CA2194909C - Tissue injectable composition and method of use - Google Patents
Tissue injectable composition and method of useInfo
- Publication number
- CA2194909C CA2194909C CA002194909A CA2194909A CA2194909C CA 2194909 C CA2194909 C CA 2194909C CA 002194909 A CA002194909 A CA 002194909A CA 2194909 A CA2194909 A CA 2194909A CA 2194909 C CA2194909 C CA 2194909C
- Authority
- CA
- Canada
- Prior art keywords
- composition
- particles
- carbon
- substrate particles
- carrier
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/0059—Cosmetic or alloplastic implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/0004—Closure means for urethra or rectum, i.e. anti-incontinence devices or support slings against pelvic prolapse
- A61F2/0031—Closure means for urethra or rectum, i.e. anti-incontinence devices or support slings against pelvic prolapse for constricting the lumen; Support slings for the urethra
- A61F2/0036—Closure means for urethra or rectum, i.e. anti-incontinence devices or support slings against pelvic prolapse for constricting the lumen; Support slings for the urethra implantable
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/042—Urinary bladders
-
- 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
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
-
- 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
- A61L27/303—Carbon
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00389—The prosthesis being coated or covered with a particular material
- A61F2310/00574—Coating or prosthesis-covering structure made of carbon, e.g. of pyrocarbon
-
- 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
Abstract
An improved biocompatible composition consisting of physiologically stable microparticles carried in a lubricative suspension, solution, other fluid or gel is presented. The composition is intended to be delivered into the body through a small-bore needle, cannula, or catheter and to a tissue site for the purpose of augmenting the tissue site and surrounding area, thereby con-ectlng a defect, filling a void, or strengthening the support structures of the tissue. The particles are a hard, metallic substance and are carbon-coated.
Description
WO 96/02209 Q i ~~ i3 PCT/US95I07454 This invention relates to an injectable composition of physiologically compatible and appropriately sized particles carried in a lubricative, biologically compatible fluid or gel. The composition is formulated to be delivered into the body to a tissue site through a small-bore instniment to strengthen, bulk-up and otherwise augment the tissue site and surrounding area.
The percutaneous injection of substances into tissues to augment, support, or reco~gure anatomic structure has been the subject of significant research and product development and is well known in the arr. ~, for example, U. S . Patent No' s.
4, 803 , 075 and 5,204,382 to Wallace et al and 5,258,028 to Ersek et al. Procedures have been described in the medical literature for correction of dermatological, otolaryngological problems and for treatment of urological disorders, e. g. , Walker et al. , "Injectable Bioglass as a Potential Substitute for Injectable Polytettafluoroethylene," J.J. Urol., l48:645-7, 1992 and the references cited therein.
Urinary incontinence and vesicourethral reflux are urological disorders that have responded to treatments with augumentive materials. U.S. Patent No's.
5,007,940;
5,158,573; and 5,116, 387 to Berg disclose biocompatible compositions comprising discrete, polymeric and silicone rubber bodies injectable into urethral tissue for the purpose of treatment of urinary incontinence by tissue bulking. The most serious adverse effect that may occur from therapies of this type relates to the migration of the solid materials from the original site of placement and into repository sites in various body organs. An important factor in assuring nonmigration is the administration of properly sized particles. If the particle is too small, it WO 96I02209 2 ~ C~ ~ ~~ Js ~ PCT/US95107454 is likely to enter the microvasculature system and travel until it reaches a site of greater constriction. Target organs for reposition include the lungs, liver, spleen, brain, kidney, and lymph nodes.
The primary focus of this invention has been directed toward the development of biocompatible, nonmigratory particles that are effectively delivered to the desired tissue site in a lubricative, biocompatible fluid or gel carrier. The preferred carrier shall not cause any deleterious effects at or near the site of particle delivery and will be removed from the site by normal biological or biochemical processes such as excretion or metabolic breakdown.
In accordance with the present invention there is provided an injectable, biocompatible composition comprised of a plurality of discrete, physiologically compatible, carbon-coated particles of a predetermined size range and a lubricative fluid or gel in which the particles are carried. The carrier is preferably a biologically compatible solution or suspension. The particles range in size from 100 microns to 1,000 microns in transverse, cross-sectional dimension.
The composition is designed to be delivered into the body through a small-bore needle, cannula, or catheter and to a tissue site for the purpose of augmenting the tissue site and surrounding area, thereby correcting a defect, filling a void or strengthening the support structures of the tissue.
The invention is comprised of two components.
The first is a plurality of carbon-coated particles ranging in size as microbeads or microparticles from a minimum of l00 microns to a maximum of 1,000 microns.
The WO 96I02209 219 ~~ ii v' ~ PCT~S95/07454 particles are subjected to a coating process in which carbon is deposited as a thin coating or film on an appropriate, particulate substrate, thereby creating a particle that has a highly biocompatible surface. A hard, metallic substance capable of withstanding the high temperature conditions of the coating process for low temperature isotropic (LTI), pyrolytic carbon is the preferred particulate material. Zirconium oxide has been found to be especially suitable as such a substrate. However, other metallic substrates, including but not limited to medical grade (504) stainless steel, titanium and titanium alloys are also quite acceptable as the substrate material. Gold and silver, which have lower melting temperatures, may be utilized as the particulate substrate in the vacuum vapor deposition process for ultra low temperature isotropic carbon.
The second component acts as the lubricative carrier for the carbon-coated particles and in the preferred embodiment is comprised of a suspension, solution, or other biologically compatible fluid or a gel. Examples of biologically compatible carriers include but are not limited to beta-glucan, hyaluronic acid and derivatives thereof, polyvinyl pyrrolidone or a hydrogel derivative thereof, dextrans or a hydrogel derivative thereof, glycerol, polyethylene glycol, succinaylated collagen, liquid collagen, and other polysaccharides or biocompatible polymers either singly or in combinations with one or more of the above-referenced solutions.
The preferred carrier must be capable of being formulated into a viscous fluid or into a self-supporting gel. For purposes of this invention, the carrier shall be of sufficient viscosity to suspend the particles.
The percutaneous injection of substances into tissues to augment, support, or reco~gure anatomic structure has been the subject of significant research and product development and is well known in the arr. ~, for example, U. S . Patent No' s.
4, 803 , 075 and 5,204,382 to Wallace et al and 5,258,028 to Ersek et al. Procedures have been described in the medical literature for correction of dermatological, otolaryngological problems and for treatment of urological disorders, e. g. , Walker et al. , "Injectable Bioglass as a Potential Substitute for Injectable Polytettafluoroethylene," J.J. Urol., l48:645-7, 1992 and the references cited therein.
Urinary incontinence and vesicourethral reflux are urological disorders that have responded to treatments with augumentive materials. U.S. Patent No's.
5,007,940;
5,158,573; and 5,116, 387 to Berg disclose biocompatible compositions comprising discrete, polymeric and silicone rubber bodies injectable into urethral tissue for the purpose of treatment of urinary incontinence by tissue bulking. The most serious adverse effect that may occur from therapies of this type relates to the migration of the solid materials from the original site of placement and into repository sites in various body organs. An important factor in assuring nonmigration is the administration of properly sized particles. If the particle is too small, it WO 96I02209 2 ~ C~ ~ ~~ Js ~ PCT/US95107454 is likely to enter the microvasculature system and travel until it reaches a site of greater constriction. Target organs for reposition include the lungs, liver, spleen, brain, kidney, and lymph nodes.
The primary focus of this invention has been directed toward the development of biocompatible, nonmigratory particles that are effectively delivered to the desired tissue site in a lubricative, biocompatible fluid or gel carrier. The preferred carrier shall not cause any deleterious effects at or near the site of particle delivery and will be removed from the site by normal biological or biochemical processes such as excretion or metabolic breakdown.
In accordance with the present invention there is provided an injectable, biocompatible composition comprised of a plurality of discrete, physiologically compatible, carbon-coated particles of a predetermined size range and a lubricative fluid or gel in which the particles are carried. The carrier is preferably a biologically compatible solution or suspension. The particles range in size from 100 microns to 1,000 microns in transverse, cross-sectional dimension.
The composition is designed to be delivered into the body through a small-bore needle, cannula, or catheter and to a tissue site for the purpose of augmenting the tissue site and surrounding area, thereby correcting a defect, filling a void or strengthening the support structures of the tissue.
The invention is comprised of two components.
The first is a plurality of carbon-coated particles ranging in size as microbeads or microparticles from a minimum of l00 microns to a maximum of 1,000 microns.
The WO 96I02209 219 ~~ ii v' ~ PCT~S95/07454 particles are subjected to a coating process in which carbon is deposited as a thin coating or film on an appropriate, particulate substrate, thereby creating a particle that has a highly biocompatible surface. A hard, metallic substance capable of withstanding the high temperature conditions of the coating process for low temperature isotropic (LTI), pyrolytic carbon is the preferred particulate material. Zirconium oxide has been found to be especially suitable as such a substrate. However, other metallic substrates, including but not limited to medical grade (504) stainless steel, titanium and titanium alloys are also quite acceptable as the substrate material. Gold and silver, which have lower melting temperatures, may be utilized as the particulate substrate in the vacuum vapor deposition process for ultra low temperature isotropic carbon.
The second component acts as the lubricative carrier for the carbon-coated particles and in the preferred embodiment is comprised of a suspension, solution, or other biologically compatible fluid or a gel. Examples of biologically compatible carriers include but are not limited to beta-glucan, hyaluronic acid and derivatives thereof, polyvinyl pyrrolidone or a hydrogel derivative thereof, dextrans or a hydrogel derivative thereof, glycerol, polyethylene glycol, succinaylated collagen, liquid collagen, and other polysaccharides or biocompatible polymers either singly or in combinations with one or more of the above-referenced solutions.
The preferred carrier must be capable of being formulated into a viscous fluid or into a self-supporting gel. For purposes of this invention, the carrier shall be of sufficient viscosity to suspend the particles.
21 G ~ ~ ~' ~ PCT/US95107454 WO 96I02209 ~ ~ _~ i The invention consists of an injectable composition that is a combination of a plurality of small, smooth-surfaced particles that are carried in a lubricative fluid or gel that is preferably comprised of a biologically compatible, lubricous solution, suspension, other fluid or gel.
The particles comprise microbeads or microparticles of a hard, material serving as a substrate and having a thin coating or film of biocompatible, isotropic carbon deposited on their surfaces. The substrate material is preferably radiopaque. Different types of carbon coating processes may be utilized, with the particulate substrate being a metallic substance selected for compatibility with the coating process.
Low temperature isotropic (LTI) pyrolytic carbon is a preferred carbon coating.
Pyrolytic derives from the term pyrolysis, which is a thermal decomposition of hydrocarbons to produce a carbon material. Pyrolytic carbon is produced in a process in which hydrocarbons and alloying gases are decomposed in a fluidized or floating bed.
Inert gas flow is used to float the bed and the substrate particles. The hydrocarbon pyrolysis results in high carbon, low hydrogen content spheres, which deposit as solids upon the substrate in the fluidized bed. As they deposit at temperatures of 1200-l500~C, the spheres may coalesce, deform, or grow due to atom movement, resulting in a high density coating. A
hard, metallic substance capable of withstanding the high temperature conditions of the coating process is the preferred particulate material. Zirconium oxide has been found to be especially suitable as such a substrate. However, other metallic substrates, including but not limited to medical grade stainless steel, titanium and titanium alloys and all oxide derivatives of each, are also quite acceptable as the substrate material.
The particles comprise microbeads or microparticles of a hard, material serving as a substrate and having a thin coating or film of biocompatible, isotropic carbon deposited on their surfaces. The substrate material is preferably radiopaque. Different types of carbon coating processes may be utilized, with the particulate substrate being a metallic substance selected for compatibility with the coating process.
Low temperature isotropic (LTI) pyrolytic carbon is a preferred carbon coating.
Pyrolytic derives from the term pyrolysis, which is a thermal decomposition of hydrocarbons to produce a carbon material. Pyrolytic carbon is produced in a process in which hydrocarbons and alloying gases are decomposed in a fluidized or floating bed.
Inert gas flow is used to float the bed and the substrate particles. The hydrocarbon pyrolysis results in high carbon, low hydrogen content spheres, which deposit as solids upon the substrate in the fluidized bed. As they deposit at temperatures of 1200-l500~C, the spheres may coalesce, deform, or grow due to atom movement, resulting in a high density coating. A
hard, metallic substance capable of withstanding the high temperature conditions of the coating process is the preferred particulate material. Zirconium oxide has been found to be especially suitable as such a substrate. However, other metallic substrates, including but not limited to medical grade stainless steel, titanium and titanium alloys and all oxide derivatives of each, are also quite acceptable as the substrate material.
WO 96I02209 ~ 9 ~ ~ PCT/US95/07454 Ultra-low-temperature isotropic carbon may be applied as a coating in vacuum vapor deposition processes. Carbon can be deposited effectively utilizing ion beams generated from the disassociation of CO2, reactive disassociation in vacuum of a hydrocarbon as a result of a glow discharge, sublimation of a solid graphite source or cathode sputtering of a graphite source, as examples of such processes. Gold has been found to be suitable as a substrate material ideal for vacuum vapor deposited capon, however, other substrates, including but not limited to nickel, silver, stainless steel, or titanium are also quite acceptable as the substrate material.
Vitreous or glass carbons may also serve as the coating material. These are also isotropic, monolithic carbons, which are formed by pyrolysis of carbonaceous preforms, during which gaseous pyrolysis products diffuse through the shape and are liberated.
The atomic structure of either pyrolitic LTI carbon or vitreous carbon is similar to graphite, the common form of carbon, but the alignment between hexagonal planes of atoms is not as well ordered. Pyrolitic carbon is characterized by a more chaotic atomic structure with warped hexagonal planes, missing atoms and generally a more turbostatic appearance.
This results in better bonding between layer planes.
The coating process is applied to small substrate particles to produce final, rounded particles that have a smooth carbon-coated surface in the form of a thin, black film. The resulting smooth surface on the particles enhances their passage through an injection needle, cannula or catheter and into body tissue. The high strength, resistance to breakdown or corrosion, and durability of the carbon coating insures the effective, long term functioning of the particles in tissue augmentation at the injection site. The established biocompatibility of pyrolytic carbon renders it particularly suitable for the anticipated body tissue applications.
WO 96I02209 ~ ~ ~ ~ j.~ ~ Q PCT/US95/07454 After the carbon coating has been applied, the particles are subjected to a cleaning and sieving process to remove contaminants and to separate out particles of a size less than or greater than the desired size range. The particles may range in size from 100 microns to 1,000 microns in average, transverse cross-sectional dimension, and a preferred size range is between 200 and 500 microns. That size avoids particle migration from the injection site and facilitates injection through a small bore instniment. The substrate particles are initially milled, extruded or otheravise formed to the desired particle size, in a substantially rounded shape prior to being subjected to the coating process. The particles are randomly shaped and rounded, ranging from oblong to generally spherical. The sieving process is such that the minimum particle dimension will pass through a U. S . No. 18 Screen Mesh ( 1000 micron grid size opening) but will not pass through a U.S. No. 140 Screen Mesh (106 micron grid size). That minimum dimension will be the transverse, cross-sectional dimension on oblong or elongated particles, with that dimension coinciding with the particle diameter on generally spherical particles.
The carrier is preferably an aqueous suspension or solution, other fluid or gel of polymeric chains of B-D-glucose, commonly referred to as B-glucan. The glucose units are linked to each other at the 1-3, 1-4, or 1-6 positions and form polymeric chains ranging to several thousand daltons in weight.
B-glucan is a naturally occurring constituent of cell walls in essentially all living systems including plants, yeast, bacteria, and mammalian systems. Its effects and modulating actions on living systems have been studied extensively (see Abel, G. , and Czop, J. K. , "Stimulation of Human Monocyte B-Glucan Receptors by Glucan Particles Induces Production of TNF-a and 1L-B" Int. J. Immunopharmacol., 14(8):1363-1373, 1992 and references included therein). B-glucan, when administered in experimental studies, elicits and augments WO 96/02209 ~ ~ 9 4 9 0 9 pCT/US95/07454 host defense mechanisms including the steps required to promote healing by first intent, thereby stimulating the reparative processes in the host system. B-glucan is rapidly removed from tissue sites through macrophagic phagocytosis or by enzymatic destruction by serous enzymes. The rapid destmction or removal of B-glucan, as well as its available viscosity and lubricous nature, makes it an optimum carrier for the particles.
Aqueous solutions, suspensions, fluids, or gels of B-glucan can be produced that have favorable physical characteristics as a carrier for carbon-coated particles.
The viscosity can vary from a thin liquid to a firm, self supporting gel. Irrespective of viscosity, the B-glucan has excellent lubricity, thereby creating a particle-carrier composition which is easily administered by delivery to a predetermined body site through a small bore needle, cannula, or catheter. The carrier will be of sufficient viscosity to assure that the carbon-coated particles remain suspended therein. . Other examples of appropriate carriers include hyaluronic acid, polyvinyl pyrrolidone or a hydrogel derivative thereof, dextran or a hydrogel derivative thereof, glycerol, polyethylene glycol, succinylated collagen, liquid collagen, oil based emulsions such as corn oil or safflower, or other polysaccharides or biocompatible organic polymers either singly or in combination with one or more of the above-referenced solutions.
In use, the above-described composition will be injected in a fluid state, e.g., as a slurry, fluid suspension or emulsion, or as a gel through a syringe needle or cannula into a body tissue site. When deposited into a soft tissue site, the preferred B-glucan carrier will disperse or be destroyed as set forth above. The particles are of an optimum size which will prevent their being carried away by capillary blood flow. They will thus remain at the site and will serve to fill voids, provide additional support, or correct other soft-tissue defects. For urological applications, the composition may be injected into the tissue of the urinary tract, ~~~4.(~~~~
wherein the selected site may be, for example, the bladder neck, the urethra or urethral sphincter. The resulting bulking or augmentation of the urethral tissue will restrict the size of the urethra or urinary passage and thus assist in overcoming incontinence.
In an experimental study, a syringe was utilized to contain and inject a fluid composition comprised of:
pyrolytic isotropic LTI carbon-coated zirconium oxide particles in a size range from 200 to 500 microns of a total mass of 400 mg suspended in;
B-glucan formulated as a 1 ~ weight by weight aqueous suspension, as the carrier.
The test composition was administered by periurethral injection into dogs.
Injections were performed such that the bulk of the bladder neck/periurethral tissue was increased but such that the urethral lumen diameter was not compromised. One or more injections of the test material were administered in total volumes ranging from 1.9 to 2.5 milliliters.
The study was conducted in accordance with good laboratory practices and confirmed that the handling characteristics of the test material were favorable, as the material was easily injected with minimal to moderate resistance. No evidence of migration of the implant material was noted.
Vitreous or glass carbons may also serve as the coating material. These are also isotropic, monolithic carbons, which are formed by pyrolysis of carbonaceous preforms, during which gaseous pyrolysis products diffuse through the shape and are liberated.
The atomic structure of either pyrolitic LTI carbon or vitreous carbon is similar to graphite, the common form of carbon, but the alignment between hexagonal planes of atoms is not as well ordered. Pyrolitic carbon is characterized by a more chaotic atomic structure with warped hexagonal planes, missing atoms and generally a more turbostatic appearance.
This results in better bonding between layer planes.
The coating process is applied to small substrate particles to produce final, rounded particles that have a smooth carbon-coated surface in the form of a thin, black film. The resulting smooth surface on the particles enhances their passage through an injection needle, cannula or catheter and into body tissue. The high strength, resistance to breakdown or corrosion, and durability of the carbon coating insures the effective, long term functioning of the particles in tissue augmentation at the injection site. The established biocompatibility of pyrolytic carbon renders it particularly suitable for the anticipated body tissue applications.
WO 96I02209 ~ ~ ~ ~ j.~ ~ Q PCT/US95/07454 After the carbon coating has been applied, the particles are subjected to a cleaning and sieving process to remove contaminants and to separate out particles of a size less than or greater than the desired size range. The particles may range in size from 100 microns to 1,000 microns in average, transverse cross-sectional dimension, and a preferred size range is between 200 and 500 microns. That size avoids particle migration from the injection site and facilitates injection through a small bore instniment. The substrate particles are initially milled, extruded or otheravise formed to the desired particle size, in a substantially rounded shape prior to being subjected to the coating process. The particles are randomly shaped and rounded, ranging from oblong to generally spherical. The sieving process is such that the minimum particle dimension will pass through a U. S . No. 18 Screen Mesh ( 1000 micron grid size opening) but will not pass through a U.S. No. 140 Screen Mesh (106 micron grid size). That minimum dimension will be the transverse, cross-sectional dimension on oblong or elongated particles, with that dimension coinciding with the particle diameter on generally spherical particles.
The carrier is preferably an aqueous suspension or solution, other fluid or gel of polymeric chains of B-D-glucose, commonly referred to as B-glucan. The glucose units are linked to each other at the 1-3, 1-4, or 1-6 positions and form polymeric chains ranging to several thousand daltons in weight.
B-glucan is a naturally occurring constituent of cell walls in essentially all living systems including plants, yeast, bacteria, and mammalian systems. Its effects and modulating actions on living systems have been studied extensively (see Abel, G. , and Czop, J. K. , "Stimulation of Human Monocyte B-Glucan Receptors by Glucan Particles Induces Production of TNF-a and 1L-B" Int. J. Immunopharmacol., 14(8):1363-1373, 1992 and references included therein). B-glucan, when administered in experimental studies, elicits and augments WO 96/02209 ~ ~ 9 4 9 0 9 pCT/US95/07454 host defense mechanisms including the steps required to promote healing by first intent, thereby stimulating the reparative processes in the host system. B-glucan is rapidly removed from tissue sites through macrophagic phagocytosis or by enzymatic destruction by serous enzymes. The rapid destmction or removal of B-glucan, as well as its available viscosity and lubricous nature, makes it an optimum carrier for the particles.
Aqueous solutions, suspensions, fluids, or gels of B-glucan can be produced that have favorable physical characteristics as a carrier for carbon-coated particles.
The viscosity can vary from a thin liquid to a firm, self supporting gel. Irrespective of viscosity, the B-glucan has excellent lubricity, thereby creating a particle-carrier composition which is easily administered by delivery to a predetermined body site through a small bore needle, cannula, or catheter. The carrier will be of sufficient viscosity to assure that the carbon-coated particles remain suspended therein. . Other examples of appropriate carriers include hyaluronic acid, polyvinyl pyrrolidone or a hydrogel derivative thereof, dextran or a hydrogel derivative thereof, glycerol, polyethylene glycol, succinylated collagen, liquid collagen, oil based emulsions such as corn oil or safflower, or other polysaccharides or biocompatible organic polymers either singly or in combination with one or more of the above-referenced solutions.
In use, the above-described composition will be injected in a fluid state, e.g., as a slurry, fluid suspension or emulsion, or as a gel through a syringe needle or cannula into a body tissue site. When deposited into a soft tissue site, the preferred B-glucan carrier will disperse or be destroyed as set forth above. The particles are of an optimum size which will prevent their being carried away by capillary blood flow. They will thus remain at the site and will serve to fill voids, provide additional support, or correct other soft-tissue defects. For urological applications, the composition may be injected into the tissue of the urinary tract, ~~~4.(~~~~
wherein the selected site may be, for example, the bladder neck, the urethra or urethral sphincter. The resulting bulking or augmentation of the urethral tissue will restrict the size of the urethra or urinary passage and thus assist in overcoming incontinence.
In an experimental study, a syringe was utilized to contain and inject a fluid composition comprised of:
pyrolytic isotropic LTI carbon-coated zirconium oxide particles in a size range from 200 to 500 microns of a total mass of 400 mg suspended in;
B-glucan formulated as a 1 ~ weight by weight aqueous suspension, as the carrier.
The test composition was administered by periurethral injection into dogs.
Injections were performed such that the bulk of the bladder neck/periurethral tissue was increased but such that the urethral lumen diameter was not compromised. One or more injections of the test material were administered in total volumes ranging from 1.9 to 2.5 milliliters.
The study was conducted in accordance with good laboratory practices and confirmed that the handling characteristics of the test material were favorable, as the material was easily injected with minimal to moderate resistance. No evidence of migration of the implant material was noted.
Claims (20)
1. An injectable, biocompatible composition for tissue augmentation comprising:
a plurality of discrete particles in a carrier, wherein the particles are substrate particles with a carbon coating and have an average, transverse cross-sectional dimension of between 100 and 1,000 microns and the carrier is a biocompatible medium having sufficient fluidity to carry and deliver the particles, and has lubricative qualities.
a plurality of discrete particles in a carrier, wherein the particles are substrate particles with a carbon coating and have an average, transverse cross-sectional dimension of between 100 and 1,000 microns and the carrier is a biocompatible medium having sufficient fluidity to carry and deliver the particles, and has lubricative qualities.
2. The composition of claim 1 wherein:
said carbon coating is isotropic carbon.
said carbon coating is isotropic carbon.
3. The composition of claim 2 wherein:
said isotropic carbon coating is low temperature isotropic (LTI), pyrolytic carbon.
said isotropic carbon coating is low temperature isotropic (LTI), pyrolytic carbon.
4. The composition of claim 3 wherein:
said substrate particles are zirconium oxide.
said substrate particles are zirconium oxide.
5. The composition of claim 2 wherein:
said carbon coating is vitreous carbon.
said carbon coating is vitreous carbon.
6. The composition of claim 2 wherein:
said isotropic carbon coating is ultra low temperature isotropic carbon which is vapor deposited.
said isotropic carbon coating is ultra low temperature isotropic carbon which is vapor deposited.
7. The composition of claim 6 wherein:
said substrate particles are gold or silver.
said substrate particles are gold or silver.
8. The composition of claim 1 wherein:
said substrate particles are zirconium oxide.
said substrate particles are zirconium oxide.
9. The composition of claim 1 wherein:
said carbon coating is pyrolytic, isotropic carbon.
said carbon coating is pyrolytic, isotropic carbon.
10. The composition of claim 1 wherein:
the carrier is a solution, suspension or gel of polysaccharides.
the carrier is a solution, suspension or gel of polysaccharides.
11. The composition of claim 10 wherein:
the polysaccharide is beta-glucan.
the polysaccharide is beta-glucan.
12. The composition of claim 1 wherein:
the carrier is a solution or suspension selected from the group comprised of hyaluronic acid, polyvinyl pyrrolidone or a hydrogel derivative thereof, dextran or a hydrogel derivative thereof, glycerol, polyethylene glycol, succinylated collagen, liquid collagen, or other polysaccharides or biocompatible organic polymers, either singly or in combination.
the carrier is a solution or suspension selected from the group comprised of hyaluronic acid, polyvinyl pyrrolidone or a hydrogel derivative thereof, dextran or a hydrogel derivative thereof, glycerol, polyethylene glycol, succinylated collagen, liquid collagen, or other polysaccharides or biocompatible organic polymers, either singly or in combination.
13. The composition of claim 1 wherein:
said carbon coating is a smooth surface film.
said carbon coating is a smooth surface film.
14. The composition of claim 13 wherein:
said substrate particles are zirconium oxide.
said substrate particles are zirconium oxide.
15. The composition of claim 2 wherein:
said coating is a smooth surface film.
said coating is a smooth surface film.
16. The composition of claim 2 wherein:
said substrate particles are of rounded shape and said dimension is between microns and 500 microns.
said substrate particles are of rounded shape and said dimension is between microns and 500 microns.
17. The composition of claim 1 wherein:
the substrate particles are radiopaque.
the substrate particles are radiopaque.
18. The composition of claim 1 wherein:
the substrate particles are selected from the group comprising stainless steel, titanium and titanium alloys, and their oxides.
the substrate particles are selected from the group comprising stainless steel, titanium and titanium alloys, and their oxides.
19. The composition of claim 1 wherein:
said substrate particles are a metallic substance.
said substrate particles are a metallic substance.
20. The use of the injectable biocompatable composition of any one of claims 1 to 19 for augmenting tissue in a human.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/274,777 US5451406A (en) | 1994-07-14 | 1994-07-14 | Tissue injectable composition and method of use |
US08/274,777 | 1994-07-14 | ||
PCT/US1995/007454 WO1996002209A1 (en) | 1994-07-14 | 1995-06-13 | Tissue injectable composition and method of use |
Publications (2)
Publication Number | Publication Date |
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CA2194909A1 CA2194909A1 (en) | 1996-02-01 |
CA2194909C true CA2194909C (en) | 1999-07-13 |
Family
ID=23049577
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Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002194909A Expired - Fee Related CA2194909C (en) | 1994-07-14 | 1995-06-13 | Tissue injectable composition and method of use |
Country Status (6)
Country | Link |
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US (1) | US5451406A (en) |
EP (1) | EP0771179B1 (en) |
AT (1) | ATE246475T1 (en) |
CA (1) | CA2194909C (en) |
DE (1) | DE69531450T2 (en) |
WO (1) | WO1996002209A1 (en) |
Families Citing this family (138)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7060287B1 (en) | 1992-02-11 | 2006-06-13 | Bioform Inc. | Tissue augmentation material and method |
US7968110B2 (en) * | 1992-02-11 | 2011-06-28 | Merz Aesthetics, Inc. | Tissue augmentation material and method |
US6537574B1 (en) | 1992-02-11 | 2003-03-25 | Bioform, Inc. | Soft tissue augmentation material |
US6051247A (en) * | 1996-05-30 | 2000-04-18 | University Of Florida Research Foundation, Inc. | Moldable bioactive compositions |
US5840290A (en) * | 1996-05-30 | 1998-11-24 | University Of Florida Research Foundation | Injectable bio-active glass in a dextran suspension |
US5792478A (en) * | 1996-07-08 | 1998-08-11 | Advanced Uro Science | Tissue injectable composition and method of use |
JP5053470B2 (en) * | 1996-08-23 | 2012-10-17 | クック バイオテク インコーポレイティド | Graft prosthesis and materials and methods thereof |
US8716227B2 (en) * | 1996-08-23 | 2014-05-06 | Cook Biotech Incorporated | Graft prosthesis, materials and methods |
US6666892B2 (en) * | 1996-08-23 | 2003-12-23 | Cook Biotech Incorporated | Multi-formed collagenous biomaterial medical device |
US6579224B1 (en) | 1999-10-11 | 2003-06-17 | Uromedica, Inc. | Apparatus and method for inserting an adjustable implantable genitourinary device |
US6419624B1 (en) * | 1999-10-11 | 2002-07-16 | Uromedica, Inc. | Apparatus and method for inserting an adjustable implantable genitourinary device |
US7364540B1 (en) * | 1997-06-12 | 2008-04-29 | Uromedica, Inc. | Implantable device and method for adjustably restricting a body lumen |
US6645138B2 (en) * | 1997-09-12 | 2003-11-11 | Uromedica, Inc. | Adjustable implantable genitourinary device |
US6045498A (en) | 1997-06-12 | 2000-04-04 | Uromedica, Inc. | Method for adjustably restricting a body lumen |
FR2764514B1 (en) | 1997-06-13 | 1999-09-03 | Biopharmex Holding Sa | IMPLANT INJECTED IN SUBCUTANEOUS OR INTRADERMAL WITH CONTROLLED BIORESORBABILITY FOR REPAIR OR PLASTIC SURGERY AND AESTHETIC DERMATOLOGY |
BR9810693A (en) * | 1997-07-10 | 2000-08-15 | Usbiomaterials Corp | Moldable bioactive composition, biocompatible pharmaceutical composition, and, processes for repair, replacement, reconfiguration, reconstruction or augmentation of anatomical structures of hard tissue and to induce osteogenesis |
US8668737B2 (en) | 1997-10-10 | 2014-03-11 | Senorx, Inc. | Tissue marking implant |
US7637948B2 (en) | 1997-10-10 | 2009-12-29 | Senorx, Inc. | Tissue marking implant |
US6309420B1 (en) * | 1997-10-14 | 2001-10-30 | Parallax Medical, Inc. | Enhanced visibility materials for implantation in hard tissue |
US20030135206A1 (en) | 1998-02-27 | 2003-07-17 | Curon Medical, Inc. | Method for treating a sphincter |
JP5095049B2 (en) | 1998-03-06 | 2012-12-12 | バイオスフィアー メディカル,インク. | Implantable particles for the treatment of tissue bulking and gastroesophageal reflux disease, urinary incontinence, skin wrinkles |
US6660301B1 (en) * | 1998-03-06 | 2003-12-09 | Biosphere Medical, Inc. | Injectable microspheres for dermal augmentation and tissue bulking |
AU3203599A (en) | 1998-04-01 | 1999-10-18 | Parallax Medical, Inc. | Pressure applicator for hard tissue implant placement |
US6161034A (en) * | 1999-02-02 | 2000-12-12 | Senorx, Inc. | Methods and chemical preparations for time-limited marking of biopsy sites |
US8882850B2 (en) * | 1998-12-01 | 2014-11-11 | Cook Biotech Incorporated | Multi-formed collagenous biomaterial medical device |
US6595910B2 (en) * | 1998-12-11 | 2003-07-22 | Scimed Life Systems, Inc. | Method for treating fecal incontinence |
US7132582B2 (en) * | 2003-05-30 | 2006-11-07 | Council Of Scientific And Industrial Research | Catalytic process for the preparation of isolongifolene |
US6251064B1 (en) * | 1998-12-11 | 2001-06-26 | Enteric Medical Technologies, Inc. | Method for creating valve-like mechanism in natural body passageway |
US6238335B1 (en) | 1998-12-11 | 2001-05-29 | Enteric Medical Technologies, Inc. | Method for treating gastroesophageal reflux disease and apparatus for use therewith |
US6371904B1 (en) | 1998-12-24 | 2002-04-16 | Vivant Medical, Inc. | Subcutaneous cavity marking device and method |
US6356782B1 (en) | 1998-12-24 | 2002-03-12 | Vivant Medical, Inc. | Subcutaneous cavity marking device and method |
US9669113B1 (en) | 1998-12-24 | 2017-06-06 | Devicor Medical Products, Inc. | Device and method for safe location and marking of a biopsy cavity |
US7651505B2 (en) | 2002-06-17 | 2010-01-26 | Senorx, Inc. | Plugged tip delivery for marker placement |
US7983734B2 (en) * | 2003-05-23 | 2011-07-19 | Senorx, Inc. | Fibrous marker and intracorporeal delivery thereof |
US20080039819A1 (en) * | 2006-08-04 | 2008-02-14 | Senorx, Inc. | Marker formed of starch or other suitable polysaccharide |
US6725083B1 (en) | 1999-02-02 | 2004-04-20 | Senorx, Inc. | Tissue site markers for in VIVO imaging |
US6862470B2 (en) * | 1999-02-02 | 2005-03-01 | Senorx, Inc. | Cavity-filling biopsy site markers |
US20090030309A1 (en) | 2007-07-26 | 2009-01-29 | Senorx, Inc. | Deployment of polysaccharide markers |
US8498693B2 (en) | 1999-02-02 | 2013-07-30 | Senorx, Inc. | Intracorporeal marker and marker delivery device |
US8361082B2 (en) | 1999-02-02 | 2013-01-29 | Senorx, Inc. | Marker delivery device with releasable plug |
US9820824B2 (en) | 1999-02-02 | 2017-11-21 | Senorx, Inc. | Deployment of polysaccharide markers for treating a site within a patent |
WO2000051676A1 (en) * | 1999-03-01 | 2000-09-08 | Advanced Biomedical Devices, Inc. | Implant positioning system and method |
WO2000056254A1 (en) | 1999-03-24 | 2000-09-28 | Parallax Medical, Inc. | Non-compliant system for delivery of implant material |
US7395822B1 (en) | 1999-04-30 | 2008-07-08 | Uromedica, Inc. | Method and apparatus for adjustable sling for treatment of urinary stress incontinence |
US20040229295A1 (en) * | 1999-05-17 | 2004-11-18 | Marchitto Kevin S. | Activated delivery of biomolecules using electromagnetic energy |
US6575991B1 (en) | 1999-06-17 | 2003-06-10 | Inrad, Inc. | Apparatus for the percutaneous marking of a lesion |
US6835200B2 (en) | 1999-06-22 | 2004-12-28 | Ndo Surgical. Inc. | Method and devices for tissue reconfiguration |
US6821285B2 (en) | 1999-06-22 | 2004-11-23 | Ndo Surgical, Inc. | Tissue reconfiguration |
US6494888B1 (en) | 1999-06-22 | 2002-12-17 | Ndo Surgical, Inc. | Tissue reconfiguration |
US7846180B2 (en) | 1999-06-22 | 2010-12-07 | Ethicon Endo-Surgery, Inc. | Tissue fixation devices and methods of fixing tissue |
US6663639B1 (en) | 1999-06-22 | 2003-12-16 | Ndo Surgical, Inc. | Methods and devices for tissue reconfiguration |
US8287554B2 (en) | 1999-06-22 | 2012-10-16 | Ethicon Endo-Surgery, Inc. | Method and devices for tissue reconfiguration |
TW434006B (en) * | 1999-08-13 | 2001-05-16 | Bioform Inc | Tissue augmentation material and method |
US6358197B1 (en) | 1999-08-13 | 2002-03-19 | Enteric Medical Technologies, Inc. | Apparatus for forming implants in gastrointestinal tract and kit for use therewith |
US6277392B1 (en) | 1999-09-16 | 2001-08-21 | Carbon Medical Technologies, Inc. | Tissue injectable composition |
US6502574B2 (en) | 1999-09-17 | 2003-01-07 | Pi Medical, Inc. | Lateral stiffening snoring treatment |
US6431174B1 (en) * | 2000-08-10 | 2002-08-13 | Pi Medical, Inc. | Method and apparatus to treat conditions of the naso-pharyngeal area |
US6783515B1 (en) | 1999-09-30 | 2004-08-31 | Arthrocare Corporation | High pressure delivery system |
EP1114618A3 (en) | 2000-01-04 | 2001-08-22 | Ethicon Endo-Surgery, Inc. | Surgical instrument for applying beads to tissue |
EP1274472A2 (en) | 2000-03-20 | 2003-01-15 | Biosphere Medical, Inc. | Injectable and swellable microspheres for tissue bulking |
US7338657B2 (en) * | 2001-03-15 | 2008-03-04 | Biosphere Medical, Inc. | Injectable microspheres for tissue construction |
US6436424B1 (en) | 2000-03-20 | 2002-08-20 | Biosphere Medical, Inc. | Injectable and swellable microspheres for dermal augmentation |
WO2001072281A2 (en) | 2000-03-24 | 2001-10-04 | Biosphere Medical Inc. | Microspheres for active embolization |
US6540789B1 (en) * | 2000-06-15 | 2003-04-01 | Scimed Life Systems, Inc. | Method for treating morbid obesity |
US6355275B1 (en) | 2000-06-23 | 2002-03-12 | Carbon Medical Technologies, Inc. | Embolization using carbon coated microparticles |
WO2002011696A2 (en) * | 2000-08-08 | 2002-02-14 | Ev & M | Active tissue augmentation materials and method |
US6394965B1 (en) | 2000-08-15 | 2002-05-28 | Carbon Medical Technologies, Inc. | Tissue marking using biocompatible microparticles |
US6425854B1 (en) * | 2000-10-02 | 2002-07-30 | Genyx Medical, Inc. | Method for delivering non-biodegradable bulking composition to a urological site |
US6576226B1 (en) | 2000-11-17 | 2003-06-10 | Gary R. Jernberg | Local delivery of agents for disruption and inhibition of bacterial biofilm for treatment of periodontal disease |
US6726898B2 (en) | 2000-11-17 | 2004-04-27 | Gary R. Jernberg | Local delivery of agents for disruption and inhibition of bacterial biofilm for treatment of periodontal disease |
ES2409758T3 (en) | 2000-11-20 | 2013-06-27 | Senorx, Inc. | Tissue site markers for in vivo imaging |
US9080146B2 (en) | 2001-01-11 | 2015-07-14 | Celonova Biosciences, Inc. | Substrates containing polyphosphazene as matrices and substrates containing polyphosphazene with a micro-structured surface |
US20070191964A1 (en) * | 2001-04-04 | 2007-08-16 | Arthrocare Corporation | Enhanced visibility materials for implantation in hard tissue |
WO2002100444A1 (en) * | 2001-06-08 | 2002-12-19 | Biosphere Medical Inc. | Colloidal metal labelled microparticles, their production and use |
US20030161824A1 (en) * | 2002-02-27 | 2003-08-28 | Rackley Raymond R. | Bulking agent needle apparatus and method of using the needle apparatus |
US20030171451A1 (en) * | 2002-03-11 | 2003-09-11 | White Daniel A. | Bony tissue fillers and restoratives containing biocompatible particle |
US7695427B2 (en) | 2002-04-26 | 2010-04-13 | Torax Medical, Inc. | Methods and apparatus for treating body tissue sphincters and the like |
US20040105890A1 (en) * | 2002-05-28 | 2004-06-03 | Carbon Medical Technologies, Inc. | Biocompatible injectable materials |
US7175589B2 (en) * | 2002-07-02 | 2007-02-13 | The Foundry Inc. | Methods and devices for luminal and sphincter augmentation |
US20040194266A1 (en) * | 2002-08-19 | 2004-10-07 | Carter Linda A. | Burn, sunburn, and cellulite treatment system |
US20060036158A1 (en) | 2003-11-17 | 2006-02-16 | Inrad, Inc. | Self-contained, self-piercing, side-expelling marking apparatus |
US7691087B2 (en) * | 2002-11-25 | 2010-04-06 | Scimed Life Systems, Inc. | Injection device |
US7381222B2 (en) * | 2002-12-30 | 2008-06-03 | Quiescence Medical, Inc. | Stent for maintaining patency of a body region |
US7647931B2 (en) | 2002-12-30 | 2010-01-19 | Quiescence Medical, Inc. | Stent for maintaining patency of a body region |
US7992566B2 (en) | 2002-12-30 | 2011-08-09 | Quiescence Medical, Inc. | Apparatus and methods for treating sleep apnea |
US7877133B2 (en) * | 2003-05-23 | 2011-01-25 | Senorx, Inc. | Marker or filler forming fluid |
US20050119562A1 (en) * | 2003-05-23 | 2005-06-02 | Senorx, Inc. | Fibrous marker formed of synthetic polymer strands |
US20050033157A1 (en) * | 2003-07-25 | 2005-02-10 | Klein Dean A. | Multi-modality marking material and method |
BRPI0413086A (en) * | 2003-07-30 | 2006-10-03 | Anteis Sa | complex matrix, use thereof, and process for preparing a poorly biodegradable biocompatible matrix |
US20050084672A1 (en) * | 2003-10-20 | 2005-04-21 | O'brien Robert C. | Implantable electrical lead wire |
US20050273002A1 (en) | 2004-06-04 | 2005-12-08 | Goosen Ryan L | Multi-mode imaging marker |
US8124120B2 (en) | 2003-12-22 | 2012-02-28 | Anika Therapeutics, Inc. | Crosslinked hyaluronic acid compositions for tissue augmentation |
US20100261951A1 (en) * | 2004-02-23 | 2010-10-14 | Uromedica, Inc. | Method and apparatus for an adjustable implantable continence device |
US20050226936A1 (en) * | 2004-04-08 | 2005-10-13 | Q-Med Ab | Method of soft tissue augmentation |
WO2005118060A2 (en) * | 2004-04-30 | 2005-12-15 | Boston Scientific Limited | Apparatus with partially insulated needle for measuring tissue impedance and method using same |
US9114162B2 (en) | 2004-10-25 | 2015-08-25 | Celonova Biosciences, Inc. | Loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same |
JP4885866B2 (en) | 2004-10-25 | 2012-02-29 | セロノヴァ バイオサイエンスィズ ジャーマニー ゲーエムベーハー | Fillable polyphosphazene-containing particles for therapeutic and / or diagnostic applications and methods for their preparation and use |
US9107850B2 (en) | 2004-10-25 | 2015-08-18 | Celonova Biosciences, Inc. | Color-coded and sized loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same |
US20210299056A9 (en) | 2004-10-25 | 2021-09-30 | Varian Medical Systems, Inc. | Color-Coded Polymeric Particles of Predetermined Size for Therapeutic and/or Diagnostic Applications and Related Methods |
US8663225B2 (en) * | 2004-11-12 | 2014-03-04 | Medtronic, Inc. | Hydrogel bone void filler |
WO2006091786A1 (en) * | 2005-02-23 | 2006-08-31 | Uromedica, Inc. | Method and apparatus for an adjustable implantable continence device |
US10357328B2 (en) | 2005-04-20 | 2019-07-23 | Bard Peripheral Vascular, Inc. and Bard Shannon Limited | Marking device with retractable cannula |
US7984717B2 (en) * | 2005-04-29 | 2011-07-26 | Medtronic, Inc. | Devices for augmentation of lumen walls |
US20060257445A1 (en) * | 2005-04-29 | 2006-11-16 | Medtronic, Inc. | Devices for augmentation of lumen walls |
US20060257444A1 (en) * | 2005-04-29 | 2006-11-16 | Medtronic, Inc. | Devices for augmentation of lumen walls |
AU2006245950B2 (en) | 2005-05-09 | 2012-01-12 | Biosphere Medical S.A. | Compositions and methods using microspheres and non-ionic contrast agents |
CA2562580C (en) | 2005-10-07 | 2014-04-29 | Inrad, Inc. | Drug-eluting tissue marker |
US20070184087A1 (en) | 2006-02-06 | 2007-08-09 | Bioform Medical, Inc. | Polysaccharide compositions for use in tissue augmentation |
FR2897775B1 (en) * | 2006-02-24 | 2013-05-03 | Elisabeth Laugier | BIOMATERIAU, INJECTABLE IMPLANT COMPRISING IT, PROCESS FOR PREPARING THE SAME AND USES THEREOF |
US8147397B1 (en) | 2006-05-19 | 2012-04-03 | Carbon Medical Technologies, Inc. | Urethral needle guide device |
JP5406025B2 (en) | 2006-07-06 | 2014-02-05 | クワイエセンス メディカル インコーポレイテッド | Apparatus and system for treatment of sleep apnea |
ES2443526T3 (en) | 2006-10-23 | 2014-02-19 | C.R. Bard, Inc. | Breast marker |
US20080107744A1 (en) * | 2006-11-06 | 2008-05-08 | Jack Fa-De Chu | Injectable hollow tissue filler |
EP3542748B1 (en) | 2006-12-12 | 2023-08-16 | C. R. Bard, Inc. | Multiple imaging mode tissue marker |
US8401622B2 (en) | 2006-12-18 | 2013-03-19 | C. R. Bard, Inc. | Biopsy marker with in situ-generated imaging properties |
US7776840B2 (en) | 2007-02-21 | 2010-08-17 | Cutanea Life Sciences, Inc. | Methods of use of biomaterial and injectable implant containing biomaterial |
US8852216B2 (en) | 2007-03-23 | 2014-10-07 | Ethicon Endo-Surgery, Inc. | Tissue approximation methods |
AU2008266311A1 (en) * | 2007-06-15 | 2008-12-24 | Ethicon, Inc. | Tissue fragment compositions for the treatment of incontinence |
US20090177192A1 (en) * | 2007-07-13 | 2009-07-09 | Scimed Life Systems, Inc. | Method for ablating tissue to facilitate implantation and apparatus and kit for use therewith |
EP2219536B1 (en) * | 2007-10-23 | 2012-12-19 | Boston Scientific Scimed, Inc. | Apparatus for treating tissue |
CA2709581C (en) * | 2007-12-17 | 2013-06-11 | Anna Love | Soft tissue filler |
US8311610B2 (en) | 2008-01-31 | 2012-11-13 | C. R. Bard, Inc. | Biopsy tissue marker |
AU2009218436A1 (en) | 2008-02-29 | 2009-09-03 | Coloplast A/S | Compositions and methods for augmentation and regeneration of living tissue in a subject |
US20100016808A1 (en) * | 2008-07-17 | 2010-01-21 | Bioform Medical, Inc. | Thin-Walled Delivery System |
US9327061B2 (en) | 2008-09-23 | 2016-05-03 | Senorx, Inc. | Porous bioabsorbable implant |
CA2742765C (en) | 2008-12-30 | 2016-04-12 | C.R. Bard Inc. | Marker delivery device for tissue marker placement |
US20100204570A1 (en) * | 2009-02-06 | 2010-08-12 | Paul Lubock | Anchor markers |
US20110098731A1 (en) * | 2009-10-26 | 2011-04-28 | Eric Whitbrook | Magnetically assisted clasps for prosthetic implants, and related methods |
CN106913902A (en) | 2009-11-09 | 2017-07-04 | 聚光灯技术合伙有限责任公司 | Polysaccharide based aquagel |
US8795727B2 (en) | 2009-11-09 | 2014-08-05 | Spotlight Technology Partners Llc | Fragmented hydrogels |
WO2012082791A2 (en) | 2010-12-13 | 2012-06-21 | Quiescence Medical, Inc. | Apparatus and methods for treating sleep apnea |
USD715942S1 (en) | 2013-09-24 | 2014-10-21 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD716450S1 (en) | 2013-09-24 | 2014-10-28 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD716451S1 (en) | 2013-09-24 | 2014-10-28 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD715442S1 (en) | 2013-09-24 | 2014-10-14 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
US11918728B2 (en) * | 2014-04-17 | 2024-03-05 | ImMutriX Therapeutics, Inc. | Therapeutic compositions for viral-associated disease states and methods of making and using same |
US9669151B2 (en) * | 2014-04-17 | 2017-06-06 | ImMutriX Therapeutics, Inc. | Therapeutic compositions for viral-associated disease states and methods of making and using same |
US11510766B2 (en) | 2019-02-14 | 2022-11-29 | Uromedica, Inc. | Method and apparatus for monitoring implantable device for urinary continence |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3783868A (en) * | 1971-05-06 | 1974-01-08 | Gulf Oil Corp | Percutaneous implant |
US3977896A (en) * | 1972-03-09 | 1976-08-31 | General Atomic Company | Process for depositing pyrolytic carbon coatings |
US4803075A (en) * | 1986-06-25 | 1989-02-07 | Collagen Corporation | Injectable implant composition having improved intrudability |
US4773393A (en) * | 1986-07-03 | 1988-09-27 | C. R. Bard, Inc. | Hypodermically implantable genitourinary prosthesis |
US5258028A (en) * | 1988-12-12 | 1993-11-02 | Ersek Robert A | Textured micro implants |
US5007940A (en) * | 1989-06-09 | 1991-04-16 | American Medical Systems, Inc. | Injectable polymeric bodies |
US5158573A (en) * | 1989-06-09 | 1992-10-27 | American Medical Systems, Inc. | Injectable polymeric bodies |
US5116387A (en) * | 1989-06-09 | 1992-05-26 | American Medical Systems, Inc. | Preparation of injectable polymeric bodies |
FR2654345A1 (en) * | 1989-09-05 | 1991-05-17 | Hamann Sylvie | Biocompatible covering consisting of a carbon powder |
US5204382A (en) * | 1992-02-28 | 1993-04-20 | Collagen Corporation | Injectable ceramic compositions and methods for their preparation and use |
-
1994
- 1994-07-14 US US08/274,777 patent/US5451406A/en not_active Expired - Lifetime
-
1995
- 1995-06-13 EP EP95923819A patent/EP0771179B1/en not_active Expired - Lifetime
- 1995-06-13 AT AT95923819T patent/ATE246475T1/en not_active IP Right Cessation
- 1995-06-13 WO PCT/US1995/007454 patent/WO1996002209A1/en active IP Right Grant
- 1995-06-13 CA CA002194909A patent/CA2194909C/en not_active Expired - Fee Related
- 1995-06-13 DE DE69531450T patent/DE69531450T2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
DE69531450T2 (en) | 2004-05-06 |
ATE246475T1 (en) | 2003-08-15 |
CA2194909A1 (en) | 1996-02-01 |
US5451406A (en) | 1995-09-19 |
EP0771179A1 (en) | 1997-05-07 |
DE69531450D1 (en) | 2003-09-11 |
EP0771179B1 (en) | 2003-08-06 |
EP0771179A4 (en) | 1998-07-08 |
WO1996002209A1 (en) | 1996-02-01 |
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