CA2526541C - Novel biomaterial drug delivery and surface modification compositions - Google Patents
Novel biomaterial drug delivery and surface modification compositions Download PDFInfo
- Publication number
- CA2526541C CA2526541C CA2526541A CA2526541A CA2526541C CA 2526541 C CA2526541 C CA 2526541C CA 2526541 A CA2526541 A CA 2526541A CA 2526541 A CA2526541 A CA 2526541A CA 2526541 C CA2526541 C CA 2526541C
- Authority
- CA
- Canada
- Prior art keywords
- lactylate
- blend
- polymer
- fatty acid
- palmityl
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
- C08L71/02—Polyalkylene oxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- 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
- A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
- A61L17/06—At least partially resorbable materials
- A61L17/10—At least partially resorbable materials containing macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/04—Surgical instruments, devices or methods, e.g. tourniquets for suturing wounds; Holders or packages for needles or suture materials
- A61B17/06—Needles ; Sutures; Needle-suture combinations; Holders or packages for needles or suture materials
- A61B17/06166—Sutures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/064—Surgical staples, i.e. penetrating the tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/08—Wound clamps or clips, i.e. not or only partly penetrating the tissue ; Devices for bringing together the edges of a wound
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/11—Surgical instruments, devices or methods, e.g. tourniquets for performing anastomosis; Buttons for anastomosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/122—Clamps or clips, e.g. for the umbilical cord
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00831—Material properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00831—Material properties
- A61B2017/00889—Material properties antimicrobial, disinfectant
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Surgery (AREA)
- Medicinal Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Materials Engineering (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Materials For Medical Uses (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Compositions are provided which include a polymer made at least in part from a polyoxyalkylene copolymer, such as a poloxamer. The polymer may be combined with a second component to form a blend or emulsion. The resulting composition may be utilized to form medical devices, drug delivery devices, or coatings for other medical devices.
Description
NOVEL BIOMATERIAL DRUG DELIVERY
AND SURFACE MODIFICATION COMPOSITIONS
TECHNICAL FIELD
The present disclosure is related to polymer compositions which are particularly useful in the manufacture of medical devices such as sutures, staples, clips, anastomosis rings, bone plates and screws, matrices for the sustained and/or controlled release of pharmaceutically active ingredients, etc. In some embodiments, the polymer compositions may be utilized as coatings for medical devices.
DESCRIPTION OF THE RELATED ART
Coatings for medical devices are also known. Such coatings for medical devices may be utilized to improve surface properties of the device such as, for example, cell and protein adhesion, lubricity, drug delivery, protein or DNA delivery, etc. For sutures, coatings can enhance the suture's handling characteristics, such as surgeon's throw, lubricity, knot run down and/or knot security.
Although present coatings on medical devices perform satisfactorily, there is room for improvement in connection with polymers having enhanced properties for the formation of medical devices and coatings on medical devices.
SUMMARY
Compositions are provided having a polymer made at least in part from a polyoxyalkylene copolymer, such as a poloxamer. In some embodiments the polymer made at least in part from a polyoxyalkylene copolymer may include a bioabsorbable terpolymer.
The polymers made at least in part from a polyoxyalkylene copolymer may be utilized alone or, in some useful embodiments, may be combined with another polymer or oligomer to form a blend or emulsion. In some embodiments the blend or emulsion may include a medicinal agent. The resulting compositions may be utilized to form medical devices, drug delivery devices, or coatings for medical devices.
In accordance with one embodiment of the present invention, there is provided a blend comprising: a bioabsorbable terpolymer comprising about 30 to about 50 weight percent of a polyoxyalkylene copolymer, about 40 to about 50 weight percent epsilon-caprolactone derived units, the balance of the copolymer being derived from at least one other copolymerizable monomer selected from the group consisting of glycolide, lactide, p-dioxanone and trimethylene carbonate; and a polymer derived from two or more monomers selected from the group consisting of lactide, glycolide, lactic acid, lactones, glycolic acid, carbonates, orthoesters, absorbable urethanes, and absorbable nylons.
Yet another embodiment of the present invention provides a surgical suture coated with a composition comprising: an effective antimicrobial amount of a terpolymer having a polyoxyalkylene copolymer component, a plurality of e-caprolactone derived units, and a plurality of repeating units derived from glycolide; and a salt of a C6- or higher fatty acid.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graph comparing bacterial colonization of an untreated POLYSORBO
suture with a suture coated with a blend of the present disclosure having triclosan incorporated therein.
DETAILED DESCRIPTION
The compositions described herein are useful for the formation of medical devices, especially for forming coatings on medical devices and include a blend or emulsion of a first polymer made at least in part from a polyoxyalkylene copolymer and a second component which may be a polymer or oligomer.
The first component in the composition of the present disclosure can be a polymer made at least in part from a polyoxyalkylene block copolymer. Suitable polyoxyalkylene block copolymers include those having an A-B or A-B-A structure wherein "A" is a block made from repeating units of the formula ¨0(CH2)n- where n is from 1 to 4 and "B" is a block made from repeating units that are different from the repeating units in the A block and are selected from groups of the formula ¨0(CFI2)õ-- where n is from 1 to 4.
In particularly useful embodiments, a co-polymer designated as "PEO-PPO-PEO", wherein "PEO" denotes a block of repeating units of the formula ¨OCH2CH2¨ and "PPO" denotes a block of repeating units of the formula ¨OCH2CH2C1-12--.
Particularly useful are triblock copolymers of the formula HO(C2H40)a(C31160)b(C2H40)c1-1 wherein a and c are independently from 1-150 units and b ranges from 10-200 units, with the overall molecular weight ranging from 1,000 to 50,000 daltons. Such polyoxyalkylene block copolymers are typically referred to by those skilled in the art as "poloxamers".
Particularly useful poloxamers include those where a equals c and b ranges from 10-200 units.
Examples of polyoxyalkylene block copolymers which may be utilized to form the first polymer of the compositions of the present disclosure include poloxamers sold under the trade names PLURONIC (BASF Corp.) or SYNPERONIC (ICI).
PLURONIC copolymers are identified by a specific letter-number combination.
The alphabetical designation describes the physical form of the product: 'L' for liquids, 'P' for pastes, 'F' for solid forms. The first digit (two digits in a three-digit number) in the numerical designation, multiplied by 300, indicates the approximate molecular weight of the hydrophobic component (propylene oxide). The last digit, when multiplied by 10, indicates the approximate hydrophilic (ethylene oxide) content of the molecule as a percentage by weight. Thus, for example, PLURONIC F68 is a solid material.
The molecular weight of the hydrophobic (propylene oxide) component is approximately 1800 (6 X 300). The hydrophilic (ethylene oxide) component represents approximately 80% of the molecule by weight (8 X 10).
AND SURFACE MODIFICATION COMPOSITIONS
TECHNICAL FIELD
The present disclosure is related to polymer compositions which are particularly useful in the manufacture of medical devices such as sutures, staples, clips, anastomosis rings, bone plates and screws, matrices for the sustained and/or controlled release of pharmaceutically active ingredients, etc. In some embodiments, the polymer compositions may be utilized as coatings for medical devices.
DESCRIPTION OF THE RELATED ART
Coatings for medical devices are also known. Such coatings for medical devices may be utilized to improve surface properties of the device such as, for example, cell and protein adhesion, lubricity, drug delivery, protein or DNA delivery, etc. For sutures, coatings can enhance the suture's handling characteristics, such as surgeon's throw, lubricity, knot run down and/or knot security.
Although present coatings on medical devices perform satisfactorily, there is room for improvement in connection with polymers having enhanced properties for the formation of medical devices and coatings on medical devices.
SUMMARY
Compositions are provided having a polymer made at least in part from a polyoxyalkylene copolymer, such as a poloxamer. In some embodiments the polymer made at least in part from a polyoxyalkylene copolymer may include a bioabsorbable terpolymer.
The polymers made at least in part from a polyoxyalkylene copolymer may be utilized alone or, in some useful embodiments, may be combined with another polymer or oligomer to form a blend or emulsion. In some embodiments the blend or emulsion may include a medicinal agent. The resulting compositions may be utilized to form medical devices, drug delivery devices, or coatings for medical devices.
In accordance with one embodiment of the present invention, there is provided a blend comprising: a bioabsorbable terpolymer comprising about 30 to about 50 weight percent of a polyoxyalkylene copolymer, about 40 to about 50 weight percent epsilon-caprolactone derived units, the balance of the copolymer being derived from at least one other copolymerizable monomer selected from the group consisting of glycolide, lactide, p-dioxanone and trimethylene carbonate; and a polymer derived from two or more monomers selected from the group consisting of lactide, glycolide, lactic acid, lactones, glycolic acid, carbonates, orthoesters, absorbable urethanes, and absorbable nylons.
Yet another embodiment of the present invention provides a surgical suture coated with a composition comprising: an effective antimicrobial amount of a terpolymer having a polyoxyalkylene copolymer component, a plurality of e-caprolactone derived units, and a plurality of repeating units derived from glycolide; and a salt of a C6- or higher fatty acid.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graph comparing bacterial colonization of an untreated POLYSORBO
suture with a suture coated with a blend of the present disclosure having triclosan incorporated therein.
DETAILED DESCRIPTION
The compositions described herein are useful for the formation of medical devices, especially for forming coatings on medical devices and include a blend or emulsion of a first polymer made at least in part from a polyoxyalkylene copolymer and a second component which may be a polymer or oligomer.
The first component in the composition of the present disclosure can be a polymer made at least in part from a polyoxyalkylene block copolymer. Suitable polyoxyalkylene block copolymers include those having an A-B or A-B-A structure wherein "A" is a block made from repeating units of the formula ¨0(CH2)n- where n is from 1 to 4 and "B" is a block made from repeating units that are different from the repeating units in the A block and are selected from groups of the formula ¨0(CFI2)õ-- where n is from 1 to 4.
In particularly useful embodiments, a co-polymer designated as "PEO-PPO-PEO", wherein "PEO" denotes a block of repeating units of the formula ¨OCH2CH2¨ and "PPO" denotes a block of repeating units of the formula ¨OCH2CH2C1-12--.
Particularly useful are triblock copolymers of the formula HO(C2H40)a(C31160)b(C2H40)c1-1 wherein a and c are independently from 1-150 units and b ranges from 10-200 units, with the overall molecular weight ranging from 1,000 to 50,000 daltons. Such polyoxyalkylene block copolymers are typically referred to by those skilled in the art as "poloxamers".
Particularly useful poloxamers include those where a equals c and b ranges from 10-200 units.
Examples of polyoxyalkylene block copolymers which may be utilized to form the first polymer of the compositions of the present disclosure include poloxamers sold under the trade names PLURONIC (BASF Corp.) or SYNPERONIC (ICI).
PLURONIC copolymers are identified by a specific letter-number combination.
The alphabetical designation describes the physical form of the product: 'L' for liquids, 'P' for pastes, 'F' for solid forms. The first digit (two digits in a three-digit number) in the numerical designation, multiplied by 300, indicates the approximate molecular weight of the hydrophobic component (propylene oxide). The last digit, when multiplied by 10, indicates the approximate hydrophilic (ethylene oxide) content of the molecule as a percentage by weight. Thus, for example, PLURONIC F68 is a solid material.
The molecular weight of the hydrophobic (propylene oxide) component is approximately 1800 (6 X 300). The hydrophilic (ethylene oxide) component represents approximately 80% of the molecule by weight (8 X 10).
Poloxamers can be roughly divided into 3 main categories, all of which can be useful in making the first bioabsorbable polymer of the blends of the present disclosure, namely emulsion forming, micelle forming, and water soluble poloxamers.
Various factors which determine poloxamer characteristics and behavior are the molecular weight, PPO:PEO ratio, temperature conditions, concentration, and presence of ionic materials. There is thus a wide range of characteristics in existing commercially available poloxamers which can be exploited in formulating the compositions of the present disclosure, especially where the composition further includes a medicinal agent and is utilized for drug delivery purposes.
In one embodiment, a suitable poloxamer which may be utilized to form the first polymer of the composition of the present disclosure includes a polyoxyethylene-polyoxypropylene triblock copolymer known as poloxamer 188, sold under the trade name PLURONIC F68 by BASF (Parsippany, N.J.). Other poloxamers which may be utilized in the compositions of the present disclosure include poloxamer 403 (sold as PLURONIC P123), poloxamer 407 (sold as PLURONIC P127), poloxamer 402 (sold as PLURONIC P122), poloxamer 181 (sold as PLURONIC L61), poloxamer 401 (sold as PLURONIC L121), poloxamer 185 (sold as PLURONIC P65), and poloxamer 338 (sold as PLURONIC F108).
The polyoxyalkylene block copolymers may, in some particularly useful embodiments, be reacted with additional biocompatible, biodegradable monomers to form the first polymer. Suitable monomers which may be reacted with the polyoxyalkylene block copolymers include, for example, alpha-hydroxy acids, lactones, carbonates, esteramides, anhydrides, amino acids, orthoesters, alkylene alkylates, alkylene oxides, biodegradable urethanes, and combinations thereof. Specific examples of suitable biocompatible, biodegradable monomers which may be added to the poloxamer include glycolide, lactide, hydroxybutyric acid, hydroxyvaleric acid, caprolactone, trimethylene carbonate, dimethyl trimethylene carbonate, p-dioxanone, and combinations thereof. These monomers, alone or in combination, can constitute up to about 90% to by total weight of the first polymer component, typically from about 10%
to about 75% by total weight of the first polymer component, more typically about 30%
to about 65% by total weight of the first polymer component, with the polyoxyalkylene block copolymer making up the balance of the first polymer component. It should, of course, be understood that the other monomers may be reacted first to form a polymer (homopolymer or copolymer (e.g., random, block or the like)) prior to reaction with the polyoxyalkylene block copolymer. Conditions suitable for conducting such reactions are within the purview of one skilled in the art.
In some particularly useful embodiments, in addition to a polyoxyalkylene block copolymer component, the first biocompatible polymer is made at least in part from epsilon-caprolactone, alone or in combination with other monomers. In one such embodiment, a polyoxyalkylene block copolymer is reacted with a s-caprolactone polymer containing a major amount of epsilon-caprolactone and a minor amount of at least one other copolymerizable monomer or mixture of such monomers. In another embodiment, a polyoxyalkylene block copolymer is reacted with a monomer mixture that includes a major amount of epsilon-caprolactone and a minor amount of at least one other copolymerizable monomer or mixture of such monomers in the presence of a polyhydric alcohol initiator as disclosed in U.S. Patent No. 6,177,094. The polymerization of these monomers contemplates all of the various types of monomer addition, i.e., simultaneous, sequential, simultaneous followed by sequential, sequential followed by simultaneous, etc. Suitable monomers which can be copolymerized with epsilon-caprolactone include glycolide, lactide, p-dioxanone and trimethylene carbonate.
In one particularly useful embodiment, the first polymer component includes a copolymer composed of about 40% to about 95% (w/w) s-caprolactone, about 5% to about 15% (w/w) glycolide, and about 5% to about 50% (w/w) poloxamer 188. In some embodiments, the first polymer utilized in forming the composition of the present disclosure may be a bioabsorbable terpolymer composed of about 51% s-caprolactone, about 9% glycolide, and about 40% poloxamer 188, which is commercially available as POLYTRIBOLATe (Tyco Healthcare, Mansfield, MA).
Methods for forming the first polymer component, including a bioabsorbable terpolymer, are known to those skilled in the art utilizing standard reaction conditions that may be varied depending upon the monomers and poloxamer utilized to form, the first bioabsorbable polymer. In some embodiments, the monomers and poloxamer can be combined in the presence of a catalyst such as stannous octoate, sometimes under an inert atmosphere, such as nitrogen gas. In other embodiments it may be desirable to allow the polymerization to occur under a vacuum, e.g., at a pressure less than about 1 Torr. In one particularly useful embodiment, the poloxamer, such as poloxamer 188, may be combined in a reaction vessel with additional monomers such as s-caprolactone and glycolide in the presence of stannous octoate, heated to a suitable temperature ranging from about 170 C. to about 185 C., typically from about 175 C. to about 180 C., such as about 178 C. The monomers may be allowed to polymerize for a suitable period of time which can range from about 4 hours to about 6 hours, typically from about 4.25 hours to about 4.75 hours. After this time, the molten bioabsorbable polymer may be extruded. While not necessary, in some embodiments the bioabsorbable polymer may be subjected to a further heat treatment by heating to a temperature ranging from about 10:"
C. to about 120 C., typically from about 107 C. to about 113 C., for a period of time ranging from about 25 hours to about 35 hours, typically from about 28 hours to about 32 hours. In some cases it may be desirable for this second heat treatment to occur under a vacuum, at a pressure typically less than about 1 Torr.
In some embodiments, the first polymer component may be utilized alone in at effective antimicrobial amount to form a medical device or a coating for a substrate. An "effective antimicrobial amount" of a given component is an amount at which the component hinders the growth of bacteria associated with infections, and promotes the healing of a wound. Such coatings can prevent bacterial colonization on surfaces at levels of clinical infection, in some cases as much as 14 days or more.
However, the compositions of the present disclosure typically include a first polymer component made at least in part from a polyoxyalkylene copolymer combined with a second polymer or oligomer. Suitable polymers and/or oligomers for use as the second component include lactides, glycolides, lactide-co-glycolides, lactic acids, lactones, glycolic acids, carbonates, dioxanones, esteramides, anhydrides, amino acids, orthoesters, dioxepanones, alkylene alkylates, alkylene oxides, absorbable urethanes, absorbable nylons, and homopolymers and copolymers thereof.
In some embodiments, the second component may be derived from two or more monomers, including polyethylene glycol-polypropylene glycol (PEG-PPG), polystyrene, n-vinyl pyrrolidine, n-vinyl pyridine, Ci-C12 acrylate monomer, C1-C12 methacrylate monomer, hydroxyethyl methacrylate, hydroxypropyl methacrylate, acrylic acid, potassium sulfopropyl acrylate, potassium sulfopropyl methacrylate, and 2-methacryloyl phosphorocholine. In some particularly useful embodiments, the second component may be a copolymer of epsilon caprolactone and glycolide having approximately 85-95%
(w/w) s-caprolactone and 5-15% (w/w) glycolide.
In some embodiments, the first polymer component made at least in part from a polyoxyalkylene copolymer may be combined with the second component to form a blend. In other embodiments, the first polymer component made at least in part from a polyoxyalkylene copolymer may be combined with the second component to form an emulsion or suspension.
In some embodiments, the present compositions also include a fatty acid component that contains a fatty acid or a fatty acid salt or a salt of a fatty acid ester.
Suitable fatty acids may be saturated or unsaturated, and include higher fatty acids having more than about 12 carbon atoms. Suitable saturated fatty acids include, for example, stearic acid, palmitic acid, myristic acid and lauric acid. Suitable unsaturated fatty acids include oleic acid, linoleic acid, and linolenic acid. In addition, an ester of fatty acids, such as sorbitan tristearate or hydrogenated castor oil, may be used.
Suitable fatty acid salts include the polyvalent metal ion salts of C6 and higher fatty acids, particularly those having from about 12 to 22 carbon atoms, and mixtures thereof. Fatty acid salts including the calcium, magnesium, barium, aluminum, and zinc salts of stearic, palmitic and oleic acids may be useful in some embodiments of the present disclosure. Particularly useful salts include commercial "food grade"
calcium stearate which consists of a mixture of about one-third C16 and two-thirds C18 fatty acids.
with small amounts of the C14 and C22 fatty acids.
Suitable salts of fatty acid esters which may be included in the compositions of the present disclosure include calcium, magnesium, aluminum, barium, or zinc stearoyl lactylate; calcium, magnesium, aluminum, barium, or zinc palmityl lactylate;
calcium, magnesium, aluminum, barium, or zinc olelyl lactylate; with calcium stearoyl-2-lactylate (such as the calcium stearoyl-2-lactylate commercially available under the tradename VERV from American Ingredients Co., Kansas City, Mo.) being particularly useful.
Other fatty acid ester salts which may be utilized include those selected from the group consisting of lithium stearoyl lactylate, potassium stearoyl lactylate, rubidium stearoyl lactylate, cesium stearoyl lactylate, francium stearoyl lactylate, sodium palmityl lactylate, lithium palmityl lactylate, potassium palmityl lactylate, rubidium palmityl lactylate, cesium palmityl lactylate, francium palmityl lactylate, sodium olelyl lactylate, lithium olelyl lactylate, potassium olelyl lactylate, rubidium olelyl lactylate, cesium olelyl lactylate, and francium olelyl lactylate.
In some embodiments it may be desirable to include a wax in the composition of the present disclosure. Suitable waxes which may be utilized include polyethylene wax, ethylene copolymer wax, halogenated hydrocarbon waxes, hydrogenated vegetable oil, beeswax, caranuba wax, paraffin, microcrystalline wax, candelillia, spermacetic wax, and mixtures thereof.
In other embodiments, omega-6 fatty acids, including arachidonic acid, may be added to the compositions of the present disclosure.
Various factors which determine poloxamer characteristics and behavior are the molecular weight, PPO:PEO ratio, temperature conditions, concentration, and presence of ionic materials. There is thus a wide range of characteristics in existing commercially available poloxamers which can be exploited in formulating the compositions of the present disclosure, especially where the composition further includes a medicinal agent and is utilized for drug delivery purposes.
In one embodiment, a suitable poloxamer which may be utilized to form the first polymer of the composition of the present disclosure includes a polyoxyethylene-polyoxypropylene triblock copolymer known as poloxamer 188, sold under the trade name PLURONIC F68 by BASF (Parsippany, N.J.). Other poloxamers which may be utilized in the compositions of the present disclosure include poloxamer 403 (sold as PLURONIC P123), poloxamer 407 (sold as PLURONIC P127), poloxamer 402 (sold as PLURONIC P122), poloxamer 181 (sold as PLURONIC L61), poloxamer 401 (sold as PLURONIC L121), poloxamer 185 (sold as PLURONIC P65), and poloxamer 338 (sold as PLURONIC F108).
The polyoxyalkylene block copolymers may, in some particularly useful embodiments, be reacted with additional biocompatible, biodegradable monomers to form the first polymer. Suitable monomers which may be reacted with the polyoxyalkylene block copolymers include, for example, alpha-hydroxy acids, lactones, carbonates, esteramides, anhydrides, amino acids, orthoesters, alkylene alkylates, alkylene oxides, biodegradable urethanes, and combinations thereof. Specific examples of suitable biocompatible, biodegradable monomers which may be added to the poloxamer include glycolide, lactide, hydroxybutyric acid, hydroxyvaleric acid, caprolactone, trimethylene carbonate, dimethyl trimethylene carbonate, p-dioxanone, and combinations thereof. These monomers, alone or in combination, can constitute up to about 90% to by total weight of the first polymer component, typically from about 10%
to about 75% by total weight of the first polymer component, more typically about 30%
to about 65% by total weight of the first polymer component, with the polyoxyalkylene block copolymer making up the balance of the first polymer component. It should, of course, be understood that the other monomers may be reacted first to form a polymer (homopolymer or copolymer (e.g., random, block or the like)) prior to reaction with the polyoxyalkylene block copolymer. Conditions suitable for conducting such reactions are within the purview of one skilled in the art.
In some particularly useful embodiments, in addition to a polyoxyalkylene block copolymer component, the first biocompatible polymer is made at least in part from epsilon-caprolactone, alone or in combination with other monomers. In one such embodiment, a polyoxyalkylene block copolymer is reacted with a s-caprolactone polymer containing a major amount of epsilon-caprolactone and a minor amount of at least one other copolymerizable monomer or mixture of such monomers. In another embodiment, a polyoxyalkylene block copolymer is reacted with a monomer mixture that includes a major amount of epsilon-caprolactone and a minor amount of at least one other copolymerizable monomer or mixture of such monomers in the presence of a polyhydric alcohol initiator as disclosed in U.S. Patent No. 6,177,094. The polymerization of these monomers contemplates all of the various types of monomer addition, i.e., simultaneous, sequential, simultaneous followed by sequential, sequential followed by simultaneous, etc. Suitable monomers which can be copolymerized with epsilon-caprolactone include glycolide, lactide, p-dioxanone and trimethylene carbonate.
In one particularly useful embodiment, the first polymer component includes a copolymer composed of about 40% to about 95% (w/w) s-caprolactone, about 5% to about 15% (w/w) glycolide, and about 5% to about 50% (w/w) poloxamer 188. In some embodiments, the first polymer utilized in forming the composition of the present disclosure may be a bioabsorbable terpolymer composed of about 51% s-caprolactone, about 9% glycolide, and about 40% poloxamer 188, which is commercially available as POLYTRIBOLATe (Tyco Healthcare, Mansfield, MA).
Methods for forming the first polymer component, including a bioabsorbable terpolymer, are known to those skilled in the art utilizing standard reaction conditions that may be varied depending upon the monomers and poloxamer utilized to form, the first bioabsorbable polymer. In some embodiments, the monomers and poloxamer can be combined in the presence of a catalyst such as stannous octoate, sometimes under an inert atmosphere, such as nitrogen gas. In other embodiments it may be desirable to allow the polymerization to occur under a vacuum, e.g., at a pressure less than about 1 Torr. In one particularly useful embodiment, the poloxamer, such as poloxamer 188, may be combined in a reaction vessel with additional monomers such as s-caprolactone and glycolide in the presence of stannous octoate, heated to a suitable temperature ranging from about 170 C. to about 185 C., typically from about 175 C. to about 180 C., such as about 178 C. The monomers may be allowed to polymerize for a suitable period of time which can range from about 4 hours to about 6 hours, typically from about 4.25 hours to about 4.75 hours. After this time, the molten bioabsorbable polymer may be extruded. While not necessary, in some embodiments the bioabsorbable polymer may be subjected to a further heat treatment by heating to a temperature ranging from about 10:"
C. to about 120 C., typically from about 107 C. to about 113 C., for a period of time ranging from about 25 hours to about 35 hours, typically from about 28 hours to about 32 hours. In some cases it may be desirable for this second heat treatment to occur under a vacuum, at a pressure typically less than about 1 Torr.
In some embodiments, the first polymer component may be utilized alone in at effective antimicrobial amount to form a medical device or a coating for a substrate. An "effective antimicrobial amount" of a given component is an amount at which the component hinders the growth of bacteria associated with infections, and promotes the healing of a wound. Such coatings can prevent bacterial colonization on surfaces at levels of clinical infection, in some cases as much as 14 days or more.
However, the compositions of the present disclosure typically include a first polymer component made at least in part from a polyoxyalkylene copolymer combined with a second polymer or oligomer. Suitable polymers and/or oligomers for use as the second component include lactides, glycolides, lactide-co-glycolides, lactic acids, lactones, glycolic acids, carbonates, dioxanones, esteramides, anhydrides, amino acids, orthoesters, dioxepanones, alkylene alkylates, alkylene oxides, absorbable urethanes, absorbable nylons, and homopolymers and copolymers thereof.
In some embodiments, the second component may be derived from two or more monomers, including polyethylene glycol-polypropylene glycol (PEG-PPG), polystyrene, n-vinyl pyrrolidine, n-vinyl pyridine, Ci-C12 acrylate monomer, C1-C12 methacrylate monomer, hydroxyethyl methacrylate, hydroxypropyl methacrylate, acrylic acid, potassium sulfopropyl acrylate, potassium sulfopropyl methacrylate, and 2-methacryloyl phosphorocholine. In some particularly useful embodiments, the second component may be a copolymer of epsilon caprolactone and glycolide having approximately 85-95%
(w/w) s-caprolactone and 5-15% (w/w) glycolide.
In some embodiments, the first polymer component made at least in part from a polyoxyalkylene copolymer may be combined with the second component to form a blend. In other embodiments, the first polymer component made at least in part from a polyoxyalkylene copolymer may be combined with the second component to form an emulsion or suspension.
In some embodiments, the present compositions also include a fatty acid component that contains a fatty acid or a fatty acid salt or a salt of a fatty acid ester.
Suitable fatty acids may be saturated or unsaturated, and include higher fatty acids having more than about 12 carbon atoms. Suitable saturated fatty acids include, for example, stearic acid, palmitic acid, myristic acid and lauric acid. Suitable unsaturated fatty acids include oleic acid, linoleic acid, and linolenic acid. In addition, an ester of fatty acids, such as sorbitan tristearate or hydrogenated castor oil, may be used.
Suitable fatty acid salts include the polyvalent metal ion salts of C6 and higher fatty acids, particularly those having from about 12 to 22 carbon atoms, and mixtures thereof. Fatty acid salts including the calcium, magnesium, barium, aluminum, and zinc salts of stearic, palmitic and oleic acids may be useful in some embodiments of the present disclosure. Particularly useful salts include commercial "food grade"
calcium stearate which consists of a mixture of about one-third C16 and two-thirds C18 fatty acids.
with small amounts of the C14 and C22 fatty acids.
Suitable salts of fatty acid esters which may be included in the compositions of the present disclosure include calcium, magnesium, aluminum, barium, or zinc stearoyl lactylate; calcium, magnesium, aluminum, barium, or zinc palmityl lactylate;
calcium, magnesium, aluminum, barium, or zinc olelyl lactylate; with calcium stearoyl-2-lactylate (such as the calcium stearoyl-2-lactylate commercially available under the tradename VERV from American Ingredients Co., Kansas City, Mo.) being particularly useful.
Other fatty acid ester salts which may be utilized include those selected from the group consisting of lithium stearoyl lactylate, potassium stearoyl lactylate, rubidium stearoyl lactylate, cesium stearoyl lactylate, francium stearoyl lactylate, sodium palmityl lactylate, lithium palmityl lactylate, potassium palmityl lactylate, rubidium palmityl lactylate, cesium palmityl lactylate, francium palmityl lactylate, sodium olelyl lactylate, lithium olelyl lactylate, potassium olelyl lactylate, rubidium olelyl lactylate, cesium olelyl lactylate, and francium olelyl lactylate.
In some embodiments it may be desirable to include a wax in the composition of the present disclosure. Suitable waxes which may be utilized include polyethylene wax, ethylene copolymer wax, halogenated hydrocarbon waxes, hydrogenated vegetable oil, beeswax, caranuba wax, paraffin, microcrystalline wax, candelillia, spermacetic wax, and mixtures thereof.
In other embodiments, omega-6 fatty acids, including arachidonic acid, may be added to the compositions of the present disclosure.
In yet additional embodiments, phospholipids may be added to the compositions of the present disclosure. Suitable phospholipids include, but are not limited to, phosphatidylcholine (PC), mono-acyl phosphatidylcholine (MAPC), diacyl phosphatidylcholine (DAPC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylglycerol (PG), plasmalogen, sphingomyelin, ceramide, ciliatin, polymers having phospholipid groups, and derivatives thereof. In some embodiments copolymers having phosphorylcholine groups may be added to the compositions of the present disclosure, such as copolymers of 2-methacryloyloxyethyl phosphorylcholine with other monomers, including methacrylates such as butyl methacrylate, benzyl methacrylate, methacryloyloxyethyl phenylcarbamate, and phenyl methacryloyloxyethyl carbamate.
The amount of the first polymer made at least in part from a polyoxyalkylene copolymer in the compositions of the present disclosure can range from about 2% by weight to about 100% by weight, typically from about 5% by weight to about 80%
by weight, more typically from about 10% by weight to about 50% by weight of the bioabsorbable composition. The amount of second component in the blends or emulsions of the present disclosure may be up to about 98% by weight and typically ranges from about 20% by weight to about 95% by weight, more typically from about 50% by weight to about 90% by weight of the composition of the present disclosure.
Where utilized, the amount of fatty acid component can range in an amount from about 5 percent to about 50 percent by weight of the total composition.
Typically, the fatty acid component may be present in an amount from about 10 percent to about 20 percent by weight of the total composition.
In other embodiments, the polymer components utilized to form the blend or emulsion of the present disclosure may be added separately to coat a substrate. In such a case, the substrate may be first coated with either of the components, i.e., the first polymer made at least in part from a polyoxyalkylene copolymer or the second component, followed by application of the other. Thus, in one useful embodiment, the substrate may be first coated using a first composition containing a bioabsorbable polymer comprising e-caprolactone, glycolide, and optionally a fatty acid component, such as a salt of a fatty acid ester (e.g., calcium stearoy1-2-lactylate).
After the first coating has been applied, a second composition can be used to apply the other bioabsorbable polymer, such as a copolymer of e-caprolactone, glycolide, and poloxamer 188, (e.g., the commercially available POLYTRIBOLATE'' copolymer). Depending on the conditions of application, the two components can be applied as separate coatings or the two components can be sequentially applied and allowed to combine with each other on the surface of the substrate such as, for example, by controlling the rate of evaporation of the solvent.
In some embodiments, the composition of the present disclosure may also include one or more medicinal agents which are released from the bioabsorbable blend in vivo.
As used herein, "medicinal agent" is used in its broadest sense and includes any substance or mixture of substances that have clinical use. Consequently, medicinal agents may or may not have pharmacological activity per se, e.g., a dye.
Examples of classes of medicinal agents which may be combined or mixed into the bioabsorbable blend of the present disclosure include antimicrobials, analgesics, antipyretics, anesthetics, antiepileptics, an' tihistamines, anti-inflammatories, cardiovascular drugs, diagnostic agents, sympathomimetics, cholinomimetics, antimuscarinics, antispasmodics, hormones, growth factors, muscle relaxants, adrenergic neuron blockers, antineoplastics, immunosuppressants, gastrointestinal drugs, diuretics, steroids, polysaccharides, and enzymes. It is also intended that combinations of medicinal agents may be used.
Suitable antimicrobial agents which may be included as a medicinal agent in the bioabsorbable blend of the present disclosure include triclosan, also known as 2,4,4'-trichloro-2'-hydroxydiphenyl ether, chlorhexidine and its salts, including chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate, silver and its salts, including silver acetate, silver benzoate, silver carbonate, silver citrate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver sulfadiazine, polymyxin, tetracycline, aminoglycosides, such as tobramycin and gentamicin, rifampicin, bacitracin, neomycin, chloramphenicol, miconazole, quinolones such as oxolinic acid, norfloxacin, nalidixic acid, pefloxacin, enoxacin and ciprofloxacin, penicillins such as oxacillin and pipracil, nonoxynol 9, fusidic acid, cephalosporins, and combinations thereof. In addition, antimicrobial proteins and peptides such as bovine lactoferrin and lactoferricin B may be included as a medicinal agent in the blend or emulsion of the present disclosure.
Other medicinal agents which may be included as a medicinal agent in the composition of the present disclosure include: local anesthetics; non-steroidal antifertility agents; parasympathomimetic agents; psychotherapeutic agents;
tranquilizers;
decongestants; sedative hypnotics; steroids; sulfonamides; sympathomimetic agents;
vaccines; vitamins; antimalarials; anti-migraine agents; anti-parlcinson agents such as L-dopa; anti-spasmodics; anticholinergic agents (e.g. oxybutynin); antitussives;
bronchodilators; cardiovascular agents such as coronary vasodilators and nitroglycerin;
alkaloids; analgesics; narcotics such as codeine, dihydrocodeinone, meperidine, morphine and the like; non-narcotics such as salicylates, aspirin, acetaminophen, d-propoxyphene and the like; opioid receptor antagonists, such as naltrexone and naloxone;
anti-cancer agents; anti-convulsants; anti-emetics; antihistamines; anti-inflammatory agents such as hormonal agents, hydrocortisone, prednisolone, prednisone, non-hormonal agents, allopurinol, indomethacin, phenylbutazone and the like; prostaglandins and cytotoxic drugs; estrogens; antibacterials; antiftmgals; antivirals; anticoagulants;
anticonvulsants;
antidepressants; antihistamines; and immunological agents.
Other examples of suitable medicinal agents which may be included in the composition, such as a bioabsorbable blend or emulsion of the present disclosure, include viruses and cells, peptides (e.g., luteinizing-hormone-releasing-hormone analogues, such as goserelin and exendin) and proteins, analogs, muteins, and active fragments thereof, such as immunoglobulins, antibodies, cytokines (e.g. lymphokines, monokines, chemokines), blood clotting factors, hemopoietic factors, interleukins (IL-2, IL-3, IL-4, IL-6), interferons (13-IFN, (a-IFN and 7-IFN), erythropoietin, nucleases, tumor necrosis factor, colony stimulating factors (e.g., GCSF, GM-CSF, MCSF), insulin, enzymes (e.g., superoxide dismutase, tissue plasminogen activator), tumor suppressors, blood proteins, gonadotropins (e.g., FSH, LH, CG, etc.), hormones and hormone analogs (e.g., growth hormone, adrenocorticotropic hormone and luteinizing hormone releasing hormone (LHRH)), vaccines (e.g., tumoral, bacterial and viral antigens); somatostatin;
antigens;
blood coagulation factors; growth factors (e.g., nerve growth factor, insulin-like growth factor); protein inhibitors, protein antagonists, and protein agonists;
nucleic acids, such as antisense molecules, DNA and RNA; oligonucleotides; and ribozymes.
The amount of medicinal agent present will depend upon the particular medicinal agent chosen, but typically the amount used will be in the range of 0.01 to 10 % by weight of the composition.
The compositions of the present disclosure can be prepared using any technique within the purview of those skilled in the art. Where the polymers utilized to form the composition are both soluble in the same solvent, the appropriate amounts of each polymer can be dissolved in the solvent and applied to the medical device as a solution.
Upon evaporation of the solvent, a coating of the blend will remain on the medical device. Some blends may be obtained with ordinary mixing. In other embodiments, especially where the bioabsorbable blend is to be utilized to deliver a medicinal agent, it may be desirable to mix the medicinal agent in the composition by processes such as ball mill, disc mill, sand mill, attritor, rotor stator mixer, ultrasonication, etc. In other embodiments, the two polymers can be melt blended and used to form or coat a medical device. Other methods for making and using the present blends will be readily apparent to those skilled in the art.
Alternatively, where the two components of the composition of the present disclosure are not completely miscible with each other or the solvents utilized to form the compositions, emulsions may be formed and utilized by any means known to those skilled in the art to form medical devices including drug delivery devices or coatings for medical devices.
When a medicinal agent is used, the medicinal agent may be placed in solution, the composition of the present disclosure may be placed in a separate solution, and the two combined to form an emulsion or suspension. Biocompatible dispersing agents in the form of surfactants, emulsifiers, or stablilizers may be added to the blend to assist in dispersion of the medicinal agent throughout the composition of the present disclosure.
Adjuvants may be added to stabilize or preserve the compositions described above. Such adjuvants include nonionic surfactants which include alcohol ethoxylates, glycerol esters, polyoxyethylene esters, and glycol esters of fatty acids.
Preferable nonionic surfactants are glycerol esters of stearic, oleic, and/or lauric acid as well as ethylene and/or diethylene glycol esters of fatty acids.
The compositions described herein are non-toxic. Depending on its particular physical and properties (to a large extent influenced by the nature of the polymers from which it is prepared), the blends and/or emulsions herein can be used in the fabrication in whole or in part of a variety of implantable medical devices and prostheses, e.g., clips, staples, sutures, suture coatings, etc. Applied to a suture, a coating composition containing the composition herein results in a suture having suitable lubricity, knot tiedown, and knot security characteristics.
Where the composition of the present disclosure is used to form a medical device, the devices may be made by injection molding the blend at temperatures and pressures known to those skilled in the art. Typically, the feed for the injection molding apparatus is a melt blend of the two polymer components in pellet form. The components should be quite dry when being injection molded in order to avoid hydrolytic degradation during processing. After molding, the surgical devices can be packaged and sterilized by conventional procedures. It may be desirable to anneal the devices to remove residual stresses and strains, to stabilize the shape of the device, and to reduce or eliminate defects in the piece. Annealing typically comprises reheating the medical device to above its glass transition temperature where chain mobility is greatest, and then slowly and gradually cooling the device to avoid reintroducing. Procedures, conditions and apparatus for annealing polymeric structures are well known in the art.
Where the composition of the present disclosure is used as an absorbable coating for a medical device, the coating may be formed using any known technique such as, for example, extrusion, molding and/or solvent casting. The composition can be used alone, blended with absorbable compositions, or blended with non-absorbable components. A
wide variety of surgical articles can be coated with the compositions herein.
These include, but are not limited to, clips and other fasteners, staples, sutures, pins, screws, prosthetic device, wound dressings, drug delivery devices, anastomosis rings, and other implantable devices. Fibers coated with the present compositions can be knitted or woven with other fibers, either absorbable or nonabsorbable to form meshes or fabrics.
In one embodiment the composition of the present disclosure may be applied as a coating by dissolving it in a solvent which is a non-solvent for any polymeric device to which the coating is to be applied. The solution containing the composition of the presentslisclosure may then be applied to a medical device by dipping the medical device into the solution, by passing the medical device past a brush or other applicator, or by spraying the solution onto the surface of the medical device. Suitable solvents for use in dissolving the composition of the present disclosure include, but are not limited to, volatile solvents such as methylene chloride and acetone. The medical device wetted with the coating solution may then be subsequently passed through or held in a drying oven for a time and at a temperature sufficient to vaporize and drive off the solvent. If desired, the suture coating composition can optionally contain additional components, e.g., dyes, antibiotics, antiseptics, growth factors, anti-inflammatory agents, etc.
Where applied in solution, the amount of solvent utilized can range from about 85% to about 99% by weight, typically from about 90% to about 98% by weight of the solution utilized to apply the composition of the present disclosure, including the blend or emulsion described above, and any additional medicinal agents or adjuvants. In some embodiments the solvent may be present at about 95% by weight of the solution utilized to apply the composition of the present disclosure.
While the above description focuses on the use of a blend or emulsion as a medical device, drug delivery device, or coating composition in accordance with the present disclosure, optionally in combination with medicinal agents or adjuvants, similar methods and procedures may be utilized where the composition of the present disclosure includes the polymer made at least in part from a polyoxyalkylene copolymer in combination with a medicinal agent or adjuvant, without the addition of a second component, which can be a polymer or oligomer. As would be readily apparent to one skilled in the art, one could utilize the same or similar solvents, processing conditions, etc. in utilizing a polymer made at least in part from a polyoxyalkylene copolymer as the composition of the present disclosure.
While the composition herein can be applied to any type of medical device, it may be especially useful as a coating for a suture. The amount of composition applied to a suture will vary depending upon the structure of the suture, e.g., monofilament or =
multifilament, the size of the suture and its composition. For multifilament sutures, the number of filaments and the tightness of the braid or twist may also influence the amount of coating.
The coating may be applied to both monofilament and multifilament braided sutures which may, in some embodiments, also be bioabsorbable. Suitable bioabsorbable monomers and polymers utilized for the sutures, including bioabsorbable braided sutures, include lactide, glycolide, trimethylcarbonate, s-caprolactone, caprolactam, polyesters, nylons, etc. The coating can typically be present in an amount ranging from about 0.5 to about 15% (w/w) of the base suture substrate, more typically from about 1 to about 5%
(w/w) of the base suture substrate. The thickness of the coating will depend on a number of factors, but typically can be from submicron thicknesses up to several millimeters in thickness.
The composition of the present disclosure, where utilized as a coating for a medical device, improves surface properties of the device such as, for example, cell and protein adhesion, lubricity, drug delivery, protein or DNA delivery, etc. The bioabsorbable blend coating may be especially useful in preventing bacterial adhesion/colonization, infection caused by or exacerbated by the device itself, and improving the handling properties of the device.
The composition of the present disclosure may also be formed into films and/or foams which, in turn, may be applied to wounds such as cuts, gashes, ulcers and burns to aid healing. Medicinal agents such as wound healing agents and antimicrobials may be incorporated to speed healing of damaged tissues. In this manner, various growth factors, antibiotics and antifungals can be incorporated into the bioabsorbable blend of the present disclosure.
Where medicinal agents are included in the bioabsorbable blend of the present disclosure, the composition of the present disclosure may be utilized as a drug delivery device to provide site-specific release of medicinal agents which may be immediate release, delayed release or sustained release. Immediate release systems provide a drug dose instantly. Delayed release systems provide repetitive intermittent dosings of drug.
Sustained release systems achieve slow release of a drug over an extended period of time and should maintain a therapeutically effective concentration of drug at the target site.
Medicinal agents that are mingled with the compositions herein typically provide delayed or sustained release therapy by diffusion from the bioabsorbable implant and/or bioabsorbable coating as it degrades.
The following examples are illustrative of specific embodiments of the polymeric compositions and should not be construed as limitations thereof.
A biocompatible, biodegradable polymer was produced as follows. A one gallon reactor vessel was cleaned and subjected to a vacuum to reach a pressure of less than 1 Ton. 1000 1 grams of poloxamer 188 (PLURONIC F68) was added to the one gallon reactor vessel, after which time a vacuum was again applied to obtain a pressure less than 1 Ton. The temperature was raised to about 105 C. and the PLURONIC F68 was dried in the reactor for about 14 ( 4) hours. During this time period, 1275 1 grams of e-caprolactone was added to a 3 liter round bottom flask, and 225 1 grams of glycolide was added to a 500 ml round bottom flask, Between 75 and 90 minutes prior to the end of the drying of the PLURONIC F68, the a-caprolactone and glycolide were placed in an oven heated to a temperature of 105 C. After the drying of the PLURONIC
was complete, the glycolide was added to the reactor, followed by the addition of the E-S caprolactone. The reactor was then backfilled with nitrogen, and then 295 1.11., of stannous octoate was added to the reactor as a catalyst.
The reactor was then heated to 178 C. ( 3 C.), and the reaction was allowed to continue for 4.5 ( 0.25) hours. After the reaction was complete, the polymerized bioabsorbable polymer was extruded and allowed to cool for a minimum of 16 hours.
The resulting bioabsorbable polymer was then subjected to an additional heat treatment. The bioabsorbable polymer was placed in a vacuum oven, which was heated to a temperature of 110 C. ( 3 C.) in a vacuum at a pressure less than 1 Ton, for 30 2 hours. After heating, the polymer was allowed to cool under vacuum for a minimum of 6 hours.
NMR of the bioabsorbable polymer was conducted utilizing a Bruker AC300 NMR spectrometer. The proton spectra obtained had peaks which permitted the identification of the components of the bioabsorbable polymer.
The resulting bioabsorbable terpolymer was found to possess about 40% by weight PLURONIC F68, about 51% by weight of caprolactoyl groups, about 9% by weight of glycoyl groups, and < 1 % by weight of residual caprolactone monomer.
Monofilament surgical sutures which prevented the attachment and colonization of bacteria and provided enhanced suture handling characteristics, including reduced tissue drag, were prepared as follows. The polymer of Example 1 was solvated in methylene chloride at concentrations of 2, 5 and 10% (w/w). Monofilament polybutester (a copolymer of butylene terephthalate and polytetramethylene ether glycol) surgical sutures were coated by dip coating with each solution, to produce a uniform coating on the sutures. The resulting coating levels were 1.08%, 3.64% and 6.80% based on the weight of the suture for the 2%, 5% and 10% solutions, respectively. The coating from the 10% solution was found to prevent bacterial colonization of sutures at levels of clinical infection for at least 8 days. In contrast, other monofilaments, including uncoated polybutester sutures reached levels of clinical infection in as little as 3 days.
Braided multifilaments made of a glycolide/lactide copolymer coated with a mixture of a caprolactone/glycolide copolymer and calcium stearoyl lactylate as described in the Examples of U.S. Patent No. 5,716,376 were coated with the polymer of Example 1. The coating polymer was solvated in methylene chloride (2, 5 and 10%
(w/w)) and the sutures coated with one of three solutions by dip coating. The additional coating polymer prevented bacterial adhesion and colonization in a more effective manner than observed with the uncoated sutures or with Ethicon's VICRYL Plus suture (a suture made of a glycolide/lactide copolymer having a coating including triclosan).
This bioabsorbable polymer of Example 1 was blended with the solution of Example 3 of U.S. Patent No. 5,716,376 containing an E-caprolactone/glycolide copolymer and calcium stearoyl lactylate represented about 2, 5 and 10% (w/w) of the resulting solution.
Multifilament braided glycolide/lactide surgical sutures were coated with the bioabsorbable blend by dip coating the suture in the solution having the bioabsorbable blend, and driving off the solvent by heating to produce a useable surgical suture.
Varying amounts (2%, 5% and 10% w/w) of the bioabsorbable polymer of Example I were blended into the solution of Example 2 of U.S. Patent No.
5,716,376 which was then modified by adding 2% triclosan. The resulting solutions were applied to multifilament, braided glycolide/lactide copolymer sutures.
The resulting suture having the coating of the bioabsorbable blend with triclosan and untreated sutures are tested for resistance to bacterial colonization using standard techniques. Generally, the sutures are exposed to Escherichia coli and the amount of bacteria growing on the suture is determined by counting the number of colony forming units. The results of these experiments are set forth in Figure 1. As is apparent from Figure 1, the suture having the coating of the bioabsorbable blend with triclosan prevented bacterial colonization on the suture material for up to 21 days, a marked improvement over the untreated suture. In addition, suture having the coating of the bioabsorbable blend with triclosan exhibited a lame zone of inhibition (ZOT) of bacterial growth (approximately 20mm).
An anti-inflammatory coated surgical suture is prepared as follows. The bioabsorbable polymer of Example 1 of is solvated in methylene chloride at a concentration of 10% (w/w). Then, a 2% (w/w) salicylate solution is prepared in reverse osmosis (RO) water. Water/organic emulsions are prepared with the ratio of the bioabsorbable polymer solution:salicylate solution ranging from 8:2 to 2:8.
Emulsions are formed under vigorous stirring and a surgical suture is coated with the bioabsorbable polymer and salicylate solution by dip coating techniques. The amount of the resulting coating ranges from 1-5% (w/w) of the base suture substrate. The polymer coating containing salicylate prevents bacterial colonization on the suture material for up to 14 days and exhibits a large zone of inhibition (ZOI) of bacterial growth (approximately 20mm).
Antimicrobial surgical suture coatings containing ionic silver and/or silver glass particles are prepared as follows. The bioabsorbable polymer of Example 1 is solvated in methylene chloride at concentration of 10% (w/w). Suspension/solutions of various silver salts (nitrate, citrate, sulfadiazine, lactate, etc.) are prepared in reverse osmosis (RO) water under high speed mixing. Water/organic emulsions are prepared with the ratio of the bioabsorbable polymer coating solution:silver suspension/solutions ranging from 8:2 to 2:8. Emulsions are formed under vigorous stirring and surgical sutures were coated by dip coating techniques. The coating is present in an amount from 0.5% to 15%
(w/w) of the base suture substrate, preferably 1-5% (w/w). The polymer coating containing ionic silver prevents bacterial colonization on the suture material.
It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore the above description should not be construed as limiting, but merely as examplifications of preferred embodiments. The scope of the claims should not be limited by the preferred embodiments set forth herein, but should be given the broadest interpretation consistent with the description as a whole.
The amount of the first polymer made at least in part from a polyoxyalkylene copolymer in the compositions of the present disclosure can range from about 2% by weight to about 100% by weight, typically from about 5% by weight to about 80%
by weight, more typically from about 10% by weight to about 50% by weight of the bioabsorbable composition. The amount of second component in the blends or emulsions of the present disclosure may be up to about 98% by weight and typically ranges from about 20% by weight to about 95% by weight, more typically from about 50% by weight to about 90% by weight of the composition of the present disclosure.
Where utilized, the amount of fatty acid component can range in an amount from about 5 percent to about 50 percent by weight of the total composition.
Typically, the fatty acid component may be present in an amount from about 10 percent to about 20 percent by weight of the total composition.
In other embodiments, the polymer components utilized to form the blend or emulsion of the present disclosure may be added separately to coat a substrate. In such a case, the substrate may be first coated with either of the components, i.e., the first polymer made at least in part from a polyoxyalkylene copolymer or the second component, followed by application of the other. Thus, in one useful embodiment, the substrate may be first coated using a first composition containing a bioabsorbable polymer comprising e-caprolactone, glycolide, and optionally a fatty acid component, such as a salt of a fatty acid ester (e.g., calcium stearoy1-2-lactylate).
After the first coating has been applied, a second composition can be used to apply the other bioabsorbable polymer, such as a copolymer of e-caprolactone, glycolide, and poloxamer 188, (e.g., the commercially available POLYTRIBOLATE'' copolymer). Depending on the conditions of application, the two components can be applied as separate coatings or the two components can be sequentially applied and allowed to combine with each other on the surface of the substrate such as, for example, by controlling the rate of evaporation of the solvent.
In some embodiments, the composition of the present disclosure may also include one or more medicinal agents which are released from the bioabsorbable blend in vivo.
As used herein, "medicinal agent" is used in its broadest sense and includes any substance or mixture of substances that have clinical use. Consequently, medicinal agents may or may not have pharmacological activity per se, e.g., a dye.
Examples of classes of medicinal agents which may be combined or mixed into the bioabsorbable blend of the present disclosure include antimicrobials, analgesics, antipyretics, anesthetics, antiepileptics, an' tihistamines, anti-inflammatories, cardiovascular drugs, diagnostic agents, sympathomimetics, cholinomimetics, antimuscarinics, antispasmodics, hormones, growth factors, muscle relaxants, adrenergic neuron blockers, antineoplastics, immunosuppressants, gastrointestinal drugs, diuretics, steroids, polysaccharides, and enzymes. It is also intended that combinations of medicinal agents may be used.
Suitable antimicrobial agents which may be included as a medicinal agent in the bioabsorbable blend of the present disclosure include triclosan, also known as 2,4,4'-trichloro-2'-hydroxydiphenyl ether, chlorhexidine and its salts, including chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate, silver and its salts, including silver acetate, silver benzoate, silver carbonate, silver citrate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver sulfadiazine, polymyxin, tetracycline, aminoglycosides, such as tobramycin and gentamicin, rifampicin, bacitracin, neomycin, chloramphenicol, miconazole, quinolones such as oxolinic acid, norfloxacin, nalidixic acid, pefloxacin, enoxacin and ciprofloxacin, penicillins such as oxacillin and pipracil, nonoxynol 9, fusidic acid, cephalosporins, and combinations thereof. In addition, antimicrobial proteins and peptides such as bovine lactoferrin and lactoferricin B may be included as a medicinal agent in the blend or emulsion of the present disclosure.
Other medicinal agents which may be included as a medicinal agent in the composition of the present disclosure include: local anesthetics; non-steroidal antifertility agents; parasympathomimetic agents; psychotherapeutic agents;
tranquilizers;
decongestants; sedative hypnotics; steroids; sulfonamides; sympathomimetic agents;
vaccines; vitamins; antimalarials; anti-migraine agents; anti-parlcinson agents such as L-dopa; anti-spasmodics; anticholinergic agents (e.g. oxybutynin); antitussives;
bronchodilators; cardiovascular agents such as coronary vasodilators and nitroglycerin;
alkaloids; analgesics; narcotics such as codeine, dihydrocodeinone, meperidine, morphine and the like; non-narcotics such as salicylates, aspirin, acetaminophen, d-propoxyphene and the like; opioid receptor antagonists, such as naltrexone and naloxone;
anti-cancer agents; anti-convulsants; anti-emetics; antihistamines; anti-inflammatory agents such as hormonal agents, hydrocortisone, prednisolone, prednisone, non-hormonal agents, allopurinol, indomethacin, phenylbutazone and the like; prostaglandins and cytotoxic drugs; estrogens; antibacterials; antiftmgals; antivirals; anticoagulants;
anticonvulsants;
antidepressants; antihistamines; and immunological agents.
Other examples of suitable medicinal agents which may be included in the composition, such as a bioabsorbable blend or emulsion of the present disclosure, include viruses and cells, peptides (e.g., luteinizing-hormone-releasing-hormone analogues, such as goserelin and exendin) and proteins, analogs, muteins, and active fragments thereof, such as immunoglobulins, antibodies, cytokines (e.g. lymphokines, monokines, chemokines), blood clotting factors, hemopoietic factors, interleukins (IL-2, IL-3, IL-4, IL-6), interferons (13-IFN, (a-IFN and 7-IFN), erythropoietin, nucleases, tumor necrosis factor, colony stimulating factors (e.g., GCSF, GM-CSF, MCSF), insulin, enzymes (e.g., superoxide dismutase, tissue plasminogen activator), tumor suppressors, blood proteins, gonadotropins (e.g., FSH, LH, CG, etc.), hormones and hormone analogs (e.g., growth hormone, adrenocorticotropic hormone and luteinizing hormone releasing hormone (LHRH)), vaccines (e.g., tumoral, bacterial and viral antigens); somatostatin;
antigens;
blood coagulation factors; growth factors (e.g., nerve growth factor, insulin-like growth factor); protein inhibitors, protein antagonists, and protein agonists;
nucleic acids, such as antisense molecules, DNA and RNA; oligonucleotides; and ribozymes.
The amount of medicinal agent present will depend upon the particular medicinal agent chosen, but typically the amount used will be in the range of 0.01 to 10 % by weight of the composition.
The compositions of the present disclosure can be prepared using any technique within the purview of those skilled in the art. Where the polymers utilized to form the composition are both soluble in the same solvent, the appropriate amounts of each polymer can be dissolved in the solvent and applied to the medical device as a solution.
Upon evaporation of the solvent, a coating of the blend will remain on the medical device. Some blends may be obtained with ordinary mixing. In other embodiments, especially where the bioabsorbable blend is to be utilized to deliver a medicinal agent, it may be desirable to mix the medicinal agent in the composition by processes such as ball mill, disc mill, sand mill, attritor, rotor stator mixer, ultrasonication, etc. In other embodiments, the two polymers can be melt blended and used to form or coat a medical device. Other methods for making and using the present blends will be readily apparent to those skilled in the art.
Alternatively, where the two components of the composition of the present disclosure are not completely miscible with each other or the solvents utilized to form the compositions, emulsions may be formed and utilized by any means known to those skilled in the art to form medical devices including drug delivery devices or coatings for medical devices.
When a medicinal agent is used, the medicinal agent may be placed in solution, the composition of the present disclosure may be placed in a separate solution, and the two combined to form an emulsion or suspension. Biocompatible dispersing agents in the form of surfactants, emulsifiers, or stablilizers may be added to the blend to assist in dispersion of the medicinal agent throughout the composition of the present disclosure.
Adjuvants may be added to stabilize or preserve the compositions described above. Such adjuvants include nonionic surfactants which include alcohol ethoxylates, glycerol esters, polyoxyethylene esters, and glycol esters of fatty acids.
Preferable nonionic surfactants are glycerol esters of stearic, oleic, and/or lauric acid as well as ethylene and/or diethylene glycol esters of fatty acids.
The compositions described herein are non-toxic. Depending on its particular physical and properties (to a large extent influenced by the nature of the polymers from which it is prepared), the blends and/or emulsions herein can be used in the fabrication in whole or in part of a variety of implantable medical devices and prostheses, e.g., clips, staples, sutures, suture coatings, etc. Applied to a suture, a coating composition containing the composition herein results in a suture having suitable lubricity, knot tiedown, and knot security characteristics.
Where the composition of the present disclosure is used to form a medical device, the devices may be made by injection molding the blend at temperatures and pressures known to those skilled in the art. Typically, the feed for the injection molding apparatus is a melt blend of the two polymer components in pellet form. The components should be quite dry when being injection molded in order to avoid hydrolytic degradation during processing. After molding, the surgical devices can be packaged and sterilized by conventional procedures. It may be desirable to anneal the devices to remove residual stresses and strains, to stabilize the shape of the device, and to reduce or eliminate defects in the piece. Annealing typically comprises reheating the medical device to above its glass transition temperature where chain mobility is greatest, and then slowly and gradually cooling the device to avoid reintroducing. Procedures, conditions and apparatus for annealing polymeric structures are well known in the art.
Where the composition of the present disclosure is used as an absorbable coating for a medical device, the coating may be formed using any known technique such as, for example, extrusion, molding and/or solvent casting. The composition can be used alone, blended with absorbable compositions, or blended with non-absorbable components. A
wide variety of surgical articles can be coated with the compositions herein.
These include, but are not limited to, clips and other fasteners, staples, sutures, pins, screws, prosthetic device, wound dressings, drug delivery devices, anastomosis rings, and other implantable devices. Fibers coated with the present compositions can be knitted or woven with other fibers, either absorbable or nonabsorbable to form meshes or fabrics.
In one embodiment the composition of the present disclosure may be applied as a coating by dissolving it in a solvent which is a non-solvent for any polymeric device to which the coating is to be applied. The solution containing the composition of the presentslisclosure may then be applied to a medical device by dipping the medical device into the solution, by passing the medical device past a brush or other applicator, or by spraying the solution onto the surface of the medical device. Suitable solvents for use in dissolving the composition of the present disclosure include, but are not limited to, volatile solvents such as methylene chloride and acetone. The medical device wetted with the coating solution may then be subsequently passed through or held in a drying oven for a time and at a temperature sufficient to vaporize and drive off the solvent. If desired, the suture coating composition can optionally contain additional components, e.g., dyes, antibiotics, antiseptics, growth factors, anti-inflammatory agents, etc.
Where applied in solution, the amount of solvent utilized can range from about 85% to about 99% by weight, typically from about 90% to about 98% by weight of the solution utilized to apply the composition of the present disclosure, including the blend or emulsion described above, and any additional medicinal agents or adjuvants. In some embodiments the solvent may be present at about 95% by weight of the solution utilized to apply the composition of the present disclosure.
While the above description focuses on the use of a blend or emulsion as a medical device, drug delivery device, or coating composition in accordance with the present disclosure, optionally in combination with medicinal agents or adjuvants, similar methods and procedures may be utilized where the composition of the present disclosure includes the polymer made at least in part from a polyoxyalkylene copolymer in combination with a medicinal agent or adjuvant, without the addition of a second component, which can be a polymer or oligomer. As would be readily apparent to one skilled in the art, one could utilize the same or similar solvents, processing conditions, etc. in utilizing a polymer made at least in part from a polyoxyalkylene copolymer as the composition of the present disclosure.
While the composition herein can be applied to any type of medical device, it may be especially useful as a coating for a suture. The amount of composition applied to a suture will vary depending upon the structure of the suture, e.g., monofilament or =
multifilament, the size of the suture and its composition. For multifilament sutures, the number of filaments and the tightness of the braid or twist may also influence the amount of coating.
The coating may be applied to both monofilament and multifilament braided sutures which may, in some embodiments, also be bioabsorbable. Suitable bioabsorbable monomers and polymers utilized for the sutures, including bioabsorbable braided sutures, include lactide, glycolide, trimethylcarbonate, s-caprolactone, caprolactam, polyesters, nylons, etc. The coating can typically be present in an amount ranging from about 0.5 to about 15% (w/w) of the base suture substrate, more typically from about 1 to about 5%
(w/w) of the base suture substrate. The thickness of the coating will depend on a number of factors, but typically can be from submicron thicknesses up to several millimeters in thickness.
The composition of the present disclosure, where utilized as a coating for a medical device, improves surface properties of the device such as, for example, cell and protein adhesion, lubricity, drug delivery, protein or DNA delivery, etc. The bioabsorbable blend coating may be especially useful in preventing bacterial adhesion/colonization, infection caused by or exacerbated by the device itself, and improving the handling properties of the device.
The composition of the present disclosure may also be formed into films and/or foams which, in turn, may be applied to wounds such as cuts, gashes, ulcers and burns to aid healing. Medicinal agents such as wound healing agents and antimicrobials may be incorporated to speed healing of damaged tissues. In this manner, various growth factors, antibiotics and antifungals can be incorporated into the bioabsorbable blend of the present disclosure.
Where medicinal agents are included in the bioabsorbable blend of the present disclosure, the composition of the present disclosure may be utilized as a drug delivery device to provide site-specific release of medicinal agents which may be immediate release, delayed release or sustained release. Immediate release systems provide a drug dose instantly. Delayed release systems provide repetitive intermittent dosings of drug.
Sustained release systems achieve slow release of a drug over an extended period of time and should maintain a therapeutically effective concentration of drug at the target site.
Medicinal agents that are mingled with the compositions herein typically provide delayed or sustained release therapy by diffusion from the bioabsorbable implant and/or bioabsorbable coating as it degrades.
The following examples are illustrative of specific embodiments of the polymeric compositions and should not be construed as limitations thereof.
A biocompatible, biodegradable polymer was produced as follows. A one gallon reactor vessel was cleaned and subjected to a vacuum to reach a pressure of less than 1 Ton. 1000 1 grams of poloxamer 188 (PLURONIC F68) was added to the one gallon reactor vessel, after which time a vacuum was again applied to obtain a pressure less than 1 Ton. The temperature was raised to about 105 C. and the PLURONIC F68 was dried in the reactor for about 14 ( 4) hours. During this time period, 1275 1 grams of e-caprolactone was added to a 3 liter round bottom flask, and 225 1 grams of glycolide was added to a 500 ml round bottom flask, Between 75 and 90 minutes prior to the end of the drying of the PLURONIC F68, the a-caprolactone and glycolide were placed in an oven heated to a temperature of 105 C. After the drying of the PLURONIC
was complete, the glycolide was added to the reactor, followed by the addition of the E-S caprolactone. The reactor was then backfilled with nitrogen, and then 295 1.11., of stannous octoate was added to the reactor as a catalyst.
The reactor was then heated to 178 C. ( 3 C.), and the reaction was allowed to continue for 4.5 ( 0.25) hours. After the reaction was complete, the polymerized bioabsorbable polymer was extruded and allowed to cool for a minimum of 16 hours.
The resulting bioabsorbable polymer was then subjected to an additional heat treatment. The bioabsorbable polymer was placed in a vacuum oven, which was heated to a temperature of 110 C. ( 3 C.) in a vacuum at a pressure less than 1 Ton, for 30 2 hours. After heating, the polymer was allowed to cool under vacuum for a minimum of 6 hours.
NMR of the bioabsorbable polymer was conducted utilizing a Bruker AC300 NMR spectrometer. The proton spectra obtained had peaks which permitted the identification of the components of the bioabsorbable polymer.
The resulting bioabsorbable terpolymer was found to possess about 40% by weight PLURONIC F68, about 51% by weight of caprolactoyl groups, about 9% by weight of glycoyl groups, and < 1 % by weight of residual caprolactone monomer.
Monofilament surgical sutures which prevented the attachment and colonization of bacteria and provided enhanced suture handling characteristics, including reduced tissue drag, were prepared as follows. The polymer of Example 1 was solvated in methylene chloride at concentrations of 2, 5 and 10% (w/w). Monofilament polybutester (a copolymer of butylene terephthalate and polytetramethylene ether glycol) surgical sutures were coated by dip coating with each solution, to produce a uniform coating on the sutures. The resulting coating levels were 1.08%, 3.64% and 6.80% based on the weight of the suture for the 2%, 5% and 10% solutions, respectively. The coating from the 10% solution was found to prevent bacterial colonization of sutures at levels of clinical infection for at least 8 days. In contrast, other monofilaments, including uncoated polybutester sutures reached levels of clinical infection in as little as 3 days.
Braided multifilaments made of a glycolide/lactide copolymer coated with a mixture of a caprolactone/glycolide copolymer and calcium stearoyl lactylate as described in the Examples of U.S. Patent No. 5,716,376 were coated with the polymer of Example 1. The coating polymer was solvated in methylene chloride (2, 5 and 10%
(w/w)) and the sutures coated with one of three solutions by dip coating. The additional coating polymer prevented bacterial adhesion and colonization in a more effective manner than observed with the uncoated sutures or with Ethicon's VICRYL Plus suture (a suture made of a glycolide/lactide copolymer having a coating including triclosan).
This bioabsorbable polymer of Example 1 was blended with the solution of Example 3 of U.S. Patent No. 5,716,376 containing an E-caprolactone/glycolide copolymer and calcium stearoyl lactylate represented about 2, 5 and 10% (w/w) of the resulting solution.
Multifilament braided glycolide/lactide surgical sutures were coated with the bioabsorbable blend by dip coating the suture in the solution having the bioabsorbable blend, and driving off the solvent by heating to produce a useable surgical suture.
Varying amounts (2%, 5% and 10% w/w) of the bioabsorbable polymer of Example I were blended into the solution of Example 2 of U.S. Patent No.
5,716,376 which was then modified by adding 2% triclosan. The resulting solutions were applied to multifilament, braided glycolide/lactide copolymer sutures.
The resulting suture having the coating of the bioabsorbable blend with triclosan and untreated sutures are tested for resistance to bacterial colonization using standard techniques. Generally, the sutures are exposed to Escherichia coli and the amount of bacteria growing on the suture is determined by counting the number of colony forming units. The results of these experiments are set forth in Figure 1. As is apparent from Figure 1, the suture having the coating of the bioabsorbable blend with triclosan prevented bacterial colonization on the suture material for up to 21 days, a marked improvement over the untreated suture. In addition, suture having the coating of the bioabsorbable blend with triclosan exhibited a lame zone of inhibition (ZOT) of bacterial growth (approximately 20mm).
An anti-inflammatory coated surgical suture is prepared as follows. The bioabsorbable polymer of Example 1 of is solvated in methylene chloride at a concentration of 10% (w/w). Then, a 2% (w/w) salicylate solution is prepared in reverse osmosis (RO) water. Water/organic emulsions are prepared with the ratio of the bioabsorbable polymer solution:salicylate solution ranging from 8:2 to 2:8.
Emulsions are formed under vigorous stirring and a surgical suture is coated with the bioabsorbable polymer and salicylate solution by dip coating techniques. The amount of the resulting coating ranges from 1-5% (w/w) of the base suture substrate. The polymer coating containing salicylate prevents bacterial colonization on the suture material for up to 14 days and exhibits a large zone of inhibition (ZOI) of bacterial growth (approximately 20mm).
Antimicrobial surgical suture coatings containing ionic silver and/or silver glass particles are prepared as follows. The bioabsorbable polymer of Example 1 is solvated in methylene chloride at concentration of 10% (w/w). Suspension/solutions of various silver salts (nitrate, citrate, sulfadiazine, lactate, etc.) are prepared in reverse osmosis (RO) water under high speed mixing. Water/organic emulsions are prepared with the ratio of the bioabsorbable polymer coating solution:silver suspension/solutions ranging from 8:2 to 2:8. Emulsions are formed under vigorous stirring and surgical sutures were coated by dip coating techniques. The coating is present in an amount from 0.5% to 15%
(w/w) of the base suture substrate, preferably 1-5% (w/w). The polymer coating containing ionic silver prevents bacterial colonization on the suture material.
It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore the above description should not be construed as limiting, but merely as examplifications of preferred embodiments. The scope of the claims should not be limited by the preferred embodiments set forth herein, but should be given the broadest interpretation consistent with the description as a whole.
Claims (20)
1. A blend comprising:
a bioabsorbable terpolymer comprising about 30 to about 50 weight percent of a polyoxyalkylene copolymer, about 40 to about 50 weight percent epsilon-caprolactone derived units, the balance of the copolymer being derived from at least one other copolymerizable monomer selected from the group consisting of glycolide, lactide, p-dioxanone and trimethylene carbonate; and a polymer derived from two or more monomers selected from the group consisting of lactide, glycolide, lactic acid, lactones, glycolic acid, carbonates, orthoesters, absorbable urethanes, and absorbable nylons.
a bioabsorbable terpolymer comprising about 30 to about 50 weight percent of a polyoxyalkylene copolymer, about 40 to about 50 weight percent epsilon-caprolactone derived units, the balance of the copolymer being derived from at least one other copolymerizable monomer selected from the group consisting of glycolide, lactide, p-dioxanone and trimethylene carbonate; and a polymer derived from two or more monomers selected from the group consisting of lactide, glycolide, lactic acid, lactones, glycolic acid, carbonates, orthoesters, absorbable urethanes, and absorbable nylons.
2. The blend of claim 1, which is present in form of an emulsion.
3. The blend of claim 1 or 2, wherein the polymer is derived from two or more monomers selected from polyethylene glycol-polypropylene glycol, polystyrene, n-vinyl pyrrolidine, n-vinyl pyridine, C1-11-acrylate monomer, C1-C12 methacrylate monomer, hydroxyethyl methacrylate, hydroxypropyl methacrylate, acrylic acid, potassium sulfopropyl acrylate, potassium sulfopropyl methacrylate, and 2-methacryloyl phosphorocholine.
4. The blend of claim 1 or 2, wherein the polymer comprises a copolymer of ~-caprolactone and glycolide.
5. The blend of claim 1 or 2, further comprising a fatty acid component,
6. The blend of claim 5, wherein the fatty acid component comprises a salt of a C6 or higher fatty acid.
7. The blend of claim 6, wherein the fatty acid .salt is selected from the group consisting of calcium, magnesium, barium, aluminum, and zinc salts of C6 or higher fatty acids.
8. The blend of any one of claims 5-7, wherein the fatty acid salt comprises calcium stearate.
9. The blend of any one of claims 5-7, wherein the fatty acid component comprises a fatty acid ester salt selected from the group consisting of magnesium stearoyl lactylate, aluminum stearoyl lactylate, barium stearoyl lactylate, zinc stearoyl lactylate, calcium palmityl lactylate, magnesium palmityl lactylate, aluminum palmityl lactylate, barium palmityl lactylate, or zinc palmityl lactylate, calcium olelyl lactylate, magnesium olelyl laetylate, aluminum olelyl lactylate, barium olelyl lactylate, zinc olelY1 lactylate and calcium stearoyl lactylate.
10. The blend of claim 1 or 2, further comprising a wax.
11.. The blend of claim 10, wherein the wax is selected from polyethylene wax., ethylene copolymer wax, halogenated hydrocarbon waxes, hydrogenated vegetable oil, beeswax, carannba wax, paraffin, microcrystalline wax, candelillia, spermacetic wax, and mixtures thereof.
12. The blend of claim 1 or 2, further comprising a phospholipid.
13. The blend of claim 12, wherein the phospholipid is selected from phosphatidylcholine, mono-acyl phosphatidylcholine, diacyl phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, plasmalogen, sphingomyelin, ceramide, ciliatin, polymers having phospholipid groups, copolymers having phosphorylcholine groups, and derivatives thereof.
14. The blend of claim 1 or 2, which further comprises a medicinal agent.
15. The blend of claim 14, wherein the medicinal agent is selected from antimicrobials, analgesics, antipyretics, anesthetics, antiepileptics, antihistamines, anti-inflammatories, cardiovascular drugs, diagnostic agents, sympathomimetics, cholinomimetics, antimuscarinics, antispasmodics, hormones, growth factors. muscle relaxants, adrenergic neuron blockers, antineoplastics, immunosuppressants, gastrointestinal drugs, diuretics, proteins, nucleic acids, steroids, polysaccharides, and enzymes.
16. A medical device fabricated in whole or in part from the blend of any one of claims 1-15.
17. A surgical suture coated with a composition comprising the blend of any one of claims 1-15.
18. A drug delivery device fabricated in whole or in part from the emulsion of claim 2, or any one of claims 3-15 referring to claim 2.
19. A surgical suture coated with a composition comprising:
an effective antimicrobial amount of a terpolymer having a polyoxyalkylene copolymer component, a plurality of e-caprolactone derived units, and a plurality of repeating units derived from glycolide; and a salt of a C6- or higher fatty acid.
an effective antimicrobial amount of a terpolymer having a polyoxyalkylene copolymer component, a plurality of e-caprolactone derived units, and a plurality of repeating units derived from glycolide; and a salt of a C6- or higher fatty acid.
20. The surgical suture of claim 19, wherein the composition further comprises a salt of a fatty acid ester selected from the group consisting of magnesium stearoyl lactylate, aluminum stearoyl lactylate, barium stearoyl lactylate, zinc stearoyl lactylate, calcium palmityl laetylate, magnesium palmityl lactylate, aluminum palmityl lactylate, barium palmityl lactylate, or zinc palmityl lactylate, calcium olelyl lactylate, magnesium olelyl lactylate, aluminum olelyl lactylate. barium olelyl lactylate, zinc olelyl lactylate and calcium stearoyl lactylate.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US63242904P | 2004-12-01 | 2004-12-01 | |
US60/632,429 | 2004-12-01 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2526541A1 CA2526541A1 (en) | 2006-06-01 |
CA2526541C true CA2526541C (en) | 2013-09-03 |
Family
ID=36084797
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2526541A Expired - Fee Related CA2526541C (en) | 2004-12-01 | 2005-11-10 | Novel biomaterial drug delivery and surface modification compositions |
Country Status (7)
Country | Link |
---|---|
US (1) | US7850982B2 (en) |
EP (1) | EP1669093B1 (en) |
JP (1) | JP2006152306A (en) |
AU (1) | AU2005234622B2 (en) |
CA (1) | CA2526541C (en) |
DE (1) | DE602005019523D1 (en) |
ES (1) | ES2340044T3 (en) |
Families Citing this family (508)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9616150B2 (en) | 1999-10-29 | 2017-04-11 | Children's Hospital Los Angeles | Bone hemostasis method and materials |
EP2407125A1 (en) * | 2003-01-24 | 2012-01-18 | Tyco Healthcare Group, LP | Bioabsorbable composition and coatings including same |
EP1601326A4 (en) | 2003-02-12 | 2011-05-11 | Ceremed Inc | Random alkylene oxide copolymers for medical and surgical utilities |
US9060770B2 (en) | 2003-05-20 | 2015-06-23 | Ethicon Endo-Surgery, Inc. | Robotically-driven surgical instrument with E-beam driver |
US20070084897A1 (en) | 2003-05-20 | 2007-04-19 | Shelton Frederick E Iv | Articulating surgical stapling instrument incorporating a two-piece e-beam firing mechanism |
US8215531B2 (en) | 2004-07-28 | 2012-07-10 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument having a medical substance dispenser |
US11896225B2 (en) | 2004-07-28 | 2024-02-13 | Cilag Gmbh International | Staple cartridge comprising a pan |
JP4934036B2 (en) * | 2004-08-17 | 2012-05-16 | タイコ ヘルスケア グループ リミテッド パートナーシップ | Anti-adhesion barrier |
US8263105B2 (en) * | 2004-12-01 | 2012-09-11 | Tyco Healthcare Group Lp | Biomaterial drug delivery and surface modification compositions |
CA2526541C (en) | 2004-12-01 | 2013-09-03 | Tyco Healthcare Group Lp | Novel biomaterial drug delivery and surface modification compositions |
US9237891B2 (en) | 2005-08-31 | 2016-01-19 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical stapling devices that produce formed staples having different lengths |
US10159482B2 (en) | 2005-08-31 | 2018-12-25 | Ethicon Llc | Fastener cartridge assembly comprising a fixed anvil and different staple heights |
US7669746B2 (en) | 2005-08-31 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US11246590B2 (en) | 2005-08-31 | 2022-02-15 | Cilag Gmbh International | Staple cartridge including staple drivers having different unfired heights |
US20070194082A1 (en) | 2005-08-31 | 2007-08-23 | Morgan Jerome R | Surgical stapling device with anvil having staple forming pockets of varying depths |
US11484312B2 (en) | 2005-08-31 | 2022-11-01 | Cilag Gmbh International | Staple cartridge comprising a staple driver arrangement |
US7934630B2 (en) | 2005-08-31 | 2011-05-03 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US20070106317A1 (en) | 2005-11-09 | 2007-05-10 | Shelton Frederick E Iv | Hydraulically and electrically actuated articulation joints for surgical instruments |
CA2573472A1 (en) * | 2006-01-23 | 2007-07-23 | Tyco Healthcare Group Lp | Biodegradable hemostatic compositions |
US20090209031A1 (en) * | 2006-01-26 | 2009-08-20 | Tyco Healthcare Group Lp | Medical device package |
US20070170080A1 (en) * | 2006-01-26 | 2007-07-26 | Joshua Stopek | Medical device package |
US9364215B2 (en) * | 2006-01-26 | 2016-06-14 | Covidien Lp | Medical device package |
US20120292367A1 (en) | 2006-01-31 | 2012-11-22 | Ethicon Endo-Surgery, Inc. | Robotically-controlled end effector |
US8186555B2 (en) | 2006-01-31 | 2012-05-29 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting and fastening instrument with mechanical closure system |
US11793518B2 (en) | 2006-01-31 | 2023-10-24 | Cilag Gmbh International | Powered surgical instruments with firing system lockout arrangements |
US9861359B2 (en) | 2006-01-31 | 2018-01-09 | Ethicon Llc | Powered surgical instruments with firing system lockout arrangements |
US8708213B2 (en) | 2006-01-31 | 2014-04-29 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a feedback system |
US20110295295A1 (en) | 2006-01-31 | 2011-12-01 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical instrument having recording capabilities |
US7753904B2 (en) | 2006-01-31 | 2010-07-13 | Ethicon Endo-Surgery, Inc. | Endoscopic surgical instrument with a handle that can articulate with respect to the shaft |
US20110006101A1 (en) | 2009-02-06 | 2011-01-13 | EthiconEndo-Surgery, Inc. | Motor driven surgical fastener device with cutting member lockout arrangements |
US20110024477A1 (en) | 2009-02-06 | 2011-02-03 | Hall Steven G | Driven Surgical Stapler Improvements |
US11224427B2 (en) | 2006-01-31 | 2022-01-18 | Cilag Gmbh International | Surgical stapling system including a console and retraction assembly |
US8820603B2 (en) | 2006-01-31 | 2014-09-02 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
US7845537B2 (en) | 2006-01-31 | 2010-12-07 | Ethicon Endo-Surgery, Inc. | Surgical instrument having recording capabilities |
US11278279B2 (en) | 2006-01-31 | 2022-03-22 | Cilag Gmbh International | Surgical instrument assembly |
US8992422B2 (en) | 2006-03-23 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Robotically-controlled endoscopic accessory channel |
US20070225562A1 (en) | 2006-03-23 | 2007-09-27 | Ethicon Endo-Surgery, Inc. | Articulating endoscopic accessory channel |
US8322455B2 (en) | 2006-06-27 | 2012-12-04 | Ethicon Endo-Surgery, Inc. | Manually driven surgical cutting and fastening instrument |
WO2008008365A2 (en) * | 2006-07-11 | 2008-01-17 | Tyco Healthcare Group Lp | Biocompatible hydrogels |
US8348973B2 (en) | 2006-09-06 | 2013-01-08 | Covidien Lp | Bioactive substance in a barbed suture |
EP1897500B1 (en) | 2006-09-06 | 2009-07-29 | Tyco Healthcare Group, LP | Barbed sutures |
US10568652B2 (en) | 2006-09-29 | 2020-02-25 | Ethicon Llc | Surgical staples having attached drivers of different heights and stapling instruments for deploying the same |
US10130359B2 (en) | 2006-09-29 | 2018-11-20 | Ethicon Llc | Method for forming a staple |
US7506791B2 (en) | 2006-09-29 | 2009-03-24 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument with mechanical mechanism for limiting maximum tissue compression |
CA2604433A1 (en) * | 2006-10-06 | 2008-04-06 | Tyco Healthcare Group Lp | Medical device package including self-puncturable port |
US20080171972A1 (en) * | 2006-10-06 | 2008-07-17 | Stopek Joshua B | Medical device package |
DE102006051093B4 (en) * | 2006-10-25 | 2011-03-17 | Heraeus Kulzer Gmbh | Surgical suture with antimicrobial surface and method for antimicrobial coating surgical suture |
EP2079396A2 (en) * | 2006-10-30 | 2009-07-22 | Poly-Med, Inc. | Suture-specific coatings for modulated release of biocative agents |
US8353931B2 (en) | 2006-11-02 | 2013-01-15 | Covidien Lp | Long term bioabsorbable barbed sutures |
US20080132943A1 (en) * | 2006-12-05 | 2008-06-05 | Nicholas Maiorino | Knotless wound closure device |
US8597673B2 (en) * | 2006-12-13 | 2013-12-03 | Advanced Cardiovascular Systems, Inc. | Coating of fast absorption or dissolution |
WO2008143654A1 (en) * | 2006-12-22 | 2008-11-27 | Tyco Healthcare Group Lp | Coating compositions |
US11291441B2 (en) | 2007-01-10 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with wireless communication between control unit and remote sensor |
US8652120B2 (en) | 2007-01-10 | 2014-02-18 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and sensor transponders |
US8684253B2 (en) | 2007-01-10 | 2014-04-01 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor |
US8701958B2 (en) | 2007-01-11 | 2014-04-22 | Ethicon Endo-Surgery, Inc. | Curved end effector for a surgical stapling device |
US11039836B2 (en) | 2007-01-11 | 2021-06-22 | Cilag Gmbh International | Staple cartridge for use with a surgical stapling instrument |
US20080195147A1 (en) * | 2007-02-09 | 2008-08-14 | Tyco Healthcare Group Lp | Surface eroding barbed sutures |
US7669747B2 (en) | 2007-03-15 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Washer for use with a surgical stapling instrument |
US20080234672A1 (en) * | 2007-03-20 | 2008-09-25 | Tyco Healthcare Goup Lp | Non-stick surface coated electrodes and method for manufacturing same |
US8893946B2 (en) | 2007-03-28 | 2014-11-25 | Ethicon Endo-Surgery, Inc. | Laparoscopic tissue thickness and clamp load measuring devices |
US20100069957A1 (en) * | 2007-04-25 | 2010-03-18 | Ferass Abuzaina | Coated Filaments |
US8309222B2 (en) * | 2007-04-25 | 2012-11-13 | Covidien Lp | Coated filaments |
WO2008144247A1 (en) * | 2007-05-14 | 2008-11-27 | Tyco Healthcare Group Lp | Antimicrobial materials and coatings |
US11564682B2 (en) | 2007-06-04 | 2023-01-31 | Cilag Gmbh International | Surgical stapler device |
US8931682B2 (en) | 2007-06-04 | 2015-01-13 | Ethicon Endo-Surgery, Inc. | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US8308040B2 (en) | 2007-06-22 | 2012-11-13 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument with an articulatable end effector |
US7753245B2 (en) | 2007-06-22 | 2010-07-13 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments |
US11849941B2 (en) | 2007-06-29 | 2023-12-26 | Cilag Gmbh International | Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis |
US7666973B2 (en) | 2007-07-30 | 2010-02-23 | Tyco Healthcare Group Lp | Carbonate copolymers |
GB0715376D0 (en) * | 2007-08-07 | 2007-09-19 | Smith & Nephew | Coating |
US20090048423A1 (en) * | 2007-08-15 | 2009-02-19 | Tyco Healthcare Group Lp | Phospholipid Copolymers |
US8268958B2 (en) * | 2007-08-15 | 2012-09-18 | Tyco Healthcare Group Ip | Phospholipid copolymers |
US7905381B2 (en) | 2008-09-19 | 2011-03-15 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument with cutting member arrangement |
US8561870B2 (en) | 2008-02-13 | 2013-10-22 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument |
US8657174B2 (en) | 2008-02-14 | 2014-02-25 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument having handle based power source |
JP5410110B2 (en) | 2008-02-14 | 2014-02-05 | エシコン・エンド−サージェリィ・インコーポレイテッド | Surgical cutting / fixing instrument with RF electrode |
US8636736B2 (en) | 2008-02-14 | 2014-01-28 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument |
US7819298B2 (en) | 2008-02-14 | 2010-10-26 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with control features operable with one hand |
US8758391B2 (en) | 2008-02-14 | 2014-06-24 | Ethicon Endo-Surgery, Inc. | Interchangeable tools for surgical instruments |
US9179912B2 (en) | 2008-02-14 | 2015-11-10 | Ethicon Endo-Surgery, Inc. | Robotically-controlled motorized surgical cutting and fastening instrument |
US7866527B2 (en) | 2008-02-14 | 2011-01-11 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with interlockable firing system |
US8573465B2 (en) | 2008-02-14 | 2013-11-05 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical end effector system with rotary actuated closure systems |
US20130153641A1 (en) | 2008-02-15 | 2013-06-20 | Ethicon Endo-Surgery, Inc. | Releasable layer of material and surgical end effector having the same |
US11272927B2 (en) | 2008-02-15 | 2022-03-15 | Cilag Gmbh International | Layer arrangements for surgical staple cartridges |
US8273105B2 (en) | 2008-02-20 | 2012-09-25 | Tyco Healthcare Group Lp | Compound barb medical device and method |
US8888810B2 (en) | 2008-02-20 | 2014-11-18 | Covidien Lp | Compound barb medical device and method |
US8454653B2 (en) | 2008-02-20 | 2013-06-04 | Covidien Lp | Compound barb medical device and method |
US9358002B2 (en) | 2008-04-01 | 2016-06-07 | Covidien Lp | Anchoring device |
US10376261B2 (en) | 2008-04-01 | 2019-08-13 | Covidien Lp | Anchoring suture |
US8932327B2 (en) | 2008-04-01 | 2015-01-13 | Covidien Lp | Anchoring device |
US9034011B2 (en) | 2008-04-01 | 2015-05-19 | Covidien Lp | Anchoring device |
US8263704B2 (en) | 2008-04-23 | 2012-09-11 | Tyco Healthcare Group Lp | Bioabsorbable surgical composition |
PL3476312T3 (en) | 2008-09-19 | 2024-03-11 | Ethicon Llc | Surgical stapler with apparatus for adjusting staple height |
US9005230B2 (en) | 2008-09-23 | 2015-04-14 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US8210411B2 (en) | 2008-09-23 | 2012-07-03 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting instrument |
US9386983B2 (en) | 2008-09-23 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Robotically-controlled motorized surgical instrument |
US11648005B2 (en) | 2008-09-23 | 2023-05-16 | Cilag Gmbh International | Robotically-controlled motorized surgical instrument with an end effector |
US8608045B2 (en) | 2008-10-10 | 2013-12-17 | Ethicon Endo-Sugery, Inc. | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US7923439B2 (en) | 2008-10-15 | 2011-04-12 | Tyco Healthcare Group Lp | Hydroxamate compositions |
EP2365942A1 (en) * | 2008-11-20 | 2011-09-21 | Watervisions International, Inc | Antimicrobial device and materials for fluid treatment |
CN101745142A (en) * | 2008-12-21 | 2010-06-23 | 赵伶 | Chinese medicine sterilizing and bacteriostasis coating material for medical instruments |
US8517239B2 (en) | 2009-02-05 | 2013-08-27 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument comprising a magnetic element driver |
EP2393430A1 (en) | 2009-02-06 | 2011-12-14 | Ethicon Endo-Surgery, Inc. | Driven surgical stapler improvements |
US8444036B2 (en) | 2009-02-06 | 2013-05-21 | Ethicon Endo-Surgery, Inc. | Motor driven surgical fastener device with mechanisms for adjusting a tissue gap within the end effector |
US20110076312A1 (en) * | 2009-09-29 | 2011-03-31 | Ethicon, Inc. | Antimicrobial/antibacterial medical devices coated with traditional chinese medicines |
US20110086078A1 (en) | 2009-10-14 | 2011-04-14 | Water Visions International, Inc. | Fibrous antimicrobial materials, structures, and barrier applications |
US8851354B2 (en) | 2009-12-24 | 2014-10-07 | Ethicon Endo-Surgery, Inc. | Surgical cutting instrument that analyzes tissue thickness |
US8220688B2 (en) | 2009-12-24 | 2012-07-17 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting instrument with electric actuator directional control assembly |
US9044224B2 (en) | 2010-04-12 | 2015-06-02 | Covidien Lp | Barbed medical device and method |
US8783543B2 (en) | 2010-07-30 | 2014-07-22 | Ethicon Endo-Surgery, Inc. | Tissue acquisition arrangements and methods for surgical stapling devices |
US11298125B2 (en) | 2010-09-30 | 2022-04-12 | Cilag Gmbh International | Tissue stapler having a thickness compensator |
US9629814B2 (en) | 2010-09-30 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator configured to redistribute compressive forces |
US9364233B2 (en) | 2010-09-30 | 2016-06-14 | Ethicon Endo-Surgery, Llc | Tissue thickness compensators for circular surgical staplers |
US8746535B2 (en) | 2010-09-30 | 2014-06-10 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising detachable portions |
US9220501B2 (en) | 2010-09-30 | 2015-12-29 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensators |
US9301753B2 (en) | 2010-09-30 | 2016-04-05 | Ethicon Endo-Surgery, Llc | Expandable tissue thickness compensator |
US9332974B2 (en) | 2010-09-30 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Layered tissue thickness compensator |
US9314246B2 (en) | 2010-09-30 | 2016-04-19 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorporating an anti-inflammatory agent |
US9566061B2 (en) | 2010-09-30 | 2017-02-14 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a releasably attached tissue thickness compensator |
US9414838B2 (en) | 2012-03-28 | 2016-08-16 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprised of a plurality of materials |
US11812965B2 (en) | 2010-09-30 | 2023-11-14 | Cilag Gmbh International | Layer of material for a surgical end effector |
US9839420B2 (en) | 2010-09-30 | 2017-12-12 | Ethicon Llc | Tissue thickness compensator comprising at least one medicament |
US9517063B2 (en) | 2012-03-28 | 2016-12-13 | Ethicon Endo-Surgery, Llc | Movable member for use with a tissue thickness compensator |
US10945731B2 (en) | 2010-09-30 | 2021-03-16 | Ethicon Llc | Tissue thickness compensator comprising controlled release and expansion |
US9216019B2 (en) | 2011-09-23 | 2015-12-22 | Ethicon Endo-Surgery, Inc. | Surgical stapler with stationary staple drivers |
US9307989B2 (en) | 2012-03-28 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorportating a hydrophobic agent |
US11849952B2 (en) | 2010-09-30 | 2023-12-26 | Cilag Gmbh International | Staple cartridge comprising staples positioned within a compressible portion thereof |
EP2621356B1 (en) | 2010-09-30 | 2018-03-07 | Ethicon LLC | Fastener system comprising a retention matrix and an alignment matrix |
US9277919B2 (en) | 2010-09-30 | 2016-03-08 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising fibers to produce a resilient load |
US9386988B2 (en) | 2010-09-30 | 2016-07-12 | Ethicon End-Surgery, LLC | Retainer assembly including a tissue thickness compensator |
US8695866B2 (en) | 2010-10-01 | 2014-04-15 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a power control circuit |
US8414612B2 (en) | 2010-11-08 | 2013-04-09 | Covidien Lp | Multifilament barbed suture |
AU2012250197B2 (en) | 2011-04-29 | 2017-08-10 | Ethicon Endo-Surgery, Inc. | Staple cartridge comprising staples positioned within a compressible portion thereof |
US9072535B2 (en) | 2011-05-27 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments with rotatable staple deployment arrangements |
US11207064B2 (en) | 2011-05-27 | 2021-12-28 | Cilag Gmbh International | Automated end effector component reloading system for use with a robotic system |
US20130005829A1 (en) * | 2011-06-30 | 2013-01-03 | Advanced Technologies And Regenerative Medicine, Llc. | Segmented, epsilon-Caprolactone-Rich, Poly(epsilon-Caprolactone-co-p-Dioxanone) Copolymers for Medical Applications and Devices Therefrom |
US9050084B2 (en) | 2011-09-23 | 2015-06-09 | Ethicon Endo-Surgery, Inc. | Staple cartridge including collapsible deck arrangement |
JP2014528264A (en) | 2011-09-30 | 2014-10-27 | ソフラディム・プロダクション | Reversible hardness of light weight mesh |
US9044230B2 (en) | 2012-02-13 | 2015-06-02 | Ethicon Endo-Surgery, Inc. | Surgical cutting and fastening instrument with apparatus for determining cartridge and firing motion status |
RU2639857C2 (en) | 2012-03-28 | 2017-12-22 | Этикон Эндо-Серджери, Инк. | Tissue thickness compensator containing capsule for medium with low pressure |
US9198662B2 (en) | 2012-03-28 | 2015-12-01 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator having improved visibility |
RU2644272C2 (en) | 2012-03-28 | 2018-02-08 | Этикон Эндо-Серджери, Инк. | Limitation node with tissue thickness compensator |
MX358135B (en) | 2012-03-28 | 2018-08-06 | Ethicon Endo Surgery Inc | Tissue thickness compensator comprising a plurality of layers. |
US9101358B2 (en) | 2012-06-15 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Articulatable surgical instrument comprising a firing drive |
US20140005718A1 (en) | 2012-06-28 | 2014-01-02 | Ethicon Endo-Surgery, Inc. | Multi-functional powered surgical device with external dissection features |
US11202631B2 (en) | 2012-06-28 | 2021-12-21 | Cilag Gmbh International | Stapling assembly comprising a firing lockout |
EP2866686A1 (en) | 2012-06-28 | 2015-05-06 | Ethicon Endo-Surgery, Inc. | Empty clip cartridge lockout |
US9101385B2 (en) | 2012-06-28 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Electrode connections for rotary driven surgical tools |
US9289256B2 (en) | 2012-06-28 | 2016-03-22 | Ethicon Endo-Surgery, Llc | Surgical end effectors having angled tissue-contacting surfaces |
US9226751B2 (en) | 2012-06-28 | 2016-01-05 | Ethicon Endo-Surgery, Inc. | Surgical instrument system including replaceable end effectors |
US20140001231A1 (en) | 2012-06-28 | 2014-01-02 | Ethicon Endo-Surgery, Inc. | Firing system lockout arrangements for surgical instruments |
BR112014032776B1 (en) | 2012-06-28 | 2021-09-08 | Ethicon Endo-Surgery, Inc | SURGICAL INSTRUMENT SYSTEM AND SURGICAL KIT FOR USE WITH A SURGICAL INSTRUMENT SYSTEM |
US9649111B2 (en) | 2012-06-28 | 2017-05-16 | Ethicon Endo-Surgery, Llc | Replaceable clip cartridge for a clip applier |
US9447205B2 (en) | 2012-11-19 | 2016-09-20 | Ut-Battelle, Llc | Atmospheric pressure plasma processing of polymeric materials utilizing close proximity indirect exposure |
US9386984B2 (en) | 2013-02-08 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Staple cartridge comprising a releasable cover |
RU2669463C2 (en) | 2013-03-01 | 2018-10-11 | Этикон Эндо-Серджери, Инк. | Surgical instrument with soft stop |
RU2672520C2 (en) | 2013-03-01 | 2018-11-15 | Этикон Эндо-Серджери, Инк. | Hingedly turnable surgical instruments with conducting ways for signal transfer |
US9358003B2 (en) | 2013-03-01 | 2016-06-07 | Ethicon Endo-Surgery, Llc | Electromechanical surgical device with signal relay arrangement |
US9345481B2 (en) | 2013-03-13 | 2016-05-24 | Ethicon Endo-Surgery, Llc | Staple cartridge tissue thickness sensor system |
US9629629B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgey, LLC | Control systems for surgical instruments |
US9332987B2 (en) | 2013-03-14 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Control arrangements for a drive member of a surgical instrument |
US9332984B2 (en) | 2013-03-27 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Fastener cartridge assemblies |
US9795384B2 (en) | 2013-03-27 | 2017-10-24 | Ethicon Llc | Fastener cartridge comprising a tissue thickness compensator and a gap setting element |
US9572577B2 (en) | 2013-03-27 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a tissue thickness compensator including openings therein |
BR112015026109B1 (en) | 2013-04-16 | 2022-02-22 | Ethicon Endo-Surgery, Inc | surgical instrument |
US9867612B2 (en) | 2013-04-16 | 2018-01-16 | Ethicon Llc | Powered surgical stapler |
US9574644B2 (en) | 2013-05-30 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Power module for use with a surgical instrument |
US9775609B2 (en) | 2013-08-23 | 2017-10-03 | Ethicon Llc | Tamper proof circuit for surgical instrument battery pack |
MX369362B (en) | 2013-08-23 | 2019-11-06 | Ethicon Endo Surgery Llc | Firing member retraction devices for powered surgical instruments. |
US9839428B2 (en) | 2013-12-23 | 2017-12-12 | Ethicon Llc | Surgical cutting and stapling instruments with independent jaw control features |
US9763662B2 (en) | 2013-12-23 | 2017-09-19 | Ethicon Llc | Fastener cartridge comprising a firing member configured to directly engage and eject fasteners from the fastener cartridge |
US20150173756A1 (en) | 2013-12-23 | 2015-06-25 | Ethicon Endo-Surgery, Inc. | Surgical cutting and stapling methods |
US9724092B2 (en) | 2013-12-23 | 2017-08-08 | Ethicon Llc | Modular surgical instruments |
US9962161B2 (en) | 2014-02-12 | 2018-05-08 | Ethicon Llc | Deliverable surgical instrument |
JP6462004B2 (en) | 2014-02-24 | 2019-01-30 | エシコン エルエルシー | Fastening system with launcher lockout |
US20140166725A1 (en) | 2014-02-24 | 2014-06-19 | Ethicon Endo-Surgery, Inc. | Staple cartridge including a barbed staple. |
BR112016021943B1 (en) | 2014-03-26 | 2022-06-14 | Ethicon Endo-Surgery, Llc | SURGICAL INSTRUMENT FOR USE BY AN OPERATOR IN A SURGICAL PROCEDURE |
US9826977B2 (en) | 2014-03-26 | 2017-11-28 | Ethicon Llc | Sterilization verification circuit |
US9913642B2 (en) | 2014-03-26 | 2018-03-13 | Ethicon Llc | Surgical instrument comprising a sensor system |
US20150272557A1 (en) | 2014-03-26 | 2015-10-01 | Ethicon Endo-Surgery, Inc. | Modular surgical instrument system |
US10028761B2 (en) | 2014-03-26 | 2018-07-24 | Ethicon Llc | Feedback algorithms for manual bailout systems for surgical instruments |
CN106456176B (en) | 2014-04-16 | 2019-06-28 | 伊西康内外科有限责任公司 | Fastener cartridge including the extension with various configuration |
US10206677B2 (en) | 2014-09-26 | 2019-02-19 | Ethicon Llc | Surgical staple and driver arrangements for staple cartridges |
US9844369B2 (en) | 2014-04-16 | 2017-12-19 | Ethicon Llc | Surgical end effectors with firing element monitoring arrangements |
US20150297223A1 (en) | 2014-04-16 | 2015-10-22 | Ethicon Endo-Surgery, Inc. | Fastener cartridges including extensions having different configurations |
JP6532889B2 (en) | 2014-04-16 | 2019-06-19 | エシコン エルエルシーEthicon LLC | Fastener cartridge assembly and staple holder cover arrangement |
JP6612256B2 (en) | 2014-04-16 | 2019-11-27 | エシコン エルエルシー | Fastener cartridge with non-uniform fastener |
US10045781B2 (en) | 2014-06-13 | 2018-08-14 | Ethicon Llc | Closure lockout systems for surgical instruments |
US20160066913A1 (en) | 2014-09-05 | 2016-03-10 | Ethicon Endo-Surgery, Inc. | Local display of tissue parameter stabilization |
US11311294B2 (en) | 2014-09-05 | 2022-04-26 | Cilag Gmbh International | Powered medical device including measurement of closure state of jaws |
BR112017004361B1 (en) | 2014-09-05 | 2023-04-11 | Ethicon Llc | ELECTRONIC SYSTEM FOR A SURGICAL INSTRUMENT |
US10105142B2 (en) | 2014-09-18 | 2018-10-23 | Ethicon Llc | Surgical stapler with plurality of cutting elements |
US11523821B2 (en) | 2014-09-26 | 2022-12-13 | Cilag Gmbh International | Method for creating a flexible staple line |
JP6648119B2 (en) | 2014-09-26 | 2020-02-14 | エシコン エルエルシーEthicon LLC | Surgical stapling buttress and accessory materials |
US10076325B2 (en) | 2014-10-13 | 2018-09-18 | Ethicon Llc | Surgical stapling apparatus comprising a tissue stop |
US9924944B2 (en) | 2014-10-16 | 2018-03-27 | Ethicon Llc | Staple cartridge comprising an adjunct material |
US11141153B2 (en) | 2014-10-29 | 2021-10-12 | Cilag Gmbh International | Staple cartridges comprising driver arrangements |
US10517594B2 (en) | 2014-10-29 | 2019-12-31 | Ethicon Llc | Cartridge assemblies for surgical staplers |
US9844376B2 (en) | 2014-11-06 | 2017-12-19 | Ethicon Llc | Staple cartridge comprising a releasable adjunct material |
WO2016093377A1 (en) * | 2014-12-08 | 2016-06-16 | 주식회사 네이처인랩 | Suture thread prepared using compound containing phosphorylcholine-like group |
US10736636B2 (en) | 2014-12-10 | 2020-08-11 | Ethicon Llc | Articulatable surgical instrument system |
US10188385B2 (en) | 2014-12-18 | 2019-01-29 | Ethicon Llc | Surgical instrument system comprising lockable systems |
US10117649B2 (en) | 2014-12-18 | 2018-11-06 | Ethicon Llc | Surgical instrument assembly comprising a lockable articulation system |
US9987000B2 (en) | 2014-12-18 | 2018-06-05 | Ethicon Llc | Surgical instrument assembly comprising a flexible articulation system |
RU2703684C2 (en) | 2014-12-18 | 2019-10-21 | ЭТИКОН ЭНДО-СЕРДЖЕРИ, ЭлЭлСи | Surgical instrument with anvil which is selectively movable relative to staple cartridge around discrete fixed axis |
US10085748B2 (en) | 2014-12-18 | 2018-10-02 | Ethicon Llc | Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors |
US9844374B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member |
US10004501B2 (en) | 2014-12-18 | 2018-06-26 | Ethicon Llc | Surgical instruments with improved closure arrangements |
US9844375B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Drive arrangements for articulatable surgical instruments |
US10180463B2 (en) | 2015-02-27 | 2019-01-15 | Ethicon Llc | Surgical apparatus configured to assess whether a performance parameter of the surgical apparatus is within an acceptable performance band |
US20160249910A1 (en) | 2015-02-27 | 2016-09-01 | Ethicon Endo-Surgery, Llc | Surgical charging system that charges and/or conditions one or more batteries |
US10226250B2 (en) | 2015-02-27 | 2019-03-12 | Ethicon Llc | Modular stapling assembly |
US11154301B2 (en) | 2015-02-27 | 2021-10-26 | Cilag Gmbh International | Modular stapling assembly |
US10045776B2 (en) | 2015-03-06 | 2018-08-14 | Ethicon Llc | Control techniques and sub-processor contained within modular shaft with select control processing from handle |
US10052044B2 (en) | 2015-03-06 | 2018-08-21 | Ethicon Llc | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US10441279B2 (en) | 2015-03-06 | 2019-10-15 | Ethicon Llc | Multiple level thresholds to modify operation of powered surgical instruments |
US9808246B2 (en) | 2015-03-06 | 2017-11-07 | Ethicon Endo-Surgery, Llc | Method of operating a powered surgical instrument |
US10245033B2 (en) | 2015-03-06 | 2019-04-02 | Ethicon Llc | Surgical instrument comprising a lockable battery housing |
JP2020121162A (en) | 2015-03-06 | 2020-08-13 | エシコン エルエルシーEthicon LLC | Time dependent evaluation of sensor data to determine stability element, creep element and viscoelastic element of measurement |
US9895148B2 (en) | 2015-03-06 | 2018-02-20 | Ethicon Endo-Surgery, Llc | Monitoring speed control and precision incrementing of motor for powered surgical instruments |
US10687806B2 (en) | 2015-03-06 | 2020-06-23 | Ethicon Llc | Adaptive tissue compression techniques to adjust closure rates for multiple tissue types |
US9993248B2 (en) | 2015-03-06 | 2018-06-12 | Ethicon Endo-Surgery, Llc | Smart sensors with local signal processing |
US9924961B2 (en) | 2015-03-06 | 2018-03-27 | Ethicon Endo-Surgery, Llc | Interactive feedback system for powered surgical instruments |
US9901342B2 (en) | 2015-03-06 | 2018-02-27 | Ethicon Endo-Surgery, Llc | Signal and power communication system positioned on a rotatable shaft |
US10617412B2 (en) | 2015-03-06 | 2020-04-14 | Ethicon Llc | System for detecting the mis-insertion of a staple cartridge into a surgical stapler |
US10433844B2 (en) | 2015-03-31 | 2019-10-08 | Ethicon Llc | Surgical instrument with selectively disengageable threaded drive systems |
US10368861B2 (en) | 2015-06-18 | 2019-08-06 | Ethicon Llc | Dual articulation drive system arrangements for articulatable surgical instruments |
US10835249B2 (en) | 2015-08-17 | 2020-11-17 | Ethicon Llc | Implantable layers for a surgical instrument |
BR112018003693B1 (en) | 2015-08-26 | 2022-11-22 | Ethicon Llc | SURGICAL STAPLE CARTRIDGE FOR USE WITH A SURGICAL STAPPING INSTRUMENT |
US10357251B2 (en) | 2015-08-26 | 2019-07-23 | Ethicon Llc | Surgical staples comprising hardness variations for improved fastening of tissue |
MX2022009705A (en) | 2015-08-26 | 2022-11-07 | Ethicon Llc | Surgical staples comprising hardness variations for improved fastening of tissue. |
US10251648B2 (en) | 2015-09-02 | 2019-04-09 | Ethicon Llc | Surgical staple cartridge staple drivers with central support features |
MX2022006189A (en) | 2015-09-02 | 2022-06-16 | Ethicon Llc | Surgical staple configurations with camming surfaces located between portions supporting surgical staples. |
US10327769B2 (en) | 2015-09-23 | 2019-06-25 | Ethicon Llc | Surgical stapler having motor control based on a drive system component |
US10238386B2 (en) | 2015-09-23 | 2019-03-26 | Ethicon Llc | Surgical stapler having motor control based on an electrical parameter related to a motor current |
US10105139B2 (en) | 2015-09-23 | 2018-10-23 | Ethicon Llc | Surgical stapler having downstream current-based motor control |
US10363036B2 (en) | 2015-09-23 | 2019-07-30 | Ethicon Llc | Surgical stapler having force-based motor control |
US10076326B2 (en) | 2015-09-23 | 2018-09-18 | Ethicon Llc | Surgical stapler having current mirror-based motor control |
US10085751B2 (en) | 2015-09-23 | 2018-10-02 | Ethicon Llc | Surgical stapler having temperature-based motor control |
US10299878B2 (en) | 2015-09-25 | 2019-05-28 | Ethicon Llc | Implantable adjunct systems for determining adjunct skew |
US10603039B2 (en) | 2015-09-30 | 2020-03-31 | Ethicon Llc | Progressively releasable implantable adjunct for use with a surgical stapling instrument |
US10271849B2 (en) | 2015-09-30 | 2019-04-30 | Ethicon Llc | Woven constructs with interlocked standing fibers |
US11890015B2 (en) | 2015-09-30 | 2024-02-06 | Cilag Gmbh International | Compressible adjunct with crossing spacer fibers |
US10980539B2 (en) | 2015-09-30 | 2021-04-20 | Ethicon Llc | Implantable adjunct comprising bonded layers |
KR20180082477A (en) * | 2015-11-12 | 2018-07-18 | 큐리컬 테크놀로지스 엘티디. | A biocompatible article having a built-in copper ion and copper ion release coating |
US10292704B2 (en) | 2015-12-30 | 2019-05-21 | Ethicon Llc | Mechanisms for compensating for battery pack failure in powered surgical instruments |
US10368865B2 (en) | 2015-12-30 | 2019-08-06 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10265068B2 (en) | 2015-12-30 | 2019-04-23 | Ethicon Llc | Surgical instruments with separable motors and motor control circuits |
US10433837B2 (en) | 2016-02-09 | 2019-10-08 | Ethicon Llc | Surgical instruments with multiple link articulation arrangements |
BR112018016098B1 (en) | 2016-02-09 | 2023-02-23 | Ethicon Llc | SURGICAL INSTRUMENT |
US11213293B2 (en) | 2016-02-09 | 2022-01-04 | Cilag Gmbh International | Articulatable surgical instruments with single articulation link arrangements |
US11224426B2 (en) | 2016-02-12 | 2022-01-18 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10258331B2 (en) | 2016-02-12 | 2019-04-16 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10448948B2 (en) | 2016-02-12 | 2019-10-22 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10314582B2 (en) | 2016-04-01 | 2019-06-11 | Ethicon Llc | Surgical instrument comprising a shifting mechanism |
US10617413B2 (en) | 2016-04-01 | 2020-04-14 | Ethicon Llc | Closure system arrangements for surgical cutting and stapling devices with separate and distinct firing shafts |
US10492783B2 (en) | 2016-04-15 | 2019-12-03 | Ethicon, Llc | Surgical instrument with improved stop/start control during a firing motion |
US10456137B2 (en) | 2016-04-15 | 2019-10-29 | Ethicon Llc | Staple formation detection mechanisms |
US10405859B2 (en) | 2016-04-15 | 2019-09-10 | Ethicon Llc | Surgical instrument with adjustable stop/start control during a firing motion |
US10335145B2 (en) | 2016-04-15 | 2019-07-02 | Ethicon Llc | Modular surgical instrument with configurable operating mode |
US10828028B2 (en) | 2016-04-15 | 2020-11-10 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US11607239B2 (en) | 2016-04-15 | 2023-03-21 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10357247B2 (en) | 2016-04-15 | 2019-07-23 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US10426467B2 (en) | 2016-04-15 | 2019-10-01 | Ethicon Llc | Surgical instrument with detection sensors |
US11179150B2 (en) | 2016-04-15 | 2021-11-23 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10426469B2 (en) | 2016-04-18 | 2019-10-01 | Ethicon Llc | Surgical instrument comprising a primary firing lockout and a secondary firing lockout |
US20170296173A1 (en) | 2016-04-18 | 2017-10-19 | Ethicon Endo-Surgery, Llc | Method for operating a surgical instrument |
US11317917B2 (en) | 2016-04-18 | 2022-05-03 | Cilag Gmbh International | Surgical stapling system comprising a lockable firing assembly |
CN109310431B (en) | 2016-06-24 | 2022-03-04 | 伊西康有限责任公司 | Staple cartridge comprising wire staples and punch staples |
USD847989S1 (en) | 2016-06-24 | 2019-05-07 | Ethicon Llc | Surgical fastener cartridge |
US11000278B2 (en) | 2016-06-24 | 2021-05-11 | Ethicon Llc | Staple cartridge comprising wire staples and stamped staples |
USD826405S1 (en) | 2016-06-24 | 2018-08-21 | Ethicon Llc | Surgical fastener |
USD850617S1 (en) | 2016-06-24 | 2019-06-04 | Ethicon Llc | Surgical fastener cartridge |
US10993715B2 (en) | 2016-12-21 | 2021-05-04 | Ethicon Llc | Staple cartridge comprising staples with different clamping breadths |
US20180168625A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Surgical stapling instruments with smart staple cartridges |
US11684367B2 (en) | 2016-12-21 | 2023-06-27 | Cilag Gmbh International | Stepped assembly having and end-of-life indicator |
US20180168598A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Staple forming pocket arrangements comprising zoned forming surface grooves |
JP7010956B2 (en) | 2016-12-21 | 2022-01-26 | エシコン エルエルシー | How to staple tissue |
US10588630B2 (en) | 2016-12-21 | 2020-03-17 | Ethicon Llc | Surgical tool assemblies with closure stroke reduction features |
US10568625B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Staple cartridges and arrangements of staples and staple cavities therein |
US11134942B2 (en) | 2016-12-21 | 2021-10-05 | Cilag Gmbh International | Surgical stapling instruments and staple-forming anvils |
US20180168615A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument |
US10856868B2 (en) | 2016-12-21 | 2020-12-08 | Ethicon Llc | Firing member pin configurations |
US10945727B2 (en) | 2016-12-21 | 2021-03-16 | Ethicon Llc | Staple cartridge with deformable driver retention features |
US10568624B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Surgical instruments with jaws that are pivotable about a fixed axis and include separate and distinct closure and firing systems |
US10888322B2 (en) | 2016-12-21 | 2021-01-12 | Ethicon Llc | Surgical instrument comprising a cutting member |
JP6983893B2 (en) | 2016-12-21 | 2021-12-17 | エシコン エルエルシーEthicon LLC | Lockout configuration for surgical end effectors and replaceable tool assemblies |
US10687810B2 (en) | 2016-12-21 | 2020-06-23 | Ethicon Llc | Stepped staple cartridge with tissue retention and gap setting features |
US10675025B2 (en) | 2016-12-21 | 2020-06-09 | Ethicon Llc | Shaft assembly comprising separately actuatable and retractable systems |
MX2019007311A (en) | 2016-12-21 | 2019-11-18 | Ethicon Llc | Surgical stapling systems. |
US11191540B2 (en) | 2016-12-21 | 2021-12-07 | Cilag Gmbh International | Protective cover arrangements for a joint interface between a movable jaw and actuator shaft of a surgical instrument |
US20180168648A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Durability features for end effectors and firing assemblies of surgical stapling instruments |
US10426471B2 (en) | 2016-12-21 | 2019-10-01 | Ethicon Llc | Surgical instrument with multiple failure response modes |
US10610224B2 (en) | 2016-12-21 | 2020-04-07 | Ethicon Llc | Lockout arrangements for surgical end effectors and replaceable tool assemblies |
US11419606B2 (en) | 2016-12-21 | 2022-08-23 | Cilag Gmbh International | Shaft assembly comprising a clutch configured to adapt the output of a rotary firing member to two different systems |
US10695055B2 (en) | 2016-12-21 | 2020-06-30 | Ethicon Llc | Firing assembly comprising a lockout |
US11090048B2 (en) | 2016-12-21 | 2021-08-17 | Cilag Gmbh International | Method for resetting a fuse of a surgical instrument shaft |
US10390841B2 (en) | 2017-06-20 | 2019-08-27 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
US10779820B2 (en) | 2017-06-20 | 2020-09-22 | Ethicon Llc | Systems and methods for controlling motor speed according to user input for a surgical instrument |
US11653914B2 (en) | 2017-06-20 | 2023-05-23 | Cilag Gmbh International | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector |
US11382638B2 (en) | 2017-06-20 | 2022-07-12 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified displacement distance |
US10888321B2 (en) | 2017-06-20 | 2021-01-12 | Ethicon Llc | Systems and methods for controlling velocity of a displacement member of a surgical stapling and cutting instrument |
US11071554B2 (en) | 2017-06-20 | 2021-07-27 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on magnitude of velocity error measurements |
US10368864B2 (en) | 2017-06-20 | 2019-08-06 | Ethicon Llc | Systems and methods for controlling displaying motor velocity for a surgical instrument |
US10307170B2 (en) | 2017-06-20 | 2019-06-04 | Ethicon Llc | Method for closed loop control of motor velocity of a surgical stapling and cutting instrument |
USD890784S1 (en) | 2017-06-20 | 2020-07-21 | Ethicon Llc | Display panel with changeable graphical user interface |
USD879809S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with changeable graphical user interface |
US10624633B2 (en) | 2017-06-20 | 2020-04-21 | Ethicon Llc | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument |
US11090046B2 (en) | 2017-06-20 | 2021-08-17 | Cilag Gmbh International | Systems and methods for controlling displacement member motion of a surgical stapling and cutting instrument |
US10327767B2 (en) | 2017-06-20 | 2019-06-25 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
US10646220B2 (en) | 2017-06-20 | 2020-05-12 | Ethicon Llc | Systems and methods for controlling displacement member velocity for a surgical instrument |
US10980537B2 (en) | 2017-06-20 | 2021-04-20 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified number of shaft rotations |
US10881396B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Surgical instrument with variable duration trigger arrangement |
US11517325B2 (en) | 2017-06-20 | 2022-12-06 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval |
US10813639B2 (en) | 2017-06-20 | 2020-10-27 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on system conditions |
US10881399B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument |
USD879808S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with graphical user interface |
US10856869B2 (en) | 2017-06-27 | 2020-12-08 | Ethicon Llc | Surgical anvil arrangements |
US10993716B2 (en) | 2017-06-27 | 2021-05-04 | Ethicon Llc | Surgical anvil arrangements |
US11266405B2 (en) | 2017-06-27 | 2022-03-08 | Cilag Gmbh International | Surgical anvil manufacturing methods |
US10631859B2 (en) | 2017-06-27 | 2020-04-28 | Ethicon Llc | Articulation systems for surgical instruments |
US11324503B2 (en) | 2017-06-27 | 2022-05-10 | Cilag Gmbh International | Surgical firing member arrangements |
US10772629B2 (en) | 2017-06-27 | 2020-09-15 | Ethicon Llc | Surgical anvil arrangements |
USD854151S1 (en) | 2017-06-28 | 2019-07-16 | Ethicon Llc | Surgical instrument shaft |
US10903685B2 (en) | 2017-06-28 | 2021-01-26 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies forming capacitive channels |
US10716614B2 (en) | 2017-06-28 | 2020-07-21 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies with increased contact pressure |
US10765427B2 (en) | 2017-06-28 | 2020-09-08 | Ethicon Llc | Method for articulating a surgical instrument |
US11564686B2 (en) | 2017-06-28 | 2023-01-31 | Cilag Gmbh International | Surgical shaft assemblies with flexible interfaces |
USD906355S1 (en) | 2017-06-28 | 2020-12-29 | Ethicon Llc | Display screen or portion thereof with a graphical user interface for a surgical instrument |
EP4070740A1 (en) | 2017-06-28 | 2022-10-12 | Cilag GmbH International | Surgical instrument comprising selectively actuatable rotatable couplers |
US11678880B2 (en) | 2017-06-28 | 2023-06-20 | Cilag Gmbh International | Surgical instrument comprising a shaft including a housing arrangement |
USD851762S1 (en) | 2017-06-28 | 2019-06-18 | Ethicon Llc | Anvil |
US20190000461A1 (en) | 2017-06-28 | 2019-01-03 | Ethicon Llc | Surgical cutting and fastening devices with pivotable anvil with a tissue locating arrangement in close proximity to an anvil pivot axis |
US11259805B2 (en) | 2017-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical instrument comprising firing member supports |
USD869655S1 (en) | 2017-06-28 | 2019-12-10 | Ethicon Llc | Surgical fastener cartridge |
US10211586B2 (en) | 2017-06-28 | 2019-02-19 | Ethicon Llc | Surgical shaft assemblies with watertight housings |
US11246592B2 (en) | 2017-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical instrument comprising an articulation system lockable to a frame |
US11007022B2 (en) | 2017-06-29 | 2021-05-18 | Ethicon Llc | Closed loop velocity control techniques based on sensed tissue parameters for robotic surgical instrument |
US10258418B2 (en) | 2017-06-29 | 2019-04-16 | Ethicon Llc | System for controlling articulation forces |
US10932772B2 (en) | 2017-06-29 | 2021-03-02 | Ethicon Llc | Methods for closed loop velocity control for robotic surgical instrument |
US10898183B2 (en) | 2017-06-29 | 2021-01-26 | Ethicon Llc | Robotic surgical instrument with closed loop feedback techniques for advancement of closure member during firing |
US10398434B2 (en) | 2017-06-29 | 2019-09-03 | Ethicon Llc | Closed loop velocity control of closure member for robotic surgical instrument |
US11944300B2 (en) | 2017-08-03 | 2024-04-02 | Cilag Gmbh International | Method for operating a surgical system bailout |
US11471155B2 (en) | 2017-08-03 | 2022-10-18 | Cilag Gmbh International | Surgical system bailout |
US11304695B2 (en) | 2017-08-03 | 2022-04-19 | Cilag Gmbh International | Surgical system shaft interconnection |
USD907648S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
USD917500S1 (en) | 2017-09-29 | 2021-04-27 | Ethicon Llc | Display screen or portion thereof with graphical user interface |
USD907647S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
US10743872B2 (en) | 2017-09-29 | 2020-08-18 | Ethicon Llc | System and methods for controlling a display of a surgical instrument |
US10765429B2 (en) | 2017-09-29 | 2020-09-08 | Ethicon Llc | Systems and methods for providing alerts according to the operational state of a surgical instrument |
US11399829B2 (en) | 2017-09-29 | 2022-08-02 | Cilag Gmbh International | Systems and methods of initiating a power shutdown mode for a surgical instrument |
US10796471B2 (en) | 2017-09-29 | 2020-10-06 | Ethicon Llc | Systems and methods of displaying a knife position for a surgical instrument |
US10729501B2 (en) | 2017-09-29 | 2020-08-04 | Ethicon Llc | Systems and methods for language selection of a surgical instrument |
US11134944B2 (en) | 2017-10-30 | 2021-10-05 | Cilag Gmbh International | Surgical stapler knife motion controls |
US11090075B2 (en) | 2017-10-30 | 2021-08-17 | Cilag Gmbh International | Articulation features for surgical end effector |
US10842490B2 (en) | 2017-10-31 | 2020-11-24 | Ethicon Llc | Cartridge body design with force reduction based on firing completion |
US10779903B2 (en) | 2017-10-31 | 2020-09-22 | Ethicon Llc | Positive shaft rotation lock activated by jaw closure |
US10966718B2 (en) | 2017-12-15 | 2021-04-06 | Ethicon Llc | Dynamic clamping assemblies with improved wear characteristics for use in connection with electromechanical surgical instruments |
US11197670B2 (en) | 2017-12-15 | 2021-12-14 | Cilag Gmbh International | Surgical end effectors with pivotal jaws configured to touch at their respective distal ends when fully closed |
US10779826B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Methods of operating surgical end effectors |
US10743874B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Sealed adapters for use with electromechanical surgical instruments |
US10779825B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Adapters with end effector position sensing and control arrangements for use in connection with electromechanical surgical instruments |
US11071543B2 (en) | 2017-12-15 | 2021-07-27 | Cilag Gmbh International | Surgical end effectors with clamping assemblies configured to increase jaw aperture ranges |
US10687813B2 (en) | 2017-12-15 | 2020-06-23 | Ethicon Llc | Adapters with firing stroke sensing arrangements for use in connection with electromechanical surgical instruments |
US10828033B2 (en) | 2017-12-15 | 2020-11-10 | Ethicon Llc | Handheld electromechanical surgical instruments with improved motor control arrangements for positioning components of an adapter coupled thereto |
US10869666B2 (en) | 2017-12-15 | 2020-12-22 | Ethicon Llc | Adapters with control systems for controlling multiple motors of an electromechanical surgical instrument |
US10743875B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Surgical end effectors with jaw stiffener arrangements configured to permit monitoring of firing member |
US11006955B2 (en) | 2017-12-15 | 2021-05-18 | Ethicon Llc | End effectors with positive jaw opening features for use with adapters for electromechanical surgical instruments |
US11033267B2 (en) | 2017-12-15 | 2021-06-15 | Ethicon Llc | Systems and methods of controlling a clamping member firing rate of a surgical instrument |
USD910847S1 (en) | 2017-12-19 | 2021-02-16 | Ethicon Llc | Surgical instrument assembly |
US11045270B2 (en) | 2017-12-19 | 2021-06-29 | Cilag Gmbh International | Robotic attachment comprising exterior drive actuator |
US11020112B2 (en) | 2017-12-19 | 2021-06-01 | Ethicon Llc | Surgical tools configured for interchangeable use with different controller interfaces |
US10729509B2 (en) | 2017-12-19 | 2020-08-04 | Ethicon Llc | Surgical instrument comprising closure and firing locking mechanism |
US10835330B2 (en) | 2017-12-19 | 2020-11-17 | Ethicon Llc | Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly |
US10716565B2 (en) | 2017-12-19 | 2020-07-21 | Ethicon Llc | Surgical instruments with dual articulation drivers |
US11076853B2 (en) | 2017-12-21 | 2021-08-03 | Cilag Gmbh International | Systems and methods of displaying a knife position during transection for a surgical instrument |
US11311290B2 (en) | 2017-12-21 | 2022-04-26 | Cilag Gmbh International | Surgical instrument comprising an end effector dampener |
US11129680B2 (en) | 2017-12-21 | 2021-09-28 | Cilag Gmbh International | Surgical instrument comprising a projector |
US11337691B2 (en) | 2017-12-21 | 2022-05-24 | Cilag Gmbh International | Surgical instrument configured to determine firing path |
US11440867B2 (en) * | 2018-05-07 | 2022-09-13 | Kvi Llc | Medical lubricant |
US11207065B2 (en) | 2018-08-20 | 2021-12-28 | Cilag Gmbh International | Method for fabricating surgical stapler anvils |
US11324501B2 (en) | 2018-08-20 | 2022-05-10 | Cilag Gmbh International | Surgical stapling devices with improved closure members |
US10779821B2 (en) | 2018-08-20 | 2020-09-22 | Ethicon Llc | Surgical stapler anvils with tissue stop features configured to avoid tissue pinch |
US11253256B2 (en) | 2018-08-20 | 2022-02-22 | Cilag Gmbh International | Articulatable motor powered surgical instruments with dedicated articulation motor arrangements |
USD914878S1 (en) | 2018-08-20 | 2021-03-30 | Ethicon Llc | Surgical instrument anvil |
US11039834B2 (en) | 2018-08-20 | 2021-06-22 | Cilag Gmbh International | Surgical stapler anvils with staple directing protrusions and tissue stability features |
US11083458B2 (en) | 2018-08-20 | 2021-08-10 | Cilag Gmbh International | Powered surgical instruments with clutching arrangements to convert linear drive motions to rotary drive motions |
US10856870B2 (en) | 2018-08-20 | 2020-12-08 | Ethicon Llc | Switching arrangements for motor powered articulatable surgical instruments |
US10912559B2 (en) | 2018-08-20 | 2021-02-09 | Ethicon Llc | Reinforced deformable anvil tip for surgical stapler anvil |
US11291440B2 (en) | 2018-08-20 | 2022-04-05 | Cilag Gmbh International | Method for operating a powered articulatable surgical instrument |
US11045192B2 (en) | 2018-08-20 | 2021-06-29 | Cilag Gmbh International | Fabricating techniques for surgical stapler anvils |
US10842492B2 (en) | 2018-08-20 | 2020-11-24 | Ethicon Llc | Powered articulatable surgical instruments with clutching and locking arrangements for linking an articulation drive system to a firing drive system |
US11147553B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11696761B2 (en) | 2019-03-25 | 2023-07-11 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11147551B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11172929B2 (en) | 2019-03-25 | 2021-11-16 | Cilag Gmbh International | Articulation drive arrangements for surgical systems |
US11452528B2 (en) | 2019-04-30 | 2022-09-27 | Cilag Gmbh International | Articulation actuators for a surgical instrument |
US11471157B2 (en) | 2019-04-30 | 2022-10-18 | Cilag Gmbh International | Articulation control mapping for a surgical instrument |
US11648009B2 (en) | 2019-04-30 | 2023-05-16 | Cilag Gmbh International | Rotatable jaw tip for a surgical instrument |
US11426251B2 (en) | 2019-04-30 | 2022-08-30 | Cilag Gmbh International | Articulation directional lights on a surgical instrument |
US11432816B2 (en) | 2019-04-30 | 2022-09-06 | Cilag Gmbh International | Articulation pin for a surgical instrument |
US11903581B2 (en) | 2019-04-30 | 2024-02-20 | Cilag Gmbh International | Methods for stapling tissue using a surgical instrument |
US11253254B2 (en) | 2019-04-30 | 2022-02-22 | Cilag Gmbh International | Shaft rotation actuator on a surgical instrument |
US11291451B2 (en) | 2019-06-28 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with battery compatibility verification functionality |
US11224497B2 (en) | 2019-06-28 | 2022-01-18 | Cilag Gmbh International | Surgical systems with multiple RFID tags |
US11246678B2 (en) | 2019-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical stapling system having a frangible RFID tag |
US11523822B2 (en) | 2019-06-28 | 2022-12-13 | Cilag Gmbh International | Battery pack including a circuit interrupter |
US11051807B2 (en) | 2019-06-28 | 2021-07-06 | Cilag Gmbh International | Packaging assembly including a particulate trap |
US11376098B2 (en) | 2019-06-28 | 2022-07-05 | Cilag Gmbh International | Surgical instrument system comprising an RFID system |
US11684434B2 (en) | 2019-06-28 | 2023-06-27 | Cilag Gmbh International | Surgical RFID assemblies for instrument operational setting control |
US11771419B2 (en) | 2019-06-28 | 2023-10-03 | Cilag Gmbh International | Packaging for a replaceable component of a surgical stapling system |
US11219455B2 (en) | 2019-06-28 | 2022-01-11 | Cilag Gmbh International | Surgical instrument including a lockout key |
US11638587B2 (en) | 2019-06-28 | 2023-05-02 | Cilag Gmbh International | RFID identification systems for surgical instruments |
US11298127B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Interational | Surgical stapling system having a lockout mechanism for an incompatible cartridge |
US11497492B2 (en) | 2019-06-28 | 2022-11-15 | Cilag Gmbh International | Surgical instrument including an articulation lock |
US11627959B2 (en) | 2019-06-28 | 2023-04-18 | Cilag Gmbh International | Surgical instruments including manual and powered system lockouts |
US11259803B2 (en) | 2019-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical stapling system having an information encryption protocol |
US11298132B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Inlernational | Staple cartridge including a honeycomb extension |
US11478241B2 (en) | 2019-06-28 | 2022-10-25 | Cilag Gmbh International | Staple cartridge including projections |
US11241235B2 (en) | 2019-06-28 | 2022-02-08 | Cilag Gmbh International | Method of using multiple RFID chips with a surgical assembly |
US11660163B2 (en) | 2019-06-28 | 2023-05-30 | Cilag Gmbh International | Surgical system with RFID tags for updating motor assembly parameters |
US11399837B2 (en) | 2019-06-28 | 2022-08-02 | Cilag Gmbh International | Mechanisms for motor control adjustments of a motorized surgical instrument |
US11464601B2 (en) | 2019-06-28 | 2022-10-11 | Cilag Gmbh International | Surgical instrument comprising an RFID system for tracking a movable component |
US11426167B2 (en) | 2019-06-28 | 2022-08-30 | Cilag Gmbh International | Mechanisms for proper anvil attachment surgical stapling head assembly |
US11553971B2 (en) | 2019-06-28 | 2023-01-17 | Cilag Gmbh International | Surgical RFID assemblies for display and communication |
JP6896241B2 (en) * | 2019-12-11 | 2021-06-30 | ケイセイ医科工業株式会社 | Medical suture |
JP6896240B2 (en) * | 2019-12-11 | 2021-06-30 | ケイセイ医科工業株式会社 | Medical suture |
US11931033B2 (en) | 2019-12-19 | 2024-03-19 | Cilag Gmbh International | Staple cartridge comprising a latch lockout |
US11559304B2 (en) | 2019-12-19 | 2023-01-24 | Cilag Gmbh International | Surgical instrument comprising a rapid closure mechanism |
US11701111B2 (en) | 2019-12-19 | 2023-07-18 | Cilag Gmbh International | Method for operating a surgical stapling instrument |
US11446029B2 (en) | 2019-12-19 | 2022-09-20 | Cilag Gmbh International | Staple cartridge comprising projections extending from a curved deck surface |
US11464512B2 (en) | 2019-12-19 | 2022-10-11 | Cilag Gmbh International | Staple cartridge comprising a curved deck surface |
US11504122B2 (en) | 2019-12-19 | 2022-11-22 | Cilag Gmbh International | Surgical instrument comprising a nested firing member |
US11844520B2 (en) | 2019-12-19 | 2023-12-19 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11607219B2 (en) | 2019-12-19 | 2023-03-21 | Cilag Gmbh International | Staple cartridge comprising a detachable tissue cutting knife |
US11291447B2 (en) | 2019-12-19 | 2022-04-05 | Cilag Gmbh International | Stapling instrument comprising independent jaw closing and staple firing systems |
US11529139B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Motor driven surgical instrument |
US11234698B2 (en) | 2019-12-19 | 2022-02-01 | Cilag Gmbh International | Stapling system comprising a clamp lockout and a firing lockout |
US11529137B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11911032B2 (en) | 2019-12-19 | 2024-02-27 | Cilag Gmbh International | Staple cartridge comprising a seating cam |
US11304696B2 (en) | 2019-12-19 | 2022-04-19 | Cilag Gmbh International | Surgical instrument comprising a powered articulation system |
US11576672B2 (en) | 2019-12-19 | 2023-02-14 | Cilag Gmbh International | Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw |
AU2021102033A4 (en) * | 2020-04-17 | 2021-06-10 | Kraton Polymers Research B.V. | Self-sterilizing wound dressing |
USD976401S1 (en) | 2020-06-02 | 2023-01-24 | Cilag Gmbh International | Staple cartridge |
USD975278S1 (en) | 2020-06-02 | 2023-01-10 | Cilag Gmbh International | Staple cartridge |
USD975850S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD966512S1 (en) | 2020-06-02 | 2022-10-11 | Cilag Gmbh International | Staple cartridge |
USD974560S1 (en) | 2020-06-02 | 2023-01-03 | Cilag Gmbh International | Staple cartridge |
USD975851S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD967421S1 (en) | 2020-06-02 | 2022-10-18 | Cilag Gmbh International | Staple cartridge |
US11883024B2 (en) | 2020-07-28 | 2024-01-30 | Cilag Gmbh International | Method of operating a surgical instrument |
US11517390B2 (en) | 2020-10-29 | 2022-12-06 | Cilag Gmbh International | Surgical instrument comprising a limited travel switch |
US11844518B2 (en) | 2020-10-29 | 2023-12-19 | Cilag Gmbh International | Method for operating a surgical instrument |
US11534259B2 (en) | 2020-10-29 | 2022-12-27 | Cilag Gmbh International | Surgical instrument comprising an articulation indicator |
US11896217B2 (en) | 2020-10-29 | 2024-02-13 | Cilag Gmbh International | Surgical instrument comprising an articulation lock |
US11452526B2 (en) | 2020-10-29 | 2022-09-27 | Cilag Gmbh International | Surgical instrument comprising a staged voltage regulation start-up system |
USD980425S1 (en) | 2020-10-29 | 2023-03-07 | Cilag Gmbh International | Surgical instrument assembly |
US11779330B2 (en) | 2020-10-29 | 2023-10-10 | Cilag Gmbh International | Surgical instrument comprising a jaw alignment system |
US11617577B2 (en) | 2020-10-29 | 2023-04-04 | Cilag Gmbh International | Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable |
US11931025B2 (en) | 2020-10-29 | 2024-03-19 | Cilag Gmbh International | Surgical instrument comprising a releasable closure drive lock |
US11717289B2 (en) | 2020-10-29 | 2023-08-08 | Cilag Gmbh International | Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable |
USD1013170S1 (en) | 2020-10-29 | 2024-01-30 | Cilag Gmbh International | Surgical instrument assembly |
US11890010B2 (en) | 2020-12-02 | 2024-02-06 | Cllag GmbH International | Dual-sided reinforced reload for surgical instruments |
US11744581B2 (en) | 2020-12-02 | 2023-09-05 | Cilag Gmbh International | Powered surgical instruments with multi-phase tissue treatment |
US11653920B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Powered surgical instruments with communication interfaces through sterile barrier |
US11737751B2 (en) | 2020-12-02 | 2023-08-29 | Cilag Gmbh International | Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings |
US11944296B2 (en) | 2020-12-02 | 2024-04-02 | Cilag Gmbh International | Powered surgical instruments with external connectors |
US11849943B2 (en) | 2020-12-02 | 2023-12-26 | Cilag Gmbh International | Surgical instrument with cartridge release mechanisms |
US11653915B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Surgical instruments with sled location detection and adjustment features |
US11627960B2 (en) | 2020-12-02 | 2023-04-18 | Cilag Gmbh International | Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections |
US11678882B2 (en) | 2020-12-02 | 2023-06-20 | Cilag Gmbh International | Surgical instruments with interactive features to remedy incidental sled movements |
US11751869B2 (en) | 2021-02-26 | 2023-09-12 | Cilag Gmbh International | Monitoring of multiple sensors over time to detect moving characteristics of tissue |
US11793514B2 (en) | 2021-02-26 | 2023-10-24 | Cilag Gmbh International | Staple cartridge comprising sensor array which may be embedded in cartridge body |
US11812964B2 (en) | 2021-02-26 | 2023-11-14 | Cilag Gmbh International | Staple cartridge comprising a power management circuit |
US11744583B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Distal communication array to tune frequency of RF systems |
US11701113B2 (en) | 2021-02-26 | 2023-07-18 | Cilag Gmbh International | Stapling instrument comprising a separate power antenna and a data transfer antenna |
US11925349B2 (en) | 2021-02-26 | 2024-03-12 | Cilag Gmbh International | Adjustment to transfer parameters to improve available power |
US11696757B2 (en) | 2021-02-26 | 2023-07-11 | Cilag Gmbh International | Monitoring of internal systems to detect and track cartridge motion status |
US11749877B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Stapling instrument comprising a signal antenna |
US11950777B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Staple cartridge comprising an information access control system |
US11730473B2 (en) | 2021-02-26 | 2023-08-22 | Cilag Gmbh International | Monitoring of manufacturing life-cycle |
US11723657B2 (en) | 2021-02-26 | 2023-08-15 | Cilag Gmbh International | Adjustable communication based on available bandwidth and power capacity |
US11950779B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Method of powering and communicating with a staple cartridge |
US11826012B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Stapling instrument comprising a pulsed motor-driven firing rack |
US11717291B2 (en) | 2021-03-22 | 2023-08-08 | Cilag Gmbh International | Staple cartridge comprising staples configured to apply different tissue compression |
US11759202B2 (en) | 2021-03-22 | 2023-09-19 | Cilag Gmbh International | Staple cartridge comprising an implantable layer |
US11826042B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Surgical instrument comprising a firing drive including a selectable leverage mechanism |
US11723658B2 (en) | 2021-03-22 | 2023-08-15 | Cilag Gmbh International | Staple cartridge comprising a firing lockout |
US11737749B2 (en) | 2021-03-22 | 2023-08-29 | Cilag Gmbh International | Surgical stapling instrument comprising a retraction system |
US11806011B2 (en) | 2021-03-22 | 2023-11-07 | Cilag Gmbh International | Stapling instrument comprising tissue compression systems |
US11793516B2 (en) | 2021-03-24 | 2023-10-24 | Cilag Gmbh International | Surgical staple cartridge comprising longitudinal support beam |
US11832816B2 (en) | 2021-03-24 | 2023-12-05 | Cilag Gmbh International | Surgical stapling assembly comprising nonplanar staples and planar staples |
US11944336B2 (en) | 2021-03-24 | 2024-04-02 | Cilag Gmbh International | Joint arrangements for multi-planar alignment and support of operational drive shafts in articulatable surgical instruments |
US11786239B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Surgical instrument articulation joint arrangements comprising multiple moving linkage features |
US11903582B2 (en) | 2021-03-24 | 2024-02-20 | Cilag Gmbh International | Leveraging surfaces for cartridge installation |
US11849944B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Drivers for fastener cartridge assemblies having rotary drive screws |
US11849945B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Rotary-driven surgical stapling assembly comprising eccentrically driven firing member |
US11896219B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Mating features between drivers and underside of a cartridge deck |
US11786243B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Firing members having flexible portions for adapting to a load during a surgical firing stroke |
US11744603B2 (en) | 2021-03-24 | 2023-09-05 | Cilag Gmbh International | Multi-axis pivot joints for surgical instruments and methods for manufacturing same |
US11896218B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Method of using a powered stapling device |
US11857183B2 (en) | 2021-03-24 | 2024-01-02 | Cilag Gmbh International | Stapling assembly components having metal substrates and plastic bodies |
US11826047B2 (en) | 2021-05-28 | 2023-11-28 | Cilag Gmbh International | Stapling instrument comprising jaw mounts |
US11957337B2 (en) | 2021-10-18 | 2024-04-16 | Cilag Gmbh International | Surgical stapling assembly with offset ramped drive surfaces |
US11877745B2 (en) | 2021-10-18 | 2024-01-23 | Cilag Gmbh International | Surgical stapling assembly having longitudinally-repeating staple leg clusters |
US11937816B2 (en) | 2021-10-28 | 2024-03-26 | Cilag Gmbh International | Electrical lead arrangements for surgical instruments |
WO2023214966A1 (en) * | 2022-05-04 | 2023-11-09 | Intrinsic Advanced Materials, LLC | Continuous production of biodegradable polyesters |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4047533A (en) * | 1976-09-20 | 1977-09-13 | American Cyanamid Company | Absorbable surgical sutures coated with polyoxyethylene-polyoxypropylene copolymer lubricant |
US4954593A (en) * | 1989-08-18 | 1990-09-04 | Gaf Chemical Corporation | Furanone/vinyl ether copolymers |
US6228954B1 (en) * | 1991-02-12 | 2001-05-08 | United States Surgical Corporation | Blends of glycolide and/or lactide polymers and caprolactone and/or trimethylene carbonate polymers and absorabable surgical devices made therefrom |
US5330768A (en) * | 1991-07-05 | 1994-07-19 | Massachusetts Institute Of Technology | Controlled drug delivery using polymer/pluronic blends |
US5352515A (en) * | 1992-03-02 | 1994-10-04 | American Cyanamid Company | Coating for tissue drag reduction |
CA2092646A1 (en) * | 1992-03-25 | 1993-09-26 | Ross R. Muth | Bioabsorbable blends of a bioabsorbable copolymer and a poly(oxyalkylene) |
DK1125577T3 (en) * | 1994-04-08 | 2006-06-19 | Qlt Usa Inc | Liquid drug delivery preparations |
DK0752245T3 (en) * | 1995-07-05 | 2002-09-09 | Europ Economic Community | Biocompatible and biodegradable nanoparticles developed for the absorption and delivery of proteinaceous drugs |
US6143037A (en) * | 1996-06-12 | 2000-11-07 | The Regents Of The University Of Michigan | Compositions and methods for coating medical devices |
US5716376A (en) * | 1996-06-28 | 1998-02-10 | United States Surgical Corporation | Absorbable mixture and coatings for surgical articles fabricated therefrom |
AUPP297898A0 (en) * | 1998-04-16 | 1998-05-07 | Unisearch Limited | Production of furanones |
US6177094B1 (en) * | 1998-04-30 | 2001-01-23 | United States Surgical Corporation | Bioabsorbable blends and coating composition containing same |
EP1095665B1 (en) * | 1998-07-07 | 2008-09-03 | Nof Corporation | Wound-covering preparation, wound-covering material, and method of wound healing |
US6653423B1 (en) * | 1999-07-14 | 2003-11-25 | Nof Corporation | Random copolymers, process for the production thereof and medical material |
US6730313B2 (en) * | 2000-01-25 | 2004-05-04 | Edwards Lifesciences Corporation | Delivery systems for periadventitial delivery for treatment of restenosis and anastomotic intimal hyperplasia |
WO2001068052A2 (en) * | 2000-03-10 | 2001-09-20 | Johns Hopkins University | Phosphate based biodegradable polymers |
CA2451432A1 (en) * | 2001-06-23 | 2003-01-03 | Lyotropic Therapeutics, Inc. | Particles with improved solubilization capacity |
CN1303155C (en) * | 2001-10-18 | 2007-03-07 | 株式会社三养社 | Polymeric michelle composition with improved stability |
US6939554B2 (en) * | 2002-02-05 | 2005-09-06 | Michigan Biotechnology Institute | Antimicrobial polymer |
US7279174B2 (en) * | 2003-05-08 | 2007-10-09 | Advanced Cardiovascular Systems, Inc. | Stent coatings comprising hydrophilic additives |
US20050175667A1 (en) * | 2004-02-10 | 2005-08-11 | Wenda Carlyle | Use of endothelin antagonists to prevent restenosis |
CA2526541C (en) | 2004-12-01 | 2013-09-03 | Tyco Healthcare Group Lp | Novel biomaterial drug delivery and surface modification compositions |
EP2024113A4 (en) | 2006-05-15 | 2012-07-25 | Tyco Healthcare | Antimicrobial coatings |
EP2046932A2 (en) * | 2006-08-03 | 2009-04-15 | Ciba Holding Inc. | Composition for improving wettability of surfaces |
-
2005
- 2005-11-10 CA CA2526541A patent/CA2526541C/en not_active Expired - Fee Related
- 2005-11-16 AU AU2005234622A patent/AU2005234622B2/en not_active Ceased
- 2005-11-24 ES ES05025635T patent/ES2340044T3/en active Active
- 2005-11-24 EP EP05025635A patent/EP1669093B1/en not_active Expired - Fee Related
- 2005-11-24 DE DE602005019523T patent/DE602005019523D1/en active Active
- 2005-11-30 JP JP2005347327A patent/JP2006152306A/en not_active Withdrawn
- 2005-12-01 US US11/292,172 patent/US7850982B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
DE602005019523D1 (en) | 2010-04-08 |
US7850982B2 (en) | 2010-12-14 |
JP2006152306A (en) | 2006-06-15 |
EP1669093A1 (en) | 2006-06-14 |
AU2005234622B2 (en) | 2011-07-28 |
CA2526541A1 (en) | 2006-06-01 |
US20060193884A1 (en) | 2006-08-31 |
EP1669093B1 (en) | 2010-02-24 |
ES2340044T3 (en) | 2010-05-28 |
AU2005234622A1 (en) | 2006-06-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2526541C (en) | Novel biomaterial drug delivery and surface modification compositions | |
US8263105B2 (en) | Biomaterial drug delivery and surface modification compositions | |
AU2008203080B2 (en) | Phospholipid copolymers | |
US7901705B2 (en) | Antimicrobial releasing polymers | |
EP1825928A1 (en) | Pressurized dip coating system | |
JP2010240411A (en) | Wound closure material | |
JP2008272467A (en) | Coated filament | |
US7666973B2 (en) | Carbonate copolymers | |
Hernandez et al. | Reduction of suture associated inflammation after 28 days using novel biocompatible pseudoprotein poly (ester amide) biomaterials | |
US9433639B2 (en) | Synthetic mechanical hemostatic composition, method of making and use thereof | |
JP2011019902A (en) | Method for coating medical device | |
US8268958B2 (en) | Phospholipid copolymers | |
WO2013154570A1 (en) | Synthetic mechanical hemostatic composition, method of making and use thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed |
Effective date: 20161110 |
|
MKLA | Lapsed |
Effective date: 20161110 |