Barbed sutures

ES 2 329 092 T3

DESCRIPTION

Barbed sutures.

Technical field

This application claims the rights to US Provisional Patent Application No. 60 / 842,763 filed on September 6, 2006.

Background of Related Art

Barbed sutures, which are generally made of the same materials as conventional sutures, offer several advantages for closing wounds compared to conventional sutures. A barbed suture includes an elongated body having one or more spaced barbs, protruding from the surface of the suture body along the length of the body. The barbs are arranged to allow passage of the barbed suture in one direction through tissue, but resist movement of the barbed suture in the opposite direction. Thus, one advantage of barbed sutures has been to provide a slip-resistant attribute.

Barbed sutures are known for use in cosmetic, laparoscopic, and endoscopic procedures. The use of barbed sutures makes it possible to apply tension to the tissue with less slippage of the suture in the wound. The number of suture barbs can be influenced by the size of the wound and the force required to hold the wound closed. Like a conventional suture, a barbed suture can be inserted into tissue using a surgical needle.

Bioactive agents such as antimicrobial agents have been associated with surgical devices to prevent microbial infections during the wound healing process. It is also known to coat surgical sutures with antimicrobial compounds to prevent and treat microbial infections.

Although antimicrobial agents have been used for surgical sutures and wound dressings to prevent infection, there remains a need for improved barbed sutures that can remain in vivo for extended periods of time with enhanced antimicrobial efficacy. There is also a need for simple and inexpensive procedures to improve the antimicrobial characteristics of barbed sutures for extended periods of time, thus allowing the use of lesser amounts of antimicrobial agents to achieve the desired in vivo antimicrobial effect. There is also a need to deliver other bioactive agents to wound sites to promote healing and the like.

WO 2006/079469 discloses a surgical suture system comprising a needle-like applicator, a barbed surgical suture material, and a cover. The surgical suture material may comprise an active ingredient that prevents infection and improves the uptake of the suture material in the tissue.

US 2003/0149447 discloses a barbed surgical suture, the barbs eliminating the need for knots in the suture. Optionally, specialized coatings can be added to improve lubricity, reduce inflammatory response, aid insertion, and enhance healing.

Summary

A surgical suture is provided as defined in claim 1 having an elongated body comprising at least one filament having a proximal end and a distal end. The suture includes barbs that protrude from the elongated body toward at least one end thereby forming an angle of less than about 90 degrees between the barbs and the suture body into which a bioactive agent is deposited within the barb angles, that is, the angle formed between the barb and the surface of the suture.

A method of repairing tissue is also provided with the sutures of the present disclosure.

Brief description of the drawings

Various of the embodiments of the present description will be described hereinafter with reference to the figures in which:

Figure 1 is a perspective view of a barbed suture according to the present disclosure attached to a needle; and Figure 2 is a perspective view of a bidirectional barbed suture attached to a needle at each end;

Figures 3A-3C are plan views of a tubular insertion device used with a barbed suture in accordance with the present disclosure; and Figures 4A-4B are plan views of a cover used with a barbed suture.

ES 2 329 092 T3

Detailed description

Surgical barbed sutures are described herein. Sutures according to the present disclosure may be of monofilament or multifilament construction. The suture may have both a proximal and a distal end, with barbs protruding from the elongated body towards at least one end thereby forming an angle of less than about 90 degrees between the barbs and the suture body. A bioactive agent is deposited within the barb angles, that is, the angle formed between the barb and the surface of the suture. Placing a bioactive agent at the angle formed between the barbs and the surface of the suture places the bioactive agent in precisely defined locations within a wound closure in a tissue, thus providing a controlled, sustained release dosage form only.

Barbed sutures according to the present disclosure can be formed of degradable materials, non-degradable materials, and combinations thereof. Suitable degradable materials that can be used to form the medical device include natural collagenous materials or synthetic resins including those derived from alkylene carbonates such as trimethylene carbonate, tetramethylene carbonate and the like, caprolactone, valerolactone, dioxanone, polyanhydrides, polyesters, polyacrylates, poly (methyl methacrylates), polyurethanes, glycolic acid, lactic acid, glycolide, lactide, polyhydroxybutyrates (PHB), polyorthoester, polyhydroxyalkanoates, homopolymers thereof, copolymers thereof, and combinations thereof. In some embodiments, polyesters based on glycolide and lactide, especially copolymers of glycolide and lactide, can be used to form a suture of the present disclosure.

Suitable non-degradable materials that can be used to form the sutures of the present disclosure include polyolefins; such as polyethylene, polypropylene, copolymers of polyethylene and polypropylene, and blends of polyethylene and polypropylene; ultra-high molecular weight polyethylene, polyamides (also known as nylon); polyesters such as polyethylene terephthalate; polytetrafluoroethylene; polyether esters such as polybutester; polytetramethylene ether glycol; 1,4-butanediol; polyurethanes; and combinations thereof. In other embodiments, the non-degradable materials can include silk, catgut, cotton, linen, carbon fibers, and the like. In some useful embodiments, polypropylene can be used to form the suture. The polypropylene can be isotactic polypropylene or a mixture of isotactic and syndiotactic or atactic polypropylene.

The filaments used to form sutures of the present disclosure can be formed using any technique known to those skilled in the art, such as, for example, extrusion, molding, and / or solvent casting.

In embodiments, the suture of the present disclosure can include a thread composed of more than one filament, which can contain multiple filaments of the same or different materials. When the sutures are composed of multiple filaments, the suture can be prepared using any known technique such as, for example, braiding, weaving or knitting. The filaments can also be combined to produce a nonwoven suture. The filaments themselves can be stretched, oriented, kinked, twisted, mixed together, or air entangled to form threads as part of the suture formation process. In one embodiment, a multifilament suture of the present disclosure can be produced by braiding. Braiding can be done by any method known to those skilled in the art.

Once the suture is constructed, it can be sterilized by any means known to those of skill in the art.

Sutures according to the present disclosure can be coated or impregnated with one or more medically-surgically useful substances, for example bioactive agents that beneficially accelerate or modify the healing process when the suture is applied to a wound or surgical site. Suitable bioactive agents include, for example, biocidal agents, antimicrobial agents, drugs, growth factors, anticoagulant agents, clotting agents, analgesics, anesthetics, anti-inflammatory agents, healing agents and the like, chemotherapeutic agents, biological agents, protein therapeutics, antibodies. , DNA, RNA, peptides, polysaccharides, lectins, lipids, antiangiogenic drugs, polymeric drugs, and combinations thereof.

Bioactive agents include substances that are beneficial to the animal and tend to promote the healing process. For example, a suture can be provided with a bioactive agent that can be deposited at the sutured site. The bioactive agent can be chosen for its antimicrobial properties, ability to promote wound repair and / or tissue growth, or for specific indications such as thrombosis. In embodiments, combinations of such agents can be applied to a suture of the present disclosure.

The term "antimicrobial agent" as used herein includes an agent that helps the body destroy or resist pathogenic (disease-causing) microorganisms. An antimicrobial agent includes antibiotics, antiseptics, disinfectants, and combinations thereof. Antimicrobial agents that are slowly released to tissue can be applied in this manner to help combat clinical and subclinical infections at a trauma or surgical wound site. In embodiments, suitable antimicrobial agents can be soluble in one or more solvents.

In embodiments, the following antimicrobial agents can be used alone or in combination with other bioactive agents described herein: an anthracycline, doxorubicin, mitoxantrone, a fluoropyrimidine, 5-fluorouracil (5-FU), a folic acid antagonist , methotrexate, a podophyllotoxin, etoposide,

ES 2 329 092 T3 camptothecin, a hydroxyurea, a platinum complex, cisplatin, doxycycline, metronidazole, trimethoprim-sulfamethoxazole, rifamycins such as rifampin, a fourth-generation penicillin (for example, a ureidopenicillin, a carboxypenicillin, mezzocillin, a carbonate and ticarcillin, and an analog or derivative thereof), a first-generation cephalosporin (for example, cefazolin sodium, cephalexin, cefazolin, cephapirin, and cephalothin), a carboxypenicillin (eg, ticarcillin), a second-generation cephalosporin (eg, cefuroxime, cefotetan, and cefoxitin), a third-generation cephalosporin (eg, naxcel, cefdinir, cefoperazone, ceftazidime, ceftriaxone, and cefotaxime), polyvinylpyrone (PVProlidone) ), a fourth generation cephalosporin (for example, cefepime), a monobactam (for example, aztreonam), a carbapenem (for example, imipenem, ertapenem and meropenem), an aminoglycoside (for example, streptomycin, gentamicin, tobramycin, and amikacin), a member of the MSL group (eg, a macrolide, a long-acting macrolide, a lincosamide, a streptogramin, erythromycin, azithromycin, clindamycin, sineroid, clarithromycin, and kanamycin sulfate), such as tetracycline minocycline, fusidic acid, trimethoprim, metronidazole; a quinolone (for example, ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, levofloxacin, and trovafloxacin), or synthesis inhibitor (eg, metronidazole), a sulfonamide (eg sulfamethoxazole, trimethoprim, including tetrafixin, spectycin nitrofurantoin, polymyxin B and neomycin sulfate), beta-lactam inhibitors such as sulbactam, chloramphenicol, glycopeptides such as vancomycin, mupirocin, polyenes such as amphotericin B, azoles such as fluconazole, and other known antimicrobial agents known in the art.

Examples of antiseptics and disinfectants that can be used as an antimicrobial agent include hexachlorophene; cationic biguanides such as chlorhexidine and cyclohexidine; iodine and iodophors such as polyvidone iodine; halo-substituted phenolic compounds such as PCMX (ie, p-chloro-m-xylenol) and triclosan (ie, 2,4,4'-trichloro-2'-hydroxy-diphenyl ether); medical furan preparations such as nitrofurantoin and nitrofurazone; methenamine; aldehydes such as glutaraldehyde and formaldehyde; and alcohols. In some useful embodiments, at least one of the antimicrobial agents can be an antiseptic such as triclosan.

To promote wound repair and / or tissue growth, one or more bioactive agents known to achieve either or both of these objectives can be applied to the suture as healing agents or tissue growth agents. Such "fibrosis inducing agents" or coagulants are used for the promotion of aneurysm or embolism when desired for the treatment of particular vascular diseases or lesions, or for example, blocking the primary blood supply of a tumor. In embodiments, the barbed suture having a clotting agent deposited within the barb angles according to the present disclosure can contribute to the capture of blood components and platelets.

Examples of chemotherapeutic agents that can be used include one or more of the following: doxorubicin (Dox), paclitaxel (PTX), or camptothecin (CPT), polyglutamate-PTX (CT-2103 or Xyotax), N- (2-hydroxypropyl) methacrylamide (HPMA) copolymer, anthracycline, letrozole, anastrozole, receptor inhibitors epidermal growth inhibitors, tyrosine kinase inhibitors, apoptosis modulators, anthracycline antibiotics such as daunorubicin and doxorubicin, alkylating agents such as cyclophosphamide and melphalan, antimetabolites such as methotrexate and 5-fluorouracil, poly (ethylene glycol) (PEG), poly (glutamic acid) (PGA), polysaccharides, polymer-drug conjugates thereof, copolymers thereof, and combinations thereof.

Clotting agents include one or more of the following: a fibrosing agent that promotes cell regeneration, a fibrosing agent that promotes angiogenesis, a fibrosing agent that promotes fibroblast migration, a fibrosing agent that promotes fibroblast proliferation, a fibrosing agent that promotes extracellular matrix deposition, an agent fibrosing that promotes tissue remodeling, a fibrosing agent that is an irritant to the diverticular wall, silk (such as silkworm silk, spider silk, recombinant silk, raw silk, hydrolyzed silk, acid-treated silk, and acylated silk), talc, chitosan, polylysine, fibronectin, bleomycin, or an analog or derivative thereof, connective tissue growth factor (CTGF), beryllium metal, or a oxide thereof, copper, sarazine, silica, crystalline silicates, quartz powder, talcum powder, ethanol, a component of the extracellular matrix, collagen, fibrin, fibrinogen, poly (ethylene terephthalate), poly (ethylene-co-acetate vinyl), N-carboxybutyl chitosan, an RGD protein, a vinyl chloride polymer, cyanoacrylate, cross-linked poly (ethylene glycol) -methylated collagen, an inflammatory cytokine, TGI / i, PDGF, VEGF, TNFa, NGF, GM-CSF, IGFa, IL -1, IL-8, IL-6, a growth hormone, a bone morphogenic protein, a cell proliferation agent, dexamethasone, isotretinoin, 17- / i-estradiol, estradiol, diethylstibesterol, cyclosporin a, all-trans-retinoic acid or an analog or derivative thereof, wool (including animal wool, wood wool, and mineral wool), cotton, bFGF, polyurethane, polytetrafluoroethylene, poly (alkyl cyanoacrylate), activin, angiopoietin, insulin-like growth factor (IGF), hepatocyte growth factor ( HGF), a colony stimulating factor (CSF), erythropoietin, an interferon, endothelin 1, angiotensin II, bromocriptine, methyl sergide, fibrosin, fibrin, an adhesive glycoprotein, proteoglycan, hyaluronan, Acid and cysteine-rich secreted protein (SPaRC), a thrombospondin, tenacin, a cell adhesion molecule, a matrix metalloproteinase inhibitor, magainin, renal or tissue plasminogen activator, a tissue matrix metalloproteinase inhibitor, methotrexate, carbon tetrachloride, thioacetamide, superoxide dismutase to scavenge tissue damaging free radicals, tumor necrosis factor for cancer treatment, colony stimulating factor, interferon, interleukin 2 or other lymphokines to boost the immune system, platelet rich plasma, thrombin, combinations thereof, and so on.

A wide variety of antiangiogenic factors can easily be used within the context of the present disclosure. Representative examples include anti-invasive factor; retinoic acid and derivatives thereof; paclitaxel, a highly derivatized diterpenoid; suramina; tissue inhibitor of metalloproteinase 1; tissue inhibitor

ES 2 329 092 T3 of metalloproteinase 2; plasminogen activator inhibitor 1; plasminogen activator inhibitor 2; various forms of the lighter "group d" transition metals such as, for example, vanadium, molybdenum, tungsten, titanium, niobium and tantalum species and complexes thereof; platelet factor 4; protamine sulfate (clupein); sulfated chitin derivatives (prepared from snow crab shells); sulfated peptidoglycan-polysaccharide complex (SP-PG) (the function of this compound can be enhanced by the presence of steroids such as estrogen and tamoxifen citrate); staurosporine; matrix metabolism modulators, including for example proline analogs {[(L-azetidine-2-carboxylic acid (LACA), cishydroxyproline, d, L3,4-dehydroproline, thiaproline, α, α-dipyridyl, j6-aminopropionitrile fumarate; MDL 27032 (4-propyl-5- (4-pyridinyl) 2 (3H) -oxazolone; methotrexate; mitoxantrone; heparin; interferons; 2-macroglobulin in serum; ChIMP-3; chymostatin; ^ -cyclodextrin tetradecasulfate; eponemycin; camptothecin; fumagillin, gold sodium thiomalate ("GST"); Dpenicillamine ("CDPT"); serum β-1-anticolagenase; a2-antiplasmin; bisantreno; lobenzarite disodium (N- (2) carboxyphenyl-4-chloroanthroneyl disodium acid or "CCA", thalidomide, angiostatic steroid, AGM-1470, carboxinaminoimidazole; metalloproteinase inhibitors such as BB94, analogs and derivatives thereof, and combinations thereof.

A wide variety of polymeric drugs can be readily used within the context of the present disclosure. Representative examples include steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, and combinations thereof. Examples of the non-steroidal anti-inflammatory agent that can be used with the present disclosure are aspirin, indomethacin, ibuprofen, phenylbutazone, diflusinal, and combinations thereof.

Examples of the steroidal anti-inflammatory agent that can be used are glucocorticoids such as cortisone and hydrocortisone, betamethasone, dexamethasone, fluprednisolone, prednisone, methylprednisolone, prednisolone, triamcinolone, paramethasone, and combinations thereof.

Although the above bioactive agents have been provided for illustrative purposes, it should be understood that the present disclosure is not limited thereto. In particular, although reference is specifically made above to certain bioactive agents, it is to be understood that the present disclosure includes analogs, derivatives and conjugates of such agents.

Sutures according to this disclosure may also include, for example, biologically acceptable colorants, antioxidants, plasticizers, which may be impregnated into the filament (s) used to form a suture of the present disclosure or included in a coating over it. /the same).

As indicated above, bioactive agents can be impregnated in the materials used to form sutures of the present disclosure or deposited on the surface thereof. Bioactive agents can be applied to a barbed suture of the present disclosure using any method known to those skilled in the art including, for example, dipping, spraying, vapor deposition, brushing, compounding, and the like.

In embodiments the bioactive agent, such as an antimicrobial agent, can be applied to a barbed suture of the present disclosure as part of a bioactive agent solution. The bioactive agent solution can include any suitable solvent or combination of solvents for the chosen bioactive agent. To be suitable, the solvent must (1) be miscible with the bioactive agent, and (2) not appreciably affect the integrity of any material used to form a medical device, such as barbed suture. In some useful embodiments, the solvent used is a polar solvent. Some examples of suitable solvents include methylene chloride, chloroform, ethyl acetate, methyl acetate, N-methyl-2-pyrrolidone, 2-pyrrolidone, propylene glycol, tetrahydrofuran (THF), acetone, oleic acid, methyl ethyl ketone, water, and mixtures thereof. In one embodiment, methylene chloride can be used as the solvent.

The procedure for preparing the bioactive agent solution can be a relatively simple procedure including mixing, combining, and the like. Any known technique can be used to apply the bioactive agent solution to the medical device. Suitable techniques include dipping, spraying, spreading, brushing, and the like.

The bioactive agent solution generally contains from about 0.1% to about 20% of the bioactive agent by weight, in embodiments from about 0.5% to about 5% of the bioactive agent by weight. The exact amount of the bioactive agent will depend on several factors, such as the particular agent used, the medical device with which it comes in contact, and the choice of solvent used. In one embodiment, where the bioactive agent is an antimicrobial agent, the antimicrobial solution may contain from about 0.1% to about 10% of the chosen antimicrobial agent, in embodiments from about 1% to about 5% of the antimicrobial agent.

The amount of the bioactive agent solution applied should be an amount effective to provide the desired bioactive properties to the suture. The exact amount will depend on the configuration of the suture and the formulation of the solution. Since the bioactive agent solution contains a solvent, a curing step can be used in useful embodiments to remove the solvent, leaving the bioactive agent on the suture. The stages

Suitable curing agents for solvent removal include, but are not limited to, evaporation and / or lyophilization. After removal of the solvent, the bioactive agent remains attached to the suture at the angle formed between the barb and the suture body.

Regardless of the application method, the amount of the bioactive agent on the suture can be from about 0.01% by weight of the suture to about 2% by weight of the suture, in embodiments from about 0, 02% by weight of the suture to about 1% by weight of the suture, typically from about 0.05% by weight of the suture to about 0.5% by weight of the suture.

Once applied, the bioactive agent will not be lost due to evaporation, sublimation, volatilization, etc. during subsequent handling, processing, and storage of the barbed suture. However, upon application of the barbed suture in vivo, that is, after its use in suturing a wound, the attachment of the barbs to the tissue will release the bioactive agent to the tissue.

In other embodiments, the bioactive agent can be included in a coating applied to the suture. Suitable coatings that can be used are known to one skilled in the art and include, for example, biodegradable coatings such as those disclosed in US Patent Publication No. 20040153125. Biodegradable polymers may be especially suitable as they will release the bioactive agent in vivo as the biodegradable polymer is reabsorbed by the body.

In embodiments, mixtures useful in forming the aforementioned coatings include a bioactive agent such as an antimicrobial agent as the predominant component in an antimicrobial effective amount. A "predominant amount" refers to one or more components that are present in an amount greater than about 50 percent by weight. A "minor amount" refers to one or more components that are present in an amount of up to about 50 percent by weight. The minor component can include copolymers containing biodegradable monomers such as caprolactone.

An "antimicrobial effective amount" of a given component is an amount at which the component prevents the growth of bacteria to reduce or prevent contamination of the wound site.

In embodiments, the antimicrobial degradable coating composition for biocompatible surgical implantable devices is inexpensive, biocompatible, and does not undergo excessive diffusion. "Biocompatible" means that no serious systemic toxicity is caused by the presence of an object in a living system. It is contemplated that biocompatible objects can cause certain amounts of clinically acceptable toxicity including irritation and / or other adverse reactions in certain individuals.

Any biodegradable polymer known to those skilled in the art can be used in the present coatings. In embodiments, the biodegradable polymer may contain epsilon-caprolactone as a component thereof. Suitable caprolactone-containing copolymers include copolymers that can be synthesized by well-known conventional polymerization techniques. In some embodiments, suitable caprolactone-containing copolymers are "star" copolymers obtained by polymerizing a predominant amount of epsilon-caprolactone and a minor amount of another biodegradable monomer that can be polymerized therewith in the presence of a polyhydric alcohol initiator.

In embodiments, the caprolactone-containing copolymer can be obtained by polymerizing a predominant amount of epsilon-caprolactone and a minor amount of at least one other copolymerizable monomer or mixture of such monomers in the presence of a polyhydric alcohol initiator. The polymerization of these monomers contemplates all the various types of monomer addition, i.e., simultaneous, sequential, simultaneous followed by sequential, sequential followed by simultaneous, etc.

In certain embodiments, the copolymer herein may contain from about 70 to about 98, and preferably from about 80 to about 95, weight percent of units derived from epsilon-caprolactone, with the remainder being derived from the copolymer of the other copolymerizable monomer (s).

Suitable monomers that can be copolymerized with epsilon-caprolactone include alkylene carbonates such as trimethylene carbonate, tetramethylene carbonate, dimethyltrimethylene carbonate; dioxanones; dioxepanones; degradable cyclic amides; degradable cyclic ether-esters derived from crown ethers; hydroxy acids that can undergo esterification, including both alpha-hydroxy acids (such as glycolic acid and lactic acid) and beta-hydroxy acids (such as beta-hydroxybutyric acid and gamma-hydroxyvaleric acid); poly (alkyl ethers) (such as polyethylene glycol and polypropylene glycol and combinations thereof); polyvinylpyrrolidone, hydroxyethyl methacrylate, phosphorylcholine, acrylic acid, methacrylic acid, vinyl monomers, vinyl alcohols, vinyl acetate, and combinations thereof. In embodiments, a suitable monomer for use with the present disclosure is glycolide.

Suitable polyhydric alcohol initiators include glycerol, trimethylolpropane, 1,2,4-butanetriol, 1,2,6hexanetriol, triethanolamine, triisopropanolamine, erythritol, threitol, pentaerythritol, ribitol, arabinitol, xylitol, N, N, N ', N'

ES 2 329 092 T3 tetrakis (2-hydroxyethyl) ethylenediamine, N, N, N ', N'-tetrakis (2-hydroxypropyl) ethylenediamine, dipentaerythritol, alitol, dulcitol, glucitol, altritol, iditol, sorbitol, mannitol, inositol and the like ; mannitol being preferred.

The polyhydric alcohol initiator is generally used in relatively small amounts, for example, from about 0.01 to about 5, and preferably from about 0.1 to about 3, percent by weight of the total monomer mixture. .

The coating composition may contain from about 0.3 to about 10, and preferably from about 0.5 to about 5, percent by weight of the copolymer. Such a coating provides sutures with the combined desirable properties of antimicrobial activity and improved handling characteristics.

In addition to the antimicrobial agents described above, in some embodiments the coating can include one or more fatty acid components such as fatty acids, fatty acid salts, and fatty acid ester salts that can confer antimicrobial characteristics to the suture.

When the coating includes a fatty acid metal salt, the fatty acid metal salt used as an antimicrobial agent can include metal stearates. In one embodiment, the fatty acid salt used as an antimicrobial agent is silver stearate. In another embodiment, the fatty acid salt (s) used as an antimicrobial agent can be combined with fatty acid esters such as stearoyl lactylates, particularly calcium stearoyl lactylate.

Suitable fatty acids that can be used in the present coatings include the biocompatible monovalent and polyvalent metal salts of fatty acids having 6 or more carbon atoms. Examples of fatty acids useful for forming a metal salt of a fatty acid useful herein include butyric, caproic, caprylic, capric, lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, etc. Examples of monovalent metals useful for forming a metal salt of a fatty acid useful in the various embodiments described herein include lithium, rubidium, cesium, francium, copper, silver, and gold. Examples of polyvalent metals useful to form a metal salt of a fatty acid useful in the various embodiments described herein include aluminum, tin, lead, bismuth, and the polyvalent transition metals. Thus, suitable fatty acid metal salts useful herein include fatty acid salts of lithium, rubidium, cesium, francium, copper, silver, gold, beryllium, magnesium, strontium, barium, radium, aluminum, tin, lead. , bismuth, zinc, cadmium, mercury, etc.

The metal salt of a fatty acid is present in the coating composition in an antimicrobial effective amount as defined above. The metal salt of a fatty acid can consist of a single chemical compound. However, the metal salt of a fatty acid can also be a mixture of various metal salts of fatty acids. The metal salt of a fatty acid may be present in an amount of from about 30 percent to about 70 percent by weight of the coating composition, in embodiments from about 45 percent to about 55 percent. by weight of the coating composition.

The metal salt of a fatty acid can be relatively insoluble in cold water. Where desirable, a solvent can be used to improve the working properties, eg, viscosity, miscibility, etc., of the metal salt of a fatty acid. Suitable solvents include, for example, alcohols, for example methanol, ethanol, propanol, chlorinated hydrocarbons (such as methylene chloride, chloroform, 1,2-dichloroethane), aliphatic hydrocarbons such as hexane, heptene, ethyl acetate ). Where desirable, heat can be applied to the fatty acid metal salt solvent mixture to improve its solubility. For example, temperatures between about 30 ° C and about 60 ° C are appropriate.

In certain embodiments, the fatty acid esters can be combined with the metal salt of a fatty acid in the coating composition. Such esters include, for example, calcium stearate, stearoyl lactylate esters, palmityl lactylate esters, oleyl lactylate esters such as calcium, magnesium, aluminum, barium or zinc stearoyl lactylate; calcium, magnesium, aluminum, barium or zinc palmityl lactylate; calcium, magnesium, aluminum, barium or zinc oleyl lactylate; with calcium stearate and calcium stearoyl-2-lactylate (such as calcium stearoyl-2-lactylate commercially available under the trade name VERV from American Ingredients Co., Kansas City, Mo.) being preferred. When desired, the fatty acid ester can be combined with a solvent. Suitable solvents include those mentioned above.

When the bioactive agent is included as part of a coating, the bioactive agent and coating components can be added to separate solvents, and the resulting solvent mixtures can then be combined to form a coating solution. In other embodiments, the bioactive agent and coating components can be combined with each other and then mixed with a solvent to form a coating solution or any combination. The order of addition is not critical and therefore can be determined by routine experimentation depending on the intended use.

The coating can be applied to a suture by any suitable process, for example, by passing the suture through a solution of the coating mixture, passing through a brush or other dissolution applicator.

ES 2 329 092 T3 coating, or passing through one or more spray nozzles that dispense the coating solution from the suture. The coating solution may contain from about 30 to about 70, in embodiments from about 45 to about 55, percent by weight solvent. In embodiments, a mixture of methylene chloride, hexane, and ethanol can be used as the solvent. The suture moistened with the coating solution can optionally be passed through or maintained in a drying oven for a time and at a temperature sufficient to vaporize and dry the solvent. If desired, the suture coating composition may optionally contain additional bioactive components or agents described above, for example coloring matters, antibiotics, antiseptics, growth factors, anti-inflammatory agents, etc.

The barbs can be formed on the body surface of a suture using any procedure within the scope of one of ordinary skill in the art. Such procedures include, but are not limited to, cutting, molding, and the like. In some embodiments, the barbs can be formed by making sharp angled cuts directly into the suture body, the cut portions being pushed outward and away from the suture body. The depth of the barbs thus formed in the suture body may depend on the diameter of the suture material and the depth of the cut. In some embodiments, a device suitable for cutting a plurality of axially spaced barbs on the outside of a suture filament may utilize a cutting pad, a cutting pad vise, a cutting jig, and a set of blades. to perform the cut. In operation, the cutting device exhibits the ability to produce a plurality of axially spaced tines in the same or a random configuration and at different angles to each other. Other suitable procedures for cutting the barbs include the use of a laser or manual procedures. The suture can also be formed by injection molding, extrusion, stamping, and the like. The suture can be packaged in any number of desired pre-cut lengths and pre-shaped curves.

In embodiments, all of the barbs may be aligned to allow the suture to move through tissue in one direction and resist movement through tissue in the opposite direction. For example, referring to Figure 1, barbs 12 in a suture 10 can be formed into a monodirectional suture. In embodiments, suture 10 may be attached to needle 16. Barbs 12 may yield toward body 14 of suture 10. Barbs 12 allow movement of suture 10 through tissue in the direction of movement of a needle end 16 but are generally rigid in the opposite direction and prevent movement of suture 10 in the direction opposite to the direction of movement of a needle end 16.

Suture 10 includes a bioactive agent (not shown) disposed within the angle between barb 12 and suture body 14.

Alternatively, a multifilament suture (not shown) can be used which can include filaments made from biocompatible degradable polymers, biocompatible non-degradable polymers, or combinations thereof. In embodiments, a multifilament suture may be provided that includes a biocompatible degradable polymer that includes a bioactive agent disposed within the angle between the barb and the suture body. In another embodiment, a multifilament suture can include individual filaments made from a combination of biocompatible degradable polymer or biocompatible non-degradable polymer that includes a bioactive agent disposed within the angle between the barb and the suture body.

In other embodiments, the barbs may be aligned in a first part of a length of a suture to allow movement of a first end of the suture through the tissue in one direction, while the barbs in a second part of the Suture length may be aligned to allow movement of the second end of the suture in the opposite direction. For example, as depicted in Figure 2, a suture 110 can be bi-directional. Barbed suture 110 includes elongated body 114 having two zones, body part 114a and body part 114b, distal first and second needle ends 116a and 116b for penetrating tissue, and a plurality of barbs 112a. and 112b extending from the periphery of body 114. An antimicrobial agent may be disposed within the angle formed between barbs 112a and 112b and suture body 114. Barbs 112a in a first body part 114a between the first end of suture 110 and a first axial location in the suture body allow movement of suture 110 through tissue in the direction of movement of first needle end 116a. and prevent movement of the suture 110 relative to the tissue in the opposite direction to the direction of movement of the first needle end 116a. Barbs 112b in a second body part 114b between a second needle end 116b of a suture 114 and a second axial location in the body that is less than the distance from the second needle end 116b to the first axial location allow movement of a suture 114 through the tissue in the direction of movement of a second needle end 116b and prevent movement of a suture 114 with respect to the tissue in the opposite direction to the direction of movement of the second needle end 116b.

The barbs can be arranged in any suitable pattern, for example, in a helical pattern. The number, configuration, spacing, and surface area of ​​the barbs may vary depending on the tissue in which the suture is used, as well as the composition and geometry of the material used to form the suture. Additionally, the barb ratios can be kept relatively constant while the overall barb length and barb spacing can be determined based on the tissue being connected. For example, if the suture is to be used to connect the edges of a wound in the skin or a tendon, the barbs can be made relatively short and stiffer to facilitate entry into this fairly firm tissue. Alternatively, if the suture is designed to

ES 2 329 092 T3 for use in adipose tissue, which is relatively soft, the barbs can be made longer and more widely spaced to increase the ability of the suture to hold the soft tissue.

The surface area of ​​the tines can also vary. For example, tines with more rounded tips of varying sizes can be manufactured designed for specific surgical applications. For joining adipose and relatively soft tissues, longer tines may be desirable, while smaller tines may be more suitable for collagen-dense tissues. In some embodiments, a combination of large and small barbs within the same framework may be beneficial, for example when using a suture in the repair of tissue with different layered structures. The use of the combination of large and small barbs with the same suture where the barb sizes are adapted for each layer of tissue will ensure maximum anchoring properties. In embodiments, a monodirectional suture as depicted in Figure 1 can have both large and small barbs; In other embodiments, a bidirectional suture as depicted in Figure 2 may have both large and small barbs.

In embodiments, the sutures of the present disclosure may be colored in order to increase the visibility of the suture in the surgical field. Any suitable coloring material can be used for incorporation into sutures. Such coloring matters include, but are not limited to, carbon black, bone black, D&C green # 6, and D&C violet # 2. In embodiments, the sutures according to the present disclosure can be dyed by adding coloring matter in an amount of up to about a small percent, in other embodiments by adding coloring matter in an amount of about 0.2%, in forms of still further embodiment in an amount of from about 0.06% to about 0.08%.

In order to facilitate attachment of the needle to a suture of the present disclosure, conventional tip forming agents may be applied to the braid. Two pointed ends for attaching a needle to each end of the suture may be desirable to provide a so-called double-armed suture. Attachment of the needle can be accomplished by any conventional procedure such as crimping, drawing, etc., as is known to those skilled in the art. Wounds can be sutured by passing the needle suture through tissue to create a wound closure. The coating, in addition to enhancing the handling characteristics of the suture, advantageously exhibits antimicrobial properties to promote healing and prevent infection.

In some embodiments, the contribution of the barb to the architecture of the suture or a wound closure device can contribute to the capture of blood components and platelets. Referring to Figures 3A, 3B, 3C, a tubular insertion device 22 can be used to introduce a barbed suture 10 according to the present disclosure into a blood vessel 20. Such a tubular insertion device 22 may have a tubular body in which the barbed suture 10 is disposed, as well as a distal end 24 and a proximal end 26. In use, the pointed end of a barbed suture 10 of the present disclosure can be pushed with the distal end 24 of the tubular insertion device through skin, tissue, vessels, and the like at an insertion point. The pointed end of the barbed suture 10 and the distal end 24 of the tubular insertion device are pushed through the tissue until they reach an end point. The proximal end 26 of the tubular inserter 22 is then grasped and pulled to remove the inserter 22, leaving the barbed suture 10 in place.

For ease of movement of the tubular insertion device, the tubular insertion device 22 may include a cord, thread, or the like to pull and remove the insertion device 22 from the barbed suture as illustrated in FIG. 3B. In exemplary embodiments, tubular insertion device 22 detaches from barbed suture 10, allowing barbed suture 10 to expand to the full thickness of the vessel and anchor itself to vessel 20 . As illustrated in Figure 3C, the detachment of the tubular insertion device 22 and the expansion of the barbed suture 10 allows the capture of circulating blood components and platelets to instigate vascular blockage and / or coagulation of the vessel 20.

The barbed suture in Figures 3A-3C illustrates a bended, flexible configuration. However, it is envisioned that a variety of fiber or suture configurations may be used. In other embodiments, the fiber configurations may include twisting the barbed device within the cover (not shown).

In an exemplary embodiment, when present, a tubular insertion device surrounding a barbed suture of the present disclosure protects the bioactive agent that is disposed within the barb angle formed by the barb and the suture body. Thus, the tubular insertion device can help keep the barbed suture intact and the bioactive agent attached to the surface of the suture during insertion, as well as during handling and storage of the suture. This minimizes the loss of bioactive agent in the packaging of the medical device, the environment, etc. However, after engaging the barbed suture and tubular insertion device in vivo, movement of the sheath relative to the suture to remove the sheath from the tissue exposes the bioactive agent to the tissue and aids in the release of the bioactive agent from the tissue. contact surface of the barb and the suture body towards the wound closure. The barbed suture expands to the full thickness of the vessel and acts as an anchor for the patient's tissue.

In embodiments where a clotting agent is used, the barbed suture also captures circulating blood components and platelets and instigates vascular blockage or clotting. If the mechanical property requirements are not too restrictive, a superabsorbent material or hydrogel can be used to concentrate

ES 2 329 092 T3 additionally the blood components, or the barbed device can also direct and place the hydrogel-like material in its final location.

Referring to Figures 4A-4B, a cover 23 may be used to introduce a barbed suture 10 according to the present disclosure into a blood vessel 20. Such a cover 23 can have a tubular body in which the barbed suture is arranged. barbs 10. In one embodiment, cover 23 may be provided at one end of barbed suture 10 and in other embodiments, cover 23 can be provided at both ends of barbed suture 10 (not shown). In embodiments, cover 23 may be formed of materials such as, but not limited to, filament fibers, nylon fibers, polyester (PET), polyester copolymer (coPET), polypropylene (PP), and polyethylene (PE). , which are designed to swell in order to block vessel 20 and induce coagulation as the barbs in the suture, expanded and fully engaged within vessel 20, They capture platelets and blood components to aid in clotting. Barbed suture 10 includes a bioactive agent within the span angle of the barb and elongated body of the suture to enhance coagulation of vessel 20.

Methods for repairing tissue are also provided with the sutures of the present disclosure. The sutures of the present disclosure can be used in any cosmetic, endoscopic, or laparoscopic procedure. In addition, the sutures of the present disclosure can be used to join tissue to tissue including, but not limited to, joining tissue to a ligament.

In embodiments, the sutures of the present disclosure can be held in place without the need for knots. In such cases, the tissue located above a suture of the present disclosure placed in vivo can be physically massaged or manipulated to a desired position to enhance the holding of the tissue in the desired position. In embodiments, physical manipulation of tissue located above a suture of the present disclosure can enhance the release of any pharmaceutical agent located on the suture, including any pharmaceutical agent that is at the angle between a barb and the body of the a suture of the present disclosure.

For example, sutures of the present disclosure can be used to provide lift to tissue, which may be desirable in certain cosmetic applications. In embodiments, a method of closing tissue using sutures includes inserting a first end of a suture, optionally attached to a needle, at an insertion point on the surface of a person's body. The first end of the suture can be pushed through the soft tissue until the first end extends out of the soft tissue at an exit point. The first end of the suture can then be grasped and pulled to draw the first part of the suture through the soft tissue so that a length of the first part of the suture remains in the soft tissue between the insertion point and the exit point of the first end. The soft tissue can then be manually grouped and at least a portion of the suture advanced to provide the desired amount of lift.

Specific cosmetic surgical applications that may utilize this physical manipulation of a suture as described above include, for example, facelifts, browlifts, thigh lifts, and breast lifts.

Although the above description contains many details, these details should not be construed as limiting the scope of the description, but only by way of example of the embodiments thereof. Those skilled in the art will appreciate many other possibilities, including the use of other wound closure devices, within the scope of the description as defined by the claims appended hereto.