WO2002000270A1 - Materiaux polymeres biocompatibles - Google Patents

Materiaux polymeres biocompatibles Download PDF

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Publication number
WO2002000270A1
WO2002000270A1 PCT/GB2001/002758 GB0102758W WO0200270A1 WO 2002000270 A1 WO2002000270 A1 WO 2002000270A1 GB 0102758 W GB0102758 W GB 0102758W WO 0200270 A1 WO0200270 A1 WO 0200270A1
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Prior art keywords
polymer
bio
moieties
compatible
polymeric material
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PCT/GB2001/002758
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English (en)
Inventor
John Neil Devine
David John Kemmish
Brian Wilson
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Victrex Manufacturing Limited
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Priority to AU74305/01A priority Critical patent/AU7430501A/en
Publication of WO2002000270A1 publication Critical patent/WO2002000270A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
    • C08G65/34—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from hydroxy compounds or their metallic derivatives
    • C08G65/48—Polymers modified by chemical after-treatment
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds

Definitions

  • This invention relates to bio-compatible polymeric materials and particularly, although not exclusively, provides a bio-compatible polymeric material, a method of producing such a material and the use of such a material in medical treatment, for example in a prosthesis.
  • prosthetic devices such as orthopaedic, dental or maxillofacial implants.
  • prosthetic devices such as orthopaedic, dental or maxillofacial implants.
  • nearly half a million patients receive bone implants each year in the US with the majority being artifical hip and knee joints made from titanium or colbalt-chrome alloys.
  • these materials are too stiff leading to bone resorption, loosening of the implant and, consequently, have lifetimes of less than 10 years.
  • medical devices or prostheses such as pacemakers, vascular grafts, stents, heart valves, catheters and dental implants that contact body tissues or fluids of living persons or animals have been developed and used clinically.
  • a bio-compatible polymeric material for use in medical applications, wherein said material comprises a polymer having bio-compatible moieties associated with chain ends thereof .
  • bio-compatible has generally been used to refer to a material which is compatible with use in medical applications, for example by not being toxic or otherwise harmful to living materials. It also encompasses materials which have a biological or physiological effect when associated with living materials.
  • Bio-compatible moieties suitably refer to moieties which are compatible with use in medical applications, for example by not being toxic or otherwise harmful to living material. Such bio-compatible moieties may be arranged to bond (for example to form ionic or covended bonds) or otherwise interact with materials present in human or animal bodies in order to improve their integration and acceptance by such bodies .
  • any alkyl, akenyl or alkynyl moiety suitably has up to 8, preferably up to 6, more preferably up to 4, especially up to 2, carbon atoms and may be of straight chain or, where possible, of branched chain structure.
  • methyl and ethyl are preferred alkyl groups and C 2 alkenyl and alkynyl groups are preferred.
  • optional substituents of an alkyl group may include halogen atoms, for example fluorine, chlorine, bromine and iodine atoms, and nitro, cyano, alkoxy, hydroxy, amino, alkylamino, sulphinyl, alkylsulphinyl, sulphonyl, alkylsulphonyl, amido, alkylamido, alkoxycarbonyl , haloalkoxycarbonyl and haloalkyl groups.
  • halogen atoms for example fluorine, chlorine, bromine and iodine atoms
  • said bio-compatible polymeric material has improved or enhanced bio-compatibility compared to said polymer in the absence of bio-compatible moieties associated with chain ends thereof .
  • Bio-compatible moieties suitably include moieties arranged to reduce adverse biological reactions when the polymeric material is introduced into (or otherwise associated with) a human or animal body.
  • adverse biological reactions associated with introduction into a human or animal body of said polymer having said bio-compatible moieties may be less compared to use of the same polymer but which does not include associated bio- compatible moieties.
  • said polymer has phenyl moieties; carbonyl or sulphone moieties; and ether or thioether moieties in the polymer backbone.
  • said polymer has a moiety of formula
  • phenyl moieties in units I, II, and III are independently optionally substituted and optionally cross- linked; and wherein m,r,s,t,v,w and z independently represent zero or a positive integer, E and E' independently represent an oxygen or a sulphur atom or a direct link, G represents an oxygen or sulphur atom, a direct link or a -O-Ph-O- moiety where Ph represents a phenyl group and Ar is selected from one of the following moieties (i)*, (i)**, (i) to (x) which is bonded via one or more of its phenyl moieties to adjacent moieties
  • a phenyl moiety may have 1,4- or 1,3-, especially 1,4-, linkages to moieties to which it is bonded.
  • Said polymer may include more than one different type of repeat unit of formula I; more than one different type of repeat unit of formula II; and more than one different type of repeat unit of formula III. Preferably, however, only one type of repeat unit of formula I, II and/or III is provided.
  • Said moieties I, II and III are suitably repeat units.
  • units I, II and/or III are suitably bonded to one another - that is, with no other atoms or groups being bonded between units I, II, and III.
  • phenyl moieties in units I, II or III are optionally substituted, they may be optionally substituted by one or more halogen, especially fluorine and chlorine, atoms or alkyl , cycloalkyl or phenyl groups .
  • Preferred alkyl groups are C ⁇ _ ⁇ 0 , especially C ⁇ - 4 , alkyl groups.
  • Preferred cycloalkyl groups include cyclohexyl and multicyclic groups, for example adamantyl .
  • said phenyl moieties are not optionally- substituted as described.
  • said polymer is cross-linked, it is suitably cross-linked so as to improve its properties.
  • Any suitable means may be used to effect cross-linking.
  • cross-linking between polymer chains may be effected via sulphur atoms on respective chains.
  • said polymer is not optionally cross-linked as described.
  • the respective phenylene moieties may independently have 1,4- or 1,3-linkages to the other moieties in the repeat units of formulae II and/or III.
  • said phenylene moieties have 1,4- linkages.
  • the polymeric chain of the polymer does not include a -S- moiety.
  • G represents a direct link.
  • a represents the mole % of units of formula I in said polymer, suitably wherein each unit I is the same;
  • "b” represents the mole % of units of formula II in said polymer, suitably wherein each unit II is the same;
  • "c” represents the mole % of units of formula III in said polymer, suitably wherein each unit III is the same.
  • a is in the range 45-100, more preferably in the range 45-55, especially in the range 48-52.
  • the sum of b and c is in the range 0-55, more preferably in the range 45-55, especially in the range 48- 52.
  • the ratio of a to the sum of b and c is in the range 0.9 to 1.1 and, more preferably, is about 1.
  • the sum of a, b and c is at least 90, preferably at least 95, more preferably at least 99, especially about 100.
  • said polymer consists essentially of moieties I, II and/or III.
  • Said polymer may be a homopolymer having a repeat unit of general formula or a homopolymer having a repeat unit of general formula
  • A, B, C and D independently represent 0 or 1 and E,E ' ,G,Ar,m, r, s, t,v, w and z are as described in any statement herein.
  • said polymer may be a homopolymer having a repeat unit of general formula
  • m is in the range 0-3, more preferably 0-2, especially 0-1.
  • r is in the range 0-3, more preferably 0-2, especially 0-1.
  • t is in the range 0-3, more preferably 0-2, especially 0-1.
  • s is 0 or 1.
  • v is 0 or 1.
  • w is 0 or 1.
  • z is 0 or 1.
  • said polymer is a homopolymer having a repeat unit of general formula IV.
  • Ar is selected from the following moieties (xi)*, (xi)**,(xi) to (xxi) :
  • the middle phenyl may be 1,4- or 1,3- substituted.
  • (xv) is selected from a 1,2-, 1,3-, or a 1,5- moiety
  • (xvi) is selected from a 1,6-, 2,3-, 2,6- or a 2,7- moiety
  • (xvii) is selected from a 1,2-, 1,4-, 1,5- , 1,8- or a 2,6- moiety.
  • One preferred class of polymers does not include any moieties of formula III, but suitably only includes moieties of formulae I and/or II .
  • said polymer is a homopolymer or random or block copolymer as described, said homopolymer or copolymer suitably includes a repeat unit of general formula IV.
  • Such a polymer may, in some embodiments, not include any repeat unit of general formula V.
  • Suitable moieties Ar are moieties (i)*, (i) , (ii) ,
  • polymers which consist essentially of phenyl moieties in conjunction with ketone and/or ether moieties. That is, in the preferred class, the polymer does not include repeat units which include -S-, -S0 2 - or aromatic groups other than phenyl .
  • Preferred polymers of the type described include :
  • B represents 0 (i.e. polyetherketone) ;
  • E' represent oxygen atoms
  • G represents a direct link
  • m represents 0, w represents 1, r represents 0, s represents 1 and
  • a and B represent 1. (i.e. polyetherketoneetherketoneketone) .
  • polymers described in (a) and (b) are preferred, with the polymer described in (a) being especially preferred.
  • bio-compatible moieties are preferably associated with the surface of said bio-compatible polymeric material and, suitably, do not substantially penetrate the bulk of the material.
  • moieties at the ends of chains of said polymer within the bulk thereof are different compared to bio- compatible moieties associated with ends of chains of said polymer at the surface of the bio-compatible polymeric material.
  • the concentration of bio-compatible moieties at a surface of said bio-compatible polymeric material is preferably greater than the concentration in the bulk of said material. Consequently, said bio- compatible moieties are suitably associated with chain ends of said polymer which are at the surface of the polymer.
  • the concentration of chain end groups at the surface may be greater than the concentration in the bulk. Chain ends of said polymer below the surface of the polymeric material preferably do not include associated bio-compatible moieties.
  • the invention extends to a bio-compatible polymeric material for use in medical applications, wherein said material comprises a polymer, wherein a surface of said material comprises said polymer having bio-compatible moieties associated with chain ends thereof and wherein the bulk of said material comprises said polymer without associated bio-compatible moieties.
  • the concentration of bio-compatible moieties associated with chain ends at the surface of said polymer is greater than the concentration associated with ends in the bulk.
  • Said polymer having bio-compatible moieties associated with chain ends thereof preferably includes moieties other than fluorine atoms associated with its chain ends. Since said polymer having bio-compatible moieties associated with ends thereof is suitably present only at a surface of said bio-compatible polymeric material and is present at a small fraction of the total weight of polymer (the majority of which will not include associated bio- compatible moieties) the existence of said bio-compatible moieties may have limited effect on the bulk properties of said bio-compatible polymeric material compared to said polymer in the absence of said associated bio-compatible moieties.— • ⁇
  • the glass transition temperature (T g ) of said polymer may be at least 135°C, suitably at least 150°C, preferably at least 154°C, more preferably at least 160°C, especially at least 164°C. In some cases, the Tg may be at least 170°C, or at least 190°C or greater than 250°C or even 300°C.
  • Said polymer suitably the bulk thereof, (in the absence of associated bio-compatible moieties) may have an inherent viscosity (IV) of at least 0.1, suitably at least 0.3, preferably at least 0.4, more preferably at least 0.6, especially at least 0.7 (which corresponds to a reduced viscosity (RV) of least 0.8) wherein RV is measured at 25°C on a solution of the polymer in concentrated sulphuric acid of density 1.84gcm "3 , said solution containing lg of polymer per 100cm "3 of solution. IV is measured at 25°C on a solution of polymer in concentrated sulphuric acid of density 1.84gcm 3 , said solution containing 0. lg of polymer per 100cm 3 of solution.
  • RV inherent viscosity
  • RV reduced viscosity
  • the main peak of the melting endotherm (Tm) for said polymer suitably the bulk thereof, (if crystalline) may be at least 300°C.
  • said polymer suitably the bulk thereof, (in the absence of associated bio-compatible moieties) has —at—least some- crystailinity or -is—erysfeallisable.
  • the existence and/or extent of crystallinity in a polymer is preferably measured by wide angle X-ray diffraction, for example as described by Blundell and Osborn (Polymer 24, 953, 1983). Alternatively, crystallinity may be assessed by Differential Scanning Calorimetry (DSC) .
  • DSC Differential Scanning Calorimetry
  • Said polymer suitably the bulk thereof, (in the absence of associated bio-compatible moieties) may have a number average molecular weight in the range 2000-80000.
  • said molecular weight is at least 14,000.
  • the molecular weight may be less than 60,000.
  • Said bio-compatible polymeric material may consist essentially of a single polymer with associated bio- compatible moieties.
  • said bio-compatible polymeric material may comprise a blend of polymers, suitably having different molecular weights.
  • a blend may comprise a relatively low molecular weight polymer and a relatively high molecular weight polymer.
  • a said low molecular weight polymer will have a greater proportion of ends per unit weight and, consequently, may be used to increase the concentration of ends in said bio- compatible polymeric material and, accordingly, to increase the concentration of bio-compatible moieties of said bio-compatible polymer material.
  • a blend comprises a relatively low molecular weight polymer
  • the molecular weight of said low molecular weight polymer may be less than 14,000, but preferably greater than 2,000.
  • the relatively high molecular weight polymer may have a molecular weight of at least 14,000 and suitably less than 80,000, especially less than 60,000.
  • Said bio-compatible polymeric material suitably has a tensile strength (according to ISO R527) of at least 80, preferably at least 90, especially at least 95 MPa.
  • the tensile strength may be less than 360, suitably less than 250, preferably less than 140 MPa. It preferably has an elongate at break (according to ISO R527) of at least 40, preferably at least 50%. It preferably has a tensile modulus (according to ISO R527) of greater than 2.5, preferably greater than 3, especially greater than 3.5 GPa.
  • the tensile modulus may be less than 40, suitably less than 30, preferably less than 20, more preferably less than 10 GPa.
  • flexural strength (according to ASTM D695) of at least 100, more preferably at least 110, especially at least 115 MPa.
  • the flexural strength may be less than 650, preferably less than 400, more preferably less than 260, especially less than 200 MPa.
  • the flexural modulus may be less than 60 , suitably less than 25, preferably less than 20 especially less than 10 GPa.
  • the aforementioned properties can be adjusted by appropriate selection of polymers and/or any reinforcement means included in said support material to suit particular applications.
  • a continuous carbon fibre polyetheretherketone may typically have a tensile strength of about 350 MPa, a tensile modulus of 36 GPa, an elongation of 2%, a flexural modulus of 50 GPa and a flexural strength of 620 MPa.
  • a polyaryletherketone with 30% of high performance fibres typically may have a tensile strength of 224 MPa, a tensile modulus of 13 GPa, a tensile elongation of 2%, a flexural modulus of 20 GPa and a—f-lexural- strength of 250 MPa. -- -
  • Said bio-compatible polymeric material may include one or more fillers for providing desired properties.
  • Said material preferably incorporates an X-ray contrast medium. Fillers and/or said X-ray contrast medium is/are preferably distributed substantially uniformly throughout said material .
  • an X-ray contrast medium suitably comprises less than 25wt%, preferably less than 20wt%, more preferably less than 15wt%, especially less than 10wt% of said bio-compatible material. Where it is provided, at least 2wt% may be included.
  • Preferred X-ray contrast mediums are particulate and preferably are inorganic. They preferably have low solubility in body fluids. They preferably also have a sufficient density compared to that of the polymer to create an image if a compounded mixture of the polymer and contrast medium are X-ray imaged. Barium sulphate and zirconium oxide are examples. Said particulate material is suitably physically held in position by entrapment within the polymer.
  • said bio-compatible polymeric material includes a major amount of said polymer, especially one having moieties I, II and/or III, described according to said first aspect.
  • a “major” amount may mean greater than 50 wt%, suitably greater than 65 wt%, preferably greater than 80 wt%, more preferably greater than 95 wt%, especially greater than 98 wt% of the referenced material is present relative to the total
  • said blend preferably includes at least two polymers of a type according to said first aspect.
  • said at least two polymers preferably include moieties I, II and/or III as described above.
  • a said blend preferably includes a major amount of higher (or the highest) number average molecular weight polymer.
  • Said bio-compatible polymeric material preferably includes a major amount of a higher molecular weight polymer.
  • a said bio-compatible moiety may be selected from an anticoagulant agent such as heparin and heparin sulfate, an antithrombotic agent, a clotting agent, a platelet agent, an anti-inflammatory agent, an antibody, an antigen, an immunoglobulin, a defence agent, an enzyme, a hormone, a growth factor, a neurotransmitter, a cytokine, a blood agent, a regulatory agent, a transport agent, a fibrous agent, a protein such as avidin, a glycoprotein, a globular protein, a structural protein, a membrane protein and a cell attachment protein, a peptide such as a glycopeptide, a structural peptide, a membrane peptide and a cell attachment peptide, a proteoglycan, a toxin, an antibiotic agent, an antibacterial agent, an antimicrobial agent such as pencillin, ticarcillin, carbenicillin, ampicillin, oxacillian, cefazolin
  • PEG poly (ethylene oxide)
  • PEO poly (ethylene oxide)
  • PNVP poly (N-vinyl-2- pyrrolidone)
  • pHEMA poly (2-hydroxyethyl methacrylate
  • HEMA HEMA co-polymers
  • PVD poly(vinyl alcohol)
  • PVA polyacrylamide, its derivatives, poly (methyl methacrylate)
  • PMMA suitably having a PEG chain on each of the side groups, polysiloxanes (e.g. polydimethylsiloxanes (PDMS) ) , ionic water-soluble polymers like poly (acrylic acid) (PAAc) ) and a polyurethane .
  • PDMS polydimethylsiloxanes
  • PAAc polyacrylic acid
  • said bio-compatible moieties may comprise bone morphogenic protein (BMP) as described in US4563489 and patents cited therein and the contents of the aforesaid are incorporated herein.
  • BMP bone morphogenic protein
  • Said BMP may be provided in combination, for example in admixture, with a physiologically acceptable biodegradable organic polymer and said biodegradable polymer may be associated with ends of said polymer of said bio-compatible polymeric material, for example by being covalently bonded to end groups .
  • the combination of said biodegradable polymer and BMP defines said bio-compatible moieties.
  • Said biodegradable polymer is preferably a biodegradable polylactic acid; or alternatively, other physiologically acceptable biodegradable organic polymers which are
  • polylactic acid can be used as the delivery system for BMP.
  • examples include poly (hydroxy organic carboxylic acids) e.g. poly (hydroxy aliphatic carboxylic acids) , polyglycollic acid, polyglactin, polyglactic acid and poly adonic acids.
  • said bio-compatible moieties may be selected from inorganic crystalline structures, inorganic amorphous structures, organic crystalline structures and organic amorphous structures.
  • Preferred bio-compatible moieties are phosphorous based ceramics, for example calcium-phosphorous ceramics. Phosphates in general are suitable but calcium phosphates and calcium apatite are preferred. Especially preferred is hydroxyapatite, a synthetic Ca-P ceramic.
  • Linking moieties for example linking atoms or groups may extend between repeat units of the polymer and said bio-compatible moieties.
  • Said linking moieties may be covalently bonded to ends of respective repeat units of the polymer.
  • Said linking moieties may be covalently bonded to said bio-compatible moieties or may otherwise be associated with said moieties.
  • a said linking moiety may be associated with a single bio-compatible moiety or, alternatively, a said linking moiety may be associated with more than one bio-compatible moiety.
  • said linking moiety may be mono-func ional or multi-functional, for association with one or more bio- compatible moieties.
  • Multi-functional linking moieties may be able advantageously to be associated with more bio- compatible moieties and may, therefore, provide a means to increase the concentration of bio-compatible moieties associated with said bio-compatible material.
  • bio-compatible moieties may be associated with said chain ends of the polymer by any suitable means, for example covended bond(s), hydrogen bond(s), encapsulation in a matrix which is bonded to or otherwise interacts with said end groups, or ionic interaction (s) , it is preferred that there are covended bonds between the bio-compatible moieties and said chain ends or there are ionic interactions between said bio-compatible moieties and said ends .
  • bio-compatible moieties are associated with end groups of the polymer.
  • end group suitably refers to moieties at the end of polymer chains.
  • said bio-compatible polymeric material may be represented by the formula
  • PC represents a polymer chain which suitably comprises repeat units and may, for example, include moieties I, II, III, IV, V, IV*, V* as described above; EG' represents an end-group; and BM' represents a bio- compatible moiety.
  • EG' may represent said aforementioned linking moiety.
  • EG' and- EG'.BM' may be the same, for example where an end group is itself bio-compatible. A -SO3H end group may fall into this category.
  • EG' and EG'.BM 1 represent different moieties.
  • the bond-between PC- and EG' is preferably a covED bond.
  • the interaction between EG' and BM' may be by any suitable means as described above.
  • the interaction is preferably by means of a covended bond or an ionic interaction.
  • a method of making a bio-compatible polymeric material for use in medical applications including the step of causing bio-compatible moieties to become associated with ends, preferably with end groups, of a polymer.
  • the method may provide a relatively easy way of preparing a bio-compatible polymeric material which may avoid the need to post-functionalise repeat units of the polymer.
  • end groups may be produced in a polymerisation reaction in which the polymer is prepared and may then, optionally, be functionalised to enable association with bio-compatible moieties.
  • said end groups may themselves be bio- compatible. It is found that the concentration of end groups of the polymer at a surface of a solid material made from the polymer is much greater than would be expected from a consideration of the molecular weight of the polymer and, accordingly, the concentration of bio- compatible moieties at the surface may be correspondingly greater.
  • the method preferably includes the step of treating said polymer with a material for providing bio-compatible moieties (hereinafter "BCM material”) arranged to provide bio-compatible moieties for association with said chain ends, for example end groups-.
  • BCM material may be arranged to provide any of the bio-compatible moieties described herein.
  • Said polymer may be provided as a solid.
  • said bio-compatible moieties are caused to become associated with a surface of said solid, preferably with end groups present at a surface of said solid.
  • Said solid is preferably shaped so as to represent at least a part of a device for use in medical applications.
  • said device may be a component of an implant for a human or animal body, for example an orthopaedic or dental implant or vascular graft .
  • Said solid may be provided in a desired shape by any suitable means, for example by injection or compression moulding or by film formation techniques or extrusion.
  • the bio-compatible polymeric material is not engineered or otherwise treated in a manner which may result in substantial depletion of the bio-compatible moieties associated with its surface.
  • association of bio-compatible moieties with said chain ends may be effected in any suitable way which will depend on the nature of the BCM material and/or the identity of chain ends of the polymer.
  • the method may include causing covended bond formation between the polymer and said bio-compatible moieties.
  • association of chain ends of the polymer and bio-compatible moieties may be effected by other means, for example by ionic interactions .
  • the method may include the step of treating a polymer of general formula
  • PC represents a polymer chain and EG represents an end group thereof with a material (BM) arranged to supply a bio-compatible material (BM') thereby to produce said bio-compatible polymeric material which may be represented by the formula
  • EG' .BM' represents an association between the end group and the bio-compatible material, wherein EG' represents a residue of end group EG or may represent EG, for example where there is no covended bond formation between EG' and BM' ; and BM' represents a residue of bio- compatible material BM or may represent BM where there is no covended bond formation between EG' and BM' .
  • EG may include any suitable functional groups arranged to become associated with suitable functional groups provided on BM.
  • BM may include any suitable functional group that is arranged to become associated with functional groups included in EG and may be selected from any of the functional groups referred to above for EG provided that a selected functional group provided by EG is capable of becoming associated with, suitably reacting, with a selected functional group provided by BM.
  • BM may be provided by reaction of EG with more than one functional group.
  • a BM' may represent a polyurethane which may be prepared when EG provides a hydroxy group and BM provides a diisocyanate and a diol; or wherein EG provides an isocyanate group and BM provides a diisocyanate and a diol.
  • two different compounds BM may be used, (see Example 12 hereinafter) .
  • BM may be provided by a monomer or monomers having a functional group arranged to react with EG and being arranged to polymerise to provide a polymeric moiety BM' (see Example 11 hereinafter) .
  • EG may be ionic in character, for example it may be -COOM or -S0 3 M and such a group may be arranged to ionically associate with an ionic moiety provided by BM (see Example 9) .
  • an amide bond may be formed between EG and BM (see Examples 8 and 13) .
  • said group EG may be multi-functional, thereby enabling it to associate with a plurality of bio- compatible moieties.
  • multi-functionality may be provided by dendritic or hyperbranched end groups .
  • Preparation of said polymer of general formula PC-EG may include the step of making a polymer of general formula
  • FG represents a functional group at the end of the polymer chain PC.
  • FG may represent EG in which case the polymer having end groups which are caused to be associated with said bio-compatible moieties in the method may not need to be functionalised after polymer formation.
  • said polymer of formula PC-FG may be derivatised to provide the polymer which is caused to be associated with bio-compatible moieties in the method.
  • an end-capper which includes EG may be contacted with monomers used in the preparation of said polymer.
  • Example 5b hereinafter is of this type.
  • said polymer of formula PC-FG may be derivatised with a multi-functional material.
  • said multi-functional material may include a first functional group capable of reacting with said group FG to form a covending bond and, additionally, includes at least two, preferably" at"- least three; other functional groups, suitably different to said first functional group, wherein said other functional groups, after optional derivatisation, may be caused to associate with bio- compatible moieties.
  • Example 13 hereinafter is of this type.
  • Said moiety FG may include or consist of any of the functional groups described above which enable EG to become associated with functional groups provided by BM.
  • FG groups are suitably such that they can survive the polymerisation reaction wherein PC-FG is made and/or subsequent processing.
  • FG and EG represent the same atoms or groups
  • FG preferably represents a functional group that can both survive the polymerisation reaction and/or further processing and be caused to associate with BM.
  • Preferred examples, of groups FG that may survive the polymerisation reaction and/or further processing include -OH, -NH 2 and - S0 3 M, especially where M is an alkali metal.
  • said polymer of formula PC- FG is made into a solid as described above. Then, optionally, the solid polymer may be treated so as to form
  • PC-EG and such treatment suitably involved a surface treatment of said solid.
  • the treatment may be used to functionalise FG thereby to provide groups EG at the surface, wherein EG are of a type which would be less able to survive the polymerisation reaction and/or steps taken
  • FG and EG may be the same as described in which case no treatment of the type described needs to be undertaken) .
  • the EG groups at the surface of the solid are treated thereby to enable bio-compatible moieties to be associated therewith and, accordingly, with the surface of the bio-compatible polymeric material.
  • said polymer of general formula PC-FG may be prepared by polycondensation of a difunctional monomer with itself, wherein said monomer includes a group of formula -FG.
  • said polymer of formula PC-FG may be prepared by polycondensing first and second different difunctional monomers, wherein the monomers have at least two reactive groups each and wherein at least two of the at least four reactive groups provided by the two monomers include a reactive group of formula -FG.
  • one of the monomers includes two FG groups.
  • said polymer of formula PC- FG may be prepared by polycondensing difunctional monomers in the presence of a monomer which includes only a single reactive grou — hich is able to participate in the polycondensation, but, additionally, incorporates a group of formula -FG (which in this case is suitably of a type which cannot polycondense with the other monomers) .
  • one embodiment of the third type of method may use a first difunctional monomer having two reactive groups of the same identity; a second difunctional monomer having two reactive groups of the same identity but which are different to those of said first difunctional monomers; and a third monomer having one reactive group which is able to polycondense with said first or second monomers, for example by virtue of it having one reactive group which is the same as a reactive group of the first or second monomers and a second group which is of formula -FG (which is suitably of a type which cannot polycondense with the other monomers) .
  • the third monomer acts as a chain terminator thereby leading to FG groups at the end of polymer chains .
  • polymers of general formula PC-FG described herein may be prepared by:
  • Y 1 represents a halogen atom or a group -EH and Y 2 represents a halogen atom or, if Y 1 represents a halogen atom, Y 2 represents a group E'H; or
  • Y 1 represents a halogen atom or a group -EH (or -E'H if appropriate) and X 1 represents the other one of a halogen atom or group -EH (or -E'H if appropriate) and Y 2 represents a halogen atom or a group -E'H and X 2 represents the other one of a halogen atom or a group -E'H (or -EH if appropriate) .
  • repeat units of the polymer prepared may be optionally substituted with the groups hereinabove described after polymer formation.
  • the repeats units are not functionalised.
  • Y 1 , Y 2 , X 1 and/or X 2 represent a halogen, especially a fluorine, atom, an activating group, especially a carbonyl or sulphone group, being arranged ortho- or para- to the halogen atom.
  • halogen atoms are fluorine and chlorine atoms, with fluorine atoms being especially preferred.
  • halogen atoms are arranged meta- or para- to activating groups, especially carbonyl groups.
  • one of Y 1 and Y 2 represents a fluorine atom and the other represents an hydroxy group. More preferably in this case, Y 1 represents a fluorine atom and Y 2 represents an hydroxy group.
  • the process described in paragraph (a) may be used when Ar represents a moiety of structure (i) and m represents 1.
  • Y 1 and Y 2 each represent an hydroxy group.
  • X 1 and X 2 each represent a halogen atom, suitably the same halogen atom.
  • a* represents the mole% of compound VI used in the process
  • » b* represents the mole % of compound VII used in the process
  • “c*” represents the mole % of compound VIII used in the process.
  • a* is in the range 45-55, especially in the range 48-52.
  • the sum of b* and c* is in the range 45-55, especially in the range 48-52.
  • the sum of a*, b* and c* is 100.
  • one of either the total mole % of halogen atoms or groups -EH/-E ⁇ in compounds VI, VII and VIII is greater, for example by up to 10%, especially up to 5%, than the total mole % of the other one of either the total mole % of halogen atoms or groups -EH/-E'H in compounds VI, VII and VIII.
  • the polymer may have halogen end groups whereas when the mole % of groups -EH/-E'H is greater the polymer will have -EH/-E ⁇ end groups.
  • the molecular weight of the polymer can also be controlled by using an excess of halogen or hydroxy reactants.
  • the excess may typically be in the range 0.1 to 5.0 mole %.
  • the polymerisation reaction may be terminated by addition of one or more monofunctional reactants as end- cappers and such end-cappers may include said group FG.
  • a device for use in medical applications wherein said device comprises a bio- compatible polymeric material according to said first aspect or made in a method according to said second aspect .
  • Said device is preferably a prosthetic device, for example an implant such as an orthopaedic, dental or maxillofacila implant or a component thereof; or a device, for example a catheter, which is arranged to be temporarily associated with a human or animal body.
  • Said device is preferably a prosthetic device as described.
  • An orthopaedic device may be- an implant for a body joint, for example a hip or knee joint or spine fusion device.
  • a said device may include a part or parts made out of said bio-compatible polymeric material and a part or parts made out of other materials.
  • said device includes at least 50wt%, preferably at least 65wt%, more preferably at least 80wt%, especially at least 95wt% of said bio-compatible polymeric material.
  • said device may consist essential of said bio- compatible polymeric material .
  • a method of making a device comprising: forming a material into a shape which represents or is a precursor of a device or a part of a device for use in medical applications wherein said material comprises a polymer; and treating material in said shape (preferably the surface thereof) thereby to cause bio-compatible moieties to associate with chain ends of said polymer (preferably chain ends present at or near the surface of said polymer) .
  • the invention extends to the use of a polymer having bio-compatible moieties associated with chain ends thereof in the manufacture of a device for use in a medical treatment, for example in surgery.
  • Example 1 Fluorine-terminated polyetheretherketone .
  • the temperature was raised to 175°C, held for 60 min; heated to 200 °C, held for 30mins; heated to 250°C, held for 30 mins; heated to 300°C and held for 120 mins .
  • the reaction mixture was allowed to cool, milled and washed with acetone and water.
  • the resulting polymer was dried in an air oven at 120°C.
  • the polymer had Inherent Viscosity (IV) of 0.71. IV is measured at 25°C on a solution of polymer in concentrated sulphuric acid of density 1.84gcm 3 , said solution containing 0. lg of polymer per 100cm 3 of solution.
  • 4-Hydroxybenzoic acid (30.36g, 0.22 mol) was added to a 500ml reaction flask containing a magnetic follower and sodium carbonate (46.64g, 0.440 mol) dissolved in deionised water (250ml) and heated at 80°C for 1 hour. The solution was cooled to room temperature, the insoluble material was removed by filtration, the water was evaporated and the residue was finely ground and dried under vacuum at 60°C overnight.
  • Example 3 Carboxylic acid-surface modified polyetheretherketone .
  • the surface modified polyetheretherketone of Example 3 was stirred at 10°C for 1 hr under an atmosphere of nitrogen in an aqueous solution of the water soluble carbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) - carbodiimide) (0.4g) dissolved in buffer at pH 4.5 (0.1M 2- (N-morpholino) ethanesulphonic acid) (40ml).
  • the sample of polyetheretherketone was removed and washed with buffer solution.
  • the sample was stirred at 20°C for 24 hr under an atmosphere of nitrogen in a solution of the peptide GRGDS (80mg) in phosphate-buffered saline solution (40ml) (Na 2 HP0 4 , 1.15g; KH 2 P0 4 , 0.2g; NaCl. 8g; KCl, 0.2g; MgCl 2 , O.lg; CaCl 2 . 0. lg in 1 Litre of distilled water).
  • the functionalised polyetherethereketone was washed successively with phosphate buffer and distilled water.
  • the reaction mixture was allowed to cool, milled and washed with acetone and water.
  • the resulting polymer was dried in an air oven at 120°C.
  • the polymer had an IV of
  • the hydroxy-terminated polymer was injection moulded into a specimen 4cm x 1cm x 0.4cm.
  • Example 5b Dimethoxy-terminated polyetherethereketone .
  • the reaction mixture was allowed to cool, milled and washed with acetone and water.
  • the resulting polymer was dried in an air oven at 120°C.
  • the polymer had an IV of 0.75.
  • the dimethoxy-terminated polymer was injection moulded into a specimen 4cm x 1cm x 0.4cm.
  • Example 5c Dihydroxy-terminated polyetheretherketone .
  • the reaction mixture was allowed to cool, milled and washed with acetone and water.
  • the resulting polymer was dried in an air oven at 120°C.
  • Example 7a Sodium sulphonate-terminated polyetheretherketone .
  • the reaction mixture was allowed to cool, milled and washed with acetone and water.
  • the resulting polymer was dried in an air oven at 120°C.
  • the polymer had an IV of 0.81. Thereafter, the polymer was injection moulded into a specimen 4cm x 1cm x 0.4cm.
  • Example 7b Sulphonic acid-terminated polyetheretherketone .
  • Example 7a The specimen of Example 7a was placed in a 700ml flanged flask fitted with a reflux condenser, a magnetic follower and a nitrogen inlet and outlet and charged with 0.1M hydrochloric acid (500ml). Under a nitrogen atmosphere and with continuous stirring the contents were heated to 50°C for 6 hrs. The reaction mixture was allowed to cool to room temperature, the sample was removed, washed with deionised water until the pH was neutral and dried.
  • 0.1M hydrochloric acid 500ml
  • Example 7c Sulphonyl chloride-terminated polyetheretherketone .
  • Example 7b The plaque of Example 7b was placed in a 700ml flanged flask fitted with a reflux condenser, a magnetic follower and a nitrogen inlet and outlet and charged with thionyl chloride (250ml), dichloromethane (250ml) and dimethylformamide (30ml) . Under a nitrogen atmosphere and with continuous stirring the mixture was heated to under reflux for 15 hrs. The reaction mixture was allowed to cool to room temperature, the plaque was removed and washed with ether and dried in vacuo.
  • thionyl chloride 250ml
  • dichloromethane 250ml
  • dimethylformamide 30ml
  • Example 8 Reaction of Amino-surface modified polyetherketone with the peptide GRGDS
  • the contents were stirred under an atmosphere of nitrogen at room temperature for 2hrs.
  • the specimen was removed, washed with ether and dried in vacuo for lOhrs at 50°C.
  • the dried sample was stirred at 20°C for 24 hr under an atmosphere of nitrogen in a solution of the peptide —GRGDS (-80mg) in--an- aqueous buffer solution (-40ml), pH 9.
  • the functionalised PEK was washed successively with the buffer solution and ether.
  • Example 9 Calcium Phosphate Deposition on a sulphonic acid and sodium sulphonate-surface modified polyetherethereketone .
  • a supersaturated calcium phosphate solution containing 5mM CaCl 2 , 1.5mM KH 2 P0 4 and 1.5mM Na 2 HP0 4 was prepared by mixing 0.1M Na 2 HP0 4 solution (1.5ml) and deionised water
  • Example 10 Reaction of sulphonyl chloride-surface modified polyetheretherketone with 4-aminostyrene.
  • Example 11 Reaction of Styrene-surface modified polyetheretherketone of Example 10 with hydroxyethylmethacrylate to produce polyetheretherketone with a surface coating of PHEMA.
  • the styrene-surface modified polyetheretherketone of Example 10 was placed in a 100ml round-bottomed flask, fitted with a magnetic follower, a nitrogen inlet and outlet and containing toluene (50ml) and hydroxyethylmethacrylate (3.25g) and benzoyl peroxide (0.005g). The mixture was stirred under nitrogen at 80°C for 2 hours. The sample of polyetheretherketone was removed washed with fresh toluene, followed by ethanol and water and dried in vacuum at 50°C for 24 hours.
  • Example 12 Reaction of hydroxyl-surface modified polyetheretherketone with diphenylmethane-4, 4' - diisocyanate and diol to produce polyetheretherketone with a surface coating of polyurethane.
  • a 100ml round-bottomed flask, fitted with a magnetic follower, a nitrogen inlet and outlet was provided with THF (50ml), polyethylene glycol, PEG 1000 (lOg, 0.01 mol), diphenylmethane 4, 4' -diisocyanate (2.53g, 0.0101 mol) and stannous octanoate (0. Olg) .
  • THF 50ml
  • polyethylene glycol polyethylene glycol
  • PEG 1000 lOg, 0.01 mol
  • diphenylmethane 4, 4' -diisocyanate (2.53g, 0.0101 mol) and stannous octanoate (0. Olg) The mixture was stirred under nitrogen at 50°C for 3 hours.
  • the dihydroxy-modified polyetheretherketone of Example 5c was placed in flask and stirring was continued for a further 5 hours at 50°C.
  • the sample of polyetheretherketone was removed washed with fresh THF and dried
  • Example 13 An injection moulded specimen of polymer of Example 6, 4cm x 1cm x 0.4cm, was placed in a 100ml round-bottomed flask fitted with a magnetic follower

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Abstract

Cette invention concerne un matériau polymère biocompatible pouvant être utilisé dans des applications médicales, par exemple pour un implant orthopédique. Ce matériau comprend un polymère, en particulier un polymère avec fractions phényle, fractions carbonyle ou sulphone et des fractions éther ou thioéther dans le squelette polymère. Les fractions biocompatibles sont associées aux extrémité de chaîne du polymère, ce qui améliore la biocompatibilité du polymère par rapport à celle du polymère seul. Selon des modes de réalisations préférés, on peut donner à un polymère dont la chaîne possède des groupes fonctionnels à ses extrémités une forme qui représente en tout ou en partie un dispositif ou qui est un précurseur de dispositif - destiné à des applications médicales, les fractions biocompatibles pouvant s'associer avec les extrémités de la chaîne du polymère à la surface ou prés de la surface du polymère.
PCT/GB2001/002758 2000-06-24 2001-06-22 Materiaux polymeres biocompatibles WO2002000270A1 (fr)

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Cited By (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1348454A1 (fr) * 2002-03-28 2003-10-01 Depuy Products, Inc. Prothèse avec un composant de polyaryléthercétone
US7670282B2 (en) 2004-06-14 2010-03-02 Pneumrx, Inc. Lung access device
US7674293B2 (en) 2004-04-22 2010-03-09 Facet Solutions, Inc. Crossbar spinal prosthesis having a modular design and related implantation methods
WO2010030993A1 (fr) 2008-09-12 2010-03-18 Pneumrx, Inc. Modèles améliorés et/ou rallongés de dispositifs de réduction de volume pulmonaire à effraction minimale et leur mise en place
US7691145B2 (en) 1999-10-22 2010-04-06 Facet Solutions, Inc. Prostheses, systems and methods for replacement of natural facet joints with artificial facet joint surfaces
US7766891B2 (en) 2004-07-08 2010-08-03 Pneumrx, Inc. Lung device with sealing features
US7766938B2 (en) 2004-07-08 2010-08-03 Pneumrx, Inc. Pleural effusion treatment device, method and material
WO2010135352A1 (fr) 2009-05-18 2010-11-25 Pneumrx, Inc. Modification de section transversale durant le déploiement d'un dispositif allongé de réduction du volume pulmonaire
US7846162B2 (en) 2005-05-18 2010-12-07 Sonoma Orthopedic Products, Inc. Minimally invasive actuable bone fixation devices
EP2292188A2 (fr) 2002-11-27 2011-03-09 Conformis, Inc. Outils chirurgicaux pouvant etre selectionnes en fonction du patient
US7909825B2 (en) 2006-11-22 2011-03-22 Sonoma Orthepedic Products, Inc. Fracture fixation device, tools and methods
US7914556B2 (en) 2005-03-02 2011-03-29 Gmedelaware 2 Llc Arthroplasty revision system and method
EP2324799A2 (fr) 2004-11-24 2011-05-25 Conformis, Inc. Dispositifs d'arthroplastie de l'articulation du genou, sélectionnables selon le patient
EP2335654A1 (fr) 2003-11-25 2011-06-22 Conformis, Inc. Dispositifs d'arthroplastie d'articulation du genou selectionnables selon le patient
US8070811B2 (en) 1999-10-22 2011-12-06 Gmedelaware 2 Llc Facet arthroplasty devices and methods
USRE43282E1 (en) 1998-09-14 2012-03-27 The Board Of Trustees Of The Leland Stanford Junior University Assessing the condition of a joint and devising treatment
US8157837B2 (en) 2006-03-13 2012-04-17 Pneumrx, Inc. Minimally invasive lung volume reduction device and method
WO2012008837A3 (fr) * 2010-07-16 2012-05-10 X-Flow Bv Poly(arylsulfone) greffée et procédé de greffage d'une poly(arylsulfone)
US8187303B2 (en) 2004-04-22 2012-05-29 Gmedelaware 2 Llc Anti-rotation fixation element for spinal prostheses
US8221461B2 (en) 2004-10-25 2012-07-17 Gmedelaware 2 Llc Crossbar spinal prosthesis having a modular design and systems for treating spinal pathologies
US8231655B2 (en) 2003-07-08 2012-07-31 Gmedelaware 2 Llc Prostheses and methods for replacement of natural facet joints with artificial facet joint surfaces
US8287541B2 (en) 2005-05-18 2012-10-16 Sonoma Orthopedic Products, Inc. Fracture fixation device, tools and methods
EP2520255A1 (fr) 2005-11-21 2012-11-07 Vertegen, Inc. Dispositifs et procédés de traitement de facettes articulaires lombaires, d'articulations uncovertébrales, d'articulations costovertébrales et d'autres articulations
US8398681B2 (en) 2004-08-18 2013-03-19 Gmedelaware 2 Llc Adjacent level facet arthroplasty devices, spine stabilization systems, and methods
US8409254B2 (en) 2003-05-14 2013-04-02 Gmedelaware 2 Llc Prostheses, tools and methods for replacement of natural facet joints with artificial facet joint surfaces
US8496686B2 (en) 2005-03-22 2013-07-30 Gmedelaware 2 Llc Minimally invasive spine restoration systems, devices, methods and kits
WO2013131066A1 (fr) 2012-03-02 2013-09-06 Conformis, Inc. Implants du genou stabilisés postérieurs adaptés au patient, conceptions et procédés et outils associés
EP2649951A2 (fr) 2006-02-06 2013-10-16 ConforMIS, Inc. Dispositifs d'arthroplastie articulaire et outils chirurgicaux selectionnables par le patient
US8675930B2 (en) 2004-04-22 2014-03-18 Gmedelaware 2 Llc Implantable orthopedic device component selection instrument and methods
US8702755B2 (en) 2006-08-11 2014-04-22 Gmedelaware 2 Llc Angled washer polyaxial connection for dynamic spine prosthesis
EP2754419A2 (fr) 2011-02-15 2014-07-16 Conformis, Inc. Implants orthopédiques améliorés et adaptés au patient, conceptions et outils associés
WO2014151557A2 (fr) 2013-03-15 2014-09-25 Pneumrx, Inc. Structures d'implant compressif à réduction de volume pulmonaire dans les voies aériennes à soulagement de couple
US8862202B2 (en) 1998-09-14 2014-10-14 The Board Of Trustees Of The Leland Stanford Junior University Assessing the condition of a joint and preventing damage
US8888800B2 (en) 2006-03-13 2014-11-18 Pneumrx, Inc. Lung volume reduction devices, methods, and systems
US8951260B2 (en) 2001-05-25 2015-02-10 Conformis, Inc. Surgical cutting guide
US8961516B2 (en) 2005-05-18 2015-02-24 Sonoma Orthopedic Products, Inc. Straight intramedullary fracture fixation devices and methods
US9017334B2 (en) 2009-02-24 2015-04-28 Microport Orthopedics Holdings Inc. Patient specific surgical guide locator and mount
US9023050B2 (en) 2001-05-25 2015-05-05 Conformis, Inc. Surgical tools for arthroplasty
US9055953B2 (en) 2001-05-25 2015-06-16 Conformis, Inc. Methods and compositions for articular repair
US9056016B2 (en) 2003-12-15 2015-06-16 Gmedelaware 2 Llc Polyaxial adjustment of facet joint prostheses
US9060820B2 (en) 2005-05-18 2015-06-23 Sonoma Orthopedic Products, Inc. Segmented intramedullary fracture fixation devices and methods
US9066728B2 (en) 2001-05-25 2015-06-30 Conformis, Inc. Surgical tools facilitating increased accuracy, speed and simplicity in performing joint arthroplasty
US9125639B2 (en) 2004-11-23 2015-09-08 Pneumrx, Inc. Steerable device for accessing a target site and methods
US9155574B2 (en) 2006-05-17 2015-10-13 Sonoma Orthopedic Products, Inc. Bone fixation device, tools and methods
US9198766B2 (en) 2003-05-14 2015-12-01 Gmedelaware 2 Llc Prostheses, tools, and methods for replacement of natural facet joints with artificial facet joint surfaces
US9286686B2 (en) 1998-09-14 2016-03-15 The Board Of Trustees Of The Leland Stanford Junior University Assessing the condition of a joint and assessing cartilage loss
US9308053B2 (en) 2006-02-06 2016-04-12 Conformis, Inc. Patient-specific joint arthroplasty devices for ligament repair
US9326780B2 (en) 2006-02-06 2016-05-03 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools incorporating anatomical relief
US9402633B2 (en) 2006-03-13 2016-08-02 Pneumrx, Inc. Torque alleviating intra-airway lung volume reduction compressive implant structures
US9486226B2 (en) 2012-04-18 2016-11-08 Conformis, Inc. Tibial guides, tools, and techniques for resecting the tibial plateau
US9579110B2 (en) 2001-05-25 2017-02-28 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9642632B2 (en) 2009-02-24 2017-05-09 Microport Orthopedics Holdings Inc. Orthopedic surgical guide
US9649117B2 (en) 2009-02-24 2017-05-16 Microport Orthopedics Holdings, Inc. Orthopedic surgical guide
US9675471B2 (en) 2012-06-11 2017-06-13 Conformis, Inc. Devices, techniques and methods for assessing joint spacing, balancing soft tissues and obtaining desired kinematics for joint implant components
EP3187153A2 (fr) 2005-09-30 2017-07-05 Conformis, Inc. Implant porteur
US9770278B2 (en) 2014-01-17 2017-09-26 Arthrex, Inc. Dual tip guide wire
US9801637B2 (en) 2006-03-13 2017-10-31 Pneumrx, Inc. Genetically-associated chronic obstructive pulmonary disease treatment
US9814499B2 (en) 2014-09-30 2017-11-14 Arthrex, Inc. Intramedullary fracture fixation devices and methods
US10100144B2 (en) 2014-05-22 2018-10-16 Ketonex Limited Method for making particulate amine-functionalized polyaryletherketone polymers and copolymers thereof
US10390838B1 (en) 2014-08-20 2019-08-27 Pneumrx, Inc. Tuned strength chronic obstructive pulmonary disease treatment
US10450408B2 (en) 2014-09-10 2019-10-22 Ketonex Limited Method for making polyarylaliphaticetherketone polymers and copolymers thereof
US10537334B2 (en) 2013-10-25 2020-01-21 Pneumrx, Inc. Genetically-associated chronic obstructive pulmonary disease treatment
US10800876B2 (en) 2014-05-22 2020-10-13 Ketonex Limited Amine and non-amine derivatized polyaryletherketone random and block copolymers
WO2022230934A1 (fr) * 2021-04-27 2022-11-03 出光興産株式会社 Polyétheréthercétone, et procédé de fabrication de celui-ci
US12108959B2 (en) 2019-05-29 2024-10-08 Wright Medical Technology, Inc. Preparing a tibia for receiving tibial implant component of a replacement ankle

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4959424A (en) * 1986-07-25 1990-09-25 Amoco Corporation Amino-terminated poly(aryl ether ketones)

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4959424A (en) * 1986-07-25 1990-09-25 Amoco Corporation Amino-terminated poly(aryl ether ketones)

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
G.S.BENNETT: "Poly(Aryl Ether Ketone)s, Amine-terminated", POLYMERIC MATERIALS ENCYCLOPEDIA, J.C.SALAMONE (ED), CRC PRESS, BOCA RATON, FL,USA, vol. 7, 1996, pages 5555 - 5561, XP002181440 *
MARCHAND-BRYNAERT J ET AL: "Surface fluorination of PEEK film by selective wet-chemistry", POLYMER, ELSEVIER SCIENCE PUBLISHERS B.V, GB, vol. 38, no. 6, 1 March 1997 (1997-03-01), pages 1387 - 1394, XP004055782, ISSN: 0032-3861 *
NOISET OLIVIER ET AL: "Surface modification of poly(aryl ether ether ketone) (PEEK) film by covalent coupling of amines and amino acids through a spacer arm", J POLYM SCI PART A;JOURNAL OF POLYMER SCIENCE, PART A: POLYMER CHEMISTRY DEC 1997 JOHN WILEY & SONS INC, NEW YORK, NY, USA, vol. 35, no. 17, December 1997 (1997-12-01), pages 3779 - 3790, XP002180806 *

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Publication number Priority date Publication date Assignee Title
US8862202B2 (en) 1998-09-14 2014-10-14 The Board Of Trustees Of The Leland Stanford Junior University Assessing the condition of a joint and preventing damage
USRE43282E1 (en) 1998-09-14 2012-03-27 The Board Of Trustees Of The Leland Stanford Junior University Assessing the condition of a joint and devising treatment
US9286686B2 (en) 1998-09-14 2016-03-15 The Board Of Trustees Of The Leland Stanford Junior University Assessing the condition of a joint and assessing cartilage loss
US7691145B2 (en) 1999-10-22 2010-04-06 Facet Solutions, Inc. Prostheses, systems and methods for replacement of natural facet joints with artificial facet joint surfaces
US8092532B2 (en) 1999-10-22 2012-01-10 Gmedelaware 2 Llc Facet arthroplasty devices and methods
US8070811B2 (en) 1999-10-22 2011-12-06 Gmedelaware 2 Llc Facet arthroplasty devices and methods
US8066740B2 (en) 1999-10-22 2011-11-29 Gmedelaware 2 Llc Facet joint prostheses
US9084617B2 (en) 2001-05-25 2015-07-21 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9579110B2 (en) 2001-05-25 2017-02-28 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9216025B2 (en) 2001-05-25 2015-12-22 Conformis, Inc. Joint arthroplasty devices and surgical tools
US8951259B2 (en) 2001-05-25 2015-02-10 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9186161B2 (en) 2001-05-25 2015-11-17 Conformis, Inc. Surgical tools for arthroplasty
US9125673B2 (en) 2001-05-25 2015-09-08 Conformis, Inc. Joint arthroplasty devices and surgical tools
US8951260B2 (en) 2001-05-25 2015-02-10 Conformis, Inc. Surgical cutting guide
US8998915B2 (en) 2001-05-25 2015-04-07 Conformis, Inc. Joint arthroplasty devices and surgical tools
US9125672B2 (en) 2001-05-25 2015-09-08 Conformis, Inc. Joint arthroplasty devices and surgical tools
US9107679B2 (en) 2001-05-25 2015-08-18 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9107680B2 (en) 2001-05-25 2015-08-18 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9023050B2 (en) 2001-05-25 2015-05-05 Conformis, Inc. Surgical tools for arthroplasty
US9072531B2 (en) 2001-05-25 2015-07-07 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9055953B2 (en) 2001-05-25 2015-06-16 Conformis, Inc. Methods and compositions for articular repair
US9358018B2 (en) 2001-05-25 2016-06-07 Conformis, Inc. Joint arthroplasty devices and surgical tools
US9295482B2 (en) 2001-05-25 2016-03-29 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9066728B2 (en) 2001-05-25 2015-06-30 Conformis, Inc. Surgical tools facilitating increased accuracy, speed and simplicity in performing joint arthroplasty
US7022798B2 (en) 2002-03-28 2006-04-04 Depuy Products, Inc. Prosthetic device having a polyaryletherketone component with enhanced wettability and method for making the same
AU2003203473B2 (en) * 2002-03-28 2009-04-09 Depuy Products, Inc. Prosthetic device having a polyaryletherketone, component with enhanced wetability and a method for making the same
US6711755B2 (en) 2002-03-28 2004-03-30 Depuy Products, Inc. Prosthetic device having a polyaryletherketone component with enhanced wettability and a method for making the same
EP1348454A1 (fr) * 2002-03-28 2003-10-01 Depuy Products, Inc. Prothèse avec un composant de polyaryléthercétone
EP2292189A2 (fr) 2002-11-27 2011-03-09 Conformis, Inc. Outils chirurgicaux pouvant etre selectionnes en fonction du patient
EP2292188A2 (fr) 2002-11-27 2011-03-09 Conformis, Inc. Outils chirurgicaux pouvant etre selectionnes en fonction du patient
US9198766B2 (en) 2003-05-14 2015-12-01 Gmedelaware 2 Llc Prostheses, tools, and methods for replacement of natural facet joints with artificial facet joint surfaces
US8409254B2 (en) 2003-05-14 2013-04-02 Gmedelaware 2 Llc Prostheses, tools and methods for replacement of natural facet joints with artificial facet joint surfaces
US8523907B2 (en) 2003-07-08 2013-09-03 Gmedelaware 2 Llc Prostheses, tools and methods for replacement of natural facet joints with artificial facet joint surfaces
US8231655B2 (en) 2003-07-08 2012-07-31 Gmedelaware 2 Llc Prostheses and methods for replacement of natural facet joints with artificial facet joint surfaces
EP2335654A1 (fr) 2003-11-25 2011-06-22 Conformis, Inc. Dispositifs d'arthroplastie d'articulation du genou selectionnables selon le patient
US9056016B2 (en) 2003-12-15 2015-06-16 Gmedelaware 2 Llc Polyaxial adjustment of facet joint prostheses
US8425557B2 (en) 2004-04-22 2013-04-23 Gmedelaware 2 Llc Crossbar spinal prosthesis having a modular design and related implantation methods
US8675930B2 (en) 2004-04-22 2014-03-18 Gmedelaware 2 Llc Implantable orthopedic device component selection instrument and methods
US8496687B2 (en) 2004-04-22 2013-07-30 Gmedelaware 2 Llc Crossbar spinal prosthesis having a modular design and related implantation methods
US8491635B2 (en) 2004-04-22 2013-07-23 Gmedelaware 2 Llc Crossbar spinal prosthesis having a modular design and related implantation methods
US7674293B2 (en) 2004-04-22 2010-03-09 Facet Solutions, Inc. Crossbar spinal prosthesis having a modular design and related implantation methods
US8187303B2 (en) 2004-04-22 2012-05-29 Gmedelaware 2 Llc Anti-rotation fixation element for spinal prostheses
US7670282B2 (en) 2004-06-14 2010-03-02 Pneumrx, Inc. Lung access device
US7775968B2 (en) 2004-06-14 2010-08-17 Pneumrx, Inc. Guided access to lung tissues
US7766891B2 (en) 2004-07-08 2010-08-03 Pneumrx, Inc. Lung device with sealing features
US7766938B2 (en) 2004-07-08 2010-08-03 Pneumrx, Inc. Pleural effusion treatment device, method and material
US8398681B2 (en) 2004-08-18 2013-03-19 Gmedelaware 2 Llc Adjacent level facet arthroplasty devices, spine stabilization systems, and methods
US8221461B2 (en) 2004-10-25 2012-07-17 Gmedelaware 2 Llc Crossbar spinal prosthesis having a modular design and systems for treating spinal pathologies
US10034999B2 (en) 2004-11-23 2018-07-31 Pneumrx, Inc. Steerable device for accessing a target site and methods
US9125639B2 (en) 2004-11-23 2015-09-08 Pneumrx, Inc. Steerable device for accessing a target site and methods
EP2324799A2 (fr) 2004-11-24 2011-05-25 Conformis, Inc. Dispositifs d'arthroplastie de l'articulation du genou, sélectionnables selon le patient
US7914556B2 (en) 2005-03-02 2011-03-29 Gmedelaware 2 Llc Arthroplasty revision system and method
US8496686B2 (en) 2005-03-22 2013-07-30 Gmedelaware 2 Llc Minimally invasive spine restoration systems, devices, methods and kits
US7846162B2 (en) 2005-05-18 2010-12-07 Sonoma Orthopedic Products, Inc. Minimally invasive actuable bone fixation devices
US7942875B2 (en) 2005-05-18 2011-05-17 Sonoma Orthopedic Products, Inc. Methods of using minimally invasive actuable bone fixation devices
US8287539B2 (en) 2005-05-18 2012-10-16 Sonoma Orthopedic Products, Inc. Fracture fixation device, tools and methods
US8961516B2 (en) 2005-05-18 2015-02-24 Sonoma Orthopedic Products, Inc. Straight intramedullary fracture fixation devices and methods
US7914533B2 (en) 2005-05-18 2011-03-29 Sonoma Orthopedic Products, Inc. Minimally invasive actuable bone fixation devices
US9060820B2 (en) 2005-05-18 2015-06-23 Sonoma Orthopedic Products, Inc. Segmented intramedullary fracture fixation devices and methods
US8287541B2 (en) 2005-05-18 2012-10-16 Sonoma Orthopedic Products, Inc. Fracture fixation device, tools and methods
EP3187153A2 (fr) 2005-09-30 2017-07-05 Conformis, Inc. Implant porteur
EP2520255A1 (fr) 2005-11-21 2012-11-07 Vertegen, Inc. Dispositifs et procédés de traitement de facettes articulaires lombaires, d'articulations uncovertébrales, d'articulations costovertébrales et d'autres articulations
US9308053B2 (en) 2006-02-06 2016-04-12 Conformis, Inc. Patient-specific joint arthroplasty devices for ligament repair
EP2649951A2 (fr) 2006-02-06 2013-10-16 ConforMIS, Inc. Dispositifs d'arthroplastie articulaire et outils chirurgicaux selectionnables par le patient
US9326780B2 (en) 2006-02-06 2016-05-03 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools incorporating anatomical relief
EP2671521A2 (fr) 2006-02-06 2013-12-11 ConforMIS, Inc. Dispositifs d'arthroplastie articulaire et outils chirurgicaux selectionnables par le patient
EP2710967A2 (fr) 2006-02-06 2014-03-26 ConforMIS, Inc. Dispositifs d'arthroplastie articulaire et outils chirurgicaux selectionnables par le patient
US9220517B2 (en) 2006-02-06 2015-12-29 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
US9220516B2 (en) 2006-02-06 2015-12-29 Conformis, Inc. Patient selectable joint arthroplasty devices and surgical tools
EP2671522A2 (fr) 2006-02-06 2013-12-11 ConforMIS, Inc. Dispositifs d'arthroplastie articulaire et outils chirurgicaux selectionnables par le patient
EP2671520A2 (fr) 2006-02-06 2013-12-11 ConforMIS, Inc. Dispositifs d'arthroplastie articulaire et outils chirurgicaux selectionnables par le patient
EP3143962A1 (fr) 2006-03-13 2017-03-22 Pneumrx, Inc. Dispositifs, procédés et systèmes de réduction du volume pulmonaire invasif minimal
US9402633B2 (en) 2006-03-13 2016-08-02 Pneumrx, Inc. Torque alleviating intra-airway lung volume reduction compressive implant structures
US10226257B2 (en) 2006-03-13 2019-03-12 Pneumrx, Inc. Lung volume reduction devices, methods, and systems
EP3167821A1 (fr) 2006-03-13 2017-05-17 PneumRx, Inc. Dispositifs de réduction du volume pulmonaire
US9782558B2 (en) 2006-03-13 2017-10-10 Pneumrx, Inc. Minimally invasive lung volume reduction devices, methods, and systems
DE202007019683U1 (de) 2006-03-13 2015-09-16 PNEUMRX. lnc. Minimalinvasive Lungenvolumenreduktionsvorrichtungen und -systeme
US10188397B2 (en) 2006-03-13 2019-01-29 Pneumrx, Inc. Torque alleviating intra-airway lung volume reduction compressive implant structures
US9801637B2 (en) 2006-03-13 2017-10-31 Pneumrx, Inc. Genetically-associated chronic obstructive pulmonary disease treatment
US9474533B2 (en) 2006-03-13 2016-10-25 Pneumrx, Inc. Cross-sectional modification during deployment of an elongate lung volume reduction device
US8888800B2 (en) 2006-03-13 2014-11-18 Pneumrx, Inc. Lung volume reduction devices, methods, and systems
US9402971B2 (en) 2006-03-13 2016-08-02 Pneumrx, Inc. Minimally invasive lung volume reduction devices, methods, and systems
US9402632B2 (en) 2006-03-13 2016-08-02 Pneumrx, Inc. Lung volume reduction devices, methods, and systems
US8932310B2 (en) 2006-03-13 2015-01-13 Pneumrx, Inc. Minimally invasive lung volume reduction devices, methods, and systems
EP2842501A1 (fr) 2006-03-13 2015-03-04 Pneumrx, Inc. Dispositifs, procédés et systèmes de réduction du volume pulmonaire invasif minimal
US8157837B2 (en) 2006-03-13 2012-04-17 Pneumrx, Inc. Minimally invasive lung volume reduction device and method
US9155574B2 (en) 2006-05-17 2015-10-13 Sonoma Orthopedic Products, Inc. Bone fixation device, tools and methods
US8702755B2 (en) 2006-08-11 2014-04-22 Gmedelaware 2 Llc Angled washer polyaxial connection for dynamic spine prosthesis
US9259250B2 (en) 2006-11-22 2016-02-16 Sonoma Orthopedic Products, Inc. Fracture fixation device, tools and methods
US7909825B2 (en) 2006-11-22 2011-03-22 Sonoma Orthepedic Products, Inc. Fracture fixation device, tools and methods
US10285707B2 (en) 2008-09-12 2019-05-14 Pneumrx, Inc. Enhanced efficacy lung volume reduction devices, methods, and systems
US9173669B2 (en) 2008-09-12 2015-11-03 Pneumrx, Inc. Enhanced efficacy lung volume reduction devices, methods, and systems
EP2848208A2 (fr) 2008-09-12 2015-03-18 Pneumrx, Inc. Dispositifs mini-invasifs de réduction du volume pulmonaire et leur administration
US9192403B2 (en) 2008-09-12 2015-11-24 Pneumrx, Inc. Elongated lung volume reduction devices, methods, and systems
US10058331B2 (en) 2008-09-12 2018-08-28 Pneumrx, Inc. Enhanced efficacy lung volume reduction devices, methods, and systems
EP3305234A1 (fr) 2008-09-12 2018-04-11 PneumRx, Inc. Dispositifs de réduction du volume pulmonaire minimalement invasifs et methodes de planification de telles procédures
WO2010030993A1 (fr) 2008-09-12 2010-03-18 Pneumrx, Inc. Modèles améliorés et/ou rallongés de dispositifs de réduction de volume pulmonaire à effraction minimale et leur mise en place
US9089342B2 (en) 2009-02-24 2015-07-28 Microport Orthopedics Holdings Inc. Patient specific surgical guide locator and mount
US9949747B2 (en) 2009-02-24 2018-04-24 Microport Orthopedics Holdings, Inc. Systems and methods for installing an orthopedic implant
US9642632B2 (en) 2009-02-24 2017-05-09 Microport Orthopedics Holdings Inc. Orthopedic surgical guide
US9649117B2 (en) 2009-02-24 2017-05-16 Microport Orthopedics Holdings, Inc. Orthopedic surgical guide
US11911046B2 (en) 2009-02-24 2024-02-27 Microport Orthopedics Holdings, Inc. Patient specific surgical guide locator and mount
US9675365B2 (en) 2009-02-24 2017-06-13 Microport Orthopedics Holdings Inc. System and method for anterior approach for installing tibial stem
US9566075B2 (en) 2009-02-24 2017-02-14 Microport Orthopedics Holdings Inc. Patient specific surgical guide locator and mount
US9113914B2 (en) 2009-02-24 2015-08-25 Microport Orthopedics Holdings Inc. Method for forming a patient specific surgical guide mount
US11779356B2 (en) 2009-02-24 2023-10-10 Microport Orthopedics Holdings, Inc. Orthopedic surgical guide
US10660654B2 (en) 2009-02-24 2020-05-26 Microport Orthopedics Holdings Inc. Method for forming a patient specific surgical guide mount
US10646238B2 (en) 2009-02-24 2020-05-12 Microport Orthopedics Holdings, Inc. Systems and methods for installing an orthopedic implant
US11779347B2 (en) 2009-02-24 2023-10-10 Microport Orthopedics Holdings Inc. System for forming a patient specific surgical guide mount
US9883870B2 (en) 2009-02-24 2018-02-06 Microport Orthopedics Holdings Inc. Method for forming a patient specific surgical guide mount
US9901353B2 (en) 2009-02-24 2018-02-27 Microport Holdings Inc. Patient specific surgical guide locator and mount
US10973536B2 (en) 2009-02-24 2021-04-13 Microport Orthopedics Holdings, Inc. Orthopedic surgical guide
US10512476B2 (en) 2009-02-24 2019-12-24 Microport Orthopedics Holdings, Inc. Orthopedic surgical guide
US11154305B2 (en) 2009-02-24 2021-10-26 Microport Orthopedics Holdings Inc. Patient specific surgical guide locator and mount
US10039557B2 (en) 2009-02-24 2018-08-07 Micorport Orthopedics Holdings, Inc. Orthopedic surgical guide
US11534186B2 (en) 2009-02-24 2022-12-27 Microport Orthopedics Holdings Inc. Orthopedic surgical guide
US11389177B2 (en) 2009-02-24 2022-07-19 Microport Orthopedics Holdings Inc. Method for forming a patient specific surgical guide mount
US11464527B2 (en) 2009-02-24 2022-10-11 Microport Orthopedics Holdings Inc. Systems and methods for installing an orthopedic implant
US9017334B2 (en) 2009-02-24 2015-04-28 Microport Orthopedics Holdings Inc. Patient specific surgical guide locator and mount
WO2010135352A1 (fr) 2009-05-18 2010-11-25 Pneumrx, Inc. Modification de section transversale durant le déploiement d'un dispositif allongé de réduction du volume pulmonaire
WO2012008837A3 (fr) * 2010-07-16 2012-05-10 X-Flow Bv Poly(arylsulfone) greffée et procédé de greffage d'une poly(arylsulfone)
AU2011277176B2 (en) * 2010-07-16 2014-08-21 X-Flow Bv Grafted poly(arylsulfone) and a process for grafting a poly(arylsulfone)
US8889824B2 (en) 2010-07-16 2014-11-18 X-Flow Bv Grafted poly(arylsulfone) and a process for grafting a poly(arylsulfone)
EP2754419A2 (fr) 2011-02-15 2014-07-16 Conformis, Inc. Implants orthopédiques améliorés et adaptés au patient, conceptions et outils associés
WO2013131066A1 (fr) 2012-03-02 2013-09-06 Conformis, Inc. Implants du genou stabilisés postérieurs adaptés au patient, conceptions et procédés et outils associés
US9486226B2 (en) 2012-04-18 2016-11-08 Conformis, Inc. Tibial guides, tools, and techniques for resecting the tibial plateau
US9675471B2 (en) 2012-06-11 2017-06-13 Conformis, Inc. Devices, techniques and methods for assessing joint spacing, balancing soft tissues and obtaining desired kinematics for joint implant components
EP3632375A1 (fr) 2013-03-15 2020-04-08 PneumRx Inc. Atténuation du couple dans des structures d'implant de compression de réduction du volume pulmonaire à l'intérieur des voies respiratoires
WO2014151557A2 (fr) 2013-03-15 2014-09-25 Pneumrx, Inc. Structures d'implant compressif à réduction de volume pulmonaire dans les voies aériennes à soulagement de couple
EP3357455A2 (fr) 2013-03-15 2018-08-08 PneumRx, Inc. Atténuation du couple dans des structures d'implant de compression de réduction du volume pulmonaire à l'intérieur des voies respiratoires
US10537334B2 (en) 2013-10-25 2020-01-21 Pneumrx, Inc. Genetically-associated chronic obstructive pulmonary disease treatment
US9770278B2 (en) 2014-01-17 2017-09-26 Arthrex, Inc. Dual tip guide wire
US10100144B2 (en) 2014-05-22 2018-10-16 Ketonex Limited Method for making particulate amine-functionalized polyaryletherketone polymers and copolymers thereof
US10800876B2 (en) 2014-05-22 2020-10-13 Ketonex Limited Amine and non-amine derivatized polyaryletherketone random and block copolymers
US10390838B1 (en) 2014-08-20 2019-08-27 Pneumrx, Inc. Tuned strength chronic obstructive pulmonary disease treatment
US10450408B2 (en) 2014-09-10 2019-10-22 Ketonex Limited Method for making polyarylaliphaticetherketone polymers and copolymers thereof
US9814499B2 (en) 2014-09-30 2017-11-14 Arthrex, Inc. Intramedullary fracture fixation devices and methods
US10548648B2 (en) 2014-09-30 2020-02-04 Arthrex, Inc. Intramedullary fracture fixation devices and methods
US12108959B2 (en) 2019-05-29 2024-10-08 Wright Medical Technology, Inc. Preparing a tibia for receiving tibial implant component of a replacement ankle
WO2022230934A1 (fr) * 2021-04-27 2022-11-03 出光興産株式会社 Polyétheréthercétone, et procédé de fabrication de celui-ci

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