TWI322001B - Antimicrobial packaged medical device and method of preparing same - Google Patents

Description

B7 Description of Invention (1) Inter-shareholding of the relevant application This patent application is filed in the US Patent No. 10/367,497 filed on February 15, 2003, which is the United States of the United States. Patent Application Serial No. 10/603,317, the entire disclosure of which is incorporated herein by reference in its entirety in its entirety in its entirety in the entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire all all all all all all all each BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to an antimicrobial medical device and a packaged medical device and a method of preparing the same. 10 Background of the Invention In the United States, patients undergo multiple surgical operations each year. According to the current data, the annual surgery is about 27,00 〇, 〇〇〇 times. All 2 cases The incidence of infection ("SSIs") after surgery or surgery is about 2 to 3 〇 /. The total number of SSIs that occur each year is more than 675,000 cases. 15 The occurrence of SSIs is usually associated with bacteria that are propagated on implantable surgical devices. During surgery, bacteria from the surrounding environment can enter the surgical site and attach to the medical device. In particular, bacteria can invade their surrounding tissues using implanted medical devices. The bacteria that are propagated on the medical device can cause infection and trauma to the patient. Therefore, SSIs will significantly increase the patient's 20 medical costs. Such a film or an implantable medical device containing an antimicrobial agent is disclosed and/or exemplified in the art. An embodiment of the device is disclosed in European Patent Application No. EP 0 761 243. Physical devices exemplified in the application include French Percuflex catheters. This catheter is impregnated with 24,4'_three gas_2'_ via basic paper ruler 1® with Chinese National Standard (CNS) A4 specification (210x297 public). V. Description of invention (2) Monophenyl ether [Ciba Gaki Irgasar^DP3〇〇)] and other additives in the coating solution. The catheter is then sterilized with ethylene oxide and stored for several days. The catheter coated with the liquid has an antimicrobial effect after storage for 30 days, i.e., when it is placed in the medium and attacked by microorganisms, a zone of inhibition can be produced. Sterilization temperatures, storage of coated catheters are technically not difficult. Implantable medical devices are mostly placed in the package prior to use in surgery after being manufactured and sterilized. During the surgical procedure, after disassembling the package containing the packaging member, the medical device is exposed to the environment of the operating room, and thus bacteria in the air may be introduced. Packaging and packaging components having antimicrobial properties substantially prevent bacterial contamination on the packaging and packaging components after unpacking. The antimicrobial-resistant packaging and packaging components substantially ensure the antimicrobial environment of the sterilized medical device upon combining antimicrobial properties on the medical device. SUMMARY OF THE INVENTION The present invention relates to an antimicrobial medical device and a packaged medical device printed by the Intellectual Property Office of the Ministry of Defense, and a method of preparing the same. According to a specific example of the invention, a medical device with or without one or more packaging members is placed in a package using an antimicrobial source and, under appropriate conditions, the antimicrobial agent can be delivered from the antimicrobial source to the package, Packaging components (if used) 20 and medical devices. The amount of antimicrobial agent delivered can be sufficient to inhibit the growth of the package, the packaging components (if used), and the bacteria on the medical device. ^ According to various embodiments of the present invention, the package may be combined with a source of corpse, which may be attached to the inner surface of the package or to the source of the antimicrobial agent in combination with one or more packaging members. -4- The paper size applies to the National Standard (CNS) A4 specification (210 X 297 public 1322001 A7 5. Invention description (3) In the package or in combination with the package itself. Or, the medical device is placed in the package, and Exposing the package with the medical device to an external source of anti-drug agent. In these embodiments, the medical device is placed in the package and may initially be free of antimicrobial agent or may initially contain one or more The surface of the antimicrobial agent. The time, temperature, and pressure of the packaging, antimicrobial source, and medical device are then sufficient to vaporize the antimicrobial agent source to deliver an effective amount of the antimicrobial agent to the inner surface of the packaging and medical device. It can substantially inhibit the proliferation of bacteria on medical devices. Ministry of Economic Affairs, Intellectual Property Bureau, employee consumption cooperation, du-printing*-- The invention also indicates a system A method of an antimicrobial medical device, the 10 steps comprising placing the source of the antimicrobial agent in a package having a medical device, attaching the source of the antimicrobial agent to the inner surface of the package having the medical device, or providing a source of antimicrobial agent, One or more packaging members have been incorporated into or combined with the packaging itself in a package having a medical device. In these embodiments, the medical device placed within the package may initially be free of antimicrobial agents or 15 may initially contain one or more a surface on which the antimicrobial agent is placed. The time, temperature, and pressure conditions of the package, antimicrobial source, and medical device are then sufficient to vaporize an effective amount of the antimicrobial agent from the antimicrobial source to the medical device, thereby The growth of bacteria on a medical device can be substantially inhibited. 20 BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a diagram illustrating the transfer of an antimicrobial agent from a medical device to a package member at a time function of 55 ° C. Details of a specific embodiment of the present invention Description The packaged anti-microbial equipment is based on the Chinese National Standard (CNS) A4. Grid (210x297 mm) 1322001 A7 B7 V. INSTRUCTIONS (4) The medical devices described herein generally refer to implantable medical devices and implants, including but not limited to single and multi-fiber configurations, surgical mesh Such as 疝 repair network, hernia plugs, hernia plugs (brachy seed Ministry of Economic Affairs Intellectual Property Bureau staff consumption cooperative printing * - spacer), suture clips, suture island nails, anti-dry screen and film And the sewing machine 5 folder. It also includes an absorbable and non-absorbable implantable medical device. An absorbable polymer is defined as a polymer that can be decomposed and absorbed by the body after exposure to a physiological environment for a period of time. Absorbable medical devices can generally be prepared by conventional methods including, but not limited to, glycolide, lactide, glycolic acid copolymers, or mixtures of polymers 10. Such as polydioxanone, polyhexanone, hemostatic oxidized cellulose and their equivalents. Preferably <polymer comprises a polyglycolic acid selected from greater than about 70%; polylactic acid greater than about 70%; poly(l,4-dioxo-2-one); greater than about 70% polypeptide; glycolic acid And a lactic acid copolymer; a polymeric material of greater than about 70% of the base of the cellulosic plastic and the cellulosic plastic derivative. A preferred absorbable medical device is made using a polydioxanone, a poliglecaprone, or a glycolic acid/lactic acid copolymer. Examples of absorbable medical devices include single and multi-fiber sutures. The multi-fiber construction includes stitches woven from a plurality of fibers. Examples of non-absorbable medical devices include single and multi-fiber sutures, surgical meshes such as hernia repair meshes, hernia plugs, close-range 20 seed spacers' which may be polymeric or non-polymeric. Non-absorbent medical devices may be prepared from all or part of a polymeric material, including but not limited to polycarbonates such as polyisopropene; polyamines such as nylon; chlorinated and/or fluorinated hydrocarbons such as Teflon (Teflon®) material; or polyester such as Daclon pacron® synthetic polyester; or made of non-polymeric materials, including but not limited to artificial paper scales, standard (CNS) A4 regulations ^ ~^21() x 297 1322001 A7 B7 V. INSTRUCTIONS (5) Silk, collagen, stainless steel, titanium, cobalt-chromium alloy, nidnol. A preferred non-absorbent medical device is made of nylon or polyisopropene.

Suitable antimicrobial agents can be selected from, but not limited to, functionalized hydroxy 5 ethers, acyloxydiphenyl ethers, or combinations thereof. In particular, the antimicrobial agent can be a halogenated 2-hydroxydiphenyl ether and/or a halogenated 2-decyloxydiphenyl ether as described in U.S. Patent No. 3,629,477, which is incorporated herein by reference:

In the above formula, Hal represents the same or different halogen atom, z represents hydrogen or a fluorenyl group, and w represents a positive integer of 1 to 5, and preferably each ring of the benzene ring may contain one or several low-burning A group which may be a dentate, a low alkoxy group, an allyl group, a monocyano group, an amine group, or a lower alkyl group. Preferably, the lower alkyl and lower alkoxy groups are substituted for the methyl or methoxy group in the phenyl ring, respectively. It is preferred to self-develop a lower alkyl group or a trifluorofluorene group. In practical applications, it has also been attempted to utilize a partially or fully hydrolyzed indole-indenyl derivative similar to the antimicrobial activity of the above formula. Particularly suitable esters are acetic acid, gas acetic acid, mercapto or dimercaptocarboxylic acid, and the paper size is applicable to China National Standard (CNS) A4 specification (210x297 mm) --------- ---

Ministry of Economic Affairs, Zhihui Property Bureau, Consumer and Pharmaceutical Co., Ltd. Printed 1322001 A7 B7 V. Inventions (6) 10 15 20 Formic acid, gas benzoic acid, methanesulfonic acid and gas methyl sulfonic acid. The specific preferred antimicrobial agent in the above formula is the 2,4,4'-tris-2'-hydroxydiphenyl ether known as Triclosan (manufactured by Ciba Giga Corporation under the trade name Irgasan DP300). Or Irgacare MP). Triclosan is a broad-spectrum antimicrobial agent for many products and is effective against many microorganisms commonly associated with SSIs. Such microorganisms include, but are not limited to, Staphylococcus, Staphylococcus epidermidis, Staphylococcus aureus, Staphylococcus epidermidis, Penicillin-resistant Staphylococcus aureus, and combinations thereof. The antimicrobial agent can be delivered to the medical device from an antimicrobial source placed or attached to the inner surface of the package. More specifically, when the source of the packaged antimicrobial agent and the medical device encounter changes in time, temperature, and pressure as described below, the antimicrobial agent can be delivered from the anti-microbial to the medical device. For example, the antimicrobial agent may be a source containing an antimicrobial __reservoir, containing an anti-microbial porphyrin, a steroid storage containing an antimicrobial agent, containing an antimicrobial __ or a reservoir, a microbial agent _ , or a source of microbial agents containing an antimicrobial agent can be fused with the package itself, that is, the resistance is set to be mounted, but not directly touched. When the source of the antimicrobial agent is placed on paper, the coffee may contain a package (four)-type package: in the reservoir, in addition, the medical device may optionally have an overlay thereon: in. Ά Α (η ΑΛ Λ 'Π: ίύί Membrane and/or optionally containing an antimicrobial agent placed on it from the source of the antimicrobial agent. 1322001 A7 B7 5. Inventive Note (7). For example, coating The coated composition of the antimicrobial agent on the surface of the medical device provides excellent results. Examples of medical devices and coated films can be found in U.S. Patent Nos. 4,201,216, 4,027,676, 4,105,034 '4,126,221 > 4,185,637 ' 3, 839, 297 ' 6, 260, 699 ' 5 5, 230, 424, 5, 555, 976, 5, 868, 244 and 5, 972, 008, the entire disclosure of which is incorporated herein by reference. a water-insoluble salt of a high fatty acid. As described in another embodiment, an absorbable coating composition for an absorbable medical device includes an alkylene moiety derived from 〇6 10 or 匕 to C1Z A poly(olefin oxide) of a mixture, which is coated with a solvent solution in a medical device as disclosed in U.S. Patent No. 4,105,034. The coating composition may include a polymer or copolymer as an adhesive, including Lactic acid and glycolic acid. The coating composition may also include calcium stearate as a lubricant, and an antimicrobial agent. The film may be applied to the device by a solvent-based coating 15 technique, for example , dipping coating, spray coating, or hanging drop coating, or any other coating method. Absorbable medical devices are extremely sensitive to moisture, that is, when the device is exposed to outside air or body moisture It is easy to decompose under the environment. It is well known to those skilled in the art that the medical device made of the absorbable poly 20 compound will cause deterioration of quality and loss of strength if it is exposed to water vapor before surgery. In contrast, the suture will quickly lose its desired tensile strength that can be maintained in the body after exposure to a humid environment for a period of time before use. Therefore, the absorbable medical device is preferably fully used. Sealed packaging. The fully sealed package described here means the Chinese National Standard (CNS) A4 specification (210χ 297 public) for the sterilizable -9-paper scale. 4. - Booking. 4 Ministry of Economics Intellectual Property Bureau employee consumption cooperative printed 丄W2001 A7

10 15 Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperatives Prints I- 20 and air-based packaging, that is, materials that can be avoided or substantially invaded by air. The packaging material of the absorbable medical device, for example, includes a single layer and a plurality of conventional metal foils, commonly referred to as heat sealable aluminum foil. These types of aluminum are disclosed in U.S. Patent No. 3,815,315, the disclosure of which is incorporated herein by reference in its entirety for the entire disclosure of the utility of the disclosure of the disclosure of the disclosure of the disclosure of the entire disclosure of the entire disclosure. The embodiment of the peelable film and the substrate is disclosed in U.S. Patent No. 5,623,810, the disclosure of which is incorporated herein by reference. A conventional non-metallic film may also be added to or substituted for the metal foil to form a package for an absorbable medical device. Such films are a polymer and may contain conventional polyenes, polyesters, acrylics, halogenated hydrocarbons, and the like, combinations and laminates thereof. These polymeric films can substantially inhibit the intrusion of moisture and oxygen, and can coat conventional coatings, for example, metal and metal oxide coatings that reduce gas intrusion. The package may comprise a combination of a polymer and a metal foil, particularly a multilayer polymer/metal foil mixture, such as ' a polyester/aluminum foil/ethyl acrylate laminate. Non-soluble medical devices can be packaged using any of the above materials. In addition, packaging for non-soluble medical devices is often made from materials that can be sterilized by sterilization, for example, medical grade porous paper, or a polymer that can penetrate moisture and air. Film or fiber, such as TYVEK® nonwoven fabric made from high density polyethylene fibers from DuPont. When the antimicrobial medical device requires a storage time of at least 6 months, preferably at least 1 year, and more preferably at least 2 years, the packaging material of the non-soluble medical device is preferably used for use with a soluble medical device. Packaging materials, such as complete -10- paper scale applicable to China National Standard (CNS) A4 specification (210 x 297 mm)

1322001 A7 Ministry of Economic Affairs Intellectual Property Bureau Employees Consumption Cooperative Printed 5, Invention Description (o Sealed packaging. The most common microorganism in the surgical infection site associated with the device is Staphylococcus. Staphylococcus aureus and Staphylococcus epidermidis are most common The patient's skin, therefore, the wound is susceptible to infection by the above bacteria. 2,4,4,- 5 Tris-2'-hydroxydiphenyl ether is the most effective antimicrobial against staphylococcus. This compound fights against golden yellow grapes. The minimum inhibitory concentration (MIC) of cocci is 0.01 ppm. It is in the appropriate medium according to the method described by Bhargava, H. et al., June 1986, 1982-218.

The measurements performed. The MIC 1 特定 of a particular antimicrobial against a particular microorganism is defined as the minimum concentration of antimicrobial agent that prevents growth of that particular microorganism in a suitable medium, thus making the medium unsuitable for growth of the microorganism, ie, the lowest concentration that inhibits growth of the microorganism . As used herein, 'a sufficient dose that substantially inhibits bacterial growth' and the 'effective dose' of an antimicrobial agent is defined as the minimum inhibitory wave of S. aureus or other bacteria of the same type. The susceptibility test of the method indicates the MIC. The filter paper tray or other object impregnated with the specific antimicrobial agent is placed on the agar medium inoculated with the test microorganism. The antimicrobial agent can start to diffuse in the medium, and the concentration of the antimicrobial agent is higher than the minimum inhibitory concentration. In the circumferential range of (MIC), the sensitive microorganism cannot grow. This distance is called the inhibition zone. It is assumed that the anti-20 microbial agent has a certain diffusion rate in the medium, and if the inhibition zone appears around the paper disk impregnated with the antimicrobial agent, Indicates that there is an antimicrobial agent in the area, otherwise the microorganisms can continue to grow. The diameter of the inhibition zone is inversely proportional to the MIC. Method for preparing an antimicrobial medical climbing system

1322001 A7 _ B7 V. INSTRUCTION DESCRIPTION (10) According to various methods of the present invention, a medical device can be directly exposed to an antimicrobial agent, i.e., an antimicrobial source can be placed in a package having a medical device. For example, the package may contain a source of antimicrobial agent that allows a source of antimicrobial agent to be attached to the inner surface of the package, or the source of antimicrobial agent in combination with one or more of the five packaging members can be placed in the package or combined with the package itself. . In these specific examples, the medical device is placed in a package and may initially be free of antimicrobial agents or may initially contain one or more surfaces having an antimicrobial agent disposed thereon. The time, temperature, and pressure of the package, antimicrobial source, and medical device are then sufficient to vaporize from the antimicrobial source and 10 deliver an effective amount of the antimicrobial agent to the medical device, thereby substantially inhibiting the bacteria on the medical device. Reproduction. In embodiments where the medical device is initially free of antimicrobial agents, the time, temperature, and pressure of the packaging, antimicrobial source, and medical device are sufficient to vaporize the antimicrobial agent to deliver an effective amount of the antimicrobial agent to 15 In the case of a medical device, the antimicrobial agent can be delivered from the source of the antimicrobial agent to the medical device. The Ministry of Economic Affairs, the Intellectual Property Office - I Co., Ltd., printed in the medical device initially containing one or more embodiments with an antimicrobial agent placed thereon, when the time, temperature and pressure conditions are sufficient to vaporize a portion of the transmission When the microbial agent is placed on the medical device and the antimicrobial agent in the source of the anti-microbial agent is delivered to the inner surface of the package, an effective amount of the antimicrobial agent can be maintained on the medical device, thereby substantially inhibiting the medical device Propagation of bacteria on the inner surface of the package. In this particular embodiment, the antimicrobial agent on the medical device can be maintained in a stable amount or concentration by the continued provision of the antimicrobial agent in the packaging environment. -12- This paper scale applies to Chinese national standard specifications (2丨0jc297 mm) A7 V. Invention description—or, medical device can be placed in the package, and the medical device can be directly exposed to (4) The source of the antimicrobial agent, ie the antimicrobial: the source of the sputum is placed outside the package containing the medical device. Specifically, the anti-micro 5 _ source and the package containing the medical device can vaporize the effective amount of the antimicrobial agent from the source of the antimicrobial agent according to the time, temperature and pressure, and the condition, so that the medical device can be substantially Suppresses fine propagation on medical devices. In this specific wealth, the packaging can be prepared from materials, such as porous materials or polymeric films that can be permeable to moisture and air, and the gasification anti-microfluidizer can be used to penetrate or transport gas into the package. Inside. For example, the package containing the medical device can be placed in a sealed environment. The sealing ring contains a source of antimicrobial agent or can be subsequently introduced into the sealed environment. The source of the antimicrobial agent can be any antimicrobial agent. Gasification type. The Department of Economic Intelligence's Intellectual Property Office Employees' Cooperatives prints the rate of gasification transfer from anti-microbial sources, such as three-gas to medical devices, to the processing, storage and delivery time of packaging and medical devices. , temperature and pressure conditions. For example, Figure 1 illustrates the amount of three gas that is transferred from the suture to the packaging member (in a sealed bottle at atmospheric pressure) after the temperature is maintained at 55 °C for a period of time. Effective Gasification Conditions for the delivery of antimicrobial agents such as dioxins include a sealed ambient atmosphere 20 at a temperature greater than 40. (:, takes about 4 to 8 hours. It also includes any combination of pressure and temperature that allows the partial pressure of the antimicrobial agent to be equal to or greater than the partial pressure of the above conditions, and with a period of sufficient antimicrobial resistance on the medical device. The amount of time during which the agent produces an effective amount or concentration, ie, the concentration above the minimum inhibitory concentration (MIC) against S. aureus. Specifically, the level of this paper is applicable to the Chinese National Standard (CNS) A4 specification (210x297). Public love 3----- 1322001 V. Invention description (12) A7 B7

It is conventional for those skilled in the art to reduce the temperature simultaneously to achieve the same effective partial pressure if the pressure is reduced. Alternatively, if the pressure is reduced while the temperature remains constant, the time required to produce an effective amount or concentration of the antimicrobial agent may be shorter. In general, the amount of antimicrobial agent within the antimicrobial source when exposed to an environment is at least the amount required to deliver an effective amount of the antimicrobial agent to the medical device.

Generally, a sterilized medical device can substantially kill microorganisms attached thereto. Specifically, sterilization in this field means maintaining a minimum sterile concentration of 1〇-6. Examples of sterilizing treatments are described in U.S. Patent Nos. 3, 815, 315, 3, 068, 864, 3, 767, 362, 5, 464, 580, 5, 228, PCT, and 5, 868, 244, each incorporated herein by reference. In particular, absorbable medical devices may be extremely sensitive to radiation and heat. Therefore, sterilization of such devices can be carried out using a general disinfecting gas or a disinfectant such as ethylene oxide gas. 15 Due to the time, temperature and pressure conditions in the sterilization process of ethylene oxide

The Department of Hydropower and Economics's Bureau of Employees and Consumers' Printing Co., Ltd. is printing enough to vaporize the antimicrobial agent from the antimicrobial source to the medical device. Therefore, the sterilization process of ethylene oxide is described below. However, the time, temperature, and pressure conditions sufficient to vaporize the antimicrobial agent from the antimicrobial source to the medical device may be singularly or by other types of sterilization treatments, and it is not limited to ethylene oxide alone. Detoxification treatment or general sterilization treatment. As mentioned above, the absorbable medical device is very sensitive to moisture and is therefore typically packaged in a completely sealed package such as (4) paper. However, Mina pig paper also prevents the entry of disinfectant gas. To solve this problem and in the epoxy -14-

--~ ” 1322001 A7 B7 V. INSTRUCTIONS (13) This aluminum foil is used in the gas sterilization process of ethylene, so it has been developed into a foil package that can be vented or previously described (for example, TYVEK polymer). Process. The venting holes are disposed at the end of the opening of the package and allow access to the interior of the package by air, water vapor, and epoxy. After the completion of the sterilization treatment, the package is sealed close to the vent hole to separate the vent hole from the sealed package, and the vent hole is cut or otherwise removed, so that a gas-tight sealed package can be prepared. Another type of inlaid foil package is a venting opening in a pouch-like package having a venting opening at the end of the package, wherein the venting opening is sealed to one side of the package to create a venting zone. After the sterilization is completed, the package is sealed close to the venting zone and the sealed package is then cut away from the venting zone. Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative Printing > - In a specific example, the source of antimicrobial agent is placed in the package, attached to the inner surface of the package, or the source of antimicrobial agent that will incorporate one or more packaging members Placed in the package or combined with the package itself. After the 15 surrounding seals and side seals are formed in the package, the packaged medical device is placed in a conventional ethylene glycol sterilization apparatus. If it is in an aluminum foil package, the source of the antimicrobial agent can be any of the above sources of antimicrobial agent or the source of the antimicrobial agent can be a venting port containing an antimicrobial agent. For example, an antimicrobial agent such as a trigastric 20 can be implanted on a Tyvek vent via a Tyvek sheet coated with ethyl acetate and a triclosan solution; the venting port loaded with the antimicrobial agent is fixed to a completely sealed The material is placed in the package; the medical device is placed in a completely sealed packaging material; the surrounding of the packaging material is sealed after placement in the medical device, and then air is allowed to enter the interior of the sealed packaging material via the venting opening; the packaging material has The venting hole loaded with the antimicrobial agent, -15- The paper size is applicable to the medium specification (210x297 public)--1322001 > A7 ----- B7 V. Invention description. 4) and bringing the medical device to a time, temperature and pressure condition sufficient to vaporize an effective amount of the antimicrobial agent from the venting port loaded with the antimicrobial agent to the medical device; sealing the packaging material containing the medical device and venting the venting hole Excluding; and removing the venting holes, thereby completing the preparation of the antimicrobial medical device 5. In another embodiment, the source of the antimicrobial agent can be placed together in a sterilization device or placed in other external devices having a package for the medical device. For example, the medical device can be placed in a package; the package with the medical device can be exposed to the entrance of the antimicrobial agent; and the source of the package 10 containing the medical device and the antimicrobial agent is sufficient to provide an effective amount of the antimicrobial agent from The source of antimicrobial agent is vaporized to the time, temperature, and pressure conditions of the medical device within the package, thereby 'substantially inhibiting the propagation of bacteria on the medical device. The package can be made from a sterilizing barrier material, such as a porous or polymeric film that is permeable to moisture and air, or a material that can form a completely sealed package. Printed by the Intellectual Property Office of the Ministry of Economic Affairs and the Consumer Cooperatives I- The internal temperature of the sterilization equipment can be heated to approximately 25 °C before the start of the cycle. The sterilization equipment is maintained at about 22 to 37 °C throughout the humidification and sterilization cycle. Next, the air in the sterilization apparatus is withdrawn to a vacuum of about 1.8 to 6.0 kpa. During the humidification cycle, steam is injected to provide a source of water vapor in the sterilized environment. The packaged medical device can be exposed to water vapor in the sterilization device for about 60 to 90 minutes. However, the sterilization time varies depending on the medical device to be sterilized. After the sterilization cycle of the humidification, a dry inert gas having a pressure of about 42 to 48 kPa, for example, nitrogen, may be introduced by pressure. Once the required -16-paper scale is achieved, the Chinese National Standard (CNS) A4 specification (210 X 297 mm) is applied. 5. Invention Description 15 Α7 Β7 10 15 Ministry of Economic Affairs Intellectual Property Bureau 'i Gongxiao-f Cooperative Printing After 20 cycles, pure ethylene oxide can be introduced into the sterilization equipment until the pressure reaches about 95 kPa. The ethylene oxide can be maintained for a period of time sufficient to effect the effect of the packaged medical device. For example, the surgical suture is maintained in the sterilizing device for a period of from about 360 to about 600 minutes. Other medical devices The required sterilization time will vary depending on the product and the type of packaging. In order to remove residual moisture and ethylene oxide from the packaged medical device, the ethylene oxide is withdrawn from the sterilization apparatus and maintained at a pressure of about 〇7 for about 15 to 300 minutes. The pressure in the sterilization unit can then be restored to atmospheric pressure. The following are the processing steps for the drying cycle. The packaged medical device can be dried by exposure to a plurality of dry nitrogen and vacuum cycles sufficient to effectively remove moisture and water vapor from the packaged device to a predetermined level. During these cycles, the packaged medical device can undergo a number of pressurization and depressurization processes at temperatures greater than room temperature. In particular, the sleeve temperature of the drying chamber can be maintained between 53 ° C and 57 ° C throughout the drying cycle. However, higher temperatures can also be utilized, for example, sutures can utilize about 65. (; to a temperature of 70 ° C, and depending on the medical device to be sterilized can use a higher temperature. The typical drying cycle steps include increasing the pressure of nitrogen to about 100 kPa, pumping the chamber pressure to about 100 to 240 minutes 〇 〇 7 kPa, re-introducing nitrogen to a pressure of 1 kPa and then circulating nitrogen for about 90 minutes, pumping the chamber pressure to about 〇·01 kPa in about 240 to 360 minutes and then maintaining the pressure at no more than 0.005 kPa. About 4 to 96 hours. At the end of the humidification, sterilization and drying cycle, which generally takes about 24 hours, the container containing dry nitrogen is returned to the external pressure. Once the drying is completed to the predetermined humidity, the package can be taken out from the drying chamber. -17-

This paper scale applies to the Chinese National Standard (CNS) A4 specification (210x297 male cage). 5. Invention Description (16) The installed medical m is stored in a storage area under humidity control. After completion of the sterilization procedure, the antimicrobial medical device, packaging, and/or packaging member having the antimicrobial agent can substantially effectively inhibit the proliferation of bacteria on or near the antimicrobial device, package, and/or packaging member. The following examples illustrate that an antimicrobial medical device containing an effective amount of an antimicrobial agent can be prepared which, after sterilization and packaging of the medical device, is used in a surgical procedure to maintain at least the effect when placed in a completely sealed package. 6 months, preferably 1 year and best 2 years. 10 Example 15 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed - 20 .27吋 long 5_〇 and dyed vkryl® suture (a type sold by Axon with 90% glycolic acid and 1编织% woven polyfilament suture of a copolymer of L-lactic acid, which was initially substantially free of antimicrobial agent and placed in a polypropylene suture tray, placed in a package having an antimicrobial source. In these embodiments, the wrapping member for covering about 0.45 grams of the medical special paper cover 'kraft paper', each having a weight of the suture tray, is coated by immersing the ethyl acetate containing 5% by weight of three breaths. In solution. Each paper cover was left in solution for about 5 seconds, then air dried at room temperature overnight and placed on a suture tray. Each paper cover contains 2 to 3% by weight of the total weight of the dry paper cover. Each suture assembly having a suture, a suture tray, and a three-weather paper cover is respectively placed in a bag of each of the tear-off aluminum foil packaging materials, that is, a composite coated with an aluminum acrylate foil, which has Tyvek® vents are placed at one end of the opening of the packaging material and allow access to the interior of the packaging material through air, water vapor and ethylene oxide. Then the suture -18- paper scale is applicable to the Chinese National Standard (CnS) a4 specification (210x297 Gongdong 1322001 A7 ______B7 V, invention description (η) ' component sterilization, which can easily suspend the assembly time, Temperature and pressure conditions - adjusted to vaporize an effective amount of antimicrobial agent from the antimicrobial source containing the three gas paper cover to the suture. After the sterilization process, seal the bag opening and exclude the venting holes The sealed package containing the suture assembly is removed from the package. The suture is then removed from the package for bacterial inhibition loop testing. The following table shows the data obtained from the bacterial inhibition loop test for sutures against Staphylococcus aureus. ATCC 6538; penicillin-resistant surface Staphylococcus aureus ATCC 51625 'E. coli ATCC 8739, pancomycin-resistant Enterococcus faecalis ATCC 700221, or Streptococcus agalactiae ATCC 624, allowing it to be cultured in pancreas at 10 37 °C The solution was grown for 24 hours in liquid (TSB). The culture medium was diluted with 0.85% sterile saline to produce an inoculum at a concentration of about 1000,000 cfu (colony forming unit) per ml. The suture was cut into 5 cm sections under the operation of the bacteria. The small sections were placed in a glass dish containing 0.1 ml of inoculum. The pancreatized soybean broth was poured into 15 flat pans, and the flat plate was cultured at 37 〇. 48 hours after C. The centrimetric distance of the inhibition zone was judged from the visual growth edge around the suture. Microbial η Minimum Southern Average Example 1 Staphylococcus aureus 8 15 19 16 Escherichia coli 8 6 9 7 11 = Determination of sample number economy Ministry of Intellectual Property Office Employees' Cooperatives Printed - 20 Example 2 In this example, the suture is PDS®II suture (19% sold by Aiscon). This paper scale applies to China National Standard (CNS). A4 specification (21〇X 297 public) 1322001 A7 B7 V. Invention description ( 〇 〇 单 单 单 ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) 以及 以及 以及 以及 以及 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸 纸The procedure was the same as in Example 1 except for the intragastric ethyl acetate solution. Microbial η Minimum highest average Example 2 Streptococcus agalactiae 3 0 4 2 Staphylococcus aureus 3 NCP NCP NCP Escherichia coli 3 11 20 15 5 NCP=Aseptic drop on the flat plate 3 In this example, the suture is a PROLENE® suture (an early silk polyacrylic suture sold by Axon) and the paper cover is coated by immersing 10% by weight of 10%. The procedure was the same as in Example 1 except for the raw ethyl acetate solution. Microbial η Minimum highest average Example 3 Streptococcus agalactiae 300 Staphylococcus aureus 3 17 20 18 Escherichia coli 3 0 6 2 Economy Ministry of Intellectual Property Bureau Staff Consumer Cooperatives Printing Examples 4 to 5 These examples were prepared by using three gases containing 1.1 〇/0 (Example 4) or 5.6% (Example 5) by weight. 15% by weight of copolymer of glycolic acid and lactic acid' and the rest of ethyl acetate as an antimicrobial agent-20- This paper scale applies to China National Standard (CNS) A4 specification (2丨0jc 297 mm) 1322001 Description of the Invention (19) In addition to the paper cover of the air, the rest of the preparation method and the embodiment (4) package 2: the inner solution of the above solution is placed in each of the removable inscriptions (4), which are respectively placed in each The suture assembly is then dried under temperature until overnight, so Example 4 Each bag has a gas content of 5 mg, while the three gas content of Example 5 is 25 mg. The suture assembly with a pair of wound sutures placed on the polypropylene barbed tray and the cover paper is placed in the bag. And then sterilized.

Staphylococcus epidermidis 6 6 Escherichia coli Enterococcus faecalis Streptococcus mutans Example Staphylococcus aureus Epidermidis Escherichia coli Enterococcus faecium 15 13 15 20 6 16 On 0 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed with No Keyococcus 10 Examples 4 and 5 show an effective method for preparing a product having inhibition of Staphylococcus aureus and Staphylococcus epidermidis using an antimicrobial container in an aluminum foil pouch. The following table shows the assembly using the twisted wire prepared in Example 5 -21- 1322001 A7 B7

Printed by the Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative I I. Invention description (2〇) Information obtained from the internal test. In particular, the needles of the sterilized suture were manually put through 10 raw chicken breasts to determine whether the three gas was removed. The data showed that the suture through the tissue still had significant inhibition when attacked by S. aureus and S. epidermidis. 5 Microbial test 1 Example 5a Staphylococcus aureus 15 Staphylococcus epidermidis 15 Escherichia coli 0 Examples 6-7 The preparation method of Example 6 was the same as that of Example 4 except that PDS®II was used as the suture. At the same time, the preparation method of Example 7 was the same as that of 10 Example 5. Microbial test 1 Test 2 Test 3 Example 6 Staphylococcus aureus 7 7 6 Staphylococcus epidermidis 7 6 6 Escherichia coli 0 0 0 Enterococcus faecalis 0 0 0 Streptococcus agalactiae 0 0 0 Example 7 Staphylococcus aureus 12 14 22 Epidermis Staphylococcus 14 18 18 Escherichia coli 3 1 1 Enterococcus faecalis 0 0 0 Streptococcus agalactiae 0 0 0 -22- This paper scale applies to China National Standard (CNS) A4 specification (2丨0 X 297 mm)

1322001 A7 B7 V. INSTRUCTIONS (21) Examples 6 and 7 show an effective method for preparing a product having an inhibitory action against Staphylococcus aureus and Staphylococcus epidermidis in an aluminum foil pouch using an antimicrobial container. The following table shows the data obtained by performing the intra-tissue test using the suture prepared in Example 7. In particular, the needles 5 of the sterilized suture are manually put on. The pig's breast is passed through 1 〇 to determine whether or not the triclosan is removed. The data showed that the suture through the tissue still had significant inhibition when attacked by S. aureus and S. epidermidis. Microbial test 1 Example 7a Staphylococcus aureus 13 Staphylococcus epidermidis 15 Escherichia coli 5 10 Paste Example 8~10 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperation Du printing. In addition to the use of size 5-0 and dyed Vicryl® Plus seam Thread (a woven multifilament anti-microbial suture containing a copolymer of 90% glycolic acid and 10% L-lactic acid sold by Axon, a copolymer of glycolic acid and lactic acid and hard These examples are the same as in Example 1 except that the coating mixture consisting of calcium humate and ethyl acetate contains three 15 gas groups. The coating mixture of Example 8 had 1.0% by weight of trisomies according to the total weight of the coating mixture; Example 9 had 2.0%; and Example 1 had 3.0%. Microbial η Minimum 13⁄4 Average Example 8 Staphylococcus aureus 8 16 19 18 E. coli 8 7 9 8 -23- This paper scale applies to Chinese National Standard (CNS) A4 specification (210x297 mm) 1322001 A7 B7 V. Description of invention ( 22) Example 9 Staphylococcus aureus 8 15 21 18 Escherichia coli 8 7 9 8 Example 10 Staphylococcus aureus 8 15 20 17 Escherichia coli 8 7 10 8 眚 Examples 11 to 12 These examples except for the use size 2-0 The coating mixture contained 2% by weight of triclosan and the dyed Vicryl® Plus suture, and the remainder was the same as in Examples 5 to 5. Microbial test 1 Test 2 Test 3 Example 11 Staphylococcus aureus 17 14 14 Staphylococcus epidermidis 15 15 15 Escherichia coli 1 1 0 Enterococcus faecalis 0 0 0 Streptococcus agalactiae 0 0 0 Example 12 Golden grape ball 喆 >25 25 20 Staphylococcus epidermidis >25 >25 20 Escherichia coli 4 4 6 Enterococcus faecalis 0 0 0 Streptococcus agalactiae 0 0 0 Ministry of Economic Affairs Intellectual Property Bureau 'Employees' Cooperatives Printed Example 13 These examples except the size of use The 2-0 dyed Vicryl® suture was the same as Example 1 except that the antimicrobial source was 10 and the Tyvek® breathable sheet was used. The Tyvek® breathable sheet is manually coated with 2% by weight of trisodium acetate. Each with suture, polypropylene suture tray and paper cover-24- This paper scale is applicable to China National Standard (CNS) A4 specification (210x297 mm) 1322001 ' A7 B7 V. Inventive Note (23) i Suture assembly They are placed in pockets respectively, which have a three-gas Tyvek® breathable sheet that is attached to the open end of the package to allow air, water vapor and ethylene oxide to enter the bag of packaging material. Sterilize the suture assembly. After the sterilization process is completed, the bag opening is sealed and the venting holes are excluded from the sealed package of the inner suture group 5. The suture was then taken out of the package for the inhibition loop test of the bacteria. Three samples were selected from each suture; all samples showed significant inhibition when challenged with Staphylococcus aureus and Staphylococcus epidermidis.

Printed by the Consumer Intellectual Property Office of the Ministry of Economic Affairs *I This paper scale applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm)

Claims (1)

I3ps Ministry of Economic Affairs Intellectual Property Bureau staff's consumption. Cooperatives printed A8 B8 C8 D8 R〇m„1fp§n^〇279421192lt.9 ROC Patent Applr No 1J line of “Gas Patent Poverty Every Amended Claims in C (^ a QS a Chinese 2) Chinese i submitted) VI. Patent application range February 25 __ . i.iuomiitea on February zd, 5 10 2. 15 20 25 An anti-microbial suture prepared according to the following steps: Place a seam The line and an antimicrobial agent are derived from a package selected from the group consisting of halogenated hydroxy ethers, decyloxydiphenyl hydrazines, and combinations thereof; and the time, temperature and time of packaging, suture, and antimicrobial source The pressure conditions are sufficient to vaporize the effective microbial agent from the antimicrobial source to the suture and thus substantially inhibit = multiplication. An antimicrobial suture assembly having a suture and at least a component prepared in accordance with the following steps: ^ placing a suture assembly and an anti-microbial sword derived from the inclusion of the antimicrobial agent selected from the group consisting of hydroxyl-containing hydroxyl groups, μ^w, ^-oxyl-diphenyl ether, and combinations thereof; The packaging, suture assembly and antimicrobial source, field and pressure conditions are sufficient to vaporize the antimicrobial agent from the antimicrobial source to the suture, thus allowing for the propagation of the L 1 A々S component. Inhibition of bacteria in suture-species according to the following steps: the preparation of a medical device and / t placing a medical device and - the antimicrobial agent is derived from the surface-containing package - the anti-micro is selected from the inclusion of self-chemical Epoxy 2, and combinations thereof; and 4 make the packaging, the source of the antimicrobial agent and the doctor: the time door, field and pressure conditions of the bottom 1 sound device are sufficient to get from the antimicrobial agent传送 传送 Η 26 本 26 - This paper scale applies to the national standard (CNS) A4 specification (210x297 public) 92510- 接1322001 A8 B8 C8 D8 VI. Surface and medical device, thereby substantially inhibiting the proliferation of bacteria on the inner surface of the package and on the medical device. 4. A packaged medical device according to claim 3, wherein the source of the antimicrobial agent is an anti-micro 5. A container for a biological agent. 5. The packaged medical device of claim 3, wherein the source of the antimicrobial agent is placed in a package. 6. The packaged medical device of claim 3, wherein The source of the antimicrobial agent is placed on the inner surface of the package. 7. The packaged medical device of claim 3, wherein the source of the anti-10 microbial agent can be combined with one or more packaging members or packages within the package. 8. The packaged medical device of claim 3, wherein the medical device comprises one or more surfaces having an antimicrobial agent disposed thereon, the antimicrobial agent being selected from the group consisting of halogenated hydroxy ethers, helium oxygen Diphenyl 15-ether, and combinations thereof; and when the packaging, the source of the antimicrobial agent, and the Intellectual Property Manager of the Ministry of Health and Economy C consume the cold-worker printing device under the time, temperature and pressure conditions, a portion is placed on the medical device The antimicrobial agent and the antimicrobial agent in the source of the antimicrobial agent are vaporized and delivered to the inner surface of the package while maintaining an effective amount of the antimicrobial agent on the medical device, thereby substantially inhibiting the bacteria on the inner surface 20 of the package and the medical device. Breeding. 9. A method of preparing an antimicrobial suture, the method comprising: placing a suture and an antimicrobial agent derived from a package selected from the group consisting of a toothed hydroxy ether, a decyl diphenyl ether, and Combinations; and -27 - This paper scale applies to National Standards (CNS) A4 (210x297 mm) AB c D 1322001 VI. Patent coverage for time, temperature and pressure of packaging, suture and antimicrobial sources The conditions are sufficient to vaporize an effective amount of the antimicrobial agent from the antimicrobial source to the suture, thereby substantially inhibiting bacterial growth on the suture. 5. 10. The method of claim 9, wherein an effective amount of the antimicrobial agent is vaporized from the antimicrobial source to the inner surface of the package, thereby substantially inhibiting the propagation of the bacteria on the package. 11. A method of preparing an antimicrobial medical device, the method comprising: placing a medical device and an antimicrobial agent in a package comprising an inner surface of the inner surface, the antimicrobial agent being selected from the group consisting of a halogenated hydroxy ether, a decyl diphenyl ether, and a combination thereof; and a time, temperature, and pressure condition for the package, antimicrobial source, and medical device sufficient to vaporize an effective amount of the antimicrobial agent from the antimicrobial source to the medical device Thus, the proliferation of bacteria on 15 medical devices can be substantially inhibited. 12. The method of claim 11, wherein an effective amount of the antimicrobial agent is vaporized from the antimicrobial source to the inner surface of the package, thereby substantially inhibiting the propagation of the bacteria on the package. Printed by the Intellectual Property Office of the Ministry of Economic Affairs. 13. For the method of claim 12, the source of the antimicrobial agent 20 is a container containing an antimicrobial agent. 14. The method of claim 12, wherein the source of the antimicrobial agent is placed in a package. 15. The method of claim 12, wherein the source of the antimicrobial agent is placed on the inner surface of the package. -28 - This paper scale applies to China National Standard (CNS) A4 specification (210x297 mm). VI. Patent application scope 16. The method of claim 12, wherein the source of the antimicrobial agent can be combined with one of the packages. Or a plurality of packaging members or the packaging. 17. A method of preparing an antimicrobial medical device, the method comprising: exposing the medical device to an antimicrobial source; and 5 equating the time, temperature, and pressure conditions of the medical device and the antimicrobial agent from the source of the antimicrobial agent Gasification delivers an effective amount of the antimicrobial agent to the medical device, thereby substantially inhibiting the rarity of the bacteria on the medical device. 18. The method of claim 17, wherein the time, temperature, and pressure conditions sufficient to vaporize an effective amount of the antimicrobial agent from the antimicrobial 10 agent source to the medical device are sufficient to equal the partial pressure to the antimicrobial agent Or greater than the pressure and temperature at 40 ° C and atmospheric pressure, and a period of time from 4 to 8 hours. 19. A packaged antimicrobial medical device having an antimicrobial agent at least for 6 months after sterilization and packaging 15, and at least 6 months prior to disassembly and use in surgery, wherein the medical device is placed in a package Within and under sufficient conditions, an effective amount of the antimicrobial agent is vaporized and delivered to the inner surface of the package and the medical device. -29 - This paper size applies to China National Standard (CNS) A4 specification (210x297 mm)