Urinary catheters

Abstract

The invention provides a method of sterilising a urinary catheter, the method comprising the steps of: a. Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and b. Irradiating the urinary catheter and the medium.

Description

[0001] URINARY CATHETERS

[0002] Technical Field of the Invention

[0003] The present invention relates to the use of octenidine or a salt thereof for urinary 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 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 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. 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.

[0010] 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.

[0011] 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.

[0012] Summary of the Invention According to a first aspect of the invention, there is provided a method of sterilising a urinary catheter, the method comprising the steps of:

[0013] (a) Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and

[0014] (b) Irradiating the urinary catheter and the medium.

[0015] The medium of the invention has been found to provide excellent antimicrobial activity when contacted with a urinary catheter, showing long-term, broad spectrum and rapid kill of bacteria. Such a medium poses substantially no safety issues when used with catheters and also provides excellent and stable catheter lubricity.

[0016] To ensure thorough sterilisation of a urinary catheter, the catheter should be sterilised by exposing it to irradiation. What is especially surprising about the medium of the invention and what particularly sets it apart from known antimicrobial media, is that it has been found that when the medium is exposed to irradiation during sterilisation of the catheter, the antimicrobial activity and lubricating performance of the octenidine species is substantially retained. This property of the octenidine-containing medium of the invention is unexpected, and other known antimicrobial compounds degrade when exposed to irradiation, such that there is minimal or a reduced amount of the active compound present after irradiation, leading to a dramatic reduction in antimicrobial performance. This also negatively impacts lubricity performance of media containing such antimicrobials, and the surface properties of the catheters are as a result negatively impacted.

[0017] In other cases, known antimicrobial media undergo physical changes, and may degrade into a form which is visibly and / or texturally undesired in catheter packaging when exposed to irradiation. The medium of the invention surprisingly is also not so physically affected by irradiation and does not substantially create visible and / or textural change into undesirable forms in catheter packaging, so there is no need to sterilise the catheter by irradiation in isolation of the medium.

[0018] Furthermore, there is no requirement for the medium of the invention to be packaged in hermetically sealed packaging for the medium to demonstrate its resistance to sterilisation discussed above.

[0019] The urinary catheter may be an intermittent catheter or an indwelling catheter. Preferably, 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.

[0020] The catheter may be a reusable or single-use catheter. Preferably, the catheter is a singleuse catheter.

[0021] 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.

[0022] 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.

[0023] 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, medium 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 medium of the invention, and additive migration from the catheter remains unaffected.

[0024] In some embodiments, at least one additive is a hydrophilic additive.

[0025] 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 blockcopolymer surfactants, gelatin, collagen, albumin, chitin, heparin, elastin, fibrin, and combinations thereof.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] At least one hydrophilic additive may comprise PVP or a derivative thereof.

[0030] 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.

[0031] In some embodiments, the catheter comprises a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive.

[0032] In some embodiments, at least one additive is polymeric or oligomeric. 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.

[0033] In some embodiments, the additive is a B-A-B tri-block copolymer comprising a hydrophobic hydrocarbon A-block and hydrophilic B -blocks.

[0034] 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.

[0035] 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.

[0036] In further embodiments, the additive is a star-block or multi-block copolymer comprising hydrophilic and hydrophobic monomer units.

[0037] In preferred embodiments, the additive is an A-B block copolymer comprising a hydrophobic A-block and a hydrophilic B-block. It is especially surprising that when such an additive is used, the medium of the invention shows excellent compatibility with the additive. There is little to no negative interference between the medium and the additive, and additive migration from the catheter remains substantially unaffected even when the combination of catheter and medium are exposed to irradiation. This is in contrast to many known antimicrobials which are known to interact with such additives and cause them to migrate from the catheter. Such negative effects are typically severely exemplified post-irradiation, and the additives and media of the prior art have been known to combine to form a messy gloop after irradiation.

[0038] Statements of invention below relating to the additive or a part thereof may be applied mutatis mutandis to each of the copolymer forms above.

[0039] 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.

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] 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. In some embodiments, the additive comprises a layer that is on or that comprises a surface of the body, preferably the outer surface.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] In some embodiments, the layer comprising the additive is on or comprises at least 50,

[0054] 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.

[0055] 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. 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.

[0060] The layer comprising the additive may have an additive concentration of between 10- 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.

[0061] 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.

[0062] 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.

[0063] In some embodiments, the layer comprising the additive has a thickness of between SO- SOO pm.

[0064] 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.

[0065] 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-

[0066] 80, or of between 50-60 pm. 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.

[0067] 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.

[0068] 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. 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.

[0069] 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.

[0070] 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.

[0071] In some embodiments, said water disintegrable or enzymatically hydrolysable material comprises a material chosen from: polyvinyl alcohol, extrudable polyvinyl alcohol, polylactic acid, polyesters, poly glycolide, poly glycolic 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.

[0072] 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.

[0073] 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.

[0074] 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.

[0075] In some preferred embodiments, the base polymer comprises a polyolefin, especially polyethylene and / or polypropylene.

[0076] In some preferred embodiments, the base polymer comprises a thermoplastic elastomeric material. The base polymer may comprise a thermoplastic polyolefin.

[0077] 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. The thermoplastic base polymer may comprise a hydrophobic polymer chosen from: Accurel ™, Styroflex™, Styrolux™, MelifleX™, and Mediprene™ and any combination thereof.

[0078] 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.

[0079] The thermoplastic base polymer may comprise Estane™ 58315, which is both hydrophobic and hydrophilic.

[0080] In some embodiments, the octenidine is present as octenidine free base.

[0081] In other embodiments, the medium comprises an octenidine salt.

[0082] The octenidine salt may be independently chosen from: a halide salt, a sulfate salt, a nitrate salt, a phosphate salt, a carboxylate salt, a carbonate salt, an oxalate salt, a sulfonate salt, and combinations thereof.

[0083] In some preferred embodiments, the octenidine salt is or comprises an octenidine dihalide. The octenidine salt may be or comprise an octenidine dihalide that is independently chosen from: octenidine dihydrochloride, octenidine dihydrobromide, octenidine dihydroiodide, and combinations thereof. In particularly preferred embodiments, the octenidine salt is or comprises octenidine dihydrochloride.

[0084] In some preferred embodiments, the octenidine salt is independently chosen from: octenidine dihydrochloride, octenidine dihydrobromide, octenidine disulfate, octenidine digluconate, and combinations thereof. The medium may comprise octenidine or the salt thereof in a total concentration of between 1.9-30000 ppm.

[0085] In some embodiments, the medium comprises octenidine or the salt thereof in a total concentration of at 2 ppm, or at least 3, 4, 5 6, 7, 8, 9, or at least 10 ppm, or at least 20, 30, 40, 50, 60, 70, 80, 90, or at least 100 ppm, or at least 150, 200, 250, 300, 350, 400, 450, or at least 500 ppm. The medium may comprise octenidine or the salt thereof in a total concentration of no greater than 10000 ppm, or no greater than 8000, 6000, 4000, 2000 ppm, or no greater than 1900, 1800, 1700, 1600, 1500, 1400, 1300, 1200, 1100, or preferably no greater than 1000, 900, 800, 700, 600, or no greater than 500 ppm.

[0086] In some embodiments, the medium comprises octenidine or the salt thereof in a total concentration of between 2-10000 ppm, or between 10-8000, 50-6000, 100-4000, 200- 2000, 300-1500, or between 400-1250, or preferably between 500-1000 ppm.

[0087] In some preferred embodiments, the medium comprises at least one further species that is independently chosen from: glycerol and ethylhexylglycerin. The medium may comprise at least one further species independently selected from the group consisting of: glycerol and ethylhexylglycerin.

[0088] In some embodiments, the medium comprises glycerol in a total concentration of at least 0.01 wt.%, or at least 0.02, 0.04, 0.06, 0.08, 0.1, 0.2, 0.4, 0.6, 0.8, or at least 1.0 wt.% of the medium. The medium may comprise glycerol in a total concentration of no greater than 10 wt.%, or no greater than 9, 8, 6, or no greater than 5 wt.% of the medium. The medium may comprise glycerol in a total concentration of between 0.01-10 wt.%, or between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%. In some embodiments, the medium comprises ethylhexylglycerin in a total concentration of at least 0.01 wt.%, or at least 0.02, 0.04, 0.06, 0.08, 0.1, 0.2, 0.3, 0.4, or at least 0.5 wt.% of the medium. The medium may comprise ethylhexylglycerin in a total concentration of no greater than 10 wt.% of the medium, or no greater than 9, 8, 7, 6, 5, 4, 3, 2, or no greater than 1 wt.% of the medium. The medium may comprise ethylhexylglycerin in a total concentration of between 0.01-5 wt.%, or between 0.1-4 wt.%, or between 0.2-2, or between 0.5-1.5 wt.% of the medium.

[0089] In some embodiments, the medium comprises glycerol and ethylhexylglycerin.

[0090] In some embodiments, the medium comprises glycerol in a total concentration of between 0.01-10 wt.% and ethylhexylglycerin in a total concentration of between 0.01-5 wt.%, or the medium comprises glycerol in a total concentration of between 1-5 wt.% and ethylhexylglycerin in a total concentration of between 0.5-1.5 wt.%

[0091] The medium is preferably present in liquid form. In some embodiments, the medium is present as a solution, preferably an aqueous solution.

[0092] Aqueous solutions are particularly effective, as water allows for optimal catheter surface lubricity.

[0093] In some embodiments, the medium is a gel.

[0094] The gel medium may be an aqueous gel medium comprising water and a gelling agent.

[0095] In some embodiments, the gelling agent is independently chosen from: a polysaccharide gelling agent, a protein-based gelling agent, a synthetic polymer gelling agent, an inorganic gelling agent, and combinations thereof. In some embodiments, the gelling agent may comprise a polysaccharide gelling agent that is independently chosen from: a seaweed-derived polysaccharide, a plant or seed gum, a cellulose derivative, a starch-based gelling agent, and combinations thereof.

[0096] The gelling agent may comprise a polysaccharide gelling agent that is independently chosen from: agar-agar, alginate, carrageenan, guar gum, xanthan gum, locust bean gum, pectin, hydroxyethylcellulose, hydroxypropyl methylcellulose, carboxymethycellulose, methylcellulose, modified corn starch, potato starch, and combinations thereof.

[0097] The gelling agent may comprise a protein-based gelling agent that is independently chosen from: gelatin, collagen, and combinations thereof.

[0098] The gelling agent may comprise a synthetic polymer gelling agent that is independently chosen from: a carbomer, polyvinyl alcohol, polyacrylamide, polyethylene glycol, and combinations thereof.

[0099] The gelling agent may comprise an inorganic gelling agent that is independently chosen from: bentonite or a clay-based gelling agent, silica gel, and combinations thereof.

[0100] In some embodiments, the gelling agent may comprise glycerin or a derivative thereof.

[0101] In some embodiments, the aqueous 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.

[0102] 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.%.

[0103] In some preferred embodiments, the gel comprises water in a total amount of between 20- 98 wt.%, or between 50-98 wt.%.

[0104] In some embodiments, the gel comprises the gelling agent 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 the gelling agent in a total amount of no greater than 90 wt.%, or no greater than 85, 80, 75, 70, 65, 60, 55, 50, 45, or no greater than 40 wt.%.

[0105] In some embodiments, the gel comprises the gelling agent in a total amount of between 5-80 wt.%, or between 7-77 wt.%, or between 9-75 wt.%. In some embodiments, the gel comprises the gelling agent 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.%.

[0106] 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.

[0107] 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-

[0108] 30000, or between 11000-29000, or between 12000-28000, or between 13000-27000 cP.

[0109] In some embodiments, the gel has a pH of at least 1, or at least 2, 3, 4, or at least 5. In some embodiments, the gel has a pH of no greater than 12, or no greater than 11, 10, 9, or no greater than 8.

[0110] In some embodiments, the gel has a pH of between 3-9, or between 4-8, or between 5-8. In some embodiments, the gel has a pH of between 4-7, or preferably between 5-6. In some embodiments, the gel has a pH of between 5.5-8, or between 6-7.5, or between 6-7.

[0111] In some embodiments, the gel medium is a non-aqueous gel medium.

[0112] The non-aqueous gel medium may comprise a non-aqueous base. In some embodiments, the non-aqueous gel comprises an oil or non-aqueous solvent base.

[0113] The non-aqueous gel may be independently chosen from: an oleogel, an organogel, an alcohol-based gel, a silicone gel, an anhydrous lipid gel, and combinations thereof.

[0114] The non-aqueous gel may comprise an oleogel that is independently chosen from: a hydrocarbon-based oleogel, a mineral-oil based oleogel, a synthetic-oil based oleogel, a vegetable-oil based oleogel, and combinations thereof.

[0115] The non-aqueous gel may comprise an organogel that is independently chosen from: a surfactant-based organogel, a polymer-based organogel, an ionic liquid gel, and combinations thereof.

[0116] The non-aqueous gel may comprise an alcohol-based gel that is independently chosen from: a carbomer-alcohol gel, a cellulose derivative-alcohol gel, and combinations thereof. The non-aqueous gel may comprise a silicone gel that is independently chosen from: a dimethicone gel, a silicone-elastomer gel, and combinations thereof.

[0117] The non-aqueous gel may comprise an anhydrous lipid gel that is independently chosen from: a wax or a fatty alcohol gel, a gelled fat or butter, and combinations thereof.

[0118] In some embodiments, the non-aqueous gel comprises a non-aqueous base, preferably an oil or non-aqueous solvent base 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 a non-aqueous base, preferably an oil or non-aqueous solvent base 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.

[0119] In some embodiments, the gel comprises a non-aqueous base, preferably an oil or nonaqueous solvent base in a total amount of between 5-99 wt.%, or between 10-98 wt.%, or between 20-98 wt.%. In some embodiments, the gel comprises a non-aqueous base, preferably an oil or non-aqueous solvent base 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.%.

[0120] In some embodiments, the gel comprises a non-aqueous base, preferably an oil or nonaqueous solvent base in a total amount of between 20-98 wt.%, or between 50-98 wt.%.

[0121] In some embodiments, the medium is present in a total volume of at least 0.1 mL, or at least 0.2, 0.3, 0.4, or at least 0.5 mL.

[0122] In some embodiments, the medium is present in a total volume of no greater than 15 mL, or no greater than 14, 13, 12, 11, or in a total volume of no greater than 10 mL. The medium may be present in a total volume of between 0.1-15 mL, or between 0.5-13 mL, or between 1-12 mL, or between 5-10 mL.

[0123] 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.

[0124] In some embodiments, the medium has a pH of at least 3.0, or at least 3.2, 3.4, 3.6, 3.8, or at least 4.0. The medium may have a pH of no greater than 7.0, or no greater than 6.0, or no greater than 5.8, 5.6, or no greater than 5.5, 5.4, or no greater than 5.3. The medium may have a pH of between 3.0-6.0, or between 3.5-5.5, or between 4.0-5.5.

[0125] In preferred embodiments, the catheter and the medium are packaged.

[0126] The catheter and medium may be packaged in a container. The container may be a case, pouch or bag. The container may have at least one cavity configured to hold the catheter and medium.

[0127] The container may be rigid. Alternatively, the container may be flexible. In some embodiments, the container contains rigid and flexible regions. The container may comprise a tube. The tube may have a flexible centre portion and two rigid end portions neighbouring the flexible centre portion.

[0128] In some preferred embodiments, the catheter is not in direct contact with the medium.

[0129] In some embodiments, the medium may be packaged such that the medium 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. The separate compartment containing the medium may be located within the packaging compartment containing the catheter, at least partially or wholly.

[0130] 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 the catheter, preferably with an outer surface thereof. Removal of the catheter from its packaging compartment, in use, may be configured to bring the medium into direct contact with at least 20% of the outer surface area of the 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.

[0131] 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 medium to bring the medium into direct contact with the catheter.

[0132] In some embodiments, the catheter is packaged in a catheter container, and the medium is packaged in a separate container, such that the medium is 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.

[0133] In some embodiments, the separate container is pierceable, in use, to release the medium 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 the medium from the separate container and apply the medium to the outer surface of the catheter. In some embodiments the user may squeeze the separate container through the catheter container to rupture it to release the medium into the catheter container. In some embodiments, the separate container is configured to rupture or break to release the medium from the separate container and into direct contact with the catheter upon opening of the catheter container.

[0134] In some embodiments, the catheter is submerged in a liquid and / or solution which is not the medium of the invention, and the medium may be contained in a separate medium container which may be located within the compartment or container containing the catheter. The separate medium container may be as described in statements of invention above.

[0135] In embodiments in which the catheter is not in direct contact with the medium, the medium may comprise octenidine as octenidine free base. In such embodiments, the catheter may be coated on an outer surface thereof with an acid or may contain or comprise acidic moieties on the outer surface. As such, when the medium is contacted with the outer surface of the catheter, the octenidine free base present in the medium may protonate and form an octenidine salt. The octenidine salt formed may be as described in statements of invention above.

[0136] Alternatively, the catheter may be packaged in a separate container / compartment to the medium and the catheter may be packaged in a liquid and / or solution which is not the medium of the invention and which has a more acidic pH than the medium of the invention. In such embodiments, the medium of the invention may be added to the catheter container / compartment and the octenidine free base in the medium of the invention may protonate and form an octenidine salt when contacted with the acidic medium present in the separate catheter container / compartment.

[0137] In some embodiments, the catheter is in direct contact with the medium. The catheter may be packaged in direct contact with the medium. The catheter may be packaged in direct contact with the medium, such that the medium is in contact with an outer surface of the catheter. The medium may cover at least part of the outer surface of the catheter.

[0138] In some embodiments, the catheter may be packaged submerged in the medium. The catheter may be packaged in a container comprising the medium. 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.

[0139] 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.

[0140] 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.

[0141] The layer of medium may preferably be on the surface of the catheter, preferably on the surface of the catheter body. 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.

[0142] 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 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.

[0143] 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.

[0144] In preferred embodiments, the catheter and / or medium are not hermetically sealed or vacuum packaged. Preferably both the catheter and medium are not hermetically sealed and vacuum packaged.

[0145] As discussed previously, there is no requirement for the medium of the invention to be packaged in hermetically sealed packaging for the medium to demonstrate its advantageous resistance to irradiation sterilisation discussed above, and this effect is surprisingly found even when the catheter and medium are not vacuum packaged / vacuum sealed. In some embodiments, step (b) comprises irradiating the medium with at least one radiation form independently chosen from: X-ray, UV, Gamma, electron beam radiation, and combinations thereof.

[0146] In some preferred embodiments, there is provided a method of sterilising a urinary catheter, the method comprising the steps of:

[0147] (a) Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and

[0148] (b) Irradiating the urinary catheter and the medium with at least one radiation form independently chosen from: X-ray, UV, Gamma, electron beam radiation, and combinations thereof.

[0149] In some embodiments, step (b) comprises irradiating the catheter and the medium with X-ray and / or UV radiation.

[0150] Step (b) may comprise irradiating the catheter and medium 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 and medium 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 and medium with between 5-60 kGy of radiation, or preferably between 10-60 kGy of radiation. In some embodiments, step (b) comprises irradiating the catheter and medium with between 5-40 kGy, or between 10-30 kGy of radiation. Step (b) may comprise irradiating the catheter and medium with around 10 kGy of radiation, or around 15 kGy of radiation, or around and medium with between 25-60 kGy of radiation, or between 25-55 kGy, or preferably between 30-55 kGy of radiation.

[0151] In some preferred embodiments, there is provided a method of sterilising a urinary catheter, the method comprising the steps of:

[0152] (a) Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and

[0153] (b) Irradiating the urinary catheter and the medium with between 5-60 kGy of radiation.

[0154] Step (b) may comprise irradiating the catheter and medium when the catheter and medium are packaged, preferably as described in statements of invention above. In preferred embodiments, the medium is packaged such that the medium is not in direct contact with the catheter, preferably as described in statements of invention above.

[0155] In some preferred embodiments, there is provided a method of sterilising a urinary catheter, the method comprising the steps of:

[0156] (a) Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and

[0157] (b) Irradiating the urinary catheter and the medium wherein the catheter and the medium are packaged, and wherein step (b) preferably comprises irradiating the packaged catheter and medium.

[0158] In some preferred embodiments, there is provided a method of sterilising a urinary catheter, the method comprising the steps of: (a) Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and

[0159] (b) Irradiating the urinary catheter and the medium, wherein the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0160] In some preferred embodiments, there is provided a method of sterilising a urinary catheter, the method comprising the steps of:

[0161] (a) Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and

[0162] (b) Irradiating the urinary catheter and the medium, wherein the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0163] In some preferred embodiments, there is provided a method of sterilising a urinary catheter, the method comprising the steps of:

[0164] (a) Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and

[0165] (b) Irradiating the urinary catheter and the medium, wherein the medium comprises glycerol and ethylhexylglycerin.

[0166] In some preferred embodiments, there is provided a method of sterilising a urinary catheter, the method comprising the steps of: (a) Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and

[0167] (b) Irradiating the urinary catheter and the medium, wherein the urinary catheter comprises 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 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.

[0168] According to a second aspect of the invention, there is provided a packaged urinary catheter comprising: a urinary 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 a medium comprising octenidine or a salt thereof.

[0169] It is especially surprising that when such an additive is used, the medium of the invention shows excellent compatibility with the additive. There is little to no negative interference between the medium and the additive, and additive migration from the catheter remains unaffected or highly reduced even when the combination of catheter and medium are exposed to irradiation. This is in contrast to many known antimicrobials which are known to interact with such additives and cause them to migrate from the catheter. Such negative effects are typically severely exemplified post- irradiation, and the additives and media of the prior art have been known to combine to form a messy gloop (or other undesirable visible and / or physical forms or textures) after irradiation.

[0170] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary 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 a medium comprising octenidine or a salt thereof and further comprising ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0171] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary 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 a medium comprising octenidine or a salt thereof and further comprising glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0172] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary 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 a medium comprising octenidine or a salt thereof and further comprising glycerol and ethylhexylglycerin. In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary 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 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; and a medium comprising octenidine or a salt thereof.

[0173] According to a third aspect of the invention, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereofin a total concentration of between 1.9-30000 ppm.

[0174] Such a medium containing octenidine or a salt thereof in the stated concentration range, when wetted over the surface of the urinary catheter has surprisingly been found to provide excellent antimicrobial activity, showing long-term, broad spectrum and rapid kill of bacteria, which is superior to other known antimicrobials especially following irradiation during catheter. Such a medium poses no safety issues when used with catheters and also provides excellent and stable catheter lubricity .The antimicrobial activity and lubricating performance of the octenidine species is most surprisingly retained even when the medium is exposed to irradiation during sterilisation of the catheter. This property of the octenidine-containing medium of the invention is unexpected, and other known antimicrobial compounds degrade when exposed to irradiation, such that there is a minimal amount of the active compound present after irradiation, leading to a dramatic reduction in antimicrobial performance. This also negatively impacts lubricity performance of media containing such antimicrobials, and the surface properties of the catheters are as a result negatively impacted.

[0175] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, and further comprising ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0176] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, and further comprising glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0177] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, and further comprising glycerol and ethylhexylglycerin.

[0178] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, wherein the urinary catheter comprises 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 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.

[0179] According to a fourth aspect of the invention, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof, and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

[0180] In some embodiments, the medium comprises at least one further species that is independently selected from the group consisting of: glycerol and ethylhexylglycerin.

[0181] Such a medium containing octenidine or a salt thereof in combination with a further active as stated above provides excellent antimicrobial performance, demonstrating broad spectrum, rapid and long-term kill of even challenging bacterial organisms. Such a medium can also safely be used with catheters and also provides excellent and stable catheter lubricity. Advantageously, the antimicrobial activity and lubricating performance is retained even when the medium is exposed to irradiation during sterilisation of the catheter.

[0182] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof, and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, wherein the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%. In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof, and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, wherein the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0183] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof, and further comprising glycerol and ethylhexylglycerin.

[0184] In some preferred embodiments, there is provided a packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof, and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, wherein the urinary catheter comprises 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 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.

[0185] According to a fifth aspect of the invention, there is provided a urinary 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 medium comprising octenidine or a salt thereof.

[0186] In some preferred embodiments, there is provided a urinary 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 medium comprising octenidine or a salt thereof, wherein the medium further comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0187] In some preferred embodiments, there is provided a urinary 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 medium comprising octenidine or a salt thereof, wherein the medium further comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0188] In some preferred embodiments, there is provided a urinary 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 medium comprising octenidine or a salt thereof, wherein the medium further comprises glycerol and ethylhexylglycerin.

[0189] In some preferred embodiments, there is provided a urinary 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 medium comprising octenidine or a salt thereof, 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.

[0190] According to a sixth aspect of the invention, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm.

[0191] In some preferred embodiments, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, wherein the medium further comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%. In some preferred embodiments, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, wherein the medium further comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0192] In some preferred embodiments, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, wherein the medium further comprises glycerol and ethylhexylglycerin.

[0193] In some preferred embodiments, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, wherein the urinary catheter comprises 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 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. According to a seventh aspect of the invention, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

[0194] In some preferred embodiments, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, wherein the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0195] In some preferred embodiments, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, wherein the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0196] In some preferred embodiments, there is provided a urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof and further comprising glycerol and ethylhexylglycerin.

[0197] In some preferred embodiments, there is provided a urinary 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 medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, and 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.

[0198] Statements of invention for the first aspect of the invention may also be applied mutatis mutandis to the second, third, fourth, fifth, sixth and seventh aspects of the invention.

[0199] The following statements relate to the fifth, sixth and seventh aspects of the invention.

[0200] 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.

[0201] According to an eighth aspect of the invention, there is provided a method of lubricating a urinary catheter, the method comprising the steps of: (a) Providing a urinary 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

[0202] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof

[0203] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0204] (a) Providing a urinary 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

[0205] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof, and further comprising ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0206] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0207] (a) Providing a urinary 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 (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof, and further comprising glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0208] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0209] (a) Providing a urinary 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

[0210] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof, and further comprising glycerol and ethylhexylglycerin.

[0211] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0212] (a) Providing a urinary 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 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; and

[0213] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof.

[0214] According to a ninth aspect of the invention, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0215] (a) Providing a urinary catheter comprising a hollow polymeric tubular body; and

[0216] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm.

[0217] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0218] (a) Providing a urinary catheter comprising a hollow polymeric tubular body; and

[0219] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, and further comprising ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0220] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0221] (a) Providing a urinary 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 medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, and further comprising glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0222] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0223] (a) Providing a urinary catheter comprising a hollow polymeric tubular body; and

[0224] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, and further comprising glycerol and ethylhexylglycerin.

[0225] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0226] (a) Providing a urinary 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 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; and (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm.

[0227] According to a tenth aspect of the invention, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0228] (a) Providing a urinary catheter comprising a hollow polymeric tubular body; and

[0229] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

[0230] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0231] (a) Providing a urinary catheter comprising a hollow polymeric tubular body; and

[0232] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, wherein the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0233] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0234] (a) Providing a urinary catheter comprising a hollow polymeric tubular body; and

[0235] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, wherein the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

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

[0237] (a) Providing a urinary 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 medium comprising octenidine or a salt thereof and further comprises glycerol and ethylhexylglycerin.

[0239] In some preferred embodiments, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0240] (a) Providing a urinary 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 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; and (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

[0241] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the eighth, ninth and tenth aspects of the invention.

[0242] The following statements relate to the eighth, ninth and tenth aspects of the invention.

[0243] The lubricating medium is preferably the medium of the first aspect of the invention.

[0244] 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.

[0245] 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.

[0246] 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.

[0247] In some embodiments, step (b) comprises submerging the catheter in the medium. 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 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.

[0248] 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.

[0249] 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.

[0250] The additional lubricating agent may be water or may comprise water. The additional lubricating agent may be an aqueous solution.

[0251] 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.

[0252] In some embodiments, a further lubrication step is not performed. In such embodiments, the catheter may be used directly after step (b).

[0253] According to an eleventh aspect of the invention, there is provided a method of sterilising a reusable urinary catheter, the method comprising the steps of:

[0254] (a) Providing: a reusable urinary catheter and a medium comprising octenidine or a salt thereof; and

[0255] (b) Irradiating the reusable urinary catheter and the medium.

[0256] The medium of the invention has been found to provide excellent antimicrobial activity when contacted with a urinary catheter, showing long-term, broad spectrum and rapid kill of bacteria. Such a medium poses substantially no safety issues when used with catheters and also provides excellent and stable catheter lubricity. Further, use of such a medium causes minimal change to the relevant surface chemistry of the catheter upon contact, and so allows for catheter multi-use without adversely impacting catheter lubricity. To ensure thorough sterilisation of a urinary catheter, the catheter should be sterilised by exposing it to irradiation. What is especially surprising about the medium of the invention and what particularly sets it apart from known antimicrobial media, is that it has been found that when the medium is exposed to irradiation during sterilisation of the catheter, the antimicrobial activity and lubricating performance of the octenidine species is substantially retained. This property of the octenidine-containing medium of the invention is unexpected, and other known antimicrobial compounds degrade when exposed to irradiation, such that there is minimal or a reduced amount of the active compound present after irradiation, leading to a dramatic reduction in antimicrobial performance. This also negatively impacts lubricity performance of media containing such antimicrobials, and the surface properties of the catheters are as a result negatively impacted.

[0257] In other cases, known antimicrobial media undergo physical changes, and may degrade into a form which is visibly and / or texturally undesired in catheter packaging when exposed to irradiation. The medium of the invention surprisingly is also not so physically affected by irradiation and does not substantially create visible and / or textural change into undesirable forms in catheter packaging, so there is no need to sterilise the catheter by irradiation in isolation of the medium. The medium is minimally affected even after several doses of irradiation, which is especially useful from a reuse perspective, as the catheter and medium can be used multiple times and irradiated multiple times as and when required without the risk of major damage to the medium.

[0258] Furthermore, there is no requirement for the medium of the invention to be packaged in hermetically sealed packaging for the medium to demonstrate its resistance to sterilisation discussed above. Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the eleventh aspect of the invention.

[0259] In some preferred embodiments, there is provided a method of sterilising a reusable urinary catheter, the method comprising the steps of:

[0260] (a) Providing: a reusable urinary catheter and a medium comprising octenidine or a salt thereof; and

[0261] (b) Irradiating the reusable urinary catheter and the medium with at least one radiation form independently chosen from: X-ray, UV, Gamma, electron beam radiation, and combinations thereof.

[0262] In some preferred embodiments, there is provided a method of sterilising a reusable urinary catheter, the method comprising the steps of:

[0263] (a) Providing: a reusable urinary catheter and a medium comprising octenidine or a salt thereof; and

[0264] (b) Irradiating the reusable urinary catheter and the medium with between 5-60 kGy of radiation.

[0265] In some preferred embodiments, there is provided a method of sterilising a reusable urinary catheter, the method comprising the steps of:

[0266] (a) Providing: a reusable urinary catheter and a medium comprising octenidine or a salt thereof; and

[0267] (b) Irradiating the reusable urinary catheter and the medium, wherein the catheter and medium are packaged, and wherein step (b) preferably comprises irradiating the packaged catheter and medium. In some preferred embodiments, there is provided a method of sterilising a reusable urinary catheter, the method comprising the steps of:

[0268] (a) Providing: a reusable urinary catheter and a medium comprising octenidine or a salt thereof; and

[0269] (b) Irradiating the reusable urinary catheter and the medium, wherein the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0270] In some preferred embodiments, there is provided a method of sterilising a reusable urinary catheter, the method comprising the steps of:

[0271] (a) Providing: a reusable urinary catheter and a medium comprising octenidine or a salt thereof; and

[0272] (b) Irradiating the reusable urinary catheter and the medium, wherein the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0273] In some preferred embodiments, there is provided a method of sterilising a reusable urinary catheter, the method comprising the steps of:

[0274] (a) Providing: a reusable urinary catheter and a medium comprising octenidine or a salt thereof; and

[0275] (b) Irradiating the reusable urinary catheter and the medium, wherein the medium comprises glycerol and ethylhexylglycerin. In some preferred embodiments, there is provided a method of sterilising a reusable urinary catheter, the method comprising the steps of:

[0276] (a) Providing: a reusable urinary catheter and a medium comprising octenidine or a salt thereof; and

[0277] (b) Irradiating the reusable urinary catheter and the medium, wherein the urinary catheter comprises 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 the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CHsCth CthCtbla 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.

[0278] According to a twelfth aspect of the invention, there is provided a packaged reusable urinary catheter comprising: a reusable urinary catheter; and a medium comprising octenidine or a salt thereof.

[0279] The octenidine medium of the invention allows for effective lubrication of the catheter and demonstrates excellent antimicrobial activity, which can be achieved by simply contacting the catheter with the medium. Further, use of such a medium causes minimal change to the relevant surface chemistry of the catheter upon contact, and so allows for catheter multi-use without adversely impacting catheter lubricity. The medium also provides long-term lubrication and / or antimicrobial activity, allowing the catheter to be reused safely for relatively long time periods, without the need for overly frequent resterilisation and / or re-lubrication and without the need to replace medium too frequently.

[0280] According to a related aspect of the invention, there is provided a packaged reusable urinary catheter comprising: a reusable urinary 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 a medium comprising octenidine or a salt thereof.

[0281] It is especially surprising that when such an additive is used, the medium of the invention shows excellent compatibility with the additive. There is little to no negative interference between the medium and the additive, and additive migration from the catheter remains unaffected or highly reduced even when the combination of catheter and medium are exposed to irradiation and even after reuse of the catheter. This is in contrast to many known antimicrobials which are known to interact with such additives and cause them to migrate from the catheter. Such negative effects are typically severely exemplified postirradiation and reuse, and the additives and media of the prior art have been known to combine to form a messy gloop (or other undesirable visible and / or physical forms or textures) after irradiation or reuse.

[0282] According to a related aspect of the invention, there is provided a packaged reusable urinary catheter comprising: a reusable urinary catheter; and a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm.

[0283] Such a medium containing octenidine or a salt thereof in the stated concentration range, when wetted over the surface of the urinary catheter has surprisingly been found to provide excellent antimicrobial activity, showing long-term, broad spectrum and rapid kill of bacteria, which is superior to other known antimicrobials especially following irradiation during catheter sterilisation. Such a medium lends itself particularly well to catheter reuse. Such a medium poses no safety issues when used with catheters and also provides excellent and stable catheter lubricity. The antimicrobial activity and lubricating performance of the octenidine species is most surprisingly retained even when the medium is exposed to irradiation during sterilisation of the catheter. This property of the octenidine-containing medium of the invention is unexpected, and other known antimicrobial compounds degrade when exposed to irradiation, such that there is a minimal amount of the active compound present after irradiation, leading to a dramatic reduction in antimicrobial performance. This also negatively impacts lubricity performance of media containing such antimicrobials, and the surface properties of the catheters are as a result negatively impacted.

[0284] According to a related aspect of the invention, there is provided a packaged reusable urinary catheter comprising: a reusable urinary catheter; and a medium comprising octenidine or a salt thereof, and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

[0285] Such a medium containing octenidine or a salt thereof in combination with a further active as stated above provides excellent antimicrobial performance, demonstrating broad spectrum, rapid and long-term kill of even challenging bacterial organisms. Such a medium can also safely be used with catheters and also provides excellent and stable catheter lubricity, which lends itself particularly well to catheter reuse. Advantageously, the antimicrobial activity and lubricating performance is retained even when the medium is exposed to irradiation during sterilisation of the catheter and even after reuse of the catheter.

[0286] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the twelfth and related aspects of the invention.

[0287] The following statements relating to the twelfth and related aspects of the invention may also be applied mutatis mutandis to the other aspects of the invention.

[0288] The catheter and medium may be packaged in a container. The catheter may preferably be configured to be repeatedly inserted and removed from the container.

[0289] In some embodiments, the reusable catheter may be configured to be reused at least 1 time, or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or at least 20 times. The reusable catheter may be configured to be reused up to 5 times, or up to 10, 15, 20, 25, 30, 35, 40, 45, or up to 50 times.

[0290] In some embodiments, the reusable catheter may be configured to be reused for up to 1 day, or up to 2, 3, 4, 5, or up to 6 days, or up to 1 week, or up to 8 days, or up to 9, 10, 11 , 12, or up to 13 days, or up to 2 weeks, or up to 3 weeks, or up to 1 month, or up to 2 months. The reusable catheter may be configured to be reused for up to between 1 day to 2 month, or up to between 1 week to 1.5 months, or for up to between 2 weeks to 1 month.

[0291] In some embodiments, the reusable catheter is configured to be reused without needing to replenish and / or change the medium. In some embodiments, the reusable catheter is configured to be reused for up to 5 hours without needing to replenish and / or change the medium, or for up to 10 hours, or for up to 15, or 20, or for up to 24 hours without needing to replenish and / or change the medium. In some preferred embodiments, the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0292] In some preferred embodiments, the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0293] In some preferred embodiments, the medium comprises glycerol and ethylhexylglycerin.

[0294] In some preferred embodiments, the urinary catheter comprises 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 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.

[0295] According to a thirteenth aspect of the invention, there is provided a reusable urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof.

[0296] According to a related aspect of the invention, there is provided a reusable urinary 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 medium comprising octenidine or a salt thereof.

[0297] According to a related aspect of the invention, there is provided a reusable urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm.

[0298] According to a related aspect of the invention, there is provided a reusable urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

[0299] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the thirteenth and related aspects of the invention.

[0300] The following statements relating to the thirteenth and related aspects of the invention may also be applied mutatis mutandis to the other aspects of the invention.

[0301] In some preferred embodiments, the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0302] In some preferred embodiments, the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0303] In some preferred embodiments, the medium comprises glycerol and ethylhexylglycerin.

[0304] In some preferred embodiments, the urinary catheter comprises 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 the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CH Cth CtpCTh 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.

[0305] According to a fourteenth aspect of the invention, there is provided a method of lubricating a reusable urinary catheter, the method comprising the steps of:

[0306] (a) Providing a reusable urinary catheter comprising a hollow polymeric tubular body; and

[0307] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof.

[0308] According to a related aspect of the invention, there is provided a method of lubricating a reusable urinary catheter, the method comprising the steps of:

[0309] (a) Providing a reusable urinary 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

[0310] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof According to a related aspect of the invention, there is provided a method of lubricating a reusable urinary catheter, the method comprising the steps of:

[0311] (a) Providing a reusable urinary catheter comprising a hollow polymeric tubular body; and

[0312] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm.

[0313] According to a related aspect of the invention, there is provided a method of lubricating a reusable urinary catheter, the method comprising the steps of:

[0314] (a) Providing a reusable urinary catheter comprising a hollow polymeric tubular body; and

[0315] (b) Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

[0316] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the fourteenth and related aspects of the invention.

[0317] The following statements relating to the fourteenth and related aspects of the invention may also be applied mutatis mutandis to the other aspects of the invention.

[0318] In some embodiments, the catheter in step (a) is provided before first use of the catheter. In some embodiments, the catheter in step (a) is provided after first use of the catheter. Steps (a) and (b) may be repeated. In such embodiments step (a) may comprise providing an unused catheter, followed by step (b) and then catheter used, followed by providing the used catheter in a further step (a) and then performing step (b). Such repetition of step (a) and / or (b) may be completed a plurality of times.

[0319] In some embodiments, the method comprises a washing step before each step (b). In some embodiments, the washing step takes place directly before step (b). The washing step may comprise washing a surface of the catheter, preferably the outer surface thereof, in some embodiments, the washing step comprises washing the catheter with water. In some embodiments, the washing step comprises washing the catheter with an aqueous solution. The washing step may comprise washing the catheter with a detergent and with water or an aqueous solution. In some embodiments, the washing step comprises applying a detergent to the catheter, preferably to the outer surface thereof, and then rinsing the catheter with water or an aqueous solution.

[0320] In some embodiments, step (b) comprises treating the catheter with the medium for a total time of at least 5 seconds, or at least 10, 20, 30, 40, or at least 50 seconds, or at least 1 minute, or at least 2, 3, 4, or at least 5 minutes, or at least 10, 20, 30, 40, or at least 50 minutes, or at least 1 hour, or at least 1.5, 2, 2.5, 3, 3.5, or at least 4 hours. Step (b) may comprise treating the catheter with the medium for a total time of no greater than 1 week, or no greater than 6 days, or no greater than 5, 4, 3, 2, or no greater than 1 day, or no greater than 20 hours, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, or no greater than 5 hours.

[0321] In some embodiments, step (b) is performed at a temperature of at least 1 °C, or at least 2, 3, 4, or at least 5 °C. In some embodiments, step (b) is performed at a temperature of no greater than 60 °C, or no greater than 55, 50, 45, 40, 35, 30, or no greater than 25 °C. In some embodiments, step (b) is performed at a temperature of between 1-60 °C, or between 5-50, or between 10-40 °C.

[0322] In some embodiments, step (b) is performed when the catheter is held in a container. The container may preferably be as described in statements of invention above. The container may comprise the medium. Step (b) may comprise placing the catheter into the container to bring the catheter into direct contact with the medium. Step (b) may preferably comprise submerging the catheter in the medium. Step (b) may comprise placing the catheter in the container after each use of the catheter, and may preferably comprise submerging the catheter in the medium after each use of the catheter. There may be a plurality of containers containing medium, and each step (b) may comprise placing or submerging the catheter in a different medium container.

[0323] In some embodiments, the method is repeated at least once. The method may be performed before and / or after each use of the catheter. In some embodiments, the method is performed 3 times a day, or 2 times a day, or once a day, or once every 2 days, or once every 3 days, or once every 4 days, or once every 5 days, or once every 6 days, or once a week, or once every 2 weeks, or once every 3 weeks, or once a month.

[0324] In some embodiments, the or each step (b) comprises treating the catheter with fresh medium that has not been used previously to treat the catheter. In such embodiments, the medium may be replaced with fresh medium before and / or after each step (b).

[0325] In some embodiments, the medium may be replaced with fresh medium at least every 6- hour period, or at least every 12, 18, or at least after every 24 hour period.

[0326] Replenishing the medium in a catheter reuse scenario has been shown to be optimal with respect to both the effectiveness of catheter sterilisation and catheter lubricity. In some preferred embodiments, the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0327] In some preferred embodiments, the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0328] In some preferred embodiments, the medium comprises glycerol and ethylhexylglycerin.

[0329] In some preferred embodiments, the urinary catheter comprises 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 the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CHsClfclCFhCFhla 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.

[0330] According to a fifteenth aspect of the invention, there is provided the use of a medium comprising octenidine or a salt thereof to lubricate a reusable urinary catheter between uses.

[0331] According to a related aspect of the invention, there is provided the use of a medium comprising octenidine or a salt thereof to lubricate a reusable urinary catheter between uses, said reusable urinary 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.

[0332] According to a related aspect of the invention, there is provided the use of a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, to lubricate a reusable urinary catheter between uses.

[0333] According to a related aspect of the invention, there is provided the use of a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, to lubricate a reusable urinary catheter between uses.

[0334] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the fifteenth and related aspects of the invention.

[0335] The following statements relating to the fifteenth and related aspects of the invention may also be applied mutatis mutandis to the other aspects of the invention.

[0336] In some preferred embodiments, the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0337] In some preferred embodiments, the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0338] In some preferred embodiments, the medium comprises glycerol and ethylhexylglycerin.

[0339] In some preferred embodiments, the urinary catheter comprises 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 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.

[0340] According to a sixteenth aspect of the invention, there is provided a packaged reusable urinary catheter comprising: a reusable urinary catheter; and a medium comprising octenidine or a salt thereof, wherein the catheter and medium are packaged in a resealable container.

[0341] The medium of the invention allows for effective lubrication of the catheter and excellent antimicrobial activity, which can be achieved by simply contacting the catheter with the medium in the container. This setup therefore allows for the catheter to be removed from the resealable container for use and then sterilised after use by simply reinserting the catheter back into the container and bringing the catheter into contact with the medium in the container. The catheter can then simply be removed from the container again for the next use without the need for any further sterilisation / lubrication steps.

[0342] This re-use / sterilisation cycle can also be repeated multiple times with a single catheter and without the need to replace the medium between uses, and catheters are still safe to use and maintain their performance.

[0343] Further, use of such a medium causes minimal change to the relevant surface chemistry of the catheter upon contact, and so allows for catheter multi-use without adversely impacting catheter lubricity. The medium also provides for long-term antimicrobial activity and / or lubrication, allowing the catheter to be reused safely for relatively long time periods, without the need for overly frequent re-sterilisation and / or re-lubrication.

[0344] According to a related aspect of the invention, there is provided a packaged reusable urinary catheter comprising: a reusable urinary 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 a medium comprising octenidine or a salt thereof, wherein the catheter and medium are packaged in a resealable container.

[0345] According to a related aspect of the invention, there is provided a packaged reusable urinary catheter comprising: a reusable urinary catheter; and a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm, wherein the catheter and medium are packaged in a resealable container.

[0346] According to a related aspect of the invention, there is provided a packaged reusable urinary catheter comprising: a reusable urinary catheter; and a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin, wherein the catheter and medium are packaged in a resealable container.

[0347] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the sixteenth and related aspects of the invention.

[0348] The following statements relating to the sixteenth and related aspects of the invention may also be applied mutatis mutandis to the other aspects of the invention.

[0349] The container preferably comprises a resealable opening. The resealable opening may be configured such that the catheter can be removed and inserted through the resealable opening. The resealable opening may be opened and closed using a resealable opening mechanism that is independently chosen from: a zipper closure, a press-to-seal closure, a resealable lid, a peel-and-seal closure, a slider closure, and a Velcro closure. The resealable opening may be opened and closed using a resealable opening mechanism that is independently selected from the group consisting of: a zipper closure, a press-to-seal closure, a resealable lid, a peel-and-seal closure, a slider closure, and a Velcro closure.

[0350] The container may preferably define a cavity configured to hold the catheter, and preferably comprise a resealable opening. The catheter may preferably be configured to be repeatedly inserted and removed from the container, preferably through the resealable opening thereof.

[0351] In some embodiments, the container is rigid. In other embodiments, the container is flexible. In some embodiments, the container contains rigid and flexible regions. The container may comprise a tube. The tube may have a flexible centre portion and two rigid side portions neighbouring the flexible centre portion. The tube may be resealable at a side portion thereof.

[0352] In some embodiments, the container is a pouch comprising a resealable opening. The catheter may preferably be configured to be repeatedly inserted and removed from the pouch, preferably through the resealable opening thereof.

[0353] The catheter may preferably be configured to be repeatedly inserted and removed from the container, preferably through the resealable opening thereof.

[0354] In some preferred embodiments, the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%. In some preferred embodiments, the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0355] In some preferred embodiments, the medium comprises glycerol and ethylhexylglycerin.

[0356] In some preferred embodiments, the urinary catheter comprises 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 the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CHsClfclCFbCFhla 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.

[0357] According to a seventeenth aspect of the invention, there is provided a method of lubricating a reusable urinary catheter, the method comprising the steps of:

[0358] (a) Providing a resealable container in its sealed configuration, said container comprising a urinary catheter, and further providing a medium comprising octenidine or a salt thereof;

[0359] (b) Unsealing the container;

[0360] (c) Removing the urinary catheter from the unsealed container;

[0361] (d) Performing catheterisation with the catheter; 'll

[0362] (e) Reinserting the catheter into the container and contacting the catheter with the medium in the container; and

[0363] (f) Resealing the container.

[0364] According to a related aspect of the invention, there is provided a method of lubricating a reusable urinary catheter, the method comprising the steps of:

[0365] (a) Providing a resealable container in its sealed configuration, said container comprising a urinary 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 further providing a medium comprising octenidine or a salt thereof;

[0366] (b) Unsealing the container;

[0367] (c) Removing the urinary catheter from the unsealed container;

[0368] (d) Performing catheterisation with the catheter;

[0369] (e) Reinserting the catheter into the container and contacting the catheter with the medium in the container; and

[0370] (f) Resealing the container.

[0371] According to a related aspect of the invention, there is provided a method of lubricating a reusable urinary catheter, the method comprising the steps of:

[0372] (a) Providing a resealable container in its sealed configuration, said container comprising a urinary catheter, and further providing a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm; (b) Unsealing the container;

[0373] (c) Removing the urinary catheter from the unsealed container;

[0374] (d) Performing catheterisation with the catheter;

[0375] (e) Reinserting the catheter into the container and contacting the catheter with the medium in the container; and

[0376] (f) Resealing the container.

[0377] According to a related aspect of the invention, there is provided a method of lubricating a reusable urinary catheter, the method comprising the steps of:

[0378] (a) Providing a resealable container in its sealed configuration, said container comprising a urinary catheter, and further providing a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin;

[0379] (b) Unsealing the container;

[0380] (c) Removing the urinary catheter from the unsealed container;

[0381] (d) Performing catheterisation with the catheter;

[0382] (e) Reinserting the catheter into the container and contacting the catheter with the medium in the container; and

[0383] (f) Resealing the container.

[0384] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the seventeenth and related aspects of the invention. The following statements relating to the seventeenth and related aspects of the invention may also be applied mutatis mutandis to the other aspects of the invention.

[0385] In some embodiments, the medium is contained in the container in step (a) of the method. The catheter may be in direct contact with the medium in the container in step (a), preferably as described in statements of invention for the first aspect of the invention above. At least one surface of the catheter may be in direct contact with the medium in the container in step (a). The catheter may be submerged in the medium in step (a).

[0386] In some embodiments, the medium is contained in a separate medium container that is located in the catheter container in step (a) and the medium is not in direct contact with the catheter. The separate medium container may preferably be as described in statements of invention above. The method may further comprise the step of releasing the contained medium from the separate medium container and into direct contact with the catheter. The step of releasing the contained medium may be performed between steps (a) and (b) of the method. The step of releasing the contained medium may comprise piercing the medium container to release the contained medium from the medium container and into direct contact with the catheter in the catheter container.

[0387] In some embodiments, unsealing the catheter container in step (b) causes contained medium to be released from the separate medium container and into direct contact with the catheter in the catheter container. In some embodiments, unsealing the catheter container in step (b) causes the medium container to rupture or break to release the contained medium from the separate medium container and into direct contact with the catheter in the catheter container. In some embodiments, the medium is not contained in the container in step (a) of the method, and the method comprises the further step of adding the medium into the container. The step of adding the medium into the container may comprise filling the container with the medium.

[0388] In some embodiments, the method further comprises the step of adding the medium into the container after step (b). The method may comprise the step of adding the medium into the container after step (b) and before reinserting the catheter into the container in step (e).

[0389] In some embodiments, the method further comprises the step of adding the medium into the container after reinserting the catheter into the container in step (e).

[0390] In some embodiments, step (e) comprises contacting at least one surface of the catheter with the medium, preferably at least an outer surface of the catheter.

[0391] In some embodiments, step (e) comprises contacting 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.

[0392] In some embodiments, step (e) comprises submerging the catheter in the medium.

[0393] Submerging the catheter in the medium, especially between uses, has been shown to result in optimal catheter lubricity.

[0394] In some embodiments, step (e) comprises contacting the catheter with the medium in the container for a total time of at least 5 seconds, or at least 10, 20, 30, 40, or at least 50 seconds, or at least 1 minute, or at least 2, 3, 4, or at least 5 minutes, or at least 10, 20, 30, 40, or at least 50 minutes, or at least 1 hour, or at least 1.5, 2, 2.5, 3, 3.5, or at least 4 hours. Step (e) may comprise contacting the catheter with the medium for a total time of no greater than 1 week, or no greater than 6 days, or no greater than 5, 4, 3, 2, or no greater than 1 day, or no greater than 20 hours, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, or no greater than 5 hours.

[0395] In some embodiments, step (e) is performed at a temperature of at least 1 °C, or at least 2, 3, 4, or at least 5 °C. In some embodiments, step (e) is performed at a temperature of no greater than 60 °C, or no greater than 55, 50, 45, 40, 35, 30, or no greater than 25 °C. In some embodiments, step (e) is performed at a temperature of between 1-60 °C, or between 5-50, or between 10-40 °C.

[0396] In some embodiments, the container in step (a) is provided before first use of the catheter. In some embodiments, the container in step (a) is provided after first use of the catheter. Steps (b) to (f) may be repeated. The method may comprise repeating steps (b) to (f) for each subsequent use of the catheter. In some embodiments, step (a) may comprise providing the container comprising an unused catheter, followed by initial steps (b) to (f), followed by a repetition of steps (b) to (f) for a subsequent use of the catheter. Such repetition of steps (b) to (f) may be completed a plurality of times. Steps (b) to (f) may be repeated at least 1, 2, 3, 4, 5, 6, or at least 7 times, preferably over a 24-hour period. Steps (b) to (f) may be repeated between 1-10 times, or between 1-7 times, preferably over a

[0397] 24-hour period. In some embodiments, the catheter is used for at least 5 hours after first use, or at least 10, 15, 20, or at least 24 hours after first use. In some embodiments, the catheter is used for up to 24 hours after first use.

[0398] There is no requirement to replenish or replace the medium contained in the catheter container between uses of the catheter. In embodiments wherein steps (b) to (f) are repeated, a repeated step (e) may comprise reinserting the catheter into the container and contacting the catheter with the same medium in the container as from the previous step (e), without the need to replenish or replace the medium between runs.

[0399] In some embodiments, the medium may not be replaced or replenished for at least 6 hours after the first catheter use, or at least 12, 18, or for at least 24 hours after the first catheter use.

[0400] In some embodiments, the medium may be replaced or replenished 18 hours or more after the first catheter use, or 20 hours or more, or 22 hours or more, or 24 hours or more after the first catheter use.

[0401] In some embodiments, the method further comprises a step of washing and / or rinsing the catheter before reinserting the catheter into the container in step (e). The method may comprise such a washing and / or rinsing step before each step (e) of the method. In some embodiments, the washing and / or rinsing step takes place directly before reinserting the catheter into the container in step (e). The washing and / or rinsing step may comprise washing and / or rinsing a surface of the catheter, preferably the outer surface thereof. In some embodiments, the washing and / or rinsing step comprises washing and / or rinsing the catheter with water. In some embodiments, the washing and / or rinsing step comprises washing and / or rinsing the catheter with an aqueous solution. The washing and / or rinsing step may comprise washing and / or rinsing the catheter with a detergent and with water or an aqueous solution. In some embodiments, the washing and / or rinsing step comprises applying a detergent to the catheter, preferably to the outer surface thereof, and then rinsing the catheter with water or an aqueous solution.

[0402] 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 (c). In some embodiments, the catheter may be dried after step (c) 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 (c) and before use of the catheter.

[0403] The additional lubricating agent may be water or may comprise water. The additional lubricating agent may be an aqueous solution.

[0404] 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.

[0405] In some embodiments, a further lubrication step is not performed. In such embodiments, the catheter may be used directly after step (c). Treating the catheter with the medium comprising the chlorine-containing species provides both catheter sterilisation and lubrication and allows for optimal catheter lubrication even in the absence of a further lubrication step. In some preferred embodiments, the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

[0406] In some preferred embodiments, the medium comprises glycerol in a total concentration of between 0.1-8 wt.%, or between 0.5-6 wt.%, or between 1-5 wt.%.

[0407] In some preferred embodiments, the medium comprises glycerol and ethylhexylglycerin.

[0408] In some preferred embodiments, the urinary catheter comprises 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 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.

[0409] The following statements may be applied mutatis mutandis to all aspects of the present invention.

[0410] Catheter assemblies or components thereof disclosed in one or more of the following applications, which are hereby incorporated by reference in their entirety, may be used: W02019 / 123004A1, W02019 / 123003A1, WO2022 / 223986A1, WO2022 / 223987A1, WO2022 / 223985A1, WO2022 / 223984A1, WO2022 / 223983A1, WO2022 / 223982A1,

[0411] WO2022 / 223981A1, WO2022 / 223980A1, WO2022 / 223979A1, WO2022 / 223978A1,

[0412] PCT / GB2023 / 052464, PCT / GB2023 / 052467, PCT / GB2023 / 052469, PCT / GB 2023 / 052470, PCT / GB 2023 / 052693, GB2305009.9, GB2314379.5, GB2314382.9, GB2314381.1, and PCT / GB 2023 / 052465. In particular, the chemistry of the present invention may be used with the catheter assemblies or components thereof disclosed in the examples and figures of the above applications, or with any other devices / technologies as set out in the statements, examples and / or claims of the above applications.

[0413] Catheters, kits and components thereof marketed under the ConvaTec GentleCath (RTM) product range, including catheter kits sold under the GentleCath (RTM) Glide and GentleCath (RTM) Glide Hydrophilic ranges (comprising elongated packaging containing a catheter and burstable sachets containing a wetting agent), may be used. In particular, the chemistry of the present invention may be used with the catheters, kits and components thereof marketed under the GentleCath (RTM) range. For instance, the medium of the invention may be used as a wetting agent with the catheter kits sold under the GentleCath (RTM) Glide and GentleCath (RTM) Glide Hydrophilic ranges.

[0414] Flip open catheter packaging or components thereof disclosed in Hollister Inc EP patent application 3445436 and US patents 10,561,817, 11,534,573 and 11,103,676, which are hereby incorporated by reference in their entirety, may be used. In particular, the chemistry of the present invention may be used with the flip open catheter packaging or components thereof disclosed in the examples and figures of the above application and patents, or with any other devices / technologies as set out in the statements, examples and / or claims of the above application and patents.

[0415] Catheters, kits and components thereof marketed under the SpeediCath (RTM) product range by Coloplast Ltd, including catheter kits sold under the SpeediCath (RTM) Standard range (comprising elongated packaging containing a catheter and burstable sachets containing a wetting agent, or comprising a packaging containing a catheter in direct contact with a wetting agent), may be used. In particular, the chemistry of the present invention may be used with the catheters, kits and components thereof marketed under the SpeediCath (RTM) range. For instance, the medium of the invention may be used as a wetting agent with the catheter kits sold under the SpeediCath (RTM) Standard range.

[0416] Detailed Description of the Invention

[0417] 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:

[0418] Figure 1 graph of E. coli colony forming units (CFU) / 30 mL versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the end of the channel) for intermittent catheters that were washed with different aqueous solutions before being inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. coli, as described in Example 4. Lines represent: Catheter 1 (inventive) - washed with aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin; Catheter 2 (control) - washed with aqueous solution comprising hypochlorous acid (300 ppm); Catheter 3 (control) - washed with aqueous solution comprising chlorhexidine gluconate (500 ppm); Catheter 4 (control) - washed with aqueous solution comprising dimethyloctadecyl [3 - (trimethoxy silyl)propyl] ammonium chloride (organosilane), benzalkonium chloride (0.1 wt.%), didecyldimonium chloride (0.1 wt.%), chlorhexidine digluconate (0.1 wt.%), cocamidopropyl betaine (0.36 wt.%), tetrasodium EDTA (0.05 wt.%), carriers (0.3 wt.%); Catheter 5 (control) - washed with water; and Bacterial growth control - catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria. The limit of detection is 30 CFU.

[0419] Figure 2 graph of E. faecalis colony forming units (CFU) / 30 mL versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the end of the channel) for intermittent catheters that were washed with different aqueous solutions before being inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. faecalis, as described in Example 4. Lines represent: Catheter 1 (inventive) - washed with aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin; Catheter 2 (control) - washed with aqueous solution comprising hypochlorous acid (300 ppm); Catheter 3 (control) - washed with aqueous solution comprising chlorhexidine gluconate (500 ppm); Catheter 4 (control) - washed with aqueous solution comprising dimethyloctadecyl [3-

[0420] (trimethoxysilyl)propyl] ammonium chloride (organosilane), benzalkonium chloride (0.1 wt.%), didecyldimonium chloride (0.1 wt.%), chlorhexidine digluconate (0.1 wt.%), cocamidopropyl betaine (0.36 wt.%), tetrasodium EDTA (0.05 wt.%), carriers (0.3 wt.%); Catheter 5 (control) - washed with water; and Bacterial growth control - catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria. The limit of detection is 30 CFU.

[0421] Figure 3 UV-vis spectra showing absorption versus wavelength (nm) for an aqueous medium comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin, when exposed to the following different doses of X-ray radiation: 0 kGy, 10 kGy, 15 kGy and 30 kGy.

[0422] Figure 4 UV-vis spectra showing absorption versus wavelength (nm) for an aqueous medium comprising chlorhexidine gluconate (CHG) (500 ppm), when exposed to the following different doses of X-ray radiation: 0 kGy, 10 kGy, 15 kGy and 30 kGy.

[0423] Figure 5 UV-vis spectra showing absorption versus wavelength (nm) for an aqueous medium comprising dimethyloctadecyl [3-

[0424] (trimethoxysilyl)propyl] ammonium chloride (organosilane), benzalkonium chloride (0.1 wt.%), didecyldimonium chloride (0.1 wt.%), chlorhexidine digluconate (0.1 wt.%), cocamidopropyl betaine (0.36 wt.%), tetrasodium EDTA (0.05 wt.%), carriers (0.3 wt.%), when exposed to the following different doses of X-ray radiation: 0 kGy, 10 kGy, 15 kGy and 30 kGy.

[0425] Figure 6 graph of E. coli colony forming units (CFU) / 20 mL against time (hours) for filters hydrated on empty Petri-dishes with an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin, or maximum recovery diluent (MRD) as a negative control, inoculated with the challenge organism E. coli NCTC 13353. The limit of detection for this test was 20 CFU / mL.

[0426] Figure 7 graph of E. faecalis colony forming units (CFU) / 20 mL against time (hours) for filters hydrated on empty Petri-dishes with an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin, or maximum recovery diluent (MRD) as a negative control, inoculated with the challenge organism E. faecalis (VRE) NCTC 12201. The limit of detection for this test was 20 CFU / mL.

[0427] Figure 8 graph of E. coli colony forming units (CFU) / 20 mL against time (minutes) for filters hydrated on TSA plates with an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin, or maximum recovery diluent (MRD) as a negative control, inoculated with the challenge organism E. coli NCTC 13353. The limit of detection for this test was 20 CFU / mL.

[0428] Figure 9 graph of E. faecalis colony forming units (CFU) / 20 mL against time (minutes) for filters hydrated on TSA plates with an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin, or maximum recovery diluent (MRD) as a negative control, inoculated with the challenge organism E. faecalis (VRE) NCTC 12201. The limit of detection for this test was 20 CFU / mL.

[0429] Figure 10 graph of Log 10 CFU / section of E. coli against catheter section for intermittent catheters that were hydrated with an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol and ethylhexylglycerin; or with water (water control); and for catheters inoculated with the challenge organism (E. coli NCTC 13353) only. The limit of detection for this test was 10 CFU / mL.

[0430] Figure 11 graph of Log 10 CFU / section of E. faecalis against catheter section for intermittent catheters that were hydrated with an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol and ethylhexylglycerin; or with water (water control); and for catheters inoculated with the challenge organism (E. faecalis NCTC 12201) only. The limit of detection for this test was 10 CFU / mL.

[0431] Figure 12 graph of CFU / mL of various challenge organisms (E. coli NCTC 13353, E. faecalis NCTC 12201, E. coli NCTC 13441, P. aeruginosa NCIMB 8626, K. pneumoniae NCTC 13465, P. mirabilis NCTC 9559, P. stuartii NCTC 11800 and M. morganii NCTC 235) after 30 seconds and after 2 minutes of addition of an inoculum of the challenge organism to: an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol and ethylhexylglycerin; and to a maximum recovery diluent (MRD) control. The limit of detection for this test was 10 CFU / mL.

[0432] Figure 13 graph of E. coli colony forming units (CFU) / 30 mL versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the end of the channel) for intermittent catheters that were coated with different gels before being inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. coli, as described in Example 10. Lines represent: Hydrophilic catheter with OCT gel = Catheter 1 (inventive) - PVC catheter coated with 0.5 mL of a gel comprising octenidine dihydrochloride, propylene glycol, hydroxyethylcellulose and water; Hydrophilic catheter with water = Catheter 2 (control) - 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 was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a, where “a” is 5-25 and preferably 9-25, and a hydrophilic B-block, wherein the B- block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. The catheter surface was hydrated with water; and Bacterial growth control - catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria. The limit of detection is 30 CFU.

[0433] Figure 14 graph of E. faecalis colony forming units (CFU) / 30 mL versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the end of the channel) for intermittent catheters that were coated with different gels before being inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. faecalis, as described in Example 10. Lines represent: Hydrophilic catheter with OCT gel = Catheter 1 (inventive) - PVC catheter coated with 0.5 mL of a gel comprising octenidine dihydrochloride, propylene glycol, hydroxyethylcellulose and water; Hydrophilic catheter with water = Catheter 2 (control) - 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 was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a, where “a” is 5-25 and preferably 9-25, and a hydrophilic B-block, wherein the B- block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. The catheter surface was hydrated with water; and Bacterial growth control - catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria. The limit of detection is 30 CFU.

[0434] Figure 15 is a boxplot showing Coefficient of Friction (COF) for intermittent urinary catheters 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 was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a, where “a” is 5-25 and preferably 9-25 , and a hydrophilic B-block, wherein the B-block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. The different bars correspond to the catheter surface being treated with a solution or gel as follows, as described in Example 11: GC Control - catheter hydrated with water; H0C1 wash - hypochlorous acid; CHG wash - chlorhexidine gluconate solution; CHG gel 1 - chlorhexidine gluconate gel; CHG gel 2 - chlorhexidine gluconate gel ; OrgS wash - organosilane solution; OCT wash (inventive) - octenidine dihydrochloride solution; and OCT gel (inventive) - octenidine dihydrochloride gel.

[0435] Figure 16 is a boxplot showing Coefficient of Friction (COF) for PV C catheters that were treated on their surface with a gel as follows, as described in Example 11: CT Control - catheter coated with water-based gel; CU Control - catheter coated with water-based gel; H0C1 (2.75% GA) - hypochlorous acid gel containing 2.75% gelling agent; H0C1 (3% GA) - hypochlorous acid gel containing 3% gelling agent; H0C1 (3.5% GA) - hypochlorous acid gel containing 3.5% gelling agent; H0C1 (4% GA) - hypochlorous acid gel containing 4% gelling agent; CHG gel 1 - chlorhexidine gluconate gel; CHG gel 2 - chlorhexidine gluconate gel; PHMB gel - poly hexamethylene biguanide gel; and OCT gel (inventive) - octenidine dihydrochloride gel.

[0436] Figure 17 is a front view of an embodiment of packaged reusable catheter of the invention showing a resealable container of the packaging in its sealed configuration. Figure 18 is a front view ofthe packaged reusable catheter of Figure 17 showing the resealable container in an open configuration.

[0437] Packaged intermittent catheters of the invention

[0438] The following packaged intermittent urinary catheters of the invention are provided.

[0439] Packaged catheter 1 (inventive) - catheter packaged with medium comprising aqueous solution comprising octenidine dihydrochloride (catheter not in direct contact with medium)

[0440] The 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.

[0441] The catheter packaging also contains a second packaging compartment which contains an aqueous solution lubricating medium comprising 500 ppm octenidine dihydrochloride.

[0442] The catheter is packaged such that it is not in direct contact with the medium. 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. 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 medium retains excellent lubricity and antimicrobial performance. This property of the octenidine dihydrochloride medium of the invention is unexpected, and other known antimicrobial compounds, especially other chlorine-containing antimicrobial compounds, degrade when exposed to irradiation, such that there is a minimal amount of the active compound present after irradiation, leading to a dramatic reduction in antimicrobial performance. This also negatively impacts lubricity performance of media containing such antimicrobials, and the surface properties of the catheters are as a result negatively impacted.

[0443] On removal from the packaging the lubricated catheter has excellent surface lubricity and the octenidine dihydrochloride in the aqueous medium 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.

[0444] The aqueous medium also shows excellent compatibility with the catheter amphiphilic additive. No negative interference between the additive and the aqueous solution occur.

[0445] Packaged Catheter 2 (inventive) - catheter packaged submerged in an aqueous medium comprising octenidine dihydrochloride

[0446] 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: CH3CH2(CH2CH2)7(OCH2CH2)7OH.

[0447] The catheter is contained in a sealed container and is submerged entirely in an aqueous solution lubricating medium. The aqueous medium contains octenidine dihydrochloride in a concentration of 750 ppm.

[0448] 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 solution and before use.

[0449] Before removal of the catheter from the container, the entire packaged catheter is sterilised by UV irradiation (the aqueous medium is also subjected to UV irradiation). As for Packaged Catheter 1 above, even after sterilisation by irradiation, the aqueous medium retains excellent lubricity and antimicrobial performance.

[0450] On removal from the container, the outer surface of the catheter body is coated with a layer of the aqueous medium. Catheter surface lubricity is excellent, and the catheter can be inserted and removed easily with minimal discomfort caused. The octenidine dihydrochloride in the aqueous medium provides excellent antimicrobial effects, as described for Packaged Catheter 1 above.

[0451] The aqueous medium also shows excellent compatibility with the catheter amphiphilic additive, as described for Packaged Catheter 1 above.

[0452] Packaged Catheter 3 (inventive) - catheter packaged with medium comprising aqueous solution comprising octenidine dihydrochloride, glycerol and ethylhexylglycerin

[0453] (catheter not in direct contact with medium) 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 further comprises glycerol in a total concentration of 5 wt.% of the medium and also comprises ethylhexylglycerin in a total concentration of 1 wt.% of the medium.

[0454] The aqueous medium again shows no sensitivity to irradiation and provides excellent catheter lubricity and antimicrobial activity even against challenging organisms.

[0455] Control Packaged Catheter 1 (not of the invention)

[0456] 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 contains 500 ppm hypochlorous acid instead of 500 ppm octenidine dihydrochloride.

[0457] 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.

[0458] Disadvantageously, the antimicrobial activity of the aqueous solution drops dramatically relative to the activity observed for the Packaged Catheter 1 of the invention.

[0459] Example 1 - Laboratory testing based on direct inoculation to assess antimicrobial activity of a medium of the invention before and after X-ray irradiation The ability of a medium of the invention to kill a clinically relevant number of urinary tract infection (UTI) related bacteria both before and after irradiation of the medium with X-ray irradiation.

[0460] Testing was performed by direct inoculation of 1 x 105CFU / mL of either E. coli or E. faecalis bacteria with 0.5 mL of an aqueous solution comprising an antimicrobial compound for varying time periods both before and after irradiation of the aqueous solution with X-ray radiation.

[0461] The following aqueous media were tested:

[0462] Aqueous medium 1 (inventive) - octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin.

[0463] Aqueous medium 2 (control) - chlorhexidine gluconate (CHG) (500 ppm).

[0464] The results of the direct inoculation test are displayed in Table 1 below.

[0465] Table 1

[0466] The inventive medium displayed excellent, rapid antimicrobial activity against both challenge organisms, E. coli and E. faecalis, both before and after X-ray irradiation. For all runs tested, the inventive aqueous medium provided a greater than 4 log reduction in bacterial numbers.

[0467] In contrast, the control medium 2 containing the antimicrobial active, chlorhexidine gluconate, was only able to reduce the bacterial numbers to the detection limit for E. coli prior to X-ray irradiation. Antimicrobial performance was negatively affected by irradiation and even a 2-minute inoculation was not sufficient to reduce bacterial numbers to the detection limit.

[0468] In the case of the more challenging organism, E. faecalis, the control medium 2 was unable to reduce bacterial numbers to the detection limit even before X-ray irradiation.

[0469] Example 2 - Residual antimicrobial activity testing

[0470] The following test was performed to model how long-lasting the antimicrobial activity of media of the invention is when residual medium is left within the urethra following insertion and removal of a catheter that has been treated with a medium of the invention.

[0471] Representative E. coli and E. faecalis bacterial colonies from an 18-24 hour challenge culture plate were dispersed in maximum recovery diluent (MRD) to obtain an optical density (OD540nm) equivalent to approx. 1 x 108CFU / mL. This was diluted to obtain a working concentration of 1 x 104CFU / mL. 10 |iL volumes of this working concentration were used for testing.

[0472] Before performing the test, some initial method development testing was performed to establish how much residual antimicrobial solution was left within a urethral agar channel (UAC) following bacterial displacement testing. This was performed by weighing the UAC before and after insertion of a catheter. Results obtained suggested that a range from 19.5 pl to 36.7 pl was left within the UAC. Therefore, testing moving forward was based on worst case, which was the maximum left in the UAC at approximately 40 pl.

[0473] Sterile 25mm Whatman filters were placed onto the centre of a Petri plate and 40 pl of the test sample (antimicrobial solutions) was placed onto the centre of the filter (n=3 per sample). Filter / sample plates were set up for 0 hour, 30 minute, 4 hour and 24 hour time points. The timepoint was started immediately after adding the sample to the filter. To minimise sample evaporation, Filter / sample plates were parafilmed and left at room temperature.

[0474] At the different time points, 10 pL of the working concentration of bacteria were added to the centre of the filter containing the test sample.

[0475] The bacteria and antimicrobial solutions were allowed 2 min contact time before the presence of growth or no growth of bacteria on the plates was determined for each time point.

[0476] The samples tested were:

[0477] Aqueous medium 1 (inventive) - octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin. Aqueous medium 2 (control) - chlorhexidine gluconate (CHG) (500 ppm).

[0478] Aqueous medium 3 (control) -dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (organosilane), benzalkonium chloride (0.1 wt.%), didecyldimonium chloride (0.1 wt.%), chlorhexidine digluconate (0.1 wt.%), cocamidopropyl betaine (0.36 wt.%), tetrasodium EDTA (0.05 wt.%), carriers (0.3 wt.%).

[0479] The results of the tests are displayed in Table 2 below.

[0480] Table 2

[0481] The plate treated with the inventive aqueous medium 1 showed excellent, long-lasting antimicrobial activity, with no bacterial growth found even after 24 hours for either microorganism tested. In contrast, the control media did not show the same long-lasting antimicrobial activity, with activity for medium 3 tailing off at the 30-minute time point. Medium 2 was not even able to stop bacterial growth at the 0-hour timepoint.

[0482] The above results indicate the ability of the medium of the invention to provide long- lasting protection against the growth of pathogenic microorganisms whilst a catheter is left in urethral tissue during and after catheterisation.

[0483] Example 3 - Minimum amount required to kill testing

[0484] Testing was performed to investigate the concentration range of an antimicrobial active in an aqueous medium required to kill a known number of bacteria.

[0485] Testing was performed by direct inoculation of 1 x 105CFU / mL of either E. coli or E. faecalis bacteria with 0.5 mL of an aqueous solution comprising different concentrations of an antimicrobial compound for 2 minutes in deep 96 well plates. After the 2 minutes of inoculation, neutralisation was performed. Bacterial growth was assessed within the well plates after 24 hours to determine the minimum concentration of antimicrobial compound required to kill bacteria for the different solutions and for the two microorganisms tested.

[0486] The following aqueous media were tested: Inventive medium - octenidine dihydrochloride (500 ppm) (active antimicrobial compound), glycerol, and ethylhexylglycerin.

[0487] Control medium 1 - chlorhexidine gluconate (CHG) (500 ppm) (active antimicrobial compound).

[0488] Control medium 2 - hypochlorous acid (HOC1) (300 ppm) (active antimicrobial compound).

[0489] Control medium 3 - chlorhexidine gluconate (CHG) (20%) (active antimicrobial compound).

[0490] Control medium 4 - organosilane (0.1%) (active antimicrobial compound).

[0491] The results of the tests are displayed in Table 3 below. Table 3

[0492] The above results show that the medium of the invention provides bacterial kill for both challenge organisms at concentrations of the active octenidine dihydrochloride as low as < 2 ppm, which demonstrates the potency of octenidine dihydrochloride as an antimicrobial agent.

[0493] With the exception of Control medium 4, all other antimicrobial media tested required the active to be present at a concentration at least 32 times higher than the minimal concentration of octenidine dihydrochloride required for E. coli, and at least 38 times higher than the minimal concentration of octenidine dihydrochloride required for E. faecalis. These results demonstrate just how much more effective the medium of the invention is compared other known antimicrobial media.

[0494] Example 4 - Bacterial displacement testing The following test was performed to evaluate the ability of media of the invention to prevent transfer of bacteria through the urethra upon insertion of a catheter.

[0495] Agar test channels with entrance and exit holes on either end were provided to model a catheter being passed through the body.

[0496] The entrances of the channels were independently inoculated with bacterial strains of E. coli and E. faecalis.

[0497] Intermittent catheters were independently inserted in through the entrance hole of the agar gel channel, pushed to the end of the channel and then removed.

[0498] Following removal of the catheters, agar gel channels were cut into 7 sections and the number of bacteria in each section was determined allowing for a graph to be plotted showing migration of the bacteria through the channels.

[0499] Bacterial presence and amounts were determined at 7 sections along the length of the channels (sections 1-7). Section 1 being at the entrance of the channel and section 7 being at the exit of the channel.

[0500] Intermittent catheters were provided 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 was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a, where “a” is 5-25 and preferably 9-25, and a hydrophilic B -block, wherein the B -block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. The intermittent catheters were washed with different aqueous solutions containing antimicrobial agents.

[0501] The catheters tested were:

[0502] Catheter 1 (inventive) - washed with aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin.

[0503] Catheter 2 (control) - washed with aqueous solution comprising hypochlorous acid (300 PPm).

[0504] Catheter 3 (control) - washed with aqueous solution comprising chlorhexidine gluconate (500 ppm).

[0505] Catheter 4 (control) - washed with aqueous solution comprising dimethyloctadecyl[3- (trimethoxysilyl)propyl]ammonium chloride (organosilane), benzalkonium chloride (0.1 wt.%), didecyldimonium chloride (0.1 wt.%), chlorhexidine digluconate (0.1 wt.%), cocamidopropyl betaine (0.36 wt.%), tetrasodium EDTA (0.05 wt.%), carriers (0.3 wt.%).

[0506] Catheter 5 (control) - washed with water.

[0507] Bacterial growth control - catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria.

[0508] The results of the tests are displayed in Figures 1 and 2.

[0509] Catheter 1 (inventive) that was washed with an aqueous medium of the invention comprising octenidine dihydrochloride allows for a significant reduction in bacteria transfer along the channel compared to catheters washed with water and other antimicrobial solutions. At section 3 of the channel for the inventive run, an around 2-3 order of magnitude reduction in bacterial colony forming units per mL was observed for both E. coli and E. faecalis.

[0510] Example 5 - Laboratory testing to determine the effect of X-ray irradiation on aqueous media of the invention The tests below were performed to determine the effect of X-ray irradiation on aqueous media of the invention. pH testing

[0511] The pH of the following aqueous solution was tested both before and after different doses of X-ray irradiation. The solution tested was an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin.

[0512] The results are displayed in Table 4 below.

[0513] Table 4 Whilst a drop in pH was observed when the solution was irradiated, the pH remained well within acceptable levels even after the highest dose of radiation (30 kGy), demonstrating the high chemical stability of the solution.

[0514] UV spectral analysis

[0515] To investigate the effect of the irradiation further, UV analysis of the following aqueous media was performed both before and after irradiation of the media with different doses of X-ray radiation (0 kGy, 10 kGy, 15 kGy, and 30 kGy).

[0516] Aqueous media tested were:

[0517] Aqueous medium 1 (inventive) - octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin.

[0518] Aqueous medium 2 (control) - chlorhexidine gluconate (CHG) (500 ppm).

[0519] Aqueous medium 3 (control) -dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (organosilane), benzalkonium chloride (0.1 wt.%), didecyldimonium chloride (0.1 wt.%), chlorhexidine digluconate (0.1 wt.%), cocamidopropyl betaine (0.36 wt.%), tetrasodium EDTA (0.05 wt.%), carriers (0.3 wt.%).

[0520] The UV spectral results are displayed in Figures 3-5.

[0521] For aqueous medium 1, even after all doses of radiation, the characteristic peak of octenidine dihydrochloride at 285 nm was retained and the intensity of this peak did not decrease by a large amount even at high doses of radiation.

[0522] This demonstrates the excellent stability of octenidine dihydrochloride and media of the invention when exposed to irradiation. In contrast, the UV spectra of aqueous media 2 and 3 change significantly postirradiation compared to pre-irradiation. The peaks of spectra for both media lose resolution after just 10 kGy of irradiation and shoulders of the main peaks appear. In the case of medium 2, one of the peaks even fully disappears upon irradiation. These results suggest that the antimicrobial actives of media 2 and 3 degrade to another species when exposed to even small doses of irradiation.

[0523] Example 6 - Antimicrobial efficacy testing of residual activity of octenidine solution against E. coli NCTC 13353 and E.faecalis NCTC 12201

[0524] The test sample (inventive) undergoing testing was an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin.

[0525] Testing was performed using n=3 replicates for each sample and n=l for the negative control for total viable count (TVC) results.

[0526] Preparation of the challenge inoculum

[0527] The representative colonies of the challenge organism (E. coli NCTC 13353 and E. faecalis (VRE) NCTC 12201) were dispersed in maximum recovery diluent (MRD) to obtain an optical density (OD540nm) equivalent to approximately 1 x 108CFU / ml. This suspension was diluted in MRD to achieve the final concentration of 1 x 106CFU / ml. This was repeated with tryptone soy broth (TSB), to provide an additional challenge. A quantitative plate count was performed on this suspension to determine the total number of viable organisms inoculated.

[0528] Residual antimicrobial efficacy testing (empty petri dishes) A sterile 27 mm grade 4 filter was placed in an empty sterile 90 mm petri dish aseptically. 40pl of test sample was then pipetted onto the filter. The lid was then placed onto the petri dish and left for 48 hours (separate were prepared for 0, 72 and 96 hours) at room temperature. After 48 hours, the challenge organism diluted in MRD (or TSB) in 10 pl volumes, was pipetted onto the filter. This was left for 2 minutes (approximate urination time). Following the 2 minutes, the filter / sample / inoculum, was transferred to a stomacher bag containing 20ml of Dey-Engley Neutralising Broth (DENB). The resulting solution was homogenised on high for 4 minutes and total viable counts (TVCs) were carried out, for neat and 101dilutions, 0.5ml was plated across duplicate plates, and for subsequent dilutions lOOpl was plated onto duplicate plates. This was repeated for the negative control which involved placing 40pl of MRD or TSB onto the filter before inoculating, and the remaining occasions (0, 72 and 96 hours). All plates were spread using sterile L-shaped spreaders and incubated at 35+3 °C for at least 48 hours. Following the incubation period, the number of colonies were counted on the most appropriate dilution for each sample i.e., between 25-250 CFU / plate.

[0529] Residual antimicrobial efficacy testing (TSA plates)

[0530] This test method was similar to the method described above with a few differences. A sterile 27 mm grade 4 filter was placed in a TSA plate aseptically. 40 pl of the sample was pipetted onto the filter and left for 30 minutes at room temperature. After 30 minutes, the challenge organism in 10 pl volumes, prepared in MRD, was pipetted onto the filter and a contact time of 2 minutes was performed. Following the 2 minutes, the filter / sample / inoculum, was transferred to a stomacher bag containing 20 ml of DENB. This was repeated with the challenge organisms diluted in TSB instead of MRD as an additional challenge to the antimicrobial. The resulting filter / sample / inoculum was homogenised on high for 4 minutes and TVCs were carried out, for neat and 101dilutions, 0.5 ml was plated across duplicate plates, and for subsequent dilutions 100 pl was plated onto duplicate plates. The negative control was also tested in the same manner following 40 pl of MRD or TSB being pipetted onto the filter. This was repeated for the relevant timepoint (0, 4, 24, 48 and 72 hours). All plates were spread using sterile L- shaped spreaders and incubated at 35+3 °C for 48 hours. Following the incubation period, the number of colonies were counted on the most appropriate dilution for each sample i.e., between 25-250 CFU / plate.

[0531] Results

[0532] Data presented in Figures 6 and 7 show residual antimicrobial activity when the octenidine containing solution is placed on the filter only. Low numbers of bacterial recovery were obtained over the time points tested, with low and undetectable numbers (<20 CFU / ml) of E. coli NCTC 13353 and E. faecalis (VRE) NCTC 12201. Therefore, sustained antimicrobial activity in the residual amount of octenidine solution was present throughout the 96-hour testing period. This was also true when bacterial inoculum was added within TSB, a more nutritious media which increased the challenge to the antimicrobial (data not shown).

[0533] When testing was performed with TSA plates under the filter, this added an extra challenge, with the presence of sugars, salts and a buffering capacity, and less antimicrobial residual activity was observed (see Figures 8 and 9). Despite this, there was a decrease in the number of bacteria at the 0 hour timepoint suggesting that the octenidine solution’ s antimicrobial properties work rapidly, but then over the remaining time points tested there was reduced antimicrobial activity observed against E. coli NCTC13353. However, there was some residual antimicrobial activity observed at the 30-minute time point for E. faecalis NCTC 12201. The same trend was observed when bacterial inoculum was added within TSB, a more nutritious media which increased the challenge to the antimicrobial (data not shown).

[0534] Example 7 - Testing of the effect of octenidine solution and octenidine gel on bacterial movement of antibiotic resistant E. coli NCTC 13353 and E. faecalis (VRE) NCTC 12201

[0535] Bacteria can translocate using various mechanisms to ensure survival due to adherence to suitable environments. This test aimed to assess the disruption of the movement of both motile (Escherichia coli NCTC 13353) and non-motile (Enterococcus faecalis (VRE) NCTC 12201) microorganisms in the presence of water, an octenidine solution and an octenidine gel. In brief, the testing consisted of using bacterial displacement urethra agar channels (UACs) which were split in half lengthways and bacteria inoculated along the agar on one side of the channel, water, octenidine solution or octenidine gel was added to the channel. Following incubation of 24 hours, a visual assessment as to whether the bacteria were able to move into the channel or across to the other side of the channel was performed.

[0536] The test samples (inventive) undergoing testing were:

[0537] An aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin.

[0538] A gel comprising octenidine dihydrochloride, propylene glycol, hydroxyethylcellulose, and water. Testing was performed using n=3 replicates for the octenidine gel and solution and n=l for the sterile deionised water (SDW) samples (bacterial growth control), for visual mobility images.

[0539] UAC preparation

[0540] Selective agar channels were made by aseptically dispensing 30 ml of molten Harlequin tryptone bile glucuronide agar (TBXA) + 0.4% agar bacteriological (AB) (a selective agar for E. coli NCTC 13353) and molten rapid enterococci chromoselect agar (RECA) + 0.8% AB (a selective agar for E. faecalis NCTC 12201) into 30 ml universal containers. Sterile 4 mm stainless steel rods, held in place by sterile stainless steel locating discs, were placed into the universal containers and removed once set to create a channel down the centre of the agar the same diameter as CH12 catheters. The channels were left standing, with their lids removed, within the laminar flow cabinet to dry for 18-24 hours. Additionally, to prepare the channels, just before testing, any fluid within the agar channel was removed using a sterile needle and syringe, and a sterile swab was then inserted slowly (around 3 seconds) down the length of the channel, rotated anticlockwise twice at the base of the channel and slowly removed. These were the urethra agar channels (UACs) for this testing.

[0541] Representative colonies from an 18-24 hour challenge culture plate, were dispersed in maximum recovery diluent (MRD) to obtain an optical density (OD540nm) equivalent to approximately fxfO8CFU / ml. This was diluted ten-fold to obtain a working concentration of fxfO7CFU / ml. 50 pl volumes of this working concentration were transferred into separate bijous for inoculation. Testing performed

[0542] The UACs were aseptically tipped from the container onto a sterile surface and under aseptic conditions, the UACs were the split in half lengthways. The two halves of the UACs were then separated so the inside of the channel was visible. The visible channel was filled with 100 pl of the octenidine test solution, the octenidine test gel or SDW and placed in a petri dish. A sterile Flocked swab was placed into the 50 pl inoculum of the above working concentration and left to sit for 10 seconds, the inoculated swab was then swiped along one of the inner edges of the channel. To each half of the channel, one side was inoculated using a swab from one side to another lengthways. This was performed for all the test sample replicates and bacterial growth control UACs. The petri dish was placed in the incubator at 35 ± 3 °C for approximately 24 hours. This step was repeated for each replicate and each challenge organism. Following the incubation period, images were taken to observe the bacteria’s motility through the UACs.

[0543] Results

[0544] E. coli NCTC 13353 on Harlequin TBXA with 0.4% AB selective agar appears bluegreen, which allowed visualisation of bacteria. E.faecalis (VRE) NCTC 12201 on RECA with 0.8% AB, a selective agar, where colonies appear green, which allowed visualisation of bacteria.

[0545] For UACs containing octenidine solution or octenidine gel, bacteria had grown in the inoculated area (the top side of the agar) as expected, however, bacteria were not observed within or at the bottom of the channel. This suggests that the octenidine solution / gel prevented the movement of bacteria. Channels containing SDW for both challenge organisms showed copious amounts of bacteria within the channel and the other side of the channel. An increased growth was present on the UAC for the challenge organism E. coli NCTC 13353 compared to E. faecalis (VRE) NCTC 12201 due to E. coli being a motile bacteria and E.faecalis being non-motile.

[0546] Example 8 - Antimicrobial efficacy testing of intermittent catheters hydrated with an octenidine solution against E. coli NCTC 13353 and E. faecalis (VRE) NCTC 12201

[0547] Intermittent catheters were provided 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 was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a, where “a” is 5-25 and preferably 9-25, and a hydrophilic B -block, wherein the B -block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0548] The following catheters were tested:

[0549] • The above catheters hydrated with an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin.

[0550] • The above catheters unhydrated (control)

[0551] For the octenidine solution containing catheters, the solution was placed in the catheter wetting chambers instead of water, and the catheter was hydrated upon removal. The Ill catheter was then applied to three areas inoculated with bacteria, which represented three sections (tip area, middle, and end of the catheter). The test aimed to establish if hydration with octenidine solution occurred along the whole catheter and that hydration was enough to kill inoculated bacteria effectively. The samples were tested against the challenge organisms, Escherichia coli NCTC 13353 and Enterococcus faecalis (VRE) NCTC 12201.

[0552] Testing was performed using n=3 replicates for each sample and n=3 for the negative control for total viable counts (TVC) results.

[0553] Preparation of the challenge inoculum

[0554] The representative colonies of the challenge organism (E. coli NCTC 13353 and E. faecalis (VRE) NCTC 12201) were dispersed in maximum recovery diluent (MRD) to obtain an optical density (OD540nm) equivalent to approximately 1 x 108CFU / ml. This suspension was diluted in MRD to achieve the final concentration of 1 x 107CFU / ml. A quantitative plate count was performed on this suspension to determine the total number of viable organisms inoculated.

[0555] Sample preparation

[0556] Prior to testing, the catheters which were to contain octenidine solution were prepared. The catheters were removed from their packaging, and both the catheters and the packaging were placed onto a sterile cut-open stomacher bag within the laminar flow cabinet, and they were left overnight to allow the catheter and the wetting chamber within the packaging to dry. After 18-24 hours, the catheters were inserted back into their packaging and 0.5 ml of the octenidine solution was added to the now empty wetting chambers using a syringe and needle (while the catheters were most of the way into the packaging). The catheters were then ready for testing.

[0557] No pre-preparation was required for the negative control, as the chamber within the catheter packaging already contained water.

[0558] Antimicrobial efficacy testing

[0559] The challenge organism, in 1 pl volumes, was pipetted onto a sterile surface, 3 times, to represent the 3 sections of the catheter. The catheter was placed onto the inoculated stomacher bag and was kept there for a contact time of 2 minutes. The catheter handle was allowed to hang from the lab bench to ensure the catheter section is in contact with the inoculum. Following the 2 minutes, the catheter was cut, using a sterile disposable scalpel, into 3 x 2.5 cm sections starting from the tip of the catheter (section 1), central area (section 2) and ending near the funnel of the catheter (section 3). Each section of the catheter was then placed into 10 ml of Dey-Engley Neutralising Broth (DENB) and sonicated for 5 minutes followed by 2 minutes vortexing at 950 rpm. Following vortexing, total viable counts were carried out. For neat and 101dilutions, 0.5 ml was plated across duplicate plates. For subsequent dilutions, 100 pl was plated onto duplicate plates. All plates were spread using sterile L-shaped spreaders and incubated at 35 ± 3 °C for 48 hours. Following the incubation period, the number of CFUs were counted on the most appropriate dilution for each sample i.e., between 25-250 CFU / plate.

[0560] Results

[0561] As shown in Figure 10, catheters hydrated with octenidine solution resulted in undetectable numbers of E. coli in all tested sections. As shown in Figure 11, similar results were observed E. faecalis. For the water control, the majority of both challenge organisms were found to transfer to the catheter during the 2-minute contact (see Figures 10 and 11).

[0562] Overall, catheters hydrated with octenidine solution reduced both E. coli NCTC 13353 and E. faecalis (VRE) NCTC 12201 numbers to undetectable / near undetectable levels, respectively, showing that the catheter was hydrated fully along the length of the catheter and that the amount present was enough to kill the majority, if not all the bacteria inoculate.

[0563] Example 9 - Broad screen testing of the antimicrobial efficacy of octenidine solution using a direct inoculation method

[0564] The test sample (inventive) undergoing testing was an aqueous solution comprising octenidine dihydrochloride (500 ppm), glycerol, and ethylhexylglycerin.

[0565] The octenidine solution was tested against the following challenge organisms:

[0566] Escherichia coli NCTC 13353

[0567] Enterococcus faecalis NCTC 12201

[0568] Escherichia coli NCTC 13441- antibiotic-resistant uropathogenic strain (produces CTX- M-15 ESBL)

[0569] Pseudomonas aeruginosa NCIMB 8626

[0570] Klebsiella pneumoniae NCTC 13465

[0571] Proteus mirabilis NCTC 9559

[0572] Providencia stuartii NCTC 11800

[0573] Morganella morganii NCTC 235 Challenge organism preparation

[0574] Representative colonies from an 18-24 hour challenge culture plate, were dispersed in MRD to obtain an optical density (OD540nm) equivalent to approximately IxlO8CFU / ml. This was diluted to obtain a working concentration of IxlO7CFU / ml. A quantitative count was performed to confirm the inoculum level.

[0575] Testing

[0576] The samples and MRD controls were aliquoted in 0.5 ml volumes into sterile bijous (n=3 per sample and n=l per control per challenge organism). The challenge inoculum was prepared as a 1 x 107CFU / ml working suspension, 5 pl of this suspension was added to the sample / control aliquots and mixed (therefore 1 xlO5CFU / 0.5ml).

[0577] The solution was left to sit for either 30 seconds, to investigate speed of kill, or 2 minutes, to replicate the approximate length of time an antimicrobial catheter would be sat in place during approximate urination period. Following 30 seconds or 2 minutes, 100 pl volumes were sampled and transferred to 0.9 ml and 9.9 ml DENB (for 1:10 and 1 : 100 dilutions respectively). 100 pl volumes of the most appropriate dilutions were inoculated onto duplicate pre-dried TS A plates and spread using separate sterile L-shaped spreaders (for 101and 10’2dilutions 0.5ml were placed onto duplicate plates). The TSA plates were allowed to dry before being inverted and incubated at 35 ± 3 °C for at least 48 hours. Following the incubation period, the number of CFUs were counted on the most appropriate dilution for each dressing type i.e. between 25-250 CFU / plate.

[0578] Results

[0579] Testing results are shown in Figure 12 for both testing periods, 30 seconds and 2 minutes, post- inoculation for all challenge organisms. The graph shows that the addition of any challenge organism inoculum to 0.5 ml of the octenidine solution resulted in undetectable numbers of bacteria (<10 CFU / ml). In comparison, the MRD control after both timepoints for all challenge organisms remained as high as the initial inoculum count.

[0580] Overall, octenidine solution tested with this method resulted in undetectable numbers of all challenge organisms, E. coli NCTC 13353, E. faecalis NCTC 12201, E. coli NCTC 13441, P. aeruginosa NCIMB 8626, K. pneumoniae NCTC 13465, P. mirabilis NCTC 9559, P. stuartii NCTC 11800 and M. morganii NCTC 235, after 30 seconds and 2 minutes post-inoculation.

[0581] Example 10 - Bacterial displacement testing of gels

[0582] The following test was performed to evaluate the ability of media of the invention to prevent transfer of bacteria through the urethra upon insertion of a catheter.

[0583] Agar test channels with entrance and exit holes on either end were provided to model a catheter being passed through the body.

[0584] The entrances of the channels were independently inoculated with bacterial strains of E. coli and E. faecalis.

[0585] Intermittent catheters were independently inserted in through the entrance hole of the agar gel channel, pushed to the end of the channel and then removed.

[0586] Following removal of the catheters, agar gel channels were cut into 7 sections and the number of bacteria in each section was determined allowing for a graph to be plotted showing migration of the bacteria through the channels. Bacterial presence and amounts were determined at 7 sections along the length of the channels (sections 1-7). Section 1 being at the entrance of the channel and section 7 being at the exit of the channel.

[0587] The intermittent catheters were coated with different gels containing antimicrobial agents.

[0588] The catheters tested were:

[0589] Catheter 1 (inventive) - PVC catheter coated with 0.5 mL of a gel comprising octenidine dihydrochloride, propylene glycol, hydroxyethylcellulose, and water.

[0590] Catheter 2 (control) - 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 was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a, where “a” is 5-25 and preferably 9-25, and a hydrophilic B -block, wherein the B -block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. The catheter surface was hydrated with water.

[0591] Bacterial growth control - catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria.

[0592] The results of the tests are displayed in Figures 13 and 14.

[0593] Catheter 1 (inventive) that was coated with a gel medium of the invention comprising octenidine dihydrochloride allowed for a significant reduction in bacteria transfer along the channel compared to catheters washed with water. At section 3 of the channel for the inventive run, an around 3 order of magnitude reduction in bacterial colony forming units per mL was observed for both E. coli and E. faecalis.

[0594] Example 11 - Coefficient of friction testing

[0595] The following tests were performed to evaluate the lubricity effects of a range of antimicrobial actives in wash and gel form. The lubricity was measured using coefficient of friction testing.

[0596] Test procedure

[0597] To analyse the antimicrobial washes, a catheter tube is submerged in the wash for a minimum of 10 seconds and then tested immediately for coefficient of friction.

[0598] Antimicrobial gels were analysed as described below:

[0599] Sample preparation:

[0600] To apply the gel, uncoated PVC catheters were removed from their packaging. 2 mL of the test gel was added and the test catheter was inserted. The test catheter was stored in the gel for one hour prior to testing. A separate catheter was used for each test replicate.

[0601] Sample analysis:

[0602] Following sample preparation as described above, the catheter was pulled through a chamber and tested immediately for coefficient of friction.

[0603] A sample size of n=10 for each variant was applied.

[0604] Results and discussion The first catheter tested was an 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 was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CHsCth CthCthla, where “a” is 5-25 and preferably 9-25, and a hydrophilic B -block, wherein the B -block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0605] The catheter was treated with the following antimicrobial solutions / gels for coefficient of friction testing.

[0606] GC Control - Catheter hydrated with water.

[0607] HOC1 wash (Control) - hypochlorous acid solution

[0608] CHG wash (Control) - chlorhexidine gluconate solution

[0609] CHG gel 1 (Control) - chlorhexidine gluconate gel

[0610] CHG gel 2 (Control) - chlorhexidine gluconate gel

[0611] OrgS wash (Control) - organosilane solution

[0612] OCT wash (inventive) - octenidine dihydrochloride solution

[0613] OCT gel (inventive) - octenidine dihydrochloride gel

[0614] The coefficient of friction results are displayed in Table 5 below and in Figure 15.

[0615] Table 5

[0616] All results fall comfortably below the maximum specification limit for the test catheter of 0.17. Advantageously, both the OCT wash and gel runs provided a coefficient of friction that is similar to the GC control specification standard, indicating excellent lubricity performance.

[0617] It was especially surprising that despite the presence of viscous gel on the catheter surface for OCT gel, coefficient of friction results were in line with values for the GC Control specification standard.

[0618] The second catheter tested was an uncoated PVC catheter. The catheter was treated with the following antimicrobial gels for coefficient of friction testing.

[0619] CT Control - Catheter coated with water-based gel.

[0620] CU Control - Catheter coated with water-based gel.

[0621] HOC1 (2.75% GA) (Control) - hypochlorous acid gel containing 2.75% gelling agent. HOC1 (3% GA) (Control) - hypochlorous acid gel containing 3% gelling agent.

[0622] H0C1 (3.5% GA) (Control) - hypochlorous acid gel containing 3.5% gelling agent. H0C1 (4% GA) (Control) - hypochlorous acid gel containing 4% gelling agent.

[0623] CHG gel 1 (Control) - chlorhexidine gluconate gel

[0624] CHG gel 2 (Control) - chlorhexidine gluconate gel

[0625] PHMB gel (Control) - polyhexamethylene biguanide gel OCT gel (inventive) - octenidine dihydrochloride gel

[0626] The coefficient of friction results are displayed in Table 6 below and in Figure 16.

[0627] Table 6

[0628] To analyse the data for the gel tests with the uncoated PVC catheter, results were compared to the CT and CU Control standards, and to the specification coefficient of friction of a hydrophilic catheter (<0.17) and a gel-lubricated catheter (<1.33).

[0629] Poor lubricity was observed for the hypochlorous acid gels. Results were elevated and high variability in results were observed. Beading of the gel on the catheter surface was observed which confirms a mismatch in the polarity of the catheter surface and the lubricant. To optimise the HOC1 gel formulation, gels with varying levels of gelling agent were trialled. However, altering the gelling agent content did not translate to a reduced coefficient of friction.

[0630] The inventive octenidine gel provided improved coefficient of friction results. However, beading was also evident for the octenidine gel. Overall, performance of the octenidine gel with the catheter coated with an A-B block copolymer additive was far superior to performance of the octenidine gel with the uncoated catheter, suggesting the presence of a synergistic effect between the octenidine gel and the A-B block copolymer catheter coating.

[0631] The third catheter to be tested was a catheter coated with a polyvinylpyrrolidone (PVP) coating.

[0632] The catheter was treated with the following antimicrobial solutions for coefficient of friction testing.

[0633] OCT wash (inventive) - octenidine dihydrochloride solution

[0634] OrgS wash (Control) - organosilane solution The coefficient of friction results are displayed in Table 7 below.

[0635] Table 7

[0636] Again, the octenidine solution lubricity results fall comfortably below the maximum specification limit for the test catheter of 0.17, indicating excellent lubricity performance.

[0637] Packaged reusable intermittent catheter of the invention

[0638] The following packaged reusable intermittent urinary catheter of the invention is provided.

[0639] The packaged reusable catheter of the invention comprises a reusable 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.

[0640] The catheter is contained in a container in the form of a tube comprising a flexible central portion and two rigid side portions.

[0641] The container is filled with an aqueous solution lubricating medium comprising 500 ppm octenidine dihydrochloride, and further comprising glycerol in a total concentration of 5 wt.% of the medium and also comprises ethylhexylglycerin in a total concentration of 1 wt.% of the medium.

[0642] The catheter is packaged submerged in the medium.

[0643] An end of the container comprises a lid which is releasably attached to the container and allows for the container to be opened and closed allowing for the catheter to be removed for use and re-inserted for storage between uses. 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 solution and before use.

[0644] Prior to removal of the catheter, the entire packaged catheter is sterilised by X-ray irradiation (the aqueous medium is also subjected to X-ray irradiation). Surprisingly, even after sterilisation by irradiation, the aqueous medium retains excellent lubricity and antimicrobial performance. This property of the octenidine dihydrochloride medium of the invention is unexpected, and other known antimicrobial compounds, especially other chlorine-containing antimicrobial compounds, degrade when exposed to irradiation, such that there is a minimal amount of the active compound present after irradiation, leading to a dramatic reduction in antimicrobial performance. This also negatively impacts lubricity performance of media containing such antimicrobials, and the surface properties of the catheters are as a result negatively impacted.

[0645] On removal from the packaging the lubricated catheter has excellent surface lubricity and the octenidine dihydrochloride in the aqueous medium provides excellent antimicrobial effects, allowing for bacteria to be killed on the outer surface of the catheter. Antimicrobial effects remain even during and after multiple uses of the intermittent catheter.

[0646] The aqueous medium also shows excellent compatibility with the catheter amphiphilic additive. No negative interference between the additive and the aqueous solution occurs.

[0647] Reusable intermittent catheter of the invention packaged in a resealable pouch

[0648] Figures 17 and 18 illustrate an embodiment of a reusable packaged catheter of the invention. The packaging comprises a resealable container 1 in the form of a catheter pouch 1. Pouch 1 defines an internal cavity 2 that is configured to hold a urinary catheter

[0649] 3. The urinary catheter 3 is an intermittent catheter 3 comprising a hollow polymeric tubular body comprising a base polymer formed from a thermoplastic elastomeric material and further comprising an amphiphilic additive. The pouch 1 is also filled with an aqueous medium 4 comprising 500 ppm octenidine dihydrochloride, and further comprising glycerol in a total concentration of 5 wt.% of the medium and also comprises ethylhexylglycerin in a total concentration of 1 wt.% of the medium. The pouch 1 further comprises a resealable opening 5 formed at an edge of the pouch 1 , which allows the pouch 1 to be repeatedly opened and closed. The resealable opening 5 comprises a resealable opening mechanism in the form of a press-to-seal closure. Such resealable opening mechanisms are known to those skilled in the art, who would also appreciate that in other embodiments, a range of alternative opening mechanisms may be employed.

[0650] In the sealed configuration of the pouch 1, as depicted in Figure 17, the resealable opening 5 is in its sealed configuration. The catheter 3 is contained in the internal cavity

[0651] 2 of the pouch 1 and is fully submerged in the medium 4 within the pouch 1. Both outer and inner surfaces (not shown) of the catheter 3 are in direct contact with the medium 4 along the full length of the catheter 3. In other embodiments, the medium 4 may be contained in a separate medium container that may be configured to release the medium 4 into the cavity 2 of the pouch to bring the catheter 3 into direct contact with the medium

[0652] 4, before or upon first opening of the pouch.

[0653] In use, the user opens the pouch 1 at the resealable opening 5 and removes the catheter 3 from the pouch 1 through the resealable opening 5, as depicted in Figure 18. The catheter

[0654] 3 is then used in the conventional manner, without any requirement to rinse the catheter 3 after removal from the medium 4 and before use. After use, the catheter 3 is simply reinserted into the pouch 1 through the resealable opening 5, thus re-submerging the catheter 3 in the medium 4, and the pouch 1 resealed at the resealable opening 5. No rinsing / washing steps are necessary after use of the catheter 3, as reinserting the catheter 3 into the medium 4 effectively sterilises the catheter 3. However, it would also be possible for the user to rinse / wash the catheter 3 after use, depending on individual preference.

[0655] The catheter 3 is then re-used simply by removing the catheter 3 from the resealable pouch 1 , as described, and re-using. Again, no further rinse / wash steps are required.

[0656] 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 a urinary catheter, the method comprising the steps of: a. Providing: a urinary catheter and a medium comprising octenidine or a salt thereof; and b. Irradiating the urinary catheter and the medium.

2. A method as claimed in claim 1 , wherein step (b) comprises irradiating the catheter and medium with at least one radiation form independently chosen from: X-ray, UV, Gamma, electron beam radiation, and combinations thereof.

3. A method as claimed in any preceding claim, wherein step (b) comprises irradiating the catheter and medium with between 5-60 kGy of radiation.

4. A method as claimed in any preceding claim, wherein the catheter and the medium are packaged, and wherein step (b) preferably comprises irradiating the packaged catheter and medium.

5. A method as claimed in any preceding claim, wherein the 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.

6. A packaged urinary catheter comprising: a urinary 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 a medium comprising octenidine or a salt thereof.

7. A method as claimed in claim 5 or a packaged urinary catheter as claimed in claim 6, wherein the A-block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CHsCth CthCthla 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.

8. A method as claimed in any one of claims 1-5 or in claim 7 or a packaged urinary catheter as claimed in claim 6 or 7, wherein the medium comprises octenidine or the salt thereof in a total concentration of between 1.9-30000 ppm , preferably between 500-1000 ppm.

9. A method as claimed in any one of claims 1-5 or in any one of claims 7-8 or a packaged urinary catheter as claimed in any one of claims 6-8, wherein the medium comprises glycerol in a total concentration of between 0.1-8 wt.% of the medium, or between 0.5-6 wt.%, or between 1-5 wt.% of the medium.

10. A method as claimed in any one of claims 1-5 or in any one of claims 7-9 or a packaged urinary catheter as claimed in any one of claims 6-9, wherein the medium comprises ethylhexylglycerin, preferably in a total concentration of between 0.01-5 wt.%.

11. A method as claimed in any one of claims 1-5 or in any one of claims 7-10 or a packaged urinary catheter as claimed in any one of claims 6-10, wherein the medium comprises glycerol and ethylhexylglycerin.

12. A method as claimed in any one of claims 1-5 or in any one of claims 7-11 or a packaged urinary catheter as claimed in any one of claims 6-11, wherein the urinary catheter is a reusable urinary catheter, preferably an intermittent reusable urinary catheter.

13. A packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof in a total concentration of between 1.9- 30000 ppm.

14. A packaged urinary catheter comprising: a urinary catheter; and a medium comprising octenidine or a salt thereof, and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

15. A urinary 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 medium comprising octenidine or a salt thereof.

16. A urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm.

17. A urinary catheter comprising a hollow polymeric tubular body, wherein at least part of an outer surface of the tubular body of the catheter comprises a medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

18. A method of lubricating a urinary catheter, the method comprising the steps of: a. Providing a urinary 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 b. Treating at least part of an outer surface of the tubular body of the catheter with a medium comprising octenidine or a salt thereof.

19. A method of lubricating a urinary catheter, the method comprising the steps of: a. Providing a urinary 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 medium comprising octenidine or a salt thereof in a total concentration of between 1.9-30000 ppm.

20. A method of lubricating a urinary catheter, the method comprising the steps of:a. Providing a urinary 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 medium comprising octenidine or a salt thereof and at least one further species that is independently chosen from: glycerol and ethylhexylglycerin.

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