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WO1999007326A2 - Compositions de ciment antimicrobiennes - Google Patents

Compositions de ciment antimicrobiennes Download PDF

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Publication number
WO1999007326A2
WO1999007326A2 PCT/CA1998/000754 CA9800754W WO9907326A2 WO 1999007326 A2 WO1999007326 A2 WO 1999007326A2 CA 9800754 W CA9800754 W CA 9800754W WO 9907326 A2 WO9907326 A2 WO 9907326A2
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WO
WIPO (PCT)
Prior art keywords
antimicrobial
cement
composition
zeolite
particles
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Application number
PCT/CA1998/000754
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English (en)
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WO1999007326A3 (fr
Inventor
Joseph Paul Santerre
Shimon Friedman
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The University Of Toronto Innovations Foundation
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Publication date
Application filed by The University Of Toronto Innovations Foundation filed Critical The University Of Toronto Innovations Foundation
Priority to AU88463/98A priority Critical patent/AU8846398A/en
Priority to CA002268478A priority patent/CA2268478A1/fr
Publication of WO1999007326A2 publication Critical patent/WO1999007326A2/fr
Publication of WO1999007326A3 publication Critical patent/WO1999007326A3/fr

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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
    • A61L24/0015—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/20—Protective coatings for natural or artificial teeth, e.g. sealings, dye coatings or varnish
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/30—Compositions for temporarily or permanently fixing teeth or palates, e.g. primers for dental adhesives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
    • A61K6/849—Preparations for artificial teeth, for filling teeth or for capping teeth comprising inorganic cements
    • A61K6/869—Zeolites
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
    • A61K6/884—Preparations for artificial teeth, for filling teeth or for capping teeth comprising natural or synthetic resins
    • A61K6/887—Compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A61K6/889—Polycarboxylate cements; Glass ionomer cements
    • 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
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • 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
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104—Silver, e.g. silver sulfadiazine
    • 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
    • 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

Definitions

  • This invention relates to cement compositions having antimicrobial properties, and particularly to cement compositions containing antimicrobial zeolites.
  • cements Numerous types of cements have been developed for use in medicine and dentistry.
  • medical and dental cements comprise a powder component comprising finely divided metal oxides, metal hydroxides, calcium hydroxyapatite bioglasses, silicate-cement glazes, or glass ionomer particles, which is induced to react with a liquid medium containing phosphoric acid, polyelectrolytes such as polycarboxylic acid, or salicylic acid derivatives.
  • cements are typically used in medicine as bone cements, implant components and bone substitutes, and in dentistry as adhesives, sealants and restorative (filling) materials.
  • glass ionomer cement One cement type used in dentistry and medicine is glass ionomer cement (GIC).
  • GIC glass ionomer cement
  • glass ionomer cements are preferred for use as dental adhesives and restoratives, for example to restore cavities in dental tissue, and to seal the interfacial area between a filling and surrounding dental tissue, for example as sealers in root fillings.
  • glass inomer cements are less frequently used as restorative materials for surfaces that undergo considerable physical stress.
  • Glass ionomer cements typically comprise at least two components; firstly, a glass ionomer cement powder comprising an acid-soluble calcium fluoroaluminosilicate glass powder; and secondly, a polyanion, also referred to as a "polyelectrolyte", in a water base.
  • a glass ionomer cement powder comprising an acid-soluble calcium fluoroaluminosilicate glass powder
  • a polyanion also referred to as a "polyelectrolyte”
  • the surfaces of the glass particles are attacked by the polyanion.
  • Calcium, aluminum, sodium and fluorine ions are leached into the aqueous medium, and the polyanion chains are cross-linked by the calcium ions to form a solid mass.
  • the aluminum ions also become ionically bound within the cement mix.
  • the unreacted portions of the glass particles become sheathed by silica gel, so that the set cement consists of an agglomeration of unreacted powder particles surrounded by silica gel in an amorphous matrix of hydrated calcium and aluminum polysalts.
  • the polyanion also reacts with calcium ions in the substrate, for example a tooth, forming a chemical bond between the cement and the substrate.
  • Other monomer components may be added in order to carry out a dual cure process, for example where polymer chains are generated by light-curing the monomer components.
  • glass ionomer cement cures primarily by means of ionic reactions in which "ion bridges" are formed between the polyanion, the ions originating from the glass ionomer particles, and the substrate to which the cement is being adhered.
  • ion bridges are formed between the polyanion, the ions originating from the glass ionomer particles, and the substrate to which the cement is being adhered.
  • glass ionomer cements have satisfactory adhesion to hard dental tissue, such as teeth and bones, which are comprised of calcium hydroxyapatite. It is desirable to provide dental cements having antimicrobial properties.
  • One particularly important potential application of antimicrobial cements is in endodontic treatment of root canal systems. The goals of endodontic therapy include disinfection of the root canal system and subsequent bacteria-tight sealing of the root canal system.
  • Disinfection is accomplished during the root canal treatment by instruments, irrigants and medicaments.
  • Sealing is accomplished by root filling materials, such as gutta percha (rubber) and sealer cements.
  • root filling materials such as gutta percha (rubber) and sealer cements.
  • known root filling materials are insufficient to prevent leakage and bacterial ingress into the filled root canal.
  • the interfacial area between the endodontic filling materials and the dentin wall of the root canal is particularly susceptible to bacterial ingress, particularly where the technical quality of the root filling is poor Consequently, bacteria that challenge the endodontically treated tooth may proliferate through the filled root canal system and cause treatment failure
  • fluoride-releasing glass ionomer cements have several disadvantages Firstly, fluoride ions may participate in ionic bridging between dental tissue and the glass ionomer cement, and thus form part of the cement matrix When the fluoride is released from the cement into the oral cavity and is replaced by other anions, structural changes occur in the cement which may compromise its mechanical strength Secondly, the quick release rate of fluoride from the cement provides a high initial dose, which rapidly decreases within a few days or weeks The fluoride ions must be regenerated regularly in order to provide a continuous effect against bacteria
  • M represents an ion-exchangeable ion and in general a monovalent or divalent metal ion
  • n represents atomic valency of the (metal) ion
  • X and Y represent coefficients of metal oxide and silica respectively
  • Z represents the number of water of crystallization
  • ion-exchangeable ions present in the zeolite are completely or partially replaced by ammonium and antimicrobial metal ions such as silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium and thallium.
  • Composite materials comprising a polymerizable binder reinforced with inert organic or inorganic filler particles. Such materials are commonly used as dental restorative materials such as fillings. It would be desirable to provide such materials having antimicrobial properties, and antimicrobial zeolites are known to be incorporated into polymeric materials. However, the inventors are not aware of any commercially available composite materials incorporating antimicrobial zeolites for use as dental restorative materials. Several disadvantages exist with respect to incorporation of antimicrobial zeolites in polymeric materials, which may explain their lack of use. Firstly, the exchangeable ions contained in the zeolite diffuse poorly through polymeric materials. Therefore, a high concentration of antimicrobial zeolite is required to produce an antimicrobial composite material.
  • antimicrobial zeolites have been known to cause staining of the polymeric materials in which they are incorporated. This is particularly disadvantageous in composites for dental restorative materials, which must be colour-stable. The staining problem is aggravated by the need to incorporate large amounts of zeolites in the polymeric material. Thirdly, it is believed by some that zeolites do not incorporate antimicrobial metal ions in amounts sufficient to provide an antimicrobial effect, for example in U.S. Patent No. 5,009,898, issued April 23, 1991 to Sakuma et al., at column 2, lines 29 to 3 1.
  • the cement compositions of the invention generally comprise a cement containing an antimicrobial zeolite in an amount sufficient to prevent growth of bacteria in the composition and over the hardened cement formed when the composition is cured
  • the antimicrobial cement compositions according to the present invention have a wide variety of possible applications, including dentistry, medicine, as well as in building materials for institutional, industrial and domestic use
  • the antimicrobial dental cement compositions according to the present invention are used in dentistry or medicine
  • the antimicrobial dental cement compositions according to the present invention preferably comprise an anionic component, an inorganic particulate component, and an antimicrobial zeolite
  • the anionic component preferably comprises a liquid medium containing an acid such as phosphoric acid, a polyelectrolyte such as a polycarboxylic acid, or a salicylic acid derivative
  • the inorganic particulate component preferably comprises finely divided metal oxides, metal hydroxides, calcium hydroxyapatite bioglasses, silicate-cement glazes, or glass ionomer particles
  • the antimicrobial zeolite is preferably as described in Niira et al '958, discussed above, and most preferably contains silver ions Most preferably, the antimicrobial cement
  • the antimicrobial zeolite is preferably contained in the cement composition of the invention in an amount of from about 0.1 to about 30 percent by weight of the powder component, more preferably from about 0.2 to about 20 percent by weight of the powder component.
  • the most preferred dental uses of the antimicrobial cement compositions of the invention include endodontic filling materials, dental cements, dental lining and restorative materials, dental sealers, and dental luting adhesives, for example to adhere metal brackets to dental tissue.
  • the most preferred medical uses include bone cements, implant components and bone substitutes.
  • antimicrobial glass ionomer cement compositions of the invention are used in endodontic therapy to provide a bacteria-tight seal in a root canal system.
  • the antimicrobial glass ionomer cement composition of the invention may preferably be used to fill the root canal or may preferably be used as a sealer in combination with a core root canal filling material such as gutta percha (rubber).
  • the cement compositions of the present invention overcome many of the difficulties experienced with previously known antimicrobial cement compositions. It is believed that when zeolites are incorporated into a cement composition according to the invention, for example a glass ionomer cement composition, it is the zeolites, and not the exchangeable metal ions contained therein, which form ionic bridges with the polyacrylic acid, the glass particles and the substrate. Therefore, when antimicrobial ions are released from within the zeolites, the structures of the zeolites and the cement matrix as a whole are not significantly altered.
  • antimicrobial zeolites contained in cement compositions of the invention release antimicrobial metal ions in a highly controlled fashion, providing a substantially constant release of such ions over an extended period of time. Therefore, the inventors expect that antimicrobial cement compositions according to the invention will retain their mechanical stability as well as their antimicrobial activity over a relatively long period of time.
  • the cement compositions of the invention overcome many of the problems experienced with polymer resins containing antimicrobial zeolites.
  • the inventors have found that antimicrobial ions contained in the zeolites of the cement compositions of the invention may more easily diffuse through the cement matrix to be released in the oral cavity or at the interface between the root filling and the dental tissue This permits the amount of zeolite in the cement to be relatively low, yet sustain the antimicrobial activity of the cement.
  • the use of smaller amounts of zeolites permits cements of the invention to be produced economically, and also avoids problems such as staining which becomes more severe when zeolite content is increased
  • antimicrobial metal ions may diffuse to the surface from the interior of the cement, more antimicrobial metal ions are available for release, and therefore the cement composition of the present invention is expected to maintain its antimicrobial activity for a longer period of time
  • an antimicrobial cement composition containing antimicrobial zeolites containing antimicrobial zeolites.
  • Figure 1 is a plot of optical density versus incubation times, comparing the antimicrobial activity of an antimicrobial GIC composition according to Example 1 of the invention with a conventional GIC composition,
  • Figure 2 is a flow chart description of the microbiology study of Example 2,
  • Figure 3 shows bacterial colony counts from substrates of Example 2 following exposure to bacteria for 1, 3, 7, 10, 15, 30 hours Prior to inoculation the substrates were incubated in a bacteria free medium for 84 days Averages of three measurements were taken for bacterial colony counts (1000 colonies were labelled as having complete growth),
  • Figure 4 shows the change in the average optical density values measured for each group from Example 2 at 84 days as a function of bacteria culture time
  • Figure 5 shows the statistical significance of interactions between the different ZUT materials of Example 2 as measured by the lumped optical density values (over the entire 84 day experiment) versus the bacteria culture time Statistical differences were found between the ZUT materials at 7 and 10 hours (p ⁇ 0 0001)
  • Figure 6 shows the cumulative silver ion release (ppm) for ZUT 2% and ZUT 2% of Example 2 over a period of 84 days
  • Preferred antimicrobial cement compositions according to the present invention comprise a cement and an antimicrobial zeolite
  • antimicrobial cements for building materials used in industrial, institutional and domestic applications preferably comprise a hydraulic cement and an antimicrobial zeolite
  • hydraulic cement is to be understood as including any mixture of fine- ground lime, alumna and silica that will set to a hard product by admixture of water which combines chemically with the other ingredients to form hydrate
  • a preferred hydraulic cement is Portland cement
  • Preferred types of building materials into which antimicrobial cement compositions according to the present invention may be incorporated include grout, mortar and concrete, which are preferably formed by admixture of the antimicrobial cement composition with an aggregate selected from the group comprising sand, gravel and crushed stone, and optionally with other conventional ingredients
  • a cement composition of the invention may be used as a component in a mildew and bacterial resistant tile grout for use in bathrooms, hospitals or other areas where cleanliness is important
  • the present invention also includes within its scope tiles and similar building materials incorporating antimicrobial zeolites, whether or not such tiles or other materials are made from or contain cement
  • the antimicrobial cement composition of the invention contains a cement for medical or dental use
  • Preferred medical cements include bone cements, implant components and bone substitutes
  • preferred dental cements include cements for use as dental adhesives, sealers, fillers and restorative materials
  • the cement is an endodontic filler or an endodontic sealer to be used in combination with a core filling material of different composition, for endodontic treatment of root canal systems
  • Preferred types of cements for medical and dental use preferably comprise an anionic component, an inorganic particulate component, and an antimicrobial zeolite
  • the anionic component preferably comprises a liquid medium containing an acid such as phosphoric acid, a polyelectrolyte such as a polycarboxylic acid, or a salicylic acid derivative
  • the inorganic particulate component preferably comprises a finely divided metal oxides, metal hydroxides, calcium hydroxyapatite bioglasses, silicate-cement glazes, or glass ionomer particles
  • the antimicrobial cement composition according to the invention is an antimicrobial glass ionomer cement composition comprising a polyelectrolyte, glass ionomer particles and antimicrobial zeolite particles
  • This antimicrobial cement composition is particularly preferred as an endodontic filling and sealing material for use in endodontic treatment of root canal systems.
  • the preferred antimicrobial glass ionomer cement compositions according to the present invention include resin modified glass ionomer cements which include a small amount of a resin monomer to provide the cement with improved compliance, as well as metal-modified glass ionomer cements.
  • Zeolitic structures are comprised primarily of an aluminosilicate framework of alkali or alkali earth metals, with a regular three-dimensional skeleton consisting of a methane-type tetrahedron of linked SiO and AJO , the oxygen atoms being shared.
  • This framework can house exchangeable ions, typically cations.
  • Antimicrobial zeolites which are preferably used in the antimicrobial cement compositions of the present invention include any zeolites in which the exchangeable ions have antimicrobial activity.
  • Preferred ions include ammonium ion and antimicrobial metal ions.
  • the antimicrobial metal ions are selected from one or more members of the group comprising silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium and thallium ions; more preferably silver, copper and zinc ions; and most preferably silver ions.
  • the content of the antimicrobial metal ions in the zeolite is preferably from about 0.1% to about 15% by weight of the zeolite.
  • Particularly preferred zeolites used in the cement compositions of the invention contain silver ions and ammonium ions, and may preferably also contain copper and/or zinc ions.
  • Silver ions are preferably contained in the zeolite in an amount of from about 0.1% to about 15% by weight of the zeolite.
  • the preferred total content of copper and/or zinc ions is from about 0.1% to about 8% by weight of the zeolite.
  • Ammonium ion is preferably contained in the zeolite in an amount of less than about 20% by weight of the zeolite, more preferably from about 0.5% to about 15% of the zeolite, and most preferably from about 1.5% to about 5% by weight of the zeolite.
  • the most preferred zeolites for use in the cement composition according to the invention are zeolites sold under the trade mark ZeomicTM by Shinagawa Fuel Co., Ltd.
  • the particle size of the zeolite particles is preferably from about 20 to about 50 microns.
  • Cement compositions according to the present invention preferably contain from about 10%) to about 95% filler, with the antimicrobial zeolite being present in amounts of up to about 30%) by weight of the filler.
  • More preferred cements according to the present invention are antimicrobial glass ionomer cement compositions containing antimicrobial zeolite particles in amounts of up to about 20%> by weight of the glass ionomer particles, and more preferably from about 0.2% to about 20%> by weight of the glass ionomer particles.
  • the cement compositions contain antimicrobial zeolites in amounts which substantially do not cause staining of the cement composition, but which provide the cement composition with acceptable antimicrobial activity.
  • the preferred amount of antimicrobial zeolite to accomplish these objects is from about 0.2%> to about 2%o by weight of the powder component of the antimicrobial cement composition.
  • the present invention also includes within its scope the incorporation of antimicrobial zeolites in dental cements selected from the group comprising zinc phosphate, zinc oxide eugenol (ZOE), silicophosphate and polycarboxylate dental cements.
  • antimicrobial zeolites selected from the group comprising zinc phosphate, zinc oxide eugenol (ZOE), silicophosphate and polycarboxylate dental cements.
  • the present invention also includes within its scope the use of antimicrobial zeolite cements in combination with conventional, non-cementitious dental restorative materials including polymeric materials such as gutta percha, polymeric composite materials, calcium hydroxide, and pulp canal sealers, as well as in combination with porcelain for crowns.
  • conventional, non-cementitious dental restorative materials including polymeric materials such as gutta percha, polymeric composite materials, calcium hydroxide, and pulp canal sealers, as well as in combination with porcelain for crowns.
  • antimicrobial cement compositions according to the present invention are capable of preventing, or reducing by at least 50%>, the ability of bacteria to penetrate through filled root canals for periods of at least 90 days.
  • the ions leach out of the antimicrobial zeolite to the surface of the root canal filler or sealer of the invention, and are believed to disrupt bacterial activities such as cellular respiration, enzyme activation and active transport from the cell wall, with subsequent inhibition of the bacterial cell function and proliferation.
  • the antimicrobial cement compositions of the present invention are also expected to have efficacy against a wide range of bacteria, including the at least fifty strains of bacteria which have been isolated from root canals, such as Enterococcus faecalis, Actinomyces, Lactobacillus, black-pigmented Bacteroides, Peptostreptococcus, non- pigmented Bacteroides, Veillonetia, Fusobacterium nucleatiim, and Streptococcus mutans.
  • the cement compositions of the invention preferably also have activity against molds, fungi and algae.
  • DCT direct contact test
  • Example 1 The results of Example 1 are shown in Figure 1.
  • the antimicrobial cement composition tested comprised a glass ionomer cement sold under the trade mark ChemFill IITM, containing 2% by weight of a silver-containing zeolite sold under the trade mark ZEOMIC by Shinagawa Fuel Co., Ltd., which is identified in figure 1 as ZUT2.
  • the antimicrobial glass ionomer cement ZUT2 was placed in a vial containing brain heart infusion (BFfl) culture media and was inoculated with Enterococcus faecalis. The optical density of the vial was observed over a period of 30 hours, turbidity in the culture media being indicative of bacterial proliferation.
  • the optical density of antimicrobial glass ionomer cement sample ZUT2 was compared with samples containing inoculated media, inoculated ChemFill II without zeolite (CF), and a paper disc control (PD).
  • Optical density is a means by which to measure the clarity of a solution containing particulate, in this case bacterial, growth. Optical density is measured by determining the degree of light that can be transmitted through the test specimen. A low value indicates low bacterial growth activity, while a high value indicates the presence of elevated bacterial growth activity.
  • the objective of this study was to assess the efficacy of a modified endodontic filler (ZUT), consisting of an experimental glass ionomer (GI), KT-308 (GC Corp.,
  • the materials were arranged into five study groups, comprised of the following: Group 1 - KT-308 (a GIC); Group 2 - ZUT 0.2%; Group 3 - ZUT 2%; Group 4 - ZUT 20%; Group 5 - a paper disc (blank control).
  • KT-308 is an experimental cement/sealer glass ionomer provided in kind by GC Corp., Japan.
  • ZUT formulations were prepared with the GIC and Zeomic AJ 10D (Shinagawa Fuel Co., Nagoya, Japan), which is a silver containing zeolitic agent.
  • ZUT formulations were prepared by blending KT with Zeomic® in percentages of 20%, 2%>, and .2%) with respect to the ceramic content.
  • BHI Brain Heart Infusion
  • the purity of the culture was maintained by quadrant streaking on a weekly basis. Discs were incubated in a humid environment at 37°C to allow for bacterial adherence. At pre-defined incubation periods of 1, 3, 7, 10, 15 and 30 hours, three discs from each group were removed and gently rinsed with 3 ml of fresh BHI in sterile petridishes in order to discard non-adherent bacteria. Each disc was then transferred to a test tube containing 0.5 ml of fresh BHI, and incubated for 8 hours.
  • the remaining incubation solution was pippeted into individual plastic curettes, and the optical density was measured with a spectrophotometer (LKB Biochrome, Cambridge, U.K.) at a wavelength of 560 nm.
  • the absorbency of pure BHI was measured as a reference sample.
  • Each disc that showed a significant reduction in growth, in the fore-mentioned procedures, was subjected to a direct sampling of its surface to assess for cell viability.
  • the surface of each disc was gently scraped with a sterile scalpel blade (Lance, Sheffield, U.K.) and the shavings washed with 3 ml fresh BHI into a sterile petridish.
  • the resulting medium was pippeted onto an agar plate, incubated for 8 hours, and assessed for growth of bacterial colonies.
  • Discs from groups 2 to 4 were characterized for changes in hardness using a Knoop value hardness test (Leitz Wetzlar, Germany). A weight of 300 ponds was used for this test and ten disc specimens were measured from each group. Three measurements were taken and averaged for each disc. Measurements were obtained for post incubation periods of 28 days and 84 days.
  • the incubation stock from 28, 56 and 84 days was analyzed for silver ions that diffused from ZUT materials into the incubation stock.
  • Ten samples each of ZUT .2% and ZUT 2% from each of the above time periods were diluted 1 : 121 with 1% Triton X- 100. All samples were measured by a graphite furnace atomic absorption spectrophotometry (GFAAS) located in Dr Stanley Lugowski's laboratory at the Centre of Biomaterials, using Varian AA-875 spectrophotometer and Varian GTA-95 (Melbourne, Australia).
  • GFAAS graphite furnace atomic absorption spectrophotometry
  • Colony counts and optical density data were statistically analyzed by a factor analysis of variance (Statistical Analytical Systems, Cary, NC). Interactions among the three factors (materials, days and hours) were tested using the same statistical method, ANOVA. The least square means comparison was applied to examine interactions. Correlation coefficients were calculated between optical density and colonies for the data combining interactions among the three factors.
  • Bacterial colony counts for the 84-day samples are shown in Figure 3 and typically represent the observed performance of all materials for the different time points over the 84-day experiment.
  • the data reflect the measure of each material's ability to sustain adhesion and eventual growth of E. faecalis. While all materials showed evidence of growth after three hours of incubation with the bacteria, ZUT materials exhibited a complete elimination of bacteria within 15 hours of incubation. The strongest effect was exhibited by ZUT 20, which only had 43 colonies while ZUT .2%,
  • the non-ZUT materials exhibited no anti-microbial activity towards E. faecalis throughout the complete incubation period.
  • a plot of the optical density versus incubation times revealed a gradual drop in turbidity over 30 hours for media that contained ZUT materials (Figure 4). This gradual drop in turbidity corresponds to the drop in colonies observed for the different materials in Figure 3.
  • media containing non-ZUT materials permitted growth of bacteria, which was exhibited by the high turbidity value.
  • ANOVA was highly significant (p ⁇ 0.0001).
  • a three way ANOVA was also used to assess the effects of media exposure time on the materials and their ability to sustain growth of bacteria as measured by optical density.
  • the ZUT materials were shown to have a significant material/bacteria interaction (p ⁇ 0.0001 ) for the 7 and 10 hour bacteria incubation periods (Figure 5), with all media exposure times (i.e. 14, 28.... and 84 days). Based on this analysis, it was also shown that there was no prominent anti-bacterial activity demonstrated by Groups 1 and 5 for any time interval.
  • Table 1 Viable E. faecalis cells removed from the surface of ZUT materials is indicated by '+' at 10 hours. Absence of cells is denoted by '-', indicating no cells were recovered after 15 hours.
  • Table 2 The Knoop values in the above table are of ZUT materials after they were incubated for 28 and 84 days. A weight of 300 ponds was used for all three materials. The microhardness of each material is measured in kp/mm2.
  • E. faecalis The purpose of this study was to assess the ability of ZUT materials to suppress the growth of E. faecalis. Materials were exposed to culture media for different intervals over a period of 84 days and then exposed to bacteria. Groups 2, 3, 4, which contained Zeomic® in ratios of .2%, 2%, 20% proved to be effective against E. faecalis.
  • E. faecalis is one of the few facultative microorganisms and the most resistant to be found in the root canal. A common isolate found in infected root canals, it makes up a small percentage of the root canal flora, and may be favoured by ecological changes that establish infections, which are difficult to treat. E. faecalis has been used previously in studies of root canal dis-infection and is known to survive in environments where the pH is as high as 1 1.5.
  • DCT direct contact test

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Abstract

L'invention concerne des compositions de ciment antimicrobiennes renfermant des zéolites antimicrobiennes. Les compositions de ciment antimicrobiennes préférées ont des applications en orthodontie, par exemple pour des matériaux d'obturation, des adhésifs, des résines de scellement, et des matériaux de restauration, et des applications en médecine, notamment pour des ciments osseux, des éléments d'implants, et des substituts osseux. Une composition de ciment de verre ionomère à usage dentaire constitue un ciment préféré, cette composition renfermant un polyélectrolyte, des particules de verre ionomère, et des particules de zéolites antimicrobiennes. Lorsque cette composition durcit afin de former un ciment durci, lesdites particules de verre ionomère et de zéolites antimicrobiennes forment des liaisons ioniques avec le polyélectrolyte. Les particules de zéolites sont en outre présentes dans la composition en quantité suffisante pour prévenir la croissance de bactéries dans ladite composition, ou sur le ciment durci formé par durcissement de celle-ci. La zéolite renferme de préférence un ion métallique antimicrobien comme un ion argent, cette zéolite étant en outre présente dans ladite composition de ciment de verre ionomère à hauteur de 0,2 % à 20 % en poids environ des particules de verre ionomère.
PCT/CA1998/000754 1997-08-11 1998-08-07 Compositions de ciment antimicrobiennes WO1999007326A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU88463/98A AU8846398A (en) 1997-08-11 1998-08-07 Antimicrobial cement compositions
CA002268478A CA2268478A1 (fr) 1997-08-11 1998-08-07 Compositions de ciment antimicrobiennes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US5536197P 1997-08-11 1997-08-11
US60/055,361 1997-08-11

Publications (2)

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WO1999007326A2 true WO1999007326A2 (fr) 1999-02-18
WO1999007326A3 WO1999007326A3 (fr) 1999-05-20

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PCT/CA1998/000754 WO1999007326A2 (fr) 1997-08-11 1998-08-07 Compositions de ciment antimicrobiennes

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AU (1) AU8846398A (fr)
CA (1) CA2268478A1 (fr)
WO (1) WO1999007326A2 (fr)

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WO2000064505A1 (fr) * 1999-04-27 2000-11-02 Agion Technologies, L.L.C. Implants orthopediques antimicrobiens
EP1374830A1 (fr) * 2002-06-21 2004-01-02 Kerr Corporation Composition dentaire à base d'argent
US7090720B2 (en) 2001-03-09 2006-08-15 Schott Ag Use of bioactive glass in dental filling material
FR2896124A1 (fr) * 2006-01-19 2007-07-20 Le Cam Soc Par Actions Simplif Procede de conservation d'oeufs, compositions et installations pour la mise en oeuvre d'un tel procede
DE102009035970A1 (de) * 2009-08-04 2011-02-17 Heraeus Kulzer Gmbh Antimikrobiell ausgestattete Dentalmaterialien, insbesondere zur Verhinderung von Plaqueanlagerungen
GB2470088B (en) * 2009-11-10 2011-06-29 Landmark Innovations Ltd Root canal therapy
US20120141599A1 (en) * 2009-04-01 2012-06-07 Difusion Technologies, Inc. Regulation Of Bone Growth Using Zeolite In Combination With Bone Graft Substitutes
US8278368B2 (en) 2004-11-16 2012-10-02 3M Innnovatve Properties Company Dental fillers, methods, compositions including a caseinate
US8710114B2 (en) 2004-11-16 2014-04-29 3M Innovative Properties Company Dental fillers including a phosphorus containing surface treatment, and compositions and methods thereof
US8957126B2 (en) 2004-11-16 2015-02-17 3M Innovative Properties Company Dental compositions with calcium phosphorus releasing glass
US9107765B2 (en) 2010-05-07 2015-08-18 Difusion Technologies, Inc. Medical implants with increased hydrophilicity
US9132576B2 (en) 2009-12-11 2015-09-15 Difusion Technologies, Inc. Method of manufacturing antimicrobial implants of polyetheretherketone
US20150274595A1 (en) * 2012-10-24 2015-10-01 Clariant S.A. Method For Avoiding Fungal Growth In Mineral Construction Materials
US9492584B2 (en) 2009-11-25 2016-11-15 Difusion Technologies, Inc. Post-charging of zeolite doped plastics with antimicrobial metal ions
ITUB20156054A1 (it) * 2015-12-01 2017-06-01 Univ Degli Studi Di Messina Metodo di sintesi di un rivestimento composito antigraffio con azione anti-microbiche/anti-fungine, e materiale composito di rivestimento, per impiego in ambito medico/odontoiatrico.
US10131574B2 (en) 2013-06-17 2018-11-20 Corning Incorporated Antimicrobial glass articles and methods of making and using same
US10137061B2 (en) 2004-11-16 2018-11-27 3M Innovative Properties Company Dental fillers and compositions including phosphate salts
CN111012951A (zh) * 2019-12-31 2020-04-17 同济大学 具有光热效应的可注射复合骨水泥及其制备方法和应用
WO2024136824A1 (fr) * 2022-12-23 2024-06-27 Atatürk Üni̇versi̇tesi̇ Fi̇kri̇ Mülki̇yet Haklari Koordi̇natörlüğü Döner Sermaye İşletmesi̇ Matériau de ciment verre ionomère innovant
US12178936B2 (en) 2020-06-30 2024-12-31 Difusion, Inc. Medical implants and methods of manufacture

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US10045801B2 (en) 2012-07-30 2018-08-14 The Governing Council Of The University Of Toronto Bone stabilization device and method of production
US11643574B2 (en) 2021-05-28 2023-05-09 Cohesys Inc. Adhesive devices and uses thereof

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JPS61232253A (ja) * 1985-04-08 1986-10-16 株式会社イナックス タイル目地材
US4938958A (en) * 1986-12-05 1990-07-03 Shinagawa Fuel Co., Ltd. Antibiotic zeolite
JPH0217107A (ja) * 1988-07-04 1990-01-22 Yukiko Hirano 歯科用抗菌性セメント
JPH05321358A (ja) * 1992-05-26 1993-12-07 Kubota Corp 防黴無機質建材
JPH08109108A (ja) * 1994-10-07 1996-04-30 Yuusuke Ogura モルデナイトを利用した複合素材からなる抗菌性を具えた建築用資材と、その製造方法
JP3889082B2 (ja) * 1996-06-05 2007-03-07 シナネン株式会社 歯冠修復材

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000064505A1 (fr) * 1999-04-27 2000-11-02 Agion Technologies, L.L.C. Implants orthopediques antimicrobiens
US7090720B2 (en) 2001-03-09 2006-08-15 Schott Ag Use of bioactive glass in dental filling material
EP1374830A1 (fr) * 2002-06-21 2004-01-02 Kerr Corporation Composition dentaire à base d'argent
US6924325B2 (en) 2002-06-21 2005-08-02 Kerr Corporation Silver-containing dental composition
EP1749514A1 (fr) * 2002-06-21 2007-02-07 Kerr Corporation Composition dentaire à base d'argent
US8278368B2 (en) 2004-11-16 2012-10-02 3M Innnovatve Properties Company Dental fillers, methods, compositions including a caseinate
US8957126B2 (en) 2004-11-16 2015-02-17 3M Innovative Properties Company Dental compositions with calcium phosphorus releasing glass
US8710114B2 (en) 2004-11-16 2014-04-29 3M Innovative Properties Company Dental fillers including a phosphorus containing surface treatment, and compositions and methods thereof
US10137061B2 (en) 2004-11-16 2018-11-27 3M Innovative Properties Company Dental fillers and compositions including phosphate salts
EP1810574A1 (fr) * 2006-01-19 2007-07-25 Etablissements LE CAM Procédé de conservation d'oeufs, compositions et installations pour la mise en oeuvre d'un tel procédé
FR2896124A1 (fr) * 2006-01-19 2007-07-20 Le Cam Soc Par Actions Simplif Procede de conservation d'oeufs, compositions et installations pour la mise en oeuvre d'un tel procede
US20120141599A1 (en) * 2009-04-01 2012-06-07 Difusion Technologies, Inc. Regulation Of Bone Growth Using Zeolite In Combination With Bone Graft Substitutes
EP2942068A1 (fr) * 2009-04-01 2015-11-11 Difusion Technologies Inc. Régulation de la croissance osseuse au moyen de zéolite en combinaison avec des substituts de greffe osseuse
DE102009035970A1 (de) * 2009-08-04 2011-02-17 Heraeus Kulzer Gmbh Antimikrobiell ausgestattete Dentalmaterialien, insbesondere zur Verhinderung von Plaqueanlagerungen
WO2011015293A3 (fr) * 2009-08-04 2012-03-01 Heraeus Kulzer Gmbh Matériaux dentaires dotés de propriétés antimicrobiennenes, en particulier pour l'inhibition de plaques dentaires
JP2013501011A (ja) * 2009-08-04 2013-01-10 ヘレーウス クルツァー ゲゼルシャフト ミット ベシュレンクテル ハフツング 特に歯垢付着防止のための、抗微生物性が付与された歯科材料
GB2470088B (en) * 2009-11-10 2011-06-29 Landmark Innovations Ltd Root canal therapy
US9492584B2 (en) 2009-11-25 2016-11-15 Difusion Technologies, Inc. Post-charging of zeolite doped plastics with antimicrobial metal ions
US9132576B2 (en) 2009-12-11 2015-09-15 Difusion Technologies, Inc. Method of manufacturing antimicrobial implants of polyetheretherketone
US9107765B2 (en) 2010-05-07 2015-08-18 Difusion Technologies, Inc. Medical implants with increased hydrophilicity
US9375321B2 (en) 2010-05-07 2016-06-28 Difusion Technologies, Inc. Medical implants with increased hydrophilicity
US9434649B2 (en) * 2012-10-24 2016-09-06 Clariant S.A. Method for avoiding fungal growth in mineral construction materials
US20150274595A1 (en) * 2012-10-24 2015-10-01 Clariant S.A. Method For Avoiding Fungal Growth In Mineral Construction Materials
US10131574B2 (en) 2013-06-17 2018-11-20 Corning Incorporated Antimicrobial glass articles and methods of making and using same
US10676394B2 (en) 2013-06-17 2020-06-09 Corning Incorporated Antimicrobial glass articles and methods of making and using same
ITUB20156054A1 (it) * 2015-12-01 2017-06-01 Univ Degli Studi Di Messina Metodo di sintesi di un rivestimento composito antigraffio con azione anti-microbiche/anti-fungine, e materiale composito di rivestimento, per impiego in ambito medico/odontoiatrico.
CN111012951A (zh) * 2019-12-31 2020-04-17 同济大学 具有光热效应的可注射复合骨水泥及其制备方法和应用
US12178936B2 (en) 2020-06-30 2024-12-31 Difusion, Inc. Medical implants and methods of manufacture
WO2024136824A1 (fr) * 2022-12-23 2024-06-27 Atatürk Üni̇versi̇tesi̇ Fi̇kri̇ Mülki̇yet Haklari Koordi̇natörlüğü Döner Sermaye İşletmesi̇ Matériau de ciment verre ionomère innovant

Also Published As

Publication number Publication date
AU8846398A (en) 1999-03-01
WO1999007326A3 (fr) 1999-05-20
CA2268478A1 (fr) 1999-02-18

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