.

The invention provides the medical stopper of the sort of type that illustrates at the beginning and comprise fabric according to previous described preferred embodiment, it is synthetic from the polymer composites that comprises at least a Biodegradable material.

The particularly preferred enforcement of the embodiment of back provides to polymer composites, to manifest the hydrolysis degradable polymer, and especially poly-(hydroxy carboxylic acid) or corresponding copolymers.Hydrolytic degradation has the following advantages, and the speed that degraded takes place and the location independent of implantation are because water is present in the whole system.

Yet the utilization of enzyme degradable polymer also envisions in another embodiment.Feasible especially is that polymer composites is revealed as biodegradable thermoplastic amorphous polyurethane-copolyester polymer network.

For the chemical constituent of the polymer composites of medical stopper of the present invention same indispensable be that polymer composites is revealed as biodegradable elastomeric polymer networks, by oligomer diol and crosslinking with diisocyanate acquisition.

But conceivable selection mode is that polymer composites is formed as the covalent networks based on oligomerization (6-caprolactone) dimethylacrylate and butyl acrylate.

For the fabric of stopper configurations of the present invention, the present invention requires the hydrolyzable and the enzyme degradable polymer composite of degradable polymer.As mentioned above, hydrolytic degradation has following benefit, and promptly Jiang Xie speed and implantation position are irrelevant.By contrast, local enzyme concentration greatly changes.Given biodegradable polymer or material, so degrade and can separate by pure water, their combination generation is reacted or is passed through in enzyme induction.

The typical hydrolyzable chemical bond that is used for the polymer composites of stopper is an amide, ester or acetal bonds.Two mechanism can propose with respect to the Degradation of reality.Under the superficial degradation effect, the hydrolysis of chemical bond takes place from the teeth outwards exclusively.Because hydrophobe characteristic, depolymerization is propagated faster than the water at material internal.These mechanism can be found out in poly-(acid anhydride) and poly-(ortho esters) especially.

Poly-when relating to (hydroxycarboxylic acid) especially significantly relates to the present invention, such as poly-(lactic acid) or poly-(glycol acid), and each corresponding copolymer, depolymerization occurs in the whole volume.This step is determined the speed of the hydrolysis fission of binding agent, because the water in hydrophilic polymer matrix is a little propagated occurs under the fast relatively speed.

Decisive being that biodegradable polymer uses, on the one hand, they are degenerated under controlled or variable velocity, and on the other hand, catabolite is nontoxic.

The resorbent notion of polymeric material is meant utilizes natural metabolism to remove fully from health up to material from material or quality degradation.Under the situation of an only degradable polymer homogeneity implantation (stopper), absorb the time point of finishing loss that begins to mechanical performance again.The detailed description of soak time covers from implanting beginning and running through up to the cycle of eliminating fully of finishing implant again.

Among the most important biodegradable synthetic classification of polymer, the braid over braid of stopper of the present invention advantageously synthesizes: such as the polyester of poly-(lactic acid) PLA, poly-(glycol acid) PGA, poly-(3-hydroxybutyric acid) PBA, poly-(4-polyvinyl acetate) PVA or poly-(6-caprolactone) PCL or corresponding copolymer; From the synthetic poly-anhydride of handling of dicarboxylic acids, such as glutamic acid PAG, succinum PAB or decanedioic acid PAS; Poly-(aminoacid) or polyamide are such as poly-(serine ester) PSE or poly-(aspartic acid) PAA (Fig. 9).

Fig. 7 shows the example of biodegradable polyester, and Fig. 8 shows biodegradable poly-anhydride, the example of poly-(aminoacid) and polyamide.

In a word, accountable is that shape memory character is played the part of important role with respect to implant, special with regard to the medical treatment of minimum intrusion.In this, the degradable implant with shape memory character is effective especially.For example, the degradable implant of this class is incorporated in the health by small-sized cutting with compression (interim) form, presents the shape memory relevant with its application then after warm by body temperature.Then, after given interval, this implant is degenerated, thereby does not need operation for the second time to remove it.

Based on known biodegradable polymer, structural detail can be from derivation biodegradable shape-memory polymer synthetic.In this case, thereby fixedly the necessary selection like this of the suitable crosslinked and network chain that serves as conversion element of permanent shape is feasible, and the one side inversion temperature can realize that the toxicology problem that is relevant to any catabolite on the other hand can be got rid of by physiological conditions.Therefore, can select based on the thermal characteristics of known degradable implant material for the conversion segment that is fit to of biodegradable shape-memory polymer.In this, interested especially is the heat deflection of the conversion element in the temperature range of room temperature and body temperature.For this transformetion range, biodegradable polymer segment can optionally synthesize by the molecular weight of the polymer that changes the monomeric stoichiometric proportion of known beginning relation and form in approximate 500 to 10000g/mol scopes.

Suitable polymer segment is to have at for example poly-(6-caprolactone) glycol of the melting temperature between 46 and 64 ℃ or based on amorphous copolyester of lactic acid with the glass transition temperature between 35 and 50 ℃ and glycol acid.This phase transition temperature in view of the above; That is, segmental the unwinding or glass transition temperature of polymer conversion also can further be reduced by their chain length or the degraded by concrete end group.Then, the polymer conversion element of setting can focus in crosslinking polymer network physics or covalency, produces the biodegradable shape memory polymer material of forming by selecting.

In a possible embodiment, the biodegradable thermoplastic amorphous polyurethane copolyester polymer network with shape memory characteristic can use the material as stopper of the present invention.At first, based on commercial available lactide DL (circulation lactic acid dimer), Acetic acid, hydroxy-, bimol. cyclic ester DG (circulation glycol acid dimer) and trimethylolpropane TP (degree of functionality F=3) or tetramethylolmethane PE (F=4), wherein glass transition temperature is between 36 and 59 ℃, and is mutually crosslinked to form biodegradable polyurethane network with industrial trimethyl hexamethylene diisocyanate TMDI then.

Fig. 9 shows the example of the monomer component of the amorphous polyurethane copolyester polymer network with shape memory characteristic.

Amorphous polyurethane copolyester polymer network with shape memory characteristic has the glass transformation temperature T between 48 and 66 ℃ _gAnd be presented at 330 and 600MPa between the modulus of elasticity of extension, 18.3 and 34.7MPa between each hot strength.Heat these networks to the about 20 ℃ of elastomeric materials that produce deformable 50-265% to interim shape that are higher than this inversion temperature.Drop under the room temperature situation, form the polymer network of the shape memory of distortion, it has obvious higher modulus of elasticity from 770 to 5890MPa extension.Under the situation of reheat to 70 subsequently ℃, the example redeformation of the deformed sample that produces after 300 seconds of reacceesing turns back to the shape of permanent corkscrew shape.What finally illustrate is in period between about 80 and 150 days, and the polyurethane copolyester polymer network in the water-bearing phosphate salt buffer fully decomposes at 37 ℃.By the segmental composition of the biodegradable conversion of optimization, in fact the degradable polyurethane copolyester polymer network with shape memory characteristic can produce rapidly, for example in 14 days.

Similar biodegradable elastic shape memory polymer networks can be from having vulcabond TMDI, produces in the oligomer diol of melting temperature between 38 and 85 ℃ crosslinked, and it is suitable for stopper of the present invention equally.Utilize these materials, fiber is synthesized and stretches 200% and enters interim longer fiber and the Lignum Pini Nodi that from then on forms.After two ends of fixed-node, add hot junction to 40 ℃; Promptly higher than inversion temperature, after about 20 seconds, strain node once more originally as semi-permanent length by the transformation of line.Also finally assess degradability, thereby for 37 ℃ the time, these polymer in the water-bearing phosphate salt buffer can be seen the loss of 50% quality after about 250 days.

In one of stopper of the present invention possible implementation, this fabric forms on the biodegradable shape-memory polymer on the network of covalency based on oligomerization (6-caprolactone) dimethylacrylate and butyl acrylate.Be clear that in subcutaneous implantation process subsequently this polymer composites can not have passive influence in the wound healing processing procedure.The synthetic of this biodegradable shape-memory polymer can obtain from the n-butyl acrylate, because can be used as soft chain segment formation component for-55 ℃ the lower glass transition temperatures of pure poly-(n-butyl acrylate).

Figure 10 shows the monomer component of the biodegradable network that is used for covalency.The degradable segment of this biology guides at this via oligomerization (6-caprolactone) dimethylacrylate cross-linking agent.Network is synthetic to be taken place by photopolymerization.Based on the mole and the comonomer n-content of butyl acrylate of macromolecule oligomerization (6-caprolactone) dimethylacrylate, the inversion temperature of the network of covalency and mechanical performance can be controlled.Therefore, in the enforcement of solution of the present invention, the mole of oligomerization (6-caprolactone) dimethylacrylate 2000 and 10000g/mol between change, this n-butyl acrylate content is between 11 and 90 mass percents.Based under the polymer network situation of the mixture of low molecular oligomerization (6-caprolactone) dimethylacrylate of the n-of 11 mass percents butyl acrylate, can realize 25 ℃ fusing point.

Biodegradable covalency and polymer network physics with aforesaid shape memory effect also can be used as the matrix that controlled active substance discharges.Yet also can envision biodegradable polyurethane segmented copolymer based on as poly-(to the dioxy Ketohexamethylene) PDO of hard segment with as the TMDI of vulcabond with shape memory.

Figure 11 is presented at the polymer segment in biodegradable poly-(to the dioxy Ketohexamethylene) polyurethane segmented copolymer.Has poly-(the common glycolic of diminishing lactic acid) PDLG or poly-(6-caprolactone) PCL changes the segmented copolymer that segmental combination produces the inversion temperature with 37 or 42 ℃ respectively.The hydrolytic degradation of this polymer illustrates this polymer-matrix and degrades with littler speed in PCL.In the test of a PCL polymer, after 266 days of hydrolysis, simultaneously under the situation of PDLG polymer, 50 to 90% of initial mass still exists, and only after 210 days, can detect 14 to 26%.

Can keep be the polymer network of biodegradable shape memory can be from the combination of shape memory polymer networks physics or covalency with biodegradable polymer segment synthetic obtaining.Selectively component is selected to allow for each application corresponding optimal parameter to be set, such as mechanical performance, deformability, phase transition temperature and especially, the speed of inversion temperature and polymer unwinds.

All biodegradable shape-memory polymers of enumerating are prescriptions, to be used for the material of stopper as the present invention.

Contour shape with respect to the present invention's medical treatment stopper, advantageously provide the second confirmable in advance shape of stopper to be configured to seal abnormal structure's breach in the heart of patient, thereby under its expanded state, this stopper shows that near-end keeps the district, far-end keeps the central area between district and two zones, and wherein this stopper in the central area than keeping the district to show littler diameter at near-end and/or far-end.The advantage of this embodiment is that the endovascular stopper that provides is particularly suitable for handling septal defect, and the damaged and persistent ductus arteriosus of patent foramen ovale is damaged, and utilizes the conduit system plugging system to be incorporated into to treat in shutoff damaged.

Septal defect is meant atrial septal defect (ASD); That is, the hole in the atrial septum, and interventricular septal defect (VSD); That is the hole in Interventricular interval.

Patent foramen ovale damaged (PFO) is the avette opening (groove) in the atrial septum of heart, and its adhesion by the flap edge will be normally closed the day after tomorrow, though in all births, there is about 25% imperfect bonding (persistency), thus stay the oval foramen of opening.

Term " patent ductus arteriosus is damaged " (PDA) is meant open passageway between aorta and pulmonary artery, an open passageway of closing in the day after tomorrow usually.

Main target of the present invention be to provide a kind of use in heart reliably, simple stopper, its structure is can handle patent foramen ovale damaged (PFO), atrial septal defect (ASD), interventricular septal defect (VSD) and patent ductus arteriosus damaged (PDA); And handle with such form, wherein fabric as mentioned above, it is substituted by shape-memory polymer or Biodegradable shape memory polymer.

The second confirmable in advance shape of the medical stopper of structure exists a plurality of flexible twisted wires or line the fabric of forming from polymer, thereby this line so weaves so that produce elastomeric material.Then, this fabric distortion makes it consistent with the outer surface of mould element.This fabric is arranged on the surface of mould element and is subjected to heat treatment when ascending temperature.Select heat treated persistent period and temperature so that keep distortion to fabric.In heat treatment process subsequently, this fabric is removed from mould element, keeps its distortion.So the fabric of handling can be determined the shape of (expansions) in advance corresponding to second of medical stopper, and it utilizes conduit system with in the passage among the folded state introducing patient.

Application type of the present invention comprises the special shape that is used for medical apparatus and instruments, and it can be constructed in accordance then, so that use in concrete medical conditions.This stopper with smooth expansible shape and available folding anchor clamps setting can be fixed to the end of inserting device or seal wire, so that make the stopper retraction after the location.In use, the degree of conduit introducing patient body is to make the far-end at catheter position just be positioned at the position that needs physiological processes.Then, the previous medical treatment device of selecting is folding according to the present invention enters in predetermined second shape and inserts in the catheter opening.This stopper passes conduit and withdraws from once more at its far-end, because its memory characteristic, and its original-shape when returning elastically the point that approaches to handle.Then, this seal wire or insertion conduit discharge from anchor clamps and withdraw.

In its second predetermined shape, this stopper preferentially shows rectangle, and it has one as the pipe of its central area and at the segment of each end place swell diameter of described central area.The thickness of the central area roughly wall thickness with the organ for the treatment of shutoff is suitable, for example membranous thickness.

Can stagger with respect to the central horizontal of central area in the center of at least one swell diameter segment (near-end or far-end keep the district).Therefore, use when the interventricular septal defect of thin film can be by supportive device and close, this device enough comes to close reliably membranous irregular opening greatly.Each braiding end of this stopper is kept by anchor clamps.These anchor clamps are partially retracted in the swell diameter of this stopper, thus the closed mechanism that the total length of this stopper reduces and generation more flushes.

In the Another application type, this stopper is apparently as the bell with rectangular body, and it has taper and bigger latter end.This bigger end has fabric panel, and it is provided with common axle perpendicular to the unfolded passage of this stopper under the expansion situation.Keep braiding end anchor clamps together to be withdrawn into the center of ＂ bell ＂, therefore produce the stopper that flushes with low overall height.

In a particularly preferred embodiment, because the near-end of fabric keeps the enlarging of district's demonstration towards the near-end of stopper, therefore this allows stopper in particularly advantageous mode, be independent of the damaged associated diameters for the treatment of shutoff and the thickness that is independent of septum wall, and adapt to septal defect automatically, do like this so that stopper does not have part protruding from the plane of septum wall, wherein this is damaged in this damaged proximal lateral.Therefore, can not occur in the common complication that takes place usually in this case.What emphasize is to this means that the stopper of use advances in the meat significantly faster than plugging system well known in the prior art by the tissue life of health oneself.The fabric that stopper utilization of the present invention is made up of fine rule can produce the further advantage of long-term mechanical stability as raw material.Therefore, this has prevented the diaclase in the implant of inserting in a large number.In addition, this fabric also provides sufficient rigidity.This damaged lateral edges that keeps the enlarging of the near-end in district to allow the near-end of this stopper to keep the district to be in relatively under the insertion state in addition to the fabric near-end flattens fully, and so in fact irrelevant with the thickness to damaged diameter or septum wall.Therefore, this stopper can be used for the septal defect of large-scale different size.Because do not have and need keep the place, district to be provided for tying or merging the support of fabric at near-end, so any component of stopper is not outstanding by septum wall, this component that has prevented implant constantly contacts with blood.This can produce following advantage, can not exist health that the threat that the complication of thromboembolism is reacted or existed to defense mechanism will take place.

Particularly preferred embodiment provides center that near-end/far-end keeps the district to stagger with respect to the central horizontal of central area.So, but the interventricular septal defect shutoff of thin film, and simultaneously, spendable supportive device enough comes to close reliably membranous irregular opening greatly.In addition, each braiding end of also supposing stopper is kept by anchor clamps.These anchor clamps produce the length overall of stopper minimizing and the closed mechanism that more flushes in the swell diameter of this stopper partially retracted (near-end and far-end keep the district).

Advantageous embodiments provides the shape that shows concave profile in the second confirmable in advance shape of inside stopper under expanded state that near-end and/or far-end keep the district.This allows expansion plugging device to obtain good especially location in treating shutoff damaged.It is tapered to be fit to use the diameter of the conduit system in the blood vessel internal procedure with the first confirmable in advance shape particularly preferably to be the stopper of being made by fabric.Therefore, this makes that be used for the damaged stopper of shutoff is inserted into the conduit of introducing, for example by vein, eliminates the needs for the operation on practical significance.When fabric comprised the polymeric material of shape memory, as mentioned above, the stopper tapered with the diameter of conduit was called as ＂ self-expansion plugging device ＂, and it launches after withdrawing from conduit automatically, made two to keep distinguishing the near-end/distal sides that can be arranged on this curve.Produce the stopper of self-expanding and self-align plugging system in addition for the design of the continuous weaving of stopper of the present invention, it prevents to take place permanent mechanical stress between stopper that inserts and septum wall.Conceivable enforcement is that the near-end of fabric keeps the district to show the enlarging of bell shape towards near-end.

Further the imagination is that near-end keeps the district to be shown to the enlarging of the bell shape of near-end.Therefore, this allows this stopper can be used in the damaged processing procedure of a plurality of differences, be used in particular for interventricular septal defect (VSD), atrial septal defect (ASD) and patent ductus arteriosus damaged (PDA), thus can select to keep the optimal profile in district basically for near-end for a plurality of different sizes and type damaged.Certainly, can also conceive other profile in this, for example barbell shape shape.In order to make expansion plugging device in keeping the district, good especially location be arranged, to such an extent as to advantageously the size of the length of central area is prescribed peripheral edge that far-end or near-end keep the district and keeps the peripheral edge distinguished overlapping with another.

The particularly preferred embodiment of stopper of the present invention provides near-end and/or far-end to keep the district to show recess, is provided with the support of the end that is used for the bale packing fabric in recess.By in the recess of the near-end of being located at stopper or far-end support being set, the component of stopper is given prominence to septum wall, and this component that has prevented implant constantly contacts with blood.This can produce following advantage, can not exist health that the complication that thromboembolism is reacted or existed to defense mechanism will take place.Especially because expansion plugging device keeps distinguishing in radially exerted pressure damaged, so this stopper can be used for the damaged on a large scale of different hole dimensions with itself being provided with and being fixed on far-end and near-end.

The particularly preferred far-end of stopper of the present invention keeps the district to show that the embodiment of a recess also provides the far-end of stopper further to dispose Connection Element in recess, thus described Connection Element can with catheter abutment.This Connection Element provide stopper of the present invention can recover additional function, this Connection Element is arranged on the stopper so that outstanding septum wall, thereby makes the component of implant not continue to contact with blood.And, be convenient in treating shutoff damaged, implant and location stopper (folding during the implantation in reality) with the Connection Element of catheter abutment.Different stoppers can be contemplated that Connection Element.For example, closed block is feasible, even can be hook/eyelet, the complementary Connection Element interference fit of the relative configurations of itself and conduit.

Another advantageous embodiments provides stopper so to construct so that it is reversibly inside and folded-out, thereby makes this stopper folding with its expanded state under the help of for example transfer catheter.In being attached to this, can imagine that for example, the conduit in the migration process engages with the Connection Element of the far-end that is configured in stopper and makes stopper folding in response to the peripheral operation of conduit.Thereby this stopper can fully reversibly be withdrawn in conduit, makes this stopper remove fully.

Last but be not least important, for stopper especially preferably have the far-end that is arranged on stopper keep in the district or far-end keep in the district or be arranged at least one fabric dummy slider in the central area, it makes this damagedly close fully.This fabric dummy slider is used for closure and remains on breach in the swell diameter of central area and stopper, follows the insertion and the expansion of the stopper in shutoff damaged.For example, on the fabric of this fabric dummy slider attached to the stopper in far-end maintenance district, thereby make it keep stretching in the district at far-end as cloth.The advantage of this design be far-end keep the lateral margin in district to flush with barrier film and seldom foreign body be introduced in patient's the health.For example, this fabric dummy slider is made by terylene.Certainly this also can be envisaged in the stopper or on other material and other location of fabric dummy slider.

Below provide the more fine detail of stopper preferred embodiment of the present invention with quoted figures.

Description of drawings

Fig. 1 is the sketch map of shape memory effect;

Fig. 2 is the sketch map of the molecular mechanism of shape-memory transformation that the semi-crystalline polymer network takes place;

Fig. 3 has described the composite diagram of thermoplastic polyurethane segmented copolymer;

Fig. 4 has described the chemical constitution of the monomer component of thermoplastic polyurethane segmented copolymer;

Fig. 5 has described to have the structure of the diblock or the triblock copolymer of shape memory effect;

Fig. 6 is the monomeric explanation that is used for the covalency shape memory polymer networks;

Fig. 7 has described the example of biodegradable polyester;

Fig. 8 has described the example of biodegradable poly-anhydrides, poly-(aminoacid) and polyamide;

Fig. 9 has described to be used to have the monomer component of the amorphous state polyurethane copolyester polymer network of shape-memory properties;

Figure 10 has described to be used for the monomer component of the biodegradable network of covalency;

Figure 11 has described the polymer segment in biodegradable poly-(right-the dioxy Ketohexamethylene)-polyurethane segmented copolymer;

Figure 12 a, b have described the side isometric view of 1 type PFO stopper;

Figure 13 a, b are the isometric illustration of 1 type PFO stopper;

Figure 14 has described the side view of 2 type PFO stoppers;

Figure 15 has described the side view of 3 type PFO;

Figure 16 has described the top plan view of 3 type PFO stoppers;

Figure 17 a, b have described the routinize side view and the cross-sectional illustration of 4 type PFO stoppers;

Figure 18 a has described to have an X-rayed the enlarged detail of the section of the 1 type stopper (1 type ASD stopper) that is used to stop up atrial septal defect (ASD); This stopper partly elongates and extends the breach of insertion conduit;

Figure 18 b has described the enlarged detail of the section of 2 type stoppers in the perspective conventional embodiment;

Figure 18 c has described the hot harness of perspective polymer line in the enlarged detail of the section of 3 type ASD stoppers of left atrium curve;

Figure 18 d has described to have an X-rayed the enlarged detail of the section of the 4 type ASD stoppers with a class fabric with the type that can compare with 1 type stopper (Figure 19-21);

Figure 19 a has described the front view according to 1 type ASD stopper of Figure 18 a preform shape;

Figure 19 b has described the ASD stopper of elongated shape slightly according to Figure 19 a;

Figure 19 c has described the side view according to the ASD stopper of the further elongated shape of Figure 19 a;

Figure 20 a has described the front view according to 2 type ASD stoppers of Figure 18 b preform shape;

Figure 20 b has described the ASD stopper of elongated shape slightly according to Figure 20 a;

Figure 20 c has described the ASD stopper according to the further elongated shape of Figure 20 a;

Figure 21 a has described the front view according to 3 type ASD stoppers of Figure 18 c preform shape;

Figure 21 b has described the side view of the ASD stopper of elongated shape slightly according to Figure 21 a;

Figure 21 c has described the side view according to the ASD stopper of the further elongated shape of Figure 21 a;

Figure 22 a has described the front view according to 4 type ASD stoppers of Figure 18 d preform shape;

Figure 22 b has described the side view of the ASD stopper of elongated shape slightly according to Figure 22 a;

Figure 22 c has described the side view according to the ASD stopper of the further slightly elongated shape of Figure 22 a;

Figure 23 has described among the ASD of perspective heart the detail drawing according to the ASD stopper lateral section of Figure 21;

Figure 24 has described the enlarged front view of stopper that is used to stop up VSD that forms shape pre-;

Figure 25 has described the side view according to the VSD stopper of Figure 24;

Figure 26 has described the detail drawing of perspective according to the section in the VSD stopper front of Figure 24;

Figure 27 has described from according to being seen exterior view above the VSD stopper of Figure 24;

Figure 28 has described from being seen exterior view below the VSD stopper of Figure 24;

Figure 29 has described another front view that amplifies at the VSD of preform shape stopper;

Figure 30 has described the detail drawing of perspective according to the lateral section of VSD stopper of Figure 29;

Figure 31 has described another front view that amplifies at the VSD of preform shape stopper;

Figure 32 has described the detail drawing of perspective according to the lateral section of VSD stopper of Figure 31;

Figure 33 has described the front view of the amplification of the VSD of another preform shape or PDA stopper;

Figure 34 has described perspective according to the VSD of Figure 33 or the detail drawing of the lateral section of PDA stopper;

Figure 35 has described according to medical stopper perspective view of the present invention;

Figure 36 has described the side view according to the stopper of Figure 35;

Figure 37 has described the top plan view according to the stopper of Figure 35;

Figure 38 has described to be used for the be shaped partial sectional view of molded element of stopper according to Figure 35;

Figure 39 has described according to shown in Figure 35 at the proximal end region perspective view according to medical stopper of the present invention of relevant collar (associated sleeve);

Figure 40 has described the detailed perspective at the section of unfolded heart of patient vessel's center siphunculus and stopper according to Figure 35;

Figure 41 has described to be used for the front view of the amplification of the stopper that PDA stops up;

Figure 42 has described the detail drawing according to the section of the PDA stopper of Figure 41;

Figure 43 has described the top plan view according to the PDA stopper of Figure 41;

Figure 44 has described from being seen plan view below the stopper of Figure 41; And

Figure 45 has described to insert the PDA stopper in the conduit.

The specific embodiment

The present invention relates to a kind of for example stopper of the transdermal catheter guidance of the unusual breach of atrial septal defect (ASD, PFO), interventricular septal defect (VSD), patent ductus arteriosus damaged (PDA) or the like of shutoff that is used for.The present invention also provides a kind of method that is formed a kind of medical stopper by flat or piped synthetic or polymer fabrics.

The two has flat and tubing the predetermined thread that is arranged relative to each other and forms by a plurality of.This tubing has synthetic strand that is different from two groups of substantially parallel spiral thighs, and wherein one group of thigh has and another group burst opposite rotation direction.This fabric also is known on industry as tubular braid.

The braiding shape is mainly used in 2 types (Figure 14) and 3 types (Figure 15) PFO stopper, thus silk/the line of near-end curve by hot harness at near-end 2, specifically in a kind of element of being appointed as the hot support ＂ of ＂ by hot harness.Here heat energy is used for silk is melted in together.

This tubing 10 according to 2 type ASD (Figure 18 b and Figure 20 a-20c) and 3 type stoppers (Figure 18 c, Figure 21 a-21c) similarly mode use, also be used in addition VSD type stopper (Figure 24, Figure 25, Figure 26), with the stopper of Figure 35 and 39 consistent types and last but be not unessential and PDA stopper Figure 41 unanimity.

Use the cited at the beginning additional preferred configuration that can produce this stopper by the weaving method according to No. 10338702 German patent applications on August 22nd, 2003 of JEN.meditec GmbH exploitation, it is economical especially aspect material, and this method that is used to produce this braiding shape material makes PFO and ASD stopper have flat net shape.Medical stopper by this weaving method production comprises PFO, 1 type (Figure 12 a, b and Figure 13 a, b) and 4 types (Figure 17 a, b) type stopper and ASD1 type (Figure 18 a, Figure 19 a-19c) and 4 types (Figure 18 d, Figure 22 a-22c) stopper.

The number that synthetic strand pitch (pitch) and weft yarn (pick) (the upset number on the unit length just) and other factors for example are used for the silk of tubular braid is necessary for numerous important performances of determining stopper.The weft yarn of fabric 10 and pitch are tight more, mean that synthetic strand weaves closely more each other, and this stopper is hard more.Bigger silk density means bigger silk surface, therefore improves the shut-off capacity of stopper.Blood coagulation activity or can be for example be enhanced by applying thrombolytic agent perhaps for example is lowered by lubricious antiprothrombin coating like this.

In the formation of stopper 1 according to the present invention, the tubulose of corresponding size or flat synthetic textiles 10 are inserted into mould, and fiber 10 conforms to the mould cavity in mould.This cavity is provided so that the shape that makes synthetic textiles 10 present required stopper.Synthetic strand end of tubulose or flat synthetic textiles 10 should be fixed in order to avoid wear and tear.Anchor clamps can be used for this end (for example aforesaid 2 type PFO and ASD stopper) and maybe for example welding (for example 3 type PFO and ASD stopper) can be heat-treated in the end that should synthesize thigh.

Under the tubular braid situation, before being inserted mould, molded element can be inserted in the pipe of fabric fabric.This causes that profile can determine more accurately.The clamped or welding when the end of tubulose synthetic textiles, molded element can separately be introduced in the pipe with the synthetic burst bending of hands by fabric 10.This class molded element is used to provide the fully accurately control of final size and by guaranteeing the shape of the stopper that fabric conforms to the cavity of mould.

Can select to be used for the material of molded element, and this molded element can be broken into little block or by removing in the synthetic textiles.Therefore this molded element can be made up of for example fragile material.After this material of heat treatment and the molded element, molded element is broken into little block easily by removing in the synthetic textiles in die cavity.

But modeling tool (molded element) can be used in the whole medical stopper that can accurately determine its shape based on outer collar (may be partitioned into different independent blocks) described herein usually.Because medical stopper is to make by having the synthetic material that is lower than 350 ℃ of fusing points, the molded element of this modeling tool can be by aluminum, tool steel, non-ferrous metal or even titanium or titanium alloy manufacturing.

Yet the specific die cavity that it is pointed out that special molded element will produce specific shape, and can use the molded element of other configuration as requested.If require complicated shape, molded element and mould can have annexing ingredient, comprise that cam connects.For better simply shape, mould can have less element.The number of the element in a given mould and their shape almost only depend on the shape of the required stopper that synthetic textiles will be consistent with it.At relaxed state, the synthetic thigh of this tubular braid shows as confirmable in advance orientation relative to each other.When tubular braid along its axle when being compressed, the shape fabric according to mould in expansion tilts away from axle.In the distortion fabric, the relative orientation of the thread of synthetic textiles changes.The compression mould causes the surperficial consistent of synthetic textiles and cavity.This stopper has predetermined expansible configuration and folding configuration so that it can be by conduit or similarly inserts device and be introduced into.This expansible configuration shape with fabric after being formed on mold surface changes.

In case tubulose or flat synthetic textiles are inserted in the selected mould, thereby fabric is filled with cavity surface in mould, heat treatment then, and then fabric 10 just remains in the mould.The thread of synthetic textiles is recalibrated by heat treatment relative to each other and is formed again, and fabric is consistent with mould thus.The given shape of mould cavity surface is removed and kept to fabric from mould then, promptly constitutes desired stopper now.Heat treatment depends on the certain material of the thread of making synthetic textiles to a great extent, is used for heat treated persistent period and temperature in addition and should selects like this so that fabric is set in its new shape; That is, behind fabric and mould surperficial consistent, thread presents relative relocating.

After heat treatment, its new shape is removed and kept to fabric from molded element.In those occasions of using molded element, remove fabric as mentioned above equally.Heat treated persistent period and temperature seriously depend on the material of thread to be formed, and this is above elaborating.

After stopper 1 was formed the shape of predesignating, it can be used in the treatment patient.Stopper can be chosen according to the various medical care problems that are suitable for treating.This type of stopper will with the application's the above-mentioned type in a kind of consistent.In case choose corresponding stopper, conduit or other insert device and are introduced into patient and are provided with like this so that inserts the end of device and the position that will treat is close to, and for example are directly adjacent to the siphunculus of (or at equal height) the unusual breach in organ.

To insert device can be different shape but should preferably comprise metal shaft and the line of easily bending in its end, this insertion device be used to promote medical stopper by conduit pipe and be positioned in the patient body.When stopper is pushed out the end of conduit, it still is fixed.Be located in the siphunculus inside of unusual breach up to stopper, the axle of conduit just along its axial rotation so that from conduit this stopper of outwarding winding.

As long as this stopper still is connected to conduit, the surgeon can relative to unusual breach forward and oppositely moving this stopper be accurately positioned desired position in siphunculus up to it.Use the screw thread anchor clamps, when being attached to stopper, the surgeon can control this stopper moving outside end of conduit.In case stopper 1 is pushed out conduit, it will spring back to the expanded state that is presented by heat treatment owing to fabric.When that time that springs back to original-shape, it may impact the end of conduit and therefore be pushed into.This may cause the incorrect location of stopper, if when siphunculus between two blood vessels takes place to be positioned same situation, this is especially dangerous.The surgeon can clench this stopper by the screw thread anchor clamps when the location; This stopper will be not can ejection out of control and can accurately be located.

This stopper is folded and is inserted in the breach of conduit.The collapsed shape of this stopper should make it easily to be inserted in the pipe of conduit and can accurately be taken out from end of conduit equally.Therefore for example the ASD stopper can have oval-shaped relatively collapsed shape, and individual components is configured (referring to Figure 18 a-18d) along axle thus.This can be reached in the following way: this stopper is drawn along its axial opposite direction, for example grasp anchor clamps and draw back in case expansible diameter parts to the axle folded inside.

The PDA stopper is running in a similar manner also.It can also be by making it folding so that allow insertion conduit (referring to Figure 45) along its stretching, it is folded and enters itself when drawing in opposite direction.

If this stopper is used to the intravital passage of permanent shutoff patient, this conduit is easily extracted.This stopper remaines in the patient's blood vessel system with shutoff blood vessel or corresponding passage.In some occasions, this stopper may be attached to insertion system makes this stopper be fixedly joined to the end of this insertion device.Before conduit is removed from this system, before taking out conduit and inserting device, perhaps need to take off medical stopper from inserting device.

Though this stopper springs back to its initial inflated configuration (that is, in order to enable to insert the shape that keeps before conduit folding), here must be clear and definite be that it is not always to present the original-shape that it is measured fully.Therefore preferably, for example, this stopper has maximum outside diameter when its inflated configuration, the internal diameter of this maximum outside diameter and the inner chamber that will be attached to unusual breach wherein the same at least big be preferably greater than this internal diameter.When this stopper was suitable for blood vessel or have the unusual breach of little inner chamber, it expanded up to filling up inner chamber.When doing like this, this stopper may take place does not need fully to be expanded to its initial inflated configuration.It still needs suitably to adhere to because it has cut off the inwall of inner chamber and has been fixed on the residue there.

When this stopper is used in patient, form thrombosis on the silk surface.Under the bigger situation of silk density, to such an extent as to the total surface area of the silk increase blood vessel that the thrombosis activity also increases and it adheres in this stopper is with fast relatively speed shutoff.If wish to quicken duration of congestion, many thrombosis devices can be configured in this stopper.

Be introduced into so that for example so-called patent foramen ovale of shutoff (PFO) damaged according to the stopper (stopper 1) of Figure 12-17.For 1 to the 4 type PFO variant of describing here (only synthetic fibers), the case of serious defect also can be in this position treatment.Can mention before August in 2003 JEN.meditec on the 22nd the patent application of series number 10/338,702 in find detailed description by 1 type PFO plugging device of nickel-titanium alloy material molding.

Figure 18-22 has shown the shape of the application's stopper (stopper 1) further, can proofread and correct atrial septal defect (ASD) by it.The stopper (stopper 1) that is presented at Figure 19-22 is that 1-4 type ASD stopper is in frame description loose, when expanded state is not up to the demi-inflation attitude.

ASD is the birth defect of the atrial septum that causes of the structural weakness by the atrial septum.On the atrial septum, exist siphunculus to pass through its blood and flow into left atrium by the right side.More damaged when having, and this is damaged when having from left to right by damaged obvious siphunculus, right atrium and right ventricle overflow and surplus are injected the lung blood vessel of lower resistance.

Sealed and the adult's generation lung atrium hypertension of lung blood vessel.Patient with trouble secondary ASD of sizable siphunculus (ratio of pulmonary's blood flow and system's blood flow is greater than 1.5) preferably in 5 years old, have an operation or at the age when bigger in case diagnosis have an operation at once.Along with the appearance of two-dimensional ultrasonic cardiagraphy and Doppler effect colour developing streamlines pattern, this damaged precise anatomical can realize.Suitable ASD stopper is selected based on damaged size.

The size of ASD plugging device valve with to be directly proportional by the size of shutoff siphunculus.At relaxed state, (Figure 19 is a) respectively by axially-aligned and the cylindrical segment or the central area 4 that are connected to a weak point to such an extent as to synthetic textiles is promptly kept distinguishing 2 and 3 by two fuel plates of molding.The length of cylindrical segment 4 is corresponding to the thickness of atrial septum, and just 2 to 20mm thickness.Proximal plate 2 and distal plate 3 have than the much bigger external diameter of siphunculus so that get rid of the leakage of all stoppers 1, and distal plate 3 is overlapping to a certain extent to it and proximal plate 2 of near-end bending to such an extent as to proximal plate 2 is flat relatively.By the above, the peripheral edge that flicks compressing end plate 3 of stopper 1 is concordant with membranous sidewall.The outward flange of proximal plate 2 leans against membranous another sidewall so that the same manner is oppressed.

The similar aforesaid clamp method in end of the stopper made from tubular metal fabric 10 1 is soldered or be sandwiched in support 5 to stop wearing and tearing.The support 5 that thread is held in together in the end also has the effect (referring to Figure 18) that connects stopper and be inserted into system.Shown in the application in, common columniform support 5 have one at the recess of wire cloth end to stop fabric 10 conversion toward each other.Dispose threading in the recess of support 5, it is provided so that the end that can receive and hold insertion system.

ASD plugging device 1 can use the method for above explanation to be produced to being used for shape of the present invention easily.

Figure 23 has described the lateral detailed section view of ASD plugging device at Figure 21 of the ASD inside of a heart.

Figure 24-28 has shown the different modification of plugging device, is preferred for the situation of thin film VSD.In the form of adjusting in advance, these stoppers 1 have 2 and 3 and parts than minor diameter (central area) 4 that are configured between described two

expansible diameter parts

2 and 3 of two expansible diameter parts (keeping the district), each expansible diameter parts 2 and recess that is protruded to the center by the outer surface of

expansible diameter parts

2 and 3 of 3 configurations, the recess in the end of each tubulose synthetic textiles 10 is provided with anchor clamps 7.

Smaller diameter portion (central area) 4 have with septum wall in the unusual corresponding length of breach.The VSD stopper can be deformed in its expansible shape of adjusting in advance, thereby reduces its cross section, so that be introduced into by the intravital passage of body as mentioned above.The inner surface of expansible diameter parts can be recessed into or bending so that the neighboring can touch each diameter parts in the barrier film.

At least one

diameter parts

2 or 3 smaller diameter portion 4 relatively is arranged to offset.Under the unusual breach situation adjacent with aorta, therefore this stop supportive device or

expansible diameter parts

2 and 3 shutoff aorta after insertion of offset.

Figure 29 and 30 shown two

expansible diameter parts

2 and 3 and the center of smaller diameter portion 4 along the VSD stopper 1 of straight line, anchor clamps (showing clearly) are attached to the end of synthetic textiles 10 and are pulled to the center so that produce flat stopper.These anchor clamps can have inside or the outside threading that is used for fastening insertion device or seal wire (guidewire).This class VSD stopper 1 is preferred for shutoff pars muscularis interventricular septal defect.This VSD stopper is inserted into as mentioned above.

Figure 31 and 32 has shown the Another application form of the stopper 1 in shutoff VSD.Though should be similar to the VSD stopper of Figure 29 and 30 according to the described stopper of Figure 32, also have some difference really: the length of smaller diameter portion 4 is reduced and two

expansible diameter parts

2 and 3 are compressed so that reduce the thickness of each diameter parts.

Figure 33 and 34 has shown and has been used for and Figure 31 and 32 another kind of application forms of describing similar stopper 1.Should can shutoff make patient suffer the patent ductus arteriosus of pulmonary hypertension damaged (PDA) according to the stopper of Figure 33 and 34, two

expansible diameter parts

2 and 3 be formed thin cross section in case not overslaugh by pulmonary vein or aortal fluidic flowing, in addition, smaller diameter portion 4 tapers to a point so that improve around damaged fabric contact area.

PDA comes down to following state: two blood vessels, near aorta and the pulmonary artery the heart normally, and between both cavitys, have siphunculus.In this case, blood will directly flow to another blood vessel by this siphunculus by a blood vessel, and the normal blood flow that blocks patient flows.PDA stopper according to Figure 35 and Figure 36-37 has campanula halleri 3 and the outside leading portion 2 that protrudes.This campanula halleri 3 is suitable to be attached to siphunculus between two blood vessels and leading portion 2 is suitable is positioned at aorta so that hold the main body of stopper in the bypass.The size of body 3 and end 2 can be as requested and the corresponding size coupling of siphunculus.Therefore body 3 can have, for example, usually in its thin central area, the approximately diameter and the about axial length of 25mm of 10mm.

The pedestal of PDA stopper main body will radially expand to the external diameter of leading portion 2, and leading portion 2 has the diameter of the order of magnitude of about 20mm.

Pedestal 4 should have tangible enlarging so that form from the radially tapered shoulder sheet in 3 center, when the PDA stopper is inserted in the blood vessel, this shoulder sheet with will be by the edges abut of the inner chamber of HIGH PRESSURE TREATMENT.Leading portion 2 remain in the blood vessel and apply pressure to body 3 the lower end in case the shoulder sheet lean against on the blood vessel wall.This has stoped stopper to leave original position by siphunculus inside.

The PDA plugging device of application form of the present invention can easily be out of shape surperficial consistent production that makes it with mould according to method described above by making the tubular metal silk fabrics.This fabric is heat-treated so that fix its new shape then.

Because synthetic silk is welded together in proximal end region, thereby use synthetic material to allow to be provided with collar, and then realized simplification according to the PDA device of Figure 39 in proximal end region.

Figure 40 is the accompanying drawing for the PDA stopper of PDA shutoff in heart of patient.This accompanying drawing has shown at one and has extended to stopper in the Pulmonic bypass of ＂ P ＂ by ＂ A ＂ aorta.This stopper is conducted through the PDA of folded state by a conduit.Subsequently, the shoulder sheet be allowed to spring back to it ＂ remember condition ＂ such as its previous heat treatment cause this stopper is released end by conduit, this shoulder sheet should be bigger than the siphunculus inner chamber of PDA.

Draw this stopper a little then so that the shoulder sheet is fixed on the Pulmonic wall of ＂ P ＂.If continue pull catheter, stopper will be attached on the PDA wall, thereby its body 3 is pulled out conduit.Body 3 can expand now.Body 3 like this selected size in case its by friction engagement in the inner chamber of PDA.By the friction between the inner chamber of body 3 and siphunculus, by the shoulder sheet of aortal blood pressure against this stopper, this stopper is maintained at its position on the other hand on the one hand.Thrombosis be formed at short notice in the stopper and stopper on and shutoff PDA.The shutoff of stopper may be quickened further by applying thrombolytic agent, filling polyester fiber or nylon material or weaving more substantial thread as shown here.

Figure 41 to 44 has shown another modification of PDA stopper.This stopper has the

cylinder

3,4 that tapers to a point and by the radially extended shoulder sheet 2 of body end.The end of fabric is pressed into the cavity of main part 3, and anchor clamps are configured in each end of the tubular fabric of stopper, and the whole length by its PDA stopper is shortened and its manipulation is simplified.

It is emphasized that realization of the present invention is not limited to and the accompanying drawing related embodiment, but can realize by not departing from the present invention's a plurality of distortion of included scope here.The full content that above-mentioned narration shown in accompanying drawing, description and claim comprised should be understood that illustrative and be not limited significance.

Claims (according to the modification of the 19th of treaty)

1, a kind ofly be used for the treatment of damaged, the self-expanding medical treatment stopper of unusual breach in the sealing tissue especially of heart of patient, thereby this stopper (1) utilizes conduit system to be introduced into patient body by Wicresoft's mode, comprising: the fabric of fine rule (10); Wherein said fabric (10) manifests the first confirmable in advance shape when stopper is inserted into patient body; And the second confirmable in advance shape under the stopper implanting state; And the fabric of wherein said stopper (10) is to be in contracted state and this fabric (10) is to be in expanded state at second contour shape at first contour shape; And wherein the line of fabric (10) by shape memory polymer composite material form so that this fabric (10) will be by environmental stimuli from interim warpage to permanent shape; And wherein this interim shape is given as first contour shape of fabric (10) and second contour shape that this permanent shape is given as fabric (10), and wherein said environmental stimuli is confirmable inversion temperature.

2, stopper as claimed in claim 1, wherein this inversion temperature is within the scope of room temperature and patient temperature.

3, stopper as claimed in

claim

1 or 2, wherein polymer composites comprises the polymer conversion element; And the interim shape of wherein said fabric (10) is stabilized in below the confirmable inversion temperature based on the characteristic phase transformation of polymer conversion element.

4, stopper as claimed in claim 3, wherein polymer composites is revealed as and has crystalline state and change segmental crystalline state or semi-crystalline polymer network; The interim shape of wherein said fabric (10) is fixed and stablizes by solidifying crystalline state conversion segment when crystalline transition; And wherein inversion temperature is respectively the function that crystallization temperature, crystalline state are changed segmental inversion temperature.

5, stopper as claimed in claim 3, wherein polymer composites is revealed as and has amorphous state and change segmental amorphous polymer network; And the interim shape of wherein said fabric (10) is fixed by solidifying amorphous conversion segment when conversion segment glass transition and stablizes; Inversion temperature is the function of the glass transition temperature of amorphous state conversion chains link section thus.

6, each described stopper of claim as described above, wherein polymer composites comprise can manifest at least two out of phase linearities, the segmented copolymer network is separated; And wherein first is that hard segment forms phase mutually, wherein is used for the physical crosslinking of polymer architecture and determines and stablize that the block that a plurality of hard segments of the permanent shape of described fabric (10) form is formed on polymer; And wherein second is that the conversion segment forms phase mutually, and a plurality of conversion segments that wherein are used for fixing the interim shape of described fabric (10) form block and are formed in the polymer; And wherein forming mutually the transition temperature that hard segment forms phase by the conversion segment is inversion temperature; And the conventional method that can use for example injection moulding or expressing technique on the transition temperature that is higher than hard segment formation phase is set the contour shape of described fabric (10).

7, stopper as claimed in claim 6, wherein polymer composites manifests the Polyurethane Thermoplastic Elastomer of many block structures; And wherein to form be that the 4-butanediol transforms formation by vulcabond especially di-2-ethylhexylphosphine oxide (4-phenyl isocyanate) or hexamethylene diisocyanate and glycol especially 1 to hard segment mutually; And wherein changing segment forms by oligomeric polyether/polyester glycol, especially produces based on OH end capped poly-(oxolane), poly-(6-caprolactone), poly-(ethylene glycol adipate), poly-(ethylene glycol) or poly-(propylene glycol).

8, stopper as claimed in claim 6, wherein the diblock copolymer that is separated of polymer composites manifests amorphous A-block and hemicrystalline B-block; And the glass transition of wherein amorphous A-block constitutes hard segment and forms phase; And wherein the melting temperature of half amorphous B-block is as the inversion temperature that is used for hot shape memory effect.

9, stopper as claimed in claim 8, wherein polymer composites have polystyrene as amorphous A-block and poly-(1, the 4-butadiene) as semi-crystalline state B-block.

10, stopper as claimed in claim 6, wherein polymer composites manifests the center B-block with semi-crystalline state and the triblock copolymer that is separated of two amorphous terminal A-blocks; Wherein A-block formation hard segment and B-block are determined inversion temperature.

11, stopper as claimed in claim 10, wherein polymer composites manifests as the semi-crystalline state of center B-block poly-(oxolane) and as the amorphous poly (2-Jia oxazolin) of far-end A-block.

12, each described stopper of claim as described above, wherein polymer composites comprises polynorbornene, polyethylene/nylon-6-graft copolymers and/or crosslinked poly-(ethylene-co-vinyl acetate) copolymer.

13, each described stopper of claim as described above, wherein polymer composites manifests the covalent cross-linking polymer network, and it is formed with ternary or the polymerization of higher official energy crosslinking additives, polycondensation and/or addition polymerization by bifunctional monomer or big monomer; And wherein give the suitable selection of the ratio of order body, their degree of functionality and cross-linking agent, then the chemistry of this polymer network of Xing Chenging, heat and mechanical performance can be set particularly and selectively.

14, stopper as claimed in claim 13; wherein polymer composites is the covalent polymer network; it comprises by octadecyl acrylate and methacrylic acid and N; the cross-linking agent of the copolymerzation with cross-linking of N '-methylene-bisacrylamide, thus the shape memory effect of polymer composites is based on crystallization stearyl side chain.

15, each described stopper of claim as described above, wherein polymer composites manifests the follow-up covalent cross-linking polymer network that is cross-linked to form by linearity or branched polymer.

16, stopper as claimed in claim 15, wherein crosslinked is to be driven by the thermal fission that a kind of and free radical in the ionizing radiation forms group.

17, any one described stopper of claim as described above, wherein polymer composites comprises at least a biodegradable material.

18, stopper as claimed in claim 17, wherein polymer composites is revealed as the hydrolysis degradable polymer, especially poly-(hydroxy carboxylic acid) or corresponding copolymers.

19, as claim 17 or 18 described stoppers, wherein polymer composites is revealed as the enzyme degradable polymer.

20, as each described stopper of claim 17-19, wherein polymer composites is revealed as biodegradable thermoplastic amorphous polyurethane-copolyester polymer network.

21, as each described stopper of claim 17-20, wherein polymer composites is revealed as biodegradable elastomeric polymer networks, is obtained by oligomer diol and crosslinking with diisocyanate.

22, as each described stopper of claim 17-20, wherein polymer composites is formed as the covalent networks based on oligomerization (6-caprolactone) dimethylacrylate and butyl acrylate.

23, each described stopper of claim as described above, wherein second of the stopper confirmable in advance shape is configured to seal the abnormal structure's breach in the heart of patient; And wherein under its expanded state, stopper (1) demonstration near-end keeps district (2), far-end to keep district (3) and insertion central area (4) between the two; (4) ratio keeps district (2,3) to show littler diameter at near-end and/or far-end to wherein said stopper in the central area.

24, stopper as claimed in claim 23, the end of wherein said fabric (10) line converge at the support (5) in far-end maintenance district (3); And wherein near-end maintenance district (2) manifests the enlarging towards near-end.

25, as claim 23 or 24 described stoppers, stagger with respect to the central horizontal of central area (4) in the center in wherein said near-end and/or far-end maintenance district (2,3).

26, as each described stopper of claim 23-25, wherein near-end and/or far-end keep the inside in district (2,3) to be shown as concave profile.

27, as each described stopper of claim 23-26, the near-end of wherein said fabric (10) keeps district (2) to extend to near-end with opening bell shape.

28, as each described stopper of claim 23-26, the near-end of wherein said fabric (10) keeps district (2) to extend to near-end with the bell shape.

29, as each described stopper of claim 23-26, wherein said stopper (1) shows the profile of barbell shape in its expanded state.

30, as each described stopper of claim 23-29, wherein said central area (4) keep district (2,3) to show less diameter than described near-end and far-end; And the corresponding length of thickness of the unusual breach of wherein said central area (4) demonstration and tissue wall.

31, as each described stopper of claim 23-30, wherein central area (4) to such an extent as to the size of length to be prescribed peripheral edge that far-end or near-end keep district (3,2) overlapping with the peripheral edge that another keeps distinguishing (3,2).

32, as each described stopper of claim 23-31, wherein near-end and/or far-end keep district (2,3) to manifest recess (6), are provided with described support (5) in recess.

33, stopper as claimed in claim 32, wherein at least one Connection Element (7) is configured in the recess (6) in near-end and/or far-end maintenance district (2,3) further; And wherein said Connection Element can with catheter abutment.

Claims

1. one kind is used for the treatment of damaged, the self-expanding medical treatment stopper of unusual breach in the sealing tissue especially of heart of patient, thereby this stopper utilizes conduit system to be introduced into patient body by Wicresoft's mode, comprising: the fabric of fine rule; Wherein said fabric manifests the first confirmable in advance shape when stopper is inserted into patient body; And the second confirmable in advance shape under the stopper implanting state; And the fabric of wherein said stopper is to be in folded state and this fabric is to be in expanded state at second contour shape at first contour shape; And wherein the line of fabric by shape memory polymer composite material form so that this fabric will be by environmental stimuli from interim warpage to permanent shape; And wherein this interim shape is given as first contour shape of fabric and second contour shape that this permanent shape is given as fabric.

2. stopper as claimed in claim 1, wherein said environmental stimuli are confirmable inversion temperature.

3. stopper as claimed in claim 2, wherein this inversion temperature is within the scope of room temperature and patient temperature.

4. stopper as claimed in claim 2, wherein polymer composites comprises the polymer conversion element; And the interim shape of wherein said fabric is stabilized in below the confirmable inversion temperature based on the characteristic phase transformation of polymer conversion element.

5. stopper as claimed in claim 4, wherein polymer composites is revealed as and has crystalline state and change segmental crystalline state or semi-crystalline polymer network; The interim shape of wherein said fabric is fixed and stablizes by solidifying crystalline state conversion segment when crystalline transition; And wherein inversion temperature is respectively the function that crystallization temperature, crystalline state are changed segmental inversion temperature.

6. stopper as claimed in claim 4, wherein polymer composites is revealed as and has amorphous state and change segmental amorphous polymer network; And the interim shape of wherein said fabric is fixed by solidifying amorphous conversion segment when conversion segment glass transition and stablizes; Inversion temperature is the function of the glass transition temperature of amorphous state conversion chains link section thus.

7. stopper as claimed in claim 1, wherein polymer composites comprise can manifest at least two out of phase linearities, the segmented copolymer network is separated; And wherein first is that hard segment forms phase mutually, wherein is used for the physical crosslinking of polymer architecture and determines and a plurality of hard segments of stablizing the permanent shape of described fabric form blocks and are formed on polymer; And wherein second is that the conversion segment forms phase mutually, and a plurality of conversion segments that wherein are used for fixing the interim shape of described fabric form block and are formed in the polymer; And wherein forming mutually the transition temperature that hard segment forms phase by the conversion segment is inversion temperature; And the conventional method that wherein can use for example injection moulding or expressing technique on the transition temperature that is higher than hard segment formation phase is set the contour shape of described fabric.

8. stopper as claimed in claim 7, wherein polymer composites manifests the Polyurethane Thermoplastic Elastomer of many block structures; And wherein to form be that the 4-butanediol transforms formation by vulcabond especially di-2-ethylhexylphosphine oxide (4-phenyl isocyanate) or hexamethylene diisocyanate and glycol especially 1 to hard segment mutually; And wherein changing segment forms by oligomeric polyether/polyester glycol, especially produces based on OH end capped poly-(oxolane), poly-(6-caprolactone), poly-(ethylene glycol adipate), poly-(ethylene glycol) or poly-(propylene glycol).

9. stopper as claimed in claim 7, wherein the diblock copolymer that is separated of polymer composites manifests amorphous A-block and hemicrystalline B-block; And the glass transition of wherein amorphous A-block constitutes hard segment and forms phase; And wherein the melting temperature of the B-block of semi-crystalline state is as the inversion temperature that is used for hot shape memory effect.

10. stopper as claimed in claim 9, wherein polymer composites has polystyrene as amorphous A-block and poly-(1, the 4-butadiene) B-block as semi-crystalline state.

11. stopper as claimed in claim 7, wherein polymer composites manifests the center B-block with semi-crystalline state and the triblock copolymer that is separated of two amorphous terminal A-blocks; Wherein A-block formation hard segment and B-block are determined inversion temperature.

12. stopper as claimed in claim 11, wherein polymer composites manifests as the semi-crystalline state of center B-block poly-(oxolane) and as the amorphous poly (2-Jia oxazolin) of far-end A-block.

13. stopper as claimed in claim 1, wherein polymer composites comprises polynorbornene, polyethylene/nylon-6-graft copolymers and/or crosslinked poly-(ethylene-co-vinyl acetate) copolymer.

14. stopper as claimed in claim 1, wherein polymer composites manifests the covalent cross-linking polymer network, and it is formed with ternary or the polymerization of higher official energy crosslinking additives, polycondensation and/or addition polymerization by bifunctional monomer or big monomer; And wherein give the suitable selection of the ratio of order body, their degree of functionality and cross-linking agent, then the chemistry of this polymer network of Xing Chenging, heat and mechanical performance can be set particularly and selectively.

15. stopper as claimed in claim 14; wherein polymer composites is the covalent polymer network; it comprises by octadecyl acrylate and methacrylic acid and N; the cross-linking agent of the copolymerzation with cross-linking of N '-methylene-bisacrylamide, thus the shape memory effect of polymer composites is based on crystallization stearyl side chain.

16. stopper as claimed in claim 1, wherein polymer composites manifests the follow-up covalent cross-linking polymer network that is cross-linked to form by linearity or branched polymer.

17. stopper as claimed in claim 16, wherein crosslinked is to be driven by the thermal fission that a kind of and free radical in the ionizing radiation forms group.

18. stopper as claimed in claim 1, wherein polymer composites comprises at least a Biodegradable material.

19. stopper as claimed in claim 18, wherein polymer composites is revealed as the hydrolysis degradable polymer, especially poly-(hydroxy carboxylic acid) or corresponding copolymers.

20. stopper as claimed in claim 18, wherein polymer composites is revealed as the enzyme degradable polymer.

21. stopper as claimed in claim 18, wherein polymer composites is revealed as biodegradable thermoplastic amorphous polyurethane-copolyester polymer network.

22. stopper as claimed in claim 18, wherein polymer composites is revealed as biodegradable elastomeric polymer networks, is obtained by oligomer diol and crosslinking with diisocyanate.

23. stopper as claimed in claim 18, wherein polymer composites is formed as the covalent networks based on oligomerization (6-caprolactone) dimethylacrylate and butyl acrylate.

24. stopper as claimed in claim 1, wherein second of the stopper confirmable in advance shape is configured to seal the abnormal structure's breach in the heart of patient; And wherein under its expanded state, stopper shows that near-end keeps district, far-end maintenance to distinguish and insert central area between the two; Wherein said stopper keeps the district to show littler diameter at the central area ratio at near-end and/or far-end.

25. stopper as claimed in claim 24, the end of wherein said fabric line converge at the support in far-end keeps distinguishing; And wherein near-end keeps the enlarging of district's demonstration towards near-end.

26. stopper as claimed in claim 24, stagger with respect to the central horizontal of central area in the center in wherein said near-end and/or far-end maintenance district.

27. stopper as claimed in claim 24, wherein near-end and/or far-end keep the inside in district to be shown as concave profile.

28. stopper as claimed in claim 24, the near-end of wherein said fabric keep the district to extend to near-end with opening bell shape.

29. stopper as claimed in claim 24, the near-end of wherein said fabric keep the district to extend to near-end with the bell shape.

30. stopper as claimed in claim 24, wherein said stopper show the profile of barbell shape in its expanded state.

31. stopper as claimed in claim 24, wherein said central area keeps the district to show less diameter than described near-end and far-end; And wherein said central area shows and the corresponding length of thickness of the unusual breach of tissue wall.

32. stopper as claimed in claim 24, to such an extent as to wherein the size of the length of central area is prescribed peripheral edge that far-end or near-end keep the district and keeps the peripheral edge distinguished overlapping with another.

33. stopper as claimed in claim 24, wherein near-end and/or far-end keep the district to show recess, are provided with described support in recess.

34. stopper as claimed in claim 33, wherein at least one Connection Element is configured in the recess in near-end and/or far-end maintenance district further; And wherein said Connection Element can with catheter abutment.