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
  • A61L24/0042—Materials resorbable by the body
• • 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
  • A61L24/02—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
  • A61L27/28—Materials for coating prostheses
  • A61L27/30—Inorganic materials
  • A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
• • 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
  • C04B28/34—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
• • 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
  • A61L2400/00—Materials characterised by their function or physical properties
  • A61L2400/06—Flowable or injectable implant compositions
• • 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

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 slurry and a cured ceramic material, a method of manufacturing said cured material, and medical implants and carrier materials made from said cured or non-cured precursor composition.
• 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.
• Ca-silicate is mentioned as an additional phase for drug uses (less than 10%) and for bone substitute products as an additional divalent compound.
• biocompability of Ca-silicate materials work have been done on the endodontic treatment material, Proroot or MTA, and on the Wollastonite materials. See J. Saidon, et al, "Cells and tissue reactions to mineral trioxide 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 cements and fillers: A Review", Journal of Materials Science: Materials in Medicine, 14 (2003) 923-938.
• the present invention provides ceramic precursor 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 phases, which when cured, provides a sufficiently high-strength (compressive strength more than 50 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 phases 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 comprising one or more particulate Ca-silicate, a Ca-sulphate as essential features, and an acidic soluble Ca-salt. Said compounds will form the main binding phases in the cured material. The remainder, if any, comprises additives.
• the ceramic precursor composition is defined in claim 1.
• the constituents of the ceramic precursor composition are particulate matter, unless stated otherwise.
• the percentages given represent wt-%, unless stated otherwise, based on the total weight of the precursor composition.
• an injectable ceramic slurry which is obtained by mixing the precursor composition and a curing liquid, i.e. water, in a specified water-to-cement-ratio.
• the injectable ceramic slurry is defined in claim 14.
• a cured ceramic material which is obtained by mixing the precursor composition and a curing liquid, i.e. water, such that a slurry is formed, and allowing said slurry to cure.
• a curing liquid i.e. water
• a method of manufacturing the cured ceramic material from the ceramic precursor composition is defined in claim 32.
• a medical implant which comprises the non-cured precursor composition or cured material. Said medical implant is defined in claim 30.
• a carrier material for drug delivery comprising the non-cured precursor composition or cured material. Said carrier material is defined in claim 31.
• the major advantages of the present invention precursor composition, cured material and product, after having been inserted or injected into a body, is that they have a resorbability, 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.
• the material sets within 20 minutes and have a static immersion pH (i.e. a pH in a medium without stirring the material (slurry, paste)) of less than 11.
• the compressive strength level obtained with the cured material according to the present invention is within the interval more than 50 MPa - to be compared with that of other resorbable biomaterials with a compressive strength in the interval 20- 50 MPa.
• 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. 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 comprises main binding phase (s) of chemically bonded ceramics, preferably Ca-silicates, with Ca as the main cation.
• the Ca-silicate preferably comprises one or more of the following phases:
• the main binding phase(s) of the ceramic precursor composition comprises 40-70 wt-% of one ore more Ca- silicate.
• the main binding phase comprises 3CaO-SiO 2 .
• the main binding phase(s) of the cured ceramic material comprises hydrates of 3CaO-SiO 2 .
• Said main binding phase(s) also comprise a Ca- based sulphate.
• soluble chemically bonded ceramic based on 3CaO-SiO 2 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 application of the ceramic precursor composition mixed with a curing liquid.
• a phase which improves initial closure of pores in the ceramic material by pure water up-take, e.g. the non-hydrated pure CaSO 4 , the semi-hydrate CaSO 4 -VaH 2 O and/ or mixtures of these and the hydrated CaSO 4 -2H 2 O (gypsum).
• These phases will not contribute to the medium- term or long-term properties, only enhance the initial pore closure and initial strength.
• the ceramic precursor composition comprises 40-20 wt-% of the Ca-based sulphate.
• the composition preferably comprises 35-22 wt-% of the Ca-based sulphate.
• the initial high pH can be reduced by the addition of an acidic soluble Ca salt, selected from compounds having the molecular composition [CaHX ], where the anion X- is a phosphate and/ or carbonate.
• an acidic soluble Ca salt selected from compounds having the molecular composition [CaHX ], where the anion X- is a phosphate and/ or carbonate.
• MCPM mono calcium phosphate monohydrate
• Said salt is preferably present in an amount greater than 0 wt-% to 5 wt-%.
• the ceramic precursor composition may also comprise additional Ca-based phosphates and carbonates, having calcium as the major cation, in an amount greater than 0 wt-% to 30 wt-%, preferably greater than 0 wt-% to 20 wt-%.
• additional Ca-based phosphates and carbonates having calcium as the major cation, in an amount greater than 0 wt-% to 30 wt-%, preferably greater than 0 wt-% to 20 wt-%.
• Examples of such calcium phosphates are calcium phosphates, ⁇ -TCP, hydroxyapatites, etc.
• the ceramic precursor composition may further comprise particles of hydrated chemically bonded ceramics of the same or similar composition as that of main the binding phase(s) and in amounts greater than zero wt-% to 40 wt-%.
• the preferred amount is 10-30 wt-%. This improves the homogeneity of the microstructure and enhances the binding between reacting chemically bonded ceramics and the filler material in the early stage of curing.
• 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 water-to-cement (w/c) ratio as much as possible in order to obtain the appropriate viscosity for any given application.
• the w/c ratio should be equal to or less than 0,55, more preferably equal to or less than 0,45, but not less than 0,2.
• the slurry should be injectable through a surgical needle, and preferably a size 11 Gauge needle.
• the materials also show slow disintegration rate in water and body liquid, i.e. that more than 95% of the inserted mass is intact after a setting time of 5 minutes, more preferably after a setting time of 10 minutes, which 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 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 after having been inserted into a body, has a low disintegration rate in water and body liquid throughout the setting time.
• the cured ceramic material exhibits a compressive strength exceeding 50 MPa. It has a compressive strength within 24 hours of at least 40 MPa, preferably more than 50 MPa.
• the pressure the material exerts during setting and curing (hardening) is less than 5 MPa, in some cases less than 3 MPa, on the surrounding environment, i.e. normally the body tissue. This is due to the fact that the expansion of the material during curing is very moderate.
• the cured ceramic product according to the present invention after having been inserted into a body, has a resorption rate that is less or equal to that of the bone in-growth rate. More than 60 wt-% of the material is resorbed within 3 years, preferably more than 50 wt-% within 2 years, and more preferably more than 40 wt- % within 1 year.
• bioelement is intended all types of ceramic objects or coated objects intended for insertion into a body, such as medical implants, and particularly orthopaedic implants.
• the ceramic precursor composition according to the invention, mixed with a curing liquid, may also be inserted as a slurry, paste or putty, which after curing, forms said biolement.
• the term "cured" when used to describe the ceramic material is taken to mean the ceramic material in any stage of the curing period, i.e. from the moment that a slurry, paste or putty is manufactured from the precursor composition and a hydration liquid, to the completion of the curing period and the obtaining of a fully cured material. Therefore, when the properties of the cured material is described in the specification, the referral to injection of a "cured” material actually means that a not fully cured slurry, paste or putty made from the precursor composition has been injected or inserted. The properties of the cured material thus reflects its properties from the moment it is inserted or injected. Examples
• a pure calcium silicate 3Ca ⁇ 3*Si ⁇ 2 -based paste was injected into predrilled hole in the left femur of 6 New Zeeland white rabbits.
• Norian SRS (Synthes) was injected.
• the inflammatory response in the tissue surrounding the implant was studied macroscopically and on paraffin sections after 14 days implantation time.
• the results showed a marked inflammation in the tissue surrounding the calcium silicate-based material.
• the inflammatory response could be coupled to the high pH of the calcium silicate material.
• Tests were performed to lower the reaction pH of injectable biomaterials containing calcium silicate Ca ⁇ 3»Si ⁇ 2.
• the setting time and compressive strength should be controlled to be within 20 minutes and more than 50 MPa.
• compositions 5-9 below represent comparative examples that do not fall within the scope of the present invention.
• Precursor formulations were mixed according to:
• the setting time were measured by static immersion testing in water with a water to-cement ratio of 0.2.
• the setting time was measured using the Gillmore needle method and the compressive strength according to ISO 9917. All powders were mixed with water to a w/c of 0.4.
• Example 3 An animal study was performed to study the inflammatory response to formulation 3 in Example 2.
• the paste was injected into predrilled hole in the left femur of 6 New Zeeland white rabbits.
• Norian SRS (Synthes) was injected.
• the inflammatory response in the tissue surrounding the implants was studied macroscopically and on paraffin sections after 14 days implantation time.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Engineering & Computer Science (AREA)
• Inorganic Chemistry (AREA)
• Surgery (AREA)
• Medicinal Chemistry (AREA)
• Materials Engineering (AREA)
• Ceramic Engineering (AREA)
• Transplantation (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Dermatology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Chemistry (AREA)
• Structural Engineering (AREA)
• Materials For Medical Uses (AREA)

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Citations (4)

• 2007
  • 2007-10-16 EP EP07835330A patent/EP2073855A4/de not_active Withdrawn
  • 2007-10-16 WO PCT/SE2007/050745 patent/WO2008048182A1/en active Application Filing

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