CN106149127A - Assorted fibre material - Google Patents

Abstract

The present invention relates to assorted fibre yarn, comprise: bio-compatible, biological absorbable and bioactive glass fibre；Bio-compatible and the polymer fiber of biological absorbable；The biocompatible coupling agent of polar covalent bond can be formed；And bio-compatible and the film former of biological absorbable, and also the method relating to manufacturing described assorted fibre yarn.Also disclose the composite of the assorted fibre yarn comprising the present invention.

Description

Assorted fibre material

Technical field

The present invention relates to assorted fibre material, comprise: bio-compatible, biological absorbable and biology The glass fibre of activity；Bio-compatible and the polymer fiber of biological absorbable；Coupling agent and Film former.This assorted fibre material is useful in the manufacture of composite.The present invention also relates to And assorted fibre material is as the purposes of composite, and comprise described assorted fibre for The purposes of the composite of medical apparatus and biological applications.The invention still further relates to manufacture and mix fibre Dimension yarn and the method for composite.

Background technology

Skeleton is cellular hard and the composite of light weight, and it has is tied by its microcosmic The biology performance of structure feature generation and mechanical performance.Osseous tissue is by the most eurypalynous organic and nothing Unit is grouped into, including water, salt, enzyme, free radical etc..Inorganic phase or mineral facies account for total dry bone The 60-70% of weight.Organic facies is the viscogel class material being mainly made up of collagen, and mineral group Point be made up of the calcium phosphate comprising following crystal form: carbonate ions, a small amount of sodium, magnesium, Phosphoric acid hydrogen radical ion and other trace element.Osseous tissue can be described as chemism environment.

Can be by alloy, ceramic or not only absorbable and but also stable polymer and composite manufacture Medical implant.Bond material performance need, the consolidating of needs are wanted in the selection of implant material all the time Determine type, the knowledge and skills of doctor, the needs of patient and expectation, and sometimes must be can Material and the needs of agglutination and wound, fixing etc. after quality of life between reach Balance.It is said that in general, the shortage of suitable material limits certain form of implantable on market The development of device and design.

As a rule, fracture is fixing, to give knochenbruch during agglutination in needing Stability is also alignd.Traditionally, in orthopaedy, use that metal device carries out fracturing is interior solid Fixed.At present, due to titanium alloy, there is fabulous biocompatibility [Linder et al., Acta Orthop Scand.54,45-52,1983], excellent mechanical performance [Niinomi, J Mech Behav Biomed Mater.1,30-42,2008] and changeable product form, therefore it is for most of bones The standard material of folding fixation for treatment.Due to the improvement on material and manufacturing technology in the recent period, with more Carry out the least metal fixed system and can realize enough fixing [Tatum et al., J Craniofac Surg.8,135-140,1997].Compared with metal, the device tool made with absorbable material There is the biggest size to realize identical mechanical strength (that is, weight capacity).

Traditionally, alloy has been used to prepare spicule, bone screw and blade plate, and actual On, some to be applied, they are still well suited for carrying external load.Although they account for According to fracture fixation region, but metal implant material is not without problem.Metal is implanted Thing material may need to be removed by second time operation after fracture healing, and foreign body may be caused anti- Should, and disturb X-ray and NMR (Nuclear Magnetic Resonance)-imaging (MRI) to check.Except these shortcomings, at skin Hardness between matter bone (E-modulus is 10-20GPa) and metal (E-modulus is 100-200GPa) Greatest differences has inhibited the fast breeding of periosteum callus and has exhausted the direct stress mould of skeleton Formula.Bone growth is to respond to the needs of new skeleton according to the stress being placed on skeleton.This Result in the stress shielding phenomenon (that is, structural change) at implantation site, thinning including cortex, Porotical changes and final Cranial defect [Sumner-Smith, Bone in clinical Orthopaedics, second edition, AO Pub., Switzerland, 2002；Kennady et al., Int J Oral Maxillofac Surg.18,170-174,1989；Kennady et al., Int J Oral Maxillofac Surg.18,307-310,1989；Gerhardt and Boccaccini,Materials, 3,3867-3910,2010].Except this stiffness issue, another shortcoming is material degradation in vivo Property lack.In order to avoid the bone resorption after agglutination, need second time operation to remove implantation Thing, this usually causes extra risk and adds the sickness rate of patient, and occupying clinic can By property and add holistic cost [Bradley et al., J Bone Joint Surg；61A:866-72, 1979]。

The polymer of Biostatic and composite thereof, such as, based on polymethacrylates, Ultra-high molecular weight polyethylene (UHMWPE), politef (PTFE), polyether-ether-ketone (PEEK), Polysiloxanes and acrylate copolymer are known in the literature [S.Dumitriu, Polymeric , and be already used to manufacture medical embedded Biomaterials second edition, CRC Press, 2001] Thing.But, they are neither bioactive is not absorbable, and therefore will not Substituted by nature bone.Although be not as firm as alloy implants, but they still stand and alloy Similar problem and may need certain point in the life-span of implant carry out second time perform the operation with Displacement or removal implant.

Various bioactive glass compositions are known in the art.They can with skeleton and Soft tissue combines, and they may be used for the tissue growth in stimulation mammal body or skeleton Growth.Usual bioactive glass also guides neoblastic formation, and wherein new organization is described Inside glass grows.When bioactive glass contact physiological environment, on the surface of the glass Form layer of silica gel.After the reaction, calcium phosphate deposition to this layer and finally crystallizes into hydroxyl carbon Acid apatite.Due to this hydroxy carbonate apatite layer, therefore when embedding in mammal body, The absorption of bioactive glass is slowed down.In decades, have studied as bone filling material The bioactive glass of material, it can be combined with skeleton, even chemical combination.The most excellent The discovery of the bioactive glass of matter makes this material the most interesting.Some is biological The trade name commercially sold of glass of activity such as,Novabonea andBioactive glass for medical application, such as, is used for the most in different forms The bone defect filling in orthopedic and cranium jaw face and the granule of bone remoulding and plate.Some bioactive glass Glass preparation discloses the most in the prior art, such as, at the open EP802890 of patent and In EP1405647.The some compositions of known bioactive glass has antibacterial effect, ginseng See in the open US 6,190,643 and US 6,342,207 of such as patent.

Other kinds of absorbable glass composition is also as known in the art.Absorbable Glass needs not to be bioactive, i.e. they form hydroxy carbonate phosphorus ash the most on the glass surface Rock layers.Absorbable glass composition is used for fiber glass industry, to solve installing glass The glass fibre such as problem of termination in lung during fiber insulation.The disappearance of fiber is preferably Relatively fast, therefore health is not caused illeffects.Disclose at the open EP412878 of patent A kind of absorbable glass composition.Fiber was degraded in 32 days.But, for most of medical science For application, such as, for for the screw of fix bone defect or fracture or pin, so Degradation rate is the fastest.

Although biological activity and the glass of biological absorbable and glass fibre are accepted well by health And it turned out it is the fabulous biomaterial for skeletal fixation application, but biological alive Property glass lack for load apply needed for mechanical performance.It practice, bioactive glass Glass is hard and frangible material.Document EP802890 discloses the life with big working range The glass composition of thing activity.Devitrification has been evaded by interpolation potassium and optional magnesium in glass Problem.In the spinal fusion of rabbit model, containing the biodegradable of potassium for test The experiment of fabric BG 1-98/PLGA80 there occurs, unexpected serious adverse events is (stupid Solidity pain, paralysis and death).In vitro culture shows that the human world of neighbouring BG 1-98 fiber is filled The growth inhibited of matter stem cell and free radical pH change [Frantz é n, Bioactive glass in lumbar spondylodesis,a pre-clinical and clinical study,ISBN 978-951-29-5117-8,Painosalama Oy,Finland 2012].Therefore, fibrous glass group One aspect of compound is to stop effects on neural system and/or cytotoxic effect, and both is derived from and comprises The fiber glass compositions of the potassium of high-load and/or due to the fastest degradation rate of glass fibre And the high local pH produced raises.

Machined parameters has important effect in fibre machinery characteristic (intensity and modulus). [Paradini and Manhani,Materials Research 5,411-420,2002].Several in the past In 10 years, many different bioactive glass compositions are manufactured and have studied.But, Due to thermophysical property, the great majority of these glass be already unsuitable for drawing of fiber [Arstila, Doctoral dissertation, Abo Akademi University, Turku, Finland, 2008], or Person is at least unsuitable for the continuous process of industrial type and has produced low compared to such as E-glass Glass fiber strength [Pirhonen et al., J.Biomed.Mat.Res.App.Biomat.77B, 227-233,2006；Rinehart et al., J.Biomed.Mat.Res.App.Biomat.48, 833-840,1999], it is typically used as the increasing in dentistry and artistic glass fibre reinforced composites Strong thing.In addition to good mechanical performance, the degradation rate of fiber must be of a sufficiently low to meet load The requirement of the mechanical performance of medical apparatus in application.[Ahmed et al., J.Biomed.Mat.Res. B 89B 18-27,2008；Cozien-Cazuc et al., Proceed.Int.Conf.on Composite materials,ICCM15,Durban,South Africa,2005].In view of glass biodissolution rate depends on Relying the fact that in S/V rate, the rate of dissolution of fiber and behavior can not be directly by comprising Similar combination of oxides but the master that makes with the granule with much smaller S/V rate The public value of body bio-vitric is derived.

In the recent period, the biomaterial promotion skeleton that many work it turned out containing strontium is formed thin with skeletonization Born of the same parents replicate and suppress the good effect of the bone resorption via osteoclast.Such as, by colloidal sol- The bioactive SiO of the doping strontium that gel method is formed₂Base glass particle is to tire Mus calvaria cell There is beneficial effect [Isaac, Europ.Cells and Materials, 21,130-143,2011], and And in human osteosarcoma cell grows test, the boron phosphate glass fibre of doping strontium shows biology Activity and biocompatibility [Zheng, J Non-Cystalline Solids, 358,387-391,2012].

For the suitable bio-compatible of drawing of fiber and the glass of biological absorbable and be used for bearing Lotus application glass fibre needed for mechanical performance have been disclosed in WO2010/122019 and Lehtonen et al., J.Mech.Behav.Biomed.Mat., 20,376-386,2013.Additionally, The open WO2010/122019 of patent discloses in the melt deriving from glass fiber compound Potassium limits to < 0.05wt% adds biocompatibility and eliminates neurotoxic effect with thin Cellular toxicity effect.It is well known in the art that, when the potassium of the amount increased is at the extracellular matrix organized Time middle, the cell of such as muscle cell and neurocyte may be impaired, i.e. may be to human body group It is poisonous for knitting.

The great majority of the implant material of currently available biological absorbable by PLLA, PLDLA and PGA and its copolymer are made.The advantage using absorbable polymer is polymerization Thing and the implant re-absorption in vivo therefore obtained, and non-toxic degradation products will pass through generation The system of thanking carries out metabolism.The implant material of currently used biological absorbable is hard not as skeleton, Therefore they eliminate the potential stress shielding relevant to the life-time service of metal implant, but It is that the device of these biological absorbables does not maintain the fixing of needs, i.e. initial strength and intensity Reservation with modulus.Fixing in order to realize needing, implant need bigger size and so The most significant antixenic risk [Bergsma et al., J Oral may be increased Maxillofac Surg.51,666-670,1993].Another shortcoming of absorbable polymer is Their own is not bioactive.In order to realize the polymer of bioactive biological absorbable Device, needs bioactive compound, such as, and bioactive glass, adds to dress Put.Have been developed for some composites to increase synosteosis ability；Generally filler material is hydroxyl Base apatite, calcium phosphate or bioactive glass particle.But, bioactive glass or The interpolation of other biological activating agent typically reduces mechanical strength, even decreases below pure gathering The mechanical strength of compound.[Konan and Haddad,The Knee.16,6-13,2009； Gerhardt and Boccaccini,Materials.3,3867-3910,2010；Ara et al., Biomaterials.23,2479-2483,2002；Jiang et al., Biomaterials.261, 2281-2288,2005；Furukawa et al., Biomaterials.21,889-898,2000；Ph.D.thesis,Tampere University of Technology.Finland,2010； Felfel et al., J Mech Behav Biomed Mater.4,1462-1472,2011].

Self-reinforcing is that wherein polymer molecule is forced into a certain orientation and causes changing of polymer and device The polymer processing techniques of kind intensity.It has been reported that the polymer of the biological absorbable of self-reinforcing Composite improves the intensity of absorbable device.But, intensity, modulus and intensity retain Not in the level required by load application.[Et al., Clinic.Mat., 10,29-34, 1992；S.Snyder and E.Schneider, J.Orthopedic Res.9,422-431,1991； Majola et al., J.Mat.Sci.:Mat.In Med., 3,43-47,1992].

In order to improve the mechanical strength of device based on absorbable polymer, have been developed for not Fibre-reinforced absorbable polymer composite with type.It is used for poly-(hydroxyl second Acid) (PGA) fiber, PLG (PLGA) fiber, poly-(lactic acid) (PLA) Fiber composite in PLA or PDLA (poly-(D-ALPHA-Hydroxypropionic acid)) matrix.Initial strength is the most non- Chang Hao, but, PGA and PLGA fiber re-absorption quickly have lost high intensity.Wherein strengthen The composite that fiber is made up of identical chemical composition with matrix has shown that longer time section Intensity retain.By increasing the hydrophobicity of polymer and/or by adding substantial amounts of buffering Agent has been slowed down polymeric matrix degraded.These two technology all disturb the interaction between mutually and The reduction (seeing WO2008/067531) of composite may be caused.

In the open EP1874366 of patent,Et al. disclose composite, it is in poly- Compound matrix comprises two kinds of reinforcing fibers, a kind of polymer fiber and a kind of ceramic fibre, and And report good initial mechanical result, i.e. the bending strength of 420+/-39MPa and 21.5 The bending modulus of GPa, this is identical level with bending strength and the bending modulus of cortical bone. But, they also do not report any inner or in vitro conduct hydrolysis, and teaching in prior art: There is no the idol that can make interaction physically or chemically between ceramic phase and polymer phase In the case of connection agent or bulking agent, with answering of the biological absorbable of absorbability glass fiber reinforcement Condensation material has high initial flexural modulus, but composite loses them rapidly in vitro Intensity and modulus.

The interaction of hard frangible mineral facies and flexible organic matrix gives skeleton, and it is only Special mechanical performance.The exploitation of bone renovating material or succedaneum is generally oriented in mineral material (i.e., The glass of biological absorbable) with the combination of organic polymer matrix to generate composite, it shows The toughness of polymer and flexible and mineral filler and/or strengthen intensity and the hardness of thing.Many special Sharp preparation and the composition disclosing this type of composite, such as, WO2006/114483, US 7,270,813, WO2008/067531 and WO2008/035088.

The ultimate aim of the biomaterial in skeleton and fracture fixation field is that material should be simulated The all properties of skeleton, is bioactive, bone guided and biocompatible.Although it is existing Composite in technology already leads to the composite with tempting characteristic, but they are still So need to improve.At present, the composite of prior art does not the most demonstrate have and nature bone Suitable internal mechanical performance.

The typical problem of prior art composite is polymer and the phase interaction strengthening thing interface With and poor adhesion.Polymeric matrix and pottery strengthen the adhesion of the difference between thing and cause physiological environment Initial failure at median surface, and therefore composite mechanical performance degraded the fastest.This type of Degraded is generally occurred by the hydrolysis at interface.Therefore, the improvement of interface cohesion is by biology The key to medical domain successfully applied by degradable polymer composite.

In the case of lacking good Interface Adhesion between polymer and inorganic enhancing thing, will not There will be the stress stood by loaded composite and be transferred to hard enhancing thing from elastomeric polymer. Lack biphase between real adhesion cause the initial failure of mechanical performance in hydrolysis environment.Example As the coupling agent of silane have found they maximum application in composite industry, it is strengthening There is between thing and polymer the compatibility, the most known by using the surface of several types Coating and coupling agent improve.Generally, any silane strengthening the adhesion of polymer is claimed For " coupling agent ", no matter between polymer and silane, whether form covalent bond.

In technical field of biological material, the most the method for applications similar uses coupling agent to improve Hydroxyapatite orThe interface of/polymer composites.In most of the cases, this A little process cause composite final hardness significantly improve (see for example WO98/46164). But, when polymeric matrix is made up of Biodegradable polymeric, they lack enhancing thing Or real physical bond between filler and main polymer chain and/or active end group or covalency knot Close.Fragile main polymer chain attempts typically result in when forming covalent bond random chain fracture, The effusion of low-down molecular weight fragment, gas, unsaturation and autocatalysis degraded, this will be Cause bad mechanical property and the thermal instability of composite eventually.

Up to now, the highest mechanical performance of bioresorbable composite material has been presented on In document Lehtonen, Acta Biomaterialia 9,4868-4877,2013.High mechanical strength Performance is owing to adhesion chemistry [seeing EP2243500] and the absorbable glass of high tensile Fiber [sees WO2010/122019].Composite is based on bio-compatible and biological absorbable Glass, bio-compatible and biological absorbable matrix polymer and can glass fibre with The coupling agent of covalent bond, the wherein construction unit of at least 10% in bulking agent is formed between bulking agent Identical with the construction unit of matrix polymer, and the molecular weight of bulking agent is less than 30000g/mol. It has been shown that within 4-8 week, external intensity is retained in acceptable level, this is department of pediatrics and cranium In the range of Maxillary region Healing Rate.But, the soonest and therefore the loss of initial strength Require that composite obtains the highest initial strength so that intensity and modulus levels are maintained cortex Until bone has been fully recovered on bone level.The shortcoming of the system presented is glass phase and polymer Rupturing of adhesion between Xiang relatively early starts, in SBF about 4 weeks, i.e. demonstrate institute The adhesive systems presented retains application for long-term intensity, and (such as, long bone is fixed and at regiones vertebralis Territory) it not optimal.

Additionally, the method for similar type is applied the composite (example to not-bio-absorbable As, US6,399,693).It is well known, however, that these materials to internal and external hydrolysis and Absorbability all has high resistance.Therefore, these materials will have and metal and biological stability The shortcoming that material is similar, such as, the bone resorption when as implant material in medical apparatus And stress shielding.

Hybrid yarns technology is a kind of method [N. manufacturing the fibre-reinforced thermoplastic of seriality Svensson et al., J of Thermopl Comp Mat 11,22-56,1998].It the most excellent Point relates to the highly flexible of the net shape about composite and relates to the high of composite Fiber volume fraction and the highest mechanical performance.Yarn is mixed for manufacture composite Line technology discloses, such as, in the open US5 of patent, and 674,286；US7,820,289 and In US7632765, but due to the shortage of suitable adhesive systems, therefore intensity level is not at load The acceptable level of application.Lehtonen et al. [Presentation at 18^th International Conference on composites, Jeju Island, South Korea, 2011] will mix yarn The manufacture of line technology application extremely absorbable composite.But, with result earlier [Lehtonen, Acta Biomaterialia 9,4868-4877,2013] compares, intensity and modulus knot Fruit is not improved, but gives the result of level identical with using fiber impregnation technology.

Summary of the invention

Surprisingly, present inventors have found that at coupling agent and low-molecular-weight polymeric The theory between thing with covalent bond will not produce between inorganic phase with organic (polymer) phase Good adhesion.The dry strength of composite is relatively high, but in aqueous or under conditions in vitro Reducing due to the infiltration of water, wherein the infiltration of water is of a relatively high, this be due to high molecular Film former or matrix polymer are compared, and the bulking agent of relatively low molecular weight has bigger hydrophilic, Because comparing with chain length (that is, molecular weight), the hydroxyl end groups of the bulking agent of relatively low molecular weight and/ Or the amount of acid end group is relatively high；The probability of chain rupture increases, and has produced entanglement (that is, at base Adhesion between body) low-molecular weight polymer chain with matrix polymer phase same rate or higher Speed shorten.Can assume that due to the impact of end group hydrophilic Yu the ratio of molecular weight, have The degradation rate of the low-molecular weight polymer of the constitutional repeating unit identical with heavy polymer It is to degrade with identical speed or faster speed.Therefore, this bulking agent (compatibilizer) molecule loses for (that is, the thing between bulking agent and matrix polymer that tangles Reason combines) if the probability of Len req has the feelings of higher molecular weight higher than bulking agent/film former Condition.The most weak point of prior art systems (such as, being disclosed in EP2243500) is due to bulking agent Length and produce adhesive systems.In the invention it has unexpectedly been found that the key of good adhesion It is to form semi-intercrossing network or interpenetrating networks or long-chain between inorganic phase with organic (polymer) phase Tangle, and if film former molecular weight is not high enough and its to biphase affinity not high enough time, Then it is not likely to form above-mentioned.Covalent bond between coupling agent and bulking agent or film former will not Damage this system, but be unwanted certainly, because when semi-intercrossing network or interpenetrating networks generate Time, this network can not be physically separated unless chemical bond rupture.If film former and polymer base The chemical affinity of body is close, and the molecular weight of film former up to be enough to form entanglement, Then the intensity of adhesive systems is the level in covalent bond or interconnected system.

It is an object of the invention to provide assorted fibre thread material, the most by disadvantages mentioned above Littleization or even completely eliminate.This type of assorted fibre thread material may be used for composite Manufacture.

Further objective is that of the present invention provides the assorted fibre that can be used for manufacturing medical implant Thread material, wherein the modulus of this medical implant is at least high as the modulus of cortical bone, makes Implant once use, the most almost with the elasticity such as skeleton.

The superelevation that the other purpose of the present invention is to provide between inorganic phase and organic facies adheres to change Kind initial strength and external intensity retain.

The other purpose of the present invention is to provide the assorted fibre yarn material for manufacturing composite Material, described composite does not have any or only has inappreciable effects on neural system and/or cell Toxic action.Yet a further object is to provide to be had and material phase well known in the prior art Than the biocompatibility increased and bioactive material.

The other purpose of the present invention is by with strontium or strontium compound doped-glass and/or matrix And/or starching, the biological activity of improvement is provided.

According to the first aspect of the invention, assorted fibre yarn comprises: bio-compatible, biology can Absorb and bioactive glass fibre；Bio-compatible and the polymer fiber of biological absorbable； The biocompatibility coupling agent of polar covalent bond can be formed；And bio-compatible and biology can inhale The film former received.In preferred embodiments, after fusing assorted fibre yarn, film former Entanglement and/or interpenetrating networks or Semi-IPN net can be formed between coupling agent phase and polymer phase Network.

A second aspect of the present invention provides the composite wood of the assorted fibre yarn comprising first aspect Material, wherein melts polymer fiber to form continuous print polymeric matrix, wherein by glass fibers Dimension is embedded in polymeric matrix to form discontinuous dispersion phase.

A third aspect of the present invention provides the medical dress of the assorted fibre yarn comprising first aspect Put.

A fourth aspect of the present invention provides the medical apparatus of the composite comprising second aspect.

According to the fifth aspect of the invention, the method bag of the assorted fibre yarn of first aspect is manufactured Include following steps: (i) spinning polymeric fiber；(ii) spinning glass fibre, fine with spinning polymeric Dimension separately carries out or carries out simultaneously；(iii) glass fibre and polymer fiber are mixed into hybrid yarns； (iv) by starching, the surface of hybrid yarns is carried out in-situ treatment, wherein go up pulp mixture by with become One or more coupling agents composition of membrane, catalyst, additive and/or deionized water combination； V () is by fiber cake/yarn winding；And (vi) cure/dry.

According to the sixth aspect of the invention, manufacture the method for composite of second aspect include with Lower step: (a) places the assorted fibre yarn of first aspect with preferred orientation；And (b) will be polymerized Fibres is fused into the shape of needs.

Detailed description of the invention

Definition

As used herein, term " bioactive material " refers to be designed to cause or regulate Bioactive material.Bioactive material typically can be carried out with the tissue of mammal Chemically combined surface active material.In vitro, the biological activity of material may be displayed in mould Intend body fluid is formed on the surface of the research material of dissolving calcium phosphate.Biodegradable material is Decompose in vivo but do not have evidence to prove its material from internal elimination.

As used herein, term " biological absorbable " mean when embed in mammal body with And when it contacts with physiological environment, it is being chronically implanted lower material by disintegrate, i.e. be decomposed. The by-product of the material of biological absorbable is passed through or filters or in they generations due to simple Natural route after thanking and eliminate.Term " absorbable " means that biomaterial is because of the most molten Solve and decompose.Term " biological absorbable " and " absorbable " can exchange use.

As used herein, term " absorbable glass " means when contacting with physiological environment not The silica containing glass of richness of hydroxy-carbonate apatite layer can be formed in its surface.Can inhale The glass received disappears from health and will not significantly activate during its catabolic process by absorbing carefully Born of the same parents or cell growth.

As used herein, term " bioresorbable " means to dissolve in body fluid and not have There is any molecular degradation and subsequently from the material of health excretion.

As used herein, term " biomaterial " means to be intended to be connected with biosystem to assess, Treat, increase or substitute the material of any tissue, organ or the function of health.With regard to bio-compatible For property, it means by causing suitable host response at ad-hoc location, do not cause foreign body anti- Should and nontoxic and with safely and the ability of material that is sufficiently carried out in the medical apparatus.

As used herein, term " composite " means following polymeric matrix composite material: It is made up of two or more composite material with dramatically different physically or chemically performance Material, when this two or more composite material combines, the properties of materials of generation is different In single component.Basic difference between blend and composite is two kinds in composite Main component is still that identifiable, and these in blend can not be identifiable. These single compositions work to give the required mechanical strength of composite portions or hard together Degree.Matrix is the principal phase with continuation property mutually.Matrix be typically the most more ductility and less Hard phase.It accommodates dispersion phase and shares load with dispersion phase.Dispersion (enhancing) is not to connect Continuous form embeds in the base.This secondary is referred to as mutually dispersion phase.Dispersion phase is generally than matrix Firmer, therefore, sometimes dispersion phase is referred to as strengthened phase.

As used herein, term " spinning glass fibre " or " traction " mean the system of glass fibre Make, wherein glass is melted in the sleeve pipe of 700 DEG C-2000 DEG C, and by the bottom of via sleeve pipe The nozzle in portion stretches and forms glass fibre through the glass of fusing, and this produces a diameter of 1 micron The fiber of-300 microns.

As used herein, term " medical apparatus " means for internal any kind of implantation Thing, and it is used for supporting tissue or bone healing or the device of regeneration.According to " implant " herein Including any kind of implant applied for surgery flesh skeleton, such as, it is used for heal Fix fracture and/or osteotomy screw, plate, pin, stud or the nail with fixing bone segment；With In fixing soft tissue-to-bone, soft tissue-deeply-bone (soft tissue-into-bone) and soft tissue- To-soft tissue stitching thread, sew up anchor, stud, screw, bolt, nail, fixture, Frame and other devices；And it is used for supporting tissue or bone healing or the device of regeneration；Or In operation on vertebra for spinal fusion and the cervical vertebra wedge of other operations and lumbar vertebra cage and lumbar vertebra plate and Lumbar vertebra screw.

As used herein, term " spreading mass " means coupling agent and catalyst, film former, table Face modifying agent, bulking agent, emulsifying agent, water, solvent, additive, stabilizer and lubricant Mixture, if you are using, it can be with emulsion or the form of solution.Spreading mass is being spun Apply to fiber and also can be later as single processing step during system or traction fiber Application.

As used herein, term " coupling agent " means any organic of the adhesion of enhancing polymer Metallic compound, such as, silane, organic titanate (salt) or organozirconates (salt), no matter exist Whether covalent bond is formed between polymer and coupling agent." surface modifier " can not strengthen inorganic Adhesion mutually and between polymer phase but protection glass from mechanical shock or chemical erosion and Enhance processing characteristics.

As used herein, term " interpenetrating polymer networks " (IPN) means to comprise two or more Planting the polymer of network, wherein these two or more networks are at least part of on polymer yardstick Interlock but there is no covalent bonding each other.This network can not separate unless chemical bond rupture.Can be by Two or more networks are thought of as tangling in the following manner: they linked together and not Can pull open, but the most not by any chemical bonds.Two or more preformed polymerizations The mixture of thing network is not IPN.

As used herein, term " semi-interpenetrating polymer network " (SIPN) mean to comprise one or Multiple network and one or more linear or polymer of branched polymer, it is characterised in that network In at least one is linear by least some or branched macromolecules permeates on molecular scale.Half mutually Wear polymer network and be different from interpenetrating polymer networks, because linear in principle or branched polymer Composition can separate with polymer network composition and not destroy chemical bond；They are that polymer blends Thing.

The typical assorted fibre thread material of the present invention comprises: bio-compatible, biological absorbable And bioactive glass fibre；Bio-compatible and the polymer fiber of biological absorbable；And The biocompatibility coupling agent of polar covalent bond can be formed.It also comprises bio-compatible and biology Absorbable film former.Preferably, the film former of bio-compatible and biological absorbable can be molten Entanglement, IPN net is formed between the coupling agent phase and the polymer phase that are formed after changing assorted fibre yarn Network or semi-intercrossing network.

Therefore, the invention provides the assorted fibre thread material being applicable to manufacture composite, Described composite is used as the structural fixing of carrying purpose, demonstrates the interface knot owing to strengthening Mechanical performance, stability and the biological activity closed and improve, and assorted fibre yarn is in complexity Medical implant manufacture in ease for operation, this is with composite described in the prior art Different.It is true that the present invention overcomes or at least minimizes the shortcoming of prior art, this Bright provide composite, wherein with physical entanglement by polymeric matrix and biocompatible glass Combined by coupling agent and film former, wherein film former can coupling agent phase and polymer phase it Between formed tangle, interpenetrating networks or semi-intercrossing network.Present invention provide for composite Assorted fibre thread material, can by the shortcoming of prior art material in described composite Littleization or even eliminate, i.e. composite keeps it strong within the time period that be enough to knitting Degree and modulus and improve the biological activity of such as implant.It is true that for the present invention, can With good by being implemented in combination with under high initial strength and modulus and conditions in vitro between interface Intensity retains.Mechanical strength used herein includes that bending strength, torsional strength, impact are strong Degree, compressive strength and hot strength.

Present invention also offers preparation method, it allows to control at fibrous glass and polymeric matrix Between the chemical strength of key that formed and physical strength and stability.Can be by changing coupling agent Or the chemical constitution of the combination and/or film former by using coupling agent changes these keys Strength and stability.A kind of method on the surface modifying glass is to use hydrophobic surface modifying agent Together with coupling agent.

If needing to strengthen or at device the hydrolytic stability of the alkane key between silane and glass In corrosive aqueous liquid environment, both arms (dipodal) silane generally demonstrates that significant performance changes Kind.Compared with conventional coupling agent, these materials form tighter network, and can provide Up to the hydrolytic resistance of 100000 times bigger than conventional coupling agents.Inorganic filler or enhancing thing, example Such as calcium carbonate and high phosphate and the glass of sodium, it is generally unsuitable for silane coupler.Additionally, For coupling agent and surface modification reaction, the glass containing high phosphate and sodium it is most to be typically Dejected substrate of glass.The main inorganic constituents of glass is silicon dioxide and will expect that it holds Change places and silane coupler reacts.But, it is steady that alkali metal and phosphate not only form hydrolysis with silicon Fixed key, and the most what is worse, be catalyzed the fracture of siliconoxygen bond and redistribute.Generally will Hydrophobicity both arms silane or multi-arm (multipodal) silane are applied in combination with organo functional silanes. In some cases, the polymer silane in the sites with multiple and substrate interaction is used [Gelest Inc.Silane Coupling Agents:Connecting Across Boundaries]。

According to another embodiment of the invention, assorted fibre thread material can comprise two kinds or More types of absorbable biocompatible and bioactive glass, each type has Different compositions.Composite can also comprise at least one biological activity, bio-compatible and life The absorbable glass of thing and at least one bio-compatible and the glass of biological absorbable, above-mentioned glass Glass has different compositions.The glass of Second Type it may be that such as, has higher biological alive Property and the glass of absorption rate, it can be being with the form of granule, spheroid, block or fiber.? Faster in the case of absorption rate and higher biological activity, major function is not composite Enhancing thing, but the material of more bone guided, it means that this glass is with such asGranule and/or the form of powder promote and help knitting.

Assorted fibre thread material can also comprise the polymer of two or more type, two kinds Or more types of coupling agent and the film former of two or more type.Additionally, mix fibre Dimension thread material can also comprise and has the fiber group of different median diameters with two or more The glass of (groups of fibers) form.

Bio-compatible, biological absorbable and bioactive glass fibre

According to the invention, it is possible to use different bio-compatible, biological absorbable and bioactive Glass.For machining angle, major requirement is that glass allows for being drawn or being spun into carefully Fiber, i.e. there is suitable hot property.Bio-compatible, biological absorbable and bioactive The selection of glass is typically based on following two facts: first, absorption rate must slowly, together with In physiological environment, pH increases slowly, and wherein physiological environment will not result in film former and polymer The fracture of the polar covalent bond in the premature degradation of matrix and fibrous glass surface.Second, The mechanical strength of glass fibre and activity hydroxy quantity need to be sufficient.Can be by such as existing Fiber manufacture process use spreading mass based on deionized water guarantee on the surface of fibrous glass Hydroxyl quantity.

It is said that in general, biological activity becomes with glass fibre composition, and the absorption of glass fibre With composition and become with S/V rate, i.e. through the surface erosion of physiological environment.By In the high S/V rate of fiber, understand and can control glass absorption rate and In physiological environment, discharge alkali metal ion and alkaline-earth metal ions is required.Alkali metal ion Cause high local pH to increase and may cause in some cases such as neurotoxic effect and The physiological problem of cytotoxic effect, particularly when the potassium of high-load is present in glass fibre. In glass fiber compound, potassium is limited increasing to the least quantity (0.05wt%-1wt%) Add its biocompatibility and eliminate neurotoxic effect and cytotoxic effect.Additionally, pass through Change silicon dioxide and other components (that is, SrO, Na in glass composition₂O、CaO、MgO、 P₂O₅、B₂O₃And Al₂O₃) amount, can easily control glass fibre absorption rate and Increase biological activity.

In preferred embodiments, bio-compatible, biological absorbable and bioactive glass Fiber is made up of the bio-compatible of the strontium that adulterates and the glass fibre of biological absorbable.It is applicable to this The bright typical doping bio-compatible of strontium, biological absorbable and bioactive glass fibre group Compound comprises:

The SrO of 0.1wt% to 12wt%,

The SiO of 60wt% to 70wt%₂,

The Na of 5wt% to 20wt%₂O,

The CaO of 5wt% to 25wt%,

The MgO of 0wt% to 10wt%,

The P of 0.5wt% to 5wt%₂O₅,

The B of 0wt% to 15wt%₂O₃,

The Al of 0wt% to 5wt%₂O₃, and

The K of 0.05wt% to 1wt%₂O。

According to one embodiment of the invention, suitable glass fibre display 800MPa-2500 The hot strength of MPa.According to an aspect of the present invention, it should by SiO₂Content is maintained at excellent Select 60 weight % to the quantity of 70 weight %, to remain the desired amount of in the surface of fibrous glass Activity hydroxy is so that the reaction between coupling agent and fibrous glass can be carried out.Additionally, a side Face, owing to alkali metal and phosphate not only form the key of hydrolysis-stable with silicon, and also the most even worse , the fact that be catalyzed the fracture of silicon-oxygen key and redistribute, Na₂O and P₂O₅Amount should phase To low.On the other hand, substantial amounts of release is not produced for maintaining the absorbability of glass fibre Alkali metal thus stop the situation of the harmful or toxicologic local pH peak value in physiological environment, Sodium is required.

Furthermore, it is necessary to the phosphorus calcium oxide of q.s is to keep long-term biological activity, i.e. CaP Formation.It is believed that glass and synestotic premise be with shape on the glass surface of bioresorbable Become the layer rich in calcium phosphate.The unbodied calcium phosphate originally formed crystallizes into hydroxyl over time Apatite, hydroxyapatite is the main component of bone.

The diameter of the glass fibre being applicable to the present invention is less than 300 μm, usually 1 μm-75 μm, It is more typically 2 μm-30 μm, preferably 5 μm-15 μm, more preferably 8 μm-13 μm.

According to embodiment of the present invention, biocompatible, biological absorbable and bioactive The consumption of glass fibre is 1 weight %-98 weight % of the gross weight of assorted fibre thread material, excellent Elect 10 weight %-90 weight %, more preferably 20 weight %-80 weight % and most preferably 25 as Weight %-75 weight %.

Coupling agent

As used herein term coupling agent refers to be formed the organic metal of polar covalent bond Compound.Most-often used coupling agent is organosilan, organic titanate (salt), and other Uncommon coupling agent is organozirconates (salt) and Aluminate (salt).Generally, coupling agent is silane, And between glass fibre and coupling agent, generally form polar covalent bond.For between phase and phase Adhesion, the covalent bond between coupling agent and film former is unwanted, but this is not precluded from In addition to the present invention.

The formula of organosilan shows two class functionalities.

R_nSiX_(4-n)

X functional group participates in the reaction with inorganic substrates.The key between silicon atom in X and coupling agent Substituted by the key between inorganic substrates and silicon atom.X is hydrolyzable group, usually alcoxyl Base, acyloxy, amine or chlorine.Modal alkoxyl is methoxyl group and ethyoxyl, and it is in coupling Course of reaction produces methanol and ethanol as by-product.

R is the organic group of the non-hydrolytic with the functionality enabling coupling agent to be combined with polymer Group.The great majority of widely used organosilan contain an organic substituent.On the other hand, Inorganic surfaces can in close proximity to the accessibility of organo-functional group apply important steric hindrance about Bundle.If the length of junctional complex is important, then functional group has bigger mobility and can Farther to extend from inorganic substrates.If it is expected that in functional group and multicomponent organic facies or aqueous phase Single component reaction, this will have important impact [UCT Specialties, LLC., Silane coupling agent guide]。

The combination of functionality both arms silane and non-functional both arms silane and functionality both arms silane Substrate combination, hydrolytic stability and the mechanical strength of many composite systems had notable shadow Ring.The formula of both arms silane also show two class functionalities, but with conventional silane coupler Comparing, both arms silane has a more hydrolyzable group, usually six.[Gelest Inc. Silane Coupling Agents:Connecting Across Boundaries]。

As a rule, silane is made to stand hydrolysis before surface processes.After hydrolysis, Forming reactive silicon triacontanol group, it can be with other silanol (such as, in siliceous enhancing Those on the surface of body and/or filler) it is condensed to form siloxane bond.For hydrolysis Water can come from several source.It can be added, and it can be present in substrate surface On or its can be from air.Concentration and type according to the hydroxyl existed can be extensive Ground changes the substrate of hydroxyl.Storage new melted substrate in neutral conditions has minimum number The hydroxyl of amount.The hydrogen that adjacent silanol is bonded is easier to react with silane coupler, and isolates Or free hydroxyl react reluctantly.

As the organofunctional silane of coupling agent or for adhering to organic polymer and inorganic substrates Silane coupling agent is the most always in the upper use of the coverage more than monolayer (coverage) of inorganic surfaces. Which kind of method no matter applied, they all can be condensed on inorganic surfaces can be with inorganic with structure Surface forms the siloxane network of the oligomer of covalency " alkane " key.In surface treatment process, Siloxanes (the contracting of modified oligomer is carried out by its reaction in film former chain (IPN or half IPM) The silane closed) layer.

Preferably, the interface zone of gained has some characteristic for optimum performance.Such as, The formation of alkane key with inorganic surfaces should be completed.This may need at high temperature controlled It is dried or needs to use catalyst.Additionally, interface alpha region should preferably have low water suction Rate, preferably introduces hydrophobic substituent group in coupling agent and realizes.

In the present invention, it is also possible to use and can protect glass and increase the table of moistening of glass Face modifying agent.In one embodiment, by the organosilicon of such as alkyl silane and aryl-silane Alkane is used as surface modifier.In another embodiment, having such as alkyl phthalic acid ester (salt) Organic titanate (salt) is used as surface modifier.In further embodiment, by such as alkyl The organozirconates (salt) of zirconate (salt) is used as surface modifier.With the material of these non-functional Surface modification (that is, hydrophobicity, hydrophilic or infiltrating modification) interface can be had deeply Remote impact.Above-mentioned material is for changing surface energy or the wetting characteristics of substrate.By glass fibers Dimension strengthens in polymer, optimizes the method strengthened and makes silylated glass surface Critical surface tension and melting condition or uncured under the conditions of the surface tension of polymer mate. This is most useful [such as by E.P. in the polymer without functionality significantly Plueddemann, Silane coupling agents second edition, disclosed in Kluwer 1991].Therefore, Surface modifier protection glass avoids degraded and mechanical stress.This is in the feelings of the glass of fast degradation Being particularly useful under condition, and improve wettability simultaneously, it can also be changed by Physical interaction Kind adhesion.

For two or more coupling agents and the selection of the combination of optional surface modifier with make With, some important aspects are to ensure that good adhesion between phase and phase and protection glass are exempted from Suffer the premature rupture that caused by water or body fluid, thus the degraded needed for still maintaining and long-term life Thing activity.The another aspect using coupling agent and/or surface modifier is to realize fiberglass surfacing Optimal wettability, protection glass fibre avoids stress and also helps and film former and final Deep processing with polymeric matrix.If terminal applies needs special hydrolytic stability, permissible Use the both arms silane in the mixture of coupling agent and surface modifier.Coupling agent and surface change Property agent, i.e. sizing formulation, can add in fiber distraction procedure online.

The following is the silane coupler as the example that may be used for the present invention and silane surface modified The non-exhaustive list of agent.

O alkanolamine (alkanoamines), such as, two (2-ethoxy)-3-aminopropyl three ethoxy Base silane

O alkyl (surface modifier), such as, 3-propyl-triethoxysilicane, octyl group triethoxy Silane, isobutyl triethoxy silane, isooctyltrimethoxysi,ane

O pi-allyl, such as, allyltrimethoxysilanis

O amine, such as, N-(2-aminoethyl)-3-amino propyl methyl dimethoxysilane, N-(2- Aminoethyl)-3-TSL 8330,3-amino propyl methyl diethoxy silane, 3- Aminopropyltriethoxywerene werene, 3-aminopropyl trimethoxy-silane, (N-trimethoxy first silicon Alkyl-propyl group) polymine, trimethoxy-silylpropyl diethylenetriamines, positive fourth Base amino-propyl trimethoxy silane

O anhydride, such as, 3-(triethoxysilyl) propylsuccinic anhydride

O aromatic compound (surface modifier), such as, phenyl triethoxysilane, phenyl Trimethoxy silane

O alkyl chloride base class, such as, 3-chloropropyltrimethoxy silane

O chloromethyl aromatic compound, such as, 1-trimethoxysilyl-2 (right, m- Chloromethyl)-diphenylphosphino ethane

O both arms class, such as two (trimethoxy-silylpropyl) amine, two (triethoxy first silicon Alkyl ethyl) vinyl methyl silane, two (triethoxysilyl) ethane, 1-(triethoxy Silicyl)-2-(diethoxymethyl silicyl) ethane

O epoxy, such as, 2-(3,4-epoxycyclohexyl) ethyl trimethoxy silane, 3-(+)-2,3-Epoxy-1-propanol Epoxide propyl trimethoxy silicane (3-glycidoxypropyltrimethoxysilane), 3-shrink sweet Oil epoxide propyl-triethoxysilicane

O fluoroalkane base class (surface modifier), such as, 3,3,3-tri-fluoro propyl trimethoxies- Silane

O isocyanates, such as, isocyanatopropyl triethoxysilane

O sulfydryl, such as, two [3-(triethoxysilyl) propyl group] tetrasulfide, 3-sulfydryl Hydroxypropyl methyl dimethoxysilane, 3-mercaptopropyi trimethoxy silane

O methyl acrylic ester, such as, 3-methacryloxypropyl, (3-acryloxypropyl) trimethoxy silane

O phosphine, such as, 2-(diphenylphosphino) ethyl triethoxysilane

O silazane (surface modifier), such as, 1,3-divinyl tetramethyl-disilazane, six Methyl disilazane

O styryl, such as, 3-(N-styrylmethyl-2-aminoethyl amino) propyl group front three Epoxide-silane hydrochlorate

O urea groups, such as, N-(triethoxysilylpropyltetrasulfide) urea

O vinyl, such as, VTES, vinyltrimethoxy silane, Vinyl three (2-methoxy ethoxy) silane

Organic titanate (salt) can overcome many limitation of silane coupler.It is similar with silane, The universal architecture of titanate is: XO-Ti-(OY)₃, wherein XO-can be can be with inorganic substrates The monoalkoxy of reaction or new alkoxyl, and-OY is organic functional fragment.Y portion generally may be used With comprise several different group with provide polarity and nonpolar thermoplastic (such as, benzyl, Butyl) with thermosets (such as, amino, the methacrylic acid that can introduce extra function Base) and pyrophosphate group or hydroxy-acid group between interaction.Different from silane, titanium Acid esters (salt) need not the existence of water to react.Titanate esters (salt) is divided into a few class.Simplest It it is monoalkoxy (such as, isopropoxy) titanate esters (salt).These react with filling surface, Alcohol by-product is generated by solvolysis.New alkoxy titanates (salt) have more complicated but more Heat-staple structure.They are developed for high temperature application (higher than 200 DEG C, anhydrous), such as, exist Original position in the production process of thermoplastic compounding and urethane composite is added.They pass through Coordination mechanism reacts with the free proton on filling surface, and no coupling product or leaving group generate. Different from the hydroxyl needed for silane reaction, free proton is present on almost all of three-dimensional particle, This makes titanate esters (salt) have more common reactivity.It in contrast to usual and other coupling agent shapes The polymolecular layer become, the reaction with free proton generates organic monolayer on inorganic surfaces, Its chemical constitution combining titanate esters (salt) creates the mutual of surface energy modification and polymer phase Effect.Except the heat stability that they are higher, compared with their monoalkoxy homologue, newly Alkoxy titanates (salt) provides the final performance slightly strengthened.Other kinds of titanate esters (salt) It is chelate (stability in order to bigger in wet environment) and quaternary compound (water solublity system). [Farmasil Technology,Selection Guide Silane Coupling Agents]

The chemical constitution of the organozirconates (salt) of such as alkoxy zirconium ester (salt) and titanate esters (salt) Chemical constitution be similar to.The major advantage of zirconate (salt) is they bigger stability, they The most do not cause and fade, the most in the presence phenols.[Farmasil Technology,Selection Guide Silane Coupling Agents]

According to embodiment of the present invention, the consumption of coupling agent is 0.01 weight of glass fibre consumption Amount %-10 weight %, preferably 0.02 weight %-8 weight % and most preferably 0.05 weight %-5 Weight %.

Biological absorbable and biocompatible polymer fiber

The assorted fibre thread material of the present invention comprises the polymer of bio-compatible and biological absorbable Fiber.Polylactide (that is, poly-(lactic acid), PLA), PGA (PGA) and poly-(6-caprolactone) (PCL), poly-two alkanone (PDO), PTMC (PTC) and their copolymer It is central research modal, abundant the absorbable polymer used with terpolymer. The polyester of these high molecular, described ring-type list is generally generated by the ring-opening polymerisation of cyclic monomer Body i.e., lactide, 6-caprolactone, Acetic acid, hydroxy-, bimol. cyclic ester, to two alkanone and trimethylene carbonate.

Poly-(L-lactide) homopolymer is hemicrystalline polymer, and it has about 180 DEG C molten Melt temperature T_mGlass transition temperature T with 60-65 DEG C_g.Poly-(DL-lactide) homopolymer is There is T_gFor the amorphous polymer of 55-60 DEG C.PLA has glassy, hard but frangible material The characteristic of material, its hot strength with 65MPa and the Young's modulus of 3GPa-4GPa.

PCL is firm, the elastomeric polymer of ductility, and it has low the melting of 60 DEG C Melt the T of temperature and-60 DEG C_g, the hot strength of 40MPa and the modulus of 0.4GPa.

PGA has glassy, hard but frangible properties of materials, and it has 215-225 DEG C Low melt temperature and the T of 40 DEG C_g, and the hot strength of 100MPa and 3GPa-4GPa Young's modulus.

Copolyesters and the ternary polyester of PLA, PGA, PCL, PDO and PTC are used for curing in making With the best polymer fiber of the absorbable composite of device is concerned.Monomer ratio The selection of example and molecular weight interferes significantly on intensity, elasticity, modulus, hot property, degradation rate And melt viscosity.Under known all these polymer both aqueous conditions in vitro and in vivo It is degradable.Have determined that two stages in degradation process.First, ester is passed through in degraded The random hydrolysis chain rupture of key is carried out, and this reduces the molecular weight of polymer.In second stage, remove It was additionally observed that outside chain rupture that measurable weight is lost.The point reduced is started in weight, it will be seen that Mechanical performance substantially loses or the most significantly declines.The degradation rate of these polymer is not With, this depends on polymer architecture: degree of crystallinity, molecular weight, glass transition temperature, embedding Segment length, copolymerization ratio, racemization and molecular chain structure [Middleton and Tipton, Biomaterials 21,2335-2346,2000]。

According to the preferred embodiment of the present invention, following absorbable polymer, copolymer and Terpolymer may be used for polymer fiber and/or film former: polylactide (PLA), poly-L- Lactide (PLLA), poly-DL-lactide (PDLLA), poly-L-DL-lactide (PLDL)；Poly- Acetic acid, hydroxy-, bimol. cyclic ester (PGA)；Glycolide copolymer, Acetic acid, hydroxy-, bimol. cyclic ester/trimethylene carbonate copolymer (PGA/TMC)；The copolymer of other PLA, such as lactide/tetramethyl glycolide copolymer, Lactide/trimethylene carbonate copolymer, lactide/d-valerolactone copolymer, lactide/ε- Caprolactone copolymer, L-lactide/DL-lactide copolymer, Acetic acid, hydroxy-, bimol. cyclic ester/L-lactide copolymer (PGA/PLLA), PLGA；The terpolymer of PLA, such as third Lactide/Acetic acid, hydroxy-, bimol. cyclic ester/trimethylene carbonate terpolymer, lactide/glycolides/6-caprolactone three Membered copolymer, PLA/ polyethylene oxide copolymer；Bunching peptides；Asymmetric 3,6-is substituted poly- -1,4-dioxane-2,5-diketone；Polyhydroxyalkanoatefrom, such as poly butyric salt (PHB)； PHB/b-hydroxyl pentanoate copolymer (PHB/PHV)；Poly-b-hydroxy propionate (PHPA)；Poly-p- Two alkanone (PDS)；Poly-d valerolactone-poly-6-caprolactone, (6-caprolactone-DL-lactide) copolymerization Thing；Methyl methacrylate-NVP copolymer；Polyesteramide；Oxalic acid polyester； Poly-dihydropyran；Poly-alkyl-2-cyanoacrylate；Polyurethane (PU)；Polyvinyl alcohol (PVA)； Polypeptide；Poly-b-malic acid (PMLA)；Poly-b-alkanoic acid；Merlon；Poe；Poly- Phosphate ester；Poly-(ester anhydride)；And mixture；And natural polymer, such as sugar, starch, Cellulose, cellulose derivative, polysaccharide, collagen, chitosan, fibrin, hyaluronic acid, Peptide and protein.The mixture of any of above polymer fiber can also be used.

Polymer fiber according to embodiment of the present invention, bio-compatible and biological absorbable Consumption is 1 weight %-98 weight % of the gross weight of assorted fibre yarn, preferably 10 weights Amount %-90 weight %, more preferably 20 weight %-80 weight % and most preferably 25 weight %-75 Weight %.

Film former

As used herein, term " film former " refer to the surface of fiber formed thin film or The polymer of thin layer.Typical film former is absorbable and/or biocompatible polymer, its It can be linear, branched, grafting, star, highly branched, dendroid polymerization Thing or the polymer of crosslinking.Preferably, when assorted fibre yarn is dried and melts, film forming Agent can form entanglement between coupling agent phase and polymer phase.Preferably, it will be at coupling agent Interpenetrating networks or semi-intercrossing network is formed between phase and polymer phase.Therefore, the molecule of film former Amount must be sufficiently high can permeate coupling agent phase and polymer phase and to have between phase and phase Chemical affinity.

The molecular weight of film former is usually above 1,000g/mol, preferably above 5,000g/mol, more Preferably above 10,000g/mol and most preferably higher than 30,000g/mol.Any conjunction can be used Suitable commercial measurement molecular weight, described suitable technology includes using polystyrene, poly-methyl-prop E pioic acid methyl ester, glucosan, general Shandong blue (pullan) or the GPC of poly(ethylene oxide) reference material.Relatively Higher molecular weight is required, and it is in order to have for producing Physical interaction (that is, with shape Become chain entanglement and interpenetrating networks or semi-intercrossing network) rational length, and therefore make polymer Physical interaction in matrix is possibly realized, and described Physical interaction is strong such as covalent bond or extremely Few in similar level.

As used herein, " GPC " refers to gel permeation chromatography (GPC), and it is a kind of size Exclusion chromatography (SEC).Using GPC to measure the relative molecular weight of polymer samples, this is in ability Territory is conventional and those skilled in the art will be familiar with this technology.

Film former can be independently selected from the polymer for polymer fiber listed above.Root According to embodiment of the present invention, the consumption of film former is the 0.01 of the gross weight of assorted fibre yarn Weight %-30 weight %, preferably 0.05 weight %-10 weight %, and most preferably 0.1 weight Amount %-2 weight %.

The additional advantage of film former is to be maintained at by fiber yarn in unwinding and deep-processing process Together, protection glass fibre is from mechanical stress and also as in composite material manufacturing process Lubricant.

Composite and medical apparatus

One aspect of the present invention relates to assorted fibre yarn purposes in the manufacture of composite. In one embodiment, polymer fiber is melted to form continuous print polymeric matrix, its Middle glass fibre is embedded in polymeric matrix to form discontinuous dispersion phase.Implement at another In scheme, composite comprises the Granule Compound of activity at least one biology, and it is selected from raw Glass, hydroxyapatite and the tricalcium phosphate of thing activity.

The invention still further relates to manufacture and comprise assorted fibre yarn as above or the doctor of composite Use device.This medical apparatus it may be that such as, implant.Wherein mixed fibre by the present invention The assembly of the invention that the composite of dimension yarn or hybrid yarns based on the present invention manufactures, tool High initial modulus and good external intensity is had to retain and for manufacturing such as fracture fixation dress Put, because the bone that high initial modulus and the intensity under hydrolysising condition retain with healing is in a ratio of Device provides the elastic characteristics such as initial.

Medical apparatus can be used in internal any kind of implant or for supporting tissue or Knitting and/or tissue or the device of osteanagenesis.It is any that medical apparatus can also is that with in vivo The textile of kind, fabric or non-woven.

The implant of the present invention can include any kind of implantation for the application of surgery flesh skeleton Thing, such as fixing fracture and/or osteotomy with in order to heal and the fixing screw of bone segment, plate, Pin, stud, " zipper strip " or nail；For fix soft tissue-to-bone, soft tissue-deeply- Bone and soft tissue-to-soft tissue suture, sew up anchor, stud, screw, bolt, nail, Fixture, support and other devices；And it is used for supporting tissue or knitting or the device of regeneration； Or in operation on vertebra, it is used for spinal fusion and the cervical vertebra wedge of other operations and lumbar vertebra cage and lumbar vertebra Plate and lumbar vertebra screw.

According to the present invention, assorted fibre thread material is also used as the tissue engineering bracket of porous. Preferably, the porosity of this support is 60%, more preferably at least 80%, and most preferably At least 90%.

The advantage of the medical apparatus of the present invention is that they pass through to absorb from internal disappearance without passing through High local pH peak value and Potassium release produce toxic action.The medical apparatus of the present invention is additionally Advantage be owing to using bioactive glass fibre in the manufacture of medical apparatus, therefore it There is the biological activity of improvement.

The method that the invention still further relates to manufacture the assorted fibre of the present invention.The method includes following step Rapid:

(i) spinning polymeric fiber；

(ii) spinning glass fibre, separately carries out with spinning polymeric fiber or carries out simultaneously；

(iii) glass fibre and polymer fiber are mixed into hybrid yarns；

(iv) by starching, the surface of hybrid yarns is carried out in-situ treatment, wherein go up pulp mixture by One or more coupling agent groups with the combination of film former, catalyst, additive and/or deionized water Become；

V () is by fiber cake/yarn winding；And

(vi) cure/dry.

The method that the invention still further relates to manufacture the composite of the present invention.The method includes following step Rapid:

A () places assorted fibre yarn with preferred orientation；And

B polymer fiber is fused into the shape of needs by ().

In step (a), term " preferred orientation " means to be orientated by assorted fibre yarn They are substantially parallel to each other, and orientation makes the lattice forming assorted fibre yarn (basic Upper perpendicular to one another), orientation makes yarn in fan-shaped or random orientation.

In step (b), term " melts " and means the heat of sufficient degree is applied to polymer fibre Dimension is to form continuous print polymeric matrix, with shape during wherein glass fibre is embedded in polymeric matrix Become discontinuous dispersion phase.This makes them have ductility, moldable row and pliability.

In step (b), term " shapes of needs " means to be molded by polymer fiber To give the shape of composite any described implant described in detail above.

Embodiment described above and modification combine any aspect of the present invention to its of the present invention His aspect mutatis mutandis.

In this manual, unless the context requires otherwise, otherwise word " comprises/includes (comprise, comprises, comprising) " refer to respectively to mean " comprise/include (include, Includes, including) ".It is to say, when the present invention being described or being defined as comprising specific Feature time, the various embodiments of same invention can also include other feature.

Embodiment

To be more fully described now embodiment of the present invention in the examples below that.Embodiment Be illustrative but be not intended to the raw material of the present invention, compositions, method and application, this for It is apparent from for those skilled in the art.

General fabrication schedule:

The manufacture of glass by following raw materials by raw material being dry mixed, melting, casts and annealed Become: SiO₂、CaCO₃、MgCO₃、SrCO₃、Na₂CO₃、K₂CO₃、H₃BO₃、Al₂O₃ And CaHPO₄*H₂O。

Spin while utilizing glass fibre and polymer fiber and mix (commingling) and make Make hybrid yarns.With seriality glass fibre spinning unit, the glass of casting is spun into fiber.Mesh Mark average single fiber thickness is 10 μm-13 μm.Before filament mixes, spreading mass is applied to glass On glass fiber.According to spreading mass formula, spreading mass is solution based on water, emulsion or solution. Utilize the extruder spinning polymeric fiber simultaneously with multiple fiber spinning jet.Spinning polymeric Fiber and glass fibre are also wound on identical bobbin.In order to terminate hybrid yarns process, Pack into aluminium foil bag storage, be processed further and analyze before, by wet fiber cake at air stream Logical baking oven is dried 48 hours.

Embodiment 1

According to general procedure, will be shown in following glass composition (wt%) of table 1 individually and be polymerized Fibres is simultaneously spun into glass fibre:

Table 1

Embodiment 2

According to general fabrication schedule, use PLDLA7030 polymer and glass 1, glass 2, Glass 3 and glass 4, and based on 3-glycidoxypropyl triethoxysilane (GLYEO) Coupling agent, polycaprolactone (PCL, MW6000g/mol) film former, glacial acetic acid and the starching of water Material manufactures hybrid yarns together.After drying, the fineness (g/km) of hybrid yarns is: glass 1-161g/km；Glass 2-146g/km；Glass 3-140g/km；Glass 4-157g/km.

Embodiment 3

According to general procedure, use PLDLA7030 polymer and glass 1, glass 2, glass 3 and glass 4, with based on N-amino-ethyl-3-amino-propyl-trimethoxysilane coupling agent, Polycaprolactone (PCL, MW6000g/mol) film former, glacial acetic acid are made together with the spreading mass of water Make hybrid yarns.After drying, the fineness (g/km) of hybrid yarns is: glass 1-163g/km；Glass Glass 2-148g/km；Glass 3-146g/km；Glass 4-141g/km.

Embodiment 4

According to general procedure, use PLDLA7030 polymer and glass 1, glass 2, glass 3 and glass 4, and based on N-amino-ethyl-3-amino-propyl-trimethoxysilane coupling agent (AAPTS), chitosan (MW40000-60000g/mol) film former, glacial acetic acid and the starching of water Material manufactures hybrid yarns together.After drying, the fineness (g/km) of hybrid yarns is: glass 1-159g/km；Glass 2-150g/km；Glass 3-162g/km；Glass 4-140g/km.

Embodiment 5

According to general procedure, use PLDLA7030 polymer and glass 1, glass 2, glass 3 and glass 4, and based on isopropyl titanate, isopropanol, acetylacetone,2,4-pentanedione, chitosan (MW40000-60000g/mol) film former, glacial acetic acid manufacture together with the spreading mass of water and mix yarn Line.After drying, the fineness (g/km) of hybrid yarns is: glass 1-152g/km；Glass 2-145g/km； Glass 3-150g/km；Glass 4-147g/km.

Embodiment 6

According to general procedure, use PGLA8515 polymer and glass 4 and glass 5, with base In isopropyl titanate, isopropanol, acetylacetone,2,4-pentanedione, chitosan (MW40000-60000g/mol) film forming Agent, glacial acetic acid manufacture hybrid yarns together with the spreading mass of water.After drying, hybrid yarns is thin Degree (g/km) is: glass 4-143g/km and glass 5-151g/km.

Embodiment 7

Table 2 is seen by the hybrid yarns (yarn 1-18) of filament wound, compression molded unidirectional Continuous fiber composite material plate.Diamond saw is used to be prepared test sample (3 points by composite panel Bending, ASTM D790).According to ASTM D2584, thermally decompose at 565 DEG C 5 hours and survey The glass content of amount composite sample.Selected sample is ground in simulated body fluid at 37 DEG C Study carefully its degraded, continue 16 weeks.(curved to the mechanical performance measuring selected sample by the sample being dried Qu Qiangdu and modulus) and as the function of dissolution time, and with being respectively of cortical bone The bending strength of 170MPa and 15GPa and modulus versus.Result is shown in table 3.

Table 2

Table 3

Embodiment 8

Hybrid yarns (yarn 11 and yarn 17) from embodiment 7 is fused into about 2mm Thick rope and be cut into the granule of about 5mm and 7mm length.Injection by dry granule The crooked test bar (3 bendings, ASTM D790) of standard is prepared in molding.According to ASTM D2584, thermally decomposes the glass content measuring composite sample for 5 hours at 565 DEG C.Will Its degraded studied in simulated body fluid at 37 DEG C by selected sample, continues 16 weeks.By being dried Sample measure the mechanical performance (bending strength and modulus) of selected sample and as dissolution time Function, and with cortical bone be respectively the bending strength of 170MPa and 15GPa and modulus Contrast.Result is shown in table 4.

Table 4

Claims (36)

1. assorted fibre yarn, comprises:

Bio-compatible, biological absorbable and bioactive glass fibre；

Bio-compatible and the polymer fiber of biological absorbable；

The biocompatible coupling agent of polar covalent bond can be formed；And

Bio-compatible and the film former of biological absorbable.

2. assorted fibre yarn as claimed in claim 1, is wherein melting described assorted fibre After yarn, the film former of described bio-compatible and biological absorbable can coupling agent phase be polymerized Entanglement and/or interpenetrating networks or semi-intercrossing network is formed between thing phase.

3. assorted fibre yarn as claimed in claim 1 or 2, wherein said bio-compatible, Biological absorbable and bioactive glass fibre are by the bio-compatible of the strontium that adulterates and biological absorbable Glass fibre make.

4. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said biology Compatible, biological absorbable and bioactive glass fibre have a consisting of:

The SrO of 0.1wt% to 12wt%,

The SiO of 60wt% to 70wt%₂,

The Na of 5wt% to 20wt%₂O,

The CaO of 5wt% to 25wt%,

The MgO of 0wt% to 10wt%,

The P of 0.5wt% to 5wt%₂O₅,

The B of 0wt% to 15wt%₂O₃,

The Al of 0wt% to 5wt%₂O₃, and

The K of 0.05wt% to 1wt%₂O。

5., such as assorted fibre yarn in any one of the preceding claims wherein, also comprise and can protect Protect described glass fibre and increase the surface modifier of wettability of described glass fibre.

6. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said coupling Agent is organosilan.

7. assorted fibre yarn as claimed in claim 6, wherein said coupling agent is alkoxyl Silane.

8. assorted fibre yarn as claimed in claim 5, wherein said surface modifier is to have Machine silane.

9. assorted fibre yarn as claimed in claim 8, wherein said surface modifier is alkane Base silane.

10. the assorted fibre yarn as according to any one of claim 1 to 5, wherein said idol Connection agent is organic titanate.

11. assorted fibre yarns as claimed in claim 10, wherein said coupling agent is selected from alkane Epoxide titanate esters and chelating titanate.

12. assorted fibre yarns as claimed in claim 5, wherein said surface modifier is to have Organic titanate.

13. assorted fibre yarns as claimed in claim 11, wherein said surface modifier is Alkyl titanate.

The 14. assorted fibre yarns as according to any one of claim 1 to 5, wherein said idol Connection agent is organozirconates.

15. assorted fibre yarns as claimed in claim 14, wherein said coupling agent is alcoxyl Base zirconate.

16. assorted fibre yarns as claimed in claim 5, wherein said surface modifier is to have Machine zirconate.

17. assorted fibre yarns as claimed in claim 16, wherein said surface modifier is Alkylzirconate.

18. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said one-tenth The molecular weight of membrane is higher than 1000g/mol.

19. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said one-tenth The molecular weight of membrane is higher than 30000g/mol.

20. such as assorted fibre yarn in any one of the preceding claims wherein, also comprise emulsifying Agent.

21. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said life The 1wt% that thing is compatible, the amount of biological absorbable and bioactive glass fibre is component weight To 98wt%.

22. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said life Thing is compatible and the amount of the polymer fiber of biological absorbable is the 1wt% to 98 of gross weight of component Wt%.

23. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said idol The amount of connection agent is the 0.01wt%-10wt% of component weight.

24. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said one-tenth The amount of membrane is the 0.01wt%-30wt% of component weight.

25. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said poly- Compound fiber is selected from: polylactide (PLA), PLLA (PLLA), poly-DL-lactide (PDLLA), lactide copolymer, PGA (PGA), glycolide copolymer, Acetic acid, hydroxy-, bimol. cyclic ester/ Trimethylene carbonate copolymer (PGA/TMC), lactide/tetramethyl glycolide copolymer, third Lactide/trimethylene carbonate copolymer, lactide/d-valerolactone copolymer, lactide/ε-own interior Ester copolymer, L-lactide/DL-lactide copolymer (PLDLA), Acetic acid, hydroxy-, bimol. cyclic ester/L-lactide are altogether Polymers (PGA/PLLA), PLGA, lactide/glycolides/trimethylene carbon Acid esters terpolymer, lactide/glycolides/6-caprolactone terpolymer, PLA/ polycyclic oxygen second The substituted poly-1,4-dioxane-2,5-diketone of alkyl copolymer, bunching peptide, asymmetric 3,6-, poly-hydroxyl Alkanoate, poly butyric ester (PHB), PHB/b-hydroxyl pentanoate copolymer (PHB/PHV), Poly-b-hydroxy propionate (PHPA), poly-to two alkanone (PDS), poly-dioxane ketone copolymers, Poly-d-valerolactone-poly-6-caprolactone, poly-(6-caprolactone-DL-lactide) copolymer, metering system Acid methyl ester-NVP copolymer, polyesteramide, the polyester of oxalic acid, poly-dihydro pyrrole Mutter, poly-alkyl-2-cyanoacrylate, polyurethane (PU), poly ester urethane (PEU), polyester acyl Amine (PEA), polyvinyl alcohol (PVA), polypeptide, poly-b-malic acid (PMLA), poly-b-alkanoic acid, Merlon, poe, poly phosphate, poly-(ester anhydride) and such as sugar, starch, fibre Dimension element, cellulose derivative, polysaccharide, collagen, chitosan, fibrin, hyaluronic acid, Peptide and protein and the natural polymer of mixture thereof.

26. such as assorted fibre yarn in any one of the preceding claims wherein, wherein said one-tenth Membrane is selected from: polylactide (PLA), PLLA (PLLA), poly-DL-lactide (PDLLA), lactide copolymer, PGA (PGA), glycolide copolymer, Acetic acid, hydroxy-, bimol. cyclic ester/ Trimethylene carbonate copolymer (PGA/TMC), lactide/tetramethyl glycolide copolymer, third Lactide/trimethylene carbonate copolymer, lactide/d-valerolactone copolymer, lactide/ε-own interior Ester copolymer, L-lactide/DL-lactide copolymer (PLDLA), Acetic acid, hydroxy-, bimol. cyclic ester/L-lactide are altogether Polymers (PGA/PLLA), PLGA, lactide/glycolides/trimethylene carbon Acid esters terpolymer, lactide/glycolides/6-caprolactone terpolymer, PLA/ polycyclic oxygen second The substituted poly-1,4-dioxane-2,5-diketone of alkyl copolymer, bunching peptide, asymmetric 3,6-, poly-hydroxyl Alkanoate, poly butyric ester (PHB), PHB/b-hydroxyl pentanoate copolymer (PHB/PHV), Poly-b-hydroxy propionate (PHPA), poly-to two alkanone (PDS), poly-dioxane ketone copolymers, Poly-d-valerolactone-poly-6-caprolactone, poly-(6-caprolactone-DL-lactide) copolymer, metering system Acid methyl ester-NVP copolymer, polyesteramide, the polyester of oxalic acid, poly-dihydro pyrrole Mutter, poly-alkyl-2-cyanoacrylate, polyurethane (PU), poly ester urethane (PEU), polyester acyl Amine (PEA), polyvinyl alcohol (PVA), polypeptide, poly-b-malic acid (PMLA), poly-b-alkanoic acid, Merlon, poe, poly phosphate, poly-(ester anhydride) and such as sugar, starch, fibre Dimension element, cellulose derivative, polysaccharide, collagen, chitosan, fibrin, hyaluronic acid, Peptide and protein and the natural polymer of mixture thereof.

27. such as assorted fibre yarn in any one of the preceding claims wherein, comprise first raw Thing is compatible, biological absorbable and bioactive glass fibre and the second bio-compatible and biology can The glass fibre absorbed, wherein said first glass fibre and described second glass fibre have not Same composition.

28. for manufacturing the assorted fibre in any one of the preceding claims wherein of composite Yarn.

29. assorted fibre yarns in any one of the preceding claims wherein are manufacturing composite In purposes.

30. composite woods comprising the assorted fibre yarn according to any one of claim 1 to 27 Material, wherein said polymer fiber is melted to form continuous print polymeric matrix, wherein glass Fiber is embedded in the polymer matrix to form discontinuous dispersion phase.

31. composites as claimed in claim 30, wherein said composite comprises at least A kind of in bioactive glass, hydroxyapatite and tricalcium phosphate bioactive Granulation compound.

The 32. medical dresses comprising the assorted fibre yarn according to any one of claim 1 to 27 Put.

33. medical apparatus comprising the composite described in claim 30 or 31.

34. medical apparatus as described in claim 32 or 33, wherein said medical apparatus is to plant Enter thing.

The method of the assorted fibre yarn according to any one of 35. manufacturing claims 1 to 27, bag Include following steps:

I) spinning polymeric fiber；

Ii) spinning glass fibre, separately carries out with described spinning polymeric fiber or carries out simultaneously；

Iii) described glass fibre and described polymer fiber are mixed into hybrid yarns；

Iv) by starching, the surface of described hybrid yarns is carried out in-situ treatment, wherein said starching Mixture is by one or more combined with film former, catalyst, additive and/or deionized water Coupling agent forms；

V) by fiber cake/yarn winding；And

Vi) cure/dry.

The method of the composite described in 36. manufacturing claims 30 or 31, comprises the following steps:

A () places the assorted fibre yarn according to any one of claim 1 to 27 with preferred orientation； And

B described polymer fiber is fused into the shape of needs by ().