Suture with extended antibacterial properties

Abstract

The present invention relates to coated medical devices, such as implantable and coatable devices, such as sutures, having extended antibacterial properties, handling, knot slidability, and in situ performance, and methods of making and using the same.

Description

[0001] Priority declaration

[0002] This application claims priority to U.S. Provisional Patent Application Serial No. 63 / 336,543 filed on April 29, 2022, the disclosure of which is incorporated herein by reference. Technical Field

[0003] The present invention relates to sutures having extended antimicrobial properties, good handling, knot sliding and in situ performance and methods of making and using the same. Background Art

[0004] Sutures with antimicrobial properties against one or more bacterial species are known. One class of sutures with antimicrobial properties incorporates triclosan onto the suture. It is desirable to increase the antimicrobial efficacy of the suture against additional bacterial species compared to currently available antimicrobial braided sutures. Specifically, Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Enterobacter cloacae (E. cloacae). Among these species, Enterobacter cloacae requires the highest concentration of antimicrobial agents to inhibit bacterial growth. Therefore, if efficacy against Enterobacter cloacae is demonstrated, efficacy against other species should also be obtained. However, increasing the triclosan content on the suture creates new challenges because high triclosan content adversely affects suture handling, especially the ability to slide a square knot down into a locking knot. Suture coatings for antimicrobial sutures require a coating component that can absorb an antimicrobial agent and a coating component that provides lubricity. In some cases, one component can provide both functions.

[0005] Current braided antimicrobial suture technology introduces triclosan into the suture via a coating solution. The challenges with this technology are twofold: there are practical limitations with respect to the solubility of triclosan in the coating solution, and during sterilization and hot chamber processing, much of the triclosan coated on the suture will volatilize and transfer from the suture to the surrounding packaging. For example, the resulting triclosan concentration on finer sized sutures within certain packaging types is less than that required to be effective against certain bacterial strains, such as Enterobacter cloacae. Summary of the invention

[0006] Applicants have discovered that good antimicrobial efficacy and good suture handling require a balance of triclosan content, coating add-on / thickness on the suture, and ratios of coating components (if more than one component is used in the coating). More specifically, if the triclosan content is too low, there is no antimicrobial efficacy, but for a given coating system above a certain triclosan threshold, sufficient coating volume cannot be provided to accommodate the triclosan without adversely affecting handling. Both knot sliding and elution-driven inhibition zones are closely related to triclosan density in the coating (e.g., micrograms of triclosan per cubic millimeter of coating), while attachment-driven efficacy (such as bacterial colonization) is closely related to normalized triclosan content per meter of suture across suture dimensions (micrograms / meter). BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Figure 1 is a graph illustrating the relationship of factors for ensuring antimicrobial efficacy and suture treatment.

[0008] Figure 2 The relationship between the zone of inhibition after 24 hours and the density of triclosan in the coating is illustrated for a PG370 / calcium stearate coating.

[0009] Figure 3 The relationship between the zone of inhibition after 24 hours and the density of triclosan in the coating is illustrated for NVC-based coatings.

[0010] Figure 4 The relationship between the zone of inhibition after 72 hours (3 days) and the density of triclosan in the coating is illustrated for NVC-based coatings. DETAILED DESCRIPTION

[0011] It is desirable to increase the triclosan content on an antimicrobial braided suture to achieve efficacy comparable to the additional bacterial species against which current commercial antimicrobial braided sutures are effective, specifically, Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Enterobacter cloacae (E. cloacae). Of these species, E. cloacae requires the highest antimicrobial dose, and therefore, if efficacy is demonstrated against E. cloacae, efficacy against other species should also be achieved.

[0012] However, increasing the triclosan content on the suture creates new challenges because high triclosan content can adversely affect suture handling, especially the ability to slide a square knot down into a locking knot. Suture coatings for antimicrobial sutures require a coating component that can absorb antimicrobial agents (i.e., triclosan-philic) and a coating component that provides lubricity. In some cases, one component can provide both functions. The results show that enhanced antimicrobial efficacy and good suture handling require a balance of triclosan content, coating addition / thickness on the suture, and the ratio of lubricating and triclosan-philic coating components (if more than one component is used in the coating) ( Figure 1 ).

[0013] More specifically, if the triclosan content is too low, there is no antimicrobial efficacy, but for a given coating system above certain thresholds, sufficient coating volume cannot be provided to accommodate the triclosan without adversely affecting handleability. Both knot-slip and elution-driven inhibition zones are closely related to triclosan density in the coating (e.g., micrograms of triclosan per cubic millimeter of coating), while attachment-driven efficacy (such as bacterial colonization) is generally closely related to normalized triclosan content per meter of suture across suture dimensions (micrograms / meter).

[0014] For the purposes of this application, the following terms and definitions are provided:

[0015] PCG is a low crystalline, low molecular weight poly(caprolactone-co-glycolide) material in the form of a random or block polymer.

[0016] NVC refers to PCG with a target monomer unit ratio of 90 / 10 (90% caprolactone and 10% glycolide).

[0017] NVC (wt%) refers to the weight percentage of NVC in the solution used to coat the suture.

[0018] PCL is a low crystalline, low molecular weight poly(caprolactone-co-lactide) material in the form of a random or block copolymer.

[0019] PLG is a low crystalline, low molecular weight poly(glycolide-co-lactide) material in the form of block or random polymers.

[0020] PG370 is a PLG with a target monomer unit ratio of 65 / 35 (65% glycolide and 35% lactide).

[0021] CaSt (wt%) refers to the weight percentage of calcium stearate in the solution used to coat the suture.

[0022] Triclosan in coating solution (wt%) refers to the weight percent of triclosan in the solution used to coat the suture.

[0023] The triclosan reservoir dose (mg) refers to the mass of triclosan contained in the package.

[0024] Triclosan content (ug (micrograms) / m) refers to the total mass of triclosan in micrograms residing on one meter of suture.

[0025] Triclosan density in coating (ug (microgram) / mm 3 ) means the mass of triclosan in micrograms per cubic millimeter of dry coating on suture.

[0026] Coating add-on (wt %) refers to the weight percent of the coating on the suture (ie, the mass of the coating as a percentage of the total mass of the coating and the suture).

[0027] Knot slip (N / m) refers to the normalized area under the force-extension curve when the two ends of the suture are pulled to slide the square knot formed between the two ends of the suture to a closed position normalized for the travel distance.

[0028] TSB refers to Tryptic Soy Broth, a bacterial growth medium.

[0029] SST stands for serum:saline:TSB, and the % value generally refers to the ratio of serum volume to total volume. For the present invention, the TSB concentration is always at 10% volume, and the saline:serum ratio varies with serum concentration. Phosphate buffered saline of similar concentration can be used in place of saline.

[0030] TSA refers to Tryptic Soy Agar, a bacterial growth medium.

[0031] Colony forming units (CFU) are a unit of measurement used to estimate the number of viable microbial cells in a sample. CFU are visually determined using a plate count. The purpose of a plate count is to estimate the number of cells present based on their ability to produce colonies under specific conditions of nutrient medium, temperature, and time. In theory, one viable cell can produce colonies by replicating.

[0032] ZOI usually refers to the zone of inhibition after 24 hours.

[0033] ZOI Day 3 (mm) refers to the zone of inhibition in millimeters (mm) measured after 72 hours of incubation, with sutures transferred to fresh agar plates every 24 hours.

[0034] Log reduction refers to the log reduction of bacteria attached to sutures containing triclosan compared to control sutures. Unless otherwise stated, results are after 24 hours of incubation.

[0035] A triclosan reservoir refers to a composition capable of containing a specific amount of triclosan as a source for transfer to a medical device.

[0036] Plastic refers to packaging trays made of resins such as polypropylene or high-density polyethylene.

[0037] Paper refers to binders made of coated paper (clay-based coating) or uncoated paper.

[0038] The steam method involves the transfer of triclosan from a triclosan reservoir to a medical device under conditions of temperature, time, and / or reduced pressure.

[0039] In one embodiment, the present invention is directed to a medical device coating composition applied to a medical device, the medical device coating composition being a coating containing triclosan, a pro-triclosan component, and a lubricious component in an amount per length. The triclosan content in the coating is between about 150 micrograms / meter to about 2500 micrograms / meter for improved antimicrobial efficacy (including >3 log bacterial reduction) and prolonged antimicrobial efficacy (ZOI and log reduction are both prolonged for at least 3 days). The triclosan density in the coating may be between about 40 micrograms / mm 3 Coating to about 1000 μg / mm 3 Between coatings, for improved knot slip, ZOI efficacy and duration. A medical device coating composition refers to a coating that has been applied to a medical device after any solvent or other carrier used in the coating process has been removed. A medical device coating composition refers to a coating that is present on a suture in finished form.

[0040] Examples of preferred absorbable medical devices include monofilament sutures and multifilament sutures. Multifilament sutures include sutures in which multiple filaments form a braided structure. Examples of non-absorbable medical devices include monofilament sutures and multifilament sutures, surgical meshes (such as hernia repair meshes), hernia plugs, and brachytherapy seed spacers, which can be polymeric or non-polymeric. In one embodiment, the suture is selected from braided sutures, monofilament sutures, twisted sutures, and barbed sutures. Different types of sutures (including braided sutures, monofilament sutures, and barbed sutures) can use a variety of materials, including polylactide-co-glycolide (e.g., coated (polyglactin910) sutures), polycaprolactone-co-glycolide (e.g., (Polglecaprone 25) sutures), polydioxanone (e.g., II (polydioxanone) sutures), poly-caprolactone-lactide copolymers, polyglycolide, polylactide, poly-L-lactide, polycaprolactone, polyglycolide-trimethylene carbonate copolymers, polytrimethylene carbonate, surgical catgut, polyesters (e.g., ETHIBOND polyester sutures), silk (e.g. silk sutures), polypropylene (e.g. Polypropylene sutures), other absorbable or non-absorbable materials, etc. In one embodiment, the suture is a coated multifilament suture of polyglactin 910 (PG910) commercially available from Ethicon under the trade name "Coated VICRYL Suture".

[0041] Sutures of various industry conventional sizes are provided using a sizing system defined in the currently recognized United States Pharmacopeia (USP), which for absorbable sutures can range from USP size 11 / 0 to USP size 7. USP 4 / 0 sutures have a diameter of about 0.15 mm. USP 3 / 0 sutures have a diameter of about 0.2 mm. USP 2 / 0 sutures have a diameter of about 0.3 mm. USP size 0 sutures have a diameter of about 0.35 mm. In one embodiment, for a 2 / 0 suture, the coating comprises a weight percentage of between 0.5% and 8% of the weight of the suture.

[0042] Suitable antimicrobial agents can be selected from but not limited to halogenated hydroxy ethers, acyloxy diphenyl ethers or combinations thereof. In particular, the antimicrobial agent can be a halogenated 2-hydroxy diphenyl ether and / or a halogenated 2-acyloxy diphenyl ether, as described in U.S. Patent No. 3,629,477, which is incorporated herein by reference.

[0043] A particularly preferred antimicrobial agent is 2,4,4'-trichloro-2'-hydroxydiphenyl ether, commonly known as triclosan, a material commercially available from a variety of sources. Triclosan is a broad-spectrum antimicrobial agent that has been used in a variety of products and is effective against a variety of organisms commonly associated with SSIs. Such microorganisms include, but are not limited to, Staphylococcus epidermidis, Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, Enterobacter cloacae, Klebsiella pneumoniae, Escherichia coli, and combinations thereof.

[0044] The triclosan-affinitive component is a material that readily absorbs triclosan or has a high affinity for triclosan. It is advantageous to use a triclosan-affinitive composition containing a coating as a vehicle for delivering an antimicrobial agent to the surface of a device, wherein such coatings have been routinely used to manufacture devices, such as, for example, absorbable and non-absorbable multifilament sutures. Examples of medical devices and coatings that can be applied thereto can be found in U.S. Patents 4,201,216, 4,027,676, 4,105,034, 4,126,221, 4,185,637, 3,839,297, 6,260,699, 5,230,424, 5,555,976, 5,868,244, and 5,972,008, each of which is incorporated herein in its entirety. As disclosed in U.S. Pat. No. 4,201,016, suitable coating compositions may include a film-forming polymer and a substantially water-insoluble C6 or higher fatty acid salt as a lubricant. As another example, an absorbable coating composition useful for an absorbable medical device may include a poly(alkylene oxide ester), wherein the alkylene moiety is derived from a C6 diol or a mixture of C4 to C16 diols, which is applied to the medical device from a solvent solution, as disclosed in U.S. Pat. No. 4,105,034. The coating may be applied to the device by, for example, dip coating, spray coating, suspension drop coating, or any other conventional coating means. PCG or PCL (preferably NVC) and PLG (preferably PG370) provided in the coating component on the device as described herein are suitable pro-triclosan materials.

[0045] In order to enable adequate absorption of the antimicrobial agent, a minimum amount of triclosan-philic components is required in the coating. The amount required depends on the relative triclosan-philicity of the components. In the present invention, NVC has a higher affinity for triclosan than PG370, and therefore a sufficient amount of antimicrobial agent can be obtained at a lower amount of NVC than PG370. In addition, the relative triclosan-philicity of the coating can be fine-tuned by using a combination of triclosan-philic components.

[0046] The lubricating component may be provided in the coating solution and retained in the resulting coating composition. As described above, calcium stearate and PCG (preferably NVC) are examples of suitable lubricating components. The lubricating component may be provided by PCG or PCL (preferably NVC coating of PCG), and in addition, the solution containing NVC may also optionally contain calcium stearate.

[0047] The coating may be substantially homogeneous or heterogeneous in nature. In the case of a homogeneous coating, the coating components are chemically similar enough that they can mix at the molecular level. In the case of a heterogeneous coating, the coating components are not completely mixed at the molecular level and may form microdomains of the components.

[0048] In one embodiment of the invention, NVC is a pro-triclosan and lubricating component, and PG370 is optionally included to adjust the suture handling properties. In order to obtain enough triclosan to achieve antimicrobial properties, the total amount of the pro-triclosan component is preferably about 0.5% to 8% by weight of the mass of the size 2-0 suture, more preferably about 1% to 6% by weight, and most preferably about 1.5% to 5% by weight. For different suture sizes, the required coating weight percentage will be slightly different. In another embodiment, in order to obtain enough triclosan to achieve antimicrobial properties, the total amount of the pro-triclosan component is preferably about 4% to 10% by weight of the mass of the size 4-0 suture, more preferably about 4.5% to 9% by weight, and most preferably about 5% to 8% by weight. In order to maintain the appropriate suture handling properties of these substantially uniform coatings, it is necessary to limit the triclosan concentration in the coating to an upper limit of about 1000 micrograms of triclosan / m3 of coating, more preferably an upper limit of 400 micrograms of triclosan / m3 of coating, and most preferably an upper limit of 300 micrograms of triclosan / m3 of coating. Similarly, regardless of the presence of triclosan, a certain minimum thickness of the coating is required to effectively mask the surface of the fabric and obtain appropriate suture handling properties. Making the lubricating component the majority component in the coating is a preferred method for fine-tuning the suture handling properties. In this embodiment, the ratio of NVC to PG370 is preferably greater than 1, more preferably the ratio is greater than 2, and most preferably the ratio is greater than 3. Including less pro-triclosan component PG370 is another way to control the suture handling properties by limiting the amount of triclosan present in a given coating amount. In addition, small amounts of calcium stearate or other lubricating components may optionally be included to further fine-tune the properties.

[0049] In another embodiment, the coating solution for coating the suture of the present invention selected from USP size 2 to 3-0 comprises: about 3 wt % to at least about 8 wt % PCG (preferably NVC) and about 0 wt % to about at least 6 wt % PLG (preferably PG370), preferably about 4 wt % to about 8 wt % PCG (preferably NVC) and about 0 wt % to about 4 wt % PLG (preferably PG370). PCG (preferably NVC) acts as both a pro-triclosan agent and a lubricant, while the polymer component of PLG (preferably PG370) is capable of acting as a pro-triclosan agent.

[0050] In another embodiment of the invention, the pro-triclosan component is PG370 and the lubricating component is calcium stearate. In this case, the nature of the coating is non-uniform. In order to obtain enough triclosan to achieve antimicrobial properties, the total amount of the pro-triclosan component is preferably about 0.6% to 2% by weight, more preferably about 1% to 1.7% by weight of the mass of the size 2-0 suture. For different suture sizes, the required coating weight percentage will be slightly different. In order to maintain appropriate suture handling properties, it is important for this embodiment to control the ratio of the lubricating component to the pro-triclosan component. Once the pro-triclosan component is the main component and it is preferred to have an excess of the lubricating component, the suture handling properties can deteriorate rapidly.

[0051] In another embodiment, the coating solution for coating the suture of the present invention comprises: about 3 wt % to at least about 6 wt % calcium stearate and about 3 wt % to at least 6 wt % PLG (preferably PG370), preferably about 4.5 wt % to about 6 wt % calcium stearate and about 4.5 wt % to about 6 wt % PLG (preferably PG370). Calcium stearate acts as a lubricant, while the polymer component of PLG (preferably PG370) can act as a pro-triclosan agent.

[0052] The PCG or PCL coating solution contains a dilute copolymer of ε-caprolactone and glycolide formed by using glycolic acid as an initiator and stannous octoate as a catalyst. The polymerization can be carried out in a batch process that allows the formation of random copolymers. However, the polymerization can also be carried out in a manner that allows the formation of semi-block copolymers. The initiator ratio can be varied to allow the molecular weight to be obtained so that the final copolymer is in a usable form. As used herein, the term "initiator ratio" refers to the total moles of monomers divided by the total moles of initiators.

[0053] Suitable film formers for use as substitutes for the PLG component coating compositions of the present invention include homopolymers and copolymers of lactide and glycolide, i.e., polylactide, polyglycolide, and copolymers of lactide and glycolide with each other and with other reactive monomers; copolymers of poly(p-dioxanone), poly(alkylene oxalate), vinyl acetate and unsaturated carboxylic acids (such as crotonic acid, acrylic acid and methacrylic acid); water-soluble or water-dispersible cellulose derivatives such as methylcellulose, hydroxymethylcellulose and carboxymethylcellulose; natural gums; ethylene oxide polymers; polyacrylamide; collagen; gelatin; polyamino acids; polyvinyl alcohol; polyvinyl pyrrolidone; polyvinyl esters; polybutilate; absorbable conjugated unsaturated triglycerides such as dehydrated castor oil, and mixtures of such polymers. Particularly preferred film-forming polymers are copolymers of lactide and glycolide of low molecular weight and exhibit no or low levels of crystallinity. These polymers are water-insoluble, rapidly absorbable, and soluble in many common organic solvents (such as acetone, chloroform, toluene, xylene, and 1,1,2-trichloroethane), which facilitates their application to the suture as a solution.

[0054] In addition to PCG and PLG coatings, other suitable coatings may include, but are not limited to, copolymers of polyglucose esters, glycolic acid and trimethylene carbonate, and copolymer coatings containing caprolactone and fatty acid esters. Mixtures that can be used to form such coatings include esters of fatty acids as a major component. Minor components of such mixtures include copolymers containing caprolactone. Examples of useful copolymers containing caprolactone are "star" copolymers obtained by polymerizing a major amount of ε-caprolactone and a small amount of another bioabsorbable monomer that can be polymerized therewith in the presence of a polyol initiator. Suitable monomers copolymerizable with ε-caprolactone include alkylene carbonates, such as trimethylene carbonate, tetramethylene carbonate, dimethyltrimethylene carbonate; dioxanone; dioxepanones; absorbable cyclic amides; absorbable cyclic ether-esters derived from crown ethers; hydroxy acids capable of 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); polyalkyl ethers (such as polyethylene glycol and polyloropyline glycol and combinations thereof); wherein glycolide is a preferred monomer. Examples of useful fatty acid esters include calcium stearyl lactate, which is soluble in the copolymer solution.

[0055] In one embodiment, a packaged antimicrobial medical device comprises: at least one package having an inner surface on which an antimicrobial agent is disposed, the antimicrobial agent being selected from the above-mentioned halogenated hydroxy ethers, acyloxy diphenyl ethers, and combinations thereof, in an amount sufficient to substantially inhibit bacterial colonization on the package; and at least one medical device located within the package, the medical device having one or more surfaces having an antimicrobial agent disposed thereon and therein, the antimicrobial agent being selected from the group consisting of halogenated hydroxy ethers, acyloxy diphenyl ethers, and combinations thereof, in an amount sufficient to substantially inhibit bacterial colonization on the medical device.

[0056] Another embodiment of the antimicrobial medical device with package includes packaging, which has an inner surface and a containing compartment for fixing the medical device and being located in the packaging. In this embodiment, at least one surface of the containing compartment includes an antimicrobial agent disposed thereon, and the presence of the antimicrobial agent is sufficient to substantially inhibit bacterial colonization on the containing compartment. In an alternative embodiment, the inner surface of the packaging and at least one surface of the containing compartment include an antimicrobial agent disposed thereon, and the presence of the antimicrobial agent is sufficient to substantially inhibit bacterial colonization on the packaging and containing compartment. The medical device with package also includes at least one medical device positioned in the containing compartment. The medical device also has one or more surfaces, and the antimicrobial agent is disposed on the one or more surfaces. The antimicrobial agent is present on the medical device in an amount sufficient to substantially inhibit bacterial colonization on the medical device. The antimicrobial agent disposed on the packaging, containing compartment and medical device can be selected from antimicrobial compounds, and the antimicrobial compound comprises halogenated hydroxy ethers, acyloxy diphenyl ethers and combinations thereof.

[0057] Packages for surgical needles, sutures, and combinations thereof typically include suture trays as a containment compartment for holding sutures and / or surgical needles securely in place. A type of containment compartment typically used for surgical needles and / or sutures is a folding package made of hard medical grade paper. The folding package will typically have a plurality of foldable panels and cut tabs and tab bags. Folding packages for surgical needles and sutures are shown and disclosed in the following patents, each of which is incorporated herein by reference in its entirety: U.S. Patents 4,126,221, 4,120,395, and 5,555,976.

[0058] Another conventionally used accommodation compartment for surgical needles and / or sutures is a molded plastic tray having a central floor surrounded by an outer winding channel (e.g., an oval channel) for receiving and holding sutures. The accommodation compartment may also include a medical grade paper or plastic cover that can be mounted to the top of the winding channel, or the molded plastic tray may have a molded retainer element to keep the sutures in the channel. Molded thermoplastic material. The molded plastic tray may be made of a thermoplastic material selected from the group consisting of: polyester, polyvinyl chloride, polypropylene, polystyrene, and polyethylene. Accommodation compartments with winding channels are exemplified in the following patents, each of which is incorporated herein by reference in its entirety: U.S. Patents 4,967,902, 5,213,210, and 5,230,424.

[0059] The present invention also relates to a method for preparing a packaged antimicrobial medical device, the method comprising the steps of: providing a package and / or a containing compartment that is substantially free of an antimicrobial agent; positioning a medical device in the package or the containing compartment, the medical device comprising one or more surfaces having an antimicrobial agent disposed thereon, the antimicrobial agent being selected from the group consisting of a halogenated hydroxy ether, an acyloxydiphenyl ether, and combinations thereof; subjecting the package and / or the containing compartment and the medical device to conditions sufficient to transfer a first portion of the antimicrobial agent from the medical device to the package and / or the containing compartment while retaining a second portion of the antimicrobial agent on a surface of the medical device, thereby substantially inhibiting bacterial colonization on the medical device, the package and / or the containing compartment.

[0060] According to various methods of the present invention, in one embodiment, a package and a containment compartment can be provided that are initially substantially free of an antimicrobial agent (i.e., no antimicrobial agent is present on the surface of the package or containment compartment). A medical device having a preselected amount of an antimicrobial agent disposed thereon is positioned within the package or containment compartment. Subsequently, the package, containment compartment (if used), and the medical device are subjected to preselected time, temperature, and pressure conditions sufficient to vapor transfer a portion of the antimicrobial agent from the medical device to the package and / or containment compartment.

[0061] The speed that antimicrobial (such as triclosan) is transferred to packaging and / or containing compartment from medical device depends on the time, temperature and pressure conditions of storage and processing packaging with containing compartment and medical device substantially. Also comprise any combination of pressure and temperature, to provide the antimicrobial partial pressure identical with the partial pressure provided under the above conditions, and be enough to provide the time period of the antimicrobial of effective amount or concentration on packaging and / or containing compartment.Specifically, it is known to those of ordinary skill in the art that if pressure is reduced, then temperature can be reduced to realize the same partial pressure.Alternatively, if pressure is reduced but temperature remains constant, then the time required for providing the antimicrobial of effective amount or concentration on packaging and / or containing compartment can be shortened.During this process, when a part of antimicrobial is transferred to packaging and / or containing compartment, the second part is retained on the surface of medical device.Therefore, after transfer, medical device and packaging and / or containing compartment contain the antimicrobial of effective amount, to suppress the colonization of bacteria thereon and near it substantially.

[0062] Medical devices are often sterilized so that microorganisms located thereon cannot survive. In particular, sterility is understood in the art to mean 10 -6 The invention relates to a method for sterilizing an absorbable medical device. The invention relates to a method for sterilizing an absorbable medical device. The invention relates to a method for sterilizing an absorbable medical device. The invention relates to a method for sterilizing an absorbable medical device. The invention relates to a method for sterilizing an absorbable medical device. The invention relates to a method for sterilizing an absorbable medical device. The invention relates to a method for sterilizing an absorbable medical device. The invention relates to a method for sterilizing an absorbable medical device. The invention relates to a method for sterilizing an absorbable medical device.

[0063] In one embodiment, an ethylene oxide sterilization process is utilized to transfer a volatile antimicrobial agent (e.g., triclosan) because the time, temperature, and pressure conditions of the sterilization process are sufficient to vapor transfer a portion of the antimicrobial agent from the medical device to the packaging and / or containing compartment. However, many ethylene oxide sterilization processes have different time, temperature, and pressure conditions, which in turn provide more or less vapor transfer of the antimicrobial agent.

[0064] In another embodiment, pre-sterilization treatment of the medical device (e.g., placement in a vacuum oven) can provide time, temperature, and pressure conditions to provide sufficient vapor transfer of the antimicrobial agent from the packaging and / or containment compartment to the medical device prior to sterilization in a subsequent step.

[0065] In another embodiment, post-sterilization processing of the sterilized medical device (e.g., placement in a vacuum oven) can provide time, temperature, and pressure conditions to provide sufficient vapor transfer of the antimicrobial agent from the packaging and / or containment compartment to the medical device.

[0066] It is known to those skilled in the art that any combination of the three embodiments described above can be used.

[0067] In one embodiment, the invention is directed to a method of introducing an antimicrobial agent, such as triclosan, into a coated suture by exposing the suture to a patch having a triclosan reservoir, wherein the transfer occurs at elevated temperature and / or reduced pressure.

[0068] In one embodiment, the invention relates to a method of introducing an antimicrobial agent, such as triclosan, into a coated suture by exposing the suture to a triclosan reservoir located within a tray, wherein the transfer occurs at elevated temperature and / or reduced pressure. In another embodiment, triclosan is embedded in a tray and transferred to the suture at elevated temperature and / or reduced pressure.

[0069] In one embodiment, the present invention is directed to a coated braided suture wherein the triclosan content on the suture is greater than 150 ug / m and the triclosan density in the coating is greater than 70 ug / mm 3 , more preferably greater than 85ug / mm 3 , most preferably greater than 100ug / mm 3 , and maintained an inhibition zone of >3 mm against Enterobacter cloacae for at least 3 days.

[0070] In one embodiment, the present invention relates to a coated braided suture wherein the triclosan content in the coating is greater than 150 ug / m, more preferably greater than 200 ug / m, and exhibits a greater than 3 log reduction in bacterial attachment of Enterobacter cloacae relative to a triclosan-free suture of the same chemistry, architecture, and size in the presence of 20% serum. The magnitude of the reduction depends on both the triclosan content on the suture and the amount of serum present in the bacterial growth medium. As a rule of thumb, smaller log reductions are observed with increasing serum content, and larger log reductions are observed with increasing triclosan content. In another embodiment, the present invention relates to a coated braided suture wherein the initial triclosan content on the suture is greater than 200 ug / m, more preferably greater than 250 ug / m, most preferably greater than 300 ug / m, and exhibits a greater than 3 log reduction in bacterial attachment of Enterobacter cloacae relative to a triclosan-free suture of the same chemistry, architecture, and size for 2 days. In another embodiment, the invention is directed to a coated braided suture wherein the initial triclosan level on the suture is greater than 300 ug / m, wherein the coating thickness exceeds 2 microns, more preferably exceeds 2.5 microns, and exhibits greater than a 3 log reduction in bacterial attachment of Enterobacter cloacae for 3 days relative to a suture of the same chemistry, architecture, and size without triclosan.

[0071] In one embodiment, the present invention is directed to a coated braided suture having a USP size 4 / 0 to 0 as described above, having a quantitative knot slip value of less than 60 N / m, preferably less than 30 N / m, most preferably less than 20 N / m.

[0072] In one embodiment, the coated braided suture USP size is between and including 0 to 4 / 0.

[0073] Example

[0074] Example 1: Description of the test method

[0075] 1. Triclosan Content: Determination of Triclosan in Polyglactin 910 Sutures

[0076] Sample preparation and determination were done by extracting triclosan from sutures. Quantification of triclosan in the extracts was done by high performance liquid chromatography (HPLC).

[0077] 2. Add-On: Determine the total weight of coating material on the suture

[0078] An analytical test method was previously developed to determine the total weight of coating material on suture products. Sample preparation was accomplished by extracting the coating material with chloroform and quantification was performed by gravimetric analysis.

[0079] The coating addition amount is calculated as follows:

[0080] % Total coating = [(initial weight - final weight) / initial weight] x 100

[0081] 3. Measurement of the Zone of Inhibition (ZOI)

[0082] 5 cm sections of antimicrobial sutures were placed in petri dishes and inoculated with 1-5x106 CFU / ml of Enterobacter cloacae (ATCC 13047) to achieve a final concentration of 1-5x105 CFU bacteria in the plate. An appropriate volume of TSA medium was added and mixed with the inoculum in the plate. After incubation for 18 to 24 hours, the in vitro efficacy of the sterilized antimicrobial sutures against the test organisms was evaluated by measuring the inhibition zone produced in the plate around the antimicrobial sutures.

[0083] The inhibition zone is measured using a digital caliper. The shortest vertical distance will be measured from the edge of the suture to the edge of confluent bacterial growth at 3 locations on the suture (center and 2 endpoints). The 3 measurements are then averaged to obtain the final area measurement. If the measurement is less than 1.0 mm, there is no inhibition zone.

[0084] 4. Methods to determine and quantify bacterial attachment to sutures in vitro (log reduction)

[0085] Logarithmic attachment assays are performed in serum-supplemented media (SST) consisting of serum, saline or (phosphate buffered saline) and TSB media. Different levels of serum can be used to change the challenge level of the test. Generally, the higher the serum content in the growth medium, the lower the efficacy of the antimicrobial agent. Briefly, a 10 cm sutured test article is placed in a well plate, after which 2 mL of SST medium inoculated with approximately 1-5x105 CFU / ml of Enterobacter cloacae (ATCC 13047) is added to the well. The well plate is incubated at 37°C for the desired duration (usually 24 hours) while shaking at 60 rpm.

[0086] After the incubation period is complete, the sutures are removed and placed in neutralization buffer and sonicated to dissociate bacteria attached to the test article. The bacterial suspension is then plated and the CFU / device of the test sample is compared to the CFU / device of the control sample and then reported as a log difference / reduction.

[0087] Example 2: Sample production process, including triclosan introduction method -

[0088] Exemplary Example 2A: Coating Process for Applying Antimicrobial Agents via Coating Solutions; Other Coating Components May Be Used and concentration .

[0089] The reel of the braid is placed on the pay-out device and the braid is passed through the coating wire guide and coating bath, drying tunnel guide, godet roller, and finally through the take-up shaft. The coating bath is filled with a coating solution containing 89% ethyl acetate solvent, 4.5% PG370 coating copolymer, 2% triclosan (antibacterial agent) and 4.5% calcium stearate. The braided wire is pulled out from the winding body, passed through the guide in the coating bath, and coated at the coating bath. The coated braid is then pulled through the drying tunnel, where the ethyl acetate solvent evaporates from the braid, leaving copolymer, triclosan and calcium stearate on the braid. The coated, dried braid is wound on the take-up shaft. The coating amount of the material is tested and sent for cutting and, if necessary, needle attachment. After the needle is attached to the wire, it is wound into an inner package, placed in an outer foil package, and sterilized.

[0090] Exemplary Example 2B: Application of Antimicrobial Agents via Vapor Deposition

[0091] The material is coated in the same manner as described in illustrative embodiment 2A, but triclosan is not included in the coating solution. After coating, the material is cut into strands, and if necessary, a needle is attached. The thread with a needle is wound into the inner package of a polymer or paper. The Tyvek patch is used as a reservoir for holding triclosan. Triclosan is dissolved in a solvent, accurately measured to 3mg, and applied to the patch. The patch is placed on the lower side of the paper cover of the inner package of a polymer tray or on the wing of the inner package of paper. The assembly is placed in an outer package (foil) and sterilized and vacuum dried. Alternatively, in the case of plastic packaging, triclosan can be embedded in the plastic itself and does not need a patch. The method uses elevated temperature and vacuum, and the method evaporates triclosan from the patch and evaporates it onto the suture (steam method).

[0092] Example 3: Quantitative Knot Slip Test

[0093] Sterile antimicrobial suture is taken out of the package and cut into 14 inches of length. The 14-inch suture strand is placed in water for 60 seconds to simulate in vivo conditions. Subsequently, a square knot is tied around a cylindrical fixture with a diameter of 2 inches. The end of the suture with a square knot and a 2-inch diameter ring is fixed in an Instron fixture with a gauge length of 2 inches. The tensile test is carried out at a speed of 20 inches / minute. In order to determine the work required for sliding and closing the knot, the area under the curve (until the beginning of the peak associated with the fracture of the closed suture) is integrated and standardized to elongation, to adjust any differences in braid elasticity, and reported as knot sliding in N / m. Less than 60N / m is considered to be acceptable (that is, non-locking) suture processing; It is preferred for smooth knot formation to be lower than 30N / m.

[0094] Example 4: Achievable Triclosan Levels on Sutures Coated with PG370 / Calcium Stearate / Triclosan Examples

[0095] Current methods for antimicrobial braided sutures introduce antimicrobial agents during the coating process. When sutures are prepared as described in Example 2A and triclosan is provided in the coating solution, limited triclosan content can be obtained (Table 1). Using a typical suture coating system (4.5 wt% PG370 / 4.5 wt% CaSt with 2 wt% triclosan in the coating solution), a maximum of about 16 ug / m can be achieved in plastic suture packaging, while a maximum of about 31 ug / m can be achieved in paper suture packaging. Increasing the triclosan content solution to 5 wt% results in a triclosan content of 93 ug / m on the suture. Even increasing the coating solution concentration to the maximum practical concentration for a functional suture (6 wt% PG370 / 6 wt% CaSt with 5 wt% triclosan in the coating) results in a triclosan content of about 112 ug / m on the suture.

[0096] Table 1:

[0097]

[0098] Example 5: USP size 2-0 suture coated with PG370 / calcium stearate prepared using the triclosan steam process Examples of Antimicrobial Efficacy and Suture Treatment Properties .

[0099] When triclosan was introduced using the steam method, significantly higher triclosan levels were achieved in the sutures. Figure 2 It is shown that when the triclosan density in the coating is greater than about (+ / - 2.5ug / mm 3 )20ug / mm 3 A consistent average ZOI of greater than 3 mm was obtained for E. cloacae. Considering the fact that about half of the coating cannot accommodate triclosan in a meaningful way, the effective triclosan density in the pro-triclosan component needs to be greater than about (+ / - 5 ug / mm 3 )40ug / mm 3 .

[0100] Table 2:

[0101]

[0102]

[0103] However, Table 3 shows that for a given coating, as the triclosan level increases, the suture handling properties begin to deteriorate to the point of being non-functional. Table 4 shows that the handling properties at a given triclosan level can be improved by increasing the calcium stearate level in the coating.

[0104] Table 3:

[0105]

[0106] *5 out of 10 samples locked and broke during testing

[0107] Table 4:

[0108]

[0109] Table 5 shows some extreme combinations of calcium stearate to PG370 ratios and coating thicknesses that produce sutures with both good antimicrobial properties and suture handling properties.

[0110] Table 5:

[0111]

[0112] Example 6: Example of suture coated with NVC and optionally PG370, with 3 mm of E. cloacae ZOI

[0113] The coating combination of NVC and PG370 can be used to achieve efficacy. Table 6 below shows some examples with different coating ratios and triclosan delivery methods. It can be seen that this coating combination of NVC and PG370 can achieve significantly higher triclosan levels on the suture using either delivery method compared to the coating systems described in Examples 4 and 5. Higher triclosan levels can be achieved on the suture using the steam method compared to the triclosan-containing coating method. Note that all conditions provide suture treatment characteristics within the most preferred range, although the triclosan levels are significantly higher than those described in Example 5.

[0114] In order to have a sufficient ZOI against Enterobacter cloacae, a certain minimum triclosan content is necessary. However, the triclosan density in the coating needs to be such that the elution of the antimicrobial agent into the environment is fast enough. Table 6 shows samples that show a favorable ZOI for Enterobacter cloacae, where triclosan is about (+ / -10ug / m) 100ug / m, more preferably above about 150ug / m, while samples below 100ug / m do not show a sufficient ZOI. In addition, Figure 3 It was shown that for samples with about 100 ug / m triclosan, in order to obtain a consistently favorable ZOI (>3 mm) for E. cloacae, the triclosan density needed to exceed about (+ / - 5 ug / mm 3 )40ug / mm 3 .

[0115] Table 6:

[0116]

[0117] Table 7 shows that the different USP size sutures performed similarly to the USP size 2-0 suture. The minimum density observed for USP size 1 was 41 ug / mm 3 , resulting in an average ZOI of 4.2 mm. For USP size 4-0, when the triclosan density in the coating is less than about (+ / - 5 ug / mm 3 )40ug / mm 3 When the triclosan density was greater than about 40 ug / mm 3 , a sufficient average ZOI is obtained.

[0118] Table 7:

[0119]

[0120] Example 7: Example of a suture coated with NVC and optionally PG370, wherein compared to a control suture, Reduction of Enterobacter cloacae colonization

[0121] A series of log reduction experiments were performed to evaluate the reduction of bacteria attached to antimicrobial sutures (in the presence of 20% serum) compared to a control of VICRYL sutures coated with Ethicon. Examples are shown in Table 8 for USP size 2-0 sutures, with good (defined as >3 logs in 20% serum) and poor E. cloacae log reduction.

[0122] It can be seen that in order to consistently obtain a greater than 3 log reduction in attached bacteria relative to the control suture, a triclosan level on the suture of greater than about (+ / - 10 ug / m) 150 ug / m is required. Furthermore, it can be seen that once the aforementioned criteria are met, the composition of the coating affects the magnitude of the reduction.

[0123] Table 8:

[0124]

[0125]

[0126] Example 8: Example of Suture Coated with NVC and Optional PG370 with Acceptable Suture Handling characteristic

[0127] Table 9 shows the suture handling properties of USP size 2-0 braided sutures. For acceptable suture handling, knot slip values ​​need to be below about (+ / - 5N / m) 60N / m for this suture size. Preferably, knot slip is below 30N / m, and for more preferred sutures, it should be below 20N / m in the test method described in Example 3.

[0128] As can be seen in Table 9, triclosan density is a critical parameter for suture handling properties. For functional sutures, triclosan density should not exceed about (+ / - 20 ug / mm 3 )1000ug / mm 3 More preferably, the triclosan density should be less than about 400 ug / mm 3 , and for more preferred performance, should be less than about 300ug / mm 3 .

[0129] Table 9:

[0130]

[0131]

[0132] USP size 1 and 2 braids have different braid constructions, resulting in higher inherent friction than USP size 0 and below braids. For size 1, the acceptable threshold is below about (+ / -5N / m) 85N / m, more preferably below about 55N / m, and more preferably below about 45N / m. For size 2, the acceptable threshold is below about (+ / -5N / m) 130N / m, preferably below about 100N / m, and more preferably below about 90N / m. The following table shows that USP size 1 and 2 sutures have similar dependence on triclosan density for suture handling properties.

[0133] Table 10:

[0134]

[0135] The importance of coating thickness relative to triclosan content is highlighted in Table 11 (below). At similar triclosan content and similar triclosan density, a certain minimum coating thickness is required to have a non-locking suture. For the thinnest coatings, the minimum thickness limits how much triclosan can be incorporated before the handling properties are insufficient.

[0136] Table 11

[0137]

[0138] The effect of the NVC / PG370 ratio on the handling properties of sutures is exemplified in Table 12. As can be seen, at similar triclosan content and triclosan density on the suture, knot slippage improves (decreases) as the NVC / PG370 ratio increases.

[0139] Table 12 :

[0140]

[0141] Table 13 shows a comparison of the suture handling properties of the NVC-based coating system and the PG370 / CaSt coating system described in Example 5. It can be seen that at a triclosan content on the suture of about 300 ug / m, about 3 times lower knot slip values ​​were obtained for the NVC-based coating system. In addition, at about 750 ug / m, the CaSt / PG370-based coating system resulted in unacceptable suture handling (about 50% of the tested sutures were locked), while the NVC-based coating system still showed preferred knot slip values. Adding NVC to the PG370 / CaSt coating system significantly improved suture handling compared to PG370 / CaSt alone.

[0142] Table 13:

[0143]

[0144] *5 out of 10 samples locked and broke during testing

[0145] Example 9: Extended Inhibition Zone Experiment

[0146] To evaluate the extended antimicrobial efficacy of the antimicrobial suture, a repeated zone of inhibition (ZOI) experiment was performed. Briefly, a ZOI experiment as described in Example 3 was performed, but after 24 hours, the suture was retrieved from the assay and inoculated in a fresh agar plate with a fresh bacterial inoculum. This method was repeated for 3 days.

[0147] Various suture sizes, triclosan introduction methods, and packaging types were evaluated. The following table (Table 14) reports the mean ZOI (mm) at Day 3. Figure 4 As can be seen in the figure, when the triclosan density in the coating exceeds about (+ / -5ug / mm 3 )70ug / mm 3 When the ZOI is greater than about 3 mm, a sufficient average ZOI is obtained.

[0148] Table 14:

[0149]

[0150] Example 10: Extended anti-colonization experiment

[0151] To evaluate the prolonged antimicrobial efficacy of antimicrobial sutures, replicate anti-colonization (logarithmic attachment) experiments were performed. Three identical well plates (containing 10 cm of cut suture) were prepared. Attachment studies were performed with Enterobacter cloacae in SST (5% serum).

[0152] On the first day, one plate was inoculated with the test organism at 1-5x10^5 CFU / ml in SST (5% serum) and treated according to the standard logarithmic attachment procedure described in Example 1, while the other two plates received only SST (5%) and remained uninoculated. Each subsequent day, one of the plates was inoculated and treated according to the standard logarithmic attachment procedure until all plates were treated.

[0153] Various suture sizes, triclosan introduction methods, and packaging types were evaluated. The table below reports the average log reduction compared to the control suture. Table 15 shows the results of selected samples tested two days later. It can be seen that when the initial (day 0) total triclosan content on the suture exceeds about (+ / -10ug / m)200ug / m, a 3-log reduction in colonization relative to the control suture can be achieved in two days. Table 16 shows the results of selected samples tested three days later. It can be seen that in this case, not only does the initial total triclosan content on the suture need to exceed about 300ug / m, but the coating thickness needs to be greater than 2 microns, more preferably 2.5 microns, to maintain a 3-log reduction in colonization relative to the control suture.

[0154] Table 15:

[0155]

[0156] Table 16:

[0157]

Claims

1. A coated medical device, comprising at least one implantable segment, wherein the at least one implantable segment has a coating comprising: a. an effective amount of triclosan, its antimicrobial derivatives or blends thereof; and b. a lubricating pro-triclosan component or a pro-triclosan component and a lubricating component, or a combination thereof; wherein the amount of triclosan or its antimicrobial derivative or blend thereof is between about 150 micrograms and about 2500 micrograms, preferably between about 200 micrograms and about 1000 micrograms per meter of the implantable coated segment.

2. The coated medical device of claim 1, wherein the triclosan-philic component is lubricious.

3. The coated medical device of claim 1, wherein the coating is substantially uniform and has a viscosity between about 40 μg / mm3 and about 10 μg / mm 3 ) to about 1000ug / mm 3 The density of triclosan, its antimicrobial derivative or blend in the coating is between .

4. The coated medical device of claim 3, wherein the coating has a viscosity between about 40 ug / mm 3 To about 1000ug / mm 3 The density of triclosan in the coating is between .

5. The coated medical device of claim 1, wherein the coated medical device is a braided suture and has a suture coating, wherein the amount of triclosan, its antimicrobial derivatives, or blends thereof exceeds 150 ug (micrograms) per meter of suture (ug / m), and the density of triclosan in the pro-triclosan component is greater than about 40 ug / mm 3 , preferably greater than 50ug / mm 3 , most preferably greater than 60ug / mm 3 , and maintained an inhibition zone of at least 3 mm against Enterobacter cloacae within 24 hours.

6. The coated medical device of claim 1, wherein the coated medical device is a braided suture and has a suture coating, wherein the amount of triclosan, its antimicrobial derivatives, or blends thereof exceeds 100 ug (micrograms) per meter of suture (ug / m), and the density of triclosan in the pro-triclosan component is greater than about 40 ug / mm 3 , preferably greater than 50ug / mm 3 , most preferably greater than 60ug / mm 3, and maintained an inhibition zone of at least 3 mm against Enterobacter cloacae within 24 hours.

7. The coated medical device of claim 1, which is a braided suture and has a suture coating in which the amount of triclosan, its antimicrobial derivatives or blends exceeds 150 ug / m suture and maintains at least a 3 mm zone of inhibition against Enterobacter cloacae for at least 3 days.

8. The coated medical device of claim 7, which is a braided suture and has a suture coating, wherein the triclosan density in the coating exceeds 70 ug / mm 3 , more preferably more than 85ug / mm 3 , most preferably more than 100ug / mm 3 , and maintained an inhibition zone of at least 3 mm against Enterobacter cloacae for at least 3 days.

9. The coated medical device of claim 1, wherein the coated medical device is a braided suture and has a suture coating in which the amount of triclosan, its antimicrobial derivatives or blends thereof exceeds about 150 ug / m and reduces bacterial attachment of Enterobacter cloacae by at least 3 logs relative to a suture of the same chemistry, architecture and size without triclosan in a medium containing 20% ​​SST.

10. The coated medical device of claim 1, which is a braided suture and has a suture coating in which the amount of triclosan, its antimicrobial derivative or blend exceeds 200 ug / m suture, more preferably exceeds 250 ug / m suture, most preferably exceeds 300 ug / m suture, and maintains at least a 3 log reduction against Enterobacter cloacae in a medium containing 5% SST for at least 2 days relative to a suture of the same chemistry, architecture and size without triclosan.

11. The coated medical device of claim 1 , wherein the coated medical device is a braided suture and has a suture coating, wherein the amount of triclosan, its antimicrobial derivatives or blends thereof exceeds 300 ug / m suture, and wherein the coating thickness exceeds about 2 micrometers (μm), more preferably exceeds about 2.5 μm, and maintains at least a 3 log reduction against Enterobacter cloacae in a medium containing 5% SST for at least 3 days relative to a suture of the same chemistry, architecture and size without triclosan.

12. The coated medical device of claim 1, wherein the coated medical device is a suture having a suture USP size between size 0 and 4 / 0 and including the sizes, the suture being braided and having a quantitative knot slip value of less than 60 N / m, preferably less than 30 N / m, most preferably less than 20 N / m.

13. The coated medical device of claim 1, the coated medical device being a suture having a suture USP size between size 0 and 4 / 0, inclusive, the suture being braided, wherein the triclosan density in the coating is less than about 1000 ug / mm 3 , preferably less than about 400ug / mm 3 , most preferably less than about 300ug / mm 3 .

14. The coated medical device of claim 1, which is a suture having a suture USP size 1, which is braided and has a quantitative knot slip value of less than 85 N / m, preferably less than 55 N / m, most preferably less than 45 N / m.

15. The coated medical device of claim 1, wherein the coated medical device is a suture, the suture having a suture USP size 1, the suture being braided, wherein the triclosan density in the coating is less than 400 ug / mm 3 , preferably less than 300ug / mm 3 .

16. The coated medical device of claim 1, which is a suture having a suture USP size 2, which is braided and has a quantitative knot slip value of less than 130 N / m, preferably less than 100 N / m, most preferably less than 90 N / m.

17. The coated medical device of claim 1, wherein the coated medical device is a suture, the suture having a suture USP size 2, the suture being braided, wherein the triclosan density in the coating is less than 400 ug / mm 3 , preferably less than 300ug / mm 3 .

18. The coated medical device of claim 1, being a suture having a suture USP size between and including size 2 to 4 / 0.

19. The coated medical device of claim 1 which is a suture in the form of a polyglactin 910 coated multifilament braid.

20. The coated medical device of any one of claims 3 to 17, wherein the coated medical device is a suture having a USP size of 2 to 3 / 0, and wherein the coating is present in an amount between 0.5% and 8%, preferably in an amount between 1% and 6%, and most preferably in an amount between 1.5% and 5%, by weight of the suture.

21. The coated medical device of any one of claims 3 to 17, wherein the coated medical device is a suture having a USP size 4 / 0 and wherein the coating is present in an amount between 4% and 10%, preferably in an amount between 4.5% and 9%, and most preferably in an amount between 5% and 8%, by weight of the suture.

22. The coated medical device of claims 1 and 3, wherein the triclosan-philic component is a coating of poly(ε-caprolactone-co-glycolide) 90 / 10, poly(glycolide-co-lactide) 65 / 35, or a combination thereof.

23. The coated medical device according to claims 1 and 3, wherein the weight ratio of poly(glycolide-co-lactide) 65 / 35 to poly(ε-caprolactone-glycolide) 90 / 10 is 0 to 1.0, preferably 0 to about 0.75, preferably 0 to about 0.

5.

24. The coated medical device of claim 1, wherein the lubricious component is a coating of poly(ε-caprolactone-ω-glycolide) having a monomer ratio of caprolactone to glycolide of about 90 / 10, calcium stearate, or a combination thereof.

25. The coated medical device of claim 1, wherein the coating is substantially non-uniform.

26. The coated medical device of claim 18, wherein the triclosan-philic container is poly(glycolide-co-lactide) having a monomer ratio of glycolide to lactide of 65 / 35, and the lubricating component is calcium stearate.

27. The coated medical device of claim 19, wherein the coated medical device is a suture having a USP size of 2 to 4 / 0, wherein the weight ratio of poly(glycolide-co-lactide) having a monomer ratio of glycolide to lactide of 65 / 35 to calcium stearate is 0.4 to 1.5, preferably 0.5 to about 1.0, wherein the triclosan-proficient component accounts for a weight percentage of the suture between 0.6 wt % and 2 wt %, preferably between 1.0 wt % and 1.7 wt %.

28. The coated medical device of claim 1, 3 or 25, which is a suture in a sealed package, wherein the antimicrobial agent is on an inner surface or embedded within the material of the package.

29. The coated medical device of claim 28, wherein the sealed package is made of polypropylene, high density polyethylene (HDPE), paper, or a combination thereof.

30. The coated medical device of claim 27, wherein the antimicrobial agent has been transferred from a source of the antimicrobial agent via heat, vacuum, or a combination thereof.

31. The coated medical device of claim 30, wherein the source of the antimicrobial agent is the suture coating, patch, suture packaging, reservoir, or a combination thereof.

32. A coating solution for coating the medical device of claim 1, 2 or 3, the medical device being a braided suture having a USP size of 2 to 3 / 0, the coating solution comprising: a. from about 3 wt % to at least about 8 wt % of poly(ε-caprolactone-co-glycolide), wherein the monomer ratio of caprolactone to glycolide is 90 / 10, and b. From about 0 wt % to about 6 wt % of poly(glycolide-co-lactide) wherein the monomer ratio of glycolide to lactide is 65 / 35.

33. The coating solution of claim 32, comprising: a. from about 4 wt % to about 8 wt % of poly(ε-caprolactone-co-glycolide), wherein the monomer ratio of caprolactone to glycolide is 90 / 10, and b. From about 0 wt % to about 4 wt % of poly(glycolide-co-lactide) wherein the monomer ratio of glycolide to lactide is 65 / 35.

34. A coating solution for coating the medical device of claim 1, 2 or 3, the medical device being a braided suture having a USP size 4 / 0, the coating solution comprising: a. from about 8 wt % to at least about 16 wt % of poly(ε-caprolactone-co-glycolide), wherein the monomer ratio of caprolactone to glycolide is 90 / 10, and b. about 0 wt % to about 8 wt % of poly(glycolide-co-lactide), wherein the monomer ratio of glycolide to lactide is 65 / 35, preferably about 5 wt % to 8 wt % of poly(glycolide-co-lactide), wherein the monomer ratio of glycolide to lactide is 65 / 35.

35. A coating solution for coating the medical device according to claim 1 or 25, wherein the medical device is a braided suture, the coating solution comprising: a. from about 3% to at least about 8% by weight of calcium stearate; and b. From about 3 wt% to about at least 8 wt% of poly(glycolide-co-lactide) wherein the monomer ratio of glycolide to lactide is 65 / 35.

36. The coating solution of claim 34, comprising: a. from about 4.5 wt % to about 6 wt % calcium stearate; and from about 4.5 wt % to about 6 wt % poly(glycolide-co-lactide), wherein the monomer ratio of glycolide to lactide is 65 / 35.

37. A method of introducing triclosan into a medical device according to claim 1, 3 or 25, wherein the medical device is a coated braided suture, by exposing the coated suture to a patch having a triclosan reservoir, wherein the transfer is performed at an elevated temperature and / or reduced pressure.

38. A method of introducing triclosan into a medical device according to claim 1, 3 or 25, wherein the medical device is a coated braided suture, exposing the suture to a triclosan reservoir located or embedded in a dosage disk, wherein the transfer is performed at an elevated temperature and / or reduced pressure.

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