CN1805763A - Biodegradable stents - Google Patents
Biodegradable stents Download PDFInfo
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- CN1805763A CN1805763A CN 200480016573 CN200480016573A CN1805763A CN 1805763 A CN1805763 A CN 1805763A CN 200480016573 CN200480016573 CN 200480016573 CN 200480016573 A CN200480016573 A CN 200480016573A CN 1805763 A CN1805763 A CN 1805763A
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- Prior art keywords
- support
- smp
- described support
- shape
- tube
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/16—Materials with shape-memory or superelastic properties
Abstract
The invention relates to a biodegradable stent, made from an SMP material, for application in vascular or non-vascular regions.
Description
Technical field
Theme of the present invention is a kind of temporary stent of being made by biodegradable shape memory polymeric (SMP) that is used for avascular area (non-vascular field) or area vasculosa (vascular field).Described support can pass through micro-wound surgical operation (minimally invasivesurgery) to be implanted with compressed format, and utilizes shape memory effect to reach required size at the place, use location.Described support decomposes gradually by biodegradation, thereby needn't carry out the surgical operation that other removes support.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.
US 4950258 has described a kind of pressor device that is used to expand.This device is by making based on the biodegradable polymer of levorotatory lactide and/or Acetic acid, hydroxy-, bimol. cyclic ester, and exists with the form of coil or pipe.Because shape memory effect can blood vessel dilating thereby cause diameter to increase.The shortcoming of institute's materials used is the embrittlement in the degradation process and the generation of particulate matter, and the particulate matter that produces may cause vascular occlusion when device discharges.
EP 1033145 has also described a kind of Biodegradable scaffold of being made by shape-memory polymer that is used for blood vessel, lymphatic vessel, gallbladder or ureter.This support is by based on levorotatory lactide, Acetic acid, hydroxy-, bimol. cyclic ester, 6-caprolactone, constitute the homopolymer of dioxy Ketohexamethylene or plutonium carbonate propyl ester or the silk thread of copolymer or its mixture.Silk thread interweave for monofilament or multifibres to form eyed structure.Utilize shape memory effect to increase stent diameter and to be fixed in the place, use location.Inversion temperature is not for being higher than 70 ℃ vitrification point.Can be added to active substance or diagnostic agent (diagnostics) among the SMP or can coat the surface.
US 5964744 has described and a kind ofly has been used for urogenital tract or gastrointestinal implant by what the polymerization shape-memory material that comprises hydrophilic polymer was made, as pipe and conduit.Absorbed moisture in aqueous medium, thereby softening and generation alteration of form.Perhaps, material is by thermoplastic.In urethra rack, above-mentioned shape memory effect is used to make the flat end of support in use location place's (for example kidney or bladder) bending.Thereby urethra rack is fixed on the place, use location, so that support is not shifted under the situation of tissue wriggling.
WO 02/41929 has described a kind of tubular bulb implant with shape memory, and this implant also is suitable as for example gallbladder support.Material is the fatty poly-ester carbonate based thermoplastic polyurethane with biological stability.
The shortcoming of institute's materials used is that described material is not biodegradable in the prior art.Must in second operation, implant be removed in body.
But US 6245103 has described a kind of self expandable braided wires support of bio-absorbable.Apply outer radial power and make the support compression.Support is installed on the conduit under compressive state, and fixes with the outer sleeve of tightening.If support is separated from this layout, then diameter can increase automatically owing to the restoring force of elastomeric material.This is not by the activated shape memory effect of environmental stimuli (for example temperature rising).
US 6569191 has described a kind of self expandable support of biodegradable plait.Several biodegradable elastomeric polymer reeds are sticked to outside the support.This support has shape-memory properties.When being heated to body temperature or absorbing moisture, support shrinks.Therefore support also can shrink; The diameter of support increases simultaneously.Elastic spring has increased the outside radial force of support.This reed is by for example making based on the shape-memory polymer of lactic acid and/or glycolic.
The employed Biodegradable material of the prior art material of hydrolysis (promptly be generally can) partly shows the problem of degradation characteristic.When taking place, degraded produces small particle with potential hazard.These particulate matters may blocking channel or pipe (for example urethra).And degraded also may change the structure/character of implant to a certain extent, thereby causes itself and 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,
Do not influence the support of peripheral organization during-a kind of the degraded, simultaneously in required service time, can guarantee enough mechanical strengths, and catabolite do not produce any negative effect,
-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), and preferred a kind of biodegradable 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 shape memories.Preferred embodiment defines in independent claims.
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 insert with no damage, this support has histocompatibility and blood compatibility aspect degradation characteristic, and have enough stability/intensity, thereby when degraded takes place, also show enough stability.Especially, this type of support by material preparation used in the present invention shows no particulate matter degradation characteristic.This point is extremely important, because the particulate matter that produces in the degradation process may cause such as problems such as ureter obstruction or damages.Yet these problems do not appear in support of the present invention, because described support exists with the form of hydrogel particle thing, this particulate matter is softness but also flexible not only, therefore the problems referred to above can not occur.
Before support is in being positioned over body, must exist, therefore must under enough low temperature, preserve in the mode of fully avoiding shining with interim shape, also should be like this in transportation, to prevent the unexpected activation of shape memory effect.
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 introducing 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 known method that support is programmed (with reference to US 5591222).
The specific embodiment
In a preferred embodiment, described purpose solves by the SMP support, it is characterized in that:
The support of-interim shape is installed in the temperature control foley's tube in advance or has on the conduit that is fit to light source,
The diameter of-interim shape is less than the diameter (referring to Fig. 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 the interim shape of-compression can be implanted by the micro-wound surgical operation method, and only obtains desirable permanent shape by the SM effect in the target mode at the place, use location.
-can support be heated to its inversion temperature or be heated above inversion temperature by thermal source or IR or NIR rayed or the method that applies oscillating electric field.
-biodegradable SMP material being used for support, thus needn't subsequently support be removed.The feasible method of support is inserted by a kind of Wicresoft, may further comprise the steps (Fig. 2):
1. will be installed in support on the temperature control foley's tube and insert tubulose by the method for micro-wound surgical operation and do not have in the blood vessel organ,
2. by conduit the support of placing is heated above its T
Trans(at least 40 ℃) (sacculus is full of warm water (liquid) or heating installation) is perhaps with the described support of light source irradiation that is lower than 260nm.The support expansion.
3. support is existing exists (expansion) with permanent shape, foley's tube can be removed.
The method (Fig. 3) that support of the present invention is programmed
1. in programming process, make the diameter of support of the present invention less than green diameter.For reaching this purpose, use a kind of suitable instrument, as shown in Figure 3.This programming tool is made by thermally-stabilised parts, and these parts are by having two different-diameter (ID
1And ID
2) pipe form: this moment ID
1＞ID
2
2. the support of (permanent shape) of will not programming is inserted the instrument left part.The outer diameter D S1 of support to be programmed should only be slightly less than the inner diameter, ID 1 of instrument.
3. the instrument of Fig. 3 is heated above the temperature of Ttrans.
4. the support that utilizes seal wire (guide wire) or lead (guide thread) will be heated above the Ttrans temperature is pushed in the right side area of instrument.Thereby make the external diameter of support be reduced to DS2, obtain its interim shape.
5. the instrument with Fig. 3 is cooled to the temperature that is lower than Ttrans.Support bracket fastened thus interim shape.
6. utilize seal wire or lead will be cooled to the support that is lower than the Ttrans temperature and from instrument, take out, and it can be installed on the suitable conduit.
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 biodegradable SMP and degradable 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, support is made up of the SMP material substantially on the one hand, and support also can have by biodegradable plastic material and makes on the other hand, embedding or be coated with the basic framework of SMP material.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 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.And, use basic framework can reduce the consumption of SMP material, help saving cost.
If basic framework is made up of metal material, then should preferred biodegradable metal, for example magnesium or magnesium alloy.
This type of support of the present invention can be realized the safety placement of support, and has compatible degradation characteristic.Perhaps, the characteristic that shows after the support placement of the present invention is consistent with three-phase model (3-phasemodel) usually.
The expection of support is used and has been determined its design, for example surface composition (micro structure is handled (micro-structuring)) or have coating or the like.
Following embodiment is feasible in principle.
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.
By endotheliocyte (endothel cell) surface settlement (settlement) takes place then, corresponding surface modification (for example coating) may help the generation of described surface settlement.In this way, support is covered lentamente by endotheliocyte.
With regard to intravascular stent, handle the rack surface that forms blood compatibility by suitable coating (for example hydrogel coating) or surface micro-structure, thereby support was promptly fully contacted with blood in the short period after placement and do not influence body.Subsequently, surface settlement takes place as mentioned above, support is absorbed lentamente by tube wall thus.
The last hydrolytic degradation that takes place is usually degraded when support contacts with soft tissue, but because above-mentioned degradation characteristic (no particulate matter degraded, the influence that mechanical stability can not be degraded in a long time), described support still has required supporting role.
Perhaps, support still is retained in outside the endodermis after placing, and this can realize selection of for example Biao Mian selection, SMP material segments or the like by suitable method.
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 architectural feature characteristics: 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
Trans
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.
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).
Macromonomer is preferably the polyester macromolecule monomer, is preferably based on the polyester macromolecule monomer of 6-caprolactone especially.Other possible polyester macromolecule monomer is based on lactide unit, glycolide units, to dioxy Ketohexamethylene unit and composition thereof, and has the unitary mixture of 6-caprolactone, wherein especially preferably has the polyester macromolecule unit of caprolactone units.The preferred polyester macromonomer also has poly-(caprolactone-copolymerization-Acetic acid, hydroxy-, bimol. cyclic ester) and poly-(caprolactone-copolymerization-lactide).Deformation temperature and degradation speed can recently be set by the consumption of comonomer.
The macromonomer that the present invention especially preferably uses is to include the polyester that can connect end group.The particularly preferred polyester that the present invention uses is the polyester based on 6-caprolactone or pentadecanolide, and its mole is as indicated above.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 is based on pentadecanolide (PDL) and the macromolecular diol of 6-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 ℃.
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.
Because above-mentioned material is based on aliphatic polyester, therefore employed SMP material hydrolyzable is also biodegradable.Beat allly be, verified this material is degraded (being that catabolite is nontoxic) in biocompatible mode on the one hand, and the mechanically stable of support is still kept in degradation process simultaneously, thereby guarantees the functionalized enough of support.
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.
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.
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.
Support is functionalized
In order to insert support more easily, can be coated with the coating (for example siloxanes or hydrogel) that one deck improves its sliding to support.
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 biodegradable 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 active substance is introduced in the hydrophilic coating, then as long as support carries out is that DIFFUSION CONTROLLED discharges, then described active substance will be released.It should be noted that speed that active substance diffuses out must be higher than the degradation speed of timbering material from hydrophilic coating.
If active substance is introduced in the material of support of the present invention, then being released in the degradation process of active substance taken place, may support covered by endotheliocyte and with take place after soft tissue contacts.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.
For intravascular stent, following content is suitable for:
If active substance is introduced in the hydrophilic coating, then as long as support contacts described active substance with mobile blood and will be released.It should be noted that speed that active substance diffuses out must be higher than the degradation speed of timbering material from hydrophilic coating.
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.In this case " slotted-tube design " be fit to.Can use in this embodiment ray opaque markers thing (marker).At this moment, guarantee that the accuracy that the safety of catheter-balloon upper bracket installs and insert in the process is very 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.In this case " slotted-tube design " be fit to, 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 is by macromolecular diol and the preparation of two Carbimide .s based on pentadecanolide (PDL) and 6-caprolactone (PCL).Pentadecanolide part (not considering vulcabond bridge chain) in the 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 %/ | 78 weight %/ | 120000 | 1,4 | 5 |
| 10000g/mol | 10000g/mol | ||||
| 3 | 41 weight %/10000g/mol | 59 weight %/10000g/mol | 196000 | 3 | 10 |
| 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 glycolide units and unitary macromole dimethylacrylate of 6-caprolactone and n-butyl acrylate generation copolyreaction, 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 destination carrier 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.
| Numbering | The content of monomer of mixture (mmol) | Q (％) | G (％) | |||||
| BA | HEMA -CA | HEA-CA | HPMA- CA | HPA- CA | PEGMA CA | |||
| 1A | 10 | 0.25 | - | - | - | - | 720 | 97.2 |
| 1B | 10 | 0.5 | - | - | - | - | 550 | 94.9 |
| 1C | 10 | 1 | - | - | - | - | 400 | 91.6 |
| 2A | 10 | - | 0.1 | - | - | - | 620 | 89.0 |
| 2B | 10 | - | 0.25 | - | - | - | 900 | 96.2 |
| 2C | 10 | - | 0.5 | - | - | - | 680 | 95.7 |
| 2D | 10 | - | 1 | - | - | - | 1320 | 96.5 |
| 2E | 10 | - | 2 | - | - | - | 1320 | 96.5 |
| 3A | 10 | - | - | 0.25 | - | - | 950 | 98.7 |
| 3B | 10 | - | - | 0.5 | - | - | 650 | 93.4 |
| 3C | 10 | - | - | 1 | - | - | 450 | 98.4 |
| 4A | 10 | - | - | - | 0.25 | - | 830 | 95.9 |
| 4B | 10 | - | - | - | 0.5 | - | 700 | 98.1 |
| 4C | 10 | - | - | - | 1 | - | 550 | 94.3 |
| 5A | 10 | - | - | - | - | 0.25 | 600 | 98.2 |
| 5B | 10 | - | - | - | - | 0.5 | 550 | 97.3 |
| 5C | 10 | - | - | - | - | 1 | 530 | 92.4 |
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.
| Numbering | The content of monomer of mixture (mmol) | Q (％) | G (％) | ||||||
| BA | HEMA | HEMA-CA | HEA-CA | HPMA-CA | HPA-CA | PEGMA -CA | |||
| 6A | 10 | 2 | 1 | - | - | - | - | 370 | 95.5 |
| 6B | 10 | 2 | 2 | - | - | - | - | 350 | 99.2 |
| 6C | 10 | 2 | 3 | - | - | - | - | 420 | 96.8 |
| 7A | 10 | 2 | - | 1 | - | - | - | 390 | 98.5 |
| 7B | 10 | 2 | - | 2 | - | - | - | 300 | 92.8 |
| 7C | 10 | 2 | - | 3 | - | - | - | 250 | 96.4 |
| 8A | 10 | 2 | - | - | 1 | - | - | 240 | 94.4 |
| 8B | 10 | 2 | - | - | 2 | - | - | 310 | 92.3 |
| 8C | 10 | 2 | - | - | 3 | - | - | 310 | 92.9 |
| 9A | 10 | 2 | - | - | - | 1 | - | 450 | 94.7 |
| 9B | 10 | 2 | - | - | - | 2 | - | 360 | 82.7 |
| 9C | 10 | 2 | - | - | - | 3 | - | 380 | 80.2 |
| 10A | 10 | 2 | - | - | - | - | 1 | 1300 | 83.4 |
| 10B | 10 | 2 | - | - | - | - | 2 | 1450 | 83.8 |
| 10C | 10 | 2 | - | - | - | - | 3 | 2150 | 84.8 |
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 |
| 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 |
| 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.
Narrated the example of the shape-memory polymer with two kinds of shape memories among the US 6388043, described patent comprises in this application by the mode of quoting.
Claims (14)
1. a support includes biodegradable SMP material to be used for avascular area or area vasculosa.
2. the described support of claim 1, wherein this support comprises the basic structure of biodegradable plastic material or is coated with the basic structure of the degradation material of SMP material.
3. the described support of claim 2, wherein the degradable metal is the composite of magnesium alloy, pure magnesium or magnesium or magnesium alloy and biodegradable polymers.
4. each described support further comprises supplemented by additives in the aforementioned claim, and described additive is selected from x-ray imaging material and medicative chemical compound.
5. at least one described support in the aforementioned claim, wherein the SMP material is selected from polymer network, thermoplasticity SMP material, composite or mixture.
6. at least one described support in the aforementioned claim, wherein the SMP material be selected from have thermal induction SMP effect, the SMP material of photoinduction SMP effect and/or wherein the SMP material have biocompatibility and/or have blood compatibility and/or wherein the SMP material list reveal no particulate matter degradation characteristic.
7. the described support of claim 5, wherein network comprises caprolactone units and/or pentadecanolide unit.
8. the described support of claim 7, wherein network is made up of crosslinked caprolactone macromonomer.
9. each described support in the aforementioned claim, its medium-height trestle also comprises face coat.
10. the described support of claim 9, wherein face coat is selected from the coating of improving blood compatibility.
Each requires the method for described support in the aforementioned right 11. prepare, and comprises that be support by extrusion molding, rubbing method, metal injection molded method or weaving method with SMP materials processing.
12. a tool set comprises at least one described support in the claim 1 to 10, also comprises the temperature control foley's tube and/or has the foley's tube of optical fiber.
13. the method for Wicresoft's implant frame may further comprise the steps:
-each described support in the claim 1 to 10 is positioned over the temperature control foley's tube or has on the foley's tube of optical fiber, wherein the SMP material has two kinds of shape memories and wherein described material is programmed for two kinds of shapes, wherein compares first kind with second kind of shape and is shaped as bigger tubular of diameter
-will place in this way be placed on the desired location place, wherein the SMP material exists with second kind of shape,
-by thermal medium being inserted in the conduit, perhaps introduce the light (preferred UV light) that is fit to wavelength with heated holder,
-activate the SMP effect to make support become first kind of shape,
-remove foley's tube.
14. the method for Wicresoft's implant frame may further comprise the steps:
-each described support in the claim 1 to 10 is positioned over the temperature control foley's tube or has on the foley's tube of optical fiber,
-will place in this way be placed on the desired location place
-by thermal medium being inserted the light (preferred UV light) that is fit to wavelength in the conduit with heated holder or introducing
-activate the SMP effect to make support become permanent shape
-remove foley's tube.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10326782.4 | 2003-06-13 | ||
| DE10326778.6 | 2003-06-13 | ||
| DE10326782 | 2003-06-13 | ||
| DE10357744.0 | 2003-12-10 | ||
| DE10357747.5 | 2003-12-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1805763A true CN1805763A (en) | 2006-07-19 |
Family
ID=33495034
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200480016573 Pending CN1805763A (en) | 2003-06-13 | 2004-06-09 | Biodegradable stents |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1805763A (en) |
| DE (1) | DE10357747A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101817915A (en) * | 2010-04-01 | 2010-09-01 | 四川大学 | Poly (p-dioxanone)/polytetrahydrofuran multi-block copolyether ester with shape memory function and preparation method thereof |
| CN105073143A (en) * | 2013-02-08 | 2015-11-18 | 恩多沙普公司 | Radiopaque polymers for medical devices |
| CN105101913A (en) * | 2013-03-13 | 2015-11-25 | 雅培心血管系统有限公司 | Short pulse laser machining of polymers enhanced with light absorbers for fabricating medical devices such as stents |
| CN105907059A (en) * | 2016-04-29 | 2016-08-31 | 哈尔滨工业大学 | Shape memory composite based plugging device, and manufacture method and application method thereof |
| WO2022120902A1 (en) * | 2020-12-11 | 2022-06-16 | 深圳先进技术研究院 | Bone repair scaffold and preparation method therefor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8172897B2 (en) | 1997-04-15 | 2012-05-08 | Advanced Cardiovascular Systems, Inc. | Polymer and metal composite implantable medical devices |
| US6240616B1 (en) | 1997-04-15 | 2001-06-05 | Advanced Cardiovascular Systems, Inc. | Method of manufacturing a medicated porous metal prosthesis |
| US10028851B2 (en) | 1997-04-15 | 2018-07-24 | Advanced Cardiovascular Systems, Inc. | Coatings for controlling erosion of a substrate of an implantable medical device |
| DE102005003188A1 (en) | 2005-01-20 | 2006-07-27 | Restate Patent Ag | Medical implant made of an amorphous or nanocrystalline alloy |
| DE102005056529A1 (en) * | 2005-11-28 | 2007-05-31 | Mnemoscience Gmbh | Compressible tubular material support or stent for insertion into vessels to be supported has tube folded one or more times in its longitudinal axis in temporary form of shape memory material |
| DE102005056532A1 (en) * | 2005-11-28 | 2007-05-31 | Mnemoscience Gmbh | Method for removal of tubular tissue supports e.g. stents from human or animal hollow organs, involves heating of tissue support to temperature below transition temperature, till softening |
| US20070225799A1 (en) * | 2006-03-24 | 2007-09-27 | Medtronic Vascular, Inc. | Stent, intraluminal stent delivery system, and method of treating a vascular condition |
| WO2007136969A2 (en) * | 2006-05-16 | 2007-11-29 | Medtronic Vascular, Inc. | Bioabsorbable magnesium-reinforced polymer stents |
| US9265866B2 (en) | 2006-08-01 | 2016-02-23 | Abbott Cardiovascular Systems Inc. | Composite polymeric and metallic stent with radiopacity |
| DE102008040786A1 (en) * | 2008-07-28 | 2010-02-04 | Biotronik Vi Patent Ag | Biocorrodible implant with a coating containing a drug-carrying polymer matrix |
| DE102008040787A1 (en) * | 2008-07-28 | 2010-02-04 | Biotronik Vi Patent Ag | Biocorrodible implant with a coating containing a hydrogel |
-
2003
- 2003-12-10 DE DE10357747A patent/DE10357747A1/en not_active Withdrawn
-
2004
- 2004-06-09 CN CN 200480016573 patent/CN1805763A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101817915A (en) * | 2010-04-01 | 2010-09-01 | 四川大学 | Poly (p-dioxanone)/polytetrahydrofuran multi-block copolyether ester with shape memory function and preparation method thereof |
| CN101817915B (en) * | 2010-04-01 | 2012-05-02 | 四川大学 | Poly (p-dioxanone)/polytetrahydrofuran multi-block copolyether ester with shape memory function and preparation method thereof |
| CN105073143A (en) * | 2013-02-08 | 2015-11-18 | 恩多沙普公司 | Radiopaque polymers for medical devices |
| CN105101913A (en) * | 2013-03-13 | 2015-11-25 | 雅培心血管系统有限公司 | Short pulse laser machining of polymers enhanced with light absorbers for fabricating medical devices such as stents |
| CN105101913B (en) * | 2013-03-13 | 2017-09-05 | 雅培心血管系统有限公司 | The enhanced polymer short-pulse laser processing of use light absorber for manufacturing medical treatment device such as support |
| CN105907059A (en) * | 2016-04-29 | 2016-08-31 | 哈尔滨工业大学 | Shape memory composite based plugging device, and manufacture method and application method thereof |
| CN105907059B (en) * | 2016-04-29 | 2017-12-01 | 哈尔滨工业大学 | Plugging device and its methods for making and using same based on composite material of shape memory |
| WO2022120902A1 (en) * | 2020-12-11 | 2022-06-16 | 深圳先进技术研究院 | Bone repair scaffold and preparation method therefor |
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| DE10357747A1 (en) | 2005-01-05 |
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