Packaged urinary catheters

Abstract

The invention provides 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 an aqueous liquid medium comprising at least one species that is independently chosen from: a citric acid or citrate buffer, polyvinylpyrrolidone (PVP), polypropylene, glycerol, lactic acid, itaconic acid, succinic acid, tartaric acid, carbonic acid, ethanoic acid, boric acid, sorbic acid, mandelic acid, malic acid, propionic acid, hippuric acid, benzoic acid, pyruvic acid, formic acid, glycolic acid, m-chlorobenzoic acid, and combinations thereof, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

Description

[0001] PACKAGED URINARY CATHETERS

[0002] Technical Field of the Invention

[0003] The present invention relates to storing urinary catheters in direct contact with liquid and gel media.

[0004] Background to the Invention

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

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

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

[0008] Lubricious surface coatings and additives for catheters have been used to help in alleviating these issues. However, catheter surface coatings and additives have the tendency to migrate out of the catheter with time and use, which causes the surface of the catheter to become less lubricious.

[0009] In use, scraping of the catheter surface may occur, further accelerating the removal of any surface coatings or additives. Furthermore, when a person uses a catheter, some of the coating may be left inside the user’ s body, which can be harmful and thus unacceptable.

[0010] A number of surface coatings and additives require that the outer surface of the catheter is first wetted (e.g. with water) before the surface coatings and additives demonstrate their lubricious properties. However, wetting a catheter is typically known to further accelerate leaching of the surface coatings and additives. As such, catheters cannot typically be stored in their ready-to-use wet state, as coatings and additives would migrate out of the catheter even when the catheter is not in use and packaged.

[0011] This has often meant that catheters must be stored in a dry state and the user must first remove them from their packaging and then wet them before they are ready for use. This makes the catheterisation process much more inconvenient for the user, which is not ideal, especially in the case of self-catheterisation where users may already have limited dexterity and may struggle with the extra requirement to wet the catheter before use.

[0012] Prior art methods for overcoming the problems have often involved the development of complex storage containers which minimise the contact between water and the catheter until the point of removal. However, these methods are far from ideal given that such storage containers are typically more difficult and expensive to make.

[0013] There is 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.

[0014] 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.

[0015] Summary of the Invention

[0016] According to a first 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 an aqueous liquid medium comprising at least one species that is independently chosen from: a citric acid or citrate buffer, polyvinylpyrrolidone (PVP), polypropylene, glycerol, lactic acid, itaconic acid, succinic acid, tartaric acid, carbonic acid, ethanoic acid, boric acid, sorbic acid, mandelic acid, malic acid, propionic acid, hippuric acid, benzoic acid, pyruvic acid, formic acid, glycolic acid, m-chlorobenzoic acid, and combinations thereof, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

[0017] Such a medium has surprisingly been found to reduce migration of the amphiphilic additive out of the urinary catheter when the catheter is stored in direct contact with the medium, allowing the catheter to be packaged wet (i.e. in direct contact with the medium) for long periods of time and simply removed and used when needed without the user needing to take any further steps. In addition, the packaging used can be simple and no special precautions must be taken to keep the catheter out of direct contact with the medium until the time of use. When packaged in direct contact with the medium, the catheter is able to retain its lubricious surface provided by the amphiphilic additive after even very long storage periods, without loss of lubricious additive into the surrounding solution.

[0018] Furthermore, the medium poses substantially no safety issues when used with catheters and does not interfere with the performance of the catheter or with the catheter properties.

[0019] To ensure thorough sterilisation of a urinary catheter, the catheter should be sterilised by exposing it to irradiation. What is also surprising is that irradiation has minimal to no negative effects on the medium of the invention. The ability of the medium to reduce additive migration from the catheter is retained and irradiation does not cause any negative interference to occur between the amphiphilic additive and the medium. In addition, the lubricating performance of the medium is substantially retained. This property of the medium of the invention is unexpected, and other media have been known to degrade when exposed to irradiation, which has been found to severely impact catheter lubricity and the surface properties of the catheters in general.

[0020] In other cases, other known 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. 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.

[0021] 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.

[0022] The catheter may be a reusable or single-use catheter. Preferably, the catheter is a singleuse catheter.

[0023] The body of the catheter comprises an amphiphilic additive. 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, 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 is reduced. 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.

[0024] 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.

[0025] 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.

[0026] 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 A-block may preferably comprise a carbon chain of between 20-52 carbon atoms.

[0027] 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.

[0028] 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.

[0029] 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. 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.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] 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.

[0034] In some embodiments, the additive comprises a layer that is on or that comprises a surface of the body, preferably the outer surface. 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.

[0035] 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.

[0036] 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.

[0037] 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.

[0038] In some embodiments, the layer comprising the additive is on or comprises at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99% of the or each surface area of the body, preferably at least 75% or at least 90% of the or each surface area or between

[0039] 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.

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] 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.

[0049] In some embodiments, the layer comprising the additive has a thickness of between SO- SOO pm.

[0050] 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.

[0051] 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-

[0052] 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.

[0053] 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.

[0054] 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.

[0055] 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.

[0056] 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.

[0057] In some embodiments, said water disintegrable or enzymatically hydrolysable material comprises a material chosen from: polyvinyl alcohol, extrudable polyvinyl alcohol, polyacrylic acids, polylactic acid, polyesters, polyglycolide, polyglycolic acid, poly lactic-co-glycolic acid, polylactide, amines, polyacrylamides, poly(? / -(2-Hydroxypropyl) methacrylamide), starch, modified starches or derivatives, amylopectin, pectin, xanthan, scleroglucan, dextrin, chitosans, chitins, agar, alginate, carrageenans, laminarin, saccharides, polysaccharides, sucrose, polyethylene oxide, polypropylene oxide, acrylics, polyacrylic acid blends, poly(methacrylic acid), polystyrene sulfonate, polyethylene sulfonate, lignin sulfonate, polymethacrylamides, copolymers of aminoalkyl-acrylamides and methacrylamides, melamine-formaldehyde copolymers, vinyl alcohol copolymers, cellulose ethers, poly-ethers, polyethylene oxide, blends of polyethylene- polypropylene glycol, carboxymethyl cellulose, guar gum, locust bean gum, hydroxypropyl cellulose, vinylpyrrolidone polymers and copolymers, polyvinyl pyrrolidone-ethylene- vinyl acetate, polyvinyl pyrrolidone-carboxymethyl cellulose, carboxymethyl cellulose shellac, copolymers of vinylpyrrolidone with vinyl acetate, hydroxyethyl cellulose, gelatin, polycaprolactone, poly(p-dioxanone), or combinations, blends or co-polymers of any of the above materials.

[0058] 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.

[0059] 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.

[0060] 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.

[0061] In some preferred embodiments, the base polymer comprises a polyolefin, especially polyethylene and / or polypropylene.

[0062] In some preferred embodiments, the base polymer comprises a thermoplastic elastomeric material. The base polymer may comprise a thermoplastic polyolefin.

[0063] 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.

[0064] 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.

[0065] The thermoplastic base polymer may comprise Estane™ 58315, which is both hydrophobic and hydrophilic.

[0066] In some embodiments, the at least one species is present in a total concentration of at least 0.02 %w / v, or at least 0.04, 0.06, 0.08, or at least 0.1 %w / v, or at least 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, or at least 0.9 %w / v.

[0067] In some embodiments, the at least one species is present in a total concentration of no greater than 50 %w / v, or no greater than 40, 30, 20, or no greater than 10 %w / v.

[0068] The at least one species may be present in a total concentration of between 0.02-50 %w / v, or between 0.05-25 %w / v, or between 0.1-10 %w / v, or between 0.1-7 %w / v, or between 0.5-7 %w / v.

[0069] In other embodiments, the at least one species is present in a total concentration of at least 5 ppm, or at least 6, 7, 8, 9, or at least 10 ppm, 11, 12, 13, 14, 15, 16, 17, 18, 19, or at least 20 ppm. The at least one species may be present in a total concentration of no greater than 1000 ppm, or no greater than 900, 800, 700, 600, 500, 400, 300, 200, 100, or no greater than 50 ppm. The at least one species may be present in a total concentration of between 5-1000 ppm, or between 5-500 ppm, or between 5-100 ppm, or between 5-50 ppm, or between 5-20 ppm. In some embodiments, the medium comprises the citric acid or citrate buffer in a total concentration of at least 0.02% w / v, or at least 0.04, 0.06, 0.08, or at least 0.1% w / v, or at least 0.15% w / v. The medium may comprise the citric acid or citrate buffer in a total concentration of no greater than 5% w / v, or no greater than 4, 3, 2, 1, 0.5, 0.4, 0.3, or no greater than 0.2% w / v. The medium may comprise the citric acid or citrate buffer in a total concentration of between 0.02-5% w / v, or between 0.06-1% w / v, or between 0.1- 0.5% w / v, or between 0.1 -0.2% w / v.

[0070] In some embodiments, the medium comprises the citric acid or citrate buffer in a total concentration of at least 5 mM, or at least 10 mM, or at least 20, 30, 40, 50, 60, 70, or at least 80 mM. The medium may comprise the citric acid or citrate buffer in a total concentration of no greater than 1000 mM, or no greater than 900, 800, 700, 600, or no greater than 500 mM, or no greater than 400, 300, 200, or no greater than 150 mM. The medium may comprise the citric acid or citrate buffer in a total concentration of between 10-500 mM, or between 50-150 mM, or between 80-120 mM. The medium may comprise the citric acid or citrate buffer in a total concentration of 100 mM.

[0071] In some embodiments, the medium comprises PVP in a total concentration of at least 0.1% w / v, or at least 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or at least 1% w / v. The medium may comprise PVP in a total concentration of no greater than 15% w / v, or no greater than 14, 13, 12, 11, or no greater than 10% w / v. The medium may comprise PVP in a total concentration of between 1-12% w / v, or between 2-10% w / v, or between 4-8% w / v.

[0072] In some embodiments, the medium comprises polypropylene in a total concentration of at least 0.1% w / v, or at least 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or at least 1% w / v. The medium may comprise polypropylene in a total concentration of no greater than 15% w / v, or no greater than 14, 13, 12, 11, or no greater than 10% w / v. The medium may comprise polypropylene in a total concentration of between 1-12% w / v, or between 2- 10% w / v, or between 4-8% w / v.

[0073] In some embodiments, the medium comprises glycerol in a total concentration of at least 0.1% w / v, or at least 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or at least 1% w / v. The medium may comprise glycerol in a total concentration of no greater than 15% w / v, or no greater than 14, 13, 12, 11, or no greater than 10 % w / v . The medium may comprise glycerol in a total concentration of between 1-12% w / v, or between 2-10% w / v, or between 4-8% w / v.

[0074] In some embodiments, the medium comprises at least one weak acid species that is independently chosen from: lactic acid, itanconic acid, succinic acid, tartaric acid, carbonic acid, ethanoic acid, boric acid, sorbic acid, mandelic acid, malic acid, propionic acid, hippuric acid, benzoic acid, pyruvic acid, formic acid, glycolic acid, m- chlorobenzoic acid, and combinations thereof.

[0075] In some preferred embodiments, the medium comprises at least one weak acid species that is independently chosen from: lactic acid, succinic acid, itaconic acid, and combinations thereof.

[0076] The medium may comprise said at least one weak acid in a total concentration of at least 5 ppm, or at least 6, 7, 8, 9, or at least 10 ppm, 11, 12, 13, 14, 15, 16, 17, 18, 19, or at least 20 ppm. The medium may comprise said at least one weak acid in a total concentration of no greater than 1000 ppm, or no greater than 900, 800, 700, 600, 500, 400, 300, 200, 100, or no greater than 50 ppm. The medium may comprise said at least one weak acid in a total concentration of between 5-1000 ppm, or between 5-500 ppm, or between 5-100 ppm, or between 5-50 ppm, or between 5-20 ppm. In some preferred embodiments, the medium comprises at least one species that is independently chosen from: a citric acid or citrate buffer, polyvinylpyrrolidone (PVP), glycerol, lactic acid, succinic acid, itaconic acid, and combinations thereof.

[0077] In some preferred embodiments, the medium further comprises polyethylene glycol (PEG) and / or sodium chloride.

[0078] In some embodiments, the medium comprises at least one species that is independently chosen from: a citric acid or citrate buffer, polyvinylpyrrolidone (PVP), glycerol, lactic acid, succinic acid, itaconic acid, and combinations thereof; and the medium further comprises PEG and / or sodium chloride.

[0079] In some preferred embodiments, the medium comprises PEG and a citric acid or citrate buffer.

[0080] In some embodiments, the medium further comprises PEG. The medium may comprise PEG in a total concentration of at least 0.5% w / v, or at least 1.0, 1.5, or at least 2.0% w / v of the medium, or at least 2.5% w / v, or at least 3.0, 3.5, or at least 4.0% w / v of the medium. The medium may comprise PEG in a total concentration of no greater than 15.0% w / v of the medium, or no greater than 14.0, 13.0, 12.0, 11.0, or no greater than 10.0% w / v of the medium, or no greater than 9.5% w / v of the medium, or no greater than 9.0, 8.5, 8.0, 7.5, or no greater than 7.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 2.0-10.0% w / v of the medium, or between 3.0- 9.0% w / v of the medium, or between 4.0-8.0, or between 5.0-7.0% w / v of the medium.

[0081] In some embodiments, the PEG has a weight average molecular weight (Mw) of at least 50 g / mol, or at least 100, 150, or at least 200 g / mol. The PEG may have an Mwof no greater than 10000 g / mol, or no greater than 9000, 8000, 7000, or no greater than 6000 g / mol. The PEG may have an Mwof between 200-6000 g / mol, or between 300-3000 g / mol, or between 350-2500 g / mol, or between 400-2000 g / mol. The PEG may have an Mwof 400 g / mol or 2000 g / mol.

[0082] The PEG may have the formula: H(OCH2CH2)nOH, wherein n is between 4-160, or between 6-160. In some embodiments, n is between 4-15, or between 7-10. In other embodiments, n is between 100-160, or between 120-150.

[0083] In some embodiments, the medium further comprises sodium chloride. The medium may comprise sodium chloride in a total concentration of at least 0.05% w / v, or at least 0.1, 0.2, 0.3, 0.4, or at least 0.5% w / v. The medium may comprise sodium chloride in a total concentration of no greater than 5.0% w / v of the medium, or no greater than 4.0, 3.0, 2.0, or no greater than 1.0% w / v of the medium. The medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7- 1.0% w / v of the medium. In some embodiments, the medium may comprise sodium chloride in a total concentration of 0.9% w / v.

[0084] In some embodiments, the medium further comprises PEG and sodium chloride. In such embodiments, the medium may comprise PEG in a total concentration of between 2.0- 10.0% w / v of the medium; and the medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7- 1.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 3.0-9.0% w / v of the medium; and the medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7-1.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 4.0-8.0% w / v of the medium; and the medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7-1.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 5.0-7.0% w / v of the medium; and the medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7-1.0% w / v of the medium.

[0085] In some embodiments, the medium further comprises at least one surfactant. In such embodiments, the pH of the medium may be at least 7.0, or at least 8.0, or at least 9.0, or at least 10.0. The medium may have a pH of between 7.0-14.0, or between 8.0-14.0, or between 9.0-14.0, or between 10.0-14.0.

[0086] In some embodiments, at least one surfactant is an amphiphilic molecule having a hydrophilic-lipophilic balance (HLB) of at least 5, or of at least 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, or of at least 18.

[0087] In some embodiments, the amphiphilic molecule has an HLB of between 7-20.

[0088] In some embodiments, the amphiphilic molecule has an HLB of between 8-20, 9-20, 10- 20, 11-20, 12-20, 13-20, 14-20, 15-20, 16-20, 17-20, 18-20, or of between 19-20.

[0089] In some embodiments, the amphiphilic molecule has an HLB of between 7-19, 7-18, 7- 17, 7-16, 7-15, 7-14, 7-13, 7-12, 7-11, 7-10, 7-9, or of between 7-8.

[0090] In further embodiments, the amphiphilic molecule has an HLB of between 8-19, 9-19, 10-19, 11-19, 12-19, 13-19, 14-19, 15-19, 16-19, 17-19, 18-19, 8-18, 9-18, 10-18, 11-18, 12-18, 13-18, 14-18, 15-18, 16-18, 17-18, 8-17, 9-17, 10-17, 11-17, 12-17, 13-17, 14-17, 15-17, 16-17, 8-16, 9-16, 10-16, 11-16, 12-16, 13-16, 14-16, 15-16, 8-15, 9-15, 10-15, 11-15, 12-15, 13-15, 14-15, 8-14, 9-14, 10-14, 11-14, 12-14, 13-14, 8-13, 9-13, 10-13, 11-13, 12-13, 8-12, 9-12, 10-12, 11-12, 8-11, 9-11, 10-11, 8-10, 9-10, or of between 8-9.

[0091] The HLB value of the amphiphilic surfactant is calculated using Griffin’s method, wherein HLB = 20 * Mh / M (Mh is the molecular mass of the hydrophilic portion of the amphiphilic surfactant, and M is the molecular mass of the whole surfactant molecule).

[0092] At least one surfactant may be ionic or non-ionic. At least one ionic surfactant may comprise a functional group that is independently chosen from: sulfate, sulfonate, phosphate, carboxylate, and ammonium. At least one ionic surfactant may be independently chosen from: sodium lauryl sulfate, sodium laureth sulfate, ammonium lauryl sulfate, ammonium laureth sulfate, sodium stearate, potassium cocoate, sodium lauryl sarcosinate, sodium myreth sulfate, sodium pareth sulfate, sodium dodecylbenzenesulfonate, cetyltrimethylammonium bromide, potassium cetyl phosphate, sodium stearoyl glutamate, glyceryl stearate citrate, and combinations thereof.

[0093] At least one non-ionic surfactant may be independently chosen from: alkyl polyglucosides, such as decyl glucoside, lauryl glucoside and octyl glucoside; fatty acid esters of polyhydroxy compounds, which may comprise fatty acid esters of glycerol (such as glycerol monostearate and glycerol monolaurate), fatty acid esters of sorbitol (such as Spans, such as sorbitan monolaurate, sorbitan monostearate and sorbitan tristearate, and Tweens, such as Tween 20, Tween 40, Tween 60, and Tween 80), and fatty acid esters of sucrose; and ethoxylates, which may comprise fatty alcohol ethoxylates (such as narrow-range ethoxylates, octaethylene glycol monododecyl ether, and pentaethylene glycol monododecyl ether), fatty acid ethoxylates, ethoxylated fatty esters and oils, ethoxylated amines and / or fatty acid amides (such as polyethoxylated tallow amine, cocamide monoethanolamine, and cocamide diethanolamine), terminally blocked ethoxylates (such as poloxamers), and alkylphenol ethoxylates (such as nonoxynols and Triton-X); and combinations thereof.

[0094] In some embodiments, the surfactant is present in a total concentration of at least 0.02 %w / v, or at least 0.04, 0.06, 0.08, or at least 0.1 %w / v, or at least 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, or at least 0.9 %w / v.

[0095] In some embodiments, the surfactant is present in a total concentration of no greater than 50 %w / v, or no greater than 40, 30, 20, or no greater than 10 %w / v.

[0096] The surfactant may be present in a total concentration of between 0.02-50 %w / v, or between 0.05-25 %w / v, or between 0.1-10 %w / v, or between 0.1-7 %w / v, or between 0.5-7 %w / v.

[0097] The aqueous liquid medium may preferably be present as an aqueous solution. The aqueous solution may comprise the species dissolved in water.

[0098] Aqueous solutions are particularly effective, as water allows for optimal catheter surface lubricity.

[0099] 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.

[0100] 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.

[0101] 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. 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.

[0102] 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 14.0, or no greater than 13.0, 12.0, 11.0, 10.0, 9.0, 8.0, 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- 8.0, or between 3.0-6.5, or between 3.0-6.0, or between 3.5-5.5, or between 4.0-5.5.

[0103] In other embodiments, the medium may have a pH of at least 7.0, or at least 8.0, or at least 9.0, or at least 10.0. The medium may have a pH of between 7.0-14.0, or between 8.0-14.0, or between 9.0-14.0, or between 10.0-14.0.

[0104] 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.

[0105] 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.

[0106] 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.

[0107] In some embodiments, the medium is in direct contact with at least 50% of the outer surface area of the body of the catheter, or at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99% of the outer surface area of the catheter body, preferably at least 75%, or at least 90% of the outer surface area, or between 75% and 100% of the outer surface area.

[0108] 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.

[0109] 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 one surface of the catheter. 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.

[0110] 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.

[0111] The layer of medium may preferably be on the surface of the catheter, preferably on the surface of the catheter body.

[0112] 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.

[0113] 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.

[0114] 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.

[0115] In some embodiments, the packaged urinary catheter has a shelf-life of at least 3 months, or at least 4, 5, or at least 6 months, or at least 7, 8, 9, 10, or at least 11 months, or at least 12 months, or at least 14, 16, 18, 20, 22, or at least 24 months, or at least 26, 28, 30, 32, 34, or at least 36 months.

[0116] 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 an aqueous liquid medium comprising polyethylene glycol (PEG) in a total concentration of between 2-10% w / v of the medium, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

[0117] Such a medium containing PEG at the stated concentration has also been found to reduce migration of the amphiphilic additive out of the urinary catheter when the catheter is stored in direct contact with the PEG medium, as described for the first aspect of the invention. Similarly, there are substantially no safety issues when the PEG medium of the invention is used with catheters and the PEG medium is substantially unaffected by irradiation sterilisation.

[0118] In addition, the PEG containing medium has been found to provide a lubricious interfacial layer on the catheter surface, which provides the catheter surface with a low coefficient of friction (CoF), which means that the catheter may simply be removed from the packaging and used and the low CoF would allow the catheter to be inserted and removed easily with far less pain experienced by the user.

[0119] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the second aspect of the invention.

[0120] The following statements apply to the second aspect of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0121] In some embodiments, the medium further comprises PEG. The medium may comprise PEG in a total concentration of at least 2.5% w / v, or at least 3.0, 3.5, or at least 4.0% w / v of the medium. The medium may comprise PEG in a total concentration of no greater than 9.5% w / v of the medium, or no greater than 9.0, 8.5, 8.0, 7.5, or no greater than

[0122] 7.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 3.0-9.0% w / v of the medium, or between 4.0-8.0, or between 5.0-7.0% w / v of the medium.

[0123] In some embodiments, the PEG has a weight average molecular weight (Mw) of at least 50 g / mol, or at least 100, 150, or at least 200 g / mol. The PEG may have an Mwof no greater than 10000 g / mol, or no greater than 9000, 8000, 7000, or no greater than 6000 g / mol. The PEG may have an Mwof between 200-6000 g / mol, or between 300-3000 g / mol, or between 350-2500 g / mol, or between 400-2000 g / mol. The PEG may have an Mwof 400 g / mol or 2000 g / mol.

[0124] The PEG may have the formula: H(OCH2CH2)nOH, wherein n is between 4-160, or between 6-160. In some embodiments, n is between 4-15, or between 7-10. In other embodiments, n is between 100-160, or between 120-150.

[0125] According to a third 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 an aqueous liquid medium comprising sodium chloride in a total concentration of between 0.1-4% w / v of the medium, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

[0126] Such a medium containing sodium chloride at the stated concentration has also been found to reduce migration of the amphiphilic additive out of the urinary catheter when the catheter is stored in direct contact with the sodium chloride medium, as described for the first aspect of the invention. Similarly, there are substantially no safety issues when the sodium chloride medium of the invention is used with catheters and the sodium chloride medium is substantially unaffected by irradiation sterilisation.

[0127] In particular, the use of sodium chloride at the stated concentrations provides excellent resistance to leaching of the amphiphilic additive from the catheter.

[0128] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the third aspect of the invention.

[0129] The following statements apply to the third aspect of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0130] The medium may comprise sodium chloride in a total concentration of at least 0.2% w / v, 0.3, 0.4, or at least 0.5% w / v. The medium may comprise sodium chloride in a total concentration of no greater than 3.0% w / v of the medium, or no greater than 2.0, or no greater than 1.0% w / v of the medium. The medium may comprise sodium chloride in a total concentration of between 0.5-1.5% w / v, or between 0.7- 1.0% w / v of the medium. In some embodiments, the medium may comprise sodium chloride in a total concentration of 0.9% w / v.

[0131] According to a fourth 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 an aqueous liquid medium comprising polyethylene glycol (PEG) and sodium chloride, wherein at least part of the catheter is in direct contact with the aqueous liquid medium. Such a medium containing PEG and sodium chloride has also been found to reduce migration of the amphiphilic additive out of the urinary catheter when the catheter is stored in direct contact with the medium, as described for the first aspect of the invention. Similarly, there are substantially no safety issues when the medium of the invention is used with catheters and the medium is substantially unaffected by irradiation sterilisation.

[0132] In particular, the use of a combination of PEG and sodium chloride provides excellent resistance to leaching of the amphiphilic additive from the catheter and the medium has been found to provide a lubricious interfacial layer on the catheter surface, which provides the catheter surface with a low coefficient of friction (CoF), which means that the catheter may simply be removed from the packaging and used and the low CoF would allow the catheter to be inserted and removed easily with far less pain experienced by the user. The CoF of the catheter packaged in direct contact with the medium containing both sodium chloride and PEG has surprisingly been found to be lower than the CoF of the catheter packaged in a medium containing either of sodium chloride or PEG alone. The CoF and lubricity properties are comparable with wetting of the catheter with water alone (i.e. the gold standard), but the catheter does not suffer from the additive leaching issues experienced when storing the catheter in water only.

[0133] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the fourth aspect of the invention.

[0134] The following statements apply to the fourth aspect of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0135] The medium may comprise PEG in a total concentration of at least 0.5% w / v, or at least

[0136] 1.0, 1.5, or at least 2.0% w / v of the medium, or at least 2.5% w / v, or at least 3.0, 3.5, or at least 4.0% w / v of the medium. The medium may comprise PEG in a total concentration of no greater than 15.0% w / v of the medium, or no greater than 14.0, 13.0, 12.0, 11.0, or no greater than 10.0% w / v of the medium, or no greater than 9.5% w / v of the medium, or no greater than 9.0, 8.5, 8.0, 7.5, or no greater than 7.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 2.0-10.0% w / v of the medium, or between 3.0-9.0% w / v of the medium, or between 4.0-8.0, or between 5.0-7.0% w / v of the medium.

[0137] In some embodiments, the PEG has a weight average molecular weight (Mw) of at least 50 g / mol, or at least 100, 150, or at least 200 g / mol. The PEG may have an Mwof no greater than 10000 g / mol, or no greater than 9000, 8000, 7000, or no greater than 6000 g / mol. The PEG may have an Mwof between 200-6000 g / mol, or between 300-3000 g / mol, or between 350-2500 g / mol, or between 400-2000 g / mol. The PEG may have an Mwof 400 g / mol or 2000 g / mol.

[0138] The PEG may have the formula: H(OCH2CH2)nOH, wherein n is between 4-160, or between 6-160. In some embodiments, n is between 4-15, or between 7-10. In other embodiments, n is between 100-160, or between 120-150.

[0139] The medium may comprise sodium chloride in a total concentration of at least 0.05% w / v, or at least 0.1, 0.2, 0.3, 0.4, or at least 0.5% w / v. The medium may comprise sodium chloride in a total concentration of no greater than 5.0% w / v of the medium, or no greater than 4.0, 3.0, 2.0, or no greater than 1.0% w / v of the medium. The medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7-1.0% w / v of the medium. In some embodiments, the medium may comprise sodium chloride in a total concentration of 0.9% w / v. In some embodiments, the medium may comprise PEG in a total concentration of between 2.0-10.0% w / v of the medium; and the medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7- 1.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 3.0-9.0% w / v of the medium; and the medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7-1.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 4.0-8.0% w / v of the medium; and the medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7-1.0% w / v of the medium. The medium may comprise PEG in a total concentration of between 5.0-7.0% w / v of the medium; and the medium may comprise sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium, or between 0.5-1.5% w / v, or between 0.7-1.0% w / v of the medium.

[0140] According to a fifth 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 an aqueous liquid medium comprising at least one surfactant, wherein the aqueous liquid medium has a pH of at least 7, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

[0141] Such a medium containing at least one surfactant and having the stated pH has also been found to reduce migration of the amphiphilic additive out of the urinary catheter when the catheter is stored in direct contact with the medium, as described for the first aspect of the invention. Similarly, there are substantially no safety issues when the medium of the invention is used with catheters and the medium is substantially unaffected by irradiation sterilisation.

[0142] In particular, the use of a surfactant at the stated pH means that the surfactant is more soluble in the aqueous medium and thus far more effective at reducing additive migration from the catheter.

[0143] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the fifth aspect of the invention.

[0144] The following statements apply to the fifth aspect of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0145] The pH of the medium may be at least 8.0, or at least 9.0, or at least 10.0. The medium may have a pH of between 7.0-14.0, or between 8.0-14.0, or between 9.0-14.0, or between 10.0-14.0.

[0146] In some embodiments, at least one surfactant is an amphiphilic molecule having a hydrophilic-lipophilic balance (HLB) of at least 5, or of at least 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, or of at least 18.

[0147] In some embodiments, the amphiphilic molecule has an HLB of between 7-20.

[0148] In some embodiments, the amphiphilic molecule has an HLB of between 8-20, 9-20, 10- 20, 11-20, 12-20, 13-20, 14-20, 15-20, 16-20, 17-20, 18-20, or of between 19-20.

[0149] In some embodiments, the amphiphilic molecule has an HLB of between 7-19, 7-18, 7- 17, 7-16, 7-15, 7-14, 7-13, 7-12, 7-11, 7-10, 7-9, or of between 7-8. In further embodiments, the amphiphilic molecule has an HLB of between 8-19, 9-19,

[0150] 10-19, 11-19, 12-19, 13-19, 14-19, 15-19, 16-19, 17-19, 18-19, 8-18, 9-18, 10-18, 11-18, 12-18, 13-18, 14-18, 15-18, 16-18, 17-18, 8-17, 9-17, 10-17, 11-17, 12-17, 13-17, 14-17, 15-17, 16-17, 8-16, 9-16, 10-16, 11-16, 12-16, 13-16, 14-16, 15-16, 8-15, 9-15, 10-15,

[0151] 11-15, 12-15, 13-15, 14-15, 8-14, 9-14, 10-14, 11-14, 12-14, 13-14, 8-13, 9-13, 10-13, 11-13, 12-13, 8-12, 9-12, 10-12, 11-12, 8-11, 9-11, 10-11, 8-10, 9-10, or of between 8-9.

[0152] The HLB value of the amphiphilic surfactant is calculated using Griffin’s method, wherein HLB = 20 * Mh / M (Mh is the molecular mass of the hydrophilic portion of the amphiphilic surfactant, and M is the molecular mass of the whole surfactant molecule).

[0153] At least one surfactant may be ionic or non-ionic. At least one ionic surfactant may comprise a functional group that is independently chosen from: sulfate, sulfonate, phosphate, carboxylate, and ammonium. At least one ionic surfactant may be independently chosen from: sodium lauryl sulfate, sodium laureth sulfate, ammonium lauryl sulfate, ammonium laureth sulfate, sodium stearate, potassium cocoate, sodium lauryl sarcosinate, sodium myreth sulfate, sodium pareth sulfate, sodium dodecylbenzenesulfonate, cetyltrimethylammonium bromide, potassium cetyl phosphate, sodium stearoyl glutamate, glyceryl stearate citrate, and combinations thereof.

[0154] At least one non-ionic surfactant may be independently chosen from: alkyl polyglucosides, such as decyl glucoside, lauryl glucoside and octyl glucoside; fatty acid esters of polyhydroxy compounds, which may comprise fatty acid esters of glycerol (such as glycerol monostearate and glycerol monolaurate), fatty acid esters of sorbitol (such as Spans, such as sorbitan monolaurate, sorbitan monostearate and sorbitan tristearate, and Tweens, such as Tween 20, Tween 40, Tween 60, and Tween 80), and fatty acid esters of sucrose; and ethoxylates, which may comprise fatty alcohol ethoxylates (such as narrow-range ethoxylates, octaethylene glycol monododecyl ether, and pentaethylene glycol monododecyl ether), fatty acid ethoxylates, ethoxylated fatty esters and oils, ethoxylated amines and / or fatty acid amides (such as polyethoxylated tallow amine, cocamide monoethanolamine, and cocamide diethanolamine), terminally blocked ethoxylates (such as poloxamers), and alkylphenol ethoxylates (such as nonoxynols and Triton-X); and combinations thereof.

[0155] In some embodiments, the surfactant is present in a total concentration of at least 0.02% w / v, or at least 0.04, 0.06, 0.08, or at least 0.1% w / v, or at least 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, or at least 0.9% w / v.

[0156] In some embodiments, the surfactant is present in a total concentration of no greater than 50% w / v, or no greater than 40, 30, 20, or no greater than 10% w / v.

[0157] The surfactant may be present in a total concentration of between 0.02-50% w / v, or between 0.05-25% w / v, or between 0.1-10% w / v, or between 0.1-7% w / v, or between 0.5-7% w / v.

[0158] According to a sixth, seventh, eighth, ninth and tenth aspect of the invention, there is provided a method of packaging a urinary catheter, said 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, the method comprising the steps of:

[0159] (a) Providing the urinary catheter; (b) Providing an aqueous liquid medium as defined in the first, second, third, fourth or fifth aspect of the invention; and

[0160] (c) Packaging the urinary catheter such that at least part of the catheter is in direct contact with the aqueous liquid medium.

[0161] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the sixth to the tenth aspects of the invention.

[0162] Step (c) may preferably comprise packaging the urinary catheter as described for the first aspect of the invention above.

[0163] According to an eleventh, twelfth, thirteenth, fourteenth and fifteenth aspect of the invention, there is provided a method of sterilising a packaged urinary catheter, the method comprising the steps of:

[0164] (a) Providing the packaged urinary catheter of the first, second, third, fourth or fifth aspect of the invention; and

[0165] (b) Irradiating the packaged urinary catheter.

[0166] Statements of invention for the other aspects of the invention above may also be applied mutatis mutandis to the eleventh to the fifteenth aspects of the invention.

[0167] The following statements apply to the eleventh to the fifteenth aspects of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0168] 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. 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.

[0169] In some embodiments, step (b) comprises irradiating the packaged catheter with at least one radiation form independently chosen from: X-ray, UV, Gamma, electron beam radiation, and combinations thereof.

[0170] In some embodiments, step (b) comprises irradiating the packaged catheter with X-ray and / or UV radiation.

[0171] Step (b) may comprise irradiating the packaged catheter 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 packaged catheter 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 packaged catheter with between 5-60 kGy of radiation, or preferably between 10-60 kGy of radiation. In some embodiments, step (b) comprises irradiating the packaged catheter with between 5-40 kGy, or between 10-30 kGy of radiation. Step (b) may comprise irradiating the packaged catheter with around 10 kGy of radiation, or around 15 kGy of radiation, or around 30 kGy of radiation. In other embodiments, step (b) may comprise irradiating the packaged catheter with between 25-60 kGy of radiation, or between 25-55 kGy, or preferably between 30-

[0172] 55 kGy of radiation. According to a sixteenth, seventeenth, eighteenth, nineteenth and twentieth aspect of the invention, there is provided a method of lubricating a urinary catheter, the method comprising the steps of:

[0173] (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

[0174] (b) Treating at least part of an outer surface of the tubular body of the catheter with an aqueous liquid medium as defined in the first, second, third, fourth or fifth aspect of the invention.

[0175] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the sixteenth to the twentieth aspects of the invention.

[0176] The following statements apply to the sixteenth to the twentieth aspects of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0177] 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.

[0178] Treatment in step (b) may involve one or more treatment methods independently chosen from: submersion, spray coating, soaking, dipping, wetting, and combinations thereof.

[0179] 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.

[0180] 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.

[0181] In some embodiments, step (b) comprises submerging the catheter in the medium.

[0182] 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.

[0183] The additional lubricating agent may be water or may comprise water. The additional lubricating agent may be an aqueous solution.

[0184] 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.

[0185] In preferred embodiments, a further lubrication step is not performed. In such embodiments, the catheter may be used directly after step (b). According to a twenty-first, twenty-second, twenty-third, twenty-fourth and twenty-fifth aspect of the invention, there is provided a method of extending the shelf-life of a urinary catheter, said 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, the method comprising the steps of:

[0186] (a) Providing the urinary catheter;

[0187] (b) Providing an aqueous liquid medium as defined in the first, second, third, fourth or fifth aspect of the invention;

[0188] (c) Packaging the urinary catheter such that at least part of the catheter is in direct contact with the aqueous liquid medium; and

[0189] (d) Leaving the urinary catheter packaged such that at least part of the catheter is in direct contact with the aqueous liquid medium throughout the shelf-life of the catheter.

[0190] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the twenty-first to the twenty-fifth aspects of the invention.

[0191] The following statements apply to the twenty-first to the twenty-fifth aspects of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0192] Step (c) may preferably comprise packaging the urinary catheter as described for the first aspect of the invention above. In some embodiments, the packaged urinary catheter has a shelf-life of at least 6 months, or at least 7, 8, 9, 10, or at least 11 months, or at least 12 months, or at least 14, 16, 18, 20, 22, or at least 24 months, or at least 26, 28, 30, 32, 34, or at least 36 months.

[0193] According to a twenty-sixth, twenty-seventh, twenty-eighth, twenty-ninth and thirtieth aspect of the invention, there is provided the use of an aqueous liquid medium as defined in the first, second, third, fourth or fifth aspect of the invention to reduce migration of an amphiphilic lubricious additive from a surface of a urinary catheter, the urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and the amphiphilic lubricious additive, wherein the additive comprises an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0194] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the twenty- sixth to the thirtieth aspects of the invention.

[0195] The following statements apply to the twenty-sixth to the thirtieth aspects of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0196] The aqueous liquid medium may be applied to the surface of the catheter to reduce migration of the lubricious additive from the surface.

[0197] The catheter may preferably be packaged as described in statements of invention for the first aspect of the invention above to bring the catheter surface into direct contact with the aqueous liquid medium and to reduce migration of the lubricious additive from the surface.

[0198] The catheter may be submerged in the aqueous liquid medium to reduce migration of the additive from the surface of the catheter. The surface of the catheter may comprise an outer surface or an inner surface of the catheter, and preferably an outer surface.

[0199] The aqueous liquid medium may be used to reduce migration of the lubricious additive from the surface of the catheter during transportation of the catheter.

[0200] The aqueous liquid medium may be used to reduce migration of the lubricious additive from the surface of the catheter during use of the catheter. The aqueous medium may be used to both reduce additive migration out of the catheter and encourage hydrophilic portions of the amphiphilic additive molecules to seek towards the outer surface of the catheter due to their affinity with the hydrophilic aqueous medium. Increased numbers of hydrophilic portions of additive molecules at or on the outer surface increase the lubricity of the surface, which makes the catheter easier and less painful to insert and remove.

[0201] According to a thirty-first 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 an aqueous gel medium consisting of water and a gelling agent, wherein at least part of the catheter is in direct contact with the aqueous gel medium.

[0202] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the thirty-first aspect of the invention.

[0203] The following statements apply to the thirty-first aspect of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention. 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.

[0204] 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.

[0205] 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.

[0206] The gelling agent may comprise a protein-based gelling agent that is independently chosen from: gelatin, collagen, and combinations thereof.

[0207] 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.

[0208] 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.

[0209] In some embodiments, the gelling agent may comprise glycerin or a derivative thereof.

[0210] 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.

[0211] 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.%.

[0212] In some preferred embodiments, the gel comprises water in a total amount of between 20- 98 wt.%, or between 50-98 wt.%.

[0213] 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.%.

[0214] 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.%.

[0215] 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.

[0216] In some embodiments, the gel has a viscosity of between 1000-1000000 cP, or between

[0217] 1500-900000, or between 300000-850000, or between 5000-800000, or between 6000- 700000, or between 7000-600000, or between 8000-500000, or between 9000-400000 cP. In some embodiments, the gel has a viscosity of between 100000-500000 cP, or between 150000-450000, or between 200000-400000 cP. In some embodiments, the gel has a viscosity of between 8000-32000 cP, or between 9000-31000, or between 10000- 30000, or between 11000-29000, or between 12000-28000, or between 13000-27000 cP.

[0218] 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.

[0219] 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.

[0220] In some embodiments, the urinary catheter and gel are packaged as described for the first aspect of the invention above. Statements of invention for the first aspect of the invention above may also be applied mutatis mutandis to gel media.

[0221] According to a thirty-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 non-aqueous gel medium, wherein at least part of the catheter is in direct contact with the non-aqueous gel medium.

[0222] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the thirty-second aspect of the invention. The following statements apply to the thirty-second aspect of the invention. Said statements may also be applied mutatis mutandis to the other aspects of the invention.

[0223] 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.

[0224] 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.

[0225] 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.

[0226] 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.

[0227] 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.

[0228] The non-aqueous gel may comprise a silicone gel that is independently chosen from: a dimethicone gel, a silicone-elastomer gel, and combinations thereof.

[0229] 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.

[0230] 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.

[0231] 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.%.

[0232] 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.%.

[0233] According to a thirty-third and thirty-fourth aspect of the invention, there is provided a method of packaging a urinary catheter, said 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, the method comprising the steps of:

[0234] (a) Providing the urinary catheter;

[0235] (b) Providing a gel medium as defined in the thirty-first or thirty-second aspect of the invention; and

[0236] (c) Packaging the urinary catheter such that at least part of the catheter is in direct contact with the gel medium. According to a thirty-fifth and thirty-sixth aspect of the invention, there is provided a method of sterilising a packaged urinary catheter, the method comprising the steps of:

[0237] (a) Providing the packaged urinary catheter of the thirty-first or thirty-second aspect of the invention; and

[0238] (b) Irradiating the packaged urinary catheter.

[0239] According to a thirty-seventh and thirty-eighth aspect of the invention, 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; and

[0241] (b) Treating at least part of an outer surface of the tubular body of the catheter with a gel medium as defined in the thirty-first or thirty-second aspect of the invention.

[0242] According to a thirty-ninth and fortieth aspect of the invention, there is provided a method of extending the shelf life of a urinary catheter, said 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, the method comprising the steps of:

[0243] (a) Providing the urinary catheter;

[0244] (b) Providing a gel medium as defined in the thirty-first or thirty-second aspect of the invention; (c) Packaging the urinary catheter such that at least part of the catheter is in direct contact with the gel medium; and

[0245] (d) Leaving the urinary catheter packaged such that at least part of the catheter is in direct contact with the gel medium throughout the shelf life of the catheter.

[0246] According to a forty-first and forty-second aspect of the invention, there is provided the use of a gel medium as defined in the thirty-first or thirty-second aspect of the invention to reduce migration of an amphiphilic lubricious additive from a surface of a urinary catheter, the urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and the amphiphilic lubricious additive, wherein the additive comprises an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0247] Statements of invention for the other aspects of the invention may also be applied mutatis mutandis to the thirty-third to the forty-second aspects of the invention.

[0248] Detailed Description of the Invention

[0249] 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:

[0250] Figure 1 is a bar graph that shows measured pH of different solutions both before and after storage of a catheter therein for 48 h at 50 °C, as per Example 2 below.

[0251] Figure 2 is a boxplot showing Coefficient of Friction (CoF) for catheters stored in different solutions for 24 h at 50 °C, according to Example 5 below. A reference measurement is also provided in which the CoF is shown of a catheter which was stored dry and wet just before use (“Just wet”).

[0252] Figure 3 is a boxplot showing Coefficient of Friction (CoF) for catheters stored in different solutions for 24 h at 50 °C, according to Example 6 below. A reference measurement is also provided in which the CoF is shown of a catheter which was stored dry and wet just before use (“Just wet”).

[0253] Figure 4 is a graph showing Coefficient of Friction (CoF) and Contact Angle for catheters stored in different solutions for 48 h at 50 °C, according to Example 7 below. A reference measurement is also provided for a catheter which was stored dry and wet just before use (“Just wet”).

[0254] Solution packaged intermittent catheters of the invention

[0255] The following packaged intermittent urinary catheters of the invention are provided. tive) - catheter in direct contact with at least one chosen from: a citric acid , lactic acid, itaconic acid, succinic acid, tartaric acid, carbonic acid, ethanoic acid, boric acid, sorbic acid, mandelic acid, malic acid, ic acid, hippuric acid, benzoic acid, ic acid, formic acid, ic acid, m-chlorobenzoic acid, and combinations thereof

[0256] 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:

[0257] CH3CH2(CH2CH2)IO(OCH2CH2)5OH. The catheter is contained in a container. The catheter is fully submerged in an aqueous solution medium containing at least one species independently chosen from: a citric acid or citrate buffer, polyvinylpyrrolidone (PVP), polypropylene, glycerol, lactic acid, itaconic acid, succinic acid, tartaric acid, carbonic acid, ethanoic acid, boric acid, sorbic acid, mandelic acid, malic acid, propionic acid, hippuric acid, benzoic acid, pyruvic acid, formic acid, glycolic acid, m- chlorobenzoic acid, and combinations thereof.

[0258] Such a medium surprisingly reduces migration of the amphiphilic additive out of the catheter, even when the catheter is stored wet (fully submerged) in the medium for long periods of time. The catheter can thus retain its lubricious surface provided by the amphiphilic additive after even very long storage periods, without loss of the lubricious additive into the surrounding solution. The catheter therefore has a long shelf-life of around 36 months.

[0259] The catheter can simply be removed from the packaging and used directly in the conventional manner, without the need for the user to take any additional steps. Storage in the aqueous medium also lubricates the catheter so that no further lubrication steps are required.

[0260] Prior to removal of the catheter, the entire packaged catheter is sterilised by X-ray irradiation (including the medium). Surprisingly, even after sterilisation by irradiation, the aqueous medium retains excellent lubricity, and irradiation has minimal to no negative effects on the medium. The ability of the medium to reduce additive migration from the catheter is retained and irradiation does not cause any negative interference to occur between the amphiphilic additive and the medium. In addition, the lubricating performance of the medium is substantially retained. This property of the medium of the invention is unexpected, and other media have been known to degrade when exposed to irradiation, which has been found to severely impact catheter lubricity and the surface properties of the catheters in general.

[0261] Packaged Catheter 2 (inventive) - catheter packaged in direct contact with aqueous solution medium comprising polyethylene glycol in a total concentration of between 2- 10% w / v

[0262] 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: CHaC^ClfcCl HOCl Clfc^OH.

[0263] The catheter is contained in a sealed container and is submerged entirely in an aqueous solution medium. The aqueous medium contains polyethylene glycol in a concentration of 2-10% w / v, preferably between 5-7% w / v.

[0264] 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.

[0265] 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 ability to reduce additive migration, excellent lubricity and is not affected negatively by the irradiation. On removal from the container, the outer surface of the catheter body is provided with a lubricious interfacial layer of the PEG containing medium. The interfacial layer provides the catheter with a low coefficient of friction (CoF), which means that the catheter can be inserted and removed easily with far less pain experienced by the user.

[0266] The aqueous medium also shows excellent compatibility with the catheter amphiphilic additive, as described for Packaged Catheter 1 above.

[0267] Packaged Catheter 3 (inventive) - catheter packaged in direct contact with aqueous solution medium comprising sodium chloride in a total concentration of between 0.1-4% w / v

[0268] A packaged catheter is provided as for Packaged Catheter 2 of the invention above, with the sole difference being that a different aqueous solution medium is used.

[0269] The aqueous medium contains sodium chloride in a concentration of 0.1-4% w / v, preferably between 0.7- 1.0% w / v.

[0270] Similar results are obtained using Packaged Catheter 3 to results obtained with Packaged Catheters 1 and 2. The medium has been found to reduce migration of the amphiphilic additive out of the urinary catheter when the catheter is stored in direct contact with the sodium chloride medium. Similarly, there are substantially no safety issues when the sodium chloride medium of the invention is used with the catheter and the sodium chloride medium is substantially unaffected by irradiation sterilisation.

[0271] In particular, the use of sodium chloride at the stated concentrations provides excellent resistance to leaching of the amphiphilic additive from the catheter. Packaged Catheter 4 (inventive) - catheter packaged in direct contact with aqueous solution medium comprising polyethylene glycol and sodium chloride

[0272] A packaged catheter is provided as for Packaged Catheter 2 of the invention above, with the sole difference being that a different aqueous solution medium is used.

[0273] The aqueous medium contains polyethylene glycol in a concentration of 2-10% w / v, preferably between 5-7% w / v; and also contains sodium chloride in a concentration of 0.1-4% w / v, preferably between 0.7- 1.0% w / v.

[0274] Similar results are obtained using Packaged Catheter 4 to results obtained with Packaged Catheters 1-3.

[0275] The use of a combination of PEG and sodium chloride provides excellent resistance to leaching of the amphiphilic additive from the catheter and the medium has been found to provide a lubricious interfacial layer on the catheter surface, which provides the catheter surface with a low coefficient of friction (CoF), which means that the catheter may simply be removed from the packaging and used and the low CoF allows the catheter to be inserted and removed easily with far less pain experienced by the user. The CoF of the catheter packaged in direct contact with the medium containing both sodium chloride and PEG has surprisingly been found to be lower than the CoF of the catheter packaged in a medium containing either of sodium chloride or PEG alone. The CoF and lubricity properties are comparable with wetting of the catheter with water alone (i.e. the gold standard), but the catheter does not suffer from the additive leaching issues often experienced when storing the catheter in water only.

[0276] Packaged Catheter 5 (inventive) - catheter packaged in direct contact with aqueous solution medium comprising a surfactant and having a pH of above 7 A packaged catheter is provided as for Packaged Catheter 2 of the invention above, with the sole difference being that a different aqueous solution medium is used.

[0277] The aqueous medium contains a sodium lauryl sulfate ionic surfactant in a concentration of 0.5-7% w / v. The aqueous medium has a pH of 10.

[0278] Similar results are obtained using Packaged Catheter 5 to results obtained with Packaged Catheters 1-4.

[0279] Furthermore, the use of the surfactant at the elevated pH of the medium allows it to be much more soluble in the aqueous medium and thus far more effective at reducing additive migration from the catheter.

[0280] Control Packaged Catheter 1 (not of the invention)

[0281] A packaged catheter is provided as for Packaged Catheter 1 of the invention above, with the sole difference being that the aqueous solution medium is replaced with water alone.

[0282] Large amounts of additive leach out from the catheter when stored submerged in the water. When the catheter is removed from the packaging, its outer surface is rough and has a high CoF given that much of the amphiphilic additive has migrated out of the catheter. This makes the catheter difficult and painful to insert and remove in use.

[0283] There is also a risk of further additive leaching from the catheter when in the body of a user, increasing the safety risk.

[0284] Example 1 - Laboratory testing for visual evaluation of amphiphilic additive leaching in solution

[0285] To visually evaluate the extent of amphiphilic additive leaching from catheters when stored in different solutions, the following laboratory test was performed. Intermittent catheter samples 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.

[0286] The catheter samples were placed into glass vials and were stored fully submerged in the following solutions at 50 °C (accelerated aging temperatures). Visible evaluations of the amount of additive which had leached from the catheter into solution were performed at the following time points: 2 h, 4 h, 6 h, 24 h and 48 h.

[0287] The solutions tested were aqueous solutions containing the following species dissolved in water:

[0288] Solution 1 (inventive): citrate buffer (sodium citrate + citric acid) (0.01 M (yields pH 4.0))

[0289] Solution 2 (inventive): lactic acid (appropriate for the solution to reach pH 4.03)

[0290] Solution 3 (inventive): succinic acid (appropriate for the solution to reach pH 4.03)

[0291] Solution 4 (inventive): itaconic acid (appropriate for the solution to reach pH 4.02)

[0292] Solution 5 (inventive): glycerol (6.0% w / v)

[0293] Solution 6 (inventive): polyvinylpyrrolidone (PVP) (6.0% w / v) Solution 7 (inventive): sodium chloride (0.9% w / v)

[0294] Solution 8 (inventive): polyethylene glycol (PEG) 400 (6.0% v / v = approx. 6.8% w / v)

[0295] Solution 9 (inventive): polyethylene glycol (PEG) 2000 (6.0% w / v)

[0296] Control solution 1 : water

[0297] Results

[0298] After only 2 h at 50 °C, the catheter sample stored in water alone showed noticeable leaching of the amphiphilic additive into the supernatant. The majority of the other solutions appeared clear, with only traces of additive visible in the glycerol, PEG 400 and PEG 2000 solutions.

[0299] After 4 h, the additive in the water only test had leached out to an even greater extent. Minute traces of amphiphilic additive were visible in the succinic, itaconic and lactic acid solutions. However, the remaining solutions still appeared clear with minimal to no additive leaching.

[0300] The same observation was noted for the samples stored at 50 °C for 6 h, 24 h and 48 h.

[0301] Surprisingly, the citrate buffer solution, the PVP solution and the sodium chloride solution contained substantially no traces of leached additive even after the full 48 h, demonstrating the excellent ability of the solutions of the invention to minimise additive leaching from the catheter.

[0302] After 48 h, catheter samples stored in the citrate buffer, PVP and sodium chloride solutions were found to have small “spots” homogenously distributed on the catheter surface. The catheter samples stored in the PEG solutions showed a “soapier” surface appearance. The other samples, stored in glycerol, itaconic acid, succinic acid and lactic acid, appeared smooth.

[0303] The above visual appearances were not found to impact the catheter in a negative manner and the catheter properties remained unaffected, including the catheter surface properties. Overall, all the inventive solutions displayed delayed amphiphilic additive leaching compared to catheter samples stored directly in water alone, indicating an active effect of all tested solutions to reduced additive migration out of the catheter.

[0304] Example 2 - Analysis of pH of tested solutions

[0305] In order to understand how the storing of the catheters in the solutions tested in Example 1 affects the pH of the solutions, pH was measured both in pristine solutions that were never contacted with a catheter and the same solution after storing the catheter therein for 48 h at 50 °C. The results are summarised in Table 1 below and plotted in a bar chart in Figure 1.

[0306] Table 1

[0307] As expected, the citrate buffer was able to maintain pH 4.0 during the storing of the catheter, while the other acidic solutions (itaconic, succinic and lactic) saw a raise in pH. The increase of pH after storage was also noted in the H2O and glycerol solutions. This data suggests the release of amphiphilic additive brings an increase in the pH of the storing solutions, and this is supported by the fact that the 3 solutions that maintained a constant pH, citrate buffer, NaCl and PVP, did not see a significant release of amphiphilic additive from the catheter.

[0308] The two PEG solutions showed a different trend, with a significantly lower pH after storing of the catheter.

[0309] Example 3 - Extended monitoring of samples stored at 50 °C

[0310] The catheter samples stored in the solutions of Example 1 were left stored in the solutions for longer time periods at 50 °C to assess the leaching of the amphiphilic additive from the catheters after an extended time period at an accelerated aging temperature. The samples were analysed at the following storage time periods: 1 week, 3 weeks, 4 weeks and 5 weeks. After 1 week, only traces of amphiphilic additive were visible in the PVP solution, and no traces of amphiphilic additive were visible in the citrate buffer and NaCl solutions. Surprisingly, even under such harsh temperature conditions, traces of amphiphilic additive were only visible in the citrate buffer solution after 3 weeks of storage, and for the NaCl it took as long as 5 weeks for the first traces of amphiphilic additive to be visible. This demonstrates the excellent ability of the solutions to minimise additive migration out of the catheter.

[0311] Example 4 - Accelerated aging conditions and correspondent storing at room temperature

[0312] The accelerated aging conditions used in the above tests (high temperature and humidity) also allow data to be acquired that provides an estimate of the shelf life of a catheter when stored wet in ambient conditions in different solutions. The Arrhenius equation was applied to calculate the ageing factor which determines the ratio between the incubation time at increased temperature and shelf time in ambient conditions:

[0313] Ap0>2[(TAA-TRT) / 10]

[0314] Where: AFQ = original ageing factor

[0315] 2 = rate of ageing at a temperature elevated 10 °C above shelf life conditions as twice as fast as ageing at shelf life conditions (derived from Arrhenius’ description of the rates of chemical reactions)

[0316] TAA = absolute elevated temperature at which devices are aged

[0317] TRT = room temperature of device storage conditions A TAA of 50 °C and a TRT of 25 °C yielded a AFQ of 5.66, which allowed the corresponding storage times at 25 °C to be calculated from the incubation times at 50 °C used in Examples 1 and 3 above. The results are displayed in Table 2 below.

[0318] Table 2

[0319] The leaching of amphiphilic additives from catheters stored in water does not correlate with the Arrhenius equation for accelerated ageing, as higher amphiphilic additive leaching and catheter CoFs were observed when catheters were stored at 50 °C compared to catheters stored for the corresponding time at 25 °C. As such, the solutions of the invention are expected to have shelf-lives which are much longer than the corresponding storage times tabulated in Table 2 above, when stored under ambient conditions, which is highly advantageous given that catheters stored wet in water alone leach the amphiphilic additive far quicker. This means that storing catheters wet in the solutions of the invention is a viable approach providing catheter shelf-lives which are at least on par with known products that employ dry catheter storage.

[0320] Example 5 - Coefficient of Friction testing of catheters stored wet in aqueous solutions The amphiphilic additive grants hydrophilicity to the catheter outer surface and water binding to the surface grants a low friction surface to the catheters. It was therefore important to assess if the leaching of amphiphilic additive observed in tests performed in Examples 1 and 3 above led to an increase in the Coefficient of Friction (CoF) of the catheter outer surface.

[0321] CoF measurements were obtained for the solutions tested in Example 1 after 24 h of wet storage at 50 °C.

[0322] A further reference measurement was taken of the CoF of catheters which were stored dry and wet just before use as per manufacturer’s instructions (“Just wet”) - this represents the gold standard CoF.

[0323] The results are tabulated in Table 3 below and shown in the boxplot in Figure 2.

[0324] Table 3

[0325] An expected increase in CoF was observed for all catheters that were stored wet in solutions compared to the catheter stored dry and wet just before use (Just wet). However, all CoF values were well within the recommended CoF range (<0.17), demonstrating that the catheters are safe to use.

[0326] Catheters stored in PEG solutions advantageously even demonstrated a reduction in CoF compared to the water Control.

[0327] Example 6 - Catheters stored in a PEG 2000 + NaCl solution

[0328] The tests performed in Example 1 above were repeated using the following new aqueous solution.

[0329] Solution 10 (inventive): polyethylene glycol (PEG) 2000 (6.0% w / v) and sodium chloride (0.9% w / v)

[0330] Surprisingly, no visible leaching of the amphiphilic additive was observed after 48 h of wet storage in Solution 10. The pH of the solution was measured to be 5.73 before contact with the catheter and 5.76 after catheter storage for 8 days.

[0331] Furthermore, after storage of the catheter in Solution 10, the catheter surface did not have a “spotty” appearance as was the case for the catheter stored in the NaCl Solution 7. Instead, the catheter stored in Solution 10 appeared smooth and transparent with no visible “spots”.

[0332] The CoF of catheters stored in Solution 10 were measured as per Example 5 above. Surprisingly, the CoF was lower than the CoF of catheters stored in both Solutions 7 and 9 - i.e. solutions containing just NaCl and just PEG 2000. CoF values were in fact similar to the gold standard “Just wet” CoF values and were significantly lower than the CoF values of catheters stored in any of the other solutions. The CoF measurements are displayed in Figure 3.

[0333] Example 7 - Contact angle measurements of catheter samples stored in aqueous solution

[0334] In order to assess the hydrophilicity of the catheter samples after storage at 50 °C for 48 h, contact angle measurements were performed in captive bubble mode at CTEC Boston. The experimental set-up involved submerging the sample in water and measuring the angle created between its surface and an air bubble released from a needle placed underneath. A hydrophobic sample would allow the water at its interface to be displaced, therefore the air bubble would spread on its surface yielding a high contact angle. A low contact angle between the sample and the air bubble is measured on a hydrophilic surface, that due to its hydrophilicity does not allow the water at its interface to be displaced, therefore forcing the air bubble to maintain a round shape. The contact angle measurement results are tabulated in Table 4 below and shown along with the corresponding CoF values in Figure 4.

[0335] Table 4

[0336] The contact angle results showed a degree of correlation with the CoF results, as shown in the graph shown in Figure 4. The samples stored in PEG 2000 + NaCl displayed both the lowest CoF and highest hydrophilicity amongst the catheters stored wet in solution. The samples stored in PEG 2000 alone also displayed high hydrophilicity and a low CoF, while lower hydrophilicity and higher CoF were measured for the samples stored in PVP and the weak acids, despite the observed low leaching of the amphiphilic additive. The samples stored in glycerol in NaCl show a lower correlation between surface hydrophilicity and CoF, both displaying higher surface hydrophilicity than their CoF would suggest.

[0337] Gel packaged intermittent catheters of the invention

[0338] The following packaged intermittent urinary catheters of the invention are provided.

[0339] Packaged Catheter 6 (inventive) - catheter packaged in direct contact with aqueous gel medium consisting only of water and a gelling agent 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)50H. The catheter is contained in a container. The catheter is fully submerged in an aqueous gel medium that consists only of 88 wt.% water and 12 wt.% of agar-agar gelling agent.

[0340] Surprisingly, such a simple gel medium that consists only of water and a gelling agent is able to reduce migration of the amphiphilic additive from the catheter, even when the catheter is stored wet (fully submerged) in the gel for long periods of time. The catheter can thus retain its lubricious surface provided by the amphiphilic additive after even very long storage periods, without loss of the lubricious additive into the surrounding gel medium. The catheter therefore has a long shelf-life of around 36 months.

[0341] The catheter can simply be removed from the packaging and used directly in the conventional manner, without the need for the user to take any additional steps. Storage in the aqueous gel medium also lubricates the catheter so that no further lubrication steps are required.

[0342] Prior to removal of the catheter, the entire packaged catheter is sterilised by X-ray irradiation (including the medium). Surprisingly, even after sterilisation by irradiation, the aqueous gel medium retains excellent lubricity, and irradiation has minimal to no negative effects on the medium. The ability of the medium to reduce additive migration from the catheter is retained and irradiation does not cause any negative interference to occur between the amphiphilic additive and the medium. In addition, the lubricating performance of the medium is substantially retained. This property of the medium of the invention is unexpected, and other media have been known to degrade when exposed to irradiation, which has been found to severely impact catheter lubricity and the surface properties of the catheters in general. Packaged Catheter 6 (inventive) - catheter packaged in direct contact with a non-aqueous gel medium

[0343] This packaged catheter of the invention is the same as Packaged Catheter 5, with the sole difference being that the aqueous gel medium is replaced for a non-aqueous silicone gel medium.

[0344] The silicone gel shows excellent compatibility with the catheter amphiphilic additive. Migration of the additive out of the catheter is also minimised when the catheter is in contact with the gel.

[0345] The catheter can simply be removed from the container and used in the conventional manner, without any requirement to rinse the catheter after removal from the gel and before use.

[0346] As for Packaged Catheter 5 above, even after sterilisation by irradiation, the gel medium retains excellent ability to reduce additive migration, excellent lubricity and is not affected negatively by the irradiation.

[0347] Example 8 - Coefficient of friction testing of silicone-based gel

[0348] In order to assess the effect of a silicone-based non-aqueous gel on the lubricity of a catheter having an amphiphilic additive, the following CoF testing was performed.

[0349] A single-use intermittent catheter was provided comprising a hollow polymeric tubular body comprising a base polymer formed from a thermoplastic elastomeric material and further comprising an A-B block copolymer amphiphilic additive having a hydrophobic hydrocarbon A-block and a hydrophilic B-block. The catheter was stored in a silicone-based non-aqueous gel for one hour prior to testing. The catheter was then removed from the gel and the gel cleaned out. 2 mL of the gel was then added to the surface of the catheter body before testing.

[0350] The catheter was then tested to determine the CoF. Mean CoF is shown in Table 5 below. A reference measurement is also displayed in Table 5 which is the CoF of catheters which were stored dry and wet just before use as per manufacturer’s instructions (“Just wet”) - i.e. the gold standard CoF.

[0351] Table 5 Surprisingly, CoF values for the silicone gel-coated catheter were in line with CoF values for the gold-standard “Just wet” catheter, despite the catheter being stored in direct contact with the silicone gel and despite the presence of a viscous gel on the catheter surface.

[0352] It is also surprising that a hydrophobic silicone-based gel is able to successfully lubricate a catheter having an amphiphilic additive, which would generate a hydrophilic catheter outer surface. 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 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 an aqueous liquid medium comprising at least one species that is independently chosen from: a citric acid or citrate buffer, polyvinylpyrrolidone (PVP), polypropylene, glycerol, lactic acid, itaconic acid, succinic acid, tartaric acid, carbonic acid, ethanoic acid, boric acid, sorbic acid, mandelic acid, malic acid, propionic acid, hippuric acid, benzoic acid, pyruvic acid, formic acid, glycolic acid, m-chlorobenzoic acid, and combinations thereof, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

2. A packaged urinary catheter as claimed in claim 1, wherein the medium comprises at least one species that is independently chosen from: a citric acid or citrate buffer, polyvinylpyrrolidone (PVP), glycerol, lactic acid, succinic acid, itaconic acid, and combinations thereof.

3. A packaged urinary catheter as claimed in any preceding claim, wherein the at least one species is present in a total concentration of between 0.1-10% w / v of the medium.

4. A packaged urinary catheter as claimed in any preceding claim, wherein the medium further comprises polyethylene glycol (PEG) and / or sodium chloride, preferably wherein the medium comprises polyethylene glycol (PEG) and a'll citric acid or citrate buffer, preferably wherein the medium comprises polyethylene glycol (PEG) in a total concentration of between 2.0-10.0% w / v of the medium, and preferably wherein the medium comprises sodium chloride in a total concentration of between 0.1-4.0% w / v of the medium.

5. 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 an aqueous liquid medium comprising polyethylene glycol (PEG) in a total concentration of between 2-10% w / v of the medium, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

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 an aqueous liquid medium comprising sodium chloride in a total concentration of between 0.1-4% w / v of the medium, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

7. 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 an aqueous liquid medium comprising polyethylene glycol (PEG) andsodium chloride, wherein at least part of the catheter is in direct contact with the aqueous liquid medium, wherein sodium chloride is preferably present in a total concentration of between 0.1 -4.0% w / v of the medium and polyethylene glycol (PEG) is preferably present in a total concentration of between 2.0- 10.0% w / v of the medium.

8. A packaged urinary catheter as claimed in claim 4 or 5 or in claim 7, wherein the medium comprises polyethylene glycol (PEG) in a total concentration of between 4-8% w / v, or between 5-7% w / v of the medium, wherein the polyethylene glycol (PEG) preferably has a weight average molecular weight (Mw) of between 200-6000 g / mol, or between 400-2000 g / mol, and wherein the polyethylene glycol (PEG) preferably has the formula: H(OCH2CH2)nOH, wherein n is between 4-160, or between 6-160.

9. A packaged urinary catheter as claimed in claim 4, in claim 6 or 7 or in claim 8 when dependent on claim 4 or 7, wherein the medium comprises sodium chloride in a total concentration of between 0.5- 1.5% w / v of the medium, or between 0.7- 1.0% w / v of the medium.

10. A packaged urinary catheter as claimed in any preceding claim, wherein the medium has a pH of between 3.0-8.0, or between 3.0-6.0.

11. 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 an aqueous liquid medium comprising at least one surfactant, wherein theaqueous liquid medium has a pH of at least 7, wherein at least part of the catheter is in direct contact with the aqueous liquid medium.

12. 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 an aqueous gel medium consisting of water and a gelling agent, wherein at least part of the catheter is in direct contact with the aqueous gel medium.

13. 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 non-aqueous gel medium, wherein at least part of the catheter is in direct contact with the non-aqueous gel medium.

14. A packaged urinary catheter as claimed in any preceding claim, wherein the medium is in direct contact with at least part of an outer surface of the tubular body of the catheter, preferably with at least 50% of the outer surface area of the body of the catheter, and wherein the catheter is preferably submerged in the medium.

15. A packaged urinary catheter as claimed in any preceding claim, wherein the A block of the A-B block copolymer additive comprises a hydrocarbon chain block of the formula CH3CH2(CH2CH2)awhere “a” is 5-25 and preferably 9-25, and wherein the B -block of the A-B block copolymer additive ispreferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers selected from the group comprising: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

16. A method of packaging a urinary catheter, said 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, the method comprising the steps of: a. Providing the urinary catheter; b. Providing a medium according to any preceding claim; and c. Packaging the urinary catheter such that at least part of the catheter is in direct contact with the medium.

17. A method of sterilising a packaged urinary catheter, the method comprising the steps of: a. Providing a packaged urinary catheter as claimed in any one of claims 1 to 15; and b. Irradiating the packaged urinary catheter.

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 lubriciousadditive, 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 according to any one of claims 1 to 15.

19. A method of extending the shelf-life of a urinary catheter, said 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, the method comprising the steps of: a. Providing the urinary catheter; b. Providing a medium according to any one of claims 1 to 15; c. Packaging the urinary catheter such that at least part of the catheter is in direct contact with the medium; and d. Leaving the urinary catheter packaged such that at least part of the catheter is in direct contact with the medium throughout the shelf-life of the catheter.

20. Use of a medium according to any one of claims 1 to 15 to reduce migration of an amphiphilic lubricious additive from a surface of a urinary catheter, the urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and the amphiphilic lubricious additive, wherein the additive comprises an A-B block copolymer comprising a hydrophobic hydrocarbon A- block and a hydrophilic B-block.

Images