WO2010112955A1 - Trousse de ciment osseux et procédés d'utilisation associés - Google Patents

Trousse de ciment osseux et procédés d'utilisation associés Download PDF

Info

Publication number
WO2010112955A1
WO2010112955A1 PCT/IB2009/005447 IB2009005447W WO2010112955A1 WO 2010112955 A1 WO2010112955 A1 WO 2010112955A1 IB 2009005447 W IB2009005447 W IB 2009005447W WO 2010112955 A1 WO2010112955 A1 WO 2010112955A1
Authority
WO
WIPO (PCT)
Prior art keywords
component
bone
additive
powder
kit according
Prior art date
Application number
PCT/IB2009/005447
Other languages
English (en)
Inventor
Jean-François OGLAZA
Cécile VIENNEY
Original Assignee
Vexim
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vexim filed Critical Vexim
Priority to PCT/IB2009/005447 priority Critical patent/WO2010112955A1/fr
Publication of WO2010112955A1 publication Critical patent/WO2010112955A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/043—Mixtures of macromolecular 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • Embodiments of the present disclosure relate to bone cements, and more particularly, to a kit for a bone cement and its use thereof, where the components of the bone cement when mixed according to predetermined amounts, provide for a bone cement with a predetermined compression strength/stiffness.
  • Bones have a complex internal and external structure that allows them to achieve various functions.
  • bones are comprised of a variety of tissues including mineralized osseous tissue (e.g., bone tissue), marrow, endosteum and periosteum, nerves, blood vessels, and cartilage.
  • a major portion of bone tissue is comprised mostly of calcium phosphate, in the form of calcium hydroxylapatite, and living cells, which are embedded in a mineralized organic matrix that makes up the osseous tissue.
  • Osseous tissue has an internal structure that is both very rigid and light weight. This internal structure gives bone a relatively high compressive strength but also makes them brittle.
  • bones can be more or less brittle, given certain conditions, e.g., osteoporosis, bones may be prone to fracture. Such a fracture may result from a high force impact or stress, e.g., compression or over extension, or as a result of a preexistent medical condition that predisposes one to a weakening of the bones, such as osteoporosis or some cancers.
  • a compression fracture may occur when a bone of the body is stressed beyond which its internal structure can support. This may happen as a result of a traumatic accident, such as a fall, or it may result from a preexistent medical condition, such as osteoporosis (thinning of the bone), making it is less capable of supporting a load or resisting an impact.
  • a traumatic accident such as a fall
  • osteoporosis thinning of the bone
  • Genetic factors and certain lifestyle choices for instance, a low calcium diet, can also result in damage to the bones, such that over time, the bones become so weak that normal activities can cause a bone fracture.
  • a bone fracture When a bone fractures it should be, and in most instances, must be repaired.
  • surgical cement may be applied to one or more fractured bone portions for the treatment thereof.
  • intravertebral fractures e.g., a fracture of a vertebra of the spinal column
  • a bone filler or cement into the fractured portion of bone so as to fill the fractured portion and thereby fix, support, and/or otherwise restore the compromised bone to its natural state.
  • vertebroplasty including kyphoplasty
  • other such procedures include procedures involving the correction of fractures to the tibia, radius, calcaneus, and other bone to of the hand.
  • kits, systems, and methods for restoring fractured bone are directed to a kit for producing a bone cement of a predetermined stiffness, which bone cement may be used so as to restore or repair a fractured bone.
  • the kit may include a powder component, such as a polymeric component, and a liquid component, such as a monomer component.
  • the kit may include an additive component, such as a solid or liquid additive, which additive may be combined with one or both of a powder and liquid component.
  • the kit may further include instructions for combining and mixing the various kit components, e.g., in accordance with the instructions provided therein, so as to produce a final cement product having a predetermined stiffness.
  • a representative powder component may be a polymeric component.
  • a suitable polymeric component may be, for example, a polymethylmethacrylate powder, a polyacrylonitrile powder, a barium sulphate powder, a zirconium dioxide radio- opacity powder, and a benzoyl peroxide powder.
  • a representative liquid component may be a monomer component.
  • a suitable monomer component may be, for example, a monomethylmethacrylate (MMA) liquid, a dimethyl-para- toluidine liquid, and/or hydroquinone liquid.
  • a representative additive may be an additional solid or a liquid component that is capable of producing one or more pores in a final cement product, wherein the generated pores function to adjust the stiffness of the final bone cement product in a predetermined manner.
  • a representative solid additive component may include elastic particles (e.g. silicone) and/or bioresorbable particles (e.g. bioceramics, hydrosoluble polymer, jelly).
  • a representative liquid additive component may include an aqueous solution of hyaluronate sodium.
  • a representative set of instructions may include the combining of one or more suitable powder components, one or more suitable liquid components, and/or one or more suitable liquid components, which components may be combined and mixed to produce a final cement end product within a predetermined stiffness range.
  • the instructions may include directions pertaining to one or more of the amounts of the various components to be combined, the sequence of combining the components, as well as the timing involved with mixing the various components.
  • the instructions may further include directions, e.g., a table, for determining the stiffness of a resident bone in the area to which the bone cement is to be administered, directions for determining the desired stiffness of the final bone cement product, and directions for how to combine the components in such a manner so as to produce a bone cement product that when administered will harden into a bone cement with in that desired stiffness range.
  • directions e.g., a table
  • Figures IA- IE provide exemplary embodiments of various components of exemplary kits in accordance with the disclosure provided herein.
  • Figure 2 provides another exemplary embodiment of the subject kit in accordance with the disclosure provided herein.
  • Figure 3 provides another exemplary embodiment of the subject kit in accordance with the disclosure provided herein.
  • Figure 4 provides another exemplary embodiment of the subject kit in accordance with the disclosure provided herein.
  • Figure 5 provides another exemplary embodiment of the subject kit in accordance with the disclosure provided herein.
  • kits, system, and method for restoring a fractured bone portion are directed to a kit for producing a bone cement of a predetermined stiffness, which bone cement may be used either alone or in conjunction with one or more implantable devices or non-implantable devices (e.g. bone tamp instruments), so as to restore a fractured bone.
  • the kit may include a powder component, such as a polymeric component, and a liquid component, such as a monomer component.
  • the kit may include an additive component.
  • the kit may include both a powder component and a liquid component as well as an additive component.
  • the kit may further include instructions for the combining and mixing of the various kit components, in accordance with instructions provided therewith, so as to produce a final cement product having a predetermined stiffness.
  • some embodiments of the subject disclosure provide a method for producing a bone cement having a predetermined stiffness.
  • the method may include one or more of the following steps, which may be performed in any logical order.
  • at least one container is provided, wherein the container includes a polymeric component, a monomer component, and an additive component.
  • the stiffness of bone at a target bone site may be determined, in any suitable manner, and the amount of additive to be added to the polymeric component and monomer component may be determined.
  • the amount of additive to be added may be determined in any suitable manner so long as the amount of additive to be added is such that when mixed with the polymeric and monomer components the combination will produce a final bone cement product having the predetermined stiffness.
  • the stiffness of a bone at the target bone site and/or the amount of additive to be added is determined by reference to a set of instructions, at least a portion of which instructions may be included in the kit.
  • the amount of additive to be added to the polymeric component and the monomer component may include reviewing a table of amounts of predetermined additive to be included and/or may simply include adding a predetermined amount that has been included in a kit, wherein the predetermined amount is set forth as one or more aliquots of additive to be added. Once the appropriate amount of additive to be added has been determined, suitable amounts of the polymeric, monomer, and additive components may be mixed at the determined amounts in a manner sufficient to produce a bone cement product with the predetermined stiffness.
  • some embodiments of the subject disclosure provide a method for treating a subject suffering from a bone fracture, for instance, a compression fracture within or between one or more vertebral bones.
  • the method may include one or more of the following steps, which may be performed in any logical order.
  • an incision may be made in a tissue of a subject so as to expose a treatment site, wherein the treatment site includes a portion of bone, for instance, a vertebral bone, or a bone or the arm, leg, or hand.
  • a suitable device e.g., a cannula
  • the device may then be manipulated in a manner sufficient to create an access in the bone, for instance vertebral bone.
  • this step may be omitted.
  • the stiffness of at least one vertebral bone at the treatment site may be determined.
  • the stiffness of the at least one vertebral bone may be determined in any suitable manner, for instance, by reference to a set of instructions that may be provided in conjunction with a kit containing a bone cement composition for use in the procedure.
  • Such instructions may include a table which list typical bone stiffness for patients of a certain age and/or sex, depending on densitometry. Accordingly, a bone cement paste composition may then be produced in a manner, as described above, such that when the bone cement paste composition hardens a hardened cement having the predetermined stiffness (selected) will result.
  • the predetermined stiffness corresponds to the stiffness of the at least one vertebral bone.
  • An instrument for the application of the bone cement paste composition may be inserted through the incision so that a distal portion of the instrument contacts the treatment site and/or optionally contacts the access, if such an access has been created.
  • the instrument may then be employed in a manner sufficient to apply the bone cement paste composition to the treatment site.
  • the bone cement paste composition is allowed to harden, e.g., self- harden, in to a hardened bone cement product having a predetermined stiffness so as to treat the subject.
  • kits for producing a bone cement having a predetermined stiffness.
  • the subject kit may include one or more of a powder component, and/or a liquid component, and/or an additive component.
  • the powder, liquid, and/or additive components are provided at least in amounts such that upon mixture, a bone cement paste is formed such that when allowed to harden the bone cement paste composition will produce a bone cement product that evidences a predetermined stiffness.
  • the kit may include a powder component wherein the powder component is present in an amount that ranges from about 20% or less to about 80% or more, for instance, from about 30% to about 70%, such as from about 40% to about 60%, including about 50% of the mass of the final cement product.
  • the kit may include a liquid component wherein the liquid component is present in an amount that ranges from about 10% or less to about 60% or more, for instance, from about 20% to about 50%, such as from about 30% to about 40%, including about 35% of the mass of the final cement product.
  • the kit may include an additive component that is present in an amount that ranges from about 0% to about 50% or more, for instance, from about 10% to about 40%, such as from about 20% to about 30%, including about 25% of the mass of the final cement product.
  • the kit may include an additive component that is present in an amount that ranges from about 0.1% or less to about 50% or more, for instance, from about 5% to about 40%, such as from about 10% to about 30%, including about 15% to about 20% of the mass of the final cement product.
  • the additive is a sodium hyaluronate
  • the amount of the additive may range from about 5% or less to about 40% or more.
  • the additive is a silicone bawl, for example, the additive may range from about 5% or less to about 20% or more.
  • the additive is a bioresorbable component, for example, the additive may range from about 5% or less to about 30% or more.
  • the kit may include an opacifying component that is present in an amount that ranges from about 10% or less to about 50% or more, for instance, from about 5% to about 40%, such as from about 10% to about 30%, including about 15% to about 20% of the mass of the final cement product.
  • the subject kit may also include instructions, which instructions may include one or more of directions for determining the stiffness of a bone portion located at a target bone site, as well as directions for determining the amount of powder, liquid, and/or additive component to be added to a preliminary cement composition mixture so as to produce a predetermined quantity of a bone cement paste that hardens into a final bone cement product having the predetermined stiffness, e.g., a stiffness that corresponds to the stiffness one or more bone portions located at a target bone site.
  • instructions may include one or more of directions for determining the stiffness of a bone portion located at a target bone site, as well as directions for determining the amount of powder, liquid, and/or additive component to be added to a preliminary cement composition mixture so as to produce a predetermined quantity of a bone cement paste that hardens into a final bone cement product having the predetermined stiffness, e.g., a stiffness that corresponds to the stiffness one or more bone portions located at a target bone site.
  • an element that may be supplied with a kit of the present disclosure is a powder component.
  • a suitable powder component may be any component that is capable of being mixed with a suitable liquid component and/or additive component to produce a bone cement product that includes a stiffness that is within a predetermined stiffness range.
  • a suitable powder component may be a polymeric component, such as when the end product is a polyacrylic cement product, or may be an ionic component, such as when the end product is a calcium phosphate cement product.
  • a suitable polymeric component may include an acrylic, acrylic fiber, and/or acrylic glass.
  • a suitable polymeric component may be a polymethylmethacrylate or polyacrylonitrile powder, for instance, where the final cement product is a polymethylmethacrylate (PMMA) cement.
  • Other suitable polymeric components may include polycarbonates.
  • Another suitable powder component may be an ionic component, wherein the ionic component may include one or more of a calcium source and/or a phosphate source, for instance, where the final cement product is a calcium/phosphate cement product.
  • a suitable calcium source may include any suitable calcium compound, such as but not limited to, calcium carbonate (CaCO 3 ), calcium bicarbonate (Ca(CO 3 ) 2 ), calcium oxide (CaO), calcium hydroxide (Ca(OH) 2 ), and the like.
  • a suitable phosphate source may include any suitable phosphate compound, such as but not limited to, phosphoric acid (H 3 PO 4 ), all soluble phosphates, and the like.
  • the calcium and phosphate sources may be provided as separate powders or may be provided in a single powder source.
  • a suitable calcium-phosphate source may include, but is not here limited to, MCPM (monocalcium phosphate monohydrate or Ca(H 2 P ⁇ 4 ) 2 H.
  • DCPD dihydrate, brushite or CaHPO 4 2H 2 O
  • ACP amorphous calcium phosphate or Ca 3 (PO 4 ) 2 H 2 O
  • DCP diicalcium phosphate, monetite or CaHPO 4
  • tricalcium phosphate including both ⁇ - and ⁇ - (Ca 3 (PO 4 ) 2 , tetracalcium phosphate (Ca 4 (PO 4 ) 2 O, and the like.
  • suitable powder components may include silicone glass powders, such as fluoroaluminosilicate, for instance, where the final cement product is a glass ionomer cement.
  • the powder source may include a particulate composition of any suitable size and any suitable diameter.
  • the particle size of the component(s) of the particulate composition may range from about less than 1 to about 1000 microns or more, for instance, from about 1 to about 300 microns, such as from about 1 to about 250 microns, including about 40 microns or 80 microns.
  • the size of at least 80% of all powder particles may be in the range of about 50 to about 300 micrometers, such as in the range of about 80 to about 250 micrometers.
  • an element that may be supplied with a kit of the present disclosure is a liquid component.
  • a suitable liquid component may be any component that is capable of being mixed with a suitable powder component and/or additive component to produce a bone cement product that includes a stiffness that is within a predetermined stiffness range.
  • a suitable liquid component may be a monomer liquid component, such as when the end product is a polyacrylic cement product, or may be a silicate fluid component, such as when the end product is a calcium phosphate cement product.
  • a suitable monomer liquid component may include a monomethylmethacrylate
  • MMA liquid
  • Other liquid components may include a variety of physiologically and/or chemically compatible liquids known to those of skill in the art, including, but not limited to: water (including purified forms thereof, e.g., deionized water); silicate solutions; aqueous alkanol solutions; e.g. glycerol, where the alkanol is present in minor amounts; pH buffered or non-buffered solutions; solutions of an alkali metal hydroxide, acetate, phosphate or carbonate, for instance, sodium, more particularly sodium phosphate or carbonate.
  • a suitable liquid component may include a silicate setting fluid, e.g., a setting fluid that is a solution of a soluble silicate.
  • a suitable liquid component may include an aqueous solution in which a silicate compound is dissolved and/or suspended.
  • the silicate compound may be any silicone containing compound that is physiologically and chemically compatible and is soluble in water.
  • Representative silicates that may be used include, but are not limited to: sodium silicates, potassium silicates, borosilicates, magnesium silicates, aluminum silicates, zirconium silicates, potassium aluminum silicates, magnesium aluminum silicates, sodium aluminum silicates, sodium methylsilicates, potassium methylsilicates, sodium butylsilicates, sodium propylsilicates, lithium propylsilicates, triethanol ammonium silicates, tetramethanolamine silicates, zinc hexafluorosilicate, ammonium hexafluorosilicate, cobalt hexafluorosilicate, iron hexafluorosilicate, potassium hexafluorosilicate, nickel hexafluorosilicate, barium hexafluorosilicate, hydroxyammonium hexafluoros
  • an element that may be supplied with a kit of the present disclosure is an additive component.
  • a suitable additive component may be any component that is capable of being mixed with a suitable powder component and/or liquid component to produce a bone cement product that includes a stiffness that is within a predetermined, selected stiffness range.
  • a suitable additive may be any component that is capable of being mixed with the powder and/or liquid component to produce a self-curing cement paste such that when the cement paste cures, the final cement product includes a porosity that gives the hardened cement a stiffness within a predetermined range.
  • the additive component may be a powder, and thus suitable for addition to the powder component, or may be a liquid, and thus suitable for addition to the liquid component.
  • the powder and/or liquid additive component should be such that it is capable of being easily removed from, e.g., washed out of, the final cement product upon hardening so as to produce a porous hardened bone cement product, which product has a predetermined stiffness, for instance, a stiffness corresponding to the adjacent bone material to which the cement paste has been added or otherwise contacted with.
  • a suitable additive component may be a powder.
  • a suitable powder component may include one or more silicone particles, a water soluble solid substance, or the like.
  • the additive component may include discrete particles of a water-soluble solid substance such as a polysaccharide, such as a member of the group including, but not limited to: chondroitin sulfate, carboxymethyl cellulose, hydroxyethylmethyl cellulose, fucan, carregeenan, dextran, heparin, heparan sulfate, hydroxyethlycellulose (HEC), hydroxypropylmethyl cellulose, sodium alginate, chitosan or a hyaluronate (in powder form).
  • a suitable water-soluble solid substance may include gelatin or collagen.
  • a suitable additive component may be a liquid, such as a liquid that is immiscible with the other components of the cement composition, and thus is capable of being easily removed from, e.g., washed out of, the final hardened cement product so as to produce a porous cement product having a predetermined stiffness.
  • a suitable liquid component may be an aqueous solution of hyaluronate sodium, such as when the end product is a polyacrylic cement product.
  • Suitable liquid additive components may include a hydrophobic liquid such as one or more of: ricinoleic acid, linoleic acid, palmitic acid, palmitoleic acid, stearic acid, linolenic acid, arachidic acid, myristic acid, lauric acid, capric acid, caproic acid, oleic acid, caprylic acid, erucic acid, butyric acid, ethyl myristate, ethyl oleate, ethyl palmitate, ethyl linoleate, ethyl laurate, ethyl linolenate, ethyl stearate, ethyl arachidate, ethyl caprilate, ethyl caprate, ethyl caproate, ethyl butyrate, triacetin, alpha tocopherol, beta tocopherol, delta tocopherol, gamma tocop
  • a suitable additive includes a plurality of additives, which plurality of additives may be suitable for inclusion in the powder component and thus may include two or more powder additives; or which plurality of additives may be suitable for inclusion in the liquid component and thus may include two or more liquid components; or which plurality of additives may include an additive that is suitable for inclusion in the powder component, and an additive that is suitable for inclusion in the liquid component, thus the plurality of additives may include at least one powder additive and at least one liquid additive.
  • a suitable additive may be a powder, such as, for example, a basic, powdered material.
  • the basic powdered material may be any basic material in powder form that is capable of interacting with a suitable acid in liquid form so as to produce a gas, such as carbon dioxide, which gas is capable of escaping out of a final cement product during the setting thereof in a manner sufficient to produce pores, e.g., interconnected pores, therein.
  • a suitable powdered basic additive may be, for example, a carbonate base, such as sodium carbonate, sodium bicarbonate, calcium carbonate, calcium bicarbonate, combinations thereof, and the like.
  • an additional liquid additive may also be included where in the liquid additive is an acid.
  • the acidic material may be any acidic material in liquid form that is capable of interacting with a suitable base in powder form so as to produce a gas, which gas is capable of escaping out of a final cement product in a manner sufficient to produce pores, e.g., interconnected pores, therein.
  • a suitable liquid acidic additive may be, for instance, citric acid, malic acid, fumaric acid, lactic acid, succinic acid, orthophosphoric acid, combinations thereof, and the like.
  • a suitable acid may be an aqueous solution of citric acid monohydrate.
  • the ratio of the base to acid may be such that upon mixture produces a neutral pH, for instance, a suitable ratio may be 1.0 gram of base to 0.7 grams of acid. In some embodiments, the ratio of base and acid to the combined powder and liquid components may be about 10 to about 20% by weight.
  • a further component, which may be included in the cement mixture composition is a radio-opacifier.
  • a radio-opacifier may be any suitable radio-opacifier so long as it is distinguishable from the flowable cement paste produced from the mixture of the various components, and allows for the observation of the cement flow during delivery.
  • a suitable radio-opacifier may be a water-soluble and/or organic contrast agent.
  • water- soluble contrast agent is meant an agent that readily dissolves in water.
  • the water-soluble contrast agent is a water-soluble salt of a radio-opaque element, e.g., an element that is visible under standard imaging techniques and protocols employed by those of skill in the art, e.g., fluoroscopic X-ray imaging protocols, etc.
  • the flowable cement paste may include one or more collections of contrast particles (for example, for use as tracers during delivery of the flowable cement paste) such as those described in U.S. Pat. No. 6,273,916; the disclosure of which is herein incorporated by reference.
  • the radio-opaque element may be one that appears different from the powder component (e.g., polymethylmethacrylate, calcium and/or phosphate powder components) when viewed using such imaging techniques (e.g., fluoroscopy) as those well known in the art, where representative elements of interest include, but are not limited to: barium and/or water-soluble barium salts, (e.g., barium halides, including barium chloride, and barium sulphate), oxalate, zirconium (e.g., zirconium dioxide), tantalum, tungsten, iodine, and the like.
  • barium and/or water-soluble barium salts e.g., barium halides, including barium chloride, and barium sulphate
  • oxalate e.g., zirconium dioxide
  • tantalum tungsten, iodine, and the like.
  • the contrast agent may be based on iodine such as an iodine compound selected from the following group: iopromidum, iopamidol, aminotrizoate acid, iotroxin acid, iopodin acid, iomeprol, iodamid, ioxithalamate, iothalamate, ioxaglin acid, and the like.
  • iodine such as an iodine compound selected from the following group: iopromidum, iopamidol, aminotrizoate acid, iotroxin acid, iopodin acid, iomeprol, iodamid, ioxithalamate, iothalamate, ioxaglin acid, and the like.
  • radio-opaque elements may initially be present as a component separate from the powder and liquid components, or combined with one or both of these initially disparate components, such that it may be present in the powder and/or liquid when they are combined.
  • the radio-opaque element may be added to the powder or liquid component, dependent on its formulation, or the cement mixture composition produced after combining the powder and the liquid components together.
  • a contrast agent may be a powdered substance, or a liquid substance, such as a substance dissolved in a liquid solvent, e.g., in water.
  • the radio-opaque element may be used in an aqueous solution, for example, at a concentration of 30 to 80 weight %.
  • the amount of contrast agent that may be combined with the powder and/or liquid components should be sufficiently great so as to provide for the desired amount of contrast during imaging, yet sufficiently small such that there is little if any excess agent available following production of the cement product that can move beyond the site of implantation, e.g., and systemically contact the host.
  • the amount of contrast agent ranges in from about 1 to about 50% by weight of powder, such as from about 2-5 to about 40% by weight, including from about 10 to about 35% by weight, for instance, from about 20 to about 30 % by weigh of the contrast agent.
  • one or both of the powder and liquid components may include an active agent, such as an agent that modulates the properties of the final hardened cement product.
  • additional active agents include, but are not limited to: organic polymers, e.g., proteins, including bone associated proteins which impart a number of properties, such as enhancing resorption, angiogenesis, cell entry and proliferation, mineralization, bone formation, growth of osteoclasts and/or osteoblasts, and the like.
  • Such proteins may include, but are not limited to: osteonectin, bone sialoproteins (Bsp), ⁇ -2HS-glycoproteins, bone GIa- protein (Bgp), matrix Gla-protein, bone phosphoglycoprotein, bone phosphoprotein, bone proteoglycan, protolipids, bone morphogenic protein, cartilage induction factor, platelet derived growth factor, skeletal growth factor, and the like; particulate extenders; inorganic water soluble salts, e.g., NaCl, calcium sulfate; sugars, e.g., sucrose, fructose and glucose; pharmaceutically active agents, e.g., antibiotics; and the like.
  • Additional active agents may include an osteoinductive substance, which osteoinductive substance may be chosen from the following group of substances: a) bone morphogenetic proteins, such as: BMP2, BMP4 or BMP7; b) growth factors, such as TGFb-3 (transforming growth factor) or IGF-I (insulin-like growth factor); c) platelet-derived growth factor (PDGF); d) an anabolic substance, such as parathyroid hormone (e.g., estrogen), parathyroid hormone-related protein, or other anabolic substance that activates bone producing cells; e) sexual hormones, such as estrogen; and f) prostaglandins.
  • An active agent may further include an antiresorptive substance, for instance, a drug, such as bisphosphonate, which drug inhibits bone resorbtion.
  • a hydrogen pump inhibitor such as basilomycin Al, may be included for local administration thereof.
  • the powder, liquid, additive, and any other additional components may be provided in at least one container.
  • Any suitable container may be used so long as the container is capable of storing one or more of the bone cement components and is inert with respect to the component(s) contained therein.
  • the container may have any suitable configuration, for instance, the container may be configured as a tube, syringe, or the like.
  • the container may be sealable and/or re-sealable.
  • a kit including a plurality of suitable containers for storing the various cement composition components is provided.
  • a representative kit 10 of the disclosure may include a plurality, for instance, two, three, or four containers.
  • FIG. IA depicts a representative kit 10 with three containers.
  • the first container 20 includes a single compartment 22, which compartment includes powder component 23.
  • the second container 30 includes a single compartment 32, which compartment includes a liquid component 33.
  • the third container 40 includes a single compartment 42 which compartment includes additive components 43.
  • container 40 includes a single compartment 42, in certain variations, this or any container disclosed herein, may include one or more sub-compartments, such as sub-compartments wherein each sub-compartment includes a separate component, for instance, separate additive components.
  • FIG. IB depicts an alternative embodiment of a representative kit
  • the first container 20 includes a single compartment 22, which compartment includes powder component 23.
  • the second container 30 includes a single compartment 32, which compartment includes a liquid component 33.
  • the third container 40 includes a plurality of compartments 42 and 44, which compartments include additive components 43 and 45, respectively.
  • additive 43 and additive 45 can be the same or different additives or different types of additives (e.g., a powder and/or a liquid additive). Where the additive is the same additive, double the amount of the additive may be employed to provide a final cement product of different stiffness.
  • container 40 includes a container with two compartments including separate additives, e.g., different additives, it is understood that container 40, or any other container disclosed herein, may include one, two, three, or more compartments, which may include one, two, or more separate elements, for example, as described in greater detail herein below. Further, although additives 43 and 45 are included in separate compartments of the same container it is understood that these additive components, as well as any other components, may be included in separate individual containers.
  • FIG. 1C depicts a representative kit 10 with two containers.
  • the second container 30 includes a single compartment 32, which compartment includes a liquid component 23.
  • the additive component may be, for example, a solid component, such as a plurality of silicone particles or balls, or jelly, or bio-ceramics, or hydrosoluble polymers.
  • FIG. ID depicts a representative kit 10 with two containers.
  • the 20 includes a single compartment 22, which compartment includes powder component 23.
  • the second container 30 includes a single compartment 32, which compartment includes a liquid component 33 and an additive component 45.
  • the additive component may be, for example, a liquid component, such as an aqueous solution of sodium hyaluronate.
  • FIG. IE depicts a representative kit 10 with three containers.
  • the first container 20 includes a single compartment 22, which compartment includes powder component 23.
  • the second container 30 includes a single compartments 32, which compartment includes liquid component 33.
  • the third container 40 includes a plurality of compartments 42 and 44, which compartments include additive components 43 and 45, respectively.
  • container 40 includes a container with two compartments including separate additives, e.g., the same or different additives, it is understood that container 40, or any other container disclosed herein, may include one, two, three, or more compartments, which may include one, two, or more separate elements, for example, as described in greater detail herein below.
  • FIG. 2 depicts a kit 10.
  • the kit may include instructions for how to mix various kit components so as to produce a cement, such as a bone cement, having an end product of a predetermined stiffness range.
  • the kit 10 may include a powder component 23, a liquid component 33, and one or more additive components as well as instructions directing a user how to mix the various components and, in some variations, in what order to mix the components so as to produce a given cement product.
  • the kit includes two additive components (e.g. 43 and 45).
  • the instructions may indicate that the powder component 23 can be mixed with the liquid component 33 to obtain a first type of cement 50, which cement has a high final elasticity.
  • the instructions may further indicate that the powder component 23 can be mixed with the liquid component 33 and the additive 43 to obtain a second type of cement 52, which cement has a middle/high final elasticity.
  • the instructions may additionally indicate that the powder component 23 can be mixed with the liquid component 33 and the additive 45 to obtain a third type of cement 53, which cement has a middle/low final elasticity.
  • the instructions may also indicate that the powder component 23 can be mixed with the liquid component 33 and both additives 43 and 45 to obtain a forth type of cement 51, which cement has a low final elasticity.
  • the kit may further include instructions directing a user as to how to mix the one or more additives with the other components of the kit so as to produce the desired final cement end product.
  • the kit may include instructions directing a user to add the additive to the liquid component prior to adding the combined liquid and additive mix to the powder component. This may be particularly suitable in instances wherein the additive is a liquid, although, in certain instances it may be beneficial to add the additive component to the powder component even where the additive component is a liquid.
  • the instructions could also include directions for adding one additive component (or a portion thereof) to the liquid component and one additive component (or a portion thereof) to the powder component.
  • FIG. 3 depicts a kit 10.
  • the kit may include instructions for how to mix various components so as to produce a cement, such as a bone cement, having an end product of a predetermined stiffness range.
  • the kit 10 may include a powder component 23, a liquid component 33, and one or more additive components as well as instructions directing a user how to mix the various components and in what order so as to produce a given cement product.
  • the kit includes two additive components (e.g. 43 and 45).
  • the instructions may indicate that the powder component 23 can be mixed with the liquid component 33 to obtain a first type of cement 50, which cement has a high final elasticity.
  • the instructions may further indicate that the powder component 23 can be mixed with the liquid component 33 and the additive 43 to obtain a second type of cement 52, which cement has a middle high final elasticity.
  • the instructions may additionally indicate that the powder component 23 can be mixed with the liquid component 33 and the additive 45 to obtain a third type of cement 53, which cement has a middle low final elasticity.
  • the instructions may also indicate that the powder component 23 can be mixed with the liquid component 33 and both additives 43 and 45 to obtain a forth type of cement 51, which cement has a low final elasticity.
  • the kit may further include instructions directing a user as to how to mix the one or more additives with the other components of the kit so as to produce the desired final cement end product.
  • the kit may include instructions directing a user to add the additive to the powder component prior to adding the combined powder and additive mix to the liquid component. This may be particularly suitable in instances wherein the additive is a powder, although, in certain instances it may be beneficial to add the additive component to the liquid component even where the additive component is a powder component.
  • FIG. 4 depicts a kit 10.
  • the kit may include instructions for how to mix various components so as to produce a cement, such as a bone cement, having an end product of a predetermined stiffness range.
  • the kit 10 may include a powder component 23, and a plurality of liquid components, for example, liquid components 33, 35 and 37.
  • the kit may also include one or more additive components as described above.
  • the kit may also include instructions directing a user how to mix the various components and in what order so as to produce a given cement product.
  • the kit does not include any additive components, but it is understood that in certain variations, such a kit could include one or more additive components as well as instructions as how to combine the additive components to the powder and/or plurality of liquid components in a manner similar to that provided in the examples above.
  • the instructions may indicate that the powder component 23 can be mixed with the liquid component 33 to obtain a first type of cement 50, which cement has a high final elasticity.
  • the instructions may further indicate that the powder component 23 can be mixed with the liquid component 35 to obtain a second type of cement 52, which cement has a middle final elasticity.
  • the instructions may additionally indicate that the powder component 23 can be mixed with the liquid component 37 to obtain a third type of cement 51, which cement has a low final elasticity.
  • the kit may further include instructions directing a user as to how to mix the one or more liquid components with one another prior to combination with the powder component, so as to produce the desired final cement end product. Additionally, as mentioned above, although not depicted, the kit may also include one or more additive components as well as instructions directing a user as to how to combine the additive component(s) with the powder and/or one or more of the plurality of liquid components.
  • FIG. 5 depicts a kit 10.
  • the kit may include instructions for how to mix various components so as to produce a cement, such as a bone cement, having an end product of a predetermined stiffness range.
  • the kit 10 may include a plurality of powder components, such as for example, powder components 23, 25, and 27, as well as a liquid component 33.
  • the kit may also include one or more additive components as described above.
  • the kit may also include instructions directing a user how to mix the various components and in what order so as to produce a given cement product.
  • kit does not include any additive components, but it is understood that in certain variations such a kit could include one or more additive components as well as instructions as how to combine the additive components to the liquid and/or plurality of powder components in a manner similar to that provided in the examples above.
  • the instructions may indicate that the powder component 23 can be mixed with the liquid component 33 to obtain a first type of cement 50, which cement has a high final elasticity.
  • the instructions may further indicate that the powder component 25 can be mixed with the liquid component 33 to obtain a second type of cement 52, which cement has a middle final elasticity.
  • the instructions may additionally indicate that the powder component 27 can be mixed with the liquid component 33 to obtain a third type of cement 51, which cement has a low final elasticity.
  • the kit may further include instructions directing a user as to how to mix the one or more powder components with one another prior to combination with the liquid component, so as to produce the desired final cement end product. Additionally, as mentioned above, although not depicted, the kit may also include one or more additive components as well as instructions directing a user as to how to combine the additive component(s) with the powder and/or one or more of the plurality of liquid components.
  • kit includes a plurality of powder components in addition to a plurality of liquid components, and/or a plurality of additives as well as the relevant instructions for how to combine the various components so as to produce a final cement product with a desired elasticity.
  • the various cement composition components may be included in a single container.
  • the container may include at least two compartments.
  • a first compartment may store the powder component of the bone cement composition and the second component may store the liquid component.
  • the additive component may be stored in either the, powder component compartment, along with the powder component, or in the liquid component compartment, along with the liquid component, dependent on the composition of the additive component.
  • the additive component is a powder it may be stored in the powder compartment
  • the additive component is a liquid it may be stored in the liquid compartment.
  • a two-compartment container is provided, wherein the powder component is in one compartment, a liquid component is in the other compartment, and at least one additive component is included in one or more of the powder and liquid component compartments.
  • the container may include at least three compartments.
  • a first compartment may store the powder component of the bone cement composition
  • the second compartment may store the liquid component
  • the third compartment may store tthhee additive component.
  • a three compartment container may be provided, wherein the powder component is included within a first compartment, a liquid component is included in a second compartment, and an additive component is included in a third compartment.
  • a multi-compartment container wherein the container includes four or more compartments, or sub compartments, for instance, where each additional compartment or sub-compartment may include a separate amount of additive component or one or more additional agents as described above.
  • the amount of additive component to be added to the flowable composition may be "tailored" so as to produce a cement product that includes a predetermined stiffness, e.g., dependent upon the stiffness of the surrounding bone to which the flowable cement is to be applied.
  • Additional compartments may be present for additional components as desired, e.g., water- soluble contrast agent, cement modifiers, etc.
  • the container is configured for both storing and mixing the cement paste composition components together prior to delivery.
  • a suitable container may be formed from a material, e.g., a plastic material, which material is non- reactive with respect to the individual cement composition components and includes one or a plurality of separate compartments that are configured for both storing one or more of the components in individual cells therein, and allowing the components to be mixed when desired.
  • a suitable container is further configured for assisting in the delivery of the cement paste composition to a further container, e.g., for mixing, and/or to a target bone site after the components have been properly mixed, e.g., within the container.
  • a suitable container may include one, two, three or more cells or compartments.
  • the one or more compartments may be separated one from the other by a membrane, such as a membrane that is capable of bursting with the application of a sufficient force.
  • a simple cylindrical tube may be used as a storage and packaging container as well as a mixing and delivery device.
  • a plastic tube, or analogous containment structure may be provided wherein the tube includes at least two separated sections, compartments or portions.
  • One compartment or section may include the powder component, and at least one compartment may include the liquid component. Where two sections are provided, the additive component may be included along with the powder or the liquid component, dependent on the constitution of the additive component.
  • an additional, e.g., third, compartment or section is provided, wherein the third compartment includes one or more predetermined amounts of additive.
  • the third compartment may include one or more partitions forming a plurality of sub-compartments or sub-sections wherein each sub- section includes a predetermined amount of additive component.
  • the container may allow for flexibility in the amount of additive to be added to the powder and/or liquid components forming the cement mixture composition.
  • the two or more compartments of the container may be separated from each other by an easily removable, e.g., burstable, barrier that can readily be removed during preparation of the packaged cement composition components.
  • a representative barrier may be a dialysis bag clip or analogous means.
  • Another representative barrier may be a frangible barrier, such as that described in WO 98/28068 and U.S. Pat. No. 5,362,654; the disclosures of which are herein incorporated by reference.
  • the cement composition components may be readily mixed within the container, for instance, by removal or bursting of the clip or other barrier element, which separates the various compartments of the container.
  • the barrier is removed, e.g., undipped or burst, the contents may be mixed and/or kneaded together by hand or other technique.
  • a plurality of containers are supplied in the kit and used for the storing and/or mixing of the cement paste composition components.
  • one, two, three, or more of the components may be contained and/or stored within separate containers, as described above.
  • the separate containers may be configured to be coupled together so as to allow for mixing within the joined containers, or the separate containers may be configured for easily expelling the cement composition components contained therein, e.g., for delivery into an additional container, such as a mixing or delivery container.
  • a suitable container(s) may also be adapted so as to deliver the one or more stored components, for instance, to a separate container for mixing and/or to a target bone site.
  • the bone cement composition components may be stored, and/or mixed, and/or delivered by using a single or multiple containers.
  • the container may be modified to include one or more additional components that may be employed during use/delivery of the cement composition, such as removable delivery elements, elements for transferring the cement composition components, or a mixture thereof, into an attached delivery element, elements that assist in combining the components to produce the desired cement mixture composition, etc.
  • a method for producing a bone cement having a predetermined stiffness may include providing a kit, which kit includes one or more containers, wherein the container(s) at least includes a powder, e.g., polymeric component; a liquid, e.g., a monomer component, and an additive component, as described above.
  • the one or more containers of the kit may individually or corporately include suitable amounts of the powder component, the liquid component, and the additive component, which components are included at least in amounts so as to produce a bone cement product of a predetermined stiffness upon mixing of the components and hardening of the resultant bone cement composition.
  • the kit provided may also include instructions for the production of a hardened cement product, which such instructions include the ability to customize the resulting cured bone cement having a predetermined stiffness.
  • the instructions may include a description, table, chart, and/or the like, which description, etc. instructs a user as to how to determine the stiffness of bone at a target delivery site and/or the amounts to use and how to mix the various cement composition components in the appropriate amounts and in the appropriate manner so as to produce a flowable cement mixture composition that upon curing and/or otherwise hardening forms a final cement product having a predetermined stiffness, for instance, a stiffness that corresponds to the stiffness of the bone surrounding a target site to which the flowable cement composition is to be delivered.
  • the method may include determining the stiffness of one or more bone portions, which bone portions may constitute different portions of the same bone or separate bones, at a target bone site.
  • the stiffness of one or more bones present at a target bone site may be determined by any suitable manner, such as by use of a scanner, MRI or densitometry measurement, or by a table that lists typical bone stiffness (e.g., of vertebral bones) for at least one of (and preferably two or more of) an age, height, weight and/or sex, densitometry.
  • the method may also include determining an amount of one or more of the powder, liquid, and/or additive components to be included in the cement composition mixture.
  • a method for producing a bone cement having a predetermined stiffness may include determining an amount of a powder component, and/or a liquid component, and/or an additive component to be added to a preliminary cement mixture composition so as to produce a bone cement capable of hardening into a final cement product having a predetermined stiffness. Such determination may be had via a chart which lists the amounts of various components to mix to produce a certain bone stiffness.
  • the method may include determining the stiffness of bone at a target site, wherein a table and/or chart which lists the typical compression strength of bone with regard to at least one of age and sex of the patient and densitometry may be reviewed.
  • densitometry methods known in the art may be employed to measure bone density and these may be compared to a biomechanical table and/or chart that sets forth the stiffness of the bone and/or the suitable relationship between bone density and bone stiffness so as to select the desired components and amounts thereof to be mixed so as to achieve a final cement product having a predetermined stiffness.
  • the bone cement to be produced (e.g., PMMA bone cement) should be produced in such a manner so that the stiffness of the final cement product resembles and/or models that of the surrounding bone tissue (e.g., the adjacent vertebra stiffness) to which the cement is to be added.
  • the subject kit may include one or more containers, as described above, wherein the container(s) have an excess of powder, liquid, and/or additive components, from which container(s) the appropriate amounts of components may be removed and mixed to form a flowable cement mixture composition of the subject disclosure.
  • the subject kit may include one or more containers having a predetermined amount of a powder, liquid, and/or additive component, which one or more containers may additionally include one or more of the other components in excess, from which container(s) the appropriate amounts of components may be removed and/or mixed to form a flowable cement mixture composition of the subject disclosure.
  • the kit may include one or more containers within which a predetermined amount of powder and liquid components are contained, such as an amount sufficient to produce a desired cement product. This predetermined amount may be in excess to what is needed to produce the desired cement product, or may be a relatively precise amount needed to produce the desired cement product such that very little, if any, excess remains after formulation of the mixture.
  • the one or more containers may additionally include an amount of additive component, which amount may be predetermined or not, wherein the amount of additive component included and to be added to the powder and liquid components determines the porosity and/or stiffness of the final cement product that results when the powder, liquid, additive cement mixture compositions sets into a hardened cement product.
  • the kit may include a predetermined amount of powder and liquid components, which amount is based upon the quantity of cement product to be produced, and the kit may additionally include an amount of additive component, which amount of additive, or a portion thereof, may be added to the powder component and liquid component of the cement composition mixture in a quantity that is determinative of the stiffness of the final cement product to be produced.
  • a kit of the subject disclosure allows for the stiffness of a final bone cement product to be determined, for example, by the quantity of an additive that is to be added to a preliminary cement composition mixture that upon setting will harden into a final cement product having a predetermined stiffness.
  • the kit may include instructions, which instructions detail one or more of the amount of powder and liquid components to be added to a cement composition mixture, so as to determine the quantity of cement product to be produced, and/or the instructions may detail the amount of additive component to be added to a cement composition mixture, so as to determine the porosity and/or stiffness of the final cement product produced (i.e., a determined stiffness)
  • the quantity of the flowable, e.g., injectable, cement composition mixture to be delivered and/or used at a target site may depend on the application to which the final cement product is to be used.
  • the overall quantity of the bone cement mixture may be in the range of about 2 ml or less to about 10 ml or more.
  • the injected volumes may be very large, for instance, up to 40 ml or more.
  • the amount of one or more of the powder, liquid and additive components to be included in a mixture for use in producing a cement composition mixture may be predetermined.
  • the one or more containers containing the powder, liquid, and/or additive components may include demarcated dosages
  • the kit itself may include instructions as to how many doses of each component should be added to a mixture of the components so as to produce the desired cement composition.
  • the kit may include instructions that one dose of powder is to be combined with one dose of liquid and/or one or more doses of additive and mixed together to produce the desired cement product.
  • the amount of powder, liquid and/or additive components are predetermined and packaged in demarcated predetermined doses.
  • the dosages to be combined are set forth herein as an exemplary 1:1:1 ratio, this ratio may be different according to producing a cement product of a given stiffness, and in some instances the ratio may be more or less that 1:1 :1, for instance, 1:1:2, 1 :2:2, 2:1:1, etc.
  • the amount of the one or more of the powder, liquid, and/or additive components to be included in a mixture for use in producing a cement composition mixture may not be predetermined but may vary.
  • the kit may include directions for determining the amount of each component to be added to a mixture which mixture may then be used to produce a cement composition of the desired stiffness.
  • a table may be provided, wherein the table indicates what quantities of the powder, liquid, and/or additive components are to be mixed so as to produce a final cement product with the various predetermined stiffness ranges.
  • the amount of powder component that may be included in a kit of the subject disclosure and used for the production of a cement product may range from about 10 grams to about 60 grams, for instance, about 20 grams to about 50 grams, including about 30 grams to about 40 grams.
  • the amount of liquid component that may be included in a kit of the subject disclosure and used for the production of a cement product may range from about 5 ml to about 30 ml, for instance, about 10 ml to about 25 ml, including about 15 ml to about 20 ml.
  • the amount of additive component to be added to the preliminary cement mixture composition may depend at least partially on a determined or predicted stiffness of one or more bones positioned at a target bone site to which the cement composition is to be delivered, and at least partially on the overall amount of cement product to be produced. Accordingly, the amount of additive to be added may be determined in any suitable manner so long as the amount of additive to be added is such that when mixed with an amount of powder and liquid components the combination will produce a final bone cement product having the predetermined stiffness.
  • the following % amount of additive could be added to the preliminary cement mixture composition to produce a final cured bone cement product with the following stiffness:
  • the amount of additive component that may be included in a kit of the subject disclosure and used for the production of a cement product may range from about 5 grams to about 30 grams, for instance, about 10 grams to about 25 grams, including about 15 grams to about 20 grams.
  • the polymeric, monomer, and additive components may be mixed at the determined amounts in a manner sufficient to produce a bone cement with the predetermined stiffness.
  • the amount and overall ratio of the solid to liquid components of the cement composition mixture may be selected so as to provide for a "settable” or “flowable” composition, where by a “settable” or “flowable” composition is meant a composition that goes from a first non-solid (and also nongaseous) state to a second, solid state having a predetermined stiffness after setting/curing.
  • the amount of additive to be included as well as the type of additive should be included in the calculation of the appropriate solid to liquid ratio.
  • the solid to liquids ratio is chosen to provide for a flowable and/or injectable composition that has a viscosity ranging from that of milk (for example) to that of modeling clay.
  • the solid to liquids ratio employed in the subject methods may range. For instance, in some embodiments, they may range from about 1.0 to about 0.2, for instance, from about 0.6 to about 0.3.
  • a paste-like composition is produced, where the solid to liquids ratio employed in such methods may ranges form about 0.5 to about 0.25, such as from about 0.3 to about 0.45. .
  • the powder and liquid component may be in a ratio selected from the ratios of about 1 :1, about 1:4, about 1:2, and about 3:4.
  • the liquid to powder component ratio may be in a ratio of about 1:4, about 1:2, and about 3:4.
  • the ratio may be about 20% powder to about 80% liquid; or about 80% powder to about 20% liquid.
  • the additive component may be included, for example, in a ratio of about 0% to 75%, including about 50% with respect to the powder and the liquid components combined.
  • the requisite amounts of powder, liquid, additive may be combined under conditions sufficient to produce the flowable cement mixture composition.
  • the powder, liquid, and additive components may be combined in any logical order and in any suitable manner known in the art so as to produce a flowable cement mixture, which mixture is capable of hardening into a final cement product that includes a stiffness which is within a predetermined stiffness range.
  • all three of the powder, liquid, and additive components may be added and mixed together; or the powder and liquid components of the bone cement composition may be mixed first and subsequently the obtained mixture may further be mixed with the additive component.
  • the additive component may first be pre-mixed with one or more of the powder and liquid components, which powder and liquid components are subsequently mixed together.
  • the various components of the cement composition may be combined under agitation or mixing conditions, such that a homogenous flolwable cement mixture composition is produced from the composition components.
  • Mixing may be accomplished using any convenient means, including manual mixing as described in U.S. Pat. No. 6,005,162 and automated mixing as described in WO 98/28068, the disclosures of which are herein incorporated by reference. Also of interest is the device disclosed in U.S. Pat. No. 5,980,482, the disclosure of which is herein incorporated by reference.
  • the temperature of the environment in which combination or mixing of the powder, liquid, and additive components takes place sufficient to provide for a final cement product that has desired setting, strength, and stiffness characteristics may range from about 0 to about 50° C, for instance, from about 15 to about 25° C.
  • Mixing time may also play a role in determining a bone cement product having certain properties.
  • the mixing may take place for a period of time sufficient for a flowable cement mixture composition to be produced, and may takes place, for instance, for a period of time ranging from about 5 to about 100 seconds, such as from about 10 to about 50 seconds, including from about 15 to about 30 seconds.
  • the flowable cement mixture composition produced, for instance, by the above-described method may set into a biologically compatible, and often resorbable and/or remodelable, cement product, where the cement product is characterized by having a predetermined stiffness, for instance, a stiffness that corresponds to the stiffness of one or more bones surrounding a target delivery site to which the bone cement mixture is to be applied or otherwise delivered.
  • the term "flowable” is meant to include more viscous, e.g., paste- like, compositions, as well as less viscous, more liquid-like compositions.
  • the viscosity time of the subject flowable compositions typically ranges up to about 20 minutes, for instance, up to about 15 minutes, such as up to about 12 minutes.
  • a paste-like composition is provided that has an injectable viscosity that injects in a time period ranging up to about 5 minutes, such as about up to about 4 minutes.
  • the period of time required for the compositions to harden or "set" may vary.
  • set is meant: the Gilmore Needle Test (ASTM C266-89), modified with the cement submerged under 37° C physiological saline.
  • the set times of the subject cements may range from about 30 seconds to about 30 minutes, and may range from about 2 to about 15 minutes, for instance, from about 4 to about 12 minutes, such as from about 7 to about 10 minutes, including about 8 to about 9 minutes after mixing of the various components.
  • the flowable composition sets in a clinically relevant period of time.
  • the paste-like composition sets in less than about 20 minutes, for instance, less than about 15 minutes, such as less than about 10 minutes, where the composition remains flowable for at least about 1 minute, for instance, at least about 2 minutes and, in some embodiments, for at least about 5 minutes following combination or mixture of the precursor solid and liquid cement components.
  • the flowable paste-like cement mixture is capable of setting in a fluid environment, such as an in vivo environment at a target bone repair site.
  • the flowable cement mixture composition is capable of setting in a wet environment, e.g., one that may be at least partially filled with blood and other physiological fluids. Therefore, the target site to which the flowable composition is administered during use need not, but can be maintained in a dry state.
  • the compressive strength (i.e., stiffness) of the final cement product into which the flowable cement mixture composition sets may vary significantly depending on the particular amount and type of additive component(s) included in the cement mixture composition used to produce the cement product.
  • the cement product is such that it has a compressive strength sufficient for it to serve as at least a cancellous bone structural material, but further includes a porosity that gives the cement product a stiffness that is within a predetermined range, such as a stiffness that corresponds to the bone material, e.g., endogenous bone material, surrounding the target site to which the composition is delivered.
  • cancellous bone structural material is meant to be a material that can be used as a cancellous bone substitute material capable of withstanding the physiological compressive loads experienced by compressive bone under at least normal physiological conditions, but not so stiff that increases the chance of fractures in the various surrounding bone material.
  • the Young modulus of PMMA bone cement is between 200 MPa and 2500
  • the subject flowable paste-like cement mixture composition may be one that sets into a final cement product that has a compressive strength/stiffness or Young's Modulus that falls within that range. Accordingly, in certain embodiments, the subject flowable paste- like cement mixture composition may be one that sets into a final cement product that has a compressive strength/stiffness or Young's Modulus that is at least about 200 MPa, at least about 500 MPa, at least about 1000 MPa, at least about 1500 MPa, at least about 2000 Mpa, and at least about 2500 Mpa.
  • the subject flowable paste-like cement mixture composition may be one that sets into a final cement product that has a compressive strength/stiffness or Young's Modulus that is at least about 20 MPa, for instance, at least about 40 MPa, such as at least about 50 MPa, including at least about 60 MPa or higher, as measured by methods well known and practiced in the art.
  • the elasticity of the cement is not limited solely by the porosity of the final cement product.
  • the elasticity may be due in part to the porosity and/or the elasticity of the raw material itself, for example, the raw material of a silicone additive.
  • the final cement product may have a Young's Modulus that ranges as high as about 100 to about 2000 MPa or more, such as about 125 to about 1500 MPa, or about 175 MPa to about 1000 Mpa, including about 150 MPa to about 500 MPa, including about 200 MPa, as well as ranges there between.
  • the resultant cement product may have a tensile strength of at least about 0.5 MPa, such as at least about 1 MPa, including at least about 5 MPa, at least about 10 MPa or more, e.g., from about 0.5 to about 10 MPa, as determined by tensile strength assays well known in the art. Further, in some embodiments, the resultant cement product may have a porosity that ranges from about 0% to about 60% , such as from about 5% to about 45% , including from about 15% to about 25% .
  • the resultant cement product is stable in vivo for extended periods of time, by which is meant that the hardened and porous cement product does not dissolve or degrade (exclusive of the remodeling activity of osteoclasts) under in vivo conditions, e.g., when implanted into a living body, for extended periods of time.
  • the resultant cement product may be stable for at least about 4 months, at least about 6 months, at least about 1 year or longer, e.g., 2.5 years, 5 years, 10 or 15 years, or more, etc.
  • the resultant cement product is stable in vitro when placed in an aqueous environment for extended periods of time, by which is meant that the cement product does not dissolve or degrade in an aqueous environment, e.g., when immersed in water, for extended periods of time.
  • the resultant product may be stable for at least about 4 months, at least about 6 months, at least about 1 year or longer, e.g., 2.5 years, 5 years, etc.
  • the subject disclosure is directed to a method for treating a subject suffering from a compression fracture, for instance, a compression fracture within or between one or more vertebral bones.
  • the method may include one or more of the following steps, which may be performed in any logical order, though one embodiment of the order of steps is presented.
  • an incision is made in a tissue of a subject so as to expose a treatment site, wherein the treatment site includes a portion of at least one vertebral bone.
  • a suitable device may be inserted through the tissue so as to contact the exposed vertebral bone. The device may then be manipulated in a manner sufficient to create an access in the vertebral bone.
  • the stiffness of at least one vertebral bone at the treatment site is determined.
  • a bone cement paste composition may then be produced in a manner, as described above, such that when the bone cement paste composition hardens a hardened cement having a predetermined stiffness will result.
  • the predetermined stiffness corresponds to the stiffness of the at least one vertebral bone.
  • An instrument for the application of the bone cement paste composition may be inserted through the incision so that a distal portion of the instrument contacts the treatment site and/or optionally contacts the access, if such an access has been created.
  • the instrument may then be employed in a manner sufficient to apply the bone cement paste composition to the treatment site.
  • the bone cement paste composition is allowed to harden, e.g., self-harden, in to a hardened bone cement product so as to treat the subject.
  • the subject methods and compositions produced thereby, as described above find use in applications where it is desired to introduce a flowable cement mixture composition that is capable of setting into a final cement product into a physiological site of interest, such as in orthopedic applications, for example.
  • Four main indications often requiring orthopedic resolution are benign osteoporotic fractures, malignant metastatic disease, and benign tumors of the bone, and traumatic fracture.
  • the cement used to treat the compromised bone condition will generally be prepared, as described above, and be introduced to a bone repair site, such as a bone site comprising cancellous and/or cortical bone.
  • percutaneous vertebroplasty is a procedure involving the injection of a bone cement, such as that described herein, into a vertebral body via a percutaneous route.
  • a flowable cement composition may be produced, as described above, and may be injected as a semi-liquid substance through an instrument that has been passed into the vertebral body, for instance, along a transpedicular or posterolateral approach.
  • Percutaneous vertebroplasty is intended to provide structural reinforcement and repair of a vertebral body that has been damaged through compression fractures, through injection, by a minimally invasive percutaneous approach, of bone cement into the vertebral body. See, for example, Cotton A., et al "Percutaneous vertebroplasty: State of the Art.” Radiograhics 1998 March- April; 18(2):311-20; discussion at 320-3.
  • the general steps for performing a vertebroplasty are as follows.
  • the subject is placed in a prone position and the skin overlying the fractured vertebrae is prepped and draped.
  • a suitable local anesthetic such as 1% Lidocaine is injected into the skin underlying fat and into the periosteum of the pedicle to be entered.
  • a skin incision for instance, about five millimeters is made with a scalpel blade or other suitable surgical implement.
  • the decision regarding which pedicle to use may be made based on CT (computed tomography) 10 and MR (magnetic resonance) images.
  • An injection instrument e.g., a needle of an appropriate gauge (such as an eleven gauge or thirteen gauge needle for use in a smaller vertebral body), may be passed down the pedicle until it enters the vertebral body and reaches the junction of the anterior and middle thirds. This area is the region of maximum mechanical moment and may be the area of greatest compression.
  • a vertebrogram can be performed, if desired, by the injection of non-ionic X-ray contrast into the vertebral body to look for epidural draining veins.
  • a cement such as that described above may be prepared, e.g., according to the methods as described herein, and then injected into the target bone site.
  • the posterior aspect of the vertebral body may be an important area to observe for posterior extension of cement, and may be watched constantly during the injection.
  • the injection may be stopped once adequate vertebral filling is achieved.
  • the injection may be discontinued if the cement starts to extend into some unwanted location, such as the disc space or toward the posterior quarter of the vertebral body, where the risk of epidural venous filling and hence spinal cord compression may be greatest.
  • any suitable amount of cement mixture may be applied to the target bone site, but in some embodiments the amount may range from about less than one to about ten or more cubic centimeters, for instance, from about two to about eight cubic centimeters, including about four to about five cubic-centimeters of cement can be injected on each side, and it is known to inject up to about six to eight to nine cubic-centimeters per side.

Landscapes

  • Health & Medical Sciences (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Dans des modes de réalisation, l'invention concerne des trousses, des systèmes et des procédés de restauration d'os fracturé. Dans certains modes de réalisation, l'invention concerne en particulier une trousse destinée à produire un ciment osseux de rigidité prédéterminée. Ce ciment osseux peut être utilisé soit seul soit conjointement à un ou plusieurs dispositifs implantables ou non, afin de restaurer un os fracturé. Dans certains modes de réalisation, la trousse peut comprendre un ou plusieurs constituants en poudre, tels qu'un constituant polymère, un constituant liquide, tel qu'un constituant monomère, et un constituant d'additif. Dans certains modes de réalisation, la trousse peut également comprendre des instructions pour mélanger et combiner les constituants variés de la trousse afin de produire un produit de ciment final présentant une rigidité prédéterminée. L'invention concerne également des procédés d'utilisation de la trousse pour administrer des traitements thérapeutiques divers.
PCT/IB2009/005447 2009-03-30 2009-03-30 Trousse de ciment osseux et procédés d'utilisation associés WO2010112955A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/IB2009/005447 WO2010112955A1 (fr) 2009-03-30 2009-03-30 Trousse de ciment osseux et procédés d'utilisation associés

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2009/005447 WO2010112955A1 (fr) 2009-03-30 2009-03-30 Trousse de ciment osseux et procédés d'utilisation associés

Publications (1)

Publication Number Publication Date
WO2010112955A1 true WO2010112955A1 (fr) 2010-10-07

Family

ID=41343109

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2009/005447 WO2010112955A1 (fr) 2009-03-30 2009-03-30 Trousse de ciment osseux et procédés d'utilisation associés

Country Status (1)

Country Link
WO (1) WO2010112955A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014168565A1 (fr) 2013-04-08 2014-10-16 Persson Cecilia Ciments acrylique pour l'augmentation osseuse
CN107007888A (zh) * 2016-12-13 2017-08-04 杭州市萧山区中医院 一种基于光固化3d打印技术个体化定制型的二氧化锆多孔生物骨修复支架及其制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0747114A1 (fr) * 1995-06-06 1996-12-11 Kwan-Ho Chan Ciment liquide préemballé pour os
WO2007064304A1 (fr) * 2005-12-01 2007-06-07 National University Of Singapore Composition biocompatible et utilisations de celle-ci
WO2007097710A1 (fr) * 2006-02-27 2007-08-30 Agency For Science, Technology And Research Ciment osseux durcissable
WO2007133355A2 (fr) * 2006-05-02 2007-11-22 Kyphon, Inc. Compositions de ciment osseux comprenant un agent indicateur et procédés associés
WO2008103296A1 (fr) * 2007-02-16 2008-08-28 Spinal Restoration, Inc. Procédé pour réparer des disques intervertébraux

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0747114A1 (fr) * 1995-06-06 1996-12-11 Kwan-Ho Chan Ciment liquide préemballé pour os
WO2007064304A1 (fr) * 2005-12-01 2007-06-07 National University Of Singapore Composition biocompatible et utilisations de celle-ci
WO2007097710A1 (fr) * 2006-02-27 2007-08-30 Agency For Science, Technology And Research Ciment osseux durcissable
WO2007133355A2 (fr) * 2006-05-02 2007-11-22 Kyphon, Inc. Compositions de ciment osseux comprenant un agent indicateur et procédés associés
WO2008103296A1 (fr) * 2007-02-16 2008-08-28 Spinal Restoration, Inc. Procédé pour réparer des disques intervertébraux

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014168565A1 (fr) 2013-04-08 2014-10-16 Persson Cecilia Ciments acrylique pour l'augmentation osseuse
KR20150140746A (ko) * 2013-04-08 2015-12-16 이노시아 에이비 골 보강용 아크릴 시멘트
CN105246517A (zh) * 2013-04-08 2016-01-13 伊诺西亚公司 用于骨质增大的丙烯酸粘固剂
EP2983725A4 (fr) * 2013-04-08 2016-12-21 Inossia Ab Ciments acrylique pour l'augmentation osseuse
CN105246517B (zh) * 2013-04-08 2018-06-12 伊诺西亚公司 用于骨质增大的丙烯酸粘固剂
US10603403B2 (en) 2013-04-08 2020-03-31 Inossia Ab Acrylic cements for bone augmentation
KR102247732B1 (ko) * 2013-04-08 2021-05-03 이노시아 에이비 골 보강용 아크릴 시멘트
CN107007888A (zh) * 2016-12-13 2017-08-04 杭州市萧山区中医院 一种基于光固化3d打印技术个体化定制型的二氧化锆多孔生物骨修复支架及其制备方法
CN107007888B (zh) * 2016-12-13 2020-09-08 杭州市萧山区中医院 一种基于光固化3d打印技术个体化定制型的二氧化锆多孔生物骨修复支架及其制备方法

Similar Documents

Publication Publication Date Title
US20210244422A1 (en) Methods of treating degenerative bone conditions
He et al. Bone cements for percutaneous vertebroplasty and balloon kyphoplasty: Current status and future developments
EP1246651B1 (fr) Ciment osseux osteoporotique et bioactif
US8168692B2 (en) Bone substitute compositions and method of use
ES2269973T3 (es) Mezcla inyectable para sustituir un tejido oseo.
US7261717B2 (en) Methods and devices for delivering orthopedic cements to a target bone site
TWI556842B (zh) 包含鍶化合物之纖維蛋白組合物
KR101417148B1 (ko) 주입 가능한 골 증강용 피브린 조성물
WO2005112851A2 (fr) Ciments orthopediques comprenant un agent de contraste a l'apatite au baryum
MX2014009213A (es) Cementos óseos biodegradables, inyectables, y métodos para fabricar y usar los mismos.
US7306786B2 (en) Calcium phosphate cements comprising a water-soluble contrast agent
Ozdemir et al. Calcium phosphate cements for medical applications
WO2010112955A1 (fr) Trousse de ciment osseux et procédés d'utilisation associés
JP2017520596A (ja) インプラントの固定を補強する注入用骨代用材
Bumgardner et al. Ceramic composites for bone graft applications
AU2015200464B2 (en) Composition comprising calcium phosphate and sulfate powders and tri - calcium phosphate particles used in the treatment of degenerative bone conditions

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09785889

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09785889

Country of ref document: EP

Kind code of ref document: A1