Packaged antimicrobial medical device having improved shelf life and method of preparing same

The present invention relates to an antibacterial medical device, an antibacterial packaged medical device, and a method for manufacturing the same.

Each year, patients undergo numerous surgeries in the United States. Current data show that about 2,700 procedures are performed annually. Postoperative or surgical site infections (SSI) occur in approximately 2-3% of all cases. This is equivalent to 675,000 SSIs annually.

Outbreaks of SSI are often associated with bacteria that can colonize implantable medical devices used in surgery. During surgery, bacteria in the surrounding atmosphere can invade the surgical site and attach to medical equipment. In particular, bacteria can spread by using an implantable medical device as a route to surrounding tissue. Such bacterial colonization of medical devices can lead to infection and trauma to the patient. Therefore, SSI can significantly increase the cost of treating a patient.

Implantable medical devices containing an internally coated or impregnated antibacterial agent have been disclosed and / or exemplified in the art. An example of such an instrument is disclosed in European Patent Application EP 0 761 243. The actual instruments exemplified in this application include a French Percuflex catheter. These catheters are dip-coated in a coating bath containing 2,4,4'-trichloro-2-hydroxydiphenyl ether (Irgasan (DP300) from Ciba Geigy) and other additives. These catheters were then sterilized with ethylene oxide and stored for 30 days. Catheter coated with such a solution exhibited antibacterial properties. That is, the catheter produced a blocking zone when placed in growth medium and attacked by microorganisms for 30 days after coating. It is not clear from this application at what temperature this sterile and coated catheter was stored.

Most implantable medical devices are manufactured, sterilized, and housed in a package until opened for surgical use. During surgery, the opened package containing the medical device, the package components contained therein, and the medical device are exposed to the atmosphere of the operating room, where bacteria in the air can be drawn. By imparting antibacterial properties to the package and / or the package components contained therein, bacterial colonization of the package and components after the package is opened is significantly prevented. The antibacterial package and / or package component, coupled with imparting antibacterial properties to the medical device itself, considerably ensures the antibacterial environment around the antibacterial medical device.

<p> Packaged medical devices with antibacterial properties may exhibit a limited shelf life. Therefore, there is a need for packaged antibacterial medical devices with long shelf life and methods for extending the shelf life of packaged antibacterial medical devices.</p>

<p> In one aspect, a method of producing a packaged antibacterial suture with an improved shelf life is disclosed herein. This method involves providing an inner package with a source of antibacterial agent, providing an adsorbent effective for adsorbing a portion of the antibacterial agent over time, and placing sutures within the inner package. A step in which the suture comprises one or more surfaces, a step of covering the inner package with an outer package having an inner surface, and an inner surface of the suture, the inner package, and the outer package. Substantially inhibiting bacterial colonization on the suture and inner package by subjecting it to sufficient time, temperature and pressure conditions to steam transfer an effective amount of antimicrobial from the source of the suture to the suture and inner package. The packaged antibacterial suture exhibits an improved shelf life.</p><p> In one embodiment, the adsorbent is provided by coating the adsorbent on at least a portion of one surface of the inner package.</p><p> In another embodiment, the adsorbent is provided by placing the adsorbent substrate within the outer package.</p><p> In yet another embodiment, the adsorption substrate is formed by coating the substrate with an adsorbent.</p><p> In yet another embodiment, the adsorbent substrate is formed of an adsorbent.</p><p> In a further embodiment, the antibacterial agent is selected from the group consisting of halogenated hydroxyl ethers, acyloxydiphenyl ethers, and combinations thereof.</p><p> In a further embodiment, an effective amount of antimicrobial agent transferred from the source of the antimicrobial agent to the suture and inner package is transferred during the ethylene oxidative sterilization process.</p><p> In another embodiment, the step of subjecting the inner surface of the suture, inner package, and outer package to sufficient conditions for steam transfer of an effective amount of antibacterial agent is the outer having the inner package and suture inside. The process of placing the package in the sterilization unit, the process of heating the sterilization unit to the first temperature, the process of adjusting the pressure inside the sterilization unit to the first pressure value, and the process of injecting steam into the sterilization unit to inject steam into the outer package. The step of exposing the inner surface, inner package and suture of the suture to steam for the first period, the step of adjusting the pressure in the sterilization unit to the second pressure value, and the step of introducing a chemical sterilizer into the sterilization unit. The step of keeping the chemical sterilizer in the sterilization unit for a second period to incapacitate a sufficient amount of microorganisms, the step of removing residual water and the chemical sterilizer from the suture, and the packaged antibacterial suture Includes a step of drying the suture to a desired moisture level.</p><p> In yet another embodiment, the inner package comprises a common envelope made of paperboard stock having at least one surface coated with an adsorbent.</p><p> In yet another embodiment, the inner package comprises a containment compartment having an outer cover, which outer cover has one surface coated with an adsorbent.</p><p> In a further embodiment, the adsorbents are bentonite, activated carbon, activated alumina, silica gel, zeolite, superabsorbent polymers, wetting agents, polymer coatings, ground polypeptide coatings, natural products, non-paper substrates, and Selected from clays containing kaolin.</p><p> Another object of the present invention is a method for extending the shelf life of a packaged antibacterial medical device. This method involves providing an inner package with a source of antibacterial agent, providing an adsorbent that is effective in adsorbing a portion of the antibacterial agent over time, and placing the medical device within the inner package. A process in which the medical device comprises one or more surfaces, a process of covering the inner package with an outer package having an inner surface, and an inner surface of the medical device, inner package, and outer package. Subjecting to sufficient time, temperature and pressure conditions to steam transfer an effective amount of antimicrobial agent from the source of the antimicrobial agent to the medical device and inner package effectively inhibits bacterial colonization on the medical device and inner package. The packaged antimicrobial medical device exhibits an improved shelf life, including the steps to be performed.</p><p> The present invention also relates to packaged antibacterial sutures with improved shelf life. This packaged antibacterial suture is an inner package having a source of the antibacterial agent, an adsorbent effective for adsorbing a part of the antibacterial agent over time, and a suture arranged in the inner package. , Suture, inner package, and outer package having an inner surface, including one or more surfaces, and an outer package having an inner package located inside. The inner surface of the outer package is subjected to conditions of sufficient time, temperature and pressure to steam transfer an effective amount of antimicrobial agent from the source of the antimicrobial agent to the suture and inner package on the suture and inner package. Substantially inhibits bacterial colonization in.</p><p> In one embodiment, the packaged antibacterial suture exhibits an improved shelf life.</p><p> The present invention also aims at a packaged medical device. This packaged antibacterial device is an inner package having a source of the antibacterial agent, an adsorbent effective for adsorbing a part of the antibacterial agent over time, and a medical device placed in the inner package. Includes a medical device containing one or more surfaces and an outer package having an inner surface and having an inner package disposed inside, including the medical device, inner package, and outer. The inner surface of the package is subjected to conditions of sufficient time, temperature and pressure to steam transfer an effective amount of the antimicrobial agent from the source of the antimicrobial agent to the medical device and the inner package on the medical device and the inner package. Substantially inhibits bacterial colonization.</p>

The present invention will become more apparent in the discussion that follows with reference to the drawings, which illustrate various embodiments of the invention as non-limiting examples.<figref num="1">Top view of a form of a packaged antibacterial medical device according to the present specification, wherein the medical device is a needle and a suture.</figref><figref num="2">Top view of another form of the packaged antibacterial medical device according to this specification, wherein the medical device is a needle and a suture.</figref><figref num="3">Top view of the packaged antibacterial medical device of FIG. 2 with the outer cover of the containment compartment removed and the substrate member completely exposed.</figref><figref num="4">Bottom view of the outer cover of the containment compartment of the packaged antibacterial medical device in Figure 2.</figref><figref num="5">Top view of the substrate member of the containment compartment of the packaged antibacterial medical device of FIG.</figref><figref num="6">A lay flat view of another embodiment of the inner package in the form of a general folder according to the specification.</figref><figref num="7">Comparison of increase in triclosan as a function of shelf life at 25 ° C for suture packages containing the types of adsorbents disclosed herein, as opposed to adsorbent-free suture packages.</figref><figref num="8">Comparison of increase in triclosan as a function of shelf life at 25 ° C for suture packages containing the types of adsorbents disclosed herein, as opposed to adsorbent-free suture packages.</figref><figref num="9">Comparison of triclosan increase as a function of shelf life at 50 ° C for suture packages containing the types of adsorbents disclosed herein compared to adsorbent-free suture packages.</figref><figref num="10">Comparison of triclosan increase as a function of shelf life at 50 ° C for suture packages containing the types of adsorbents disclosed herein compared to adsorbent-free suture packages.</figref><figref num="11">Comparison of increase in triclosan as a function of shelf life at 25 ° C for suture packages containing the types of adsorbents disclosed herein, as opposed to adsorbent-free suture packages.</figref><figref num="12">Comparison of increase in triclosan as a function of shelf life at 25 ° C for suture packages containing the types of adsorbents disclosed herein, as opposed to adsorbent-free suture packages.</figref><figref num="13">Comparison of triclosan increase as a function of shelf life at 50 ° C for suture packages containing the types of adsorbents disclosed herein compared to adsorbent-free suture packages.</figref><figref num="14">Comparison of triclosan increase as a function of shelf life at 50 ° C for suture packages containing the types of adsorbents disclosed herein compared to adsorbent-free suture packages.</figref>

References are made herein to FIGS. 1-14, but throughout, similar reference numerals are used to indicate similar elements.

Here, with reference to FIG. 1, one embodiment of a packaged antibacterial medical device 10 is illustrated. The packaged antibacterial medical device 10 includes an inner package 11 having a source of antibacterial agent. The medical device 14 may be a needle 16 and a suture 18 having one or more surfaces 20 and is located within the inner package 11. In one embodiment, the inner package 11 includes a containment compartment 12 and an outer cover 22, which has one surface 24 that may be coated with an adsorbent. In one embodiment, the adsorbent is effective in adsorbing some of the antibacterial agent over time. The outer package 50 with the inner surface 52 is provided to seal the inner package 11 when placed inside.

The containment compartment 12 of the packaged antibacterial medical device 10 includes a substrate member 26 and a channel cover member 28. The substrate member 26 includes an upper portion, a lower portion, and an outer peripheral edge portion 30. As shown, the outer cover 22 may be placed on top of the channel cover member 28 and within the outer peripheral edge 30 so as to at least partially enclose the medical device 14. The substrate member 26 may be a substantially flat and substantially egg-shaped member having a longitudinal axis. In the case of packaged sutures, the substrate member 26 of the packaged antibacterial medical device 10 may be desired to have an oval shape, such as circular, polygonal, square with rounded corners, and the like. And other shapes can be used, including combinations of their equivalents. The channel cover 28 includes an upper portion, a lower portion, an edge portion 32, and a longitudinal axis.

The packaged antibacterial medical device 10 of the present invention may be assembled by the following method. If a rivet is used, the substrate member 26 aligns with the rivet receiving hole and, if a positioning pin is used, the positioning pin aligns with the corresponding opening. Aligned with 28. Further, if a wrapping pin opening is used, the wrapping pin opening is aligned with the corresponding opening. Then, when a rivet is used, the rivet is inserted and penetrated into the corresponding hole, and when a positioning pin is used, the positioning pin is inserted and penetrated into the corresponding hole. The channel cover member 28 is then mounted on the substrate member 26. When rivets are used, the ends of the rivets may be deployed using conventional techniques such as heating, sonication, etc. so that the channel cover member 28 is firmly secured to the substrate member 26. In this embodiment, when the containment compartment 12 is formed in this way, a channel 34 is formed, which can advantageously accommodate the wound suture 18.

With reference to FIGS. 2-5, another embodiment of the packaged antibacterial medical device 100 is illustrated. The packaged antibacterial medical device 10 includes an inner package 111 having a source of antibacterial agent. The medical device 114 may be a needle 116 and a suture 118 having one or more surfaces 120 and is located within the inner package 111. In one embodiment, the inner package 111 includes a containment compartment 112 and an outer cover 122, the outer cover 122 having one surface 124 coated with an adsorbent. In one embodiment, the adsorbent is effective in adsorbing some of the antibacterial agent over time. The outer package 150 having the inner surface 152 is provided to seal the inner package 111 arranged inside.

The containment compartment 112 of the packaged antibacterial medical device 100 includes a substrate member 126 and a plurality of channel cover tab members 128. The substrate member 126 includes an upper portion, a lower portion, and an outer peripheral edge portion 130. In one embodiment, the outer cover 122 may be placed on top of the containment compartment 112 and within the outer peripheral edge 130 so as to at least partially enclose the medical device 114.

The substrate member 126 may be a substantially flat and substantially egg-shaped member having a longitudinal axis. In the case of packaged sutures, it may be desirable for the substrate member 126 of the packaged antibacterial medical device 100 to have an oval shape, such as circular, polygonal, square with rounded corners, etc. Other shapes may be used that include these combinations and their equivalents.

In particular, referring to FIGS. 2 to 4, the packaged antibacterial medical device 100 of the present invention can be assembled by the following method. The board member 126 may include a plurality of retaining pins 140. The channel cover tab member 128 may be provided with a plurality of stop pin receiving holes 142 for receiving the corresponding stop pin 140 when the channel cover tab member 128 folds over the stop pin 140. The channel cover tab member 128 is then fixed to the retaining pin 140 of the substrate member 126. Advantageously, the use of heating or sonication to securely secure the channel cover tab member 128 to the substrate member 126 can be avoided. In this embodiment, when the containment compartment 112 is formed in this way, a channel 134 is formed, which can advantageously accommodate the wound suture 118.

In one embodiment, as illustrated in FIGS. 2-4, the outer cover 122 is secured to the substrate member 126 in the outer peripheral edge 130 for placement within the tab receiving member 144. Therefore, a plurality of tabs 146 may be provided to at least partially enclose the medical device 114.

Further details regarding the structure and geometry of the containment compartment and the packages formed in the containment compartment are fully described in US Pat. Nos. 6,047,815, 6,135,272, and 6,915,623, each patent. The contents of are incorporated herein by reference with respect to all the contents they disclose.

Containment compartments 12 and 120 can be made from conventional moldable materials. It is particularly preferred to use polyolefin materials such as polyethylene and polypropylene, other thermoplastic materials, polyester materials such as nylon, and their equivalents. In one embodiment, the containment compartments 12 and 120 of the present invention may be injection molded, but they may be formed by other conventional processes and equivalent processes including thermoforming. If desired, the package may be manufactured as individual assemblies or components to be assembled later.

With reference to FIG. 6, another embodiment of a packaged antibacterial medical device comprising an inner package 211 having a source of antibacterial agent is illustrated. As will be appreciated by those skilled in the art, the inner package 211 is in the form of a common folder and is illustrated in the form of an unfolded lay flat.

As shown, the inner package 211 includes a first main outer panel 202, a second main outer panel 204, a first inner panel 206, and a second inner panel 208. The first inner panel 206 is folded inward along the fold line 216 and the second inner panel 208 is along the fold line 218 to form the inner package 211 to form a general envelope. Folds inward. Medical devices (not shown) that may be needles and sutures with one or more surfaces are under the second inner panel 208 of the inner package 211 and on the second main outer panel 204. It is placed in contact with the inner surface. The first main outer panel 202 may be provided with the tab 210 to fit into the tab receiving means 212 which may be provided within the second inner panel 208 as shown. To complete, the inner package 211, the first main outer panel 202, and the second main outer panel 204 are folded along the fold line 214 and the tab 210 is placed within the tab receiving means 212. As in other embodiments, one surface is coated with an adsorbent so that the packaged antibacterial medical device exhibits an improved shelf life for the packaged antibacterial medical device without the adsorbent. Make it possible.

Similar to other embodiments described herein, an outer package (not shown) having an inner surface is provided to seal the inner package 211 when placed inside.

The medical devices described herein generally include single-fiber and multi-fiber sutures, surgical meshes such as hernia repair meshes, hernia plugs, blackie seed spacers, suture clips, suture anchors, anti-adhesive meshes and Implantable medical devices and implants, including, but not limited to, films and suture knot clips. Also included are absorbable and non-absorbable implantable medical devices.

Absorbent polymers are defined herein as polymers that, when exposed to physiological conditions, decompose over time and are absorbed by the body. Absorbable medical devices typically include, but are not limited to, glycolides, lactides, copolymers of glycolides, or mixtures of polymers such as polydioxanone, polycaprolactone, oxidized regenerated cellulose and their equivalents, but are generally known. Formed from conventional absorbent polymers. Preferably, these polymers include over about 70% polymerized glycolide, over about 70% polymerized lactide, polymerized 1,4-dioxan-2-one, over about 70% polypeptide, glycolide and lactide. Selected from the group consisting of polymers of over 70% cellulose and cellulose derivatives. Preferably, the absorbent medical device is made from polydioxanone, polygrecapron, or glycolide / lactide copolymer. Examples of absorbent medical devices include single fiber and multifiber sutures. The multi-fiber suture includes a suture in which a plurality of fibers are formed in a braided structure. Examples of non-absorbable medical devices include single-fiber and multi-fiber sutures, surgical meshes such as hernia repair meshes, hernia plugs and blackie seed spacers, which may be polymer but non-polymeric. It may be. Non-absorbable medical devices, in whole or in part, include polyolefins such as polypropylene, polyamides such as nylon, fluorinated hydrocarbons such as Teflon® materials, and polyesters such as Dacron® synthetic polyester. Examples thereof include, but are not limited to, polymer materials such as silk, collagen, stainless steel, titanium, cobalt chloride alloy, and nitinol, and the like, and non-polymer materials which are not limited thereto can be produced. Preferably, the non-absorbable medical device is made from nylon or polypropylene.

In one embodiment, sutures and needles that can be packaged within the packages disclosed herein include conventional surgical sutures and conventional bioabsorbable sutures, and their equivalents. .. The packages of the present invention are useful for packaging small diameter sutures because, until now, small diameter sutures have the problem of being removed or caught when pulling such sutures out of the package. In addition, it was difficult to package in a tray package.

Suitable antibacterial agents may be selected from, but are not limited to, halogenated hydroxy ethers, acyloxydiphenyl ethers, or combinations thereof. In particular, as described in US Pat. No. 3,629,477 and represented by the following formula, the antibacterial agent may be a halogenated 2-hydroxydiphenyl ether and / or a halogenated 2-acyloxydiphenyl ether.<chemistry num="1"><img file="JP2012531969A_D0001.tif" /></chemistry>

In the above equation, each Hal represents the same or different halogen atom, Z represents a hydrogen or acyl group, w represents a positive natural number in the range 1-5, and each of the benzene rings is preferably ring A. However, it may also contain one or more lower alkyl groups, lower alkoxy groups, allyl groups, cyano groups, amino groups, or lower alkanoyl groups that can be halogenated. Preferably, the lower alkyl group and lower alkoxy group, which are useful as substituents on the benzene ring, have a methyl group or a methoxy group, respectively. Lower halogenated alkyl groups and trifluoromethyl groups are preferred.

Also, antibacterial activity similar to the halogen-o-hydroxy-diphenyl ether of the above formula can be obtained using those O-acyl derivatives that are partially or completely hydrolyzed under the conditions of actual use. Ethers of acetic acid, chloroacetic acid, methyl or dimethylcarbamic acid, benzoic acid, chlorobenzoic acid, methylsulfonic acid, and chloromethylsulfonic acid are particularly preferred.

One of the particularly preferred antibacterial agents within the range of the above formula is 2,4,4'-trichloro-2'-hydroxydiphenyl ether, commonly referred to as triclosan (manufactured by Ciba Geigy under the trade name Irgasan DP300 or Irgacare MP). Is. Triclosan is a white powder solid with a slight aromatic / phenolic odor. As is clear, it is a chlorinated aromatic compound with functional groups representing both ethers and phenols.

Triclosan is a broad-spectrum antibacterial agent used in a variety of products and is effective against a large number of organisms commonly associated with SSI. Such microorganisms include, but are not limited to, Staphylococcus epidermidis, Staphylococcus epidermidis, Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus, and combinations thereof.

In addition to the antibacterial agents mentioned above, this medical device optionally comprises alcohols such as ethanol and isopropanol; aldehydes such as glutarualdehyde and formaldehyde; anilides such as trichlorocarbanolide; biguanides such as chlorhexidine; hypochlorite. Chlorine release agents such as sodium, chlorine dioxide and acidic sodium chlorite; iodine release agents such as povidone iodine and poroxamayode; metals such as silver nitrate, sulfaziazine silver, other silver agents, copper-8-quinolinolate, and bismuththiol. Peroxidized compounds such as hydrogen peroxide and peracetic acid; phenols; benzalkonium chloride, cetrimid and ionic polyquaternary ammonium compounds, although they may have biogenic agents, disinfectants and / or disinfectants. , Not limited to these. This medical device can optionally be penicillins such as amoxicillin, oxacillin and piperacillin; cephalosporin parenteral agents such as cefazolin, cefazolin, cefoxitin, cefprodil, cefotaxime and cefdinir; monobactams such as azutreonum; Β-lactamase inhibitors; glycopeptides such as vancomycin; polymyxin; naridixic acid; quinolones such as cefazolin and lebakin; metronidazole; novobiocin; actinomycin; rifampins; aminoglycosides such as neomycin and gentamycin; Cole; macrolides such as erythromycin; clindamycin; sulfonamides such as sulfaziazine; trimetprim; topical antibacterial agents; vacitracin; glamoxicillin; mupirocin; It is not limited to. If desired, this medical device may include antibacterial peptides such as defensin, maginin and nisin; lytic bacteriophage; surfactants; adhesion inhibitors such as antibodies, oligosaccharides and glycolipids;

The antibacterial agent can be delivered to the medical device from a source of the antibacterial agent placed internally or immobilized on the inner surface of the package. Specifically, the antimicrobial agent moves from the antimicrobial source to the medical device when the package is subjected to the antimicrobial source and the medical device under the following time, temperature and pressure conditions. For example, sources of antibacterial agents include paper reservoirs containing antibacterial agents, porous pouch reservoirs containing antibacterial agents, plastic reservoirs containing antibacterial agents, sponge or foam reservoirs containing antibacterial agents, antibacterial agents. It may be a tape (see element) or a tablet containing an antibacterial agent. Alternatively, the source of the antibacterial agent may be integrated with the package itself, i.e., the antibacterial agent may be applied directly onto the inner surface of the package, but is not limited to the inside of the package itself or the package itself. Built on top. If the source of the antibacterial agent is a paper or plastic reservoir, such a reservoir may be integrated with one or more packaging components within the package.

As described, the packaged antibacterial medical devices disclosed herein utilize adsorbents to improve shelf life over packaged antibacterial sutures that do not utilize adsorbents. It has been shown that the shelf life of antibacterial medical devices such as triclosan-containing sutures is considered to be limited by the amount of triclosan that increases over time during normal and accelerated storage conditions. Surprisingly, it has been found that certain adsorbents can act as buffers to moderate the rate of increase in triclosan on medical devices.

With reference to FIGS. 1, 2 and 6 again, in one embodiment the adsorbent is provided by coating the adsorbent on at least a portion of one surface of the inner package 11, 111 or 211. In another embodiment, the adsorbent is provided by placing an adsorbent substrate (not shown) within the outer package. In another embodiment, the adsorbent substrate is formed by coating the substrate with an adsorbent. In yet another embodiment, the adsorbent substrate is formed of an adsorbent. In yet another embodiment, the adsorbent provided on at least a portion of one surface of the inner package is provided on at least one surface of the outer cover 22 or 122.

Adsorbents useful in the practice of the present invention include bentonite, activated carbon, activated alumina, silica gel, zeolites, superabsorbent polymers, wetting agents, polymer coatings, ground polymer coatings, natural products, non-paper substrates, and kaolin. Any material having adsorptive properties, including clay containing. Clays such as kaolin have proven to be particularly effective.

Referring to FIG. 6, the inner package 211 includes a common envelope formed from a paperboard material having at least one surface coated with an adsorbent. A suitable paperboard material that has utility in the practice of the inventions disclosed herein is Invercote T2®, available from the Iggesund Paperboard of Edison, New Jersey.

In addition, the medical device may optionally have a coating on it, and / or optionally, an antibacterial agent placed on the antibacterial agent prior to transfer from the source of the antibacterial agent to the medical device. May include one or more surfaces with. For example, it is advantageous to apply a coating composition with an antibacterial agent to the surface of a medical device. Examples of medical devices and coatings that can be applied to them are U.S. Pat. Nos. 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 by reference in its entirety. As disclosed in U.S. Pat. No. 4,201,216, the coating composition comprises a film-forming polymer and C.I.₆It may contain a substantially water-insoluble salt of the above fatty acids. As another example, absorbent coating compositions that can be used in absorbent medical devices have a C alkylene moiety.₆Or C₄~ C₁₂It may contain a poly (alkylene oxylate) derived from a mixture of diols, which is applied to medical devices from a solvent solution as disclosed in US Pat. No. 4,105,034. The coating composition may comprise a polymer or copolymer, which polymer or copolymer may include lactide and glycolide as binders. The coating composition may also include calcium stearate as a lubricant and an antibacterial agent. The coating can be applied to the device by solvent-based coating techniques such as dip coating, spray coating, or suspension drop coating, or any other coating means.

Absorbent medical devices are moisture sensitive, that is, devices that decompose when exposed to moisture in the air or in the body. It is known to those skilled in the art that medical devices made from absorbent polymers will decompose and lose strength when exposed to water vapor prior to use during surgery. For example, the desirable properties of sutures that maintain tensile strength in vivo will be rapidly lost if the suture is exposed to moisture for extended periods of time prior to use. Therefore, for absorbable medical devices, it is desirable to use a sealed package. An airtightly sealed package is used herein to mean a package made of a material that acts as both a sterile barrier and a gas barrier, i.e., a material that prevents or substantially blocks the permeation of moisture and gas. It is defined to be.

With reference to FIGS. 1 and 2 again, materials useful for constructing outer packages 50 and 150 and outer packages for use with common envelopes are often referred to, for example, heat-sealable foils. Examples include single-layer and multi-layer conventional metal leaf products. These types of foil products are described in US Pat. No. 3,815,315, the entire contents of which are incorporated herein by reference. Another type of foil product that can be used is a foil laminate, referred to in the art as peelable foil. Examples of such removable foils and substrates are described in US Pat. No. 5,623,810, the entire contents of which are incorporated herein by reference. If desired, in addition to or in place of the metal leaf, a conventional non-metallic polymer film may be used to form the packaging of the absorbent medical device. Such films are macromolecules and may include combinations and laminates thereof such as conventional polyolefins, polyesters, acrylics, halogenated hydrocarbons and the like. These polymeric films substantially block the permeation of moisture and oxygen and may be coated with conventional coating materials such as mineral and oxidized mineral coatings that reduce or reduce gas ingress. The package may include a combination of polymer and metal leaf, in particular a multilayer polymer / metal leaf composite such as a polyester / aluminum foil / ethylacrylic acid laminate.

Non-absorbable medical devices may be packaged in any of the materials described above. In addition, porous materials, ie medical paper, or polymeric films or fabrics that are permeable to moisture and gas, ie, high density produced by EIdu Pont de Nemours and Company (Wilmington, Delaware). It is desirable to package non-absorbable medical devices in a package made of a material that acts as a sterile barrier, such as a Tyvek® non-woven material made of polyethylene fibers. Preferably, the non-absorbable medical device is an absorbent medical device such as a sealed package when it is desirable that the antibacterial medical device has a shelf life of at least 6 months, preferably at least 1 year, most preferably at least 2 years. It is packaged in the same packaging material used for.

Staphylococcus epidermidis microorganisms are the most common of all bacteria associated with instrument-related surgical site infections. Staphylococcus aureus and Staphylococcus epidermidis are widespread in the patient's skin and are therefore easily introduced into the wound. An effective antibacterial agent against staphylococci is 2,4,4'-trichloro-2'-hydroxydiphenyl ether. The minimum inhibitory concentration (MIC) of this compound against Staphylococcus aureus was measured in a suitable growth medium and also by Bhargava, H. et al., The American Journal of Infection Control, June 1996, pages. As described in 209 to 218, it is 0.01 ppm. A MIC for a particular antimicrobial agent and a particular microorganism is the minimum concentration of antimicrobial agent that must be present in the growth medium that is otherwise suitable for the microorganism in order to make the growth medium unsuitable for that microorganism. That is, it is defined as the minimum concentration for inhibiting the growth of microorganisms. The phrase "amount useful to substantially inhibit bacterial colonization" and "effective amount" of an antibacterial agent are defined as greater than or equal to the minimum inhibitory concentration against S. aureus when used herein. To.

Demonstration examples of this MIC are found in the sensitive disc diffusion method. A filter paper disc or other object impregnated with a particular antibacterial agent is applied to the agar medium inoculated with the test microorganism. Sensitive microorganisms do not grow on or around the disc over a distance if the antimicrobial agent diffuses through the medium and as long as the antimicrobial agent concentration exceeds the minimum inhibitory concentration (MIC). This distance is called the blocking zone. Assuming that the antimicrobial agent has a diffusion rate in the medium, there is a blocking zone around the disc impregnated with the antimicrobial agent, and thus the presence of the antimicrobial agent in the growth medium, which would otherwise be good Is suggested to be blocked. The diameter of the blocking zone is inversely proportional to the MIC.

According to various methods of the present invention, there are provided methods for producing packaged antibacterial sutures with improved shelf life. The method includes a step of providing an inner package having a source of the antibacterial agent, a step of providing an adsorbent effective for adsorbing a part of the antibacterial agent over time, and a step of arranging a suture in the inner package. And the steps in which the suture comprises one or more surfaces, the step of covering the inner package with an outer package having an inner surface, and the inner surface of the suture, the inner package, and the outer package are antibacterial. Subjecting to sufficient time, temperature and pressure conditions to steam transfer an effective amount of antibacterial agent from the source of the agent to the suture and inner package effectively inhibits bacterial colonization on the suture and inner package. Including the process. Advantageously, the packaged antibacterial sutures thus produced exhibit improved shelf life over the adsorbent-free packaged antibacterial sutures thus provided.

As described in more detail below, the step of subjecting the inner surface of the suture, inner package, and outer package to sufficient conditions to steam transfer an effective amount of antibacterial agent is to place the inner package and suture inside. The step of arranging the outer package to be held in the sterilization unit, the step of heating the sterilization unit to the first temperature, the step of adjusting the pressure in the sterilization unit to the first pressure value, and the step of injecting steam into the sterilization unit. The step of exposing the inner surface of the outer package, the inner package and the suture to steam for the first period, the step of adjusting the pressure in the sterilization unit to the second pressure value, and the step of introducing the chemical sterilizer into the sterilization unit. And the step of keeping the chemical sterilizer in the sterilization unit for a second period to incapacitate a sufficient amount of microorganisms, the step of removing residual water and the chemical sterilizer from the suture, and packaging antibacterial properties. It comprises a step of drying the suture to a desired moisture level. In one embodiment, the step of introducing a chemical sterilizer comprises introducing ethylene oxide gas into the sterilization unit.

In one embodiment, the medical device is directly exposed to the antibacterial agent, i.e., the source of the antibacterial agent is located within the package with the medical device. For example, the package may contain a source of antibacterial agent, the source of antibacterial agent fixed to the inner surface of the package may be contained, and the source of antibacterial agent may be one or more packages within the package. It may be integrated with the sterilizing component or the package itself. In these embodiments, the medical device is placed within the package and may be initially free of antimicrobial agents and may initially include one or more surfaces with antibacterial agents placed on it. Good. As described, the package, antimicrobial source and medical device are then subjected to conditions of sufficient time, temperature and pressure to vapor transfer an effective amount of antimicrobial agent from the antimicrobial source to the medical device. It substantially inhibits bacterial colonization on medical devices.

If the medical device does not initially contain an antimicrobial agent, the antimicrobial agent is sufficient time for the packaging, the source of the antimicrobial agent, and the medical device to steam some of the antimicrobial agent from the source of the antimicrobial agent to the medical device. , Delivered from the source of the antimicrobial agent to the medical device when subjected to temperature and pressure conditions.

If the medical device contains one or more surfaces with antibacterial agents initially placed on it, the time, temperature and pressure conditions will keep an effective amount of antimicrobial agent on the medical device. As such, a portion of each of the antimicrobial agent placed on the medical device and the antimicrobial agent in the source of the antimicrobial agent is vapor-transferred to the inner surface of the package to substantially colonize the bacteria on the inner surface of the medical device and package. Sufficient to inhibit. In this embodiment, the amount or concentration of antibacterial agent on the medical device is stabilized by providing additional antibacterial agent in the packaging environment.

Alternatively, the medical device may be placed within the package and the package with the medical device is indirectly exposed to an external source of antimicrobial agent, i.e. the source of the antimicrobial agent is the package having the medical device. Exists outside. Specifically, a package with a medical device is subjected to medical conditions of sufficient time, temperature and pressure to vapor transfer an effective amount of the antimicrobial agent from the source of the antimicrobial agent to the medical device in the package. It substantially inhibits bacterial colonization on the tool. In this embodiment, the package is made from a material that acts as a sterile barrier, such as a porous material that is water and gas permeable or a polymer film, so that the source of the gaseous antimicrobial agent can permeate or move as vapor through the package. can do. For example, the package with the medical device may be placed in a closed environment, and the source of the antibacterial agent may be housed in the closed environment or later introduced into the closed environment. The source of the antibacterial agent may be any vapor form of the antibacterial agent.

The rate of vapor transfer of an antimicrobial agent, such as triclosan, from the source of the antimicrobial agent to the medical device depends substantially on the time, temperature and pressure conditions under which the package and medical device are processed, stored and handled. Conditions for effective vapor transfer of antibacterial agents such as triclosan include a closed environment, atmospheric pressure, and temperatures above 40 ° C for a period of 4 to 8 hours. In addition, any combination of pressure and temperature that gives the antibacterial agent a partial pressure greater than or equal to the partial pressure given under the conditions described above is an effective amount or concentration, that is, antibacterial activity equal to or greater than the minimum inhibitory concentration (MIC) of Staphylococcus aureus. Listed with a period sufficient to give the drug to the medical device. In particular, as known to those of skill in the art, when the pressure is reduced, the temperature can be lowered to achieve the same partial pressure. Alternatively, if the pressure is reduced and the temperature is kept constant, the time required to deliver an effective amount or concentration of antimicrobial agent to the medical device can be reduced. In general, the amount of antimicrobial agent in the source of the antimicrobial agent is at least the amount required to deliver an effective amount of antimicrobial agent on the medical device when exposed to the following conditions:

Medical devices are typically sterilized to virtually render the microorganisms on them incapacitated. In particular, sterilization is 10 in the technical field.^-6It is understood to mean the minimum sterilization assurance level of. Examples of sterilization processes are described in US Pat. Nos. 3,815,315, 3,068,864, 3,767,362, 5,464,580, 5,128,101 and 5,868,244, respectively, all of which. Is incorporated herein by reference. In particular, absorbent medical devices can be sensitive to radiation and heat. Therefore, it may be desirable to sterilize such devices using conventional sterile gases or agents, such as ethylene oxide gas.

The ethylene oxide sterilization process is described below as there are sufficient time, temperature and pressure conditions in the ethylene oxide sterilization process to steam the antimicrobial agent from the source of the antimicrobial agent to the medical device. However, sufficient time, temperature and pressure conditions to vapor transfer the antimicrobial agent from the source of the antimicrobial agent to the medical device can be achieved alone or in other types of sterilization processes and ethylene oxide sterilization. It is not limited to the process or the sterilization process in general.

As discussed above, absorbent medical devices can be sensitive to moisture and are therefore often packaged in airtight sealed packages, such as sealed foil packages. However, the sealing foil package is also impermeable to sterile gases. To compensate for this and utilize the foil package in the ethylene oxide gas sterilization process, foil packages with gas permeability or permeation vents (eg, Tyvek® nonwoven fabric material, EIdu Pont de Nemours and Processes using the Company (manufactured by Wilmington, Delaware) have been developed. The gas permeation vent is attached to the open end of the package and allows air, water vapor and ethylene oxide to pass through the inside of the package. After the sterilization process is complete, the vent is effectively evacuated from the sealed package and the package is sealed adjacent to the vent so that the vent is cut out or otherwise removed to give a gas permeable sealed package. To do. Another type of foil package with vents is a pouch-type package with vents mounted adjacent to the ends of the package, where the vents are sealed on one side of the package to form a vent section. Will be done. After the sterilization process is complete, the package is sealed adjacent to the vent section and the sealed package is cut over the vent section.

In one embodiment, the source of the antimicrobial agent is located within the package, attached to the inner surface of the package, or integrated with one or more packaging components of the package or the package itself. After the peripheral and side seals have been formed into the package, the packaged medical device may be placed in a conventional ethylene oxide sterilization unit. When the package is a foil package, the source of the antibacterial agent may be any of the above sources of the antibacterial agent, and the source of the antibacterial agent may be a gas permeable vent containing the antibacterial agent. For example, an antimicrobial agent such as triclosan may be loaded into a Tyvek® gas permeable vent by coating a Tyvek® strip with a solution of ethyl acetate and triclosan, and the gas permeable including the antibacterial agent. The vent is placed in the package by mounting it on the sealing material, the medical device is placed in the sealed package, and the outer periphery of the sealed package encloses the medical device and through the vent to the inside of the sealed packaging material. Packaging materials that are hermetically sealed by a gas-permeable method and have a gas permeable vent containing an antimicrobial agent and a medical device are used to steam transfer an effective amount of the antimicrobial agent from the gas permeable vent containing the antimicrobial agent to the medical device. Subject to sufficient time, temperature and pressure conditions, the packaging material is hermetically sealed, encapsulating the medical device, evacuating from the vent, and the vent is cut off to produce an antibacterial medical device.

In another embodiment, the source of the antimicrobial agent may be introduced into a sterilization unit or other unit outside the package with the medical device. For example, the medical device is placed within the package, the package with the medical device is exposed to the source of the antimicrobial agent, and the package with the medical device and the source of the antimicrobial agent are from the source of the antimicrobial agent to the medical device in the package. Subject to conditions of sufficient time, temperature and pressure to vapor transfer an effective amount of antimicrobial agent, it substantially inhibits bacterial colonization on medical devices. The package can be made from a material that acts as a sterilization barrier, such as a water and gas permeable porous material or polymer film, or from a material that provides a sealed package.

Prior to the start of the cycle, the sterilization unit may be heated to an internal temperature of about 25 ° C. or higher. The sterilization unit is maintained at approximately 22 ° C to 37 ° C throughout the humidification and sterilization cycle. Next, decompression is introduced into the sterilization unit to achieve a decompression of about 1.8-6.0 kPa. In the humidification cycle, steam may be injected to provide a source of steam for sterilizing the product. The packaged medical device may be exposed to water vapor in the sterilization unit for a period of about 60-90 minutes. However, the time can vary depending on the medical device being sterilized.

Following this moisturized portion of the cycle, the sterilization unit may be pressurized to a pressure of approximately 42-48 kPa by the introduction of a dry inert gas such as nitrogen gas. When the desired pressure is reached, pure ethylene oxide can be introduced into the sterilization unit until the pressure reaches about 95 kPa. Ethylene oxide may be maintained for a period of time that is effective in sterilizing packaged medical devices. For example, ethylene oxide may be maintained in the sterilization unit for about 360-600 minutes for sutures. The time required to sterilize other medical devices may vary depending on the type and packaging of the product. Ethylene oxide may then be evacuated from the sterilization unit, which unit under reduced pressure at a pressure of about 0.07 kPa for about 150-300 minutes to remove residual water and ethylene oxide from the sterilization packaged medical device. May be maintained. The pressure in the sterilization unit can be returned to atmospheric pressure.

The next step in the process is the drying cycle. Packaged medical devices are dried by exposing them to dry nitrogen and reduced pressure for a number of cycles sufficient to effectively remove residual moisture and water vapor from the packaged medical device to a preselected level. Can be done. During these cycles, the packaged medical device may undergo multiple pressure increases and decreases at temperatures above room temperature. In particular, the jacket temperature of the drying chamber may be maintained at a temperature of about 53 ° C to 57 ° C throughout the drying cycle. However, higher temperatures may be used for sutures, such as about 65 ° C to 70 ° C, and higher temperatures may be used depending on the medical device to be sterilized. A typical drying cycle consists of raising the pressure to about 100 kPa with nitrogen, exhausting the pressure from the drying chamber to a pressure of about 0.07 kPa over a period of 180-240 minutes, and 100 kPa over a period of about 90 minutes. The process of reintroducing nitrogen to the pressure of about 0.01 kPa and exhausting it from the drying chamber for a period of about 240 to 360 minutes and further 4 to 96 hours. Includes a step of maintaining a pressure of 0.005 kPa or higher. At the end of the humidification, sterilization and drying cycle, which typically takes about 24 hours, the vessel is returned to ambient pressure with dry nitrogen gas. Upon completion of drying to a preselected moisture level, the packaged medical device may be removed from the drying chamber and stored in a humidity controlled storage area.

Once the sterilization process is complete, the antibacterial medical device, packaging and / or packaging component is in an amount effective to substantially prevent bacterial colonization on or near the antibacterial device, packaging and / or packaging component. It has an antibacterial agent on it.

As mentioned above, it has been shown that the shelf life of antibacterial medical devices such as triclosan-containing sutures can be limited by the increase in triclosan content that occurs over time during normal and accelerated storage conditions. In some cases, shelf life is limited to no more than two years due to the effects of this phenomenon. The packaged antibacterial medical devices disclosed herein utilize adsorbents to improve shelf life over packaged antibacterial sutures that do not utilize adsorbents. According to the methods disclosed herein, in one embodiment, the method of making a packaged antibacterial device comprises coating at least a portion of one surface of the inner package with an adsorbent. In another embodiment, the adsorbent is provided by placing the adsorbent substrate within the outer package. In yet another embodiment, the adsorption substrate is formed by coating the substrate with an adsorbent. In yet another embodiment, the adsorbent substrate is formed of an adsorbent. In yet another embodiment, the inner package comprises a common envelope formed from a paperboard material having at least one surface coated with an adsorbent.

Adsorbents useful in the practice of the present invention include bentonite, activated carbon, activated alumina, silica gel, zeolites, superabsorbent polymers, wetting agents, polymer coatings, ground polymer coatings, natural products, non-paper substrates, and kaolin. Any material having adsorptive properties, including clay containing. Clays such as kaolin have proven to be particularly effective.

In one embodiment, a method of extending the shelf life of a packaged antibacterial medical device is provided. This method includes a step of providing an inner package having a source of the antibacterial agent, a step of providing an adsorbent effective for adsorbing a part of the antibacterial agent over time, and placing a medical device in the inner package. A step in which the medical device comprises one or more surfaces, a step of covering the inner package with an outer package having an inner surface, and an inner surface of the medical device, inner package, and outer package. Subjecting to sufficient time, temperature and pressure conditions to vapor transfer an effective amount of antimicrobial agent from the source of the antimicrobial agent to the medical device and inner package effectively inhibits bacterial colonization on the medical device and inner package. Including the process of Packaged antibacterial medical devices exhibit an improved shelf life over the adsorbent-free packaged antibacterial medical devices provided in this way.

Here, the present invention will be described in more detail with reference to the following non-limiting examples.

<p> A series of stability experiments were performed using PDS Plus® sutures (single fiber polydioxanone sutures commercially available from Ethicon, Inc.) packaged in common folders and relay trays. Experiments were performed on size 1 and size 3/0 sutures. Uncoated and clay-coated paper (Invercote T2®, Iggesund Paperboard (Edison, New Jersey)) obtained from Monadnock Paper Mills, Inc., (Bennington, New Hampshire) for the size / packaging of each suture. Samples were made using (available from). The experimental names are shown below: VAP2005-003 PDS Plus®-General Folders-Uncoated Paper VAP2007-058 PDS Plus®-General Folders-Coated Paper VAP2005-003 PDS Plus®-Relay Tray-Uncoated Paper VAP2007-054 PDS Plus®-Relay Tray-Coated Paper</p><p> For each experiment, the finished product was stored at 50 ° C for up to 5 months and at 25 ° C for up to 24 months. For a specified period of time, samples were tested for triclosan content in sutures and compared to starting values. Multiple triclosan distribution levels were used for each test condition.</p><p> Example 1 PDS Plus size 1 in a common folder stored at 25 ° C Stability experiments were performed using size 1 PDS Plus® sutures packaged in common folders. For each experiment, the finished product was stored at 25 ° C for up to 24 months. Samples were tested for triclosan content in sutures and compared to starting values. The results of these experiments are shown below and are shown graphically in FIG.<tables num="1"><img file="JP2012531969A_D0002.tif" /></tables></p><p> Example 2 PDS Plus size 3/0 in a common folder stored at 25 ° C Stability experiments were performed using PDS Plus® sutures of size 3/0 packaged in common folders. For each experiment, the finished product was stored at 25 ° C for up to 24 months. Samples were tested for triclosan content in sutures and compared to starting values. The results of these experiments are shown below and are shown graphically in FIG.<tables num="2"><img file="JP2012531969A_D0003.tif" /></tables></p><p> Example 3 PDS Plus size 1 in a common folder stored at -50 ° C Stability experiments were performed using size 1 PDS Plus® sutures packaged in common folders. For each experiment, the finished product was stored at 50 ° C for up to 5 months. Samples were tested for triclosan content in sutures and compared to starting values. The results of these experiments are shown below and are shown graphically in FIG.<tables num="3"><img file="JP2012531969A_D0004.tif" /></tables></p><p> Example 4 PDS Plus size 3/0 in a common folder stored at -50 ° C Stability experiments were performed using PDS Plus® sutures of size 3/0 packaged in common folders. For each experiment, the finished product was stored at 50 ° C for up to 5 months. Samples were tested for triclosan content in sutures and compared to starting values. The results of these experiments are shown below and are shown graphically in FIG.<tables num="4"><img file="JP2012531969A_D0005.tif" /></tables></p><p> Example 5 PDS Plus size 1 in a relay tray stored at 25 ° C Stability experiments were performed using size 1 PDS Plus® sutures packaged in the types of relay trays shown in Figures 2-5. For each experiment, the finished product was stored at 25 ° C for up to 24 months. Samples were tested for triclosan content in sutures and compared to starting values. The results of these experiments are shown below and are shown graphically in FIG.<tables num="5"><img file="JP2012531969A_D0006.tif" /></tables></p><p> Example 6 PDS Plus size 3/0 in a relay tray stored at 25 ° C Stability experiments were performed using size 3/0 PDS Plus® sutures packaged in the types of relay trays shown in Figures 2-5. For each experiment, the finished product was stored at 25 ° C for up to 24 months. Samples were tested for triclosan content in sutures and compared to starting values. The results of these experiments are shown below and are shown graphically in FIG.<tables num="6"><img file="JP2012531969A_D0007.tif" /></tables></p><p> Example 7 PDS Plus size 1 in a relay tray stored at -50 ° C Stability experiments were performed using size 1 PDS Plus® sutures packaged in the types of relay trays shown in Figures 2-5. For each experiment, the finished product was stored at 50 ° C for up to 5 months. Samples were tested for triclosan content in sutures and compared to starting values. The results of these experiments are shown below and are shown graphically in FIG.<tables num="7"><img file="JP2012531969A_D0008.tif" /></tables></p><p> Example 8 PDS Plus size 3/0 in a relay tray stored at 50 ° C Stability experiments were performed using size 3/0 PDS Plus® sutures packaged in the types of relay trays shown in Figures 2-5. For each experiment, the finished product was stored at 50 ° C for up to 5 months. Samples were tested for triclosan content in sutures and compared to starting values. The results of these experiments are shown below and are shown graphically in FIG.<tables num="8"><img file="JP2012531969A_D0009.tif" /></tables></p><p> All patents, test procedures, and other documents referred to herein are by reference, including certificates of priority, as long as such disclosures are consistent and with respect to all laws permitting them to be incorporated. Fully incorporated.</p><p> Although exemplary embodiments disclosed herein are specifically described, various other variants are apparent and can be readily made by one of ordinary skill in the art without departing from the spirit and scope of the disclosure. Will be understood. Therefore, the scope of the accompanying "Claims" is not intended to be limited to the examples and the description described herein, and the "Claims" are areas to which this disclosure relates. It should be construed to include all the new patentable features present herein, including all features treated as equivalent to those skilled in the art.</p><p> When the lower limit of the numerical value and the upper limit of the numerical value are listed in the present specification, the range from the lower limit to the upper limit is considered.</p><p> A further aspect of the present invention As described, methods of extending the shelf life of packaged antibacterial medical devices are disclosed and claimed herein. In one embodiment, the adsorbent is provided by coating the adsorbent on at least a portion of one surface of the inner package. In another embodiment, the adsorbent is provided by placing the adsorbent substrate within the outer package. In another embodiment, the adsorbent substrate is formed by coating the substrate with an adsorbent. In yet another embodiment, the adsorbent substrate is formed of an adsorbent. In another embodiment, the inner package comprises a common envelope formed from a paperboard material having at least one surface coated with an adsorbent. In another embodiment, the adsorbent is from bentonite, activated carbon, activated alumina, silica gel, zeolite, superabsorbent polymers, wetting agents, polymer coatings, ground polymer coatings, natural products, non-paper substrates, and clays containing kaolin. Be selected. In another embodiment, the inner package comprises a containment compartment and an outer cover, the outer cover having one surface coated with an adsorbent. In another embodiment, the adsorbent is from bentonite, activated carbon, activated alumina, silica gel, zeolite, superabsorbent polymers, wetting agents, polymer coatings, ground polymer coatings, natural products, non-paper substrates, and clays containing kaolin. Be selected.</p><p> As described, packaged antibacterial sutures with improved shelf life are disclosed and claimed herein. In one embodiment, the packaged antibacterial suture exhibits an improved shelf life. In another embodiment, the adsorbent is provided by coating the adsorbent on at least a portion of one surface of the inner package. In another embodiment, the adsorbent is provided by placing the adsorbent substrate within the outer package. In another embodiment, the adsorbent substrate is formed by coating the substrate with an adsorbent. In yet another embodiment, the adsorbent substrate is formed of an adsorbent. In yet another embodiment, the antibacterial agent is selected from the group consisting of halogenated hydroxy ethers, acyloxydiphenyl ethers, and combinations thereof. In another embodiment, the inner package comprises a common envelope formed from a paperboard material having one surface coated with an adsorbent. In another embodiment, the adsorbent is from bentonite, activated carbon, activated alumina, silica gel, zeolite, superabsorbent polymers, wetting agents, polymer coatings, ground polymer coatings, natural products, non-paper substrates, and clays containing kaolin. Be selected. In another embodiment, the inner package comprises a containment compartment and an outer cover, the outer cover having one surface coated with an adsorbent. In another embodiment, the adsorbent is from bentonite, activated carbon, activated alumina, silica gel, zeolite, superabsorbent polymers, wetting agents, polymer coatings, ground polymer coatings, natural products, non-paper substrates, and clays containing kaolin. Be selected.</p><p>[Implementation mode] (1) A method of producing a packaged antibacterial suture with an improved shelf life. The process of providing an inner package with a source of antibacterial agent, A step of providing an adsorbent effective for adsorbing a part of the antibacterial agent over time, and A step of placing a suture in the inner package, wherein the suture comprises one or more surfaces. The process of covering the inner package with an outer package having an inner surface, Sufficient time and temperature to vapor transfer the suture, the inner package, and the inner surface of the outer package from the source of the antibacterial agent to the suture and the inner package in an effective amount of the antibacterial agent. And a step of substantially inhibiting bacterial colonization on the suture and the inner package under pressure conditions. A method in which the packaged antibacterial suture exhibits an improved shelf life. (2) The method for producing a packaged antibacterial suture according to the first embodiment, wherein the adsorbent is provided by coating the adsorbent on at least a part of one surface of the inner package. (3) The method for producing a packaged antibacterial suture according to Embodiment 1, wherein the adsorbent is provided by arranging an adsorbent substrate in the outer package. (4) The method for producing a packaged antibacterial suture according to the third embodiment, wherein the adsorbent base material is formed by coating the base material with an adsorbent. (5) The method for producing a packaged antibacterial suture according to the third embodiment, wherein the adsorbent base material is formed of an adsorbent. (6) The method for producing a packaged antibacterial suture according to any one of embodiments 1 to 5, wherein the suture disposed in the inner package is substantially free of antibacterial agents. (7) The method for producing a packaged antibacterial suture according to any one of embodiments 1 to 5, wherein the suture placed in the inner package is coated with an antibacterial agent. (8) The method for producing a packaged antibacterial suture according to any one of embodiments 1 to 7, wherein the antibacterial agent is selected from the group consisting of a halogenated hydroxy ether, an acyloxydiphenyl ether, and a combination thereof. (9) The packaged antibacterial suture according to any of embodiments 1-8, wherein the effective amount of the antibacterial agent transferred from the source of the antibacterial agent to the suture and the inner package is transferred during the ethylene oxide sterilization process. How to make a thread. (10) A step of subjecting the suture, the inner package, and the inner surface of the outer package to conditions sufficient to vapor transfer an effective amount of the antibacterial agent. The step of arranging the inner package and the outer package having the suture inside in the sterilization unit, and The step of heating the sterilization unit to the first temperature and The step of adjusting the pressure in the sterilization unit to the first pressure value and A step of injecting steam into the sterilization unit to expose the inner surface of the outer package, the inner package and the suture to steam for a first period. The step of adjusting the pressure in the sterilization unit to the second pressure value, and The process of introducing the chemical sterilizer into the sterilization unit and A step of maintaining the chemical sterilizer in the sterilization unit for a second period to incapacitate a sufficient amount of microorganisms. The step of removing residual water and the chemical sterilizing agent from the suture, and The method for producing a packaged antibacterial suture according to any one of embodiments 1 to 9, comprising drying the packaged antibacterial suture to a desired moisture level.</p><p>(11) The method for producing a packaged antibacterial suture according to embodiment 10, wherein the step of introducing a chemical sterilizing agent comprises introducing ethylene oxide gas into the sterilizing unit. (12) The packaged antibacterial suture according to any of embodiments 1-11, wherein the inner package comprises a common envelope formed from a paperboard material having at least one surface coated with an adsorbent. How to manufacture. (13) The adsorbent is selected from bentonite, activated carbon, activated alumina, silica gel, zeolite, superabsorbent polymer, wetting agent, polymer coating, ground polymer coating, natural products, non-paper substrate, and clay containing kaolin. The method for producing the packaged antibacterial suture according to the twelfth embodiment. (14) The packaged antibacterial suture according to any of embodiments 1-11, wherein the inner package comprises a containment compartment and an outer cover, the outer cover having one surface coated with an adsorbent. How to manufacture. (15) The adsorbent is selected from bentonite, activated carbon, activated alumina, silica gel, zeolites, superabsorbent polymers, wetting agents, polymer coatings, ground polymer coatings, natural products, non-paper substrates, and clays containing kaolin. The method for producing a packaged antibacterial suture according to aspect 14. (16) A method of extending the shelf life of packaged antibacterial medical devices. The process of providing an inner package with a source of antibacterial agent, A step of providing an adsorbent effective for adsorbing a part of the antibacterial agent over time, and A step of placing a medical device in the inner package, wherein the medical device comprises one or more surfaces. The process of covering the inner package with an outer package having an inner surface, Sufficient time and temperature to vapor transfer the medical device, the inner package, and the inner surface of the outer package to the medical device and the inner package in an effective amount from the source of the antibacterial agent. And a step of substantially inhibiting bacterial colonization on the medical device and the inner package under pressure conditions. A method by which the packaged antibacterial medical device exhibits an improved shelf life. (17) Extend the shelf life of the packaged antibacterial medical device according to embodiment 16, wherein the adsorbent is provided by coating the adsorbent on at least a portion of one surface of the inner package. Method. (18) The method of extending the shelf life of a packaged antibacterial medical device according to embodiment 16, wherein the adsorbent is provided by arranging an adsorbent substrate within the outer package. (19) A packaged antibacterial suture with improved shelf life. An inner package with a source of antibacterial agent and An adsorbent that is effective in adsorbing a part of the antibacterial agent over time, A suture that is placed within the inner package and comprises one or more surfaces. An outer package having an inner surface, the outer package having said inner package disposed inside, and the like. Sufficient time and temperature for the suture, the inner package, and the inner surface of the outer package to steam transfer an effective amount of the antibacterial agent from the source of the antibacterial agent to the suture and the inner package. And under pressure conditions, a packaged antibacterial suture that substantially inhibits bacterial colonization on the suture and the inner package. (20) Packaged medical equipment An inner package with a source of antibacterial agent and An adsorbent that is effective in adsorbing a part of the antibacterial agent over time, A medical device placed within the inner package, comprising one or more surfaces. An outer package having an inner surface, the outer package having said inner package disposed inside, and the like. Sufficient time and temperature for the medical device, the inner package, and the inner surface of the outer package to vapor transfer an effective amount of the antimicrobial agent from the source of the antimicrobial agent to the medical device and the inner package. And under pressure conditions, a packaged medical device that substantially inhibits bacterial colonization on the medical device and the inner package.</p>