CA2663447A1 - Polymeric bone cement and methods of use thereof - Google Patents
Polymeric bone cement and methods of use thereof Download PDFInfo
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- CA2663447A1 CA2663447A1 CA002663447A CA2663447A CA2663447A1 CA 2663447 A1 CA2663447 A1 CA 2663447A1 CA 002663447 A CA002663447 A CA 002663447A CA 2663447 A CA2663447 A CA 2663447A CA 2663447 A1 CA2663447 A1 CA 2663447A1
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- 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
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L24/0005—Ingredients of undetermined constitution or reaction products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/15—Compositions characterised by their 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
-
- 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
Abstract
A bone cement comprising an acrylic polymer mixture which is formulated to have a relatively high viscosity for a relatively long window, due to distributions of molecular weights and/or sizes of acrylic beads.
Description
BONE CEMENT AND METHODS OF USE THEREOF
RELATED APPLICATIONS
The present application claims the benefit under 119(e) of 60/825,609 filed September 14, 2006, the disclosure of which is incorporated herein by reference.
The present application is related to US patent application 11/461,072 filed on July 31, 2006 and entitled "Bone Cement and Methods of Use Thereof', which is a Continuation-in-Part of US application 11/360,251 filed on February 22, 2006, entitled "Methods, Materials and Apparatus for Treating Bone and Other Tissue" and is also a Continuation-in Part of PCT/IL2005/000812 filed on July 31, 2005. The disclosures of these applications are incorporated herein by reference.
The present application is related to PCT application PCT/IL2006/052612 filed on July 31, 2006 and entitled "Bone Cement and Methods of Use thereof' the disclosure of which is incorporated herein by reference.
The present application is related to Israel application No. 174347 filed on March 16, 2006 and entitled "Bone Cement and Methods of Use thereof' the disclosure of which is incorporated herein by reference.
The present application is also related to a series of US provisional applications entitled "Methods, Materials and Apparatus for Treating Bone and Other Tissue":
60/765,484 filed on February 2, 2006; 60/762,789 filed on January 26, 2006; 60/738,556 filed November 22, 2005;
60/729,505 filed October 25, 2005; 60/720,725 filed on September 28, 2005 and 60/721,094 filed on September 28, 2005. The disclosures of these applications are incorporated herein by reference.
The present application is related to PCT application PCT/IL2006/000239 filed on February 22, 2006; US provisional application 60/763,003, entitled "Cannula"
filed on January 26, 2006; US provisional application No. 60/654,495 entitled "Materials, devices and methods for treating bones". filed February 22, 2005; US 11/194,411 filed August 1, 2005; IL 166017 filed December 28, 2004; IL 160987 filed March 21, 2004; US Provisional Application No.
60/654,784 filed on January 31, 2005; US Provisional Application No.
60/592,149 filed on July 30, 2004; PCT Application No. PCT/IL2004/000527 filed on June 17, 2004, Israel Application No. 160987 filed on March 21, 2004, U.S. Provisional Applications:
60/478,841 filed on June 17, 2003; 60/529,612 filed on December 16, 2003; 60/534,377 filed on January 6, 2004 and 60/554,558 filed on March 18, 2004; U.S. Application No. 09/890,172 filed on July 25, 2001; U.S. Application No. 09/890,318 filed on July 25, 2001 and US
application 10/549,409 entitled "Hydraulic Device for the injection of Bone Cement in Percutaneous Vertebroplasty filed on September 14, 2005. The disclosures of all of these applications are incorporated herein by reference.
FIELD OF THE INVENTION
The present invention relates to bone cement, formulations thereof and methods of use thereof.
BACKGROUND OF THE INVENTION
It is common to employ cement to repair bones in a variety of clinical scenarios.
For example, compression fractures of the vertebrae, which are a common occurrence in older persons, cause pain and/or a shortening (or other distortion) of stature. In a procedure known as vertebroplasty cement is injected into a fractured vertebra.
Vertebroplasty stabilizes the fracture and reduces pain, although it does not restore the vertebra and person to their original height. In vertebroplasty the cement is typically injected in a liquid phase so that resistance to injection is not too great. Liquid cement may unintentionally be injected outside of the vertebra and/or may migrate out through cracks in the vertebra.
In another procedure, known as kyphoplasty, the fracture is reduced by expanding a device, such as a balloon inside the vertebra and then injecting a fixing material and/or an implant. Kyphoplasty reduces the problem of cement leakage by permitting a lower pressure,to be used for injection of the cement.
In general, polymeric cements become more viscous as the polymer chain grows by reacting directly with the double bond of a monomer. Polymerization begins by the "addition mechanism" in which a monomer becomes unstable by reacting with an initiator, a volatile molecule that is most commonly a radical (molecules that contain a single unpaired electron).
Radicals bond with monomers, forming monomer radicals that can attack the double bond of the next monomer to propagate the polymer chain. Because radicals are so transient, initiators are often added in the form of an un-reactive peroxide form which is stable in solution.
Radicals are formed when heat or light cleaves the peroxide molecule. For applications in which high temperatures are not practical (such as the use of bone cement in vivo), peroxide is typically cleaved by adding a chemical activator such as N, N-dimethyl-p-toluidine.
(Nussbaum DA et al: "The Chemistry of Acrylic Bone Cement and Implication for Clinical Use in Image-guided Therapy", J Vasc Interv Radiol (2004); 15:121-126; the content of which is fully incorporated herein by reference).
Examples of commercially available viscous bone cements include, but are not limited to, CMW Nos. 1, 2-and 3 (DePuy Orthopaedics Inc.; Warsaw, IN, USA) and SimplexTM -P
RELATED APPLICATIONS
The present application claims the benefit under 119(e) of 60/825,609 filed September 14, 2006, the disclosure of which is incorporated herein by reference.
The present application is related to US patent application 11/461,072 filed on July 31, 2006 and entitled "Bone Cement and Methods of Use Thereof', which is a Continuation-in-Part of US application 11/360,251 filed on February 22, 2006, entitled "Methods, Materials and Apparatus for Treating Bone and Other Tissue" and is also a Continuation-in Part of PCT/IL2005/000812 filed on July 31, 2005. The disclosures of these applications are incorporated herein by reference.
The present application is related to PCT application PCT/IL2006/052612 filed on July 31, 2006 and entitled "Bone Cement and Methods of Use thereof' the disclosure of which is incorporated herein by reference.
The present application is related to Israel application No. 174347 filed on March 16, 2006 and entitled "Bone Cement and Methods of Use thereof' the disclosure of which is incorporated herein by reference.
The present application is also related to a series of US provisional applications entitled "Methods, Materials and Apparatus for Treating Bone and Other Tissue":
60/765,484 filed on February 2, 2006; 60/762,789 filed on January 26, 2006; 60/738,556 filed November 22, 2005;
60/729,505 filed October 25, 2005; 60/720,725 filed on September 28, 2005 and 60/721,094 filed on September 28, 2005. The disclosures of these applications are incorporated herein by reference.
The present application is related to PCT application PCT/IL2006/000239 filed on February 22, 2006; US provisional application 60/763,003, entitled "Cannula"
filed on January 26, 2006; US provisional application No. 60/654,495 entitled "Materials, devices and methods for treating bones". filed February 22, 2005; US 11/194,411 filed August 1, 2005; IL 166017 filed December 28, 2004; IL 160987 filed March 21, 2004; US Provisional Application No.
60/654,784 filed on January 31, 2005; US Provisional Application No.
60/592,149 filed on July 30, 2004; PCT Application No. PCT/IL2004/000527 filed on June 17, 2004, Israel Application No. 160987 filed on March 21, 2004, U.S. Provisional Applications:
60/478,841 filed on June 17, 2003; 60/529,612 filed on December 16, 2003; 60/534,377 filed on January 6, 2004 and 60/554,558 filed on March 18, 2004; U.S. Application No. 09/890,172 filed on July 25, 2001; U.S. Application No. 09/890,318 filed on July 25, 2001 and US
application 10/549,409 entitled "Hydraulic Device for the injection of Bone Cement in Percutaneous Vertebroplasty filed on September 14, 2005. The disclosures of all of these applications are incorporated herein by reference.
FIELD OF THE INVENTION
The present invention relates to bone cement, formulations thereof and methods of use thereof.
BACKGROUND OF THE INVENTION
It is common to employ cement to repair bones in a variety of clinical scenarios.
For example, compression fractures of the vertebrae, which are a common occurrence in older persons, cause pain and/or a shortening (or other distortion) of stature. In a procedure known as vertebroplasty cement is injected into a fractured vertebra.
Vertebroplasty stabilizes the fracture and reduces pain, although it does not restore the vertebra and person to their original height. In vertebroplasty the cement is typically injected in a liquid phase so that resistance to injection is not too great. Liquid cement may unintentionally be injected outside of the vertebra and/or may migrate out through cracks in the vertebra.
In another procedure, known as kyphoplasty, the fracture is reduced by expanding a device, such as a balloon inside the vertebra and then injecting a fixing material and/or an implant. Kyphoplasty reduces the problem of cement leakage by permitting a lower pressure,to be used for injection of the cement.
In general, polymeric cements become more viscous as the polymer chain grows by reacting directly with the double bond of a monomer. Polymerization begins by the "addition mechanism" in which a monomer becomes unstable by reacting with an initiator, a volatile molecule that is most commonly a radical (molecules that contain a single unpaired electron).
Radicals bond with monomers, forming monomer radicals that can attack the double bond of the next monomer to propagate the polymer chain. Because radicals are so transient, initiators are often added in the form of an un-reactive peroxide form which is stable in solution.
Radicals are formed when heat or light cleaves the peroxide molecule. For applications in which high temperatures are not practical (such as the use of bone cement in vivo), peroxide is typically cleaved by adding a chemical activator such as N, N-dimethyl-p-toluidine.
(Nussbaum DA et al: "The Chemistry of Acrylic Bone Cement and Implication for Clinical Use in Image-guided Therapy", J Vasc Interv Radiol (2004); 15:121-126; the content of which is fully incorporated herein by reference).
Examples of commercially available viscous bone cements include, but are not limited to, CMW Nos. 1, 2-and 3 (DePuy Orthopaedics Inc.; Warsaw, IN, USA) and SimplexTM -P
and -RO (Stryker Orthopaedics; Mahwah, NJ, USA). These cements are characterized by a liquid phase after mixing and prior to achieving a viscosity of 500 Pascal-second. In a typical use scenario, these previously available cements are poured, while in a liquid phase, into a delivery device.
There have also been attempts to reduce cement leakage by injecting more viscous cement, for example, during the doughing time and the beginning of polymerization. However, the viscous materials, such as hardening PMMA, typically harden very quickly once they reach a high viscosity. This has generally prevented injection of viscous materials in orthopedic procedures.
Some bone fixing materials, such as polymethylmethacrylate (PMMA), emit heat and possibly toxic materials while setting.
US patents and publication 4,969,888, 5,108,404, 6,383,188, 2003/0109883, 2002/0068974, 6,348,055, 6,383,190, 4,494,535, 4,653,489 and 4,653,487, the disclosures of which are incorporated herein by reference describe various tools and methods for treating bone.
US patent publication 2004/0260303, the disclosure of which is incorporated herein by reference, teaches an apparatus for delivering bone cement into a vertebra.
Pascual, B., et al., "New Aspects of the Effect of Size and Size Distribution on the Setting Parameters and Mechanical Properties of Acrylic Bone Cements,"
Biomaterials, 17(5):
509-516 (1996) considers the effect of PMMA bead size on setting parameters of cement. This article is fully incorporated herein by reference.
Hemandez, et al., (2005) "Influence of Powder Particle Size Distribution on Complex Viscosity and Other Properties of Acrylic Bone Cement for Vertebroplasty and Kyphoplasty"
Wiley International Science D01:10:1002/jbm.b.30409 (pages 98-103) considers the effect of PMMA bead size distribution on setting parameters of cement. Hernandez suggests that it is advantageous to formulate cement with a liquid phase to facilitate injection.
This article is fully incorporated herein by reference.
US 5,276,070 to Arroyo discloses use of acrylic polymers with a molecular weight in the range of 0.5 to 1.5 million Daltons in formulation of bone cement. The disclosure of this patent is fully incorporated herein by reference.
US 5,336,699 to Cooke discloses use of acrylic polymers with a molecular weight of about one hundred thousand Daltons in formulation of bone cement. The disclosure of this patent is fully incorporated herein by reference.
There have also been attempts to reduce cement leakage by injecting more viscous cement, for example, during the doughing time and the beginning of polymerization. However, the viscous materials, such as hardening PMMA, typically harden very quickly once they reach a high viscosity. This has generally prevented injection of viscous materials in orthopedic procedures.
Some bone fixing materials, such as polymethylmethacrylate (PMMA), emit heat and possibly toxic materials while setting.
US patents and publication 4,969,888, 5,108,404, 6,383,188, 2003/0109883, 2002/0068974, 6,348,055, 6,383,190, 4,494,535, 4,653,489 and 4,653,487, the disclosures of which are incorporated herein by reference describe various tools and methods for treating bone.
US patent publication 2004/0260303, the disclosure of which is incorporated herein by reference, teaches an apparatus for delivering bone cement into a vertebra.
Pascual, B., et al., "New Aspects of the Effect of Size and Size Distribution on the Setting Parameters and Mechanical Properties of Acrylic Bone Cements,"
Biomaterials, 17(5):
509-516 (1996) considers the effect of PMMA bead size on setting parameters of cement. This article is fully incorporated herein by reference.
Hemandez, et al., (2005) "Influence of Powder Particle Size Distribution on Complex Viscosity and Other Properties of Acrylic Bone Cement for Vertebroplasty and Kyphoplasty"
Wiley International Science D01:10:1002/jbm.b.30409 (pages 98-103) considers the effect of PMMA bead size distribution on setting parameters of cement. Hernandez suggests that it is advantageous to formulate cement with a liquid phase to facilitate injection.
This article is fully incorporated herein by reference.
US 5,276,070 to Arroyo discloses use of acrylic polymers with a molecular weight in the range of 0.5 to 1.5 million Daltons in formulation of bone cement. The disclosure of this patent is fully incorporated herein by reference.
US 5,336,699 to Cooke discloses use of acrylic polymers with a molecular weight of about one hundred thousand Daltons in formulation of bone cement. The disclosure of this patent is fully incorporated herein by reference.
SUMMARY OF THE INVENTION
A broad aspect of the invention relates to a bone cement characterized by a rapid transition from separate liquid monomer and powdered polymer components to a single phase characterized by a high viscosity when the components are mixed together with substantially no intervening liquid phase. Optionally, high viscosity indicates 500 Pascal-second or more.
Mixing is deemed complete when 95-100% of the polymer beads are wetted by monomer. In an exemplary embodiment of the invention, mixing is complete in within 60, optionally within 45, optionally within 30 seconds.
In an exemplary embodiment of the invention, the cement is characterized by a working window of several minutes during which the viscosity remains high prior to hardening of the cement. Optionally, viscosity during the working window does not vary to a degree which significantly influences injection parameters. In an exemplary embodiment of the invention, viscosity increases by less than 10% during a sub-window of at least 2 minutes during the working window. Optionally, the viscosity in the working window does not exceed 500, optionally 1,000, optionally 1,500, optionally 2,000 Pascal-second or. lesser or greater or intermediate values. In an exemplary embodiment of the invention, the working window lasts 6, optionally 8, optionally 10, optionally 15 minutes or lesser or greater or intermediate tirnes.
Optionally, ambient temperature influences a duration of the working window.
In an exemplary embodiment of the invention, the cement can be cooled or heated to influence a length of the working window.
An aspect of some embodiments of the invention relates to formulations of bone cement which rely upon two, optionally three or more, sub-populations of polymer beads which are mixed with liquid monomer.
According to exemplary embodiments of the invention, sub-populations may be characterized by average molecular weight (MW) and/or physical size and/or geometry, and/or density. In an exemplary embodiment of the invention, size based and MW based sub-populations are defined independently. In an exemplary embodiment of the invention, the sub-populations are selected to produce desired viscosity characterization and/or polymerization kinetics. Optionally, the polymer beads comprise polymethylmethacrylate (PMMA) and/or a PMMA styrene copolymer. Optionally, PMMA is employed in conjunction with a methylmethacrylate (MMA) monomer.
Optionally, a high molecular weight sub-population contributes to a rapid transition to a high viscosity with substantially no liquid phase. Optionally, a low molecular weight subpopulation contributes to a longer working window.
Optionally, a sub-population with small size contributes to rapid wetting of polymer beads with monomer solution. In an exemplary embodiment of the invention, rapid wetting contributes to a direct transition to a viscous cement with substantially no liquid phase.
In some cases a small percentage of beads may not belong to any relevant sub-5 population. The small percentage may be, for example 1%, 1.5%, 2%, 3%, 4%, 5% or lesser or intermediate or greater percentages.
In one exemplary embodiment of the invention, there are at least two sub-populations of PMMA polymer beads characterized by molecular weights. For example, a first sub-population comprising 95 to 97% (w/w) of the total PMMA beads can be characterized by an average MW of 270,000-300,000 Dalton; a second sub-population (2-3% w/w) can be characterized by an average MW of 3,500,000-4,000,000 Dalton; and a third sub-populatiori (0-3% w/w) can be characterized by an average MW of 10,000-15,000 Dalton.
In an exemplary embodiment of the invention, the polymer beads are characterized by a high surface area per unit weight. Optionally, the beads have a surface area of 0.5 to 1, optionally 0.5 to 0.8 optionally about 0.66 m2/gram or intermediate or lesser or greater values.
Optionally, the high surface area/weight ratio improves wetting properties and/or shortens polymerization times, for example by contributing to polymer monomer contact.
In an exemplary embodiment of the invention, a cement characterized by an immediate transition to high viscosity is injected during a working window in a vertebroplasty or kyphoplasty procedure. Optionally, injection is under sufficient pressure to move fractured bone, such as vertebral plates of a collapsed vertebra. Optionally, injection of viscous cement nder high pressure contributes to fracture reduction and/or restoration of vertebral height.
In an exemplary embodiment of the invention, the material (e.g., bone cement) includes processed bone (from human or animals origin) and/or synthetic bone.
Optionally, the cement has osteoconductive and/or osteoinductive behavior. Additional additives as commonly used in bone cement preparation may optionally be added. These additives include, but are not limited to, barium sulfate and benzoyl peroxide.
According to some embodiments of the invention, a working window length is determined by an interaction between an immediate effect and a late effect. In an exemplary embodiment of the invention, the immediate effect includes MMA solvation and/or encapsulation of PMMA polymer beads. The immediate effect contributes to a high viscosity of the initial mixture resulting from solvation and/or friction between the beads. The late effect is increasing average polymer MW as the beads dissolve and the polymerization reaction proceeds. This increasing average polymer MW keeps viscosity high throughout the working window.
In an exemplary embodiment of the invention, a set of viscosity parameters are used to adjust a cement formulation to produce a cement characterized by a desired working window at a desired viscosity.
In an exemplary embodiment of the invention, there is provided a bone cement comprising an acrylic polymer mixture, the cement characterized in that it achieves a viscosity of at least 500 Pascal-second within 180 seconds following initiation of mixing of a monomer component and a polymer component and characterized by sufficient biocompatibility to permit in-vivo use.
Optionally, the viscosity of the mixture remains between 500 and 2000 Pascal-second for a working window of at least 5 minutes after the initial period.
Optionally, the working window is at least 8 minutes long.
Optionally, the mixture includes PMMA.
Optionally, the mixture includes Barium Sulfate.
Optionally, the PMMA is provided as a PMMA/styrene copolymer.
Optionally, the PMMA is provided as a population of beads divided into at least two sub-populations, each sub-population characterized by an average molecular weight.
Optionally, a largest sub-population of PMMA beads is characterized by an MW
of 150,000 Dalton to 300,000 Dalton.
Optionally, a largest sub-population of PMMA beads includes 90-98% (w/w) of the beads.
Optionally, a high molecular weight sub-population of PMMA beads is characterized by an average MW of at least 3,000,000 Dalton.
Optionally, a high molecular weight sub-population of PMMA beads includes 2 to 3%
(w/w) of the beads.
Optionally, a low molecular weight sub-population of PMMA beads is characterized by an average MW of less than 15,000 Dalton.
Optionally, a low molecular weight sub-population of PMMA beads includes 0.75 to 1.5 %(W/W) of the beads.
Optionally, the PMMA is provided as a population of beads divided into at least two sub-populations, each sub-population characterized by an average bead diameter.
A broad aspect of the invention relates to a bone cement characterized by a rapid transition from separate liquid monomer and powdered polymer components to a single phase characterized by a high viscosity when the components are mixed together with substantially no intervening liquid phase. Optionally, high viscosity indicates 500 Pascal-second or more.
Mixing is deemed complete when 95-100% of the polymer beads are wetted by monomer. In an exemplary embodiment of the invention, mixing is complete in within 60, optionally within 45, optionally within 30 seconds.
In an exemplary embodiment of the invention, the cement is characterized by a working window of several minutes during which the viscosity remains high prior to hardening of the cement. Optionally, viscosity during the working window does not vary to a degree which significantly influences injection parameters. In an exemplary embodiment of the invention, viscosity increases by less than 10% during a sub-window of at least 2 minutes during the working window. Optionally, the viscosity in the working window does not exceed 500, optionally 1,000, optionally 1,500, optionally 2,000 Pascal-second or. lesser or greater or intermediate values. In an exemplary embodiment of the invention, the working window lasts 6, optionally 8, optionally 10, optionally 15 minutes or lesser or greater or intermediate tirnes.
Optionally, ambient temperature influences a duration of the working window.
In an exemplary embodiment of the invention, the cement can be cooled or heated to influence a length of the working window.
An aspect of some embodiments of the invention relates to formulations of bone cement which rely upon two, optionally three or more, sub-populations of polymer beads which are mixed with liquid monomer.
According to exemplary embodiments of the invention, sub-populations may be characterized by average molecular weight (MW) and/or physical size and/or geometry, and/or density. In an exemplary embodiment of the invention, size based and MW based sub-populations are defined independently. In an exemplary embodiment of the invention, the sub-populations are selected to produce desired viscosity characterization and/or polymerization kinetics. Optionally, the polymer beads comprise polymethylmethacrylate (PMMA) and/or a PMMA styrene copolymer. Optionally, PMMA is employed in conjunction with a methylmethacrylate (MMA) monomer.
Optionally, a high molecular weight sub-population contributes to a rapid transition to a high viscosity with substantially no liquid phase. Optionally, a low molecular weight subpopulation contributes to a longer working window.
Optionally, a sub-population with small size contributes to rapid wetting of polymer beads with monomer solution. In an exemplary embodiment of the invention, rapid wetting contributes to a direct transition to a viscous cement with substantially no liquid phase.
In some cases a small percentage of beads may not belong to any relevant sub-5 population. The small percentage may be, for example 1%, 1.5%, 2%, 3%, 4%, 5% or lesser or intermediate or greater percentages.
In one exemplary embodiment of the invention, there are at least two sub-populations of PMMA polymer beads characterized by molecular weights. For example, a first sub-population comprising 95 to 97% (w/w) of the total PMMA beads can be characterized by an average MW of 270,000-300,000 Dalton; a second sub-population (2-3% w/w) can be characterized by an average MW of 3,500,000-4,000,000 Dalton; and a third sub-populatiori (0-3% w/w) can be characterized by an average MW of 10,000-15,000 Dalton.
In an exemplary embodiment of the invention, the polymer beads are characterized by a high surface area per unit weight. Optionally, the beads have a surface area of 0.5 to 1, optionally 0.5 to 0.8 optionally about 0.66 m2/gram or intermediate or lesser or greater values.
Optionally, the high surface area/weight ratio improves wetting properties and/or shortens polymerization times, for example by contributing to polymer monomer contact.
In an exemplary embodiment of the invention, a cement characterized by an immediate transition to high viscosity is injected during a working window in a vertebroplasty or kyphoplasty procedure. Optionally, injection is under sufficient pressure to move fractured bone, such as vertebral plates of a collapsed vertebra. Optionally, injection of viscous cement nder high pressure contributes to fracture reduction and/or restoration of vertebral height.
In an exemplary embodiment of the invention, the material (e.g., bone cement) includes processed bone (from human or animals origin) and/or synthetic bone.
Optionally, the cement has osteoconductive and/or osteoinductive behavior. Additional additives as commonly used in bone cement preparation may optionally be added. These additives include, but are not limited to, barium sulfate and benzoyl peroxide.
According to some embodiments of the invention, a working window length is determined by an interaction between an immediate effect and a late effect. In an exemplary embodiment of the invention, the immediate effect includes MMA solvation and/or encapsulation of PMMA polymer beads. The immediate effect contributes to a high viscosity of the initial mixture resulting from solvation and/or friction between the beads. The late effect is increasing average polymer MW as the beads dissolve and the polymerization reaction proceeds. This increasing average polymer MW keeps viscosity high throughout the working window.
In an exemplary embodiment of the invention, a set of viscosity parameters are used to adjust a cement formulation to produce a cement characterized by a desired working window at a desired viscosity.
In an exemplary embodiment of the invention, there is provided a bone cement comprising an acrylic polymer mixture, the cement characterized in that it achieves a viscosity of at least 500 Pascal-second within 180 seconds following initiation of mixing of a monomer component and a polymer component and characterized by sufficient biocompatibility to permit in-vivo use.
Optionally, the viscosity of the mixture remains between 500 and 2000 Pascal-second for a working window of at least 5 minutes after the initial period.
Optionally, the working window is at least 8 minutes long.
Optionally, the mixture includes PMMA.
Optionally, the mixture includes Barium Sulfate.
Optionally, the PMMA is provided as a PMMA/styrene copolymer.
Optionally, the PMMA is provided as a population of beads divided into at least two sub-populations, each sub-population characterized by an average molecular weight.
Optionally, a largest sub-population of PMMA beads is characterized by an MW
of 150,000 Dalton to 300,000 Dalton.
Optionally, a largest sub-population of PMMA beads includes 90-98% (w/w) of the beads.
Optionally, a high molecular weight sub-population of PMMA beads is characterized by an average MW of at least 3,000,000 Dalton.
Optionally, a high molecular weight sub-population of PMMA beads includes 2 to 3%
(w/w) of the beads.
Optionally, a low molecular weight sub-population of PMMA beads is characterized by an average MW of less than 15,000 Dalton.
Optionally, a low molecular weight sub-population of PMMA beads includes 0.75 to 1.5 %(W/W) of the beads.
Optionally, the PMMA is provided as a population of beads divided into at least two sub-populations, each sub-population characterized by an average bead diameter.
Optionally, at least one bead sub- population characterized by an average diameter is further divided into at least two sub-sub-populations, each sub-sub-population characterized by an average molecular weight.
Optionally, the PMMA is provided as a population of beads divided into at least three sub-populations, each sub-population characterized by an average bead diameter.
Optionally, the cement further includes processed bone and/or synthetic bone.
Optionally, the cement is characterized in that the cement achieves a viscosity of at least 500 Pascal-second when 100% of a polymer component is wetted by a monomer component.
Optionally, the viscosity is at least 800 Pascal-second.
Optionally, the viscosity is at least 1500 Pascal-second.
Optionally, the viscosity is achieved within 2 minutes.
Optionally, the viscosity is achieved within 1 minute.
Optionally, the viscosity is achieved within 45 seconds.
In an exemplary embodiment of the invention, there is provided a bone cement comprising:
a polymer component; and a monomer component, wherein, contacting the polymer component and the monomer component produces a mixture which attains a viscosity greater than 200 Pascal-second within 1 minute from onset 'of mixing and remains below 2000 Pascal-second until at least 6 minutes from onset of mixing.
Optionally, the polymer component comprises an acrylic polymer.
In an exemplary embodiment of the invention, there is provided a particulate mixture formulated for preparation of a bone cement, the mixture comprising:
(a) 60 to 80% polymer beads comprising a main sub-population characterized by an MW
of 150,000 Dalton to 300,000 Dalton and a high molecular weight sub-population characterized by an MW of 3,000,000 Dalton to 4,000,000 Dalton; and (b) 20 to 40% of a material which is non-transparent with respect to X-ray.
Optionally, the polymer beads comprise a third subpopulation characterized by an MW
of 10,000 Dalton to 15,000 Dalton.
In an exemplary embodiment of the invention, there is provided a method of making a polymeric bone cement, the method comprising:
(a) defining a viscosity profile including a rapid transition to a working window characterized by a high viscosity;
Optionally, the PMMA is provided as a population of beads divided into at least three sub-populations, each sub-population characterized by an average bead diameter.
Optionally, the cement further includes processed bone and/or synthetic bone.
Optionally, the cement is characterized in that the cement achieves a viscosity of at least 500 Pascal-second when 100% of a polymer component is wetted by a monomer component.
Optionally, the viscosity is at least 800 Pascal-second.
Optionally, the viscosity is at least 1500 Pascal-second.
Optionally, the viscosity is achieved within 2 minutes.
Optionally, the viscosity is achieved within 1 minute.
Optionally, the viscosity is achieved within 45 seconds.
In an exemplary embodiment of the invention, there is provided a bone cement comprising:
a polymer component; and a monomer component, wherein, contacting the polymer component and the monomer component produces a mixture which attains a viscosity greater than 200 Pascal-second within 1 minute from onset 'of mixing and remains below 2000 Pascal-second until at least 6 minutes from onset of mixing.
Optionally, the polymer component comprises an acrylic polymer.
In an exemplary embodiment of the invention, there is provided a particulate mixture formulated for preparation of a bone cement, the mixture comprising:
(a) 60 to 80% polymer beads comprising a main sub-population characterized by an MW
of 150,000 Dalton to 300,000 Dalton and a high molecular weight sub-population characterized by an MW of 3,000,000 Dalton to 4,000,000 Dalton; and (b) 20 to 40% of a material which is non-transparent with respect to X-ray.
Optionally, the polymer beads comprise a third subpopulation characterized by an MW
of 10,000 Dalton to 15,000 Dalton.
In an exemplary embodiment of the invention, there is provided a method of making a polymeric bone cement, the method comprising:
(a) defining a viscosity profile including a rapid transition to a working window characterized by a high viscosity;
(b) selecting a polymer component and a monomer component to produce a cement conforming to the viscosity profile; and (c) mixing the polymer component and a monomer component to produce a cement which conforms to the viscosity profile.
In an exemplary embodiment of the invention, there is provided a cement kit, comprising:
(a) a liquid component including a monomer; and (b) a powder component including polymeric beads, characterized in that said powder component is provided in a substantially non-normal distribution of at least one of molecular weight of the polymeric beads and size of powder particles such that a cement mixed from the kit has both an increased immediate viscosity and an increased working window as compared to a cement having a substantially normal distribution.
Optionally, the substantially non-normal distribution is a skewed distribution.
. Optionally, the substantially non-normal distribution comprises a relatively small component including higher molecular weight beads. Optionally, said component has an average molecular weight of at least a factor of 2 of an average molecular weight of said polymeric beads. Optionally, said factor is at least 3 or is at least 5.
Optionally, the substantially non-normal distribution comprises a relatively small component including smaller sized particles.
BRIEF DESCRIPTION OF THE FIGURES
Exemplary non-limiting embodiments of the invention will be described with reference to the following description of embodiments in conjunction with the figures.
Identical structures, elements or parts which appear in more than one figure are generally labeled with a same or similar number in all the figures in which they appear, in which:
Fig. 1 is a flow diagram illustrating an exemplary method 100 of preparation and behavior of exemplary cements according to the present invention;
Fig. 2 is a graph of viscosity profiles depicting viscosity (Pascal-second) as a function of time (minutes) for an exemplary cement according to the invention and an exemplary prior art cement;
Figs. 3 and 4 are graphs indicating viscosity as Newtons of applied force per unit displacement (mm) under defined conditions for exemplary cements according to the invention and illustrate the time window for injection which is both early and long; and Fig. 5 is a graph showing the results of bead size distribution analysis, for a bead formulation in accordance with an exemplary embodiment of the invention.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
Overview of preparation of exemplary bone cement Fig. 1 is a flow diagram illustrating preparation and behavior of exemplary cements according to some embodiments of the present invention.
In an exemplary embodiment of the invention, a liquid monomer and a powdered polymer component of a bone cement are combined 110. Optionally, liquid monomer is poured onto powdered polymer.
According to various embodiments of the invention, average polymer molecular weight and/or polymer molecular weight distribution and/or polymer bead size is precisely controlled in order to influence polymerization kinetics and/or cement viscosity.
Alternatively or additionally, polymer and/or monomer components may contain ingredients which are not directly involved in the polymerization reaction.
In an exemplary embodiment of the invention, the polymer (e.g. an acrylic polymer such as PMMA) beads are divided into two or more sub-populations. Optionally, the sub-populations are defined by molecular weight (MW). In an exemplary embodiment of the invention, the average molecular weight of the acrylic polymer in all the beads is in the range of about 300,000 to 400,000, optionally about 373,000 Dalton. This average MW
for all beads was determined experimentally for a batch of beads which produced cement with a desired =
polymerization profile.
Optionally, the polymer beads are provided as part of an acvrylic polymer mixture, for example a mixture including barium sulfate.
At 112 the components are mixed until the polymer is wetted by the monomer.
Optionally, when wetting is 95 to 100% complete, the mixture has achieved a desired high viscosity, for example 500 Pascal-second or more. Optionally, mixing 112 is complete within 1, 5, 10, 15, 30, 60, 90, 120 or 180 seconds. In a modern medical facility, it can be advantageous to shorten the mixing time in order to reduce the demand on physical facilities and/or medical personnel. A savings of even 1 to 2 minutes with respect to previously available alternatives can be significant. In an exemplary embodiment of the invention, mixing 112 is conducted in a mixing apparatus of the type described in co-pending application US
11/428,908, the disclosure of which is fully incorporate herein by reference.
After mixing 112 is complete, a working window 114 during which the cement remains viscous but has not fully hardened occurs. According to various exemplary embodiments of the invention, working window 114 may be about 2, 5, 8, 10, 15 or 20 minutes or intermediate or greater times. The duration of the working window may vary with the exact cement formulation and/or ambient conditions (e.g. temperature and/or humidity).
Formulation considerations include, but are not limited to polymer MW (average and/or distribution), 5 polymer bead size, concentrations of non-polymerizing ingredient and polymer: monomer ratio.
Working window 114, permits a medical practitioner sufficient time to load a high pressure injection device and inject 120 the cement into a desired location.
Optionally, an injection needle or cannula is inserted into the body prior to, or concurrent with mixing 112 so 10 that window 114 need only be long enough for loading and injection 120.
Exemplary injection systems are disclosed in co-pending application US 11/360,251 entitled "Methods, materials, and apparatus for treating bone and other tissue" filed February 22, 2006, the disclosure of which is fully incorporated herein by reference.
In an exemplary embodiment of the invention, hardening 116 to a hardened condition occurs after working window 114. The cement hardens 116 even if it has not been injected.
Advantages with Respect to Relevant Medical Procedures In an exemplary embodiment of the invention, cement with a viscosity profile as described above is useful in vertebral repair, for example in vertebroplasty and/or kyphoplasty procedures.
Optionally, use of cement which is viscous at the time of injection reduces the risk of material leakage and/or infiltrates into the intravertebral cancellous bone (interdigitaion) and/or reduces the fracture [see G Baroud et al, Injection biomechanics of bone cements used in vertebroplasty, Bio-Medical Materials and Engineering 00 (2004) 1-18]. Reduced leakage optionally contributes to increased likelihood of a positive clinical outcome.
In an exemplary embodiment of the invention, the viscosity of the bone cement is 500, optionally 1,000, optionally 1,500, optionally 2,000 Pascal-second or lesser or greater or intermediate values at the time injection begins, optionally 3, 2 or 1 minutes or lesser or intermediate times after mixing 112 begins. Optionally, the viscosity does not exceed 2,000 Pascal-second during working window 114. In an exemplary embodiment of the invention, this viscosity is achieved substantially as soon as 95-100% of the polymer beads are wetted by monomer.
Cement characterized by a high viscosity as described above may optionally be manually manipulated.
ll In an exemplary embodiment of the invention, cement is sufficiently viscous to move surrounding tissue as it is injected. Optionally, moving of the surrounding tissue contributes to fracture reduction and/or restoration of vertebral height.
An injected volume of cement may vary, depending upon the type and/or number of orthopedic procedures being performed. The volume injected may be, for example, 2-5 cc for a typical vertebral repair and as high as 8-12 cc or higher for repairs of other types of bones.
Other volumes may be appropriate, depending for example, on the volume of space and the desired effect of the injection. In some cases, a large volume of viscous cement is loaded into a delivery device and several vertebrae are repaired in a single medical procedure. Optionally, one or more cannulae or needles are employed to perform multiple procedures.
Viscous cements according to exemplary embodiments of the invention may be delivered at a desired flow rate through standard orthopedic cannulae by applying sufficient pressure. Exemplary average injection rates may be in the range of 0.01 to 0.5 ml/sec, optionally about 0.05, about 0.075 or 0.1 ml/sec or lesser or intermediate or greater average flow rates. Optionally, the flow rate varies significantly during an injection period (e.g., pulse injections). Optionally, the flow rate is controlled manually or using electronic or mechanical circuitry. In an exemplary embodiment of the invention, medical personnel view the cement as it is being injected (e.g. via fluoroscopy) and adjust a flow rate and/or delivery volume based upon observed results. Optionally, the flow rate is adjusted and/or controlled to allow a medical practitioner to evaluate progress of the procedure based upon medical images (e.g.
fluoroscopy) acquired during the procedure. In an exemplary embodiment of the invention, the cement is sufficiently viscous that advances into the body when pressure is applied above a threshold and ceases to advance when pressure is reduced below a threshold.
Optionally, the threshold varies with one or more of cement viscosity, cannula diameter and cannula length.
Comparison of exemplary formulations according to some embodiments of the invention to previously available formulations Although PMMA has been widely used in preparation of bone cement, previously available PMMA based cements were typically characterized by a persistent liquid state after mixing of components.
In sharp contrast, cements according to some exemplary embodiments of the invention are characterized by essentially no liquid state. Optionally, a direct transition from separate polymer and monomer components to a highly viscous state results from the presence of two or more sub-populations of polymer beads.
As a result of formulations based upon bead sub-populations, a viscosity profile of a cement according to an exemplary embodiment of the invention is significantly different from a viscosity profile of a previously available polymer based cement (e.g. PMMA) with a similar average molecular.
Because the viscosity profile of previously available PMMA cements is typically characterized by a rapid transition from high viscosity to fully hardened, these cements are typically injected into bone in a liquid phase so that they do not harden during injection.
In sharp contrast, exemplary cements according to the invention remain highly viscous during a long working window 114 before they harden. This long working window permits performance of a medical procedure of several minutes duration and imparts the advantages of the high viscosity material to the procedure.
It should be noted that while specific examples are described, it is often the case that the formulation will be varied to achieve particular desired mechanical properties. For example, different diagnoses may suggest different material viscosities which may, in turn lead to adjustment of one or more of MW (average and/or distribution), bead size and bead surface area.
In an exemplary embodiment of the invention, the cement is mixed 112 and reaches high viscosity outside the body. Optionally the materials are mixed under vacuum or ventilated. In this manner, some materials with potentially hazardous by-products can be safely ' mixed and then used in the body.
In an exemplary embodiment of the invention, the cement is formulated so that its mechanical properties match the bone in which it will be injected/implanted.
In an exemplary embodiment of the invention, the cement is formulated to mechanically match healthy or osteoporotic trabecular (cancellous) bone. Optionally, the mechanical properties of the bone are measured during access, for example, based on a resistance to advance or using sensors provided through a cannula or by taking samples, or based on x-ray densitometry measurements. In an exemplary embodiment of the invention, strength of the cement varies as a function of one or more of a size of the high MW sub-population and/or a relationship between bead size and bead MW.
In general, PMMA is stronger and has a higher Young modulus than trabecular bone.
For example, healthy Trabecular bone can have a strength of between 1.5-8.0 mega Pascal and a Young modulus of 60-500 mega Pascal. Cortical bone, for example, has strength values of 65-160 mega Pascal and Young modulus of 12-40 giga Pascal. PMMA typically has values about half of Cortical bone (70-120 mega Pascal strength).
Fig. 2 is a plot of viscosity as a function of time for an exemplary bone cement according to the present invention. The figure is not drawn to scale and is provided to illustrate the principles of exemplary embodiments of the invention. The end of a mixing process is denoted as time 0. Mixing is deemed to end when 95-100% of acrylic polymer beads have been wetted with monomer. The graph illustrates an exemplary bone cement which enters a high viscosity plastic phase upon mixing so that it has substantially no liquid phase.
Fig. 2 illustrates that once a high viscosity is achieved, the viscosity remains relatively stable for 2, optionally 5, optionally 8 minutes or more. In an exemplary embodiment of the invention, this interval of stable viscosity provides a working window 114 (indicated here as Atl) for performance of a medical procedure. In an exemplary embodiment of the invention, stable viscosity means that the viscosity of the cement changes by less than 200 Pascal-second during a window of at least 2 minutes optionally at least 4 minutes after mixing is complete.
Optionally, the window begins 1, 2, 3, 4 or 5 minutes after mixing begins or lesser or intermediate times. In an exemplary embodiment of the invention, the viscosity of the cement remains below 1500, optionally 2000 Pascal-second for at least 4, optionally at least 6, optionally at least 8, optionally at least 10 minutes or intermediate or greater times from onset of mixing.
For purposes of comparison, the graph illustrates that an exemplary prior art cement ' reaches a viscosity comparable to that achieved by an exemplary cement according to the invention at time zero at a time of approximately 10.5 minutes post mixing and is completely set by about 15.5 minutes (Ot2).
A working window 114 during which viscosity is between 400 and 2000 Pascal-second for an exemplary cement according to some embodiments of the invention (At,) is both longer and earlier than a comparable window for an exemplary prior, art cement (At2).
Optionally, (Otl) begins substantially as soon as mixing is complete.
Exemplary cement formulations According to various exemplary embodiments of the invention, changes in the ratios between a powdered polymer component and a liquid monomer component can effect the duration of working window 114 and/or a viscosity of the cement during that window.
Optionally, these ratios are adjusted to achieve desired results.
In an exemplary embodiment of the invention, the powdered polymer component contains PMMA (69.3% w/w); Barium sulfate (30.07% w/w) and Benzoyl peroxide (0.54%
w/w).
In an exemplary embodiment of the invention, the liquid monomer component contains MMA (98.5% v/v); N, N-dimethyl-p-toluidine (DMPT) (1.5% v/v) and Hydroquinone (20 ppm).
In a first exemplary embodiment of the invention, 20 + 0.3 grams of polymer powder and 9 0.3grams of liquid monomer are combined (weight ratio of -2.2:1).
In a second exemplary embodiment of the invention, 20+ 0.3 grams of polymer powder and 8+ 0.3 grams of liquid are combined (weight ratio of 2.5:1).
Under same weight ratio of second exemplary embodiment (2.5:1), a third exemplary embodiment may include a combination of 22.5 0.3 grams of polymer powder and 9 0.3 grams of liquid.
In general, increasing the weight ratio of polymer to monomer produces a cement which reaches a higher viscosity in less time. However, there is a limit beyond which there is not sufficient monomer to wet all of the polymer beads.
Optionally the powdered polymer component may vary in composition and contain PMMA (67-77%, optionally 67.5-71.5% w/w); Barium sulfate (25-35%; optionally 28-32%
w/w) and Benzoyl peroxide (0.4 -0.6 % w/w) and still behave substantially as the powder component recipe set forth above.
Optionally the liquid monomer component may vary in composition and contain Hydroquinone (1-30 ppm; optionally 20-25 ppm) and still behave substantially as the liquid component recipe set forth above.
Viscosity measurements over time for exemplary cements In order to evaluate the viscosity profile of different exemplary batches of cement according to some embodiments of the invention, a bulk of pre-mixed bone cement is placed inside a Stainless Steel injector body. Krause et al. described a method for calculating viscosity in terms of applied force. ("The viscosity of acrylic bone cements", Journal of Biomedical Materials Research, (1982): 16:219-243). This article is fully incorporated herein by reference.
In the experimental apparatus an inner diameter of the injector body is approximately 18 mm. A distal cylindrical outlet has an inner diameter of approximately 3 mm and a length of more than 4 mm. This configuration simulates a connection to standard bone cement delivery cannula/bone access needle. A piston applies force (F), thus causing the bone cement to flow through the outlet. The piston is set to move with constant velocity of approximately 3 mm/min. As a result, piston deflection is indicative of elapsed time.
The experimental procedure serves as a kind of capillary extrusion rheometer.
The rheometer measures the pressure difference from an end to end of the capillary tube. The device is made of an 18 inm cylindrical reservoir and a piston. The distal end of the reservoir consist of 4 mm long 3 mm diameter hole. This procedure employs a small diameter needle and high pressure. Assuming steady flow, isothermal conditions and incompressibility of the tested material, the viscous force resisting the motion of the fluid in the capillary is equal 5 to the applied force acting on the piston measured by a load cell and friction. Results are presented as force vs. displacement. As displacement rate was constant and set to 3 mm/min, the shear rate was constant as well. In order to measure the time elapses from test beginning, the displacement rate is divided by 3(jog speed).
Fig. 3 indicates a viscosity profile of a first exemplary batch of cement according to the 10 invention as force (Newtons) vs. displacement (mm). The cement used in this experiment included a liquid component and a powder component as described above in "Exemplary cement formulations".
In this test (Average temperature: 22.3 C; Relative Humidity: app. 48%) the cement was mixed for 30-60 seconds, then manipulated by hand and placed inside the injector. Force 15 was applied via the piston approximately 150 seconds after end of mixing, and measurements of force and piston deflection were taken.
At a time of 2.5 minutes after mixing (0 mm deflection) the force applied was higher' than 30 N.
At a time of 6.5 minutes after mixing (12 mm deflection) the force applied was about '`
150 N.
At a time of 7.5 minutes after mixing (15 mm deflection) the force applied was higher than 200 N.
At a time of 8.5 minutes after mixing (18 mm deflection) the force applied was higher than 500 N.
At a time of 9.17 minutes after mixing (20 mm deflection) the force applied was higher than 1300 N.
Fig. 4 indicates a viscosity profile of an additional exemplary batch of cement according to the invention as force (Newtons) vs. displacement (mm). The cement in this test was prepared according to the same formula described for the experiment of Fig. 3. In this test (Average 21.1 C; Relative Humidity: app. 43%) the cement was mixed for approximately 45 seconds, then manipulated by hand and placed inside the injector. Force was applied via piston approximately 150 seconds after end of mixing, and measurements of force and piston deflection were taken.
At a time of 2.25 minutes after mixing (0 mm deflection) the force applied was higher than 30 N.
At a time of 8.25 minutes after mixing (18 mm deflection) the force applied was about 90 N.
At a time of 10.3 minutes after mixing (25 mm deflection) the force applied was higher than 150 N.
At a time of 11.4 minutes after mixing (28.5 mm deflection) the force applied was higher than 500 N.
At a time of 12.25 minutes after mixing (30 mm deflection) the force applied was higher than 800 N.
Results shown in Figs. 3 and 4 and summarized hereinabove illustrate that exemplary bone cements according to some embodiments the invention achieve high viscosity in 2.25 minutes or less after mixing is completed. Alternatively or additionally, these cements are characterized by short mixing time (i.e. transition to highly viscous plastic phase in 30 to 60 seconds). The exemplary cements provide a "working window" for injection of 4.5 to 6.3 minutes, optionally longer if more pressure is applied and/or ambient temperatures are lower.
These times correspond to delivery volumes of 14.9 and 20.8 ml respectively (vertebroplasty of a single vertebra typically requires about 5 ml of cement). These volumes are sufficient for most vertebral repair procedures. These results comply with the desired characteristics described in Fig. 2. Differences between the two experiments may reflect the influence of temperature and humidity on reaction kinetics.
Molecular weight distribution In an exemplary embodiment of the invention, the average molecular weight (MW) is skewed by the presence of one or more small sub-population of beads with a molecular weight which is significantly different from a main sub-population of polymer beads.
The one or more small sub-population of beads may have a MW which is significantly higher and/or significantly lower than the average MW.
In an exemplary embodiment of the invention, the presence of even a relatively small sub-population of polymer beads with a MW significantly above the average MW
causes the cement to achieve a high viscosity in a short time after wetting of polymer beads with monomer solution. Optionally, increasing a size of the high MW sub-population increases the achieved viscosity. Alternatively or additionally, increasing an average MW of the high MW
sub-population increases the achieved viscosity and/or decreases the time to reach high viscosity.
Optionally, the one or more small sub- population of beads are provided in a formulation in which, the average molecular weight of PMMA in all beads is 80,000, optionally 100,000, optionally 120,000, optionally 140,000, optionally 160,000, optionally 180,000, optionally, 250,000, optionally 325,000, optionally 375.000, optionally 400,000, optionally 500,000 Dalton or intermediate or lesser or greater values.
In another exemplary embodiment of the invention, the average molecular weight of the acrylic polymer in the beads is in the range of about 130,000 to 170,000, optionally about 160,000 Dalton.
In an exemplary embodiment of the invention, a main sub-population of PMMA
beads has a MW of about 150,000 Dalton to about 500,000 Dalton, optionally about 250,000 Dalton to about 300,000 Dalton, optionally about 275,000 Dalton to about 280,000 Dalton. Optionally, about 90-98% [w/w], optionally about 93% to 98%, optionally about 95% to 97%
of the beads belong to the main sub-population.
In an exemplary embodiment of the invention, a second high MW sub-population of PMMA beads has a MW of about 600,000 Dalton, to about 5,000,000 Dalton, optionally about 3,000,000 Dalton to about 4,000,000 Dalton, Optionally about 3,500,000 Dalton to about 3,900,000 Dalton. Optionally, approximately 0.25% to 5% [w/w], optionally about 1% to 4%, optionally about 2% to 3% of the beads belong to this high MW sub-population.
Optionally, this high molecular weight sub-population comprises a styrene co-polymer. In an exemplary embodiment of the invention, a higher molecular weight in this sub-population of beads -contributes to a high viscosity within 2, optionally within 1, optionally within 0.5 minutes or less of wetting of polymer beads with monomer solution.
In an exemplary embodiment of the invention, a third low MW sub-population of PMMA beads has a MW in the range of about 1,000 Dalton to about 75,000 Dalton, optionally about 10,000 Dalton to about 15,000 Dalton, optionally about 11,000 Dalton to about 13,000 Dalton. Optionally, approximately 0.5 to 2.0% [w/w], optionally about 1% of the beads belong to this sub-population.
Optionally the MW sub-populations are distinct from one another. This can cause gaps between sub-populations with respect to one or more parameters. In an exemplary embodiment of the invention, the sub-populations are represented as distinct peaks in a chromatographic separation process. Optionally, the peaks are separated by a return to baseline. Depending upon the sensitivity of detection, a background level of noise may be present.
Optionally, gaps are measured relative to the noise level.
Optionally the sub-populations abut one another so that no gaps are apparent.
In an exemplary embodiment of the invention, the sub-populations are represented as overlapping peaks in a chromatographic separation process. In this case, there is no return to baseline between the peaks.
Experimental analysis of an exemplary batch of cement Sub-populations characterized by an average molecular weight were identified and quantitated using chromatographic techniques known in the art. Exemplary results described herein are based upon GPC analysis. Each peak in the GPC analysis is considered a sub-population. Similar analyses may be conducted using HPLC. Results are summarized in table 1.
Table 1: MW distribution of polymer beads based upon GPC analysis of a bone cement according to the powdered polymer component described in "Exemplary cement formulations"
hereinabove.
Fraction % of total PDI Mw Mn 1 96.5 1.957 278,986 142,547 2 2.5 1.048 3,781,414 3,608,941 3 1.0 1.009 12,357 12,245 100.0 2.955 373,046 126,248 1 polydispersity index (PDI), is a measure of the distribution of molecular weights in a given polymer sample and is equal to MW/Mn..
2 MW is the weight average molecular weight in Daltons 3 Mn is the number average molecular weight in Daltons Table I illustrates an exemplary embodiment of the invention with three sub-populations of acrylic polymer beads.
The main sub-population (fraction 1) of PMMA beads has a molecular weight (MW) of 278,986 Dalton. About 96.5% of the beads belong to this sub-population.
A second sub-population (fraction 2) of PMMA beads has MW of 3,781,414 Dalton.
Approximately 2.5% of the beads belong to this sub-population.
A third sub-population of PMMA beads (fraction 3) has an MW of 12,357 Dalton.
Approximately I% of the beads belong to this sub-population.
In an exemplary embodiment of the invention, cement comprising these three sub-populations is characterized by a short mixing time and/or achieves a viscosity of 500 to 900 Pascal-second in 0.5 to 3, optionally 0.5 to 1.5 minutes from the beginning of mixing and/or which remains below 2000 Pascal-second for at least 6 to 10 minutes after mixing. A short mixing time followed by a long working window is considered advantageous in orthopedic procedures where operating room availability and medical staff are at a premium.
Size Distribution In an exemplary embodiment of the invention, the bone cement is characterized by beads with a size distribution including at least two sub-populations of polymer beads.
In an exemplary embodiment of the invention, polymer bead diameter is in the range of 10-250 microns, with a mean value of approximately 25, 30, 40, 50, 60 microns, or a lower or a higher or an intermediate diameter. In an exemplary embodiment of the invention, sub-populations of beads are defined by their size.
Optionally, a main sub-population of polymer (e.g. PMMA) beads is characterized by a diameter of about 20 to about 150, optionally about 25 to about 35, optionally an average of about 30 microns. Beads in this main sub-population are optionally far smaller than the smallest beads employed by Hernandez et al. (2005; as cited above). Presence of small beads can contribute to a rapid increase in viscosity after wetting with monomer.
Optionally a second sub-population of large polymer beads is characterized by a diameter of about 150 microns or more. Presence of large beads can slow down the polymerization reaction and prevent hardening, contributing to a long working window.
Optionally, the remaining beads are characterized by a very small average diameter, for example less than 20, optionally less than 15, optionally about 10 microns or less. Presence of very small beads can facilitate rapid wetting with monomer liquid during mixing and contribute to a fast transition to a viscous state with substantially no liquid phase.
Microscopic analysis indicates that the beads are typically spherical or spheroid.
Hernandez et al. (2005; as cited above) examined the possibility of adjusting the average polymer bead size by combining two types of beads with average sizes of 118.4 (Colacry) and 69.7 (Plexigum) together in different ratios. However, Hernandez's goal was a formulation which is "liquid enough to be injected". All formulations described by Hernandez are characterized by an increase in viscosity from 500 Pascal-sec to 2000 Pascal-sec in about two minutes or less (corresponds to window 114). Hernandez does not hint or suggest that there is any necessity or advantage to increasing the size of this window.
Microscopic analysis also indicated that the barium sulfate particles are present as elongate amorphous masses with a length of approximately 1 micron. In some cases aggregates of up to 70 microns in size were observed. In some cases, barium sulfate particles and polymer beads aggregated together. Optionally, aggregates of Barium sulfate and polymer beads can delay wetting of polymer beads by monomer.
In an exemplary embodiment of the invention, MMA solvates and/or encapsulates the PMMA polymer beads and the viscosity of the initial mixture is high due to the solvation and/or friction between the beads. As the beads dissolve viscosity remains high due to polymerization which increases the average polymer MW.
The following table II shows an exemplary particle size distribution, for example, one suitable for the cement of Table I, based on an analysis of particles within the ranges of 0.375-5 2000 microns:
Table II: Particles size distribution of an exemplary powdered component Vol. % 10 25 50 75 90 Max Beads 2.3 25.75 45.07 60.68 76.34 Diameter [microns]
Experimental analysis of a second exemplary batch of cement Another example of a cement kit for mixture includes a liquid and a powder, which 10 includes a mass of acrylic polymer beads. This cement kit is formulated as follows:
(a) liquid (9.2 gr) (i) Methylmethacrylate (MMA) 98.5% (vol) (ii) N,N-dimethyl-p-toluidine 1.5% (vol) (iii) Hydroquinone 20ppm (vol) 15 (b) powder (20 gr) (i) Polymethylmethacrylate (PMMA) 69.39% (weight) (ii) Barium Sulfate 30.07% (weight) (iii) Benzoyl Peroxide 0.54% (weight) As noted above, in other formulations the amounts may be varied, for example, to 20 achieve specific mechanical (or other) properties, or they may be varied and achieve same mechanical properties. In another variation, medication may be added to the powder and/or liquid phases. Other liquid phases may be used as well, for example, as known in the art for PMMA-type cements. The ratios may be varied, for example, as described above.
Table III summarizes a molecular weight distribution of the acrylic bead component of this exemplary cement. It is hypothesized that providing a non-normal distribution of molecular weights with a heavier molecular weight component (e.g., by skewing the MW
distribution by including relatively higher molecular weight beads) provides an increased immediate viscosity. In an exemplary embodiment of the invention, the higher MW beads are in a relatively small amount (for example, less than 20%, less than 10%, less than 5%) and have a MW of between 500,000 to 2,000,000 Dalton, optionally 600,000 to 1,200,000 Dalton (for example as shown in the table below).
Table III: MW distribution of polymer beads of a bone cement of the second exemplary batch Range of Molecular Weights [Dalton] % of total 1,000,000-2,000,000 0.38%
500,000-1,000,000 3.6%
250,000-500,000 12.4%
100,000-250,000 36.4%
50,000-100,000 26.6%
25,000-50,000 14.2%
10,000-25,000 5.3%
8,000-10,000 0.5%
5,000-8,000 0.4%
In an exemplary embodiment of the invention, the bone cement is characterized by beads with a size distribution including at least two sub-populations of different materials.
Optionally, at least two sub-populations include polymer (e.g. PMMA) beads and Barium Sulfate particles. Optionally, the range of particles diameter of the Barium Sulfate is 0.01-15 microns, optionally 0.3 to 3 microns, optionally with an average of about 0.5 microns or lesser or intermediate or greater sizes.
In an exemplary embodiment of the invention, polymer bead diameter is in the range of 10-250 microns, optionally 15-150 microns, with a mean value of approximately 25, 30, 40, 50, 60 microns. Lower or a higher or intermediate diameters are possible as well, for example, based on the setting considerations described above. In some cases, large particle sizes, for example, particles having diameters exceeding 120 microns (e.g., when the average diameter is on the order of 60 microns) are the result of Barium sulfate primary particle aggregation on, PMMA particle beads.
An exemplary distribution of bead sizes for the exemplary cement of table III, based on.`
an analysis of particles within the range of 0.04-2000 microns, is described in Table IV:
Table IV: Particles size distribution of a second exemplary powdered component of bone cement Vol. % 10 25 50 75 90 Max Beads 2 9 46.5 70.7 90.5 Diameter [microns]
Fig. 5 is a graph which visually shows the values of table IV
Size and MW are independent variables In an exemplary embodiment of the invention, size based and MW based sub-populations are determined independently. For example, MW may be determined chromatographically and size may be determined by microscopic analysis. As a result, beads classed in a single size sub-population may be classed in two or more MW sub-populations and/or beads classed in a single MW sub-population may be classed in two or more size sub-populations.
Mechanical viscosity increasing agents In an exemplary embodiment of the invention, the cement includes particles characterized by a large surface which do not participate in the polymerization reaction. The large surface area particles can impart added viscosity to the cement mixture independent of polymerization. Optionally, the added viscosity comes from friction of particles against one another in the cement.
Examples of materials which do not participate in the polymerization reaction but increase viscosity include, but are not limited to Zirconium, hardened acrylic polymer, barium sulfate and bone.
Optionally, materials which do not participate in the polymerization reaction but increase viscosity can at least partially substitute for high MW polymers in influencing a viscosity profile.
Desired Polymerization Reaction Kinetics In an exemplary embodiment of the invention, mixture of polymer and monomer produces a high viscosity mixture with substantially no intervening liquid phase within 180, optionally within 120, optionally within 100, optionally within 60, optionally within 30, optionally within 15 seconds or greater or intermediate times from onset of mixing. =
In an exemplary embodiment of the invention, once a high viscosity is achieved, the viscosity remains stable for 5 minutes, optionally 8 minutes, optionally 10 minutes or lesser`or intermediate or greater times. Optionally, stable viscosity indicates a change of 10% or less in two minutes and/or a change of 20% or less in 8 minutes. The time during which viscosity is stable provides a working window for performance of a medical procedure.
These desired reaction kinetics can be achieved by adjusting one or more of average polymer MW, polymer MW distribution, polymer to monomer ratio and polymer bead size and/or size distribution.
General considerations In an exemplary embodiment of the invention, a powdered polymer component and a liquid monomer component are provided as a kit. Optionally, the kit includes instructions for use. Optionally, the instructions for use specify different proportions of powder and liquid for different desired polymerization reaction kinetics.
In an exemplary embodiment of the invention, a bone cement kit including at least two, optionally three or more separately packaged sub-populations of beads and a monomer liquid is provided. Optionally, the kit includes a table which provides formulations based on combinations of different amounts of bead sub-populations and monomer to achieve desired properties.
It is common practice in formulation of acrylic polymer cements to include an initiator (e.g. benzoyl peroxide; BPO) in the powdered polymer component and/or a chemical activator (e.g. DMPT) into the liquid monomer component. These components can optionally be added to formulations according to exemplary embodiments of the invention without detracting from the desired properties of the cement.
Optionally, an easily oxidized molecule (e.g. hydroquinone) is added to the liquid component to prevent spontaneous polymerization during storage (stabilizer).
The hydroquinone can be oxidized during storage.
Optionally, cement may be rendered radio-opaque, for example by adding a radio-opaque material such as barium sulfate and/or zirconium compounds and/or bone (e.g. chips or powder) to the powder and/or liquid component.
While the above description has focused on the spine, other tissue can be treated as well, for example, compacted tibia plate and other bones with compression fractures and for fixation of implants, for example, hip implants or other bone implants that loosened, or during implantation. Optionally, for tightening an existing implant, a small hole is drilled to a location where there is a void in the bone and material is extruded into the void. .
It should be noted that while use of the disclosed material as bone cement is described;
non-bone tissue may optionally be treated. For example, cartilage or soft tissue in need of tightening may be injected with a high viscosity polymeric mixture.
Optionally, the delivered material includes an encapsulated pharmaceutical and is used as a matrix to slowly release the pharmaceutical over time. Optionally, this is used as a means to provide anti-arthritis drugs to a joint, by forming a void and implanting an eluting material near the joint.
It should be noted that while use of PMMA has been described, a wide variety of materials can be suitable for use in formulating cements with viscosity characteristics as described above. Optionally, other polymers could be employed by considering polymer molecular weight (average and/or distribution) and/or bead size as described above. Optionally, at least some of the beads include styrene. In an exemplary embodiment of the invention, styrene is added to MMA beads in a volumetric ratio of 5-25%. Optionally, addition of styrene increases creep resistance.
According to various embodiments of the invention, a bone cement according to the invention is injected into a bone void as a preventive therapy and/or as a treatment for a fracture, deformity, deficiency or other abnormality. Optionally, the bone is a vertebral body and/or a long bone. In an exemplary embodiment of the invention, the cement is inserted into the medullary canal of a long bone. Optionally, the cement is molded into a rod prior to or during placement into the bone. In an exemplary embodiment of the invention, the rod serves as an intra-medular nail.
Exemplary Characterization Tools Molecular weight and polydispersity can be analyzed, for example by Gel permeation chromatography(GPC) system (e.g. Waters 1515 isocratic HPLC pump with a Waters refractive-index detector and a Rheodyne (Coatati, CA) injection valve with a 20- L loop (Waters Ma)). Elution of samples with CHC13 through a linear Ultrastyragel column (Waters;
500-A pore size) at a flow rate of 1 ml/min provides satisfactory results.
It will be appreciated that various tradeoffs may be desirable, for example, between available injection force, viscosity, degree of resistance and forces that can be withstood (e.g.
by bone or injection tools). In addition, a multiplicity of various features, both of method and of cement formulation have been described. It should be appreciated that different features may be combined in different ways. In particular, not all the features shown above in a particular embodiment are necessary in every similar exemplary embodiment of the invention. Further, combinations of the above features are also considered to be within the scope of some exemplary embodiments of the invention. In addition, some of the features of the invention described herein may be adapted for use with prior art devices, in accordance with other exemplary embodiments of the invention.
Section headers are provided only to assist in navigating the application and should not be construed as necessarily limiting the contents described in a certain section, to that section.
Measurements are provided to serve only as exemplary measurements for particular cases, the exact measurements applied will vary depending on the application. When used in the following claims, the terms "comprises", "comprising", "includes", "including"
or the like means "including but not limited to".
It will be appreciated by a person skilled in the art that the present invention is not limited by what has thus far been described. Rather, the scope of the present invention is limited only by the following claims.
In an exemplary embodiment of the invention, there is provided a cement kit, comprising:
(a) a liquid component including a monomer; and (b) a powder component including polymeric beads, characterized in that said powder component is provided in a substantially non-normal distribution of at least one of molecular weight of the polymeric beads and size of powder particles such that a cement mixed from the kit has both an increased immediate viscosity and an increased working window as compared to a cement having a substantially normal distribution.
Optionally, the substantially non-normal distribution is a skewed distribution.
. Optionally, the substantially non-normal distribution comprises a relatively small component including higher molecular weight beads. Optionally, said component has an average molecular weight of at least a factor of 2 of an average molecular weight of said polymeric beads. Optionally, said factor is at least 3 or is at least 5.
Optionally, the substantially non-normal distribution comprises a relatively small component including smaller sized particles.
BRIEF DESCRIPTION OF THE FIGURES
Exemplary non-limiting embodiments of the invention will be described with reference to the following description of embodiments in conjunction with the figures.
Identical structures, elements or parts which appear in more than one figure are generally labeled with a same or similar number in all the figures in which they appear, in which:
Fig. 1 is a flow diagram illustrating an exemplary method 100 of preparation and behavior of exemplary cements according to the present invention;
Fig. 2 is a graph of viscosity profiles depicting viscosity (Pascal-second) as a function of time (minutes) for an exemplary cement according to the invention and an exemplary prior art cement;
Figs. 3 and 4 are graphs indicating viscosity as Newtons of applied force per unit displacement (mm) under defined conditions for exemplary cements according to the invention and illustrate the time window for injection which is both early and long; and Fig. 5 is a graph showing the results of bead size distribution analysis, for a bead formulation in accordance with an exemplary embodiment of the invention.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
Overview of preparation of exemplary bone cement Fig. 1 is a flow diagram illustrating preparation and behavior of exemplary cements according to some embodiments of the present invention.
In an exemplary embodiment of the invention, a liquid monomer and a powdered polymer component of a bone cement are combined 110. Optionally, liquid monomer is poured onto powdered polymer.
According to various embodiments of the invention, average polymer molecular weight and/or polymer molecular weight distribution and/or polymer bead size is precisely controlled in order to influence polymerization kinetics and/or cement viscosity.
Alternatively or additionally, polymer and/or monomer components may contain ingredients which are not directly involved in the polymerization reaction.
In an exemplary embodiment of the invention, the polymer (e.g. an acrylic polymer such as PMMA) beads are divided into two or more sub-populations. Optionally, the sub-populations are defined by molecular weight (MW). In an exemplary embodiment of the invention, the average molecular weight of the acrylic polymer in all the beads is in the range of about 300,000 to 400,000, optionally about 373,000 Dalton. This average MW
for all beads was determined experimentally for a batch of beads which produced cement with a desired =
polymerization profile.
Optionally, the polymer beads are provided as part of an acvrylic polymer mixture, for example a mixture including barium sulfate.
At 112 the components are mixed until the polymer is wetted by the monomer.
Optionally, when wetting is 95 to 100% complete, the mixture has achieved a desired high viscosity, for example 500 Pascal-second or more. Optionally, mixing 112 is complete within 1, 5, 10, 15, 30, 60, 90, 120 or 180 seconds. In a modern medical facility, it can be advantageous to shorten the mixing time in order to reduce the demand on physical facilities and/or medical personnel. A savings of even 1 to 2 minutes with respect to previously available alternatives can be significant. In an exemplary embodiment of the invention, mixing 112 is conducted in a mixing apparatus of the type described in co-pending application US
11/428,908, the disclosure of which is fully incorporate herein by reference.
After mixing 112 is complete, a working window 114 during which the cement remains viscous but has not fully hardened occurs. According to various exemplary embodiments of the invention, working window 114 may be about 2, 5, 8, 10, 15 or 20 minutes or intermediate or greater times. The duration of the working window may vary with the exact cement formulation and/or ambient conditions (e.g. temperature and/or humidity).
Formulation considerations include, but are not limited to polymer MW (average and/or distribution), 5 polymer bead size, concentrations of non-polymerizing ingredient and polymer: monomer ratio.
Working window 114, permits a medical practitioner sufficient time to load a high pressure injection device and inject 120 the cement into a desired location.
Optionally, an injection needle or cannula is inserted into the body prior to, or concurrent with mixing 112 so 10 that window 114 need only be long enough for loading and injection 120.
Exemplary injection systems are disclosed in co-pending application US 11/360,251 entitled "Methods, materials, and apparatus for treating bone and other tissue" filed February 22, 2006, the disclosure of which is fully incorporated herein by reference.
In an exemplary embodiment of the invention, hardening 116 to a hardened condition occurs after working window 114. The cement hardens 116 even if it has not been injected.
Advantages with Respect to Relevant Medical Procedures In an exemplary embodiment of the invention, cement with a viscosity profile as described above is useful in vertebral repair, for example in vertebroplasty and/or kyphoplasty procedures.
Optionally, use of cement which is viscous at the time of injection reduces the risk of material leakage and/or infiltrates into the intravertebral cancellous bone (interdigitaion) and/or reduces the fracture [see G Baroud et al, Injection biomechanics of bone cements used in vertebroplasty, Bio-Medical Materials and Engineering 00 (2004) 1-18]. Reduced leakage optionally contributes to increased likelihood of a positive clinical outcome.
In an exemplary embodiment of the invention, the viscosity of the bone cement is 500, optionally 1,000, optionally 1,500, optionally 2,000 Pascal-second or lesser or greater or intermediate values at the time injection begins, optionally 3, 2 or 1 minutes or lesser or intermediate times after mixing 112 begins. Optionally, the viscosity does not exceed 2,000 Pascal-second during working window 114. In an exemplary embodiment of the invention, this viscosity is achieved substantially as soon as 95-100% of the polymer beads are wetted by monomer.
Cement characterized by a high viscosity as described above may optionally be manually manipulated.
ll In an exemplary embodiment of the invention, cement is sufficiently viscous to move surrounding tissue as it is injected. Optionally, moving of the surrounding tissue contributes to fracture reduction and/or restoration of vertebral height.
An injected volume of cement may vary, depending upon the type and/or number of orthopedic procedures being performed. The volume injected may be, for example, 2-5 cc for a typical vertebral repair and as high as 8-12 cc or higher for repairs of other types of bones.
Other volumes may be appropriate, depending for example, on the volume of space and the desired effect of the injection. In some cases, a large volume of viscous cement is loaded into a delivery device and several vertebrae are repaired in a single medical procedure. Optionally, one or more cannulae or needles are employed to perform multiple procedures.
Viscous cements according to exemplary embodiments of the invention may be delivered at a desired flow rate through standard orthopedic cannulae by applying sufficient pressure. Exemplary average injection rates may be in the range of 0.01 to 0.5 ml/sec, optionally about 0.05, about 0.075 or 0.1 ml/sec or lesser or intermediate or greater average flow rates. Optionally, the flow rate varies significantly during an injection period (e.g., pulse injections). Optionally, the flow rate is controlled manually or using electronic or mechanical circuitry. In an exemplary embodiment of the invention, medical personnel view the cement as it is being injected (e.g. via fluoroscopy) and adjust a flow rate and/or delivery volume based upon observed results. Optionally, the flow rate is adjusted and/or controlled to allow a medical practitioner to evaluate progress of the procedure based upon medical images (e.g.
fluoroscopy) acquired during the procedure. In an exemplary embodiment of the invention, the cement is sufficiently viscous that advances into the body when pressure is applied above a threshold and ceases to advance when pressure is reduced below a threshold.
Optionally, the threshold varies with one or more of cement viscosity, cannula diameter and cannula length.
Comparison of exemplary formulations according to some embodiments of the invention to previously available formulations Although PMMA has been widely used in preparation of bone cement, previously available PMMA based cements were typically characterized by a persistent liquid state after mixing of components.
In sharp contrast, cements according to some exemplary embodiments of the invention are characterized by essentially no liquid state. Optionally, a direct transition from separate polymer and monomer components to a highly viscous state results from the presence of two or more sub-populations of polymer beads.
As a result of formulations based upon bead sub-populations, a viscosity profile of a cement according to an exemplary embodiment of the invention is significantly different from a viscosity profile of a previously available polymer based cement (e.g. PMMA) with a similar average molecular.
Because the viscosity profile of previously available PMMA cements is typically characterized by a rapid transition from high viscosity to fully hardened, these cements are typically injected into bone in a liquid phase so that they do not harden during injection.
In sharp contrast, exemplary cements according to the invention remain highly viscous during a long working window 114 before they harden. This long working window permits performance of a medical procedure of several minutes duration and imparts the advantages of the high viscosity material to the procedure.
It should be noted that while specific examples are described, it is often the case that the formulation will be varied to achieve particular desired mechanical properties. For example, different diagnoses may suggest different material viscosities which may, in turn lead to adjustment of one or more of MW (average and/or distribution), bead size and bead surface area.
In an exemplary embodiment of the invention, the cement is mixed 112 and reaches high viscosity outside the body. Optionally the materials are mixed under vacuum or ventilated. In this manner, some materials with potentially hazardous by-products can be safely ' mixed and then used in the body.
In an exemplary embodiment of the invention, the cement is formulated so that its mechanical properties match the bone in which it will be injected/implanted.
In an exemplary embodiment of the invention, the cement is formulated to mechanically match healthy or osteoporotic trabecular (cancellous) bone. Optionally, the mechanical properties of the bone are measured during access, for example, based on a resistance to advance or using sensors provided through a cannula or by taking samples, or based on x-ray densitometry measurements. In an exemplary embodiment of the invention, strength of the cement varies as a function of one or more of a size of the high MW sub-population and/or a relationship between bead size and bead MW.
In general, PMMA is stronger and has a higher Young modulus than trabecular bone.
For example, healthy Trabecular bone can have a strength of between 1.5-8.0 mega Pascal and a Young modulus of 60-500 mega Pascal. Cortical bone, for example, has strength values of 65-160 mega Pascal and Young modulus of 12-40 giga Pascal. PMMA typically has values about half of Cortical bone (70-120 mega Pascal strength).
Fig. 2 is a plot of viscosity as a function of time for an exemplary bone cement according to the present invention. The figure is not drawn to scale and is provided to illustrate the principles of exemplary embodiments of the invention. The end of a mixing process is denoted as time 0. Mixing is deemed to end when 95-100% of acrylic polymer beads have been wetted with monomer. The graph illustrates an exemplary bone cement which enters a high viscosity plastic phase upon mixing so that it has substantially no liquid phase.
Fig. 2 illustrates that once a high viscosity is achieved, the viscosity remains relatively stable for 2, optionally 5, optionally 8 minutes or more. In an exemplary embodiment of the invention, this interval of stable viscosity provides a working window 114 (indicated here as Atl) for performance of a medical procedure. In an exemplary embodiment of the invention, stable viscosity means that the viscosity of the cement changes by less than 200 Pascal-second during a window of at least 2 minutes optionally at least 4 minutes after mixing is complete.
Optionally, the window begins 1, 2, 3, 4 or 5 minutes after mixing begins or lesser or intermediate times. In an exemplary embodiment of the invention, the viscosity of the cement remains below 1500, optionally 2000 Pascal-second for at least 4, optionally at least 6, optionally at least 8, optionally at least 10 minutes or intermediate or greater times from onset of mixing.
For purposes of comparison, the graph illustrates that an exemplary prior art cement ' reaches a viscosity comparable to that achieved by an exemplary cement according to the invention at time zero at a time of approximately 10.5 minutes post mixing and is completely set by about 15.5 minutes (Ot2).
A working window 114 during which viscosity is between 400 and 2000 Pascal-second for an exemplary cement according to some embodiments of the invention (At,) is both longer and earlier than a comparable window for an exemplary prior, art cement (At2).
Optionally, (Otl) begins substantially as soon as mixing is complete.
Exemplary cement formulations According to various exemplary embodiments of the invention, changes in the ratios between a powdered polymer component and a liquid monomer component can effect the duration of working window 114 and/or a viscosity of the cement during that window.
Optionally, these ratios are adjusted to achieve desired results.
In an exemplary embodiment of the invention, the powdered polymer component contains PMMA (69.3% w/w); Barium sulfate (30.07% w/w) and Benzoyl peroxide (0.54%
w/w).
In an exemplary embodiment of the invention, the liquid monomer component contains MMA (98.5% v/v); N, N-dimethyl-p-toluidine (DMPT) (1.5% v/v) and Hydroquinone (20 ppm).
In a first exemplary embodiment of the invention, 20 + 0.3 grams of polymer powder and 9 0.3grams of liquid monomer are combined (weight ratio of -2.2:1).
In a second exemplary embodiment of the invention, 20+ 0.3 grams of polymer powder and 8+ 0.3 grams of liquid are combined (weight ratio of 2.5:1).
Under same weight ratio of second exemplary embodiment (2.5:1), a third exemplary embodiment may include a combination of 22.5 0.3 grams of polymer powder and 9 0.3 grams of liquid.
In general, increasing the weight ratio of polymer to monomer produces a cement which reaches a higher viscosity in less time. However, there is a limit beyond which there is not sufficient monomer to wet all of the polymer beads.
Optionally the powdered polymer component may vary in composition and contain PMMA (67-77%, optionally 67.5-71.5% w/w); Barium sulfate (25-35%; optionally 28-32%
w/w) and Benzoyl peroxide (0.4 -0.6 % w/w) and still behave substantially as the powder component recipe set forth above.
Optionally the liquid monomer component may vary in composition and contain Hydroquinone (1-30 ppm; optionally 20-25 ppm) and still behave substantially as the liquid component recipe set forth above.
Viscosity measurements over time for exemplary cements In order to evaluate the viscosity profile of different exemplary batches of cement according to some embodiments of the invention, a bulk of pre-mixed bone cement is placed inside a Stainless Steel injector body. Krause et al. described a method for calculating viscosity in terms of applied force. ("The viscosity of acrylic bone cements", Journal of Biomedical Materials Research, (1982): 16:219-243). This article is fully incorporated herein by reference.
In the experimental apparatus an inner diameter of the injector body is approximately 18 mm. A distal cylindrical outlet has an inner diameter of approximately 3 mm and a length of more than 4 mm. This configuration simulates a connection to standard bone cement delivery cannula/bone access needle. A piston applies force (F), thus causing the bone cement to flow through the outlet. The piston is set to move with constant velocity of approximately 3 mm/min. As a result, piston deflection is indicative of elapsed time.
The experimental procedure serves as a kind of capillary extrusion rheometer.
The rheometer measures the pressure difference from an end to end of the capillary tube. The device is made of an 18 inm cylindrical reservoir and a piston. The distal end of the reservoir consist of 4 mm long 3 mm diameter hole. This procedure employs a small diameter needle and high pressure. Assuming steady flow, isothermal conditions and incompressibility of the tested material, the viscous force resisting the motion of the fluid in the capillary is equal 5 to the applied force acting on the piston measured by a load cell and friction. Results are presented as force vs. displacement. As displacement rate was constant and set to 3 mm/min, the shear rate was constant as well. In order to measure the time elapses from test beginning, the displacement rate is divided by 3(jog speed).
Fig. 3 indicates a viscosity profile of a first exemplary batch of cement according to the 10 invention as force (Newtons) vs. displacement (mm). The cement used in this experiment included a liquid component and a powder component as described above in "Exemplary cement formulations".
In this test (Average temperature: 22.3 C; Relative Humidity: app. 48%) the cement was mixed for 30-60 seconds, then manipulated by hand and placed inside the injector. Force 15 was applied via the piston approximately 150 seconds after end of mixing, and measurements of force and piston deflection were taken.
At a time of 2.5 minutes after mixing (0 mm deflection) the force applied was higher' than 30 N.
At a time of 6.5 minutes after mixing (12 mm deflection) the force applied was about '`
150 N.
At a time of 7.5 minutes after mixing (15 mm deflection) the force applied was higher than 200 N.
At a time of 8.5 minutes after mixing (18 mm deflection) the force applied was higher than 500 N.
At a time of 9.17 minutes after mixing (20 mm deflection) the force applied was higher than 1300 N.
Fig. 4 indicates a viscosity profile of an additional exemplary batch of cement according to the invention as force (Newtons) vs. displacement (mm). The cement in this test was prepared according to the same formula described for the experiment of Fig. 3. In this test (Average 21.1 C; Relative Humidity: app. 43%) the cement was mixed for approximately 45 seconds, then manipulated by hand and placed inside the injector. Force was applied via piston approximately 150 seconds after end of mixing, and measurements of force and piston deflection were taken.
At a time of 2.25 minutes after mixing (0 mm deflection) the force applied was higher than 30 N.
At a time of 8.25 minutes after mixing (18 mm deflection) the force applied was about 90 N.
At a time of 10.3 minutes after mixing (25 mm deflection) the force applied was higher than 150 N.
At a time of 11.4 minutes after mixing (28.5 mm deflection) the force applied was higher than 500 N.
At a time of 12.25 minutes after mixing (30 mm deflection) the force applied was higher than 800 N.
Results shown in Figs. 3 and 4 and summarized hereinabove illustrate that exemplary bone cements according to some embodiments the invention achieve high viscosity in 2.25 minutes or less after mixing is completed. Alternatively or additionally, these cements are characterized by short mixing time (i.e. transition to highly viscous plastic phase in 30 to 60 seconds). The exemplary cements provide a "working window" for injection of 4.5 to 6.3 minutes, optionally longer if more pressure is applied and/or ambient temperatures are lower.
These times correspond to delivery volumes of 14.9 and 20.8 ml respectively (vertebroplasty of a single vertebra typically requires about 5 ml of cement). These volumes are sufficient for most vertebral repair procedures. These results comply with the desired characteristics described in Fig. 2. Differences between the two experiments may reflect the influence of temperature and humidity on reaction kinetics.
Molecular weight distribution In an exemplary embodiment of the invention, the average molecular weight (MW) is skewed by the presence of one or more small sub-population of beads with a molecular weight which is significantly different from a main sub-population of polymer beads.
The one or more small sub-population of beads may have a MW which is significantly higher and/or significantly lower than the average MW.
In an exemplary embodiment of the invention, the presence of even a relatively small sub-population of polymer beads with a MW significantly above the average MW
causes the cement to achieve a high viscosity in a short time after wetting of polymer beads with monomer solution. Optionally, increasing a size of the high MW sub-population increases the achieved viscosity. Alternatively or additionally, increasing an average MW of the high MW
sub-population increases the achieved viscosity and/or decreases the time to reach high viscosity.
Optionally, the one or more small sub- population of beads are provided in a formulation in which, the average molecular weight of PMMA in all beads is 80,000, optionally 100,000, optionally 120,000, optionally 140,000, optionally 160,000, optionally 180,000, optionally, 250,000, optionally 325,000, optionally 375.000, optionally 400,000, optionally 500,000 Dalton or intermediate or lesser or greater values.
In another exemplary embodiment of the invention, the average molecular weight of the acrylic polymer in the beads is in the range of about 130,000 to 170,000, optionally about 160,000 Dalton.
In an exemplary embodiment of the invention, a main sub-population of PMMA
beads has a MW of about 150,000 Dalton to about 500,000 Dalton, optionally about 250,000 Dalton to about 300,000 Dalton, optionally about 275,000 Dalton to about 280,000 Dalton. Optionally, about 90-98% [w/w], optionally about 93% to 98%, optionally about 95% to 97%
of the beads belong to the main sub-population.
In an exemplary embodiment of the invention, a second high MW sub-population of PMMA beads has a MW of about 600,000 Dalton, to about 5,000,000 Dalton, optionally about 3,000,000 Dalton to about 4,000,000 Dalton, Optionally about 3,500,000 Dalton to about 3,900,000 Dalton. Optionally, approximately 0.25% to 5% [w/w], optionally about 1% to 4%, optionally about 2% to 3% of the beads belong to this high MW sub-population.
Optionally, this high molecular weight sub-population comprises a styrene co-polymer. In an exemplary embodiment of the invention, a higher molecular weight in this sub-population of beads -contributes to a high viscosity within 2, optionally within 1, optionally within 0.5 minutes or less of wetting of polymer beads with monomer solution.
In an exemplary embodiment of the invention, a third low MW sub-population of PMMA beads has a MW in the range of about 1,000 Dalton to about 75,000 Dalton, optionally about 10,000 Dalton to about 15,000 Dalton, optionally about 11,000 Dalton to about 13,000 Dalton. Optionally, approximately 0.5 to 2.0% [w/w], optionally about 1% of the beads belong to this sub-population.
Optionally the MW sub-populations are distinct from one another. This can cause gaps between sub-populations with respect to one or more parameters. In an exemplary embodiment of the invention, the sub-populations are represented as distinct peaks in a chromatographic separation process. Optionally, the peaks are separated by a return to baseline. Depending upon the sensitivity of detection, a background level of noise may be present.
Optionally, gaps are measured relative to the noise level.
Optionally the sub-populations abut one another so that no gaps are apparent.
In an exemplary embodiment of the invention, the sub-populations are represented as overlapping peaks in a chromatographic separation process. In this case, there is no return to baseline between the peaks.
Experimental analysis of an exemplary batch of cement Sub-populations characterized by an average molecular weight were identified and quantitated using chromatographic techniques known in the art. Exemplary results described herein are based upon GPC analysis. Each peak in the GPC analysis is considered a sub-population. Similar analyses may be conducted using HPLC. Results are summarized in table 1.
Table 1: MW distribution of polymer beads based upon GPC analysis of a bone cement according to the powdered polymer component described in "Exemplary cement formulations"
hereinabove.
Fraction % of total PDI Mw Mn 1 96.5 1.957 278,986 142,547 2 2.5 1.048 3,781,414 3,608,941 3 1.0 1.009 12,357 12,245 100.0 2.955 373,046 126,248 1 polydispersity index (PDI), is a measure of the distribution of molecular weights in a given polymer sample and is equal to MW/Mn..
2 MW is the weight average molecular weight in Daltons 3 Mn is the number average molecular weight in Daltons Table I illustrates an exemplary embodiment of the invention with three sub-populations of acrylic polymer beads.
The main sub-population (fraction 1) of PMMA beads has a molecular weight (MW) of 278,986 Dalton. About 96.5% of the beads belong to this sub-population.
A second sub-population (fraction 2) of PMMA beads has MW of 3,781,414 Dalton.
Approximately 2.5% of the beads belong to this sub-population.
A third sub-population of PMMA beads (fraction 3) has an MW of 12,357 Dalton.
Approximately I% of the beads belong to this sub-population.
In an exemplary embodiment of the invention, cement comprising these three sub-populations is characterized by a short mixing time and/or achieves a viscosity of 500 to 900 Pascal-second in 0.5 to 3, optionally 0.5 to 1.5 minutes from the beginning of mixing and/or which remains below 2000 Pascal-second for at least 6 to 10 minutes after mixing. A short mixing time followed by a long working window is considered advantageous in orthopedic procedures where operating room availability and medical staff are at a premium.
Size Distribution In an exemplary embodiment of the invention, the bone cement is characterized by beads with a size distribution including at least two sub-populations of polymer beads.
In an exemplary embodiment of the invention, polymer bead diameter is in the range of 10-250 microns, with a mean value of approximately 25, 30, 40, 50, 60 microns, or a lower or a higher or an intermediate diameter. In an exemplary embodiment of the invention, sub-populations of beads are defined by their size.
Optionally, a main sub-population of polymer (e.g. PMMA) beads is characterized by a diameter of about 20 to about 150, optionally about 25 to about 35, optionally an average of about 30 microns. Beads in this main sub-population are optionally far smaller than the smallest beads employed by Hernandez et al. (2005; as cited above). Presence of small beads can contribute to a rapid increase in viscosity after wetting with monomer.
Optionally a second sub-population of large polymer beads is characterized by a diameter of about 150 microns or more. Presence of large beads can slow down the polymerization reaction and prevent hardening, contributing to a long working window.
Optionally, the remaining beads are characterized by a very small average diameter, for example less than 20, optionally less than 15, optionally about 10 microns or less. Presence of very small beads can facilitate rapid wetting with monomer liquid during mixing and contribute to a fast transition to a viscous state with substantially no liquid phase.
Microscopic analysis indicates that the beads are typically spherical or spheroid.
Hernandez et al. (2005; as cited above) examined the possibility of adjusting the average polymer bead size by combining two types of beads with average sizes of 118.4 (Colacry) and 69.7 (Plexigum) together in different ratios. However, Hernandez's goal was a formulation which is "liquid enough to be injected". All formulations described by Hernandez are characterized by an increase in viscosity from 500 Pascal-sec to 2000 Pascal-sec in about two minutes or less (corresponds to window 114). Hernandez does not hint or suggest that there is any necessity or advantage to increasing the size of this window.
Microscopic analysis also indicated that the barium sulfate particles are present as elongate amorphous masses with a length of approximately 1 micron. In some cases aggregates of up to 70 microns in size were observed. In some cases, barium sulfate particles and polymer beads aggregated together. Optionally, aggregates of Barium sulfate and polymer beads can delay wetting of polymer beads by monomer.
In an exemplary embodiment of the invention, MMA solvates and/or encapsulates the PMMA polymer beads and the viscosity of the initial mixture is high due to the solvation and/or friction between the beads. As the beads dissolve viscosity remains high due to polymerization which increases the average polymer MW.
The following table II shows an exemplary particle size distribution, for example, one suitable for the cement of Table I, based on an analysis of particles within the ranges of 0.375-5 2000 microns:
Table II: Particles size distribution of an exemplary powdered component Vol. % 10 25 50 75 90 Max Beads 2.3 25.75 45.07 60.68 76.34 Diameter [microns]
Experimental analysis of a second exemplary batch of cement Another example of a cement kit for mixture includes a liquid and a powder, which 10 includes a mass of acrylic polymer beads. This cement kit is formulated as follows:
(a) liquid (9.2 gr) (i) Methylmethacrylate (MMA) 98.5% (vol) (ii) N,N-dimethyl-p-toluidine 1.5% (vol) (iii) Hydroquinone 20ppm (vol) 15 (b) powder (20 gr) (i) Polymethylmethacrylate (PMMA) 69.39% (weight) (ii) Barium Sulfate 30.07% (weight) (iii) Benzoyl Peroxide 0.54% (weight) As noted above, in other formulations the amounts may be varied, for example, to 20 achieve specific mechanical (or other) properties, or they may be varied and achieve same mechanical properties. In another variation, medication may be added to the powder and/or liquid phases. Other liquid phases may be used as well, for example, as known in the art for PMMA-type cements. The ratios may be varied, for example, as described above.
Table III summarizes a molecular weight distribution of the acrylic bead component of this exemplary cement. It is hypothesized that providing a non-normal distribution of molecular weights with a heavier molecular weight component (e.g., by skewing the MW
distribution by including relatively higher molecular weight beads) provides an increased immediate viscosity. In an exemplary embodiment of the invention, the higher MW beads are in a relatively small amount (for example, less than 20%, less than 10%, less than 5%) and have a MW of between 500,000 to 2,000,000 Dalton, optionally 600,000 to 1,200,000 Dalton (for example as shown in the table below).
Table III: MW distribution of polymer beads of a bone cement of the second exemplary batch Range of Molecular Weights [Dalton] % of total 1,000,000-2,000,000 0.38%
500,000-1,000,000 3.6%
250,000-500,000 12.4%
100,000-250,000 36.4%
50,000-100,000 26.6%
25,000-50,000 14.2%
10,000-25,000 5.3%
8,000-10,000 0.5%
5,000-8,000 0.4%
In an exemplary embodiment of the invention, the bone cement is characterized by beads with a size distribution including at least two sub-populations of different materials.
Optionally, at least two sub-populations include polymer (e.g. PMMA) beads and Barium Sulfate particles. Optionally, the range of particles diameter of the Barium Sulfate is 0.01-15 microns, optionally 0.3 to 3 microns, optionally with an average of about 0.5 microns or lesser or intermediate or greater sizes.
In an exemplary embodiment of the invention, polymer bead diameter is in the range of 10-250 microns, optionally 15-150 microns, with a mean value of approximately 25, 30, 40, 50, 60 microns. Lower or a higher or intermediate diameters are possible as well, for example, based on the setting considerations described above. In some cases, large particle sizes, for example, particles having diameters exceeding 120 microns (e.g., when the average diameter is on the order of 60 microns) are the result of Barium sulfate primary particle aggregation on, PMMA particle beads.
An exemplary distribution of bead sizes for the exemplary cement of table III, based on.`
an analysis of particles within the range of 0.04-2000 microns, is described in Table IV:
Table IV: Particles size distribution of a second exemplary powdered component of bone cement Vol. % 10 25 50 75 90 Max Beads 2 9 46.5 70.7 90.5 Diameter [microns]
Fig. 5 is a graph which visually shows the values of table IV
Size and MW are independent variables In an exemplary embodiment of the invention, size based and MW based sub-populations are determined independently. For example, MW may be determined chromatographically and size may be determined by microscopic analysis. As a result, beads classed in a single size sub-population may be classed in two or more MW sub-populations and/or beads classed in a single MW sub-population may be classed in two or more size sub-populations.
Mechanical viscosity increasing agents In an exemplary embodiment of the invention, the cement includes particles characterized by a large surface which do not participate in the polymerization reaction. The large surface area particles can impart added viscosity to the cement mixture independent of polymerization. Optionally, the added viscosity comes from friction of particles against one another in the cement.
Examples of materials which do not participate in the polymerization reaction but increase viscosity include, but are not limited to Zirconium, hardened acrylic polymer, barium sulfate and bone.
Optionally, materials which do not participate in the polymerization reaction but increase viscosity can at least partially substitute for high MW polymers in influencing a viscosity profile.
Desired Polymerization Reaction Kinetics In an exemplary embodiment of the invention, mixture of polymer and monomer produces a high viscosity mixture with substantially no intervening liquid phase within 180, optionally within 120, optionally within 100, optionally within 60, optionally within 30, optionally within 15 seconds or greater or intermediate times from onset of mixing. =
In an exemplary embodiment of the invention, once a high viscosity is achieved, the viscosity remains stable for 5 minutes, optionally 8 minutes, optionally 10 minutes or lesser`or intermediate or greater times. Optionally, stable viscosity indicates a change of 10% or less in two minutes and/or a change of 20% or less in 8 minutes. The time during which viscosity is stable provides a working window for performance of a medical procedure.
These desired reaction kinetics can be achieved by adjusting one or more of average polymer MW, polymer MW distribution, polymer to monomer ratio and polymer bead size and/or size distribution.
General considerations In an exemplary embodiment of the invention, a powdered polymer component and a liquid monomer component are provided as a kit. Optionally, the kit includes instructions for use. Optionally, the instructions for use specify different proportions of powder and liquid for different desired polymerization reaction kinetics.
In an exemplary embodiment of the invention, a bone cement kit including at least two, optionally three or more separately packaged sub-populations of beads and a monomer liquid is provided. Optionally, the kit includes a table which provides formulations based on combinations of different amounts of bead sub-populations and monomer to achieve desired properties.
It is common practice in formulation of acrylic polymer cements to include an initiator (e.g. benzoyl peroxide; BPO) in the powdered polymer component and/or a chemical activator (e.g. DMPT) into the liquid monomer component. These components can optionally be added to formulations according to exemplary embodiments of the invention without detracting from the desired properties of the cement.
Optionally, an easily oxidized molecule (e.g. hydroquinone) is added to the liquid component to prevent spontaneous polymerization during storage (stabilizer).
The hydroquinone can be oxidized during storage.
Optionally, cement may be rendered radio-opaque, for example by adding a radio-opaque material such as barium sulfate and/or zirconium compounds and/or bone (e.g. chips or powder) to the powder and/or liquid component.
While the above description has focused on the spine, other tissue can be treated as well, for example, compacted tibia plate and other bones with compression fractures and for fixation of implants, for example, hip implants or other bone implants that loosened, or during implantation. Optionally, for tightening an existing implant, a small hole is drilled to a location where there is a void in the bone and material is extruded into the void. .
It should be noted that while use of the disclosed material as bone cement is described;
non-bone tissue may optionally be treated. For example, cartilage or soft tissue in need of tightening may be injected with a high viscosity polymeric mixture.
Optionally, the delivered material includes an encapsulated pharmaceutical and is used as a matrix to slowly release the pharmaceutical over time. Optionally, this is used as a means to provide anti-arthritis drugs to a joint, by forming a void and implanting an eluting material near the joint.
It should be noted that while use of PMMA has been described, a wide variety of materials can be suitable for use in formulating cements with viscosity characteristics as described above. Optionally, other polymers could be employed by considering polymer molecular weight (average and/or distribution) and/or bead size as described above. Optionally, at least some of the beads include styrene. In an exemplary embodiment of the invention, styrene is added to MMA beads in a volumetric ratio of 5-25%. Optionally, addition of styrene increases creep resistance.
According to various embodiments of the invention, a bone cement according to the invention is injected into a bone void as a preventive therapy and/or as a treatment for a fracture, deformity, deficiency or other abnormality. Optionally, the bone is a vertebral body and/or a long bone. In an exemplary embodiment of the invention, the cement is inserted into the medullary canal of a long bone. Optionally, the cement is molded into a rod prior to or during placement into the bone. In an exemplary embodiment of the invention, the rod serves as an intra-medular nail.
Exemplary Characterization Tools Molecular weight and polydispersity can be analyzed, for example by Gel permeation chromatography(GPC) system (e.g. Waters 1515 isocratic HPLC pump with a Waters refractive-index detector and a Rheodyne (Coatati, CA) injection valve with a 20- L loop (Waters Ma)). Elution of samples with CHC13 through a linear Ultrastyragel column (Waters;
500-A pore size) at a flow rate of 1 ml/min provides satisfactory results.
It will be appreciated that various tradeoffs may be desirable, for example, between available injection force, viscosity, degree of resistance and forces that can be withstood (e.g.
by bone or injection tools). In addition, a multiplicity of various features, both of method and of cement formulation have been described. It should be appreciated that different features may be combined in different ways. In particular, not all the features shown above in a particular embodiment are necessary in every similar exemplary embodiment of the invention. Further, combinations of the above features are also considered to be within the scope of some exemplary embodiments of the invention. In addition, some of the features of the invention described herein may be adapted for use with prior art devices, in accordance with other exemplary embodiments of the invention.
Section headers are provided only to assist in navigating the application and should not be construed as necessarily limiting the contents described in a certain section, to that section.
Measurements are provided to serve only as exemplary measurements for particular cases, the exact measurements applied will vary depending on the application. When used in the following claims, the terms "comprises", "comprising", "includes", "including"
or the like means "including but not limited to".
It will be appreciated by a person skilled in the art that the present invention is not limited by what has thus far been described. Rather, the scope of the present invention is limited only by the following claims.
Claims (35)
1. A bone cement comprising an acrylic polymer mixture, the cement characterized in that it achieves a viscosity of at least 500 Pascal-second within 180 seconds following initiation of mixing of a monomer component and a polymer component and characterized by sufficient biocompatibility to permit in-vivo use.
2. A bone cement according to claim 1, wherein the viscosity of the mixture remains between 500 and 2000 Pascal-second for a working window of at least 5 minutes after the initial period.
3. A bone cement according to claim 2, wherein the working window is at least 8 minutes long.
4. A bone cement according to claim 1, wherein the mixture includes PMMA.
5. A bone cement according to claim 1, wherein the mixture includes Barium Sulfate.
6. A bone cement according to claim 4, wherein the PMMA is provided as a PMMA/styrene copolymer.
7. A bone cement according to claim 4, wherein the PMMA is provided as a population of beads divided into at least two sub-populations, each sub-population characterized by an average molecular weight.
8. A bone cement according to claim 7, wherein a largest sub-population of PMMA beads is characterized by an MW of 150,000 Dalton to 300,000 Dalton.
9. A bone cement according to claim 7, wherein a largest sub-population of PMMA beads includes 90-98% (w/w) of the beads.
10. A bone cement according to claim 7, wherein a high molecular weight sub-population of PMMA beads is characterized by an average MW of at least 3,000,000 Dalton.
11. A bone cement according to claim 7, wherein a high molecular weight sub-population of PMMA beads includes 2 to 3% (w/w) of the beads.
12. A bone cement according to claim 7, wherein a low molecular weight sub-population of PMMA beads is characterized by an average MW of less than 15,000 Dalton.
13. A bone cement according to claim 7, wherein a low molecular weight sub-population of PMMA beads includes 0.75 to 1.5 % (W/W) of the beads.
14. A bone cement according to claim 4, wherein the PMMA is provided as a population of beads divided into at least two sub-populations, each sub-population characterized by an average bead diameter.
15. A bone cement according to claim 14, wherein at least one bead sub-population of characterized by an average diameter is further divided into at least two sub-sub-populations, each sub-sub-population characterized by an average molecular weight.
16. A bone cement according to claim 14, wherein the PMMA is provided as a population of beads divided into at least three sub-populations, each sub-population characterized by an.
average bead diameter.
average bead diameter.
17. A bone cement according to claim 1, further comprising processed bone and/or synthetic bone.
18. A bone cement according to claim 1, characterized in that the cement achieves a viscosity of at least 500 Pascal-second when 100% of a polymer component is wetted by a monomer component.
19. A bone cement according to claim 1, wherein the viscosity is at least 800 Pascal-second.
20. A bone cement according to claim 1, wherein the viscosity is at least 1500 Pascal-second.
21. A bone cement according to claim 1, wherein the viscosity is achieved within 2 minutes.
22. A bone cement according to claim 1, wherein the viscosity is achieved within 1 minute.
23. A bone cement according to claim 1, wherein the viscosity is achieved within 45 seconds.
24. A bone cement comprising:
a polymer component; and a monomer component;
wherein contacting the polymer component and the monomer component produces a mixture which attains a viscosity greater than 200 Pascal-second within 1 minute from onset of mixing and remains below 2000 Pascal-second until at least 6 minutes from onset of mixing.
a polymer component; and a monomer component;
wherein contacting the polymer component and the monomer component produces a mixture which attains a viscosity greater than 200 Pascal-second within 1 minute from onset of mixing and remains below 2000 Pascal-second until at least 6 minutes from onset of mixing.
25. A bone cement according to claim 24, wherein the polymer component comprises an acrylic polymer.
26. A particulate mixture formulated for preparation of a bone cement, the mixture comprising:
(a) 60 to 80% polymer beads comprising a main sub-population characterized by an MW
of 150,000 Dalton to 300,000 Dalton and a high molecular weight sub-population characterized by an MW of 3,000,000 Dalton to 4,000,000 Dalton; and (b) 20 to 40% of a material which is non-transparent with respect to X-ray.
(a) 60 to 80% polymer beads comprising a main sub-population characterized by an MW
of 150,000 Dalton to 300,000 Dalton and a high molecular weight sub-population characterized by an MW of 3,000,000 Dalton to 4,000,000 Dalton; and (b) 20 to 40% of a material which is non-transparent with respect to X-ray.
27. A mixture according to claim 26, wherein the polymer beads comprise a third subpopulation characterized by an MW of 10,000 Dalton to 15,000 Dalton.
28. A method of making a polymeric bone cement, the method comprising:
(a) defining a viscosity profile including a rapid transition to a working window characterized by a high viscosity;
(b) selecting a polymer component and a monomer component to produce a cement conforming to the viscosity profile; and (c) mixing the polymer component and a monomer component to produce a cement which conforms to the viscosity profile.
(a) defining a viscosity profile including a rapid transition to a working window characterized by a high viscosity;
(b) selecting a polymer component and a monomer component to produce a cement conforming to the viscosity profile; and (c) mixing the polymer component and a monomer component to produce a cement which conforms to the viscosity profile.
29. A cement kit, comprising:
(a) a liquid component including a monomer; and (b) a powder component including polymeric beads, characterized in that said powder component is provided in a substantially non-normal distribution of at least one of molecular weight of the polymeric beads and size of powder particles such that a cement mixed from the kit has both an increased immediate viscosity and an increased working window as compared to a cement having a substantially normal distribution.
(a) a liquid component including a monomer; and (b) a powder component including polymeric beads, characterized in that said powder component is provided in a substantially non-normal distribution of at least one of molecular weight of the polymeric beads and size of powder particles such that a cement mixed from the kit has both an increased immediate viscosity and an increased working window as compared to a cement having a substantially normal distribution.
30. A cement kit according to claim 29, wherein said substantially non-normal distribution is a skewed distribution.
31. A cement kit according to claim 29, wherein said substantially non-normal distribution comprises a relatively small component including higher molecular weight beads.
32. A cement kit according to claim 31, wherein said component has an average molecular weight of at least a factor of 2 of an average molecular weight of said polymeric beads.
33. A cement kit according to claim 32, wherein said factor is at least 3.
34. A cement kit according to claim 32, wherein said factor is at least 5.
35. A cement kit according to claim 29, wherein said substantially non-normal distribution comprises a relatively small component including smaller sized particles.
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Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7621950B1 (en) | 1999-01-27 | 2009-11-24 | Kyphon Sarl | Expandable intervertebral spacer |
US20060264967A1 (en) | 2003-03-14 | 2006-11-23 | Ferreyro Roque H | Hydraulic device for the injection of bone cement in percutaneous vertebroplasty |
US8066713B2 (en) | 2003-03-31 | 2011-11-29 | Depuy Spine, Inc. | Remotely-activated vertebroplasty injection device |
US8415407B2 (en) | 2004-03-21 | 2013-04-09 | Depuy Spine, Inc. | Methods, materials, and apparatus for treating bone and other tissue |
WO2006011152A2 (en) | 2004-06-17 | 2006-02-02 | Disc-O-Tech Medical Technologies, Ltd. | Methods for treating bone and other tissue |
US8579908B2 (en) | 2003-09-26 | 2013-11-12 | DePuy Synthes Products, LLC. | Device for delivering viscous material |
US9381024B2 (en) | 2005-07-31 | 2016-07-05 | DePuy Synthes Products, Inc. | Marked tools |
US9918767B2 (en) | 2005-08-01 | 2018-03-20 | DePuy Synthes Products, Inc. | Temperature control system |
US8777479B2 (en) | 2008-10-13 | 2014-07-15 | Dfine, Inc. | System for use in bone cement preparation and delivery |
US8540723B2 (en) * | 2009-04-14 | 2013-09-24 | Dfine, Inc. | Medical system and method of use |
US8562620B2 (en) * | 2008-04-21 | 2013-10-22 | Dfine, Inc. | Bone treatment systems |
US8360629B2 (en) | 2005-11-22 | 2013-01-29 | Depuy Spine, Inc. | Mixing apparatus having central and planetary mixing elements |
US9642932B2 (en) | 2006-09-14 | 2017-05-09 | DePuy Synthes Products, Inc. | Bone cement and methods of use thereof |
WO2008047371A2 (en) | 2006-10-19 | 2008-04-24 | Depuy Spine, Inc. | Fluid delivery system |
WO2008137428A2 (en) | 2007-04-30 | 2008-11-13 | Dfine, Inc. | Bone treatment systems and methods |
WO2009035165A1 (en) * | 2007-09-13 | 2009-03-19 | Sun Medical Co., Ltd. | Dental polymerizable composition and kit therefor |
US9161798B2 (en) * | 2008-02-01 | 2015-10-20 | Dfine, Inc. | Bone treatment systems and methods |
US9180416B2 (en) | 2008-04-21 | 2015-11-10 | Dfine, Inc. | System for use in bone cement preparation and delivery |
TWI506078B (en) | 2008-08-14 | 2015-11-01 | Lucite Int Uk Ltd | A hardenable two part acrylic composition |
WO2010098305A1 (en) * | 2009-02-25 | 2010-09-02 | 国立大学法人京都大学 | Bone cement composition, bone cement composition kit, and method for forming bone cement cured body |
CA2789793C (en) * | 2010-03-05 | 2019-01-15 | Synthes Usa, Llc | Bone cement system for bone augmentation |
US20130072941A1 (en) | 2011-09-16 | 2013-03-21 | Francisca Tan-Malecki | Cement Injector and Cement Injector Connectors, and Bone Cement Injector Assembly |
US8834772B2 (en) | 2011-12-07 | 2014-09-16 | Biomet Manufacturing, Llc | Antimicrobial methacrylate cements |
DE102012001637A1 (en) * | 2012-01-30 | 2013-08-01 | Heraeus Medical Gmbh | Pasty bone cement |
DE102012022134A1 (en) | 2012-11-13 | 2014-05-15 | Heraeus Medical Gmbh | Polymethylmethacrylate bone cement |
US9707314B2 (en) * | 2014-03-26 | 2017-07-18 | DePuy Synthes Products, Inc. | Acrylic bone cement having a delayed release polymerization inhibitor such as an anti-oxidant for increased working time |
DE102015217315A1 (en) * | 2015-09-10 | 2017-03-16 | Heraeus Medical Gmbh | Adjustable initial viscosity polymethyl methacrylate bone cement and a method of making a variable initial viscosity bone cement dough |
TWI646987B (en) * | 2016-12-08 | 2019-01-11 | 國立陽明大學 | Negative pressure guided bone cement injection system |
US11013543B2 (en) * | 2018-05-24 | 2021-05-25 | Medtronic Holding Company Sarl | Method of performing a balloon kyphoplasty procedure using a scoop cannula |
Family Cites Families (807)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US370335A (en) | 1887-09-20 | Mixing-machine | ||
US229932A (en) | 1880-07-13 | witsil | ||
GB179502045A (en) | Bramah Joseph | Obtaining and Applying Motive Power. | ||
US408668A (en) | 1889-08-06 | Island | ||
DE226956C (en) | ||||
DE136018C (en) | ||||
DE293485C (en) | 1900-01-01 | |||
GB190408331A (en) | 1904-02-23 | 1905-03-16 | Marc Lucien Jacques Lagarde | Improvements relating to Syringes for the Injection of Plastic Substances |
US817973A (en) | 1904-06-06 | 1906-04-17 | Caspar Friedrich Hausmann | Uterine dilator. |
US843587A (en) | 1906-01-29 | 1907-02-12 | Henry Hannon De Pew | Surgical instrument. |
US833044A (en) | 1906-03-13 | 1906-10-09 | Claudius Ash Sons & Company 1905 Ltd | Dental instrument. |
GB190720207A (en) | 1907-09-10 | 1908-06-25 | Karl Krautschneider | Medical Apparatus for Injecting Purposes. |
US1175530A (en) | 1913-04-28 | 1916-03-14 | American Bakers Machinery Company | Cake-mixer. |
US1612281A (en) | 1922-11-14 | 1926-12-28 | Columbia Metal Products Compan | Mixing apparatus |
US1612996A (en) | 1926-02-23 | 1927-01-04 | Waagbo Herman | Cream-testing device |
US1733516A (en) | 1928-12-03 | 1929-10-29 | Charles F Rodin | Agitator |
US1894274A (en) | 1930-08-22 | 1933-01-17 | Raynaldo P Jacques | Lubricating apparatus |
US1929247A (en) | 1931-01-20 | 1933-10-03 | George N Hein | Syringe equipment and apparatus |
GB408668A (en) | 1932-10-12 | 1934-04-12 | Cecil Roberts Norman | Improvements in and relating to wall plugs and similar fastening devices |
US2067458A (en) | 1934-07-13 | 1937-01-12 | Nat Rubber Machinery Co | Rubber mixing mill |
US2123712A (en) | 1935-04-29 | 1938-07-12 | Lubrication Corp | Lubricating device |
US2234558A (en) | 1936-11-13 | 1941-03-11 | Huston Tom | Combined dispensing and applying device |
GB486638A (en) | 1937-09-07 | 1938-06-08 | Heinrich Hagemeier | Improvements in dental syringes |
US2193517A (en) | 1938-02-10 | 1940-03-12 | Lindstrom Bengt | Closing means for tubes, bottles, or other containers |
US2283915A (en) | 1938-12-01 | 1942-05-26 | Samuel F Cole | Syringe |
US2362523A (en) | 1942-10-02 | 1944-11-14 | Cutter Lab | Suspension member |
US2394488A (en) | 1943-05-07 | 1946-02-05 | Lincoln Eng Co | Lubricating apparatus |
GB586638A (en) | 1944-04-20 | 1947-03-26 | Jicwood Ltd | Improved method of glueing or uniting the laminae of laminated articles |
US2435647A (en) | 1945-02-21 | 1948-02-10 | Martin O Engseth | Grease gun |
US2521569A (en) | 1945-07-27 | 1950-09-05 | Ernest W Davis | Lubricant compressor |
US2425867A (en) | 1945-09-20 | 1947-08-19 | Ernest W Davis | Lubricating apparatus |
US2497762A (en) | 1945-10-04 | 1950-02-14 | Ernest W Davis | Lubrication gun |
US2577780A (en) | 1950-05-09 | 1951-12-11 | Compule Corp | Crowned cupped resilient plug for cylindrical passages |
US2567960A (en) | 1949-10-03 | 1951-09-18 | William R Myers | Plastic extrusion gun |
US2745575A (en) | 1951-10-15 | 1956-05-15 | Alvin C Spencer | Printing ink holder and dispenser, including a cylindrical container and piston |
DE868497C (en) | 1951-11-18 | 1953-02-26 | Robert Schoettle K G | Motor-driven small kitchen machine |
DE1075561B (en) | 1953-09-15 | 1960-02-18 | zugl | Mixing and kneading machine |
US2773500A (en) | 1955-01-26 | 1956-12-11 | Harold S Young | Intraosseous fluid injection instrument |
US2874877A (en) | 1956-09-11 | 1959-02-24 | Alvin C Spencer | Dispensing device and container therefor |
US2918841A (en) | 1956-11-01 | 1959-12-29 | Illinois Tool Works | Blind fastener formed of plastic and containing longitudinal slots which permit rosette type of distortion of shank |
AT202407B (en) | 1957-08-02 | 1959-03-10 | Vertriebs Ges Ing Wagner | High pressure gun for grease and oil |
US3075746A (en) | 1958-07-10 | 1963-01-29 | Baker Perkins Inc | Mixer for explosive materials |
US3058413A (en) | 1959-09-26 | 1962-10-16 | Carle & Montanari Spa | Roller or trough machine for the final working up of chocolate |
US2970773A (en) | 1959-10-19 | 1961-02-07 | Minnesota Mining & Mfg | Fluid mixing and applying apparatus and method |
US3108593A (en) | 1961-03-13 | 1963-10-29 | Jacob A Glassman | Surgical extractor |
US3063449A (en) | 1961-05-23 | 1962-11-13 | Arthur R P Schultz | Syringe holder |
US3224744A (en) | 1962-03-19 | 1965-12-21 | Day J H Co | Vertical mixer construction |
US3151847A (en) | 1962-03-19 | 1964-10-06 | Day J H Co | Vertical mixer construction |
US3225760A (en) | 1962-11-14 | 1965-12-28 | Orthopaedic Specialties Corp | Apparatus for treatment of bone fracture |
US3198194A (en) | 1963-05-13 | 1965-08-03 | Upjohn Co | Admixing storage container with means preventing inadvertent removal of closure means |
US3216616A (en) | 1964-03-02 | 1965-11-09 | Jr Homer Blankenship | Syringe with upper and lower bores |
US3362793A (en) | 1964-06-17 | 1968-01-09 | Michelin & Cie | Back flow-preventing reactor for continuous polymerization |
US3254494A (en) | 1964-11-10 | 1966-06-07 | E H Sargent & Co | Temperature control apparatus |
US3381566A (en) | 1966-05-06 | 1968-05-07 | La Roy B. Passer | Hollow wall anchor bolt |
US3426364A (en) | 1966-08-25 | 1969-02-11 | Colorado State Univ Research F | Prosthetic appliance for replacing one or more natural vertebrae |
DE1283448B (en) | 1967-03-06 | 1968-11-21 | Bauknecht Gmbh G | Power-driven turntable for kitchen machines |
FR1528920A (en) | 1967-05-05 | 1968-06-14 | Multi-capacity cartridge for conditioning pre-dosed substances | |
FR1548575A (en) | 1967-10-25 | 1968-12-06 | ||
US3515873A (en) | 1968-01-11 | 1970-06-02 | Univ Of Kentucky Research Foun | Method and apparatus for analyzing and calibrating radiation beams of x-ray generators |
DE1992767U (en) | 1968-03-27 | 1968-08-29 | Peter Dr Pogacar | DEVICE FOR FINE DOSING AND INTRODUCTION OF LIQUIDS FOR ANALYTICAL OR TREATMENT PURPOSES INTO ANOTHER MEDIUM. |
US3559956A (en) | 1968-05-27 | 1971-02-02 | Du Pont | Planetary gear mixer |
DE1810799A1 (en) | 1968-11-25 | 1970-06-04 | Dr Med Gerhard Metz | Compression medullary nail for pressure osteosynthesis |
CH508202A (en) | 1969-02-26 | 1971-05-31 | Micromedic Systems Inc | Ratchet mechanism for driving a rotating member and use of this mechanism |
DK125488B (en) | 1969-05-30 | 1973-02-26 | L Mortensen | Tubular expansion dowel body or similar fastener and method of making the same. |
US3568885A (en) | 1969-07-30 | 1971-03-09 | Nasa | Thickness measuring and injection device |
US3605745A (en) | 1969-12-15 | 1971-09-20 | Milton Hodosh | Dental injection apparatus |
US3701350A (en) | 1970-07-28 | 1972-10-31 | Harvey C Guenther | Blood exchanging apparatus and process |
US3674011A (en) | 1971-01-12 | 1972-07-04 | United Medical Lab Inc | Means for and method of transfering blood from a patient to multiple test tubes within a vacuum |
SE391122B (en) | 1971-01-25 | 1977-02-07 | Cutter Lab | PROTESTS IN THE FORM OF A SPINE BONIC DISC AND PROCEDURES FOR MANUFACTURE THEREOF |
US3750667A (en) | 1972-01-31 | 1973-08-07 | N Pshenichny | Device for intraosseous injection of liquid substances |
US3789727A (en) | 1972-06-05 | 1974-02-05 | Eaton Corp | Fastener |
US3901408A (en) | 1972-06-07 | 1975-08-26 | Bayer Ag | Machine including means for independently adjusting the dose of two reactive, flowable components into a mixing chamber |
DE7235643U (en) | 1972-09-28 | 1974-06-27 | Fischer A | Femoral head prosthesis |
DE2250501C3 (en) | 1972-10-14 | 1975-04-30 | Artur 7241 Tumlingen Fischer | Fixing means for the socket of a hip joint prosthesis |
US3798982A (en) | 1973-04-25 | 1974-03-26 | Origo | Pump actuator including rotatable cams |
US3850158A (en) | 1973-07-09 | 1974-11-26 | E Elias | Bone biopsy instrument and method |
US3931914A (en) | 1973-07-10 | 1976-01-13 | Max Kabushiki Kaisha | Powder ejector |
US3921858A (en) | 1973-11-05 | 1975-11-25 | Robert A Bemm | Automatic confection decorating system |
SE7406449L (en) | 1974-01-08 | 1975-07-09 | Kettenbach Fab Chem A | |
CA1021767A (en) | 1974-01-11 | 1977-11-29 | Samuel J. Popeil | Orbital whipper having rotatable beaters |
US4115346A (en) | 1974-02-12 | 1978-09-19 | Kulzer & Co. Gmbh | Hydroxy group containing diesters of acrylic acids and their use in dental material |
CH581988A5 (en) | 1974-04-09 | 1976-11-30 | Messerschmitt Boelkow Blohm | |
US3875595A (en) | 1974-04-15 | 1975-04-08 | Edward C Froning | Intervertebral disc prosthesis and instruments for locating same |
CH611150A5 (en) | 1975-04-18 | 1979-05-31 | Sulzer Ag | |
US3993250A (en) | 1975-05-19 | 1976-11-23 | Shure Alan H | Apparatus for spraying liquid materials |
JPS51134465A (en) | 1975-05-19 | 1976-11-20 | Multi Supuree Kogyo Kk | A mixing and stirring device |
US4090640A (en) | 1975-07-24 | 1978-05-23 | Smith Ray V | Hot melt adhesive pumping apparatus having pressure-sensitive feedback control |
US4011602A (en) | 1975-10-06 | 1977-03-15 | Battelle Memorial Institute | Porous expandable device for attachment to bone tissue |
DE7603096U1 (en) | 1976-02-04 | 1976-08-19 | Espe Pharm Praep | Device for the dosed delivery of viscous masses |
US4062274A (en) | 1976-06-07 | 1977-12-13 | Knab James V | Exhaust system for bone cement |
US4105145A (en) | 1976-09-16 | 1978-08-08 | James D. Pauls | Mechanically operated dispensing device |
US4077494A (en) | 1976-12-15 | 1978-03-07 | Parker-Hannifin Corporation | Grease gun |
US4170990A (en) | 1977-01-28 | 1979-10-16 | Fried. Krupp Gesellschaft Mit Beschrankter Haftung | Method for implanting and subsequently removing mechanical connecting elements from living tissue |
US4185072A (en) | 1977-02-17 | 1980-01-22 | Diemolding Corporation | Orthopedic cement mixer |
DE2724814C3 (en) | 1977-06-02 | 1980-03-27 | Kulzer & Co Gmbh, 6380 Bad Homburg | Preliminary product for the preparation of bone cement |
JPS602368B2 (en) | 1977-06-23 | 1985-01-21 | 三菱電機株式会社 | Laser heating device |
US4180070A (en) | 1977-08-29 | 1979-12-25 | Abbott Laboratories | Disposable double vial syringe |
US4146334A (en) | 1977-09-09 | 1979-03-27 | Richard Farrell | Paint mixing and dispensing apparatus |
US4168787A (en) | 1977-11-18 | 1979-09-25 | Superior, Inc. | Variable stroke fluid lubricant dispenser |
SU662082A1 (en) | 1977-12-09 | 1979-05-15 | Тартуский Ордена Трудового Красного Знамени Государственный Университет | Fixative for treating tubular bone fractures |
IL53703A (en) | 1977-12-28 | 1979-10-31 | Aginsky Yacov | Intramedullary nails |
DE2815699C3 (en) | 1978-04-12 | 1981-12-24 | Jakob Preßl Söhne, 8500 Nürnberg | Grease gun |
DE2821785A1 (en) | 1978-05-18 | 1979-11-22 | Gerhard Dawidowski | Bone fracture compression nail - has distal claw sliding in proximal ones in axial direction, retained by lug |
DE2862446D1 (en) | 1978-06-29 | 1984-11-15 | Osteo Ag | Carbon fiber reinforced bone cement |
JPS559242U (en) | 1978-07-04 | 1980-01-21 | ||
US4198383A (en) | 1978-08-21 | 1980-04-15 | Deryagina Galina M | Apparatus for continuous preparation of acrylonitrilebutadienstyrene copolymer |
DE2842839C3 (en) | 1978-10-02 | 1986-11-13 | NATEC Institut für naturwissenschaftlich-technische Dienste GmbH, 2000 Hamburg | Self-hardening compound based on polymethyl methacrylate and its use |
US4198975A (en) | 1978-10-06 | 1980-04-22 | Haller J Gilbert | Self-injecting hypodermic syringe device |
US4257540A (en) | 1978-10-26 | 1981-03-24 | Mcneil Corporation | Hand-held battery-powered grease gun |
IT1194905B (en) | 1979-02-05 | 1988-09-28 | Zoppellari Carlo | DEVICE APPLICABLE PARTICULARLY IN MACHINES FOR THE DISCONTINUOUS PRODUCTION OF ICE CREAM TO OBTAIN THE TOTAL EXPULSION OF THE PRODUCT PROCESSED |
JPS55109440A (en) | 1979-02-15 | 1980-08-22 | Matsushita Electric Works Ltd | Agitating device of reaction vessel |
DE2905878A1 (en) | 1979-02-16 | 1980-08-28 | Merck Patent Gmbh | IMPLANTATION MATERIALS AND METHOD FOR THEIR PRODUCTION |
US4267829A (en) | 1979-04-11 | 1981-05-19 | American Medical Systems, Inc. | Penile prosthesis |
US4250887A (en) | 1979-04-18 | 1981-02-17 | Dardik Surgical Associates, P.A. | Remote manual injecting apparatus |
US4503673A (en) | 1979-05-25 | 1985-03-12 | Charles Schachle | Wind power generating system |
US4274163A (en) | 1979-07-16 | 1981-06-23 | The Regents Of The University Of California | Prosthetic fixation technique |
US4312343A (en) | 1979-07-30 | 1982-01-26 | Leveen Harry H | Syringe |
US4277184A (en) | 1979-08-14 | 1981-07-07 | Alan Solomon | Disposable orthopedic implement and method |
US4276878A (en) | 1979-08-20 | 1981-07-07 | Karl Storz | Injection syringe |
US4404327A (en) | 1979-10-31 | 1983-09-13 | Crugnola Aldo M | Orthopaedic cement from acrylate polymers |
DE2947875A1 (en) | 1979-11-28 | 1981-06-04 | Hans Dr. 5609 Hückeswagen Reimer | Endoprosthesis anchoring bone cement compsn. - contg. particulate organic material dissolving in body in addn. to monomer and reactive component |
US4338925A (en) | 1979-12-20 | 1982-07-13 | Jo Miller | Pressure injection of bone cement apparatus and method |
SE420009B (en) | 1979-12-21 | 1981-09-07 | Ericsson Telefon Ab L M | EXPANDER SCREW FOR FIXING IN A SPACE |
US4326567A (en) | 1979-12-26 | 1982-04-27 | Vercon Inc. | Variable volume, positive displacement sanitary liquid dispensing machine |
US4341691A (en) | 1980-02-20 | 1982-07-27 | Zimmer, Inc. | Low viscosity bone cement |
US4405249A (en) | 1980-03-28 | 1983-09-20 | National Research Development Corporation | Dispensing apparatus and method |
AT366916B (en) | 1980-04-02 | 1982-05-25 | Immuno Ag | DEVICE FOR APPLICATING A TISSUE ADHESIVE BASED ON HUMAN OR ANIMAL PROTEINS |
CA1146301A (en) | 1980-06-13 | 1983-05-17 | J. David Kuntz | Intervertebral disc prosthesis |
EP0044877B1 (en) | 1980-07-26 | 1985-03-13 | Kurz, Karl-Heinz, Dr. med. | Device for determining the internal dimensions of the uterine cavity |
US4380398A (en) | 1980-09-16 | 1983-04-19 | Burgess Basil A | Dispersion mixer |
US4313434A (en) | 1980-10-17 | 1982-02-02 | David Segal | Fracture fixation |
US4309777A (en) | 1980-11-13 | 1982-01-12 | Patil Arun A | Artificial intervertebral disc |
DE3142730A1 (en) | 1981-04-01 | 1982-10-21 | Curt Dipl.-Ing. 1000 Berlin Kranz | "JOINT PROSTHESIS" |
US4346708A (en) | 1981-04-20 | 1982-08-31 | Leveen Harry H | Syringe |
US4409966A (en) | 1981-05-29 | 1983-10-18 | Lambrecht Richard M | Method and apparatus for injecting a substance into the bloodstream of a subject |
GB2099703B (en) | 1981-06-10 | 1985-01-23 | Downs Surgical Ltd | Biopsy needle |
US4494535A (en) | 1981-06-24 | 1985-01-22 | Haig Armen C | Hip nail |
US4403989A (en) | 1981-09-14 | 1983-09-13 | Syntex (U.S.A.) Inc. | Injection device |
US4487602A (en) | 1981-09-14 | 1984-12-11 | Syntex (U.S.A.) Inc. | Injection device |
US4474572A (en) | 1981-09-29 | 1984-10-02 | Syntex (U.S.A.) Inc. | Implanting device and implant magazine |
US4400170A (en) | 1981-09-29 | 1983-08-23 | Syntex (U.S.A.) Inc. | Implanting device and implant magazine |
SU1011119A1 (en) | 1981-10-23 | 1983-04-15 | Edinak Sergej A | Fixator for intraosseous osteosynthesis |
SU1049050A1 (en) | 1982-01-15 | 1983-10-23 | Киевский Медицинский Институт Им.Акад.А.А.Богомольца | Pin for osteosynthesis |
DE3201056C1 (en) | 1982-01-15 | 1983-08-11 | Fried. Krupp Gmbh, 4300 Essen | Intramedullary nail |
US4453539A (en) | 1982-03-01 | 1984-06-12 | The University Of Toledo | Expandable intramedullary nail for the fixation of bone fractures |
US5601557A (en) | 1982-05-20 | 1997-02-11 | Hayhurst; John O. | Anchoring and manipulating tissue |
US4476866A (en) | 1982-08-06 | 1984-10-16 | Thomas J. Fogarty | Combined large and small bore syringe |
US4595006A (en) | 1982-08-16 | 1986-06-17 | Burke Dennis W | Apparatus for cemented implantation of prostheses |
CH657980A5 (en) | 1982-10-21 | 1986-10-15 | Sulzer Ag | DISPOSABLE BONE CEMENT SYRINGE. |
DE3245956A1 (en) | 1982-12-11 | 1984-06-14 | Beiersdorf Ag, 2000 Hamburg | SURGICAL MATERIAL |
GB2132488B (en) | 1982-12-31 | 1986-07-30 | Phillips Pty Ltd N J | Injector for animal dosing |
USD279499S (en) | 1983-02-18 | 1985-07-02 | Zimmer, Inc. | Mixing apparatus |
SE434332B (en) | 1983-03-23 | 1984-07-23 | Jan Ingemar Neslund | CELL SAMPLING DEVICE |
US4500658A (en) | 1983-06-06 | 1985-02-19 | Austenal International, Inc. | Radiopaque acrylic resin |
US4522200A (en) | 1983-06-10 | 1985-06-11 | Ace Orthopedic Company | Adjustable intramedullar rod |
US4558693A (en) | 1983-08-29 | 1985-12-17 | Harvey Lash | Penile implant |
FR2551350B1 (en) | 1983-09-02 | 1985-10-25 | Buffet Jacques | FLUID INJECTION DEVICE, SUITABLE FOR IMPLANTATION |
FR2552404B1 (en) | 1983-09-26 | 1987-12-24 | Merck Sharp & Dohme | ASSEMBLY FOR PREPARING AND DELIVERING A SOLUTION, SHUTTERING PLUG FOR SUCH ASSEMBLY AND METHOD FOR MANUFACTURING THE SAME |
US4554914A (en) | 1983-10-04 | 1985-11-26 | Kapp John P | Prosthetic vertebral body |
US4593685A (en) | 1983-10-17 | 1986-06-10 | Pfizer Hospital Products Group Inc. | Bone cement applicator |
US4546767A (en) | 1983-10-27 | 1985-10-15 | Smith Carl W | Cement injection device |
DE3474539D1 (en) | 1983-12-02 | 1988-11-17 | Bramlage Gmbh | Dispenser for pasty materials, especially a dispenser for toothpaste |
US4600118A (en) | 1984-02-02 | 1986-07-15 | Martin Gerald D | Ferrule dispenser |
US4722948A (en) | 1984-03-16 | 1988-02-02 | Dynatech Corporation | Bone replacement and repair putty material from unsaturated polyester resin and vinyl pyrrolidone |
AU562042B2 (en) | 1984-03-24 | 1987-05-28 | Meishintoryo Co. Ltd. | Surgical cement |
CA1227902A (en) | 1984-04-02 | 1987-10-13 | Raymond G. Tronzo | Fenestrated hip screw and method of augmented internal fixation |
US4503169A (en) | 1984-04-19 | 1985-03-05 | Minnesota Mining And Manufacturing Company | Radiopaque, low visual opacity dental composites containing non-vitreous microparticles |
US4728006A (en) | 1984-04-27 | 1988-03-01 | The Procter & Gamble Company | Flexible container including self-sealing dispensing valve to provide automatic shut-off and leak resistant inverted storage |
DE3421157A1 (en) | 1984-06-07 | 1985-12-12 | Ernst Leitz Wetzlar Gmbh, 6330 Wetzlar | PLASTIC-BASED COMPOSITE FOR PROSTHETIC PURPOSES |
DE3425566A1 (en) | 1984-07-11 | 1986-01-16 | Draenert Klaus | DEVICE AND METHOD FOR MIXING AND APPLYING BONE CEMENT |
NZ212899A (en) | 1984-07-31 | 1987-10-30 | Phillips Pty Ltd N J | Piston operated adjustable volume dose injector for animals |
AU573369B2 (en) | 1984-07-31 | 1988-06-02 | N.J. Phillips Pty. Limited | A rumen injector |
EP0177781B1 (en) | 1984-09-10 | 1990-06-27 | Draenert, Klaus, Dr.med.Dr.med.habil. | Bone cement and method for making it |
US4686973A (en) | 1984-10-12 | 1987-08-18 | Dow Corning Corporation | Method of making an intramedullary bone plug and bone plug made thereby |
US4697584A (en) | 1984-10-12 | 1987-10-06 | Darrel W. Haynes | Device and method for plugging an intramedullary bone canal |
US4650469A (en) | 1984-10-19 | 1987-03-17 | Deltec Systems, Inc. | Drug delivery system |
DE3439322A1 (en) | 1984-10-26 | 1986-05-07 | Infors GmbH, 8000 München | INFUSION PUMP |
DE3443167C2 (en) | 1984-11-27 | 1986-12-18 | orthoplant Endoprothetik GmbH, 2800 Bremen | Surgical cement syringe |
EP0190504B1 (en) | 1984-12-28 | 1993-04-21 | Johnson Matthey Public Limited Company | Antimicrobial compositions |
US4632101A (en) | 1985-01-31 | 1986-12-30 | Yosef Freedland | Orthopedic fastener |
US4636217A (en) | 1985-04-23 | 1987-01-13 | Regents Of The University Of Minnesota | Anterior spinal implant |
US4668295A (en) | 1985-04-25 | 1987-05-26 | University Of Dayton | Surgical cements |
US4664298A (en) | 1985-05-01 | 1987-05-12 | Stewart-Warner Corporation | Dual mode grease gun |
GB2174459B (en) | 1985-05-04 | 1988-05-25 | Jencons | Liquid dispensing means |
US4908017A (en) | 1985-05-14 | 1990-03-13 | Ivion Corporation | Failsafe apparatus and method for effecting syringe drive |
ATE50503T1 (en) | 1985-06-20 | 1990-03-15 | Ceraver | CEMENT FOR ANCHORING BONE PROSTHESES. |
AT382783B (en) | 1985-06-20 | 1987-04-10 | Immuno Ag | DEVICE FOR APPLICATING A TISSUE ADHESIVE |
US4670008A (en) | 1985-07-01 | 1987-06-02 | Albertini Beat | High flux threaded needle |
US4718910A (en) | 1985-07-16 | 1988-01-12 | Klaus Draenert | Bone cement and process for preparing the same |
JPH0633375B2 (en) | 1985-09-19 | 1994-05-02 | バブコツク日立株式会社 | Strainer for coal-water slurry |
GB8524152D0 (en) | 1985-10-01 | 1985-11-06 | Cole Polymers Ltd | Bone cement |
DE3536076A1 (en) | 1985-10-09 | 1987-04-09 | Muehlbauer Ernst Kg | POLYMERIZABLE CEMENT MIXTURES |
GB2182726B (en) | 1985-11-09 | 1989-10-25 | Metal Box Plc | Dispensers for pasty or viscous products |
US4676655A (en) | 1985-11-18 | 1987-06-30 | Isidore Handler | Plunger type cartridge mixer for fluent materials |
SE447785B (en) | 1985-12-23 | 1986-12-15 | Mit Ab | DEVICE FOR APPLIANCES TO ALLOW BENCEMENT MIXING UNDER VACUUM |
US4892550A (en) | 1985-12-30 | 1990-01-09 | Huebsch Donald L | Endoprosthesis device and method |
DE3766717D1 (en) | 1986-01-23 | 1991-01-31 | Al Rawi Omar Mahmood Atia | ADAPTER FOR AN INJECTION SYRINGE. |
US4653487A (en) | 1986-01-29 | 1987-03-31 | Maale Gerhard E | Intramedullary rod assembly for cement injection system |
US4758234A (en) | 1986-03-20 | 1988-07-19 | Norman Orentreich | High viscosity fluid delivery system |
US4664655A (en) | 1986-03-20 | 1987-05-12 | Norman Orentreich | High viscosity fluid delivery system |
DE3609672A1 (en) | 1986-03-21 | 1987-09-24 | Klaus Draenert | EVACUABLE BONE CEMENT SYRINGE |
US4961647A (en) | 1986-04-04 | 1990-10-09 | Dhd Medical Products | Orthopedic cement mixer |
DE3613213A1 (en) | 1986-04-18 | 1987-10-22 | Merck Patent Gmbh | TRICALCIUMPHOSPHATE FOR IMPLANTATION MATERIALS |
EP0246818B1 (en) | 1986-05-23 | 1992-04-22 | Avdel Systems Limited | Hydraulic fluid replenishment device |
DE3765472D1 (en) | 1986-07-07 | 1990-11-15 | Wilhelm A Keller | DISCHARGE DEVICE FOR OPERATING CARTRIDGES. |
GB8617350D0 (en) | 1986-07-16 | 1986-08-20 | Metal Box Plc | Pump chamber dispenser |
US4737151A (en) | 1986-07-25 | 1988-04-12 | Clement John G | Syringe injector |
US4767033A (en) | 1986-07-31 | 1988-08-30 | The Drackett Company | Manually operated gear pump spray head |
GB2197329B (en) | 1986-09-10 | 1990-01-10 | Showa Denko Kk | Hard tissue substitute composition |
US4704035A (en) | 1986-10-06 | 1987-11-03 | Baker Perkins, Inc. | Remotely transmitting batch mixer |
US5024232A (en) | 1986-10-07 | 1991-06-18 | The Research Foundation Of State University Of Ny | Novel radiopaque heavy metal polymer complexes, compositions of matter and articles prepared therefrom |
US4710179A (en) | 1986-10-27 | 1987-12-01 | Habley Medical Technology Corporation | Snap-on vernier syringe |
US4697929A (en) | 1986-10-28 | 1987-10-06 | Charles Ross & Son Company | Planetary mixers |
FR2606282B1 (en) | 1986-11-12 | 1994-05-20 | Ecole Nale Sup Ceramique Indle | CURABLE COMPOSITION FOR FILLING BONE CAVITIES |
WO1988003811A1 (en) | 1986-11-19 | 1988-06-02 | Laboratorium Für Experimentelle Chirurgie, Forschu | Method and apparatus for preparing a self-curing two-component powder liquid bone cement |
IL80731A0 (en) | 1986-11-23 | 1987-02-27 | Bron Dan | Hydraulic syringe pump |
DE3642212A1 (en) | 1986-12-10 | 1988-06-23 | Espe Stiftung | POLYMERIZABLE MEASURES, METHOD FOR THEIR PRODUCTION AND THEIR USE AS DENTAL MEASURES |
US4762515A (en) | 1987-01-06 | 1988-08-09 | Ivy Laboratories, Inc. | Medicament implant applicator |
CH671691A5 (en) | 1987-01-08 | 1989-09-29 | Sulzer Ag | |
DE3701190A1 (en) | 1987-01-16 | 1988-07-28 | Ziemann Edeltraud | DEVICE FOR EJECTING OR SUCTIONING LIQUID OR PASTOES MEDIA |
CH671525A5 (en) | 1987-01-22 | 1989-09-15 | Inst Mek Akademii Nauk Sssr | |
JPS63194722A (en) | 1987-02-06 | 1988-08-11 | インステイツウト プロブレム メハニキアカデミイ ナウク エスエスエスア−ル | Apparatus for mixing heterogenous substance |
CA1283501C (en) | 1987-02-12 | 1991-04-30 | Thomas P. Hedman | Artificial spinal disc |
DE3705741A1 (en) | 1987-02-23 | 1988-09-01 | Hilti Ag | DISPENSING DEVICE FOR FLOWABLE MEASURES |
US4813870A (en) | 1987-03-09 | 1989-03-21 | Minnesota Mining And Manufacturing Company | Dispenser for viscous liquids |
SE457417B (en) | 1987-04-14 | 1988-12-27 | Astra Meditec Ab | AUTOMATIC SQUARE SPRAY, PROCEDURE FOR MIXING AND INJECTION WITH THE SPRAYER AND AMPULA FOR PRIVATE CHAMBER SPRAY |
CH669080GA3 (en) | 1987-05-14 | 1989-02-28 | ||
US4935029A (en) | 1987-06-22 | 1990-06-19 | Matsutani Seisakusho Co., Ltd. | Surgical needle |
WO1988010129A1 (en) | 1987-06-25 | 1988-12-29 | Nova Medical Pty. Limited | Slow delivery injection device |
US4792577A (en) | 1987-07-16 | 1988-12-20 | Johnson & Johnson Consumer Products, Inc. | Stain-resistant no-mix orthodontic adhesive |
US4860927A (en) | 1987-07-29 | 1989-08-29 | Grinde James E | Blow molded two-compartment container |
US4900546A (en) | 1987-07-30 | 1990-02-13 | Pfizer Hospital Products Group, Inc. | Bone cement for sustained release of substances |
US5258420A (en) | 1987-07-30 | 1993-11-02 | Pfizer Hospital Products Group, Inc. | Bone cement for sustained release of substances |
US4863072A (en) | 1987-08-18 | 1989-09-05 | Robert Perler | Single hand operable dental composite package |
US4772287A (en) | 1987-08-20 | 1988-09-20 | Cedar Surgical, Inc. | Prosthetic disc and method of implanting |
US4978336A (en) | 1987-09-29 | 1990-12-18 | Hemaedics, Inc. | Biological syringe system |
DK517887D0 (en) | 1987-10-02 | 1987-10-02 | Westergaard Knud Erik | MULTI-FUNCTION SET FOR PRINTING LIQUID |
US4815454A (en) | 1987-11-16 | 1989-03-28 | Dozier Jr John K | Apparatus and method for injecting bone cement |
US5037473A (en) | 1987-11-18 | 1991-08-06 | Antonucci Joseph M | Denture liners |
GB8727166D0 (en) | 1987-11-20 | 1987-12-23 | Stewart K | Creating inflatable products |
US4837279A (en) | 1988-02-22 | 1989-06-06 | Pfizer Hospital Products Corp, Inc. | Bone cement |
DE3806448A1 (en) | 1988-02-29 | 1989-09-07 | Espe Stiftung | COMPATIBLE MATERIAL AND MATERIALS AVAILABLE THEREFROM |
US5019041A (en) | 1988-03-08 | 1991-05-28 | Scimed Life Systems, Inc. | Balloon catheter inflation device |
US4946077A (en) | 1988-03-11 | 1990-08-07 | Olsen Laverne R | In-line air-bleed valve for hand-operated grease guns |
FR2629337A1 (en) | 1988-03-30 | 1989-10-06 | Bigan Michel | Device for intra-osseus sealing of a prosthesis element |
US4854312A (en) | 1988-04-13 | 1989-08-08 | The University Of Toledo | Expanding intramedullary nail |
DE3817101C2 (en) | 1988-05-19 | 1998-05-20 | Axel Von Brand | Device for transferring liquid from one container to another container |
IT1234978B (en) | 1988-06-01 | 1992-06-09 | Tecres Spa | TWO-STAGE CEMENTITIOUS MIXTURE, PARTICULARLY SUITABLE FOR ORTHOPEDIC USES. |
DE3820498A1 (en) | 1988-06-16 | 1989-12-21 | Bayer Ag | DENTAL MATERIALS |
CA1333209C (en) | 1988-06-28 | 1994-11-29 | Gary Karlin Michelson | Artificial spinal fusion implants |
DE3824886A1 (en) | 1988-07-22 | 1990-01-25 | Janke & Kunkel Kg | VERTICAL STIRRING AND / OR KNEWING MACHINE WITH ROTATING BEARING GEARBOX |
US6120437A (en) | 1988-07-22 | 2000-09-19 | Inbae Yoon | Methods for creating spaces at obstructed sites endoscopically and methods therefor |
US4910259A (en) | 1988-09-26 | 1990-03-20 | Wolff & Kaaber A/S | Bone cement |
SE462012B (en) | 1988-09-27 | 1990-04-30 | Electrolux Ab | VACUUM CLEANER |
US4968303A (en) | 1988-09-27 | 1990-11-06 | Eli Lilly And Company | Hypodermic syringe holder |
US4995868A (en) | 1988-10-12 | 1991-02-26 | Bard Limited | Catheter |
JPH02122017A (en) | 1988-10-31 | 1990-05-09 | Toshiba Corp | Apparatus for removing strain of square cylindrical deep drawing product |
FR2638359A1 (en) | 1988-11-03 | 1990-05-04 | Tino Dalto | SYRINGE GUIDE WITH ADJUSTMENT OF DEPTH DEPTH OF NEEDLE IN SKIN |
US4944726A (en) | 1988-11-03 | 1990-07-31 | Applied Vascular Devices | Device for power injection of fluids |
DE3838465A1 (en) | 1988-11-12 | 1990-05-17 | Fresenius Ag | SYRINGE PUMP |
FR2638972B1 (en) | 1988-11-14 | 1990-12-14 | Osteal Medical Laboratoires | CEMENT FOR FIXING BONE PROSTHESES |
JPH02166235A (en) | 1988-12-19 | 1990-06-26 | Kawasaki Steel Corp | Method for controlling sheet temperature in metallic sheet heating furnace |
US4973168A (en) | 1989-01-13 | 1990-11-27 | Chan Kwan Ho | Vacuum mixing/bone cement cartridge and kit |
CH677202A5 (en) | 1989-01-16 | 1991-04-30 | Maag Zahnraeder & Maschinen Ag | |
US5081999A (en) | 1989-02-06 | 1992-01-21 | Board Of Regents Of The University Of Oklahoma | Biosample aspirator |
US4969888A (en) | 1989-02-09 | 1990-11-13 | Arie Scholten | Surgical protocol for fixation of osteoporotic bone using inflatable device |
US5131382A (en) | 1989-03-27 | 1992-07-21 | Meyer William F | Endoscopic percutaneous discectomy device |
JPH0534760Y2 (en) | 1989-03-28 | 1993-09-02 | ||
US5059199A (en) | 1989-04-12 | 1991-10-22 | Olympus Optical Co., Ltd. | Treating device for endoscopes |
US5018919A (en) | 1989-04-15 | 1991-05-28 | Bergwerksverband Gmbh | Combined rigid profile and stretching roof bolt with expansion element |
US5015233A (en) | 1989-04-17 | 1991-05-14 | Freedom Machine, Inc. | Pneumatic inflation device |
SE462315B (en) | 1989-05-03 | 1990-06-11 | Surgitec Ab | DEVICE FOR MANUFACTURING BENCEMENT |
CA2007210C (en) | 1989-05-10 | 1996-07-09 | Stephen D. Kuslich | Intervertebral reamer |
DK235589D0 (en) | 1989-05-12 | 1989-05-12 | Wolff & Kaaber | METHOD AND APPARATUS FOR MIXING A SOLID AND LIQUID COMPONENT |
JPH0645487B2 (en) | 1989-05-19 | 1994-06-15 | 徳山曹達株式会社 | Curing material |
DE3919534A1 (en) | 1989-06-15 | 1990-12-20 | Merck Patent Gmbh | METHOD AND DEVICE FOR PREPARING BONE CEMENT |
EP0585978A3 (en) | 1989-06-30 | 1994-03-23 | TDK Corporation | Living hard tissue replacement, its preparation, and preparation of integral body |
US4973301A (en) | 1989-07-11 | 1990-11-27 | Israel Nissenkorn | Catheter and method of using same |
US6004330A (en) | 1989-08-16 | 1999-12-21 | Medtronic, Inc. | Device or apparatus for manipulating matter |
JPH0390237A (en) | 1989-08-31 | 1991-04-16 | Matsutani Seisakusho Co Ltd | Working method for eyeless suture needle |
US5116335A (en) | 1989-09-18 | 1992-05-26 | Hannon Gerard T | Intramedullary hybrid nail and instrumentation for installation and removal |
US5318532A (en) | 1989-10-03 | 1994-06-07 | C. R. Bard, Inc. | Multilumen catheter with variable cross-section lumens |
US5035706A (en) | 1989-10-17 | 1991-07-30 | Cook Incorporated | Percutaneous stent and method for retrieval thereof |
CA2027921C (en) | 1989-10-19 | 1997-12-09 | Nobuo Nakabayashi | Bone cement composition, cured product thereof, implant material and process for the preparation of the same |
US5295980A (en) | 1989-10-30 | 1994-03-22 | Ersek Robert A | Multi-use cannula system |
DE3936703A1 (en) | 1989-11-03 | 1991-05-08 | Lutz Biedermann | BONE SCREW |
US5059193A (en) | 1989-11-20 | 1991-10-22 | Spine-Tech, Inc. | Expandable spinal implant and surgical method |
US5074871A (en) | 1989-12-07 | 1991-12-24 | Evi Corporation | Catheter atherotome |
CH680564A5 (en) | 1989-12-07 | 1992-09-30 | Experimentelle Chirurgie Schwe | |
JPH03232809A (en) | 1989-12-11 | 1991-10-16 | Jishi Toushi Kogyo Kk | Kneading liquid for dental porcelain |
IT1236864B (en) | 1989-12-29 | 1993-04-22 | Tecres Spa | PROCEDURE FOR MIXING AND ADMINISTRATING A TWO-PART BONE CONCRETE DIRECTLY ON THE SPOT, AND DEVICE THAT REALIZES IT |
US5435645A (en) | 1989-12-29 | 1995-07-25 | Tecres Spa | Process and apparatus for the mixing and direct emplacement of a two-component bone cement |
EP0462255B1 (en) | 1990-01-08 | 1994-09-21 | Becton Dickinson France S.A. | Two-compartment storage and transfer flask |
US5022563A (en) | 1990-01-10 | 1991-06-11 | Electron Fusion Devices, Inc. | Dispenser-gun assembly for viscous fluids and dispenser therefor |
ATE113483T1 (en) | 1990-01-25 | 1994-11-15 | Howmedica | BONE CEMENT. |
US5112333A (en) | 1990-02-07 | 1992-05-12 | Fixel Irving E | Intramedullary nail |
DE4104092A1 (en) | 1990-02-13 | 1991-08-14 | Christoph Dr Med Rieger | Metal cannula enclosed in outer cannula of flexible plastics - has circumferential slots in wall to increase flexibility |
DE4004678A1 (en) | 1990-02-15 | 1991-08-22 | Bayer Ag | FILLERS, SWELLABLE PEARL POLYMERISATES |
US5454365A (en) | 1990-11-05 | 1995-10-03 | Bonutti; Peter M. | Mechanically expandable arthroscopic retractors |
US5345927A (en) | 1990-03-02 | 1994-09-13 | Bonutti Peter M | Arthroscopic retractors |
US4946285A (en) | 1990-03-08 | 1990-08-07 | Hobart Corporation | Bowl scraper attachment for planetary food mixer |
US5071040A (en) | 1990-03-09 | 1991-12-10 | Pfizer Hospital Products Group, Inc. | Surgical adhesives mixing and dispensing implement |
US5078919A (en) | 1990-03-20 | 1992-01-07 | The United States Of America As Represented By The United States Department Of Energy | Composition containing aerogel substrate loaded with tritium |
DD293485A5 (en) | 1990-04-10 | 1991-09-05 | Uwe Fuhrmann,De | INTRAMEDULLAERE OSTEOSYNTHESESPINDEL |
FR2661914B1 (en) | 1990-05-11 | 1994-05-06 | Essilor Internal Cie Gle Optique | METHOD FOR MANUFACTURING A TRANSPARENT POLYMER LENS WITH MODULATED REFRACTION INDEX. |
US4994065A (en) | 1990-05-18 | 1991-02-19 | Zimmer, Inc. | Apparatus for dispensing low viscosity semi-fluid material under pressure |
DE4019617A1 (en) | 1990-06-20 | 1992-01-02 | Thera Ges Fuer Patente | IMPLANTABLE ACTIVE SUBSTITUTE MATERIAL |
US5236445A (en) | 1990-07-02 | 1993-08-17 | American Cyanamid Company | Expandable bone anchor and method of anchoring a suture to a bone |
DE9011685U1 (en) | 1990-08-10 | 1991-12-12 | Thera Patent Gmbh & Co. Kg Gesellschaft Fuer Industrielle Schutzrechte, 8031 Seefeld, De | |
ATE139126T1 (en) | 1990-09-10 | 1996-06-15 | Synthes Ag | MEMBRANE FOR BONE REGENERATION |
US6080801A (en) | 1990-09-13 | 2000-06-27 | Klaus Draenert | Multi-component material and process for its preparation |
US5702448A (en) | 1990-09-17 | 1997-12-30 | Buechel; Frederick F. | Prosthesis with biologically inert wear resistant surface |
US5725529A (en) | 1990-09-25 | 1998-03-10 | Innovasive Devices, Inc. | Bone fastener |
DE69130681T2 (en) | 1990-09-25 | 1999-06-10 | Innovasive Devices Inc | BONE FIXING DEVICE |
US5108016A (en) | 1990-10-04 | 1992-04-28 | Waring Roy F | Fuel container system |
US5108403A (en) | 1990-11-09 | 1992-04-28 | Stern Mark S | Bone waxing device |
US5102413A (en) | 1990-11-14 | 1992-04-07 | Poddar Satish B | Inflatable bone fixation device |
CS277533B6 (en) | 1990-12-29 | 1993-03-17 | Krajicek Milan | Fixed osteaosynthesis appliance |
GB9100097D0 (en) | 1991-01-04 | 1991-02-20 | Sec Dep For Health The | Biocompatible mouldable polymeric material |
US5354287A (en) | 1991-01-16 | 1994-10-11 | Senetek Plc | Injector for delivering fluid to internal target tissue |
US5188259A (en) | 1991-02-01 | 1993-02-23 | Petit Jeffrey D | Caulking gun with belt worn cartridge |
US5390683A (en) | 1991-02-22 | 1995-02-21 | Pisharodi; Madhavan | Spinal implantation methods utilizing a middle expandable implant |
US5171278A (en) | 1991-02-22 | 1992-12-15 | Madhavan Pisharodi | Middle expandable intervertebral disk implants |
JP3390431B2 (en) | 1991-02-22 | 2003-03-24 | マドハヴァン、ピシャロディ | Centrally expandable disc implant and method |
US5123926A (en) | 1991-02-22 | 1992-06-23 | Madhavan Pisharodi | Artificial spinal prosthesis |
US5171248A (en) | 1991-02-27 | 1992-12-15 | Intermedics Orthopedics, Inc. | Medullary caliper |
US5190191A (en) | 1991-03-13 | 1993-03-02 | Reyman Mark E | Apparatus for measured and unmeasured dispensing of viscous fluids |
US5480403A (en) | 1991-03-22 | 1996-01-02 | United States Surgical Corporation | Suture anchoring device and method |
FR2674119B1 (en) | 1991-03-22 | 1993-06-18 | Fixano Productions | DEVICE FOR GUIDING THE SLIDING OF OSTEOSYNTHESIS SCREWS FOR INTRA-CAPSULAR FRACTURE OF THE FEMUR'S NECK. |
US5192327A (en) | 1991-03-22 | 1993-03-09 | Brantigan John W | Surgical prosthetic implant for vertebrae |
US5720753A (en) | 1991-03-22 | 1998-02-24 | United States Surgical Corporation | Orthopedic fastener |
JPH04329956A (en) | 1991-04-30 | 1992-11-18 | Takeda Chem Ind Ltd | Germ-free holding/mixing apparatus for medicine held in individual sealed container |
DE69214005T2 (en) | 1991-05-01 | 1997-05-15 | Chichibu Onoda Cement Corp | Hardening compositions for use in medicine or dentistry |
US5160327A (en) | 1991-05-31 | 1992-11-03 | Vance Products Incorporated | Rotational pressure drive for a medical syringe |
DE4118884A1 (en) | 1991-06-07 | 1992-12-10 | List Ag | MIXING kneader |
US5591172A (en) | 1991-06-14 | 1997-01-07 | Ams Medinvent S.A. | Transluminal implantation device |
US5199419A (en) | 1991-08-05 | 1993-04-06 | United States Surgical Corporation | Surgical retractor |
US5630806A (en) | 1991-08-13 | 1997-05-20 | Hudson International Conductors | Spiral wrapped medical tubing |
IL102941A0 (en) | 1991-08-27 | 1993-01-31 | Thomas R Johnson | Injection syringe |
US5431654A (en) | 1991-09-30 | 1995-07-11 | Stryker Corporation | Bone cement injector |
US5265956A (en) | 1991-09-30 | 1993-11-30 | Stryker Corporation | Bone cement mixing and loading apparatus |
US5203773A (en) | 1991-10-18 | 1993-04-20 | United States Surgical Corporation | Tissue gripping apparatus for use with a cannula or trocar assembly |
GB9126011D0 (en) | 1991-12-06 | 1992-02-05 | Summit Medical Ltd | Bone cement mixing device |
US6190381B1 (en) | 1995-06-07 | 2001-02-20 | Arthrocare Corporation | Methods for tissue resection, ablation and aspiration |
SE510490C2 (en) | 1992-02-07 | 1999-05-31 | Scandimed International Ab | Process for producing bone cement and apparatus for carrying out the process |
US5219897A (en) | 1992-02-10 | 1993-06-15 | Murray William M | Dental and orthopedic cement method and preforms |
SE510358C2 (en) | 1992-02-20 | 1999-05-17 | Goesta Ullmark | Device for use in transplanting bone tissue material into a bone cavity |
US5336699A (en) | 1992-02-20 | 1994-08-09 | Orthopaedic Research Institute | Bone cement having chemically joined reinforcing fillers |
CA2062557A1 (en) | 1992-03-09 | 1993-09-10 | John G. Kaufman | Liquid dispenser |
US5328362A (en) | 1992-03-11 | 1994-07-12 | Watson Sherman L | Soft resilient interocclusal dental appliance, method of forming same and composition for same |
US5242983A (en) | 1992-03-19 | 1993-09-07 | Edison Polymer Innovation Corporation | Polyisobutylene toughened poly(methyl methacrylate) |
SE470177B (en) | 1992-03-23 | 1993-11-29 | Radi Medical Systems | Device for punching in hard tissue and puncture needle |
US5277339A (en) | 1992-03-26 | 1994-01-11 | Alemite Corporation | Dual mode pistol-grip grease gun |
US5637097A (en) | 1992-04-15 | 1997-06-10 | Yoon; Inbae | Penetrating instrument having an expandable anchoring portion |
US5707362A (en) | 1992-04-15 | 1998-01-13 | Yoon; Inbae | Penetrating instrument having an expandable anchoring portion for triggering protrusion of a safety member and/or retraction of a penetrating member |
CH686933A5 (en) | 1992-04-15 | 1996-08-15 | Fischer Georg Giessereianlagen | Apparatus for mixing and preparation of free-flowing materials. |
US5269762A (en) | 1992-04-21 | 1993-12-14 | Sterling Winthrop, Inc. | Portable hand-held power assister device |
FR2690332A1 (en) | 1992-04-28 | 1993-10-29 | Loutfi Rachid | Surgical instrument for injection of bone material into spine - has cylindrical body forming circular-section channel, housing rotary cylinder with endless screw surface driving bone material to outlet |
JPH05317383A (en) | 1992-05-19 | 1993-12-03 | Nissho Corp | Solution container equipped with means for communicating with chemical container |
US5501695A (en) | 1992-05-27 | 1996-03-26 | The Anspach Effort, Inc. | Fastener for attaching objects to bones |
US5334184A (en) | 1992-06-30 | 1994-08-02 | Bimman Lev A | Apparatus for intramedullary fixation broken bones |
GB2268068B (en) | 1992-07-01 | 1996-08-21 | John Bruce Clayfield Davies | Devices having expansion means for securing end portions of tubular members |
JP2660641B2 (en) | 1992-07-22 | 1997-10-08 | 株式会社東洋設計 | Material winding mechanism of roll kneader |
US5334626A (en) * | 1992-07-28 | 1994-08-02 | Zimmer, Inc. | Bone cement composition and method of manufacture |
US5531683A (en) | 1992-08-13 | 1996-07-02 | Science Incorporated | Mixing and delivery syringe assembly |
US5279555A (en) | 1992-08-24 | 1994-01-18 | Merck & Co., Inc. | Device for injecting implants |
US5395590A (en) | 1992-09-04 | 1995-03-07 | Swaniger; James R. | Valved container lid |
US5257632A (en) | 1992-09-09 | 1993-11-02 | Symbiosis Corporation | Coaxial bone marrow biopsy coring and aspirating needle assembly and method of use thereof |
US5254092A (en) | 1992-09-15 | 1993-10-19 | American Medical Systems, Inc. | Fluid flow check valve |
DE9213656U1 (en) | 1992-10-09 | 1992-12-03 | Angiomed Ag, 7500 Karlsruhe, De | |
US5356382A (en) | 1992-10-23 | 1994-10-18 | Applied Medical Research, Inc. | Percutaneous tract measuring and forming device |
US5275214A (en) | 1992-10-28 | 1994-01-04 | Rehberger Kevin M | Apparatus for unloading pressurized fluid |
GB9224573D0 (en) | 1992-11-21 | 1993-01-13 | Klinge Erwin L | Expanding intramedullary nail |
US5372583A (en) | 1992-11-25 | 1994-12-13 | Cardiopulmonary Specialities, Inc. | Bone marrow infuser and method of use |
US5331972A (en) | 1992-12-03 | 1994-07-26 | Baxter International Inc. | Bone marrow biopsy, aspiration and transplant needles |
US5527276A (en) | 1993-01-12 | 1996-06-18 | Arthroscopic Assistants, Inc. | Flexible inflow/outflow cannula |
US5398483A (en) | 1993-01-29 | 1995-03-21 | Polymers Reconstructive A/S | Method and apparatus for packaging, mixing and delivering bone cement |
US5370221A (en) | 1993-01-29 | 1994-12-06 | Biomet, Inc. | Flexible package for bone cement components |
JPH06239352A (en) | 1993-02-05 | 1994-08-30 | Nissho Corp | Solution injection set |
US5441502A (en) | 1993-02-17 | 1995-08-15 | Mitek Surgical Products, Inc. | System and method for re-attaching soft tissue to bone |
DE4305376C1 (en) | 1993-02-22 | 1994-09-29 | Wolf Gmbh Richard | Medical instrument shaft |
US5431676A (en) | 1993-03-05 | 1995-07-11 | Innerdyne Medical, Inc. | Trocar system having expandable port |
DE4310796C2 (en) | 1993-04-05 | 1996-01-25 | Reburg Patentverwertungs Gmbh | Expansion anchor |
US5534028A (en) | 1993-04-20 | 1996-07-09 | Howmedica, Inc. | Hydrogel intervertebral disc nucleus with diminished lateral bulging |
US5411180A (en) | 1993-05-07 | 1995-05-02 | Innovative Technology Sales, Inc. | Self-contained hydraulic dispensing mechanism with pressure relief regulator |
DE4315757C1 (en) | 1993-05-11 | 1994-11-10 | Plus Endoprothetik Ag | Vertebral implant |
US5558639A (en) | 1993-06-10 | 1996-09-24 | Gangemi; Ronald J. | Ambulatory patient infusion apparatus |
EP1093760B1 (en) | 1993-06-10 | 2004-11-17 | Karlin Technology, Inc. | Spinal distractor |
US5443182A (en) | 1993-06-11 | 1995-08-22 | Tanaka; Kazuna | Methods and apparatus for preparing and delivering bone cement |
FR2706309B1 (en) | 1993-06-17 | 1995-10-06 | Sofamor | Instrument for surgical treatment of an intervertebral disc by the anterior route. |
AU7324394A (en) | 1993-07-06 | 1995-02-06 | Michael L. Earle | Bone cement delivery gun |
US5531519A (en) | 1993-07-06 | 1996-07-02 | Earle; Michael L. | Automated bone cement mixing apparatus |
DE4323034C1 (en) | 1993-07-09 | 1994-07-28 | Lutz Biedermann | Placeholders, especially for an intervertebral disc |
US5385081A (en) | 1993-09-09 | 1995-01-31 | Arde Incorporated | Fluid storage tank employing a shear seal |
US5482187A (en) | 1993-09-13 | 1996-01-09 | Hygienix, Inc. | Dispenser for viscous substances |
US5763092A (en) | 1993-09-15 | 1998-06-09 | Etex Corporation | Hydroxyapatite coatings and a method of their manufacture |
DE4332307C1 (en) | 1993-09-23 | 1994-09-29 | Heraeus Kulzer Gmbh | Syringe for the metered dispensing of viscous materials, especially of dental materials |
US5480400A (en) | 1993-10-01 | 1996-01-02 | Berger; J. Lee | Method and device for internal fixation of bone fractures |
US5423850A (en) | 1993-10-01 | 1995-06-13 | Berger; J. Lee | Balloon compressor for internal fixation of bone fractures |
US5395326A (en) | 1993-10-20 | 1995-03-07 | Habley Medical Technology Corporation | Pharmaceutical storage and mixing syringe having high pressure assisted discharge |
US5573265A (en) | 1993-11-05 | 1996-11-12 | Fichtel & Sachs Ag | Stabilizer system for a motor vehicle suspension system with a rotary actuator |
US5348391A (en) | 1993-11-16 | 1994-09-20 | Murray William M | Manual bone cement mixing method |
FR2712486A1 (en) | 1993-11-19 | 1995-05-24 | Breslave Patrice | Intervertebral prosthesis |
US5514137A (en) | 1993-12-06 | 1996-05-07 | Coutts; Richard D. | Fixation of orthopedic devices |
DE9319007U1 (en) | 1993-12-10 | 1995-04-06 | Muehlbauer Ernst | Storage syringe for viscous dental materials |
US6248110B1 (en) | 1994-01-26 | 2001-06-19 | Kyphon, Inc. | Systems and methods for treating fractured or diseased bone using expandable bodies |
US6716216B1 (en) | 1998-08-14 | 2004-04-06 | Kyphon Inc. | Systems and methods for treating vertebral bodies |
US7044954B2 (en) | 1994-01-26 | 2006-05-16 | Kyphon Inc. | Method for treating a vertebral body |
ATE361028T1 (en) | 1994-01-26 | 2007-05-15 | Kyphon Inc | IMPROVED INFLATABLE DEVICE FOR USE IN SURGICAL METHODS OF FIXATION OF BONE |
US6726691B2 (en) | 1998-08-14 | 2004-04-27 | Kyphon Inc. | Methods for treating fractured and/or diseased bone |
US6241734B1 (en) | 1998-08-14 | 2001-06-05 | Kyphon, Inc. | Systems and methods for placing materials into bone |
US20060100635A1 (en) | 1994-01-26 | 2006-05-11 | Kyphon, Inc. | Inflatable device for use in surgical protocol relating to fixation of bone |
NZ279442A (en) | 1994-01-26 | 1998-02-26 | Mark A Reiley | Bone treatment device; inflatable balloon for insertion into a bone; balloon details |
US5558136A (en) | 1994-01-31 | 1996-09-24 | Stryker Corporation | Bone cement cartridge with secondary piston |
US5468245A (en) | 1994-02-03 | 1995-11-21 | Vargas, Iii; Joseph H. | Biomedical cement bonding enhancer |
GB9403362D0 (en) | 1994-02-22 | 1994-04-13 | Summit Medical Ltd | Bone cement mixing apparatus |
AT400304B (en) | 1994-02-28 | 1995-12-27 | Immuno Ag | DEVICE FOR APPLICATING A MULTI-COMPONENT TISSUE ADHESIVE |
US5522816A (en) | 1994-03-09 | 1996-06-04 | Acromed Corporation | Transverse connection for spinal column corrective devices |
US5620458A (en) | 1994-03-16 | 1997-04-15 | United States Surgical Corporation | Surgical instruments useful for endoscopic spinal procedures |
US5456267A (en) | 1994-03-18 | 1995-10-10 | Stark; John G. | Bone marrow harvesting systems and methods and bone biopsy systems and methods |
US5697977A (en) | 1994-03-18 | 1997-12-16 | Pisharodi; Madhavan | Method and apparatus for spondylolisthesis reduction |
DE4409610C3 (en) | 1994-03-21 | 2001-09-20 | Scandimed Internat Ab Sjoebo | Mixing device |
GB9407135D0 (en) | 1994-04-11 | 1994-06-01 | Aberdeen University And Plasma | Treatment of osteoporosis |
US5571189A (en) | 1994-05-20 | 1996-11-05 | Kuslich; Stephen D. | Expandable fabric implant for stabilizing the spinal motion segment |
US5492247A (en) | 1994-06-02 | 1996-02-20 | Shu; Aling | Automatic soap dispenser |
US5683451A (en) | 1994-06-08 | 1997-11-04 | Cardiovascular Concepts, Inc. | Apparatus and methods for deployment release of intraluminal prostheses |
US5501374A (en) | 1994-06-17 | 1996-03-26 | Vital Products, Co. | Device for extruding high viscosity fluid having multiple modes of operation |
WO1995035064A1 (en) | 1994-06-20 | 1995-12-28 | Slotman Gus J | Tissue spreading surgical instrument |
EP0692235A1 (en) | 1994-07-14 | 1996-01-17 | International Medication Systems (U.K.) Ltd. | Mixing & dispensing apparatus |
DE4425218A1 (en) | 1994-07-16 | 1996-01-18 | Merck Patent Gmbh | Device for mixing and discharging bone cement |
FR2722679A1 (en) | 1994-07-25 | 1996-01-26 | Daniel Felman | Expansible arthrodesis implant for insertion between vertebrae |
US6075067A (en) | 1994-08-15 | 2000-06-13 | Corpipharm Gmbh & Co | Cement for medical use, method for producing the cement, and use of the cement |
US5526853A (en) | 1994-08-17 | 1996-06-18 | Mcgaw, Inc. | Pressure-activated medication transfer system |
DE69513404T2 (en) | 1994-08-19 | 2000-07-06 | Biomat Bv | RADIO OPERATING POLYMERS AND METHOD FOR THEIR PRODUCTION |
US5588745A (en) | 1994-09-02 | 1996-12-31 | Howmedica | Methods and apparatus for mixing bone cement components using an evacuated mixing chamber |
US5536262A (en) | 1994-09-07 | 1996-07-16 | Cedars-Sinai Medical Center | Medical coupling device |
US5562736A (en) | 1994-10-17 | 1996-10-08 | Raymedica, Inc. | Method for surgical implantation of a prosthetic spinal disc nucleus |
AU700717B2 (en) | 1994-10-20 | 1999-01-14 | Intra Therapeutics, Inc. | Cystoscope delivery system |
JPH08126683A (en) | 1994-10-31 | 1996-05-21 | Fujisawa Pharmaceut Co Ltd | Container for transfusion |
US5697932A (en) | 1994-11-09 | 1997-12-16 | Osteonics Corp. | Bone graft delivery system and method |
RO116784B1 (en) | 1994-12-14 | 2001-06-29 | Inst Politehnic Iasi | Double planet stirrer |
US5836306A (en) | 1994-12-23 | 1998-11-17 | Bard Connaught | Exchange accessory for use with a monorail catheter |
JPH10511569A (en) | 1994-12-28 | 1998-11-10 | オムリクス バイオファーマス−ティカルズ エス.エー. | Applicator for one or more fluids |
US5450924A (en) | 1995-01-05 | 1995-09-19 | Tseng; Tien-Tsai | Portable oil suction device |
US5653686A (en) | 1995-01-13 | 1997-08-05 | Coulter Corporation | Closed vial transfer method and system |
GB2297488A (en) | 1995-02-02 | 1996-08-07 | Microsurgical Equipment Ltd | Trocar obturator guard |
GB0102529D0 (en) | 2001-01-31 | 2001-03-21 | Thales Optronics Staines Ltd | Improvements relating to thermal imaging cameras |
WO1996026869A1 (en) | 1995-02-27 | 1996-09-06 | James Owen Camm | Dual material dispenser comprising two containers in head to tail arrangement |
JPH08245329A (en) | 1995-03-13 | 1996-09-24 | G C:Kk | Relining material for denture base |
US5591197A (en) | 1995-03-14 | 1997-01-07 | Advanced Cardiovascular Systems, Inc. | Expandable stent forming projecting barbs and method for deploying |
US5785682A (en) | 1995-03-22 | 1998-07-28 | Abbott Laboratories | Pre-filled syringe drug delivery system |
US5603701A (en) | 1995-03-27 | 1997-02-18 | Ultradent Products, Inc. | Syringe apparatus with threaded plunger for delivering tooth composites and other solid yet pliable materials |
US5520690A (en) | 1995-04-13 | 1996-05-28 | Errico; Joseph P. | Anterior spinal polyaxial locking screw plate assembly |
DE59606028D1 (en) | 1995-04-21 | 2000-11-23 | Gerd Werding | NAIL FOR FIXING THE POSITION AND SHAPE OF BROKEN TUBULAR BONES |
US6103779A (en) | 1995-04-26 | 2000-08-15 | Reinforced Polmers, Inc. | Method of preparing molding compositions with fiber reinforcement and products obtained therefrom |
US5747553A (en) | 1995-04-26 | 1998-05-05 | Reinforced Polymer Inc. | Low pressure acrylic molding composition with fiber reinforcement |
US5578035A (en) | 1995-05-16 | 1996-11-26 | Lin; Chih-I | Expandable bone marrow cavity fixation device |
US5549381A (en) | 1995-05-19 | 1996-08-27 | Hays; Greta J. | Method and apparatus for mixing polymeric bone cement components |
US5634880A (en) | 1995-05-22 | 1997-06-03 | Johnson & Johnson Medical, Inc. | Endoscope pressure equalization system and method |
DE19519101B4 (en) | 1995-05-24 | 2009-04-23 | Harms, Jürgen, Prof. Dr. | Height adjustable vertebral body replacement |
GB9510917D0 (en) | 1995-05-30 | 1995-07-26 | Depuy Int Ltd | Bone cavity sealing assembly |
JPH08322848A (en) | 1995-06-01 | 1996-12-10 | Masato Narushima | Screw device for fixing bone fracture part |
US6409972B1 (en) | 1995-06-06 | 2002-06-25 | Kwan-Ho Chan | Prepackaged liquid bone cement |
US5795922A (en) | 1995-06-06 | 1998-08-18 | Clemson University | Bone cement composistion containing microencapsulated radiopacifier and method of making same |
US5660186A (en) | 1995-06-07 | 1997-08-26 | Marshfield Clinic | Spiral biopsy stylet |
US5556201A (en) | 1995-07-21 | 1996-09-17 | Middleby Marshall Inc. | Bowl scraper for commercial or industrial size food mixers |
US5836914A (en) | 1995-09-15 | 1998-11-17 | Becton Dickinson And Company | Method and apparatus for variably regulating the length of a combined spinal-epidural needle |
US5638997A (en) | 1995-09-18 | 1997-06-17 | Zimmer, Inc. | Bone cement injector gun |
US5893488A (en) | 1995-09-18 | 1999-04-13 | Bristol-Myers Squibb Co. | Bone cement injector gun |
US5797678A (en) | 1995-09-25 | 1998-08-25 | Murray; William M. | Bone cement mixing device and method |
US5624184A (en) | 1995-10-10 | 1997-04-29 | Chan; Kwan-Ho | Bone cement preparation kit having a breakable mixing shaft forming an output port |
US5782830A (en) | 1995-10-16 | 1998-07-21 | Sdgi Holdings, Inc. | Implant insertion device |
US6217581B1 (en) | 1995-10-18 | 2001-04-17 | John Thomas Tolson | High pressure cement injection device for bone repair |
US5782713A (en) | 1995-12-06 | 1998-07-21 | Yang; Shu-Chiung C. | Bicycle gear crank arresting device |
FR2741256A1 (en) | 1995-11-21 | 1997-05-23 | Advanced Technical Fabrication | CENTROMEDULAR NAIL |
US6228082B1 (en) | 1995-11-22 | 2001-05-08 | Arthrocare Corporation | Systems and methods for electrosurgical treatment of vascular disorders |
US5752974A (en) | 1995-12-18 | 1998-05-19 | Collagen Corporation | Injectable or implantable biomaterials for filling or blocking lumens and voids of the body |
US5766253A (en) | 1996-01-16 | 1998-06-16 | Surgical Dynamics, Inc. | Spinal fusion device |
WO1997028835A1 (en) | 1996-02-05 | 1997-08-14 | Volker Lang | Medicament application device for syringe pumps |
US5814022A (en) | 1996-02-06 | 1998-09-29 | Plasmaseal Llc | Method and apparatus for applying tissue sealant |
US5800389A (en) | 1996-02-09 | 1998-09-01 | Emx, Inc. | Biopsy device |
US5779356A (en) | 1996-02-21 | 1998-07-14 | Chan; Kwan-Ho | Apparatus and method for mixing first and second components of a bone cement in a vacuum |
US5885258A (en) | 1996-02-23 | 1999-03-23 | Memory Medical Systems, Inc. | Medical instrument with slotted memory metal tube |
DE19607517C1 (en) | 1996-02-28 | 1997-04-10 | Lutz Biedermann | Bone screw for osteosynthesis |
CA2192520A1 (en) | 1996-03-05 | 1997-09-05 | Ian M. Penn | Expandable stent and method for delivery of same |
US5800550A (en) | 1996-03-13 | 1998-09-01 | Sertich; Mario M. | Interbody fusion cage |
US5792044A (en) | 1996-03-22 | 1998-08-11 | Danek Medical, Inc. | Devices and methods for percutaneous surgery |
DE19612276A1 (en) | 1996-03-28 | 1997-10-02 | Medicad Engineering Gmbh | Bolt for mending fractures of long bones |
US5782747A (en) | 1996-04-22 | 1998-07-21 | Zimmon Science Corporation | Spring based multi-purpose medical instrument |
US5833628A (en) | 1996-04-24 | 1998-11-10 | Yuan; Hansen | Graduated bone graft harvester |
JPH09291879A (en) | 1996-04-26 | 1997-11-11 | Canyon Corp | Pump dispenser |
US5882345A (en) | 1996-05-22 | 1999-03-16 | Yoon; Inbae | Expandable endoscopic portal |
CN1062346C (en) | 1996-06-03 | 2001-02-21 | 程豹 | Self-sucking grease high effective oil ejector adapting sealed oil tank |
US5681317A (en) | 1996-06-12 | 1997-10-28 | Johnson & Johnson Professional, Inc. | Cement delivery system and method |
DE19624446C1 (en) | 1996-06-19 | 1998-03-26 | Ferton Holding | Surgical instrument for mechanical removal of bone cement, and method for generating shock waves |
US5824084A (en) | 1996-07-03 | 1998-10-20 | The Cleveland Clinic Foundation | Method of preparing a composite bone graft |
US5941851A (en) | 1996-07-12 | 1999-08-24 | C.R. Bard, Inc. | Pulsed lavage handpiece with improved handle |
US5785647A (en) | 1996-07-31 | 1998-07-28 | United States Surgical Corporation | Surgical instruments useful for spinal surgery |
DE19641775A1 (en) | 1996-08-22 | 1998-02-26 | Merck Patent Gmbh | Process for the production of active ingredient-containing bone cements |
US5827217A (en) | 1996-09-04 | 1998-10-27 | Silver; Frederick H. | Process and apparatus for harvesting tissue for processing tissue and process and apparatus for re-injecting processed tissue |
NL1004020C1 (en) | 1996-09-12 | 1998-03-13 | Rademaker B V | Kneading device for doughs and pastes. |
FR2753368B1 (en) | 1996-09-13 | 1999-01-08 | Chauvin Jean Luc | EXPANSIONAL OSTEOSYNTHESIS CAGE |
US5830194A (en) | 1996-09-20 | 1998-11-03 | Azam Anwar | Power syringe |
US5893850A (en) | 1996-11-12 | 1999-04-13 | Cachia; Victor V. | Bone fixation device |
US6033105A (en) | 1996-11-15 | 2000-03-07 | Barker; Donald | Integrated bone cement mixing and dispensing system |
US5876116A (en) | 1996-11-15 | 1999-03-02 | Barker; Donald | Integrated bone cement mixing and dispensing system |
JP3786483B2 (en) | 1996-11-20 | 2006-06-14 | 東レ・ダウコーニング株式会社 | Method and apparatus for quantitative application of highly viscous substances |
US5902839A (en) | 1996-12-02 | 1999-05-11 | Northwestern University | Bone cement and method of preparation |
AU6012998A (en) | 1996-12-13 | 1998-07-17 | Norian Corporation | Preparation, storage and administration of cements |
US6183441B1 (en) | 1996-12-18 | 2001-02-06 | Science Incorporated | Variable rate infusion apparatus with indicator and adjustable rate control |
US5868782A (en) | 1996-12-24 | 1999-02-09 | Global Therapeutics, Inc. | Radially expandable axially non-contracting surgical stent |
DE69733552T2 (en) | 1996-12-30 | 2005-12-08 | Xenon Research Inc., Lake Mary | Improved bone joining prosthesis and method of making it |
US6007496A (en) | 1996-12-30 | 1999-12-28 | Brannon; James K. | Syringe assembly for harvesting bone |
US5725341A (en) | 1997-01-08 | 1998-03-10 | Hofmeister; Oskar | Self fusing fastener |
US5718707A (en) | 1997-01-22 | 1998-02-17 | Mikhail; W. E. Michael | Method and apparatus for positioning and compacting bone graft |
DE19702907A1 (en) | 1997-01-28 | 1998-07-30 | Boehringer Mannheim Gmbh | Method and device for the purification of nucleic acids |
DE19704293A1 (en) | 1997-02-05 | 1998-08-06 | Basf Ag | Denture adhesive |
US6039761A (en) | 1997-02-12 | 2000-03-21 | Li Medical Technologies, Inc. | Intervertebral spacer and tool and method for emplacement thereof |
US20020068771A1 (en) | 1997-02-21 | 2002-06-06 | Dentsply Detrey Gmbh. | Low shrinking polymerizable dental material |
US5884818A (en) | 1997-02-24 | 1999-03-23 | Campbell; Norman | Grease gun |
EP1905392B1 (en) | 1997-03-07 | 2011-05-18 | Kyphon SÀRL | System for percutaneous bone and spinal stabilization, fixation and repair |
US5842786A (en) | 1997-03-07 | 1998-12-01 | Solomon; Alan | Method and device for mixing medical compositions |
WO2001054598A1 (en) | 1998-03-06 | 2001-08-02 | Disc-O-Tech Medical Technologies, Ltd. | Expanding bone implants |
US20070282443A1 (en) | 1997-03-07 | 2007-12-06 | Disc-O-Tech Medical Technologies Ltd. | Expandable element |
IL128261A0 (en) | 1999-01-27 | 1999-11-30 | Disc O Tech Medical Tech Ltd | Expandable element |
US5829875A (en) | 1997-04-02 | 1998-11-03 | Simpson Strong-Tie Co., Inc. | Combined barrier and mixer assembly for a cylindrical container |
EP0872223B1 (en) | 1997-04-16 | 2003-03-26 | Sulzer Orthopädie AG | Filling apparatus for bone cement |
US5800549A (en) | 1997-04-30 | 1998-09-01 | Howmedica Inc. | Method and apparatus for injecting an elastic spinal implant |
DE19718648A1 (en) | 1997-05-02 | 1998-11-05 | Merck Patent Gmbh | Method and device for producing sterile packed bone cement |
US5957929A (en) | 1997-05-02 | 1999-09-28 | Micro Therapeutics, Inc. | Expandable stent apparatus and method |
US5876457A (en) | 1997-05-20 | 1999-03-02 | George J. Picha | Spinal implant |
US5931347A (en) | 1997-05-23 | 1999-08-03 | Haubrich; Mark A. | Dispenser unit for viscous substances |
US6149651A (en) | 1997-06-02 | 2000-11-21 | Sdgi Holdings, Inc. | Device for supporting weak bony structures |
EP0882436B1 (en) | 1997-06-05 | 2002-08-21 | Sulzer Orthopädie AG | Transport and process device for two-component material |
US5972015A (en) | 1997-08-15 | 1999-10-26 | Kyphon Inc. | Expandable, asymetric structures for deployment in interior body regions |
US6599005B2 (en) | 1997-06-13 | 2003-07-29 | Hosokawa Micron Bv | Intensive mixer |
US6042262A (en) | 1997-07-29 | 2000-03-28 | Stryker Technologies Corportion | Apparatus for storing, mixing, and dispensing two-component bone cement |
US5968008A (en) | 1997-08-04 | 1999-10-19 | Grams; Guenter A. | Cannula with parallel channels and sliding sheath |
US6048346A (en) | 1997-08-13 | 2000-04-11 | Kyphon Inc. | Systems and methods for injecting flowable materials into bones |
EP0899247B1 (en) | 1997-08-28 | 2002-11-06 | Ngk Spark Plug Co., Ltd | Calcium phosphate cement and calcium phosphate cement composition |
US6217566B1 (en) | 1997-10-02 | 2001-04-17 | Target Therapeutics, Inc. | Peripheral vascular delivery catheter |
US6610004B2 (en) | 1997-10-09 | 2003-08-26 | Orqis Medical Corporation | Implantable heart assist system and method of applying same |
US6033411A (en) | 1997-10-14 | 2000-03-07 | Parallax Medical Inc. | Precision depth guided instruments for use in vertebroplasty |
US6309420B1 (en) | 1997-10-14 | 2001-10-30 | Parallax Medical, Inc. | Enhanced visibility materials for implantation in hard tissue |
US6019776A (en) | 1997-10-14 | 2000-02-01 | Parallax Medical, Inc. | Precision depth guided instruments for use in vertebroplasty |
US5968999A (en) | 1997-10-28 | 1999-10-19 | Charlotte-Mecklenburg Hospital Authority | Bone cement compositions |
US5826753A (en) | 1997-11-04 | 1998-10-27 | Mcneil (Ohio) Corporation | Grease gun locking mechanism |
US6080579A (en) | 1997-11-26 | 2000-06-27 | Charlotte-Mecklenburg Hospital Authority | Method for producing human intervertebral disc cells |
US6348518B1 (en) | 1997-12-10 | 2002-02-19 | R. Eric Montgomery | Compositions for making an artificial prosthesis |
US6348058B1 (en) | 1997-12-12 | 2002-02-19 | Surgical Navigation Technologies, Inc. | Image guided spinal surgery guide, system, and method for use thereof |
JPH11180814A (en) | 1997-12-24 | 1999-07-06 | Gc:Kk | Dentine adhesive set |
US6468279B1 (en) | 1998-01-27 | 2002-10-22 | Kyphon Inc. | Slip-fit handle for hand-held instruments that access interior body regions |
US6533807B2 (en) | 1998-02-05 | 2003-03-18 | Medtronic, Inc. | Radially-expandable stent and delivery system |
US6020396A (en) | 1998-03-13 | 2000-02-01 | The Penn State Research Foundation | Bone cement compositions |
US5928239A (en) | 1998-03-16 | 1999-07-27 | University Of Washington | Percutaneous surgical cavitation device and method |
DE69931152T2 (en) | 1998-03-27 | 2007-04-05 | Cook Urological Inc., Spencer | MINIMALLY INVASIVE APPARATUS FOR COLLECTING OBJECTS IN HOLLOWERS |
AU3203599A (en) | 1998-04-01 | 1999-10-18 | Parallax Medical, Inc. | Pressure applicator for hard tissue implant placement |
US6019789A (en) | 1998-04-01 | 2000-02-01 | Quanam Medical Corporation | Expandable unit cell and intraluminal stent |
US7572263B2 (en) | 1998-04-01 | 2009-08-11 | Arthrocare Corporation | High pressure applicator |
US6241729B1 (en) | 1998-04-09 | 2001-06-05 | Sdgi Holdings, Inc. | Method and instrumentation for posterior interbody fusion |
CA2327730A1 (en) | 1998-04-10 | 1999-10-21 | Wm Marsh Rice University | Synthesis of poly(propylene fumarate) by acylation of propylene glycol in the presence of a proton scavenger |
US5954671A (en) | 1998-04-20 | 1999-09-21 | O'neill; Michael J. | Bone harvesting method and apparatus |
DE19818210C5 (en) | 1998-04-24 | 2007-02-08 | Ivoclar Vivadent Ag | Radically polymerizable dental material |
US6019765A (en) | 1998-05-06 | 2000-02-01 | Johnson & Johnson Professional, Inc. | Morsellized bone allograft applicator device |
US6004325A (en) | 1998-05-11 | 1999-12-21 | Vargas, Iii; Joseph H. | Biomedical cement bonding enhancement tube |
US6447478B1 (en) | 1998-05-15 | 2002-09-10 | Ronald S. Maynard | Thin-film shape memory alloy actuators and processing methods |
ES2354492T3 (en) | 1998-06-01 | 2011-03-15 | Kyphon Sarl | PREFORMED STRUCTURES EXPANDABLE FOR DEPLOYMENT IN INTERNAL BODY REGIONS. |
US6719773B1 (en) | 1998-06-01 | 2004-04-13 | Kyphon Inc. | Expandable structures for deployment in interior body regions |
US6126689A (en) | 1998-06-15 | 2000-10-03 | Expanding Concepts, L.L.C. | Collapsible and expandable interbody fusion device |
US6041977A (en) | 1998-07-23 | 2000-03-28 | Lisi; Edmund T. | Dispensing system for decorating or filling edible products |
WO2000006216A1 (en) | 1998-07-27 | 2000-02-10 | Focal, Inc. | Universal modular surgical applicator systems |
US6149664A (en) | 1998-08-27 | 2000-11-21 | Micrus Corporation | Shape memory pusher introducer for vasoocclusive devices |
US6022339A (en) | 1998-09-15 | 2000-02-08 | Baxter International Inc. | Sliding reconstitution device for a diluent container |
JP2000126214A (en) | 1998-09-16 | 2000-05-09 | Sulzer Orthopedics Ltd | Packing and transferring device of bone cement |
US6183516B1 (en) | 1998-10-08 | 2001-02-06 | Sulzer Orthopedics Inc. | Method for improved bonding of prosthetic devices to bone |
US6086594A (en) | 1998-10-16 | 2000-07-11 | Brown; Byron L. | Cement pressurizing device |
US6261289B1 (en) | 1998-10-26 | 2001-07-17 | Mark Levy | Expandable orthopedic device |
US6554833B2 (en) | 1998-10-26 | 2003-04-29 | Expanding Orthopedics, Inc. | Expandable orthopedic device |
US6206058B1 (en) | 1998-11-09 | 2001-03-27 | The Procter & Gamble Company | Integrated vent and fluid transfer fitment |
CA2350706A1 (en) | 1998-11-13 | 2000-05-25 | Elan Pharma International Limited | Drug delivery systems and methods |
US6214012B1 (en) | 1998-11-13 | 2001-04-10 | Harrington Arthritis Research Center | Method and apparatus for delivering material to a desired location |
AU736964B2 (en) | 1998-12-09 | 2001-08-09 | Cook Medical Technologies Llc | Hollow, curved, superelastic medical needle |
JP4159202B2 (en) | 1998-12-21 | 2008-10-01 | 日本特殊陶業株式会社 | Calcium phosphate cement kneading apparatus and method for preparing calcium phosphate cement kneaded material |
US6120174A (en) | 1999-01-14 | 2000-09-19 | Bristol-Myers Squibb | Apparatus and method for mixing and dispensing bone cement |
US6116773A (en) | 1999-01-22 | 2000-09-12 | Murray; William M. | Bone cement mixer and method |
CA2360529A1 (en) | 1999-01-28 | 2000-08-03 | Minrad Inc. | Sampling device and method of retrieving a sample |
US6264659B1 (en) | 1999-02-22 | 2001-07-24 | Anthony C. Ross | Method of treating an intervertebral disk |
US6436143B1 (en) | 1999-02-22 | 2002-08-20 | Anthony C. Ross | Method and apparatus for treating intervertebral disks |
SE521945C2 (en) | 1999-02-26 | 2003-12-23 | Biomet Merck Cementing Technol | Mixing device for making bone cement |
EP1033125B1 (en) | 1999-03-03 | 2003-09-24 | Kuraray Co., Ltd. | Relining material for dentures |
US6770079B2 (en) | 1999-03-16 | 2004-08-03 | American Osteomedix, Inc. | Apparatus and method for fixation of osteoporotic bone |
US6395007B1 (en) | 1999-03-16 | 2002-05-28 | American Osteomedix, Inc. | Apparatus and method for fixation of osteoporotic bone |
US6709465B2 (en) | 1999-03-18 | 2004-03-23 | Fossa Medical, Inc. | Radially expanding ureteral device |
US6214037B1 (en) | 1999-03-18 | 2001-04-10 | Fossa Industries, Llc | Radially expanding stent |
US6402701B1 (en) | 1999-03-23 | 2002-06-11 | Fna Concepts, Llc | Biopsy needle instrument |
WO2000056254A1 (en) | 1999-03-24 | 2000-09-28 | Parallax Medical, Inc. | Non-compliant system for delivery of implant material |
US6689823B1 (en) | 1999-03-31 | 2004-02-10 | The Brigham And Women's Hospital, Inc. | Nanocomposite surgical materials and method of producing them |
US6254268B1 (en) | 1999-07-16 | 2001-07-03 | Depuy Orthopaedics, Inc. | Bone cement mixing apparatus |
DE60043734D1 (en) | 1999-04-20 | 2010-03-11 | Jms Co Ltd | CONTAINER CAP FOR TANK AND LIQUID TRANSFER DEVICE |
US6214016B1 (en) | 1999-04-29 | 2001-04-10 | Medtronic, Inc. | Medical instrument positioning device internal to a catheter or lead and method of use |
US6245101B1 (en) | 1999-05-03 | 2001-06-12 | William J. Drasler | Intravascular hinge stent |
US6221029B1 (en) | 1999-05-13 | 2001-04-24 | Stryker Corporation | Universal biopsy system |
US6350271B1 (en) | 1999-05-17 | 2002-02-26 | Micrus Corporation | Clot retrieval device |
US6224604B1 (en) | 1999-07-30 | 2001-05-01 | Loubert Suddaby | Expandable orthopedic drill for vertebral interbody fusion techniques |
IL131197A (en) | 1999-08-01 | 2009-12-24 | Assaf Dekel | Apparatus for spinal procedures |
ES2164548B1 (en) | 1999-08-05 | 2003-03-01 | Probitas Pharma Sa | DEVICE FOR DOSAGE OF FRAGUABLE MASS FOR VERTEBROPLASTIA AND OTHER SIMILAR OSEOS TREATMENTS. |
US6479565B1 (en) | 1999-08-16 | 2002-11-12 | Harold R. Stanley | Bioactive ceramic cement |
US6620169B1 (en) | 1999-08-26 | 2003-09-16 | Spineology Group, Llc. | Tools and method for processing and injecting bone graft |
CA2287112C (en) | 1999-09-02 | 2008-02-19 | Kieran Murphy | Method and apparatus for strengthening vertebral bodies |
US6783515B1 (en) | 1999-09-30 | 2004-08-31 | Arthrocare Corporation | High pressure delivery system |
JP2001104324A (en) | 1999-10-06 | 2001-04-17 | Ngk Spark Plug Co Ltd | Medicine extruding auxiliary device, and medicine extruding method using the same |
EP1090609A1 (en) | 1999-10-07 | 2001-04-11 | NGK Spark Plug Company Limited | Device and method for preparing calcium phosphate-based cement |
US6599520B2 (en) | 1999-10-14 | 2003-07-29 | Osteotech, Inc. | Method of inducing new bone growth in porous bone sites |
US6575919B1 (en) | 1999-10-19 | 2003-06-10 | Kyphon Inc. | Hand-held instruments that access interior body regions |
DE29919110U1 (en) | 1999-11-01 | 2000-01-27 | Dunsch Herzberg Renate | Device for introducing bone cement into a bone tube |
US6592624B1 (en) | 1999-11-24 | 2003-07-15 | Depuy Acromed, Inc. | Prosthetic implant element |
US6425885B1 (en) | 1999-12-20 | 2002-07-30 | Ultradent Products, Inc. | Hydraulic syringe |
FR2802830B1 (en) | 1999-12-27 | 2002-06-07 | Coatex Sa | USE OF WATER-SOLUBLE POLYMERS AS AN AQUEOUS SUSPENSION AGENT FOR CALCIUM CARBONATE AQUEOUS SUSPENSIONS AND THEIR USES |
US7842068B2 (en) | 2000-12-07 | 2010-11-30 | Integrated Vascular Systems, Inc. | Apparatus and methods for providing tactile feedback while delivering a closure device |
JP2003519640A (en) | 2000-01-14 | 2003-06-24 | デンフォテックス・リミテッド | Polymerizable resin composites for use in dentistry |
US6458117B1 (en) | 2000-01-19 | 2002-10-01 | Kevin Daniel Pollins, Sr. | Intraosseous infusion assembly and method for intraosseous infusion |
GB2359762B (en) | 2000-01-31 | 2003-03-12 | Summit Medical Ltd | Orthopaedic cement mixing device |
WO2001054746A2 (en) | 2000-01-31 | 2001-08-02 | Advanced Research And Technology Institute, Inc. | Composite biomaterial including anisometric calcium phosphate reinforcement particles |
US20020010471A1 (en) | 2000-02-04 | 2002-01-24 | Wironen John F. | Methods for injecting materials into bone |
US6502608B1 (en) | 2000-02-14 | 2003-01-07 | Telios Orthopedic Systems, Inc. | Delivery apparatus, nozzle, and removable tip assembly |
US6383188B2 (en) | 2000-02-15 | 2002-05-07 | The Spineology Group Llc | Expandable reamer |
US6558386B1 (en) | 2000-02-16 | 2003-05-06 | Trans1 Inc. | Axial spinal implant and method and apparatus for implanting an axial spinal implant within the vertebrae of the spine |
CN1310026A (en) | 2000-02-24 | 2001-08-29 | 宋治中 | Medical adhesive high molecular material and its preparation |
US6740093B2 (en) | 2000-02-28 | 2004-05-25 | Stephen Hochschuler | Method and apparatus for treating a vertebral body |
FR2808208B1 (en) | 2000-04-27 | 2002-06-28 | Optimex 2000 Ltd | CANNULA SET FOR HUMAN BODY INJECTIONS |
US6406175B1 (en) | 2000-05-04 | 2002-06-18 | James F. Marino | Bone cement isovolumic mixing and injection device |
DE10064202A1 (en) | 2000-05-25 | 2001-11-29 | Pajunk Gmbh | Device for applying bone cement and cannula for such a device |
US6916308B2 (en) | 2000-06-08 | 2005-07-12 | Cook Incorporated | High pressure injection syringe |
US6488667B1 (en) | 2000-06-15 | 2002-12-03 | Kieran P. J. Murphy | Needle control device |
US6450973B1 (en) | 2000-06-16 | 2002-09-17 | Kieran P. J. Murphy | Biopsy gun |
US6749614B2 (en) | 2000-06-23 | 2004-06-15 | Vertelink Corporation | Formable orthopedic fixation system with cross linking |
KR100889414B1 (en) | 2000-06-27 | 2009-03-20 | 키폰 에스에이알엘 | Systems and methods for injecting flowable materials into bones |
US7025771B2 (en) | 2000-06-30 | 2006-04-11 | Spineology, Inc. | Tool to direct bone replacement material |
CA2414351C (en) | 2000-06-30 | 2008-12-09 | Augmentation-Technology Gmbh | Device for injecting bone cement |
DE10032976A1 (en) | 2000-07-06 | 2002-01-17 | Pfeiffer Erich Gmbh & Co Kg | Discharge device for media |
CA2415389C (en) | 2000-07-14 | 2009-02-17 | Kyphon Inc. | Systems and methods for treating vertebral bodies |
DE60141653D1 (en) | 2000-07-21 | 2010-05-06 | Spineology Group Llc | A STRONG, POROUS NET BAG DEVICE AND ITS USE IN BONE SURGERY |
US20080086133A1 (en) | 2003-05-16 | 2008-04-10 | Spineology | Expandable porous mesh bag device and methods of use for reduction, filling, fixation and supporting of bone |
AU2001284857B2 (en) | 2000-08-11 | 2005-09-29 | Warsaw Orthopedic, Inc. | Surgical instrumentation and method for treatment of the spine |
US6787584B2 (en) | 2000-08-11 | 2004-09-07 | Pentron Corporation | Dental/medical compositions comprising degradable polymers and methods of manufacture thereof |
WO2002013688A2 (en) | 2000-08-16 | 2002-02-21 | Cook Vascular Incorporated | Doppler probe with shapeable portion |
EP1582166B1 (en) | 2000-09-07 | 2007-06-27 | Sherwood Services AG | Apparatus for the treatment of the intervertebral disc |
US20020191487A1 (en) | 2000-10-25 | 2002-12-19 | Kyphon Inc. | Systems and methods for mixing and transferring flowable materials |
CA2426688C (en) | 2000-10-25 | 2011-12-20 | Kyphon Inc. | Systems and methods for reducing fractured bone using a fracture reduction cannula |
JP3730216B2 (en) | 2000-11-13 | 2005-12-21 | 森永製菓株式会社 | Kneading apparatus, two-stage kneading apparatus, and kneading molding apparatus |
DE10057616B4 (en) | 2000-11-21 | 2006-09-14 | Stryker Trauma Gmbh | Method for mixing and applying flowable bone cement and bone cement mixing device |
JP4305594B2 (en) | 2000-11-28 | 2009-07-29 | 株式会社トクヤマ | Dental bonding kit |
US6800245B1 (en) | 2000-11-28 | 2004-10-05 | Vita Special Purpose Corporation | Sterile polymerizable systems and kits and methods of their manufacture and use |
US6702455B2 (en) | 2000-12-01 | 2004-03-09 | Depuy Orthopaedics, Inc. | Bone cement mixing apparatus having improved gearing arrangement for driving a mixing blade |
US6655828B2 (en) | 2000-12-01 | 2003-12-02 | Depuy Orthopaedics, Inc. | Bone cement mixing apparatus having improved mixing blade configuration |
US6712853B2 (en) | 2000-12-15 | 2004-03-30 | Spineology, Inc. | Annulus-reinforcing band |
US6439439B1 (en) | 2001-01-12 | 2002-08-27 | Telios Orthopedic Systems, Inc. | Bone cement delivery apparatus and hand-held fluent material dispensing apparatus |
ATE308278T1 (en) | 2001-01-26 | 2005-11-15 | Uab Research Foundation | BONE CEMENT |
US6450987B1 (en) | 2001-02-01 | 2002-09-17 | Innercool Therapies, Inc. | Collapsible guidewire lumen |
US6758837B2 (en) | 2001-02-08 | 2004-07-06 | Pharmacia Ab | Liquid delivery device and method of use thereof |
WO2002064194A1 (en) | 2001-02-14 | 2002-08-22 | Acist Medical Systems, Inc. | Fluid injector system |
US20020143294A1 (en) | 2001-02-14 | 2002-10-03 | Duchon Douglas J. | Catheter fluid control system |
US7008433B2 (en) | 2001-02-15 | 2006-03-07 | Depuy Acromed, Inc. | Vertebroplasty injection device |
US7544196B2 (en) | 2001-02-20 | 2009-06-09 | Orthovita, Inc. | System and kit for delivery of restorative materials |
US6375659B1 (en) | 2001-02-20 | 2002-04-23 | Vita Licensing, Inc. | Method for delivery of biocompatible material |
US6613018B2 (en) | 2001-02-20 | 2003-09-02 | Vita Licensing, Inc. | System and kit for delivery of restorative materials |
DE10108261B4 (en) | 2001-02-21 | 2006-07-20 | Ivoclar Vivadent Ag | Polymerizable composition with particulate composite based filler |
US20020118595A1 (en) | 2001-02-26 | 2002-08-29 | Miller Scott H. | Enclosed implantable material mixing system |
US7087040B2 (en) | 2001-02-28 | 2006-08-08 | Rex Medical, L.P. | Apparatus for delivering ablation fluid to treat lesions |
US7044933B2 (en) | 2001-03-01 | 2006-05-16 | Scimed Life Systems, Inc. | Fluid injection system for coronary intervention |
BR0208064A (en) | 2001-03-13 | 2006-10-10 | Mdc Invest Holdings Inc | medical device and process for injecting medicine |
AU2002245702A1 (en) | 2001-03-19 | 2002-10-03 | Cambridge Polymer Group Inc. | System and methods for reducing interfacial porosity in cements |
US20020134801A1 (en) | 2001-03-26 | 2002-09-26 | Stewart David A. | First use flow-delay membrane for pourable containerized motor oils and other viscous fluids |
US6443334B1 (en) | 2001-04-10 | 2002-09-03 | Pentalpha Hong Kong Limited | Comestible fluid dispenser apparatus and method |
US6402758B1 (en) | 2001-04-16 | 2002-06-11 | John Thomas Tolson | Methods for repairing bone using a high pressure cement injection |
US6632235B2 (en) | 2001-04-19 | 2003-10-14 | Synthes (U.S.A.) | Inflatable device and method for reducing fractures in bone and in treating the spine |
US6852439B2 (en) | 2001-05-15 | 2005-02-08 | Hydrogenics Corporation | Apparatus for and method of forming seals in fuel cells and fuel cell stacks |
ITVI20010126A1 (en) | 2001-05-30 | 2002-11-30 | Tecres Spa | RADIOPACO BONE CEMENT FOR ORTHOPEDIC USE AND METHOD OF REALIZATION |
US20020188300A1 (en) | 2001-06-06 | 2002-12-12 | Arramon Yves P. | Cannula system for hard tissue implant delivery |
DE10129842C1 (en) | 2001-06-15 | 2003-04-24 | Bam Bundesanstalt Matforschung | Process for the production of a bioactive bone cement and bone cement kit |
US6599293B2 (en) | 2001-07-16 | 2003-07-29 | Stryker Instruments | Delivery device for bone cement |
US6547432B2 (en) | 2001-07-16 | 2003-04-15 | Stryker Instruments | Bone cement mixing and delivery device for injection and method thereof |
US6796987B2 (en) | 2001-07-16 | 2004-09-28 | Stryker Instruments | Delivery device for bone cement |
US6676663B2 (en) | 2001-07-19 | 2004-01-13 | Higueras Antonio Perez | Applicator device for controllably injecting a surgical cement into bones |
WO2003007854A1 (en) | 2001-07-20 | 2003-01-30 | The Spineology Group, Llc | Device for inserting fill material particles into body cavities |
CN1835720B (en) | 2001-07-25 | 2011-09-28 | Disc整形外科技术股份有限公司 | Deformable tools and implants |
US6375682B1 (en) | 2001-08-06 | 2002-04-23 | Lewis W. Fleischmann | Collapsible, rotatable and expandable spinal hydraulic prosthetic device |
US6793660B2 (en) | 2001-08-20 | 2004-09-21 | Synthes (U.S.A.) | Threaded syringe for delivery of a bone substitute material |
US6712794B2 (en) | 2001-08-21 | 2004-03-30 | Spinal Specialties, Inc. | Apparatus for delivering a viscous liquid to a surgical site |
US7456024B2 (en) | 2001-08-29 | 2008-11-25 | Hexal Pharma Gmbh | Method and device for preparing a sample of biological origin in order to determine at least one constituent contained therein |
US20030050644A1 (en) | 2001-09-11 | 2003-03-13 | Boucher Ryan P. | Systems and methods for accessing and treating diseased or fractured bone employing a guide wire |
US6706069B2 (en) | 2001-09-13 | 2004-03-16 | J. Lee Berger | Spinal grooved director with built in balloon |
FR2829691B1 (en) | 2001-09-17 | 2004-07-09 | Sedat | DEVICE FOR BIDIRECTIONAL TRANSFER OF A LIQUID BETWEEN A BOTTLE AND A CARPULE |
US6494344B1 (en) | 2001-09-28 | 2002-12-17 | Joseph A. Kressel, Sr. | Liquid dispensing container |
US6984063B2 (en) | 2002-10-07 | 2006-01-10 | Advanced Biomaterial Systems, Inc. | Apparatus for mixing and dispensing components |
WO2003031042A1 (en) | 2001-10-09 | 2003-04-17 | Immedica (A New Jersey Corporation) | Multi-component, product handling and delivering system |
US7029163B2 (en) | 2002-10-07 | 2006-04-18 | Advanced Biomaterial Systems, Inc. | Apparatus for mixing and dispensing components |
EP1465521A4 (en) | 2001-11-01 | 2008-10-08 | Spine Wave Inc | System and method for the pretreatment of the endplates of an intervertebral disc |
JP4499327B2 (en) | 2001-12-06 | 2010-07-07 | 松崎 浩巳 | Diameter expansion instrument and surgical instrument set |
US6662969B2 (en) | 2001-12-14 | 2003-12-16 | Zaxis, Inc. | Hydraulically and volumetrically dispensing a target fluid |
US6582439B1 (en) | 2001-12-28 | 2003-06-24 | Yacmur Llc | Vertebroplasty system |
IL147783A0 (en) | 2002-01-23 | 2002-08-14 | Disc O Tech Medical Tech Ltd | Locking mechanism for intramedulliary nails |
US7186364B2 (en) | 2002-01-28 | 2007-03-06 | Depuy Products, Inc. | Composite prosthetic bearing constructed of polyethylene and an ethylene-acrylate copolymer and method for making the same |
JP4663238B2 (en) | 2002-03-14 | 2011-04-06 | ストライカー コーポレイション | Mixer assembly for mixing bone cement |
US6736835B2 (en) | 2002-03-21 | 2004-05-18 | Depuy Acromed, Inc. | Early intervention spinal treatment methods and devices for use therein |
US6921192B2 (en) | 2002-03-29 | 2005-07-26 | Depuy Orthopaedics, Inc. | Bone cement mixing apparatus |
SE0201052D0 (en) | 2002-04-04 | 2002-04-04 | Cerbio Tech Ab | Biocompatible cement compositions and method of manufacturing |
ES2269656T3 (en) | 2002-04-11 | 2007-04-01 | Synthes Gmbh | MIXING AND / OR CEMENT INJECTION DEVICE. |
SE0201180L (en) | 2002-04-18 | 2003-02-18 | Cemvac System Ab | Apparatus for preparing bone cement comprising a mixing bowl with a sealing cap, in which at least one rotatable mixing element is stored |
DK1366774T3 (en) | 2002-05-29 | 2007-10-08 | Heraeus Kulzer Gmbh | Bone cement mixture and X-ray contrast agent |
JP4808961B2 (en) | 2002-06-04 | 2011-11-02 | オフィス オブ テクノロジー ライセンシング スタンフォード ユニバーシティ | Device for rapidly aspirating and collecting body tissue from an encapsulated body space |
JP4112908B2 (en) | 2002-06-07 | 2008-07-02 | 株式会社日立プラントテクノロジー | Continuous stirring device and continuous polycondensation method of polycondensation resin |
US20060167148A1 (en) | 2002-06-20 | 2006-07-27 | Hakan Engqvist | System for a chemically bonded ceramic material, a powdered material and a hydration liquid therefore, the ceramic material, a method for its production and a device |
JP4182692B2 (en) | 2002-06-20 | 2008-11-19 | 油化電子株式会社 | Syringe type drug capsule |
US6847310B1 (en) | 2002-06-21 | 2005-01-25 | Bsquare Corporation | Keyboard |
ITVI20020140A1 (en) | 2002-06-26 | 2003-12-29 | Tecres Spa | DEVICE FOR THE MANUAL DOSING OF A MEDICAL FLUID, PARTICULARLY BONE CEMENT |
US6730095B2 (en) | 2002-06-26 | 2004-05-04 | Scimed Life Systems, Inc. | Retrograde plunger delivery system |
AU2003249036A1 (en) | 2002-07-12 | 2004-02-02 | Cook Urological, Inc. | Flexible cannula shaft |
WO2005017000A1 (en) | 2003-07-31 | 2005-02-24 | Cambridge Polymer Group | Systems and methods for controlling and forming polymer gels |
US7138442B2 (en) | 2002-08-30 | 2006-11-21 | Biomet, Inc. | Reduced exothermic bone replacement cement |
US7217254B2 (en) | 2002-09-20 | 2007-05-15 | Genzyme Corporation | Multi-pressure biocompatible agent delivery device and method |
US7326203B2 (en) | 2002-09-30 | 2008-02-05 | Depuy Acromed, Inc. | Device for advancing a functional element through tissue |
US7066942B2 (en) | 2002-10-03 | 2006-06-27 | Wright Medical Technology, Inc. | Bendable needle for delivering bone graft material and method of use |
US7294132B2 (en) | 2002-10-03 | 2007-11-13 | Wright Medical Technology, Inc. | Radially ported needle for delivering bone graft material and method of use |
US20040073139A1 (en) | 2002-10-11 | 2004-04-15 | Hirsch Joshua A. | Cannula for extracting and implanting material |
US6979352B2 (en) | 2002-11-21 | 2005-12-27 | Depuy Acromed | Methods of performing embolism-free vertebroplasty and devices therefor |
US6970734B2 (en) | 2002-12-02 | 2005-11-29 | Boston Scientific Scimed, Inc. | Flexible marker bands |
DE10258140B4 (en) | 2002-12-04 | 2005-12-22 | Aesculap Ag & Co. Kg | System for filling application containers |
US20040122438A1 (en) | 2002-12-23 | 2004-06-24 | Boston Scientific Corporation | Flex-tight interlocking connection tubing for delivery of bone cements/biomaterials for vertebroplasty |
US7270648B2 (en) | 2002-12-23 | 2007-09-18 | Farhad Kazemzadeh | Drug delivery apparatus |
US20040133124A1 (en) | 2003-01-06 | 2004-07-08 | Cook Incorporated. | Flexible biopsy needle |
US6779566B2 (en) | 2003-01-14 | 2004-08-24 | Access Business Group International Llc | Connector device for sealing and dispensing freeze-dried preparations |
JP2004236729A (en) | 2003-02-04 | 2004-08-26 | Kobayashi Pharmaceut Co Ltd | Bone cement composition |
WO2004071543A1 (en) | 2003-02-13 | 2004-08-26 | Synthes Ag Chur | Injectable bone-replacement mixture |
AU2004212942A1 (en) | 2003-02-14 | 2004-09-02 | Depuy Spine, Inc. | In-situ formed intervertebral fusion device |
US6875219B2 (en) | 2003-02-14 | 2005-04-05 | Yves P. Arramon | Bone access system |
US20040167437A1 (en) | 2003-02-26 | 2004-08-26 | Sharrow James S. | Articulating intracorporal medical device |
US7393493B2 (en) | 2003-02-27 | 2008-07-01 | A Enterprises, Inc. | Crosslinkable polymeric materials and their applications |
US20060264967A1 (en) | 2003-03-14 | 2006-11-23 | Ferreyro Roque H | Hydraulic device for the injection of bone cement in percutaneous vertebroplasty |
US8066713B2 (en) | 2003-03-31 | 2011-11-29 | Depuy Spine, Inc. | Remotely-activated vertebroplasty injection device |
US20040220672A1 (en) | 2003-05-03 | 2004-11-04 | Shadduck John H. | Orthopedic implants, methods of use and methods of fabrication |
US20040267272A1 (en) | 2003-05-12 | 2004-12-30 | Henniges Bruce D | Bone cement mixing and delivery system |
DE10321350B4 (en) | 2003-05-13 | 2005-04-21 | Lurgi Ag | mixing device |
US20040236313A1 (en) | 2003-05-21 | 2004-11-25 | Klein Jeffrey A. | Infiltration cannula |
WO2004110292A2 (en) | 2003-06-12 | 2004-12-23 | Disc-O-Tech Medical Technologies, Ltd. | Plate device |
US8415407B2 (en) | 2004-03-21 | 2013-04-09 | Depuy Spine, Inc. | Methods, materials, and apparatus for treating bone and other tissue |
US20070032567A1 (en) | 2003-06-17 | 2007-02-08 | Disc-O-Tech Medical | Bone Cement And Methods Of Use Thereof |
US7112205B2 (en) | 2003-06-17 | 2006-09-26 | Boston Scientific Scimed, Inc. | Apparatus and methods for delivering compounds into vertebrae for vertebroplasty |
WO2006011152A2 (en) | 2004-06-17 | 2006-02-02 | Disc-O-Tech Medical Technologies, Ltd. | Methods for treating bone and other tissue |
US7179232B2 (en) | 2003-06-27 | 2007-02-20 | Depuy Acromed, Inc. | Controlled orifice sampling needle |
US20050015148A1 (en) | 2003-07-18 | 2005-01-20 | Jansen Lex P. | Biocompatible wires and methods of using same to fill bone void |
US6974306B2 (en) | 2003-07-28 | 2005-12-13 | Pratt & Whitney Canada Corp. | Blade inlet cooling flow deflector apparatus and method |
US7261718B2 (en) | 2003-09-11 | 2007-08-28 | Skeletal Kinetics Llc | Use of vibration with polymeric bone cements |
US7261717B2 (en) | 2003-09-11 | 2007-08-28 | Skeletal Kinetics Llc | Methods and devices for delivering orthopedic cements to a target bone site |
US8579908B2 (en) | 2003-09-26 | 2013-11-12 | DePuy Synthes Products, LLC. | Device for delivering viscous material |
US7909833B2 (en) | 2003-09-29 | 2011-03-22 | Depuy Acromed, Inc. | Vertebroplasty device having a flexible plunger |
WO2005032326A2 (en) | 2003-10-07 | 2005-04-14 | Disc-O-Tech Medical Technologies, Ltd. | Soft tissue to bone fixation |
DE10347930A1 (en) | 2003-10-15 | 2005-05-12 | Bayer Materialscience Ag | stirrer |
WO2005051212A1 (en) | 2003-11-18 | 2005-06-09 | Somatex Medical Technologies Gmbh | Injection pump |
US20050113762A1 (en) | 2003-11-24 | 2005-05-26 | Kay John F. | Minimally invasive high viscosity material delivery system |
JP2007515228A (en) | 2003-12-18 | 2007-06-14 | ハルキー − ロバーツ コーポレイション | Needle-free access vial |
US20050154081A1 (en) | 2004-01-09 | 2005-07-14 | Bisco, Inc. | Opacity and color change polymerizable dental materials |
US8235256B2 (en) | 2004-02-12 | 2012-08-07 | Kyphon Sarl | Manual pump mechanism and delivery system |
US7641664B2 (en) | 2004-02-12 | 2010-01-05 | Warsaw Orthopedic, Inc. | Surgical instrumentation and method for treatment of a spinal structure |
GB2411849B (en) | 2004-03-08 | 2007-08-29 | Summit Medical Ltd | Apparatus for mixing and discharging bone cement |
US8945223B2 (en) | 2004-03-12 | 2015-02-03 | Warsaw Orthopedic, Inc. | In-situ formable nucleus pulposus implant with water absorption and swelling capability |
US20050209695A1 (en) | 2004-03-15 | 2005-09-22 | De Vries Jan A | Vertebroplasty method |
US20050216025A1 (en) | 2004-03-22 | 2005-09-29 | Cana Lab Corporation | Device for forming a hardened cement in a bone cavity |
GB2413280B (en) | 2004-04-19 | 2006-03-22 | Wonderland Nursery Goods | Playpen with columns |
FR2870129A1 (en) | 2004-05-14 | 2005-11-18 | Ceravic Sas Soc Par Actions Si | POLYMERIC CEMENT FOR PERCUTANEOUS VERTEBROPLASTY |
CN1984613B (en) | 2004-05-19 | 2010-09-29 | 欣蒂生物技术股份公司 | Intravertebral widening device |
US7441652B2 (en) | 2004-05-20 | 2008-10-28 | Med Institute, Inc. | Mixing system |
US7708751B2 (en) | 2004-05-21 | 2010-05-04 | Ethicon Endo-Surgery, Inc. | MRI biopsy device |
AU2005258328A1 (en) | 2004-06-16 | 2006-01-05 | Warsaw Orthopedic, Inc. | Surgical instrumentation for the repair of vertebral bodies |
US20060035997A1 (en) | 2004-08-10 | 2006-02-16 | Orlowski Jan A | Curable acrylate polymer compositions featuring improved flexural characteristics |
US20080319445A9 (en) | 2004-08-17 | 2008-12-25 | Scimed Life Systems, Inc. | Apparatus and methods for delivering compounds into vertebrae for vertebroplasty |
US8038682B2 (en) | 2004-08-17 | 2011-10-18 | Boston Scientific Scimed, Inc. | Apparatus and methods for delivering compounds into vertebrae for vertebroplasty |
US7678116B2 (en) | 2004-12-06 | 2010-03-16 | Dfine, Inc. | Bone treatment systems and methods |
US7559932B2 (en) | 2004-12-06 | 2009-07-14 | Dfine, Inc. | Bone treatment systems and methods |
US7717918B2 (en) | 2004-12-06 | 2010-05-18 | Dfine, Inc. | Bone treatment systems and methods |
US7722620B2 (en) | 2004-12-06 | 2010-05-25 | Dfine, Inc. | Bone treatment systems and methods |
US8070753B2 (en) | 2004-12-06 | 2011-12-06 | Dfine, Inc. | Bone treatment systems and methods |
US20060122614A1 (en) | 2004-12-06 | 2006-06-08 | Csaba Truckai | Bone treatment systems and methods |
WO2006062939A2 (en) | 2004-12-06 | 2006-06-15 | Dfine, Inc. | Bone treatment systems and methods |
JP2008523851A (en) | 2004-12-16 | 2008-07-10 | ツォンシャン ボタイ ファーマスーティック インスツルメンツ カンパニー リミテッド | Drug injector for mixed drug injection |
US20060164913A1 (en) | 2005-01-21 | 2006-07-27 | Arthrocare Corporation | Multi-chamber integrated mixing and delivery system |
JP2008531109A (en) * | 2005-02-22 | 2008-08-14 | ディスク−オー−テック メディカル テクノロジーズ, リミテッド | Methods, materials, and devices for treating bone and other tissues |
KR101121387B1 (en) | 2005-03-07 | 2012-03-09 | 헥터 오. 파체코 | System and methods for improved access to vertebral bodies for kyphoplasty, vertebroplasty, vertebral body biopsy or screw placement |
US7503469B2 (en) | 2005-03-09 | 2009-03-17 | Rexam Closure Systems Inc. | Integrally molded dispensing valve and method of manufacture |
US9381024B2 (en) | 2005-07-31 | 2016-07-05 | DePuy Synthes Products, Inc. | Marked tools |
IL174347A0 (en) | 2005-07-31 | 2006-08-20 | Disc O Tech Medical Tech Ltd | Bone cement and methods of use thereof |
US9918767B2 (en) | 2005-08-01 | 2018-03-20 | DePuy Synthes Products, Inc. | Temperature control system |
US7116121B1 (en) | 2005-10-27 | 2006-10-03 | Agilent Technologies, Inc. | Probe assembly with controlled impedance spring pin or resistor tip spring pin contacts |
US7713273B2 (en) | 2005-11-18 | 2010-05-11 | Carefusion 2200, Inc. | Device, system and method for delivering a curable material into bone |
US7799035B2 (en) | 2005-11-18 | 2010-09-21 | Carefusion 2200, Inc. | Device, system and method for delivering a curable material into bone |
US8360629B2 (en) | 2005-11-22 | 2013-01-29 | Depuy Spine, Inc. | Mixing apparatus having central and planetary mixing elements |
US7922690B2 (en) | 2006-02-22 | 2011-04-12 | Michael Plishka | Curable material delivery device |
US7892207B2 (en) | 2006-04-27 | 2011-02-22 | Warsaw Orthopedic, Inc. | Dilating stylet and cannula |
WO2008001385A2 (en) | 2006-06-29 | 2008-01-03 | Depuy Spine, Inc. | Integrated bone biopsy and therapy apparatus |
SE530233C2 (en) | 2006-08-11 | 2008-04-08 | Biomet Cementing Technologies | Liquid container for bone cement mixers |
SE530232C2 (en) | 2006-08-11 | 2008-04-08 | Biomet Cementing Technologies | Liquid container for bone cement mixers |
JP2008055367A (en) | 2006-09-01 | 2008-03-13 | Asada Tekko Kk | Rotary roll type dispersion machine |
US9642932B2 (en) | 2006-09-14 | 2017-05-09 | DePuy Synthes Products, Inc. | Bone cement and methods of use thereof |
WO2008047371A2 (en) | 2006-10-19 | 2008-04-24 | Depuy Spine, Inc. | Fluid delivery system |
TW200948613A (en) | 2008-04-24 | 2009-12-01 | Toppan Printing Co Ltd | Packaging container and package utilizing the same |
DE102009002630B4 (en) | 2009-04-24 | 2019-12-24 | Robert Bosch Gmbh | Device for dosing powdery substances |
US8226126B2 (en) | 2009-08-24 | 2012-07-24 | Jpro Dairy International, Inc. | Bottle mixing assembly |
-
2007
- 2007-09-11 US US12/377,894 patent/US9642932B2/en active Active
- 2007-09-11 WO PCT/IL2007/001130 patent/WO2008032322A2/en active Application Filing
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- 2007-09-11 AU AU2007297097A patent/AU2007297097A1/en not_active Abandoned
- 2007-09-11 CA CA002663447A patent/CA2663447A1/en not_active Abandoned
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CN101516412B (en) | 2014-02-12 |
US20100168271A1 (en) | 2010-07-01 |
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US20170216483A1 (en) | 2017-08-03 |
AU2007297097A1 (en) | 2008-03-20 |
CN101516412A (en) | 2009-08-26 |
WO2008032322A3 (en) | 2009-05-07 |
EP2068898A4 (en) | 2011-07-20 |
EP2068898A2 (en) | 2009-06-17 |
US10272174B2 (en) | 2019-04-30 |
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