WO2006041365A1 - Resorbable ceramic compositions - Google Patents

Resorbable ceramic compositions Download PDF

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Publication number
WO2006041365A1
WO2006041365A1 PCT/SE2005/001304 SE2005001304W WO2006041365A1 WO 2006041365 A1 WO2006041365 A1 WO 2006041365A1 SE 2005001304 W SE2005001304 W SE 2005001304W WO 2006041365 A1 WO2006041365 A1 WO 2006041365A1
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WO
WIPO (PCT)
Prior art keywords
cured
precursor composition
less
weight
ceramic material
Prior art date
Application number
PCT/SE2005/001304
Other languages
French (fr)
Inventor
Leif Hermansson
Håkan ENGQVIST
Original Assignee
Doxa Ab
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Filing date
Publication date
Application filed by Doxa Ab filed Critical Doxa Ab
Priority to CA002577535A priority Critical patent/CA2577535A1/en
Priority to EP05779214A priority patent/EP1796749A4/en
Priority to AU2005294835A priority patent/AU2005294835A1/en
Priority to JP2007531128A priority patent/JP2008512176A/en
Priority to BRPI0514636-4A priority patent/BRPI0514636A2/en
Publication of WO2006041365A1 publication Critical patent/WO2006041365A1/en

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    • 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
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/02—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing hydraulic cements other than calcium sulfates
    • C04B28/06—Aluminous cements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/70—Preparations for dentistry comprising inorganic additives
    • A61K6/71—Fillers
    • A61K6/74—Fillers comprising phosphorus-containing compounds
    • A61K6/75—Apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00—Preparations for dentistry
    • A61K6/70—Preparations for dentistry comprising inorganic additives
    • A61K6/71—Fillers
    • A61K6/77—Glass
    • 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
    • A61K6/802—Preparations for artificial teeth, for filling teeth or for capping teeth comprising ceramics
    • A61K6/818—Preparations for artificial teeth, for filling teeth or for capping teeth comprising ceramics comprising zirconium oxide
    • 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
    • A61K6/853—Silicates
    • 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
    • A61K6/876—Calcium oxide
    • A—HUMAN NECESSITIES
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    • 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
    • A61K6/878—Zirconium oxide
    • 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
    • A61L24/0052—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with an inorganic matrix
    • A61L24/0068—Inorganic materials not covered by groups A61L24/0057 or A61L24/0063
    • A—HUMAN NECESSITIES
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    • 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
    • A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/10—Ceramics or glasses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L27/427—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of other specific inorganic materials not covered by A61L27/422 or A61L27/425
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/02—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing hydraulic cements other than calcium sulfates
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/02—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing hydraulic cements other than calcium sulfates
    • C04B28/025—Belite cements
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/14—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing calcium sulfate cements
    • C04B28/145—Calcium sulfate hemi-hydrate with a specific crystal form
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/34—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders
    • C04B28/344—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders the phosphate binder being present in the starting composition solely as one or more phosphates
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
    • C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
    • C04B2111/00836—Uses not provided for elsewhere in C04B2111/00 for medical or dental applications
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P40/00—Technologies relating to the processing of minerals
    • Y02P40/10—Production of cement, e.g. improving or optimising the production methods; Cement grinding

Definitions

  • the present invention relates to ceramic precursor compositions and chemically bonded ceramic (CBC) materials, especially Ca-based, and a composite biomaterial suitable for orthopaedic applications.
  • the CBC-system includes a binding phase (chemical cement) and additional phases with specified chemistry imparting to the biomaterial the ability of initial strength followed by interaction with the body tissue including body liquid, to form a resorbable or partly resorbable biomaterial.
  • the invention also relates to a cured ceramic material, implants and surface coated de ⁇ vices.
  • biomaterials For materials to be used as bone void fillers, which have to interact with human tissue, it is advantageous to make the biomaterials as biocompatible and bioactive as possible. This can be achieved principally by at least two routes - developing stable biocompatible materials or resorbable materials allowing new bone tissue to substitute the biomaterial.
  • the first route to make more stable materials e.g. PMMA-based materials or Ca-aluminate-based materials, is especially suitable for osteoporotic clinical situations.
  • a resorbable material e.g. soluble glasses and phosphate-based materials, may be the most attractive route, where interaction with living tissue is more pronounced. It is well known that calcium aluminates and calcium silicates can have a considerably higher compres ⁇ sive strength than those of the present resorbable materials (in the order of 100 MPa).
  • the traditional resorbable phases contain oxides of Ca and P (or S) .
  • Ca-phosphates and or Ca-sulphates and glass containing CaO, P2O5, Si ⁇ 2 and Na2 ⁇ are typical representatives for this low-mechanical strength category of bioelements.
  • the present invention provides ceramic precur ⁇ sor compositions and cured products exhibiting the above-mentioned features.
  • the object of the present invention is to provide ceramic precursor compositions based on chemically bonded ceramics as main phase(s), which when cured, pro ⁇ vides a sufficiently high-strength (compressive strength 100-150 MPa) ceramic product. Said strength is achieved shortly after application of a slurry, paste or semi-hardened mixture of the ceramic precursor composition in a defective site.
  • the initial high strength makes load-bearing possible for the defective site during the resorption stage, where new bone tissue takes over the load-bearing capacity.
  • the binding phase(s) according to the present invention consumes or takes up a great deal of water, whereby the cured ceramic product exhibits a low residual porosity, which contributes to the high strength.
  • a ceramic precursor composition com ⁇ prising at least one particulate Ca-silicate, and possibly other particulate Ca- compounds selected from phosphates, carbonates, sulphates and combinations thereof, having calcium as the major cation. Said compound(s) will form the main binding phase(s) in the cured material.
  • the ceramic precursor composition is de ⁇ fined in claim 1.
  • said ceramic precursor compositions also include a second binding phase (e.g. high-strength Ca-aluminates) contributing to the high compres ⁇ sive strength, both initially and later on.
  • the constituents of the ceramic precursor composition are particulate matter, unless stated otherwise.
  • the percentages given for the precursor composition, as well as for the cured ceramic material, represent weight-%, unless stated otherwise.
  • a cured ceramic material which is obtained by mixing the precursor composition and a curing liquid, i.e. water.
  • the cured ceramic material is defined in claim 11.
  • a medical implant which comprises the non-cured ceramic precursor composition and/ or the cure ceramic material accord- ing to the invention.
  • the medical implant is defined in claim 27.
  • Said medical im ⁇ plant may be used as a carrier material for drug delivery. Said use is defined in claim 28.
  • a surface coated device selected from the group consisting of an artificial orthopaedic device, a spinal implant, a joint im ⁇ plant, an attachment element, a bone nail, a bone screw, and a bone reinforcement plate, which device or substrate is coated with the non-cured ceramic precursor and/ or the cured ceramic material according to the invention.
  • the coated device or surface is defined in claim 29.
  • the major advantages of the present invention precursor composition, cured mate ⁇ rial and product, when inserted or injected into a body, is that they have a high re- sorbability, such that a high in-growth rate of a bone is achieved.
  • the resorption rate is less or equal to that of the bone in-growth rate. This is important to keep the loading capacity during the whole healing period.
  • the compressive strength level obtained with the cured material according to the present invention is within the interval 100-150 MPa - to be compared with that of other resorbable biomaterials with a compressive strength in the interval 20-60 MPa.
  • the strength level for biomaterials according to the present invention is at least equal to that of stable biomaterials for bone void filler applications, such as PMMA - based materials, which do not exhibit the same degree of resorbability.
  • the ceramic material according to the invention have the advantages compared to prior art systems /materials, such as bioglasses, glass ionon ⁇ er cements and pure Ca- ⁇ hosphate-based systems or monomer-based filling materials, that it maintains its bioactivity, that it has improved initial strength and that it is dimensionally sta- ble - i.e. exhibits a limited expansion instead of shrinking like known resorbable materials, which benefits the contact with the tissue.
  • the ceramic materials according to the invention have been especially developed for biomaterials used as bone void filler materials for orthopaedic applications, but can also be used as resorbable filler materials- within odontology, including endodontics.
  • the present invention deals with bioactive ceramics based on resorbable ceramics. However, in addition to this, the present invention also deals in detail with the time aspects of strength development and the level of strength obtained. Accordingly, the present invention aims at providing materials, preferably biomaterials, having early and maintained strength, which with time dissolves and interacts with the body system to yield new tissue.
  • the ceramic precursor composition according to the invention com ⁇ prises main binding phase(s) of chemically bonded ceramics, preferably Ca-silicates, with Ca as the main cation.
  • the main binding phase(s) of the ceramic precursor composition comprises more than 50 weight-% of at least one Ca-silicate.
  • the main binding phase comprises 3CaOxSiO 2 .
  • the main binding phase(s) of the cured ceramic material comprises hydrates of 3CaOxSiO 2 .
  • Said main binding phase(s) may also comprise phosphates, carbonates, sulphates of calcium, and combinations thereof.
  • the remainder, if any, is constituted by additives such as inert phase and/or additives that make a material radiopaque.
  • soluble chemically bonded ceramic based on 3CaOxSiCb is preferred, since it offers both resorbability, and a high initial consumption or up-take of water that reduces the porosity, whereby a high strength is achieved early after the appli ⁇ cation of the ceramic precursor composition mixed with a curing liquid.
  • the ceramic precursor composition may further com- prise a Ca-compound based on phosphate and/ or sulphates in an amount of less than 20 weight-% of the main binding phase(s), preferably an amount of 5-10 weight-%.
  • Said second binding phase may comprise a soluble glass, e.g. a phospho ⁇ rous-containing glass, apatite-based materials, preferably a soluble CaH-phosphate.
  • the ceramic precursor composition may comprise additives conferring high radio- pacity, e.g. sulphates such as Ba-sulphate, and other very slowly dissolving inor ⁇ ganic or inert mineral phases.
  • sulphates such as Ba-sulphate
  • highly radio-opaque oxides such as zirconium oxide
  • These inert phases preferably comprises a Ca-silicate-based mineral or Ca-silicate glass.
  • These glasses can preferably contain fluorine and phosphorus to yield fluoride and phosphate ions, which contribute to fluoroapatite formation.
  • Said additives can be included in the composition in the form of glass particles, fi ⁇ bres, whiskers and/or platelets, in concentrations below 20 weight-% of the total composition, more preferably 5-15 weight-%, and most preferably 8-12 weight-%.
  • the ceramic precursor composition may further comprise particles of hydrated chemically bonded ceramics of the same or similar composition as that of the main binding phase(s) in an amount less than 40 weight-%, preferably 10-30 weight-%. This improves the homogeneity of the microstructure and enhances the binding be ⁇ tween reacting chemically bonded ceramics and the filler material in the early stage of curing.
  • additives may be included which improve initial closure of pores in the ceramic material by pure water up ⁇ take, e.g. from the semi-hydrate CaSO 4 Xl /2H2O to gypsum (CaS ⁇ 4x2H2 ⁇ ).
  • CaS ⁇ 4x2H2 ⁇ semi-hydrate CaSO 4 Xl /2H2O to gypsum
  • a combination of phosphoric acid and zinc oxide-forming Zn-phosphate is added. These phases will not contribute to the me ⁇ dium time or long-term properties, only enhance the initial pore closure and initial strength.
  • the initial strength up to a few hours after initialisation of the curing reaction may be further increased by addition of a polyacrylic (PA) -based material.
  • PA polyacrylic
  • one major con ⁇ cern is the low pH and the low chemical stability of secondary phases.
  • pure PA acid is used only in a low concentration, less than 8 weight-%, preferably less than 5 weight-% and more preferably 2-3 weight-%, and thus the acid works as an agent reducing the pH in early stages from a pH higher than 11-12 for the initially highly basic silicate and aluminate compounds, to a pH less than 10 within 60 minutes, preferably within 30 minutes in the mixture of the ceramic precursor composition and water.
  • high-strength stable addi ⁇ tives based on other chemically bonded ceramics preferably Ca-aluminates, form ⁇ ing hydrates in the cured material, are included in the ceramic precursor composi- tion in an amount less than 40 weight-%, preferably 5-30 weight-%.
  • the viscosity of the ceramic material prior to curing can be controlled within a wide range, upon initial mixing of the powdered material and the hydration liquid, from moist granules to an injectable slurry. However it is preferable to decrease the wa- ter-to-cement (w/c) ratio as much as possible in order to obtain the appropriate vis ⁇ cosity for any given application.
  • the w/c ratio should be less than 0.55, more pref ⁇ erably within the interval of 0.35-0.45.
  • the use of a somewhat higher w/c ratio than that of dental filling materials is possible and de ⁇ sirable to ensure an easily injectable biomaterial.
  • the materials also show slow disintegration rate in water and body liquid when in ⁇ serted into a body, i.e. that > 95% of the inserted mass is intact after a setting time of 5 minutes, more preferably after a setting time of 10 minutes. This is beneficial since it is important to allow the material to have time for setting without being too much mixed with the surrounding liquid.
  • the setting time is in the interval of 5-12 minutes.
  • the time for defined partial and complete disintegration can be varied within the interval of some months up to a few years.
  • the cured ceramic material exhibits a compressive strength exceeding 100 MPa. It has a compressive strength within 24 hours of at least 40 MPa, preferably more than 50 MPa within 1 h and more than 90 MPa within 24 h. The compressive strength exceeds 120 MPa after more than 7 days.
  • the cured ceramic material After more than 7 days after curing, the cured ceramic material exhibits a Kjc-value exceeding 0.5 preferably exceeding 0.7 MPam 1 / 2 , and more preferably ex ⁇ ceeding 1.0 MPam!/2.
  • the dimensional change of the material during curing is less than 0.3 linear %, and/ or exhibits an expansion pressure of less than 5 MPa, preferably less than 3 MPa.
  • the cured ceramic product according to the present invention when inserted into a body, has a resorption rate that is less or equal to that of the bone in-growth rate. More than 60 weight-% of the material is dissolved within 3 years, preferably more than 50 weight-% within 2 years, and more preferably more than 40 weight-% within 12 months.
  • bioelement means all types of ceramic or coated objects intended for insertion into a body, such as medical implants including carrier mate- rial for drug delivery, and particularly orthopaedic implants.
  • the ceramic precursor composition according to the invention, mixed with a curing liquid, may also be in ⁇ serted as a slurry, paste or putty, which after curing, forms said biolement.
  • Example An animal model was used to study the resorption rate for bone cement formula ⁇ tions containing calcium silicate as main binding phase (s).
  • the raw materials used were: tricalciumsilicate(C3S), dicalciumsilicate (C2S), monocalciumsilicate (CS) (Nycominerals), mono-calcium aluminate (CA), calcium- sulphate-semi-hydrate (Merck), tricalcmmphosphate (Merck), dicalciumphosphate (Merck), apatite (Merck) and Norian (Syntes Stratec).
  • C3S, C2S and CA powders were synthesised in-house.
  • the powder formulations were mixed with water and a hardening accelerator (30 wt.% CaCb) to a calciumsilicate /water ratio of 0.4 using a mixing machine (Rotomix 3MESPE) and plastic jars. Mixing the water and powder yielded an injectable paste.
  • the pastes were evaluated with respect to pH change and strength development (measured as compressive strength) over time.
  • the samples submitted to compres ⁇ sive strength testing were stored in simulated body fluid (changed every third day) and subsequently measured after Ih, 24h, 7days, 30 days, 3 months and 1-2 months.
  • the samples submitted to pH testing were stored in simulated body liquid for 5 minutes, 30 minutes, 24 h, 7 days and 30 days.
  • the samples were dehy ⁇ drated, embedded in methyl methacrylate, sectioned in the coronal plane and ground to 20 micrometer thickness. Histomorphometry was conducted to measure bone-to-defect area, graft-to-defect ratio, and bone-to-graft ratio.

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Abstract

The present invention relates to ceramic precursor compositions and chemically bonded ceramic (CBC) materials, especially Ca-based, and a composite biomaterial suitable for orthopaedic applications. The CBC-system includes a binding phase (chemical cement) and additional phases with specified chemistry imparting to the biomaterial the ability of initial strength followed by interaction with the body tissue including body liquid, to form a resorbable or partly resorbable biomaterial. The ceramic precursor composition comprises at least one silicate with Ca as the main cation with a resorption rate less or equal to that of the bone in-growth rate. Said silicate will form the binding phase of the cured material. The invention also relates to implants and surface coated devices. The cured material exhibits a compressive strength exceeding 100 MPa.

Description

RESORBABLE CERAMIC COMPOSITIONS
Field of the invention
The present invention relates to ceramic precursor compositions and chemically bonded ceramic (CBC) materials, especially Ca-based, and a composite biomaterial suitable for orthopaedic applications. The CBC-system includes a binding phase (chemical cement) and additional phases with specified chemistry imparting to the biomaterial the ability of initial strength followed by interaction with the body tissue including body liquid, to form a resorbable or partly resorbable biomaterial. The invention also relates to a cured ceramic material, implants and surface coated de¬ vices.
Background
For materials to be used as bone void fillers, which have to interact with human tissue, it is advantageous to make the biomaterials as biocompatible and bioactive as possible. This can be achieved principally by at least two routes - developing stable biocompatible materials or resorbable materials allowing new bone tissue to substitute the biomaterial. The first route to make more stable materials, e.g. PMMA-based materials or Ca-aluminate-based materials, is especially suitable for osteoporotic clinical situations. For active or young patients a resorbable material, e.g. soluble glasses and phosphate-based materials, may be the most attractive route, where interaction with living tissue is more pronounced. It is well known that calcium aluminates and calcium silicates can have a considerably higher compres¬ sive strength than those of the present resorbable materials (in the order of 100 MPa).
The traditional resorbable phases contain oxides of Ca and P (or S) . Ca-phosphates and or Ca-sulphates and glass containing CaO, P2O5, Siθ2 and Na2θ are typical representatives for this low-mechanical strength category of bioelements.
In EP 1 123 081 Bl and EP 0 555 807 Ca-silicate is mentioned as an additional phase for drug uses (less than 10%) and for bone substitute products as an addi¬ tional divalent compound. Regarding biocompability of Ca-silicate materials, work have been done on the endodontic treatment material Proroot or MTA and on WoI- lastonite materials. See J. Saidon, et al, "Cells and tissue reactions to mineral triox- ide aggregate and Portland cement", Oral surgery medicine pathology, April (2003) 483-489. Wollastonite is an established biomaterial in the form of sintered ceramic pieces. A survey of bone cements is found in S. M. Kenny and M. Buggy, "Bone ce¬ ments and fillers: A Review", Journal of Materials Science: Materials in Medicine, 14 (2003) 923-938.
In view of the prior art materials for use, particularly in, bone void filling, there is a need for a biocompatible material exhibiting resorbability and sufficiently high strength, and thus load-bearing capacity, shortly after application, as well as later on.
Brief description of the invention
To fulfil the above-mentioned needs, the present invention provides ceramic precur¬ sor compositions and cured products exhibiting the above-mentioned features.
The object of the present invention is to provide ceramic precursor compositions based on chemically bonded ceramics as main phase(s), which when cured, pro¬ vides a sufficiently high-strength (compressive strength 100-150 MPa) ceramic product. Said strength is achieved shortly after application of a slurry, paste or semi-hardened mixture of the ceramic precursor composition in a defective site. The initial high strength makes load-bearing possible for the defective site during the resorption stage, where new bone tissue takes over the load-bearing capacity.
During curing, the binding phase(s) according to the present invention consumes or takes up a great deal of water, whereby the cured ceramic product exhibits a low residual porosity, which contributes to the high strength.
According to a first aspect, there is provided a ceramic precursor composition com¬ prising at least one particulate Ca-silicate, and possibly other particulate Ca- compounds selected from phosphates, carbonates, sulphates and combinations thereof, having calcium as the major cation. Said compound(s) will form the main binding phase(s) in the cured material. The ceramic precursor composition is de¬ fined in claim 1. In another embodiment, said ceramic precursor compositions also include a second binding phase (e.g. high-strength Ca-aluminates) contributing to the high compres¬ sive strength, both initially and later on.
The constituents of the ceramic precursor composition are particulate matter, unless stated otherwise. The percentages given for the precursor composition, as well as for the cured ceramic material, represent weight-%, unless stated otherwise.
According to second aspect, there is provided a cured ceramic material, which is obtained by mixing the precursor composition and a curing liquid, i.e. water. The cured ceramic material is defined in claim 11.
According to third aspect, there is provided a medical implant which comprises the non-cured ceramic precursor composition and/ or the cure ceramic material accord- ing to the invention. The medical implant is defined in claim 27. Said medical im¬ plant may be used as a carrier material for drug delivery. Said use is defined in claim 28.
According to fourth aspect, there is provided a surface coated device selected from the group consisting of an artificial orthopaedic device, a spinal implant, a joint im¬ plant, an attachment element, a bone nail, a bone screw, and a bone reinforcement plate, which device or substrate is coated with the non-cured ceramic precursor and/ or the cured ceramic material according to the invention. The coated device or surface is defined in claim 29.
The major advantages of the present invention precursor composition, cured mate¬ rial and product, when inserted or injected into a body, is that they have a high re- sorbability, such that a high in-growth rate of a bone is achieved. The resorption rate is less or equal to that of the bone in-growth rate. This is important to keep the loading capacity during the whole healing period.
The compressive strength level obtained with the cured material according to the present invention is within the interval 100-150 MPa - to be compared with that of other resorbable biomaterials with a compressive strength in the interval 20-60 MPa. The strength level for biomaterials according to the present invention is at least equal to that of stable biomaterials for bone void filler applications, such as PMMA - based materials, which do not exhibit the same degree of resorbability.
The ceramic material according to the invention have the advantages compared to prior art systems /materials, such as bioglasses, glass iononαer cements and pure Ca-ρhosphate-based systems or monomer-based filling materials, that it maintains its bioactivity, that it has improved initial strength and that it is dimensionally sta- ble - i.e. exhibits a limited expansion instead of shrinking like known resorbable materials, which benefits the contact with the tissue.
The ceramic materials according to the invention have been especially developed for biomaterials used as bone void filler materials for orthopaedic applications, but can also be used as resorbable filler materials- within odontology, including endodontics.
Detailed description of the invention
The present invention deals with bioactive ceramics based on resorbable ceramics. However, in addition to this, the present invention also deals in detail with the time aspects of strength development and the level of strength obtained. Accordingly, the present invention aims at providing materials, preferably biomaterials, having early and maintained strength, which with time dissolves and interacts with the body system to yield new tissue.
In a basic form, the ceramic precursor composition according to the invention com¬ prises main binding phase(s) of chemically bonded ceramics, preferably Ca-silicates, with Ca as the main cation. The binding phase(s) preferably comprises one or more of the following phases: C3S =3(CaO)(SiO2), C2S =2 (CaO) (SiO2), and CS = (CaO)(SiO2). The main binding phase(s) of the ceramic precursor composition comprises more than 50 weight-% of at least one Ca-silicate. In a further preferred embodiment, the main binding phase comprises 3CaOxSiO2. In a preferred embodiment, the main binding phase(s) of the cured ceramic material comprises hydrates of 3CaOxSiO2. Said main binding phase(s) may also comprise phosphates, carbonates, sulphates of calcium, and combinations thereof. The remainder, if any, is constituted by additives such as inert phase and/or additives that make a material radiopaque.
The use of soluble chemically bonded ceramic based on 3CaOxSiCb is preferred, since it offers both resorbability, and a high initial consumption or up-take of water that reduces the porosity, whereby a high strength is achieved early after the appli¬ cation of the ceramic precursor composition mixed with a curing liquid.
As second binding phase(s), the ceramic precursor composition may further com- prise a Ca-compound based on phosphate and/ or sulphates in an amount of less than 20 weight-% of the main binding phase(s), preferably an amount of 5-10 weight-%. Said second binding phase may comprise a soluble glass, e.g. a phospho¬ rous-containing glass, apatite-based materials, preferably a soluble CaH-phosphate.
The ceramic precursor composition may comprise additives conferring high radio- pacity, e.g. sulphates such as Ba-sulphate, and other very slowly dissolving inor¬ ganic or inert mineral phases. Highly radio-opaque oxides, such as zirconium oxide, are preferred. These inert phases preferably comprises a Ca-silicate-based mineral or Ca-silicate glass. These glasses can preferably contain fluorine and phosphorus to yield fluoride and phosphate ions, which contribute to fluoroapatite formation. Said additives can be included in the composition in the form of glass particles, fi¬ bres, whiskers and/or platelets, in concentrations below 20 weight-% of the total composition, more preferably 5-15 weight-%, and most preferably 8-12 weight-%.
The ceramic precursor composition may further comprise particles of hydrated chemically bonded ceramics of the same or similar composition as that of the main binding phase(s) in an amount less than 40 weight-%, preferably 10-30 weight-%. This improves the homogeneity of the microstructure and enhances the binding be¬ tween reacting chemically bonded ceramics and the filler material in the early stage of curing.
In order to further enhance early strength properties, additives may be included which improve initial closure of pores in the ceramic material by pure water up¬ take, e.g. from the semi-hydrate CaSO4Xl /2H2O to gypsum (CaSθ4x2H2θ). To solid- ify the total ceramic product initially, a combination of phosphoric acid and zinc oxide-forming Zn-phosphate is added. These phases will not contribute to the me¬ dium time or long-term properties, only enhance the initial pore closure and initial strength.
The initial strength up to a few hours after initialisation of the curing reaction may be further increased by addition of a polyacrylic (PA) -based material. When prior art glass ionomer cements (with PA-additives) are used as biomaterials, one major con¬ cern is the low pH and the low chemical stability of secondary phases. However, in the ceramic precursor compositions according to the present invention pure PA acid is used only in a low concentration, less than 8 weight-%, preferably less than 5 weight-% and more preferably 2-3 weight-%, and thus the acid works as an agent reducing the pH in early stages from a pH higher than 11-12 for the initially highly basic silicate and aluminate compounds, to a pH less than 10 within 60 minutes, preferably within 30 minutes in the mixture of the ceramic precursor composition and water.
In order to improve the long-term mechanical strength, high-strength stable addi¬ tives based on other chemically bonded ceramics, preferably Ca-aluminates, form¬ ing hydrates in the cured material, are included in the ceramic precursor composi- tion in an amount less than 40 weight-%, preferably 5-30 weight-%.
The viscosity of the ceramic material prior to curing can be controlled within a wide range, upon initial mixing of the powdered material and the hydration liquid, from moist granules to an injectable slurry. However it is preferable to decrease the wa- ter-to-cement (w/c) ratio as much as possible in order to obtain the appropriate vis¬ cosity for any given application. The w/c ratio should be less than 0.55, more pref¬ erably within the interval of 0.35-0.45. For orthopaedic applications the use of a somewhat higher w/c ratio than that of dental filling materials is possible and de¬ sirable to ensure an easily injectable biomaterial.
The materials also show slow disintegration rate in water and body liquid when in¬ serted into a body, i.e. that > 95% of the inserted mass is intact after a setting time of 5 minutes, more preferably after a setting time of 10 minutes. This is beneficial since it is important to allow the material to have time for setting without being too much mixed with the surrounding liquid. The setting time is in the interval of 5-12 minutes. The time for defined partial and complete disintegration can be varied within the interval of some months up to a few years.
The cured ceramic material exhibits a compressive strength exceeding 100 MPa. It has a compressive strength within 24 hours of at least 40 MPa, preferably more than 50 MPa within 1 h and more than 90 MPa within 24 h. The compressive strength exceeds 120 MPa after more than 7 days.
After more than 7 days after curing, the cured ceramic material exhibits a Kjc-value exceeding 0.5
Figure imgf000008_0001
preferably exceeding 0.7 MPam1/2, and more preferably ex¬ ceeding 1.0 MPam!/2.
The dimensional change of the material during curing is less than 0.3 linear %, and/ or exhibits an expansion pressure of less than 5 MPa, preferably less than 3 MPa.
The cured ceramic product according to the present invention, when inserted into a body, has a resorption rate that is less or equal to that of the bone in-growth rate. More than 60 weight-% of the material is dissolved within 3 years, preferably more than 50 weight-% within 2 years, and more preferably more than 40 weight-% within 12 months.
The term "bioelement" as used herein, means all types of ceramic or coated objects intended for insertion into a body, such as medical implants including carrier mate- rial for drug delivery, and particularly orthopaedic implants. The ceramic precursor composition according to the invention, mixed with a curing liquid, may also be in¬ serted as a slurry, paste or putty, which after curing, forms said biolement.
Example An animal model was used to study the resorption rate for bone cement formula¬ tions containing calcium silicate as main binding phase (s).
Description of raw materials
The raw materials used were: tricalciumsilicate(C3S), dicalciumsilicate (C2S), monocalciumsilicate (CS) (Nycominerals), mono-calcium aluminate (CA), calcium- sulphate-semi-hydrate (Merck), tricalcmmphosphate (Merck), dicalciumphosphate (Merck), apatite (Merck) and Norian (Syntes Stratec). The C3S, C2S and CA powders were synthesised in-house.
Description of materials
A number of different powder formulations, that were prepared from the raw mate¬ rials as mentioned above, are presented in Table 1: 1.
Figure imgf000009_0001
Description of tests
The powder formulations were mixed with water and a hardening accelerator (30 wt.% CaCb) to a calciumsilicate /water ratio of 0.4 using a mixing machine (Rotomix 3MESPE) and plastic jars. Mixing the water and powder yielded an injectable paste. The pastes were evaluated with respect to pH change and strength development (measured as compressive strength) over time. The samples submitted to compres¬ sive strength testing were stored in simulated body fluid (changed every third day) and subsequently measured after Ih, 24h, 7days, 30 days, 3 months and 1-2 months. The samples submitted to pH testing were stored in simulated body liquid for 5 minutes, 30 minutes, 24 h, 7 days and 30 days. To some of the formulations (Formulations 1-2, 5-6 and 10-11) 2 wt-% of PA-acid was added. The pH change over time was detected. Each paste was also inserted into an animal model. Bilateral defects were created in the distal femur of skeletally-mature female goats. The medial femoral condyle was exposed and a 10 mm diameter transverse defect was created from the medial cor¬ tex to the lateral cortical wall. The graft was placed in this defect site. Each formu¬ lation was tested in six sites. The animals were sacrificed after 52 weeks. The me¬ dial condyle was submitted to undecalcified histology. The samples were dehy¬ drated, embedded in methyl methacrylate, sectioned in the coronal plane and ground to 20 micrometer thickness. Histomorphometry was conducted to measure bone-to-defect area, graft-to-defect ratio, and bone-to-graft ratio.
Results
The results from the strength test and the results from the resorption study is pre¬ sented in the Tables 1:2 and 1:3. In the strength test, a commercial calcium phos¬ phate cement was also tested (Norian) as a comparative ceramic. The pH shifted quickly from the initial interval of 11-12 for all formulations according to the inven¬ tion to less than 10 after 30 minutes and less than 9 after Ih. For samples includ¬ ing the addition of PA-acid, the pH change towards neutral was even quicker. The steady-state pH was higher than neutral.
Table 1:2. The compressive strength development over time for the tested formula¬ tions (MPa).
Figure imgf000010_0001
Table 1:3 Percentage of bone and graft material in defect site after 12 months
Figure imgf000011_0001
The results show that all formulations resorb over time and that the maximum strength but slowest resorption rate is achieved when using only calcium silicate as bone graft material.

Claims

1. A ceramic precursor composition used for manufacturing resorbable or partly resorbable high-strength bioelements, wherein the composition comprises at least one silicate with Ca as the main cation with a resorption rate less or equal to that of the bone in-growth rate, which at least one silicate acts as the main binding phase in the cured material, wherein the at least one Ca-silicate is present in an amount of 50 weight-% or more, the remainder, if any, is con¬ stituted by additives such as inert phase, and/or additives that make the cured material radiopaque.
2. The ceramic precursor composition according to claim 1, wherein the main binding phase(s) further comprises phosphates, carbonates, sulphates of cal¬ cium, and combinations thereof.
3. The ceramic precursor composition according to claim 1 or 2, wherein the main binding phase (s) comprises 3CaOxSiθ2.
4. The ceramic precursor composition according to any of the preceding claims, wherein it further comprises at least one second binding phase based on phosphates and/or sulphates in an amount of less than 20 weight-% of the main binding phase/phases.
5. The ceramic precursor composition according to any of the preceding claims, wherein the second binding phase comprises soluble glass, e.g. phosphorous- containing glass, apatite-based materials, preferably soluble CaH-phosphate.
6. The ceramic precursor composition according to any of the preceding claims, wherein the it further comprises glass particles, fibres, whiskers and/or plate- lets of slowly dissolving inorganic or inert mineral phases, preferably a Ca- silicate-based mineral or Ca-silicate glass and highly radio-opaque oxides, preferably zirconium oxide.
7. The ceramic precursor composition according to claim 6, wherein said inor¬ ganic slowly dissolving or inert mineral phases are present in an amount of less than 20 weight-%.
8. The ceramic precursor composition according to any of the preceding claims, wherein it further comprises hydrated particles particles of the same or of similar phases as those used for the main binding phase in an amount less than 40 weight-%.
9. The ceramic precursor composition according to any of the preceding claims, wherein it further comprises a ceramic powder of Ca-aluminate type in an amount less than 40 weight-%.
10. The ceramic precursor composition according to any of the preceding claims, wherein it further comprises low amounts of a polyacrylic-based material, less than 8 weight-%.
11. A cured chemically bonded ceramic material for high-strength bioelements used as a resorbable or partly resorbable biomaterial having a compressive strength exceeding 100 MPa, wherein the material as the main binding phase comprises at least one silicate with Ca as the main cation with a resorption rate less or equal to that of the bone in-growth rate, wherein the at least one Ca-silicate is present in an amount more than 50 weight-%, the remainder, if any, is constituted by additives such as inert phase and/ or additives that make the material radiopaque.
12. The cured ceramic material according to claim 11, wherein the main binding phase(s) further comprises phosphates, carbonates, sulphates of calcium, and combinations thereof.
13. The cured ceramic material according to claim 11 or 12, wherein the main binding phase(s) comprises hydrates of 3CaOxSiC^.
14. The cured ceramic material according to any of claims 11-13, wherein it com¬ prises at least one second phase based on phosphates and/ or sulphates in an amount of less than 20 weight-% of the main binding phase/phases.
15. The ceramic precursor composition according to claim 14, wherein the second binding phase comprises soluble glass, e.g. phosphorous-containing glass, apatite-based materials, preferably soluble CaH-phosphate.
16. The cured ceramic material according to any of claims 11-15, wherein it fur- ther comprises slowly dissolving inorganic or inert mineral phases, preferably a Ca- silicate-based mineral or Ca- silicate glass.
17. The cured ceramic material according to claim 16, wherein the inorganic slowly dissolving or inert mineral phases are present in the amount of less than 20 weight-%.
18. The cured ceramic material according to any of claims 11-17, wherein it fur¬ ther comprises a stable chemically bonded ceramic of Ca-aluminate hydrate type in an amount less than 40 weight-%.
19. The cured ceramic material according to any of claims 11-18, wherein the ma¬ terial also comprises low amounts of a polyacrylic-based material, less than 8 weight-%.
20. The cured ceramic material according to any of claims 11-19, wherein the pH of the material mixed with curing liquid changes during curing from higher than 11-12 to less than 10 in 60 minutes.
21. The cured ceramic material according to any of claims 11-20, wherein the ma- terial has a compressive strength within 24 hours of at least 40 MPa.
22. The cured ceramic material according to any of claims 11-21, wherein the ma¬ terial has a compressive strength exceeding 120 MPa after more than 7 days.
23. The cured ceramic material according to any of claims 11-22, wherein the ma¬ terial after more than 7 days after curing has a Kic- value exceeding 0.5 MPami/2.
24. The cured ceramic material according to any of claims 11-23, wherein the ma¬ terial has a dimensional change of less than 0.3 linear %, and /or an expan¬ sion pressure during hardening and curing of less than 5 MPa.
25. The cured ceramic material according to any of claims 11-24, wherein the ce¬ ramic material, when inserted or injected into a body, has a slow disintegra¬ tion rate in water and body liquid throughout the setting time, i.e. that > 95% of the inserted mass is intact after a setting time of 5 minutes.
26. The cured ceramic material according to any of claims 11-25, wherein more than 60 weight-% of the material, when inserted in a body, is dissolved within 3 years.
27. A medical implant comprising a non-cured ceramic precursor composition ac- cording to claim 1 and/ or a cured ceramic material according to claim 11.
28. Use of a medical implant according to claim 27 as a carrier material for drug delivery.
29. Surface coated device or substrate selected from the group consisting of an artificial orthopedic device, a spinal implant, a joint implant, an attachment element, a bone nail, a bone screw, and a bone reinforcement plate, wherein it is coated with a non-cured ceramic precursor composition according to claim 1 and/ or a cured ceramic material according to claim 11.
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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1861341A1 (en) * 2005-03-25 2007-12-05 Innovative Bioceramix, Inc. Hydraulic cement compositions and methods of making and using the same
WO2009038191A1 (en) * 2007-09-20 2009-03-26 Kyushu University, National University Corporation Curable composition
US7935121B2 (en) 2003-11-11 2011-05-03 Bone Support Ab Device for providing spongy bone with bone substitute and/or bone reinforcing material, bone substitute and/or bone reinforcing material and method
US7938572B2 (en) 2004-06-22 2011-05-10 Bone Support Ab Device for producing a hardenable mass
US7972630B2 (en) 2000-04-11 2011-07-05 Bone Support Ab Injectable bone mineral substitute material
US8420127B2 (en) 2003-03-05 2013-04-16 Bone Support Ab Bone substitute composition
US9180137B2 (en) 2010-02-09 2015-11-10 Bone Support Ab Preparation of bone cement compositions
US10294107B2 (en) 2013-02-20 2019-05-21 Bone Support Ab Setting of hardenable bone substitute
US11964072B2 (en) 2016-09-27 2024-04-23 Biomimetic Innovations Limited Soft tissue adhesive composition of α-TCP and phosphorylated amino acid

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE528360C2 (en) * 2004-09-10 2006-10-24 Doxa Ab Resorbable ceramic compositions intended for medical implants
US7553362B2 (en) * 2005-10-31 2009-06-30 Innovative Bioceramix, Inc. High strength biological cement composition and using the same
US9327056B2 (en) 2006-02-14 2016-05-03 Washington State University Bone replacement materials
US8916198B2 (en) * 2006-04-25 2014-12-23 Washington State University Mesoporous calcium silicate compositions and methods for synthesis of mesoporous calcium silicate for controlled release of bioactive agents
US9028871B2 (en) 2006-04-25 2015-05-12 Washington State University Resorbable ceramics with controlled strength loss rates
GB2442000A (en) 2006-06-07 2008-03-26 Apatech Ltd Biomedical materials containing gadolinium
CN100406072C (en) * 2006-07-18 2008-07-30 中国科学院上海硅酸盐研究所 Bio-activity tricalcium silicate/semi water calcium sulphate composite self-solidification material, preparation and application
EP2073855A4 (en) * 2006-10-18 2012-11-21 Doxa Ab Injectable resorbable ceramic compositions
US20080210125A1 (en) * 2007-03-01 2008-09-04 Doxa Ab Stable cement composition for orthopaedic and dental use
WO2008105737A1 (en) * 2007-03-01 2008-09-04 Doxa Ab Stable cement composition for orthopaedic and dental use
WO2010094813A1 (en) * 2009-02-10 2010-08-26 Azurebio, S. L. Osseous regeneration material from combinations of monetite with other bioactive calcium compounds
US20140050765A1 (en) * 2012-08-14 2014-02-20 Bio2 Technologies, Inc. Devices and Methods for Tissue Engineering
WO2016005822A1 (en) 2014-07-07 2016-01-14 Aduro Material Ab Cement systems, hardened cements and implants
US10485897B2 (en) * 2015-10-12 2019-11-26 Erik Erbe Osteogenic and angiogenic implant material
SE1651271A1 (en) * 2016-09-27 2018-03-28 Gpbio Ltd Composition of alfa-tcp, silicate and phosphorylated amino acid
ES2697691B2 (en) * 2017-07-24 2019-10-11 Fundacion Univ San Antonio Procedure for obtaining a material for bone regeneration and material thus obtained

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5840336A (en) * 1992-10-05 1998-11-24 Cygnus, Inc. Two-phase matrix for sustained release drug delivery device
DE19923956A1 (en) * 1999-05-25 2000-11-30 Univ Albert Ludwigs Freiburg New ceramic material and its use for dental fillings and dentures
FR2843748A1 (en) * 2002-08-23 2004-02-27 Septodont Ou Specialites Septo Material for restoring mineralized material, especially in dental restoration work, obtained by mixing aqueous liquid, solid tri- and/or dicalcium silicate, calcium chloride and water reducing agent
US20040043053A1 (en) * 2002-09-02 2004-03-04 Yu Hyun Seung Biodegradable and bioactive glass-ceramics, and method for fabricating the same
US20040117030A1 (en) * 2002-09-30 2004-06-17 Niklas Axen Heat generating biocompatible ceramic materials
WO2004058194A1 (en) * 2002-12-31 2004-07-15 Doxa Aktiebolag Chemically bonded biomaterial with tailored properties

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03109077A (en) * 1989-09-21 1991-05-09 Lion Corp Biomaterial
US5415547A (en) * 1993-04-23 1995-05-16 Loma Linda University Tooth filling material and method of use
JP2808410B2 (en) * 1994-04-26 1998-10-08 邦夫 石川 Curable composition and treating agent therefor
TW527332B (en) * 2000-05-19 2003-04-11 Akzo Nobel Nv Composition and method to prepare a concrete composition
US20020045678A1 (en) * 2000-08-22 2002-04-18 Lopez Larry A. Dental restorative compositions and method of use thereof
US20030144384A1 (en) * 2001-10-09 2003-07-31 Fu Chen Superplasticizer for concrete and self-leveling compounds
EP1494990A4 (en) * 2002-03-13 2010-05-26 Grace W R & Co Beneficiated water reducing compositions
JP2005537832A (en) * 2002-06-20 2005-12-15 ドクサ アクティボラグ Teeth filling material or implant material system and method for achieving powder material, hydration water, implant material and bonding
CN1208281C (en) 2003-03-21 2005-06-29 中国科学院上海硅酸盐研究所 Preparation of porous calsium silicate/beta-tricalsium phosphate composite bio-ceramic materials
SE528360C2 (en) * 2004-09-10 2006-10-24 Doxa Ab Resorbable ceramic compositions intended for medical implants

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5840336A (en) * 1992-10-05 1998-11-24 Cygnus, Inc. Two-phase matrix for sustained release drug delivery device
DE19923956A1 (en) * 1999-05-25 2000-11-30 Univ Albert Ludwigs Freiburg New ceramic material and its use for dental fillings and dentures
FR2843748A1 (en) * 2002-08-23 2004-02-27 Septodont Ou Specialites Septo Material for restoring mineralized material, especially in dental restoration work, obtained by mixing aqueous liquid, solid tri- and/or dicalcium silicate, calcium chloride and water reducing agent
US20040043053A1 (en) * 2002-09-02 2004-03-04 Yu Hyun Seung Biodegradable and bioactive glass-ceramics, and method for fabricating the same
US20040117030A1 (en) * 2002-09-30 2004-06-17 Niklas Axen Heat generating biocompatible ceramic materials
WO2004058194A1 (en) * 2002-12-31 2004-07-15 Doxa Aktiebolag Chemically bonded biomaterial with tailored properties

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1796749A4 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7972630B2 (en) 2000-04-11 2011-07-05 Bone Support Ab Injectable bone mineral substitute material
US8420127B2 (en) 2003-03-05 2013-04-16 Bone Support Ab Bone substitute composition
US7935121B2 (en) 2003-11-11 2011-05-03 Bone Support Ab Device for providing spongy bone with bone substitute and/or bone reinforcing material, bone substitute and/or bone reinforcing material and method
US8297831B2 (en) 2004-06-22 2012-10-30 Bone Support Ab Device for producing a hardenable mass
US7938572B2 (en) 2004-06-22 2011-05-10 Bone Support Ab Device for producing a hardenable mass
EP1861341A4 (en) * 2005-03-25 2011-12-21 Innovative Bioceramix Inc Hydraulic cement compositions and methods of making and using the same
EP1861341A1 (en) * 2005-03-25 2007-12-05 Innovative Bioceramix, Inc. Hydraulic cement compositions and methods of making and using the same
WO2009038191A1 (en) * 2007-09-20 2009-03-26 Kyushu University, National University Corporation Curable composition
JP5404407B2 (en) * 2007-09-20 2014-01-29 国立大学法人九州大学 Curable composition
US9180137B2 (en) 2010-02-09 2015-11-10 Bone Support Ab Preparation of bone cement compositions
US10294107B2 (en) 2013-02-20 2019-05-21 Bone Support Ab Setting of hardenable bone substitute
US10994998B2 (en) 2013-02-20 2021-05-04 Bone Support Ab Setting of hardenable bone substitute
US11964072B2 (en) 2016-09-27 2024-04-23 Biomimetic Innovations Limited Soft tissue adhesive composition of α-TCP and phosphorylated amino acid

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US20090192513A1 (en) 2009-07-30
BRPI0514636A2 (en) 2011-05-10
JP2008512176A (en) 2008-04-24
EP1796749A4 (en) 2011-08-17
US7531035B2 (en) 2009-05-12
SE528360C2 (en) 2006-10-24
US7972434B2 (en) 2011-07-05
CN101014376A (en) 2007-08-08
US20060078590A1 (en) 2006-04-13
SE0402196D0 (en) 2004-09-10
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RU2379061C2 (en) 2010-01-20
EP1796749A1 (en) 2007-06-20

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