System and method for sterilizing iodine phore compositions

Abstract

Systems and methods for sterilizing iodophor compositions are described. In some cases, the iodophor compositions include a complex comprising iodine and a polymer (i.e., an iodine-polymer complex). The iodine-polymer complex can be polyvinylpyrrolidone iodine (also known as "povidone-iodine" or "PVP-I") or iodine povacrilex. Methods are described in which an initial iodophor composition is heated to produce a sterile iodophor composition. The resulting sterile iodophor composition has a relatively high sterility assurance (e.g., 10 -3 Below, 10 -6 The initial iodophor composition may have a sterility assurance level below 100°C (i.e., a sterilization temperature of 100°C or less). In some cases, heating the initial iodophor composition includes exposing at least a portion of a container containing the initial iodophor composition to a heated liquid. In certain cases, the heated liquid is part of a moving liquid stream (e.g., a cascading waterfall stream produced by a cascading waterfall sterilizer). According to some embodiments, it has surprisingly been found that heating the initial iodophor composition to a relatively low maximum temperature (i.e., "sterilization temperature") while maintaining the sterilization temperature for a relatively short amount of time (i.e., "sterilization time") can still result in a relatively high sterility assurance using certain methods described herein. As a result, the sterilization systems and methods described herein can advantageously preserve certain positive attributes of the initial iodophor composition (e.g., potency, pH, viscosity).

Description

[Technical Field]

[0001] Technical field Generally, systems and methods for sterilizing iodine phore compositions are provided. [Background technology]

[0002] background Sterilization of preservative compositions containing iodine phore compositions may be beneficial in reducing and / or preventing infection. However, known sterilization methods for preservative compositions, such as exposure to gamma rays, may have adverse effects on iodine phore compositions. Therefore, improved systems and methods for sterilizing iodine phore compositions are needed. [Overview of the project] [Means for solving the problem]

[0003] overview Generally, systems and methods for sterilizing iodine compositions are provided. The subject matter disclosed herein may, in some cases, involve interrelated products, alternative solutions to specific problems, and / or multiple different uses of one or more systems and / or articles.

[0004] In some embodiments, sterile iodine compositions are provided. In some embodiments, the sterile iodine composition is sterilized by a method comprising heating an initial iodine composition to produce a sterile iodine composition. In certain embodiments, the sterile iodine composition is 10 -3 It has the following sterility assurance levels.

[0005] In some embodiments, sterile iodophore compositions are provided. In some embodiments, the sterile iodophore composition contains at least 5.0% by weight of povidone-iodine. In certain embodiments, the sterile iodophore composition contains 10 -3 The following levels of sterility assurance are provided. In certain embodiments, the sterile iodophore composition has a viscosity of 3000 cP or less.

[0006] In some embodiments, a sterilization method is provided. In some embodiments, the sterilization method involves heating the initial iodophore composition to 10 -3 This involves producing a sterile iodophore composition having the following levels of sterility assurance.

[0007] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention, in conjunction with the accompanying drawings. In the event that this specification and the documents incorporated by reference contain conflicting and / or contradictory disclosures, this specification shall prevail.

[0008] Brief explanation of the drawing Non-limiting embodiments of the present invention will be described with reference to the accompanying drawings as examples, but these are schematic and not intended to be drawn to actual size. In the drawings, each identical or nearly identical component illustrated is typically represented by a single number. For clarity, not all components are shown in every drawing, and not all components of each embodiment of the present invention are shown where an illustration is not necessary to enable the understanding of the invention by those skilled in the art. [Brief explanation of the drawing]

[0009] [Figure 1A] This is a schematic diagram of an exemplary sterilization system, including a sterilization unit, according to several embodiments. [Figure 1B] This is a schematic diagram of an exemplary sterilization system, including a cascading water sterilizer, according to several embodiments. [Figure 1C] This is a schematic diagram of an exemplary sterilization system, including a cascading water sterilizer and a heater, according to several embodiments. [Figure 2] This is a schematic diagram of an exemplary sterilization system, according to several embodiments, which includes two sterilization units, two heaters, a chiller, a chiller pump reservoir, a deionized water pump reservoir, and two drying units. [Figure 3A]This is a time-series graph of the percentage of available iodine for six povidone-iodine preparations sterilized at 110°C. [Figure 3B] This is a time-series graph of the percentage of available iodine for six povidone-iodine preparations sterilized at 115°C. [Modes for carrying out the invention]

[0010] Detailed explanation Systems and methods for sterilizing iodine phore compositions are described. In some cases, the iodine phore composition comprises a complex containing iodine and a polymer (i.e., an iodine-polymer complex). The iodine-polymer complex may be polyvinylpyrrolidone iodine (also called "povidone-iodine" or "PVP-I") or iodine povacrilex. A method for producing a sterile iodine phore composition by heating an initial iodine phore composition is described. The resulting sterile iodine phore composition provides a relatively high guarantee of sterility (e.g., 10°C). -3 The following 10 -6 The following levels of sterility assurance may be achieved. In some cases, heating the initial iodole composition involves exposing at least a portion of the container containing the initial iodole composition to the heating liquid. In certain cases, the heating liquid is part of a moving liquid stream (e.g., a cascading waterfall stream produced by a cascading waterfall sterilizer). According to some embodiments, it has been found that, surprisingly, heating the initial iodole composition to a relatively low maximum temperature (i.e., "sterilization temperature") while maintaining the sterilization temperature for a relatively short time (i.e., "sterilization time") still results in a relatively high level of sterility assurance using the specific methods described herein. As a result, the sterilization systems and methods described herein can favorably preserve certain positive attributes of the initial iodole composition (e.g., potency, pH, viscosity).

[0011] Iodophore compositions typically refer to compositions comprising iodine-containing complexes dissolved or suspended in a liquid solvent (e.g., water and / or alcohol) or other fluid carrier (including, but not limited to, creams, ointments, or gels (e.g., hydrogels)). In some cases, the iodine-containing complex is a complex comprising iodine and a polymer (i.e., an iodine-polymer complex). Non-limiting examples of suitable polymers include homopolymers and copolymers comprising vinylpyrrolidone and / or acrylates (e.g., methyl methacrylate, isooctyl acrylate). In certain embodiments, the iodophore composition comprises povidone-iodine. Povidone-iodine is a complex comprising polyvinylpyrrolidone (also called "povidone" or "PVP") and iodine. Povidone-iodine has the following chemical structure: [ka] (In the formula, m and n represent the number of repeating units of each directional structure in the entire polymer.) It generally has the following characteristics. In certain embodiments, the iodophore composition comprises iodine povacrilex. Iodine povacrilex is the active ingredient in 3M's DuraPrep® formulation (a solution of iodine povacrilex and isopropyl alcohol available from 3M Company in St. Paul, Minn.). Povacrilex is an acrylate copolymer. In certain embodiments, the iodophore composition comprises a complex containing iodine (e.g., diiodine, sodium iodide) and poly(methyl methacrylate-co-N-vinylpyrrolidone-co-isooctyl acrylate). In some such embodiments, the iodine-polymer complex has the following chemical structure: [ka] (In the formula, n1, n2, n3, and x represent the number of repeating units of each directional structure in the entire polymer.) It has.

[0012] In some cases, iodone compositions have antiseptic properties. In certain cases, antiseptic iodone compositions may be applied topically to one or more locations on a patient (e.g., human or animal) to reduce, treat and / or prevent infection (e.g., by reducing microbial load). In some cases, iodone compositions may be applied to the intact skin of a patient. In some cases, iodone compositions may be applied to and / or near surgical incisions, wounds, ulcers, cuts, abrasions and / or burns. In certain cases, iodone compositions may be used as preoperative disinfectants (i.e., to disinfect the surgical site before surgery), surgical cleansers and / or general disinfectants. In some cases, iodone compositions may be applied using a dispenser configured for topical application to a patient. The iodone compositions described herein may be formulated as solutions, suspensions, emulsions, gels, creams and / or ointments.

[0013] While we do not wish to be constrained by any particular theory, the mode of action of the preservative effect of iodophore compositions is thought to involve the release of iodine (e.g., as iodine or triiodide) from the iodine-containing complex contained in the iodophore composition. In certain embodiments, iodophore compositions containing povidone-iodine and / or iodine povacrilex provide a preservative effect by releasing iodine (e.g., as iodine or triiodide) over time. Iodine is generally considered to be an active antimicrobial agent capable of killing various types of microorganisms (e.g., bacteria, viruses, fungi, protozoa). For example, iodine can kill microorganisms and / or reduce or inhibit their growth. In certain cases, iodine can kill transient and / or resident skin flora.

[0014] In some cases, it may be necessary, advantageous, or desirable to provide an iodine composition in a sterile form. For example, certain iodine compositions themselves may have the ability to promote the growth of certain microorganisms or to rapidly kill them. In some cases, a relatively large number of microorganisms may be present in the iodine composition. Sterilization of such iodine compositions may be advantageous in reducing and / or preventing the introduction of harmful microorganisms to the patient site to which the iodine composition is applied. This may be particularly beneficial when the iodine composition is applied to and / or near surgical incisions, wounds, ulcers, cuts, abrasions, and / or burns, so that the patient does not become infected with any microorganisms that may be present in the iodine composition.

[0015] However, many conventional sterilization methods can adversely affect the efficacy and / or certain other beneficial properties of iodine compositions. For example, sterilization using gamma radiation exposure can induce the decomposition and / or gelation of povidone-iodine, potentially destroying or reducing its efficacy. In addition, it is recognized that prolonged heating and / or heating of iodine compositions at high temperatures can cause substantial decomposition of the iodine compositions. For example, prolonged heating of iodine compositions, particularly at high temperatures, can alter the pH, viscosity, color, solubility, and / or available iodine concentration of the iodine composition to a degree sufficient to reduce its efficacy, increase the difficulty of applying the iodine composition to patients, and / or reduce its safety. For these reasons, thermal sterilization is typically not used for iodine compositions formulated as preservatives.

[0016] Surprisingly, the inventors have determined that, in relation to the compositions and methods described herein, iodine phore compositions can be effectively sterilized by heating them to a relatively low sterilization temperature over a relatively short sterilization time. According to the specific sterilization systems and methods described herein, heating the iodine phore composition to a relatively low sterilization temperature over a relatively short sterilization time provides a relatively high guarantee of sterility (e.g., 10 -3 The following 10 -6 The following levels of sterility assurance can be achieved. In some cases, sterilization of iodine phore compositions by the sterilization systems and methods described herein can also reduce or minimize adverse effects on the positive attributes of the iodine phore composition (including, but not limited to, pH, viscosity, appearance, solubility, and available iodine concentration that may result from heat treatment).

[0017] Figure 1A illustrates a schematic diagram of an exemplary system for sterilizing an iodine phore composition. As shown in Figure 1A, the sterilization system 100 includes a sterilization unit 102. The sterilization unit 102 may include any device configured to heat the object. In some embodiments, the sterilization unit 102 is configured to perform moist heat sterilization. Examples of preferred sterilization units, but are not limited to, include cascading water sterilizers and autoclaves. In certain preferred embodiments, the sterilization unit 102 is a cascading water sterilizer. A non-limiting example of a preferred cascading water sterilizer is the SWS sterilizer, model number SWS-14.12.26, manufactured by Bosch Packaging Technology.

[0018] During operation, the sterilization unit 102 receives the initial iodole composition 104. The sterilization unit 102 then heats the initial iodole composition 104 to a sterilization temperature over a sterilization time period. "Sterilization temperature" means the temperature or temperature range that the iodole composition reaches and maintains over the sterilization time period. "Sterilization time" or "sterilization time period" means the length of time that the iodole composition is heated to the sterilization temperature. The sterilization temperature is set to the highest temperature that the iodole composition can reach over the sterilization time period. Exposure of the initial iodole composition 104 to the sterilization temperature ends when the sterilization time period has elapsed. In some embodiments, the initial iodole composition 104 is heated in the sterilization unit 102 to a relatively low sterilization temperature over a relatively short sterilization time period. By heating the initial iodole composition 104 to the sterilization temperature over the sterilization time period, a sterilized iodole composition 106 is produced.

[0019] In some embodiments, the initial iodine phore composition is heated to a relatively low sterilization temperature. In certain embodiments, the sterilization temperature of the iodine phore composition is 121°C or lower, 115°C or lower, 110°C or lower, 100°C or lower, 95°C or lower, 90°C or lower, 85°C or lower, 80°C or lower, 75°C or lower, 70°C or lower, or 65°C or lower. In certain embodiments, the sterilization temperature is 65°C to 85°C, 65°C to 100°C, 65°C to 110°C, 65°C to 115°C, 65°C to 121°C, 75°C to 85°C, 75°C to 100°C, 75°C to 110°C, 75°C to 115°C, 75°C to 121°C, 85°C to 100°C, 85°C to 110°C, 85°C to 115°C, 85°C to The ranges are 121°C, 90°C-100°C, 90°C-110°C, 90°C-115°C, 90°C-121°C, 95°C-110°C, 95°C-115°C, 95°C-121°C, 100°C-110°C, 100°C-115°C, 100°C-121°C, 110°C-115°C, 110°C-121°C, or 115°C-121°C. The sterilization temperature of the iodine phore composition can be measured by any method known in the art. In some cases, the temperature of the iodine phore composition may not be directly measurable (for example, in certain embodiments where the iodine phore composition is contained in a sealed ampoule, it may be difficult or inconvenient to directly measure the temperature), but it can be determined or estimated based on an appropriate correlation between the measured temperature of the fluid heating the container containing the iodine phore composition and the heating fluid temperature, and the exposure time of the iodine phore composition in the container to that temperature. Those skilled in the art know how to determine such correlations experimentally and / or theoretically. For example, it is possible to provide a temperature measuring device for measuring the temperature of recirculating water in a sterilization unit. In some such cases, experimental and / or standard heat transfer calculations are performed in advance to establish a correlation between the temperature of the iodophore composition in the container being processed (e.g., an ampoule) of the sterilization unit and the temperature of the recirculating water as a function of exposure time. In particular cases, conditions and / or containers are selected so that the temperature of the iodophore composition in the container equilibrates and rapidly becomes approximately equal to the temperature of the recirculating water in the sterilization unit in order to minimize processing time.In some cases, for each sample or reference of the iodophore composition being processed, the temperature of the iodophore composition can be measured directly, for example, by a temperature measuring device at least partially immersed in the iodophore composition during the stabilization stage.

[0020] In some embodiments, the initial iodine phore composition is heated to the sterilization temperature over a relatively short sterilization time interval. As described above, “sterilization time” or “sterilization time interval” means the length of time the iodine phore composition is heated to the sterilization temperature. The “sterilization time interval” does not include the time required for the iodine phore composition to rise from the starting temperature to the sterilization temperature (i.e., does not include the “ramp-up” time). The “sterilization time interval” also does not include the time required for the iodine phore composition to return from the sterilization temperature to the starting temperature (i.e., does not include the “cooling” time). In some embodiments, the sterilization time interval is 20 minutes or less, 15 minutes or less, 12 minutes or less, 10 minutes or less, 6 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, 1.5 minutes or less, or 1 minute or less. In some embodiments, the sterilization time ranges from 1 to 3 minutes, 1 to 6 minutes, 1 to 10 minutes, 1 to 12 minutes, 1 to 15 minutes, 1 to 20 minutes, 1.5 to 3 minutes, 1.5 to 6 minutes, 1.5 to 10 minutes, 1.5 to 12 minutes, 1.5 to 15 minutes, 1.5 to 20 minutes, 3 to 6 minutes, 3 to 10 minutes, 3 to 12 minutes, 3 to 15 minutes, 3 to 20 minutes, 6 to 10 minutes, 6 to 12 minutes, 6 to 15 minutes, 6 to 20 minutes, 10 to 12 minutes, 10 to 15 minutes, 10 to 20 minutes, 12 to 15 minutes, 12 to 20 minutes, or 15 to 20 minutes.

[0021] In some embodiments, the sterilization temperature is relatively low, and the sterilization time is relatively short. In specific cases, the sterilization temperature is 65°C to 85°C, 65°C to 100°C, 65°C to 110°C, 65°C to 115°C, 65°C to 121°C, 75°C to 85°C, 75°C to 100°C, 75°C to 110°C, 75°C to 115°C, 75°C to 121°C, 85°C to 100°C, 85°C to 110°C, 85°C to 115°C, 85°C to 121°C. The range is ℃, 90℃~100℃, 90℃~110℃, 90℃~115℃, 90℃~121℃, 95℃~110℃, 95℃~115℃, 95℃~121℃, 100℃~110℃, 100℃~115℃, 100℃~121℃, 110℃~115℃, 110℃~121℃ or 115℃~121℃, and extinguishing The bacterial exposure time ranges from 1 to 3 minutes, 1 to 6 minutes, 1 to 10 minutes, 1 to 12 minutes, 1 to 15 minutes, 1 to 20 minutes, 1.5 to 3 minutes, 1.5 to 6 minutes, 1.5 to 10 minutes, 1.5 to 12 minutes, 1.5 to 15 minutes, 1.5 to 20 minutes, 3 to 6 minutes, 3 to 10 minutes, 3 to 12 minutes, 3 to 15 minutes, 3 to 20 minutes, 6 to 10 minutes, 6 to 12 minutes, 6 to 15 minutes, 6 to 20 minutes, 10 to 12 minutes, 10 to 15 minutes, 10 to 20 minutes, 12 to 15 minutes, 12 to 20 minutes, or 15 to 20 minutes.

[0022] In specific cases, the sterilization temperature is approximately 95°C, and the sterilization time ranges are 1-3 minutes, 1-6 minutes, 1-10 minutes, 1-12 minutes, 1-15 minutes, 1-20 minutes, 1.5-3 minutes, 1.5-6 minutes, 1.5-10 minutes, 1.5-12 minutes, 1.5-15 minutes, 1.5-20 minutes, 3-6 minutes, 3-10 minutes, 3-12 minutes, 3-15 minutes, 3-20 minutes, 6-10 minutes, 6-12 minutes, 6-15 minutes, 6-20 minutes, 10-12 minutes, 10-15 minutes, 10-20 minutes, 12-15 minutes, 12-20 minutes, or 15-20 minutes. In specific cases, the sterilization temperature is approximately 100°C, and the sterilization time ranges are in the range of 1-3 minutes, 1-6 minutes, 1-10 minutes, 1-12 minutes, 1-15 minutes, 1-20 minutes, 1.5-3 minutes, 1.5-6 minutes, 1.5-10 minutes, 1.5-12 minutes, 1.5-15 minutes, 1.5-20 minutes, 3-6 minutes, 3-10 minutes, 3-12 minutes, 3-15 minutes, 3-20 minutes, 6-10 minutes, 6-12 minutes, 6-15 minutes, 6-20 minutes, 10-12 minutes, 10-15 minutes, 10-20 minutes, 12-15 minutes, 12-20 minutes, or 15-20 minutes. In specific cases, the sterilization temperature is approximately 105°C, and the sterilization time ranges are in the range of 1-3 minutes, 1-6 minutes, 1-10 minutes, 1-12 minutes, 1-15 minutes, 1-20 minutes, 1.5-3 minutes, 1.5-6 minutes, 1.5-10 minutes, 1.5-12 minutes, 1.5-15 minutes, 1.5-20 minutes, 3-6 minutes, 3-10 minutes, 3-12 minutes, 3-15 minutes, 3-20 minutes, 6-10 minutes, 6-12 minutes, 6-15 minutes, 6-20 minutes, 10-12 minutes, 10-15 minutes, 10-20 minutes, 12-15 minutes, 12-20 minutes, or 15-20 minutes.In certain cases, the sterilization temperature range is about 110°C, and the sterilization time range is from 1 minute to 3 minutes, from 1 minute to 6 minutes, from 1 minute to 10 minutes, from 1 minute to 12 minutes, from 1 minute to 15 minutes, from 1 minute to 20 minutes, from 1.5 minutes to 3 minutes, from 1.5 minutes to 6 minutes, from 1.5 minutes to 10 minutes, from 1.5 minutes to 12 minutes, from 1.5 minutes to 15 minutes, from 1.5 minutes to 20 minutes, from 3 minutes to 6 minutes, from 3 minutes to 10 minutes, from 3 minutes to 12 minutes, from 3 minutes to 15 minutes, from 3 minutes to 20 minutes, from 6 minutes to 10 minutes, from 6 minutes to 12 minutes, from 6 minutes to 15 minutes, from 6 minutes to 20 minutes, from 10 minutes to 12 minutes, from 10 minutes to 15 minutes, from 10 minutes to 20 minutes, from 12 minutes to 15 minutes, from 12 minutes to 20 minutes or from 15 minutes to 20 minutes. In certain cases, the sterilization temperature is about 115°C, and the sterilization time range is from 1 minute to 3 minutes, from 1 minute to 6 minutes, from 1 minute to 10 minutes, from 1 minute to 12 minutes, from 1 minute to 15 minutes, from 1 minute to 20 minutes, from 1.5 minutes to 3 minutes, from 1.5 minutes to 6 minutes, from 1.5 minutes to 10 minutes, from 1.5 minutes to 12 minutes, from 1.5 minutes to 15 minutes, from 1.5 minutes to 20 minutes, from 3 minutes to 6 minutes, from 3 minutes to 10 minutes, from 3 minutes to 12 minutes, from 3 minutes to 15 minutes, from 3 minutes to 20 minutes, from 6 minutes to 10 minutes, from 6 minutes to 12 minutes, from 6 minutes to 15 minutes, from 6 minutes to 20 minutes, from 10 minutes to 12 minutes, from 10 minutes to 15 minutes, from 10 minutes to 20 minutes, from 12 minutes to 15 minutes, from 12 minutes to 20 minutes or from 15 minutes to 20 minutes.

[0023] In some embodiments, by heating the initial iodine-containing composition to the sterilization temperature over the sterilization time range, a sterilized iodine-containing composition having a relatively high sterility assurance is produced. The sterility assurance level of the product (the "SAL") provides a measure of the likelihood that the product will remain non-sterile after undergoing the sterilization process. As an illustrative example, a SAL of 10 -3 means that the probability of viable microorganisms present in the sterilized product is 1 / 1,000, and a SAL of 10 -6 means that the probability of viable microorganisms present in the sterilized product is 1 / 1,000,000. A SAL of 10 -6 or less means that the probability of viable microorganisms present in the sterilized product is 1 / 10, 1 / 100, 1 / 1,000, 1 / 10,000, 1 / 100,000 or 1 / 1,000,000. -6 、10 -7 、10 -8 、10 -9It includes SAL values ​​such as the following. In some embodiments, the sterile iodophore composition is 10 -3 The following 10 -4 The following 10 -5 The following 10 -6 The following 10 -7 The following 10 -8 The following 10 -9 The following 10 -10 The following 10 -11 The following or 10 -12 The following SAL is present. In a particular embodiment, the sterile iodophore composition is 10 -4 ~10 -3 , 10 -5 ~10 -3 , 10 -6 ~10 -3 , 10 -7 ~10 -3 , 10 -8 ~10 -3 , 10 -9 ~10 -3 , 10 -10 ~10 -3 , 10 -11 ~10 -3 , 10 -12 ~10 -3 , 10 -5 ~10 -4 , 10 -6 ~10 -4 , 10 -7 ~10 -4 , 10 -8 ~10 -4 , 10 -9 ~10 -4 , 10 -10 ~10 -4 , 10 -11 ~10 -4 , 10 -12 ~10 -4 , 10 -6 ~10 -5 , 10 -7 ~10 -5 , 10 -8 ~10 -5 , 10 -9 ~10 -5 , 10 -10 ~10 -5 , 10 -11 ~10 -5 , 10 -12~10 -5 、10 -7 ~10 -6 、10 -8 ~10 -6 、10 -9 ~10 -6 、10 -10 ~10 -6 、10 -11 ~10 -6 、10 -12 ~10 -6 、10 -8 ~10 -7 、10 -9 ~10 -7 、10 -10 ~10 -7 、10 -11 ~10 -7 、10 -12 ~10 -7 、10 -9 ~10 -8 、10 -10 ~10 -8 、10 -11 ~10 -8 、10 -12 ~10 -8 、10 -10 ~10 -9 、10 -11 ~10 -9 、10 -12 ~10 -9 、10 -11 ~10 -10 、10 -12 ~10 -10 Or 10 -11 ~10 -12 has a SAL of 10 -3 The following SALs may be suitable for topical application of the composition to intact skin. In the requirements and guidance for the selection of the sterility assurance level (SAL) of "sterile" products in the standard ANSI / AAMI ST67:2011 / (R)2017 for the sterilization of healthcare products approved by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), 10 -3 The following SALs are defined to be those used for topical products that contact intact skin or mucous membranes and are not intended to contact broken skin or damaged tissue. 10 -6The following SALs may be suitable for compositions that come into contact with surgical incisions, wounds, ulcers, cuts, abrasions and / or burns. According to ANSI / AAMI ST67:2011(R)2017, 10 -6 The following SALs are specified to be used in products intended to come into contact with damaged skin or damaged tissue (i.e., tissue that has lost its natural barrier integrity or is damaged or injured).

[0024] In some cases, the sterilization time and / or sterilization temperature required to achieve SAL can be calculated from one or more “D values.” The term D value has its usual meaning as used in microbiology. Specifically, it means the time required for 90% sterilization (i.e., 1 log) of a microorganism being tested (sometimes called a “challenge microorganism”) under specific sterilization conditions (e.g., contact with sterilization temperature). A non-limiting example of a suitable challenge organism is Geobacillus stearothermophilus. As an illustrative example, at a specific temperature, 10 -6 The time required to achieve the SAL can be calculated by multiplying the D value at that temperature by 6 (i.e., to obtain the time required to obtain a 6-log reduction in the number of challenging microorganisms).

[0025] In some embodiments, heating the initial iodophore composition involves exposing at least a portion of the container containing the initial iodophore composition to the heating liquid. Non-limiting examples of suitable liquids include water, aqueous solutions, alcohols, organic solvents, and oils. In certain embodiments, the heating liquid is water.

[0026] In some embodiments, the heating liquid is part of one or more moving liquid streams. In certain cases, heating the initial iodine phore composition involves bringing at least a portion of the container containing the initial iodine phore composition into contact with one or more moving liquid streams containing the heating liquid. In some embodiments, the one or more moving liquid streams containing the heating liquid include one or more cascading waterfall streams generated by a cascading water sterilizer. An exemplary cascading water sterilizer is described in U.S. Patent No. 9,511,156 by Degala et al., filed June 30, 2015, entitled “Systems, Methods, and Devices for Sterilizing Antiseptic Solutions,” the contents of which are incorporated herein by reference in their entirety for any purpose. In some embodiments, the heating liquid is part of a liquid bath. In certain embodiments, the liquid bath includes one or more stirring elements (e.g., a stirrer, a magnetic stirrer). In some cases, heating the initial iodine phore composition involves immersing at least a portion of the container containing the initial iodine phore composition in the liquid bath.

[0027] In some embodiments, the sterilization system includes a cascading water sterilizer. Figure 1B shows a schematic diagram of an exemplary sterilization system 100 including a cascading water sterilizer 102. In certain embodiments, the cascading water sterilizer 102 includes a chamber. The chamber may have any preferred shape and volume. In some embodiments, the chamber is coupled to a water dispensing device configured to produce one or more cascading waterfall streams flowing through the chamber. In some embodiments, the water dispensing device is configured to produce one or more cascading waterfall streams flowing from the top portion of the chamber to the bottom portion of the chamber. Examples of preferred water dispensing devices, but are not limited to, include perforated sheets (e.g., sheets with multiple holes) and one or more spray nozzles.

[0028] During operation, according to some embodiments, one or more containers containing the initial iodine composition 104 may be positioned within the chamber of a cascading water sterilizer 102. Within the chamber, a water stream 108 may be directed to flow as a cascading waterfall from the top to the bottom of the chamber. The cascading waterfall may be heated to a relatively high temperature (i.e., a temperature sufficient to raise the temperature of the initial iodine composition in the containers to a desired sterilization temperature). As the water stream 108 flows from the top to the bottom of the chamber, it comes into contact with at least a portion of the one or more containers containing the initial iodine composition 104, thereby heating the one or more containers containing the initial iodine composition 104. The conditions are selected so that the contact between the water stream 108 and the one or more containers containing the initial iodine composition 104 heats the initial iodine composition 104 to a sterilization temperature over the sterilization time to produce a sterilized iodine composition 106. In some embodiments, at least a portion of the water stream 108 is recirculated from the bottom of the chamber of the cascading water sterilizer 102 to the top of the chamber. In other embodiments, the water stream 108 is not recirculated from the bottom of the chamber of the cascading water sterilizer 102.

[0029] In some embodiments, after the sterilization period ends, the chamber of the cascading water sterilizer 102 is drained of water, and the outer surfaces of one or more containers containing the sterile iodine composition 106 are dried. In some cases, one or more containers are dried within the chamber of the cascading water sterilizer 102 (e.g., exposed to heated dehumidified air). In some cases, one or more containers are transferred to individual drying units for drying.

[0030] In some embodiments, the sterilization system (e.g., including a cascading water sterilizer) further includes a heater configured to heat a liquid stream. Examples of preferred heaters, but are not limited to, include heat exchangers, boilers, electric heaters, and heat pumps. Figure 1C shows a schematic diagram of an exemplary sterilization system 100 including a cascading water sterilizer 102 and a heater 110. As shown in Figure 1C, the cascading water sterilizer 102 is in fluid communication with the heater 110.

[0031] In some embodiments, at least a portion of the water stream 108 exits the bottom of the chamber of the cascading water sterilizer 102, is directed to flow through the heater 110, and then returns to the top of the chamber of the cascading water sterilizer 102.

[0032] In some embodiments, the sterilization system includes one or more additional components. For example, Figure 2 shows a schematic diagram of an exemplary sterilization system 200, which includes two sterilization units (e.g., cascading water sterilizers) 202, two heaters 204, a chiller 206, a chiller pump reservoir 208, a deionized water pump reservoir 210, and two drying units 212. In certain embodiments, the heaters 204 are boilers.

[0033] During operation, multiple containers are filled with the iodine composition and loaded into the chambers of the sterilization unit 202. Once the containers are placed in the sterilization unit 202 and the sterilization process begins, deionized water from the deionized water pump reservoir 210 is pumped into the chambers of the sterilization unit 202 via the input line 213. The deionized water is then continuously circulated within each chamber so that it falls onto the containers.

[0034] While deionized water circulates within the chamber of the sterilization unit 202, steam from the heater 204 flows into the sterilization unit 202 via the input line 214. The steam passes through a heat exchanger, and heat is transferred from the steam to the deionized water. After cooling in the heat exchanger, the steam condensate exits the heat exchanger and returns to the heater 204 via the return line 216. The heat exchange cycle continues until the temperature of the circulating deionized water is determined to be at an appropriate temperature. The sterilization system can precisely control the steam input from the heater 204 to maintain appropriate sterilization conditions (e.g., by activating appropriate valves). During this heat exchange process, the deionized water continues to circulate within the chamber, heating the iodine composition by falling onto the container.

[0035] Once the sterilization period is complete, the cooling process can be initiated. During the cooling process, water cooled by the chiller 206 flows to the chiller pump reservoir 208 via input and return lines 211. The chilled water moves from the chiller pump reservoir 208 to the sterilization unit 202 via the input line 218. Heat is then transferred from the deionized water to the chilled water, cooling the deionized water and heating the chilled water. During this cooling heat exchange process, the deionized water continues to circulate within the chamber and cools the iodine phore composition by falling onto the container. After the heat exchange, the chilled water returns to the chiller pump reservoir 208 and chiller 206 via lines 220 and 211. The cooling process continues until the deionized water in the chamber reaches a desired temperature (e.g., room temperature).

[0036] Once the cooling process is complete, the deionized water is discharged from the chamber of the sterilization unit 202, and the container is transferred to the drying unit 212. The drying unit 212 may be used to dry the outer surface of the container. In certain embodiments, the drying unit 212 includes a dehumidifier. In some cases, the drying unit 212 may utilize heated dehumidified air to dry the container.

[0037] In some cases, a computer control system may be used to control the sterilization system 200. In certain cases, the computer control system may include a processor programmed to provide appropriate operating parameters (e.g., the amount of deionized water circulated in the sterilization unit, the sterilization temperature, the sterilization time) so that a particular iodophore composition is sterilized.

[0038] In some embodiments, the sterilization system includes multiple sterilization units. In specific cases, the sterilization system includes at least two, at least five, or at least ten sterilization units. In some embodiments, the number of sterilization units in the sterilization system ranges from 1 to 2, 1 to 5, 1 to 10, 2 to 5, 2 to 10, or 5 to 10. In some embodiments, the sterilization system includes multiple heating units and / or multiple cooling units.

[0039] In some embodiments, a method for sterilizing an iodine composition includes providing one or more containers for containing the initial iodine composition. The one or more containers may be any container suitable for containing a certain volume of liquid. Non-limiting examples of suitable containers include ampoules, jars, bottles, tubes, and pouches. In certain cases, the one or more containers are configured to stand vertically upright. In some embodiments, the one or more containers are sealed. The one or more containers may be made from any material suitable for containing the iodine composition. Non-limiting examples of suitable materials for the one or more containers include glass, plastic, polymer, and / or metal laminates. In certain embodiments, the one or more containers include glass ampoules, plastic ampoules, plastic bottles, plastic tubes, polymer pouches, or metal laminate pouches. The one or more containers may have any preferred size and shape. In certain embodiments, one or more containers may be sized to hold 0.67 mL, 0.75 mL, 1 mL, 1.5 mL, 3 mL, 5 mL, 10.5 mL, 13 mL, and / or 26 mL of liquid. In certain embodiments, one or more containers are sized to hold volumes within the ranges of 0.67 mL to 1 mL, 0.67 mL to 3 mL, 0.67 mL to 5 mL, 0.67 mL to 10.5 mL, 0.67 mL to 13 mL, 0.67 mL to 26 mL, 0.75 mL to 1 mL, 0.75 mL to 3 mL, 0.75 mL to 5 mL, 0.75 mL to 10.5 mL, 0.75 mL to 13 mL, 0.75 mL to 26 mL, 1 mL to 3 mL, 1 mL to 5 mL, 1 mL to 10.5 mL, 1 mL to 13 mL, 1 mL to 26 mL, 3 mL to 10.5 mL, 3 mL to 13 mL, 3 mL to 26 mL, 10.5 mL to 13 mL, 10.5 mL to 26 mL, or 13 mL to 26 mL. In some cases, each of the one or more containers is configured to hold the same volume of liquid. In some cases, one or more containers are configured to hold different volumes of liquid.

[0040] According to some embodiments, the initial iodophore composition has a relatively high concentration of iodine-polymer composites (e.g., PVP-I, iodine povacrilex). In some cases, the concentration of a component may be expressed as a weight percentage (W%). The weight percentage of a component in a composition generally means the ratio of the amount of the component to the total amount of the composition multiplied by 100. As an exemplary example, the weight percentage of iodine-polymer composites (e.g., PVP-I, iodine povacrilex) in the initial iodophore composition can be determined by dividing the amount of iodine-polymer composites (e.g., PVP-I, iodine povacrilex) by the total amount of the initial iodophore composition and multiplying the quotient by 100. In some embodiments, the initial iodophore composition contains an iodine-polymer composite (e.g., PVP-I, iodine povacrilex) in a concentration of at least 5.0% by weight, at least 5.5% by weight, at least 6.0% by weight, at least 6.5% by weight, at least 7.0% by weight, at least 7.5% by weight, at least 8.0% by weight, at least 8.5% by weight, at least 9.0% by weight, at least 9.5% by weight, or at least 10.0% by weight. In certain embodiments, the initial iodophore composition contains an iodine-polymer composite (e.g., PVP-I, iodine povacrilex) in concentrations ranging from 5.0% to 6.0% by weight, 5.0% to 7.0% by weight, 5.0% to 8.0% by weight, 5.0% to 9.0% by weight, 5.0% to 10.0% by weight, 6.0% to 7.0% by weight, 6.0% to 8.0% by weight, 6.0% to 9.0% by weight, 6.0% to 10.0% by weight, 7.0% to 8.0% by weight, 7.0% to 9.0% by weight, 7.0% to 10.0% by weight, 8.0% to 9.0% by weight, 8.0% to 10.0% by weight, or 9.0% to 10.0% by weight.

[0041] In some embodiments, the initial iodophore composition has a relatively high concentration of available iodine (also called the percentage of available iodine). In certain embodiments, the initial iodophore composition contains available iodine at concentrations of at least 0.30% by weight, at least 0.40% by weight, at least 0.50% by weight, at least 0.55% by weight, at least 0.60% by weight, at least 0.65% by weight, at least 0.70% by weight, at least 0.75% by weight, at least 0.80% by weight, at least 0.85% by weight, at least 0.90% by weight, at least 0.95% by weight, at least 1.0% by weight, at least 1.2% by weight, at least 1.3% by weight, at least 1.4% by weight, or at least 1.5% by weight.In some embodiments, the initial iodine phore composition is 0.30% to 0.50% by weight, 0.30% to 0.60% by weight, 0.30% to 0.70% by weight, 0.30% to 0.80% by weight, 0.30% to 0.90% by weight, 0.30% to 1.0% by weight, 0.30% to 1.1% by weight, 0.30% to 1.2%, 0.30% to 1.3% by weight, 0.30% to 1.4% by weight, 0.30% to 1.5% by weight, 0.40% to 0.60% by weight, 0.40% to 0.70% by weight, 0.40% to 0.80% by weight, 0.40% by weight Amount%~0.90wt%, 0.40wt%~1.0wt%, 0.40wt%~1.1wt%, 0.40%~1.2%, 0.40wt%~1.3wt%, 0.40wt%~1.4wt%, 0.40wt%~1.5wt%, 0.50wt%~0.70wt%, 0.50wt%~0 .80wt%, 0.50wt%~0.90wt%, 0.50wt%~1.0wt%, 0.50wt%~1.1wt%, 0.50%~1.2%, 0.50wt%~1.3wt%, 0.50wt%~1.4wt%, 0.50wt%~1.5wt%, 0.60wt%~0.80wt %, 0.60wt%~0.90wt%, 0.60wt%~1.0wt%, 0.60wt%~1.1wt%, 0.60%~1.2%, 0.60wt%~1.3wt%, 0.60wt%~1.4wt%, 0.60wt%~1.5wt%, 0.70wt%~0.90wt%, 0. 70%~1.0% by weight, 0.70%~1.1% by weight, 0.70%~1.2%, 0.70%~1.3% by weight, 0.70%~1.4% by weight, 0.70%~1.5% by weight, 0.80%~1.0% by weight, 0.80%~1.1% by weight, 0.80%~1.2 Contains iodine available in concentrations ranging from %, 0.80 wt% to 1.3 wt%, 0.80 wt% to 1.4 wt%, 0.80 wt% to 1.5 wt%, 0.90 wt% to 1.1 wt%, 0.90% to 1.2%, 0.90 wt% to 1.3 wt%, 0.90 wt% to 1.4 wt%, 0.90 wt% to 1.5 wt%, 1.0% to 1.2%, 1.0 wt% to 1.3 wt%, 1.0 wt% to 1.4 wt%, 1.0 wt% to 1.5 wt%, 1.1 wt% to 1.5 wt%, 1.2 wt% to 1.5 wt%, 1.3 wt% to 1.5 wt%, or 1.4 wt% to 1.5 wt%.The concentration of available iodine in an iodophore composition can be determined by any method known in the art. For example, the concentration of available iodine in an iodophore composition can be measured by titration using sodium thiosulfate.

[0042] In some embodiments, the initial iodophore composition comprises an iodine-polymer complex (e.g., PVP-I, iodine povacrilex) dissolved and / or suspended in a solvent. Non-limiting examples of suitable solvents include water, alcohol, acetone, polyethylene glycol, glycerol, and combinations thereof. In some embodiments, the initial and / or sterile iodophore composition contains the solvent in concentrations of at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 80% by weight, at least 90% by weight, or at least 95% by weight. In some embodiments, the initial and / or sterile iodophore composition contains the solvent in concentrations ranging from 50% to 80% by weight, 50% to 90% by weight, 50% to 95% by weight, 60% to 80% by weight, 60% to 90% by weight, 60% to 95% by weight, 70% to 90% by weight, 70% to 95% by weight, or 80% to 95% by weight.

[0043] In some embodiments, the initial iodone composition contains water and has an acidic or neutral pH. In some embodiments, the initial iodone composition has a pH of at least 1.5, at least 2.0, at least 2.5, at least 3.0, at least 3.5, at least 4.0, at least 4.5, at least 5.0, at least 5.5, at least 6.0, at least 6.5, or at least 7.0. In some embodiments, the initial iodone composition has a pH of 7.0 or less, 6.5 or less, 6.0 or less, 5.5 or less, 5.0 or less, 4.5 or less, 4.0 or less, 3.5 or less, 3.0 or less, 2.5 or less, 2.0 or less, or 1.5 or less. In some embodiments, the initial iodine phore composition has a pH in the range of 1.5-3.0, 1.5-4.0, 1.5-5.0, 1.5-6.0, 1.5-6.5, 1.5-7.0, 2.0-4.0, 2.0-5.0, 2.0-5.5, 2.0-6.0, 2.0-6.5, 2.0-7.0, 3.0-5.0, 3.0-6.0, 3.0-6.5, 3.0-7.0, 4.0-6.0, 4.0-6.5, 4.0-7.0, 5.0-6.0, 5.0-6.5, 5.0-7.0, or 6.0-7.0.

[0044] In some embodiments, the initial iodine phore composition has a viscosity that facilitates the application of the initial iodine phore composition to one or more locations on the patient. In some embodiments, the initial iodine phore composition has a viscosity of at least 500 centipoise (cP), at least 600 cP, at least 700 cP, at least 800 cP, at least 900 cP, at least 1000 cP, at least 1500 cP, at least 2000 cP, at least 2500 cP, or at least 3000 cP at ambient temperature. In some embodiments, the initial iodine phore composition has a viscosity of 3000 cP or less, 2500 cP or less, 2000 cP or less, 1500 cP or less, 1000 cP or less, or 500 cP or less at ambient temperature. In some embodiments, the initial iodine phore composition has a viscosity in the range of 500 cP to 1000 cP, 500 cP to 1500 cP, 500 cP to 2000 cP, 500 cP to 2500 cP, 500 cP to 3000 cP, 1000 cP to 1500 cP, 1000 cP to 2000 cP, 1000 cP to 2500 cP, 1000 cP to 3000 cP, 1500 cP to 2000 cP, 1500 cP to 2500 cP, 1500 cP to 3000 cP, 2000 cP to 2500 cP, or 2000 cP to 3000 cP at ambient temperature. The viscosity of the initial iodine phore composition at ambient temperature can be measured by any method known in the art. For example, the viscosity of an initial iodophore composition at ambient temperature can be measured using a rotational viscometer.

[0045] The initial iodine composition may have any form suitable for application to a patient site. In some embodiments, the initial iodine composition is a gel, solution, suspension, emulsion, cream, ointment, lotion, paste, medicinal stick, and / or balm. In some embodiments, the initial iodine composition is configured to facilitate topical application to a patient site. The initial iodine composition may have any preferred appearance. In some embodiments, the initial iodine composition does not contain any solid-phase components. In certain embodiments, for example, the initial iodine composition does not contain any visible precipitates or solid particles.

[0046] According to some embodiments, the sterile iodine phore composition retains certain advantageous properties of the initial iodine phore composition. In some cases, the sterilization systems, methods, and conditions described herein can reduce and / or minimize certain adverse effects of sterilization on one or more properties of the initial iodine phore composition that are important to its effectiveness or suitability in its intended use. In some embodiments, for example, the sterile iodine phore composition retains a relatively high concentration of the iodine-polymer composite (e.g., PVP-I, iodine povacrilex). In certain embodiments, the sterile iodine phore composition contains the iodine-polymer composite (e.g., PVP-I, iodine povacrilex) at a concentration of at least 5.0% by weight, at least 5.5% by weight, at least 6.0% by weight, at least 6.5% by weight, at least 7.0% by weight, at least 7.5% by weight, at least 8.0% by weight, at least 8.5% by weight, at least 9.0% by weight, at least 9.5% by weight, or at least 10.0% by weight. In certain embodiments, the sterile iodophore composition contains an iodine-polymer composite (e.g., PVP-I, iodine povacrilex) in concentrations ranging from 5.0% to 6.0% by weight, 5.0% to 7.0% by weight, 5.0% to 8.0% by weight, 5.0% to 9.0% by weight, 5.0% to 10.0% by weight, 6.0% to 7.0% by weight, 6.0% to 8.0% by weight, 6.0% to 9.0% by weight, 6.0% to 10.0% by weight, 7.0% to 8.0% by weight, 7.0% to 9.0% by weight, 7.0% to 10.0% by weight, 8.0% to 9.0% by weight, 8.0% to 10.0% by weight, or 9.0% to 10.0% by weight.

[0047] In some embodiments, the decrease in the concentration of the iodine-polymer complex (e.g., PVP-I, iodine povacrilex) obtained from sterilization is all relatively low. In some embodiments, the percentage difference between the concentration of the first iodine-polymer complex (e.g., PVP-I, iodine povacrilex) in the initial iodophore composition and the concentration of the second iodine-polymer complex (e.g., PVP-I, iodine povacrilex) in the sterilized iodophore composition is 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, or 0.1% or less. In some embodiments, the percentage difference between the concentration of the first iodine-polymer complex (e.g., PVP-I, iodine povacrilex) in the initial iodofore composition and the concentration of the second iodine-polymer complex (e.g., PVP-I, iodine povacrilex) in the sterile iodofore composition is 0.1%~0.5%, 0.1%~1%, 0.1%~2%, 0.1%~5%, 0.1%~6%, 0.1%~7%, The ranges are 0.1%~8%, 0.5%~1%, 0.5%~2%, 0.5%~5%, 0.5%~6%, 0.5%~7%, 0.5%~8%, 1%~2%, 1%~5%, 1%~6%, 1%~7%, 1%~8%, 2%~5%, 2%~6%, 2%~7%, 2%~8%, 3%~5%, 3%~6%, 3%~7%, 3%~8%, 4%~6%, 4%~7%, 4%~8%, 5%~7%, 5%~8%, or 6%~8%.

[0048] In some embodiments, the absolute difference between the concentration of the first iodine-polymer complex (e.g., PVP-I, iodine povacrilex) in the initial iodophore composition and the concentration of the second iodine-polymer complex (e.g., PVP-I, iodine povacrilex) in the sterile iodophore composition is 1% by weight or less, 0.9% by weight or less, 0.8% by weight or less, 0.7% by weight or less, 0.6% by weight or less, 0.5% by weight or less, 0.4% by weight or less, 0.3% by weight or less, 0.2% by weight or less, 0.1% by weight or less, 0.05% by weight or less, 0.02% by weight or less, or 0.01% by weight or less. In some embodiments, the absolute difference between the concentration of the first iodine-polymer complex (e.g., PVP-I, iodine povacrilex) in the initial iodophore composition and the concentration of the second iodine-polymer complex (e.g., PVP-I, iodine povacrilex) in the sterile iodophore composition is 0.01% to 0.05%, 0.01% to 0.1%, 0.01% to 0.2%, 0.01% to 0.3%, and 0. The ranges are 0.01% to 0.4% by weight, 0.01% to 0.5% by weight, 0.01% to 0.6% by weight, 0.01% to 0.7% by weight, 0.01% to 0.8% by weight, 0.01% to 0.9% by weight, 0.01% to 1% by weight, 0.05% to 0.1% by weight, 0.05% to 0.5% by weight, 0.05% to 1% by weight, 0.1% to 0.5% by weight, 0.1% to 1% by weight, or 0.5% to 1% by weight.

[0049] In some embodiments, the sterile iodophore composition has a relatively high concentration of available iodine. In certain embodiments, the sterile iodophore composition contains available iodine at concentrations of at least 0.30% by weight, at least 0.40% by weight, at least 0.50% by weight and at least 0.55% by weight, at least 0.60% by weight, at least 0.65% by weight, at least 0.70% by weight, at least 0.75% by weight, at least 0.80% by weight, at least 0.85% by weight, at least 0.90% by weight, at least 0.95% by weight, at least 1.0% by weight, at least 1.2% by weight, at least 1.3% by weight, at least 1.4% by weight or at least 1.5% by weight.In some embodiments, the sterile iodine composition is 0.30% to 0.50% by weight, 0.30% to 0.60% by weight, 0.30% to 0.70% by weight, 0.30% to 0.80% by weight, 0.30% to 0.90% by weight, 0.30% to 1.0% by weight, 0.30% to 1.1% by weight, 0.30% to 1.2%, 0.30% to 1.3% by weight, 0.30% to 1.4% by weight, 0.30% to 1.5% by weight, 0.40% to 0.60% by weight, 0.40% to 0.70% by weight, 0.40% to 0.80% by weight, 0.40% by weight Amount%~0.90wt%, 0.40wt%~1.0wt%, 0.40wt%~1.1wt%, 0.40%~1.2%, 0.40wt%~1.3wt%, 0.40wt%~1.4wt%, 0.40wt%~1.5wt%, 0.50wt%~0.70wt%, 0.50wt%~0 .80wt%, 0.50wt%~0.90wt%, 0.50wt%~1.0wt%, 0.50wt%~1.1wt%, 0.50%~1.2%, 0.50wt%~1.3wt%, 0.50wt%~1.4wt%, 0.50wt%~1.5wt%, 0.60wt%~0.80wt %, 0.60wt%~0.90wt%, 0.60wt%~1.0wt%, 0.60wt%~1.1wt%, 0.60%~1.2%, 0.60wt%~1.3wt%, 0.60wt%~1.4wt%, 0.60wt%~1.5wt%, 0.70wt%~0.90wt%, 0. 70%~1.0% by weight, 0.70%~1.1% by weight, 0.70%~1.2%, 0.70%~1.3% by weight, 0.70%~1.4% by weight, 0.70%~1.5% by weight, 0.80%~1.0% by weight, 0.80%~1.1% by weight, 0.80%~1.2 Contains iodine available in concentrations ranging from %, 0.80 wt% to 1.3 wt%, 0.80 wt% to 1.4 wt%, 0.80 wt% to 1.5 wt%, 0.90 wt% to 1.1 wt%, 0.90% to 1.2%, 0.90 wt% to 1.3 wt%, 0.90 wt% to 1.4 wt%, 0.90 wt% to 1.5 wt%, 1.0% to 1.2%, 1.0 wt% to 1.3 wt%, 1.0 wt% to 1.4 wt%, 1.0 wt% to 1.5 wt%, 1.1 wt% to 1.5 wt%, 1.2 wt% to 1.5 wt%, 1.3 wt% to 1.5 wt%, or 1.4 wt% to 1.5 wt%.

[0050] In some embodiments, the percentage decrease in the concentration of available iodine is relatively low. In some embodiments, the percentage difference between the first concentration of available iodine in the initial iodone composition and the second concentration of available iodine in the sterile iodone composition is 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, or 0.1% or less. In some embodiments, the percentage difference between the first concentration of available iodine in the initial iodone composition and the second concentration of available iodine in the sterile iodone composition is 0.1% to 0.5%, 0.1% to 1%, 0.1% to 2%, 0.1% to 5%, 0.1% to 6%, 0.1% to 7%, 0.1% to 8%, 0.5% to 1%, 0.5% to 2%, The ranges are 0.5%~5%, 0.5%~6%, 0.5%~7%, 0.5%~8%, 1%~2%, 1%~5%, 1%~6%, 1%~7%, 1%~8%, 2%~5%, 2%~6%, 2%~7%, 2%~8%, 3%~5%, 3%~6%, 3%~7%, 3%~8%, 4%~6%, 4%~7%, 4%~8%, 5%~7%, 5%~8%, or 6%~8%.

[0051] In some embodiments, the absolute difference between the first available iodine concentration of the initial iodine phore composition and the second available iodine concentration of the sterile iodine phore composition is 1% by weight or less, 0.9% by weight or less, 0.8% by weight or less, 0.7% by weight or less, 0.6% by weight or less, 0.5% by weight or less, 0.4% by weight or less, 0.3% by weight or less, 0.2% by weight or less, 0.1% by weight or less, 0.05% by weight or less, 0.02% by weight or less, or 0.01% by weight or less. In some embodiments, the absolute difference between the first available iodine concentration of the initial iodine phore composition and the second available iodine concentration of the sterile iodine phore composition is 0.01% to 0.05%, 0.01% to 0.1%, 0.01% to 0.2%, 0.01% to 0.3%, 0.01% to 0.4%, and 0.01% to 0.5%. The ranges are: weight%, 0.01% to 0.6% by weight, 0.01% to 0.7% by weight, 0.01% to 0.8% by weight, 0.01% to 0.9% by weight, 0.01% to 1% by weight, 0.05% to 0.1% by weight, 0.05% to 0.5% by weight, 0.05% to 1% by weight, 0.1% to 0.5% by weight, 0.1% to 1% by weight, or 0.5% to 1% by weight.

[0052] In some embodiments, the sterile iodine composition contains water and has an acidic or neutral pH. In some embodiments, the sterile iodine composition has a pH of at least 1.5, at least 2.0, at least 2.5, at least 3.0, at least 3.5, at least 4.0, at least 4.5, at least 5.0, at least 5.5, at least 6.0, at least 6.5, or at least 7.0. In some embodiments, the sterile iodine composition has a pH of 7.0 or less, 6.5 or less, 6.0 or less, 5.5 or less, 5.0 or less, 4.5 or less, 4.0 or less, 3.5 or less, 3.0 or less, 2.5 or less, 2.0 or less, or 1.5 or less. In some embodiments, the sterile iodine composition has a pH in the range of 1.5-3.0, 1.5-4.0, 1.5-5.0, 1.5-6.0, 1.5-6.5, 1.5-7.0, 2.0-4.0, 2.0-5.0, 2.0-5.5, 2.0-6.0, 2.0-6.5, 2.0-7.0, 3.0-5.0, 3.0-6.0, 3.0-6.5, 3.0-7.0, 4.0-6.0, 4.0-6.5, 4.0-7.0, 5.0-6.0, 5.0-6.5, 5.0-7.0, or 6.0-7.0.

[0053] In some embodiments, the difference in pH between the initial iodophore composition and the sterile iodophore composition is relatively small. In some cases, minimizing any pH change due to sterilization may be advantageous because the pH of the iodophore composition can have a significant impact on the potency of the composition, patient comfort, and / or patient safety. As an exemplary example, when applied to a patient's skin, highly acidic or highly basic iodophore compositions may cause irritation. In some embodiments, the absolute difference between the pH of the initial iodophore composition and the pH of the sterile iodophore composition is 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, 0.1 or less, 0.05 or less, 0.02 or less, 0.01 or less, or about 0.0. In some embodiments, the absolute value of the difference between the pH of the initial iodine phore composition and the pH of the sterile iodine phore composition is approximately 0.0-0.01, approximately 0.0-0.02, approximately 0.0-0.05, approximately 0.0-0.1, approximately 0.0-0.2, approximately 0.0-0.3, approximately 0.0-0.4, approximately 0.0-0.5, approximately 0.01-0.02, approximately 0.01-0.05, approximately The range is approximately 0.01-0.1, 0.01-0.2, 0.01-0.3, 0.01-0.4, 0.01-0.5, 0.05-0.1, 0.05-0.2, 0.05-0.3, 0.05-0.4, 0.05-0.5, 0.1-0.2, 0.1-0.3, 0.1-0.4, 0.1-0.5, or 0.2-0.5.

[0054] In some embodiments, the sterile iodine composition has a viscosity that facilitates the application of the sterile iodine composition to one or more locations on a patient at ambient temperature (i.e., about 20°C). In some embodiments, the sterile iodine composition has a viscosity of at least 500 centipoise (cP), at least 600 cP, at least 700 cP, at least 800 cP, at least 900 cP, at least 1000 cP, at least 1500 cP, at least 2000 cP, at least 2500 cP, or at least 3000 cP at ambient temperature (i.e., about 20°C). In some embodiments, the sterile iodine composition has a viscosity of 3000 cP or less, 2500 cP or less, 2000 cP or less, 1500 cP or less, 1000 cP or less, or 500 cP or less at ambient temperature. In a multiple embodiment, the sterile iodine composition has a viscosity in the range of 500 cP to 1000 cP, 500 cP to 1500 cP, 500 cP to 2000 cP, 500 cP to 2500 cP, 500 cP to 3000 cP, 1000 cP to 1500 cP, 1000 cP to 2000 cP, 1000 cP to 2500 cP, 1000 cP to 3000 cP, 1500 cP to 2000 cP, 1500 cP to 2500 cP, 1500 cP to 3000 cP, 2000 cP to 2500 cP, or 2000 cP to 3000 cP at ambient temperature.

[0055] In some embodiments, the difference between the viscosity of the initial iodone composition at ambient temperature and the viscosity of the sterile iodone composition at ambient temperature is relatively small. In some cases, minimizing any viscosity change due to sterilization may be advantageous because the viscosity of the iodone composition may have a significant impact on the application of the iodone composition to the patient. For example, the viscosity of the iodone composition may provide improved prevention and / or control of pooling throughout the application of the composition. In some embodiments, the percentage difference between the viscosity of the initial iodone composition and the viscosity of the sterile iodone composition is 60% or less, 50% or less, 40% or less, 30% or less, 20% or less, 10% or less, 5% or less, 2% or less, 1% or less, or about 0%. In some embodiments, the percentage difference between the viscosity of the initial iodine phore composition and the viscosity of the sterile iodine phore composition is 0%~1%, 0%~2%, 0%~5%, 0%~10%, 0%~20%, 0%~30%, 0%~40%, 0%~50%, 0%~60%, 1%~2%, 1%~5%, 1%~10%, 1%~20%, 1%~30%, 1%~40%, 1%~50%, 1%~60%, 5 The percentages are in the range of 10%, 5%, 20%, 30%, 40%, 5%, 50%, 60%, 10%, 20%, 30%, 40%, 50%, 60%, 20%, 30%, 40%, 50%, 60%, 30%, 50%, 50%, 60%, 30%, 50%, 50%, 60%, 40%, 60%, 50%, 60%, 50%, 60%, 60%, 60%, 60%, 60%, 60%, or 60%.

[0056] In certain embodiments, the initial and / or sterile iodofore composition contains water. In some cases, the water is deionized water and / or distilled water. In some embodiments, the initial and / or sterile iodofore composition contains water in a concentration of at least 5% by weight, at least 10% by weight, at least 15% by weight, at least 20% by weight, at least 30% by weight, at least 40% by weight, at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 80% by weight, at least 90% by weight, or at least 95% by weight. In some embodiments, the initial and / or sterile iodine phores composition is 5% to 20% by weight, 5% to 30% by weight, 5% to 40% by weight, 5% to 50% by weight, 5% to 60% by weight, 5% to 70% by weight, 5% to 80% by weight, 5% to 90% by weight, 5% to 95% by weight, 10% to 20% by weight, 10% to 30% by weight, 10% to 40% by weight, 10% to 50% by weight, 10% to 60% by weight, 10% to 70% by weight, 10% to 80% by weight, 10% to 90% by weight, 10% to 95% by weight, 20% to 40% by weight, 20% to 50% by weight, 20% to 60% by weight, 20% to 70% by weight, 20% to 80% by weight, 20wt%~90wt%, 20wt%~95wt%, 30wt%~50wt%, 30wt%~60wt%, 30wt%~70wt%, 30wt%~80wt%, 30wt% Amount%~90wt%, 30wt%~95wt%, 40wt%~60wt%, 40wt%~70wt%, 40wt%~80wt%, 40wt%~90wt%, 40wt%~ Contains water in concentrations ranging from 95% by weight, 50% to 70% by weight, 50% to 80% by weight, 50% to 90% by weight, 50% to 95% by weight, 60% to 80% by weight, 60% to 90% by weight, 60% to 95% by weight, 70% to 90% by weight, 70% to 95% by weight, 80% to 90% by weight, or 80% to 95% by weight.

[0057] In some embodiments, the initial and / or sterile iodofore composition contains alcohol. Non-limiting examples of suitable alcohols include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tert-butanol, benzyl alcohol, phenol, and combinations thereof. In certain embodiments, the alcohol includes ethanol, isopropanol, and / or n-propanol. In some cases, it may be advantageous for the initial and / or sterile iodofore composition to contain alcohol, as the alcohol may act as an antimicrobial agent. In some embodiments, the initial and / or sterile iodofore composition contains alcohol at a concentration of at least 5% by weight, at least 10% by weight, at least 15% by weight, at least 20% by weight, at least 30% by weight, at least 40% by weight, at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 80% by weight, at least 90% by weight, or at least 95% by weight.In some embodiments, the initial and / or sterile iodine phores composition is 5% to 20% by weight, 5% to 30% by weight, 5% to 40% by weight, 5% to 50% by weight, 5% to 60% by weight, 5% to 70% by weight, 5% to 80% by weight, 5% to 90% by weight, 5% to 95% by weight, 10% to 20% by weight, 10% to 30% by weight, 10% to 40% by weight, 10% to 50% by weight, 10% to 60% by weight, 10% to 70% by weight, 10% to 80% by weight, 10% to 90% by weight, 10% to 95% by weight, 20% to 40% by weight, 20% to 50% by weight, 20% to 60% by weight, 20% to 70% by weight, 20% to 80% by weight, 20% to 80% by weight, 20% to 20% by weight Contains alcohol in concentrations ranging from 90% by weight to 90% by weight, 20% by weight to 95% by weight, 30% by weight to 50% by weight, 30% by weight to 60% by weight, 30% by weight to 70% by weight, 30% by weight to 80% by weight, 30% by weight to 90% by weight, 30% by weight to 95% by weight, 40% by weight to 60% by weight, 40% by weight to 70% by weight, 40% by weight to 80% by weight, 40% by weight to 90% by weight, 40% by weight to 95% by weight, 50% by weight to 70% by weight, 50% by weight to 80% by weight, 50% by weight to 90% by weight, 50% by weight to 95% by weight, 60% by weight to 80% by weight, 60% by weight to 90% by weight, 60% by weight to 95% by weight, 70% by weight to 90% by weight, 70% by weight to 90% by weight, 70% by weight to 95% by weight, 80% by weight to 90% by weight, or 80% by weight to 95% by weight.

[0058] In some embodiments, the initial and / or sterile iodophore composition comprises one or more polymer-forming agents. In certain embodiments, the polymer-forming agent comprises a copolymer. Examples of suitable polymer-forming agents, but not limited to, include methyl methacrylate copolymer, carboxylated acrylic copolymer, and hydroxypropyl cellulose. In some embodiments, the initial and / or sterile iodophore composition comprises the polymer-forming agent in a concentration of at least 0.1% by weight, at least 0.2% by weight, at least 0.5% by weight, at least 1% by weight, at least 1.5% by weight, at least 2% by weight, at least 5% by weight, or at least 10% by weight. In some embodiments, the initial and / or sterile iodophore composition contains a polymerizing agent in concentrations ranging from 0.1% to 0.5% by weight, 0.1% to 1% by weight, 0.1% to 2% by weight, 0.1% to 5% by weight, 0.1% to 10% by weight, 0.2% to 1% by weight, 0.2% to 2% by weight, 0.2% to 5% by weight, 0.2% to 10% by weight, 0.5% to 1% by weight, 0.5% to 2% by weight, 0.5% to 5% by weight, 0.5% to 10% by weight, 1% to 2% by weight, 1% to 5% by weight, 1% to 10% by weight, 2% to 5% by weight, 2% to 10% by weight, or 5% to 10% by weight.

[0059] In some embodiments, the initial and / or sterile iodophore composition contains a polymerizing agent in a total concentration of at least 0.1% by weight, at least 0.2% by weight, at least 0.5% by weight, at least 1% by weight, at least 1.5% by weight, at least 2% by weight, at least 5% by weight, or at least 10% by weight. In some embodiments, the initial and / or sterile iodophore composition contains a polymerizing agent in a total concentration within the range of 0.1% to 0.5% by weight, 0.1% to 1% by weight, 0.1% to 2% by weight, 0.1% to 5% by weight, 0.1% to 10% by weight, 0.2% to 1% by weight, 0.2% to 2% by weight, 0.2% to 5% by weight, 0.2% to 10% by weight, 0.5% to 1% by weight, 0.5% to 2% by weight, 0.5% to 5% by weight, 0.5% to 10% by weight, 1% to 2% by weight, 1% to 5% by weight, 1% to 10% by weight, 2% to 5% by weight, 2% to 10% by weight, or 5% to 10% by weight.

[0060] In some embodiments, the initial and / or sterile iodophore composition contains one or more pH adjusters. The pH adjusters may be acids, bases, or buffer salts. Not limited examples of suitable acidic pH adjusters include citric acid, lactic acid, and acetic acid. Not limited examples of suitable basic pH adjusters include 2-amino-2-methyl-1-propanol (e.g., AMP-95), sodium hydroxide, potassium hydroxide, and disodium phosphate. In some embodiments, the initial and / or sterile iodophore composition contains the pH adjuster in a concentration of at least 0.01% by weight, at least 0.02% by weight, at least 0.05% by weight, at least 0.1% by weight, at least 0.2% by weight, at least 0.5% by weight, at least 1% by weight, at least 2% by weight, or at least 5% by weight. In some embodiments, the initial and / or sterile iodine composition contains a pH adjuster in a concentration ranging from 0.01% to 0.05% by weight, 0.01% to 0.1% by weight, 0.01% to 0.5% by weight, 0.01% to 1% by weight, 0.01% to 2% by weight, 0.01% to 5% by weight, 0.05% to 0.1% by weight, 0.05% to 0.5% by weight, 0.05% to 1% by weight, 0.05% to 2% by weight, 0.05% to 5% by weight, 0.1% to 0.5% by weight, 0.1% to 1% by weight, 0.1% to 2% by weight, 0.1% to 5% by weight, 0.5% to 1% by weight, 0.5% to 2% by weight, 0.5% to 5% by weight, or 1% to 5% by weight.

[0061] In some embodiments, the initial and / or sterile iodofore composition includes one or more additional components. In certain embodiments, the initial and / or sterile iodofore composition includes one or more surfactants. A non-limiting example of a suitable surfactant is nonoxynol-9. In certain embodiments, the initial and / or sterile iodofore composition includes one or more thickeners and / or gelling agents. Non-limiting examples of suitable thickeners and / or gelling agents include hydroxypropylcellulose, simethicone, sodium carboxymethylcellulose, and polyethylene glycol ("PEG"). In certain embodiments, the initial and / or sterile iodofore composition includes one or more irritation reducers. Non-limiting examples of suitable irritation reducers include glycerin, petroleum jelly, mineral oil, and glycerol. In some embodiments, the initial and / or sterile iodofore composition further includes one or more dyes and / or emulsifiers. In some embodiments, the iodofore composition includes one or more components that are advantageous for enhancing polymer stability. In certain cases, one or more components of an iodophore composition may perform multiple functions (for example, a single component may both reduce irritation and enhance polymer stability).

[0062] The iodine phore compositions described herein may be administered in any preferred amount. In some embodiments, the amount of iodine phore composition administered to the patient is at least 0.01 mL, at least 0.05 mL, at least 0.1 mL, at least 0.5 mL, at least 0.67 mL, at least 0.75 mL, at least 1 mL, at least 1.5 mL, at least 3 mL, at least 5 mL, at least 10 mL, at least 10.5 mL, at least 13 mL, at least 26 mL, at least 30 mL, at least 60 mL, or at least 100 mL. In some embodiments, the amount of iodine composition administered to the patient is 0.01 mL to 0.1 mL, 0.01 mL to 0.5 mL, 0.01 mL to 1 mL, 0.01 mL to 3 mL, 0.01 mL to 5 mL, 0.01 mL to 10 mL, 0.01 to 13 mL, 0.01 to 30 mL, 0.01 mL to 60 mL, 0.01 mL to 100 mL, 0.1 mL to 1 mL, 0.1 mL to 3 mL, 0.1 mL to 5 mL, 0.1 mL to 10 mL, 0.1 mL to 13 mL, 0 The ranges are 0.1mL to 30mL, 0.1mL to 60mL, 0.1mL to 100mL, 1mL to 5mL, 1mL to 10mL, 1mL to 13mL, 1mL to 30mL, 1mL to 60mL, 1mL to 100mL, 5mL to 10mL, 5mL to 13mL, 5mL to 30mL, 5mL to 60mL, 5mL to 100mL, 10mL to 30mL, 10mL to 60mL, 10mL to 100mL, 30mL to 60mL, 30mL to 100mL, or 60mL to 100mL.

[0063] The iodine compositions described herein may be administered using any applicator known in the art. Examples of suitable applicators are described in U.S. Patent No. 7,993,066 by Flores et al., filed May 18, 2010, entitled "Liquid Applicator and Method for Reducing the Concentration of By-Products from Antiseptic," and U.S. Patent No. 9,757,551 by Degala et al., filed October 4, 2013, entitled "Antiseptic Applicator" (the contents of which are incorporated herein by reference in their entirety for all purposes). [Examples]

[0064] Example 1 In this example, the D-value (i.e., the time required for a 1 log reduction in the number of challenge organisms Geobacillus stearothermophilus) at three temperatures (105°C, 110°C, and 115°C) was determined for the Prevail-FX® formulation (i.e., an iodophore composition containing PVP-I) containing 8.3% povidone-iodine in 72.5% isopropanol) and compared with the D-values ​​of (1) a solution of 70% isopropanol and (2) the ChloraPrep® formulation (i.e., an antiseptic formulation containing two active ingredients) containing 2% chlorhexidine gluconate in 70% isopropanol.

[0065] [Table 1]

[0066] The D-values ​​in the 70% isopropanol solution were approximately twice as high as those found in the Prevail-FX® formulation at all three temperatures investigated, more than five times higher at 110°C, and more than ten times higher at 105°C, as demonstrated by the results shown in Table 1. These results demonstrate that the unique sterilization range of the Prevail-FX® alcoholic PVP-I solution cannot be explained by the 70% isopropanol solution.

[0067] The results shown in Table 1 demonstrate that the sterilization D value of ChloraPrep® was significantly higher than that of Prevail-FX® in an alcoholic PVP-I solution. Like Prevail-FX®, ChloraPrep® contains two active antimicrobial agents: chlorhexidine gluconate and isopropanol. These results demonstrate that the unique sterilization range of the Prevail-FX® formulation cannot be explained by the presence of two active ingredients. Milder sterilization conditions offer a unique opportunity to preserve potency and other key formulation attributes.

[0068] Example 2 In this embodiment, an oil bath was used to simulate the efficient heat transfer characteristics of a moist heat sterilization process (i.e., a cascading water sterilization process). Samples of six test formulations were airtightly sealed in glass ampoules. Each glass ampoule, with a maximum capacity of approximately 10 mL, contained approximately 5–8 mL of one of the six test formulations. Each glass ampoule was formed from USP type I borosilicate glass and had a diameter of 19 mm. The glass ampoules were then immersed for a specified time in a recirculating oil bath pre-equilibrated to a set temperature, rapidly removed, and quenched in a cold water bath before chemical analysis. The temperature of the formulations in the glass ampoules was estimated to reach thermal equilibrium with the recirculating oil in less than approximately 30 seconds.

[0069] Six formulations containing povidone-iodine were exposed to 110°C and 115°C regimens as a function of time, and the percentage of available iodine remaining in the solution was measured by titration with sodium thiosulfate. The results at 110°C are shown in Table 2 and Figure 3A, and the results at 115°C are shown in Table 3 and Figure 3B.

[0070] [Table 2]

[0071] [Table 3]

[0072] The decrease in the percentage of available iodine as a function of time at 110°C and 115°C is demonstrated from Tables 2 and 3, along with Figures 3A and 3B.

[0073] In addition, the percentage of available iodine in the same six formulations was compared at 110°C for 3 minutes and at 121°C for 15 minutes. These results are shown in Table 4.

[0074] [Table 4]

[0075] These results demonstrate that heating the iodophore composition at 110°C for 3 minutes yields a higher percentage of usable iodine than heating the same composition at 121°C for 15 minutes.

[0076] Example 3 In this example, the pH values ​​of various formulations were investigated before and after heat treatment. This example demonstrates that heating the PVP-I formulation at 110°C for 3 minutes or 12 minutes generally has less effect on pH than heating the same formulation at 121°C for 15 minutes. This example also demonstrates that heating the PVP-I formulation at 110°C for 3 minutes generally results in a smaller pH change than heating the same formulation at 110°C for 12 minutes.

[0077] The results are shown in Tables 5 and 6.

[0078] [Table 5]

[0079] [Table 6]

[0080] Comparative Example 1 In this comparative example, the viscosity of Prevail® gel containing 5% povidone-iodine in 62% ethanol was examined before and after heating at 121°C for 20 minutes. The results are shown in Table 7. These results demonstrate that solution sterilization under these conditions significantly reduced the viscosity of the product.

[0081] [Table 7]

[0082] Comparative Example 2 In this comparative example, the appearance of the iodophore composition after heat treatment was examined. A 3M DuraPrep® formulation was heated at 121°C for 12 minutes. This heating resulted in the formation of a precipitate. One potential cause of precipitate formation is the loss of solubility of the polymeric excipient. This precipitate formation is an undesirable consequence of solution sterilization and would be significantly reduced or eliminated by using less thermally stressful sterilization conditions at 110°C or 115°C.

[0083] While several embodiments of the present invention have been described and illustrated herein, a variety of other means and / or structures for performing the functions described herein and / or obtaining one or more of the results and / or benefits will be readily foreseeable to those skilled in the art. Each of such variations and / or modifications is considered to be within the scope of the present invention. More generally, all parameters, dimensions, materials and configurations described herein are intended to be illustrative, and it will be readily apparent to those skilled in the art that the actual parameters, dimensions, materials and / or configurations will depend on the specific one or more applications in which the teachings of the present invention are used. Those skilled in the art will be able to recognize or confirm many equivalents of the specific embodiments described herein. Therefore, the above embodiments are presented merely as examples and should be understood to mean that the present invention can be practiced in ways other than those specifically described and claimed within the scope of the appended claims and their equivalents. The present invention relates to each of the individual features, systems, articles, materials and / or methods described herein. In addition, any combination of two or more such features, systems, articles, materials and / or methods is within the scope of the present invention, provided that such features, systems, articles, materials and / or methods are not inconsistent with each other.

[0084] In this specification and in the claims, the indefinite articles “a” and “an” should be understood to mean “at least one” unless otherwise clearly specified.

[0085] As used herein and in the claims, the phrase “and / or” should be understood to mean “one or both” of the thus linked elements, that is, elements that exist conjunctively in some cases and elements that exist disjunctly in other cases. Unless otherwise clearly indicated, other elements not specifically identified by the phrase “and / or” may exist, whether or not they are related to the specifically identified elements. As a non-restrictive example, when the reference term “A and / or B” is used in combination with open-ended language such as “including,” it may mean, in one embodiment, A instead of B (optionally including elements other than B), in another embodiment, B instead of A (optionally including elements other than A), and in yet another embodiment, both A and B (optionally including other elements), and so on.

[0086] As used herein and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as inclusive; that is, including at least one of several elements or elements of the list, and optionally additional items not in the list. Only terms that are clearly contradictory, such as “only one of” or “exactly one of” or, as used in the claims, “consisting of,” shall mean including several elements or elements of the list, and exactly one of them. As used in the claims, “essentially consisting of” shall have its usual meaning as used in the field of patent law.

[0087] As used herein and in the claims, the phrase “at least one” when referring to a list of one or more elements should be understood to mean at least one element selected from any one or more elements in the list of elements, but not necessarily including at least one of every element specifically enumerated in the list of elements, and not excluding any combination of elements in the list of elements. Furthermore, this definition allows for the optional presence of elements other than those specifically identified in the list of elements referred to by the phrase “at least one,” whether or not they are related to the specifically identified elements. Therefore, as a non-limiting example, "at least one of A and B" (or equally "at least one of A or B" or equally "at least one of A and / or B") may mean, in one embodiment, at least one A, with B absent (optionally including elements other than B) and optionally including two or more A's; in another embodiment, at least one B, with A absent (optionally including elements other than A) and optionally including two or more B's; and in yet another embodiment, at least one B (optionally including other elements), with two or more A's and optionally including two or more B's.

[0088] In the claims, as in the foregoing specification, transitional phrases such as “include,” “encompass,” “carry,” “have,” “contain,” “accompany,” and “hold” should all be understood as open-ended. Only the transitional phrases “consist of” and “essentially consist of” shall be considered closed or semi-closed transitional phrases, respectively, as specified in Section 2111.03 of the U.S. Patent and Trademark Office Manual of Patent Examination Procedure.

Claims

1. A method for producing a sterile iodine phore composition, comprising heating the iodine phore composition to a sterile temperature in the range of 65°C to 121°C over a sterile time period in the range of 1.5 minutes to 15 minutes, The sterile iodophore composition is a sterile iodophore composition comprising at least 5.0% by weight of an iodine-polymer composite, and 10 －３ A method having the following sterility assurance levels and a viscosity of 3000 cP or less.

2. The iodophore composition is heated, 10 －３ A sterilization method comprising generating a sterile iodine phore composition having the following levels of sterility assurance, wherein heating the iodine phore composition comprises exposing the iodine phore composition to a sterile temperature in the range of 65°C to 121°C for a sterilization time range of 1.5 minutes to 15 minutes.

3. The method according to claim 1, wherein the iodophore composition comprises an iodine-polymer composite.

4. The method according to claim 3, wherein the iodine-polymer composite is PVP-I or iodine povacrilex.

5. The method according to claim 4, wherein the iodine-polymer composite is PVP-I.

6. The method according to any one of claims 1, 3 to 5, wherein the sterile iodophore composition comprises an iodine-polymer composite.

7. The method according to claim 6, wherein the iodine-polymer composite is PVP-I or iodine povacrilex.

8. The method according to claim 7, wherein the iodine-polymer composite is PVP-I.

9. The sterile iodine composition, 10 －６ The method according to any one of claims 1, 3 to 8, having the following levels of sterility assurance.

10. The method according to any one of claims 1, 3 to 9, wherein the sterile iodine composition comprises water.

11. The method according to claim 10, wherein the sterile iodine composition contains water at a concentration of at least 10% by weight.

12. The method according to claim 11, wherein the sterile iodine composition contains water at a concentration of at least 50% by weight.

13. The method according to claim 12, wherein the sterile iodine composition contains water at a concentration of at least 70% by weight.

14. The method according to any one of claims 1, 3 to 13, wherein the sterile iodine composition comprises alcohol.

15. The method according to claim 14, wherein the alcohol is isopropanol or ethanol.

16. The sterilization method according to claim 2, wherein the sterilization temperature is in the range of 85°C to 115°C.

17. The sterilization method according to claim 16, wherein the sterilization temperature is in the range of 110°C to 115°C.

18. The sterilization method according to any one of claims 2, 16 to 17, wherein the sterilization time range is in the range of 1.5 minutes to 10 minutes.

19. The sterilization method according to claim 18, wherein the sterilization time range is in the range of 1.5 minutes to 6 minutes.

20. The sterilization method according to claim 19, wherein the sterilization time range is in the range of 1.5 minutes to 3 minutes.

21. The method according to any one of claims 1, 3 to 15, wherein the iodine phore composition has a first concentration of available iodine, and the sterile iodine phore composition has a second concentration of available iodine, and the percentage difference between the first concentration of available iodine and the second concentration of available iodine is 8% or less.

22. The method according to claim 21, wherein the percentage difference between the first concentration of available iodine and the second concentration of available iodine is 5% or less.

23. The method according to claim 21 or 22, wherein the absolute value of the difference between the first concentration of available iodine and the second concentration of available iodine is 0.1% by weight or less.

24. The method according to any one of claims 21 to 23, wherein the second concentration of available iodine is at least 0.5%.

25. The method according to any one of claims 1, 3 to 15, 21 to 24, wherein the iodine phore composition has a first pH, and the sterile iodine phore composition has a second pH, and the absolute value of the difference between the first pH and the second pH is 0.5 or less.

26. The method according to claim 25, wherein the absolute value of the difference between the first pH and the second pH is 0.2 or less.

27. The method according to claim 25 or 26, wherein the second pH is in the range of 1.5 to 6.

5.

28. The method according to claim 27, wherein the second pH is in the range of 2.0 to 5.

5.

29. The method according to any one of claims 1, 3 to 15, 21 to 28, wherein the iodine phore composition has a first viscosity, and the sterile iodine phore composition has a second viscosity, and the percentage difference between the first viscosity and the second viscosity is 50% or less.

30. The sterilization method according to any one of claims 2, 16 to 20, further comprising providing a container for containing the iodine phore composition.

31. The sterilization method according to any one of claims 2, 16 to 20, 30, wherein exposing the iodine phore composition to the sterilization temperature over the sterilization period includes exposing at least a portion of the container containing the iodine phore composition to the heated liquid.

32. The sterilization method according to claim 31, wherein the heated liquid includes water.

33. The sterilization method according to any one of claims 2, 16 to 20, or 30 to 32, further comprising heating the iodine phore composition using a cascading water sterilizer.

34. The sterilization method according to any one of claims 2, 16 to 20, 30 to 33, wherein exposing the iodine phore composition to the sterilization temperature over the sterilization period comprises bringing at least a portion of the container containing the iodine phore composition into contact with a cascading waterfall stream generated by a cascading water sterilizer over the duration of the sterilization period.

35. The sterilization method according to any one of claims 2, 16 to 20, or 30 to 34, further comprising ending exposure to the sterilization temperature when the sterilization time period has elapsed.

36. The sterilization method according to any one of claims 30 to 35, wherein the container is sealed during the heating step.

37. The sterilization method according to any one of claims 30 to 36, wherein the container includes glass.

38. The sterilization method according to any one of claims 30 to 37, wherein the container is a pouch.

39. The sterilization method according to claim 38, wherein the pouch contains a polymer.

40. The sterilization method according to claim 38 or 39, wherein the pouch includes a metal laminate.

41. The method according to any one of claims 1, 3 to 15, or 21 to 29, wherein the sterile iodine composition contains alcohol at a concentration of at least 50% by weight.

42. The method according to claim 41, wherein the sterile iodine composition contains alcohol at a concentration of at least 70% by weight.

43. The method according to any one of claims 1, 3 to 15, 21 to 29, or 41 to 42, wherein the sterile iodine composition contains PVP-I at a concentration of at least 5% by weight.

44. The method according to claim 43, wherein the sterile iodine composition contains PVP-I at a concentration of at least 7% by weight.

45. The method according to any one of claims 1, 3 to 15, 21 to 29, or 41 to 44, wherein the sterile iodine phore composition comprises iodine povacrilex at a concentration of at least 5% by weight.

46. The method according to claim 45, wherein the sterile iodine phore composition comprises iodine povacrilex at a concentration of at least 7% by weight.

47. The method according to any one of claims 1, 3 to 15, 21 to 29, or 41 to 46, wherein the sterile iodine composition contains available iodine at a concentration of at least 0.5% by weight.

48. The method according to any one of claims 1, 3 to 15, 21 to 29, or 41 to 47, wherein the sterile iodine composition contains available iodine in a concentration ranging from 0.5% to 1% by weight.

49. The method according to any one of claims 1, 3 to 15, 21 to 29, or 41 to 48, wherein the sterile iodine phore composition comprises one or more surfactants, one or more polymer-forming agents, and / or one or more pH adjusters.

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