WO2012054010A1 - Formule de ciment chirurgical et composites à base de ciment chirurgical durci biorésorbable préparés à l'aide de celle-ci - Google Patents

Formule de ciment chirurgical et composites à base de ciment chirurgical durci biorésorbable préparés à l'aide de celle-ci Download PDF

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WO2012054010A1
WO2012054010A1 PCT/US2010/002777 US2010002777W WO2012054010A1 WO 2012054010 A1 WO2012054010 A1 WO 2012054010A1 US 2010002777 W US2010002777 W US 2010002777W WO 2012054010 A1 WO2012054010 A1 WO 2012054010A1
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Prior art keywords
ttcp
phosphate
bone cement
csh
paste
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PCT/US2010/002777
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English (en)
Inventor
Jiin-Huey Chern Lin
Chien-Ping Ju
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Jiin-Huey Chern Lin
Chien-Ping Ju
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Priority to PCT/US2010/002777 priority Critical patent/WO2012054010A1/fr
Publication of WO2012054010A1 publication Critical patent/WO2012054010A1/fr

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    • 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
    • C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
    • C04B35/01—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products based on oxide ceramics
    • C04B35/447—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products based on oxide ceramics based on phosphates, e.g. hydroxyapatite
    • 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
    • A61L24/0063—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
    • 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
    • C04B38/00—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof
    • C04B38/04—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof by dissolving-out added substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • 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
    • 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
    • C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
    • C04B2235/02—Composition of constituents of the starting material or of secondary phases of the final product
    • C04B2235/30—Constituents and secondary phases not being of a fibrous nature
    • C04B2235/44—Metal salt constituents or additives chosen for the nature of the anions, e.g. hydrides or acetylacetonate
    • C04B2235/444—Halide containing anions, e.g. bromide, iodate, chlorite
    • 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
    • C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
    • C04B2235/02—Composition of constituents of the starting material or of secondary phases of the final product
    • C04B2235/30—Constituents and secondary phases not being of a fibrous nature
    • C04B2235/44—Metal salt constituents or additives chosen for the nature of the anions, e.g. hydrides or acetylacetonate
    • C04B2235/447—Phosphates or phosphites, e.g. orthophosphate or hypophosphite
    • 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
    • C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
    • C04B2235/02—Composition of constituents of the starting material or of secondary phases of the final product
    • C04B2235/30—Constituents and secondary phases not being of a fibrous nature
    • C04B2235/44—Metal salt constituents or additives chosen for the nature of the anions, e.g. hydrides or acetylacetonate
    • C04B2235/448—Sulphates or sulphites
    • 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
    • C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
    • C04B2235/02—Composition of constituents of the starting material or of secondary phases of the final product
    • C04B2235/30—Constituents and secondary phases not being of a fibrous nature
    • C04B2235/44—Metal salt constituents or additives chosen for the nature of the anions, e.g. hydrides or acetylacetonate
    • C04B2235/449—Organic acids, e.g. EDTA, citrate, acetate, oxalate

Definitions

  • the exemplary embodiment(s) of the present invention relates to bone repairing substance for medicaments. More specifically, the exemplary embodiment(s) of the present invention relates to a bone cement formula.
  • Bone cement compositions are widely used in bonding, filling, and/or repairing damaged natural bone. Bone cement is typically used in orthopedic, dental procedures, and/or other medicinal applications.
  • the composite including calcium sulfates generally has lower mechanical and/or physical strengths than calcium phosphates.
  • CPC calcium phosphate
  • Embodiment(s) of the present invention discloses a method of providing a calcium phosphate-calcium sulfate composite that exhibits enhanced strength, excellent biocompatibility, superior osteoconductivity, appropriate and adjustable bioresorption rate.
  • the objectives of embodiments are to provide a bone cement formula, a bone cement paste, a hardened bone cement composite from paste, a hardened bone cement composite with enhanced strength by pressurizing the paste while leaking solution from the paste, and porous hardened bone cement composite from the paste.
  • the embodiments of the present invention provides methods for providing a bone cement formula, bone cement paste, hardened bone cement composite, hardened bone cement composite with enhanced strength, and porous hardened bone cement composite.
  • An embodiment of the present invention provides a method for filling a hole or cavity in a bone with an exemplary embodiment of bone cement paste which will cure or harden in a hole or cavity in need of treatment.
  • Another embodiment of the present invention provides a method for implanting hardened bone cement composite during a treatment.
  • a bone cement formula which includes a powder component and a setting liquid component with a liquid to powder ratio of 0.20 cc/g to 0.50 cc/g (cc is cubic centimeter, g is gram), preferably 0.25 cc/g to 0.35 cc/g.
  • the powder component in one aspect, includes a calcium sulfate source and a calcium phosphate source with a weight ratio of the calcium sulfate source less than 65%, based on the total weight of the calcium sulfate source and the calcium phosphate source.
  • the setting liquid component in one aspect, includes ammonium ion (NH 4 + ) in a concentration of about 0.5 M to 4 M.
  • the calcium phosphate source in one aspect, includes tetracalcium phosphate (TTCP) and dicalcium phosphate in a molar ratio of TTCP to dicalcium phosphate of about 0.5 to about 2.5, preferably about 1 .0, and the calcium sulfate source is calcium sulfate hemihydrate (CSH), calcium sulfate dehydrate (CSD), or anhydrous calcium sulfate, and preferably, CSH.
  • TTCP tetracalcium phosphate
  • dicalcium phosphate in a molar ratio of TTCP to dicalcium phosphate of about 0.5 to about 2.5, preferably about 1 .0
  • the calcium sulfate source is calcium sulfate hemihydrate (CSH), calcium sulfate dehydrate (CSD), or anhydrous calcium sulfate, and preferably, CSH.
  • a resorption rate of implanted hardened cement composite can be adjustable due to co-existence of a calcium sulfate source and a calcium phosphate source.
  • Our animal study demonstrates that the resorption rate of our hardened sulfate-phosphate cement composite can be adjusted by adjusting the sulfate/phosphate ratio.
  • calcium sulfate source of the powder component is greater than 5%, and preferably in a range of 10% to 55%, based on the total weight of the calcium sulfate source and the calcium phosphate source powder.
  • Calcium phosphate source in one aspect, includes tetracalcium phosphate (TTCP) and dicalcium phosphate, preferably DCPA, in a molar ratio of TTCP to dicalcium phosphate of approximately 0.5 to 2.5, preferably about 1.0, and the calcium sulfate source is calcium sulfate hemihydrate (CSH), calcium sulfate dehydrate (CSD), or anhydrous calcium sulfate, and preferably, CSH.
  • CSH calcium sulfate hemihydrate
  • CSD calcium sulfate dehydrate
  • CSH calcium sulfate dehydrate
  • TTCP As illustrated or demonstrated in Control Examples 1-4, detailed discussion in the section of Experiential Procedures below, the combination of TTCP, DCPA and CSH is essential. As TTCP, DCPA, and CSH can be combined or mixed in a certain weight-ratio range, various unique and non-replaceable results are obtained. On the other hand, various experiments of mixtures of two compounds, such as TTCP/CSH and
  • ammonium is generally considered as a rather toxic
  • ammonium provides not only a cytotoxically acceptable cement formula, but also a cement formula with unprecedented performance.
  • concentration of ammonium ions is too low, the cement paste can be either dispersed right upon contact with liquid, such as water or body fluid (i.e., blood), or has an initial mechanical strength that is too low to maintain cement paste integrity which can cause premature fracture of cement paste.
  • ammonium ion concentration is too high, the cement paste becomes too toxic to be used as an implant.
  • the setting liquid component comprises ammonium ion (NH 4 + ) in a concentration of about 1.0 M to 2.0 M, and more preferably about 1.2 M.
  • the setting liquid component in one example, is a solution of
  • the setting liquid component is an aqueous solution.
  • the setting liquid component further comprises citric acid or tartaric acid dissolved therein.
  • the setting liquid component preferably has a pH of about 7.0 to about 9.0.
  • the powder component comprises a pore-forming agent which is to be dissolved in a solution when hardened bone cement composite is immersed in the solution.
  • the pore-forming agent is selected from the group consisting of LiCI, KCI, NaCI, MgCI 2 , CaCI 2 , NalC>3, Kl, Na 3 P0 4 , K 3 P0 4 , Na 2 C0 3 , amino acid-sodium salt, amino acid-potassium salt, glucose, polysaccharide, fatty acid-sodium salt, fatty acid-potassium salt, potassium bitartrate (KHC 4 H 4 C>6), potassium carbonate, potassium gluconate (KC 6 Hn0 7 ), potassium-sodium tartrate (KNaC 4 H 0 6 -4H 2 0), potassium sulfate (K 2 S0 ), sodium sulfate, sodium lactate and mannitol.
  • the amount of the pore-forming agent used is proportional to the porosity of the hardened
  • the calcium phosphate source is a mixture of TTCP and DCPA.
  • the bone cement formula allows bone cement paste having a desirable working time and a setting time, so that the operator has a sufficient period of time to fill the hole or cavity with the paste before the paste becomes hardened. It should be noted that filled paste will develop minimum strength required by the treatment within an acceptable short period of time.
  • the hardened bone cement composite in one embodiment, possesses a low toxicity whereby it is safe to be applied to a patient, for example.
  • hardened bone cement has a characteristic of high initial strength with an improved bioresorbable rate.
  • Embodiments of the present invention are described herein in the context of method, formula, system, and/or process for preparing a hardened bone cement composite having an enhanced bioresorbable rate for medicaments.
  • Those of ordinary skills in the art will realize that the following detailed description of the embodiment(s) is illustrative only and is not intended to be in any way limiting. Other embodiments of the present invention will readily suggest themselves to such skilled persons having the benefit of this disclosure.
  • references to "one embodiment,” “an embodiment,” “example embodiment,” “various embodiments,” “exemplary embodiment,” “one aspect,” “an aspect,” “exemplary aspect,” “various aspects,” etc. indicate that the embodiment(s) of the invention so described may include a particular feature, structure, or characteristic, but not every embodiment necessarily includes the particular feature, structure, or characteristic.
  • Embodiment(s) of the present invention is bioresorbable bone cement applicable to various medical fields, such as orthopedic, spinal, and root canal surgeries. Characteristics or properties of the bioresorbable bone cement or formula have convenient working environment(s) and setting times to form a hardened block with high strength, excellent biocompatibility and superior osteoconductivity, and adjustable (or flexible) bioresorption rate.
  • a method or process for preparing hardened bone cement composite involves producing bone cement paste and placing the paste in an environment where the paste can set.
  • a process for preparing bone cement paste comprises mixing powder component with setting liquid component by a mixing mechanism such as agitation.
  • the powder component may include mixture of calcium sulfate source and calcium phosphate source.
  • calcium sulfate source and calcium phosphate source can be separate powders. In this case, calcium sulfate source and calcium phosphate source are combined first to form a power mixture prior to mixing with setting liquid component.
  • the calcium sulfate source and calcium phosphate source discussed earlier can be tetracalcium phosphate (TTCP) and/or dicalcium phosphate anhydrous (DCPA) powders. It should be noted that other types of sources can be used as long as they have similar chemical properties or
  • the bone cement paste in one embodiment, becomes hard or cured within a period of setting time under an atmosphere environment or an environment surrounded by body fluid such as blood.
  • body fluid such as blood.
  • an operator or doctor places bone cement paste into a hole or cavity at a damaged bone via a suitable tool through an incision.
  • the hardened bone cement will be resorbed by the subject body over time in accordance with a predefined bioresorption rate.
  • bone cement paste in one embodiment, can be shaped into a rigid or semi-rigid block of bone cement composite before it is implanted in the subject body to repair damaged parts such as bones or teeth.
  • the bone cement paste in one embodiment, can be injected into a bone hole or cavity with an orthopedic paste delivering tool such as a
  • a dense block of cement can be formed if the powder component does not contain the appropriate pore-forming agents.
  • the dense block can be formed by pressurizing the bone cement paste in a mold before the paste sets in order to drain or remove a portion of liquid from the paste whereby a liquid/powder ratio of the paste decreases.
  • the pressure applied to the paste at the mold has a range from approximately 1 megapascal ("MPa") to 500 MPa, preferably from 100 MPa to 500 MPa.
  • the dense block has a superior compressive strength which can be used as a medical implant.
  • a rigid or solid dense block of calcium phosphate cement is impregnated with an impregnating liquid for a predefined period of time, so that overall compressive strength of the resulting impregnated block is increased compared to a block which has not undergone such impregnating treatment.
  • the impregnating liquid in one embodiment, is phosphate-containing solution.
  • Exemplary aqueous solution may include, but not limited to, (NH 4 ) 3 P0 4 , (NH 4 ) 2 H P0 4 , NH 4 H 2 P0 4 , K 3 P0 4 , K 2 HP0 4 , KH 2 P0 4 , Na 3 P0 4 , Na 2 HP0 4 , NaH 2 P0 4 , or H 3 P0 4 .
  • the phosphate-containing solution in one example, has a phosphate
  • concentration of about 0.1 M to about 6 M, preferably from about 1 M to about 3 M.
  • a porous block can be utilized as a tissue-engineered scaffold when the powder component of the bone cement formula contains pore-forming agent.
  • the pore-forming agent can be removed from a molded block by immersing the molded block in immersing liquid so that the pore-forming agent is dissolved in the immersing liquid.
  • the pore-forming agent may be added during the mixing of the powder component and the setting liquid component, or may be added to the resultant paste before it is placed in a mold.
  • the immersing liquid for example, can be an acidic aqueous solution, a basic aqueous solution, a physiological solution, an organic solvent or
  • the immersing liquid is the same as the above-mentioned impregnating liquid. In one embodiment, the immersing liquid is waster. In one aspect, the porous block has a porosity of 50-90 vol%.
  • the dense block or porous block prepared in accordance with the bone cement formula in one embodiment, can be deposited within living cells, a growth factor and/or a drug by impregnating the block in a suspension of living cells or a solution of the growth factor and/or drug.
  • the dense block and the porous block prepared in the present invention may be further broken up into pellets for other medical applications.
  • TTCP tetracalcium phosphate
  • DCPA dicalcium phosphate anhydrous
  • Hardened cement blocks are broken (fractured/cracked but not dispersed into powder form) after being immersed in Hanks' solution for 1 day.
  • the TTCP powder was fabricated in-house from the reaction of dicalcium pyrophosphate (Ca 2 2 0 7 ) (Sigma Chem. Co. , St. Louis, MO, USA) and calcium carbonate (CaC0 3 ) (Katayama Chem. Co. , Tokyo, Japan) using the method suggested by Brown and Epstein [Journal of Research of the National Bureau of Standards- A Physics and Chemistry 6 ( 1965) 69A 1 2].
  • TTCP powder was prepared by mixing Ca 2 P 2 0 7 powder with CaCC>3 powder uniformly for 12 hours.
  • the mixing ratio of Ca 2 P20 7 powder to CaC0 3 powder was 1 : 1 .27 (weight ratio) and the powder mixture was heated to 1400°C to allow two powders to react to form TTCP.
  • TTCP and DCPA powders were uniformly mixed in a ball miller, followed by uniformly mixing with appropriate amount of CSH powder.
  • the resultant TTCP/DCPA/CSH mixed powders were mixed uniformly with a desirable setting solution (e. g . , 0.6M (N H 4 ) 2 H P0 4 ) at a desirable UP ratio (e.g. , 0.28 cc/g) to form a TTCP/DCPA/CSH paste.
  • a desirable setting solution e. g . 0.6M (N H 4 ) 2 H P0 4
  • a desirable UP ratio e.g. , 0.28 cc/g
  • Com pressive strength testing of composite cement To measure the CS of a hardened cement, after mixing for 1 min, the cement paste was packed in a 6 mm diameter, 12 mm deep cylindrical stainless steel mold under a pressure of 1 .4 MPa for 30 min. After being removed from the mold, the hardened cement samples were immersed in Hanks' physiological solution which was maintained at 37°C and agitated daily to help maintain uniform ion concentrations. After immersion, samples were removed from the solution for CS testing while samples are still wet ("test under wet condition"). The CS testing was conducted using a desk-top mechanical tester (Shimadzu AG-10kNX, Tokyo, Japan) at a crosshead speed of 1 .0 mm/min. The test method is according to ASTM 451 -99a method.
  • the working time of cement paste was determined by the time after that the cement paste was no longer workable.
  • the setting time of cement paste was measured according to the standard method set forth in ISO 1566 for dental zinc phosphate cements. The cement is considered set when a 400 gm weight loaded onto a Vicat needle with a 1 mm diameter tip fails to make a perceptible circular indentation on the surface of the cement. pH measurement
  • the early stage (during setting process) variation in pH was determined using a pH meter (Suntex Instruments SP2000, Taipei, Taiwan) that was buried in the cement paste immediately after the powder and setting liquid were mixed. The first reading was taken at 1 minute after mixing. The measurement was continued until the paste nearly becomes set. Readings were taken every 30 seconds until 30 minutes after mixing. After then they were taken every 60 seconds.
  • the cytotoxicity test was performed according to ISO 10993-5.
  • the extraction method was used.
  • NIH/3T3 fibroblasts seeding density 5000 per well
  • DMEM Dulbecco's modified essential medium
  • bovine serum 10%
  • PSF 1%
  • An extract was prepared by immersing a hardened cement paste in the culture medium at a ratio of 0.1 (g/ml) at 37°C for 24h and then collecting the liquid by centrifugation.
  • the extract was added to the 96 well microplate (100 ⁇ per well) incubated in a 5% C0 2 humidified atmosphere at 37°C.
  • Control 1 TTCP/CSH cement and (NH 4 ) 2 HP0 4 setting solution
  • Control 2 TTCP/CSH cement and NH 4 H 2 P0 4 setting solution
  • Table 2 shows that N H 4 H 2 P0 4 setting solution used in Control 2 cannot improve the (NH 4 ) 2 H P0 setting solution used in Control 1 in term of the working/setting times and the 1 d-CS. Apparently the powder component having only TTCP and CSH phases dose not give a satisfactory result.
  • Control 3 DCPA/CSH cement and (N H 4 ) 2 HP0 4 setting solution
  • Control 4 DCPA/CSH cement and NH 4 H 2 P0 4 setting solution
  • DCPA/CSH cement cannot be measured after being immersed in Hanks' solution for 1 day as shown in Table 4. Apparently the powder component having only DCPA and CSH phases does not give a satisfactory result.
  • TTCP and DCPA have a molar ratio of 1 : 1 under all conditions
  • Example 1 (TTCP/DCPA)/CSH cement and various setting solutions
  • K 2 HP0 4 -derived hardened cement composites have too short WT/ST and low CS.
  • H2P04-derived hardened cement composites have reasonable WT/ST, but is dispersed after immersion in Hanks' solution.
  • NaH 2 P0 4 -2H 2 0-derived hardened cement composites have reasonable WT/ST, but too acidic and low strength.
  • TTCP/DCPA/CSH cement powder their CS values become too low ( ⁇ 1 5 MPa).
  • the appropriate CSH content under the test conditions should be less than about 65 wt%.
  • the CSH content should be less than about 35 wt%.
  • All 1 -d CS values are higher than 20 MPa, and, under certain conditions, higher than 30 MPa.
  • Example 7 TTCP/DCPA/CSH mixed with 0.40-0.60 M (NH 4 ) 2 HP0 4
  • TTCP and DCPA powders were uniformly mixed in a ball miller, followed by uniformly mixing with appropriate amount of CSH powder.
  • the resultant TTCP/DCPA/CSH mixed powders were mixed uniformly with a desirable setting solution (e. g . , 0.6M (N H 4 ) 2 H P0 4 ) at a desirable UP ratio (e.g. , 0.28 cc/g) to form a TTCP/DCPA/CSH paste.
  • a desirable setting solution e. g . 0.6M (N H 4 ) 2 H P0 4
  • a desirable UP ratio e.g. , 0.28 cc/g
  • the paste Prior to being fully hardened , the paste was placed in a mold under a desirable pressure (at a maximum pressure of 1 50, 300 or 450 Kgf) to squeeze a portion of the liquid out of the paste. After being removed from the mold, one group of the hardened composite samples were placed in a moisture-proof container for 1 day. Another group of samples were further impregnated in an impregnation solution ( 1 M ( N H 4 ) 2 H P0 4 or 1 M K 2 H P0 ) at a desirable temperature (37°C) for 1 day, followed by drying in an oven at 50°C for 1 day.
  • a desirable pressure at a maximum pressure of 1 50, 300 or 450 Kgf
  • TTCP and DCPA powders were uniformly mixed in a ball miller, followed by uniformly mixing with appropriate amount of CSH powder.
  • the resultant TTCP/DCPA/CSH mixed powders were mixed uniformly with a desirable setting solution (e.g . , 0.6M (NH 4 ) 2 H P0 4 ) at a desirable UP ratio (e.g . , 0.28 cc/g) to form a TTCP/DC PA/CSH paste.
  • a desirable setting solution e.g . 0.6M (NH 4 ) 2 H P0 4
  • a desirable UP ratio e.g . , 0.28 cc/g
  • the composite paste was then uniformly mixed with a pore-forming agent (e.g. KCI particles) with a desirable weight ratio (e.g.
  • the composite paste Prior to being fully hardened , the composite paste was placed in a mold under a desirable pressure (at a maximum pressure of 450 Kgf) to squeeze a portion of the liquid out of the paste. After being removed from the mold, one group of the hardened composite blocks were immersed in de-ionized water at 37°C for 3 days to allow KCI particles to dissolve, forming a porous composite block, followed by drying in an oven at 50°C for 1 day. Another group of samples were further impregnated in an impregnation solution (e.g.
  • the porosity of the various samples was measured according to ASTM C830-00 (2006) method, "Standard Test Methods for Apparent Porosity, Liquid Absorption, Apparent Specific Gravity, and Bulk Density of Refractory Shapes by Vacuum Pressure".
  • the impregnation treatment significantly enhances the strength of the porous blocks.
  • the hole was gradually widened with drills of increasing size until a final diameter of 5 mm was reached.
  • a special 5 mm diameter drill burr was used and a ring was inserted at a depth of 10mm to ensure appropriate length (10 mm) of the drill hole.
  • Two kinds of calcium phosphate/calcium sulfate composite cement paste (90wt% TTCP/DCPA: 10wt% CSH and 55wt% TTCP/DCPA: 45wt% CSH) were implanted in the prepared bone cavity. After filling of the paste, subcutaneous tissues and skin were closed up layer by layer with silk threads. To reduce the risk of peri-operative infection, the rabbits were treated with antibiotics injection subcutaneously at a dose of 40 mg/kg. The animals were sacrificed after 12 week post-operation.
  • implant resorption ratio (cross-sectional area of original implant - cross-sectional area of residual implant)/cross-sectional area of original implant.
  • the average residual implant ratios for "90/10" and "55/45" samples are 81 .1 % (resorption ratio: 18.9%) and 67.7% (resorption ratio: 32.3%), respectively, as shown in the photographs mentioned above. That means the healing speed for the 55/45 implant is about 70% faster than for the 90/10 implant.

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  • Ceramic Engineering (AREA)
  • Materials Engineering (AREA)
  • General Health & Medical Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Composite Materials (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Structural Engineering (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Manufacturing & Machinery (AREA)
  • Surgery (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Cette invention concerne une formule de ciment chirurgical contenant un composant pulvérulent et un composant de prise liquide. Le composant pulvérulent contient une source de sulfate de calcium et une source de phosphate de calcium en une proportion en poids de la source de sulfate de calcium inférieure à 65 %, sur la base du poids total de la source de sulfate de calcium et de la source de phosphate de calcium, et le composant de prise liquide comprend l'ion ammonium (NH4 +) à une concentration d'environ 0,5 à 4 M. La source de phosphate de calcium comprend le phosphate de tétracalcium (TTCP) et le phosphate de dicalcium dans un rapport molaire du TTCP au phosphate de dicalcium d'environ 0,5 à environ 2,5, et la source de sulfate de calcium est le sulfate de calcium hémihydraté (CSH), le sulfate de calcium dihydraté (CSD), ou le sulfate de calcium anhydre.
PCT/US2010/002777 2010-10-19 2010-10-19 Formule de ciment chirurgical et composites à base de ciment chirurgical durci biorésorbable préparés à l'aide de celle-ci WO2012054010A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US2010/002777 WO2012054010A1 (fr) 2010-10-19 2010-10-19 Formule de ciment chirurgical et composites à base de ciment chirurgical durci biorésorbable préparés à l'aide de celle-ci

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2010/002777 WO2012054010A1 (fr) 2010-10-19 2010-10-19 Formule de ciment chirurgical et composites à base de ciment chirurgical durci biorésorbable préparés à l'aide de celle-ci

Publications (1)

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WO2012054010A1 true WO2012054010A1 (fr) 2012-04-26

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5281265A (en) * 1992-02-03 1994-01-25 Liu Sung Tsuen Resorbable surgical cements
US20050208094A1 (en) * 2003-09-05 2005-09-22 Armitage Bryan M Bone cement compositions having fiber-reinforcement and/or increased flowability
US20050241535A1 (en) * 2002-06-19 2005-11-03 Dr. H.C. Robert Mathys Stiftund Hydraulic cement based on calcium phosphate for surgical use
US20050267593A1 (en) * 2004-05-25 2005-12-01 Calcitec, Inc. Dual function prosthetic bone implant and method for preparing the same
US20050279252A1 (en) * 2000-07-13 2005-12-22 Cana Lab Corporation Tetracalcium phosphate (TTCP) with surface whiskers and method of making same
US20070213827A1 (en) * 2005-09-28 2007-09-13 Arramon Yves P Hardened calcium phosphate cement bone implants
US20100249794A1 (en) * 2005-09-09 2010-09-30 Wright Medical Technology, Inc. Composite Bone Graft Substitute Cement and Articles Produced Therefrom

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5281265A (en) * 1992-02-03 1994-01-25 Liu Sung Tsuen Resorbable surgical cements
US20050279252A1 (en) * 2000-07-13 2005-12-22 Cana Lab Corporation Tetracalcium phosphate (TTCP) with surface whiskers and method of making same
US20050241535A1 (en) * 2002-06-19 2005-11-03 Dr. H.C. Robert Mathys Stiftund Hydraulic cement based on calcium phosphate for surgical use
US20050208094A1 (en) * 2003-09-05 2005-09-22 Armitage Bryan M Bone cement compositions having fiber-reinforcement and/or increased flowability
US20050267593A1 (en) * 2004-05-25 2005-12-01 Calcitec, Inc. Dual function prosthetic bone implant and method for preparing the same
US20100249794A1 (en) * 2005-09-09 2010-09-30 Wright Medical Technology, Inc. Composite Bone Graft Substitute Cement and Articles Produced Therefrom
US20070213827A1 (en) * 2005-09-28 2007-09-13 Arramon Yves P Hardened calcium phosphate cement bone implants

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GUO ET AL.: "Development of a Degradable Cement of Calcium Phosphate and Calcium Sulfate Composite for Bone", RECONSTRUCTION. BIOMEDICAL MATERIALS, vol. 1, no. 4, 13 September 2006 (2006-09-13), pages 193 - 197 *

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