CA2114290C - Post-surgical anti-adhesion device - Google Patents
Post-surgical anti-adhesion device Download PDFInfo
- Publication number
- CA2114290C CA2114290C CA002114290A CA2114290A CA2114290C CA 2114290 C CA2114290 C CA 2114290C CA 002114290 A CA002114290 A CA 002114290A CA 2114290 A CA2114290 A CA 2114290A CA 2114290 C CA2114290 C CA 2114290C
- Authority
- CA
- Canada
- Prior art keywords
- bioabsorbable
- layer
- adhesion barrier
- mole percent
- block
- 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 - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S602/00—Surgery: splint, brace, or bandage
- Y10S602/904—Film-forming bandage material
Abstract
Surgical adhesion barriers and methods of using such surgical adhesion barriers are provided. Surgical adhesion barriers according to the present invention have at least one layer of a bioabsorbable material comprising copolymers and/or block copolymers derived from trimethylene carbonate. Alternatively, a multilayer surgical structure having one or more bioabsorbable layers superimposed on a non-absorbable layer is useful for minimizing or preventing formation of fibrous adhesions between a healing trauma site and adjacent surrounding tissue. Alternatively, a bioabsorbable non-woven fabric in adherent contact with at least one bioabsorbable layer of foam, film, mesh, web or woven fabric is also provided. One or more medicinal agents may be interposed between or disposed within any of the aforementioned layers.
Description
POST-SURGICAL ANTI-ADHESION DEVICE
BACKGROUND OF THE INVENTION
1. Field of the Invention The present invention relates to minimization and/or prevention of post-surgical adhesions and more particularly, to devices and methods for preventing the formation of such adhesions between a healing trauma site and adjacent surrounding tissue.
BACKGROUND OF THE INVENTION
1. Field of the Invention The present invention relates to minimization and/or prevention of post-surgical adhesions and more particularly, to devices and methods for preventing the formation of such adhesions between a healing trauma site and adjacent surrounding tissue.
2. Description of Related Art Injury, surgical incision or abrasion to the peritoneum, pleural or abdominal cavity results in an outpouring of a serosanguinous exudate. The exudate subsequently coagulates, producing fibrinous bands between abutting surfaces which can become organized by fibroblast proliferation to become collagenous adhesions. Adhesions are also known to form at bone fracture sites where jagged, irregular bone edges form in the area of the fracture. Bony spurs promote the growth of fibrous adhesions between the bone fracture surface and surrounding tissue.
Adhesion formation following surgery or trauma is generally considered to be undesirable. For example, adhesions that form in relation to intestinal surgery, e.g., bowel resection, hernia repair, etc. may cause obstruction of the intestine. Adhesions that form near the bone fracture site may reduce or hinder the normal movement of the area of repair by restricting the natural movement of tendons over the adjacent bane. Adhesions may also form in the vicinity of nerves and disrupt nerve transmissions with a' resultant diminution of sensory or motor function.
Various methods and substances have been used in the hope of preventing post-operative adhesions. Certain drugs and surfactants have been suggested. For example, U.S. Patent No.
4,911,926 is directed to adhesion prevention by application of aqueous and non-aqueous compositions of a polyoxyalkylene block copolymer to injured areas of the peritoneal or pleural cavity or organs situated therein subsequent to surgical injury.
Another approach to adhesion prevention involves application of a physical barrier at the area of surgical injury.
U.S. Patent No. 4,674,488 is directed to interposing a barrier layer of soft biological tissue, such as collagen, collagen-fabric films, collagen membranes, or reconstituted collagen or Dacron~ mesh, at the interface of a bone fracture and the surrounding tissue. U.S. Patent No. 4,603,695 is directed to a molded polymeric material for preventing adhesion of vital tissues. The polymeric material is made of a biodegradable and absorbable polymer such as certain polyesters, collagen, amino acid polymers and chitin and may be placed where there is a possibility of adhesion setting in.
Other materials have also been used to form physical barriers in an attempt to prevent adhesions, including silicone elastomers, gelatin films and knit fabrics of oxidized, regenerated cellulose (hereinafter ORC). In some cases, it is suggested that heparin, heparinoid, or he~curonyl hexosaminoglycan be incorporated into a matrix of ORC fabric or other matrices of hyaluronic arid, cross-linked! and, uncross-linked collagen ;webs, synthetic resorbable polymers, gelatin films, absorbable gel films, oxidized cellulose fabrics and films which are fabricated into a form that is said to be drapable, conformable and adherent to body organs and substantially absorbable within 30 days. See, e.g., U.S. Patent No. 4,840,626 or EPA Pub. No. 0 262 890 or EPA
Pub. No. 0 372 969.
Physical barriers are also used to cover and protect wound sites. WO 9210218 is directed to a surgical article having a bioabsorbable fibrous matrix in a laminar relationship with a bioabsorbable cell barrier sheet. U.S. Patent No.
5,092,884 and EPA Pub. No. 0 334 046 are directed to a surgical composite structure having absorbable and non-absorbable components which may be useful for repairing anatomical defects, e.g., preventing hernia formation in an infected area. The nonabsorbable portion of the composite acts as a reinforcement material. Ingrowth of natural tissue is said to be enhanced by controlled degradation of the absorbable portion. U.S. Patent No. 5,035,893 relates to a wound covering composition having a sheet of biopolymeric material and a film of polyurethane resin.
An antibacterial agent may be provided between the polyurethane film and the sheet of biopolymeric material, thereby forming a three-layer wound covering material. With the cure of the wound, it is said that the biopolymeric material is taken in a living tissue and the polyurethane film can be peeled off from the sheet without hurting the surface of a wound.
SUMMARY OF THE INVENTION
The present invention provides surgical adhesion barriers and methods of using surgical adhesion barriers which have at least one layer of bioabsorbable material. The bioabsorbable material comprises copolymers, block copolymers or blends thereof. The copolymers comprises carbonates and at least one other bioabsorbable polymer forming material. The block copolymers comprise at least one block comprising trimethylene carbonate. In one embodiment the block copolymer comprises a first block formed from a copolymer having a predominant amount _4_ of trimethylene carbonate and a second block formed from a copolymer having a predominant amount of lactide.
In another embodiment, the.present invention provides a multilayer surgical structure having one bioabsorbable layer affixed to a non-absorbable layer. Both the absorbable and the non-absorbable layer may be fashioned from mesh, web, woven fabric, non-woven fabric, porous film, non-porous film or foam.
The structure is made by superimposing a layer of bioabsorbable material on a non-absorbable layer. In alternative embodiments subsequent bioabsorbable layers can be added. Additionally, one or more medicinal agents can be interposed between any of the aforementioned layers.
In another embodiment, the present invention provides a multilayer surgical structure having a bioabsorbable non-woven fabric in adherent contact with one or more bioabsorbable layers Which may be in the form of film, foam, mesh, web or woven .fabric.
The surgical adhesion barrier or multilayer surgical structure in flexible, resilient and conformable to various shapes such as body organs and tissues. During surgery, a surgical adhesion barrier according to the present invention is positioned at the area of injury to prevent adhesions as desired.
Likewise, a multilayer surgical structure according to the present invention having absorbable and non-absorbable layers is positioned at the area of injury to prevent adhesions as desired.
In the case of a multilayer adhesion barrier, the nonabsorbable layer is preferably positioned adjacent to the area of injury and the 'bioabsorbable layer('s)'fade'away from the ihjury. As the bioabsorbable layer is absorbed, any adhesions which may have attached to the bioabsorbable.layer lose their support and fall free of the injury site.
21I!~2~~
In yet another embodiment, the multilayer surgical structure incorporates a plurality of bioabsorbable layers which bioabsorb at different rates. Each layer of bioabsorbable material is absorbed over time, thus exposing and releasing any medicinal agents which may be contained between layers.
The structures of the present. invention may find application for open general surgery or less invasive surgical techniques such as endoscopic surgery, or both.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. leis a diagram of a stuffer box / crimper suitable for processing filaments used in the manufacture absorbable non-woven fabric for use in the present invention.
DETAILED DESCRIPTION OF THE INVENTION
A surgical adhesion barrier according to the present invention prevents formation of surgical adhesions at a surgical wound by interposing a unique bioabsorbable barrier between the surgical wound and surrounding tissue.
In accordance with one aspect of the present invention, a surgical adhesion barrier is constructed from a single layer of bioabsorbable material. The bioabsorbable material is made of copolymers of carbonates and at least one other bioabsorbable palymer forming material. Carbonates which are useful according to the present invention may be represented by the structural units of ,. ~ , ,, .~~ , ' ;r ~ , , , ,, formula (-Rn-O-C-0-) where~.n R is a carbon atom~and n preferably ranges from about 1 to about 8. Examples of suitable carbonates include dimethylene carbonate, trimethylene carbonate, 2~i~w~~
tetramethylene carbonate, pentamethylene carbonate, hexamethylene carbonate and the like.
Suitable bioabsorbable polymer forming materials which maybe copolymerized with a suitable carbonate include materials capable of forming hydrolyzable polyesters. Suitable materials capable of forming hydrolyzable polyesters include glycolide and lactide: hydroxyacids such as glycolic acid, lactic acid, hydroxy butyric acids, and hydroxyvaleric acids; lactones such as !3-propio-lactone, 7-caprolactone, e-caprolactone, methyl-caprolactone, dioxanone, p-dioxanone, methyl-p-dioxanone, dimethyl-p-dioxanone, and !3-malolactone; and polyalkylene oxides such as polyoxyethylene glycol and polyoxypropylene glycol and mixtures, blends, and copolymers thereof.
The single layer surgical adhesion barrier embodiment of the present invention preferably comprises a bioabsorbable copolymer of trimethylene carbonate and glycolide, the trimethylene carbonate being present in a predominant amount. A
"predominant amount", as used herein, is an amount greater than 50 mole percent of a composition. Preferably, the concentration of glycoside and trimethylene carbonate in this embodiment of the present invention is about 20 and 80 mole percent, respectively.
Suitable single layer surgical adhesion barriers of the present invention can also be fabricated from block copolymers having one or more "A" blocks comprising a carbonate as described above and a bioabsorbable polymer forming material as described above, and one or more "B" blocks comprising a bioabsorbable polymer forming material as described above. Preferably the "A"
blacks are'p~esent in~amounts-ranging from about 10% to about 90%
and the "B" blocks are present in amounts ranging from about l0%
to about 90%. In a still more preferred embodiment, the "A"
blocks are present in an amount ranging from about 15 weight percent to about 85 weight percent and the "B" blocks present in 21i~~~~
_7_ an amount ranging from about 15 weight percent to about 85 weight percent. Most preferably, the "A" and "B" blocks are present in amounts of about 50 percent by weight each.
Suitable "A" blocks include a predominant amount, i.e., greater than about 50 mole percent, of trimethylene carbonate.
Preferably the trimethylene carbonate ranges from about 75 mole percent to about 95 mole percent. A more preferable concentration of trimethylene carbonate ranges from about 80 mole percent to about 90 mole percent and is most preferably about 80 mole percent. The trim~ethylene carbonate may be copolymerized with any monomer which provides an absorbable copolymer to form the "A" block. Such monomers include but are not limited to glycolide, lactide, dioxanone, epsilon caprolactone, with glycolide being preferred.
Suitable "B" blocks include a predominant amount of lactide (i.e., greater than about 50 mole percent) but preferably ranging from about 75 mole percent to about 95 mole percent. A
more preferable concentration of lactide ranges from about 80 mole peroent to about 90 mole percent and is most preferably about 80 mole percent. The lactide may be copolymerized with any monomer such that an absorbable copolymer is provided to form the "B" block. Such monomers include but are not limited to glyaolide, dioxanone, and epsilon caprolactone,.trimethylene carbonate, with glycolide being preferred.
An adhesion barrier constructed from a single layer of bioabsorbable material may be in the form :of mesh, web, woven fabric, non-woven fabric, foam, matrix or, most preferably, film.
A noil-porous jingle layer ad~iesi'on barr'i~r is least likely' to ' allow adhesions to penetrate through to adjacent tissue.
An adhesion barrier film made of the above-described materials can be made by standard polymer film forming techniques, e.g., compression of, copolymer resin between heated _8.
polytetrafluoroethylene (PTFE) coated plates. Other film forming techniques are described in, e.g., the Encyclopedia of Polymer Science and Engineering, Vol. 12, pp. 204-210 (1988). The thickness of the film can range from about 0.1 mil to about 100 mil, and is most preferably about 1 mil to about 3 mil.
In another embodiment, a single layer foam bioabsorbable surgical adhesion barrier made of the above described materials can be made in accordance with known foam forming techniques such as those disclosed in U.S. Patent Nos.
3,902,497 or 5,102,983, whose contents are incorporated herein by reference. The foam may be sliced and/or cut to desired thickness and configuration before surgical use. The thickness of the foam layer can range from about 0.1 mil to about 100 mil, and is most preferably about 1 mil to about 3 mil.
A single layer bioabsorbable surgical adhesion barrier according to the present invention is flexible, resilient and conformable to the shape of underlying tissue. Films and foams constructed from the above-described polymers are well suited for draping over and conforming to areas of surgical wounds or injury and are especially well suited for endoscopic surgery, e.g., laparoscopy.
In another aspect of the present invention, a surgical adhesion barrier is formed from two layers, i.e., a bioabsorbable layer superimposed on a non-absorbable layer. The non-absorbable layer is flexible and provides support and shape. The non-absorbable layer can be made from biocompatible materials which are formed into a mesh, web, foam, woven fabric, non-woven fabric, porous film or non-porous film.
Biocompatible materials which are suitable for forming the non-absorbable layer are well-known and include fluoropolymers, polyesters, e.g polyethylene terephthalate or 21~9:~~C
polybutylene terephthalate, polyetherimide esters, polyolefins, polyamides, polybutesters, and/or copolymers and/or blends of the same. These materials are exemplified by polytetrafluoroethylene (PTFE), silicone rubbers, urethanes, polyethylene, polypropylene, polyvinyl alcohol, polyvinyl chloride, cellulose, cellulose derivatives, fibroin, etc. Polypropylene is a preferred non-absorbable biocompatible material.
The non-absorbable layer can range from substantially non-porous to an open mesh. A non-porous non-absorbable layer substantially prevents the transmission of vapor, fluid or other substances from the wound site to the surrounding environment and, conversely, from the surrounding environment to the wound site. A porous film, matrix, mesh, web or fabric does permit such transmission. For reasons elaborated on below, a non-absorbable layer which permits transmission of vapor, fluid, or other substance may be desirable for use in aiding the healing process or in delivering a medicinal agent to the area of injury.
Such a mesh material can promote the ingrowth of new tissue during the healing process. Methods of forming mesh, webs, woven fabrics, non-woven fabrics, matrices, foams, porous films and non-porous films from the above-noted materials are known to those with skill in the art.
The bioabsorbable layer of a two layer surgical adhesion barrier includes the same materials and forms described above in relation to a single layer bioabsorbable surgical adhesion barrier. The bioabsorbable layer according to the present invention may be in the form of mesh, web, woven-fabric, non-woven fabric, foam, matrix, or film. The thickness of ; each bioabsorbable layer can range from about 0.1 mil to about 100 mil, but preferably about l mil to about 3 mil. Non-porous films are preferred for use as the bioabsorbable layer in the present invention because adhesions are less likely to penetrate through to an underlying layer.
In a preferred embodiment of the two layer adhesion barrier, a bioabsorbable substantially non-porous layer is pressed onto a mesh (preferably about 12 inches x about 36 inches) constructed from polypropylene. The bioabsorbable layer is preferably made from either 1) a copolymer of about 20 mole percent glycolide and about 80 mole percent trimethylene carbonate or 2) a block copolymer having one block containing about 20 mole percent glycolide and about 80 mole percent trimethylene carbonate and another block containing about 20 mole percent glycolide and about 80 mole percent lactide wherein both blocks are present in equal weight ratios. In manufacturing a two layer surgical adhesion barrier according to the present invention a bioabsorbable layer is superimposed or affixed to a non-absorbable layer. For example, affixation may be accomplished by coating the bioabsorbable layer onto the non-absorbable layer.
In one embodiment, the bioabsorbable polymer forming the bioabsorbable layer is melted and then coated on the non-absorbable mesh. Alternatively, the bioabsorbable polymer is dissolved in solvent and solution coated on to the mesh. The solvent is then evaporated by drying. The bioabsorbable layer may also be applied to the non-bioabsorbable layer by transfer coating techniques, such as these described in the Encyclopedia of Polymer Science pp. 377-382 (1985). Alternatively, a commercially available press machine is used to press a preformed film on to the mesh, or the polymer is calendared to form a film and then pressed on to the mesh. Techniques used for calendaring are well-known, e.g., techniques described in the Encyclopedia of Polymer Science and Engineering, Vol. 2, pp. 606-622 (1985). The layers may 2~.~.4Z~~
also be joined by laminating the bioabsorbable layer to the non-absorbable layer. In lamination, the bioabsorbable layer may be applied to the non-absorbable layer by any method known to those with skill in the art, such as with an adhesive, for example, acrylic, silicone, polyphenolic bioadhesive, etc.
A two layer surgical adhesion barrier according to the present invention is flexible, resilient and conformable to the shape of underlying tissue. Such an adhesion barrier is well suited to be applied to a target site with minimally invasive techniques such as those involving endoscopy. After being positioned, two layer surgical adhesion barriers may optionally be sutured, stapled or otherwise fastened to the target site.
In another aspect of the present invention, a plurality of bioabsorbable layers are superimposed on a non-absorbable layer in any of the aforementioned forms to form a surgical adhesion barrier. As above, the non-absorbable layer can be formed from biocompatible materials such as fluoropolymers, polyesters e.g. polybutylene terephthalate and polyethylene terephthalate, polyolefins, polyamides, polybutesters, polyetherimide esters, and/or copolymers and/or blends of the same. These materials are exemplified by polytetrafluoroethylene (PTFE), silicone rubbers, urethanes, polyethylene, polypropylene, polyvinyl alcohol, polyvinyl chloride, cellulose, cellulose derivatives, fibroin, etc. Polypropylene is a preferred non-absorbable layer.
Non-absorbable layers useful in ahis aspect.of the present invention can range from the substantially non-porous to the 'open meshes described above.' Biocompatible~bioabsorbable materials useful in this aspect of the present invention include polymers and/or copolymers and/or blends of the aforementioned bioabsorbable materials.
2~i~~~i~
Other examples of suitable biocompatible polymers are polyhydroxyalkyl methacrylates including ethylmethacrylate, and hydrogels such as polyvinylpyrrolidone, polyacrylamides, etc.
Other suitable bioabsorbable materials are biopolymers which include collagen, gelatin, alginic acid, chitin, chitosan, fibrin, hyaluronic acid, dextran and polyamino acids. Any combination, copolymer, polymer or blend thereof of the above examples are contemplated for use according to the present invention. Such bioabsorbable materials may be prepared by known methods.
A surgical adhesion barrier having a plurality of bioabsorbable layers can be formed by superimposing a first bioabsorbable layer on a nonabsorbable layer by any of the techniques which are,described in relation to forming a two layer surgical adhesion barrier. A second bioabsorbable layer is then superimposed or affixed to the first bioabsorbable layer by such means as are. described above. In this manner, a third, fourth, fifth, etc. bioabsorbable layer may be successively incorporated into the surgical device of the present invention.
Alternatively, a first bioabsorbable layer may be superimposed on a second bioabsorbable layer to form a two layer bioabsorbable composite. Optionally, a third, fourth, fifth, etc. layer can be added successively to form a multilayer bioabsorbable composite which is then superimposed on a non-absorbable layer by such means that' are described above.
The physical form of each successive bioabsorbable layer in all above and below-described embodiments and aspects of the~pres~ent invention~can vairy'.' For example, the outermost bioabsorbable layer can be a film and an adjacent bioabsorbable layer can be, e.g., a mesh, film, foam or non-woven fabric. Any number of such combinations are contemplated by the present invention.
2~~!~2~~
In another aspect of the present invention, at least one bioabsorbable non-woven fabric layer is superimposed or affixed to at least one bioabsorbable layer which may be a film, mesh, web, foam, woven fabric or other non-woven fabric. The bioabsorbable materials used to form the non-woven fabric layers) include all known bioabsorbable materials and combinations of such materials capable of being formed into fibers including those previously referred to herein. Methods for making non-woven fabrics are generally known in the art.
Preferably, a low density non-woven bioabsorbable fabric is used to carry out the present invention. In one preferred embodiment, the low density bioabsorbable non-woven fabric is manufactured from a 92.5/7.5 (mole percent) glycolide/lactide polymer yarn. The polymer is spun and drawn into a 69 filament 14 ply multifilament yarn of about 1.6 denier per filament. The 14 plyes are combined together by using a creel and a constant speed winder to prepare 1541 denier plied yarn. The yarn is crimped into a stuffer box according to the preferred specifications shown in Table I, below, with reference to Figure 1.
TABLE I
CRIMPING STUFFERBOX CRIMPER
Conditions No. of yarn ends feeding from creel 1 ,, , r Total Yarn denier 1545 (14 ply x 69 filaments/yarn x 1.6 dpf Gate Tension 1 Setting 4 Godet Setup:
21i~2J1~
No. of wraps on the pre-heat godet19 Pre-heat Godet Set Temp. 108 C
Pre-heat Godet Indicating Temp. 110 C
Speed 31 meters/minute I'nfeed Gears (adjusts infeed yarn48 x 18 tensi Stuffer Chamber Setup:
Column Temp. Set Point (back only)96 C
Indicating Temp. of Column 99 C
8" glass column front Working Stack Height in Column 26x15 Gate Tension II Setting 0.5 Crimp Analysis:
Average No. of Crimps/inch 23.7 Range (Min./Max.) 16/36 The crimped yarn is cut into staples having fibers ranging from about 2-2.50 inches with an average length of about 2.25 inches. The staples are then carded to form a web. Prior to web formation, 'the staple fibers are passed through the card once to open the fibers. After opening, approximately 55 grams of opened fibers are used to produce a carded web having a basis weight of approximately 100 g/m2, with dimensions of about 0.22m x about 1.9m. The carding specifications are shown in Table II.
TABLE II
Carding 12" metallic card with variab speed control Card conditions Main Cylinder Speed 186-188 rpms Worker Cylinders ,, ~ ~ ~ . ,21-22 rpms , Stripper Cylinders 335 rpms Take-off Apron 53 rpms 2~~.~~~~
From about one to about four carded web layers are then cross-lapped and needle-punched twice to form the bioabsorbable non-woven fabric. All web layers are combined during the first needle-punch pass. The second needle-punch pass is "dry", i.e., no webs are added. The first needle-punch pass involves the face fabric direction with about 320 needle penetrations per square inch to a depth of about 4mm. The second needle-punch pass involves the back fabric direction with about 320 needle penetrations per square inch to a depth of about 8mm. Certain other needling parameters are shown in Table III.
TABLE III
Needling 12" James Hunter Fiberlocker Needlinct Parameters Needle Type Groz Beckert, GB 30's T5 x 18 x 36 x 3 Barb Types: 5333; 69219 Needling Rate 120 strokes/minute Needling Board Density 46 needles/linear inch When using two carded web layers, the resulting non-woven fabric is about 0.5 meters wide, less than about 2.5mm thick and has a density of between about 0.05 g/cu.cm and about 0.10 g/cu.cm. Preferably, the density is between about 0.065 g/cu.cm and about 0.085 g/cu.cm. The basis weight of the fabric depends on the number of carded web layers needled together.
Each carded web layer has a basis weight of between about 50 g/sq.m and about 100 g/sq.m.~ Preferably, the carded web layer' basis weight is about 80 g/sq.m. The basis weight of a two layer fabric, for example, is between about 100 g/sq.m and about 200 g/sq.m and preferably about 160 g/sq.m. Optionally, the fabric can be coated or filled with various storage stabilizing agents, such as those disclosed in commonly assigned U.S. Patent No. 5,032,429. Such storage stabilizing agents can include, for example, glycerol and calcium lactate.
According to the present invention, the thickness of the non-woven fabric can range from about 0.5 mm to about 5 mm, and is preferably about 1.75 mm to about 3 mm, but most preferably about 2.5 mm. In another preferred embodiment, the mole percent ratio of glycolide to lactide is about 20:80, and most preferably about 18:82, and can be manufactured in a manner as described above.
The non-woven fabric layers) are superimposed or affixed to at least one bioabsorbable layer of foam, film, mesh, web, woven fabric or other non-woven fabric. Bioabsorbable foam layers discussed previously in relation to single layer bioabsorbable surgical adhesion barriers herein are suitable for superimposing or affixing to the non-woven fabric layer.
Bioabsorbable meshes, webs, woven fabrics or other non-woven fabrics can be manufactured by known techniques and also superimposed or affixed to the non-woven fabric layers) in accordance with the present invention. In a preferred embodiment, the non-woven fabric is superimposed on or affixed to a bioabsorbable film. Bioabsorbable film made of any of the above-described bioabsorbable polymers, copolymers, or blends thereof can be manufactured by standard polymer film forming techniques, e.g. compression of polymer resin between PTFE coated platens. Other film forming techniques are described in, e.g., the Encyclopedia of Polymer Science and Engineering, Vol. 12, pp.
204-210 (1988). In a most preferred embodiment the bioabsorbable polymer is dissolved in a suitable solvent, e.g., methylene chloride, acetone, etc., to form a mixture of desired viscosity 2~~.~2~~J
which is coated onto release means such as release paper or the like to form a film. During evaporation of the solvent, a bioabsorbable non-woven fabric layers) is placed on the wet film. The film then adheres to the non-woven fabric and the release means is removed. The film may range from 0.1 mil to 4 mil and is preferably about 2 mil.
The bioabsorbable foam or film may be fabricated from any of the well known bioabsorbable polymers used in medicine. A
preferred bioabsorbable polymer for use in the foam or film is described above in accordance with a surgical adhesion barrier constructed from a single layer of bioabsorbable material, i.e., copolymers of carbonates and at least one other bioabsorbable material. A highly preferred bioabsorbable polymer for use in the foam or film is fabricated from block copolymers having about 50% by weight of an "A" block comprising about 40 mole percent glycolide and about 60 mole percent trimethylene carbonate and about 50% by weight of a "B" block comprising about 20 mole percent lactide and about 80 mole percent glycolide. Another highly preferred bioabsorbable polymer is fabricated from block copolymers having about 20% by weight of an "A" block comprising about 20 mole percent glycolide and about 80 mole percent trimethylene carbonate and about 80% by weight of a "B" block comprising about 20 mole percent glycolide and about 80 mole percent lactide.
As above, additional bioabsorbable layers may be affixed or superimposed to form surgical adhesion barriers of greater than two layers. The same techniques for affixing or super'impo5ing~~a bioabsorbabLe~layer to~a nonabsorbable layer described above are applicable to any of the layers involving non-woven bioabsorbable fabric. The successive layers may comprise differing chemical compositions and/or physical forms to yield adhesion barriers of markedly different characteristics depending. on intended use.
In all the above aspects and embodiments, the rate of bioabsorption of each bioabsorbable layer can be varied by changing the chemical make up and/or thickness of each successive layer. Various bioabsorbable polymers, copolymers and/or blends thereof are known to have different rates of absorption. For example, bioabsorbable polymers having a high degree of crystallinity are absorbed less rapidly than bioabsorbable polymers having relatively higher amounts of amorphous regions.
Thus, rates of bioabsorption can be engineered to fit particular needs. In this way, an outermost bioabsorbable layer can be constructed to slowly biodegrade and, when it does, adhesions which have formed between the outer layer and surrounding tissue fall away. Any slower forming adhesions which may have adhered through the outermost layer to an inner layer would then be disconnected by the absorption of a rapidly biodegrading inner layer. Alternatively, a rapidly bioabsorbed outer layer would act as the first line of defense against rapidly forming adhesions and a slower bioabsorbed inner layer would prevent the attachment of late forming adhesions.
Optionally, one or more medicinal agents may be interposed between one or more layers of a surgical device according to the present invention.
The present invention provides a versatile scheduled release medicinal agents) delivery system. For example, a bioabsorbable layer that has been engineered for rapid absorption releases any;~medicina~l agents'~contained between such layer and an adjacent layer within a relatively fast time frame. If the next bioabsorbable layer is engineered to be absorbed more slowly any medicinal agent contained between such layer and a next adjacent layer will be released within that time. Thus, a schedule of 2:~L~~~J~3 therapy is created with delivery at two distinct points in time, i.e., first, following implantation and absorption of the rapidly bioabsorbable layer, and second, after absorption of the more slowly absorbed layer.
Optionally, one or more medicinal agents may be mixed or ground into the above-mentioned bioabsorbable polymeric materials prior to formation of a coating or layers. See, e.g., U.S. Patent No. 3,991,766. In this manner, the medicinal agent is slowly released as the bioabsorbable layer is absorbed. The non-absorbable layer can also be manufactured such that a medicinal agent is integrally incorporated therein and diffuses or is transported to the wound site therefrom. For example, a medicinal agent can be co-extruded with a polymer such as polypropylene to form fibers containing the medicinal agent.
The term "medicinal agent", as used herein, is meant to be interpreted broadly and includes any substance or mixture of substances which may have any clinical use in medicine. Thus medicinal agents include drugs, enzymes, proteins, peptides, glycoproteins, or diagnostic agents such as releasable dyes which may have no biological activity per se.
Examples of classes of medicinal agents that can be used in accordance with the present invention include antimicrobials, analgesics, antipyretics, anesthetics, antiepi~,eptics, antihistamines, anti-inflammatories, cardiovascular drugs, diagnostic agents, sympathomimetic, cholinomimetic, anti-muscarinics, antispasmodics, hormones, growth factors, muscle relaxants, adrenergic neuron blockers, anti-neoplas~~ics, immunasuppressants , gastrointestinal drugs, .
diuretics, steroids and enzymes. It is also intended that combinations of medicinals can be used in accordance with the present invention.
2~.~.~~~~~
Thus, in one embodiment of the present invention focal delivery and application of a medicinal agent to the wound site is achieved. Focal application can be more desirable than general systemic application in some cases, e.g., chemotherapy for localized tumors, because it produces fewer side effects in distant tissues or organs and also concentrates therapy at intended sites. Focal application of growth factors, anti-inflammatories, immune system suppressants and/or antimicrobials by a the anti-adhesion device of the present invention is an ideal drug delivery system to speed healing of a wound or incision.
A post surgical anti-adhesion device or structure of the present invention is generally used in the form of a sheet of a desired size and shape. A surgeon may cut a custom shape from preformed sheets to suit particular applications. After the device is shaped for a suitable fit, the flexible nature of the device enables the surgeon to conform the device to fit around the area of injury. In one embodiment, the device is formed into a strip which wraps around the organ, e.g., an intestine, to prevent formation of adhesions. An anti-adhesion device according to the present invention can incorporate ties or straps which connect to the device and which are used to tie or otherwise secure the device to an area of injury. It is further contemplated that the anti-adhesion devices of the present invention may be affixed to the wound site by surgical fasteners or sutures. The flexible nature of the present anti-adhesion device allows the device to flex and bend along with normal movements of; the body,wiithout~being overly restrictive.
All embodiments of surgical adhesion barriers or structures as described herein are well-suited for application by techniques involving endoscopy. Endoscopic surgical procedures involve the use of cannulas or tubes which provide narrow openings into a body and allow minimally invasive access to surgical targets. In laparoscopic procedures, surgery is performed in the interior of the abdomen through small tubes inserted therein. Endoscopes are frequently used as viewing devices inserted through the cannulas which allow surgeons to see the interior of the body.
Certain endoscopic and laparoscopic procedures may require that the surgical region be insufflated. Accordingly, any instrumentation inserted into the body should be substantially sealed to ensure that gases do not enter or exit the body through the incision. Moreover, endoscopic and laparoscopic procedures often require the surgeon to operate on organs, tissues and/or vessels far removed from the incision. Thus, instruments used in such procedures are typically long and narrow while being functionally controllable from a proximal end of the instrument.
In accordance with the present invention an apparatus for deploying and positioning any of the adhesion barriers or structures disclosed herein may be inserted through a cannula and deposited at a target site. Once the barrier is positioned as desired, it may optionally be sutured, stapled or otherwise fastened to the target site with instruments designed to be inserted through a cannula.
In order that those skilled in the art may be better able to practice the present invention, the following examples are given as an illustration of the preparation and superior characteristics of the anti-adhesion devices of the present invention. It should be noted that the invention is not limited to the specific details embo'di'ed in the' examples.
21fi~~2'~' Copolymer of Glycolide/Trimethylene Carbonate (Polymer I) A 20/80 mole percent glycolide/trimethylene carbonate copolymer was prepared in a reactor by combining previously dried 53.13 grams of glycolide and 186.87 grams of trimethylene carbonate and polymerizing at 160°C for 24 hours in the presence of 0.05 grams of stannous octoate. The polymer was extruded from the reactor and post treated to remove any residual monomer present in the polymer. The inherent viscosity of the polymer was 0.9.
Copolymer of Glycolide/Trimethylene Carbonate/Lactide (Polymer II) A block copolymer having one block containing 20 mole percent glycdlide and 80 mole percent tiimethylene carbonate and another block containing 20 mole percent glycolide and 80 mole percent lactide, wherein both blocks are present in equal weight ratios was prepared in a reactor. 553.4 grams of glycolide and 1946.6 grams of trimethylene carbonate were added to the reactor along with 1.0 grams of stannous octoate and dried under vacuum in the reactor for about 16 hrs. After drying, the reactants were heated at 150°C and polymerized for about 24 hrs. At this stage 419.1 grams of dried glycolide and 2080.9 grams of Lactide were 'added'and continued poly~herizing df'additidnal 2'4 hrs~. The polymer is extruded and post treated to remove any residual monomers present in the polymer. The inherent viscosity of this polymer was 1.32.
2~.~~2~~~
Copolymer of Glycolide/Trimethylene Carbonate/Lactide (Polymer III) A block copolymer having 50% by weight of one block containing 40 mole percent glycolide and 60 mole percent trimethylene carbonate and 50% by weight of another block containing 20 mole percent glycolide and 80 mole percent lactide was prepared in a reactor. 646.7 grams of glycolide and 853 grams of trimethylene carbonate were added to the reactor along with 0.6 grams of stannous octoate and dried under vacuum in the reactor for about 24 hours at 160°C. At this stage 251 grams of glycolide and 1248 grams of lactide were added and polymerized for an additional 24 hours at 170°C. The polymer was extruded and post treated to remove any residual monomers present in the polymer. The inherent viscosity of this polymer was in the range of 0.4-0.8 dl/g.
Copolymer of Glycolide/Trimethylene Carbonate/Lactide (Polymer IV) A block copolymer having 20% by weight of one block containing 20 mole percent glycolide and 80 mole percent trimethylene carbonate and 80% by weight of another block containing 20 mole percent glycolide and .80 mole percent lactide was prepared in a reactor. 132.8 grams of glycolide and 467.2 grams of tr~;methylen'e darbdnate were added to the reactor~along with 0.6 grams of stannous octoate and dried under vacuum in the reactor for about 24 hours. At this stage 402 grams of glycolide and 1998 grams of lactide were added and polymerized for an additiona1124 hours. The polymer was extruded and post treated 2~.1~~~ ~~
to remove any residual monomers present in the polymer. The inherent viscosity of this polymer was of 0.0 to 1.1 dl/g.
Construction of Multilayer Adhesion Barrier Polymer I, made in accordance with Example 1, was pressed into a film by means of a vacuum press supplied by Technical Machine Products, Cleveland, Ohio, a standard commercial press having PTFE coated platens. The temperature of the platens was maintained at about 130°C. The platens were pressed together at a load of about 25,000 pounds for about 12 minutes. The resulting film was then removed from the press.
To bond the polymer film to a polypropylene mesh, the film was placed against the mesh and pressed together by the PTFE
coated platens of a vacuum press supplied by Technical Machine Products, Cleveland, Ohio. The temperature of the platens was maintained at about 65°C and the platens were pressed together at a load of about 1000 pounds for about 5 minutes. The multilayer adhesion barrier was then removed from the press.
., , 2~.~.~~'~'~
Construction of Multilayer Adhesion Barrier Polymer II, made in accordance with Example 2,is pressed into a film in a manner similar to that described in Example 3 except that the platens were heated to a temperature of about 190°C and pressed together at a load of about 3000 pounds.
To bond the polymer film to a polypropylene mesh, the film was placed against the mesh and pressed together by the PTFE
coated platens of a vacuum press supplied by Technical Machine Products, Cleveland, Ohio. The temperature of the platens was maintained at about 120°C and the platens were pressed together at a load of about 3000 pounds for about 5 minutes. The resulting multilayer adhesion barrier was then removed from the press.
Construction of Bioabsorbable Non-Woven Fabric A copolymer of about 18 mole percent glycolide and about 82 mole percent lactide was spun and drawn into a 40 filament 14 ply multifilament yarn. The plies were combined (1120 denier total) and crimped by stuffer box crimper. The crimped yarn was aut into staples of about 2 inches. The staple fibers were opened and carded on a carding machine and converted to a web having a basis weight of approximately 100 g/m2.. Two web layers were needled together to form non-woven fabric (200'g%m2) which was 'washed'i:n''wat8r for~5 minutes and dried in~
vacuum. The dried fabric was post treated at 90°C for 16 hours and then platen pressed at 90°C for 12 seconds with 0.20 inch shims. The pressed non-woven fabric was postwashed in water for -26- ~~~~~~ J~~
minutes and dried in vacuum to yield a bioabsorbable non-woven fabric product.
Construction of Multilayer Adhesion Barrier Polymer III, made in accordance with Example 3, was dissolved in methylene chloride at room temperature while stirring until the mixture contains about 30 to about 50% and preferably about 35% solids. Transfer coating equipment was utilized to form an adherent bond between a non-woven fabric made in accordance with Example 5 and a film described herein. The line speed ran at 6 feet per minute. Oven temperatures were read at about 112°F in the first zone, about 107 in the second zone and about 110°F in the third zone. The web temperature was about 119°F. The polymer mixture, with a viscosity of about 500 CPS is coated onto moving release paper to form an approximately 2 mil film. The bioabsorbable non-woven fabric was placed onto the wet film. 1~ light weight card board was placed on the fabric to maintain.good adherent contact with the film. The film and fabric were then passed through the ovens. The solvent evaporated and a dry product having the film and fabric in adherent contact resulted. The release.paper was peeled off the film side of the adhesion barrier. Alternatively, two layers of 1 mil film can be applied separately and adhered. By applying multiple layers, irregularities in the film layer, such as small holes, are less likely to be present in the final product.
2~.I~~~ ~~
Construction of Multilayer Adhesion Barrier An approximately 2 mil film of polymer III, made in accordance with Example 8 is produced on release paper without non-woven fabric. After drying, the film was cut to desired size and placed in contact with the film side of the adhesion barrier made in accordance with Example 8. The films inherently adhere to each other and a trilayer adhesion barrier was prepared with a manual laminator by feeding the film and the two-layer adhesion barrier into the laminator between movable rollers.
Implantation of Polymer I Adhesion Barrier Twelve female Sprague-Dawley rats weighing between 255-250 gm each were monitored for at least one week prior to surgery to insure good health and stability. The animals were anesthetized with intraperitoneal sodium pentobarbital and their abdomens prepared for surgery. The abdominal cavity was exposed through a midline incision: On the abdominal wall overlying the cecum, a 1 cm x 2 cm area of parietal peritoneum was carefully excised from the abdominal wall, removing a thin layer of muscle along with the peritoneum.
The cecum was elevated and isolated by moist gauze.
The proximal end of the cecum was emptied~of its.contents. A 1 cm x 2 cm area on the anterior surface of the proximal end of the cecum was gently abraded by~'rubbing l0'times with dry gauze: The cecum was then scraped with a scalpel blade to cause minute petechial hemorrhages. The cecal abrasion was left exposed for 15 minutes. After 15 minutes, the cecal abrasion and the abdominal wound were blotted with a gauze sponge to gently remove 2~.~.~2~~ L
any excess blood and ensure complete hemostasis. Placement of these two wounds together normally leads to reproducible formation of an adhesion.
A 2 cm x 3 cm film of Polymer I approximately 7 mil thick made in a manner according to Example 3 was placed between the wounds before they were placed in contact and the abdomen closed. The procedure was repeated on all twelve rats.
Seven days following surgery, the animals' peritoneum was evaluated for the development of an adhesion between the peritoneal defect and the cecal surface. Examination of the wound site revealed that one of twelve rats had developed an adhesion.
Implantation of Polymer II Adhesion Barrier Polymer II in accordance with Example 2 was formed into a single layer film approximately 7 mil thick and implanted in a manner similar to that described in Example 5. Examination of the wound site after seven days revealed that one of twelve rats had developed an adhesion.
2~.~.~~'~' Implantation of Polymer I/Polypropylene Mesh Adhesion Barrier 1 cm x 2 cm pads of SURGIPRO~ polypropylene mesh (commercially available from U.S. Surgical Corp.) coated with a film of Polymer I were implanted into fifteen rats in a manner similar to .that described in Example 5 except that certain different groups of the rats were analyzed at three specified time intervals: 7, 31 and 55 days, respectively. At day 7 one of five rats developed a retroperitoneal fat adhesion; no cecal adhesions were cbserved. At day 21 two of five rats were observed with cecal adhesions. At day 55 none of five rats were observed with cecal adhesions. In sum, three of fifteen rats were observed with cecal adhesions at the wound site.
Implantation of Polymer II/Polypropylene Mesh Adhesion Barrier 1 cm x 2 cm pads of SURGIPRO~ polypropylene mesh (commercially available from U.S. Surgical Corp.) coated with a film of Polymer II were implanted into fourteen rats in a manner similar to that described in Example 12. At day 7 none of five rats were observed with adhesions. At day 21 one of five rats was observed with a cecal adhesion. At day 55 none of four rats were observed with cecal adhesions. In sum, one of fourteen. rats was observed with' cecal adtlesion's ;at the wound site.
2~.1~2'~°~
Implantation of Polymer II/Polypropylene Mesh Adhesion Barrier 2cm x 3cm pads of a 2 mil film of Polymer II bonded to Surgipro~ polypropylene mesh (commercially available from U.S.
Surgical Corp.) were implanted into thirty-six rats in a manner similar to that described in Example 10 except that the pads were sutured to the abdominal wall using size 7/0 polypropylene suture in each corner of the pad and that wound cites of three groups of twelve rats were analyzed for adhesions at 7, 14 and 21 days, respectively, following implantation. After 7, 14 and 21 days none of the rats were observed with cecal adhesions at the wound site.
Implantation of Polymer II/Polypropylene Mesh Adhesion Barrier 2cm x 3cm pads of a 4 mil film of Polymer II bonded to Surgipro~ polypropylene mesh (commercially available from U.S.
Surgical Corp.) were implanted into twelve rats in a manner similar to that described in Example 14. After 7, 14 and 21 days none of the rats were observed with cecal adhesions at the wound site.
-31- 211 ~ '~ ~
Implantation of Polymer II Film Adhesion Barrier 2cm x 3cm pads of a 2 mil film of Polymer II were implanted into thirty rats in a manner similar to that described in Example 14. After 7 days the incidence of cecal adhesions was about 25% in twelve rats. Two of the cecal adhesions are believed to have been caused by technical error. At days 14 and 21 about an 11% incidence of cecal adhesions was observed, respectively, in two groups of nine rats.
Implantation of Polymer II Adhesion Barrier 2cm x 3cm pads of a 4 mil film of Polymer II were implanted into thirty-six rats in a manner similar to that described in Example 14. There were no cecal adhesions observed at day 7. At days 14 and-21, about an 8% incidence of adhesions was observed, respectively, in two groups of twelve rats.
Implantation of Polymer II/Polypropylene Mesh Adhesion Barrier Six Xorkshire gilts weighing between 38 and 46 kg received standard dosage, intramuscular injections of antibiotic and were anesthetized. A midline celiotomy incision was made and, on both ;sides of~~th;e body wall, an~ approximate 3 x 3 cm section of the peritoneum, the internal abdominal fascia and the abdominal wall muscle were removed. Each partial thickness defect was repaired with a SURGIPRO~ polypropylene mesh (U. S. Surgical 2~~.42~~ ~
Corp.) coated with a film of Polymer II. A total of twelve abdominal wall defects were created and repaired, two per animal.
The abdominal wall and defect repair sites were examined for the type and extent of adhesions after two weeks.
Adhesions were observed at three of the twelve wound sites.
2 cm x 3 cm Hyaluronic acid pads (commercially available from Med Chem) were implanted in seventeen rats in a manner similar to that described in Example 10. Examination of the wound site after seven days revealed that twelve of seventeen rats developed adhesions.
3 cm diameter Hylan NWM discs (commercially available from Biomatrix, Inc.), circulars disc containing hyaluronic acid, were implanted in eleven rats in a manner similar to that described in Example 10. Examination of the wound site after seven days revealed that two of eleven rats developed adhesions.
Hylan solution (commercially available from Biomatrix, Inc.),.a hyaluronic acid gel, was applied to both wound surfaces of twelve rats caused in a similar manner as the wound surfaces created in Example 10. Seven of twelve rats developed adhesions at the wound site.
-33_ 3% methylcellulose solution was applied to both wound surfaces of eleven rats caused in a similar manner as the wound surfaces created in Example 10. Five of eleven rats developed adhesions at the wound site.
1 cm x 2 cm pads of uncoated SURGIPRO~ polypropylene mesh (commercially available from U.S. Surgical Corp.) were implanted into fifteen rats in a manner similar to that described in Example 10 except that certain of the rats were analyzed at three specified time intervals: at 7, 21, and 55 days, respectively. It is believed that one of the fifteen rats was mislabeled and discounted in the group analyzed at 7 days; at day 7 three of four rats developed cecal adhesions; at day 21 three of five rats developed cecal adhesions; at day 55 three of five rats developed cecal adhesions. In sum, nine of fourteen remaining rats developed cecal adhesions at the wound site.
1 cm x 2 cm pads of SURGIPRO~ polypropylene mesh (commercially available from U.S. Surgical Corp.) coated with film of hydroxyethylmethacrylate (HEMA) were implanted into fifteen rats in a manner similar to that described in Comparative Example 10. At day 7, one of five rats was observed with a cecal adhesion and three of the five rats were observed with retroperitoneal fat adhesions. At day 21 two of five rats were observed with cecal adhesions: At day~55 two of five rats were observed with cecal adhesions. In sum, five of fifteen rats were observed with cecal adhesions at the wound site.
2~~.~2 Pads of Marlex~ polypropylene mesh (commercially available from C.R. Bard., Inc.) were implanted into six defect sites created in gilts in a manner similar to that described in Example 18. Four of six defect sites were observed with adhesions.
Pads of Gore-Tex~ mesh (commercially available from W.L. Gore & Co.) were implanted into six defect sites created in gilts in a manner similar to that described in Example 18. Three of six defect sites were observed with adhesions.
Pads of Interceed~ oxidized regenerated cellulose (commercially available from Ethicon, Inc.) were implanted into six defect sites created in gilts in a manner similar to that described in Example 18. Two of six defect sites were observed with adhesions.
Six defect sites were created in gifts in a manner similar to that described in Example 18, but no implant was used at the defect site, i.e., the defects were unrepaired. Two of six defect sites were observed with adhesions.
-35_ 2~~.~2J~vj 2cm x 3cm pads of Marlex~ polypropylene mesh (commercially available from C.R. Bard, Inc.) were implanted into twelve rats in a manner similar to that described in Example 10 except that the pads were sutured to the abdominal wall using size 7/0 polypropylene suture in each corner of the pad. The stitches were placed so that the knots were under the sample and not exposed. After seven days, all twelve rats were observed with adhesions at the wound site.
2cm x 3cm pads of Surgipro~ polypropylene mesh (commercially available from U.S. Surgical Corp.) were implanted into twelve rats in a manner similar to that described in Comparative Example 11. After seven days, all twelve rats were observed with adhesions at the wound site.
2cm x 3cm pads of Interceed~ oxidized regenerated cellulose (commercially available from Ethicon, Inc.) were implanted into twelve rats in a manner similar to that described in Comparative Example 11. After seven days, all twelve rats were observed with adhesions at the wound site.
2cm x 3cm pads of Gore-Tex~ soft tissue patch (commercially available from W.C. Gore & Co.) were implanted into twelve rats in-a manner~simalar.to that described in Comparative Example 11. After seven days, eight of twelve rats (about 67%) were observed with adhesions at the wound site.
Comparative Examples 7-14 also included observations of adhesions which are considered to be less important than cecal 21i42~~~
adhesions. Adhesions of lesser importance are categorized herein as Type 1, Type 2 and Type 3. Type 1 include fat, liver, or intestines adhered to the face of the test surface. Type 2 include fat, liver, or intestines adhered to a free edge of a test surface or to suture knots. Type 3 include adherence of the cecal defect to peritoneal wall caudal or lateral to the test site. The results of the observations relating to adhesions of lesser importance are summarized in Table IV.
TABLE IV
INCIDENCE Of' ADHESIONS OTHER THAN THE
CECCTM ADHERING TO THE OVERLYING TEST MATERIAL.
TEST MATERIALINCIDENCE
OF
OTHER
ADHESIONS
(A
ro~imnte DAY DAY DAY
Type Type Type Type Type Type Type Type Type lviARLEX 100 100 0 N/A
N/A
1NTERCEED92 * 0 SURGIPRO+
2 mil 0 100 33 100 42 33 92 17 42 film SURGIPRO+
Adhesion formation following surgery or trauma is generally considered to be undesirable. For example, adhesions that form in relation to intestinal surgery, e.g., bowel resection, hernia repair, etc. may cause obstruction of the intestine. Adhesions that form near the bone fracture site may reduce or hinder the normal movement of the area of repair by restricting the natural movement of tendons over the adjacent bane. Adhesions may also form in the vicinity of nerves and disrupt nerve transmissions with a' resultant diminution of sensory or motor function.
Various methods and substances have been used in the hope of preventing post-operative adhesions. Certain drugs and surfactants have been suggested. For example, U.S. Patent No.
4,911,926 is directed to adhesion prevention by application of aqueous and non-aqueous compositions of a polyoxyalkylene block copolymer to injured areas of the peritoneal or pleural cavity or organs situated therein subsequent to surgical injury.
Another approach to adhesion prevention involves application of a physical barrier at the area of surgical injury.
U.S. Patent No. 4,674,488 is directed to interposing a barrier layer of soft biological tissue, such as collagen, collagen-fabric films, collagen membranes, or reconstituted collagen or Dacron~ mesh, at the interface of a bone fracture and the surrounding tissue. U.S. Patent No. 4,603,695 is directed to a molded polymeric material for preventing adhesion of vital tissues. The polymeric material is made of a biodegradable and absorbable polymer such as certain polyesters, collagen, amino acid polymers and chitin and may be placed where there is a possibility of adhesion setting in.
Other materials have also been used to form physical barriers in an attempt to prevent adhesions, including silicone elastomers, gelatin films and knit fabrics of oxidized, regenerated cellulose (hereinafter ORC). In some cases, it is suggested that heparin, heparinoid, or he~curonyl hexosaminoglycan be incorporated into a matrix of ORC fabric or other matrices of hyaluronic arid, cross-linked! and, uncross-linked collagen ;webs, synthetic resorbable polymers, gelatin films, absorbable gel films, oxidized cellulose fabrics and films which are fabricated into a form that is said to be drapable, conformable and adherent to body organs and substantially absorbable within 30 days. See, e.g., U.S. Patent No. 4,840,626 or EPA Pub. No. 0 262 890 or EPA
Pub. No. 0 372 969.
Physical barriers are also used to cover and protect wound sites. WO 9210218 is directed to a surgical article having a bioabsorbable fibrous matrix in a laminar relationship with a bioabsorbable cell barrier sheet. U.S. Patent No.
5,092,884 and EPA Pub. No. 0 334 046 are directed to a surgical composite structure having absorbable and non-absorbable components which may be useful for repairing anatomical defects, e.g., preventing hernia formation in an infected area. The nonabsorbable portion of the composite acts as a reinforcement material. Ingrowth of natural tissue is said to be enhanced by controlled degradation of the absorbable portion. U.S. Patent No. 5,035,893 relates to a wound covering composition having a sheet of biopolymeric material and a film of polyurethane resin.
An antibacterial agent may be provided between the polyurethane film and the sheet of biopolymeric material, thereby forming a three-layer wound covering material. With the cure of the wound, it is said that the biopolymeric material is taken in a living tissue and the polyurethane film can be peeled off from the sheet without hurting the surface of a wound.
SUMMARY OF THE INVENTION
The present invention provides surgical adhesion barriers and methods of using surgical adhesion barriers which have at least one layer of bioabsorbable material. The bioabsorbable material comprises copolymers, block copolymers or blends thereof. The copolymers comprises carbonates and at least one other bioabsorbable polymer forming material. The block copolymers comprise at least one block comprising trimethylene carbonate. In one embodiment the block copolymer comprises a first block formed from a copolymer having a predominant amount _4_ of trimethylene carbonate and a second block formed from a copolymer having a predominant amount of lactide.
In another embodiment, the.present invention provides a multilayer surgical structure having one bioabsorbable layer affixed to a non-absorbable layer. Both the absorbable and the non-absorbable layer may be fashioned from mesh, web, woven fabric, non-woven fabric, porous film, non-porous film or foam.
The structure is made by superimposing a layer of bioabsorbable material on a non-absorbable layer. In alternative embodiments subsequent bioabsorbable layers can be added. Additionally, one or more medicinal agents can be interposed between any of the aforementioned layers.
In another embodiment, the present invention provides a multilayer surgical structure having a bioabsorbable non-woven fabric in adherent contact with one or more bioabsorbable layers Which may be in the form of film, foam, mesh, web or woven .fabric.
The surgical adhesion barrier or multilayer surgical structure in flexible, resilient and conformable to various shapes such as body organs and tissues. During surgery, a surgical adhesion barrier according to the present invention is positioned at the area of injury to prevent adhesions as desired.
Likewise, a multilayer surgical structure according to the present invention having absorbable and non-absorbable layers is positioned at the area of injury to prevent adhesions as desired.
In the case of a multilayer adhesion barrier, the nonabsorbable layer is preferably positioned adjacent to the area of injury and the 'bioabsorbable layer('s)'fade'away from the ihjury. As the bioabsorbable layer is absorbed, any adhesions which may have attached to the bioabsorbable.layer lose their support and fall free of the injury site.
21I!~2~~
In yet another embodiment, the multilayer surgical structure incorporates a plurality of bioabsorbable layers which bioabsorb at different rates. Each layer of bioabsorbable material is absorbed over time, thus exposing and releasing any medicinal agents which may be contained between layers.
The structures of the present. invention may find application for open general surgery or less invasive surgical techniques such as endoscopic surgery, or both.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. leis a diagram of a stuffer box / crimper suitable for processing filaments used in the manufacture absorbable non-woven fabric for use in the present invention.
DETAILED DESCRIPTION OF THE INVENTION
A surgical adhesion barrier according to the present invention prevents formation of surgical adhesions at a surgical wound by interposing a unique bioabsorbable barrier between the surgical wound and surrounding tissue.
In accordance with one aspect of the present invention, a surgical adhesion barrier is constructed from a single layer of bioabsorbable material. The bioabsorbable material is made of copolymers of carbonates and at least one other bioabsorbable palymer forming material. Carbonates which are useful according to the present invention may be represented by the structural units of ,. ~ , ,, .~~ , ' ;r ~ , , , ,, formula (-Rn-O-C-0-) where~.n R is a carbon atom~and n preferably ranges from about 1 to about 8. Examples of suitable carbonates include dimethylene carbonate, trimethylene carbonate, 2~i~w~~
tetramethylene carbonate, pentamethylene carbonate, hexamethylene carbonate and the like.
Suitable bioabsorbable polymer forming materials which maybe copolymerized with a suitable carbonate include materials capable of forming hydrolyzable polyesters. Suitable materials capable of forming hydrolyzable polyesters include glycolide and lactide: hydroxyacids such as glycolic acid, lactic acid, hydroxy butyric acids, and hydroxyvaleric acids; lactones such as !3-propio-lactone, 7-caprolactone, e-caprolactone, methyl-caprolactone, dioxanone, p-dioxanone, methyl-p-dioxanone, dimethyl-p-dioxanone, and !3-malolactone; and polyalkylene oxides such as polyoxyethylene glycol and polyoxypropylene glycol and mixtures, blends, and copolymers thereof.
The single layer surgical adhesion barrier embodiment of the present invention preferably comprises a bioabsorbable copolymer of trimethylene carbonate and glycolide, the trimethylene carbonate being present in a predominant amount. A
"predominant amount", as used herein, is an amount greater than 50 mole percent of a composition. Preferably, the concentration of glycoside and trimethylene carbonate in this embodiment of the present invention is about 20 and 80 mole percent, respectively.
Suitable single layer surgical adhesion barriers of the present invention can also be fabricated from block copolymers having one or more "A" blocks comprising a carbonate as described above and a bioabsorbable polymer forming material as described above, and one or more "B" blocks comprising a bioabsorbable polymer forming material as described above. Preferably the "A"
blacks are'p~esent in~amounts-ranging from about 10% to about 90%
and the "B" blocks are present in amounts ranging from about l0%
to about 90%. In a still more preferred embodiment, the "A"
blocks are present in an amount ranging from about 15 weight percent to about 85 weight percent and the "B" blocks present in 21i~~~~
_7_ an amount ranging from about 15 weight percent to about 85 weight percent. Most preferably, the "A" and "B" blocks are present in amounts of about 50 percent by weight each.
Suitable "A" blocks include a predominant amount, i.e., greater than about 50 mole percent, of trimethylene carbonate.
Preferably the trimethylene carbonate ranges from about 75 mole percent to about 95 mole percent. A more preferable concentration of trimethylene carbonate ranges from about 80 mole percent to about 90 mole percent and is most preferably about 80 mole percent. The trim~ethylene carbonate may be copolymerized with any monomer which provides an absorbable copolymer to form the "A" block. Such monomers include but are not limited to glycolide, lactide, dioxanone, epsilon caprolactone, with glycolide being preferred.
Suitable "B" blocks include a predominant amount of lactide (i.e., greater than about 50 mole percent) but preferably ranging from about 75 mole percent to about 95 mole percent. A
more preferable concentration of lactide ranges from about 80 mole peroent to about 90 mole percent and is most preferably about 80 mole percent. The lactide may be copolymerized with any monomer such that an absorbable copolymer is provided to form the "B" block. Such monomers include but are not limited to glyaolide, dioxanone, and epsilon caprolactone,.trimethylene carbonate, with glycolide being preferred.
An adhesion barrier constructed from a single layer of bioabsorbable material may be in the form :of mesh, web, woven fabric, non-woven fabric, foam, matrix or, most preferably, film.
A noil-porous jingle layer ad~iesi'on barr'i~r is least likely' to ' allow adhesions to penetrate through to adjacent tissue.
An adhesion barrier film made of the above-described materials can be made by standard polymer film forming techniques, e.g., compression of, copolymer resin between heated _8.
polytetrafluoroethylene (PTFE) coated plates. Other film forming techniques are described in, e.g., the Encyclopedia of Polymer Science and Engineering, Vol. 12, pp. 204-210 (1988). The thickness of the film can range from about 0.1 mil to about 100 mil, and is most preferably about 1 mil to about 3 mil.
In another embodiment, a single layer foam bioabsorbable surgical adhesion barrier made of the above described materials can be made in accordance with known foam forming techniques such as those disclosed in U.S. Patent Nos.
3,902,497 or 5,102,983, whose contents are incorporated herein by reference. The foam may be sliced and/or cut to desired thickness and configuration before surgical use. The thickness of the foam layer can range from about 0.1 mil to about 100 mil, and is most preferably about 1 mil to about 3 mil.
A single layer bioabsorbable surgical adhesion barrier according to the present invention is flexible, resilient and conformable to the shape of underlying tissue. Films and foams constructed from the above-described polymers are well suited for draping over and conforming to areas of surgical wounds or injury and are especially well suited for endoscopic surgery, e.g., laparoscopy.
In another aspect of the present invention, a surgical adhesion barrier is formed from two layers, i.e., a bioabsorbable layer superimposed on a non-absorbable layer. The non-absorbable layer is flexible and provides support and shape. The non-absorbable layer can be made from biocompatible materials which are formed into a mesh, web, foam, woven fabric, non-woven fabric, porous film or non-porous film.
Biocompatible materials which are suitable for forming the non-absorbable layer are well-known and include fluoropolymers, polyesters, e.g polyethylene terephthalate or 21~9:~~C
polybutylene terephthalate, polyetherimide esters, polyolefins, polyamides, polybutesters, and/or copolymers and/or blends of the same. These materials are exemplified by polytetrafluoroethylene (PTFE), silicone rubbers, urethanes, polyethylene, polypropylene, polyvinyl alcohol, polyvinyl chloride, cellulose, cellulose derivatives, fibroin, etc. Polypropylene is a preferred non-absorbable biocompatible material.
The non-absorbable layer can range from substantially non-porous to an open mesh. A non-porous non-absorbable layer substantially prevents the transmission of vapor, fluid or other substances from the wound site to the surrounding environment and, conversely, from the surrounding environment to the wound site. A porous film, matrix, mesh, web or fabric does permit such transmission. For reasons elaborated on below, a non-absorbable layer which permits transmission of vapor, fluid, or other substance may be desirable for use in aiding the healing process or in delivering a medicinal agent to the area of injury.
Such a mesh material can promote the ingrowth of new tissue during the healing process. Methods of forming mesh, webs, woven fabrics, non-woven fabrics, matrices, foams, porous films and non-porous films from the above-noted materials are known to those with skill in the art.
The bioabsorbable layer of a two layer surgical adhesion barrier includes the same materials and forms described above in relation to a single layer bioabsorbable surgical adhesion barrier. The bioabsorbable layer according to the present invention may be in the form of mesh, web, woven-fabric, non-woven fabric, foam, matrix, or film. The thickness of ; each bioabsorbable layer can range from about 0.1 mil to about 100 mil, but preferably about l mil to about 3 mil. Non-porous films are preferred for use as the bioabsorbable layer in the present invention because adhesions are less likely to penetrate through to an underlying layer.
In a preferred embodiment of the two layer adhesion barrier, a bioabsorbable substantially non-porous layer is pressed onto a mesh (preferably about 12 inches x about 36 inches) constructed from polypropylene. The bioabsorbable layer is preferably made from either 1) a copolymer of about 20 mole percent glycolide and about 80 mole percent trimethylene carbonate or 2) a block copolymer having one block containing about 20 mole percent glycolide and about 80 mole percent trimethylene carbonate and another block containing about 20 mole percent glycolide and about 80 mole percent lactide wherein both blocks are present in equal weight ratios. In manufacturing a two layer surgical adhesion barrier according to the present invention a bioabsorbable layer is superimposed or affixed to a non-absorbable layer. For example, affixation may be accomplished by coating the bioabsorbable layer onto the non-absorbable layer.
In one embodiment, the bioabsorbable polymer forming the bioabsorbable layer is melted and then coated on the non-absorbable mesh. Alternatively, the bioabsorbable polymer is dissolved in solvent and solution coated on to the mesh. The solvent is then evaporated by drying. The bioabsorbable layer may also be applied to the non-bioabsorbable layer by transfer coating techniques, such as these described in the Encyclopedia of Polymer Science pp. 377-382 (1985). Alternatively, a commercially available press machine is used to press a preformed film on to the mesh, or the polymer is calendared to form a film and then pressed on to the mesh. Techniques used for calendaring are well-known, e.g., techniques described in the Encyclopedia of Polymer Science and Engineering, Vol. 2, pp. 606-622 (1985). The layers may 2~.~.4Z~~
also be joined by laminating the bioabsorbable layer to the non-absorbable layer. In lamination, the bioabsorbable layer may be applied to the non-absorbable layer by any method known to those with skill in the art, such as with an adhesive, for example, acrylic, silicone, polyphenolic bioadhesive, etc.
A two layer surgical adhesion barrier according to the present invention is flexible, resilient and conformable to the shape of underlying tissue. Such an adhesion barrier is well suited to be applied to a target site with minimally invasive techniques such as those involving endoscopy. After being positioned, two layer surgical adhesion barriers may optionally be sutured, stapled or otherwise fastened to the target site.
In another aspect of the present invention, a plurality of bioabsorbable layers are superimposed on a non-absorbable layer in any of the aforementioned forms to form a surgical adhesion barrier. As above, the non-absorbable layer can be formed from biocompatible materials such as fluoropolymers, polyesters e.g. polybutylene terephthalate and polyethylene terephthalate, polyolefins, polyamides, polybutesters, polyetherimide esters, and/or copolymers and/or blends of the same. These materials are exemplified by polytetrafluoroethylene (PTFE), silicone rubbers, urethanes, polyethylene, polypropylene, polyvinyl alcohol, polyvinyl chloride, cellulose, cellulose derivatives, fibroin, etc. Polypropylene is a preferred non-absorbable layer.
Non-absorbable layers useful in ahis aspect.of the present invention can range from the substantially non-porous to the 'open meshes described above.' Biocompatible~bioabsorbable materials useful in this aspect of the present invention include polymers and/or copolymers and/or blends of the aforementioned bioabsorbable materials.
2~i~~~i~
Other examples of suitable biocompatible polymers are polyhydroxyalkyl methacrylates including ethylmethacrylate, and hydrogels such as polyvinylpyrrolidone, polyacrylamides, etc.
Other suitable bioabsorbable materials are biopolymers which include collagen, gelatin, alginic acid, chitin, chitosan, fibrin, hyaluronic acid, dextran and polyamino acids. Any combination, copolymer, polymer or blend thereof of the above examples are contemplated for use according to the present invention. Such bioabsorbable materials may be prepared by known methods.
A surgical adhesion barrier having a plurality of bioabsorbable layers can be formed by superimposing a first bioabsorbable layer on a nonabsorbable layer by any of the techniques which are,described in relation to forming a two layer surgical adhesion barrier. A second bioabsorbable layer is then superimposed or affixed to the first bioabsorbable layer by such means as are. described above. In this manner, a third, fourth, fifth, etc. bioabsorbable layer may be successively incorporated into the surgical device of the present invention.
Alternatively, a first bioabsorbable layer may be superimposed on a second bioabsorbable layer to form a two layer bioabsorbable composite. Optionally, a third, fourth, fifth, etc. layer can be added successively to form a multilayer bioabsorbable composite which is then superimposed on a non-absorbable layer by such means that' are described above.
The physical form of each successive bioabsorbable layer in all above and below-described embodiments and aspects of the~pres~ent invention~can vairy'.' For example, the outermost bioabsorbable layer can be a film and an adjacent bioabsorbable layer can be, e.g., a mesh, film, foam or non-woven fabric. Any number of such combinations are contemplated by the present invention.
2~~!~2~~
In another aspect of the present invention, at least one bioabsorbable non-woven fabric layer is superimposed or affixed to at least one bioabsorbable layer which may be a film, mesh, web, foam, woven fabric or other non-woven fabric. The bioabsorbable materials used to form the non-woven fabric layers) include all known bioabsorbable materials and combinations of such materials capable of being formed into fibers including those previously referred to herein. Methods for making non-woven fabrics are generally known in the art.
Preferably, a low density non-woven bioabsorbable fabric is used to carry out the present invention. In one preferred embodiment, the low density bioabsorbable non-woven fabric is manufactured from a 92.5/7.5 (mole percent) glycolide/lactide polymer yarn. The polymer is spun and drawn into a 69 filament 14 ply multifilament yarn of about 1.6 denier per filament. The 14 plyes are combined together by using a creel and a constant speed winder to prepare 1541 denier plied yarn. The yarn is crimped into a stuffer box according to the preferred specifications shown in Table I, below, with reference to Figure 1.
TABLE I
CRIMPING STUFFERBOX CRIMPER
Conditions No. of yarn ends feeding from creel 1 ,, , r Total Yarn denier 1545 (14 ply x 69 filaments/yarn x 1.6 dpf Gate Tension 1 Setting 4 Godet Setup:
21i~2J1~
No. of wraps on the pre-heat godet19 Pre-heat Godet Set Temp. 108 C
Pre-heat Godet Indicating Temp. 110 C
Speed 31 meters/minute I'nfeed Gears (adjusts infeed yarn48 x 18 tensi Stuffer Chamber Setup:
Column Temp. Set Point (back only)96 C
Indicating Temp. of Column 99 C
8" glass column front Working Stack Height in Column 26x15 Gate Tension II Setting 0.5 Crimp Analysis:
Average No. of Crimps/inch 23.7 Range (Min./Max.) 16/36 The crimped yarn is cut into staples having fibers ranging from about 2-2.50 inches with an average length of about 2.25 inches. The staples are then carded to form a web. Prior to web formation, 'the staple fibers are passed through the card once to open the fibers. After opening, approximately 55 grams of opened fibers are used to produce a carded web having a basis weight of approximately 100 g/m2, with dimensions of about 0.22m x about 1.9m. The carding specifications are shown in Table II.
TABLE II
Carding 12" metallic card with variab speed control Card conditions Main Cylinder Speed 186-188 rpms Worker Cylinders ,, ~ ~ ~ . ,21-22 rpms , Stripper Cylinders 335 rpms Take-off Apron 53 rpms 2~~.~~~~
From about one to about four carded web layers are then cross-lapped and needle-punched twice to form the bioabsorbable non-woven fabric. All web layers are combined during the first needle-punch pass. The second needle-punch pass is "dry", i.e., no webs are added. The first needle-punch pass involves the face fabric direction with about 320 needle penetrations per square inch to a depth of about 4mm. The second needle-punch pass involves the back fabric direction with about 320 needle penetrations per square inch to a depth of about 8mm. Certain other needling parameters are shown in Table III.
TABLE III
Needling 12" James Hunter Fiberlocker Needlinct Parameters Needle Type Groz Beckert, GB 30's T5 x 18 x 36 x 3 Barb Types: 5333; 69219 Needling Rate 120 strokes/minute Needling Board Density 46 needles/linear inch When using two carded web layers, the resulting non-woven fabric is about 0.5 meters wide, less than about 2.5mm thick and has a density of between about 0.05 g/cu.cm and about 0.10 g/cu.cm. Preferably, the density is between about 0.065 g/cu.cm and about 0.085 g/cu.cm. The basis weight of the fabric depends on the number of carded web layers needled together.
Each carded web layer has a basis weight of between about 50 g/sq.m and about 100 g/sq.m.~ Preferably, the carded web layer' basis weight is about 80 g/sq.m. The basis weight of a two layer fabric, for example, is between about 100 g/sq.m and about 200 g/sq.m and preferably about 160 g/sq.m. Optionally, the fabric can be coated or filled with various storage stabilizing agents, such as those disclosed in commonly assigned U.S. Patent No. 5,032,429. Such storage stabilizing agents can include, for example, glycerol and calcium lactate.
According to the present invention, the thickness of the non-woven fabric can range from about 0.5 mm to about 5 mm, and is preferably about 1.75 mm to about 3 mm, but most preferably about 2.5 mm. In another preferred embodiment, the mole percent ratio of glycolide to lactide is about 20:80, and most preferably about 18:82, and can be manufactured in a manner as described above.
The non-woven fabric layers) are superimposed or affixed to at least one bioabsorbable layer of foam, film, mesh, web, woven fabric or other non-woven fabric. Bioabsorbable foam layers discussed previously in relation to single layer bioabsorbable surgical adhesion barriers herein are suitable for superimposing or affixing to the non-woven fabric layer.
Bioabsorbable meshes, webs, woven fabrics or other non-woven fabrics can be manufactured by known techniques and also superimposed or affixed to the non-woven fabric layers) in accordance with the present invention. In a preferred embodiment, the non-woven fabric is superimposed on or affixed to a bioabsorbable film. Bioabsorbable film made of any of the above-described bioabsorbable polymers, copolymers, or blends thereof can be manufactured by standard polymer film forming techniques, e.g. compression of polymer resin between PTFE coated platens. Other film forming techniques are described in, e.g., the Encyclopedia of Polymer Science and Engineering, Vol. 12, pp.
204-210 (1988). In a most preferred embodiment the bioabsorbable polymer is dissolved in a suitable solvent, e.g., methylene chloride, acetone, etc., to form a mixture of desired viscosity 2~~.~2~~J
which is coated onto release means such as release paper or the like to form a film. During evaporation of the solvent, a bioabsorbable non-woven fabric layers) is placed on the wet film. The film then adheres to the non-woven fabric and the release means is removed. The film may range from 0.1 mil to 4 mil and is preferably about 2 mil.
The bioabsorbable foam or film may be fabricated from any of the well known bioabsorbable polymers used in medicine. A
preferred bioabsorbable polymer for use in the foam or film is described above in accordance with a surgical adhesion barrier constructed from a single layer of bioabsorbable material, i.e., copolymers of carbonates and at least one other bioabsorbable material. A highly preferred bioabsorbable polymer for use in the foam or film is fabricated from block copolymers having about 50% by weight of an "A" block comprising about 40 mole percent glycolide and about 60 mole percent trimethylene carbonate and about 50% by weight of a "B" block comprising about 20 mole percent lactide and about 80 mole percent glycolide. Another highly preferred bioabsorbable polymer is fabricated from block copolymers having about 20% by weight of an "A" block comprising about 20 mole percent glycolide and about 80 mole percent trimethylene carbonate and about 80% by weight of a "B" block comprising about 20 mole percent glycolide and about 80 mole percent lactide.
As above, additional bioabsorbable layers may be affixed or superimposed to form surgical adhesion barriers of greater than two layers. The same techniques for affixing or super'impo5ing~~a bioabsorbabLe~layer to~a nonabsorbable layer described above are applicable to any of the layers involving non-woven bioabsorbable fabric. The successive layers may comprise differing chemical compositions and/or physical forms to yield adhesion barriers of markedly different characteristics depending. on intended use.
In all the above aspects and embodiments, the rate of bioabsorption of each bioabsorbable layer can be varied by changing the chemical make up and/or thickness of each successive layer. Various bioabsorbable polymers, copolymers and/or blends thereof are known to have different rates of absorption. For example, bioabsorbable polymers having a high degree of crystallinity are absorbed less rapidly than bioabsorbable polymers having relatively higher amounts of amorphous regions.
Thus, rates of bioabsorption can be engineered to fit particular needs. In this way, an outermost bioabsorbable layer can be constructed to slowly biodegrade and, when it does, adhesions which have formed between the outer layer and surrounding tissue fall away. Any slower forming adhesions which may have adhered through the outermost layer to an inner layer would then be disconnected by the absorption of a rapidly biodegrading inner layer. Alternatively, a rapidly bioabsorbed outer layer would act as the first line of defense against rapidly forming adhesions and a slower bioabsorbed inner layer would prevent the attachment of late forming adhesions.
Optionally, one or more medicinal agents may be interposed between one or more layers of a surgical device according to the present invention.
The present invention provides a versatile scheduled release medicinal agents) delivery system. For example, a bioabsorbable layer that has been engineered for rapid absorption releases any;~medicina~l agents'~contained between such layer and an adjacent layer within a relatively fast time frame. If the next bioabsorbable layer is engineered to be absorbed more slowly any medicinal agent contained between such layer and a next adjacent layer will be released within that time. Thus, a schedule of 2:~L~~~J~3 therapy is created with delivery at two distinct points in time, i.e., first, following implantation and absorption of the rapidly bioabsorbable layer, and second, after absorption of the more slowly absorbed layer.
Optionally, one or more medicinal agents may be mixed or ground into the above-mentioned bioabsorbable polymeric materials prior to formation of a coating or layers. See, e.g., U.S. Patent No. 3,991,766. In this manner, the medicinal agent is slowly released as the bioabsorbable layer is absorbed. The non-absorbable layer can also be manufactured such that a medicinal agent is integrally incorporated therein and diffuses or is transported to the wound site therefrom. For example, a medicinal agent can be co-extruded with a polymer such as polypropylene to form fibers containing the medicinal agent.
The term "medicinal agent", as used herein, is meant to be interpreted broadly and includes any substance or mixture of substances which may have any clinical use in medicine. Thus medicinal agents include drugs, enzymes, proteins, peptides, glycoproteins, or diagnostic agents such as releasable dyes which may have no biological activity per se.
Examples of classes of medicinal agents that can be used in accordance with the present invention include antimicrobials, analgesics, antipyretics, anesthetics, antiepi~,eptics, antihistamines, anti-inflammatories, cardiovascular drugs, diagnostic agents, sympathomimetic, cholinomimetic, anti-muscarinics, antispasmodics, hormones, growth factors, muscle relaxants, adrenergic neuron blockers, anti-neoplas~~ics, immunasuppressants , gastrointestinal drugs, .
diuretics, steroids and enzymes. It is also intended that combinations of medicinals can be used in accordance with the present invention.
2~.~.~~~~~
Thus, in one embodiment of the present invention focal delivery and application of a medicinal agent to the wound site is achieved. Focal application can be more desirable than general systemic application in some cases, e.g., chemotherapy for localized tumors, because it produces fewer side effects in distant tissues or organs and also concentrates therapy at intended sites. Focal application of growth factors, anti-inflammatories, immune system suppressants and/or antimicrobials by a the anti-adhesion device of the present invention is an ideal drug delivery system to speed healing of a wound or incision.
A post surgical anti-adhesion device or structure of the present invention is generally used in the form of a sheet of a desired size and shape. A surgeon may cut a custom shape from preformed sheets to suit particular applications. After the device is shaped for a suitable fit, the flexible nature of the device enables the surgeon to conform the device to fit around the area of injury. In one embodiment, the device is formed into a strip which wraps around the organ, e.g., an intestine, to prevent formation of adhesions. An anti-adhesion device according to the present invention can incorporate ties or straps which connect to the device and which are used to tie or otherwise secure the device to an area of injury. It is further contemplated that the anti-adhesion devices of the present invention may be affixed to the wound site by surgical fasteners or sutures. The flexible nature of the present anti-adhesion device allows the device to flex and bend along with normal movements of; the body,wiithout~being overly restrictive.
All embodiments of surgical adhesion barriers or structures as described herein are well-suited for application by techniques involving endoscopy. Endoscopic surgical procedures involve the use of cannulas or tubes which provide narrow openings into a body and allow minimally invasive access to surgical targets. In laparoscopic procedures, surgery is performed in the interior of the abdomen through small tubes inserted therein. Endoscopes are frequently used as viewing devices inserted through the cannulas which allow surgeons to see the interior of the body.
Certain endoscopic and laparoscopic procedures may require that the surgical region be insufflated. Accordingly, any instrumentation inserted into the body should be substantially sealed to ensure that gases do not enter or exit the body through the incision. Moreover, endoscopic and laparoscopic procedures often require the surgeon to operate on organs, tissues and/or vessels far removed from the incision. Thus, instruments used in such procedures are typically long and narrow while being functionally controllable from a proximal end of the instrument.
In accordance with the present invention an apparatus for deploying and positioning any of the adhesion barriers or structures disclosed herein may be inserted through a cannula and deposited at a target site. Once the barrier is positioned as desired, it may optionally be sutured, stapled or otherwise fastened to the target site with instruments designed to be inserted through a cannula.
In order that those skilled in the art may be better able to practice the present invention, the following examples are given as an illustration of the preparation and superior characteristics of the anti-adhesion devices of the present invention. It should be noted that the invention is not limited to the specific details embo'di'ed in the' examples.
21fi~~2'~' Copolymer of Glycolide/Trimethylene Carbonate (Polymer I) A 20/80 mole percent glycolide/trimethylene carbonate copolymer was prepared in a reactor by combining previously dried 53.13 grams of glycolide and 186.87 grams of trimethylene carbonate and polymerizing at 160°C for 24 hours in the presence of 0.05 grams of stannous octoate. The polymer was extruded from the reactor and post treated to remove any residual monomer present in the polymer. The inherent viscosity of the polymer was 0.9.
Copolymer of Glycolide/Trimethylene Carbonate/Lactide (Polymer II) A block copolymer having one block containing 20 mole percent glycdlide and 80 mole percent tiimethylene carbonate and another block containing 20 mole percent glycolide and 80 mole percent lactide, wherein both blocks are present in equal weight ratios was prepared in a reactor. 553.4 grams of glycolide and 1946.6 grams of trimethylene carbonate were added to the reactor along with 1.0 grams of stannous octoate and dried under vacuum in the reactor for about 16 hrs. After drying, the reactants were heated at 150°C and polymerized for about 24 hrs. At this stage 419.1 grams of dried glycolide and 2080.9 grams of Lactide were 'added'and continued poly~herizing df'additidnal 2'4 hrs~. The polymer is extruded and post treated to remove any residual monomers present in the polymer. The inherent viscosity of this polymer was 1.32.
2~.~~2~~~
Copolymer of Glycolide/Trimethylene Carbonate/Lactide (Polymer III) A block copolymer having 50% by weight of one block containing 40 mole percent glycolide and 60 mole percent trimethylene carbonate and 50% by weight of another block containing 20 mole percent glycolide and 80 mole percent lactide was prepared in a reactor. 646.7 grams of glycolide and 853 grams of trimethylene carbonate were added to the reactor along with 0.6 grams of stannous octoate and dried under vacuum in the reactor for about 24 hours at 160°C. At this stage 251 grams of glycolide and 1248 grams of lactide were added and polymerized for an additional 24 hours at 170°C. The polymer was extruded and post treated to remove any residual monomers present in the polymer. The inherent viscosity of this polymer was in the range of 0.4-0.8 dl/g.
Copolymer of Glycolide/Trimethylene Carbonate/Lactide (Polymer IV) A block copolymer having 20% by weight of one block containing 20 mole percent glycolide and 80 mole percent trimethylene carbonate and 80% by weight of another block containing 20 mole percent glycolide and .80 mole percent lactide was prepared in a reactor. 132.8 grams of glycolide and 467.2 grams of tr~;methylen'e darbdnate were added to the reactor~along with 0.6 grams of stannous octoate and dried under vacuum in the reactor for about 24 hours. At this stage 402 grams of glycolide and 1998 grams of lactide were added and polymerized for an additiona1124 hours. The polymer was extruded and post treated 2~.1~~~ ~~
to remove any residual monomers present in the polymer. The inherent viscosity of this polymer was of 0.0 to 1.1 dl/g.
Construction of Multilayer Adhesion Barrier Polymer I, made in accordance with Example 1, was pressed into a film by means of a vacuum press supplied by Technical Machine Products, Cleveland, Ohio, a standard commercial press having PTFE coated platens. The temperature of the platens was maintained at about 130°C. The platens were pressed together at a load of about 25,000 pounds for about 12 minutes. The resulting film was then removed from the press.
To bond the polymer film to a polypropylene mesh, the film was placed against the mesh and pressed together by the PTFE
coated platens of a vacuum press supplied by Technical Machine Products, Cleveland, Ohio. The temperature of the platens was maintained at about 65°C and the platens were pressed together at a load of about 1000 pounds for about 5 minutes. The multilayer adhesion barrier was then removed from the press.
., , 2~.~.~~'~'~
Construction of Multilayer Adhesion Barrier Polymer II, made in accordance with Example 2,is pressed into a film in a manner similar to that described in Example 3 except that the platens were heated to a temperature of about 190°C and pressed together at a load of about 3000 pounds.
To bond the polymer film to a polypropylene mesh, the film was placed against the mesh and pressed together by the PTFE
coated platens of a vacuum press supplied by Technical Machine Products, Cleveland, Ohio. The temperature of the platens was maintained at about 120°C and the platens were pressed together at a load of about 3000 pounds for about 5 minutes. The resulting multilayer adhesion barrier was then removed from the press.
Construction of Bioabsorbable Non-Woven Fabric A copolymer of about 18 mole percent glycolide and about 82 mole percent lactide was spun and drawn into a 40 filament 14 ply multifilament yarn. The plies were combined (1120 denier total) and crimped by stuffer box crimper. The crimped yarn was aut into staples of about 2 inches. The staple fibers were opened and carded on a carding machine and converted to a web having a basis weight of approximately 100 g/m2.. Two web layers were needled together to form non-woven fabric (200'g%m2) which was 'washed'i:n''wat8r for~5 minutes and dried in~
vacuum. The dried fabric was post treated at 90°C for 16 hours and then platen pressed at 90°C for 12 seconds with 0.20 inch shims. The pressed non-woven fabric was postwashed in water for -26- ~~~~~~ J~~
minutes and dried in vacuum to yield a bioabsorbable non-woven fabric product.
Construction of Multilayer Adhesion Barrier Polymer III, made in accordance with Example 3, was dissolved in methylene chloride at room temperature while stirring until the mixture contains about 30 to about 50% and preferably about 35% solids. Transfer coating equipment was utilized to form an adherent bond between a non-woven fabric made in accordance with Example 5 and a film described herein. The line speed ran at 6 feet per minute. Oven temperatures were read at about 112°F in the first zone, about 107 in the second zone and about 110°F in the third zone. The web temperature was about 119°F. The polymer mixture, with a viscosity of about 500 CPS is coated onto moving release paper to form an approximately 2 mil film. The bioabsorbable non-woven fabric was placed onto the wet film. 1~ light weight card board was placed on the fabric to maintain.good adherent contact with the film. The film and fabric were then passed through the ovens. The solvent evaporated and a dry product having the film and fabric in adherent contact resulted. The release.paper was peeled off the film side of the adhesion barrier. Alternatively, two layers of 1 mil film can be applied separately and adhered. By applying multiple layers, irregularities in the film layer, such as small holes, are less likely to be present in the final product.
2~.I~~~ ~~
Construction of Multilayer Adhesion Barrier An approximately 2 mil film of polymer III, made in accordance with Example 8 is produced on release paper without non-woven fabric. After drying, the film was cut to desired size and placed in contact with the film side of the adhesion barrier made in accordance with Example 8. The films inherently adhere to each other and a trilayer adhesion barrier was prepared with a manual laminator by feeding the film and the two-layer adhesion barrier into the laminator between movable rollers.
Implantation of Polymer I Adhesion Barrier Twelve female Sprague-Dawley rats weighing between 255-250 gm each were monitored for at least one week prior to surgery to insure good health and stability. The animals were anesthetized with intraperitoneal sodium pentobarbital and their abdomens prepared for surgery. The abdominal cavity was exposed through a midline incision: On the abdominal wall overlying the cecum, a 1 cm x 2 cm area of parietal peritoneum was carefully excised from the abdominal wall, removing a thin layer of muscle along with the peritoneum.
The cecum was elevated and isolated by moist gauze.
The proximal end of the cecum was emptied~of its.contents. A 1 cm x 2 cm area on the anterior surface of the proximal end of the cecum was gently abraded by~'rubbing l0'times with dry gauze: The cecum was then scraped with a scalpel blade to cause minute petechial hemorrhages. The cecal abrasion was left exposed for 15 minutes. After 15 minutes, the cecal abrasion and the abdominal wound were blotted with a gauze sponge to gently remove 2~.~.~2~~ L
any excess blood and ensure complete hemostasis. Placement of these two wounds together normally leads to reproducible formation of an adhesion.
A 2 cm x 3 cm film of Polymer I approximately 7 mil thick made in a manner according to Example 3 was placed between the wounds before they were placed in contact and the abdomen closed. The procedure was repeated on all twelve rats.
Seven days following surgery, the animals' peritoneum was evaluated for the development of an adhesion between the peritoneal defect and the cecal surface. Examination of the wound site revealed that one of twelve rats had developed an adhesion.
Implantation of Polymer II Adhesion Barrier Polymer II in accordance with Example 2 was formed into a single layer film approximately 7 mil thick and implanted in a manner similar to that described in Example 5. Examination of the wound site after seven days revealed that one of twelve rats had developed an adhesion.
2~.~.~~'~' Implantation of Polymer I/Polypropylene Mesh Adhesion Barrier 1 cm x 2 cm pads of SURGIPRO~ polypropylene mesh (commercially available from U.S. Surgical Corp.) coated with a film of Polymer I were implanted into fifteen rats in a manner similar to .that described in Example 5 except that certain different groups of the rats were analyzed at three specified time intervals: 7, 31 and 55 days, respectively. At day 7 one of five rats developed a retroperitoneal fat adhesion; no cecal adhesions were cbserved. At day 21 two of five rats were observed with cecal adhesions. At day 55 none of five rats were observed with cecal adhesions. In sum, three of fifteen rats were observed with cecal adhesions at the wound site.
Implantation of Polymer II/Polypropylene Mesh Adhesion Barrier 1 cm x 2 cm pads of SURGIPRO~ polypropylene mesh (commercially available from U.S. Surgical Corp.) coated with a film of Polymer II were implanted into fourteen rats in a manner similar to that described in Example 12. At day 7 none of five rats were observed with adhesions. At day 21 one of five rats was observed with a cecal adhesion. At day 55 none of four rats were observed with cecal adhesions. In sum, one of fourteen. rats was observed with' cecal adtlesion's ;at the wound site.
2~.1~2'~°~
Implantation of Polymer II/Polypropylene Mesh Adhesion Barrier 2cm x 3cm pads of a 2 mil film of Polymer II bonded to Surgipro~ polypropylene mesh (commercially available from U.S.
Surgical Corp.) were implanted into thirty-six rats in a manner similar to that described in Example 10 except that the pads were sutured to the abdominal wall using size 7/0 polypropylene suture in each corner of the pad and that wound cites of three groups of twelve rats were analyzed for adhesions at 7, 14 and 21 days, respectively, following implantation. After 7, 14 and 21 days none of the rats were observed with cecal adhesions at the wound site.
Implantation of Polymer II/Polypropylene Mesh Adhesion Barrier 2cm x 3cm pads of a 4 mil film of Polymer II bonded to Surgipro~ polypropylene mesh (commercially available from U.S.
Surgical Corp.) were implanted into twelve rats in a manner similar to that described in Example 14. After 7, 14 and 21 days none of the rats were observed with cecal adhesions at the wound site.
-31- 211 ~ '~ ~
Implantation of Polymer II Film Adhesion Barrier 2cm x 3cm pads of a 2 mil film of Polymer II were implanted into thirty rats in a manner similar to that described in Example 14. After 7 days the incidence of cecal adhesions was about 25% in twelve rats. Two of the cecal adhesions are believed to have been caused by technical error. At days 14 and 21 about an 11% incidence of cecal adhesions was observed, respectively, in two groups of nine rats.
Implantation of Polymer II Adhesion Barrier 2cm x 3cm pads of a 4 mil film of Polymer II were implanted into thirty-six rats in a manner similar to that described in Example 14. There were no cecal adhesions observed at day 7. At days 14 and-21, about an 8% incidence of adhesions was observed, respectively, in two groups of twelve rats.
Implantation of Polymer II/Polypropylene Mesh Adhesion Barrier Six Xorkshire gilts weighing between 38 and 46 kg received standard dosage, intramuscular injections of antibiotic and were anesthetized. A midline celiotomy incision was made and, on both ;sides of~~th;e body wall, an~ approximate 3 x 3 cm section of the peritoneum, the internal abdominal fascia and the abdominal wall muscle were removed. Each partial thickness defect was repaired with a SURGIPRO~ polypropylene mesh (U. S. Surgical 2~~.42~~ ~
Corp.) coated with a film of Polymer II. A total of twelve abdominal wall defects were created and repaired, two per animal.
The abdominal wall and defect repair sites were examined for the type and extent of adhesions after two weeks.
Adhesions were observed at three of the twelve wound sites.
2 cm x 3 cm Hyaluronic acid pads (commercially available from Med Chem) were implanted in seventeen rats in a manner similar to that described in Example 10. Examination of the wound site after seven days revealed that twelve of seventeen rats developed adhesions.
3 cm diameter Hylan NWM discs (commercially available from Biomatrix, Inc.), circulars disc containing hyaluronic acid, were implanted in eleven rats in a manner similar to that described in Example 10. Examination of the wound site after seven days revealed that two of eleven rats developed adhesions.
Hylan solution (commercially available from Biomatrix, Inc.),.a hyaluronic acid gel, was applied to both wound surfaces of twelve rats caused in a similar manner as the wound surfaces created in Example 10. Seven of twelve rats developed adhesions at the wound site.
-33_ 3% methylcellulose solution was applied to both wound surfaces of eleven rats caused in a similar manner as the wound surfaces created in Example 10. Five of eleven rats developed adhesions at the wound site.
1 cm x 2 cm pads of uncoated SURGIPRO~ polypropylene mesh (commercially available from U.S. Surgical Corp.) were implanted into fifteen rats in a manner similar to that described in Example 10 except that certain of the rats were analyzed at three specified time intervals: at 7, 21, and 55 days, respectively. It is believed that one of the fifteen rats was mislabeled and discounted in the group analyzed at 7 days; at day 7 three of four rats developed cecal adhesions; at day 21 three of five rats developed cecal adhesions; at day 55 three of five rats developed cecal adhesions. In sum, nine of fourteen remaining rats developed cecal adhesions at the wound site.
1 cm x 2 cm pads of SURGIPRO~ polypropylene mesh (commercially available from U.S. Surgical Corp.) coated with film of hydroxyethylmethacrylate (HEMA) were implanted into fifteen rats in a manner similar to that described in Comparative Example 10. At day 7, one of five rats was observed with a cecal adhesion and three of the five rats were observed with retroperitoneal fat adhesions. At day 21 two of five rats were observed with cecal adhesions: At day~55 two of five rats were observed with cecal adhesions. In sum, five of fifteen rats were observed with cecal adhesions at the wound site.
2~~.~2 Pads of Marlex~ polypropylene mesh (commercially available from C.R. Bard., Inc.) were implanted into six defect sites created in gilts in a manner similar to that described in Example 18. Four of six defect sites were observed with adhesions.
Pads of Gore-Tex~ mesh (commercially available from W.L. Gore & Co.) were implanted into six defect sites created in gilts in a manner similar to that described in Example 18. Three of six defect sites were observed with adhesions.
Pads of Interceed~ oxidized regenerated cellulose (commercially available from Ethicon, Inc.) were implanted into six defect sites created in gilts in a manner similar to that described in Example 18. Two of six defect sites were observed with adhesions.
Six defect sites were created in gifts in a manner similar to that described in Example 18, but no implant was used at the defect site, i.e., the defects were unrepaired. Two of six defect sites were observed with adhesions.
-35_ 2~~.~2J~vj 2cm x 3cm pads of Marlex~ polypropylene mesh (commercially available from C.R. Bard, Inc.) were implanted into twelve rats in a manner similar to that described in Example 10 except that the pads were sutured to the abdominal wall using size 7/0 polypropylene suture in each corner of the pad. The stitches were placed so that the knots were under the sample and not exposed. After seven days, all twelve rats were observed with adhesions at the wound site.
2cm x 3cm pads of Surgipro~ polypropylene mesh (commercially available from U.S. Surgical Corp.) were implanted into twelve rats in a manner similar to that described in Comparative Example 11. After seven days, all twelve rats were observed with adhesions at the wound site.
2cm x 3cm pads of Interceed~ oxidized regenerated cellulose (commercially available from Ethicon, Inc.) were implanted into twelve rats in a manner similar to that described in Comparative Example 11. After seven days, all twelve rats were observed with adhesions at the wound site.
2cm x 3cm pads of Gore-Tex~ soft tissue patch (commercially available from W.C. Gore & Co.) were implanted into twelve rats in-a manner~simalar.to that described in Comparative Example 11. After seven days, eight of twelve rats (about 67%) were observed with adhesions at the wound site.
Comparative Examples 7-14 also included observations of adhesions which are considered to be less important than cecal 21i42~~~
adhesions. Adhesions of lesser importance are categorized herein as Type 1, Type 2 and Type 3. Type 1 include fat, liver, or intestines adhered to the face of the test surface. Type 2 include fat, liver, or intestines adhered to a free edge of a test surface or to suture knots. Type 3 include adherence of the cecal defect to peritoneal wall caudal or lateral to the test site. The results of the observations relating to adhesions of lesser importance are summarized in Table IV.
TABLE IV
INCIDENCE Of' ADHESIONS OTHER THAN THE
CECCTM ADHERING TO THE OVERLYING TEST MATERIAL.
TEST MATERIALINCIDENCE
OF
OTHER
ADHESIONS
(A
ro~imnte DAY DAY DAY
Type Type Type Type Type Type Type Type Type lviARLEX 100 100 0 N/A
N/A
1NTERCEED92 * 0 SURGIPRO+
2 mil 0 100 33 100 42 33 92 17 42 film SURGIPRO+
4 mil 0 100 25 91 9 18 91 36 18 film 2 mil 0 92 25 0 78 I1 0 89 22 film 4 mil 0 83 17 0 75 0 0 100 33 film * Type 2 adhesions were not possible fox Interceed since its edges were the same as its surface and the material was not sutured to the peritoneal defect.
The principles, preferred embodiments and modes of operation of the invention have, been described in the foregoing specification. The invention which is intended to be protected herein, however, is not to be construed as limited to the particular forms disclosed, since they are to be regarded as illustrative rather than restrictive. Modifications and _3~~ ~~~~~~ V
variations of the present invention are possible in light of the above teachings. It is therefore to be understood that changes may be made in particular embodiments of the invention described which are within the full intended scope of the invention as defined by the claims.
The principles, preferred embodiments and modes of operation of the invention have, been described in the foregoing specification. The invention which is intended to be protected herein, however, is not to be construed as limited to the particular forms disclosed, since they are to be regarded as illustrative rather than restrictive. Modifications and _3~~ ~~~~~~ V
variations of the present invention are possible in light of the above teachings. It is therefore to be understood that changes may be made in particular embodiments of the invention described which are within the full intended scope of the invention as defined by the claims.
Claims (17)
1. A post surgical adhesion barrier having at least one layer of a bioabsorbable material comprising at least one block copolymer which comprises:
a. about 10 to about 90% by weight of a block copolymer having at least one first block of a bioabsorbable copolymer having greater than 50 mole percent of trimethylene carbonate; and b. about 10 to about 90% by weight of the block copolymer having at least one second block of a bioabsorbable copolymer having greater than 50 mole percent of lactide.
a. about 10 to about 90% by weight of a block copolymer having at least one first block of a bioabsorbable copolymer having greater than 50 mole percent of trimethylene carbonate; and b. about 10 to about 90% by weight of the block copolymer having at least one second block of a bioabsorbable copolymer having greater than 50 mole percent of lactide.
2. A post surgical adhesion barrier according to claim 1, wherein said first block comprises about 80 mole percent trimethylene carbonate.
3. A post surgical adhesion barrier according to claim 1 or 2, wherein said second block comprises about 80 mole percent lactide.
4. A post surgical adhesion barrier according to claim 1 or 2, wherein the first block comprises about 50 percent by weight of the block copolymer.
5. A post surgical adhesion barrier according to any one of claims 1 to 4, wherein said first block is present in about 50% by weight and comprises about 40 mole percent glycolide and about 60 mole percent trimethylene carbonate and said second block is present in about 50% by weight and comprises about 20 mole percent glycolide and about 80 mole percent lactide.
6. A post surgical adhesion barrier according to claim 1, wherein said first block is present in about 20% by weight and comprises about 20 mole percent glycolide and about 80 mole percent trimethylene carbonate and said second block is present in about 80% by weight and comprises about 20 mole percent glycolide and about 80 mole percent lactide.
7. A post surgical adhesion barrier according any one of claims 1 to 6, wherein the bioabsorbable layer is selected from the group consisting of non-porous film, porous film, non-woven fabric, woven fabric, mesh, or web and foam.
8. A post surgical adhesion barrier according to any one of claims 1 to 7, comprising a plurality of bioabsorbable layers.
9. A post surgical adhesion barrier according to any one of claims 1 to 8, wherein the bioabsorbable layer is superimposed on a nonabsorbable layer.
10. A post surgical adhesion barrier according to any one of claims 1 to 6, further comprising a bioabsorbable non-woven fabric layer.
11. A post surgical adhesion barrier according to any one of claims 1 to 10, comprising a bioabsorbable non-woven layer in adherent contact with a bioabsorbable film.
12. A post surgical adhesion barrier according to claim 10 or 11, wherein said bioabsorbable non-woven layer is fabricated from a copolymer comprising glycolide and lactide.
13. A post surgical adhesion barrier according to claim 7 or 11, wherein said bioabsorbable film further comprises a copolymer comprising a carbonate and a compound selected from the group consisting of hydroxyacids, oxalates, lactones, collagen, gelatin, alginic acid, chitin, chitosan, fibrin, dextran, polyamino acids or hyaluronic acid.
14. Use of an adhesion barrier according to any one of claims 1 to 13, for reducing occurrence of post-surgical adhesions.
15. Use of a post surgical adhesion barrier according to any one of claims 1 to 13, for preventing formation of surgical adhesions.
16. Use of a post surgical adhesion barrier according to any one of claims 1 to 13, for minimization of endoscopic post-surgical adhesions.
17. A post surgical adhesion barrier comprising a plurality of bioabsorbable layers wherein at least one layer comprises a bioabsorbable material of a block copolymer having at least one block which comprises a predominant amount of trimethylene carbonate.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US972693A | 1993-01-27 | 1993-01-27 | |
US08/009,726 | 1993-01-27 | ||
US15333693A | 1993-11-16 | 1993-11-16 | |
US08/153,336 | 1993-11-16 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2114290A1 CA2114290A1 (en) | 1994-07-28 |
CA2114290C true CA2114290C (en) | 2006-01-10 |
Family
ID=26679821
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002114290A Expired - Lifetime CA2114290C (en) | 1993-01-27 | 1994-01-26 | Post-surgical anti-adhesion device |
Country Status (4)
Country | Link |
---|---|
US (1) | US5795584A (en) |
EP (1) | EP0610731B1 (en) |
CA (1) | CA2114290C (en) |
DE (1) | DE69431376T2 (en) |
Families Citing this family (174)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5800373A (en) * | 1995-03-23 | 1998-09-01 | Focal, Inc. | Initiator priming for improved adherence of gels to substrates |
US5931165A (en) * | 1994-09-06 | 1999-08-03 | Fusion Medical Technologies, Inc. | Films having improved characteristics and methods for their preparation and use |
US5607686A (en) * | 1994-11-22 | 1997-03-04 | United States Surgical Corporation | Polymeric composition |
US5900245A (en) | 1996-03-22 | 1999-05-04 | Focal, Inc. | Compliant tissue sealants |
ATE369402T1 (en) | 1995-03-23 | 2007-08-15 | Genzyme Corp | REDOX AND PHOTOINITIATOR SYSTEM FOR PRIMERING IMPROVED ADHESION OF GELS TO SUBSTRATES |
US5791352A (en) * | 1996-06-19 | 1998-08-11 | Fusion Medical Technologies, Inc. | Methods and compositions for inhibiting tissue adhesion |
ZA978537B (en) | 1996-09-23 | 1998-05-12 | Focal Inc | Polymerizable biodegradable polymers including carbonate or dioxanone linkages. |
DE19723807C2 (en) * | 1997-06-06 | 2003-04-24 | Ferring Gmbh | Process for making copolyesters |
US6458109B1 (en) | 1998-08-07 | 2002-10-01 | Hill-Rom Services, Inc. | Wound treatment apparatus |
EP2305324B1 (en) | 1999-03-25 | 2014-09-17 | Metabolix, Inc. | Medical devices and applications of polyhydroxyalkanoate polymers |
US6558423B1 (en) | 1999-05-05 | 2003-05-06 | Gary K. Michelson | Interbody spinal fusion implants with multi-lock for locking opposed screws |
NZ515585A (en) | 1999-06-01 | 2004-06-25 | Bristol Myers Squibb Co | Prevention of post surgical adhesions using a fibrin monomer sealant |
US6497650B1 (en) * | 1999-07-28 | 2002-12-24 | C. R. Bard, Inc. | Hernia prosthesis |
US9616150B2 (en) * | 1999-10-29 | 2017-04-11 | Children's Hospital Los Angeles | Bone hemostasis method and materials |
US6824533B2 (en) | 2000-11-29 | 2004-11-30 | Hill-Rom Services, Inc. | Wound treatment apparatus |
US6764462B2 (en) | 2000-11-29 | 2004-07-20 | Hill-Rom Services Inc. | Wound treatment apparatus |
KR100795613B1 (en) * | 2000-03-10 | 2008-01-21 | 마스트 바이오서저리 아게 | Resorbable Micro-Membrane for Attenuation of Scar Tissue |
US7592017B2 (en) | 2000-03-10 | 2009-09-22 | Mast Biosurgery Ag | Resorbable thin membranes |
US20010043943A1 (en) | 2000-05-22 | 2001-11-22 | Coffey Arthur C. | Combination SIS and vacuum bandage and method |
DE10041684A1 (en) | 2000-08-24 | 2002-03-07 | Inst Textil & Faserforschung | Coating material for medical treatment from resorbable synthetic material, process for its production and use in medicine |
US7404819B1 (en) | 2000-09-14 | 2008-07-29 | C.R. Bard, Inc. | Implantable prosthesis |
US6855135B2 (en) | 2000-11-29 | 2005-02-15 | Hill-Rom Services, Inc. | Vacuum therapy and cleansing dressing for wounds |
US6685681B2 (en) | 2000-11-29 | 2004-02-03 | Hill-Rom Services, Inc. | Vacuum therapy and cleansing dressing for wounds |
US7700819B2 (en) | 2001-02-16 | 2010-04-20 | Kci Licensing, Inc. | Biocompatible wound dressing |
US7666192B2 (en) | 2001-02-16 | 2010-02-23 | Kci Licensing, Inc. | Skin grafting devices and methods |
US7070584B2 (en) | 2001-02-20 | 2006-07-04 | Kci Licensing, Inc. | Biocompatible wound dressing |
US7763769B2 (en) | 2001-02-16 | 2010-07-27 | Kci Licensing, Inc. | Biocompatible wound dressing |
US6740968B2 (en) * | 2001-03-12 | 2004-05-25 | Matsushita Electric Industrial Co., Ltd. | Power source unit for driving magnetron and heatsink to be mounted on printed circuit board thereof |
EP1387670B1 (en) * | 2001-05-11 | 2008-10-15 | Ortho-McNeil-Janssen Pharmaceuticals, Inc. | Immune modulation device for use in animals |
US6685956B2 (en) | 2001-05-16 | 2004-02-03 | The Research Foundation At State University Of New York | Biodegradable and/or bioabsorbable fibrous articles and methods for using the articles for medical applications |
EP1402906A4 (en) * | 2001-06-15 | 2007-04-25 | Gunze Kk | Synechia inhibitory material |
WO2003030966A1 (en) | 2001-10-11 | 2003-04-17 | Hill-Rom Services, Inc. | Waste container for negative pressure therapy |
US6800082B2 (en) * | 2001-10-19 | 2004-10-05 | Ethicon, Inc. | Absorbable mesh device |
EP1461113A4 (en) | 2001-12-26 | 2009-05-06 | Hill Rom Services Inc | Wound vacuum therapy dressing kit |
ATE387919T1 (en) | 2001-12-26 | 2008-03-15 | Hill Rom Services Inc | VACUUM BAND PACKAGING |
EP2623138B1 (en) | 2001-12-26 | 2020-08-05 | KCI Licensing, Inc. | Vented vacuum bandage with irrigation for wound healing and method |
US6790213B2 (en) | 2002-01-07 | 2004-09-14 | C.R. Bard, Inc. | Implantable prosthesis |
CA2419831A1 (en) * | 2002-02-28 | 2003-08-28 | Macropore Biosurgery, Inc. | Methods for governing bone growth |
US20040254640A1 (en) * | 2002-03-01 | 2004-12-16 | Children's Medical Center Corporation | Needle punched textile for use in growing anatomical elements |
KR101027550B1 (en) * | 2002-04-04 | 2011-04-06 | 더 유니버시티 오브 아크론 | Non-woven fiber assemblies |
US8367570B2 (en) * | 2002-04-04 | 2013-02-05 | The University Of Akron | Mechanically strong absorbent non-woven fibrous mats |
US8168848B2 (en) | 2002-04-10 | 2012-05-01 | KCI Medical Resources, Inc. | Access openings in vacuum bandage |
WO2004010854A2 (en) * | 2002-07-31 | 2004-02-05 | Mast Biosurgery Ag | Apparatus and method for preventing adhesions between an implant and surrounding tissues |
EP1542613B1 (en) * | 2002-07-31 | 2019-04-10 | Mast Biosurgery AG | Resorbable thin membranes |
US8048444B2 (en) * | 2002-07-31 | 2011-11-01 | Mast Biosurgery Ag | Apparatus and method for preventing adhesions between an implant and surrounding tissues |
US7896856B2 (en) | 2002-08-21 | 2011-03-01 | Robert Petrosenko | Wound packing for preventing wound closure |
US7846141B2 (en) | 2002-09-03 | 2010-12-07 | Bluesky Medical Group Incorporated | Reduced pressure treatment system |
US7704520B1 (en) * | 2002-09-10 | 2010-04-27 | Mast Biosurgery Ag | Methods of promoting enhanced healing of tissues after cardiac surgery |
GB0224986D0 (en) | 2002-10-28 | 2002-12-04 | Smith & Nephew | Apparatus |
CA2509622C (en) | 2002-12-16 | 2012-02-21 | Gunze Limited | Medical film comprising gelatin and reinforcing material |
EP1596767B1 (en) * | 2003-02-12 | 2018-10-03 | Syncera, Inc. | Random and non-random alkylene oxide polymer alloy compositions |
US20060083767A1 (en) * | 2003-02-27 | 2006-04-20 | Kai Deusch | Surgical prosthesis having biodegradable and nonbiodegradable regions |
US20100114328A1 (en) * | 2003-09-10 | 2010-05-06 | Milbocker Michael T | Resorbable membrane implanting methods for reducing adhesions |
US20100266663A1 (en) * | 2003-09-10 | 2010-10-21 | Calhoun Christopher J | Tissue-treating implantable compositions |
GB0325130D0 (en) * | 2003-10-28 | 2003-12-03 | Smith & Nephew | Apparatus with scaffold |
GB0325129D0 (en) | 2003-10-28 | 2003-12-03 | Smith & Nephew | Apparatus in situ |
US7909805B2 (en) | 2004-04-05 | 2011-03-22 | Bluesky Medical Group Incorporated | Flexible reduced pressure treatment appliance |
US10058642B2 (en) | 2004-04-05 | 2018-08-28 | Bluesky Medical Group Incorporated | Reduced pressure treatment system |
CA2563347C (en) | 2004-04-20 | 2014-01-14 | Genzyme Corporation | Surgical mesh-like implant |
GB0409446D0 (en) | 2004-04-28 | 2004-06-02 | Smith & Nephew | Apparatus |
US8529548B2 (en) | 2004-04-27 | 2013-09-10 | Smith & Nephew Plc | Wound treatment apparatus and method |
GB0424046D0 (en) * | 2004-10-29 | 2004-12-01 | Smith & Nephew | Apparatus |
US7578834B2 (en) * | 2004-05-03 | 2009-08-25 | Abdou M S | Devices and methods for the preservation of spinal prosthesis function |
US7758654B2 (en) * | 2004-05-20 | 2010-07-20 | Kensey Nash Corporation | Anti-adhesion device |
US20080091277A1 (en) * | 2004-08-13 | 2008-04-17 | Kai Deusch | Surgical prosthesis having biodegradable and nonbiodegradable regions |
KR100895135B1 (en) * | 2004-08-13 | 2009-05-04 | 마스트 바이오서저리 아게 | Surgical prosthesis having biodegradable and nonbiodegradable regions |
WO2006036967A1 (en) | 2004-09-28 | 2006-04-06 | Atrium Medical Corporation | Solubilizing a drug for use in a coating |
US9012506B2 (en) | 2004-09-28 | 2015-04-21 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US8962023B2 (en) | 2004-09-28 | 2015-02-24 | Atrium Medical Corporation | UV cured gel and method of making |
US9801982B2 (en) | 2004-09-28 | 2017-10-31 | Atrium Medical Corporation | Implantable barrier device |
US8367099B2 (en) | 2004-09-28 | 2013-02-05 | Atrium Medical Corporation | Perforated fatty acid films |
US8312836B2 (en) | 2004-09-28 | 2012-11-20 | Atrium Medical Corporation | Method and apparatus for application of a fresh coating on a medical device |
US9000040B2 (en) | 2004-09-28 | 2015-04-07 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US20060258995A1 (en) * | 2004-10-20 | 2006-11-16 | Pendharkar Sanyog M | Method for making a reinforced absorbable multilayered fabric for use in medical devices |
US9358318B2 (en) | 2004-10-20 | 2016-06-07 | Ethicon, Inc. | Method of making a reinforced absorbable multilayered hemostatic wound dressing |
ES2391641T3 (en) | 2004-10-20 | 2012-11-28 | Ethicon, Inc. | Reinforced multilayer hemostatic dressing reinforced for wounds and their manufacturing procedure |
WO2006044878A2 (en) | 2004-10-20 | 2006-04-27 | Ethicon, Inc. | A reinforced absorbable multilayered fabric for use in tissue repair and regeneration |
US7390760B1 (en) | 2004-11-02 | 2008-06-24 | Kimberly-Clark Worldwide, Inc. | Composite nanofiber materials and methods for making same |
US20060094320A1 (en) * | 2004-11-02 | 2006-05-04 | Kimberly-Clark Worldwide, Inc. | Gradient nanofiber materials and methods for making same |
ATE524121T1 (en) | 2004-11-24 | 2011-09-15 | Abdou Samy | DEVICES FOR PLACING AN ORTHOPEDIC INTERVERTEBRAL IMPLANT |
US9119901B2 (en) * | 2005-04-28 | 2015-09-01 | Warsaw Orthopedic, Inc. | Surface treatments for promoting selective tissue attachment to medical impants |
US8414907B2 (en) | 2005-04-28 | 2013-04-09 | Warsaw Orthopedic, Inc. | Coatings on medical implants to guide soft tissue healing |
ES2355159T3 (en) * | 2005-08-11 | 2011-03-23 | University Of Saskatchewan | REDUCTION IN THE FORMATION OF POSTOPERATIVE ADHERENCES WITH INTRAPERITONEAL GLUTAMINE. |
US20080119878A1 (en) * | 2005-08-12 | 2008-05-22 | Kai Deusch | Surgical prosthesis having biodegradable and nonbiodegradable regions |
US9278161B2 (en) | 2005-09-28 | 2016-03-08 | Atrium Medical Corporation | Tissue-separating fatty acid adhesion barrier |
US8574627B2 (en) | 2006-11-06 | 2013-11-05 | Atrium Medical Corporation | Coated surgical mesh |
US9427423B2 (en) | 2009-03-10 | 2016-08-30 | Atrium Medical Corporation | Fatty-acid based particles |
CN103251449B (en) * | 2005-10-13 | 2016-03-02 | 斯恩蒂斯有限公司 | Drug-impregnated encasement |
EP1933991A4 (en) | 2005-10-15 | 2012-05-02 | Atrium Medical Corp | Hydrophobic cross-linked gels for bioabsorbable drug carrier coatings |
GB0524027D0 (en) * | 2005-11-25 | 2006-01-04 | Smith & Nephew | Fibrous dressing |
EP2018449A1 (en) * | 2006-04-10 | 2009-01-28 | Ethicon, Inc | A reinforced absorbable multilayered fabric for use in medical devices and method of manufacture |
CA2649081A1 (en) * | 2006-04-10 | 2007-10-18 | Ethicon, Inc. | A reinforced absorbable multilayered hemostatic wound dressing and method of making |
US8338402B2 (en) * | 2006-05-12 | 2012-12-25 | Smith & Nephew Plc | Scaffold |
US8721519B2 (en) | 2006-06-06 | 2014-05-13 | Boston Scientific Scimed, Inc. | Implantable mesh combining biodegradable and non-biodegradable fibers |
US7833284B2 (en) * | 2006-06-28 | 2010-11-16 | The Cleveland Clinic Foundation | Anti-adhesion membrane |
US9820888B2 (en) | 2006-09-26 | 2017-11-21 | Smith & Nephew, Inc. | Wound dressing |
CA2872297C (en) | 2006-09-28 | 2016-10-11 | Smith & Nephew, Inc. | Portable wound therapy system |
US9289279B2 (en) * | 2006-10-06 | 2016-03-22 | Promethean Surgical Devices, Llc | Apparatus and method for limiting surgical adhesions |
US9492596B2 (en) | 2006-11-06 | 2016-11-15 | Atrium Medical Corporation | Barrier layer with underlying medical device and one or more reinforcing support structures |
US9693841B2 (en) | 2007-04-02 | 2017-07-04 | Ension, Inc. | Surface treated staples, sutures and dental floss and methods of manufacturing the same |
US8153695B2 (en) * | 2007-06-04 | 2012-04-10 | Boston Scientific Scimed, Inc. | Methods for inhibiting post-surgical adhesions |
EP2185209A2 (en) * | 2007-08-03 | 2010-05-19 | Nicast Ltd. | Fibrous surgically implantable mesh |
US20090187197A1 (en) * | 2007-08-03 | 2009-07-23 | Roeber Peter J | Knit PTFE Articles and Mesh |
US20090036996A1 (en) * | 2007-08-03 | 2009-02-05 | Roeber Peter J | Knit PTFE Articles and Mesh |
WO2009081280A2 (en) * | 2007-08-27 | 2009-07-02 | Mast Biosurgery Ag | Resorbable barrier micro-membranes for attenuation of scar tissue during healing |
US20100034869A1 (en) * | 2007-08-27 | 2010-02-11 | Joerg Tessmar | Block-polymer membranes for attenuation of scar tissue |
EP2217298B1 (en) | 2007-11-21 | 2015-11-11 | T.J. Smith & Nephew Limited | Suction device and dressing |
GB0723872D0 (en) | 2007-12-06 | 2008-01-16 | Smith & Nephew | Apparatus for topical negative pressure therapy |
WO2009108760A2 (en) | 2008-02-26 | 2009-09-03 | Board Of Regents, The University Of Texas System | Dendritic macroporous hydrogels prepared by crystal templating |
US8021347B2 (en) | 2008-07-21 | 2011-09-20 | Tyco Healthcare Group Lp | Thin film wound dressing |
US8298200B2 (en) | 2009-06-01 | 2012-10-30 | Tyco Healthcare Group Lp | System for providing continual drainage in negative pressure wound therapy |
US9033942B2 (en) | 2008-03-07 | 2015-05-19 | Smith & Nephew, Inc. | Wound dressing port and associated wound dressing |
US9199012B2 (en) | 2008-03-13 | 2015-12-01 | Smith & Nephew, Inc. | Shear resistant wound dressing for use in vacuum wound therapy |
US20090304779A1 (en) * | 2008-06-08 | 2009-12-10 | Von Waldburg-Zeil Erich Graf | Micro-membrane implant with cusped opening |
US20100003306A1 (en) * | 2008-06-08 | 2010-01-07 | Mast Biosurgery Ag | Pre-shaped user-formable micro-membrane implants |
US8690900B2 (en) * | 2008-07-21 | 2014-04-08 | The Cleveland Clinic Foundation | Apparatus and method for connecting two elongate body tissues |
AU2009279525B2 (en) | 2008-08-08 | 2015-04-09 | Smith & Nephew Inc. | Wound dressing of continuous fibers |
US9492593B2 (en) | 2008-09-24 | 2016-11-15 | Poly-Med, Inc. | Absorbable, permeability-modulated barrier composites and applications thereof |
US20100222881A1 (en) * | 2008-10-03 | 2010-09-02 | Ann Prewett | Vessel protection device |
EP2344049B1 (en) | 2008-10-03 | 2021-01-27 | C.R.Bard, Inc. | Implantable prosthesis |
US8748508B2 (en) | 2008-12-29 | 2014-06-10 | DePuy Synthes Products, LLC | Method of forming and the resulting membrane composition for surgical site preservation |
US8162907B2 (en) | 2009-01-20 | 2012-04-24 | Tyco Healthcare Group Lp | Method and apparatus for bridging from a dressing in negative pressure wound therapy |
US20120010636A1 (en) * | 2009-02-11 | 2012-01-12 | Nanyang Technological University | Multi-layered surgical prosthesis |
GB0902368D0 (en) | 2009-02-13 | 2009-04-01 | Smith & Nephew | Wound packing |
US20100249783A1 (en) * | 2009-03-24 | 2010-09-30 | Warsaw Orthopedic, Inc. | Drug-eluting implant cover |
US20100247600A1 (en) * | 2009-03-24 | 2010-09-30 | Warsaw Orthopedic, Inc. | Therapeutic drug eluting implant cover and method of making the same |
US20100310632A1 (en) * | 2009-06-08 | 2010-12-09 | Von Waldburg-Zeil Erich Graf | Micro-membrane implant with cusped opening |
US20100310628A1 (en) * | 2009-06-08 | 2010-12-09 | Mast Biosurgery Ag | Pre-shaped user-formable micro-membrane implants |
US20100324516A1 (en) | 2009-06-18 | 2010-12-23 | Tyco Healthcare Group Lp | Apparatus for Vacuum Bridging and/or Exudate Collection |
US20110038910A1 (en) | 2009-08-11 | 2011-02-17 | Atrium Medical Corporation | Anti-infective antimicrobial-containing biomaterials |
US8349354B2 (en) | 2009-09-22 | 2013-01-08 | Ethicon, Inc. | Composite layered hemostasis device |
US8764806B2 (en) | 2009-12-07 | 2014-07-01 | Samy Abdou | Devices and methods for minimally invasive spinal stabilization and instrumentation |
JP5805659B2 (en) | 2009-12-22 | 2015-11-04 | スミス アンド ネフュー インコーポレーテッド | Apparatus and method for negative pressure closure therapy |
US8791315B2 (en) | 2010-02-26 | 2014-07-29 | Smith & Nephew, Inc. | Systems and methods for using negative pressure wound therapy to manage open abdominal wounds |
USRE48117E1 (en) | 2010-05-07 | 2020-07-28 | Smith & Nephew, Inc. | Apparatuses and methods for negative pressure wound therapy |
EP3741896A1 (en) | 2010-06-17 | 2020-11-25 | Washington University | Biomedical patches with aligned fibers |
WO2012009707A2 (en) | 2010-07-16 | 2012-01-19 | Atrium Medical Corporation | Composition and methods for altering the rate of hydrolysis of cured oil-based materials |
CA2813599A1 (en) | 2010-10-06 | 2012-04-12 | Ams Research Corporation | Implants with absorbable and non-absorbable features for the treatment of female pelvic conditions |
JP6042815B2 (en) | 2010-10-08 | 2016-12-14 | ザ ボード オブ リージェンツ オブ ザ ユニバーシティ オブ テキサス システム | Anti-adhesion barrier membranes using alginate and hyaluronic acid for biomedical applications |
US8946194B2 (en) | 2010-10-08 | 2015-02-03 | Board Of Regents, University Of Texas System | One-step processing of hydrogels for mechanically robust and chemically desired features |
MX2013007304A (en) | 2010-12-22 | 2013-07-29 | Smith & Nephew Inc | Apparatuses and methods for negative pressure wound therapy. |
US9468459B2 (en) | 2011-04-20 | 2016-10-18 | Kci Licensing, Inc. | Skin graft devices and methods |
US8845728B1 (en) | 2011-09-23 | 2014-09-30 | Samy Abdou | Spinal fixation devices and methods of use |
TWI590843B (en) | 2011-12-28 | 2017-07-11 | 信迪思有限公司 | Films and methods of manufacture |
US20130226240A1 (en) | 2012-02-22 | 2013-08-29 | Samy Abdou | Spinous process fixation devices and methods of use |
BR112014029100A2 (en) | 2012-05-23 | 2017-06-27 | Smith & Nephew | negative pressure wound therapy apparatus and methods |
US9867880B2 (en) | 2012-06-13 | 2018-01-16 | Atrium Medical Corporation | Cured oil-hydrogel biomaterial compositions for controlled drug delivery |
EP3406231B1 (en) | 2012-08-01 | 2022-04-13 | Smith & Nephew plc | Wound dressing and method of treatment |
WO2014020440A1 (en) | 2012-08-01 | 2014-02-06 | Smith & Nephew Plc | Wound dressing |
US9198767B2 (en) | 2012-08-28 | 2015-12-01 | Samy Abdou | Devices and methods for spinal stabilization and instrumentation |
WO2014039995A1 (en) | 2012-09-07 | 2014-03-13 | Fibrocell Technologies, Inc. | Fibroblast compositions for treating cardial damage after an infarct |
CA3066269C (en) | 2012-09-21 | 2022-03-29 | Washington University | Multilayered biomedical structures configured to separate after a predetermined time or upon exposure to an environmental condition |
US9320617B2 (en) | 2012-10-22 | 2016-04-26 | Cogent Spine, LLC | Devices and methods for spinal stabilization and instrumentation |
US11565027B2 (en) | 2012-12-11 | 2023-01-31 | Board Of Regents, The University Of Texas System | Hydrogel membrane for adhesion prevention |
CN103007364B (en) * | 2012-12-20 | 2014-05-14 | 北京市意华健科贸有限责任公司 | Aliphatic polyester double-layered asymmetric guided tissue regeneration membrane and preparation method thereof |
US10493184B2 (en) | 2013-03-15 | 2019-12-03 | Smith & Nephew Plc | Wound dressing and method of treatment |
EP2994176B1 (en) | 2013-05-10 | 2020-07-08 | Smith & Nephew plc | Fluidic connector for irrigation and aspiration of wounds |
EP3010560B1 (en) | 2013-06-21 | 2020-01-01 | DePuy Synthes Products, Inc. | Films and methods of manufacture |
CN103447914A (en) * | 2013-09-09 | 2013-12-18 | 江苏巨弘捆带制造有限公司 | Device for removing trimming burrs of cold-rolled steel strip |
US9907882B2 (en) | 2014-04-18 | 2018-03-06 | Warsaw Orthopedic, Inc. | Demineralized bone matrix with improved osteoinductivity |
US10076594B2 (en) | 2015-05-18 | 2018-09-18 | Smith & Nephew Plc | Fluidic connector for negative pressure wound therapy |
US10857003B1 (en) | 2015-10-14 | 2020-12-08 | Samy Abdou | Devices and methods for vertebral stabilization |
EP3390616A4 (en) | 2015-12-17 | 2019-08-07 | Dme 3D S.A.S. | Novel tissue separation barrier systems and related methods of use |
US10632228B2 (en) | 2016-05-12 | 2020-04-28 | Acera Surgical, Inc. | Tissue substitute materials and methods for tissue repair |
JP2019517892A (en) | 2016-06-15 | 2019-06-27 | チュビタック (ターキー ビリムセル ヴィ テクノロジク アラスティルマ クルム)Tubitak (Turkiye Bilimsel Ve Teknolojik Arastirma Kurumu) | Multifunctional hernia patch |
CA3030111A1 (en) | 2016-07-13 | 2018-01-18 | Mochida Pharmaceutical Co., Ltd. | Adhesion-preventing composition |
US10744000B1 (en) | 2016-10-25 | 2020-08-18 | Samy Abdou | Devices and methods for vertebral bone realignment |
US10973648B1 (en) | 2016-10-25 | 2021-04-13 | Samy Abdou | Devices and methods for vertebral bone realignment |
AU2018293063B2 (en) | 2017-06-30 | 2024-03-07 | T.J.Smith & Nephew,Limited | Negative pressure wound therapy apparatus |
GB201718014D0 (en) | 2017-11-01 | 2017-12-13 | Smith & Nephew | Dressing for negative pressure wound therapy with filter |
GB201811449D0 (en) | 2018-07-12 | 2018-08-29 | Smith & Nephew | Apparatuses and methods for negative pressure wound therapy |
US11179248B2 (en) | 2018-10-02 | 2021-11-23 | Samy Abdou | Devices and methods for spinal implantation |
US11896472B2 (en) * | 2019-10-28 | 2024-02-13 | Grant Technologies Llc | Surgical mesh having ingrowth-preventing coating on one side thereof, and method for making the same |
WO2023172636A1 (en) * | 2022-03-08 | 2023-09-14 | University Of Mississippi Medical Center | Articles and methods for improved tissue healing |
Family Cites Families (71)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US974294A (en) * | 1910-03-25 | 1910-11-01 | Edmund Morse Pond | Surgical bandage. |
US2465357A (en) * | 1944-08-14 | 1949-03-29 | Upjohn Co | Therapeutic sponge and method of making |
US3276448A (en) * | 1962-12-14 | 1966-10-04 | Ethicon Inc | Collagen coated fabric prosthesis |
US3875937A (en) * | 1963-10-31 | 1975-04-08 | American Cyanamid Co | Surgical dressings of absorbable polymers |
US3739773A (en) * | 1963-10-31 | 1973-06-19 | American Cyanamid Co | Polyglycolic acid prosthetic devices |
US3773919A (en) * | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US4135622A (en) * | 1973-03-28 | 1979-01-23 | American Cyanamid Company | Packaged, desiccated surgical elements |
US4033938A (en) * | 1974-01-21 | 1977-07-05 | American Cyanamid Company | Polymers of unsymmetrically substituted 1,4-dioxane-2,5-diones |
US3960152A (en) * | 1974-01-21 | 1976-06-01 | American Cyanamid Company | Surgical sutures of unsymmetrically substituted 1,4-dioxane-2,5-diones |
US3988411A (en) * | 1974-02-11 | 1976-10-26 | American Cyanamid Company | Spinning and shaping poly-(N-acetyl-D-glucosamine) |
US3937223A (en) * | 1974-04-19 | 1976-02-10 | American Cyanamid Company | Compacted surgical hemostatic felt |
US4074713A (en) * | 1975-03-14 | 1978-02-21 | American Cyanamid Company | Poly(N-acetyl-D-glucosamine) products |
US4186448A (en) * | 1976-04-16 | 1980-02-05 | Brekke John H | Device and method for treating and healing a newly created bone void |
US4532134A (en) * | 1981-04-06 | 1985-07-30 | Malette William Graham | Method of achieving hemostasis, inhibiting fibroplasia, and promoting tissue regeneration in a tissue wound |
US4373519A (en) * | 1981-06-26 | 1983-02-15 | Minnesota Mining And Manufacturing Company | Composite wound dressing |
US4578067A (en) * | 1982-04-12 | 1986-03-25 | Alcon (Puerto Rico) Inc. | Hemostatic-adhesive, collagen dressing for severed biological surfaces |
US4520821A (en) * | 1982-04-30 | 1985-06-04 | The Regents Of The University Of California | Growing of long-term biological tissue correction structures in vivo |
US4429080A (en) * | 1982-07-01 | 1984-01-31 | American Cyanamid Company | Synthetic copolymer surgical articles and method of manufacturing the same |
JPS6014861A (en) * | 1983-07-05 | 1985-01-25 | 株式会社日本メデイカル・サプライ | Adhesion preventing material |
US4670286A (en) * | 1983-09-20 | 1987-06-02 | Allied Corporation | Method of forming prosthetic devices |
US4594407A (en) * | 1983-09-20 | 1986-06-10 | Allied Corporation | Prosthetic devices derived from krebs-cycle dicarboxylic acids and diols |
CA1202904A (en) * | 1983-11-21 | 1986-04-08 | Brian G. Sparkes | Chitosan based wound dressing materials |
US4500676A (en) * | 1983-12-15 | 1985-02-19 | Biomatrix, Inc. | Hyaluronate modified polymeric articles |
US4549545A (en) * | 1984-03-05 | 1985-10-29 | Ethicon Inc. | Segmented polyurethane surgical buttressing pledgets |
US4633873A (en) * | 1984-04-26 | 1987-01-06 | American Cyanamid Company | Surgical repair mesh |
SE456346B (en) * | 1984-07-23 | 1988-09-26 | Pharmacia Ab | GEL TO PREVENT ADHESION BETWEEN BODY TISSUE AND SET FOR ITS PREPARATION |
US4674488A (en) * | 1985-03-04 | 1987-06-23 | American Hospital Supply Corporation | Method of treating bone fractures to reduce formation of fibrous adhesions |
US4655221A (en) * | 1985-05-06 | 1987-04-07 | American Cyanamid Company | Method of using a surgical repair mesh |
US4865031A (en) * | 1985-07-12 | 1989-09-12 | Keeffe Paul J O | Fabric and method of use for treatment of scars |
US5007916A (en) * | 1985-08-22 | 1991-04-16 | Johnson & Johnson Medical, Inc. | Method and material for prevention of surgical adhesions |
US5002551A (en) * | 1985-08-22 | 1991-03-26 | Johnson & Johnson Medical, Inc. | Method and material for prevention of surgical adhesions |
US4693720A (en) * | 1985-09-23 | 1987-09-15 | Katecho, Incorporated | Device for surgically repairing soft tissues and method for making the same |
US5061281A (en) * | 1985-12-17 | 1991-10-29 | Allied-Signal Inc. | Bioresorbable polymers and implantation devices thereof |
DE3684446D1 (en) * | 1985-12-28 | 1992-04-23 | Sumitomo Pharma | MEDICINAL PRODUCTS WITH DELAYED RELEASED RELEASE. |
US4792336A (en) * | 1986-03-03 | 1988-12-20 | American Cyanamid Company | Flat braided ligament or tendon implant device having texturized yarns |
US4840626A (en) * | 1986-09-29 | 1989-06-20 | Johnson & Johnson Patient Care, Inc. | Heparin-containing adhesion prevention barrier and process |
US5041138A (en) * | 1986-11-20 | 1991-08-20 | Massachusetts Institute Of Technology | Neomorphogenesis of cartilage in vivo from cell culture |
DE3774132D1 (en) * | 1986-12-17 | 1991-11-28 | Allied Signal Inc | IMPLANTABLE OBJECTS WITH A HYDROPHOBIC COMPONENT. |
US4906463A (en) * | 1986-12-22 | 1990-03-06 | Cygnus Research Corporation | Transdermal drug-delivery composition |
US5080893A (en) * | 1988-05-31 | 1992-01-14 | University Of Florida | Method for preventing surgical adhesions using a dilute solution of polymer |
JPS641216U (en) * | 1987-06-16 | 1989-01-06 | ||
CA1322262C (en) * | 1987-06-26 | 1993-09-21 | Yoshito Ikada | Artificial skin |
SE8802414D0 (en) * | 1988-06-27 | 1988-06-28 | Astra Meditec Ab | NEW SURGICAL MATERIAL |
US4920203A (en) * | 1987-12-17 | 1990-04-24 | Allied-Signal Inc. | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US5066772A (en) * | 1987-12-17 | 1991-11-19 | Allied-Signal Inc. | Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides |
US4916193A (en) * | 1987-12-17 | 1990-04-10 | Allied-Signal Inc. | Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides |
US4891263A (en) * | 1987-12-17 | 1990-01-02 | Allied-Signal Inc. | Polycarbonate random copolymer-based fiber compositions and method of melt-spinning same and device |
US4916207A (en) * | 1987-12-17 | 1990-04-10 | Allied-Signal, Inc. | Polycarbonate homopolymer-based fiber compositions and method of melt-spinning same and device |
US5185408A (en) * | 1987-12-17 | 1993-02-09 | Allied-Signal Inc. | Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides |
US5120802A (en) * | 1987-12-17 | 1992-06-09 | Allied-Signal Inc. | Polycarbonate-based block copolymers and devices |
US5145945A (en) * | 1987-12-17 | 1992-09-08 | Allied-Signal Inc. | Homopolymers and copolymers having recurring carbonate units |
US5152781A (en) * | 1987-12-17 | 1992-10-06 | Allied-Signal Inc. | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
DE3801426A1 (en) * | 1988-01-20 | 1989-08-03 | Ethicon Gmbh | FELTY IMPLANT |
CA1302140C (en) * | 1988-03-23 | 1992-06-02 | Melvin Bernard Herrin | Method for assembling composite carton blanks |
US5092884A (en) * | 1988-03-24 | 1992-03-03 | American Cyanamid Company | Surgical composite structure having absorbable and nonabsorbable components |
US4950483A (en) * | 1988-06-30 | 1990-08-21 | Collagen Corporation | Collagen wound healing matrices and process for their production |
US5019393A (en) * | 1988-08-03 | 1991-05-28 | New England Deaconess Hospital Corporation | Biocompatible substance with thromboresistance |
US5126140A (en) * | 1988-08-03 | 1992-06-30 | New England Deaconess Hospital Corporation | Thrombomodulin-coated bicompatible substance |
GB2222954B (en) * | 1988-08-31 | 1991-11-13 | Ethicon Inc | Tubular implant and process for the production thereof |
US5126141A (en) * | 1988-11-16 | 1992-06-30 | Mediventures Incorporated | Composition and method for post-surgical adhesion reduction with thermo-irreversible gels of polyoxyalkylene polymers and ionic polysaccharides |
US4911926A (en) * | 1988-11-16 | 1990-03-27 | Mediventures Inc. | Method and composition for reducing postsurgical adhesions |
JPH06104116B2 (en) * | 1988-11-29 | 1994-12-21 | 三菱化成株式会社 | Wound dressing |
CA2004740A1 (en) * | 1988-12-07 | 1990-06-07 | Cary Linsky | Low molecular weight heparin, heparinoid and hexuronyl hexosaminoglycan sulfate containing adhesion prevention barrier and process |
US5093319A (en) * | 1989-10-31 | 1992-03-03 | Pfizer Hospital Products Group, Inc. | Use of derivatives of chitin soluble in aqueous solutions for preventing adhesions |
US4994277A (en) * | 1989-10-31 | 1991-02-19 | Pfizer Hospital Products Group, Inc. | Use of xanthan gum for preventing adhesions |
DE3937272A1 (en) * | 1989-11-09 | 1991-05-16 | Boehringer Ingelheim Kg | NEW COPOLYMERS FROM TRIMETHYLENE CARBONATE AND OPTICALLY INACTIVE LACTIDS |
US5102983A (en) * | 1990-04-02 | 1992-04-07 | United States Surgical Corporation | Process for preparing foamed, bioabsorbable polymer particles |
US5080665A (en) * | 1990-07-06 | 1992-01-14 | American Cyanamid Company | Deformable, absorbable surgical device |
US5236447A (en) * | 1990-06-29 | 1993-08-17 | Nissho Corporation | Artificial tubular organ |
CA2094908C (en) * | 1990-12-06 | 2000-02-08 | Byron Kent Hayes | Implantable bioabsorbable article |
US5236444A (en) * | 1992-10-27 | 1993-08-17 | United States Surgical Corporation | Absorbable polymers and surgical articles made therefrom |
-
1994
- 1994-01-26 CA CA002114290A patent/CA2114290C/en not_active Expired - Lifetime
- 1994-01-27 EP EP94101218A patent/EP0610731B1/en not_active Expired - Lifetime
- 1994-01-27 DE DE69431376T patent/DE69431376T2/en not_active Expired - Lifetime
-
1995
- 1995-02-07 US US08/385,007 patent/US5795584A/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
US5795584A (en) | 1998-08-18 |
DE69431376D1 (en) | 2002-10-24 |
CA2114290A1 (en) | 1994-07-28 |
EP0610731B1 (en) | 2002-09-18 |
DE69431376T2 (en) | 2003-05-15 |
EP0610731A1 (en) | 1994-08-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2114290C (en) | Post-surgical anti-adhesion device | |
JP7235762B2 (en) | Medical device comprising poly(butylene succinate) and copolymers thereof | |
EP2954855B1 (en) | Woven and fibrous materials for reinforcing a staple line | |
US6685956B2 (en) | Biodegradable and/or bioabsorbable fibrous articles and methods for using the articles for medical applications | |
RU2574016C2 (en) | Reinforced resorbable synthetic matrix for haemostatic applications | |
RU2569057C2 (en) | Reinforced absorbable multilayer material for haemostatic applications | |
US9242026B2 (en) | Biosynthetic implant for soft tissue repair | |
EP2792351B1 (en) | Anti-adhesive composition, surgical mesh complex containing same for anti-adhesion functions, and method for manufacturing same | |
US20060083767A1 (en) | Surgical prosthesis having biodegradable and nonbiodegradable regions | |
CS213324B2 (en) | Haemostatic surgical felt | |
BR112012006453B1 (en) | HEMOSTASTIC COMPOSITE STRUCTURE AND METHOD OF PROVIDING HEMOSTASIA | |
Ikada | Bioabsorbable fibers for medical use | |
EP3106185B1 (en) | Synthetic prosthesis comprising a knit and a non porous film and method for forming same | |
KR101367978B1 (en) | Block-polymer membranes for attenuation of scar tissue | |
US20100266663A1 (en) | Tissue-treating implantable compositions | |
US20110274739A1 (en) | Methods for governing tissue growth | |
AU2012201639B9 (en) | Surgical mesh-like implant |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKEX | Expiry |
Effective date: 20140127 |
|
MKEX | Expiry |
Effective date: 20140127 |