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WO2009032956A1 - Particules de nanofil de titane - Google Patents

Particules de nanofil de titane Download PDF

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Publication number
WO2009032956A1
WO2009032956A1 PCT/US2008/075299 US2008075299W WO2009032956A1 WO 2009032956 A1 WO2009032956 A1 WO 2009032956A1 US 2008075299 W US2008075299 W US 2008075299W WO 2009032956 A1 WO2009032956 A1 WO 2009032956A1
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WIPO (PCT)
Prior art keywords
particles
nanowire
substrate
titanium
composition
Prior art date
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Ceased
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PCT/US2008/075299
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English (en)
Inventor
Martin S. Dieck
Frank P. Becking
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Covidien LP
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Nfocus Neuromedical Inc
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Publication of WO2009032956A1 publication Critical patent/WO2009032956A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/082—Inorganic materials
    • A61L31/088—Other specific inorganic materials not covered by A61L31/084 or A61L31/086
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L31/128—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/18—Materials at least partially X-ray or laser opaque
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
    • C01G23/00—Compounds of titanium
    • C01G23/04—Oxides; Hydroxides
    • C01G23/047—Titanium dioxide
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
    • C01G31/00—Compounds of vanadium
    • C01G31/02—Oxides
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
    • C01G39/00—Compounds of molybdenum
    • C01G39/02—Oxides; Hydroxides
    • 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
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/01—Particle morphology depicted by an image
    • C01P2004/03—Particle morphology depicted by an image obtained by SEM
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/10—Particle morphology extending in one dimension, e.g. needle-like
    • C01P2004/16—Nanowires or nanorods, i.e. solid nanofibres with two nearly equal dimensions between 1-100 nanometer
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/60—Particles characterised by their size
    • C01P2004/62—Submicrometer sized, i.e. from 0.1-1 micrometer
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/60—Particles characterised by their size
    • C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer

Definitions

  • Nanowires of titanium oxide have been produced previously as described in: Chem. Mater. 2007, 19, 4454-4459, "Mutlifunctional Nanowire BioscafTolds on Tilanium", Dong, W. et al. and Nanomedicine, 2006, 2, 248-252, Dong, W et al.
  • Particles of titanium oxide nanowires snd compositions comprising them are made using techniques described herein.
  • the compositions and particles are useful to fill a space in the body, treat aneurysms, and grow new tissue.
  • an aggregate or plurality of the particles or a composition comprising the particles can address any configuration of treatment site, conforming to the shape of the treatment site.
  • the matrix of nanowires formed on each particle forms a larger scaffold together with the other particles to fill a space or to attract cells for promoting growth of new tissue.
  • Figs. I A to IC illustrate different forms of titanium-containing substrates that can be made into particles.
  • Fig. 1 D depicts a hypotube having donut-shaped particles.
  • Figs.2A to 2F illustrates the pathways of two processes of cutting and treating the particles.
  • FIGS. 3A to 3C show an illustration of pre-cutting or perforating the sheet
  • Figs. 4A to 4D show an initial substrate masked and treated to form nanowire units.
  • Fig. 5 shows bone filler/cement applications.
  • Fig. 6 shows compositions used in the stem settings or coating over a stent.
  • Fig. 7 shows particles as a substitute for carbon or glass particle or chop/fill in a polyester or epoxy matrix.
  • Figs. 8A to 8C show n one composite construction application to form a multi-layer matrix.
  • Figs. 9A to 9C show variation nanowire particles of nanowire size and interstices size.
  • Fig. 9D shows nanowire particles having interstices in the matrix of about S to 10 microns.
  • the invention comprises particles including TiO 2 nanowire providing a matrix, and a method of making such particles.
  • the TiO 2 nanowire matrix acts as a scaffold for cellular activity in the body.
  • the particles are useful (as a plurality of particles in aggregrate] as an implant to recruit cells to a site, or to facilitate other cellular or biological processes initiated by the presence of the matrices of the particles, including endogenous local tissue growth.
  • the invention is also a composition comprising IiO: nanowire particles.
  • the composition comprises the nanowire particles in a pharmaceutically acceptable carrier and optionally also agents such as drugs, proteins, adhesives or bulking agents that increase the efficacy of the particles.
  • the invention comprises particles including TiO 2 nanowire providing a matrix, and a method of making such particles.
  • the TiO 2 nanowire matrix acts as a scaffold for cellular activity in the body.
  • the particles are useful (as a plurality of particles in aggregrate) as an implant to recruit cells to a site, or to facilitate other cellular or biological processes initiated by the presence of the matrices of the particles, including endogenous local tissue growth.
  • the invention is also a composition comprising TiO 2 nanowire particles.
  • the composition comprises the nanowire particles in a pharmaceutically acceptable carrier and optionally also agents such as drugs, proteins, adhesives or bulking agents that increase the efficacy of the particles.
  • the invention includes methods of making the particles, methods of making die compositions, methods of coating a medical device with the particles, methods of filling a space in the body with the particles or compositions, and methods of promoting tissue growth in the body using the particles.
  • the subject nanowire particles have various specific uses as described below, as well as others as may be apparent to those with skill in the art.
  • a substrate of titanium metal (Ti) or titanium metal alloy (Ti alloy) is treated any number of several known ways to generate TiO 2 nanowires thereon.
  • Titanium oxide ( TiO 2 ) nanowire forming the scaffolding on the particles is wire of diameter of the order of a nanometer ( 10 * meters).
  • the tenn "Ti alloy” is intended to cover common alloys such as 3-2.5 and 6-4 as well as SMA (shape memory alloy) Nickel-Titanium (NiTi) alloy.
  • the nanowires appear in electron micrographs as a matrix or lattice of filaments (e.g. nanowires).
  • the nanowire matrix on each particle forms a cell-friendly scaffold to which cells can migrate and engage in local cellular activity.
  • the particles can have their external surface partially coated with nanowires, or substantially all of the external surface of the panicle can be coated with nanowires.
  • Known methods of making titanium oxide nanowires from substrates comprising titanium include those methods published in Chem. Mater. 2007, 19, 4454-4459, "Multifunctional Nanowire Bioscaffolds on Titanium", Dong, W. et al. and Nanomedicine, 2006, 2, 248-252, Dong, W et al. Both references are hereby incorporated by reference in their entirety.
  • one method of nanowire production includes use of low temperature tailored metal oxidation (or corrosion) in NaOH solutions ranging from 0.25 to 1.0 mol/l. at about 180 to 240 degrees.
  • the resulting nanowire particles can be sterilized in EtOH or saline.
  • the substrate Ti or Ti alloy can be cut or otherwise formed into particles first, and then treated as described to form TiO 2 nanowires on the particle surface.
  • a Ti or Ti alloy substrate of larger dimension e.g. a sheet, strip, rod or hypotube
  • the substrate can be cut or otherwise formed into particles.
  • deposit Ti (or Ti alloy) on a non-titanium substrate prior to treatment treat the deposited material on the substrate and then reduce the nanowire-coated substrate to a plurality of particles by chopping, cutting, dicing, etc.
  • the non-titanium substrate can be e.g., another metal or metal alloy, or a polymer.
  • Suitable polymers include e.g., PGLA, PVA, EPTFE, and any hydrogel (either semi-solid or solid).
  • the polymers can be in any form such as e.g., sheets, strips, rods, or tubes.
  • the substrate might also be a mixture of metal and polymer, e.g.,where me materials are blended together as a composite material (e.g., melted, or pressed into one another) thus forming a unitary composite substrate of two or more different materials on which the titanium or titanium alloy can be deposited.
  • One such instance offers particular benefits according to the present invention: namely, when the titanium is deposited on a highly radiopaque material.
  • a highly radiopaque material include Gold, Platinum, Irridium, Palladium, Tantalum, alloys thereof, etc. Panicles so- produced, then offer not only the unique bioscafolding properties, but also excellent radiopacity.
  • the titanium alloy can be deposited upon a polymer substrate.
  • a biodegradable, radiopaque substrate e.g. iodized polycarbonate
  • the particle sizes are micro (in a range of about 0.001 to about 0.05 inches in diameter) or mini (in a range of about 0.01 to about 0.10 inches m diameter). Widiin these size parameters, the particles can be of various shapes. Dy "diameter", the largest radial extent (also for ovular, oblong, square, rectangular, trapezoidal, etc. geometries) of the particles is contemplated. Hollow particles of any shape may be desirable. For instance, the particles may be formed from hypotube.
  • Fig. IA, IB and 1C illustrate four different forms of titanium-containing substrates that can be made into particles.
  • Fig. IA is a wire substrate 10 from which particles 12 are cut.
  • Magnified particle 14 indicates the details of the nanowire structure of particle 12.
  • Fig. IB is a sheet substrate 10' from which panicles 12' can be stamped or cut; 14' shows the magnified nanowire structure on panicle 12'.
  • Fig. 1C shows a strip 10" having rectangular panicles 12", also shown in magnification of particle 14".
  • Fig. ID depicts a hypotube 10'" having donut-shaped particles 12"', which are also shown in magnification as 14'".
  • the size of the nanowires can vary, as can die resulting interstices of the matrix. These variations can occur with changes in temperature, concentration of NaOH, and length of time the reaction is allowed. Some variation in the nanowire size and interstices size is shown in Fig. 9A to 9C.
  • Fig. 9A shows nanowire panicles having pores of about 1 micron.
  • Fig. 9B shows nanowire particles having interstices of the matrix of about 3 microns.
  • Fig. 9D shows nanowire particles having interstices in the matrix of about S to IO microns.
  • Examples of fully covered particles include spheres, cubes and other prismatic bodies that are processed according to the teachings known in the an for making nanowires, while agitated to allow coating growth on all surfaces. Such agitation may be provided by fluid jets/currents that roll or cause the particles to rise and fall within the fluid column.
  • the panicles include a titanium or titanium alloy over a ferromagnetic core to allow for magnetic suspension or "stirring", moving or rolling of the particles during processing. Mechanical agitation, including inversion, of the vessel in which assembly of the nanosurface occurs is also possible.
  • a film, sheet or coupon of material is processed to grow the nanowire matrix. Then, the material is "diced" or cut into microparticle-sized pieces. First one side of the base material may be processed, then it is flipped to expose the other side to grow nanosurface thereon. Otherwise, the material can be suspended in solution. Or, the coating may be deposited only on one side, the resulting particles thereby having a partial coating of nanowires. Uniform and regular sized particles can be made using machining and cutting biased towards making panicles of about the same size. Alternatively, irregular particles can be made by shaving or grinding the substrate titanium or titanium alloy into irregular- shaped particles, e.g., curls, crescents, chips, shavings, and the like.
  • Ilie substrate can be treated and then cut into panicles, or cut into particles first and then the particles treated.
  • Fig. 2A through 2F illustrates the pathways of these two processes.
  • Substrate sheet 20 receives a deposit of titanium-containing material 24.
  • the titanium covered substrate can then be treated to form nanowire matrix 28 as shown in Fig. 2D, or cut into untreated panicles 26 as shown in Fig. 2C.
  • the treated sheet can then be cut into nanowire panicles 32" as shown in Fig. 2F.
  • the untreated particles 26 can then be treated as shown in Fig. 2E to yield nanowire particles 32'.
  • one-sided coating may be desirable since a flat "back" surface is provided that can be easily worked on by a laser to dice the material into platelettes.
  • Another approach contemplated employs semi-conductor or micromachining techniques, including masking and etching.
  • Yet another approach would employ EDM (electric discharge machining); still another ECM (electro chemical machining); and other various MEMs (micro electro mechanical systems) techniques.
  • Another technique that may be of assistance in producing approximately uniform* sized microparticles from foil or sheets contemplates pre-cuning or perforating the sheet.
  • the cut-outs may be simple slits, perforations, etc.
  • sheet pre-processing reduces the amount of material that must be ablated to release the microparticles.
  • fracture lines are formed, allowing the microparticles to be freed from their lattice or construction matrix by mechanical action such as crumpling, milling, tumbling, etc.
  • Perforations as illustrated in Fig. 3 A to 3C.
  • Substrate sheet 20 is perforated into perforations 22 (Fig. 3B).
  • Perforations 22 are shown in cross sectional side view in Fig. 3B ⁇
  • the perfonnated pieces 22' are then freed particles as shown in Fig. 3C.
  • the nanowire structure on the particles is indicated in magnified panicle 22".
  • the semi-solid surface having the deposited titanium can be frozen.
  • the particles are then cut from the frozen material by dicing, chipping, milling, chopping, or other suitable process, etc.
  • the microparticles are fonned by discrete dots (circular or otherwise) of titanium or titanium alloy set upon a non-titanium substrate. Release from the substrate may be achieved by dissolving it, releasing a binding agent, heating/melting (as in the case of PTFE) or otherwise.
  • the dot matrix formed may be achieved by semiconductor processing techniques including deposition and masking as understood by those with skill in the art. Otherwise, an imperforate Ti (or Ti alloy) sheet or foil can be laminated or otherwise affixed to another non-titanium substrate, and the metal sectioned (e.g., by laser machining) into a grid of independent elements. For example when the substrate is radiopaque, the resulting particles are radiopaque.
  • the wire may be all-Ti, a Ti alloy, Ti-coated (e.g., titanium coated platinum), or gold or platinum filled Ti or Ti alloy.
  • the wire can then be sectioned into micro-coins, donuts, cylinders and/or shells. Wire is advantageously handled in a reel-to-reel process fashion. Alternatively, it is fed from a reel, and sent directly to a cutter as it is fed into and out of the solution processing bath.
  • the sectioning may be performed mechanically by a shear-type cutter, by laser ablation or otherwise.
  • the wire may be pre-cut or scored with one or more kerfs (a kerf is the width of the cut from a saw) to facilitate sectioning by such means or by bulk mechanical action (such as milling, grinding, tumbling, etc.)
  • Yet another approach to microparticle production comprises providing a multi- thickness sheet or foil (formed by successive material deposition, together with masking and/or by masking and etching techniques).
  • initial substrate 50 is masked and treated to form nanowire units 52.
  • the thinner base material along microparticle separation lines becomes oxidized and brittle, as compared to fully intact Ti (or Ti alloy) substrate/base of the particles.
  • Another layer of substrate 54 is placed over the nanowire units 52, and further treatment is applied to the substrate resulting in another layer of nanowire units 56.
  • Another substrate layer 60 is then attached to the previous layer.
  • the processed material is then easily broken down into micro-particles - typically by mechanical action as described above, or otherwise. Particle size can then be selected using known sifting/screening techniques.
  • the nanowire scaffold particles After the nanowire scaffold particles are formed, they can be delivered singly, or as a plurality in an aggregate of particles. Alternatively, the particles may be formulated into a composition that has other components, and the composition then delivered to a treatment site in the body.
  • a composition may additionally include active agents (e.g. drugs) that facilitate the desired biological activity, or agents that otherwise improve particle delivery or function.
  • compositions of this invention could be administered in simple solution, they are more typically used in combination with other materials such as carriers, preferably pharmaceutical carriers.
  • Useful pharmaceutical carriers can be any compatible, non-toxic substances suitable for delivering the compositions of the invention to a patient.
  • Sterile water, alcohol, fats, waxes, and inert solids such as bulking agents may be included in a carrier.
  • a pharmaceutically acceptable carrier can contain physiologically acceptable compounds that act, for example, to stabilize or to increase desired cellular or biological activity at the site of implantation of the composition.
  • any peptide, polypeptide or variant thereof e.g. an antigen or binding-agent linked to a panicle
  • suspension may include protective agents which protect the peptide or polypeptide on storage.
  • compositions useful for parenteral administration of a nanowire particle composition will depend on the intended mode of administration (e.g. the size of the catheter lumen, the size of the treatment site, and the mode of transport of the composition to the site through the catheter lumen - e.g. pusher, or liquid infusion, etc.).
  • the pharmaceutical formulation may be a liquid, a suspension, an emulsion, a gel, a paste, an aqueous solution, granules, pellets, beads, a powder, or the like; see e.g.. Remington's Pharmaceutical Science, 17th Ed. (Mack Publishing Company. Easton, Pa., 1990).
  • compositions of active agents and panicles in the compositions may be identified in a unit dosage form that ties the panicle quantity and drug potency together in a given composition.
  • dosage forms may be prepared by any methods well known in the art of pharmacy. Sec, e.g., Gilman et al. (eds.) (1990), The Pharmacological Bases of Therapeutics, 8th Ed., Pergamon Press; and Remington's Pharmaceutical Sciences, supra, Easton, Penn.; Avis et al. (eds.) (1993) Pharmaceutical Dosage Forms: Parenteral Medications Dekker, New York; Lieberman et al.
  • the drug may impregnate the panicles, and when delivered the composition thereby provides a system of controlled drug release at the site of implantation of the particle or particles.
  • the drug may also exist as a separate component in the composition that also includes the particles.
  • a drug is any therapeutic compound or molecule having biological activity in the body including but not limited to nucleic acids, small molecules, proteins, polypeptides or peptides, etc. The drug may act locally or systemically after delivery of the composition.
  • a therapeutically effective amount of a composition of the invention is an amount that will ameliorate one or more of the well-known parameters that characterize the condition to be treated by the composition, e.g., treating an aneurysm, space filling, tissue augmentation, etc. Whatever the most appropriate form and formulation - as will be appreciated by those with skill in the art the resulting particles alone or particle compositions (e.g. a "powder" or mass of particles with carriers and/or active agents) find myriad uses.
  • the nanowire particles or compositions can facilitate filling and closing of an unwanted space (such as an aneurysm or fistula).
  • the particles can be delivered "bare” (as particles alone), or in a pharmaceutically acceptable composition, optionally also with other additives.
  • Additives can include drugs, bulking agents, proteins, antigen molecules to attach the particles to a particular tissue or each other, adhesives, and polymerizing agents, etc.
  • the material is prepared to form slurry in a gel. Injected as such a slurry or sol, the material is a bulking agent.
  • the nanowire coaled particles act as implant material and initiate tissue growth. Eventually, the composition of particles is surrounded by fibcrous tissue in-growth that "bulks-up" an affected area.
  • GID gastro esophogeal reflux disease
  • the pyloric valve leading to the stomach may become weakened or eroded allowing acid from the stomach to move backwards from the stomach into die esophagus and cause damage.
  • Bulking agents are used to fill space and create a stricture at the site of the damaged valve.
  • the particles may be sized for use in treating AV fistulas as embolic particles. Rapid tissue in growth possibilities, coupled with an ability to tune the size of both the particles delivered and the amount of particles delivered make them particularly advantageous.
  • the particles may interlock in a "Velcro" fashion, and have an excellent bio-compatibility.
  • antigen molecules affixed to the nanowires on the particles can direct the particles to target specific molecules on tissues or to target each other.
  • tissue antigen molecules specific to known cell surface molecules are selected.
  • half of the particles can have an antigen, and the other half can have the antigen-binding partner.
  • the two can be delivered in separate lumens of a dual lumen catheter so that they bind at the target site and form a bonded unit of particles in the body.
  • Specific configurations of antigens and binding-partners on the particles may configure particles to polymerize and form regular repeating units of scaffold at a given treatment site.
  • Bone fillers and cement e.g., for vertebroplasty
  • implant coatings especially dental
  • the matrix may comprise PMMA or hydroxyapatite.
  • the microparticles can assist/complement the potential bone-growth promotion properties of the hydroxyapatite matrix.
  • the particles can be added to and suspended in a hydrogcl or a glue or other sellable compositions (e.g., OnyxTM, by EV3 or polyethylene glycol (PEG) or a derivative of PEG) to fill aneurysms or other target sites in the body.
  • a hydrogcl or a glue or other sellable compositions e.g., OnyxTM, by EV3 or polyethylene glycol (PEG) or a derivative of PEG
  • the bare Ti or Ti alloy can offer relevant radiopacity in addition to tissue in-growth properties.
  • the particles 42 can provide radiopacity or guidance as well as a strong matrix (nanowire is shown in inset 40') for tissue in-growth.
  • suitable media 44 for the addition of the microparticles include; polyvinyl alcohol, cyanoacrylates, hylaronic acid and others.
  • the micropaniclcs also offer advantages in cosmetics applications. In one approach, the inicropanicles/particles are suspended and injected with collagen.
  • Such a composition can be used for Up or breast augmentation as a filler.
  • the btoscaffold nanowire surface promotes tissue growth/ingrowth so as to (in one treatment or more) yield a permanent cosmetic alteration.
  • the filler could be used as described, and as otherwise appreciated by those with skill in the an, to fill wrinkles or voids created by tissue damage, ablation, etc.
  • Breast augmentation can be achieved by serial injections.
  • a pharmaceutically acceptable composition of the particles in a matrix may comprise PLA/PGLA (or another biodegradable/resorbable polymer).
  • PLA/PGLA or another biodegradable/resorbable polymer
  • Such compositions could be used in the stent setting (e.g., in Conor Co-StarTM stent wells) or it could provide a coating over a stent (such as by processes employed by BioSensors and Surmodics), as shown in Fig. 6.
  • Use of the particles could provide an alternative to including an elutable drug in the matrix.
  • Stent 60 is coated with coating 62 that comprises particles 62.
  • nanowire particles such as 64, which is depicted in magnification.
  • the particles could be provided in addition to a drug in order to promote controlled cell adhesion and growth (thereby providing good stent encapsulation and/or endothelization) while an antiproliferative compound (e.g., a limus or taxol family drug) offers control to the process that might include restenosis.
  • an antiproliferative compound e.g., a limus or taxol family drug
  • the particles themselves can act as drug carriers, e.g. where the particles are saturated in drug, and the drug elutes from the particle in the body after delivery.
  • Such filler 70 having particles 72 which have nanowires 74 over their surface may provide an intriguing combination of high strength, and ductility to the material, especially impact resistance.
  • the composite also offers potential for protection against catastrophic failure modes due to increased interlacing of polymer matrix and/or ductility of uncorroded Ti or Ti alloy as compared to conventional glass panicles or platelette fill. Indeed, the increased elongation possibility offers potential for use of the composite in dynamic applications, including limb prostheses, etc.
  • titanium patterns dots (80), lattices (82) , etc.
  • lattices (82) are deposited (e.g., by such techniques, including MEMs (micro electro mechanical systems) and other techniques) on successive layers (84, 86, and 88) of high-temperature cpoxy resin and processed to form nanowirc structures in-siru, with additional such layers of epoxy and processed titanium to form a multi-layer matrix.
  • Laminates (90) of simple sheets or more complex forms or constructions are contemplated in such approaches, These structures may find uses in prosthetic as well as aerospace and more general mechanical applications -just as those above.
  • a FIFE laminate may be formed in a similar manner, in which successive layers are physically interlocked by melting or pressing into intermediate nanowire structure. The laminates can be chopped into particles also.
  • nanowires can be formed from substrates comprising other metals, such as, e.g., vanadium, aluminum, magnesium, molybdenum, and others.
  • the oxides of these metals are formed on a substrate using known techniques, and can be used to form particles and compositions as described for titanium substrates.
  • the invention includes all such devices, processes, and the methods associated with implanting such particles and compositions in humans and other mammals - both for treatment and clinical evaluation. Indeed, any of the concepts addressed herein can be inixed-and-matched in various combinations and be put to great effect for various uses. And for the avoidance of any doubt, it is expressly stated here that the entirety of every reference (patent, article and presentation) as well as the referenced products (identified by name) mentioned herein is incorporated by reference in its/their entirety for any purpose. In converting this provisional patent application to a full utility patent application, it is contemplated that any of that subject matter may be set forth explicitly, without introducing new matter.
  • the subject mediods may include each of the physician activities associated with particle delivery, delivery of a composition comprising particles, or treating a patient using the particles alone or the particles formulated in a composition.
  • methodology implicit to the delivery of the particles or compositions forms part of the invention.
  • Such methodology may include directing particles of specific size, specific nanowire matrix sizes and densities, selection of additional components for the composition and other decisions necessary to form the most optimal configuration of particles and compositions for a given indication.
  • any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein.
  • Reference to a singular item includes the possibility that there is a plurality of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a,” “an,” “said,” and “the” include plural referents unless specifically stated otherwise. In other words, use of the articles allow for "at least one" of the subject item in the description above as well as the claims below. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.

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Abstract

Des particules de matrices de nanofils d'oxyde de titane sont réalisées en traitant un substrat contenant du titane au moyen de procédés connus. Le substrat est composé de particules inférieures à 0,1 pouce de diamètre avant ou après le traitement. Les particules de nanofils peuvent être livrées nues (sans composants supplémentaires), ou elles peuvent être formulées dans une composition ayant un vecteur pharmaceutiquement acceptable et éventuellement un ou plusieurs autres agents, comme un médicament, un adhésif, et/ou un diluant. Les particules ou compositions peuvent être utilisées pour remplir un espace dans le corps, favoriser la croissance des tissus, ou faciliter et promouvoir d'autres activités cellulaires ou biologiques sur un site de traitement.
PCT/US2008/075299 2007-09-04 2008-09-04 Particules de nanofil de titane Ceased WO2009032956A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210145586A1 (en) * 2015-07-17 2021-05-20 Purdue Research Foundation Bioresorbable porous metals for orthopaedic applications
US12150850B2 (en) 2018-03-01 2024-11-26 Titanium Textiles Ag Tension-free titanium metal knitted fabric for surgically shaping soft tissues
US12186193B2 (en) 2018-03-01 2025-01-07 Titanium Textiles Ag Titanium matrix based on a tension-free metal warp knit fabric for guided tissue regeneration

Citations (4)

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Publication number Priority date Publication date Assignee Title
US20060115536A1 (en) * 2004-11-12 2006-06-01 Board Of Regents, The University Of Texas System Glycerin based synthesis of silver nanoparticles and nanowires
US20060167147A1 (en) * 2005-01-24 2006-07-27 Blue Membranes Gmbh Metal-containing composite materials
US20060188774A1 (en) * 2004-12-09 2006-08-24 Nanosys, Inc. Nanowire-based membrane electrode assemblies for fuel cells
US20070202334A1 (en) * 2005-12-29 2007-08-30 Rong-Cai Xie Nanoparticles containing titanium oxide

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060115536A1 (en) * 2004-11-12 2006-06-01 Board Of Regents, The University Of Texas System Glycerin based synthesis of silver nanoparticles and nanowires
US20060188774A1 (en) * 2004-12-09 2006-08-24 Nanosys, Inc. Nanowire-based membrane electrode assemblies for fuel cells
US20060167147A1 (en) * 2005-01-24 2006-07-27 Blue Membranes Gmbh Metal-containing composite materials
US20070202334A1 (en) * 2005-12-29 2007-08-30 Rong-Cai Xie Nanoparticles containing titanium oxide

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210145586A1 (en) * 2015-07-17 2021-05-20 Purdue Research Foundation Bioresorbable porous metals for orthopaedic applications
US12171903B2 (en) * 2015-07-17 2024-12-24 Purdue Research Foundation Bioresorbable porous metals for orthopaedic applications
US12150850B2 (en) 2018-03-01 2024-11-26 Titanium Textiles Ag Tension-free titanium metal knitted fabric for surgically shaping soft tissues
US12186193B2 (en) 2018-03-01 2025-01-07 Titanium Textiles Ag Titanium matrix based on a tension-free metal warp knit fabric for guided tissue regeneration

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