Intermittent catheters

Abstract

The invention provides a method of sterilising an intermittent catheter, the method comprising the steps of: a. Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and b. Irradiating the intermittent catheter, the buffer, and the halogen-containing species.

Description

[0001] INTERMITTENT CATHETERS

[0002] Technical Field of the Invention

[0003] The present invention relates to the use of buffers with hypochlorous acid for intermittent catheter treatment.

[0004] Background to the Invention

[0005] Urinary catheterisation is a process involving insertion of a catheter through an individual’s urethra and into their bladder, where it is retained to empty the bladder of urine. There are two major types of urinary catheterisation - intermittent catheterisation and long-term catheterisation. Intermittent urinary catheterisation involves retaining the catheter in the bladder for only the time period required for emptying, after which the catheter is removed. The process differs from long-term catheterisation, which makes use of an indwelling or Foley catheter that is inserted into the bladder for long periods of time (several days to months) to discharge the residual urine of the bladder continuously throughout the day.

[0006] Catheterisation is often used by patients suffering from abnormalities of the urinary system, resulting in urinary incontinence and / or a lack of control in permitting voluntary urination. Such individuals would typically make use of intermittent catheters several times a day.

[0007] Catheters are useful devices, providing users with independence and freedom to self- catheterise as and when required, without having to rely on trained personnel to be present. This, however, increases the need for catheters to be user friendly: in particular, both easy to insert and remove with minimum discomfort caused, and safe to use with features for minimising risk of infection. Users often report experiencing pain and discomfort upon insertion and / or removal of catheters. Users have, for instance, reported experiencing bladder spasms, burning sensations, and bleeding.

[0008] It is also easy for catheters to become contaminated and for bacteria to be introduced into the urethra and along the urinary tract. As a result, urinary tract infections (UTI) are common in individuals who practice self-catheterisation.

[0009] It is especially important to be able to manage and reduce the risk of infections occurring when intermittent catheters are inserted into the urethra as well as to ensure that catheters are sufficiently lubricated. However, this has been notoriously difficult to achieve in practice.

[0010] Recently, the use of antimicrobial lubricants to eliminate bacteria and to prevent catheter- associated infections has been explored. However, these antimicrobial lubricants have encountered several problems, including instability of the antimicrobial agents and variability in their efficacy. Furthermore, some antimicrobial lubricants have been found to adversely affect catheter lubricity, which increases discomfort for the catheter user when inserting and removing the catheter, especially in the case of intermittent catheterisation. The inconsistent performance of antimicrobial lubricants under different physiological conditions has limited their effectiveness and raised concerns about their reliability in clinical use.

[0011] There is therefore a need for alternative approaches that can overcome or ameliorate limitations of current methods. It is an aim of embodiments of the present invention to overcome and / or ameliorate at least one problem of the prior art above.

[0012] It is also an aim of embodiments of the present invention to overcome or mitigate at least one problem of the prior art, whether expressly described herein or not. Summary of the Invention

[0013] According to a first aspect of the invention, there is provided a method of sterilising an intermittent catheter, the method comprising the steps of:

[0014] (a) Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and

[0015] (b) Irradiating the intermittent catheter, the buffer, and the halogen-containing species.

[0016] It has surprisingly been found that the combination of a buffer and such a halogencontaining species is able to provide excellent lubricating performance and antimicrobial activity. Such performance is retained even post-sterilisation of the intermittent catheter, which is performed by irradiation.

[0017] The catheter is an intermittent catheter. Such a catheter is typically inserted into a body for short time periods, such as less than a day. This is in contrast to an indwelling (Foley) catheter, which is typically inserted and kept in a body for long periods of time, such as several days to months.

[0018] In preferred embodiments, the intermittent catheter is a urinary catheter. The catheter may be a reusable or single-use catheter. Preferably, the catheter is a single-use catheter.

[0019] In some embodiments , the catheter comprises a hollow tubular body, preferably a hollow polymeric tubular body. The hollow polymeric tubular body may comprise a base polymer. In some embodiments, the catheter further comprises at least one additive, preferably at least one lubricious additive. Preferably, the hollow tubular body comprises at least one additive.

[0020] Additives allow for improved catheter lubricity and ease of insertion and removal. However, the use of additives on a catheter, particularly on a surface thereof, provides the catheter with complex surface chemistry which can make catheter sterilisation and lubrication challenging. Such catheters have, for instance, been known to swell upon wetting during lubrication. Such catheters are also known to suffer from dry-out, which can result in considerable changes to the catheter surface morphology. As a result, catheters can become rough and sticky, and much more prone to additive delamination. However, the combination of a buffer and a halogen-containing species of the invention allows for effective catheter lubrication and antimicrobial performance, with excellent compatibility with a lubricious additive. There is no negative interference between such an additive and the combination of the buffer and halogen-containing species, and additive migration from the catheter remains unaffected.

[0021] In some embodiments, at least one additive is a hydrophilic additive.

[0022] At least one hydrophilic additive may be independently chosen from: a polyalkylene glycol, hyaluronic acid, chondroitan sulfate, chitosan, glucosaminoglucans, dextran, dextrin, dextran sulfate, cellulose acetate, carboxymethyl cellulose, hydroxyethyl cellulose, cellulosics, polypeptides, poly(2-hydroxyethyl methacrylate), polyacrylamide, polyacrylimide, poly(ethylene amine), poly(allyl amine), poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol), poly(acrylic acid), poly(methacrylic acid), acrylic acid copolymers, methacrylic acid copolymers, polyvinyl alkyl ethers, non-ionic tetrafunctional block- copolymer surfactants, gelatin, collagen, albumin, chitin, heparin, elastin, fibrin, and combinations thereof.

[0023] At least one hydrophilic additive may be independently selected from the group consisting of: a polyalkylene glycol, hyaluronic acid, chondroitan sulfate, chitosan, glucosaminoglucans, dextran, dextrin, dextran sulfate, cellulose acetate, carboxymethyl cellulose, hydroxyethyl cellulose, cellulosics, polypeptides, poly(2-hydroxyethyl methacrylate), polyacrylamide, polyacrylimide, poly(ethylene amine), poly(allyl amine), poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol), poly(acrylic acid), poly(methacrylic acid), acrylic acid copolymers, methacrylic acid copolymers, polyvinyl alkyl ethers, nonionic tetrafunctional block-copolymer surfactants, gelatin, collagen, albumin, chitin, heparin, elastin, fibrin, and combinations thereof.

[0024] In some embodiments, at least one hydrophilic additive is independently chosen from: poly (ethylene glycol), poly (ethylene oxide), poly (propylene glycol), poly (ethylene oxide- co-propylene oxide), poly(trimethylene glycol), poly(tetramethylene glycol), and combinations thereof.

[0025] In some embodiments, at least one hydrophilic additive is independently selected from the group consisting of: poly(ethylene glycol), poly(ethylene oxide), polypropylene glycol), poly(ethylene oxide-co-propylene oxide), poly(trimethylene glycol), poly (tetramethylene glycol), and combinations thereof.

[0026] At least one hydrophilic additive may comprise PVP or a derivative thereof.

[0027] At least one additive may be an amphiphilic additive. The amphiphilic additive comprises a hydrophobic portion and a hydrophilic portion. In cases where the base polymer is hydrophobic or generally hydrophobic, such as a polyolefin, the amphiphilic additive will diffuse towards and to an outer surface of the catheter body due to incompatibility of the hydrophilic portion of the amphiphilic additive with the hydrophobic base polymer.

[0028] In some embodiments, the catheter comprises a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive.

[0029] In some embodiments, at least one additive is polymeric or oligomeric.

[0030] At least one additive may be an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block. In some embodiments, one or both of the hydrophobic hydrocarbon A-block and the hydrophilic B-block may be branched. The hydrophobic A-block may comprise hydrophobic hydrocarbon chains branching therefrom. The hydrophobic hydrocarbon chains may be of shorter chain lengths than the hydrophobic hydrocarbon A-block. The hydrophilic B-block may comprise further hydrophilic B -blocks branching therefrom.

[0031] In some embodiments, the additive is a B-A-B tri-block copolymer comprising a hydrophobic hydrocarbon A-block and hydrophilic B -blocks.

[0032] In other embodiments, the additive is a graft copolymer. The graft copolymer may comprise a hydrophobic hydrocarbon A-block with hydrophilic B -blocks branching therefrom. Alternatively, the graft copolymer may comprise a hydrophilic portion with hydrophobic portions branching therefrom.

[0033] In further embodiments, the additive is a brush copolymer. The additive may comprise a single hydrophilic B-block with more than one hydrophobic A-block branching from an end thereof. Alternatively, the additive may comprise a single hydrophobic A-block with more than one hydrophilic B-block branching from an end thereof. In the respective embodiments, the B-block or A-block may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, or more hydrophobic A-blocks or hydrophilic B -blocks branching from the end thereof.

[0034] In further embodiments, the additive is a star-block or multi-block copolymer comprising hydrophilic and hydrophobic monomer units.

[0035] In preferred embodiments, the additive is an A-B block copolymer comprising a hydrophobic A-block and a hydrophilic B-block.

[0036] Statements of invention below relating to the additive or a part thereof may be applied mutatis mutandis to each of the copolymer forms above.

[0037] In some embodiments, the B-block is a hydrophilic oligomer comprising at least 1, 2, 3, 4, or at least 5 monomer units. In some embodiments, the B-block comprises no greater than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, or no greater than 6 monomer units. In some embodiments, the B-block comprises between 2 and 15 monomer units, preferably between 2 and 10 monomer units. At least one monomer unit may be selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. At least one monomer unit may be chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. At least one monomer unit may be preferably selected from the group consisting of: ethylene oxide, propylene oxide, ethylene glycol, propylene glycol, epichlorohydrin, acrylic acid, methacrylic acid, ethylene imine, caprolactone, vinyl alcohol, and vinyl acetate. At least one monomer unit may be preferably chosen from: ethylene oxide, propylene oxide, ethylene glycol, propylene glycol, epichlorohydrin, acrylic acid, methacrylic acid, ethylene imine, caprolactone, vinyl alcohol, and vinyl acetate. In some embodiments, at least one monomer unit comprises alkylene oxide groups independently selected from ethylene oxide and propylene oxide, and in preferred embodiments, all of the monomer units are ethylene oxide or all of the monomer units are propylene oxide.

[0038] The hydrophobic A-block may comprise a carbon chain of at least 5 carbon atoms, or at least 10, 15, 20, 25, 30, 35, or 40 carbon atoms. The hydrophobic portion may preferably comprise a carbon chain of between 20-52 carbon atoms.

[0039] In some embodiments, the A-block comprises a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a. The value of “a” may be between 5-25; for instance, “a” may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25, or a half integer of any of the above values. The value of “a” may preferably be between 9-25; for instance, “a” may be 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25, or a half integer of any of the above values.

[0040] In some preferred embodiments, there is provided a method of sterilising an intermittent catheter, the method comprising the steps of:

[0041] (a) Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and

[0042] (b) Irradiating the intermittent catheter, the buffer, and the halogen-containing species, wherein the intermittent catheter comprises a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the additive comprises an

[0043] A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block of the amphiphilic A-B block copolymer additive is a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers independently chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0044] In some embodiments, the additive is homogenously distributed with the base polymer. The additive may be uniformly distributed throughout the base polymer of the catheter body.

[0045] At least some of the additive may be at or on the outer surface of the body. By “at the outer surface”, it is meant that at least a portion of the additive forms part of the surface or protrudes from the surface. In some embodiments, part of the additive is retained or anchored in the body while part of the additive forms part of or protrudes from the outer surface of the body. At least part of the hydrophilic portion of the additive may protrude from or form part of the outer surface of the body, while at least part of the hydrophobic portion may be retained or anchored within the body.

[0046] The outer surface may comprise at least one member of the group consisting of: the external-facing surface of the body, the lumen of the body and any eyelets present on the body. In preferred embodiments the outer surface is the external-facing surface of the body and / or the inner lumen. In some embodiments, the outer surface may comprise the external-facing surface of the body of the catheter, the inner lumen, and the eyelets. The additive may be concentrated at or on the outer surface of the body. For example, at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or at least 95% of the number of molecules of the additive may be at or on the outer surface of the body.

[0047] In some embodiments, at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or at least 95% of the number of molecules of additive may have hydrophilic portions that are at or on the outer surface of the body.

[0048] In some embodiments, the additive is located at and / or on at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99% of the outer surface area of the polymeric tubular body, preferably at least 75% or at least 90% of the outer surface area of the polymeric tubular body or between 75% and 100% of the outer surface area.

[0049] In some embodiments, the additive is present at a concentration of at least 0.1, 0.2, 0.3. 0.4. 0.5, 0.75, 1, 2, 3, 4, 5, 10, 15 or at least 20% by weight of the combination of base polymer and additive. The additive may be present a concentration of between 0.1-20%, and more preferably between 0.5-15% or 0.5-5% by weight of the combination of base polymer and additive.

[0050] In some embodiments, the additive comprises a layer that is on or that comprises a surface of the body, preferably the outer surface.

[0051] The layer comprising the additive may be on the surface of the body. In some embodiments, the layer comprising the additive is substantially separate from the body and the layer may be bonded to the body. The layer may be bonded to the body via covalent bonds, ionic bonds, hydrogen bonds, or Van der Waals forces. The additive may be bonded to the body via one or more surface linker groups which may be present on the additive, the body of the catheter or both.

[0052] In some embodiments, the layer comprising the additive may comprise the surface of the body. In such embodiments the layer may form the surface of the body. The layer may comprise a co-extruded layer which is melded with or is physically entangled with the body, and this may form an integral layer. The layer of additive may be integrally formed with the body.

[0053] In some embodiments, polymer diffusion occurs between the layer comprising the additive and the catheter body. The layer and the body may be held together by polymer chains extending across the interface between the layer and body. In some embodiments, the additive infiltrates the catheter body.

[0054] In some embodiments, the layer comprising the additive comprises or is on an inner surface of the body, an outer surface of the body, or both. The inner surface of the body may comprise a lumen of the catheter. In preferred embodiments, the layer comprising the additive comprises or is on at least an outer surface of the body.

[0055] In some embodiments, the layer comprising the additive is on or comprises at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99% of the or each surface area of the body, preferably at least 75% or at least 90% of the or each surface area or between 75% and 100% of the or each surface area. In embodiments in which the layer comprising the additive comprises or is on both an inner and outer surface of the body, the additive may comprise at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99% of each surface area of the body, preferably at least 75% or at least 90% of each surface area or between 75% and 100% of each surface area of both surfaces. In some embodiments, at least 75% of the layer comprising the additive, or at least 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% of the layer is the additive.

[0056] In some embodiments, the layer comprising the additive has an additive concentration of at least 0.1, 0.2, 0.3. 0.4. 0.5, 0.75, 1, 2, 3, 4, 5, 10, 15 or at least 20% by weight of the combination of base polymer and additive.

[0057] In some embodiments, the layer comprising the additive has an additive concentration of no greater than 70, 65, 60, 65, 60, 55, or of no greater than 50% by weight of the combination of the base polymer and additive.

[0058] The layer comprising the additive may have an additive concentration of greater than 5% by weight of the combination of the base polymer and additive. The layer may have an additive concentration of between 6-50% by weight of the combination of the base polymer and additive.

[0059] The layer comprising the additive may have an additive concentration of between 10- 50% by weight of the combination of the base polymer and additive, or of between 15- 50, 20-50, 25-50, 30-50, 35-50, 40-50, or of between 45-50% by weight of the combination of the base polymer and additive.

[0060] The layer comprising the additive may have an additive concentration of between 6-45% by weight of the combination of the base polymer and additive, or of between 6-40, 6-35, 6-30, 6-25, 6-20, 6-15, or of between 6-10% by weight of the combination of the base polymer and additive.

[0061] The layer comprising the additive may have an additive concentration of between 10-

[0062] 45% by weight of the combination of the base polymer and additive, or of between 15- 45, 20-45, 25-45, 30-45, 35-45, 40-45, 10-40, 15-40, 20-40, 25-40, 30-40, 35-40, 10-35, 15-35, 20-35, 25-35, 30-35, 10-30, 15-30, 20-30, 25-30, 10-25, 15-25, 20-25, 10-20, 15- 20, or of between 10-15% by weight of the combination of the base polymer and additive.

[0063] In some embodiments, the layer comprising the additive has a thickness of at least 1 pm, or of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or of at least 50 pm.

[0064] In some embodiments, the layer comprising the additive has a thickness of no more than 10000 pm, or of no more than 9000, 8000, 7000, 6000, 5000, 4000, 3000, 2000, 1000, 900, 800, 700, 600, 500, 400, or of no more than 300 pm.

[0065] In some embodiments, the layer comprising the additive has a thickness of between SO- SOO pm.

[0066] The layer comprising the additive may have a thickness of between 60-300 pm, or of between 80-300, 100-300, 120-300, 140-300, 160-300, 180-300, 200-300, 220-300, 240- 300, 260-300, or of between 280-300 pm.

[0067] The layer comprising the additive may have a thickness of between 50-280 pm, or of between 50-260, 50-240, 50-220, 50-200, 50-180, 50-160, 50-140, 50-120, 50-100, 50- 80, or of between 50-60 pm.

[0068] The layer comprising the additive may have a thickness of between 60-280 pm, or of between 80-280, 100-280, 120-280, 140-280, 160-280, 180-280, 200-280, 220-280, 240- 280, 260-280, 60-260, 80-260, 100-260, 120-260, 140-260, 160-260, 180-260, 200-260, 220-260, 240-260, 60-240, 80-240, 100-240, 120-240, 140-240, 160-240, 180-240, 200- 240, 220-240, 60-220, 80-220, 100-220, 120-220, 140-220, 160-220, 180-220, 200-220, 60-200, 80-200, 100-200, 120-200, 140-200, 160-200, 180-200, 60-180, 80-180, 100- 180, 120-180, 140-180, 160-180, 60-160, 80-160, 100-160, 120-160, 140-160, 60-140, 80-140, 100-140, 120-140, 60-120, 80-120, 100-120, 60-100, 80-100, or of between 60- 80 pm.

[0069] In preferred embodiments, the catheter base polymer is hydrophobic or partly hydrophobic. A hydrophobic base polymer facilitates increased hydrophobichydrophobic interactions between the hydrophobic portion of the additive and the base polymer. This further decreases the energetic favourability for the hydrophobic portion to leave the base polymer and migrate out into the more hydrophilic external environment.

[0070] In some embodiments, the base polymer comprises a polymer chosen from: polyvinyl chloride, polytetrafluoroethylene, polyolefins, latex, silicones, synthetic rubbers, polyurethanes, polyesters, poly acrylates, polyamides, thermoplastic elastomeric materials, styrene block copolymers, polyether block amide, thermoplastic vulcanizates, thermoplastic copolyesters, thermoplastic polyamides, styrene-butadiene copolymer (SBC), styrene-ethylene-butylene-styrene copolymer (SEBS), and water disintegrable or enzymatically hydrolysable material, or combinations, blends or copolymers of any of the above materials.

[0071] In some embodiments, the base polymer comprises a polymer selected from the group consisting of: polyvinyl chloride, polytetrafluoroethylene, polyolefins, latex, silicones, synthetic rubbers, polyurethanes, polyesters, polyacrylates, polyamides, thermoplastic elastomeric materials, styrene block copolymers, poly ether block amide, thermoplastic vulcanizates, thermoplastic copolyesters, thermoplastic polyamides, styrene-butadiene copolymer (SBC), styrene-ethylene-butylene-styrene copolymer (SEBS), and water disintegrable or enzymatically hydrolysable material, or combinations, blends or copolymers of any of the above materials.

[0072] In preferred embodiments, the base polymer comprises a polymer chosen from: polyolefins, polyesters, poly acrylates, polyamides, thermoplastic elastomeric material, polyether block amide, thermoplastic vulcanizates, thermoplastic copolyesters, thermoplastic polyamides, fluororubber, and water disintegrable or enzymatically hydrolysable material or combinations, blends or copolymers of any of the above materials.

[0073] In preferred embodiments, the base polymer comprises a polymer selected from the group consisting of: polyolefins, polyesters, poly acrylates, polyamides, thermoplastic elastomeric material, polyether block amide, thermoplastic vulcanizates, thermoplastic copolyesters, thermoplastic polyamides, fluororubber, and water disintegrable or enzymatically hydrolysable material or combinations, blends or copolymers of any of the above materials.

[0074] In some embodiments, said water disintegrable or enzymatically hydrolysable material comprises a material chosen from: polyvinyl alcohol, extrudable polyvinyl alcohol, polyacrylic acids, polylactic acid, polyesters, polyglycolide, polyglycolic acid, poly lactic-co-glycolic acid, polylactide, amines, polyacrylamides, poly(? / -(2-Hydroxypropyl) methacrylamide), starch, modified starches or derivatives, amylopectin, pectin, xanthan, scleroglucan, dextrin, chitosans, chitins, agar, alginate, carrageenans, laminarin, saccharides, polysaccharides, sucrose, polyethylene oxide, polypropylene oxide, acrylics, polyacrylic acid blends, poly(methacrylic acid), polystyrene sulfonate, polyethylene sulfonate, lignin sulfonate, polymethacrylamides, copolymers of aminoalkyl-acrylamides and methacrylamides, melamine-formaldehyde copolymers, vinyl alcohol copolymers, cellulose ethers, poly-ethers, polyethylene oxide, blends of polyethylene- polypropylene glycol, carboxymethyl cellulose, guar gum, locust bean gum, hydroxypropyl cellulose, vinylpyrrolidone polymers and copolymers, polyvinyl pyrrolidone-ethylene- vinyl acetate, polyvinyl pyrrolidone-carboxymethyl cellulose, carboxymethyl cellulose shellac, copolymers of vinylpyrrolidone with vinyl acetate, hydroxyethyl cellulose, gelatin, polycaprolactone, poly(p-dioxanone), or combinations, blends or co-polymers of any of the above materials.

[0075] In some embodiments, said water disintegrable or enzymatically hydrolysable material comprises a material of the group consisting of: polyvinyl alcohol, extrudable polyvinyl alcohol, poly aery lie acids, polylactic acid, polyesters, polyglycolide, polygly colic acid, poly lactic-co-glycolic acid, polylactide, amines, polyacrylamides, poly(? / -(2- Hydroxypropyl) methacrylamide), starch, modified starches or derivatives, amylopectin, pectin, xanthan, scleroglucan, dextrin, chitosans, chitins, agar, alginate, carrageenans, laminarin, saccharides, polysaccharides, sucrose, polyethylene oxide, polypropylene oxide, acrylics, polyacrylic acid blends, poly(methacrylic acid), polystyrene sulfonate, polyethylene sulfonate, lignin sulfonate, polymethacrylamides, copolymers of aminoalkyl- acrylamides and methacrylamides, melamine-formaldehyde copolymers, vinyl alcohol copolymers, cellulose ethers, poly-ethers, polyethylene oxide, blends of polyethylene- polypropylene glycol, carboxymethyl cellulose, guar gum, locust bean gum, hydroxypropyl cellulose, vinylpyrrolidone polymers and copolymers, polyvinyl pyrrolidone-ethylene-vinyl acetate, polyvinyl pyrrolidone-carboxymethyl cellulose, carboxymethyl cellulose shellac, copolymers of vinylpyrrolidone with vinyl acetate, hydroxyethyl cellulose, gelatin, poly-caprolactone, poly(p-dioxanone), or combinations, blends or co-polymers of any of the above materials.

[0076] In other preferred embodiments, the base polymer comprises a polymer chosen from: polyolefins, polyvinyl chloride, polyurethane, styrene-butadiene copolymer (SBC), styrene-ethylene-butylene-styrene copolymer (SEBS), and thermoplastic elastomeric material or combinations, blends or copolymers of any of the above materials.

[0077] In other preferred embodiments, the base polymer comprises a polymer selected from the group consisting of: polyolefins, polyvinyl chloride, polyurethane, styrene-butadiene copolymer (SBC), styrene-ethylene-butylene-styrene copolymer (SEBS), and thermoplastic elastomeric material or combinations, blends or copolymers of any of the above materials.

[0078] In some preferred embodiments, the base polymer comprises a polyolefin, especially polyethylene and / or polypropylene.

[0079] In some preferred embodiments, the base polymer comprises a thermoplastic elastomeric material. The base polymer may comprise a thermoplastic polyolefin.

[0080] In some preferred embodiments, the base polymer may be made entirely of a polyolefin and / or a thermoplastic elastomeric material. The polyolefin may preferably comprise polyethylene and / or polypropylene.

[0081] The thermoplastic base polymer may comprise a hydrophobic polymer chosen from:

[0082] Accurel ™, Styroflex™, Styrolux™, MelifleX™, and Mediprene™ and any combination thereof. The thermoplastic base polymer may comprise a hydrophobic polymer selected from the group consisting of: Accurel ™, Styroflex™, Styrolux™, MelifleX™, and Mediprene™ and any combination thereof.

[0083] The thermoplastic base polymer may comprise Estane™ 58315, which is both hydrophobic and hydrophilic.

[0084] In preferred embodiments, the hypochlorous acid or species that is capable of forming hypochlorous acid is present in a total amount of at least 97 wt.% of the total amount of the halogen-containing species, or at least 98, 99, 99.5, 99.6, 99.7, 99.8, or at least 99.9 wt.% of the total amount of the halogen-containing species. In some preferred embodiments, the hypochlorous acid or species that is capable of forming hypochlorous acid is present in a total amount of substantially 100 wt.% of the total amount of the halogen-containing species.

[0085] In some preferred embodiments, there is provided a method of sterilising an intermittent catheter, the method comprising the steps of:

[0086] (a) Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and

[0087] (b) Irradiating the intermittent catheter, the buffer, and the halogen-containing species, wherein the hypochlorous acid or species that is capable of forming hypochlorous acid is present in an amount of at least 97 wt.% of the total amount of the halogen-containing species. In embodiments in which the halogen-containing species comprises hypochlorous acid, the total combined amount of hypochlorite salt and molecular chlorine may comprise less than 3 wt.% of the total amount of the halogen-containing species, or less than 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or less than 0.1 wt.% of the total amount of the halogen-containing species.

[0088] In embodiments in which the halogen-containing species comprises hypochlorous acid, the total amount of additional halogen-containing species may comprise less than 3 wt.% of the total amount of the halogen-containing species, or less than 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or less than 0.1 wt.% of the total amount of the halogencontaining species.

[0089] In preferred embodiments, the buffer has at least one pKa of at least 3, or at least 3.2, 3.4,

[0090] 3.6, 3.8, or at least 4. The buffer may have at least one pKa of no greater than 7, or no greater than 6.5, or no greater than 6, or no greater than 5.8, 5.6, or preferably no greater than 5.5, 5.4, 5.2, or no greater than 5. The buffer may preferably have at least one pKa of between 3-6.5, or between 3-5.5, or between 4-5.5, or between 4-5, or between 4.2-5. In some preferred embodiments, the buffer may have at least one pKa of between 3.3-6.5, or between 3.8-6.0, or between 4.0-5.8.

[0091] In some embodiments, the buffer has at least one pKa at a pH of at least 3, or at least 3.2,

[0092] 3.4. 3.6, 3.8, or at least 4. The buffer may have at least one pKa at a pH of no greater than 7, or no greater than 6.5, or no greater than 6, or no greater than 5.8, 5.6, or preferably no greater than 5.5, 5.4, 5.2, or no greater than 5. The buffer may preferably have at least onepKa at a pH of between 3-6.5, or between 3-5.5, or between 4-5.5, orbetween 4-5, or between 4.2-5. In some preferred embodiments, the buffer may have at least one pKa at a pH of between 3.3-6.5, or between 3.8-6.0, or between 4.0-5.8.

[0093] In some embodiments, the buffer comprises a species comprising at least one carboxylic acid or carboxylate moiety.

[0094] In some embodiments, the buffer is independently chosen from: a citric acid or citrate buffer, a succinic acid buffer, an acetate buffer, a malic acid buffer, and combinations thereof.

[0095] The buffer may be independently selected from the group consisting of: a citric acid or citrate buffer, a succinic acid buffer, an acetate buffer, a malic acid buffer, and combinations thereof.

[0096] In some embodiments, the intermittent catheter, the buffer and the halogen-containing species are packaged.

[0097] The catheter, buffer and halogen-containing species may be packaged in a container. The container may be a case. The case may have at least one cavity configured to hold the catheter, buffer and halogen-containing species.

[0098] The case may be rigid. Alternatively, the case may be flexible. In some embodiments, the case contains rigid and flexible regions. The case may comprise a tube. The tube may have a flexible centre portion and two rigid side portions neighbouring the flexible centre portion.

[0099] In some embodiments, the buffer and the halogen-containing species are in direct contact with each other. In such embodiments, the halogen-containing species preferably comprises hypochlorous acid. The halogen-containing species and buffer may be present as a medium that comprises the halogen-containing species and the buffer, wherein the halogen-containing species comprises hypochlorous acid.

[0100] The medium may comprise hypochlorous acid in a total concentration of at least 10 ppm, or at least 20, 30, 40, 50, 60, 70, 80, 90, or at least 100 ppm. The medium may comprise hypochlorous acid in a total concentration of no greater than 1200 ppm, or no greater than 1100, or preferably 1000, 900, 800, 700, 600, 500, or no greater than 400 ppm. In some embodiments, the medium may comprise hypochlorous acid in a total concentration of between 100-1000 ppm, or between 100-600, or preferably between 100-400 ppm, or between 200-400 ppm, or between 250-350 ppm.

[0101] The medium may comprise the buffer in a total concentration of at least 0.01 wt.% of the medium, or at least 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or at least 1 wt.% of the medium. The medium may comprise the buffer in a total concentration of no greater than 10 wt.% of the medium, or no greater than 9, 8, 7, 6, 5, 4.5, 4, 3.5, or no greater than 3 wt.% of the medium. The medium may comprise the buffer in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-8 wt.%, or between 0.5-5 wt.% of the medium, or between 1-4 wt.% of the medium, or between 2-3 wt.% of the medium, or between 2.3-2.8 wt.% of the medium. In such embodiments, the medium may comprise a citric acid or citrate buffer in the above concentrations.

[0102] In some preferred embodiments, there is provided a method of sterilising an intermittent catheter, the method comprising the steps of: (a) Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and

[0103] (b) Irradiating the intermittent catheter, the buffer, and the halogen-containing species, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, wherein the halogen-containing species comprises hypochlorous acid, and wherein the medium comprises the buffer in a total concentration of between 1-4 wt.% of the medium, or between 2-3 wt.%, or between

[0104] 2.3-2.8 wt.% of the medium.

[0105] In preferred embodiments, the medium has a pH of at least 3, or at least 3.2, 3.4, 3.6, 3.8, or at least 4. The medium may have a pH of no greater than 7, or no greater than 6, or no greater than 5.8, 5.6, or preferably no greater than 5.5, 5.4, 5.2, or no greater than 5. The medium may preferably have a pH of between 3-6, or between 3-5.5, or between 3.5-5.5, or between 4-5.5, or between 4-5, or between 4.2-5. In some preferred embodiments, the medium has a pH of between 3.8-6.0, or between 4.0-5.8, or between 4.2-5.6, or between

[0106] 4.4-5.4, or between 4.6-5.2, or between 4.8-5.0.

[0107] In preferred embodiments, hypochlorous acid is present in the medium in a total amount of at least 97 wt.% of the total amount of the halogen-containing species, or at least 98, 99, 99.5, 99.6, 99.7, 99.8, or at least 99.9 wt.% of the total amount of the halogencontaining species. In some preferred embodiments, hypochlorous acid is present in the medium in a total amount of substantially 100 wt.% of the total amount of the halogencontaining species. In such embodiments, the medium preferably has a pH of between 3.8-6.0, or between 4.0-5.8, or between 4.2-5.6, or between 4.4-5.4, or between 4.6-5.2, or between 4.8-5.0.

[0108] Such pH values allow the concentration of hypochlorous acid to be maintained at high levels, providing the medium with excellent and stable antimicrobial activity. Such pH values are achieved and maintained using the buffer of the invention.

[0109] In some embodiments, the medium is present in liquid, gel or solid form.

[0110] In some embodiments, the medium is present as solution, preferably an aqueous solution. Aqueous solutions are particularly effective, as water allows for optimal catheter surface lubricity.

[0111] In some embodiments, the medium is present in a total amount of at least 0.05 wt.% of the combination of the catheter and medium, or of at least 0.1, 0.15, 0.2, 0.25, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or at least 20 wt.% of the combination of the catheter and medium.

[0112] The medium may be present in a total amount of no greater than 40 wt.% of the combination of the catheter and medium, or no greater than 35, 30, 25, 20, 15, 10, or no greater than 5 wt.% of the combination of the catheter and medium.

[0113] The medium may be present in a total amount of between 0.1-20 wt.% of the combination of the catheter and medium, or between 0.5-15, or between 0.5-5 wt.% of the combination of the catheter and medium.

[0114] In some embodiments, the medium is present as a liquid having a viscosity of greater than 0.5 cP, or of greater than 1, 1.5, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900, or of greater than 1000 cP. The medium may have a viscosity of no greater than 100000 cP, or of no greater than 90000, 80000, 70000, 60000, 50000, 40000, 30000, 20000, 10000, 5000, 4000, 3000, 2000, 1000, 500, 400, 300, 200, 100, 50, 25, 10, 5, 4, 3, 2, or of no greater than 1 cP. The medium may have a viscosity of between 0.5-5000 cP, or of between 0.5-2500, 0.5-1000, 1-1000, 10-1000, 50-1000, 100-1000, 500-1000, 0.5-500, 1-500, 10-500, 50-500, 100-500, 250-500, 0.5- 250, 1-250, 10-250, 50-250, or of between 100-250 cP.

[0115] The medium may be a catheter wetting agent. The medium may encourage hydrophilic portions of lubricating additives within the catheter to seek towards an outer surface of the catheter, which further enhances the lubricating effect of the additive.

[0116] In some embodiments, the medium further comprises at least one additional component that is independently chosen from: an ionic compound, a free radical stabiliser, a lubricating polymer, a topical antimicrobial, boric acid, and combinations thereof. In some embodiments, the medium further comprises at least one additional component that is independently selected from the group consisting of: an ionic compound, a free radical stabiliser, a lubricating polymer, a topical antimicrobial, boric acid, and combinations thereof.

[0117] In some embodiments, at least one ionic compound comprises an ionic salt. Inclusion of such ionic compounds in the medium help to achieve physiological ion balance and / or osmolarity.

[0118] The ionic salt may comprise a cation selected from the group consisting of: ammonium, calcium, iron, magnesium, potassium, pyridinium, quaternary ammonium, sodium, copper, aluminium, lithium, beryllium, strontium, and zinc. The ionic salt may comprise an anion selected from the group consisting of: acetate, carbonate, bicarbonate, chloride, citrate, glutamate, fluoride, bromide, iodide, nitrate, nitrite, oxide, phosphate, ferrocyanide, silicate, gluconate, and sulfate.

[0119] The ionic salt may be independently chosen from: sodium chloride, potassium chloride, calcium chloride, magnesium chloride, calcium chloride, sodium nitrite, magnesium nitrate, calcium nitrate, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium iodide, copper iodide, sodium ferrocyanide, monosodium glutamate, calcium silicate, sodium citrate, potassium citrate, sodium phosphate, potassium phosphate, sodium sulfate, calcium sulfate, sodium gluconate, calcium gluconate, potassium gluconate, sodium acetate, potassium acetate, and combinations thereof. The ionic salt may be independently selected from the group consisting of: sodium chloride, potassium chloride, calcium chloride, magnesium chloride, calcium chloride, sodium nitrite, magnesium nitrate, calcium nitrate, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium iodide, copper iodide, sodium ferrocyanide, monosodium glutamate, calcium silicate, sodium citrate, potassium citrate, sodium phosphate, potassium phosphate, sodium sulfate, calcium sulfate, sodium gluconate, calcium gluconate, potassium gluconate, sodium acetate, potassium acetate, and combinations thereof.

[0120] The ionic salt may be present in a total amount of between 0.1-5 wt.% of the medium, or between 0.2-2.5 wt.%, or between 0.5-1.5 wt.% of the medium.

[0121] In some embodiments, at least one free radical stabiliser may comprise an aromatic phenol. At least one aromatic phenol may be independently chosen from: 4- methoxyphenol, butylated hydroxytoluene, vanillin, vanillyl alcohol, gallic acid, protocatechuic acid, vanillic acid, caffeic acid, ferulic acid, p-coumaric acid, sinapic acid, pyrogallol, propyl gallate, butylated hydroxyanisole, and combinations thereof. At least one aromatic phenol may be independently selected from the group consisting of: 4- methoxyphenol, butylated hydroxytoluene, vanillin, vanillyl alcohol, gallic acid, protocatechuic acid, vanillic acid, caffeic acid, ferulic acid, p-coumaric acid, sinapic acid, pyrogallol, propyl gallate, butylated hydroxyanisole, and combinations thereof. At least one aromatic phenol may preferably comprise 4-methoxyphenol and / or butylated hydroxytoluene.

[0122] In some embodiments, the medium comprises at least one radical stabiliser in a total amount of at least 0.01 wt.% of the medium, or at least 0.02, 0.03, 0.04, or at least 0.05 wt.% of the medium. In some embodiments, the medium comprises at least one radical stabiliser in a total amount of no greater than 3 wt.% of the medium, or no greater than 2, or no greater than 1 wt.% of the medium. The medium may comprise at least one radical stabiliser in a total amount of between 0.1 -1.3 wt.% of the medium, or between 0.4-1, or between 0.5-0.9, or between 0.6-0.8 wt.% of the medium. In some embodiments, the medium may comprise 4-methoxyphenol at the above concentrations.

[0123] In some embodiments, at least one topical antimicrobial is independently chosen from: a silver-based antimicrobial, polytetrafluoroethylene, hydrogel, silicone, lecithin, salicylic acid, minocycline, rifampin, fluorinated ethylene propylene, polyvinylidone, polyvinyl compounds, polylactames, polyvinyl pyrrolidones, polysaccharides, heparin, dextran, xanthan gum, derivatised polysaccharides, hydroxy propyl cellulose, methyl cellulose, polyurethanes, poly acrylates, poly hydroxy acrylates, polymethacrylates, polyacrylamides, polyalkylene oxides, polyethylene oxides, polyvinyl alcohols, polyamides, polyacrylic acid, hydroxy ethylmethyl acrylate, polymethylvinyl ether, maleinic acid anyhydride, penicillin, neomycin sulfate, cephalothin, Bacitracin, phenoxymethyl penicillin, lincoymycin hydrochloride, sulfadiazine, methyl sulfadiazine, succinoylsulfathiazole, phthalylsulfathiazde, sulfacetamine, procaine penicillin, streptomycin, aureomycin, terramycin, terramycin, quaternary ammonium halides, cetyl pyridinium chloride, triethyl dodecyl ammonium bromide, octenidine, an organosilane, hexachlorophene and nitrofurazone, or any combination thereof. In some embodiments, at least one topical antimicrobial comprises octenidine and / or an organosilane. In some embodiments, the organosilane may be or comprise dimethyloctadecyl(3 -trimethoxy silylpropyl) ammonium chloride.

[0124] In some embodiments, the medium comprises boric acid in a total concentration of at least 0.2 wt.% of the medium, or at least 0.4, 0.6, 0.8, or at least 1 wt.% of the medium. In some embodiments, the medium comprises boric acid in a total concentration of no greater than 5 wt.% of the medium, or no greater than 4, 3, or no greater than 2 wt.% of the medium. In some embodiments, the medium comprises boric acid in a total concentration of between 0.2-3 wt.% of the medium, or between 0.4-2.8, 0.6-2.6, 0.8-2.4, 1-2.2, 1.2-2, or between 1.4-1.8 wt.% of the medium.

[0125] In some embodiments, the medium comprises hypochlorous acid and a citrate buffer. In such embodiments, the medium may comprise hypochlorous acid in a total concentration of between 100-400 ppm and the medium may comprise the citrate buffer in a total concentration of between 0.5-5 wt.% of the medium. In such embodiments, the medium may have a pH of between 3-6, or between 3-5.5, or between 3.5-5.5. In other preferred embodiments, the medium may have a pH of between 3.8-6.0, or between 4.0-5.8, or between 4.2-5.6, or between 4.4-5.4, or between 4.6-5.2, or between 4.8-5.0. In some embodiments, the medium comprises hypochlorous acid; a buffer, preferably a citrate buffer; and boric acid. In such embodiments, the medium may comprise hypochlorous acid in a total concentration of between 100-400 ppm, the buffer in a total concentration of between 0.5-5 wt.% of the medium, and boric acid in a total concentration of between 1-2.2 wt.% of the medium. In such embodiments, the medium may have a pH of between 3-6, or between 3-5.5, or between 3.5-5.5. In other preferred embodiments, the medium may have a pH of between 3.8-6.0, or between 4.0-5.8, or between 4.2-5.6, or between 4.4-5.4, or between 4.6-5.2, or between 4.8-5.0.

[0126] In some embodiments, the medium comprises hypochlorous acid; a buffer, preferably a citrate buffer; and at least one free radical stabiliser, preferably 4-methoxyphenol. In such embodiments, the medium may comprise hypochlorous acid in a total concentration of between 100-400 ppm, the buffer in a total concentration of between 0.5-5 wt.% of the medium, and the free radical stabiliser, preferably 4-methoxyphenol in a total concentration of between 0.4-1 wt.% of the medium. In such embodiments, the medium may have a pH of between 3-6, or between 3-5.5, or between 3.5-5.5. In other preferred embodiments, the medium may have a pH of between 3.8-6.0, or between 4.0-5.8, or between 4.2-5.6, or between 4.4-5.4, or between 4.6-5.2, or between 4.8-5.0.

[0127] In some embodiments, the medium comprises hypochlorous acid; a buffer, preferably a citrate buffer; boric acid; and at least one free radical stabiliser, preferably 4- methoxyphenol. In such embodiments, the medium may comprise hypochlorous acid in a total concentration of between 100-400 ppm, the buffer in a total concentration of between 0.5-5 wt.% of the medium, boric acid in a total concentration of between 1-2.2 wt.% of the medium, and the free radical stabiliser, preferably 4-methoxyphenol in a total concentration of between 0.4-1 wt.% of the medium. In such embodiments, the medium may have a pH of between 3-6, or between 3-5.5, or between 3.5-5.5. In other preferred embodiments, the medium may have a pH of between 3.8-6.0, or between 4.0-5.8, or between 4.2-5.6, or between 4.4-5.4, or between 4.6-5.2, or between 4.8-5.0.

[0128] In some embodiments, the medium is present as a gel, which may be an aqueous gel.

[0129] The gel may be a nonfluid colloidal network or polymer network that is expanded throughout its whole volume by a fluid. The gel may be a porous three-dimensional semisolid network that expands in a stable fashion.

[0130] The gel may have a viscosity of at least 1000 cP, or at least 1250, 1500, 1750, 2000, 2250, 2500, 2750, 3000, 3250, 3500, 3750, 4000, 4250, 4500, 4750, or at least 5000 cP. The gel may have a viscosity of no greater than 5000000, or no greater than 4000000, 3000000, 2000000, 1000000, 900000, or no greater than 800000 cP.

[0131] In some embodiments, the gel has a viscosity of between 1000-1000000 cP, or between 1500-900000, or between 300000-850000, or between 5000-800000, or between 6000- 700000, or between 7000-600000, or between 8000-500000, or between 9000-400000 cP. In some embodiments, the gel has a viscosity of between 100000-500000 cP, or between 150000-450000, or between 200000-400000 cP. In some embodiments, the gel has a viscosity of between 8000-32000 cP, or between 9000-31000, or between 10000- 30000, or between 11000-29000, or between 12000-28000, or between 13000-27000 cP.

[0132] In some embodiments, the gel comprises water in a total amount of at least 5 wt.%, or in a total amount of at least 10, 15, or in a total amount of at least 20 wt.% of the gel. In some embodiments, the gel comprises water in a total amount of no greater than 99.5 wt.%, 99, 98.5, 98, 97.5, 97, 96.5, 96, 95.5, or in a total amount of no greater than 95 wt.% of the gel. In some embodiments, the gel comprises water in a total amount of between 5-99 wt.%, or between 10-98 wt.%, or between 20-98 wt.%. In some preferred embodiments, the gel comprises water in a total amount of between 50-98 wt.%, or between 55-98 wt.%, or between 55-95 wt.%, or between 60-95 wt.%, or between 65-95 wt.%, or between 70-95 wt.%, or between 75-95 wt.%.

[0133] In some embodiments, the gel comprises glycerin and / or at least one paraben.

[0134] In some preferred embodiments, there is provided a method of sterilising an intermittent catheter, the method comprising the steps of:

[0135] (a) Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and

[0136] (b) Irradiating the intermittent catheter, the buffer, and the halogen-containing species, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, wherein the halogen-containing species comprises hypochlorous acid, and wherein the medium is present as a gel, and wherein the gel comprises glycerin and / or at least one paraben.

[0137] In some embodiments, the gel comprises glycerin in a total amount of at least 1 wt.%, or at least 2, 3, 4, or at least 5 wt.%. In some embodiments, the gel comprises glycerin in a total amount of no greater than 90 wt.%, or no greater than 85, 80, 75, 70, 65, 60, 55, 50,

[0138] 45, or no greater than 40 wt.%. In some embodiments, the gel comprises glycerin in a total amount of between 5-80 wt.%, or between 7-77 wt.%, or between 9-75 wt.%. In some preferred embodiments, the gel comprises glycerin in a total amount of between 5-50 wt.%, or between 6-45 wt.%, or between 7-40 wt.%, or between 8-35, 8-30, 8-25, 8-20, or between 8-15 wt.%.

[0139] In some embodiments, the gel comprises the paraben in a total amount of at least 0.02 wt.%, or at least 0.04, 0.06, or at least 0.08 wt.%. In some embodiments, the gel comprises the paraben in a total amount of no greater than 1 wt.%, or no greater than 0.8, 0.6, or no greater than 0.4 wt.%.

[0140] In some embodiments, the gel comprises the paraben in a total amount of between 0.025- 0.5 wt.%, or between 0.05-0.4 wt.%, or between 0.05-0.3 wt.%.

[0141] In some embodiments, at least one paraben comprises at least one alkyl paraben. At least one alkyl paraben may comprise at least one Ci-Cio alkyl paraben, or at least one Ci-Cs alkyl paraben, or preferably at least one C1-C5 alkyl paraben. In some embodiments, at least one alkyl paraben is independently chosen from: methylparaben, ethylparaben, propylparaben, butylparaben, and combinations thereof. In some embodiments, at least one alkyl paraben is independently selected from the group consisting of: methylparaben, ethylparaben, propylparaben, butylparaben, and combinations thereof. In preferred embodiments, the gel comprises methylparaben and / or propylparaben.

[0142] In some embodiments, the gel comprises methylparaben in a total amount of at least 0.01 wt.%, or at least 0.02, 0.03, 0.04, or at least 0.05 wt.%. In some embodiments, the gel comprises methylparaben in a total amount of no greater than 0.3 wt.%, or no greater than 0.29, 0.28, 0.27, 0.26, 0.25, 0.24, 0.23, or no greater than 0.22 wt.%. In some embodiments, the gel comprises methylparaben in a total amount of between 0.03-0.3 wt.%, or between 0.04-0.26 wt.%, or between 0.05-0.25 wt.%.

[0143] In some embodiments, the gel comprises propylparaben in a total amount of at least 0.005 wt.%, or at least 0.01, 0.015, or at least 0.02 wt.%. In some embodiments, the gel comprises propylparaben in a total amount of no greater than 0.3 wt.%, or no greater than 0.28, 0.26, 0.24, 0.22, 0.2, or no greater than 0.18, 0.16, 0.14, 0.12, 0.1, 0.08, or no greater than 0.06 wt.%. In some embodiments, the gel comprises propylparaben in a total amount of between 0.005-0.3 wt.%, or between 0.01-0.2, or between 0.01-0.15, or between 0.01-0.1, or between 0.02-0.08 wt.%.

[0144] In some embodiments, the gel comprises both glycerin and at least one paraben.

[0145] The gel may comprise glycerin and at least one alkyl paraben. The gel may comprise glycerin and at least one C1-C10 alkyl paraben, C1-C8 alkyl paraben, or C1-C5 alkyl paraben. The gel may comprise glycerin and at least one alkyl paraben independently chosen from: methylparaben, ethylparaben, propylparaben, butylparaben, and combinations thereof. The gel may comprise glycerin and at least one alkyl paraben independently selected from the group consisting of: methylparaben, ethylparaben, propylparaben, butylparaben, and combinations thereof. The gel may preferably comprise glycerin and at least one alkyl paraben independently chosen from: methylparaben, propylparaben, and a combination thereof. The gel may preferably comprise glycerin and at least one alkyl paraben independently selected from the group consisting of: methylparaben, propylparaben, and a combination thereof. The gel may comprise glycerin, methylparaben and propylparaben. In some preferred embodiments, the catheter is not in direct contact with the buffer. In some preferred embodiments, the catheter is not in direct contact with the halogencontaining species. The catheter may not be in direct contact with the buffer and the catheter may not be in direct contact with the halogen-containing species.

[0146] In such embodiments, the halogen-containing species preferably comprises hypochlorous acid. In such embodiments, the halogen-containing species and the buffer are preferably in direct contact with each other and may be present as a medium as described above.

[0147] In some embodiments, the halogen-containing species and buffer are packaged such that they are not in direct contact with the intermittent catheter. The catheter may be packaged in a packaging compartment and the halogen-containing species and buffer may be packaged in a separate packaging compartment to the catheter (preferably as a medium).

[0148] In some embodiments, the catheter is packaged such that removal of the catheter from its packaging compartment, in use, brings the halogen-containing species and buffer into direct contact with the intermittent catheter, preferably with an outer surface thereof.

[0149] In some preferred embodiments, there is provided a method of sterilising an intermittent catheter, the method comprising the steps of:

[0150] (a) Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and

[0151] (b) Irradiating the intermittent catheter, the buffer, and the halogen-containing species, wherein the intermittent catheter, the buffer and the halogen-containing species are packaged, and wherein step (b) preferably comprises irradiating the packaged catheter, buffer and halogen-containing species, and wherein the halogen-containing species and buffer are packaged such that they are not in direct contact with the intermittent catheter, wherein the intermittent catheter is packaged in a packaging compartment and the halogen-containing species and buffer are packaged in a separate packaging compartment to the intermittent catheter, and wherein the intermittent catheter is packaged such that removal of the catheter from its packaging compartment, in use, brings the halogencontaining species and buffer into direct contact with the intermittent catheter, preferably with an outer surface thereof.

[0152] Removal of the catheter from its packaging compartment, in use, may be configured to bring the halogen-containing species and buffer into direct contact with at least 20% of the outer surface area of the intermittent catheter, or at least 30, 40, 50, 60, 70, 80, 90, or at least 95% of the outer surface area of the catheter, or into direct contact with substantially 100% of the outer surface area of the catheter.

[0153] In some embodiments, the catheter may be packaged such that removal of the catheter from its packaging compartment, in use, causes the catheter to pass through the packaging compartment containing the halogen-containing species and the buffer to bring the halogen-containing species and buffer into direct contact with the intermittent catheter.

[0154] In some embodiments, the intermittent catheter is packaged in a catheter container, and the halogen-containing species and buffer are packaged in a separate container, such that the halogen-containing species and buffer are not in direct contact with the catheter. The separate container may be located in the catheter container. The separate container may be a bag or sachet.

[0155] In some embodiments, the separate container is pierceable, in use, to release the halogencontaining species and buffer from the separate container and into direct contact with the catheter. Prior to removing the catheter from the packaging and / or prior to inserting the catheter, the user may release a medium comprising the halogen-containing species and buffer from the separate container and apply the medium to the outer surface of the catheter.

[0156] In some embodiments, the separate container is configured to rupture or break to release the halogen-containing species and buffer from the separate container and into direct contact with the catheter upon opening of the catheter container.

[0157] In some embodiments, the catheter is submerged in a liquid and / or solution which does not contain the halogen-containing species and buffer of the invention, and the halogencontaining species and buffer may be present as a medium and contained in a separate medium container. The separate medium container may be as described in statements of invention above.

[0158] The halogen-containing species and buffer of the invention may be present in the separate medium container in solid, liquid, or gel form. The liquid may comprise a solution comprising the halogen-containing species and buffer of the invention. In embodiments wherein the halogen-containing species and buffer of the invention are present in solid form, the solid may comprise a powder or at least one tablet.

[0159] In such embodiments, the halogen-containing species and buffer of the invention may be releasable from the separate medium container, in use. The halogen-containing species and buffer of the invention may be used to treat the catheter after release from the medium container. In embodiments wherein the halogen-containing species and buffer of the invention are present in solid form, the solid may be dissolvable in a liquid to provide a solution comprising the halogen-containing species and buffer of the invention, which may be used to treat the catheter. The liquid may be the liquid in which the catheter is submerged.

[0160] In some embodiments, the catheter is in direct contact with the halogen-containing species and the buffer. In such embodiments, the halogen-containing species and buffer are preferably present in the form of a medium comprising the halogen-containing species and buffer, as described above. In preferred embodiments, the medium is in the form of a gel. In such embodiments, the halogen-containing species preferably comprises hypochlorous acid.

[0161] The catheter may be packaged in direct contact with the halogen-containing species and the buffer.

[0162] The catheter may be packaged in direct contact with the halogen-containing species and the buffer such that the halogen-containing species and the buffer are in contact with an outer surface of the catheter. The halogen-containing species and buffer may cover at least part of the outer surface of the catheter.

[0163] In some embodiments, the catheter may be packaged submerged in the halogencontaining species and buffer, preferably a medium comprising the halogen-containing species and buffer. The catheter may be packaged in a container comprising the medium.

[0164] The catheter may be fully submerged in the medium. In such embodiments, the medium may comprise at least 30% of the internal volume of the container, or at least 40, 50, 60, 70, 80, 90, or at least 95% of the internal volume of the container.

[0165] In some embodiments, the catheter is not fully submerged in the medium. In such embodiments, the medium may comprise no greater than 30% of the internal volume of the container, or no greater than 25, 20, 15, 10, 5, 4, 3, 2, or no greater than 1% of the internal volume of the container. In such embodiments, the medium may be in direct contact with at least part of the catheter, preferably with at least one surface thereof. In some embodiments, the medium may be able to move freely within the container. In such embodiments, the medium may be configured to slosh around within the container, such as when the container is shaken and / or due to natural movement of the container by the user.

[0166] In some embodiments, the catheter comprises a layer of the medium that is on or that comprises at least part of a surface of the catheter, preferably at least part of the outer surface of the catheter. In such embodiments, the medium may be a liquid or a gel.

[0167] The layer of medium may preferably be on the surface of the catheter, preferably on the surface of the catheter body.

[0168] In some embodiments, the layer is on an inner surface of the catheter, an outer surface of the catheter, or both. The inner surface of the catheter may comprise a lumen of the catheter. In preferred embodiments, the layer is on at least an outer surface of the catheter.

[0169] In some embodiments, the layer is on at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99% of the or each surface area of the catheter, preferably at least 75%, or at least 90% of the or each surface area, or between 75% and 100% of the or each surface area. In embodiments in which the layer is on both an inner and outer surface of the catheter, the layer may be on or comprise at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99% of each surface area of the catheter, preferably at least 75% or at least 90% of each surface area or between 75% and 100% of each surface area of both surfaces.

[0170] In some embodiments, at least 75% of the layer, or at least 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% of the layer is the medium.

[0171] In some embodiments, the layer has a thickness of at least 1 pm, or of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or of at least 50 pm.

[0172] In some embodiments, the layer has a thickness of no greater than 10000 pm, or of no greater than 9000, 8000, 7000, 6000, 5000, 4000, 3000, 2000, 1000, 900, 800, 700, 600, 500, 400, or of no greater than 300 pm.

[0173] In some embodiments, the layer has a thickness of between 50-300 pm.

[0174] The layer may have a thickness of between 60-300 pm, or of between 80-300, 100-300, 120-300, 140-300, 160-300, 180-300, 200-300, 220-300, 240-300, 260-300, or of between 280-300 pm.

[0175] The layer may have a thickness of between 50-280 pm, or of between 50-260, 50-240, 50-220, 50-200, 50-180, 50-160, 50-140, 50-120, 50-100, 50-80, or of between 50-60 pm.

[0176] The layer may have a thickness of between 60-280 pm, or of between 80-280, 100-280, 120-280, 140-280, 160-280, 180-280, 200-280, 220-280, 240-280, 260-280, 60-260, 80- 260. 100-260, 120-260, 140-260, 160-260, 180-260, 200-260, 220-260, 240-260, 60-240, 80-240, 100-240, 120-240, 140-240, 160-240, 180-240, 200-240, 220-240, 60-220, 80-

[0177] 220. 100-220, 120-220, 140-220, 160-220, 180-220, 200-220, 60-200, 80-200, 100-200, 120-200, 140-200, 160-200, 180-200, 60-180, 80-180, 100-180, 120-180, 140-180, 160- 180, 60-160, 80-160, 100-160, 120-160, 140-160, 60-140, 80-140, 100-140, 120-140, 60- 120, 80-120, 100-120, 60-100, 80-100, or of between 60-80 pm.

[0178] The layer of medium may have a viscosity of at least 200 cP, or at least 400, 600, 800, or at least 1000 cP, or at least 1200, 1400, 1600, 1800, 2000, 2200, 2400, 2600, 2800, 3000, 3200, 3400, 3600, 3800, 4000, 4200, 4400, 4600, 4800, 5000, 5200, 5400, 5600, 5800, 6000, 6200, 6400, 6600, 6800, 7000, 7200, 7400, 7600, 7800, 8000, 8200, 8400, 8600, 8800, 9000, 9200, 9400, 9600, 9800, or at least 10000 cP.

[0179] The layer of medium may have a viscosity of no greater than 2000000, or no greater than 1750000, 1500000, 1250000, or no greater than 1000000 cP.

[0180] The layer of medium may have a viscosity of between 100-2000000, or between 500- 1000000, or between 1000-500000 cP.

[0181] In some embodiments, the buffer and the halogen-containing species may not be in direct contact with each other. The buffer and halogen-containing species may be packaged such that they are not in direct contact with each other.

[0182] In some embodiments, the halogen-containing species is packaged such that it is not in direct contact with the intermittent catheter and the buffer.

[0183] The intermittent catheter and the buffer may be packaged in a packaging compartment and the halogen-containing species may be packaged in a separate packaging compartment to the catheter and buffer. The catheter may be packaged such that it is in direct contact with the buffer. The buffer may be present at or on an outer surface of the catheter. The buffer may be present at or on at least 20% of the outer surface area of the intermittent catheter, or at least 30, 40, 50, 60, 70, 80, 90, or at least 95% of the outer surface area of the catheter, or substantially 100% of the outer surface area of the catheter. In some embodiments, the buffer may be or comprise part of a lubricious additive present at or on the outer surface of the catheter. In some embodiments, the buffer may comprise a moiety present in the additive structure. The moiety may be present at a terminal end of the additive structure, which may be a polymer chain end. The additive may be an amphiphilic additive.

[0184] In some embodiments, the catheter is packaged such that removal of the catheter from its packaging compartment, in use, brings the halogen-containing species into direct contact with the intermittent catheter and buffer. This may preferably be achieved analogously to that described in statements of invention above, which are also applicable here.

[0185] In some embodiments, the catheter and buffer are packaged in a catheter container, and the halogen-containing species is packaged in a separate container that is located in the catheter container, such that the halogen-containing species is not in direct contact with the catheter. Analogous statements of invention above may also be applied here.

[0186] The separate container may be pierceable, in use, to release the halogen-containing species from the separate container and into direct contact with the catheter and buffer.

[0187] The separate container may be configured to rupture or break to release the halogencontaining species from the separate container and into direct contact with the catheter and buffer upon opening of the catheter container. In such embodiments, the halogen-containing species preferably comprises hypochlorous acid.

[0188] In some embodiments, the buffer is not in direct contact with the catheter and halogencontaining species. The buffer may be packaged such that it is not in direct contact with the intermittent catheter and the halogen-containing species.

[0189] In such embodiments, the catheter may be in direct contact with the halogen-containing species.

[0190] In such embodiments, the halogen-containing species may comprise a species that is capable of forming hypochlorous acid. The species that is capable of forming hypochlorous acid may be capable of forming hypochlorous acid when dissolved in a solution, preferably an aqueous solution. The solution may have a pH of at least 3, or at least 3.2, 3.4, 3.6, 3.8, or at least 4. The solution may have a pH of no greater than 7, or no greater than 6, or no greater than 5.8, 5.6, or preferably no greater than 5.5, 5.4, 5.2, or no greater than 5. The solution may preferably have a pH of between 3-6, or between 3- 5.5, or between 3.5-5.5, or between 4-5.5, or between 4-5, or between 4.2-5. In some preferred embodiments, the solution has a pH of between 3.8-6.0, or between 4.0-5.8, or between 4.2-5.6, or between 4.4-5.4, or between 4.6-5.2, or between 4.8-5.0. In some preferred embodiments, the halogen-containing species that is capable of forming hypochlorous acid may comprise a hypochlorite salt.

[0191] The species that is capable of forming hypochlorous acid may be configured to form hypochlorous acid when contacted with the buffer, preferably with a solution comprising the buffer, in use. In some embodiments, the catheter and the halogen-containing species are packaged in a packaging compartment and the buffer is packaged in a separate packaging compartment to the intermittent catheter and the halogen-containing species. The catheter may be packaged such that it is in direct contact with the halogen-containing species. The halogen-containing species may be present on an outer surface of the intermittent catheter.

[0192] The halogen-containing species may be present on at least 20% of the outer surface area of the intermittent catheter, or at least 30, 40, 50, 60, 70, 80, 90, or at least 95% of the outer surface area of the catheter, or substantially 100% of the outer surface area of the catheter.

[0193] The catheter may be packaged such that removal of the catheter from its packaging compartment, in use, brings the buffer into direct contact with the intermittent catheter and halogen-containing species. This may preferably be achieved analogously to that described in statements of invention above, which are also applicable here.

[0194] The catheter and halogen-containing species may be packaged in a catheter container, and the buffer may be packaged in a separate container that is located in the catheter container, such that the buffer is not in direct contact with the catheter. Analogous statements of invention above may also be applied here.

[0195] The separate container may be pierceable, in use, to release the buffer from the separate container and into direct contact with the catheter and halogen-containing species.

[0196] The separate container may be configured to rupture or break to release the buffer from the separate container and into direct contact with the catheter and halogen-containing species upon opening of the catheter container. In some embodiments, step (b) comprises irradiating the catheter, the buffer and the halogen-containing species with X-ray and / or UV radiation.

[0197] Step (b) may comprise irradiating the catheter, the buffer and the halogen-containing species with at least 5 kGy of radiation, or at least 10 kGy, or at least 15 kGy of radiation, or at least 20, or at least 25 kGy of radiation, or at least 30 kGy of radiation. Step (b) may comprise irradiating the catheter, the buffer and the halogen-containing species with no greater than 80 kGy of radiation, or no greater than 75, 70, 65, or no greater than 60 kGy of radiation, or no greater than 50, 40, or no greater than 30 kGy of radiation. Step (b) may comprise irradiating the catheter, the buffer and the halogen-containing species with between 5-60 kGy of radiation, or preferably between 10-60 kGy of radiation. In some embodiments, step (b) comprises irradiating the catheter, the buffer and the halogencontaining species with between 5-40 kGy, or between 10-30 kGy of radiation. Step (b) may comprise irradiating the catheter, the buffer and the halogen-containing species with around 10 kGy of radiation, or around 15 kGy of radiation, or around 30 kGy of radiation. In other embodiments, step (b) may comprise irradiating the catheter, the buffer and the halogen-containing species with between 25-60 kGy of radiation, or preferably between 30-55 kGy of radiation.

[0198] In some preferred embodiments, there is provided a method of sterilising an intermittent catheter, the method comprising the steps of:

[0199] (a) Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and (b) Irradiating the intermittent catheter, the buffer, and the halogen-containing species, wherein step (b) comprises irradiating the catheter, the buffer and the halogen-containing species with between 25-60 kGy of radiation, or preferably between 30-55 kGy of radiation.

[0200] Step (b) may comprise irradiating the catheter, the buffer and the halogen-containing species when the catheter, buffer and halogen-containing species are packaged, preferably as described in statements of invention above.

[0201] In some preferred embodiments, there is provided a method of sterilising an intermittent catheter, the method comprising the steps of:

[0202] (a) Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and

[0203] (b) Irradiating the intermittent catheter, the buffer, and the halogen-containing species, wherein the intermittent catheter, the buffer and the halogen-containing species are packaged, and wherein step (b) preferably comprises irradiating the packaged catheter, buffer and halogen-containing species.

[0204] In preferred embodiments, the halogen-containing species and buffer are packaged such that they are not in direct contact with the catheter, preferably as described in statements of invention above. According to a second aspect of the invention, there is provided a packaged intermittent catheter comprising: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the hypochlorous acid or species that is capable of forming hypochlorous acid is present in an amount of at least 97 wt.% of the total amount of the halogen-containing species.

[0205] A combination of a buffer and such a halogen-containing species has been shown to provide excellent and stable intermittent catheter lubricity and antimicrobial activity. The presence of hypochlorous acid (or species which can form hypochlorous acid) in an amount of at least 97 wt.% of the halogen-containing species provides a composition that provides particularly optimal antimicrobial activity, which is stabilised by the buffer.

[0206] Statements of invention above for the first aspect of the invention may also be applied mutatis mutandis to the second aspect of the invention.

[0207] In preferred embodiments, the hypochlorous acid or species that is capable of forming hypochlorous acid is present in a total amount of at least 98 wt.% of the total amount of the halogen-containing species, or at least 99, 99.5, 99.6, 99.7, 99.8, or at least 99.9 wt.% of the total amount of the halogen-containing species. In some preferred embodiments, the hypochlorous acid or species that is capable of forming hypochlorous acid is present in a total amount of substantially 100 wt.% of the total amount of the halogen-containing species.

[0208] In embodiments in which the halogen-containing species comprises hypochlorous acid, the total combined amount of hypochlorite salt and molecular chlorine may comprise less than 3 wt.% of the total amount of the halogen-containing species, or less than 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or less than 0.1 wt.% of the total amount of the halogen-containing species.

[0209] In embodiments in which the halogen-containing species comprises hypochlorous acid, the total amount of additional halogen-containing species may comprise less than 3 wt.% of the total amount of the halogen-containing species, or less than 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or less than 0.1 wt.% of the total amount of the halogencontaining species.

[0210] In some preferred embodiments, there is provided a packaged intermittent catheter comprising: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the hypochlorous acid or species that is capable of forming hypochlorous acid is present in an amount of at least 97 wt.% of the total amount of the halogen-containing species, wherein the halogen-containing species and buffer are packaged such that they are not in direct contact with the intermittent catheter, and wherein the intermittent catheter is packaged in a packaging compartment and the halogen-containing species and buffer are packaged in a separate packaging compartment to the intermittent catheter, and wherein the intermittent catheter is packaged such that removal of the catheter from its packaging compartment, in use, brings the halogen-containing species and buffer into direct contact with the intermittent catheter, preferably with an outer surface thereof.

[0211] In some preferred embodiments, there is provided a packaged intermittent catheter comprising: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the hypochlorous acid or species that is capable of forming hypochlorous acid is present in an amount of at least 97 wt.% of the total amount of the halogen-containing species, wherein the intermittent catheter comprises a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the additive comprises an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5- 25 and preferably 9-25, and wherein the B -block of the amphiphilic A-B block copolymer additive is a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers independently chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0212] In some preferred embodiments, there is provided a packaged intermittent catheter comprising: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the hypochlorous acid or species that is capable of forming hypochlorous acid is present in an amount of at least 97 wt.% of the total amount of the halogen-containing species, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, wherein the halogen-containing species comprises hypochlorous acid, and wherein the medium comprises the buffer in a total concentration of between 1-4 wt.% of the medium, or between 2-3 wt.%, or between 2.3-2.8 wt.% of the medium.

[0213] In some preferred embodiments, there is provided a packaged intermittent catheter comprising: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the hypochlorous acid or species that is capable of forming hypochlorous acid is present in an amount of at least 97 wt.% of the total amount of the halogen-containing species, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, wherein the halogen-containing species comprises hypochlorous acid, and wherein the medium is present as a gel, and wherein the gel comprises glycerin and / or at least one paraben.

[0214] According to a third aspect of the invention, there is provided a packaged intermittent catheter comprising : an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid.

[0215] A combination of a buffer and such a halogen-containing species has been shown to provide excellent and stable intermittent catheter lubricity and antimicrobial activity. Surprisingly, such a combination has also been found to have excellent compatibility with an amphiphilic A-B block copolymer lubricious additive. There is no negative interference between such an additive and the combination of the buffer and halogencontaining species, and additive migration from the catheter remains unaffected.

[0216] Statements of the invention for other aspects of the invention may also be applied mutatis mutandis to the third aspect of the invention.

[0217] In some embodiments, one or both of the hydrophobic hydrocarbon A-block and the hydrophilic B -block may be branched. The hydrophobic A-block may comprise hydrophobic hydrocarbon chains branching therefrom. The hydrophobic hydrocarbon chains may be of shorter chain lengths than the hydrophobic hydrocarbon A-block. The hydrophilic B -block may comprise further hydrophilic B -blocks branching therefrom.

[0218] In some embodiments, the B-block is a hydrophilic oligomer comprising at least 1, 2, 3, 4, or at least 5 monomer units. In some embodiments, the B-block comprises no greater than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, or no greater than 6 monomer units. In some embodiments, the B-block comprises between 2 and 15 monomer units, preferably between 2 and 10 monomer units. At least one monomer unit may be selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. At least one monomer unit may be chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. At least one monomer unit may be preferably selected from the group consisting of: ethylene oxide, propylene oxide, ethylene glycol, propylene glycol, epichlorohydrin, acrylic acid, methacrylic acid, ethylene imine, caprolactone, vinyl alcohol, and vinyl acetate. At least one monomer unit may be preferably chosen from: ethylene oxide, propylene oxide, ethylene glycol, propylene glycol, epichlorohydrin, acrylic acid, methacrylic acid, ethylene imine, caprolactone, vinyl alcohol, and vinyl acetate. In some embodiments, at least one monomer unit comprises alkylene oxide groups independently selected from ethylene oxide and propylene oxide, and in preferred embodiments, all of the monomer units are ethylene oxide or all of the monomer units are propylene oxide.

[0219] The hydrophobic A-block may comprise a carbon chain of at least 5 carbon atoms, or at least 10, 15, 20, 25, 30, 35, or 40 carbon atoms. The hydrophobic portion may preferably comprise a carbon chain of between 20-52 carbon atoms. In some embodiments, the A-block comprises a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a. The value of “a” may be between 5-25; for instance, “a” may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25, or a half integer of any of the above values. The value of “a” may preferably be between 9-25; for instance, “a” may be 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25, or a half integer of any of the above values.

[0220] In some preferred embodiments, there is provided a packaged intermittent catheter comprising: an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CHaCth CthCth where “a” is 5-25 and preferably 9-25, and wherein the B -block of the amphiphilic A-B block copolymer additive is a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers independently chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0221] In some preferred embodiments, there is provided a packaged intermittent catheter comprising: an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the halogen-containing species and buffer are packaged such that they are not in direct contact with the intermittent catheter, wherein the intermittent catheter is packaged in a packaging compartment and the halogen-containing species and buffer are packaged in a separate packaging compartment to the intermittent catheter, and wherein the intermittent catheter is packaged such that removal of the catheter from its packaging compartment, in use, brings the halogen-containing species and buffer into direct contact with the intermittent catheter, preferably with an outer surface thereof.

[0222] In some preferred embodiments, there is provided a packaged intermittent catheter comprising: an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, wherein the halogen-containing species comprises hypochlorous acid, and wherein the medium comprises the buffer in a total concentration of between 1-4 wt.% of the medium, or between 2-3 wt.%, or between 2.3- 2.8 wt.% of the medium.

[0223] In some preferred embodiments, there is provided a packaged intermittent catheter comprising: an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, wherein the halogen-containing species comprises hypochlorous acid, and wherein the medium is present as a gel, and wherein the gel comprises glycerin and / or at least one paraben.

[0224] According to a fourth aspect of the invention, there is provided an intermittent catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogen-containing species.

[0225] In some preferred embodiments, there is provided an intermittent catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogencontaining species, wherein the intermittent catheter comprises a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the additive comprises an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CH Cth CthCth where “a” is 5-25 and preferably 9-25, and wherein the B-block of the amphiphilic A-B block copolymer additive is a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers independently chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. In some preferred embodiments, there is provided an intermittent catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogencontaining species, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, wherein the medium comprises the buffer in a total concentration of between 1-4 wt.% of the medium, or between 2-3 wt.%, or between 2.3-2.8 wt.% of the medium.

[0226] In some preferred embodiments, there is provided an intermittent catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogencontaining species, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, and wherein the medium is present as a gel, and wherein the gel comprises glycerin and / or at least one paraben.

[0227] According to a fifth aspect of the invention, there is provided an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid. In some preferred embodiments, there is provided an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5- 25 and preferably 9-25, and wherein the B-block of the amphiphilic A-B block copolymer additive is a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers independently chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0228] In some preferred embodiments, there is provided an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, wherein the medium comprises the buffer in a total concentration of between 1-4 wt.% of the medium, or between 2-3 wt.%, or between 2.3-2.8 wt.% of the medium.

[0229] In some preferred embodiments, there is provided an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, and wherein the medium is present as a gel, and wherein the gel comprises glycerin and / or at least one paraben.

[0230] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the fourth and fifth aspects of the invention.

[0231] The following statements relate to the fourth and fifth aspects of the invention.

[0232] The buffer and halogen-containing species may preferably be present as a medium comprising the buffer and halogen-containing species, preferably as described in statements of invention for the first aspect of the invention above.

[0233] In some embodiments, the medium is present on at least 20% of the outer surface area of the tubular body of the catheter, or on at least 30, 40, 50, 60, 70, 80, 90, or on at least 95% of the outer surface area of the tubular body of the catheter. The medium may be present on substantially 100% of the outer surface area of the tubular body of the catheter. In some embodiments, the medium is present as a coating on the outer surface of the tubular body of the catheter.

[0234] According to a sixth aspect of the invention, there is provided a method of lubricating an intermittent catheter, the method comprising the steps of:

[0235] (a) Providing an intermittent catheter comprising a hollow polymeric tubular body; and (b) Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogen-containing species.

[0236] In some preferred embodiments, there is provided a method of lubricating an intermittent catheter, the method comprising the steps of:

[0237] (a) Providing an intermittent catheter comprising a hollow polymeric tubular body; and

[0238] (b) Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogen-containing species, wherein the intermittent catheter comprises a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the additive comprises an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CtbCThlCthCtbla where “a” is 5-25 and preferably 9-25, and wherein the B-block of the amphiphilic A-B block copolymer additive is a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers independently chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. In some preferred embodiments, there is provided a method of lubricating an intermittent catheter, the method comprising the steps of:

[0239] (a) Providing an intermittent catheter comprising a hollow polymeric tubular body; and

[0240] (b) Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogen-containing species, wherein the medium comprises the buffer in a total concentration of between 1-4 wt.% of the medium, or between 2-3 wt.%, or between 2.3-2.8 wt.% of the medium.

[0241] In some preferred embodiments, there is provided a method of lubricating an intermittent catheter, the method comprising the steps of:

[0242] (a) Providing an intermittent catheter comprising a hollow polymeric tubular body; and

[0243] (b) Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogen-containing species, wherein the medium is present as a gel, and wherein the gel comprises glycerin and / or at least one paraben

[0244] According to a seventh aspect of the invention, there is provided a method of lubricating an intermittent catheter, the method comprising the steps of: (a) Providing an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A- block and a hydrophilic B-block; and

[0245] (b) Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid.

[0246] In some preferred embodiments, there is provided a method of lubricating an intermittent catheter, the method comprising the steps of:

[0247] (a) Providing an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A- block and a hydrophilic B-block; and

[0248] (b) Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CH Cth CthCth where “a” is 5-25 and preferably 9-25, and wherein the B-block of the amphiphilic A-B block copolymer additive is a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers independently chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. In some preferred embodiments, there is provided a method of lubricating an intermittent catheter, the method comprising the steps of:

[0249] (a) Providing an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A- block and a hydrophilic B-block; and

[0250] (b) Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid, wherein the medium comprises the buffer in a total concentration of between 1-4 wt.% of the medium, or between 2-3 wt.%, or between 2.3-2.8 wt.% of the medium

[0251] In some preferred embodiments, there is provided a method of lubricating an intermittent catheter, the method comprising the steps of:

[0252] (a) Providing an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A- block and a hydrophilic B-block; and

[0253] (b) Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid, wherein the medium is present as a gel, and wherein the gel comprises glycerin and / or at least one paraben. Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the sixth and seventh aspects of the invention.

[0254] The following statements relate to the sixth and seventh aspects of the invention.

[0255] The lubricating medium is preferably the medium comprising the buffer and halogencontaining species as described in statements of invention for the first aspect of the invention above.

[0256] In some embodiments, step (b) comprises treating at least 20% of the outer surface area of the catheter with the medium, or at least 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99% of the outer surface area of the catheter, preferably at least 75%, or at least 90% of the outer surface area, or between 75% and 100% of the outer surface area of the catheter.

[0257] Treatment in step (b) may involve one or more treatment methods independently chosen from: submersion, spray coating, soaking, dipping, wetting, and combinations thereof. Treatment in step (b) may involve one or more treatment methods independently selected from the group consisting of: submersion, spray coating, soaking, dipping, wetting, and combinations thereof.

[0258] In some embodiments, step (b) comprises spraying the catheter with the medium. Step (b) may comprise spraying at least part of a surface of the catheter, preferably at least part of the outer surface of the catheter.

[0259] In some embodiments, step (b) comprises submerging the catheter in the medium.

[0260] In some embodiments, the medium is packaged such that it is not in direct contact with the catheter. The catheter may be packaged in a packaging compartment and the medium may be packaged in a separate compartment to the catheter, preferably as described in statements of invention for the first aspect of the invention above. In some embodiments, the catheter is packaged such that removal of the catheter from its packaging compartment, in use, brings the medium into direct contact with an outer surface of the intermittent catheter. In such embodiments, step (b) may comprise removing the catheter from its packaging compartment to bring the catheter into direct contact with the medium and treat the catheter with the medium.

[0261] In some embodiments, the medium may be contained in a medium container and the catheter may be contained in a separate catheter container, preferably as described for the first aspect of the invention. Step (b) may comprise releasing the medium from the separate medium container, and then treating the catheter with the medium. In some embodiments, the medium container may be configured to rupture or break to release the medium from the medium container and into direct contact with the catheter upon opening of the catheter container. In such embodiments, step (b) may comprise opening the catheter container to treat the catheter with the medium.

[0262] In some embodiments, the hypochlorous acid is packaged such that it is not in direct contact with the intermittent catheter and the buffer.

[0263] The intermittent catheter and the buffer may be packaged in a packaging compartment and the hypochlorous acid may be packaged in a separate packaging compartment to the catheter and buffer.

[0264] The catheter may be packaged such that it is in direct contact with the buffer, preferably as described in statements of invention for the first aspect of the invention above. In some embodiments, the catheter is packaged such that removal of the catheter from its packaging compartment, in use, brings the hypochlorous acid into direct contact with the intermittent catheter and buffer. In such embodiments, step (b) may comprise removing the catheter from its packaging compartment to bring the hypochlorous acid into direct contact with the buffer and catheter. The buffer and hypochlorous acid may preferably form the lubricating medium as they contact each other.

[0265] In some embodiments, the catheter and buffer are packaged in a catheter container, and the hypochlorous acid is packaged in a separate container that is located in the catheter container, such that the hypochlorous acid is not in direct contact with the catheter. Step (b) may comprise releasing the hypochlorous acid from the separate container to bring the hypochlorous acid into direct contact with the catheter and buffer.

[0266] The separate container may be configured to rupture or break to release the hypochlorous acid from the separate container and into direct contact with the catheter and buffer upon opening of the catheter container. In such embodiments, step (b) may comprise opening the catheter container to treat the catheter with the medium.

[0267] In some embodiments, the buffer may be packaged such that it is not in direct contact with the intermittent catheter.

[0268] In such embodiments, the catheter may be in direct contact with a halogen-containing species that is capable of forming hypochlorous acid, preferably as described in statements of invention for the first aspect of the invention above.

[0269] The species that is capable of forming hypochlorous acid may be capable of forming hypochlorous acid when dissolved in a solution, preferably an aqueous solution. The solution may have a pH of at least 3, or at least 3.2, 3.4, 3.6, 3.8, or at least 4. The solution may have a pH of no greater than 7, or no greater than 6, or no greater than 5.8, 5.6, or preferably no greater than 5.5, 5.4, 5.2, or no greater than 5. The solution may preferably have a pH of between 3-6, or between 3-5.5, or between 3.5-5.5, or between 4- 5.5, or between 4-5, or between 4.2-5. In some preferred embodiments, the solution has a pH of between 3.8-6.0, or between 4.0-5.8, or between 4.2-5.6, or between 4.4-5.4, or between 4.6-5.2, or between 4.8-5.0. In some preferred embodiments, the halogencontaining species that is capable of forming hypochlorous acid may comprise a hypochlorite salt.

[0270] The species that is capable of forming hypochlorous acid may be configured to form hypochlorous acid when contacted with the buffer, preferably with a solution comprising the buffer, in use.

[0271] In some embodiments, the catheter and the halogen-containing species are packaged in a packaging compartment and the buffer is packaged in a separate packaging compartment to the intermittent catheter and the halogen-containing species. The catheter may be packaged such that it is in direct contact with the halogen-containing species. The halogen-containing species may be present on an outer surface of the intermittent catheter.

[0272] The catheter may be packaged such that removal of the catheter from its packaging compartment, in use, brings the buffer into direct contact with the intermittent catheter and halogen-containing species. In such embodiments, step (b) may comprise removing the catheter from its packaging compartment to bring the buffer into direct contact with the halogen-containing species and catheter. The buffer and halogen-containing species may preferably form the lubricating medium comprising the buffer and hypochlorous acid as they contact each other.

[0273] The catheter and halogen-containing species may be packaged in a catheter container, and the buffer may be packaged in a separate container that is located in the catheter container, such that the buffer is not in direct contact with the catheter. Step (b) may comprise releasing the buffer from the separate container to bring the buffer into direct contact with the catheter and halogen-containing species.

[0274] The separate container may be configured to rupture or break to release the buffer from the separate container and into direct contact with the catheter and halogen-containing species upon opening of the catheter container. In such embodiments, step (b) may comprise opening the catheter container to treat the catheter with the medium.

[0275] In some embodiments, the method comprises a further step of lubricating the catheter with an additional lubricating agent. The further lubrication step may preferably be performed after step (b). In some embodiments, the catheter may be dried after step (b) and before the further lubrication step. The drying step may comprise air drying and / or wiping the catheter to dry the catheter. In some embodiments, the further lubrication step is performed before use of the catheter, preferably directly before use of the catheter. Preferably, the further lubrication step is performed after step (b) and before use of the catheter.

[0276] The additional lubricating agent may be water or may comprise water. The additional lubricating agent may be an aqueous solution.

[0277] The further lubrication step may comprise treating the catheter, preferably at least part of the outer surface thereof with the lubricating agent. The further lubrication step may comprise applying the lubricating agent to the catheter, preferably to at least part of the outer surface of the catheter.

[0278] In some embodiments, a further lubrication step is not performed. In such embodiments, the catheter may be used directly after step (b).

[0279] Detailed Description of the Invention

[0280] In order that the invention may be more clearly understood embodiments thereof will now be described, by way of example only, with reference to the accompanying drawings, of which:

[0281] Figure 1 shows a graph displaying the results of antimicrobial testing of aqueous solutions containing hypochlorous acid pre- and post- X-ray irradiation, as per Example 1 below. The graph shows colony forming units per millilitre (CFU / mL) of bacteria against the test sample. Results are shown for irradiation performed for 30 seconds and 2 minutes respectively. Irradiation is performed using standard and maximum doses (Standard dose: 32.3-33.6 kGy; Maximum dose: 53.0-54.5 kGy). Testing was performed against two challenge organisms: E. coli NCTC 13353 and E. faecalis NCTC 12201. Results of a maximum recovery diluent (MRD) control are also included to indicate no antimicrobial activity.

[0282] Packaged intermittent catheters of the invention

[0283] The following packaged intermittent urinary catheters of the invention are provided.

[0284] Packaged catheter 1 (inventive) - Catheter packaged with aqueous solution comprising hypochlorous acid and buffer (catheter not in direct contact with aqueous solution) This packaged catheter of the invention comprises a single-use intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer formed from a thermoplastic elastomeric material and further comprising an amphiphilic additive. The amphiphilic additive is an A-B block copolymer of the formula: CH3CH2(CH2CH2)IO(OCH2CH2)5OH. The catheter is contained in a first packaging compartment.

[0285] The catheter packaging also contains a second packaging compartment which contains an aqueous solution lubricating medium comprising a citric acid / sodium citrate buffer and hypochlorous acid in a concentration of 300 ppm. Hypochlorous acid is the only halogencontaining species present in the aqueous solution. The pH of the aqueous solution is maintained at 4.5 using the buffer.

[0286] The catheter is packaged such that it is not in direct contact with the aqueous solution. However, the catheter is packaged such that removal of the catheter from the first packaging compartment and out of the packaging would result in the catheter passing through the second packaging compartment, thus bringing the aqueous medium into direct contact with the entire outer surface of the tubular body of the catheter. Removing the catheter would thus lubricate the catheter with the aqueous solution, such that the catheter could be simply removed and used in the conventional manner, without any requirement to rinse the catheter before use.

[0287] Prior to removal of the catheter, the entire packaged catheter is sterilised by X-ray irradiation (the aqueous medium remaining in the second packaging compartment is also subjected to X-ray irradiation). Surprisingly, even after sterilisation by irradiation, the aqueous solution maintains its hypochlorous acid concentration of 300 ppm and no additional halogen-containing species is detected. In addition, the pH of the solution remains constant. The aqueous solution retains excellent lubricity and antimicrobial performance even after sterilisation by irradiation.

[0288] On removal from the packaging the lubricated catheter has excellent surface lubricity and the hypochlorous acid in the aqueous solution provides excellent antimicrobial effects, allowing for bacteria to be killed on the outer surface of the catheter. Antimicrobial effects remain even during and after use of the intermittent catheter.

[0289] The aqueous solution also shows excellent compatibility with the catheter amphiphilic additive. No negative interference between the additive and the aqueous solution occur.

[0290] Packaged Catheter 2 (inventive) - Catheter packaged submerged in an aqueous gel comprising hypochlorous acid and buffer

[0291] This packaged catheter of the invention comprises a single-use intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer formed from a polyethylene thermoplastic elastomeric material and further comprising an amphiphilic additive. The amphiphilic additive is an A-B block copolymer of the formula: CHaCTh C^CTHHOCTHCTb OH.

[0292] The catheter is contained in a sealed container and is submerged entirely in an aqueous gel lubricating medium. The gel contains water and glycerin, and also contains a succinic acid buffer and hypochlorous acid in a concentration of 350 ppm. Hypochlorous acid is the only halogen-containing species present in the aqueous gel. The pH of the aqueous gel is maintained at 4.7 using the buffer. The catheter can simply be removed from the container and used in the conventional manner, without any requirement to rinse the catheter after removal from the gel and before use.

[0293] Before removal of the catheter from the container, the entire packaged catheter is sterilised by UV irradiation (the aqueous gel is also subjected to UV irradiation). As for Packaged Catheter 1 above, even after sterilisation by irradiation, the aqueous gel maintains its hypochlorous acid concentration and no additional halogen-containing species can be detected. In addition, the pH of the solution remains constant. The aqueous gel retains excellent lubricity and antimicrobial performance even after sterilisation by irradiation.

[0294] On removal from the container, the outer surface of the catheter body is coated with a layer of the gel. Catheter surface lubricity is excellent, and the catheter can be inserted and removed easily with minimal discomfort caused. The hypochlorous acid in the aqueous gel provides excellent antimicrobial effects, as described for Packaged Catheter 1 above.

[0295] The aqueous gel also shows excellent compatibility with the catheter amphiphilic additive, as described for Packaged Catheter 1 above.

[0296] Packaged Catheter 3 (inventive) - Catheter packaged in direct contact with buffer and not in direct contact with hypochlorous acid aqueous solution

[0297] This packaged catheter of the invention comprises an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer formed from a polypropylene thermoplastic elastomeric material and further comprising an amphiphilic additive. The amphiphilic additive is an A-B block copolymer of the formula: CH3CH2(CH2CH2)15(OCH2CH2)4OH. The entire outer surface area of the catheter body is also coated with an aqueous solution comprising acetate buffer. The catheter is contained in a first packaging compartment.

[0298] The catheter packaging also contains a second packaging compartment which contains an aqueous solution comprising hypochlorous acid in a concentration of 240 ppm and molecular chlorine in a concentration of 60 ppm. The pH of the aqueous solution is 3.

[0299] The catheter is packaged such that it is not in direct contact with the hypochlorous acid aqueous solution. However, the catheter is packaged such that removal of the catheter from the first packaging compartment and out of the packaging would result in the catheter passing through the second packaging compartment, thus bringing the hypochlorous acid aqueous solution into direct contact with the entire outer surface of the tubular body of the catheter and also into direct contact with the buffer solution present on the outer surface of the catheter. Removing the catheter would thus lubricate the catheter with the hypochlorous acid aqueous solution, such that the catheter could be simply removed and used in the conventional manner, without any requirement to rinse the catheter before use.

[0300] On removal from the packaging, the hypochlorous acid aqueous solution contacts the buffer solution to provide an aqueous medium on the surface of the catheter which contains hypochlorous acid as the sole halogen-containing species (no molecular chlorine is present). The pH of the solution is 5.0. The lubricated catheter has excellent surface lubricity and the hypochlorous acid in the aqueous solution provides excellent antimicrobial effects, as per Packaged Catheter 1 The aqueous solution also shows excellent compatibility with the catheter amphiphilic additive, as described for Packaged Catheter 1 above.

[0301] As for Packaged Catheter 1, even after X-ray sterilisation, the combined aqueous solution maintains its hypochlorous acid concentration, and no additional halogen-containing species can be detected. In addition, the pH of the solution remains constant. The aqueous solution retains excellent lubricity and antimicrobial performance even after sterilisation by irradiation.

[0302] Packaged Catheter 4 (inventive) - Catheter packaged in direct contact with hypochlorite salt and not in direct contact with a buffer aqueous solution

[0303] This packaged catheter of the invention comprises an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer formed from a polypropylene thermoplastic elastomeric material and further comprising an amphiphilic additive. The amphiphilic additive is an A-B block copolymer of the formula: CH3CH2(CH2CH2)2O(OCH2CH2)80H. The entire outer surface area of the catheter body is also coated with a sodium hypochlorite powder. The catheter is contained in a first packaging compartment.

[0304] The catheter packaging also contains a second packaging compartment which contains an aqueous solution comprising a malic acid buffer.

[0305] The catheter is packaged such that it is not in direct contact with the buffer aqueous solution. However, the catheter is packaged such that removal of the catheter from the first packaging compartment and out of the packaging would result in the catheter passing through the second packaging compartment, thus bringing the buffer aqueous solution into direct contact with the entire outer surface of the tubular body of the catheter and also into direct contact with the sodium hypochlorite powder present on the outer surface of the catheter. Removing the catheter would thus lubricate the catheter with the aqueous solution, such that the catheter could be simply removed and used in the conventional manner, without any requirement to rinse the catheter before use.

[0306] On removal from the packaging, the buffer aqueous solution contacts the sodium hypochlorite powder, thus dissolving the powder to provide an aqueous medium on the surface of the catheter which contains hypochlorous acid as the sole halogen-containing species in a concentration of 325 ppm (no hypochlorite salt is present, as it has formed hypochlorous acid on contact with the buffer aqueous solution). The pH of the solution is 4. The lubricated catheter has excellent surface lubricity and the hypochlorous acid in the aqueous solution provides excellent antimicrobial effects, as per Packaged Catheter 1

[0307] The aqueous solution also shows excellent compatibility with the catheter amphiphilic additive, as described for Packaged Catheter 1 above.

[0308] As for Packaged Catheter 1, even after X-ray sterilisation, the combined aqueous solution maintains its hypochlorous acid concentration, and no additional halogen-containing species can be detected. In addition, the pH of the solution remains constant. The aqueous solution retains excellent lubricity and antimicrobial performance even after sterilisation by irradiation.

[0309] Control Packaged Catheter 1 (not of the invention)

[0310] A packaged catheter is provided as for Packaged Catheter 1 of the invention above, with the sole difference being that the aqueous solution in the second packaging compartment does not contain a buffer and instead contains only hypochlorous acid in a concentration of 300 ppm. Hypochlorous acid is the only halogen-containing species present in the aqueous solution. The pH of the aqueous solution is 4.5.

[0311] The entire packaged catheter is sterilised by X-ray irradiation (the aqueous medium in the second packaging compartment is also subjected to X-ray irradiation). After sterilisation by irradiation, the hypochlorous acid concentration in the aqueous solution drops to 50% of its original value and the pH of the aqueous solution decreases to around 2.5. Hypochlorous acid is no longer the sole halogen-containing species present in the solution, and molecular chlorine is detected in an amount approximately equimolar to the amount of hypochlorous acid present. Disadvantageously, the antimicrobial activity of the aqueous solution drops dramatically relative to the activity observed for the Packaged Catheter 1 of the invention.

[0312] Example 1 - Laboratory testing to determine effects of irradiation on a nonbuffered hypochlorous acid solution

[0313] Aqueous solutions containing hypochlorous acid (no buffer) were placed into 100 mL containers and X-ray irradiated at the following standard and maximum doses (Standard dose: 32.3-33.6 kGy; Maximum dose: 53.0-54.5 kGy).

[0314] The pH and free Cl content (ppm) of the solutions were measured before and after X-ray irradiation, and the results are displayed in Table 1 below.

[0315] Table 1

[0316] In addition, the solutions pre- and post-irradiation were subjected to a microbial test to assess the antimicrobial activities of the solutions. The results are displayed in Figure 1.

[0317] As can be seen from the graph in Figure 1, antimicrobial activity against both E. coli and E. faecalis was consistently high pre-irradiation, demonstrating the excellent antimicrobial efficacy of hypochlorous acid against a broad range of challenging microorganisms.

[0318] For both organisms tested, post-irradiation, minimal efficacy was observed. This observation is consistent with the analytical testing, which showed that no free Cl was detected.

[0319] Without wishing to be bound by theory, X-ray irradiation results in a drop in the pH of the solutions, which results in a reduction of the concentration of highly active hypochlorous acid in the solutions, which results in a drop in antimicrobial activity, resulting in CFU values approaching those of the maximum recovery diluent (MRD) control.

[0320] Analogous testing was performed with hypochlorous acid solutions which also contained a citric acid / sodium citrate buffer. In this case, antimicrobial activity of the solution was unaffected even after X-ray irradiation and activity matched pre-irradiation levels. In addition, pH and free Cl content remained almost the same as pre-irradiation levels.

[0321] The above embodiments are described by way of example only. Many variations are possible without departing from the scope of the invention as defined in the appended claims.

Claims

CLAIMS1. A method of sterilising an intermittent catheter, the method comprising the steps of: a. Providing: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid; and b. Irradiating the intermittent catheter, the buffer, and the halogencontaining species.

2. A method as claimed in claim 1 , wherein step (b) comprises irradiating the catheter, the buffer and the halogen-containing species with X-ray or UV radiation.

3. A method as claimed in any preceding claim, wherein step (b) comprises irradiating the catheter, the buffer and the halogen-containing species with between 25-60 kGy of radiation, or preferably between 30-55 kGy of radiation.

4. A method as claimed in any preceding claim, wherein the intermittent catheter, the buffer and the halogen-containing species are packaged, and wherein step (b) preferably comprises irradiating the packaged catheter, buffer and halogen-containing species.

5. A method as claimed in any preceding claim, wherein the hypochlorous acid or species that is capable of forming hypochlorous acid is present in an amount of at least 97 wt.% of the total amount of the halogen-containingspecies, or preferably in an amount of substantially 100 wt.% of the total amount of the halogen-containing species.

6. A packaged intermittent catheter comprising: an intermittent catheter; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid, wherein the hypochlorous acid or species that is capable of forming hypochlorous acid is present in an amount of at least 97 wt.% of the total amount of the halogen-containing species, or preferably in an amount of substantially 100 wt.% of the total amount of the halogen-containing species.

7. A method as claimed in any one of claims 1 to 5 or a packaged intermittent catheter as claimed in claim 6, wherein the intermittent catheter comprises a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the additive comprises an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

8. A packaged intermittent catheter comprising: an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block; a buffer; and a halogen-containing species comprising hypochlorous acid or a species that is capable of forming hypochlorous acid.

9. A method as claimed in 7 or a packaged intermittent catheter as claimed in claim 7 or 8, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CHsCth CthCthlawhere “a” is 5-25 and preferably 9-25, and wherein the B-block of the amphiphilic A-B block copolymer additive is a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers independently chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

10. A method as claimed in any one of claims 1 to 5, 7, or 9 or a packaged intermittent catheter as claimed in any one of claims 6 to 9, wherein the buffer has at least one pKa of between 3.0-6.5, or preferably between 4.0-5.8, and wherein the buffer is preferably independently chosen from: a citric acid or citrate buffer, a succinic acid buffer, an acetate buffer, a malic acid buffer, and combinations thereof.

11. A method as claimed in any one of claims 1 to 5, 7, or 9 to 10 or a packaged intermittent catheter as claimed in any one of claims 6 to 10, wherein the halogen-containing species and buffer are present as a medium that comprises the halogen-containing species and the buffer, and wherein the halogencontaining species comprises hypochlorous acid.

12. A method or a packaged intermittent catheter as claimed in claim 11, wherein the medium comprises the buffer in a total concentration of between 1-4 wt.% of the medium, or between 2-3 wt.% of the medium, or between 2.3-2.8 wt.% of the medium.

13. A method or a packaged intermittent catheter as claimed in claim 11 or 12, wherein the medium comprises hypochlorous acid in a total concentration ofbetween 100-1000 ppm of the medium, preferably between 100-400 ppm of the medium.

14. A method or a packaged intermittent catheter as claimed in any one of claims 11 to 13, wherein the medium has a pH of between 3.0-6.0, or preferably between 4.0-5.8.

15. A method or a packaged intermittent catheter as claimed in any one of claims 11 to 14, wherein the medium is present in gel form, and wherein the gel comprises glycerin and / or at least one paraben.

16. A method as claimed in claim 4 or in any one of claims 5, 7, or 9 to 15 when dependent on claim 4 or a packaged intermittent catheter as claimed in any one of claims 6 to 15, wherein the halogen-containing species and buffer are packaged such that they are not in direct contact with the intermittent catheter, wherein the intermittent catheter is packaged in a packaging compartment and the halogen-containing species and buffer are packaged in a separate packaging compartment to the intermittent catheter, and wherein the intermittent catheter is packaged such that removal of the catheter from its packaging compartment, in use, brings the halogen-containing species and buffer into direct contact with the intermittent catheter, preferably with an outer surface thereof.

17. An intermittent catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid in anamount of at least 97 wt.% of the total amount of the halogen-containing species.

18. An intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein at least part of an outer surface of the tubular body of the catheter comprises: a buffer; and a halogen-containing species comprising hypochlorous acid.

19. A method of lubricating an intermittent catheter, the method comprising the steps of: a. Providing an intermittent catheter comprising a hollow polymeric tubular body; and b. Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid in an amount of at least 97 wt.% of the total amount of the halogencontaining species.

20. A method of lubricating an intermittent catheter, the method comprising the steps of: a. Providing an intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, the additive comprising an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block; andb. Treating at least part of an outer surface of the tubular body of the catheter with a lubricating medium comprising: a buffer; and a halogen-containing species comprising hypochlorous acid.

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