WO2005009481A2 - Surfactant-containing bone cement - Google Patents

Surfactant-containing bone cement Download PDF

Info

Publication number
WO2005009481A2
WO2005009481A2 PCT/DE2004/001572 DE2004001572W WO2005009481A2 WO 2005009481 A2 WO2005009481 A2 WO 2005009481A2 DE 2004001572 W DE2004001572 W DE 2004001572W WO 2005009481 A2 WO2005009481 A2 WO 2005009481A2
Authority
WO
WIPO (PCT)
Prior art keywords
weight
polyoxyethylene sorbitan
surfactant
bone cement
accelerator
Prior art date
Application number
PCT/DE2004/001572
Other languages
German (de)
French (fr)
Other versions
WO2005009481A3 (en
Inventor
Berthold Nies
Frank Schilke
Hanns Pietsch
Original Assignee
Biomet Deutschland Gmbh
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 Biomet Deutschland Gmbh filed Critical Biomet Deutschland Gmbh
Priority to DE112004001799T priority Critical patent/DE112004001799D2/en
Publication of WO2005009481A2 publication Critical patent/WO2005009481A2/en
Publication of WO2005009481A3 publication Critical patent/WO2005009481A3/en

Links

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
    • A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
    • A61L24/0094—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing macromolecular fillers
    • 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
    • A61L24/0015—Medicaments; Biocides
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406—Antibiotics
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/80—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special chemical form
    • A61L2300/802—Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
    • 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 invention relates to a bone cement based on polymethyl methacrylate (PMMA cement) consisting of a liquid and a solid component, the liquid component consisting essentially of one
  • PMMA cement polymethyl methacrylate
  • MMA methyl methacrylate
  • surfactants preferably methyl methacrylate (MMA)
  • the bone cement is to be used in particular in areas of medicine where easier handling for the inexperienced doctor, less heat release and / or use as a spacer and antibiotic carrier are more important than the maximum mechanical
  • Conventional drug-containing bone cements consist of a PMMA or copolymer powder in which, among other things, the powdered drug and a polymerization initiator are distributed.
  • the medicinal products used in conventional bone cement e.g. antibiotics must remain thermally stable at the temperatures that occur during the polymerization, so that the choice of
  • DE-2552070 A1 describes a PMMA bone cement consisting of a liquid and a solid component, the liquid component consisting essentially of a methyl methacrylate / water emulsion which is used in particular for anchoring artificial hip and knee joints.
  • This monomer emulsion could not prevail on the market because it was difficult to handle and was not stable in storage.
  • a PMMA-based bone cement consisting of a solid and a liquid component, characterized in that the liquid component consists essentially of a mixture of MMA and surfactants.
  • the liquid component or phase preferably consists of 50 to 85% by weight of monomeric MMA, 5 to 50% by weight of surfactant and 0.2 to 5% by weight of accelerator and, if appropriate, small amounts of other auxiliaries. It is even more preferred that the liquid phase contains no water.
  • the liquid phase which contains no water, particularly preferably consists of 70 to 80% by weight of monomeric MMA, 15 to 25% by weight of surfactant, 1 to 3% by weight of accelerator and, if appropriate, small amounts of other auxiliaries.
  • All surface-active fatty acid esters are suitable as surfactants.
  • sorbitan monolaurate Span 20
  • sorbitan monooleate Span 80
  • polyoxyethylene sorbitan monostearate Tween 60
  • polyoxyethylene sorbitan monooleate Tween 80
  • polyoxyethylene sorbitan trioleate Tween 85
  • the surfactant serves as
  • Solubilizer and vehicle for the drug furthermore relates to the use of nonionic surfactants such as sorbitan monolaurate (Span 20), sorbitan monooleate (Span 80), polyoxyethylene sorbitan monostearate (Tween 60), polyoxyethylene sorbitan monooleate (Tween 80) or polyoxyethylene sorbitan trioleate (Tween 85) in improved active ingredient-containing PMMA bone cements
  • nonionic surfactants such as sorbitan monolaurate (Span 20), sorbitan monooleate (Span 80), polyoxyethylene sorbitan monostearate (Tween 60), polyoxyethylene sorbitan monooleate (Tween 80) or polyoxyethylene sorbitan trioleate (Tween 85) in improved active ingredient-containing PMMA bone cements
  • a polymerization accelerator is also advantageously added to the liquid phase.
  • Tertiary aromatic amines such as dimethyl-p-toluidine or dihydroxyethyl-p-toluidine are particularly suitable for this purpose.
  • the bone cement is produced according to a conventional procedure in that the two sterile components, which are kept separate from one another, are mixed with one another in the amounts required in each case and are stirred into a uniform paste.
  • the quantitative ratio of the two components to be mixed, based on the solid to the liquid phase, is approximately in the range of 3: 1 to 1: 1, preferably approximately 2: 1 g / g. Results from the comparison tests:
  • Another advantage of substituting some of the methyl methacrylate with surfactants is the reduction in the polymerization temperature and thus the reduction in the formation of thermal necrosis in the tissue after implantation of the cement.
  • the time at which the cement hardened was not significantly influenced.
  • the maximum temperatures occurring during the polymerization and the temperatures at the time of hardening of all six cements were measured in measuring apparatus according to ISO 5833. The measurements showed that the polymerization temperature was partially reduced by the addition of surfactants. is significantly reduced.
  • the time of curing (calculated from the temp.time curve) is still within the time window that surgeons are used to.
  • the new cement should have the processing properties familiar to the surgeon. Therefore the behavior of the cement during the hardening was documented.
  • the creamy consistency of the cement after the components were mixed was striking.
  • the new cement is easier to shape than conventional Palacos ® .
  • Separated cement masses are easier to reassemble without creating separating surfaces (ie the cement flows into one another more easily).
  • the moduli of elasticity in Fig. 2 are significantly lower compared to Refobacin Palacos ® , but are still in the range of at least 1800 MPa required for bone cements (see ISO standard 5833).
  • Example: The liquid phase consisting of 3.6g ( 20% by weight) surfactant (Tween 80,

Abstract

The invention relates to a bone cement based on PMMA, comprising a liquid component and a solid component, whereby said liquid component contains 50 - 85 wt. % of monomeric methylmethacrylate, 5 - 50 wt. % of surfactant, 0.2 - 5 wt. % of an accelerator and optionally small amounts of other adjuvants. Said invention also relates to the use of non-ionic surfactants, such as sorbitan monolaurate, sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate or polyoxyethylene sorbitan trioleate in PMMA bone cements containing active substances, for an improved release of antibiotic agents.

Description

Tensidhaltiger Knochenzement Bone cement containing surfactant
Die Erfindung betrifft einen Knocheπzement auf Polymethylmethacrylat-Basis (PMMA-Zement) bestehend aus einer flüssigen und einer festen Komponente, wobei die flüssige Komponente im wesentlichen aus einerThe invention relates to a bone cement based on polymethyl methacrylate (PMMA cement) consisting of a liquid and a solid component, the liquid component consisting essentially of one
Mischung aus Methacrylaten, vorzugsweise Methylmethacrylat (MMA), und Tensiden besteht. Der Knochenzement soll insbesondere in Gebieten der Medizin eingesetzt werden, wo einfachere Handhabung für den ungeübten Arzt, eine geringere Wärmefreisetzung und/oder eine Verwendung als Spacer und Antibiotikaträger wichtiger sind als die maximale mechanischeMixture of methacrylates, preferably methyl methacrylate (MMA), and surfactants. The bone cement is to be used in particular in areas of medicine where easier handling for the inexperienced doctor, less heat release and / or use as a spacer and antibiotic carrier are more important than the maximum mechanical
Funktion des Zementes.Function of the cement.
Herkömmliche Arzneimittelhaltige Knochenzemente bestehen aus einem PMMA- bzw. Copolymer-Pulver, in welchem u.a. das pulverförmige Arzneimittel und ein Polymerisationsinitiator verteilt sind. Nach demConventional drug-containing bone cements consist of a PMMA or copolymer powder in which, among other things, the powdered drug and a polymerization initiator are distributed. After this
Vermischen mit einer Monomerflüssigkeit (mit einem Aktivator) kommt es zur Polymerisation des Monomers. Der ausgehärtete Knochenzement ist danach eine homogene Polymermasse, aus dem nur das sich in der Oberflächenschicht des Polymers befindliche Arzneimittel freigesetzt werden ann. Das im Inneren des Knochenzements vorhandene Arzneimittel bleibt unwirksam.Mixing with a monomer liquid (with an activator) causes the monomer to polymerize. The hardened bone cement is then a homogeneous polymer mass from which only the medicament located in the surface layer of the polymer can be released. The drug inside the bone cement remains ineffective.
Die im herkömmlichen Knochenzement verwendeten Arzneimittel (z.B. Antibiotika) müssen bei den während der Polymerisation auftretenden Temperaturen thermisch stabil bleiben, wodurch die Auswahl anThe medicinal products used in conventional bone cement (e.g. antibiotics) must remain thermally stable at the temperatures that occur during the polymerization, so that the choice of
Arzneimitteln stark einsgeschränkt ist. Hohe Polymerisationstemperaturen können zu Schädigungen des umgebenen Gewebes und dadurch zu einer Lockerung des Verbundes führen.Drugs is severely restricted. High polymerization temperatures can damage the surrounding tissue and thus loosen the bond.
DE-2552070 A1 beschreibt einen PMMA-Knochenzement bestehend aus einer flüssigen und einer festen Komponente, wobei die flüssige Komponente im wesentlichen aus einer Methylmethacrylat/Wasser-Emulsion besteht, der insbesondere zur Verankerung künstlicher Hüft- und Kniegelenke verwendet wird. Diese Monomeremulsion konnte sich am Markt nicht durchsetzen, da sie schlecht handhabbar und nicht lagerstabil war.DE-2552070 A1 describes a PMMA bone cement consisting of a liquid and a solid component, the liquid component consisting essentially of a methyl methacrylate / water emulsion which is used in particular for anchoring artificial hip and knee joints. This monomer emulsion could not prevail on the market because it was difficult to handle and was not stable in storage.
Aufgabe der vorliegenden Erfindung war es daher, einen Knochenzement zu entwickeln, der gegenüber den herkömmlichen Zementen eine verbesserte Freisetzung von Antibiotika-Wirkstoffen zeigt und eine niedrigere Polymerisationstemperatur aufweist Im Vergleich zu dem in DE-2552070 beschriebenen Zement soll der neu entwickelte Zement wesentlich bessere Verarbeitungseigenschaften haben.It was therefore an object of the present invention to develop a bone cement which, compared to the conventional cements, shows an improved release of antibiotic active substances and has a lower polymerization temperature. In comparison to the cement described in DE-2552070, the newly developed cement is said to have significantly better processing properties ,
Diese Aufgabe wird gelöst durch einen Knochenzement auf PMMA-Basis bestehend aus einer festen und einer flüssigen Komponente, dadurch gekennzeichnet, dass die flüssige Komponente im wesentlichen aus einer Mischung aus MMA und Tensiden besteht.This object is achieved by a PMMA-based bone cement consisting of a solid and a liquid component, characterized in that the liquid component consists essentially of a mixture of MMA and surfactants.
Vorzugsweise besteht die flüssige Komponente bzw. Phase aus 50 bis 85 Gew.% monomerem MMA, 5 bis 50 Gew. % Tensid und 0.2 bis 5 Gew.% Beschleuniger und gegebenenfalls geringen Mengen anderer Hilfsstoffe. Noch bevorzugter ist, dass die flüssige Phase kein Wasser enthält.The liquid component or phase preferably consists of 50 to 85% by weight of monomeric MMA, 5 to 50% by weight of surfactant and 0.2 to 5% by weight of accelerator and, if appropriate, small amounts of other auxiliaries. It is even more preferred that the liquid phase contains no water.
Besonders bevorzugt besteht die flüssige, kein Wasser enthaltene, Phase aus 70 bis 80 Gew.% monomerem MMA, 15 bis 25 Gew.% Tensid, 1 bis 3 Gew. % Beschleuniger sowie ggf. geringen Mengen anderer Hilfsstoffe.The liquid phase, which contains no water, particularly preferably consists of 70 to 80% by weight of monomeric MMA, 15 to 25% by weight of surfactant, 1 to 3% by weight of accelerator and, if appropriate, small amounts of other auxiliaries.
Als Tenside kommen alle oberflächenaktiven Fettsäure-Ester in Betracht. Bevorzugt werden aber Sorbitanmonolaurat (Span 20), Sorbitanmonooleat (Span 80), Polyoxyethylensorbitanmonostearat (Tween 60), Polyoxyethylen- sorbitanmonooleat (Tween 80) oder Polyoxyethylensorbitantrioleat (Tween 85) eingesetzt. Besonders bevorzugt ist Tween 80. Das Tensid dient alsAll surface-active fatty acid esters are suitable as surfactants. However, sorbitan monolaurate (Span 20), sorbitan monooleate (Span 80), polyoxyethylene sorbitan monostearate (Tween 60), polyoxyethylene sorbitan monooleate (Tween 80) or polyoxyethylene sorbitan trioleate (Tween 85) are preferably used. Tween 80 is particularly preferred. The surfactant serves as
Lösungsvermittler und Träger für das Arzneimittel. Weiterhin soll Gegenstand der Erfindung die Verwendung von nichtionischen Tensiden wie Sorbitanmonolaurat (Span 20), Sorbitanmonooleat (Span 80), Polyoxyethylensorbitanmonostearat (Tween 60), Polyoxyethylen- sorbitanmonooleat (Tween 80) oder Polyoxyethylensorbitantrioleat (Tween 85) in wirkstoffhaltigen PMMA-Knochenzementen zur verbessertenSolubilizer and vehicle for the drug. The invention furthermore relates to the use of nonionic surfactants such as sorbitan monolaurate (Span 20), sorbitan monooleate (Span 80), polyoxyethylene sorbitan monostearate (Tween 60), polyoxyethylene sorbitan monooleate (Tween 80) or polyoxyethylene sorbitan trioleate (Tween 85) in improved active ingredient-containing PMMA bone cements
Freisetzung von Antibiotika-Wirkstoffen sein.Release of antibiotic agents.
Ferner sind medizinische Implantate, die aus den Knochenzementen gemäß vorliegenden Ansprüchen hergestellt werden, Gegenstand der vorliegenden Erfindung.Furthermore, medical implants which are produced from the bone cements according to the present claims are the subject of the present invention.
Vorteilhafterweise wird der flüssigen Phase außerdem ein Polymerisationsbeschleuniger zugesetzt. Insbesondere eignen sich für diesen Zweck tertiäre aromatische Amine wie Dimethyl-p-toluidin oder Dihydroxyethyl-p-toluidin.A polymerization accelerator is also advantageously added to the liquid phase. Tertiary aromatic amines such as dimethyl-p-toluidine or dihydroxyethyl-p-toluidine are particularly suitable for this purpose.
Der Knochenzement wird nach herkömmlicher Verfahrensweise hergestellt, indem die beiden getrennt voneinander aufbewahrten, sterilen Komponenten in den jeweils erforderlichen Mengen miteinander vermischt und zu einer gleichmäßigen Paste verrührt werden.The bone cement is produced according to a conventional procedure in that the two sterile components, which are kept separate from one another, are mixed with one another in the amounts required in each case and are stirred into a uniform paste.
Das Mengenverhältnis der beiden zu mischenden Komponenten liegt, bezogen auf die feste zur flüssigen Phase, etwa in den Grenzen von 3:1 bis 1 :1 , vorzugsweise bei etwa 2:1 g/g. Ergebnisse aus den Verqleichsversuchen:The quantitative ratio of the two components to be mixed, based on the solid to the liquid phase, is approximately in the range of 3: 1 to 1: 1, preferably approximately 2: 1 g / g. Results from the comparison tests:
Release of GentamicinRelease of gentamicin
Figure imgf000005_0001
0 4 8 12 Time [d]
Figure imgf000005_0001
0 4 8 12 Time [d]
Abb. 1 aFig. 1 a
Release of GentamicinRelease of gentamicin
Figure imgf000005_0002
Figure imgf000005_0002
Abb. 1 bFig. 1 b
Wie in den Abb. 1 a und b zu sehen ist, wird aus den tensidhaltigen Zementen im Vergleich zu Refobacin Palacos deutlich mehr Gentamicin freigesetzt. Innerhalb des ersten Tages konnte eine Gentamicin- Konzentration gemessen werden, die je nach verwendetem Tensid ca. 15% bis 80% über der Vergleichsprobe lag. Nach vier bzw. acht Tagen verstärkt sich dieser Trend weiter. Polymerisationstemperatur und AushärtezeitAs can be seen in Fig. 1 a and b, significantly more gentamicin is released from the surfactant-containing cements compared to Refobacin Palacos. A gentamicin concentration was measured within the first day, which was about 15% to 80% above the comparison sample, depending on the surfactant used. After four or eight days, this trend continues. Polymerization temperature and curing time
Ein weiterer Vorteil der Substitution eines Teils des Methylmethacrylats durch Tenside ist in der Verringerung der Polymerisationstemperatur und damit der Reduzierung der Bildung von thermischen Nekrosen im Gewebe nach Implantation des Zementes zu sehen. Dabei ist der Zeitpunkt der Aushärtung des Zementes aber nicht wesentlich beeinflusst worden. In Messapparaturen nach ISO 5833 sind von allen sechs Zementen die bei der Polymerisation auftretenden maximalen Temperaturen und die Temperaturen zum Zeitpunkt der Aushärtung gemessen worden. Die Messungen zeigten, dass die Polymerisationstemperatur durch die Beimischung von Tensiden z.T. deutlich gesenkt wird. Der Zeitpunkt der Aushärtung (berechnet aus der Temp.-Zeit-Kurve) liegt weiterhin im von den Chirurgen gewohnten Zeitfenster.Another advantage of substituting some of the methyl methacrylate with surfactants is the reduction in the polymerization temperature and thus the reduction in the formation of thermal necrosis in the tissue after implantation of the cement. The time at which the cement hardened was not significantly influenced. The maximum temperatures occurring during the polymerization and the temperatures at the time of hardening of all six cements were measured in measuring apparatus according to ISO 5833. The measurements showed that the polymerization temperature was partially reduced by the addition of surfactants. is significantly reduced. The time of curing (calculated from the temp.time curve) is still within the time window that surgeons are used to.
Figure imgf000006_0001
Figure imgf000006_0001
Tab. 1 Polymerisationstemperaturen und Aushärtezeitpunkte HandhabungTab. 1 Polymerization temperatures and curing times handling
Der neue Zement sollte die vom Chirurgen gewohnten Verarbeitungseigenschaften haben. Daher wurde das Verhalten des Zementes bei der Aushärtung dokumentiert.The new cement should have the processing properties familiar to the surgeon. Therefore the behavior of the cement during the hardening was documented.
Auffällig war die cremige Konsistenz des Zementes nach dem Vermischen der Komponenten. Der neue Zement lässt sich im Vergleich zu handelsüblichen Palacos® leichter formen. Getrennte Zementmassen lassen sich leichter wieder zusammenfügen, ohne dass dabei Trennflächen entstehen, (d.h. der Zement fließt leichter ineinander.)The creamy consistency of the cement after the components were mixed was striking. The new cement is easier to shape than conventional Palacos ® . Separated cement masses are easier to reassemble without creating separating surfaces (ie the cement flows into one another more easily).
Mechanische EigenschaftenMechanical properties
Die Elastizitätsmoduln in Abb. 2 liegen zwar im Vergleich zu Refobacin Palacos® deutlich niedriger, sind aber noch im für Knochenzemente geforderten Bereich von mind. 1800 MPa (siehe ISO-Norm 5833).The moduli of elasticity in Fig. 2 are significantly lower compared to Refobacin Palacos ® , but are still in the range of at least 1800 MPa required for bone cements (see ISO standard 5833).
Young's Modulus (4-Point-Bending)Young 's modulus (4-point bending)
Figure imgf000007_0001
Tween 80 Tween 60 Tween 85 Span 20 Span 80 RefPal
Figure imgf000007_0001
Tween 80 Tween 60 Tween 85 Span 20 Span 80 RefPal
Abb. 2 Elastizitätsmoduln (4-Punkt-Biegung) modifizierter PMMA-ZementeFig. 2 Modules of elasticity (4-point bend) of modified PMMA cements
Als nicht-ionische Tenside wurden folgende Verbindungen verwendet: ■ Sorbitanmonolaurat (Span 20) ■ Sorbitanmonooleat (Span 80) ■ Polyoxyethylensorbitanmonostearat (Tween 60) ■ Polyoxyethylensorbitanmonooleat (Tween 80) ■ Polyoxyethylensorbitantrioleat (Tween 85)The following compounds were used as nonionic surfactants: ■ sorbitan monolaurate (Span 20) ■ sorbitan monooleate (Span 80) ■ polyoxyethylene sorbitan monostearate (Tween 60) ■ polyoxyethylene sorbitan monooleate (Tween 80) ■ Polyoxyethylene sorbitan trioleate (Tween 85)
Als Vergleichssubstanz diente herkömmlicher Refobacin Palacos R® ohne Tensid-Zusatz.Conventional Refobacin Palacos R ® without added surfactant was used as a reference substance.
Das nachfolgende Beispiel soll die Herstellung und die Eigenschaften des erfindungsgemäßen PMMA-Knochenzementes erläutern:The following example is intended to explain the production and the properties of the PMMA bone cement according to the invention:
Beispiel: Die flüssige Phase bestehend aus 3.6g (= 20 Gew.%) Tensid (Tween 80,Example: The liquid phase consisting of 3.6g (= 20% by weight) surfactant (Tween 80,
Tween 60, Tween 85, Span 20 bzw. Span 80), 14.11 g (= 78.4 Gew.%) Methylmethacrylat (MMA) und 0.29 g (=1.6 Gew.%) Dimethyl-p-toluidin als Beschleuniger wird mit 42 g Refobacin-Palacos-Pulver (bestehend aus PMMA-Pulver, Röntgenkontrastmittel, Antibiotikum, Farbstoff und Polymerisationsinitiator) vermischt. Der Zement härtet innerhalb von 15 min. aus. Tween 60, Tween 85, Span 20 or Span 80), 14.11 g (= 78.4% by weight) methyl methacrylate (MMA) and 0.29 g (= 1.6% by weight) dimethyl-p-toluidine as an accelerator is mixed with 42 g refobacin Palacos powder (consisting of PMMA powder, X-ray contrast agent, antibiotic, dye and polymerization initiator) mixed. The cement hardens within 15 minutes. out.

Claims

Patentansprüche claims
1. Knochenzement auf Polymethylmethacrylat-Basis bestehend aus einer flüssigen und einer festen Komponente, dadurch gekennzeichnet, dass die flüssige Komponente aus 50 - 85 Gew. % monomerem Methylmethacrylat 5 - 50 Gew. % Tensid 0.2 - 5 Gew. % Beschleuniger und gegebenenfalls geringen Mengen anderer Hilfsstoffe besteht.1. Bone cement based on polymethyl methacrylate consisting of a liquid and a solid component, characterized in that the liquid component consists of 50-85% by weight of monomeric methyl methacrylate, 5-50% by weight of surfactant, 0.2-5% by weight of accelerator and optionally small amounts other excipients.
2. Knochenzement nach Anspruch 1 , dadurch gekennzeichnet, dass die flüssige Phase kein zusätzliches Wasser enthält und aus 50 - 85 Gew. % monomerem Methylmethacrylat 5 - 50 Gew. % Tensid 0.2 - 5 Gew. % Beschleuniger und gegebenenfalls geringen Mengen anderer Hilfsstoffe besteht.2. Bone cement according to claim 1, characterized in that the liquid phase contains no additional water and consists of 50-85% by weight of monomeric methyl methacrylate, 5-50% by weight of surfactant, 0.2-5% by weight of accelerator and optionally small amounts of other auxiliaries.
3. Knochenzement nach einen der Ansprüche 1 und/oder 2, dadurch gekennzeichnet, dass die flüssige Phase kein zusätzliches Wasser enthält und aus 70 - 80 Gew.% monomerem Methylmethacrylat 15 - 25 Gew.% Tensid 1 - 3 Gew.% Beschleuniger und gegebenenfalls geringen Mengen anderer Hilfsstoffe besteht.3. Bone cement according to one of claims 1 and / or 2, characterized in that the liquid phase contains no additional water and from 70-80% by weight of monomeric methyl methacrylate 15-25% by weight of surfactant, 1-3% by weight of accelerator and optionally there are small amounts of other auxiliaries.
4. Knochenzement nach einen der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass nicht-ionische Tenside wie Sorbitanmonolaurat, Sorbitanmonooleat, Polyoxyethylensorbitanmonostearat, Polyoxy- ethylensorbitanmonooleat oder Polyoxyethylensorbitantrioleat eingesetzt werden. 4. Bone cement according to one of claims 1 to 3, characterized in that non-ionic surfactants such as sorbitan monolaurate, sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate or polyoxyethylene sorbitan trioleate are used.
5. Medizinische Implantate, hergestellt aus Knochenzementen nach einem der Ansprüche 1 bis 4.5. Medical implants made from bone cements according to one of claims 1 to 4.
6. Verwendung von nicht-ionischen Tensiden wie Sorbitanmonolaurat, Sorbitanmonooleat, Polyoxyethylensorbitanmonostearat, Polyoxy- ethylensorbitanmonooleat oder Polyoxyethylensorbitantrioleat in wirkstoffhaltigen PMMA-Knochenzementen zur verbesserten Freisetzung von Antibiotika-Wirkstoffen. 6. Use of non-ionic surfactants such as sorbitan monolaurate, sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate or polyoxyethylene sorbitan trioleate in active ingredient-containing PMMA bone cements for improved release of antibiotic active ingredients.
PCT/DE2004/001572 2003-07-18 2004-07-16 Surfactant-containing bone cement WO2005009481A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE112004001799T DE112004001799D2 (en) 2003-07-18 2004-07-16 Surfactant-containing bone cement

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10332687 2003-07-18
DE10332687.1 2003-07-18

Publications (2)

Publication Number Publication Date
WO2005009481A2 true WO2005009481A2 (en) 2005-02-03
WO2005009481A3 WO2005009481A3 (en) 2005-03-24

Family

ID=34088675

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2004/001572 WO2005009481A2 (en) 2003-07-18 2004-07-16 Surfactant-containing bone cement

Country Status (2)

Country Link
DE (1) DE112004001799D2 (en)
WO (1) WO2005009481A2 (en)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7416602B2 (en) 2005-04-08 2008-08-26 Howmedica Leibinger, Inc. Calcium phosphate cement
DE102007015698A1 (en) * 2007-03-27 2008-10-02 Innotere Gmbh Implant material based on a polymer system and its use
US7459018B2 (en) 2005-04-08 2008-12-02 Howmedica Leibinger Inc. Injectable calcium phosphate cement
US7651701B2 (en) 2005-08-29 2010-01-26 Sanatis Gmbh Bone cement composition and method of making the same
US7754005B2 (en) 2006-05-02 2010-07-13 Kyphon Sarl Bone cement compositions comprising an indicator agent and related methods thereof
US7758693B2 (en) 2002-06-07 2010-07-20 Kyphon Sarl Strontium-apatite cement preparations, cements formed therefrom, and uses thereof
US7942963B2 (en) 2000-07-03 2011-05-17 Kyhon SARL Magnesium ammonium phosphate cement composition
US7968616B2 (en) 2008-04-22 2011-06-28 Kyphon Sarl Bone cement composition and method
US7981945B2 (en) * 2006-03-01 2011-07-19 Poly-Med, Inc. Antimicrobial, radiopaque, microfiber-reinforced, polymeric methacrylate bone cement
US8118926B2 (en) 2006-06-08 2012-02-21 Warsaw Orthopedic, Inc. Self-foaming cement for void filling and/or delivery systems
US8168692B2 (en) 2004-04-27 2012-05-01 Kyphon Sarl Bone substitute compositions and method of use
JP2013521065A (en) * 2010-03-05 2013-06-10 ジンテス ゲゼルシャフト ミット ベシュレンクテル ハフツング Bone cement system for bone formation
US10182973B2 (en) 2010-11-10 2019-01-22 Stryker European Holdings I, Llc Polymeric bone foam composition and method

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2552070A1 (en) * 1975-11-20 1977-05-26 Beiersdorf Ag SURGICAL PLASTIC MATERIAL
DE2715532A1 (en) * 1977-04-07 1978-10-19 Beiersdorf Ag Acrylic! bone cements for surgical applications prepn. - by mixing powdered PMMA with emulsion contg. methyl methacrylate, accelerator and hexa:fatty acid ester of polyoxyethylene sorbitol
US4588583A (en) * 1982-12-11 1986-05-13 Beiersdorf Aktiengesellschaft Surgical material
DE3738422A1 (en) * 1987-11-12 1989-05-24 Beiersdorf Ag SURGICAL MATERIAL

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2552070A1 (en) * 1975-11-20 1977-05-26 Beiersdorf Ag SURGICAL PLASTIC MATERIAL
DE2715532A1 (en) * 1977-04-07 1978-10-19 Beiersdorf Ag Acrylic! bone cements for surgical applications prepn. - by mixing powdered PMMA with emulsion contg. methyl methacrylate, accelerator and hexa:fatty acid ester of polyoxyethylene sorbitol
US4588583A (en) * 1982-12-11 1986-05-13 Beiersdorf Aktiengesellschaft Surgical material
DE3738422A1 (en) * 1987-11-12 1989-05-24 Beiersdorf Ag SURGICAL MATERIAL

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
EDITIO CANTOR VERLAG F]R MEDIZIN UND NATURWISSENSCHAFTEN GMBH, AULENDORF: "Rote Liste 2002" 2002, ROTE LISTE SERVICE GMBH , FRANKFURT A.M., GERMANY , XP002313466 Biomaterial 88 003 - Palacos R *
LOSCHE D ET AL: "Preparation of a bone cement containing cytostatic agents" PHARMAZIE 1987 GERMANY, Bd. 42, Nr. 2, 1987, Seiten 97-99, XP001204737 *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7942963B2 (en) 2000-07-03 2011-05-17 Kyhon SARL Magnesium ammonium phosphate cement composition
US8715410B2 (en) 2002-06-07 2014-05-06 Warsaw Orthopedic, Inc. Strontium-apatite cement preparation cements formed therefrom, and use thereof
US7758693B2 (en) 2002-06-07 2010-07-20 Kyphon Sarl Strontium-apatite cement preparations, cements formed therefrom, and uses thereof
US8168692B2 (en) 2004-04-27 2012-05-01 Kyphon Sarl Bone substitute compositions and method of use
US7459018B2 (en) 2005-04-08 2008-12-02 Howmedica Leibinger Inc. Injectable calcium phosphate cement
US7416602B2 (en) 2005-04-08 2008-08-26 Howmedica Leibinger, Inc. Calcium phosphate cement
US7892346B2 (en) 2005-04-08 2011-02-22 Howmedica Osteonics Corp. Injectable calcium phosphate cement
US7892347B2 (en) 2005-04-08 2011-02-22 Howmedica Osteonics Corp. Injectable calcium phosphate cement
US9089625B2 (en) 2005-08-29 2015-07-28 Kyphon Sarl Bone cement composition and method of making the same
US7651701B2 (en) 2005-08-29 2010-01-26 Sanatis Gmbh Bone cement composition and method of making the same
US7981945B2 (en) * 2006-03-01 2011-07-19 Poly-Med, Inc. Antimicrobial, radiopaque, microfiber-reinforced, polymeric methacrylate bone cement
US7754005B2 (en) 2006-05-02 2010-07-13 Kyphon Sarl Bone cement compositions comprising an indicator agent and related methods thereof
US8118926B2 (en) 2006-06-08 2012-02-21 Warsaw Orthopedic, Inc. Self-foaming cement for void filling and/or delivery systems
US20110054392A1 (en) * 2007-03-27 2011-03-03 Innotere Gmbh Implant Material Based On A Polymer System And The Use Thereof
DE102007015698B4 (en) * 2007-03-27 2009-05-14 Innotere Gmbh Implant material based on a polymer system and its use as well as application set
US8829073B2 (en) * 2007-03-27 2014-09-09 Innotere Gmbh Implant material based on a polymer system and the use thereof
DE102007015698A1 (en) * 2007-03-27 2008-10-02 Innotere Gmbh Implant material based on a polymer system and its use
US7968616B2 (en) 2008-04-22 2011-06-28 Kyphon Sarl Bone cement composition and method
JP2013521065A (en) * 2010-03-05 2013-06-10 ジンテス ゲゼルシャフト ミット ベシュレンクテル ハフツング Bone cement system for bone formation
US10182973B2 (en) 2010-11-10 2019-01-22 Stryker European Holdings I, Llc Polymeric bone foam composition and method
US11185475B2 (en) 2010-11-10 2021-11-30 Stryker European Operations Holdings Llc Polymeric bone foam composition and method

Also Published As

Publication number Publication date
DE112004001799D2 (en) 2006-07-06
WO2005009481A3 (en) 2005-03-24

Similar Documents

Publication Publication Date Title
EP2052747B1 (en) Single component bone cement pastes and method for their hardening
DE69732431T2 (en) BONE CEMENT AND METHOD FOR THE PRODUCTION THEREOF
EP0701824B1 (en) Method of preparing bone cements containing active agents
DE102007015698B4 (en) Implant material based on a polymer system and its use as well as application set
DE602005000957T2 (en) Polymeric cement for percutaneous vertebroplasty
EP0920341B1 (en) Process for producing bone cement containing active substances
EP2052748B1 (en) Polymethyl methacrylate bone cement in paste form
EP2417988B1 (en) Bone cement in paste form
EP2359872B1 (en) Triple component bone cement
EP2236162B1 (en) Bioactive bone cement and method for its production
DE102008030312A1 (en) Polymethylmethacrylate-based paste used in single- or two-component bone cements or active substance release systems, has self-sterile composition
EP2687239B1 (en) Bone cement in paste form
WO2005009481A2 (en) Surfactant-containing bone cement
EP2550979B1 (en) Kit and method for producing bone cement
DE102008064657A1 (en) PMMA-paste
EP2664349B1 (en) Bone cement in paste form
DE2022117A1 (en) Bone cement and its production process, as well as an intermediate product for the manufacture of bone cement
EP1305055B1 (en) Modular implant system containing active substances and method for the production thereof
DE102010055759B4 (en) Bone cement paste and its use
EP0123323B1 (en) Use of difunctional acrylic and methacrylic esters for the preparation of bone cements
KR101432207B1 (en) Bone filling composition comprising caffeic acid phenethyl ester, and manufacturing method thereof
DE2715532C2 (en) Process for the production of a mass which can be used for surgical purposes
RU2811210C1 (en) Composition of bone cement for orthopedic and vertebrological surgery
DE19918295C2 (en) Compatible implant building block system in the form of a modular system for implant materials, methods for producing the same and their use

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1120040017998

Country of ref document: DE

REF Corresponds to

Ref document number: 112004001799

Country of ref document: DE

Date of ref document: 20060706

Kind code of ref document: P

WWE Wipo information: entry into national phase

Ref document number: 112004001799

Country of ref document: DE

122 Ep: pct application non-entry in european phase