EP2361077A1 - Ciments osseux multi-solutions et leurs procédés de fabrication - Google Patents

Ciments osseux multi-solutions et leurs procédés de fabrication

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Publication number
EP2361077A1
EP2361077A1 EP08781696A EP08781696A EP2361077A1 EP 2361077 A1 EP2361077 A1 EP 2361077A1 EP 08781696 A EP08781696 A EP 08781696A EP 08781696 A EP08781696 A EP 08781696A EP 2361077 A1 EP2361077 A1 EP 2361077A1
Authority
EP
European Patent Office
Prior art keywords
cross
beads
linked
pmma
solution
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08781696A
Other languages
German (de)
English (en)
Other versions
EP2361077A4 (fr
Inventor
Julie M. Hasenwinkel
Imad K. Merkhan
Jeremy L. Gilbert
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Syracuse University
Original Assignee
Syracuse University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Syracuse University filed Critical Syracuse University
Publication of EP2361077A1 publication Critical patent/EP2361077A1/fr
Publication of EP2361077A4 publication Critical patent/EP2361077A4/fr
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention relates to bone cements and, more particularly, to multi- solution bone cements and methods for making the same.
  • Multi- solution acrylic bone cements (typically referred to as a two-solution bone cement, but which could have more than two solutions) have surfaced as an alternative to powder-liquid cement, using the same chemical constituents as current commercial formulations.
  • This cement consists of PMMA powder pre-dissolved in methyl methacrylate (MMA) monomer, to form two separate solutions; one containing the initiator, benzoyl peroxide (BPO) and the other containing the activator, N,N-dimethyl-p-toluidine (DMPT), which react to initiate polymerization of the MMA when the solutions are mixed.
  • MMA methyl methacrylate
  • BPO benzoyl peroxide
  • DMPT N,N-dimethyl-p-toluidine
  • an embodiment of the present invention provides multi- solution bone cements which include cross-linked PMMA beads, thereby providing for a significant increase in the polymer-to-monomer (P:M) ratio.
  • the bone cements of the present invention have reduced polymerization exotherms, volumetric shrinkage, shrinkage induced porosity, and residual monomer, all of which are advantageous for the clinical performance of the cement.
  • the cross-linked PMMA beads exhibit improved interfacial adhesion between the beads and the polymerized cement matrix by allowing them to participate in the polymerization reaction and thus be covalently bound to the matrix, thereby improving the mechanical properties of cements made with functionalized beads.
  • One advantage of the multi- solution bone cements of the present invention is the ability to adjust viscosity by means of the P:M ratio and the ratio of cross-linked beads to linear polymer in the composition.
  • the present invention also comprises multi- solution bone cements made with PMMA-PMMA spherical brush polymers.
  • the density and molecular weight of PMMA chains grafted onto cross- linked PMMA beads are controlled through the atom transfer radical polymerization process, along with the concentration of these particles in the monomer solutions, thereby enabling the manufacture of bone cements with tailored viscosities.
  • multi-solution bone cements consist of linear polymer chains consisting of acrylate (e.g., PMMA) polymer dissolved into MMA monomer.
  • PMMA acrylate
  • the viscosity of these cements is dictated by the combination of polymer molecular weight and polymer-to- monomer ratio. Increasing either of these quantities will increase the viscosity.
  • the combination of suitable molecular weight and polymer to monomer ratio are typically in the 80,000 g/mol lower limit Mw and about 0.95:1 polymer-to-monomer ratio. Since typical powder liquid cements are in the range of 1.8:1 P:M ratio, changes in two solution cement are needed to raise the P:M ratio while still preserving suitable viscosity.
  • modified multi- solution cements contain an additional element that can comprise either cross-linked PMMA beads or reactive cross-linked beads (where reactive double bond groups are placed on the surface of the beads) that are added to the multi solution mixture.
  • the amount of crosslinking within the beads, the ratio of linear polymer (Pl) to bead-based polymer (Pb), and the bead size will all affect the viscosity of the mixture.
  • crosslinking concentration i.e., the amount of crosslinking agent used to create the cross- linked PMMA beads- e.g., EGDMA
  • cements can be made by the addition of spherical polymer brushes alone to MMA.
  • the bone cements of an embodiment of the present invention are significantly simpler for the surgeon to mix and apply in the operating room compared to current powder-liquid bone cements. Simplification of this process eliminates much of the technique-dependent variability in bone cement properties.
  • the polymerization of multi-solution based bone cements is initiated by mixing the two or more components through a static mixing nozzle (current design) or some comparable device. The cement can be simultaneously mixed and delivered to the surgical site of application if desired.
  • the use of a disposable mixing nozzle allows for metered dosing from a single batch of cement. For example, a desired volume of material can be mixed and delivered in order to cement the first component of a total knee replacement.
  • the mixing nozzle can then be removed and at the appropriate time, a new nozzle can be attached to mix the cement for the second component of the knee implant.
  • This type of approach affords the surgeon is highly advantageous from a delivery standpoint because it allows for multiple cement applications at different times during a single surgical procedure, from a single batch or dose of cement.
  • This type of approach is not possible with conventional bone cements because an entire batch must be mixed at one time, thus starting the polymerization reaction and limiting the time with which the surgeon can work with the cement before it cures.
  • Bone cements of different viscosities are desirable for different surgical procedures (e.g., khyphoplasty vs. total hip cementation vs. total knee cementation). The ability to customize cements for the various market niches within the field of orthopedics is therefore highly desirable.
  • Fig. 1 is a schematic of three bone cement systems according to an embodiment of the present invention.
  • Fig. 2 is a graph of viscosity versus polymer-to-monomer ratios for multi- solution bone cements according to an embodiment of the present invention.
  • Fig. 3 is a graph of flexural testing data for multi- solution bone cements according to an embodiment of the present invention.
  • Fig. 4 is graph of volumetric shrinkage verses bone cement composition according to an embodiment of the present invention.
  • Fig. 5 is a reaction schematic of PMMA with ethanolamine in DMF according to an embodiment of the present invention.
  • Fig. 6 is a graph of FTIR profiles in transmission mode of the modification reactions according to an embodiment of the present invention.
  • Fig. 7 is a reaction schematic of modified PMMA beads with acryloyl chloride in dimchloromethane according to an embodiment of the present invention.
  • Fig. 8 is a reaction schematic of a modification reaction according to an embodiment of the present invention.
  • Fig. 9 is a graph of the FTIR profile of 2-bromopropionyl bromide modified
  • Fig. 10 is a graph of a summary of viscosity versus Pb:Pl ratio for three different P:M ratio multi- solution bone cements according to an embodiment of the present invention.
  • Fig. 11 shows the stress to failure, the strain to failure and the modulus of modified multi-solution bone cements according to an embodiment of the present invention.
  • FIG. 1 A-C three cement systems according to the present invention.
  • Fig. l(A) shows linear polymer and cross-linked beads in monomer
  • Fig. l(B) shows linear polymer
  • C C modified cross-linked beads in monomer
  • Fig. l(C) shows polymer brushes in monomer.
  • An embodiment of the present invention generally comprises multi-solution based bone cements having polymer-to-monomer (P:M) ratios approaching 2:1 and material properties that are comparable to currently available powder- liquid cements.
  • the viscosity of the cement solutions of the present invention are a function of the total P: M ratio, the ratio of cross-linked beads to linear polymer, and the cross-link density and size of the beads.
  • the bone cements of an embodiment of the present invention are formed by adding polymer in the form of cross-linked poly(methyl methacrylate) (PMMA) beads to solutions of dissolved linear polymer.
  • PMMA cross-linked poly(methyl methacrylate)
  • the present invention is formed by replacing the linear polymer with spherical PMMA brushes.
  • Cross-linked PMMA particles swell in monomer but do not dissolve, minimizing their contribution to the viscosity of the polymer solutions compared to the dissolved linear polymer.
  • An embodiment of the present invention involves the enhancement of the interfacial bonding of this particle phase to the polymerized PMMA matrix, and subsequently the mechanical properties of the cement, by creating reactive sites at the surface of the cross- linked beads that could participate in the free radical polymerization reaction during cement curing.
  • An embodiment of the present invention also encompasses the synthesis of spherical polymer brushes, consisting of cross-linked PMMA beads with linear PMMA molecules covalently tethered to their surfaces.
  • the spherical PMMA are mixed with methyl methacrylate (MMA) monomer to create bone cement formulations which do not required additional dissolved linear PMMA.
  • MMA methyl methacrylate
  • the cross-linked bead component of the spherical brushes will swell and the tethered PMMA chains will act like dissolved polymer, although anchored at one end, thereby imparting both viscosity to the mixtures through physical chain entanglements and a mechanically coupled interface at the surface of the beads.
  • plain cross-linked polymer brushes consisting of cross-linked PMMA beads with linear PMMA molecules covalently tethered to their surfaces.
  • MMA methyl methacrylate
  • PMMA beads can be used in combination with dissolved linear PMMA in methyl methacrylate monomer (MMA) to form the first cement type, as seen in Fig. l(A).
  • MMA methyl methacrylate monomer
  • PMMA beads can be modified via chemical reaction, in order to create functional reactive sites at the surface of the beads, consisting of carbon-carbon double bonds. These bonds will be able to participate in the free radical polymerization reaction that occurs during bone cement setting, creating a covalent or chemical bond between the cross-linked beads and the polymerized cement matrix.
  • These cross-linked PMMA beads can be used in combination with dissolved linear PMMA in MMA monomer to form the second cement type, as seen in Fig. l(B).
  • Using functionalized beads in this cement composition improves interfacial bonding between the particle phase and the polymerized PMMA matrix, resulting in cements with enhanced mechanical properties.
  • the last cement type is based on the synthesis of spherical polymer brushes, consisting of cross-linked PMMA beads with linear PMMA molecules covalently tethered to their surfaces. Spherical PMMA brushes are then be mixed with methyl methacrylate (MMA) monomer to create the third cement type, as seen in Fig. l(C). This cement composition does not require additional dissolved linear PMMA.
  • spherical polymer brushes consisting of cross-linked PMMA beads with linear PMMA molecules covalently tethered to their surfaces.
  • Spherical PMMA brushes are then be mixed with methyl methacrylate (MMA) monomer to create the third cement type, as seen in Fig. l(C). This cement composition does not require additional dissolved linear PMMA.
  • the cross-linked bead component of the spherical brushes will swell and the tethered PMMA chains will act like dissolved polymer, although anchored at one end, thereby imparting both viscosity to the mixture through physical chain entanglements and a mechanically coupled interface at the surface of the beads.
  • cross-linked PMMA beads have been synthesized via suspension polymerization of methyl methacrylate, using benzoyl peroxide (BPO), 2,2'-azo-bis-isobutyrylnitrile (AIBN), or potassium persulfate (KPS) as the initiator, ethylene glycol dimethacrylate (EGDMA) as the cross-linker (in varying concentrations), and poly(vinyl alcohol) (PVA) as the stabilizer.
  • BPO benzoyl peroxide
  • AIBN 2,2'-azo-bis-isobutyrylnitrile
  • KPS potassium persulfate
  • EGDMA ethylene glycol dimethacrylate
  • PVA poly(vinyl alcohol)
  • Bead size can be controlled by varying the suspension medium and the speed of mixing during the synthesis. Beads that have been synthesized to date range in size from less than 1 ⁇ m to over 100 ⁇ m in diameter, with the majority in the 10-50 ⁇ m range. Cross-linker concentrations have been varied between 1% and 30%. The degree to which the beads swell in monomer solutions is inversely proportional to the cross-linker concentration used in the synthesis. Example 2
  • This example relates to the preparation of multi-solution based bone cement with cross-linked PMMA beads as synthesized in Example 1.
  • the desired ratio of cross- linked beads to PMMA powder (linear chains) is determined. These two components are massed and subsequently mixed together in a suitable container.
  • MMA is added to two graduated cylinders.
  • the desired concentrations of BPO initiator or DMPT activator are then dissolved in MMA in separate containers, followed by the addition of 10-30 wt% barium sulfate (if radiopacity is desired, e.g., for vertebroplasty and kyphoplasty applications).
  • the solutions are transferred to polypropylene cartridges.
  • the mixture of PMMA powder and cross-linked PMMA beads is added to the MMA solutions.
  • the cartridges are sealed, vigorously agitated by hand, and placed on a rotating drum mixer for 6 hours. This is a significant reduction in mixing time as compared to current two-solution cement formulations without cross-linked beads (18 hr).
  • the cartridges are removed and stored upright at 4°C.
  • the solutions can be mixed through a static mixing nozzle and polymerize in the same manner as two-solution bone cement without cross-linked beads.
  • Table 1 below provides the exotherm and setting time for multi- solution based cement with cross-linked beads, standard two-solution cement, and Palacos R-40 commercial cement. Values are given as the average ⁇ one standard deviation and significant differences (p ⁇ 0.05) are denoted by asterisks.
  • Figure 3 provides flexural testing data showing flexural strength, modulus, and strain-to-failure for one composition of multi- solution based bone cement with cross-linked PMMA beads at a P:M ratio of 1.7:1 and Simplex P bone cement. There is a significant reduction in the strain-to- failure for the multi- solution based cement.
  • This example relates to the surface modification of PMMA cross-linked beads as synthesized in Example 1.
  • the bead-matrix interface can be mechanically strengthened by promoting covalent bonding between the two phases. Therefore, cross-linked PMMA beads have been modified to create unsaturated carbon double bonds at their surface. These double bonds can participate in the free radical polymerization reaction during matrix formation, potentially creating a chemical bond at the bead-matrix interface.
  • Step one Surface modification of PMMA beads with ethanolamine
  • the first step in the formation of modified PMMA beads according to the invention is to modify the surface of PMMA beads by adding a hydroxyl group. This reaction replaces the ester group with a hydroxyl group, as shown in Figure 5.
  • the reaction was performed at 120 0 C in N,N dimethylformamide (DMF). Twenty grams of cross-linked PMMA beads were swollen for 12 hours in DMF. Then the beads were subjected to a reaction with 25 g of ethanolamine at 120 0 C for 9 hours. The reaction was then cooled to ambient temperature. The beads were washed with water, followed by methanol. Finally, the beads were subjected to soxholet extraction with methanol for 48 hours to extract any ethanolamine residue. FTIR analysis of the beads was performed by incorporating the modified beads in a potassium bromide (KBr) pellet.
  • KBr potassium bromide
  • Figure 6 contains three lines starting from the left (related to each other relative to the vertical axis) including a "top,” “middle,” and “bottom” line or spectrum.
  • Figure 6 illustrates the FTIR spectra of cross-linked PMMA beads (middle spectrum) and ethanolamine surface modified PMMA beads (top spectrum).
  • Figure 6 details the FTIR profiles in transmission mode of the two step modification reactions.
  • the middle line shows the spectrum of the unmodified cross-linked PMMA beads.
  • the top line shows the spectrum of ethanolamine modifies beads.
  • the bottom line shows the spectrum of acryloyl modified beads.
  • the hydroxyl group is very clear at 3450 cm “1 and amide group at 1680 cm “1 .
  • Step two Surface modification with acryloyl chloride
  • the second step in the formation of modified PMMA beads according to the invention is to subject the ethanolamine modified cross-linked PMMA beads to acryloyl chloride in dry dichloromethane in the presence of triethylamine, as seen in Figure 7.
  • Five grams of cross-linked PMMA beads were swollen in 25 g of dry dichloromethane and cooled on ice under stirring. The reaction was permitted to go for 6 hours at 0 0 C and then for another 6 hours at room temperature. The product was then washed with 0.1 N HCl followed by saturated sodium hydrogen carbonate solution, followed by water, and finally methanol. The product was dried in a vacuum at room temperature.
  • Figure 6 shows the FTIR spectrum of acryloyl chloride modified beads (bottom line) in KBR pallets. Note the drop in the hydroxyl peak at 3450 cm "1 and the formation of the carbon-carbon double bond peak at 1640 cm "1 .
  • This Example relates to the preparation of multi- solution bone cement with the surface modified PMMA as synthesized in Example 4.
  • the formation of modified PMMA beads according to the invention also requires determining the desired ratio of surface modified, cross-linked beads to PMMA powder (linear chains). These two components are massed and subsequently mixed together in a suitable container.
  • MMA is added to two graduated cylinders.
  • the desired concentration of BPO initiator or DMPT activator is then dissolved in the MMA, followed by the addition of 10-30 wt% barium sulfate (if radiopacity is desired).
  • the solutions are transferred to 200 ml polypropylene cartridges.
  • the mixture of PMMA powder and surface modified, cross-linked PMMA beads is added to the
  • MMA solutions The cartridges are sealed, vigorously agitated by hand, and placed on a rotating drum mixer for 6 hours. Following mixing, the cartridges are removed and stored upright at 4°C.
  • the solutions can be mixed through a static mixing nozzle and polymerize in the same manner as multi- solution bone cement without cross-linked beads.
  • This Example relates to the synthesis of PMMA-PMMA spherical polymer brushes.
  • the synthesis of the polymer brushes of the present invention is performed by surface modification of PMMA beads with ethanolamine as previously described in Example
  • FIG. 8 is a schematic of the reaction between ethanolamine modified PMMA beads and 2- bromoisobutyryl bromide.
  • FIG. 9 shows the FTIR profile of 2- bromoisobutyryl bromide modified cross-linked PMMA beads, where the peak at 1813 cm “1 is the COBr peak. Note the drop in the hydroxyl peak and the appearance of COBr at 1813 cm “1 and 1168 cm “1 .
  • Atom transfer radical polymerization (ATRP) reaction was carried out in a
  • the product of the reaction was cleaned thoroughly, then weighed and imaged. Before the
  • PMMA modified beads were 100 micron or less in diameter. Bead diameter increased after the reaction to as much as 200 microns. In addition, the weight of the beads was measured before and after the reaction. The weight increased by 200%.
  • This Example relates to the preparation of bone cement with PMMA-PMMA spherical brushes as synthesized in Example 6.
  • the preparation of the third type of cement according to the present invention differs from the procedures for the first two types in that the polymer brushes will be the only solid polymer component added to the MMA, initiation chemicals, and radiopacifier in order to form the cement solutions (i. e. , no linear polymer is dissolved).
  • One or more of the multi- solution bone cements according to the present invention have the capacity to meet the clinical need of improved cements for fixation of total joint replacements, along with other applications including vertebroplasty (VP) and kyphoplasty (KP) which are minimally invasive procedures used to treat vertebral compressive fractures.
  • VP vertebroplasty
  • KP kyphoplasty
  • the multi- solution bone cements according to the present invention also have well controlled viscosities which remain relatively constant during the mixing and delivery process, as opposed to the viscosity of current commercial cements which is highly dynamic and increases significantly from the point of mixing to implantation of the cement. This property is particularly desirable for VP and KP applications.
  • This example describes the effect of overall polymer-to monomer ratio (P:M) and polymer bead (Pb) to linear polymer (Pl) ratio on the viscosity of modified multi solution bone cements.
  • Cross-linked polymer beads were synthesized. These beads consisted of 12% crosslinker with a nominal bead size of about 20 to 50 ⁇ m. These were made using suspension polymerization methods. Then, multi- solution bone cements were made with MMA monomer, 80,000 g/mol molecular weight linear PMMA polymer and the cross-linked PMMA beads. Various ratios of bead to linear polymer and total polymer to monomer were fabricated and their viscosity was determined using rheometric methods at room temperature. The ranges were: P:M ratio of 1.3:1 to 1.4:1, and Pb:Pl ratio of 1:1 to 2.5:1. [0052] The results of viscosity testing are summarized in Fig. 10, which shows a summary of viscosity versus Pb:Pl ratio for three different P:M ratio multi solution bone cements.
  • This Example shows the mechanical properties of modified multi solution bone cement made from cross-linked polymer beads, linear polymer and monomer after the cements have been polymerized as they would be in- vivo.
  • Modified multi solution bone cements consisting of linear 80,000 g/mol polymer, cross-linked polymer PMMA beads (with 12% EGDMA cross linker), MMA monomer and BPO and DMPT were used to make polymerized solid cement samples for mechanical testing.
  • the Multi- solution mixtures were dispensed through a static mixing nozzle into rectangular Teflon molds approximately 3mm X 10 mm X 40 mm.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Materials For Medical Uses (AREA)

Abstract

La présente invention porte sur des ciments osseux et plus particulièrement sur des ciments osseux multi-solutions et sur leurs procédés de fabrication. Un mode de réalisation de la présente invention porte sur des ciments osseux multi-solutions qui comprennent des billes de PMMA réticulées, apportant ainsi une augmentation significative du rapport de polymère à monomère (P:M). Un autre mode de réalisation de la présente invention porte sur des billes de PMMA réticulées qui sont modifiées en surface avec des doubles liaisons de carbone non saturé. Un autre mode de réalisation de la présente invention fournit des ciments osseux multi-solutions faits de polymères en brosse sphérique PMMA-PMMA.
EP08781696A 2008-07-11 2008-07-11 Ciments osseux multi-solutions et leurs procédés de fabrication Withdrawn EP2361077A4 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2008/069797 WO2010005442A1 (fr) 2008-07-11 2008-07-11 Ciments osseux multi-solutions et leurs procédés de fabrication

Publications (2)

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EP2361077A1 true EP2361077A1 (fr) 2011-08-31
EP2361077A4 EP2361077A4 (fr) 2012-09-05

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Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2957805B1 (fr) 2010-03-23 2012-04-20 Teknimed Systeme a deux composants pour ciment osseux
FR2983734B1 (fr) 2011-12-09 2014-02-28 Polymerexpert Sa Ciments polymeres pour la fixation de protheses, la reparation osseuse et la vertebroplastie obtenus a partir de formulations monophasiques liquides
GB201205677D0 (en) * 2012-03-30 2012-05-16 Internat Uk Ltd A two part acrylic composition
GB201317299D0 (en) 2013-09-30 2013-11-13 Lucite Int Uk Ltd A hardenable multi-part acrylic composition
CN109847100B (zh) * 2019-04-09 2020-06-16 浙江科惠医疗器械股份有限公司 一种具有生物活性的骨水泥及其制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080039586A1 (en) * 2006-07-17 2008-02-14 Syracuse University Multi-Solution Bone Cements and Methods of Making the Same

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5334626A (en) * 1992-07-28 1994-08-02 Zimmer, Inc. Bone cement composition and method of manufacture
US5902839A (en) * 1996-12-02 1999-05-11 Northwestern University Bone cement and method of preparation
GB9928837D0 (en) * 1999-12-06 2000-02-02 Abonetics Ltd Novel bone cement
CA2597786C (fr) * 2005-02-22 2014-08-05 Disc-O-Tech Medical Technologies, Ltd. Ciment osseux polymere

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080039586A1 (en) * 2006-07-17 2008-02-14 Syracuse University Multi-Solution Bone Cements and Methods of Making the Same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO2010005442A1 *

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WO2010005442A1 (fr) 2010-01-14
EP2361077A4 (fr) 2012-09-05

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