CN1805718B - Stents - Google Patents

Abstract

The present invention relates to stents for use in the non-vascular and vascular field, which comprise an SMP material.

Description

Support

Technical field

Theme of the present invention is a kind of temporary stent of being made by shape-memory polymer (SMP) that is used for avascular area (non-vascular field) or area vasculosa (vascular field).Described support can minimize by shape memory effect, and can remove by micro-wound surgical operation (minimally invasive surgery).Another theme of the present invention is the implantation of described support and removes and make and programme (program) method.

Background technology

For treating the contraction of pipe plug plug or pipe or behind surgical operation, tubular tissue supporter (support) being inserted in the pipe.Above support is used to make the maintenance of contraction position to open or replace work normally the passing through or discharge in order to recovery body fluid of injured pipe.It is interior with treatment blood vessel blockage or contraction that support also can be inserted blood vessel, and described support makes the contraction position keep proper flow open and recovery blood.

Support is generally the cylindrical structural of being made by a kind of metal gauze (wire coils design), perhaps can be perforated pipe or not perforated pipe (slotted-tube design).The length of conventional bracket is 1cm and 12cm, and diameter can be 1 to 12mm.

There is contradiction aspect the mechanical performance requirement of support.On the one hand, support must apply bigger radial force to supported pipe.But require the support radial compression on the other hand again, thereby can like a cork it be inserted in the pipe, and do not damage tube wall or peripheral organization.

The solution of the problems referred to above is by support is inserted with compressed format, and only installs after arriving the tram.Diameter under the compressive state is less than the diameter of expansion state.The Wicresoft that this method also can be used for support basically removes.But the problem that may exist is that normally used metal material is rule expansion fully always not, and can't fold once more, might damage edge tissues (bordering tissue) like this.

For the Wicresoft of support inserts, set up two kinds of different technology (market report " US peripheral and vascular stent and AAA stent graft market " (Frost ﹠amp; Sullivan), 2001):

-balloon expandable stent (system is made up of sacculus, conduit, support)

-self expandable support (system is formed by inserting sleeve pipe (protective jacket (sheeth)), conduit, support);

The self expandable support is made up of shape-memory material (SM material), and what wherein occur the earliest is metal SM material, for example nitinol (nitinol).Shape memory effect is a kind of effect of the research of extensive concern in recent years, by applying change (this relevant particular content on the one hand that this effect of environmental stimuli can make shape want, but cf. publication, for example " Shape Memory Alloys ", Scientific American, the 281st volume (1979), the 74th to 82 page).Described material can specifically change its shape under the situation that temperature raises.Shape memory effect is activated and increases the diameter of support with " automatically ", and is fixed in the place, use location.

As mentioned above, removing of expandable stent is a difficult problem.If support must be extracted in tube chamber, then might be owing to friction damage peripheral organization, because support is too greatly and have a sharp edges.Therefore, if support must be removed once more, also shape memory effect can be used to reduce the diameter of support.The example of the removable formula implant of being made by shape memory metal (support) is from known in the state of the art: US 6413273 " Method and system fortemporarily supporting a tubular organ "; US 6348067 " Methodand system with shape memory heating apparatus for temporarilysupporting a tubular organ ", US 5037427 " Method of implantinga stent within a tubular organ of a living body and removingsame "; US 5197978 " Removable heat-recoverable tissue supportingdevice ".

Under to the situation of nickel sensitivity, can not use nitinol.This material is also very expensive, and can only programme by complicated method.This programmed method needs higher relatively temperature, and it is impossible therefore programming in vivo.So the SM material is programmed external, that is to say to make it become interim shape.After the implantation, shape memory effect is activated and the support expansion, promptly reverts to permanent shape.So just can not utilize shape memory effect that support is removed once more.A FAQs that not only occurs in the area vasculosa at first is the generation of restenosis (restenosis) in the metal rack.

On the other hand, though the metal rack of being made by other SM material (for example described in the US 5197978) can utilize shape memory effect that support is removed.But the manufacturing of this metal material is very complicated, and the compatibility of tissue neither total energy guarantee.Because the mechanical performance adaptability of support is not enough, inflammation and pain take place through regular meeting.

Temporary stent described in the US 5716410 " Temporary stent and method of use " is a kind of coil of being made by the shape memory plastic material.Have the heating of metal silk in the SMP material.The heating of metal silk links to each other with electronic controller by catheter shaft, and wherein, the tip of the axis is a blank pipe, and be enclosed within coil-end above.If the implant frame of interim expansion shape is heated above inversion temperature (switching temperature) T _Trans, the diameter of coil will reduce.So just can remove support at an easy rate.To such an extent as to the shortcoming of loop construction is that radial force is too little and can't expands tube chamber.On the contact surface among a small circle that the radial force of coil only is distributed in and organizes.Even having the OL danger of local mechanical, this may be because the pressure that the incision tissue is produced causes.And verified, catheter shaft (heating element heater) being connected on the heating of metal silk of implanted coil is the comparison difficulty, because must be enclosed within catheter shaft on one end of coil.

Another example of prior art relates to shape memory polymer stent, this support can be interim compression shape implant, wherein needed permanent size forms at the place, use location by shape memory effect that (S 4950285, and US 6245103, US 6569191, and EP 1033145).Removing of support can realize by other surgical operation or by intravital absorbed.The embrittlement when shortcoming of institute's materials used is its absorption and the generation of particulate matter, and the particulate matter that produces may cause obstruction when device discharges.And, absorb and also may change the structure/character of implant, thereby cause with blood and/or organize incompatible.

Another problem that often occurs be since support to the not enough pain that causes of mechanical adaptability of peripheral organization and the displacement of support.

Goal of the invention

Because support in medically use more and more widely, above-mentioned shortcoming must make great efforts to be overcome.Therefore, need to realize that Wicresoft implants the support that is used for avascular area or area vasculosa that also can steadily remove.The material of support at first should be applicable to corresponding use location, for example considers indefinite mechanical load.Described material should preferably make the support can further functionalized (functionalization), for example by embedding other can be medical material.

For overcoming the shortcoming of prior art, need:

-a kind of simple and easy method of realizing that support Wicresoft implants and removes,

But the support that-a kind of Wicresoft and not damaged remove, preferably by utilizing shape memory effect,

The support of-a kind of tube wall of under vascular applications or non-vascular applications situation, not growing into,

-a kind of surface has the support of blood compatibility (haemocompatible),

The support that has enough mechanical strength/fastnesses during-a kind of the use, even may taking place under the biodegradable situation, its function is also unaffected,

Thereby-a kind of not with the supported support of organizing together growth simply to remove, and described support can also suppress the encapsulation (encapsulation) of biomembranous formation or microorganism,

-a kind ofly make this support and to its method of programming.

Summary of the invention

This purpose can be by solving as defined theme of the present invention in the claim.This support comprises a kind of shape-memory material (SMP material), preferably shows the SMP material of thermal induction or photoinduction shape memory effect.SMP material used in the present invention can be remembered one or both shapes.

This type of support all or has at least in part solved the problems referred to above.Therefore, the invention provides a kind of support of the SMP of comprising material, described support can utilize shape memory effect Wicresoft and use with no damage, this support has histocompatibility and has enough intensity/stability, thereby can remove after required service time, described during this period support is brought into play its effect and is not lost mechanical stability.

Especially, for preventing growing into of biomembranous generation and support, can improve support at non-vascular applications, comprise: suitably select the SMP material segments, surface modification, particularly micro structure are handled (micro-structuring), perhaps suitable coating is perhaps used after implanting the disinfecting substance that can be discharged by support.

And described support also can carry out suitable improvement according to the use location makes it adapt to various requirement, because may have specific (special) requirements at the existence of for example different pH value conditions, enzyme-specific or general microbial environment.By selecting the fragment of SMP material respectively, these requirements can be taken into account.

Description of drawings

Fig. 1 schematically shows the size difference of the permanent shape and the interim shape of support of the present invention.

Fig. 2 illustrates the operating procedure sketch map of inserting and remove support.Light grey part is represented support, and Dark grey is partly represented catheter-balloon, and black part is divided the expression conduit.

Fig. 3 schematically shows the action principle of the support with two kinds of shape memories.

The specific embodiment

In a preferred embodiment, described purpose solves by the SMP support, it is characterized in that:

The support of-permanent shape is installed in the temperature control foley's tube in advance or has on the foley's tube of suitable light source (preferred UV),

The diameter of-interim shape is greater than the diameter (with reference to figure 1) of permanent shape,

-interim shape is used as and organizes supporter,

The inversion temperature of-SMP is 40 ℃ or higher, and Wavelength-converting (switchingwavelength) is 260nm or longer,

The support of-implantation becomes permanent compression shape owing to the SM effect, thereby can be easy to remove by micro-wound surgical operation.

The feasible method of support is inserted and removed in a kind of Wicresoft, may further comprise the steps (Fig. 2):

Insert:

1. will be installed in the temperature control foley's tube in advance or have support on the foley's tube that is fit to light source and insert tubulose in Wicresoft's mode and do not have in the blood vessel organ,

2. can the support of placing be heated above its Trans (at least 40 ℃) (sacculus is full of warm water or heating installation) by conduit,

3. make support become interim shape (expansion) by the following method, promptly further warm water or heating installation injection foley's tube are directly programmed to support at the implantation position place until reaching needed shape/expansion, only that is to say.

By conduit with the stent cools of expansion to be lower than Ttrans (sacculus is full of cold water or cold air) or with wavelength greater than the rayed of 260nm fixing interim shape,

5. shrink sacculus and/or stop irradiation, foley's tube is removed.

Remove:

1. for removing, foley's tube is inserted holder part,

2. conduct heat or rayed directly to contact with support and to guarantee with liquid (water) or gas flaring sacculus,

3. by conduit support is heated above Ttrans or with wavelength less than the rayed of 260nm to activate shape memory effect, make support revert to (less) shape forever,

4. slowly discharge sacculus (drain (water) or gas), its medium-height trestle shrinks (SM effect) and automatically itself is fixed on the sacculus,

5. compressed stent can be cooled off, and remove in the lump with foley's tube.

Perhaps, this method also can be as described below:

Insert:

1. the support that will be installed in advance on the temperature control foley's tube is inserted in the pipe by the method for micro-wound surgical operation,

6. by conduit the support of placing is heated above its T _Trans(at least 40 ℃) (sacculus is full of warm water or heating installation),

7. make support become interim shape (expansion) by the following method, promptly further warm water or heating installation are injected foley's tube until reaching needed shape/expansion; That is to say at the implantation position place and directly support programmed,

By conduit with the expansion stent cools to being lower than T _Trans(sacculus is full of cold water or cold air) with fixing interim shape,

9. the contraction sacculus removes foley's tube.

Remove:

10. for removing, foley's tube is inserted holder part,

11. conduct heat directly to contact with support and to guarantee with liquid (water) or gas flaring sacculus,

12. support is heated above T by conduit _Trans(sacculus is full of warm water or heating installation) makes support revert to (less) shape forever to activate shape memory effect,

13. slowly discharge sacculus (drain (water) or gas), its medium-height trestle shrinks (SM effect) and automatically itself is fixed on the sacculus,

14. compressed stent can be cooled off, and remove in the lump with foley's tube.

The feasible method that the support with photoinduction shape memory was inserted and removed in a kind of Wicresoft may further comprise the steps (Fig. 2):

Insert:

1. will be installed in the support that has on the foley's tube that is fit to light source in advance and insert in the pipe by the micro-wound surgical operation method,

2. make support become interim shape (expansion) by the following method, promptly further (temperature) water or (warming up) gas are injected foley's tube until reaching needed shape/expansion; That is to say at the implantation position place and directly support is programmed.

With wavelength greater than the support of the rayed of 260nm expansion with fixing interim shape,

4. shrink sacculus and/or stop irradiation, foley's tube is removed.

Remove:

5. for removing, foley's tube is inserted holder part,

With liquid (water) or gas flaring sacculus directly contacting and to guarantee rayed with support,

7. the usefulness wavelength to activate shape memory effect, makes support revert to (less) shape forever less than the rayed support of 260nm,

8. slowly discharge sacculus (drain (water) or gas), its medium-height trestle shrinks (SM effect) and automatically itself is fixed on the sacculus,

9. compressed stent and foley's tube are removed in the lump.

For the support of only programming at use location place because it only becomes interim shape in this position, therefore with regard to this on the one hand with regard to, if support will be particularly preferred in the external transition temperature that is heated above before in inserting body.Because this moment, power did not act on support, so the expansion of support does not change.But this heating can make the SMP material of support become soft and flexible.Compare with very firm support before the heating, pre-warmed support can be in this way better, also more easily insert.When particularly using large-scale support and/or must make support pass through severely injured situations such as pipe, this pre-warmed method has significant improvement at support aspect inserting.

In the multiple application that is equipped with support, with the physical location and the required use location of support accurate corresponding be very important.If insert two supports continuously, then this point is even more important, because accurate the placement is even more important for the success of guaranteeing to want.Yet, with regard to conventional bracket, be difficult to the placement of support is proofreaied and correct, because be difficult to solve support folding once more at the place, use location.And support of the present invention is only directly programmed at the place, use location, therefore has significant advantage.Because support of the present invention expansion state in this embodiment is interim form, therefore can realize that simply support dwindles, thereby the support that dwindles once more can be placed once more by activating the SM effect, realize the simple and easy correction of placing.After proofreading and correct, can programme again once more to support of the present invention by the said method step, it is existed as the interim form of organizing supporter.

Correction is inserted and be can be summarized as following method step:

1. the support that will be installed in advance on the temperature control foley's tube is inserted in the pipe.

2. by conduit the support of placing is heated above transition temperature.

3. make support become interim shape (expansion) and reach needed shape (expansion) until it.

By conduit with the stent cools of expansion to being lower than transition temperature with fixing interim state.

After above-mentioned steps was finished, support is still incorrect to be placed if detect, and also can carry out following aligning step:

5. by conduit support is heated above transition temperature, to activate shape memory effect and support is reverted to less shape.

6. slowly discharge sacculus, its medium-height trestle shrinks.

7. the support that is positioned on the sacculus just can correctly be placed.

Repeating step 3 and 4 reapposes support subsequently.Remove conduit then.

For the shape-memory material that shows the photoinduction shape memory effect, can certainly implement trimming process described herein with similar approach.

Support with two kinds of shape memories

The support that carries out twice programming has the following advantages: this support can at first be implanted by micro-wound surgical operation with compressed format, and is fixed in the place, use location by heating.First deformation (for example diameter increase) takes place.Through after the needed time of staying, heated holder to be causing secondary deformation (for example diameter reduces) once more, thereby can support be removed by the method for micro-wound surgical operation at use location place.

Support with two kinds of shape memories can be made by the SMP with following feature: described SMP has covalent networks node (net point) and two transformation segments (switching segment) or two deformation temperatures (transitional temperature) T _Trans, wherein adopt T _Trans1＜T _Trans2, and two inversion temperatures all are higher than body temperature.The permanent shape of covalent networks node decision support, each transformation segment determines interim shape.

In one embodiment, tubular bracket is characterised in that the diameter D of permanent shape _PermLess, the diameter D of the first interim shape _Temp1 greater than D _Perm, the diameter D of the second interim shape _Temp2 less than D _Temp1:D _Perm＜D _Temp1＞D _Temp2.

The diameter of the second interim shape can be identical or different with the diameter of permanent shape: D _Perm=D _Temp2 or D _Perm≠ D _Temp2.

Two programmings of support are made of following method step:

1. support is heated above T _Trans2,

2. be lower than T _Trans2 and be higher than T _TransExpandable stent under 1 the temperature

With stent cools to being lower than T _Trans2 and be higher than T _Trans1 temperature,

4. with support boil down to D _Temp1,

With stent cools to being lower than T _Trans1.

When the support with twice programming is heated above T _Trans1 o'clock, D _Temp1 shape becomes D _Temp2, promptly diameter increases.When being heated above T once more _Tras2 o'clock, diameter was D _Perm, promptly diameter reduces (Fig. 3) once more.

Now the present invention is done further narration.

Support of the present invention comprises a kind of SMP material.Thermoplastic, mixture and network (network) all are suitable for.The composite that SMP and inorganic nanoparticles form also is fit to.Preferably not with the heating element heater embedding to the SMP material.Shape memory effect can be carried out hot activation in the following way: but heat medium, carry out IR or NIR irradiation, apply oscillating electric field or carry out the UV irradiation.

Definition about " support of the present invention comprises a kind of SMP material " should be interpreted as, and support is made up of the SMP material substantially on the one hand, and also can be embedding or the conventional bracket that is coated with the SMP material on the other hand.These two kinds of main structures (construction) have the following advantages.

Mainly the support of being made up of the SMP material adopts the SMP material to determine the mechanical performance of support.Owing to SMP material (with being described) uses for above-mentioned purpose, thereby guaranteed the favorable tissue compatibility at once.And as mentioned above, this support can be implanted and remove by micro-wound surgical operation.The processing of SMP material is also relatively easy, helps lend some impetus to production.At last, the SMP material can be with other material compound or lamination, thereby might be further functionalized.Relevant above-mentioned aspect can be with reference to following narration.

Second feasible in principle embodiment is a kind of support that includes conventional basic framework, and described basic framework for example has " metal mesh shaped structure " or deformable tube.This basic framework is coated with the SMP material or is embedded in wherein.Especially, metal gauze columnar structure confirms that if activate shape memory effect, then the SMP material can produce enough big power, thereby basic framework is deformed.Therefore, this embodiment can combine the advantage performance of conventional bracket and the above-mentioned useful effect of SMP material.Thereby especially, can obtain the very big support of mechanical resistance by means of conventional basic framework.Therefore this embodiment is specially adapted to the high support of mechanical load.

Handle by suitable coating (for example hydrogel coating) or surface micro-structure, the physiological environment at rack surface and place, use location is compatible.On support Design, must consider primary condition according to the use location, for example pH value or micro organism quantity.

Now the material that is suitable for support of the present invention is narrated.

SMP material in the meaning of the present invention is a kind of material that required deformation can take place owing to its chemistry-physical arrangement.Except the permanent shape of reality, this material also has another kind can add thereon shape temporarily.This material is characterised in that following two construction featuress: network node (network point) (physics or covalency) and transformation segment.

SMP with thermal induction shape memory effect has at least one transformation segment, and its deformation temperature is inversion temperature.Transformation segment forms temporary transient crosslink part, and this part is resolved when being heated above deformation temperature, and cooling can form once more the time.Vitrification point T when deformation temperature can be amorphous state _gThe perhaps melt temperature T during crystalline state _mHere be typically expressed as T _TransUnder this temperature, change in shape takes place in SMP.

Be higher than T _TransThe time, material is in amorphous state and has elasticity.If sample is heated above deformation temperature T _Trans, and it is deformed under softish state, be cooled to then and be lower than deformation temperature, then according to solidifying degree of freedom, segment will be fixed as deformation state (programming).The temporary transient crosslink part (non-covalent) that forms makes sample not have can not to recover its original-shape under the situation of plus load.When being heated above deformation temperature once more, these temporary transient crosslink parts are resolved, and sample reverts to its original-shape.By programming again, can produce interim shape once more.The accuracy representing of the original-shape that obtains once more is response rate (resetting ratio).

In the SMP of light conversion, the light reaction group has replaced the effect of transformation segment, and described light reaction group can pass through the mutual reversible connection of rayed.At this moment, realize the programming of interim shape and the formation once more of permanent shape by irradiation, and not necessarily change temperature.

The SMP material of making support that is useful on all can use basically.As an example, can be with reference to material and the manufacture method described in the following application, below application directly belongs in the application's the content by the mode of quoting:

German patent application: 10208211.1,10215858.4,10217351.4,102173050.8,10228120.3,10253391.1,10300271.5,10316573.8.

European patent application: 99934294.2,99908402.3.

SMP material with two kinds of shape memories is in U.S. Pat 6,388, states in 043, and described patent comprises in this application by the mode of quoting.

Below be the conventional bracket material that can in framework of the present invention, particularly in above-mentioned second embodiment, use:

Basically the material that is applicable to the Biostatic of field of medicaments has polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), PVC, Merlon (PC), polyamide (PA), polytetrafluoroethylene (PTFE), polymethacrylates, polymethyl methacrylate (PMMA), poly hydroxy ethyl acrylate (PHEMA), polyacrylate, polyurethane (PUR), polysiloxanes, polyether-ether-ketone (PEEK), polysulfones (PSU), polyethers, polyolefin, polystyrene.

Determined that the material that can be used for avascular area has, for example polysiloxanes (conduit and tubular probe, artificial bladder), PHEMA (artificial bladder) and PA (conduit).

Determined that the material that can be used for the area vasculosa has, for example PUR (artificial blood vessel, cardiac valve), PET (artificial blood vessel, blood vessel coating (coating)), PA (Bicuspid valve), polysiloxanes (cardiac valve), PTFE (pipe implant).

For making support of the present invention, can use thermoplastic and high-elastic.The thermoplastic and high-elastic that is fit to is characterised in that to have at least two deformation temperatures.Higher deformation temperature may be prescribed as the physical network node of decision support permanent shape.The lower deformation temperature that can activate shape memory effect then can relevant (inversion temperature, T with transformation segment _Trans).With regard to the thermoplastic and high-elastic that is fit to, inversion temperature generally is higher than about 3 to 20 ℃ of body temperature.

The example of thermoplastic and high-elastic has segmented copolymer.Preferably, the block (macromolecular diol (macrodiole)) of forming segmented copolymer is by following α, the ω diol polymer is formed, perhaps by the monomeric α of described diol polymer, the ω diol copolymer is formed, described α, the ω diol polymer comprises: gather (6-caprolactone) (PCL), Polyethylene Glycol (PEG), poly-pentadecanolide, poly(ethylene oxide), poly(propylene oxide), polypropylene glycol, PolyTHF, PPDO, polylactide, poly-Acetic acid, hydroxy-, bimol. cyclic ester, poly-(lactide-Acetic acid, hydroxy-, bimol. cyclic ester) (poly (lactide-ranglycolid)), Merlon and polyethers, the molecular weight M of described segmented copolymer _nBe 250 to 500,000g/mol.By means of the difunctionality coupling reagent (particularly aliphatic diisocyanate or aromatic diisocyanates or two acid chlorides (di-acid chloride) or phosgene) that is fit to, two kinds of different macromolecular diols are linked to each other, thereby form molecular weight 500 to 50,000, the thermoplastic and high-elastic of 000g/mol.In the polymer that is separated (phase-segregated polymer), one in each block of above-mentioned polymer is accompanied and at least a heat deflection is arranged (glass transition or melting transition), and irrelevant with other block.

Be preferably based on especially pentadecanolide (PDL) and-segmented copolymer that the macromolecular diol of caprolactone (PCL) and vulcabond form.Transition temperature---be melt temperature this moment---can pass through to change the block length setting of PCL in about 30 to 55 ℃ scope.The physical network node of fixed support permanent shape forms by second crystalline phase of 87 to 95 ℃ of fusing points.The mixture of segmented copolymer also is fit to.Deformation temperature can be set in the target mode by mixing ratio.

For making support of the present invention, also can use polymer network.At least a conversion element that the polymer network that is fit to is characterised in that the covalent networks node and has at least one deformation temperature.The covalent networks node has determined the permanent shape of support.With regard to the polymer network that is fit to, about 3 to 20 ℃ of inversion temperatures usually above body temperature, shape memory effect can be activated under this temperature.

For forming the covalent polymer network, above-mentioned a kind of macromolecular diol is crosslinked by multifunctional coupling reagent.This coupling reagent can be the low molecular weight compound or the polyfunctional poly compound of trifunctional at least.With regard to polymer, can be graft polymers, dissaving polymer or the dendritic structure of the star polymer of at least three arms, at least two side chains.With regard to low molecular weight compound and polymerizable compound, end group must react with glycol.For reaching this purpose, can use isocyanate groups (polyurethane network) especially.

The amorphous polyurethane network that preferred especially triol and/or tetrol and vulcabond form.At molten monomer and have under the situation that the hydroxyl-functional initiator exists, by adding (DBTO) catalyst of dibutyltin oxide (IV), make raceme dilactide and diglycolide generation ring opening copolymer obtain representational star-shaped prepolymers, for example oligomeric [(racemic lactic acid)-copolymerization-glycolate] triol or tetrol.The initiator of ring-opening polymerization makes spent glycol, 1,1,1-three (methylol) ethane or tetramethylolmethane.Similarly, prepare oligomeric (lactic acid-copolymerization-hydroxycaproic ester) tetrol and oligomeric (lactic acid-beta-Hydroxyethoxyacetic acid ester) and [oligomeric (propylene glycol)-block-oligomeric (racemic lactic acid)-copolymerization-glycolate]] triol.Network of the present invention can be easy to obtain by the following method: in solvent, use vulcabond such as dichloromethane, and for example 2,2,4-and 2,4,4-trimethyl cyclohexane-1, the isomeric mixtures of 6-vulcabond (TMDI) transforms prepolymer, and subsequent drying.

And above-mentioned macromolecular diol can also sense turn to α, the ω-divinyl compound that can carry out heat cross-linking or photochemical crosslinking accordingly.Preferably, functionalizedly can realize the covalently bound of macromonomer by the reaction that does not produce by-product.This functionalizedly preferably provided by the ethylenic unsaturated unit especially preferably provided by acrylate group and methacrylate based group, the wherein preferred especially latter.At this moment, especially, can in the presence of suitable alkali,, be converted into α, ω-macromole dimethylacrylate or macromole diacrylate by reacting with corresponding acid chloride.The macromonomer of terminal group functional takes place crosslinked, thereby obtains network.This crosslinked irradiation fused mass that can pass through realizes that described fused mass includes the macromonomer of terminal group functional, also may include the low-molecular-weight comonomer, and related content will further make an explanation hereinafter.Its method condition that is fit to is, under preferred 40 to 100 ℃ of temperature, the rayed molten mixture of preferred 308nm wavelength.Perhaps, if use corresponding initiator system, also can carry out heat cross-linking.

Above-mentioned macromonomer takes place if use one type macromonomer, then to form the network of even structure when crosslinked.If use two types monomer, then obtain AB type network.If functionalized macromonomer and the low molecular weight compound or the oligomeric compound copolymerization that are fit to then can obtain this AB type network.During with acrylate group or the functionalized macromonomer of methacrylate based group, but the chemical compound of suitable copolymerization is low molecular weight propylene acid esters, methacrylate, diacrylate or dimethylacrylate.This compounds preferred acrylate (for example butyl acrylate or Hexyl 2-propenoate) and methacrylate (for example methyl methacrylate and hydroxyethyl methylacrylate).

This can be 5 to 70 weight % of macromonomer and low molecular weight compound network with the amount of the chemical compound of macromonomer copolymerization, preferred 15 to 60 weight %.Be added to the variable access (installation) for the treatment of to carry out in the crosslinked mixture low molecular weight compound by chemical compound with respective amount.The amount of the low molecular weight compound in the access network is corresponding with the amount of crosslinking mixture.

Now the macromonomer that the present invention is used is described in detail.

By changing the mole of macromolecular diol, the network that can obtain to have different crosslink densities (or fragment length) and mechanical performance.Number average mole by the definite covalent cross-linking macromonomer of gpc analysis is preferably 2000 to 30000g/mol, and preferred 500 to 20000g/mol, and preferred especially 7500 to 15000g/mol.Preferably all there is methacrylate based group in the macromonomer of covalent cross-linking at the two ends of its chain.This functionalized macromonomer that makes can promptly take place crosslinked by simply light-initiated (irradiation).

That macromonomer is preferably Biostatic or the very slow polyester macromolecule monomer of degraded is preferably based on-the polyester macromolecule monomer of caprolactone or pentadecanolide especially.Other possible polyester macromolecule monomer is based on lactide unit, glycolide units, to dioxy Ketohexamethylene unit and composition thereof, and have-mixture of caprolactone units, wherein especially preferably have the unitary polyester macromolecule of caprolactone units or pentadecanolide unit.The preferred polyester macromonomer also has poly-(caprolactone-copolymerization-Acetic acid, hydroxy-, bimol. cyclic ester) and poly-(caprolactone-copolymerization-lactide).Deformation temperature can recently be set by the consumption of comonomer.The particularly preferred macromonomer that also has based on the Biostatic of polyethers, Merlon, polyamide, polystyrene, polybutylene terephthalate (PBT) and polyethylene terephthalate.

The macromonomer that the present invention especially preferably uses is to include polyester, polyethers or the Merlon that can connect end group.The particularly preferred polyester that the present invention uses is that its mole is as indicated above based on the polyester of-caprolactone or pentadecanolide.This two ends functionalised, preferably use the functionalized polyester macromolecule monomer product of methacrylate based group, can make by simple method for synthesizing well known by persons skilled in the art.Under the situation of not considering other main polymers compositions of the present invention, this net list reveals the hypocrystalline performance, and its fusing point is the fusing point (can be determined by the dsc measurement method) of polyester components, and promptly this fusing point depends on the kind of used polyester components, and can be controlled by it.Known to for the fragment of caprolactone units, this temperature (T _m1) between 30 to 60 ℃, depends on the mole of macromonomer.

With melt temperature as the preferred network of transition temperature based on poly-(caprolactone-copolymerization-Acetic acid, hydroxy-, bimol. cyclic ester) dimethylacrylate of macromonomer.Macromonomer can be converted into this form, perhaps forms the AB network with the n-butyl acrylate copolymerization.The permanent shape of support is determined by the covalent networks node.This network is characterised in that the fusing point of crystalline phase can pass through, and for example the comonomer ratio of caprolactone and Acetic acid, hydroxy-, bimol. cyclic ester is set in 20 to 57 ℃ of scopes in the target mode.Can be with for example, n-butyl acrylate makes the mechanical performance optimization of support as comonomer.

Obtain as macromonomer with ABA three block dimethylacrylates with vitrification point another preferred network as transition temperature, this network is characterised in that central block B is a poly(propylene oxide), and end-blocks A is poly-(rac-lactide).The non-constant width of the scope of the inversion temperature of amorphous network.

For preparation has the support of two kinds of shape memories, the network with two deformation temperatures is fit to, for example interpenetrating networks (IPN).Covalent networks is based on poly-(the caprolactone)-dimethylacrylate as macromonomer; The IPN component be based on pentadecanolide (PDL) and-macromolecular diol of caprolactone (PCL) and the segmented copolymer of vulcabond.The permanent shape of material is determined by the covalent networks node.Two deformation temperatures---melt temperature of crystalline phase---can be used as the inversion temperature of interim shape.Lower inversion temperature T _TransCan pass through the block length setting of PCL between about 30 to 5 ℃.Higher inversion temperature T _Trans2 between 87 to 95 ℃.

Above-mentioned SMP material is mainly based on polyester or oligoester fragment.Therefore, although stability is enough for great majority are used, yet, decompose because hydrolysis relatively easily takes place ester bond, so this SMP material has the stability of showing individually not enough in physiological environment, particularly for the support that does not keep for a long time at the place, use location.Yet this type of problem can be overcome by the SMP material is comprised based on polyethers or oligo-ether unit or Merlon or the unitary fragment of oligo-ester carbonate.

This type of fragment can based on, for example poly(ethylene oxide), poly(propylene oxide) or polybutylene oxide.

For preparing support of the present invention, can also use the heliosensitivity network.The heliosensitivity network that is fit to is unbodied, and it is characterized in that determining the covalent networks node of support permanent shape.Another feature is to utilize light that but the light reaction component or the unit of inverse conversion take place, and this component or unit determine the interim shape of support.

With regard to photopolymer, employed suitable network has the heliosensitivity substituent group on amorphous segment.When the UV rayed, these groups can form covalent bond mutually.If material deforms, and by the rayed of suitable wavelength X 1, then former network also can take place crosslinked.Because crosslinked generation, material will temporarily be fixed (programming) under deformation state.Because it is reversible that light connects, therefore can shine again, thereby remove crosslinkedly once more with the light of different wave length λ 2, so just can reproduce the original-shape (reproduction) of material.This light-mechanical cycles usually can be optionally repeatedly.The basis of photosensitive material is the large-mesh polymer network, and as mentioned above, this network is transparent for the irradiation that is intended to activate deformation, that is to say to be preferably formed the UV transparent base.According to the present invention, preferred network of the present invention is based on low-molecular-weight acrylate and methacrylate, and can excite polymerization, particularly the C1-C6 ester and the hydroxy derivatives of methacrylic acid, wherein preferred 2-(Acryloyloxy)ethanol, Hydroxypropyl methacrylate, polymethylacrylic acid glycol ester and n-butyl acrylate; Preferred n-butyl acrylate and the hydroxyethyl methylacrylate of using.

A kind of component is used as the comonomer for preparing polymer network of the present invention, and it is crosslinked that the effect of this component is to make fragment to take place.The chemical property of this component depends on monomeric character certainly.

Based on for the preferred network of acrylate monomer, the cross-linking agent that is fit to is bifunctional acrylate's chemical compound for above-mentioned, this chemical compound can with segmental raw material appropriate reaction, thereby can together transform with it.This type of cross-linking agent comprises difunctionality short chain cross-linking agent (short cross linkingagent) (for example diacrylate vinyl acetate), low-molecular-weight difunctionality or multifunctional cross-linking agent, oligomer, straight chain diacrylate cross-linking agent (for example poly-(oxygen ethylene) diacrylate or poly-(oxypropylene) diacrylate) and the branched oligomer or the polymer that have acrylate end groups.

Network of the present invention comprises light reaction component (group) as another kind of component, and its effect also is to control in the target mode activation of deformation.The light reaction group is one can under the preferred UV irradiation (having the second light reaction group), carry out the unit of reversible reaction, thereby cause the generation or the parsing of covalent bond under the rayed that is fit to stimulate.Preferred light reaction group is the group that reversible light dimerization reaction can take place.As the light reaction component in the heliosensitivity network of the present invention, can preferably use different cinnamic ester (CA) and acrylic acid cinnamic ester (CAA).

Known cinnamic acid and derivant thereof pass through to form Tetramethylene. generation dimerization reaction under the UV of about 300nm light.If with the shorter wavelength irradiation of about 240nm, then dimer can also be separated again.Substituent group on the phenyl ring can change absorption maximum, but still is in the UV scope usually.Other can photodimerization derivant be 1, cinnamic acid, cinnamoyloxy group silane (silyl ether of cinnamyl alcohol) that 3-diphenyl-2-propylene-1-ketone (chalcone derivative), cinnamyl acrylic acid, 4-methylcoumarin, different ortho position replace.

The light dimerization reaction of cinnamic acid and like derivatives is [2+2] cycloaddition of two keys, obtains New cyclobutane derivative.This reaction all can take place in E-isomer and Z-isomer.Under rayed, E/Z isomerization and cycloaddition competition are carried out.But the E/Z isomerization can be suppressed during crystalline state.Because isomer has different arrangements each other, can produce 11 kinds of different stereoisomerism products (truxillic acid, truxinic acid) in theory.The bond distance of two keys is about 4 between required two cinnamate group of this reaction

The feature of network is as described below:

In general, network is the higher useful SMP material of recovery value, that is to say after repeatedly carrying out cyclic deformation still to recover original-shape with higher percentage ratio, usually above 90%.Disadvantageous mechanical performance loss does not take place.

For improving blood compatibility, can transform the chemical constitution of the SMP material of the present invention's use, for example by inserting above-mentioned polyethers or oligo-ether unit.

With Polymer Processing is support

For thermoplastic and high-elastic is processed as, for example the support of form (Fig. 1) such as hollow pipe can use all conventional polymer process methods well known by persons skilled in the art, for example injection moulding, extrusion molding, quick shaping method or the like.In addition, can also use manufacture method such as cut.With regard to thermoplastic and high-elastic, can realize different designs: spin and be the cylindrical network of eyed structure for interweaving behind monofilament and the multifibres by following method.

In the process of making polymer network, it should be noted that the permanent shape (injection moulding, then curing) of the generation form of macromonomer cross-linking reaction corresponding to support.Especially, network material of the present invention need be taked special milling method at further processing.The laser of the suitable wavelength of suggestion utilization is bored a hole to tubular body or is cut.By this technology---particularly with CAD and pulse CO ₂Laser or pulsed YAG laser combine---and can not make material be subjected to producing the shape that is up to 20 μ m sizes under the situation of higher thermal load (and the unwanted side reaction that produces from the teeth outwards thus).Perhaps, suggestion obtains the finished product support by deburring (chip removing) processing.

By suitable method with conventional material (on seeing) coating or embedding to the SMP material, to realize second embodiment.

The required mechanical performance of support depends on the use location, and requires to design accordingly.If the support of implanting is subjected to intensive mechanically deform, then need very high pliability so that support unlikely avalanche in motor process.Basically say that " wire coils design " is more suitable.In other darker zone of organ site, the mechanical load of support is less, and this mechanical load is not because distortion produces, but because external pressure is higher.For this reason, the support of Shi Heing must have the feature that can apply high radial power to surrounding tissue.As if " slotted-tube design " is more suitable in this case.The pipe of tape punching can make liquid flow in the support (drain) from surrounding tissue.

Especially, prior art goes wrong in the less blood vessel of diameter through regular meeting, because known brackets is all not enough for the pliability and the adaptability of this blood vessel.Yet; support of the present invention also can be used safely in this blood vessel; because the excellent spring of SMP material, promptly have high resiliency under the low amount of deflection and when expansion is big, having high strength, therefore can under situation, protect blood vessel such as the pulsed motion of tremulous pulse.

Because the drain effect is primary with regard to the support that is used for avascular area, therefore, especially, the design (perforated pipe or reticulate body) that is embedded with the design of conventional basic framework or is made up of the SMP material substantially all is very useful for this support, because the necessary fluid permeability of drain is very simple in above-mentioned design, and show enough mechanical strengths simultaneously.

Support is functionalized

In order to insert support more easily, can be coated with the coating that one deck improves its sliding to support

(for example siloxanes or hydrogel).

Other feasible practice of improving blood compatibility comprises, coating (necessary material is known for those skilled in the art with regard to this purpose) is provided or can carries out the surface micro-structure processing.The surface modifying method that is fit to has for example plasma polymerization and glycerol polymerization.

For by visual diagnostic method more simply with support location, x-ray contrast agent that can be by being fit to (BaSO for example ₄) cover the shape memory plastic material.The another kind of feasible practice is with in tinsel (for example rustless steel) support of packing into.The effect of this tinsel does not lie in stable (and being the location); Its purpose only is to strengthen x-ray imaging.The third feasible practice is to utilize metallic shield, and this metal also has the virus of inhibition, antifungal or kills antibacterial performance (for example nanometer silver) except having stronger x-ray imaging.The another kind of alternative method of this respect is that the opaque chromophore of X ray such as the triiodo-benzene derivant is introduced SMP material itself.

In another embodiment, SMP can be compound with inorganic nanoparticles.The granule of example for making by magnesium or magnesium alloy or Magnet.The granule of being made by carbon also is fit to.Functionalized by this way SMP can heat in oscillating electric field to activate shape memory effect.

Also can add multiple medicable material in the support of the present invention, these materials can help to treat, can suppress the restenosis of support or also can prevent the generation of follow-up disease.Can adopt following material especially:

-anti-inflammatory activity material (for example ethacridine)

-pain relieving material (for example aspirin)

-antibiosis active substance (for example enoxacin, nitrofurantoin)

-antiviral, antifungus active substance (for example elemental silver)

-anticoagulant active material (for example AAS, clopidogrel, hirudin, lepirudin, desirudin)

-inhibition cell active substance (for example sirolimus, rapamycin or sirolimus)

-immunosuppressive activity material (for example ABT-578)

The active substance (for example taxol, paclitaxel, sirolimus, actinomycin D) of-reduction restenosis.

Can add active substance in a different manner in the support of the present invention.

Described active substance can directly cover with plastics, perhaps it is adhered on the support as coating.

This type of support also can be used for field of gene.

If directly cover timbering material with active substance, then active substance both can discharge in the mode of degraded control, also can discharge in the mode of DIFFUSION CONTROLLED.During the degraded sustained release, the speed that active substance diffuses out from matrix is slower than the degradation speed of polymer.At this moment, advantageously, active substance can be embedded in the degradable coating of coated stent, and perhaps direct embedding is to polymer.When DIFFUSION CONTROLLED discharged, the speed that active substance diffuses out from matrix was faster than the degradation speed of polymer.Active substance will discharge from matrix consistently in this case.

As the third feasible practice, active substance can be introduced in the hole of porous shape memory plastic material.After adding active substance, close material hole, then support is placed on above-mentioned active position place.Open the hole by suitable environmental stimuli (heating or rayed), active substance discharges suddenly.With regard to this application, the shape memory plastic material with multiple shape memory is particularly suitable for; At this moment, wherein a kind of effect of shape is the shape that changes support, and the effect of second kind of shape is to open the hole.

If active substance is introduced in the material of support of the present invention, then the support that is released in of active substance is implanted the back generation.The release of active substance comprises the degraded of support; Therefore it should be noted that speed that active substance diffuses out must be lower than the degradation speed of timbering material from support, and the mechanical stability of support is not subjected to the influence of above-mentioned degraded.

In described embodiment, support can comprise, for example multiple SMP material, for example a kind of material that is used to guarantee the stability/fastness of support, and a kind of material that is coated on rack surface and contains active substance.

Especially, can carry out following application:

The ilium support

The length of this support is 10 to 120mm, is generally 40 to 60mm.Described support is used for abdomen area.Because microscler support is relatively more difficult in use, so generally use two supports.Yet, since support of the present invention to have pliability good, and can carry out Wicresoft and implant and remove, therefore support of the present invention can think that infeasible at all length uses with prior art.

The kidney support

At this moment because the high resiliency load of kidney tremulous pulse, the radial force of having relatively high expectations, and the machinery that higher radial force may require to improve support is strengthened." slotted-tube design " or the conventional bracket of using coating or embedding to advance the SMP material all are fit in this case.All can use ray opaque markers thing (marker) in two embodiments.At this moment, guarantee that the accuracy that the safety of catheter-balloon upper bracket installs and insert in the process is even more important.Because biological structure difference needs the length variable and the diameter that adapt with it.And suggestion is used in combination the far-end preventer with speckle filter (plaque filter).

Carotid stents

-can use microscler support to avoid the aforementioned technology that two supports are used in combination in this case.

-also can be used on the vascular bifurcations place

-can optimize and be adjusted to different-diameter

-the network that has a tight mesh is desirable, also is feasible (on seeing), because for avoiding blood clotting to enter brain, may need filtering function (speckle filtering function)

-support is necessary for pressure stability, and pressure may come from the outside, and support avalanche should not take place.

Femoral artery support (hip-knee joint)

Since endovascular high resiliency load, the radial force of having relatively high expectations, and higher radial force may need to improve the machinery reinforcement." slotted-tube design " is (can pass through to use conventional framework) that is fit in this case, can imagine especially and use two microscler supports.

Coronary stent

The design of-wire coils

-not producing frictionally not damaged to introduce the condition that is absolutely necessary, the support of the application of the invention can be realized.

The non-vessel stent design

Main application fields is whole gastrointestinal tract, trachea and esophagus, bile duct, ureter, urethra and fallopian tube.Therefore use the support of different size.When the design support, must consider the different pH value of body fluid and the existence of microorganism separately.

No matter its use location how, non-vessel stent is mainly used in body fluid, as the drain of bile, pancreatic juice or urine.Therefore the perforated flexible pipes design is adopted in suggestion, can safely fluid to be discharged be discharged cavity on the one hand, and can pass through the whole pipe absorption fluids on the other hand.And employed polymeric material must have higher pliability to guarantee comfortable wearing.In order in X ray detects, to be easier to identification, can utilize x-ray imaging material to cover raw material such as barium sulfate, perhaps the opaque chromophore of X ray is passed through, for example suitable monomer polymerization is introduced the SMP material.If use support in having the zone of microorganism, it may be wise then introducing the antibiosis active substance in the material.

Especially can reduce by suitable coating or surface modification at the frequent support crust (encrustation) that takes place of urethral region.

The fixing use location of depending on basically of support.With regard to urethra rack, nearer end is positioned at renal pelvis, is positioned at intravesical or external than far-end.After expansion was finished, nearer end formed ring-type in renal pelvis, thereby guarantees safety supports.

The another kind of support bracket fastened feasible practice is by outside radial force support to be organized to the periphery to press, and perhaps support comprises the anchoring element (anchoring element) that is used for fixing.

With regard to gallbladder or kidney support, the condition of being absolutely necessary is placed and removed to not damaged.Especially, thus must not guarantee in put procedure, to organize and can cause inflammation owing to friction is damaged.But employed support is without any the retaining element (retaining element) of damaged tissue in this zone.

Embodiment

To for example be applicable to that now suitable material of the present invention sets forth as embodiment:

Segmented copolymer embodiment

Segmented copolymer by based on pentadecanolide (PDL) and-macromolecular diol of caprolactone (PCL) and the preparation of two Carbimide .s.The pentadecanolide part (not considering the vulcabond bridging) of PDL definition block copolymer and the poly-segmental molecular weight of pentadecanolide.The caprolactone units data that the PCL definition is independent.

Embodiment	PDL	PCL	Polyurethane molecular weight M n	The E-modulus (70 ℃/MPa)	Hot strength (MPa)
						1	100 weight %/10000g/mol		192000	17	18
2	22 weight %/10000g/mol	78 weight %/10000g/mol	120000	1，4	5
						3	41 weight %/10000g/mol	59 weight %/10000g/mol	196000	3	10

Embodiment	PDL	PCL	Polyurethane molecular weight M n	The E-modulus (70 ℃/MPa)	Hot strength (MPa)
						4	60 weight %/10000g/mol	40 weight %/10000g/mol	176000	7	8
5	80 weight %/10000g/mol	20 weight %/10000g/mol	185000	8，5	7
						6	40 weight %/2000g/mol	60 weight %/4000g/mol	86000	3，5 35(RT)	4，5 23(RT)
7	50 weight %/3000g/mol	50 weight %/10000g/mol	75000	1，5 70(RT)	1，6 24(RT)
						8	40 weight %/3000g/mol	60 weight %/10000g/mol	62000	3 45(RT)	9 30(RT)

Embodiment 8 temperature variant mechanical performances are as follows:

T(℃)	Breaking strain (%)	E-modulus (MPa)	Hot strength (MPa)
				22	900	45	30
37	1000	25	30
				50	1000	12	20
55	1050	7	15
				60	1050	3	10
65	1000	3	10
				70	1000	3	9

75	1000	3	7
				80	1000	1，5	3

Polymer network embodiment

Based on the macromole dimethylacrylate and the n-butyl acrylate generation copolyreaction of glycolide units and-caprolactone units, obtain the polymer network that is fit to.The weight ratio of Acetic acid, hydroxy-, bimol. cyclic ester in the macromole dimethylacrylate is 9 weight % (or being 11 weight % in embodiment 13).The molecular weight of macromole dimethylacrylate is about 10000 to 11000g/mol.

Embodiment	The percentage by weight of butyl acrylate in network by 13C-NMR mensuration	E-modulus (MPa)	Breaking strain (%)
				9	17	11	271
10	28	8.1	422
				11	41	6.4	400
12	56	6.5	399
				13	18	8.8	372

Amorphous polymer network implementation example

Amorphous network is by the preparation of ABA three block dimethylacrylates, and wherein the A representative gathers (rac-lactide) fragment, random poly-(expoxy propane) fragment (M of B representative _n=4000g/mol).

Embodiment	ABA three block dimethylacrylate M n[H-NMR] (g/mol)	Percentage by weight A	T g1 (DSC) (℃)	T g2 (DSC) (℃)	Methacrylated degree (%) **	PD[GPC] ABA three blocks-glycol
							14	6400	38	*	*	77	1.4
15	6900	42	10	36	100	1.1
							16	8000	50	-41	-	64	1.3
17	8500	53	-50	19	56	1.7
							18	8900	55	-59	16	99	1.4
19	10300	61	-60	1	115	2.3

The PD=polydispersity

^*Polymeric sample during detecting, DSC takes place

^*It is because the existence of impurity that numerical value is higher than 100

Detect other hot property and the mechanical performance of the amorphous network of polymer.Testing result is incorporated in the following table.

Embodiment	T g1(℃)	T g2(℃)	22 ℃ of E-modulus (MPa)	22 ℃ of breaking strains (%)	22 ℃ of breaking strains (Mpa)
						14	-51	7	1.24	128	1.43
15	-60 (-43 *)	4 (11 *)	2.02	71	0.94
						16	-46	n.d.	1.38	218	2.18
17	-50	15	4.17	334	5.44
						18	-59 (-45 *)	7 (33 *)	4.54	110	1.89
19	-62 (-49 *)	29 (43 *)	6.37	210	3.92

^*DMTA determines; N.d.---can't detect

Embodiment	Fixed in shape (%)	Response rate (%) after 5 times circulates *	The transition temperature interval (℃)	The transformation initial temperature (℃)	The transformation final temperature (℃)
						14	92.9	87.5	27	-2	25
15	96.0	94.1	37	2	39
						16	92.0	102.2	29	16	45

^*T _gHeat deflection under 2

Heliosensitivity network implementation example

10mmol n-butyl acrylate (BA), cinnamate (0.1-3mmol) and about 2mmol hydroxyethyl methylacrylate (HEMA) are mixed in flask.Add poly-(propylene glycol) dimethylacrylate (M of 1mol%AiBN and 0.3mol% in the mixture _n=560).With syringe mixture is filled up a mould that has two methyl-monosilane luggage carriers (object carrier), polyflon (Teflon) sealing ring that to put into a thickness between described two luggage carriers be 0.5mm.Mixture was 80 ℃ of following polymerizations 18 hours.

Crosslinked mould takes place in it be equivalent to permanent mold.Mixture also can other Any shape carry out crosslinked.

After the polymerization network is taken out from mould, and cover with the 150mL hexane fraction.Add chloroform subsequently gradually.Repeatedly exchange solvent mixture in 24 hours so that low-molecular-weight uncrosslinked component stripping.Clean network with hexane fraction subsequently, and spend the night at 30 ℃ of following vacuum dryings.The example weight that extracts and the ratio of previous weight promptly are equivalent to the content of gel.Below two forms express monomeric consumption and the moisture content in chloroform thereof expand (moisture expansion) and gel content G.

The BA=butyl acrylate; Cinnamate: CA=cinnamic acid; The HEMA=hydroxyethyl methylacrylate; The HEA=2-(Acryloyloxy)ethanol; The HPMA=Hydroxypropyl methacrylate; The HPA=Hydroxypropyl acrylate; PEGMA=gathers (ethylene glycol) methacrylate

In other a series of embodiment, add a part of 2mmol hydroxyethyl methylacrylate (HEMA) in the binary polymer system again, this be because by this comonomer can the controlling polymers network mechanical performance.

The preparation of interpenetrating networks IPN

As mentioned above, in the presence of the AiBN of 0.1 weight %, poly-(propylene glycol) dimethylacrylate (molecular weight 560g/mol) of n-butyl acrylate and 3 weight % (0.6mol%) takes place crosslinked.Subsequently with film bubble (well) in THF with the stripping monomer of usefulness not, and then dry.Then film is steeped in the THF solution (10 weight %) of star light reaction macromonomer, dry more subsequently.The light reaction component that adds in the network is about 30 weight %.

The preparation of star heliosensitivity macromonomer

Poly-(ethylene glycol) (molecular weight 2000g/mol) is dissolved in exsiccant THF and the triethylamine with the star of four arms.For reaching this purpose, splash into the cinnamylidene chloroacetic chloride that slowly is dissolved in dry THF.Stirred reaction mixture is 12 hours under the room temperature, stirs 3 days down at 50 ℃ then.The salt that elimination is settled out, filtrate concentrates and uses the ether wash products.It is 85% that H-NMR records conversion ratio.The UV spectrophotometer shows that the absorption maximum of macromonomer is at the 310nm place before the photoreaction, and absorption maximum is at the 254nm place after the photoreaction.

Detect other hot property and the mechanical performance of the amorphous network of polymer.Testing result is incorporated in the following table.

Numbering	T g(℃)	E-modulus (MPa) under the room temperature	Hot strength σ under the room temperature r(MPa)	Breaking strain ε under the room temperature r (％)
					1A	-40.8	0.54	0.24	45

Numbering	T g(℃)	E-modulus (MPa) under the room temperature	Hot strength σ under the room temperature r(MPa)	Breaking strain ε under the room temperature r (％)
					1B	-34.5	1.10	0.21	15
1C	-21.2	1.77	0.24	10
					2A	-46.1	0.29	1.00	20
2B	-40.3	0.22	0.15	20
					2C	-35.6	0.94	0.18	20
2D	-19.9	1.69	0.42	20
					2E	-10.9	4.22	0.12	35
3A	-30.6	0.56	0.15	30
					3B	-22.8	0.90	0.31	35
3C	-18.6	2.39	0.44	25
					4A	-40.5	0.54	0.18	35
4B	-34.9	1.04	0.24	25
					4C	-24.9	1.88	0.35	25
5A	-38.8	0.36	0.08	20
					5B	-36.5	1.44	0.10	15

5C	-29.6	1.41	0.22	6
					6A	-10.0	1.80	0.34	25
6B	2.2	11.52	2.48	35
					6C	16.1	120.69	9.66	15
7A	-11.4	2.67	0.51	25

5C	-29.6	1.41	0.22	6
					7B	7.3	9.71	2.26	30
7C	12.6	39.78	5.28	25
					8A	-11.9	2.35	0.83	45
8B	6.6	25.02	5.17	50
					8C	10.4	139.9	13.06	15
9A	3.5	1.53	0.53	50
					9B	8.5	14.04	4.55	60
9C	13.9	32.42	6.42	50
					10A	-27.4 25.7	1.40	0.29	30
10B	-23.6 52.8	2.41	0.67	25
					10C	-20.0 56.6	4.74	0.96	25
11A *	-46.5	0.15	＞1.60	＞2000
					12A **Pre-irradiation	-45.0	0.17	1.0-1.5	300-500
12A **After the irradiation	-40.0	0.20	0.5-0.9	30-100

^*The n-butyl acrylate network; The 0.3mol% cross-linking agent; The Argyll Robertson pupil/sign Argyll-Robertson active component

^*IPN; The 0.6mol% cross-linking agent, physical method adds the light reaction component

In circulation light-mechanical experiment, determine shape-memory properties.For reaching this purpose, used thickness is that 0.5mm, length are that 10mm, width are barbell shape punching press (punched-out) sheet of 3mm.

Claims (22)

1. a support comprises shape memory polymer material to be used for avascular area or area vasculosa, and wherein said shape memory polymer material comprises the covalent polymer network.

2. the described support of claim 1, wherein said support design for wire coils or the pipe of slotted-tube design or tape punching.

3. the described support of claim 1, wherein this support comprises the basic structure of being made by the material that is coated with shape memory polymer material.

4. the described support of claim 3, wherein said shape memory polymer material has one or both shape memories.

5. the support described in the claim 1 or 3 further comprises supplemented by additives, and described additive is selected from one or more in x-ray imaging material and the medicative chemical compound.

6. the support described in the claim 1 or 3, wherein shape memory polymer material is selected from the mixture of polymer network, thermoplasticity shape memory polymer material, composite or above-mentioned material.

7. the support described in the claim 1 or 3, wherein shape memory polymer material is selected from the shape memory polymer material with thermal induction shape-memory polymer effect or photoinduction shape-memory polymer effect.

8. claim 1 or 3 described supports, wherein shape memory polymer material has biocompatibility and/or blood compatibility.

9. the support described in the claim 1 or 3, wherein the e-modulus of shape memory polymer material is 0.5 to 50MPa.

10. claim 1 or 3 described supports, wherein the elongation at break of shape memory polymer material is 100 to 1200%.

11. claim 1 or 3 described supports, wherein the answer fixed rate of shape memory polymer material is higher than 90%.

12. the described support of claim 11, wherein the answer fixed rate of shape memory polymer material is higher than 92%.

13. the described support of claim 11, wherein the answer fixed rate of shape memory polymer material is higher than 95%.

14. the described support of claim 11, wherein the answer fixed rate of shape memory polymer material is higher than 98%.

15. claim 1 or 3 described supports, wherein shape memory polymer material repeats five response rates behind heat-mechanical experiment and is higher than 90%.

16. the described support of claim 15, wherein shape memory polymer material repeats five response rates behind heat-mechanical experiment and is higher than 92%.

17. the described support of claim 15, wherein shape memory polymer material repeats five response rates behind heat-mechanical experiment and is higher than 95%.

18. the described support of claim 15, wherein shape memory polymer material repeats five response rates behind heat-mechanical experiment and is higher than 98%.

19. the described support of claim 7, wherein network comprises caprolactone units, pentadecanolide unit, ethylene glycol unit, propylene glycol unit, lactic acid units and/or glycolic unit.

20. claim 1 or 3 described supports, wherein network is made up of crosslinked caprolactone macromonomer.

21. prepare the method for each described support in the aforementioned claim, comprise the permanent shape that makes macromonomer generation cross-linking reaction and form described support.

22. a tool set comprises each described support in the claim 1 to 20, also comprises foley's tube.

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