Intermittent catheters

Abstract

The invention provides an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

Description

[0001] INTERMITTENT CATHETERS

[0002] Technical Field of the Invention

[0003] The present invention relates to antimicrobial peptides for intermittent catheters.

[0004] Background to the Invention

[0005] Intermittent urinary catheterisation is a process involving insertion of a urinary catheter through an individual’s urethra and into their bladder, where it is kept to empty the bladder of urine for only the time period that is 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] Intermittent 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] Intermittent 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 intermittent catheters to be safe to use with features for minimising risk of infection. It is easy for intermittent catheters to become contaminated and for bacteria to be introduced into the urethra and along the urinary tract. As a result, urinary tract infections (UTI) are common in individuals who practice self-catheterisation. On average, intermittent catheter users experience 2.7 UTIs annually and UTIs are a daily concern for 41% of users. These rates of infection are significantly greater when compared to the general population. Risk factors for intermittent catheter users are mitigated for populations with normal functioning bladders through the absence of the requirement to insert a foreign body to drain the bladder and flushing of the walls of the urethra during urination.

[0008] There is a need for means to address the increased risk of UTIs for intermittent catheter users, particularly for non-medically trained individuals practicing self-catheterisation. There is a particular need for means which provide long-term antimicrobial activity.

[0009] There is also a need for means that provide antimicrobial activity without affecting the intermittent catheter lubricity and mechanical properties, allowing for intermittent catheters which are also easy to insert and remove.

[0010] It is an aim of embodiments of the invention to overcome or mitigate at least one problem of the prior art, whether expressly described herein or not.

[0011] Summary of the Invention

[0012] According to a first aspect of the invention, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0013] Such an amphipathic antimicrobial peptide provides the intermittent catheter with longterm antimicrobial activity which leads to a dramatic decrease in the risk of infection, even in the case of self-catheterisation multiple times a day. In particular, such antimicrobial peptides act to greatly reduce bacteria transfer during catheter insertion, which allows for the dramatic reduction in risk of infection. In addition, such amphipathic antimicrobial peptides provide antimicrobial activity without affecting lubricity of the intermittent catheter or other mechanical properties. As such, the intermittent catheter maintains a lubricious non-stick surface that allows it to be easily inserted and removed.

[0014] In some embodiments, at least one amphipathic antimicrobial peptide is at least 2 amino acids in length. In some embodiments, at least one amphipathic antimicrobial peptide is no greater than 18 amino acids in length, or no greater than 16, 14, 12, 10, 8, or no greater than 6 amino acids in length. In some embodiments, the at least one amphipathic antimicrobial peptide is between 2 to 10 amino acids in length, or between 2 to 8 amino acids in length, or between 2 to 6 amino acids in length, or between 2-4 amino acids in length. In some preferred embodiments, at least one amphipathic antimicrobial peptide is 3 amino acids in length.

[0015] In some embodiments, at least one amino acid of at least one amphipathic antimicrobial peptide is the L-isomer. At least 2 amino acids, or 3 amino acids of at least one amphipathic antimicrobial peptide is the L-isomer. In some preferred embodiments, all amino acids of at least one amphipathic antimicrobial peptide are the L-isomer.

[0016] In some preferred embodiments, 2 or at least 2 of the amino acids are arginine or derivatives thereof.

[0017] In some embodiments, the tryptophan or derivative thereof is directly adjacent to at least one arginine amino acid or derivative thereof. The tryptophan or derivative thereof may preferably be directly adjacent to two arginine amino acids or derivatives thereof. In some embodiments, only a single amino acid is a tryptophan derivative. The tryptophan derivative may comprise an indole moiety that is substituted with at least one C1-C10 alkyl group, preferably at least one C1-C5 alkyl group. The tryptophan derivative may comprise an indole moiety that is substituted with at least 2, and preferably 3 C1-C10 alkyl groups, preferably C1-C5 alkyl groups. The tryptophan derivative may comprise an indole moiety substituted with at least one, preferably at least 2, and more preferably with 3 tert-butyl groups. In some preferred embodiments, the tryptophan derivative comprises an indole moiety that is substituted with 3 tert-butyl groups at the 2, 5, and 7 positions of the indole moiety.

[0018] In some preferred embodiments, at least one amphipathic antimicrobial peptide is 3 amino acids in length, and two of the amino acids are arginine or derivatives thereof and one of the amino acids is tryptophan or a derivative thereof. In some preferred embodiments, the tryptophan or derivative thereof may preferably be directly adjacent to the two arginine amino acids or derivatives thereof.

[0019] In some preferred embodiments, at least one amphipathic antimicrobial peptide is of the formula: AA1-AA2-AA3-X, wherein AA1 is arginine or a derivative thereof; AA2 is tryptophan or a derivative thereof; AA3 is arginine or a derivative thereof; and X is independently chosen from: an alkyl group, an aryl group, an alkaryl group, an alkylamino group, an arylamino group, and an alkarylamino group.

[0020] In some preferred embodiments, at least one amphipathic antimicrobial peptide is of the formula: AA1-AA2-AA3-X, wherein AA1 is arginine or a derivative thereof; AA2 is tryptophan or a derivative thereof; AA3 is arginine or a derivative thereof; and X is independently selected from the group consisting of: an alkyl group, an aryl group, an alkaryl group, an alkylamino group, an arylamino group, and an alkarylamino group.

[0021] In some preferred embodiments, AA2 is 2,5,7-tris-tert-butyltryptophan.

[0022] In some preferred embodiments, AA1 and / or A A3 are arginine.

[0023] In some preferred embodiments, AA1 and / or AA3 are arginine, and AA2 is 2,5,7-tris- tert-butyltryptophan.

[0024] The X group may be independently chosen from: an alkylamino group, an arylamino group, an alkarylamino group, an alkyl group, an aryl group, and an alkaryl group. The X group may be independently selected from the group consisting of: an alkylamino group, an arylamino group, an alkarylamino group, an alkyl group, an aryl group, and an alkaryl group. The X group may be an aminoalkaryl or alkaryl group. The X group may be a Cl- C15 or C1-C10 aminoalkaryl or C1-C15 or C1-C10 alkaryl group. The X group may preferably be -NHCH2CH2Ph or -CH2CH2Ph.

[0025] The X group may be attached to the carboxyl group of the C-terminus of the amphipathic antimicrobial peptide. The X group may preferably substitute the -OH of the carboxyl group of the C-terminus. In such embodiments, the X group may be independently chosen from: an alkylamino group, an arylamino group, and an alkarylamino group. In such embodiments, the X group may be independently selected from the group consisting of: an alkylamino group, an arylamino group, and an alkarylamino group. In such embodiments, the X group may preferably be an alkarylamino group. In such embodiments, the X group may preferably be -NHCH2CH2Ph.

[0026] The X group may be attached to the amino group of AA3. In such embodiments, the X group may be independently chosen from: an alkyl group, an aryl group, and an alkaryl group. In such embodiments, the X group may be independently selected from the group consisting of: an alkyl group, an aryl group, and an alkaryl group. In such embodiments, the X group may preferably be an alkaryl group. In such embodiments, the X group may preferably be -CH2CH2PI1. In some embodiments, the -OH of the carboxyl group of the C-terminus of the amphipathic antimicrobial peptide may be substituted with an amino group, preferably - NH2. In such embodiments, the X group may be attached to the amino group of AA3. In such embodiments, the X group may be independently chosen from: an alkyl group, an aryl group, and an alkaryl group. In such embodiments, the X group may be independently selected from the group consisting of: an alkyl group, an aryl group, and an alkaryl group. In such embodiments, the X group may preferably be an alkaryl group. In such embodiments, the X group may preferably be -CH2CH2PI1.

[0027] In some preferred embodiments, at least one amphipathic antimicrobial peptide comprises a compound of Formula (I).

[0028] Formula (I) In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide comprising a compound of Formula (I).

[0029] In some preferred embodiments, at least one amphipathic antimicrobial peptide comprises a compound of Formula (II).

[0030] Formula (II)

[0031] In some embodiments, at least one amphipathic antimicrobial peptide is at least 5, or at least 10, 15, 20, or at least 25 amino acids in length. In some embodiments, at least one amphipathic antimicrobial peptide is no greater than 60 amino acids in length, or no greater than 55, 50, 45, or no greater than 40 amino acids in length. At least one amphipathic antimicrobial peptide may be between 10-55 amino acids in length, or between 15-50 amino acids in length, or between 20-45, or preferably between 25-40 amino acids in length, or between 26-37 amino acids in length. In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one amino acid that is independently chosen from: alanine, isoleucine, proline, glycine, threonine, glutamine, leucine, and derivatives and / or combinations thereof. At least one amphipathic antimicrobial peptide may comprise at least 2 amino acids independently chosen from the above list, or at least 3, or at least 4, or at least 5, or at least 6, or at least one amphipathic antimicrobial peptide may comprise all 7 amino acids from the above list or derivatives thereof.

[0032] In some preferred embodiments, at least one amphipathic antimicrobial peptide may comprise only a single proline amino acid or derivative thereof.

[0033] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one alanine amino acid or derivative thereof, or 2 or at least 2 alanine amino acids or derivatives thereof. In some embodiments, at least one alanine amino acid or derivative thereof may be directly adjacent to a proline amino acid or derivative thereof.

[0034] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one isoleucine amino acid or derivative thereof, or at least 2, or 3 or at least 3 isoleucine amino acids or derivatives thereof.

[0035] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one glycine amino acid or derivative thereof, or at least 2, or 3 or at least 3 glycine amino acids or derivatives thereof.

[0036] In some embodiments, at least one amphipathic antimicrobial peptide is at least 5, or at least 10, 15, 20, or at least 25 amino acids in length. In some embodiments, at least one amphipathic antimicrobial peptide is no greater than 50 amino acids in length, or no greater than 45, 40, or no greater than 35 amino acids in length. At least one amphipathic antimicrobial peptide may be between 10 to 50 amino acids in length, or between 15 to

[0037] 45 amino acids in length, or between 20 to 40 amino acids in length, or preferably between 25 to 35 amino acids in length. In some preferred embodiments, at least one amphipathic antimicrobial peptide may be 30 amino acids in length.

[0038] In some embodiments, at least 5% of the total number of amino acids are arginine or derivatives thereof, or at least 6, 7, 8, 9 or at least 10% of the total number of amino acids are arginine or derivatives thereof. In some embodiments, no greater than 50% of the total number of amino acids are arginine or derivatives thereof, or no greater than 45, 40, 35, 30, 25, 20, or no greater than 15% of the total number of amino acids are arginine or derivatives thereof. In some embodiments, between 5-25% of the total number of amino acids are arginine or derivatives thereof, or between 10-20%, or preferably between 10- 15% of the total number of amino acids are arginine or derivatives thereof.

[0039] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one cysteine amino acid or derivative thereof. In some embodiments, at least 5% of the total number of amino acids are cysteine or derivatives thereof, or at least 10, or at least 15% of the total number of amino acids are cysteine or derivatives thereof. In some embodiments, no greater than 50% of the total number of amino acids are cysteine or derivatives thereof, or no greater than 45, 40, 35, 30, or no greater than 25% of the total number of amino acids are cysteine or derivatives thereof. In some embodiments, between 5-35% of the total number of amino acids are cysteine or derivatives thereof, or between 10-30%, or preferably between 15-25% of the total number of amino acids are cysteine or derivatives thereof.

[0040] At least one amphipathic antimicrobial peptide may comprise at least one cysteinecysteine disulfide bridge. At least one amphipathic antimicrobial peptide may comprise between 1-5 cysteine-cysteine disulfide bridges, or between 2-4 cysteine-cysteine disulfide bridges, or 3 cysteine-cysteine disulfide bridges. All cysteine amino acids or derivatives thereof may be involved in at least one disulfide bridge.

[0041] In some embodiments, the tryptophan or derivative thereof is directly adjacent to a leucine amino acid or derivative thereof. In some embodiments, the tryptophan or derivative thereof is directly adjacent to an alanine amino acid or derivative thereof. The tryptophan or derivative thereof may be directly adjacent to a leucine amino acid or derivative thereof and to an alanine amino acid or derivative thereof.

[0042] In some embodiments, at least one amphipathic antimicrobial peptide comprises only a single proline amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to an isoleucine amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to an alanine amino acid or derivative thereof. The proline or derivative thereof may be directly adjacent to an isoleucine amino acid or derivative thereof and to an alanine amino acid or derivative thereof.

[0043] In some preferred embodiments, at least one amphipathic antimicrobial peptide has an amino acid sequence as shown in SEQ ID NO: 1.

[0044] In some embodiments, at least one amphipathic antimicrobial peptide is at least 5, or at least 10, 15, 20, 25, or at least 30 amino acids in length. In some embodiments, at least one amphipathic antimicrobial peptide is no greater than 60 amino acids in length, or no greater than 55, 50, 45, or no greater than 40 amino acids in length. At least one amphipathic antimicrobial peptide may be between 20 to 50 amino acids in length, or between 25 to 45 amino acids in length, or between 30 to 40 amino acids in length, or preferably between 35 to 40 amino acids in length. In some preferred embodiments, at least one amphipathic antimicrobial peptide may be 37 amino acids in length.

[0045] In some embodiments, only a single amino acid of at least one amphipathic antimicrobial peptide is arginine or a derivative thereof. The arginine or derivative thereof may be directly adjacent to an isoleucine amino acid or derivative thereof. The arginine or derivative thereof may be directly adjacent to an aspartic acid amino acid or derivative thereof. The arginine or derivative thereof may be directly adjacent to an isoleucine amino acid or derivative thereof and to an aspartic acid amino acid or derivative thereof.

[0046] The tryptophan or derivative thereof may be directly adjacent to a lysine amino acid or derivative thereof. The tryptophan or derivative thereof may be directly adjacent to two lysine amino acids or derivatives thereof.

[0047] In some embodiments, at least one amphipathic antimicrobial peptide comprises only a single proline amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to a glycine amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to an alanine amino acid or derivative thereof. The proline or derivative thereof may be directly adjacent to a glycine amino acid or derivative thereof and to an alanine amino acid or derivative thereof.

[0048] In some preferred embodiments, at least one amphipathic antimicrobial peptide has an amino acid sequence as shown in SEQ ID NO: 2.

[0049] In some embodiments, at least one amphipathic antimicrobial peptide is at least 5, or at least 10, 15, 20, or at least 25 amino acids in length. In some embodiments, at least one amphipathic antimicrobial peptide is no greater than 50 amino acids in length, or no greater than 45, 40, 35, or no greater than 30 amino acids in length. In some embodiments, at least one amphipathic antimicrobial peptide may be between 10 to 40 amino acids in length, or between 15 to 35, or between 20 to 30, or between 22 to 30 amino acids in length. In some preferred embodiments, at least one amphipathic antimicrobial peptide may be 26 amino acids in length.

[0050] In some embodiments, at least one amphipathic antimicrobial peptide comprises 2 or at least 2 arginine amino acids or derivatives thereof.

[0051] In some embodiments, the tryptophan or derivative thereof is directly adjacent to an isoleucine amino acid or derivative thereof. In some embodiments, the tryptophan or derivative thereof is directly adjacent to a serine amino acid or derivative thereof. The tryptophan or derivative thereof may be directly adjacent to an isoleucine amino acid or derivative thereof and to a serine amino acid or derivative thereof.

[0052] In some embodiments, at least one amphipathic antimicrobial peptide comprises only a single proline amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to a leucine amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to an alanine amino acid or derivative thereof. The proline or derivative thereof may be directly adjacent to a leucine amino acid or derivative thereof and to an alanine amino acid or derivative thereof.

[0053] In some preferred embodiments, at least one amphipathic antimicrobial peptide has an amino acid sequence as shown in SEQ ID NO: 3.

[0054] In some preferred embodiments, at least one amphipathic antimicrobial peptide is independently chosen from: a compound of Formula (I), a compound of Formula (II), a peptide having an amino acid sequence as shown in SEQ ID NO: 1, a peptide having an amino acid sequence as shown in SEQ ID NO: 2, a peptide having an amino acid sequence as shown in SEQ ID NO: 3, and combinations thereof.

[0055] In some preferred embodiments, at least one amphipathic antimicrobial peptide is independently selected from the group consisting of: a compound of Formula (I), a compound of Formula (II), a peptide having an amino acid sequence as shown in SEQ ID NO: 1, a peptide having an amino acid sequence as shown in SEQ ID NO: 2, a peptide having an amino acid sequence as shown in SEQ ID NO: 3, and combinations thereof.

[0056] In some embodiments, the catheter comprises 2 or at least 2 amphipathic antimicrobial peptides independently selected from the above group, or 3 or at least 3 amphipathic antimicrobial peptides independently selected from the above group, or 4 or at least 4 amphipathic antimicrobial peptides independently selected from the above group, or all 5 amphipathic antimicrobial peptides from the above group.

[0057] In some embodiments, the intermittent catheter comprises a hollow tubular body, preferably a hollow polymeric tubular body. The hollow polymeric tubular body may comprise a base polymer.

[0058] In some embodiments, the catheter further comprises at least one additive, preferably at least one lubricious additive. Preferably, the hollow tubular body comprises at least one additive.

[0059] In some embodiments, at least one additive is a hydrophilic additive.

[0060] At least one hydrophilic additive may be independently chosen from: a polyalkylene glycol, hyaluronic acid, chondroitan sulfate, chitosan, glucosaminoglucans, dextran, dextrin, dextran sulfate, cellulose acetate, carboxymethyl cellulose, hydroxyethyl cellulose, cellulosics, polypeptides, poly(2-hydroxyethyl methacrylate), polyacrylamide, polyacrylimide, poly(ethylene amine), poly(allyl amine), poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol), poly(acrylic acid), poly(methacrylic acid), acrylic acid copolymers, methacrylic acid copolymers, polyvinyl alkyl ethers, non-ionic tetrafunctional blockcopolymer surfactants, gelatin, collagen, albumin, chitin, heparin, elastin, fibrin, and combinations thereof.

[0061] At least one hydrophilic additive may be independently selected from the group consisting of: a polyalkylene glycol, hyaluronic acid, chondroitan sulfate, chitosan, glucosaminoglucans, dextran, dextrin, dextran sulfate, cellulose acetate, carboxymethyl cellulose, hydroxyethyl cellulose, cellulosics, polypeptides, poly(2-hydroxyethyl methacrylate), polyacrylamide, polyacrylimide, poly(ethylene amine), poly(allyl amine), poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol), poly(acrylic acid), poly(methacrylic acid), acrylic acid copolymers, methacrylic acid copolymers, polyvinyl alkyl ethers, nonionic tetrafunctional block-copolymer surfactants, gelatin, collagen, albumin, chitin, heparin, elastin, fibrin, and combinations thereof.

[0062] In some embodiments, at least one hydrophilic additive is independently chosen from: poly (ethylene glycol), poly (ethylene oxide), poly (propylene glycol), poly (ethylene oxide- co-propylene oxide), poly(trimethylene glycol), poly(tetramethylene glycol), and combinations thereof.

[0063] In some embodiments, at least one hydrophilic additive is independently selected from the group consisting of: poly(ethylene glycol), poly(ethylene oxide), polypropylene glycol), poly(ethylene oxide-co-propylene oxide), poly(trimethylene glycol), poly (tetramethylene glycol), and combinations thereof. At least one hydrophilic additive may comprise PVP or a derivative thereof.

[0064] At least one additive may be an amphiphilic additive. The amphiphilic additive comprises a hydrophobic portion and a hydrophilic portion. In cases where the base polymer is hydrophobic or generally hydrophobic, such as a polyolefin, the amphiphilic additive will diffuse towards and to an outer surface of the catheter body due to incompatibility of the hydrophilic portion of the amphiphilic additive with the hydrophobic base polymer.

[0065] In some embodiments, the catheter comprises a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive.

[0066] In some embodiments, at least one additive is polymeric or oligomeric.

[0067] At least one additive may be an A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block.

[0068] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block.

[0069] 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.

[0070] In some embodiments, the additive is a B-A-B tri-block copolymer comprising a hydrophobic hydrocarbon A-block and hydrophilic B -blocks.

[0071] In other embodiments, the additive is a graft copolymer. The graft copolymer may comprise a hydrophobic hydrocarbon A-block with hydrophilic B -blocks branching therefrom. Alternatively, the graft copolymer may comprise a hydrophilic portion with hydrophobic portions branching therefrom.

[0072] In further embodiments, the additive is a brush copolymer. The additive may comprise a single hydrophilic B -block with more than one hydrophobic A-block branching from an end thereof. Alternatively, the additive may comprise a single hydrophobic A-block with more than one hydrophilic B -block branching from an end thereof. In the respective embodiments, the B-block or A-block may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, or more hydrophobic A-blocks or hydrophilic B -blocks branching from the end thereof.

[0073] In further embodiments, the additive is a star-block or multi-block copolymer comprising hydrophilic and hydrophobic monomer units.

[0074] In preferred embodiments, the additive is an A-B block copolymer comprising a hydrophobic A-block and a hydrophilic B-block.

[0075] Statements of invention below relating to the additive or a part thereof may be applied mutatis mutandis to each of the copolymer forms above.

[0076] 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 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 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 preferably chosen from: 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 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. 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.

[0077] The hydrophobic A-block may comprise a carbon chain of at least 5 carbon atoms, or at least 10, 15, 20, 25, 30, 35, or 40 carbon atoms. The hydrophobic portion may preferably comprise a carbon chain of between 20-52 carbon atoms.

[0078] 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.

[0079] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CHsCth CtBCthla where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0080] In some embodiments, the additive is homogenously distributed with the polymer. The additive may be uniformly distributed throughout the base polymer of the catheter body.

[0081] 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.

[0082] The outer surface may comprise at least one member chosen from: the external-facing surface of the body, the lumen of the body and any eyelets present on 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 externalfacing surface of the body of the catheter, the inner lumen, and the eyelets.

[0083] 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.

[0084] 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.

[0085] 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.

[0086] 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.

[0087] In some embodiments, the additive comprises a layer that is on or that comprises a surface of the body, preferably the outer surface.

[0088] 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.

[0089] 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.

[0090] 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.

[0091] 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. In some embodiments, the layer comprising the additive is on or comprises at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99% of the or each surface area of the body, preferably at least 75% or at least 90% of the or each surface area or between 75% and 100% of the or each surface area. In embodiments in which the layer comprising the additive comprises or is on both an inner and outer surface of the body, the additive may comprise at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99% of each surface area of the body, preferably at least 75% or at least 90% of each surface area or between 75% and 100% of each surface area of both surfaces.

[0092] 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.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] The layer comprising the additive may have an additive concentration of between 10-

[0097] 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.

[0098] 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.

[0099] 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.

[0100] 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.

[0101] 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.

[0102] In some embodiments, the layer comprising the additive has a thickness of between SO- SOO pm.

[0103] 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-

[0104] 300, 260-300, or of between 280-300 pm. The layer comprising the additive may have a thickness of between 50-280 pm, or of between 50-260, 50-240, 50-220, 50-200, 50-180, 50-160, 50-140, 50-120, 50-100, 50- 80, or of between 50-60 pm.

[0105] 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.

[0106] 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.

[0107] 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

[0108] (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.

[0109] 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.

[0110] 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.

[0111] 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. 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.

[0112] 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, 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, poly-caprolactone, poly(p-dioxanone), or combinations, blends or co-polymers of any of the above materials.

[0113] 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.

[0114] 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.

[0115] Particularly preferred for intermittent catheters are base polymers that comprise or that are made of a polyolefin and / or thermoplastic elastomeric material. In preferred embodiments, the polyolefin may comprise polyethylene and / or polypropylene. In some preferred embodiments, the base polymer of the intermittent catheter may comprise or be made of a thermoplastic polyolefin.

[0116] In some preferred embodiments, the base polymer comprises a polyolefin, especially polyethylene and / or polypropylene.

[0117] In some preferred embodiments, the base polymer comprises a thermoplastic elastomeric material. The base polymer may comprise a thermoplastic polyolefin.

[0118] The thermoplastic base polymer may comprise a hydrophobic polymer chosen from: Accurel ™, Styroflex™, Styrolux™, MelifleX™, and Mediprene™ and any combination thereof.

[0119] 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.

[0120] The thermoplastic base polymer may comprise Estane™ 58315, which is both hydrophobic and hydrophilic.

[0121] In some embodiments, the catheter is a reusable intermittent catheter. In other embodiments, the catheter is a single-use intermittent catheter.

[0122] In some embodiments, at least one amphipathic antimicrobial peptide is present as a coating on the surface of the catheter.

[0123] At least one amphipathic antimicrobial peptide may be coated on the outer and / or inner surface of the catheter.

[0124] At least one amphipathic antimicrobial peptide may be coated over 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 of the catheter or between 75% and 100% of the or each surface area.

[0125] The coating may be in the form of a liquid, gel or solid. The coating may be in the form of a paste.

[0126] In some preferred embodiments, at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0127] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, and wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0128] In some preferred embodiments, at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0129] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, and wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0130] At least one amphipathic antimicrobial peptide may be present in a total concentration of at least 0.01 wt.% of the coating, or at least 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, or at least 0.1 wt.% of the coating, or at least 0.2, 0.3, 0.4, or at least 0.5 wt.% of the coating. At least one amphipathic antimicrobial peptide may be present in a total concentration of no greater than 25 wt.% of the coating, or no greater than 20, 15, 10, 5, or no greater than 2 wt.% of the coating. At least one amphipathic antimicrobial peptide may be present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0131] In some embodiments, at least one amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0132] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a spray- coated coating on the surface of the catheter.

[0133] In some embodiments, at least one amphipathic antimicrobial peptide is present as a layer that is on the catheter surface. In some embodiments, at least one amphipathic antimicrobial peptide is adsorbed to the catheter surface to form the layer. In some embodiments, the layer is a layer of coating comprising at least one amphipathic antimicrobial peptide, which may be as described in statements of invention above. In some embodiments, at least 75% of the layer comprising at least one amphipathic antimicrobial peptide, 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 amphipathic antimicrobial peptide. In some embodiments, no greater than 95, 90, 85, or no greater than 80% of the layer is the amphipathic antimicrobial peptide.

[0134] In some embodiments, the layer comprising at least one amphipathic antimicrobial peptide 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. The layer comprising at least one amphipathic antimicrobial peptide may have 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.

[0135] In some embodiments, at least one amphipathic antimicrobial peptide is adsorbed to the surface of the catheter. At least one amphipathic antimicrobial peptide may be physisorbed and / or chemisorbed to the catheter surface. At least one amphipathic antimicrobial peptide may be covalently bonded to the catheter surface.

[0136] At least one amphipathic antimicrobial peptide may be directly bonded to the catheter surface. Alternatively, at least one amphipathic antimicrobial peptide may be bonded to the catheter surface via a linker.

[0137] At least one amphipathic antimicrobial peptide may be bonded to the surface of the catheter via one or more surface- linker groups present on the antimicrobial peptide. The surface-linker groups may be bonded to the surface of the catheter via covalent bonds, ionic bonds, hydrogen bonds, or Van der Waals forces. At least one amphipathic antimicrobial peptide may be bonded to the surface of the catheter using a tether.

[0138] In some embodiments, at least one amphipathic antimicrobial peptide comprises an integral part of the catheter surface. At least one amphipathic antimicrobial peptide may comprise an integral part of the catheter surface over at least 5% of the total area of the catheter surface, or at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or at least 99% of the total area of the catheter surface, preferably at least 75% or at least 90% of the total area of the catheter surface or between 75% and 100% of the total area of the catheter surface. In some embodiments, at least one amphipathic antimicrobial peptide forms an integral part of the catheter surface over no greater than 95% of the total area of the catheter surface, or no greater than 90, 85, or no greater than 80% of the total area of the catheter surface.

[0139] At least one amphipathic antimicrobial peptide may be present at a total concentration of at least 0.01 wt.% of the catheter, or at least 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, or at least 0.1 wt.% of the catheter, or at least 0.2, 0.3, 0.4, or at least 0.5 wt.% of the catheter. At least one amphipathic antimicrobial peptide may be present in a total concentration of no greater than 25 wt.% of the catheter, or no greater than 20, 15, 10, 5, or no greater than 2 wt.% of the catheter. At least one amphipathic antimicrobial peptide may be present in a total concentration of between 0.01-10 wt.% of the catheter, or between 0.05-5 wt.% of the catheter.

[0140] In other embodiments, at least one amphipathic antimicrobial peptide may be present at a total concentration of no greater than 2xl0-3wt.% of the catheter, or no greater than 1.5xl0-3, IxlO-3, 9xl0-4, 8xl0-4, 7xl0-4, or no greater than 6.5xl0-4wt.% of the catheter. In some embodiments, at least one amphipathic antimicrobial peptide may be present at a total concentration of between IxlO-4and 0.01 wt.% of the catheter, or between 2xl0-4and 2xl0-3wt.%, or between 4xl0-4and IxlO-3wt.% of the catheter. In such embodiments, at least one amphipathic antimicrobial peptide may have an amino acid sequence as shown in SEQ ID NO: 3.

[0141] According to a second aspect of the invention, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0142] The intermittent urinary catheter of the second aspect of the invention is preferably the intermittent urinary catheter of the first aspect of the invention. The amphipathic antimicrobial peptide of the second aspect of the invention may be the amphipathic antimicrobial peptide of the first aspect of the invention.

[0143] Statements of invention above for the first aspect of the invention may also be applied mutatis mutandis to the second aspect of the invention. Statements of invention below for the second aspect of the invention may also be applied mutatis mutandis to the other aspects of the invention.

[0144] In some embodiments, at least one amphipathic antimicrobial peptide is at least 5, or at least 10, 15, 20, or at least 25 amino acids in length. In some embodiments, at least one amphipathic antimicrobial peptide is no greater than 60 amino acids in length, or no greater than 55, 50, 45, or no greater than 40 amino acids in length. At least one amphipathic antimicrobial peptide may be between 10-55 amino acids in length, or between 15-50 amino acids in length, or between 20-45, or preferably between 25-40 amino acids in length, or between 26-37 amino acids in length.

[0145] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one amino acid that is independently chosen from: alanine, isoleucine, glycine, threonine, leucine, and derivatives and / or combinations thereof. At least one amphipathic antimicrobial peptide may comprise at least 2 amino acids independently chosen from the above list, or at least 3, or at least 4, or at least one amphipathic antimicrobial peptide may comprise all 5 amino acids from the above list or derivatives thereof.

[0146] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one alanine amino acid or derivative thereof, or 2 or at least 2 alanine amino acids or derivatives thereof. In some embodiments, at least one alanine amino acid or derivative thereof may be directly adjacent to the proline amino acid or derivative thereof.

[0147] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one isoleucine amino acid or derivative thereof, or at least 2, or 3 or at least 3 isoleucine amino acids or derivatives thereof.

[0148] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one glycine amino acid or derivative thereof, or at least 2, or 3 or at least 3 glycine amino acids or derivatives thereof. In some embodiments, at least one glycine amino acid or derivative thereof may be directly adjacent to the proline amino acid or derivative thereof.

[0149] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one arginine amino acid or derivative thereof. In some embodiments, at least one amphipathic antimicrobial peptide comprises one or at least one tryptophan amino acid or derivative thereof, preferably only a single tryptophan amino acid or derivative thereof. In some embodiments, only a single amino acid of at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0150] At least one amphipathic antimicrobial peptide may be between 10-50 amino acids in length, or between 15-45 amino acids in length, or between 20-40 amino acids in length, or preferably between 25-35 amino acids in length. In some preferred embodiments, at least one amphipathic antimicrobial peptide may be 30 amino acids in length.

[0151] In some embodiments, between 5-25% of the total number of amino acids are arginine or derivatives thereof, or between 10-20%, or preferably between 10-15% of the total number of amino acids are arginine or derivatives thereof.

[0152] In some embodiments, between 5-35% of the total number of amino acids are cysteine or derivatives thereof, or between 10-30%, or preferably between 15-25% of the total number of amino acids are cysteine or derivatives thereof.

[0153] At least one amphipathic antimicrobial peptide may comprise at least one cysteinecysteine disulfide bridge. At least one amphipathic antimicrobial peptide may comprise between 1-5 cysteine-cysteine disulfide bridges, or between 2-4 cysteine-cysteine disulfide bridges, or 3 cysteine-cysteine disulfide bridges. All cysteine amino acids or derivatives thereof may be involved in at least one disulfide bridge.

[0154] In some embodiments, the proline or derivative thereof is directly adjacent to an isoleucine amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to an alanine amino acid or derivative thereof. The proline or derivative thereof may be directly adjacent to an isoleucine amino acid or derivative thereof and to an alanine amino acid or derivative thereof.

[0155] At least one amphipathic antimicrobial peptide may comprise only a single tryptophan amino acid or derivative thereof. In some embodiments, the tryptophan or derivative thereof is directly adjacent to a leucine amino acid or derivative thereof. In some embodiments, the tryptophan or derivative thereof is directly adjacent to an alanine amino acid or derivative thereof. The tryptophan or derivative thereof may be directly adjacent to a leucine amino acid or derivative thereof and to an alanine amino acid or derivative thereof.

[0156] In some preferred embodiments, at least one amphipathic antimicrobial peptide has an amino acid sequence as shown in SEQ ID NO: 1.

[0157] At least one amphipathic antimicrobial peptide may be between 20 to 50 amino acids in length, or between 25 to 45 amino acids in length, or between 30 to 40 amino acids in length, or preferably between 35 to 40 amino acids in length. In some preferred embodiments, at least one amphipathic antimicrobial peptide may be 37 amino acids in length.

[0158] In some embodiments, only a single amino acid of at least one amphipathic antimicrobial peptide is arginine or a derivative thereof. The arginine or derivative thereof may be directly adjacent to an isoleucine amino acid or derivative thereof. The arginine or derivative thereof may be directly adjacent to an aspartic acid amino acid or derivative thereof. The arginine or derivative thereof may be directly adjacent to an isoleucine amino acid or derivative thereof and to an aspartic acid amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to a glycine amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to an alanine amino acid or derivative thereof. The proline or derivative thereof may be directly adjacent to a glycine amino acid or derivative thereof and to an alanine amino acid or derivative thereof.

[0159] At least one amphipathic antimicrobial peptide may comprise only a single tryptophan amino acid or derivative thereof. In some embodiments, the tryptophan or derivative thereof is directly adjacent to a lysine amino acid or derivative thereof. The tryptophan or derivative thereof may be directly adjacent to two lysine amino acids or derivatives thereof.

[0160] In some preferred embodiments, at least one amphipathic antimicrobial peptide has an amino acid sequence as shown in SEQ ID NO: 2.

[0161] In some embodiments, at least one amphipathic antimicrobial peptide may be between 10 to 40 amino acids in length, or between 15 to 35, or between 20 to 30, or between 22 to 30 amino acids in length. In some preferred embodiments, at least one amphipathic antimicrobial peptide may be 26 amino acids in length.

[0162] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one arginine amino acid or derivative thereof, or 2 or at least 2 arginine amino acids or derivatives thereof.

[0163] In some embodiments, the proline or derivative thereof is directly adjacent to a leucine amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to an alanine amino acid or derivative thereof. The proline or derivative thereof may be directly adjacent to a leucine amino acid or derivative thereof and to an alanine amino acid or derivative thereof.

[0164] At least one amphipathic antimicrobial peptide may comprise only a single tryptophan amino acid or derivative thereof. In some embodiments, the tryptophan or derivative thereof is directly adjacent to an isoleucine amino acid or derivative thereof. In some embodiments, the tryptophan or derivative thereof is directly adjacent to a serine amino acid or derivative thereof. The tryptophan or derivative thereof may be directly adjacent to an isoleucine amino acid or derivative thereof and to a serine amino acid or derivative thereof.

[0165] In some preferred embodiments, at least one amphipathic antimicrobial peptide has an amino acid sequence as shown in SEQ ID NO: 3.

[0166] In some embodiments, at least one amphipathic antimicrobial peptide may be between 20 to 50 amino acids in length, or between 25 to 45 amino acids in length, or between 30 to 40 amino acids in length, or preferably between 30 to 35 amino acids in length. In some preferred embodiments, at least one amphipathic antimicrobial peptide may be 34 amino acids in length.

[0167] In some embodiments, at least one amphipathic antimicrobial peptide comprises at least one cysteine amino acid or derivative thereof. In some embodiments, at least 5% of the total number of amino acids are cysteine or derivatives thereof, or at least 6, 7, 8, 9, or at least 10% of the total number of amino acids are cysteine or derivatives thereof. In some embodiments, no greater than 40% of the total number of amino acids are cysteine or derivatives thereof, or no greater than 35, 30, 25, or no greater than 20% of the total number of amino acids are cysteine or derivatives thereof. In some embodiments, between 5-25% of the total number of amino acids are cysteine or derivatives thereof, or between 10-20%, or preferably between 12-18% of the total number of amino acids are cysteine or derivatives thereof.

[0168] In some embodiments, the proline or derivative thereof is directly adjacent to a threonine amino acid or derivative thereof. In some embodiments, the proline or derivative thereof is directly adjacent to a glycine amino acid or derivative thereof. The proline or derivative thereof may be directly adjacent to a threonine amino acid or derivative thereof and to a glycine amino acid or derivative thereof.

[0169] In some preferred embodiments, at least one amphipathic antimicrobial peptide has an amino acid sequence as shown in SEQ ID NO: 4.

[0170] In some preferred embodiments, at least one amphipathic antimicrobial peptide is independently chosen from: a peptide having an amino acid sequence as shown in SEQ ID NO: 1, a peptide having an amino acid sequence as shown in SEQ ID NO: 2, a peptide having an amino acid sequence as shown in SEQ ID NO: 3, a peptide having an amino acid sequence as shown in SEQ ID NO: 4, and combinations thereof.

[0171] In some preferred embodiments, at least one amphipathic antimicrobial peptide is independently selected from the group consisting of: a peptide having an amino acid sequence as shown in SEQ ID NO: 1 , a peptide having an amino acid sequence as shown in SEQ ID NO: 2, a peptide having an amino acid sequence as shown in SEQ ID NO: 3, a peptide having an amino acid sequence as shown in SEQ ID NO: 4, and combinations thereof.

[0172] In some embodiments, the catheter comprises 2 or at least 2 amphipathic antimicrobial peptides independently selected from the above group, or 3 or at least 3 amphipathic antimicrobial peptides independently selected from the above group, or all 4 amphipathic antimicrobial peptides from the above group.

[0173] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block.

[0174] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Ctb CthCtb where “a” is 5- 25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0175] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0176] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0177] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0178] According to a third aspect of the invention, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (I).

[0179]

[0180] Formula (I)

[0181] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (I), and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0182] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (I), and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CFfeCFbCCFbCFh^ where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and

[0183] 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0184] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (I), wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0185] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (I), wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0186] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (I), wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0187] According to a fourth aspect of the invention, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (II).

[0188] Formula (II)

[0189] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (II), and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0190] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (II), and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH CF^CFBCFF where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0191] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (II), wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0192] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (II), wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0193] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide of Formula (II), wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0194] According to a fifth aspect of the invention, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0195] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0196] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0197] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1 , wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0198] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1 , wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0199] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1 , wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0200] According to a sixth aspect of the invention, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0201] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0202] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula

[0203] CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0204] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0205] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0206] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0207] According to a seventh aspect of the invention, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0208] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0209] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0210] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0211] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0212] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter

[0213] According to an eighth aspect of the invention, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0214] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0215] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, said catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the

[0216] A-block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0217] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0218] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0219] In some preferred embodiments, there is provided an intermittent urinary catheter comprising a surface comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter

[0220] The following statements apply to the third, fourth, fifth, sixth, seventh and eighth aspects of the invention.

[0221] The intermittent urinary catheter of the third, fourth, fifth, sixth, seventh and eighth aspects of the invention is preferably the intermittent urinary catheter of the first aspect of the invention. The amphipathic antimicrobial peptide of the third and fourth aspects of the invention may be the amphipathic antimicrobial peptide of the first aspect of the invention. The amphipathic antimicrobial peptide of the fifth, sixth and seventh aspects of the invention may be the amphipathic antimicrobial peptide of the first and / or second aspect of the invention. The amphipathic antimicrobial peptide of the eighth aspect of the invention may be the amphipathic antimicrobial peptide of the second aspect of the invention.

[0222] Statements of invention relating to the first and second aspects of the invention above may also be applied mutatis mutandis to the third, fourth, fifth, sixth, seventh and eighth aspects of the invention.

[0223] According to a ninth aspect of the invention, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0224] (a) Providing an intermittent urinary catheter; and

[0225] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0226] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0227] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0228] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0229] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0230] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0231] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0232] (a) Providing an intermittent urinary catheter; and (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

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

[0234] (a) Providing an intermittent urinary catheter; and

[0235] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

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

[0237] (a) Providing an intermittent urinary catheter; and

[0238] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0239] According to a tenth aspect of the invention, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0240] (a) Providing an intermittent urinary catheter; and

[0241] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0242] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0243] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0244] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0245] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0246] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0247] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0248] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0249] (a) Providing an intermittent urinary catheter; and

[0250] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

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

[0252] (a) Providing an intermittent urinary catheter; and (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0253] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0254] (a) Providing an intermittent urinary catheter; and

[0255] (b) Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a spray- coated coating on the surface of the catheter.

[0256] According to an eleventh aspect of the invention, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0257] (a) Providing an intermittent urinary catheter; and

[0258] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (I).

[0259]

[0260] Formula (I)

[0261] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of: (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0262] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (I).

[0263] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0264] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0265] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (I).

[0266] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0267] (a) Providing an intermittent urinary catheter; and

[0268] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (I), wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0269] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0270] (a) Providing an intermittent urinary catheter; and

[0271] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (I), wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating. In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0272] (a) Providing an intermittent urinary catheter; and

[0273] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (I), wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0274] According to a twelfth aspect of the invention, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0275] (a) Providing an intermittent urinary catheter; and (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (II).

[0276] Formula (II)

[0277] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of: (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0278] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (II).

[0279] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0280] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0281] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (II).

[0282] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0283] (a) Providing an intermittent urinary catheter; and (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (II), wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0284] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0285] (a) Providing an intermittent urinary catheter; and

[0286] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (II), wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0287] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0288] (a) Providing an intermittent urinary catheter; and

[0289] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide of Formula (II), wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0290] According to a thirteenth aspect of the invention, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0291] (a) Providing an intermittent urinary catheter; and

[0292] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1. In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0293] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0294] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0295] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0296] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0297] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1. In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0298] (a) Providing an intermittent urinary catheter; and

[0299] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0300] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0301] (a) Providing an intermittent urinary catheter; and

[0302] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0303] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0304] (a) Providing an intermittent urinary catheter; and

[0305] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0306] According to a fourteenth aspect of the invention, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0307] (a) Providing an intermittent urinary catheter; and

[0308] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0309] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0310] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0311] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0312] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0313] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0314] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0315] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0316] (a) Providing an intermittent urinary catheter; and

[0317] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0318] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0319] (a) Providing an intermittent urinary catheter; and

[0320] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0321] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0322] (a) Providing an intermittent urinary catheter; and

[0323] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0324] According to a fifteenth aspect of the invention, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0325] (a) Providing an intermittent urinary catheter; and

[0326] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0327] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0328] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0329] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3. In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0330] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0331] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0332] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0333] (a) Providing an intermittent urinary catheter; and

[0334] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0335] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of: (a) Providing an intermittent urinary catheter; and

[0336] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0337] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0338] (a) Providing an intermittent urinary catheter; and

[0339] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0340] According to a sixteenth aspect of the invention, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0341] (a) Providing an intermittent urinary catheter; and

[0342] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0343] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of: (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0344] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0345] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0346] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0347] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0348] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0349] (a) Providing an intermittent urinary catheter; and (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0350] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0351] (a) Providing an intermittent urinary catheter; and

[0352] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0353] In some preferred embodiments, there is provided a method of manufacturing an intermittent urinary catheter, the method comprising the steps of:

[0354] (a) Providing an intermittent urinary catheter; and

[0355] (b) Coating a surface of the intermittent urinary catheter with an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0356] The following statements apply to the ninth, tenth, eleventh, twelfth, thirteenth, fourteenth, fifteenth, and sixteenth aspects of the invention. The intermittent urinary catheter of the ninth, tenth, eleventh, twelfth, thirteenth, fourteenth, fifteenth, and sixteenth aspects of the invention is preferably the intermittent urinary catheter of the first aspect of the invention. The antimicrobial peptide of the ninth, eleventh and twelfth aspects of the invention may be the antimicrobial peptide of the first aspect of the invention. The antimicrobial peptide of the tenth and sixteenth aspects of the invention may be the antimicrobial peptide of the second aspect of the invention. The amphipathic antimicrobial peptide of the thirteenth, fourteenth, and fifteenth aspects of the invention may be the amphipathic antimicrobial peptide of the first and / or second aspect of the invention.

[0357] Statements of invention relating to the other aspects of the invention above may also be applied mutatis mutandis to the ninth to sixteenth aspects of the invention.

[0358] Step (b) may comprise coating an outer and / or inner surface of the catheter with at least one amphipathic antimicrobial peptide.

[0359] In some embodiments, step (b) comprises coating at least 20% of the outer surface area of the catheter with at least one amphipathic antimicrobial peptide, 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.

[0360] In some preferred embodiments, step (b) comprises spray-coating the surface of the catheter with at least one amphipathic antimicrobial peptide. Step (b) may preferably comprise spray-coating the outer surface of the catheter with at least one amphipathic antimicrobial peptide. 'll

[0361] According to a seventeenth aspect of the invention, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0362] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0363] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0364] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0365] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0366] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter. According to an eighteenth aspect of the invention, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0367] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block.

[0368] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0369] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0370] In some preferred embodiments, there is provided the use of at least one amphipathic antimicrobial peptide as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the at least one amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0371] According to a nineteenth aspect of the invention, there is provided the use of an amphipathic antimicrobial peptide of Formula (I) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter.

[0372]

[0373] Formula (I)

[0374] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (I) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0375] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (I) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0376] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (I) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0377] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (I) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0378] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (I) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0379] According to a twentieth aspect of the invention, there is provided the use of an amphipathic antimicrobial peptide of Formula (II) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter.

[0380] Formula (II)

[0381] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (II) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0382] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (II) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula

[0383] CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0384] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (II) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0385] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (II) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0386] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide of Formula (II) as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0387] According to a twenty-first aspect of the invention, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID

[0388] NO: 1 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter. In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0389] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Cth CtECID where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0390] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter. In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0391] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0392] According to a twenty-second aspect of the invention, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter.

[0393] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block. In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Cth CtECtb where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0394] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0395] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating. In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0396] According to a twenty-third aspect of the invention, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter.

[0397] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0398] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Cth CtbCth where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0399] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0400] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0401] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter. According to a twenty-fourth aspect of the invention, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter.

[0402] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0403] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, the intermittent catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Cth CtECID where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter.

[0404] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a gel or paste coating on the surface of the catheter, wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the coating, or between 0.05-5 wt.% of the coating.

[0405] In some preferred embodiments, there is provided the use of an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4 as a bactericidal and / or lubricating agent on a surface of an intermittent urinary catheter, wherein the amphipathic antimicrobial peptide is present as a spray-coated coating on the surface of the catheter.

[0406] The following statements apply to the seventeenth to twenty-fourth aspects of the invention.

[0407] The intermittent urinary catheter of the seventeenth to twenty-fourth aspects of the invention is preferably the intermittent urinary catheter of the first aspect of the invention. The antimicrobial peptide of the seventeenth, nineteenth and twentieth aspects of the invention may be the antimicrobial peptide of the first aspect of the invention. The antimicrobial peptide of the eighteenth and twenty-fourth aspects of the invention may be the antimicrobial peptide of the second aspect of the invention. The amphipathic antimicrobial peptide of the twenty-first, twenty-second, and twenty-third aspects of the invention may be the amphipathic antimicrobial peptide of the first and / or second aspect of the invention.

[0408] Statements of invention relating to the other aspects of the invention above may also be applied mutatis mutandis to the seventeenth to twenty-fourth aspects of the invention.

[0409] According to a twenty-fifth aspect of the invention, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0410] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0411] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0412] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the medium is a gel or paste.

[0413] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0414] According to a twenty-sixth aspect of the invention, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0415] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A- B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B- block.

[0416] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, and wherein the amphiphilic additive is an amphiphilic A- B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B- block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)awhere “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0417] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the medium is a gel or paste.

[0418] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0419] According to a twenty- seventh aspect of the invention, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide of Formula (I).

[0420]

[0421] Formula (I)

[0422] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide of Formula (I), and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block.

[0423] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide of Formula (I), and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CFfaCFhCCFbCF^a where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0424] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide of Formula (I) , wherein the medium is a gel or paste.

[0425] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide of Formula (I), wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0426] According to a twenty-eighth aspect of the invention, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide of Formula (II). Formula (II)

[0427] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide of Formula (II), and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block.

[0428] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide of Formula (II), and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B-block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH CF^CFFCFh where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0429] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide of Formula (II), wherein the medium is a gel or paste. In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide of Formula (II), wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0430] According to a twenty-ninth aspect of the invention, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0431] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0432] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Cth CtbCth where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0433] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, wherein the medium is a gel or paste.

[0434] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0435] According to a thirtieth aspect of the invention, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0436] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0437] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Cth CtbCtb where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0438] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the medium is a gel or paste.

[0439] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0440] According to a thirty-first aspect of the invention, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0441] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0442] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Cth CtECth where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0443] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the medium is a gel or paste.

[0444] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0445] According to a thirty-second aspect of the invention, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0446] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block.

[0447] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, and wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A-block preferably comprising a hydrocarbon chain block of the formula CH Cth CtECtD where “a” is 5-25 and preferably 9-25, and wherein the B-block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0448] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the medium is a gel or paste.

[0449] In some preferred embodiments, there is provided an intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0450] The following statements apply to the twenty-fifth to thirty-second aspects of the invention.

[0451] The intermittent urinary catheter of the twenty-fifth to thirty-second aspects of the invention may be the intermittent urinary catheter of the first aspect of the invention. The antimicrobial peptide of the twenty-fifth, twenty-seventh and twenty-eighth aspects of the invention may be the antimicrobial peptide of the first aspect of the invention. The antimicrobial peptide of the twenty- sixth and thirty- second aspects of the invention may be the antimicrobial peptide of the second aspect of the invention. The amphipathic antimicrobial peptide of the twenty-ninth, thirtieth, and thirty-first aspects of the invention may be the amphipathic antimicrobial peptide of the first and / or second aspect of the invention.

[0452] Statements of invention relating to any other aspect of the invention may also be applied mutatis mutandis to the twenty-fifth to thirty-second aspects of the invention.

[0453] At least one amphipathic antimicrobial peptide may be present in the medium in a total concentration of at least 0.01 wt.% of the medium, or at least 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, or at least 0.1 wt.% of the medium, or at least 0.2, 0.3, 0.4, or at least 0.5 wt.% of the medium. At least one amphipathic antimicrobial peptide may be present in the medium in a total concentration of no greater than 25 wt.% of the medium, or no greater than 20, 15, 10, 5, or no greater than 2 wt.% of the medium. At least one amphipathic antimicrobial peptide may be present in the medium in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium. In some embodiments, the medium is present in liquid, gel or solid form.

[0454] In some embodiments, the medium is present as a solution of at least one amphipathic antimicrobial peptide in a solvent. The solution may be an aqueous solution. The solvent may therefore be water or an aqueous medium.

[0455] In some embodiments, the medium is present in a total amount of at least 0.05 wt.% of the combination of the catheter and medium, or of at least 0.1, 0.15, 0.2, 0.25, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or at least 20 wt.% of the combination of the catheter and medium.

[0456] The medium may be present in a total amount of no greater than 40 wt.% of the combination of the catheter and medium, or no greater than 35, 30, 25, 20, 15, 10, or no greater than 5 wt.% of the combination of the catheter and medium.

[0457] The medium may be present in a total amount of between 0.1-20 wt.% of the combination of the catheter and medium, or between 0.5-15, or between 0.5-5 wt.% of the combination of the catheter and medium.

[0458] In some embodiments, the medium is present as a liquid having a viscosity of greater than 0.5 cP, or of greater than 1, 1.5, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900, or of greater than 1000 cP. The medium may have a viscosity of no greater than 100000 cP, or of no greater than 90000, 80000, 70000, 60000, 50000, 40000, 30000, 20000, 10000, 5000, 4000, 3000, 2000, 1000, 500, 400, 300, 200, 100, 50, 25, 10, 5, 4, 3, 2, or of no greater than 1 cP. The medium may have a viscosity of between 0.5-5000 cP, or of between 0.5-2500, 0.5-1000, 1-1000, 10-1000, 50-1000, 100-1000, 500-1000, 0.5-500, 1-500, 10-500, 50-500, 100-500, 250-500, 0.5- 250, 1-250, 10-250, 50-250, or of between 100-250 cP. 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.

[0459] In some embodiments, the medium has a pH of at least 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or of no greater than 9. In some embodiments, the medium may have a pH of no greater than 14, or of no greater than 13.5, 13, 12.5, 12, 11.5, 11, 10.5, or of no greater than 10.

[0460] In some embodiments, the medium has a pH of between 2-14, 3-13, or of between 4-12.

[0461] The container may preferably define a cavity configured to hold the catheter.

[0462] In some embodiments, the container is rigid. In other embodiments, the container is flexible. In some embodiments, the container contains rigid and flexible regions. The container may comprise a tube. The tube may have a flexible centre portion and two rigid side portions neighbouring the flexible centre portion.

[0463] The catheter may preferably be configured to be repeatedly inserted and removed from the container.

[0464] In some embodiments, the medium is in direct contact with the catheter. The medium may be in direct contact with at least one surface of the catheter. The at least one surface may comprise the outer surface of the catheter. The medium may cover at least part of the outer surface of the catheter.

[0465] The at least one surface may comprise an inner surface of the catheter and the medium may cover at least part of the inner surface. In some embodiments, the medium is in direct contact with the inner and outer surfaces of the catheter.

[0466] In some embodiments, the catheter is in direct contact with the medium along at least 30% of the catheter length, or at least 40, 50, 60, 70, 80, 90, or at least 95% of the catheter length. In some embodiments, the catheter is in direct contact with the medium along the full length of the catheter.

[0467] In some embodiments, at least the outer surface of the catheter, and preferably both the inner and outer surfaces of the catheter are in direct contact with the medium along at least 30% of the catheter length, or at least 40, 50, 60, 70, 80, 90, or at least 95% of the catheter length. In some embodiments, at least the outer surface of the catheter, and preferably both the inner and outer surfaces of the catheter are in direct contact with the medium along the full length of the catheter.

[0468] In some embodiments, the catheter is submerged in the medium. Submersion of the catheter in the medium has been shown to confer optimal catheter lubricity.

[0469] 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.

[0470] In some embodiments, the catheter is not fully submerged in the medium. In such embodiments, the medium may comprise no greater than 30% of the internal volume of the container, or no greater than 25, 20, 15, 10, 5, 4, 3, 2, or no greater than 1% of the internal volume of the container. In such embodiments, the medium may be in direct contact with at least part of the catheter, preferably with at least one surface thereof. In some embodiments, the medium may be able to move freely within the container. In such embodiments, the medium may be configured to slosh around within the container, such as when the container is shaken and / or due to natural movement of the container by the user.

[0471] In some embodiments, the catheter comprises a layer of the medium that is on or that comprises at least part of a surface of the catheter, preferably at least part of the outer surface of the catheter. In such embodiments, the medium may be a liquid or a gel.

[0472] The layer of medium may preferably be on the surface of the catheter, preferably on the surface of the catheter body.

[0473] 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.

[0474] 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 additive may be on or comprise at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99% of each surface area of the catheter, preferably at least 75% or at least 90% of each surface area or between 75% and 100% of each surface area of both surfaces.

[0475] In some embodiments, at least 75% of the layer, or at least 76, 77, 78, 79, 80, 81, 82, 83,

[0476] 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% of the layer is the medium. In some embodiments, the layer has a thickness of at least 1 |im, 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 |im.

[0477] In some embodiments, the layer has a thickness of no greater than 10000 |im, or of no greater than 9000, 8000, 7000, 6000, 5000, 4000, 3000, 2000, 1000, 900, 800, 700, 600, 500, 400, or of no greater than 300 |im.

[0478] In some embodiments, the layer has a thickness of between 50-300 |im.

[0479] The layer may have a thickness of between 60-300 |im, 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 |im.

[0480] The layer may have a thickness of between 50-280 |im, or of between 50-260, 50-240, 50-220, 50-200, 50-180, 50-160, 50-140, 50-120, 50-100, 50-80, or of between 50-60 |im.

[0481] The layer may have a thickness of between 60-280 |im, 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-

[0482] 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-

[0483] 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 |im.

[0484] The layer of medium may have a viscosity of at least 200 cP, or at least 400, 600, 800, or at least 1000 cP, or at least 1200, 1400, 1600, 1800, 2000, 2200, 2400, 2600, 2800, 3000, 3200, 3400, 3600, 3800, 4000, 4200, 4400, 4600, 4800, 5000, 5200, 5400, 5600, 5800, 6000, 6200, 6400, 6600, 6800, 7000, 7200, 7400, 7600, 7800, 8000, 8200, 8400, 8600, 8800, 9000, 9200, 9400, 9600, 9800, or at least 10000 cP.

[0485] The layer of medium may have a viscosity of no greater than 2000000, or no greater than 1750000, 1500000, 1250000, or no greater than 1000000 cP.

[0486] The layer of medium may have a viscosity of between 100-2000000, or between 500- 1000000, or between 1000-500000 cP.

[0487] In some embodiments, the medium is contained in a medium container and the catheter is contained in a separate catheter container. The medium container may be a bag or sachet. The medium container may be located in the catheter container. In some embodiments, the medium is contained in a medium container located in the catheter container and the medium is not in direct contact with the catheter. In some embodiments, the medium container is pierceable, in use, to release the contained medium from the medium container and into direct contact with the catheter in the catheter container, preferably without requiring opening of the catheter container.

[0488] Prior to opening the catheter container, prior to removing the catheter and / or prior to inserting the catheter, the user may release the medium from the medium container and apply the medium to the outer surface of the catheter.

[0489] In some embodiments, the medium container is configured to rupture or break to release the contained medium from the medium container and into direct contact with the catheter upon opening of the catheter container.

[0490] In some embodiments, the catheter is submerged in a liquid and / or solution which does not contain the amphipathic antimicrobial peptide of the invention, and the inventive amphipathic antimicrobial peptide may be contained in a separate medium container. The separate medium container may be as described in statements of invention above.

[0491] The amphipathic antimicrobial peptide of the invention may be present in the separate medium container in solid, liquid, or gel form. The liquid may comprise a solution comprising the amphipathic antimicrobial peptide of the invention. In embodiments wherein the amphipathic antimicrobial peptide of the invention is present in solid form, the solid may comprise a powder or at least one tablet.

[0492] In such embodiments, the amphipathic antimicrobial peptide of the invention may be releasable from the separate medium container, in use. The amphipathic antimicrobial peptide of the invention may be used to treat the catheter after release from the medium container. In embodiments wherein the amphipathic antimicrobial peptide of the invention is present in solid form, the solid may be dissolvable in a liquid to provide a solution comprising the amphipathic antimicrobial peptide of the invention, which may be used to treat the catheter. The liquid may be the liquid in which the catheter is submerged.

[0493] According to a thirty-third aspect of the invention, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0494] (a) Providing an intermittent urinary catheter; and

[0495] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof. In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0496] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0497] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0498] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0499] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

[0500] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0501] (a) Providing an intermittent urinary catheter; and

[0502] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the medium is a gel or paste.

[0503] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0504] (a) Providing an intermittent urinary catheter; and

[0505] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium. In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0506] (a) Providing an intermittent urinary catheter; and

[0507] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof, wherein the treatment comprises spray-coating the at least one amphipathic antimicrobial peptide onto a surface of the catheter.

[0508] According to a thirty-fourth aspect of the invention, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0509] (a) Providing an intermittent urinary catheter; and

[0510] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0511] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0512] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and I l l

[0513] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0514] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0515] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0516] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

[0517] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0518] (a) Providing an intermittent urinary catheter; and

[0519] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the medium is a gel or paste.

[0520] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0521] (a) Providing an intermittent urinary catheter; and

[0522] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0523] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0524] (a) Providing an intermittent urinary catheter; and

[0525] (b) Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof, wherein the treatment comprises spray-coating the at least one amphipathic antimicrobial peptide onto a surface of the catheter.

[0526] According to a thirty-fifth aspect of the invention, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of: (a) Providing an intermittent urinary catheter; and

[0527] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (I). Formula (I)

[0528] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0529] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0530] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (I).

[0531] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0532] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0533] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (I).

[0534] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0535] (a) Providing an intermittent urinary catheter; and

[0536] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (I) , wherein the medium is a gel or paste.

[0537] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0538] (a) Providing an intermittent urinary catheter; and

[0539] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (I) , wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0540] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of: (a) Providing an intermittent urinary catheter; and

[0541] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (I), wherein the treatment comprises spray-coating the at least one amphipathic antimicrobial peptide onto a surface of the catheter. According to a thirty-sixth aspect of the invention, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0542] (a) Providing an intermittent urinary catheter; and

[0543] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (II).

[0544]

[0545] Formula (II)

[0546] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of: (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0547] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (II).

[0548] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0549] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0550] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (II).

[0551] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0552] (a) Providing an intermittent urinary catheter; and

[0553] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (II), wherein the medium is a gel or paste.

[0554] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0555] (a) Providing an intermittent urinary catheter; and

[0556] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (II), wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium. In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0557] (a) Providing an intermittent urinary catheter; and

[0558] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide of Formula (II), wherein the treatment comprises spray-coating the at least one amphipathic antimicrobial peptide onto a surface of the catheter.

[0559] According to a thirty- seventh aspect of the invention, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0560] (a) Providing an intermittent urinary catheter; and

[0561] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0562] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0563] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0564] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0565] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0566] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0567] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0568] (a) Providing an intermittent urinary catheter; and (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, wherein the medium is a gel or paste.

[0569] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0570] (a) Providing an intermittent urinary catheter; and

[0571] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0572] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0573] (a) Providing an intermittent urinary catheter; and

[0574] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, wherein the treatment comprises spray-coating the at least one amphipathic antimicrobial peptide onto a surface of the catheter.

[0575] According to a thirty-eighth aspect of the invention, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0576] (a) Providing an intermittent urinary catheter; and (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0577] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0578] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0579] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0580] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0581] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0582] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0583] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0584] (a) Providing an intermittent urinary catheter; and

[0585] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the medium is a gel or paste.

[0586] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0587] (a) Providing an intermittent urinary catheter; and

[0588] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0589] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0590] (a) Providing an intermittent urinary catheter; and (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2, wherein the treatment comprises spray-coating the at least one amphipathic antimicrobial peptide onto a surface of the catheter.

[0591] According to a thirty-ninth aspect of the invention, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0592] (a) Providing an intermittent urinary catheter; and

[0593] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0594] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0595] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0596] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0597] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of: (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0598] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0599] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0600] (a) Providing an intermittent urinary catheter; and

[0601] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the medium is a gel or paste.

[0602] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0603] (a) Providing an intermittent urinary catheter; and (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0604] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0605] (a) Providing an intermittent urinary catheter; and

[0606] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3, wherein the treatment comprises spray-coating the at least one amphipathic antimicrobial peptide onto a surface of the catheter.

[0607] According to a fortieth aspect of the invention, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0608] (a) Providing an intermittent urinary catheter; and

[0609] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0610] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0611] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block; and

[0612] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0613] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0614] (a) Providing an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer and an amphiphilic lubricious additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the A- block preferably comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a where “a” is 5-25 and preferably 9-25, and wherein the B- block is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates; and

[0615] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0616] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0617] (a) Providing an intermittent urinary catheter; and (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the medium is a gel or paste.

[0618] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0619] (a) Providing an intermittent urinary catheter; and

[0620] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the medium is a gel or paste, and wherein said amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the medium, or between 0.05-5 wt.% of the medium.

[0621] In some preferred embodiments, there is provided a method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of:

[0622] (a) Providing an intermittent urinary catheter; and

[0623] (b) Treating the intermittent urinary catheter with a medium comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4, wherein the treatment comprises spray-coating the at least one amphipathic antimicrobial peptide onto a surface of the catheter.

[0624] The following statements apply to the thirty-third to fortieth aspects of the invention.

[0625] The intermittent urinary catheter of the thirty-third to fortieth aspects of the invention may be the intermittent urinary catheter of the first aspect of the invention. The amphipathic antimicrobial peptide of the thirty-third, thirty-fifth and thirty-sixth aspects of the invention may be the amphipathic antimicrobial peptide of the first aspect of the invention. The amphipathic antimicrobial peptide of the thirty-fourth and fortieth aspects of the invention may be the amphipathic antimicrobial peptide of the second aspect of the invention. The amphipathic antimicrobial peptide of the thirty-seventh, thirty-eighth and thirty-ninth aspects of the invention may be the amphipathic antimicrobial peptide of the first and / or second aspect of the invention.

[0626] The medium of the thirty-third to fortieth aspects of the invention may be the medium of the twenty-fifth to thirty-second aspects of the invention.

[0627] Statements of invention relating to any other aspect of the invention may also be applied mutatis mutandis to the thirty-third to fortieth aspects of the invention.

[0628] In some embodiments, the catheter in step (a) is provided before first use of the catheter. In some embodiments, the catheter in step (a) is provided after first use of the catheter. Steps (a) and (b) may be repeated. In such embodiments step (a) may comprise providing an unused catheter, followed by step (b) and then catheter used, followed by providing the used catheter in a further step (a) and then performing step (b). Such repetition of step (a) and / or (b) may be completed a plurality of times.

[0629] In some embodiments, the method comprises a washing step before each step (b). In some embodiments, the washing step takes place directly before step (b). The washing step may comprise washing a surface of the catheter, preferably the outer surface thereof, in some embodiments, the washing step comprises washing the catheter with water. In some embodiments, the washing step comprises washing the catheter with an aqueous solution. The washing step may comprise washing the catheter with a detergent and with water or an aqueous solution. In some embodiments, the washing step comprises applying a detergent to the catheter, preferably to the outer surface thereof, and then rinsing the catheter with water or an aqueous solution.

[0630] Treatment in step (b) may involve one or more treatment methods independently selected from the group comprising: submersion, spray coating, soaking, dipping, wetting, and combinations thereof.

[0631] In some embodiments, step (b) comprises treating at least one surface of the catheter with the medium, preferably at least an outer surface of the catheter.

[0632] 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.

[0633] 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.

[0634] In some embodiments, step (b) comprises submerging the catheter in the medium.

[0635] Submerging the catheter in the medium, especially between uses, has been shown to result in optimal catheter lubricity.

[0636] In some embodiments, step (b) comprises treating the catheter with the medium for a total time of at least 5 seconds, or at least 10, 20, 30, 40, or at least 50 seconds, or at least 1 minute, or at least 2, 3, 4, or at least 5 minutes, or at least 10, 20, 30, 40, or at least 50 minutes, or at least 1 hour, or at least 1.5, 2, 2.5, 3, 3.5, or at least 4 hours. Step (b) may comprise treating the catheter with the medium for a total time of no greater than 1 week, or no greater than 6 days, or no greater than 5, 4, 3, 2, or no greater than 1 day, or no greater than 20 hours, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, or no greater than 5 hours.

[0637] In some embodiments, step (b) is performed at a temperature of at least 1 °C, or at least 2, 3, 4, or at least 5 °C. In some embodiments, step (b) is performed at a temperature of no greater than 60 °C, or no greater than 55, 50, 45, 40, 35, 30, or no greater than 25 °C. In some embodiments, step (b) is performed at a temperature of between 1-60 °C, or between 5-50, or between 10-40 °C.

[0638] In some embodiments, step (b) is performed when the catheter is held in a container. The container may preferably be the container of the twenty-fifth to thirty-second aspects of the invention. The container may comprise the medium. Step (b) may comprise placing the catheter into the container to bring the catheter into direct contact with the medium. Step (b) may preferably comprise submerging the catheter in the medium. Step (b) may comprise placing the catheter in the container after each use of the catheter, and may preferably comprise submerging the catheter in the medium after each use of the catheter. There may be a plurality of containers containing medium, and each step (b) may comprise placing or submerging the catheter in a different medium container.

[0639] In some embodiments, the medium may be contained in a medium container and the catheter may be contained in a separate catheter container, preferably as described for the first aspect of the invention. Step (b) may comprise releasing the medium from the separate medium container, and then treating the catheter with the medium. In some embodiments, the method is repeated at least once. The method may be performed before and / or after each use of the catheter. In some embodiments, the method is performed 3 times a day, or 2 times a day, or once a day, or once every 2 days, or once every 3 days, or once every 4 days, or once every 5 days, or once every 6 days, or once a week, or once every 2 weeks, or once every 3 weeks, or once a month.

[0640] In some embodiments, the or each step (b) comprises treating the catheter with fresh medium that has not been used previously to treat the catheter. In such embodiments, the medium may be replaced with fresh medium before and / or after each step (b).

[0641] In some embodiments, the medium may be replaced with fresh medium at least every 6- hour period, or at least every 12, 18, or at least after every 24 hour period.

[0642] 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.

[0643] The additional lubricating agent may be water or may comprise water. The additional lubricating agent may be an aqueous solution.

[0644] 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.

[0645] In some embodiments, a further lubrication step is not performed. In such embodiments, the catheter may be used directly after step (b).

[0646] SEQ ID NO: 1

[0647] ACYCRIPACIAGERRYGTCIYQGRLWAFCC (Disulfide bridge: 2-30, 4-19, 9-29)

[0648] SEQ ID NO: 2

[0649] KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAK

[0650] SEQ ID NO: 3

[0651] GIGAVLKVLTTGLPALISWIKRKRQQ

[0652] SEQ ID NO: 4

[0653] ITSISLCTPGCKTGALMGCNMKTATCHCSIHVSK

[0654] Detailed Description of the Invention

[0655] 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:

[0656] Figure 1 graph of E. coli colony forming units (CFU) / mL versus time (seconds) for bacterial strains of E. coli directly inoculated with wash solutions containing different concentrations of antimicrobial peptide of Formula (I), as described in Example 1. Lines represent: control solution (no antimicrobial peptide); inventive solution 1 (0.05 wt.% peptide of Formula (I)); inventive solution 2 (1 wt.% peptide of Formula (I)); inventive solution 3 (2 wt.% peptide of Formula (I)); inventive solution 4 (3 wt.% peptide of Formula (I)); inventive solution 5 (4 wt.% peptide of Formula (I)); inventive solution 6 (5 wt.% peptide of Formula (I)).

[0657] Figure 2 graph of E. faecalis colony forming units (CFU) / mL versus time (seconds) for bacterial strains of E. faecalis directly inoculated with wash solutions containing different concentrations of antimicrobial peptide of Formula (I), as described in Example 1. Lines represent: control solution (no antimicrobial peptide); inventive solution 1 (0.05 wt.% peptide of Formula (I)); inventive solution 2 (1 wt.% peptide of Formula (I)); inventive solution 3 (2 wt.% peptide of Formula (I)); inventive solution 4 (3 wt.% peptide of Formula (I)); inventive solution 5 (4 wt.% peptide of Formula (I)); inventive solution 6 (5 wt.% peptide of Formula (I)).

[0658] Figure 3 graph of S. aureus colony forming units (CFU) / mL versus time (seconds) for bacterial strains of S. aureus directly inoculated with wash solutions containing different concentrations of antimicrobial peptide of Formula (I), as described in Example 1. Lines represent: control solution (no antimicrobial peptide); inventive solution 1 (0.05 wt.% peptide of Formula (I)); inventive solution 2 (1 wt.% peptide of Formula (I)); inventive solution 3 (2 wt.% peptide of Formula (I)); inventive solution 4 (3 wt.% peptide of Formula (I)); inventive solution 5 (4 wt.% peptide of Formula (I)); inventive solution 6 (5 wt.% peptide of Formula (I)). Figure 4 graph of E. coli colony forming units (CFU) / 30 mL versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the exit of the channel) for intermittent catheters that were lubricated with different gels before being inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. coli, as described in Example 2. Lines represent: Control catheter 1 (untreated - no antimicrobial peptide); Inventive catheter (lubricated with gel comprising 1 wt.% peptide of Formula (I)); Control catheter 2 (lubricated with a placebo gel); Control catheter 3 (positive control).

[0659] Figure 5 graph of E. coli colony forming units (CFU) / section versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the exit of the channel) for intermittent catheters that were spray-coated with sprays containing different concentrations of antimicrobial peptide of Formula (I) before being inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. coli, as described in Example 2. Lines represent: Control catheter 1 (uncoated - no antimicrobial peptide); Inventive catheter 1 (spray-coated with spray containing 0.5 wt.% peptide of Formula (I)); Inventive catheter 2 (spray- coated with spray containing 1 wt.% peptide of Formula (I)); Control catheter 2 (bacterial growth control).

[0660] Figure 6 graph of E. coli colony forming units (CFU) / mL versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the exit of the channel) for intermittent catheters that were washed with aqueous solutions having different concentrations of antimicrobial peptide of Formula (I) before being inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. coli, as described in Example 2. Lines represent: Control catheter 1 (unwashed - no antimicrobial peptide); Inventive catheter 1 (washed with aqueous solution comprising 0.05 wt.% peptide of Formula (I)); Inventive catheter 2 (washed with aqueous solution comprising 1 wt.% peptide of Formula (I)); Inventive catheter 3 (washed with aqueous solution comprising 2 wt.% peptide of Formula (I)); Inventive catheter 4 (washed with aqueous solution comprising 3 wt.% peptide of Formula (I)); Inventive catheter 5 (washed with aqueous solution comprising 4 wt.% peptide of Formula (I)); Inventive catheter 6 (washed with aqueous solution comprising 5 wt.% peptide of Formula (I)); Control catheter 2 (positive control).

[0661] Figure 7 graph of E. coli NCIMB 14067 colony forming units CFU / section versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the exit of the channel) for intermittent catheters that were hydrated with solutions before being inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. coli NCIMB 14067, as described in Example 3. Lines represent: Inventive run (catheter hydrated with solution of antimicrobial peptide of SEQ ID NO: 3 - melittin); Control run 1 (catheter used per instructions for use (IFU) and containing no antimicrobial peptide); Control run 2 (catheter not inserted into agar channel. Agar channel inoculated with E. coli NCIMB 14067 in first 1 cm of channel - positive control). Figure 8 graph of E. faecalis NCTC 12201 colony forming units CFU / section versus agar gel channel section (1-7, where 1 is at the entrance of the channel and 7 is at the exit of the channel) for intermittent catheters that were inserted into agar gel channels whose entrances were inoculated with bacterial strains of E. faecalis NCTC 12201, as described in Example 3. Lines represent: Inventive run (catheter hydrated with solution of antimicrobial peptide of SEQ ID NO: 4 - nisin); Control run 1 (catheter used per instructions for use (IFU) and containing no antimicrobial peptide); Control run 2 (catheter not inserted into agar channel. Agar channel inoculated with E. faecalis NCTC 12201 in first 1 cm of channel - positive control).

[0662] Example 1 - Rate of Kill Testing

[0663] The following test was performed to evaluate the rate at which amphipathic antimicrobial peptides of the invention are able to kill bacteria.

[0664] Test procedure

[0665] Wash solutions of antimicrobial peptides of the invention in water were independently inoculated with three bacterial strains: E. coli, E. faecalis, and S. aureus.

[0666] Presence and amounts of the bacteria were monitored over time.

[0667] Solutions tested and results

[0668] Solutions containing amphipathic antimicrobial peptide of Formula (I)

[0669] The solutions tested were:

[0670] Inventive solution 1: 0.05 wt.% peptide of Formula (I) Inventive solution 2: 1 wt.% peptide of Formula (I)

[0671] Inventive solution 3: 2 wt.% peptide of Formula (I)

[0672] Inventive solution 4: 3 wt.% peptide of Formula (I)

[0673] Inventive solution 5: 4 wt.% peptide of Formula (I)

[0674] Inventive solution 6: 5 wt.% peptide of Formula (I)

[0675] Control solution: no antimicrobial peptide

[0676] The results of the tests are displayed in Figures 1-3.

[0677] Rapid bacterial kill was demonstrated for the majority of solutions of amphipathic antimicrobial peptide of Formula (I) and for all bacterial strains c.f. the control runs for which bacterial content remained almost unchanged over the time periods tested. E. coli was the most susceptible to the antimicrobial peptide, showing an approximate 4-orders of magnitude reduction in bacterial colony forming units per mL after just 60 seconds and for all concentrations of antimicrobial peptide tested.

[0678] The results demonstrate the ability of the amphipathic antimicrobial peptide of Formula (I) to rapidly kill bacteria within short timeframes, which mirror typical indwell times of intermittent catheters.

[0679] Solutions containing amphipathic antimicrobial peptides of Formula (II), antimicrobial peptides having an amino acid sequence as shown in SEQ ID NO: 1, antimicrobial peptides having an amino acid sequence as shown in SEQ ID NO: 2, antimicrobial peptides having an amino acid sequence as shown in SEQ ID NO: 3, and antimicrobial peptides having an amino acid sequence as shown in SEQ ID NO: 4. The same test as above was also performed with analogous solutions that instead contained the following different amphipathic antimicrobial peptides of the invention:

[0680] • An amphipathic antimicrobial peptide of Formula (II).

[0681] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0682] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0683] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0684] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0685] Analogous results were achieved compared with solutions containing an antimicrobial peptide of Formula (I), demonstrating the ability of all inventive peptides to rapidly kill bacteria within short timeframes, which mirror typical indwell times of intermittent catheters.

[0686] Example 2 - Bacterial Displacement Testing

[0687] The following test was performed to evaluate the ability of amphipathic antimicrobial peptides of the invention to prevent transfer of bacteria through the urethra upon insertion of an intermittent catheter.

[0688] Test procedure

[0689] Agar test channels with entrance and exit holes on either end were provided to model a catheter being passed through the body. The entrances of the channels were independently inoculated with bacterial strains of E. coli.

[0690] Intermittent catheters were independently inserted in through the entrance hole of the agar gel channel, pushed through, and then removed from the exit hole.

[0691] Following removal of the catheters, agar gel channels were cut in half and the presence and amounts of bacteria along the insides of the channels were measured to determine migration of the bacteria through the channels.

[0692] Bacterial presence and amounts were determined at 7 sections along the length of the channels (sections 1-7). Section 1 being at the entrance of the channel and section 7 being at the exit of the channel.

[0693] Catheters tested and results

[0694] Intermittent catheters lubricated with gels comprising amphipathic antimicrobial peptides of the invention

[0695] Intermittent catheter coated with a gel comprising an amphipathic antimicrobial peptide of Formula (I)

[0696] Intermittent catheters were provided comprising a hollow polymeric tubular body comprising a base polymer formed from a thermoplastic elastomeric material and further comprising an amphiphilic additive. The amphiphilic additive was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a, where “a” is 5-25 and preferably 9-25, and a hydrophilic B -block, wherein the B-block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0697] The intermittent catheters were lubricated on their entire outer surfaces with different gelbased lubricating agents before performing the above test.

[0698] The catheters tested were:

[0699] Inventive run: catheter lubricated with a gel comprising 1 wt.% peptide of Formula (I)

[0700] Control run 1 : untreated catheter (no antimicrobial peptide)

[0701] Control run 2: catheter lubricated with a placebo gel

[0702] Control run 3 (positive control): catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria.

[0703] The results are displayed in Figure 4.

[0704] The inventive intermittent catheter lubricated with a gel comprising the antimicrobial peptide of Formula (I) allows for a significant reduction in bacteria transfer along the channel compared to the untreated and placebo gel lubricated controls. At section 3 of the channel for the inventive run, an at least 3 order of magnitude reduction in bacterial colony forming units per mL was observed.

[0705] Intermittent catheters lubricated with a gel comprising an amphipathic antimicrobial peptide of Formula (II), with a gel comprising an antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and with a gel comprising an antimicrobial peptide having an amino acid sequence as shown in SEQ ID

[0706] NO: 4. The same test as above was also performed with analogous intermittent catheters that were instead lubricated with the following different gels comprising amphipathic antimicrobial peptides of the invention:

[0707] • A gel comprising an amphipathic antimicrobial peptide of Formula (II).

[0708] • A gel comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0709] • A gel comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0710] • A gel comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0711] • A gel comprising an amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0712] Analogous results were achieved compared with the intermittent catheter lubricated with a gel comprising an antimicrobial peptide of Formula (I), indicating the ability of all inventive peptides to greatly reduce bacteria transfer along the urethra when the lubricated intermittent catheters are inserted.

[0713] Intermittent catheters spray-coated with amphipathic antimicrobial peptides of the invention

[0714] Intermittent catheters spray-coated with an amphipathic antimicrobial peptide of Formula m Intermittent catheters were provided comprising a hollow polymeric tubular body comprising a base polymer formed from a thermoplastic elastomeric material and further comprising a hydrophilic polyvinylpyrrolidone additive.

[0715] The intermittent catheters were spray-coated on their entire outer surfaces with different concentrations of the antimicrobial peptide of Formula (I) before performing the above test.

[0716] The catheters tested were:

[0717] Inventive catheter 1 : spray-coated with spray containing 0.5 wt.% peptide of Formula (I)

[0718] Inventive catheter 2: spray-coated with spray containing 1 wt.% peptide of Formula (I)

[0719] Control catheter 1 : uncoated (no antimicrobial peptide)

[0720] Control catheter 2 (bacterial growth control) : catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria.

[0721] The results of the tests are displayed in Figure 5.

[0722] Performance of the inventive intermittent catheters spray-coated with the antimicrobial peptide of Formula (I) is similar to that of intermittent catheters lubricated with gels comprising the same peptide. Both inventive spray-coated catheters allow for a rapid bacterial kill and a significant reduction in bacteria transfer along the channel compared to the uncoated control. As for the inventive gel run, at section 3 of the channel for both spray-coated inventive runs, an at least 3 order of magnitude reduction in bacterial colony forming units per section was observed.

[0723] Intermittent catheters spray-coated with amphipathic antimicrobial peptides of Formula (II), with antimicrobial peptides having an amino acid sequence as shown in SEO ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and with antimicrobial peptides having an amino acid sequence as shown in SEQ ID NO: 4.

[0724] The same test as above was also performed with analogous intermittent catheters that were instead spray-coated with the following different amphipathic antimicrobial peptides of the invention:

[0725] • An amphipathic antimicrobial peptide of Formula (II).

[0726] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0727] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0728] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0729] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0730] Analogous results were achieved compared with the intermittent catheters spray-coated with antimicrobial peptides of Formula (I), again indicating the ability of all inventive peptides to greatly reduce bacteria transfer along the urethra when the coated intermittent catheters are inserted.

[0731] Intermittent catheters washed in solutions of amphipathic antimicrobial peptides of the invention

[0732] Intermittent catheters washed in aqueous solutions of amphipathic antimicrobial peptide of Formula (I) Intermittent catheters were provided comprising a hollow polymeric tubular body comprising a base polymer formed from a thermoplastic elastomeric material and further comprising an amphiphilic additive. The amphiphilic additive was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CH3CH2(CH2CH2)a, where “a” is 5-25 and preferably 9-25, and a hydrophilic B -block, wherein the B-block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

[0733] The intermittent catheters were washed with aqueous solutions having different concentrations of the antimicrobial peptide of Formula (I) before performing the above test.

[0734] The catheters tested were:

[0735] Inventive catheter 1: washed with aqueous solution comprising 0.05 wt.% peptide of Formula (I)

[0736] Inventive catheter 2: washed with aqueous solution comprising 1 wt.% peptide of Formula (I)

[0737] Inventive catheter 3: washed with aqueous solution comprising 2 wt.% peptide of Formula (I)

[0738] Inventive catheter 4: washed with aqueous solution comprising 3 wt.% peptide of

[0739] Formula (I) Inventive catheter 5: washed with aqueous solution comprising 4 wt.% peptide of Formula (I)

[0740] Inventive catheter 6: washed with aqueous solution comprising 5 wt.% peptide of Formula (I)

[0741] Control catheter 1 : unwashed (no antimicrobial peptide)

[0742] Control catheter 2 (positive control): catheter not inserted into agar channel, but entrance of agar channel still inoculated with bacteria.

[0743] The results of the tests are displayed in Figure 6.

[0744] Performance of the inventive washed intermittent catheters is similar to that of intermittent catheters lubricated with gels comprising the same peptide and catheters that are spray-coated with the same peptide. All inventive washed catheters allow for rapid bacterial kill and a significant reduction in bacteria transfer along the channel compared to the uncoated control. However, performance is best using aqueous solutions comprising the peptide of Formula (I) in concentrations of 1 wt.% and above. At section 3 of the channel for inventive runs using aqueous solutions comprising the peptide of Formula (I) in concentrations of 1 wt.% and above, an at least 3 order of magnitude reduction in bacterial colony forming units per section was observed.

[0745] Intermittent catheters washed with aqueous solutions comprising amphipathic antimicrobial peptides of Formula (II), with aqueous solutions comprising antimicrobial peptides having an amino acid sequence as shown in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and with aqueous solutions comprising antimicrobial peptides having an amino acid sequence as shown in SEQ ID NO: 4. The same test as above was also performed with analogous intermittent catheters that were instead washed with aqueous solutions comprising the following different amphipathic antimicrobial peptides of the invention:

[0746] • An amphipathic antimicrobial peptide of Formula (II).

[0747] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0748] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0749] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0750] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0751] Analogous results were achieved compared with the intermittent catheters washed with aqueous solutions comprising an antimicrobial peptide of Formula (I), again indicating the ability of all inventive peptides to greatly reduce bacteria transfer along the urethra when the coated intermittent catheters are inserted.

[0752] Example 3 - Bacterial displacement testing using challenge organisms E. coli

[0753] NCIMB 14067 and E. faecalis NCTC 12201

[0754] Bacterial displacement testing was performed as for Example 3 above, but using two challenge organisms, E. coli NCIMB 14067 and E. faecalis NCTC 12201 which are typically found in the urethral meatus.

[0755] Urethra agar channel (UAC) preparation Selective agar channels were made by aseptically dispensing 30 mL of molten Harlequin tryptone bile glucuronide (TBX) agar + 0.4% AB (agar bacteriological) (a selective agar for E. coli NCIMB 14067) and molten Harlequin VRE chromogenic agar + 1% AB (a selective agar for E. faecalis NCTC 12201) into 30 mL universal containers. Sterile 4 mm stainless steel rods, held in place by sterile stainless steel locating discs, were placed into the universal containers and removed once set to create a channel down the centre of the agar the same diameter as the tested catheters. The channels were left standing, with their lids removed, within the laminar flow cabinet to dry for 18-24 hours. Additionally, to prepare the channels, just before testing, any fluid within the agar channel was removed using a sterile needle and syringe, a sterile swab was then inserted slowly (around 3 seconds) down the length of the channel, rotated anticlockwise twice at the base of the channel and slowly removed. The resultant channels were used for testing.

[0756] Challenge organism preparation

[0757] Representative colonies from an 18-24 hour challenge culture plate, were dispersed in maximum recovery diluent (MRD) to obtain an optical density (OD540nm) equivalent to approximately IxlO8CFU / mL. This will be diluted ten-fold to obtain a working concentration of IxlO7CFU / mL. 50 pL volumes of this working concentration were transferred into separate bijous for inoculation.

[0758] UAC inoculation

[0759] A sterile Flocked swab was placed into the 50 pL inoculum of the above working concentration and left to sit for 10 seconds. The inoculated swab was then inserted 1 cm into the insertion entrance of the UAC, rotated anticlockwise twice, and removed. This was performed for all the test and bacterial growth control UACs. The inoculated UACs were then left lying horizontally with the lid off and the open, inoculated end facing the flame to dry for 15 minutes. The bacterial growth control image UAC was incubated at 35 ± 3 °C for 24 hours after inoculation and the bacterial growth control total viable counts (TVC) UAC was immediately tested as stated below.

[0760] Testing performed

[0761] Intermittent catheters were tested, which had a hollow polymeric tubular body comprising a base polymer formed from a thermoplastic elastomeric polyolefin 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 CHsdh ClhCFhla, 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.

[0762] The intermittent catheters were hydrated with 10 mL solutions of either an antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3 (solution concentration = 25 mg / mL) or an antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4 (solution concentration 6.25 pg / mL). Catheters were then tested against E. coli NCIMB 14067 or E. faecalis NCTC 12201 (n=3 for TVCs and n=l for visual displacement images).

[0763] Test method - testing for visual displacement images

[0764] Catheters were slowly inserted into UACs (approximately 3 seconds) and left in place for

[0765] 2 minutes to represent urination. Following insertion and removal of the catheter and a 15 minute drying time, the UACs were incubated at 35 ± 3 °C for 24 hours. Following incubation, the UACs were aseptically tipped from the container onto a sterile surface and under aseptic conditions the UACs were split in half lengthways. The two halves of the UACs were then separated so the inside of the channels were visible and growth of the bacteria was therefore also visible, images were taken to observe the bacteria’s displacement through the UACs.

[0766] Test method - testing for total viable counts (TVCs)

[0767] Catheters were slowly inserted into UACs (approximately 3 seconds) and left in place for 2 minutes to represent urination. Following insertion and removal of the catheter and a 15 minute drying time, the UACs were aseptically tipped from the universal containers and cut into 7x 1 cm sections starting at the insertion entry of the UAC. The 1st, 3rd, 5th and 7th cm were stomached on high for 4 minutes in phosphate buffered saline (PBS) + 2% polyanetholsulfonic acid sodium salt (SPS) and plated out onto pre-dried tryptone soy agar (TSA) plates in appropriate dilutions. Plates were incubated at 35 ± 3 °C for 48 hours.

[0768] Results

[0769] The presence of E. coli NCIMB 14067 on Harlequin TBX selective agar appears blue / green and E.faecalis NCTC 12201 on Harlequin VRE selective agar appears green which allowed for clear visualisation of bacterial displacement along the channel.

[0770] The challenge organism, E. coli NCIMB 14067 and E. faecalis NCTC 12201 were inoculated in the first 1 cm of the UAC (which were seen by blue-green / green colonies on the UAC respectively). Images of the agar channels after testing with intermittent catheters hydrated with both inventive antimicrobial peptides (SEQ ID NO: 3 and SEQ ID NO: 4) showed that bacterial displacement along the UACs was reduced for both E. coli NCIMB 14067 and E. faecalis NCTC 12201. For E. coli NCIMB 14067, only a few colonies were present towards the end of the UAC. However, for E. faecalis NCTC 12201, almost no bacterial colonies were observed throughout the entire UAC.

[0771] TVC results also reflected the image tests obtained for both challenge organisms tested. Bacterial presence and amounts were determined at 7 sections along the length of the agar channels (sections 1-7). Section 1 being at the entrance of the channel and section 7 being at the exit of the channel.

[0772] Intermittent catheter hydrated with amphipathic antimicrobial peptide of SEO ID NO: 3

[0773] The catheters tested were:

[0774] Inventive run: catheter hydrated as described above with solution of antimicrobial peptide of SEQ ID NO: 3 (melittin).

[0775] Control run 1: catheter used as per instructions for use (IFU) and containing no antimicrobial peptide.

[0776] Control run 2: catheter not inserted into UAC. UAC inoculated with E. coli NCIMB 14067 in first 1 cm (positive control).

[0777] The results are displayed in Figure 7.

[0778] The inventive intermittent catheter hydrated with a solution of antimicrobial peptide of SEQ ID NO: 3 allowed for a significant reduction in bacteria transfer along the channel compared to the IFU control.

[0779] Intermittent catheter hydrated with amphipathic antimicrobial peptide of SEQ ID NO: 4

[0780] The catheters tested were: Inventive run: catheter hydrated as described above with solution of antimicrobial peptide of SEQ ID NO: 4 (nisin).

[0781] Control run 1: catheter used as per instructions for use (IFU) and containing no antimicrobial peptide.

[0782] Control run 2: catheter not inserted into UAC. UAC inoculated with E. faecalis NCTC 12201 in first 1 cm (positive control).

[0783] The results are displayed in Figure 8.

[0784] The inventive intermittent catheter hydrated with a solution of antimicrobial peptide of SEQ ID NO: 4 allowed for a dramatic reduction in bacteria transfer along the channel compared to the IFU control, with bacterial counts reaching undetectable levels by section 3 of the agar channel.

[0785] Example 4 - Residual Antimicrobial Activity Testing

[0786] The following test was performed to model how long-lasting the antimicrobial activity of amphipathic antimicrobial peptides of the invention is when residual antimicrobial peptides of the invention are left within the urethra following insertion and removal of an intermittent catheter that has been treated with the respective peptide of the invention.

[0787] Test procedure

[0788] Representative E. coli bacterial colonies from an 18-24 hour challenge culture plate were dispersed in maximum recovery diluent (MRD) to obtain an optical density (OD540nm) equivalent to approx. IxlO8CFU / mE. This was diluted to obtain a working concentration of IxlO4CFU / ml. 10 pF volumes of this working concentration were used for testing. Before performing the test, some initial method development testing was performed to establish how much residual antimicrobial solution was left within a urethral agar channel (UAC) following bacterial displacement testing. This was performed by weighing the UAC before and after insertion of a catheter. Results obtained suggested that a range from 19.5 pl to 36.7 pl was left within the UAC. Therefore, testing moving forward was based on worst case, which was the maximum left in the UAC at approximately 40 pl.

[0789] Sterile 25mm Whatman filters were placed onto the centre of a Pre-dried Tryptone Soy Agar (TSA) plate and 40 pl of the test sample (antimicrobial solutions) was placed onto the centre of the filter (n=3 per sample). TSA / filter / sample plates were set up for 0 hour, 30 minute, 4 hour and 24 hour time points. The timepoint was started immediately after adding the sample to the filter. To minimise sample evaporation, TSA / filter / sample plates were parafilmed and left at room temperature.

[0790] At the different time points, 10 pL of the working concentration of bacteria were added to the centre of the filter containing the test sample.

[0791] The presence of growth or no growth of bacteria on the plates was determined for each time point.

[0792] Samples tested and results of Formula

[0793] The samples tested were:

[0794] Inventive sample: aqueous solution comprising 1 wt.% peptide of Formula (I)

[0795] Control sample 1: no sample Control sample 2: sterile deionised water

[0796] Control sample 3 (positive control): aqueous solution comprising 2 wt.% Presept

[0797] The results of the tests are displayed in Table 1 below.

[0798] Table 1

[0799] The plate treated with the solution of the inventive peptide of Formula (I) shows rapid antimicrobial activity, with no bacterial growth found immediately after treatment of the plate. In addition, antimicrobial activity is long-lasting, with the peptide of Formula (I) showing activity beyond the positive control and for up to 24 hours. The above results indicate the ability of the antimicrobial peptide of the invention to provide long lasting protection against the growth of pathogenic microorganisms whilst an intermittent catheter is left in urethral tissue during and after catheterisation, and also between catheter uses.

[0800] Amphipathic antimicrobial peptides of Formula (II), antimicrobial peptides having an amino acid sequence as shown in SEO ID NO: 1, SEO ID NO: 2, SEO ID NO: 3, and antimicrobial peptides having an amino acid sequence as shown in SEQ ID NO: 4.

[0801] The same test as above was also performed with analogous TS A plates that were instead treated with aqueous solutions of the following different amphipathic antimicrobial peptides of the invention:

[0802] • An amphipathic antimicrobial peptide of Formula (II).

[0803] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 1.

[0804] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 2.

[0805] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 3.

[0806] • An amphipathic antimicrobial peptide having an amino acid sequence as shown in SEQ ID NO: 4.

[0807] Analogous results were achieved compared with samples treated with an antimicrobial peptide of Formula (I), demonstrating the ability of all inventive peptides to provide long-lasting antimicrobial activity.

[0808] Example 5 - Antimicrobial efficacy of sulfanilamide (comparative compound - not of the invention) For comparison purposes with the antimicrobial peptides of the invention, the sterilisation potential of a known antimicrobial agent was investigated.

[0809] An in vitro direct inoculation method was used to assess the antimicrobial activity of sulfanilamide in an intermittent urinary catheter scenario against gram-positive Escherichia co / z' NCIMB 14067 and gram-negative Enterococcus faecalis NCTC 12201; two microorganisms associated with urinary tract infections. Sulfanilamide concentrations of 0.1% and 0.01% were tested and bacterial levels monitored over a period of 5 minutes.

[0810] Representative colonies of the challenge microorganisms, from an 18-24 hour challenge culture plate, were dispersed in MRD to obtain an optical density (OD540nm) equivalent to approximately 1 x 108CFU / mL. This was diluted to obtain a working concentration of 1 x 106CFU / mL. A quantitative count was performed to confirm the inoculum level.

[0811] The challenge organism was prepared in MRD to a concentration of approximately 1 x 106CFU / mL. This suspension was added in a 1 mL volume to 9 mL of sample (n=3 per sample, n=2 per control) in a sterile 30 mL universal and pipetted up and down to mix. Following each testing period, 5 seconds, 30 seconds, 1 minute, 2 minutes and 5 minutes, 100 pL of the test solution was transferred to 0.9 mL and 9.9 mL volumes of Dey-Engley Neutralising Broth (DENB) (1:10 and 1 : 100 dilutions respectively). The most appropriate dilutions were inoculated (100 pL) onto duplicate pre-dried (tryptone soy agar) TSA plates and the inoculum spread using separate sterile L-shaped spreaders (for 101and 10’2dilutions, 0.5 mL were placed onto duplicate plates). The TSA plates were allowed to dry before being inverted and incubated at 35 ± 3 °C for at least 48 hours. Following the incubation period, the number of bacterial colonies were counted on the most appropriate dilution for each sample i.e. between 25-250 CFU / plate.

[0812] The samples tested were: 0.1% sulfanilamide in sterile deionised water (SDW); 0.01% sulfanilamide in SDW; and a SDW control.

[0813] There was no decrease in challenge organism numbers of E. coli NCIMB 14067 or E. faecalis NCTC 12201 when added to sulfanilamide (at both concentrations tested) when compared to the control for any of the timepoints tested.

[0814] Intermittent urinary catheter kit of the invention

[0815] Intermittent urinary catheter kits of the invention were provided. The kits comprised a container in the form of a tube comprising a flexible central portion and two rigid side portions. The tubes contained an intermittent urinary catheter comprising a hollow polymeric tubular body comprising a base polymer formed from a thermoplastic elastomeric material and further comprising an amphiphilic additive. The amphiphilic additive was an A-B block copolymer comprising an A-block comprising a hydrocarbon chain block of the formula CHsCth CthCthla, where “a” is 5-25 and preferably 9-25, and a hydrophilic B -block, wherein the B -block was a hydrophilic oligomer comprising between 2 and 10 monomer units derived from monomers selected from the group consisting of: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates. Containers of the kits were independently filled with media comprising the following amphipathic antimicrobial peptides of the invention: a peptide of Formula (I), a peptide of Formula (II), a peptide having an amino acid sequence as shown in SEQ ID NO: 1, a peptide having an amino acid sequence as shown in SEQ ID NO: 2, a peptide having an amino acid sequence as shown in SEQ ID NO: 3, and a peptide having an amino acid sequence as shown in SEQ ID NO: 4. The intermittent catheters were submerged in the media in the containers. An end of the containers comprised a lid which was releasably attached to the container and allowed for the container to be opened and closed allowing for the catheter to be removed for use and re-inserted for storage between uses.

[0816] The catheters could simply be removed from the containers and used in the conventional manner. Catheter lubricity was excellent and wholly unaffected by storage in the antimicrobial peptide media. The media also provided excellent, long-term antimicrobial performance and overall catheter sterility. 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. An intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is tryptophan or a derivative thereof, and at least one amino acid is arginine or a derivative thereof.

2. An intermittent urinary catheter comprising a surface comprising at least one amphipathic antimicrobial peptide, wherein only a single amino acid of the at least one amphipathic antimicrobial peptide is proline or a derivative thereof.

3. An intermittent urinary catheter as claimed in any preceding claim, wherein the at least one amphipathic antimicrobial peptide comprises a peptide in which all amino acids are the L-isomer.

4. An intermittent urinary catheter as claimed in any preceding claim when dependent on claim 1, wherein the at least one amphipathic antimicrobial peptide comprises a peptide of the formula: AA1-AA2-AA3-X, wherein AA1 is arginine or a derivative thereof; AA2 is tryptophan or a derivative thereof, preferably 2,5,7- lris- / c / 7-bulyl tryptophan; AA3 is arginine or a derivative thereof; and X is independently chosen from: an alkyl group, an aryl group, an alkaryl group, an alkylamino group, an arylamino group, and an alkarylamino group.

5. An intermittent urinary catheter as claimed in claim 4, wherein the at least one amphipathic antimicrobial peptide comprises a compound of Formula (I).Formula (I)6. An intermittent urinary catheter as claimed in any preceding claim, wherein the at least one amphipathic antimicrobial peptide comprises a peptide that is between 10 to 55 amino acids in length, and preferably between 25 to 45 amino acids in length.

7. An intermittent catheter as claimed in any preceding claim, wherein the at least one amphipathic antimicrobial peptide comprises a peptide in which an alanine amino acid or derivative thereof is directly adjacent to a proline amino acid or derivative thereof, and / or in which a glycine amino acid or derivative thereof is directly adjacent to a proline amino acid or derivative thereof.

8. An intermittent urinary catheter as claimed in any preceding claim, wherein the at least one amphipathic antimicrobial peptide comprises a peptide comprising at least one cysteine amino acid or derivative thereof, and wherein preferably between 15-25% of the total number of amino acids of the peptide are cysteine or derivatives thereof, and wherein the at least one amphipathic antimicrobial peptide preferably comprises a peptide comprising at least onecysteine-cysteine disulfide bridge, preferably between 1-5 cysteine-cysteine disulfide bridges, and wherein the at least one amphipathic antimicrobial peptide preferably comprises a peptide in which a tryptophan amino acid or derivative thereof is directly adjacent to a leucine amino acid or derivative thereof and to an alanine amino acid or derivative thereof, and wherein the at least one amphipathic antimicrobial peptide preferably comprises a peptide having an amino acid sequence as shown in SEQ ID NO: 1.

9. An intermittent urinary catheter as claimed in any preceding claim, wherein the at least one amphipathic antimicrobial peptide comprises a peptide in which a tryptophan amino acid or derivative thereof is directly adjacent to two lysine amino acids or derivatives thereof, and wherein the at least one amphipathic antimicrobial peptide preferably comprises a peptide having an amino acid sequence as shown in SEQ ID NO: 2.

10. An intermittent urinary catheter as claimed in any preceding claim, wherein the at least one amphipathic antimicrobial peptide comprises a peptide in which a tryptophan amino acid or derivative thereof is directly adjacent to an isoleucine amino acid or derivative thereof and to a serine amino acid or derivative thereof, and wherein the at least one amphipathic antimicrobial peptide preferably comprises a peptide having an amino acid sequence as shown in SEQ ID NO: 3.

11. An intermittent urinary catheter as claimed in any preceding claim, wherein the at least one amphipathic antimicrobial peptide comprises a peptide in which a proline amino acid or derivative thereof is directly adjacent to athreonine amino acid or derivative thereof and to a glycine amino acid or derivative thereof, and wherein the at least one amphipathic antimicrobial peptide preferably comprises a peptide having an amino acid sequence as shown in SEQ ID NO: 4.

12. An intermittent urinary catheter as claimed in any preceding claim, wherein the catheter further comprises at least one amphiphilic additive, wherein the amphiphilic additive is an amphiphilic A-B block copolymer comprising a hydrophobic hydrocarbon A-block and a hydrophilic B -block, wherein the amphiphilic additive is preferably 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 is preferably a hydrophilic oligomer comprising between 2 and 10 monomer units optionally derived from monomers chosen from: alkylene oxides, alkylene glycols, epihalohydrins, unsaturated carboxylic acids, alkylene imines, lactones, vinyl alcohol, and vinyl alkanoates.

13. An intermittent urinary catheter as claimed in any preceding claim, wherein the catheter comprises a hollow polymeric tubular body comprising a base polymer that is independently chosen from: polyolefins, polyesters, poly acrylates, polyamides, thermoplastic elastomeric material, poly ether block amide, thermoplastic vulcanizates, thermoplastic copolyesters, thermoplastic polyamides, fluororubber, water disintegrable or enzymatically hydrolysable material, and combinations, blends or copolymers of any of the above materials.

14. An intermittent urinary catheter as claimed in any preceding claim, wherein the at least one amphipathic antimicrobial peptide is present as a spray-coated coating, and wherein the at least one amphipathic antimicrobial peptide is preferably present in a total concentration of between 0.01-10 wt.% of the coating.

15. An intermittent urinary catheter as claimed in any one of claims 1 to 13, wherein the at least one amphipathic antimicrobial peptide is present as a gel or paste coating.

16. An intermittent catheter as claimed in claim 15, wherein the at least one amphipathic antimicrobial peptide is present in a total concentration of between 0.01-10 wt.% of the gel or paste coating, or preferably between 0.05- 5 wt.% of the gel or paste coating.

17. A method of manufacturing an intermittent urinary catheter, the method comprising the steps of: a. Providing an intermittent urinary catheter; and b. Coating a surface of the intermittent urinary catheter with at least one amphipathic antimicrobial peptide according to any preceding claim.

18. Use of at least one amphipathic antimicrobial peptide according to any one of claims 1 to 16 as a bactericidal and / or lubricating agent on a surface of an intermittent catheter.

19. An intermittent urinary catheter kit comprising a container comprising: an intermittent urinary catheter; and a medium comprising at least one amphipathic antimicrobial peptide according to any one of claims 1 to 16.

20. A method of sterilising and / or lubricating an intermittent urinary catheter, the method comprising the steps of: a. Providing an intermittent urinary catheter; and b. Treating the intermittent urinary catheter with a medium comprising at least one amphipathic antimicrobial peptide according to any one of claims 1 to 16.

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