Compressible device containing sterile rinsing fluid

Abstract

Described is a compressible device having a compressible body portion containing a sterile rinsing fluid and a dispensing portion for dispensing the sterile rinsing fluid contained in the compressible body portion, the compressible device having been subjected to a gamma sterilization treatment sufficient to provide the sterile rinsing fluid, and the compressible device having a degradation on-set temperature after the gamma sterilization treatment that is no more than about 2% lower from an initial degradation on-set temperature of the compressible device prior to the gamma sterilization treatment. Also included is a method of making a compressible device as described.

Description

COMPRESSIBLE DEVICE CONTAINING STERILE RINSING FLUIDCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 669,179, which was filed on July 9, 2024, the contents of which are incorporated expressly herein by reference in their entirety.TECHNICAL FIELD

[0002] The present disclosure is directed to compressible devices containing a rinsing fluid and methods of making the same.BACKGROUND

[0003] Irrigation solutions are used during and after surgical procedures in order to remove and minimize any debris or microbial contamination that might be present. When not using a battery-operated device, the effectiveness of the irrigation procedure is dependent on the ability to generate mechanical force of the irrigation solution through manual compression of an irrigation container.

[0004] Currently available ready-to-use surgical wound irrigation solutions require healthcare practitioners to generate mechanical force on a container by manually compressing the container, thus expelling the irrigation solution with force into the surgical cavity. The manual compression of the container can result in a wide ranges of force being applied to the container and therefore requires a robust design for the product. However, the design of such products is complicated by the requirement that the ready-to-use irrigation product contains a sterile solution, as sterility of the solution is mandatory for increased patient safety.SUMMARY

[0005] The present disclosure is directed to a compressible device containing a sterile rinsing fluid, the compressible device comprising one or more polymeric materials. According to some aspects, the compressible device has been subjected to a gamma sterilization treatment sufficient to sterilize the rinsing fluid contained therein. The compressible device of the present disclosure may further have a degradation on-set temperature after the gamma sterilization treatment that is within a certain range of an initial degradation on-set temperature of the compressible device prior to gammasterilization. Also disclosed herein are methods for making and methods of using the compressible devices disclosed herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0006] FIG. 1 shows an example compressible device according to aspects of the present disclosure.DETAILED DESCRIPTION

[0001] The present disclosure is directed to a compressible device containing a sterile rinsing fluid, the compressible device comprising one or more polymeric materials. According to some aspects, the compressible device has been subjected to a gamma sterilization treatment sufficient to sterilize the rinsing fluid contained therein. The compressible device of the present disclosure may further have a degradation on-set temperature after the gamma sterilization treatment that is within a certain range of an initial degradation on-set temperature of the compressible device prior to gamma sterilization. Also disclosed herein are methods for making and methods of using the compressible devices disclosed herein.

[0002] As used herein, the term “fluid” refers to a substance that has no fixed shape, such as a liquid or a gas. As used herein, the term “rinsing fluid” refers to a fluid suitable for a rinsing process. Non-limiting examples of rinsing processes include processes for flushing of a body cavity, a surgical cavity, and / or an external wound and processes involving the flushing of a medical device prior to contact with a subject. Example medical devices include, but are not limited to, surgical equipment and medical implants.

[0003] According to some aspects, the rinsing fluid may include an antiseptic solution. As used herein, an “antiseptic solution” refers to a solution including at least a solvent and one or more antiseptic agents. According to some aspects, the antiseptic solution is an aqueous solution. As used herein, the term “aqueous solution” refers to a solution wherein the solvent includes at least a majority of water. It should be understood that in some examples, the solvent may consist of water. According to some aspects, the antiseptic solution is an alcoholic solution. As used herein, the term “alcoholic solution” refers to a solution wherein the solvent includes at least a majority of an alcoholic component. It should be understood that in some examples, the solvent may consist of one or more alcoholic components. Non-limiting examples of alcoholic componentsinclude, but are not limited to, ethanol, isopropyl alcohol, n-propanol, and combinations thereof. According to some aspects, the solvent may include both water and an alcoholic component. In some non-limiting examples, the solvent may include about 90% (v / v) of an alcoholic component and the remaining volume water, optionally about 80% (v / v) of an alcoholic component and the remaining volume water, optionally about 70% (v / v) of an alcoholic component and the remaining volume water, optionally about 60% (v / v) of an alcoholic component and the remaining volume water, optionally about 50% (v / v) of an alcoholic component and the remaining volume water, optionally about 40% (v / v) of an alcoholic component and the remaining volume water, optionally about 30% (v / v) of an alcoholic component and the remaining volume water, optionally about 20% (v / v) of an alcoholic component and the remaining volume water, and optionally about 10% (v / v) of an alcoholic component and the remaining volume water.

[0004] In some non-limiting examples, the solvent may include about 90% (v / v) or less of an alcoholic component and the remaining volume water, optionally about 80% (v / v) or less of an alcoholic component and the remaining volume water, optionally about 70% (v / v) or less of an alcoholic component and the remaining volume water, optionally about 60% (v / v) or less of an alcoholic component and the remaining volume water, optionally about 50% (v / v) or less of an alcoholic component and the remaining volume water, optionally about 40% (v / v) or less of an alcoholic component and the remaining volume water, optionally about 30% (v / v) or less of an alcoholic component and the remaining volume water, optionally about 20% (v / v) or less of an alcoholic component and the remaining volume water, and optionally about 10% (v / v) or less of an alcoholic component and the remaining volume water.

[0005] In one non-limiting example, the antiseptic agent may include a cationic molecule (i.e., a molecule having a positive charge), such as a cationic surfactant or a cationic biguanide derivative (i.e., a compound derived from biguanide). According to some aspects, the antiseptic agent may include a bis-(dihydropyridinyl)-decane derivative (i.e., a compound derived from bis-(dihydropyridinyl)-decane). According to some aspects, the antiseptic agent may include an octenidine salt and / or a chlorhexidine salt. According to some aspects, the antiseptic agent may include alexidine, octenidine dihydrochloride, chlorhexidine gluconate, or a combination thereof.

[0006] Additionally or alternatively, the antiseptic agent may include iodine. According to some aspects, the iodine may be provided as an iodine complex, such aspovidone-iodine (PVPI), nonylphenoxy-(ethyleneoxy)-iodine, polyethylene oxy polyprop leneoxy-iodine, undecoylinium-chloride-iodine, iodine povacrylex, and combinations thereof.

[0007] Additionally or alternatively, the antiseptic agent may include an oxidant (i.e., an oxidizing agent). Non-limiting examples of oxidants according to the present disclosure include, but are not limited to, sodium hypochlorite, hydrogen peroxide, and combinations thereof.

[0008] Additionally or alternatively, the antiseptic agent may include a quaternary ammonium salt. Non-limiting examples of quaternary ammonium salts include benzalkonium chloride, benzethonium chloride, methylbenzethonium chloride, cetalkonium chloride, cetylpyridinium chloride, cetrimonium, cetrimide, dofanium chloride, tetraethylammonium bromide, didecyldimethylammonium chloride, domiphen bromide, and combinations thereof.

[0009] Additionally or alternatively, the antiseptic agent may include one or more surfactants. The one or more surfactants may include an ionic surfactant, a non-ionic surfactant, a zwitterionic surfactant, or a combination thereof. In some non-limiting examples, the one or more surfactants may include sodium lauryl sulfate, sodium laureth sulfate, citric acid, sodium citrate, oleic acid, cetylpyridinium chloride, soya lecithin, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (10) stearyl ether, polyoxyethylene (2) oleyl ether, polyoxyethylene-polyoxypropylene- ethylenediamine block copolymer, polyoxypropylene-polyoxyethylene block copolymers, castor oil ethoxylate, polyoxyethylene nonylphenol ether, Cremophor, 2- (2-ethoxy-ethoxy) ethanol, salts thereof, and mixtures thereof.

[0010] Additionally or alternatively, the antiseptic agent may include one or more antibiotics. Non-limiting examples of antibiotics include cefazolin, vancomycin, gentamicin, bacitracin, and combinations thereof.

[0011] According to some aspects, the rinsing fluid may include any combinations of the antiseptic agents as described herein.

[0012] The antiseptic agent and / or combination of antiseptic agents may have an antimicrobial activity sufficient to provide an acceptable log reduction of microbes in a certain time period. It should be understood that as used herein, the term “microbe” may refer to any microorganism to be killed and / or removed as a result of rinsing. Example microbes include bacteria, fungi, viruses, and combinations thereof.

[0013] Example bacteria include, but are not limited to, Streptococcus mutans, S. pyogenes (group A P-hemolytic streptococci), S. salivarius, S. sanguis, Staphylococcus aureus S. epidermidis, S. haemolyticus, S. hominis, S. simulans, S. saprophyticus, methicillin oxacillin-resislanl (MRSA / ORSA) and methicillin / oxacillin-susceptible Staphylococci (MSSA / OSSA), Enterococcus (e.g., E. faecalis E. faecium, andE. hirae), vancomycin-resistant Enterococcus (VRE) and vancomycin-susceptible Enterococcus (VSE), Bacteroides fragilis, Propionibacterium acnes, Clostridium difficile (spore and vegetative cells), Selenomonas, Pseudomonas aeruginosa, Escherichia coli, Burkholderia cepacia, Proteus mirabilis, Gardnerella vaginalis, Klebsiella aerogenes, K. pneumoniae, K. pneumoniae multidrug resistant (MDR), Acinetobacter baumannii, A. baumannii MDR, Achromobacter xylosoxidans . Micrococus luteus, Ralstonia pickettii, Haemophilus influenza, and Serratia marcescens.

[0014] Example fungi include, but are not limited to, Aspergillus niger, Candida albicans, C. aurus, C. dubliniensis, C. glabrata (formerly Torulopsis glabrata), C. guillermondii, C. kefyr (formerly C. pseudotropicalis), C. krusei, C. lusitaniae, C. tropicalis, Epidermophyton floccosum, Microsporum gypseum, M. canis, and Trichophyton mentagrophytes .

[0015] Example viruses include, but are not limited to, those having a lipid component in their outer coat or have an outer envelope such as cytomegalovirus (CMV), human immunodeficiency virus (HIV), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), influenza virus, parainfluenza virus, variola virus (smallpox virus), vaccinia, norovirus, and coronavirus.

[0016] However, it should be understood that the rinsing fluid is not necessarily an antiseptic solution as described herein and may be any medically acceptable fluid sufficient for performing a rinsing process as described herein. In one non-limiting example, the rinsing fluid may include a saline solution. The saline solution may include water and sodium chloride in a medically acceptable concentration, such as between about 0.1 and 1%, w / v, optionally about 0.45% w / v, and optionally about 0.9% w / v.

[0017] According to some aspects, the rinsing fluid may include a buffer system having one or more buffer components. As used herein, the term “buffer system” refers to a component of a rinsing fluid that provides a resistance to significant change in pH caused by a strong acid or base. A buffer system may include two or more buffer components, such as a weak acid and its conjugate base. A buffer system may providea resistance to a significant pH change by interacting with a strong acid or strong base in a rinsing fluid, thereby at least partially preventing the pH of the rinsing fluid from changing significantly.

[0018] Generally, a buffer system has one or more buffer ranges wherein the buffer system has the ability to provide resistance to significant pH change. When a rinsing fluid having the buffer system has a pH inside the buffer system’s buffer range, the pH of the rinsing fluid will not change significantly with the addition of equimolar amounts of a strong acid or strong base.

[0019] The buffer range of a buffer system is related to the acid dissociation constant (Ka) of one or more weak acids included by the buffer system. The term “acid dissociation constant” refers to the equilibrium constant of a dissociation reaction of an acid. The midpoint of a buffer range for a buffer system is generally about the logarithmic measure of the acid dissociation constant (i.e., the pKa, equal to -logioKa) of a weak acid included by the buffer system.

[0020] According to some aspects, the one or more buffer components may include the acid or salt forms of one or more of lactate, phosphate, borate, tartrate, glutamate, malate, citrate, gluconate, benzoate, succinate, acetate, glycine, and aspartate. According to some aspects, the one or more buffer components may include lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, strontium hydroxide, sodium phosphate dibasic dihydrate, and / or barium hydroxide.

[0021] According to some aspects, the rinsing fluid may include a pH adjusting agent. The term “pH adjusting agent” refers to a component of a rinsing fluid that modifies the rinsing fluid’s pH.

[0022] According to some aspects, the pH adjusting agent may include one or more of acetic acid, adipic acid, ascorbic acid, citric acid, hydrochloric acid, lactic acid, malic acid, monopotassium phosphate, monosodium phosphate, phosphoric acid, pyrophosphoric acid, succinic acid, sulfuric acid, tartaric acid, and solutions thereof.

[0023] According to some aspects, the rinsing fluid is sterile. As used herein, “sterile” may mean “7 day sterility” as tested following the procedures described in U.S. Pharmacopeial Convention (USP) Chapter 55 “Biological Indicators - Resistance Performance Tests,” USP 36; Official from May 1, 2013. Additionally or alternatively, “sterile” may mean completely free of microbes immediately following a sterilization treatment. According to some aspects, Geobacillus stearothermophilus may be used asa test microbe. Thus, according to some aspects, a sterile solution would have no growth of Geobacillus stearothermophilus shown by the ‘7 day sterility’ testing described above. According to some aspects, a solution inoculated with Geobacillus stearothermophilus would be completely free of viable Geobacillus stearothermophilus immediately following a sterilization treatment. According to some aspects, the sterilization treatment may include gamma sterilization. In some examples, the sterilization treatment is terminal sterilization treatment, that is, a sterilization treatment of a final product (e.g., a compressible device having a rinsing fluid contained therein). It should be understood that a terminal sterilization treatment may thus eliminate the need for an aseptic fill process.

[0024] The rinsing fluid as described herein may be contained within a compressible device. As used herein, the term “compressible” refers to the ability to reversibly reduce in volume without unacceptable changes, such as an unacceptable permanent change to size, to shape, and / or to one or more of the properties as described herein

[0025] According to some aspects, the compressible device may be at least partially formed from one or more polymeric materials. For example, the compressible body portion may be formed from the one or more polymeric materials disclosed herein, while the dispensing portion may be made of the same or different polymeric material, or a wholly different (non-polymeric) material. Example polymeric materials useful for at least the compressible body portion according to the present disclosure include, but are not limited to, high-density polyethylene (HDPE), low-density polyethylene (LDPE), polystyrene, polyvinyl chloride (PVC), polyethylene terephthalate (PET), and any combination thereof. According to some aspects, the polymeric material may include one or more polymers having a chemical structure that is capable of supporting and / or quenching a radical so as to reduce and / or eliminate radical cross-linking of the polymeric material.

[0026] FIG. 1 shows one example of a compressible device according to aspects of the present disclosure. In particular, FIG. 1 shows a device 100 having a compressible body portion 101 configured to contain a rinsing fluid as described herein. Device 100 further includes a dispensing portion 102 configured to dispense the rinsing fluid contained in compressible body portion 101, such as by compressing (e.g., squeezing) compressible body portion 101. It should be understood, however, that the compressible device according to the present disclosure is not necessarily limited to the example shown in FIG. 1. For example, the compressible device may include one or more featuresdescribed in U.S. Patent Publication No. 2022 / 0118169, the contents of which are incorporated herein in their entirety by reference.

[0027] According to some aspects, the compressible device may be provided as a “ready-to-use” device. As used herein, a “ready-to-use” device refers to a device that requires no setup steps prior to its use (e.g., prior to performing a rinsing process as described herein). For example, a ready-to-use compressible device according to the present disclosure may include a compressible device having a sterile rinsing fluid contained therein such that using the compressible device includes no priming or filling steps.

[0028] According to some aspects, the compressible device has been subjected to a gamma sterilization treatment sufficient to sterilize a rinsing fluid contained therein. Optionally, all or a portion of the compressible device (such as the compressible body portion) may have been sterilized by the gamma sterilization treatment.

[0029] According to some aspects, the compressible device may have a degradation on-set temperature after the gamma sterilization treatment that is within a certain range of an initial degradation on-set temperature of the compressible device prior to gamma sterilization. As used herein, a “degradation on-set temperature” refers to the temperature at which degradation of a polymeric material may be observed using thermal gravimetric analysis (TGA), i.e., the temperature corresponding with the peak of the first derivative, which represents the greatest rate of change in the weight loss curve with temperature.

[0030] According to some aspects, the compressible device may have an initial degradation on-set temperature prior to being subjected to a gamma sterilization treatment as described herein. In some non-limiting examples, the initial degradation on-set temperature may be at least 365°C, optionally at least 370°C, optionally at least 375°C, optionally at least 380°C, optionally at least 385°C, optionally at least 390°C, optionally at least 395°C, optionally at least 400°C, optionally at least 405°C, optionally at least 410°C, optionally at least 415°C, optionally at least 420°C, optionally at least 425°C, optionally at least 430°C, optionally at least 435°C, optionally at least 440°C, optionally at least 445°C, and optionally at least 450°C.

[0031] According to some aspects, the compressible device may have a degradation on-set temperature after being subjected to a gamma sterilization treatment that is within a certain range of the initial degradation on-set temperature. In some nonlimiting examples, the degradation on-set temperature after gamma sterilizationtreatment may be at least 365°C, optionally at least 370°C, optionally at least 375°C, optionally at least 380°C, optionally at least 385°C, optionally at least 390°C, optionally at least 395°C, optionally at least 400°C, optionally at least 405°C, optionally at least 410°C, optionally at least 415°C, optionally at least 420°C, optionally at least 425°C, optionally at least 430°C, optionally at least 435°C, optionally at least 440°C, optionally at least 445°C, and optionally at least 450°C.

[0032] According to some aspects, the compressible device may have a degradation on-set temperature after the gamma sterilization treatment that is no more than about 3% lower than the initial degradation on-set temperature, optionally no more than about 2.9% lower, optionally no more than about 2.8% lower, optionally no more than about 2.7% lower, optionally no more than about 2.6% lower, optionally no more than about 2.5% lower, optionally no more than about 2.4% lower, optionally no more than about 2.3% lower, optionally no more than about 2.2% lower, optionally no more than about 2.1% lower, optionally no more than about 2% lower, optionally no more than about 1.9% lower, optionally no more than about 1.8% lower, optionally no more than about 1.7% lower, optionally no more than about 1.6% lower, optionally no more than about 1.5% lower, optionally no more than about 1.4% lower, optionally no more than about 1.3% lower, optionally no more than about 1.2% lower, optionally no more than about 1.1% lower, optionally no more than about 1% lower, optionally no more than about 0.9% lower, optionally no more than about 0.8% lower, optionally no more than about 0.7% lower, optionally no more than about 0.6% lower, optionally no more than about 0.5% lower, optionally no more than about 0.4% lower, optionally no more than about 0.3% lower, optionally no more than about 0.2% lower, and optionally no more than about 0.1% lower.

[0033] Also disclosed herein are methods for making the compressible devices disclosed herein. According to some aspects, the method may include providing a rinsing fluid within a compressible device as described herein, and performing a sterilization treatment on the compressible device sufficient to sterilize the compressible device and / or a portion thereof and / or the rinsing fluid contained therein. According to some aspects, the sterilization treatment may include a gamma radiation sterilization treatment. In some non-limiting examples, a gamma radiation sterilization treatment may include subjecting an object (e.g., a compressible device having a rinsing fluid contained therein) to gamma radiation at a dosage and / or for a time period sufficient to sterilize the object.

[0034] In some non-limiting examples, gamma radiation sterilization treatment may include subjecting an object (e.g., a compressible device having a rinsing fluid contained therein) to gamma radiation at a dosage of between about 15 and 45 kGy, optionally between about 20 and 40 kGy, and optionally between about 22 and 38 kGy. In some non-limiting examples, gamma radiation sterilization treatment may include subjecting an object to gamma radiation at a dosage of at least about 15 kGy. In some non-limiting examples, gamma radiation sterilization treatment may include subjecting an object to gamma radiation at a dosage of no more than about 45 kGy.

[0035] Also disclosed herein are methods of using a compressible device as disclosed herein, such as by compressing the compressible device to perform a rinsing process as described herein.

[0036] The present disclosure also includes kits having a compressible device containing a sterile rinsing fluid as described herein, the compressible device contained within a packaging.

[0037] While the aspects described herein have been described in conjunction with the example aspects outlined above, various alternatives, modifications, variations, improvements, and / or substantial equivalents, whether known or that are or may be presently unforeseen, may become apparent to those having at least ordinary skill in the art. Accordingly, the example aspects, as set forth above, are intended to be illustrative, not limiting. Various changes may be made without departing from the spirit and scope of the disclosure. Therefore, the disclosure is intended to embrace all known or later- developed alternatives, modifications, variations, improvements, and / or substantial equivalents.

[0038] Thus, the claims are not intended to be limited to the aspects shown herein, but are to be accorded the full scope consistent with the language of the claims, wherein reference to an element in the singular is not intended to mean “one and only one” unless specifically so stated, but rather “one or more.” All structural and functional equivalents to the elements of the various aspects described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the claims. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims. No claim element is to be construed as a means plus function unless the element is expressly recited using the phrase “means for.”

[0039] Herein, the recitation of numerical ranges by endpoints (e.g. between about 50: 1 and 1 : 1, between about 100 and 500 °C, between about 1 minute and 60 minutes) include all numbers subsumed within that range, for example, between about 1 minute and 60 minutes includes 21, 22, 23, and 24 minutes as endpoints within the specified range. Thus, for example, ranges 22-36, 25-32, 23-29, etc. are also ranges with endpoints subsumed within the range 1-60 depending on the starting materials used, temperature, specific applications, specific embodiments, or limitations of the claims if needed. The Examples and methods disclosed herein demonstrate the recited ranges subsume every point within the ranges because different synthetic products result from changing one or more reaction parameters. Further, the methods and Examples disclosed herein describe various aspects of the disclosed ranges and the effects if the ranges are changed individually or in combination with other recited ranges.

[0040] Further, the word “example” is used herein to mean “serving as an example, instance, or illustration.” Any aspect described herein as “example” is not necessarily to be construed as preferred or advantageous over other aspects. Unless specifically stated otherwise, the term “some” refers to one or more. Combinations such as “at least one of A, B, or C,” “at least one of A, B, and C,” and “A, B, C, or any combination thereof’ include any combination of A, B, and / or C, and may include multiples of A, multiples of B, or multiples of C. Specifically, combinations such as “at least one of A, B, or C,” “at least one of A, B, and C,” and “A, B, C, or any combination thereof’ may be A only, B only, C only, A and B, A and C, B and C, or A and B and C, where any such combinations may contain one or more member or members of A, B, or C. Nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims.

[0041] As used herein, the term “about” and “approximately” are defined to being close to as understood by one of ordinary skill in the art. In one non-limiting embodiment, the term “about” and “approximately” are defined to be within 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%.EXAMPLES

[0042] EXAMPLE I: Sterilizing Rinsing Fluids

[0043] The effect of gamma sterilization on a povidone iodine (PVP-I) solution within a polymeric device was evaluated using thermal gravimetric analysis (TGA). This methodology measures the on-set temperature for degradation of the polymeric deviceand therefore can provide insight into a potential change in the polymer itself. In particular, a change in the on-set temperature as measured by TGA indicates that a change to the polymer has occurred. A change in the TGA value would thus correspond with a potential adverse impact on the polymeric device, thereby reducing the performance of the device during manual compression of the same.

[0044] To perform the study, first, four containers were constructed from polypropylene (PP) and were filled with either a rinsing fluid (an aqueous 0.5% PVP-I solution) or water. Two of the containers were then sterilized by exposing them to gamma sterilization, and two of the containers were not sterilized as controls, as shown in Table 1. The containers were then analyzed using TGA, the results of which are also shown in Table 1.Table 1* Container weight corresponds to the weight of the empty container itself.

[0045] As shown in Table 1, sample 1 (i.e., containing water) showed minimal change (i.e., -1.2%) in the on-set temperature upon gamma sterilization compared with the nonsterilized control. It was thus concluded that gamma sterilization of a polypropylene container filled with water has minimal impact on the polymer itself. However, a significantly larger change in the degradation on-set temperature was observed upon gamma sterilization of the polypropylene containers filled with the 0.5% PVP-I solution. In particular, while the non-sterilized control had a degradation on-set temperature of 362.75°C, the gamma sterilized container of sample 2 had a more pronounced reduced degradation on-set temperature of 340.76°C (i.e., a -6.06%change). It was thus concluded that these conditions unexpectedly led to a change in the polypropylene polymer itself and therefore a change in the physical performance of the container manufactured with such a polymer should be expected. In that regard, given that a compressible device containing a rinsing fluid is generally subjected to tremendous force during manual compression, this change in the polymer could led to an adverse long-term performance for compressible devices.

[0046] Next, five containers were constructed from HDPE and were filled with a rinsing fluid (an aqueous 0.5% PVP-I solution), as shown in Table 2. Four of the containers were then sterilized by exposing them to gamma sterilization at the doses shown in Table 2, and one container was not sterilized as a control. The containers were then analyzed using TGA, the results of which are also shown in Table 2.Table 2* Container weight corresponds to the weight of the empty container itself.

[0047] As shown in Table 2, it was unexpectedly found that the HDPE containers having the 0.5% PVP-I solution showed virtually no change in the degradation on-set temperature upon gamma sterilization. In particular, sample 3 showed a change of only -0.06% compared with the non-sterilized control. This result was notably different from the change observed in the polypropylene containers and indicates that a compressibledevice having HDPE could preserve its physicochemical characteristics through gamma sterilization, thus providing improved long-term performance of such devices.

[0048] In addition, as shown by sample 4 of Table 2, the impact of the empty weight of the container on the degradation on-set temperature after gamma sterilization was minimal, as an increase in the weight of the empty container (corresponding to the container wall thickness) did not alter the measured degradation on-set temperature. This result supports the conclusion that the stability of the HDPE container filled with a PVP-I solution upon gamma sterilization is not dependent on the container wall thickness.

[0049] Finally, the results of samples 5 and 6 in Table 2 show that only a minor difference was observed in the change in degradation on-set temperature using ~24kGy and ~48kGy gamma sterilization doses. In fact, the difference in degradation on-set temperature for sample 6 (sterilized with a dose of ~48kGy) vs. the non-sterilized control was much less than the difference observed for sample 2 (the ~24kGy dosed polypropylene container) vs. the non-sterilized control. These results therefore strongly support the conclusion that HDPE is a more robust material of construction for a compressible device filled with a PVP-I solution that will undergo gamma sterilization.

Claims

WHAT IS CLAIMED IS:

1. A compressible device comprising: a compressible body portion containing a sterile rinsing fluid, and a dispensing portion configured to dispense the sterile rinsing fluid contained in the compressible body portion, wherein the compressible device has been subjected to a gamma sterilization treatment sufficient to provide the sterile rinsing fluid, and wherein the compressible device has a degradation on-set temperature after the gamma sterilization treatment that is no more than about 2% lower from an initial degradation on-set temperature of the compressible device prior to the gamma sterilization treatment.

2. The compressible device according to claim 1, wherein the sterile rinsing fluid comprises iodine.

3. The compressible device according to claim 1, wherein the sterile rinsing fluid comprises povidone-iodine.

4. The compressible device according to claim 1, wherein the compressible device is a ready-to-use compressible device.

5. The compressible device according to claim 1, wherein the compressible body portion comprises high-density polyethylene.

6. The compressible device according to claim 1, wherein the compressible body portion comprises low-density polyethylene.

7. The compressible device according to claim 1, wherein the compressible body portion comprises polyethylene terephthalate.

8. The compressible device according to claim 1, wherein the compressible body portion comprises polystyrene.

9. The compressible device according to claim 1, wherein the compressible body portion comprises polyvinyl chloride.

10. The compressible device according to claim 1, wherein the degradation on-set temperature after the gamma sterilization treatment is no more than about 1% lower from the initial degradation on-set temperature of the compressible device prior to the gamma sterilization treatment.

11. A method of making a compressible device comprising: providing a rinsing fluid within a compressible body portion of a compressible device, and performing a gamma sterilization treatment on the compressible device sufficient to sterilize the rinsing fluid, wherein the compressible device has a degradation on-set temperature after the gamma sterilization treatment that is no more than about 2% lower from an initial degradation on-set temperature of the compressible device prior to the gamma sterilization treatment.

12. The method according to claim 11, wherein the rinsing fluid comprises iodine.

13. The method according to claim 11, wherein the rinsing fluid comprises povidone-iodine.

14. The method according to claim 11, wherein the compressible device is a ready-to-use compressible device.

15. The method according to claim 11, wherein the compressible body portion comprises high-density polyethylene.

16. The method according to claim 11, wherein the compressible body portion comprises low-density polyethylene.

17. The method according to claim 11, wherein the compressible body portion comprises polyethylene terephthalate.

18. The method according to claim 11, wherein the compressible body portion comprises polystyrene.

19. The method according to claim 11, wherein the compressible body portion comprises polyvinyl chloride.

20. The method according to claim 11, wherein the degradation on-set temperature after the gamma sterilization treatment is no more than about 1% lower from the initial degradation on-set temperature of the compressible device prior to the gamma sterilization treatment.

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